Sharon Worcester

Major Finding: The rate of STDs in the year before receiving a prescription was 214 per 100,000 ED drug users, compared with 106 per 100,000 nonusers, and the rate in the year after receiving a prescription was 105 per 100,000 ED drug users, compared with 65 per 100,000 (adjusted odds ratios of 2.80 and 2.65 for an STD in ED users in the year before and after a prescription, respectively).

Data Source: A retrospective cohort study of 1,410,806 men.

Disclosures: The Bing Study Center for Health Economics and the RAND Roybal Center for Health Policy Simulation sponsored the research for this study. Dr. Jena received support from the National Institutes of Health and the Agency for Healthcare Research and Quality.

Men who use pharmacologic treatment for erectile dysfunction have higher rates of sexually transmitted diseases than do nonusers both before and after they receive a prescription for ED drugs, according to the findings of a retrospective cohort study of 1,410,806 men over age 40.

The rate of sexually transmitted diseases in the year before receiving a prescription was 214 per 100,000 ED drug users, compared with 106 per 100,000 nonusers. In the year after receiving a prescription, the rate was 105/100,000 ED drug users, compared with 65/100,000. The adjusted odds ratios were 2.80 and 2.65 for an STD in ED users in the year before and after a prescription, respectively, Dr. Anupam B. Jena of Massachusetts General Hospital, Boston, and colleagues reported.

The finding of increased risk both before and after receiving a prescription suggests that the association seen in this study has more to do with the types of patients who use ED drugs, than with the actual use of ED drugs, the investigators said (Ann. Intern. Med. 2010;153:1-7).

“Risk assessment for STDs and counseling about safe sexual practices” should accompany the prescription of ED drugs, they wrote, citing their findings as well as those from prior studies showing that condom use declines with age Fue investigators also noted researchindnking ED druguse h high-risksexuavior in men who have sex with men.

For their study, the investigators used a database of insurance claims from 1997 to 2006, including data on 33,968 men with at least 1 filled prescription for an ED drug, and 1,376,838 men with no ED drug prescription. They adjusted for age and comorbid conditions, and found that the differences in STD rates between ED drug users and nonusers were due largely to HIV infection.

The adjusted odds ratios for HIV infection in the year before and after an ED drug prescription were 3.32 and 3.19, respectively.

They noted, however, thatalterall rates of STDs remain low, and the routine testing for STDs in men requesting ED treatment would probably not be cost effective.

My Take

Counsel About Safe Sex After Age 40

Sex after age 40 years remains safer than during adolescence, but the age-related differences in risk have been eroding in recent decades as the rate of STDs in older adults increased, Dr. Thomas Fekete wrote in an editorial.

The increase has occurred in tandem with dramatic increases in the use of the drugs for erectile dysfunction, at least in the last decade, and the findings of Dr. Jena and associates regarding an increased rate of STDs in men over age 40 who use ED drugs (as compared with nonusers) serve as a reminder that STD counseling should not stop at age 40 years (Ann. Intern. Med. 2010;153:49-50).

Indeed, the higher baseline risk for STDs among men who use ED drugs, as demonstrated in this study, must be addressed when prescribing the drugs to these patients and thus enhancing the opportunity for transmission of STDs, he said, noting that although counseling about safer sex practices should not wait until a patient requests ED treatment, “the presence of higher rates of serious STDs, such as HIV infection, in men who use ED drugs compared with those who do not make it critical that all ED drug prescriptions be accompanied by assessment of STD risk and counseling about safe sex.”

DR. FEKETE is professor of medicine and chief of infectious diseases at Temple University, Philadelphia.

VITALS

Major Finding: The rate of STDs in the year before receiving a prescription was 214 per 100,000 ED drug users, compared with 106 per 100,000 nonusers, and the rate in the year after receiving a prescription was 105 per 100,000 ED drug users, compared with 65 per 100,000 (adjusted odds ratios of 2.80 and 2.65 for an STD in ED users in the year before and after a prescription, respectively).

Data Source: A retrospective cohort study of 1,410,806 men.

Disclosures: The Bing Study Center for Health Economics and the RAND Roybal Center for Health Policy Simulation sponsored the research for this study. Dr. Jena received support from the National Institutes of Health and the Agency for Healthcare Research and Quality.

Men who use pharmacologic treatment for erectile dysfunction have higher rates of sexually transmitted diseases than do nonusers both before and after they receive a prescription for ED drugs, according to the findings of a retrospective cohort study of 1,410,806 men over age 40.

The rate of sexually transmitted diseases in the year before receiving a prescription was 214 per 100,000 ED drug users, compared with 106 per 100,000 nonusers. In the year after receiving a prescription, the rate was 105/100,000 ED drug users, compared with 65/100,000. The adjusted odds ratios were 2.80 and 2.65 for an STD in ED users in the year before and after a prescription, respectively, Dr. Anupam B. Jena of Massachusetts General Hospital, Boston, and colleagues reported.

The finding of increased risk both before and after receiving a prescription suggests that the association seen in this study has more to do with the types of patients who use ED drugs, than with the actual use of ED drugs, the investigators said (Ann. Intern. Med. 2010;153:1-7).

“Risk assessment for STDs and counseling about safe sexual practices” should accompany the prescription of ED drugs, they wrote, citing their findings as well as those from prior studies showing that condom use declines with age Fue investigators also noted researchindnking ED druguse h high-risksexuavior in men who have sex with men.

For their study, the investigators used a database of insurance claims from 1997 to 2006, including data on 33,968 men with at least 1 filled prescription for an ED drug, and 1,376,838 men with no ED drug prescription. They adjusted for age and comorbid conditions, and found that the differences in STD rates between ED drug users and nonusers were due largely to HIV infection.

The adjusted odds ratios for HIV infection in the year before and after an ED drug prescription were 3.32 and 3.19, respectively.

They noted, however, thatalterall rates of STDs remain low, and the routine testing for STDs in men requesting ED treatment would probably not be cost effective.

My Take

Counsel About Safe Sex After Age 40

Sex after age 40 years remains safer than during adolescence, but the age-related differences in risk have been eroding in recent decades as the rate of STDs in older adults increased, Dr. Thomas Fekete wrote in an editorial.

The increase has occurred in tandem with dramatic increases in the use of the drugs for erectile dysfunction, at least in the last decade, and the findings of Dr. Jena and associates regarding an increased rate of STDs in men over age 40 who use ED drugs (as compared with nonusers) serve as a reminder that STD counseling should not stop at age 40 years (Ann. Intern. Med. 2010;153:49-50).

Indeed, the higher baseline risk for STDs among men who use ED drugs, as demonstrated in this study, must be addressed when prescribing the drugs to these patients and thus enhancing the opportunity for transmission of STDs, he said, noting that although counseling about safer sex practices should not wait until a patient requests ED treatment, “the presence of higher rates of serious STDs, such as HIV infection, in men who use ED drugs compared with those who do not make it critical that all ED drug prescriptions be accompanied by assessment of STD risk and counseling about safe sex.”

DR. FEKETE is professor of medicine and chief of infectious diseases at Temple University, Philadelphia.

VITALS

Major Finding: The rate of STDs in the year before receiving a prescription was 214 per 100,000 ED drug users, compared with 106 per 100,000 nonusers, and the rate in the year after receiving a prescription was 105 per 100,000 ED drug users, compared with 65 per 100,000 (adjusted odds ratios of 2.80 and 2.65 for an STD in ED users in the year before and after a prescription, respectively).

Data Source: A retrospective cohort study of 1,410,806 men.

Disclosures: The Bing Study Center for Health Economics and the RAND Roybal Center for Health Policy Simulation sponsored the research for this study. Dr. Jena received support from the National Institutes of Health and the Agency for Healthcare Research and Quality.

Men who use pharmacologic treatment for erectile dysfunction have higher rates of sexually transmitted diseases than do nonusers both before and after they receive a prescription for ED drugs, according to the findings of a retrospective cohort study of 1,410,806 men over age 40.

The rate of sexually transmitted diseases in the year before receiving a prescription was 214 per 100,000 ED drug users, compared with 106 per 100,000 nonusers. In the year after receiving a prescription, the rate was 105/100,000 ED drug users, compared with 65/100,000. The adjusted odds ratios were 2.80 and 2.65 for an STD in ED users in the year before and after a prescription, respectively, Dr. Anupam B. Jena of Massachusetts General Hospital, Boston, and colleagues reported.

The finding of increased risk both before and after receiving a prescription suggests that the association seen in this study has more to do with the types of patients who use ED drugs, than with the actual use of ED drugs, the investigators said (Ann. Intern. Med. 2010;153:1-7).

“Risk assessment for STDs and counseling about safe sexual practices” should accompany the prescription of ED drugs, they wrote, citing their findings as well as those from prior studies showing that condom use declines with age Fue investigators also noted researchindnking ED druguse h high-risksexuavior in men who have sex with men.

For their study, the investigators used a database of insurance claims from 1997 to 2006, including data on 33,968 men with at least 1 filled prescription for an ED drug, and 1,376,838 men with no ED drug prescription. They adjusted for age and comorbid conditions, and found that the differences in STD rates between ED drug users and nonusers were due largely to HIV infection.

The adjusted odds ratios for HIV infection in the year before and after an ED drug prescription were 3.32 and 3.19, respectively.

They noted, however, thatalterall rates of STDs remain low, and the routine testing for STDs in men requesting ED treatment would probably not be cost effective.

My Take

Counsel About Safe Sex After Age 40

Sex after age 40 years remains safer than during adolescence, but the age-related differences in risk have been eroding in recent decades as the rate of STDs in older adults increased, Dr. Thomas Fekete wrote in an editorial.

The increase has occurred in tandem with dramatic increases in the use of the drugs for erectile dysfunction, at least in the last decade, and the findings of Dr. Jena and associates regarding an increased rate of STDs in men over age 40 who use ED drugs (as compared with nonusers) serve as a reminder that STD counseling should not stop at age 40 years (Ann. Intern. Med. 2010;153:49-50).

Indeed, the higher baseline risk for STDs among men who use ED drugs, as demonstrated in this study, must be addressed when prescribing the drugs to these patients and thus enhancing the opportunity for transmission of STDs, he said, noting that although counseling about safer sex practices should not wait until a patient requests ED treatment, “the presence of higher rates of serious STDs, such as HIV infection, in men who use ED drugs compared with those who do not make it critical that all ED drug prescriptions be accompanied by assessment of STD risk and counseling about safe sex.”

DR. FEKETE is professor of medicine and chief of infectious diseases at Temple University, Philadelphia.

VITALS

Major Finding: In 8,900 patients treated daily with 20 mg rosuvastatin and who had a median LDL cholesterol level of 1.42 mmol/L on treatment, there was no significant association between HDL levels and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartile of HDL levels).

Data Source: An analysis of the randomized, double-blind, placebo-controlled JUPITER study.

Disclosures: AstraZeneca, maker of the trial drug, funded the study. Dr. Ridker reported receiving grant support and/or consulting and lecture fees from AstraZeneca and other drug manufacturers. He is listed as a co-inventor on patents held by the Brigham and Women's Hospital, which relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to AstraZeneca and other entities. Some authors also reported receiving research support and/or consulting and lecture fees from AstraZeneca and numerous drug manufacturers.

High-density lipoprotein cholesterol concentrations are inversely associated with risk for cardiovascular events, but this association does not persist in patients who achieve very low concentrations of low-density lipoprotein cholesterol on statin therapy, according to an analysis of data from the JUPITER study.

In 8,901 patients in the study who received placebo and who had a median LDL cholesterol level of 2.8 mmol/L (108 mg/dL), HDL cholesterol levels were inversely associated with risk for cardiovascular events both at baseline and on placebo (hazard ratios, 0.54 and 0.55, respectively, for the top versus the bottom quartiles of HDL cholesterol levels).

However, in 8,900 patients in the study who were treated daily with 20 mg rosuvastatin (Crestor, AstraZeneca) and who had a median LDL level of 1.42 mmol/L (55 mg/dL) on treatment, there was no significant association between HDL cholesterol concentrations and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top versus bottom quartiles of HDL cholesterol levels), Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston and his colleagues reported.

The investigators also noted that, like HDL levels, apolipoprotein A1 levels were strongly and inversely associated with risk for cardiovascular events in the placebo group, but these associations were attenuated and not statistically significant in the treatment group.

Patients were part of the JUPITER study, which enrolled 17,802 participants from March 2003 to December 2006 to investigate whether rosuvastatin lowered the rate of first-ever cardiovascular events.

Study participants had LDL cholesterol levels of less than 3.4 mmol/L (130 mg/dL) and were at high vascular risk because of elevated high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more, but were otherwise healthy, without cardiovascular disease or diabetes.

Indeed, rosuvastatin reduced LDL levels to a median of 1.4 mmol/L (55 mg/dL), with 25% of patients achieving concentrations of less than 1.1 mmol/L 44 mg/dL) in the trial, and treatment was associated with a 54% reduction in MI, a 48% reduction in stroke, a 46% reduction in revascularization, and a 20% reduction in total mortality (N. Engl. J. Med. 2008;359:2195-20), the investigators noted.

Now, based on the findings of the current analysis of data from the JUPITER primary prevention study, it appears that treatment also reduces the clinical relevance of HDL cholesterol concentrations, they said (Lancet 2010;376:333-9).

“This analysis provides little evidence that residual risk after aggressive use of statin therapy is related to HDL-cholesterol concentration,” the investigators wrote, noting that their findings are supported by similar findings in one other primary prevention trial and two secondary prevention trials involving high-dose statin therapy.

The current study is strengthened by the investigators' ability to adjust for a wide range of covariates, including age, sex, smoking status, metabolic syndrome, family history of premature atherosclerosis, body mass index, systolic blood pressure, fasting glucose, and estimated glomerular filtration rate.

Analyses of HDL cholesterol were controlled for baseline concentrations of LDL cholesterol, triglyceride, and hsCRP (and in the case of on-treatment HDL cholesterol, for changes in the latter three), they said.

It is limited, however, by the exclusion of diabetic patients and the inclusion of patients with LDL cholesterol of less than 3.4 mmol/L, and generalization of the findings should therefore be done with caution, they noted.

The investigators concluded that their primary prevention data, along with data from other primary and secondary prevention studies, provide little evidence in support of the hypothesis that HDL cholesterol concentrations predict risk of vascular events in patients on high-dose statins.

But they noted that their findings should not “reduce enthusiasm for measurement of HDL-cholesterol concentration as part of an initial cardiovascular risk assessment.”

Future randomized trials of potent HDL cholesterol raising agents are needed to determine if such treatment would provide added benefit in terms of cardiovascular risk reduction in patients whose LDL levels are successfully lowered on statin therapy, they said.

In an accompanying editorial comment, Dr. Derek Hausenloy of The Hatter Cardiovascular Institute, University College London Hospital, and his colleagues noted that although the researchers had shown that HDL cholesterol concentrations do not predict residual cardiovascular risk in patients with very low LDL cholesterol concentrations, the reasons for this observation remain unclear (Lancet 2010;376:305-6).

“Perhaps, in patients with a low cardiovascular risk … who are treated to very low concentrations of LDL cholesterol, the relation between HDL cholesterol and cardiovascular risk is lessened; however, [the researchers] were not able to find a relation between apolipoprotein A1 and reduced cardiovascular risk,” they wrote.

They added that in the setting of very low LDL cholesterol, other lipid measures such as apolipoprotein B to A1 ratio may provide a better prediction of cardiovascular risk.

Regardless, the findings should not “detract from the fact that raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol,” wrote Dr. Hausenloy and his colleagues, none of whom had any disclosures to make in relation to the study.

It still needs to be determined in large randomized trials whether increasing HDL cholesterol in patients with very low LDL cholesterol is of benefit, they noted.

They added that such trials will be particularly important given that two new inhibitors of cholesterol ester transfer proteins—anacetrapib and dalcetrapib—are now in clinical testing.

VITALS

Source Elsevier Global Medical News

Major Finding: In 8,900 patients treated daily with 20 mg rosuvastatin and who had a median LDL cholesterol level of 1.42 mmol/L on treatment, there was no significant association between HDL levels and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartile of HDL levels).

Data Source: An analysis of the randomized, double-blind, placebo-controlled JUPITER study.

Disclosures: AstraZeneca, maker of the trial drug, funded the study. Dr. Ridker reported receiving grant support and/or consulting and lecture fees from AstraZeneca and other drug manufacturers. He is listed as a co-inventor on patents held by the Brigham and Women's Hospital, which relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to AstraZeneca and other entities. Some authors also reported receiving research support and/or consulting and lecture fees from AstraZeneca and numerous drug manufacturers.

High-density lipoprotein cholesterol concentrations are inversely associated with risk for cardiovascular events, but this association does not persist in patients who achieve very low concentrations of low-density lipoprotein cholesterol on statin therapy, according to an analysis of data from the JUPITER study.

In 8,901 patients in the study who received placebo and who had a median LDL cholesterol level of 2.8 mmol/L (108 mg/dL), HDL cholesterol levels were inversely associated with risk for cardiovascular events both at baseline and on placebo (hazard ratios, 0.54 and 0.55, respectively, for the top versus the bottom quartiles of HDL cholesterol levels).

However, in 8,900 patients in the study who were treated daily with 20 mg rosuvastatin (Crestor, AstraZeneca) and who had a median LDL level of 1.42 mmol/L (55 mg/dL) on treatment, there was no significant association between HDL cholesterol concentrations and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top versus bottom quartiles of HDL cholesterol levels), Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston and his colleagues reported.

The investigators also noted that, like HDL levels, apolipoprotein A1 levels were strongly and inversely associated with risk for cardiovascular events in the placebo group, but these associations were attenuated and not statistically significant in the treatment group.

Patients were part of the JUPITER study, which enrolled 17,802 participants from March 2003 to December 2006 to investigate whether rosuvastatin lowered the rate of first-ever cardiovascular events.

Study participants had LDL cholesterol levels of less than 3.4 mmol/L (130 mg/dL) and were at high vascular risk because of elevated high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more, but were otherwise healthy, without cardiovascular disease or diabetes.

Indeed, rosuvastatin reduced LDL levels to a median of 1.4 mmol/L (55 mg/dL), with 25% of patients achieving concentrations of less than 1.1 mmol/L 44 mg/dL) in the trial, and treatment was associated with a 54% reduction in MI, a 48% reduction in stroke, a 46% reduction in revascularization, and a 20% reduction in total mortality (N. Engl. J. Med. 2008;359:2195-20), the investigators noted.

Now, based on the findings of the current analysis of data from the JUPITER primary prevention study, it appears that treatment also reduces the clinical relevance of HDL cholesterol concentrations, they said (Lancet 2010;376:333-9).

“This analysis provides little evidence that residual risk after aggressive use of statin therapy is related to HDL-cholesterol concentration,” the investigators wrote, noting that their findings are supported by similar findings in one other primary prevention trial and two secondary prevention trials involving high-dose statin therapy.

The current study is strengthened by the investigators' ability to adjust for a wide range of covariates, including age, sex, smoking status, metabolic syndrome, family history of premature atherosclerosis, body mass index, systolic blood pressure, fasting glucose, and estimated glomerular filtration rate.

Analyses of HDL cholesterol were controlled for baseline concentrations of LDL cholesterol, triglyceride, and hsCRP (and in the case of on-treatment HDL cholesterol, for changes in the latter three), they said.

It is limited, however, by the exclusion of diabetic patients and the inclusion of patients with LDL cholesterol of less than 3.4 mmol/L, and generalization of the findings should therefore be done with caution, they noted.

The investigators concluded that their primary prevention data, along with data from other primary and secondary prevention studies, provide little evidence in support of the hypothesis that HDL cholesterol concentrations predict risk of vascular events in patients on high-dose statins.

But they noted that their findings should not “reduce enthusiasm for measurement of HDL-cholesterol concentration as part of an initial cardiovascular risk assessment.”

Future randomized trials of potent HDL cholesterol raising agents are needed to determine if such treatment would provide added benefit in terms of cardiovascular risk reduction in patients whose LDL levels are successfully lowered on statin therapy, they said.

In an accompanying editorial comment, Dr. Derek Hausenloy of The Hatter Cardiovascular Institute, University College London Hospital, and his colleagues noted that although the researchers had shown that HDL cholesterol concentrations do not predict residual cardiovascular risk in patients with very low LDL cholesterol concentrations, the reasons for this observation remain unclear (Lancet 2010;376:305-6).

“Perhaps, in patients with a low cardiovascular risk … who are treated to very low concentrations of LDL cholesterol, the relation between HDL cholesterol and cardiovascular risk is lessened; however, [the researchers] were not able to find a relation between apolipoprotein A1 and reduced cardiovascular risk,” they wrote.

They added that in the setting of very low LDL cholesterol, other lipid measures such as apolipoprotein B to A1 ratio may provide a better prediction of cardiovascular risk.

Regardless, the findings should not “detract from the fact that raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol,” wrote Dr. Hausenloy and his colleagues, none of whom had any disclosures to make in relation to the study.

It still needs to be determined in large randomized trials whether increasing HDL cholesterol in patients with very low LDL cholesterol is of benefit, they noted.

They added that such trials will be particularly important given that two new inhibitors of cholesterol ester transfer proteins—anacetrapib and dalcetrapib—are now in clinical testing.

VITALS

Source Elsevier Global Medical News

Major Finding: In 8,900 patients treated daily with 20 mg rosuvastatin and who had a median LDL cholesterol level of 1.42 mmol/L on treatment, there was no significant association between HDL levels and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartile of HDL levels).

Data Source: An analysis of the randomized, double-blind, placebo-controlled JUPITER study.

Disclosures: AstraZeneca, maker of the trial drug, funded the study. Dr. Ridker reported receiving grant support and/or consulting and lecture fees from AstraZeneca and other drug manufacturers. He is listed as a co-inventor on patents held by the Brigham and Women's Hospital, which relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to AstraZeneca and other entities. Some authors also reported receiving research support and/or consulting and lecture fees from AstraZeneca and numerous drug manufacturers.

High-density lipoprotein cholesterol concentrations are inversely associated with risk for cardiovascular events, but this association does not persist in patients who achieve very low concentrations of low-density lipoprotein cholesterol on statin therapy, according to an analysis of data from the JUPITER study.

In 8,901 patients in the study who received placebo and who had a median LDL cholesterol level of 2.8 mmol/L (108 mg/dL), HDL cholesterol levels were inversely associated with risk for cardiovascular events both at baseline and on placebo (hazard ratios, 0.54 and 0.55, respectively, for the top versus the bottom quartiles of HDL cholesterol levels).

However, in 8,900 patients in the study who were treated daily with 20 mg rosuvastatin (Crestor, AstraZeneca) and who had a median LDL level of 1.42 mmol/L (55 mg/dL) on treatment, there was no significant association between HDL cholesterol concentrations and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top versus bottom quartiles of HDL cholesterol levels), Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston and his colleagues reported.

The investigators also noted that, like HDL levels, apolipoprotein A1 levels were strongly and inversely associated with risk for cardiovascular events in the placebo group, but these associations were attenuated and not statistically significant in the treatment group.

Patients were part of the JUPITER study, which enrolled 17,802 participants from March 2003 to December 2006 to investigate whether rosuvastatin lowered the rate of first-ever cardiovascular events.

Study participants had LDL cholesterol levels of less than 3.4 mmol/L (130 mg/dL) and were at high vascular risk because of elevated high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more, but were otherwise healthy, without cardiovascular disease or diabetes.

Indeed, rosuvastatin reduced LDL levels to a median of 1.4 mmol/L (55 mg/dL), with 25% of patients achieving concentrations of less than 1.1 mmol/L 44 mg/dL) in the trial, and treatment was associated with a 54% reduction in MI, a 48% reduction in stroke, a 46% reduction in revascularization, and a 20% reduction in total mortality (N. Engl. J. Med. 2008;359:2195-20), the investigators noted.

Now, based on the findings of the current analysis of data from the JUPITER primary prevention study, it appears that treatment also reduces the clinical relevance of HDL cholesterol concentrations, they said (Lancet 2010;376:333-9).

“This analysis provides little evidence that residual risk after aggressive use of statin therapy is related to HDL-cholesterol concentration,” the investigators wrote, noting that their findings are supported by similar findings in one other primary prevention trial and two secondary prevention trials involving high-dose statin therapy.

The current study is strengthened by the investigators' ability to adjust for a wide range of covariates, including age, sex, smoking status, metabolic syndrome, family history of premature atherosclerosis, body mass index, systolic blood pressure, fasting glucose, and estimated glomerular filtration rate.

Analyses of HDL cholesterol were controlled for baseline concentrations of LDL cholesterol, triglyceride, and hsCRP (and in the case of on-treatment HDL cholesterol, for changes in the latter three), they said.

It is limited, however, by the exclusion of diabetic patients and the inclusion of patients with LDL cholesterol of less than 3.4 mmol/L, and generalization of the findings should therefore be done with caution, they noted.

The investigators concluded that their primary prevention data, along with data from other primary and secondary prevention studies, provide little evidence in support of the hypothesis that HDL cholesterol concentrations predict risk of vascular events in patients on high-dose statins.

But they noted that their findings should not “reduce enthusiasm for measurement of HDL-cholesterol concentration as part of an initial cardiovascular risk assessment.”

Future randomized trials of potent HDL cholesterol raising agents are needed to determine if such treatment would provide added benefit in terms of cardiovascular risk reduction in patients whose LDL levels are successfully lowered on statin therapy, they said.

In an accompanying editorial comment, Dr. Derek Hausenloy of The Hatter Cardiovascular Institute, University College London Hospital, and his colleagues noted that although the researchers had shown that HDL cholesterol concentrations do not predict residual cardiovascular risk in patients with very low LDL cholesterol concentrations, the reasons for this observation remain unclear (Lancet 2010;376:305-6).

“Perhaps, in patients with a low cardiovascular risk … who are treated to very low concentrations of LDL cholesterol, the relation between HDL cholesterol and cardiovascular risk is lessened; however, [the researchers] were not able to find a relation between apolipoprotein A1 and reduced cardiovascular risk,” they wrote.

They added that in the setting of very low LDL cholesterol, other lipid measures such as apolipoprotein B to A1 ratio may provide a better prediction of cardiovascular risk.

Regardless, the findings should not “detract from the fact that raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol,” wrote Dr. Hausenloy and his colleagues, none of whom had any disclosures to make in relation to the study.

It still needs to be determined in large randomized trials whether increasing HDL cholesterol in patients with very low LDL cholesterol is of benefit, they noted.

They added that such trials will be particularly important given that two new inhibitors of cholesterol ester transfer proteins—anacetrapib and dalcetrapib—are now in clinical testing.

VITALS

Source Elsevier Global Medical News

The earlier an advanced biologic therapy is initiated in a patient with a diabetic foot ulcer, the sooner the wound is likely to heal, with first use of engineered skin resulting in the fastest healing, findings from a large retrospective cohort study suggest.

First use of an advanced biologic therapy occurred at a mean of 28 days in 2,517 patients who presented with a diabetic neuropathic foot ulcer between Jan. 1, 2001, and Dec. 31, 2004, and who were treated with at least one such therapy. Healing occurred at a median of 100 days, Dr. Robert S. Kirsner of the University of Miami and his colleagues reported in the August issues of Archives of Dermatology.

The advanced biologic therapies reviewed in this study included bi-layered living skin substitute (Apligraf), recombinant human platelet–derived growth factor (becaplermin [Regranex]), and platelet releasate (Procuren). Human fibroblast–derived dermal substitute (Dermagraft) was not commercially available at the start of the study and therefore was not included.

A total of 1,892 patients (75%) were treated with recombinant growth factor, 446 (18%) were treated with bi-layered living cell therapy, 125 (5%) were treated with platelet releasate, and 54 (2%) were treated with platelet releasate or recombinant growth factor followed by bi-layered living cell therapy.

Healing was faster in those who received engineered skin as the first advanced biologic therapy used (median of 84 days vs. 101 days for recombinant growth factor therapy and 108 days for platelet releasate, after researchers adjusted for confounding factors). In addition, healing was 31.2% more likely than when topical recombinant growth factor was used first, and 40% more likely than when platelet releasate was used first, the investigators found. The differences were statistically significant (Arch. Dermatol. 2010;146:857-62).

However, the median time to use of engineered skin was 6 weeks, compared with 4 weeks for platelet releasate and 3 weeks for recombinant growth factor, and 25% of wounds treated with engineered skin were not treated until after 24 weeks, the investigators said.

The delay in using engineered skin vs. the other biologic treatments might be related to cost concerns, they suggested, but they also noted that several studies have found that use of advanced biologic therapies reduced costs.

Longer time to healing after the first advanced biologic therapy was used was significantly associated with larger wound area, more severe wound grade, longer duration prior to first visit, and longer time from first visit to use of advanced biologic therapy. These associations were present across all treatment groups, the investigators said.

The findings are important because diabetic foot ulcers are a major complication of diabetes, affecting up to 15% of diabetic patients during their lifetime and accounting for 20% of all diabetes-related hospital admissions in the United States. Faster foot healing can reduce the incidence of amputation in diabetic patients, the investigators said.

Although the findings underscore the importance of appropriate treatment for the management of chronic diabetic foot ulcers, this study focused on usage patterns with advanced biologic therapies and did not compare outcomes with these therapies and with standard therapy. Because of this and other limitations of the study—including its retrospective nature and the lack of detail on wound history and therapy for some patients—the results "should not be used in isolation when making decisions regarding when to use adjuvant therapy in combination with standard care," the investigators wrote.

Nonetheless, proper treatment is critical, and delays in providing that treatment will lengthen time to healing, they concluded.

Disclosures: This study was supported in part by Organogenesis, makers of Apligraf. Coauthor Laure Stasik reported that she was employed by Diversified Clinical Services during the study but is now employed by Organogenesis.

The earlier an advanced biologic therapy is initiated in a patient with a diabetic foot ulcer, the sooner the wound is likely to heal, with first use of engineered skin resulting in the fastest healing, findings from a large retrospective cohort study suggest.

First use of an advanced biologic therapy occurred at a mean of 28 days in 2,517 patients who presented with a diabetic neuropathic foot ulcer between Jan. 1, 2001, and Dec. 31, 2004, and who were treated with at least one such therapy. Healing occurred at a median of 100 days, Dr. Robert S. Kirsner of the University of Miami and his colleagues reported in the August issues of Archives of Dermatology.

The advanced biologic therapies reviewed in this study included bi-layered living skin substitute (Apligraf), recombinant human platelet–derived growth factor (becaplermin [Regranex]), and platelet releasate (Procuren). Human fibroblast–derived dermal substitute (Dermagraft) was not commercially available at the start of the study and therefore was not included.

A total of 1,892 patients (75%) were treated with recombinant growth factor, 446 (18%) were treated with bi-layered living cell therapy, 125 (5%) were treated with platelet releasate, and 54 (2%) were treated with platelet releasate or recombinant growth factor followed by bi-layered living cell therapy.

Healing was faster in those who received engineered skin as the first advanced biologic therapy used (median of 84 days vs. 101 days for recombinant growth factor therapy and 108 days for platelet releasate, after researchers adjusted for confounding factors). In addition, healing was 31.2% more likely than when topical recombinant growth factor was used first, and 40% more likely than when platelet releasate was used first, the investigators found. The differences were statistically significant (Arch. Dermatol. 2010;146:857-62).

However, the median time to use of engineered skin was 6 weeks, compared with 4 weeks for platelet releasate and 3 weeks for recombinant growth factor, and 25% of wounds treated with engineered skin were not treated until after 24 weeks, the investigators said.

The delay in using engineered skin vs. the other biologic treatments might be related to cost concerns, they suggested, but they also noted that several studies have found that use of advanced biologic therapies reduced costs.

Longer time to healing after the first advanced biologic therapy was used was significantly associated with larger wound area, more severe wound grade, longer duration prior to first visit, and longer time from first visit to use of advanced biologic therapy. These associations were present across all treatment groups, the investigators said.

The findings are important because diabetic foot ulcers are a major complication of diabetes, affecting up to 15% of diabetic patients during their lifetime and accounting for 20% of all diabetes-related hospital admissions in the United States. Faster foot healing can reduce the incidence of amputation in diabetic patients, the investigators said.

Although the findings underscore the importance of appropriate treatment for the management of chronic diabetic foot ulcers, this study focused on usage patterns with advanced biologic therapies and did not compare outcomes with these therapies and with standard therapy. Because of this and other limitations of the study—including its retrospective nature and the lack of detail on wound history and therapy for some patients—the results "should not be used in isolation when making decisions regarding when to use adjuvant therapy in combination with standard care," the investigators wrote.

Nonetheless, proper treatment is critical, and delays in providing that treatment will lengthen time to healing, they concluded.

Disclosures: This study was supported in part by Organogenesis, makers of Apligraf. Coauthor Laure Stasik reported that she was employed by Diversified Clinical Services during the study but is now employed by Organogenesis.

The earlier an advanced biologic therapy is initiated in a patient with a diabetic foot ulcer, the sooner the wound is likely to heal, with first use of engineered skin resulting in the fastest healing, findings from a large retrospective cohort study suggest.

First use of an advanced biologic therapy occurred at a mean of 28 days in 2,517 patients who presented with a diabetic neuropathic foot ulcer between Jan. 1, 2001, and Dec. 31, 2004, and who were treated with at least one such therapy. Healing occurred at a median of 100 days, Dr. Robert S. Kirsner of the University of Miami and his colleagues reported in the August issues of Archives of Dermatology.

The advanced biologic therapies reviewed in this study included bi-layered living skin substitute (Apligraf), recombinant human platelet–derived growth factor (becaplermin [Regranex]), and platelet releasate (Procuren). Human fibroblast–derived dermal substitute (Dermagraft) was not commercially available at the start of the study and therefore was not included.

A total of 1,892 patients (75%) were treated with recombinant growth factor, 446 (18%) were treated with bi-layered living cell therapy, 125 (5%) were treated with platelet releasate, and 54 (2%) were treated with platelet releasate or recombinant growth factor followed by bi-layered living cell therapy.

Healing was faster in those who received engineered skin as the first advanced biologic therapy used (median of 84 days vs. 101 days for recombinant growth factor therapy and 108 days for platelet releasate, after researchers adjusted for confounding factors). In addition, healing was 31.2% more likely than when topical recombinant growth factor was used first, and 40% more likely than when platelet releasate was used first, the investigators found. The differences were statistically significant (Arch. Dermatol. 2010;146:857-62).

However, the median time to use of engineered skin was 6 weeks, compared with 4 weeks for platelet releasate and 3 weeks for recombinant growth factor, and 25% of wounds treated with engineered skin were not treated until after 24 weeks, the investigators said.

The delay in using engineered skin vs. the other biologic treatments might be related to cost concerns, they suggested, but they also noted that several studies have found that use of advanced biologic therapies reduced costs.

Longer time to healing after the first advanced biologic therapy was used was significantly associated with larger wound area, more severe wound grade, longer duration prior to first visit, and longer time from first visit to use of advanced biologic therapy. These associations were present across all treatment groups, the investigators said.

The findings are important because diabetic foot ulcers are a major complication of diabetes, affecting up to 15% of diabetic patients during their lifetime and accounting for 20% of all diabetes-related hospital admissions in the United States. Faster foot healing can reduce the incidence of amputation in diabetic patients, the investigators said.

Although the findings underscore the importance of appropriate treatment for the management of chronic diabetic foot ulcers, this study focused on usage patterns with advanced biologic therapies and did not compare outcomes with these therapies and with standard therapy. Because of this and other limitations of the study—including its retrospective nature and the lack of detail on wound history and therapy for some patients—the results "should not be used in isolation when making decisions regarding when to use adjuvant therapy in combination with standard care," the investigators wrote.

Nonetheless, proper treatment is critical, and delays in providing that treatment will lengthen time to healing, they concluded.

Disclosures: This study was supported in part by Organogenesis, makers of Apligraf. Coauthor Laure Stasik reported that she was employed by Diversified Clinical Services during the study but is now employed by Organogenesis.

The use of implantable gentamicin-impregnated collagen sponges did not reduce the sternal wound infection rate following cardiac surgery in a prospective, randomized, controlled trial of 1,502 patients who were at high risk of infection because of diabetes and/or obesity.

Dr. Elliott Bennett-Guerrero of Duke University in Durham, N.C., and his colleagues reported their findings Aug. 18 in JAMA.

The findings directly contradicted those of a 2005 Swedish study, which found that the sponges reduced surgical wound infections by 53%, and which served as strong preliminary data for the current trial (Ann. Thoracic. Surg. 2005;79:153-62).

The sponges are approved in 54 countries, and the current phase III study was designed to "confirm these promising data and support regulatory approval in the United States." However, the overall wound infection rates at 90 days were statistically similar at 8.4% and 8.7%, respectively, in patients who received standard care plus surgical site implantation of two of the topical antibiotic sponges, and in patients who received standard care with no additional intervention, researchers found. There were 753 patients in the sponge group and 749 in the standard care group,

Like the overall wound infection rates, the superficial and deep sternal wound infection rates were also similar in the treatment and control groups, at 6.5% and 6.1%, and 1.9% and 2.5%, respectively. Additionally, no differences were seen between the treatment and control groups in regard to the rehospitalization rate for sternal wound infection (3.1% and 3.2%, respectively), or in ASEPSIS score (mean, 1.9 and. 2.0, respectively) the investigators found (JAMA 2010;304:755-62).

The ASEPSIS score is a measure of additional treatment, presence of serous discharge, erythema, purulent exudates, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay. Points are assigned for each variable and the scale has a minimum score of 0, with no theoretical maximum, the investigators explained.

Patients in the single-blind study were enrolled at 48 U.S. centers between Dec. 21, 2007, and March 11, 2009. Those randomized to the treatment group underwent insertion of two sponges with a total gentamicin dose of 260 mg, which was the same dose used in the Swedish study. Both groups received standardized care with prophylactic systemic antibiotics and rigid sternal fixation, with the treatment group also undergoing implantation with the sponges.

The groups were balanced regarding baseline characteristics, including age, weight, diabetes, and smoking history, and also in regard to perioperative variables.

As for why the antibiotic sponges failed to reduce infection rates in this study as they did in the Swedish study, the investigators suggested that important quality control measures used in their study – but not in the Swedish study – might be to blame. They cited measures including on-site monitoring and source data verification, central adjudication of outcomes by an independent blinded committee, and the inclusion of a large number of hospitals (48 in the U.S. study, compared with 2 in the Swedish study).

The researchers also wrote that ethnic and regional differences, such as varying distribution of bacterial pathogens between countries, could also explain the differing outcomes. For example, no cases of methicillin-resistant Staphylococcus aureus occurred in the Swedish trial, but in the U.S. study 6.3% of patients had MRSA growth from sternal wound infection, which may not be sensitive to gentamicin.

"Thus, variations in the distribution of bacterial pathogens among countries could affect efficacy in a trial of infection prevention such as the present one" they said, also noting that the findings underscore the importance of large validation trials, as "positive single-center trials are often not confirmed in larger multicenter trials."

Disclosures: The U.S. study was sponsored by Innocoll Technologies Ltd., the maker of the gentamicin-collagen sponges, and Dr. Bennett-Guerrero reported that he is in discussions with Excited States LLC regarding a consulting agreement to advise on a clinical trial involving surgical wound infection prevention. Another author on the study, Dr. T. Bruce Ferguson Jr., reported receiving honoraria from Innocoll Technologies Ltd. for serving on a steering committee.

The use of implantable gentamicin-impregnated collagen sponges did not reduce the sternal wound infection rate following cardiac surgery in a prospective, randomized, controlled trial of 1,502 patients who were at high risk of infection because of diabetes and/or obesity.

Dr. Elliott Bennett-Guerrero of Duke University in Durham, N.C., and his colleagues reported their findings Aug. 18 in JAMA.

The findings directly contradicted those of a 2005 Swedish study, which found that the sponges reduced surgical wound infections by 53%, and which served as strong preliminary data for the current trial (Ann. Thoracic. Surg. 2005;79:153-62).

The sponges are approved in 54 countries, and the current phase III study was designed to "confirm these promising data and support regulatory approval in the United States." However, the overall wound infection rates at 90 days were statistically similar at 8.4% and 8.7%, respectively, in patients who received standard care plus surgical site implantation of two of the topical antibiotic sponges, and in patients who received standard care with no additional intervention, researchers found. There were 753 patients in the sponge group and 749 in the standard care group,

Like the overall wound infection rates, the superficial and deep sternal wound infection rates were also similar in the treatment and control groups, at 6.5% and 6.1%, and 1.9% and 2.5%, respectively. Additionally, no differences were seen between the treatment and control groups in regard to the rehospitalization rate for sternal wound infection (3.1% and 3.2%, respectively), or in ASEPSIS score (mean, 1.9 and. 2.0, respectively) the investigators found (JAMA 2010;304:755-62).

The ASEPSIS score is a measure of additional treatment, presence of serous discharge, erythema, purulent exudates, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay. Points are assigned for each variable and the scale has a minimum score of 0, with no theoretical maximum, the investigators explained.

Patients in the single-blind study were enrolled at 48 U.S. centers between Dec. 21, 2007, and March 11, 2009. Those randomized to the treatment group underwent insertion of two sponges with a total gentamicin dose of 260 mg, which was the same dose used in the Swedish study. Both groups received standardized care with prophylactic systemic antibiotics and rigid sternal fixation, with the treatment group also undergoing implantation with the sponges.

The groups were balanced regarding baseline characteristics, including age, weight, diabetes, and smoking history, and also in regard to perioperative variables.

As for why the antibiotic sponges failed to reduce infection rates in this study as they did in the Swedish study, the investigators suggested that important quality control measures used in their study – but not in the Swedish study – might be to blame. They cited measures including on-site monitoring and source data verification, central adjudication of outcomes by an independent blinded committee, and the inclusion of a large number of hospitals (48 in the U.S. study, compared with 2 in the Swedish study).

The researchers also wrote that ethnic and regional differences, such as varying distribution of bacterial pathogens between countries, could also explain the differing outcomes. For example, no cases of methicillin-resistant Staphylococcus aureus occurred in the Swedish trial, but in the U.S. study 6.3% of patients had MRSA growth from sternal wound infection, which may not be sensitive to gentamicin.

"Thus, variations in the distribution of bacterial pathogens among countries could affect efficacy in a trial of infection prevention such as the present one" they said, also noting that the findings underscore the importance of large validation trials, as "positive single-center trials are often not confirmed in larger multicenter trials."

Disclosures: The U.S. study was sponsored by Innocoll Technologies Ltd., the maker of the gentamicin-collagen sponges, and Dr. Bennett-Guerrero reported that he is in discussions with Excited States LLC regarding a consulting agreement to advise on a clinical trial involving surgical wound infection prevention. Another author on the study, Dr. T. Bruce Ferguson Jr., reported receiving honoraria from Innocoll Technologies Ltd. for serving on a steering committee.

The use of implantable gentamicin-impregnated collagen sponges did not reduce the sternal wound infection rate following cardiac surgery in a prospective, randomized, controlled trial of 1,502 patients who were at high risk of infection because of diabetes and/or obesity.

Dr. Elliott Bennett-Guerrero of Duke University in Durham, N.C., and his colleagues reported their findings Aug. 18 in JAMA.

The findings directly contradicted those of a 2005 Swedish study, which found that the sponges reduced surgical wound infections by 53%, and which served as strong preliminary data for the current trial (Ann. Thoracic. Surg. 2005;79:153-62).

The sponges are approved in 54 countries, and the current phase III study was designed to "confirm these promising data and support regulatory approval in the United States." However, the overall wound infection rates at 90 days were statistically similar at 8.4% and 8.7%, respectively, in patients who received standard care plus surgical site implantation of two of the topical antibiotic sponges, and in patients who received standard care with no additional intervention, researchers found. There were 753 patients in the sponge group and 749 in the standard care group,

Like the overall wound infection rates, the superficial and deep sternal wound infection rates were also similar in the treatment and control groups, at 6.5% and 6.1%, and 1.9% and 2.5%, respectively. Additionally, no differences were seen between the treatment and control groups in regard to the rehospitalization rate for sternal wound infection (3.1% and 3.2%, respectively), or in ASEPSIS score (mean, 1.9 and. 2.0, respectively) the investigators found (JAMA 2010;304:755-62).

The ASEPSIS score is a measure of additional treatment, presence of serous discharge, erythema, purulent exudates, separation of the deep tissues, isolation of bacteria, and duration of inpatient stay. Points are assigned for each variable and the scale has a minimum score of 0, with no theoretical maximum, the investigators explained.

Patients in the single-blind study were enrolled at 48 U.S. centers between Dec. 21, 2007, and March 11, 2009. Those randomized to the treatment group underwent insertion of two sponges with a total gentamicin dose of 260 mg, which was the same dose used in the Swedish study. Both groups received standardized care with prophylactic systemic antibiotics and rigid sternal fixation, with the treatment group also undergoing implantation with the sponges.

The groups were balanced regarding baseline characteristics, including age, weight, diabetes, and smoking history, and also in regard to perioperative variables.

As for why the antibiotic sponges failed to reduce infection rates in this study as they did in the Swedish study, the investigators suggested that important quality control measures used in their study – but not in the Swedish study – might be to blame. They cited measures including on-site monitoring and source data verification, central adjudication of outcomes by an independent blinded committee, and the inclusion of a large number of hospitals (48 in the U.S. study, compared with 2 in the Swedish study).

The researchers also wrote that ethnic and regional differences, such as varying distribution of bacterial pathogens between countries, could also explain the differing outcomes. For example, no cases of methicillin-resistant Staphylococcus aureus occurred in the Swedish trial, but in the U.S. study 6.3% of patients had MRSA growth from sternal wound infection, which may not be sensitive to gentamicin.

"Thus, variations in the distribution of bacterial pathogens among countries could affect efficacy in a trial of infection prevention such as the present one" they said, also noting that the findings underscore the importance of large validation trials, as "positive single-center trials are often not confirmed in larger multicenter trials."

Disclosures: The U.S. study was sponsored by Innocoll Technologies Ltd., the maker of the gentamicin-collagen sponges, and Dr. Bennett-Guerrero reported that he is in discussions with Excited States LLC regarding a consulting agreement to advise on a clinical trial involving surgical wound infection prevention. Another author on the study, Dr. T. Bruce Ferguson Jr., reported receiving honoraria from Innocoll Technologies Ltd. for serving on a steering committee.

The risk profiles for individuals who develop single vs. multiple basal cell carcinoma lesions differ, according to findings from the Rotterdam Study.

Of the 10,820 eligible members of the two cohorts used for the large, Dutch, population-based study, 361 (3%) were diagnosed with a single initial basal cell carcinoma (BCC) lesion, and 163 (1.5%) were diagnosed with subsequent BCC lesions during the study period.

After adjusting for numerous factors such as sex, age, hair and eye color, tendency to develop sunburn, smoking history, body mass index, and educational level, factors found to be significantly associated with developing a first BCC lesion were age (odds ratios of 1.39 and 1.01 for those aged 65-74 years and for those aged 75 years and older, respectively, vs. those younger than age 65 years), and red hair color (OR of 1.98 for red vs. brown or black hair), Dr. Ville Kiiski and colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, reported in the August issue of Archives of Dermatology.

After adjusting for age at index lesion, sex, hair color, eye color, all ultraviolet-related factors, smoking history, and alcohol consumption, the factors found to be associated with a significantly increased risk of developing multiple lesions were lesion location on an upper extremity (hazard ratio 1.49), age younger than 65 years (HRs of 0.58 and 0.65 for those aged 75 years and older and for those aged 65 to 74 years, respectively, vs. those younger than age 65 years), hair color (HR of 1.43 for red vs. brown/black hair), and education level (HR of 1.42 for high vs. low education level), the investigators found (Arch. Dermatol. 2010;146:848-55).

This last finding “may be explained by the probability that people with higher levels of education (which correlates strongly with socioeconomic status) have different lifestyles,” such as more frequent exposure to ultraviolet rays for intermittent periods, they said. Also, people of higher socioeconomic status generally may be expected to live longer and, thus have more time to acquire lesions.

Patients were adults aged 55 years or older from the two Rotterdam Study cohorts, including one studied in 1990, and one studied in 1999. Participants were followed for a mean of 9.5 years.

The findings – particularly regarding increased risk among younger patients and red-heads – largely support those of previous studies, although in the current study men were not shown to be at significantly increased risk of developing a first lesion, which contrasts with findings from some prior studies, the investigators noted.

The differences in risk factor profiles for those who develop single vs. multiple BCC lesions, as seen in the current study, may suggest that phenotypic characteristics of patients are less important for determining risk once “cumulative environmental-genetic interaction has surpassed a certain threshold and resulted in a lesion,” Dr. Ville Kiiski and colleagues wrote.

“The clinical relevance of this finding is that physicians’ risk assessment efforts should differentiate between patients at risk for a first lesion and those who have a history of BCC,” they said, noting that those with the identified risk factors for multiple lesions may require a more stringent follow-up regimen.

That’s not to say, however, that other BCC patients do not require follow-up. In this sample of the general population, more than 30% of the patients with BCC developed subsequent skin cancer, emphasizing the need for annual follow-up for several years,” Dr. Ville Kiiski and colleagues stressed.

Given that more than 1 million people are diagnosed with BCC in the United States each year, and given the strain that is put on limited specialized care by the need for follow-up of the large group of patients with BCCs, additional research is needed to better identify those at risk of developing multiple lesions, they concluded.

The investigators reported no financial disclosures relevant to their study.

The risk profiles for individuals who develop single vs. multiple basal cell carcinoma lesions differ, according to findings from the Rotterdam Study.

Of the 10,820 eligible members of the two cohorts used for the large, Dutch, population-based study, 361 (3%) were diagnosed with a single initial basal cell carcinoma (BCC) lesion, and 163 (1.5%) were diagnosed with subsequent BCC lesions during the study period.

After adjusting for numerous factors such as sex, age, hair and eye color, tendency to develop sunburn, smoking history, body mass index, and educational level, factors found to be significantly associated with developing a first BCC lesion were age (odds ratios of 1.39 and 1.01 for those aged 65-74 years and for those aged 75 years and older, respectively, vs. those younger than age 65 years), and red hair color (OR of 1.98 for red vs. brown or black hair), Dr. Ville Kiiski and colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, reported in the August issue of Archives of Dermatology.

After adjusting for age at index lesion, sex, hair color, eye color, all ultraviolet-related factors, smoking history, and alcohol consumption, the factors found to be associated with a significantly increased risk of developing multiple lesions were lesion location on an upper extremity (hazard ratio 1.49), age younger than 65 years (HRs of 0.58 and 0.65 for those aged 75 years and older and for those aged 65 to 74 years, respectively, vs. those younger than age 65 years), hair color (HR of 1.43 for red vs. brown/black hair), and education level (HR of 1.42 for high vs. low education level), the investigators found (Arch. Dermatol. 2010;146:848-55).

This last finding “may be explained by the probability that people with higher levels of education (which correlates strongly with socioeconomic status) have different lifestyles,” such as more frequent exposure to ultraviolet rays for intermittent periods, they said. Also, people of higher socioeconomic status generally may be expected to live longer and, thus have more time to acquire lesions.

Patients were adults aged 55 years or older from the two Rotterdam Study cohorts, including one studied in 1990, and one studied in 1999. Participants were followed for a mean of 9.5 years.

The findings – particularly regarding increased risk among younger patients and red-heads – largely support those of previous studies, although in the current study men were not shown to be at significantly increased risk of developing a first lesion, which contrasts with findings from some prior studies, the investigators noted.

The differences in risk factor profiles for those who develop single vs. multiple BCC lesions, as seen in the current study, may suggest that phenotypic characteristics of patients are less important for determining risk once “cumulative environmental-genetic interaction has surpassed a certain threshold and resulted in a lesion,” Dr. Ville Kiiski and colleagues wrote.

“The clinical relevance of this finding is that physicians’ risk assessment efforts should differentiate between patients at risk for a first lesion and those who have a history of BCC,” they said, noting that those with the identified risk factors for multiple lesions may require a more stringent follow-up regimen.

That’s not to say, however, that other BCC patients do not require follow-up. In this sample of the general population, more than 30% of the patients with BCC developed subsequent skin cancer, emphasizing the need for annual follow-up for several years,” Dr. Ville Kiiski and colleagues stressed.

Given that more than 1 million people are diagnosed with BCC in the United States each year, and given the strain that is put on limited specialized care by the need for follow-up of the large group of patients with BCCs, additional research is needed to better identify those at risk of developing multiple lesions, they concluded.

The investigators reported no financial disclosures relevant to their study.

The risk profiles for individuals who develop single vs. multiple basal cell carcinoma lesions differ, according to findings from the Rotterdam Study.

Of the 10,820 eligible members of the two cohorts used for the large, Dutch, population-based study, 361 (3%) were diagnosed with a single initial basal cell carcinoma (BCC) lesion, and 163 (1.5%) were diagnosed with subsequent BCC lesions during the study period.

After adjusting for numerous factors such as sex, age, hair and eye color, tendency to develop sunburn, smoking history, body mass index, and educational level, factors found to be significantly associated with developing a first BCC lesion were age (odds ratios of 1.39 and 1.01 for those aged 65-74 years and for those aged 75 years and older, respectively, vs. those younger than age 65 years), and red hair color (OR of 1.98 for red vs. brown or black hair), Dr. Ville Kiiski and colleagues at Erasmus Medical Center, Rotterdam, the Netherlands, reported in the August issue of Archives of Dermatology.

After adjusting for age at index lesion, sex, hair color, eye color, all ultraviolet-related factors, smoking history, and alcohol consumption, the factors found to be associated with a significantly increased risk of developing multiple lesions were lesion location on an upper extremity (hazard ratio 1.49), age younger than 65 years (HRs of 0.58 and 0.65 for those aged 75 years and older and for those aged 65 to 74 years, respectively, vs. those younger than age 65 years), hair color (HR of 1.43 for red vs. brown/black hair), and education level (HR of 1.42 for high vs. low education level), the investigators found (Arch. Dermatol. 2010;146:848-55).

This last finding “may be explained by the probability that people with higher levels of education (which correlates strongly with socioeconomic status) have different lifestyles,” such as more frequent exposure to ultraviolet rays for intermittent periods, they said. Also, people of higher socioeconomic status generally may be expected to live longer and, thus have more time to acquire lesions.

Patients were adults aged 55 years or older from the two Rotterdam Study cohorts, including one studied in 1990, and one studied in 1999. Participants were followed for a mean of 9.5 years.

The findings – particularly regarding increased risk among younger patients and red-heads – largely support those of previous studies, although in the current study men were not shown to be at significantly increased risk of developing a first lesion, which contrasts with findings from some prior studies, the investigators noted.

The differences in risk factor profiles for those who develop single vs. multiple BCC lesions, as seen in the current study, may suggest that phenotypic characteristics of patients are less important for determining risk once “cumulative environmental-genetic interaction has surpassed a certain threshold and resulted in a lesion,” Dr. Ville Kiiski and colleagues wrote.

“The clinical relevance of this finding is that physicians’ risk assessment efforts should differentiate between patients at risk for a first lesion and those who have a history of BCC,” they said, noting that those with the identified risk factors for multiple lesions may require a more stringent follow-up regimen.

That’s not to say, however, that other BCC patients do not require follow-up. In this sample of the general population, more than 30% of the patients with BCC developed subsequent skin cancer, emphasizing the need for annual follow-up for several years,” Dr. Ville Kiiski and colleagues stressed.

Given that more than 1 million people are diagnosed with BCC in the United States each year, and given the strain that is put on limited specialized care by the need for follow-up of the large group of patients with BCCs, additional research is needed to better identify those at risk of developing multiple lesions, they concluded.

The investigators reported no financial disclosures relevant to their study.

ATLANTA — A limited number of studies suggest that immunity following meningococcal vaccination may wane earlier than initially expected, leaving those who are vaccinated at ages 11-12 years vulnerable to the disease at an age when they are at increased risk of contracting the disease, according to information from the Centers for Disease Control and Prevention.

As a result of these findings, a CDC working group on meningococcal disease is developing proposed revisions to the current recommendations, and will likely present its proposals to the CDC's Advisory Committee on Immunization Practices (ACIP) at its October meeting.

Dr. Amanda Cohn of the working group outlined the options currently under consideration to the committee at the June meeting. They are:

▸ Adding a booster dose at age 17 years, either for those who are or those who will be living in college dorms—a group at increased risk of meningococcal disease.

▸ Adding a booster dose for all adolescents.

▸ Moving the first dose closer to the period of risk by shifting the recommended vaccination age from 11-12 years to 14-15 years, for example.

The recommendations initially made for adolescents were made with the assumption that the vaccine would provide protection for 10 years or more. One study, however, showed that at 3 years of follow-up, protective levels of circulating antibody were present in only 35% of nearly 100 children vaccinated at ages 11-18 years. Another study showed that at 5 years, only 54% had protective titers, which was only 12% higher than the proportion in vaccine-naive individuals with naturally occurring protective antibodies, said Dr. Cohn, a medical epidemiologist with the CDC's meningitis and vaccine preventable diseases branch.

“These limited data do not support that children vaccinated at age 11-12 years will maintain protective antibody levels through college,” she said, adding that data coming available in the near future will “not likely change this picture.”

Based on these findings, it appears that the current vaccination program does not meet the CDC's prevention goals for meningococcal disease, Dr. Cohn said.

That is, vaccination of 11- to 12-year-olds at their preteen vaccination visit and vaccination of 13- to 18-year-olds not previously vaccinated, is not likely to provide adequate protection in late adolescence.

Although the program has had early success in terms of improving vaccination coverage and reducing disease burden, the working group feels compelled to address the matter of waning immunity, Dr. Cohn told ACIP.

When asked to weigh in on the pros and cons of adding a booster dose or moving back the recommended age for vaccination, ACIP members urged the working group to consider how any changes might affect other adolescent vaccination needs and recommendations to ensure overall vaccination goals are not adversely affected. Concerns also were raised about insurance coverage for vaccination, which might end for some individuals at the age of 18.

Disclosures: Dr. Cohn said she had no conflicts of interest to disclose.

ATLANTA — A limited number of studies suggest that immunity following meningococcal vaccination may wane earlier than initially expected, leaving those who are vaccinated at ages 11-12 years vulnerable to the disease at an age when they are at increased risk of contracting the disease, according to information from the Centers for Disease Control and Prevention.

As a result of these findings, a CDC working group on meningococcal disease is developing proposed revisions to the current recommendations, and will likely present its proposals to the CDC's Advisory Committee on Immunization Practices (ACIP) at its October meeting.

Dr. Amanda Cohn of the working group outlined the options currently under consideration to the committee at the June meeting. They are:

▸ Adding a booster dose at age 17 years, either for those who are or those who will be living in college dorms—a group at increased risk of meningococcal disease.

▸ Adding a booster dose for all adolescents.

▸ Moving the first dose closer to the period of risk by shifting the recommended vaccination age from 11-12 years to 14-15 years, for example.

The recommendations initially made for adolescents were made with the assumption that the vaccine would provide protection for 10 years or more. One study, however, showed that at 3 years of follow-up, protective levels of circulating antibody were present in only 35% of nearly 100 children vaccinated at ages 11-18 years. Another study showed that at 5 years, only 54% had protective titers, which was only 12% higher than the proportion in vaccine-naive individuals with naturally occurring protective antibodies, said Dr. Cohn, a medical epidemiologist with the CDC's meningitis and vaccine preventable diseases branch.

“These limited data do not support that children vaccinated at age 11-12 years will maintain protective antibody levels through college,” she said, adding that data coming available in the near future will “not likely change this picture.”

Based on these findings, it appears that the current vaccination program does not meet the CDC's prevention goals for meningococcal disease, Dr. Cohn said.

That is, vaccination of 11- to 12-year-olds at their preteen vaccination visit and vaccination of 13- to 18-year-olds not previously vaccinated, is not likely to provide adequate protection in late adolescence.

Although the program has had early success in terms of improving vaccination coverage and reducing disease burden, the working group feels compelled to address the matter of waning immunity, Dr. Cohn told ACIP.

When asked to weigh in on the pros and cons of adding a booster dose or moving back the recommended age for vaccination, ACIP members urged the working group to consider how any changes might affect other adolescent vaccination needs and recommendations to ensure overall vaccination goals are not adversely affected. Concerns also were raised about insurance coverage for vaccination, which might end for some individuals at the age of 18.

Disclosures: Dr. Cohn said she had no conflicts of interest to disclose.

ATLANTA — A limited number of studies suggest that immunity following meningococcal vaccination may wane earlier than initially expected, leaving those who are vaccinated at ages 11-12 years vulnerable to the disease at an age when they are at increased risk of contracting the disease, according to information from the Centers for Disease Control and Prevention.

As a result of these findings, a CDC working group on meningococcal disease is developing proposed revisions to the current recommendations, and will likely present its proposals to the CDC's Advisory Committee on Immunization Practices (ACIP) at its October meeting.

Dr. Amanda Cohn of the working group outlined the options currently under consideration to the committee at the June meeting. They are:

▸ Adding a booster dose at age 17 years, either for those who are or those who will be living in college dorms—a group at increased risk of meningococcal disease.

▸ Adding a booster dose for all adolescents.

▸ Moving the first dose closer to the period of risk by shifting the recommended vaccination age from 11-12 years to 14-15 years, for example.

The recommendations initially made for adolescents were made with the assumption that the vaccine would provide protection for 10 years or more. One study, however, showed that at 3 years of follow-up, protective levels of circulating antibody were present in only 35% of nearly 100 children vaccinated at ages 11-18 years. Another study showed that at 5 years, only 54% had protective titers, which was only 12% higher than the proportion in vaccine-naive individuals with naturally occurring protective antibodies, said Dr. Cohn, a medical epidemiologist with the CDC's meningitis and vaccine preventable diseases branch.

“These limited data do not support that children vaccinated at age 11-12 years will maintain protective antibody levels through college,” she said, adding that data coming available in the near future will “not likely change this picture.”

Based on these findings, it appears that the current vaccination program does not meet the CDC's prevention goals for meningococcal disease, Dr. Cohn said.

That is, vaccination of 11- to 12-year-olds at their preteen vaccination visit and vaccination of 13- to 18-year-olds not previously vaccinated, is not likely to provide adequate protection in late adolescence.

Although the program has had early success in terms of improving vaccination coverage and reducing disease burden, the working group feels compelled to address the matter of waning immunity, Dr. Cohn told ACIP.

When asked to weigh in on the pros and cons of adding a booster dose or moving back the recommended age for vaccination, ACIP members urged the working group to consider how any changes might affect other adolescent vaccination needs and recommendations to ensure overall vaccination goals are not adversely affected. Concerns also were raised about insurance coverage for vaccination, which might end for some individuals at the age of 18.

Disclosures: Dr. Cohn said she had no conflicts of interest to disclose.

Both operative and nonoperative approaches to the management of rotator cuff tears appear to result in substantial improvement, but a paucity of data from well-constructed studies means that no firm conclusions can be made about the best approach or the optimal overall management of the condition, according to authors of a meta-analysis of data from 137 studies.

The review showed that the benefits of being treated for a rotator cuff appear to outweigh the risks and that patients experience substantial improvement across all interventions.

Few differences of clinical importance were apparent in studies that compared interventions, and complications—most of which were not clinically important—occurred only rarely, reported Jennifer C. Seida of the University of Alberta, Edmonton, and her colleagues.

The authors searched 12 electronic databases, grey literature, trial registries, and reference lists to identify controlled and uncontrolled studies conducted between January 1990 and September 2009 that assessed the management of rotator cuff tears in adults.

All trials included in the meta-analysis were rated by a reviewer as having high risk of bias, and cohort and uncontrolled studies were, on average, rated as being of moderate quality.

No differences in reported functional outcomes were found in studies comparing open and mini-open repairs, mini-open and arthroscopic repairs, arthroscopic repairs with or without acromioplasty, and single- or double-row fixation.

However, earlier return to work occurred with mini-open compared with open repair; and with continuous passive motion plus physical therapy compared with physical therapy alone. Greater improvement in function was seen with open repairs compared with arthroscopic debridement, they said.

Still, they characterized the available evidence as limited and frequently low in quality across all interventions.

The lack of data on the best approach to management leaves physicians and patients uncertain about when nonoperative approaches should be aborted in favor of surgery, so future research should focus on comparing early with delayed surgical repair, they said.

“Investigators should use a streamlined approach in evaluating operative treatments, beginning with broad treatment questions before focusing on detailed procedures,” they wrote, adding that a comparative study design and appropriate confirmation of the diagnosis of rotator cuff are important.

Researchers should provide detailed reporting of study methodology and interventions to allow for appropriate interpretation of the results and for replication of treatments, the authors said.

The Agency for Healthcare Research and Quality funded this study. The authors had no disclosures.

Both operative and nonoperative approaches to the management of rotator cuff tears appear to result in substantial improvement, but a paucity of data from well-constructed studies means that no firm conclusions can be made about the best approach or the optimal overall management of the condition, according to authors of a meta-analysis of data from 137 studies.

The review showed that the benefits of being treated for a rotator cuff appear to outweigh the risks and that patients experience substantial improvement across all interventions.

Few differences of clinical importance were apparent in studies that compared interventions, and complications—most of which were not clinically important—occurred only rarely, reported Jennifer C. Seida of the University of Alberta, Edmonton, and her colleagues.

The authors searched 12 electronic databases, grey literature, trial registries, and reference lists to identify controlled and uncontrolled studies conducted between January 1990 and September 2009 that assessed the management of rotator cuff tears in adults.

All trials included in the meta-analysis were rated by a reviewer as having high risk of bias, and cohort and uncontrolled studies were, on average, rated as being of moderate quality.

No differences in reported functional outcomes were found in studies comparing open and mini-open repairs, mini-open and arthroscopic repairs, arthroscopic repairs with or without acromioplasty, and single- or double-row fixation.

However, earlier return to work occurred with mini-open compared with open repair; and with continuous passive motion plus physical therapy compared with physical therapy alone. Greater improvement in function was seen with open repairs compared with arthroscopic debridement, they said.

Still, they characterized the available evidence as limited and frequently low in quality across all interventions.

The lack of data on the best approach to management leaves physicians and patients uncertain about when nonoperative approaches should be aborted in favor of surgery, so future research should focus on comparing early with delayed surgical repair, they said.

“Investigators should use a streamlined approach in evaluating operative treatments, beginning with broad treatment questions before focusing on detailed procedures,” they wrote, adding that a comparative study design and appropriate confirmation of the diagnosis of rotator cuff are important.

Researchers should provide detailed reporting of study methodology and interventions to allow for appropriate interpretation of the results and for replication of treatments, the authors said.

The Agency for Healthcare Research and Quality funded this study. The authors had no disclosures.

Both operative and nonoperative approaches to the management of rotator cuff tears appear to result in substantial improvement, but a paucity of data from well-constructed studies means that no firm conclusions can be made about the best approach or the optimal overall management of the condition, according to authors of a meta-analysis of data from 137 studies.

The review showed that the benefits of being treated for a rotator cuff appear to outweigh the risks and that patients experience substantial improvement across all interventions.

Few differences of clinical importance were apparent in studies that compared interventions, and complications—most of which were not clinically important—occurred only rarely, reported Jennifer C. Seida of the University of Alberta, Edmonton, and her colleagues.

The authors searched 12 electronic databases, grey literature, trial registries, and reference lists to identify controlled and uncontrolled studies conducted between January 1990 and September 2009 that assessed the management of rotator cuff tears in adults.

All trials included in the meta-analysis were rated by a reviewer as having high risk of bias, and cohort and uncontrolled studies were, on average, rated as being of moderate quality.

No differences in reported functional outcomes were found in studies comparing open and mini-open repairs, mini-open and arthroscopic repairs, arthroscopic repairs with or without acromioplasty, and single- or double-row fixation.

However, earlier return to work occurred with mini-open compared with open repair; and with continuous passive motion plus physical therapy compared with physical therapy alone. Greater improvement in function was seen with open repairs compared with arthroscopic debridement, they said.

Still, they characterized the available evidence as limited and frequently low in quality across all interventions.

The lack of data on the best approach to management leaves physicians and patients uncertain about when nonoperative approaches should be aborted in favor of surgery, so future research should focus on comparing early with delayed surgical repair, they said.

“Investigators should use a streamlined approach in evaluating operative treatments, beginning with broad treatment questions before focusing on detailed procedures,” they wrote, adding that a comparative study design and appropriate confirmation of the diagnosis of rotator cuff are important.

Researchers should provide detailed reporting of study methodology and interventions to allow for appropriate interpretation of the results and for replication of treatments, the authors said.

The Agency for Healthcare Research and Quality funded this study. The authors had no disclosures.

Patients are most likely to make the lifestyle changes necessary for reducing cardiovascular disease risks if they receive a combination of behavioral interventions, including counseling, extended follow-up with a health care provider, and tools for self-monitoring of diet and exercise, according to a scientific statement from the American Heart Association.

The statement urges clinicians to move beyond simply telling patients they are at risk for cardiovascular disease and recommending appropriate lifestyle changes, to encouraging the particular interventions likely to promote change.

Specifically, clinicians can best promote effective change by using motivational interviewing techniques to encourage healthier lifestyle choices, by counseling patients that setbacks are normal, and by scheduling regular follow-up sessions, lead author Nancy T. Artinian, Ph.D., of Wayne State University, Detroit, and her colleagues wrote on behalf of the AHA Prevention Committee of the Council on Cardiovascular Nursing (Circulation 2010 July 12 [doi:10.1161/CIR.0b013e3181e8edf1]).

Among other interventions recommended are providing for direct or peer-based long-term support and follow-up (through community-based programs, for example); using incentives, modeling, and problem-solving strategies; and using group sessions with cognitive-behavioral strategies to teach skills to modify the diet and develop a fitness program, provide role modeling and positive observational learning, and maximize the benefits of peer support and group problem solving.

The statement is based on an extensive review of 74 peer-reviewed scientific studies conducted in the United States during January 1997 through May 2007. The studies looked at the effects of behavioral programs on blood pressure, cholesterol levels, activity levels and fitness, and diet.

Evidence-based and expert opinion–based recommendations on designing and implementing interventions—with specific advice for culturally diverse and socioeconomically disadvantaged patients—are included in the statement, and are graded based on the type and strength of the evidence. For example, class I, level A evidence exists for the recommendation that clinicians combine strategies such as motivational interviewing and regular follow-up to best promote change.

The statement also provides recommendations on policy changes that will help make it more feasible for clinicians to follow the recommendations. Currently, clinicians face numerous barriers, including limited resources for counseling and sustained follow-up support, time restraints, and lack of financial incentives and reimbursement, the authors noted.

Indeed, current health care policies should be modified to encourage the interventions identified during the development of the statement as being effective for promoting behavioral change, the authors argued.

In a press statement from the AHA, Dr. Artinian expressed the hope that federal health reform legislation along with the policy changes recommended in the scientific statement will lead to “a health care system that gives more weight to the importance of prevention and changing lifestyle behavior to help people stay healthy and reduce cardiovascular risk.”

Disclosures: Dr. Artinian reported having no relevant financial ties to disclose, but several authors of the statement reported disclosures including receiving research support from, serving on the speakers bureau or as a consultant for, or having an ownership or other interest in one or more companies or organizations. The complete list of disclosures is included in the AHA statement.

Patients are most likely to make the lifestyle changes necessary for reducing cardiovascular disease risks if they receive a combination of behavioral interventions, including counseling, extended follow-up with a health care provider, and tools for self-monitoring of diet and exercise, according to a scientific statement from the American Heart Association.

The statement urges clinicians to move beyond simply telling patients they are at risk for cardiovascular disease and recommending appropriate lifestyle changes, to encouraging the particular interventions likely to promote change.

Specifically, clinicians can best promote effective change by using motivational interviewing techniques to encourage healthier lifestyle choices, by counseling patients that setbacks are normal, and by scheduling regular follow-up sessions, lead author Nancy T. Artinian, Ph.D., of Wayne State University, Detroit, and her colleagues wrote on behalf of the AHA Prevention Committee of the Council on Cardiovascular Nursing (Circulation 2010 July 12 [doi:10.1161/CIR.0b013e3181e8edf1]).

Among other interventions recommended are providing for direct or peer-based long-term support and follow-up (through community-based programs, for example); using incentives, modeling, and problem-solving strategies; and using group sessions with cognitive-behavioral strategies to teach skills to modify the diet and develop a fitness program, provide role modeling and positive observational learning, and maximize the benefits of peer support and group problem solving.

The statement is based on an extensive review of 74 peer-reviewed scientific studies conducted in the United States during January 1997 through May 2007. The studies looked at the effects of behavioral programs on blood pressure, cholesterol levels, activity levels and fitness, and diet.

Evidence-based and expert opinion–based recommendations on designing and implementing interventions—with specific advice for culturally diverse and socioeconomically disadvantaged patients—are included in the statement, and are graded based on the type and strength of the evidence. For example, class I, level A evidence exists for the recommendation that clinicians combine strategies such as motivational interviewing and regular follow-up to best promote change.

The statement also provides recommendations on policy changes that will help make it more feasible for clinicians to follow the recommendations. Currently, clinicians face numerous barriers, including limited resources for counseling and sustained follow-up support, time restraints, and lack of financial incentives and reimbursement, the authors noted.

Indeed, current health care policies should be modified to encourage the interventions identified during the development of the statement as being effective for promoting behavioral change, the authors argued.

In a press statement from the AHA, Dr. Artinian expressed the hope that federal health reform legislation along with the policy changes recommended in the scientific statement will lead to “a health care system that gives more weight to the importance of prevention and changing lifestyle behavior to help people stay healthy and reduce cardiovascular risk.”

Disclosures: Dr. Artinian reported having no relevant financial ties to disclose, but several authors of the statement reported disclosures including receiving research support from, serving on the speakers bureau or as a consultant for, or having an ownership or other interest in one or more companies or organizations. The complete list of disclosures is included in the AHA statement.

Patients are most likely to make the lifestyle changes necessary for reducing cardiovascular disease risks if they receive a combination of behavioral interventions, including counseling, extended follow-up with a health care provider, and tools for self-monitoring of diet and exercise, according to a scientific statement from the American Heart Association.

The statement urges clinicians to move beyond simply telling patients they are at risk for cardiovascular disease and recommending appropriate lifestyle changes, to encouraging the particular interventions likely to promote change.

Specifically, clinicians can best promote effective change by using motivational interviewing techniques to encourage healthier lifestyle choices, by counseling patients that setbacks are normal, and by scheduling regular follow-up sessions, lead author Nancy T. Artinian, Ph.D., of Wayne State University, Detroit, and her colleagues wrote on behalf of the AHA Prevention Committee of the Council on Cardiovascular Nursing (Circulation 2010 July 12 [doi:10.1161/CIR.0b013e3181e8edf1]).

Among other interventions recommended are providing for direct or peer-based long-term support and follow-up (through community-based programs, for example); using incentives, modeling, and problem-solving strategies; and using group sessions with cognitive-behavioral strategies to teach skills to modify the diet and develop a fitness program, provide role modeling and positive observational learning, and maximize the benefits of peer support and group problem solving.

The statement is based on an extensive review of 74 peer-reviewed scientific studies conducted in the United States during January 1997 through May 2007. The studies looked at the effects of behavioral programs on blood pressure, cholesterol levels, activity levels and fitness, and diet.

Evidence-based and expert opinion–based recommendations on designing and implementing interventions—with specific advice for culturally diverse and socioeconomically disadvantaged patients—are included in the statement, and are graded based on the type and strength of the evidence. For example, class I, level A evidence exists for the recommendation that clinicians combine strategies such as motivational interviewing and regular follow-up to best promote change.

The statement also provides recommendations on policy changes that will help make it more feasible for clinicians to follow the recommendations. Currently, clinicians face numerous barriers, including limited resources for counseling and sustained follow-up support, time restraints, and lack of financial incentives and reimbursement, the authors noted.

Indeed, current health care policies should be modified to encourage the interventions identified during the development of the statement as being effective for promoting behavioral change, the authors argued.

In a press statement from the AHA, Dr. Artinian expressed the hope that federal health reform legislation along with the policy changes recommended in the scientific statement will lead to “a health care system that gives more weight to the importance of prevention and changing lifestyle behavior to help people stay healthy and reduce cardiovascular risk.”

Disclosures: Dr. Artinian reported having no relevant financial ties to disclose, but several authors of the statement reported disclosures including receiving research support from, serving on the speakers bureau or as a consultant for, or having an ownership or other interest in one or more companies or organizations. The complete list of disclosures is included in the AHA statement.

ATLANTA — The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices may soon consider whether routine human papillomavirus vaccination should be recommended for males aged 9–26 years, but it does not seem likely that a catch-up dose will be recommended for women who are older than 26.

The HPV vaccine (Gardasil, Merck & Co.) is licensed for males aged 9–26 years for prevention of genital warts associated with HPV-6 and -11, in addition to being routinely recommended for girls aged 11–12 years and for those aged 13–26 who have not already been vaccinated. Data also show that the vaccine has 75% efficacy for preventing anal intraepithelial neoplasia grades 2 and 3 in males, Dr. Lauri Markowitz of the center's HPV working group reported to the committee.

A review by the Food and Drug Administration, which is considering a supplemental biologic license application by Merck for the latter indication, is not expected to be complete before the next ACIP meeting in October, but the working group is reviewing vaccine trial data and cost-effectiveness data on male vaccination, and plans to present its findings at that meeting.

Specifically, the group is looking at cost-effectiveness based on different coverage assumptions. From currently available data, vaccination of males does not appear to be cost effective when female vaccination coverage is high, but it may be more cost effective if female vaccination coverage is low, said Dr. Markowitz, who is also with the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC.

The group is also looking at epidemiology and cost-effectiveness data in men who have sex with men, and at the feasibility of reaching men who have sex with men when they would benefit most from vaccination. These findings will also be presented at the October meeting.

Dr. Markowitz noted that ACIP had previously stated that the HPV vaccine “may be given” to males aged 9–26 years, but did not include the HPV vaccine in the routine vaccination schedule for this population.

She added that most working group members are opposed to a catch-up dose in women over age 26 on the basis of currently available data. ACIP first considered vaccination in women in this group in 2008, and Merck submitted a supplemental biologic license application to the FDA in 2009 for that indication. That application remains under review.

National Immunization Survey data show that 25% of girls aged 13–17 years received at least one HPV vaccine dose in 2007 and 37% received it in 2008. Additional data on vaccination rates, vaccine safety, and private insurance coverage will be presented at the October meeting, Dr. Markowitz said.

Disclosures: Dr. Markowitz said that she has no relevant conflicts of interest.

ATLANTA — The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices may soon consider whether routine human papillomavirus vaccination should be recommended for males aged 9–26 years, but it does not seem likely that a catch-up dose will be recommended for women who are older than 26.

The HPV vaccine (Gardasil, Merck & Co.) is licensed for males aged 9–26 years for prevention of genital warts associated with HPV-6 and -11, in addition to being routinely recommended for girls aged 11–12 years and for those aged 13–26 who have not already been vaccinated. Data also show that the vaccine has 75% efficacy for preventing anal intraepithelial neoplasia grades 2 and 3 in males, Dr. Lauri Markowitz of the center's HPV working group reported to the committee.

A review by the Food and Drug Administration, which is considering a supplemental biologic license application by Merck for the latter indication, is not expected to be complete before the next ACIP meeting in October, but the working group is reviewing vaccine trial data and cost-effectiveness data on male vaccination, and plans to present its findings at that meeting.

Specifically, the group is looking at cost-effectiveness based on different coverage assumptions. From currently available data, vaccination of males does not appear to be cost effective when female vaccination coverage is high, but it may be more cost effective if female vaccination coverage is low, said Dr. Markowitz, who is also with the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC.

The group is also looking at epidemiology and cost-effectiveness data in men who have sex with men, and at the feasibility of reaching men who have sex with men when they would benefit most from vaccination. These findings will also be presented at the October meeting.

Dr. Markowitz noted that ACIP had previously stated that the HPV vaccine “may be given” to males aged 9–26 years, but did not include the HPV vaccine in the routine vaccination schedule for this population.

She added that most working group members are opposed to a catch-up dose in women over age 26 on the basis of currently available data. ACIP first considered vaccination in women in this group in 2008, and Merck submitted a supplemental biologic license application to the FDA in 2009 for that indication. That application remains under review.

National Immunization Survey data show that 25% of girls aged 13–17 years received at least one HPV vaccine dose in 2007 and 37% received it in 2008. Additional data on vaccination rates, vaccine safety, and private insurance coverage will be presented at the October meeting, Dr. Markowitz said.

Disclosures: Dr. Markowitz said that she has no relevant conflicts of interest.

ATLANTA — The Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices may soon consider whether routine human papillomavirus vaccination should be recommended for males aged 9–26 years, but it does not seem likely that a catch-up dose will be recommended for women who are older than 26.

The HPV vaccine (Gardasil, Merck & Co.) is licensed for males aged 9–26 years for prevention of genital warts associated with HPV-6 and -11, in addition to being routinely recommended for girls aged 11–12 years and for those aged 13–26 who have not already been vaccinated. Data also show that the vaccine has 75% efficacy for preventing anal intraepithelial neoplasia grades 2 and 3 in males, Dr. Lauri Markowitz of the center's HPV working group reported to the committee.

A review by the Food and Drug Administration, which is considering a supplemental biologic license application by Merck for the latter indication, is not expected to be complete before the next ACIP meeting in October, but the working group is reviewing vaccine trial data and cost-effectiveness data on male vaccination, and plans to present its findings at that meeting.

Specifically, the group is looking at cost-effectiveness based on different coverage assumptions. From currently available data, vaccination of males does not appear to be cost effective when female vaccination coverage is high, but it may be more cost effective if female vaccination coverage is low, said Dr. Markowitz, who is also with the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the CDC.

The group is also looking at epidemiology and cost-effectiveness data in men who have sex with men, and at the feasibility of reaching men who have sex with men when they would benefit most from vaccination. These findings will also be presented at the October meeting.

Dr. Markowitz noted that ACIP had previously stated that the HPV vaccine “may be given” to males aged 9–26 years, but did not include the HPV vaccine in the routine vaccination schedule for this population.

She added that most working group members are opposed to a catch-up dose in women over age 26 on the basis of currently available data. ACIP first considered vaccination in women in this group in 2008, and Merck submitted a supplemental biologic license application to the FDA in 2009 for that indication. That application remains under review.

National Immunization Survey data show that 25% of girls aged 13–17 years received at least one HPV vaccine dose in 2007 and 37% received it in 2008. Additional data on vaccination rates, vaccine safety, and private insurance coverage will be presented at the October meeting, Dr. Markowitz said.

Disclosures: Dr. Markowitz said that she has no relevant conflicts of interest.

Major Finding: In 8,900 patients treated daily with 20 mg rosuvastatin and who had a median LDL cholesterol level of 1.42 mmol/L on treatment, there was no significant association between HDL levels and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartile of HDL levels).

Data Source: An analysis of the randomized, double-blind, placebo-controlled JUPITER trial.

Disclosures: AstraZeneca, maker of the trial drug, funded the study. Dr. Ridker reported receiving grant support and/or consulting and lecture fees from AstraZeneca and other drug manufacturers. He is listed as a co-inventor on patents held by the Brigham and Women's Hospital, which relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to AstraZeneca and other entities. Some authors also reported receiving research support and/or consulting and lecture fees from AstraZeneca and numerous drug manufacturers.

High-density lipoprotein cholesterol concentrations are inversely associated with risk for cardiovascular events, but this association does not persist in patients who achieve very low concentrations of low-density lipoprotein cholesterol on statin therapy, according to an analysis of data from the JUPITER (Justification for the Use of Statins in Primary Prevention) trial.

In 8,901 patients in the study who received placebo and who had a median LDL cholesterol level of 2.8 mmol/L (108 mg/dL), HDL cholesterol levels were inversely associated with risk for cardiovascular events both at baseline and on placebo (hazard ratios, 0.54 and 0.55, respectively, for the top vs. the bottom quartiles of HDL cholesterol levels).

However, in 8,900 patients in the study who were treated daily with 20 mg rosuvastatin (Crestor) and who had a median LDL cholesterol level of 1.42 mmol/L (55 mg/dL) on treatment, there was no significant association between HDL cholesterol concentrations and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartiles of HDL cholesterol levels), Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston and his colleagues reported.

They also noted that, like HDL cholesterol levels, apolipoprotein A1 levels were strongly and inversely associated with risk for cardiovascular events in the placebo group, but these associations were attenuated and not statistically significant in the treatment group.

Patients were part of the JUPITER trial, which enrolled 17,802 participants from March 2003 to December 2006 to investigate whether rosuvastatin lowered the rate of first-ever cardiovascular events.

Study participants had LDL cholesterol levels of less than 3.4 mmol/L (130 mg/dL) and were at high vascular risk because of elevated high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more, but were otherwise healthy, without cardiovascular disease or diabetes.

Indeed, rosuvastatin reduced LDL levels to a median of 1.4 mmol/L (55 mg/dL), with 25% of patients achieving concentrations of less than 1.1 mmol/L 44 mg/dL) in the trial, and treatment was associated with a 54% reduction in MI, a 48% reduction in stroke, a 46% reduction in revascularization, and a 20% reduction in total mortality (N. Engl. J. Med. 2008;359:2195-20), the investigators noted.

Now, based on the findings of the current analysis of data from the JUPITER primary prevention trial, it appears that treatment also reduces the clinical relevance of HDL cholesterol concentrations, they said (Lancet 2010 July 22 [doi:10.1016/So140-6736(10)60713-1]).

“This analysis provides little evidence that residual risk after aggressive use of statin therapy is related to HDL-cholesterol concentration,” the investigators wrote, noting that their findings are supported by similar findings in one other primary prevention trial and two secondary prevention trials involving high-dose statin therapy.

The current study is strengthened by the investigators' ability to adjust for a wide range of covariates, including age, sex, smoking status, metabolic syndrome, family history of premature atherosclerosis, body mass index, systolic blood pressure, fasting glucose, and estimated glomerular filtration rate. Analyses of HDL cholesterol were controlled for baseline concentrations of LDL cholesterol, triglyceride, and hsCRP (and in the case of on-treatment HDL cholesterol, for changes in the latter three), they said.

The study is limited, however, by the exclusion of diabetic patients and the inclusion of patients with LDL cholesterol of less than 3.4 mmol/L. Generalization of the findings should therefore be done with caution, they noted.

The investigators concluded that their primary prevention data, along with data from other primary and secondary prevention studies, provide little evidence in support of the hypothesis that HDL cholesterol concentrations predict risk of vascular events in patients on high-dose statins.

They noted, however, that their findings should not “reduce enthusiasm for measurement [of HDL cholesterol concentration] as part of an initial cardiovascular risk assessment.”

Future randomized trials of potent HDL cholesterol–raising agents are needed to determine if such treatment would provide added benefit in terms of cardiovascular risk reduction in patients whose LDL levels are successfully lowered on statin therapy, they said.

In an accompanying editorial comment, Dr. Derek Hausenloy of the Hatter Cardiovascular Institute at University College London Hospital and his colleagues noted that although the researchers had shown that HDL cholesterol concentrations do not predict residual cardiovascular risk in patients with very low LDL cholesterol concentrations, the reasons for this observation remain unclear (Lancet 2010 July 22 [doi:10.1016/S0140-6736(10)61021-5]).

“Perhaps, in patients with a low cardiovascular risk … who are treated to very low concentrations of LDL cholesterol, the relation between HDL cholesterol and cardiovascular risk is lessened; however, [the researchers] were not able to find a relation between apolipoprotein A1 and reduced cardiovascular risk,” the commentators wrote.

They added that in the setting of very low LDL cholesterol, other lipid measures, such as apolipoprotein B to A1 ratio, may provide a better prediction of cardiovascular risk.

Regardless, the findings should not “detract from the fact that raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol,” wrote Dr. Hausenloy and his colleagues, none of whom had any disclosures to make in relation to the study.

It still needs to be determined in large randomized trials whether increasing HDL cholesterol in patients with very low LDL cholesterol is of benefit, they noted, adding that such trials will be particularly important given that two new inhibitors of cholesterol ester transfer proteins—anacetrapib and dalcetrapib—are now in clinical testing.

Elsevier Global Medical News

Major Finding: In 8,900 patients treated daily with 20 mg rosuvastatin and who had a median LDL cholesterol level of 1.42 mmol/L on treatment, there was no significant association between HDL levels and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartile of HDL levels).

Data Source: An analysis of the randomized, double-blind, placebo-controlled JUPITER trial.

Disclosures: AstraZeneca, maker of the trial drug, funded the study. Dr. Ridker reported receiving grant support and/or consulting and lecture fees from AstraZeneca and other drug manufacturers. He is listed as a co-inventor on patents held by the Brigham and Women's Hospital, which relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to AstraZeneca and other entities. Some authors also reported receiving research support and/or consulting and lecture fees from AstraZeneca and numerous drug manufacturers.

High-density lipoprotein cholesterol concentrations are inversely associated with risk for cardiovascular events, but this association does not persist in patients who achieve very low concentrations of low-density lipoprotein cholesterol on statin therapy, according to an analysis of data from the JUPITER (Justification for the Use of Statins in Primary Prevention) trial.

In 8,901 patients in the study who received placebo and who had a median LDL cholesterol level of 2.8 mmol/L (108 mg/dL), HDL cholesterol levels were inversely associated with risk for cardiovascular events both at baseline and on placebo (hazard ratios, 0.54 and 0.55, respectively, for the top vs. the bottom quartiles of HDL cholesterol levels).

However, in 8,900 patients in the study who were treated daily with 20 mg rosuvastatin (Crestor) and who had a median LDL cholesterol level of 1.42 mmol/L (55 mg/dL) on treatment, there was no significant association between HDL cholesterol concentrations and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartiles of HDL cholesterol levels), Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston and his colleagues reported.

They also noted that, like HDL cholesterol levels, apolipoprotein A1 levels were strongly and inversely associated with risk for cardiovascular events in the placebo group, but these associations were attenuated and not statistically significant in the treatment group.

Patients were part of the JUPITER trial, which enrolled 17,802 participants from March 2003 to December 2006 to investigate whether rosuvastatin lowered the rate of first-ever cardiovascular events.

Study participants had LDL cholesterol levels of less than 3.4 mmol/L (130 mg/dL) and were at high vascular risk because of elevated high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more, but were otherwise healthy, without cardiovascular disease or diabetes.

Indeed, rosuvastatin reduced LDL levels to a median of 1.4 mmol/L (55 mg/dL), with 25% of patients achieving concentrations of less than 1.1 mmol/L 44 mg/dL) in the trial, and treatment was associated with a 54% reduction in MI, a 48% reduction in stroke, a 46% reduction in revascularization, and a 20% reduction in total mortality (N. Engl. J. Med. 2008;359:2195-20), the investigators noted.

Now, based on the findings of the current analysis of data from the JUPITER primary prevention trial, it appears that treatment also reduces the clinical relevance of HDL cholesterol concentrations, they said (Lancet 2010 July 22 [doi:10.1016/So140-6736(10)60713-1]).

“This analysis provides little evidence that residual risk after aggressive use of statin therapy is related to HDL-cholesterol concentration,” the investigators wrote, noting that their findings are supported by similar findings in one other primary prevention trial and two secondary prevention trials involving high-dose statin therapy.

The current study is strengthened by the investigators' ability to adjust for a wide range of covariates, including age, sex, smoking status, metabolic syndrome, family history of premature atherosclerosis, body mass index, systolic blood pressure, fasting glucose, and estimated glomerular filtration rate. Analyses of HDL cholesterol were controlled for baseline concentrations of LDL cholesterol, triglyceride, and hsCRP (and in the case of on-treatment HDL cholesterol, for changes in the latter three), they said.

The study is limited, however, by the exclusion of diabetic patients and the inclusion of patients with LDL cholesterol of less than 3.4 mmol/L. Generalization of the findings should therefore be done with caution, they noted.

The investigators concluded that their primary prevention data, along with data from other primary and secondary prevention studies, provide little evidence in support of the hypothesis that HDL cholesterol concentrations predict risk of vascular events in patients on high-dose statins.

They noted, however, that their findings should not “reduce enthusiasm for measurement [of HDL cholesterol concentration] as part of an initial cardiovascular risk assessment.”

Future randomized trials of potent HDL cholesterol–raising agents are needed to determine if such treatment would provide added benefit in terms of cardiovascular risk reduction in patients whose LDL levels are successfully lowered on statin therapy, they said.

In an accompanying editorial comment, Dr. Derek Hausenloy of the Hatter Cardiovascular Institute at University College London Hospital and his colleagues noted that although the researchers had shown that HDL cholesterol concentrations do not predict residual cardiovascular risk in patients with very low LDL cholesterol concentrations, the reasons for this observation remain unclear (Lancet 2010 July 22 [doi:10.1016/S0140-6736(10)61021-5]).

“Perhaps, in patients with a low cardiovascular risk … who are treated to very low concentrations of LDL cholesterol, the relation between HDL cholesterol and cardiovascular risk is lessened; however, [the researchers] were not able to find a relation between apolipoprotein A1 and reduced cardiovascular risk,” the commentators wrote.

They added that in the setting of very low LDL cholesterol, other lipid measures, such as apolipoprotein B to A1 ratio, may provide a better prediction of cardiovascular risk.

Regardless, the findings should not “detract from the fact that raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol,” wrote Dr. Hausenloy and his colleagues, none of whom had any disclosures to make in relation to the study.

It still needs to be determined in large randomized trials whether increasing HDL cholesterol in patients with very low LDL cholesterol is of benefit, they noted, adding that such trials will be particularly important given that two new inhibitors of cholesterol ester transfer proteins—anacetrapib and dalcetrapib—are now in clinical testing.

Elsevier Global Medical News

Major Finding: In 8,900 patients treated daily with 20 mg rosuvastatin and who had a median LDL cholesterol level of 1.42 mmol/L on treatment, there was no significant association between HDL levels and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartile of HDL levels).

Data Source: An analysis of the randomized, double-blind, placebo-controlled JUPITER trial.

Disclosures: AstraZeneca, maker of the trial drug, funded the study. Dr. Ridker reported receiving grant support and/or consulting and lecture fees from AstraZeneca and other drug manufacturers. He is listed as a co-inventor on patents held by the Brigham and Women's Hospital, which relate to the use of inflammatory biomarkers in cardiovascular disease and have been licensed to AstraZeneca and other entities. Some authors also reported receiving research support and/or consulting and lecture fees from AstraZeneca and numerous drug manufacturers.

High-density lipoprotein cholesterol concentrations are inversely associated with risk for cardiovascular events, but this association does not persist in patients who achieve very low concentrations of low-density lipoprotein cholesterol on statin therapy, according to an analysis of data from the JUPITER (Justification for the Use of Statins in Primary Prevention) trial.

In 8,901 patients in the study who received placebo and who had a median LDL cholesterol level of 2.8 mmol/L (108 mg/dL), HDL cholesterol levels were inversely associated with risk for cardiovascular events both at baseline and on placebo (hazard ratios, 0.54 and 0.55, respectively, for the top vs. the bottom quartiles of HDL cholesterol levels).

However, in 8,900 patients in the study who were treated daily with 20 mg rosuvastatin (Crestor) and who had a median LDL cholesterol level of 1.42 mmol/L (55 mg/dL) on treatment, there was no significant association between HDL cholesterol concentrations and vascular risk at baseline or on treatment (hazard ratios, 1.12 and 1.03, respectively, for the top vs. bottom quartiles of HDL cholesterol levels), Dr. Paul M. Ridker of Brigham and Women's Hospital, Boston and his colleagues reported.

They also noted that, like HDL cholesterol levels, apolipoprotein A1 levels were strongly and inversely associated with risk for cardiovascular events in the placebo group, but these associations were attenuated and not statistically significant in the treatment group.

Patients were part of the JUPITER trial, which enrolled 17,802 participants from March 2003 to December 2006 to investigate whether rosuvastatin lowered the rate of first-ever cardiovascular events.

Study participants had LDL cholesterol levels of less than 3.4 mmol/L (130 mg/dL) and were at high vascular risk because of elevated high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or more, but were otherwise healthy, without cardiovascular disease or diabetes.

Indeed, rosuvastatin reduced LDL levels to a median of 1.4 mmol/L (55 mg/dL), with 25% of patients achieving concentrations of less than 1.1 mmol/L 44 mg/dL) in the trial, and treatment was associated with a 54% reduction in MI, a 48% reduction in stroke, a 46% reduction in revascularization, and a 20% reduction in total mortality (N. Engl. J. Med. 2008;359:2195-20), the investigators noted.

Now, based on the findings of the current analysis of data from the JUPITER primary prevention trial, it appears that treatment also reduces the clinical relevance of HDL cholesterol concentrations, they said (Lancet 2010 July 22 [doi:10.1016/So140-6736(10)60713-1]).

“This analysis provides little evidence that residual risk after aggressive use of statin therapy is related to HDL-cholesterol concentration,” the investigators wrote, noting that their findings are supported by similar findings in one other primary prevention trial and two secondary prevention trials involving high-dose statin therapy.

The current study is strengthened by the investigators' ability to adjust for a wide range of covariates, including age, sex, smoking status, metabolic syndrome, family history of premature atherosclerosis, body mass index, systolic blood pressure, fasting glucose, and estimated glomerular filtration rate. Analyses of HDL cholesterol were controlled for baseline concentrations of LDL cholesterol, triglyceride, and hsCRP (and in the case of on-treatment HDL cholesterol, for changes in the latter three), they said.

The study is limited, however, by the exclusion of diabetic patients and the inclusion of patients with LDL cholesterol of less than 3.4 mmol/L. Generalization of the findings should therefore be done with caution, they noted.

The investigators concluded that their primary prevention data, along with data from other primary and secondary prevention studies, provide little evidence in support of the hypothesis that HDL cholesterol concentrations predict risk of vascular events in patients on high-dose statins.

They noted, however, that their findings should not “reduce enthusiasm for measurement [of HDL cholesterol concentration] as part of an initial cardiovascular risk assessment.”

Future randomized trials of potent HDL cholesterol–raising agents are needed to determine if such treatment would provide added benefit in terms of cardiovascular risk reduction in patients whose LDL levels are successfully lowered on statin therapy, they said.

In an accompanying editorial comment, Dr. Derek Hausenloy of the Hatter Cardiovascular Institute at University College London Hospital and his colleagues noted that although the researchers had shown that HDL cholesterol concentrations do not predict residual cardiovascular risk in patients with very low LDL cholesterol concentrations, the reasons for this observation remain unclear (Lancet 2010 July 22 [doi:10.1016/S0140-6736(10)61021-5]).

“Perhaps, in patients with a low cardiovascular risk … who are treated to very low concentrations of LDL cholesterol, the relation between HDL cholesterol and cardiovascular risk is lessened; however, [the researchers] were not able to find a relation between apolipoprotein A1 and reduced cardiovascular risk,” the commentators wrote.

They added that in the setting of very low LDL cholesterol, other lipid measures, such as apolipoprotein B to A1 ratio, may provide a better prediction of cardiovascular risk.

Regardless, the findings should not “detract from the fact that raising HDL cholesterol remains a major treatment strategy for the reduction of cardiovascular risk in the large majority of patients who do not have very low LDL cholesterol,” wrote Dr. Hausenloy and his colleagues, none of whom had any disclosures to make in relation to the study.

It still needs to be determined in large randomized trials whether increasing HDL cholesterol in patients with very low LDL cholesterol is of benefit, they noted, adding that such trials will be particularly important given that two new inhibitors of cholesterol ester transfer proteins—anacetrapib and dalcetrapib—are now in clinical testing.

Elsevier Global Medical News