Successful Treatment With Antihypertensives May Not Eliminate Stroke Risk

Successful treatment with antihypertensive medications does not reduce the risk of stroke to the level of a person who is normotensive without medication, according to research published in the June issue of Stroke. Furthermore, stroke risk increases with the number of medications required to normalize blood pressure. The study results suggest that preventing the development of cardiovascular risk factors is more beneficial than treating hypertension successfully, according to the researchers.

The Affordable Care Act and organizations such as the American Heart Association are focusing public attention on prevention as a key to maintaining health. The stroke literature and clinical practice related to stroke, however, emphasize blood pressure control for people with established hypertension, said George Howard, DrPH, Professor of Biostatistics at the University of Alabama at Birmingham School of Public Health. Because of the dearth of literature describing differences in risk between people receiving and not receiving antihypertensive drugs, Dr. Howard and colleagues examined data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether hypertensive people with well-controlled blood pressure have a residual increased risk of stroke. The researchers also sought to assess how the intensiveness of antihypertensive treatment affects risk.

Analyzing Data From REGARDS
In the REGARDS study, 30,239 community-dwelling black and white participants age 45 or older completed in-home medical assessments that included blood pressure measurement, fasting blood and urine collection, ECG, and an inventory of medications. Participants also underwent telephone interviews at six-month intervals. The investigators retrieved medical records for suspected strokes, and physicians adjudicated stroke end points using published methods.

The investigators categorized participants’ blood pressure as normal (ie, <120 mmHg), prehypertensive (ie, 120–139 mmHg), stage 1 hypertension (ie, 140–159 mmHg), or stage 2 hypertension (ie, ≥160 mmHg). Participants were similarly grouped according to whether they were taking no, one, two, or three or more antihypertensive medications. After excluding ineligible participants, Dr. Howard and colleagues restricted their analysis to 26,875 people. During 6.2 years of follow-up, 860 participants had a stroke.

Within strata defined by the number of medications, participants with higher blood pressure tended to be older and were more likely black. For each group defined by blood pressure, patients on more medications also tended to be older and were more likely black.

Stroke Risk Increased With Number of Medications
For patients who were normotensive, stroke risk increased with increasing medication use. Normotensive patients taking one, two, and three or more antihypertensive medication classes had a 42%, 60%, and 148% increased stroke risk, respectively. Each additional class of antihypertensive medication taken increased stroke risk by approximately 33%.

Similarly, stroke risk tended to be higher for patients in higher blood-pressure categories who took more classes of antihypertensive medications. Although the researchers found no evidence of a difference in the association of stroke risk associated with increasing numbers of antihypertensive medications across blood-pressure categories, the increase in stroke risk per category of medication use was numerically smaller for people with prehypertension, stage 1 hypertension, and stage 2 hypertension, compared with normotensive people. Among individuals receiving more medications, the increase in stroke risk was statistically significant for people with prehypertension and people with stage 1 hypertension.

Among patients who did not take antihypertensive medication, stroke risk increased with higher blood pressure. For people who took one or two antihypertensive medications, the data suggested that the increased stroke risk at higher blood-pressure levels was smaller than that for people on no medications. People on no medications had a 49% increase in risk per blood-pressure stratum, compared with a 16% increase in risk per blood-pressure stratum for people on one or two medications.

The Importance of Prevention
“These results suggest that successful pharmacologic treatment of hypertension reduces, but does not eliminate, the harmful effects of hypertension,” said Dr. Howard. “Even with normalization of systolic blood pressure, there is substantial residual increased stroke risk among those on antihypertensive treatment, and the stroke risk is higher if more aggressive treatment is required to achieve normal systolic blood pressure.”

Dr. Howard and his colleagues suggested several reasons why hypertensive people with normal blood pressure on medication may have increased stroke risk. These individuals’ hypertension may not always have been well controlled, they said, and they may have had periods of undetected hypertension. In addition, elevated blood pressure earlier in life may have caused vascular damage, such as atherosclerosis and accelerated vascular aging, that increased these participants’ stroke risk.

“There is a substantial lost opportunity from not focusing prevention efforts on primordial prevention of hypertension—that is, interventions to prevent individuals from developing prehypertension and hypertension,” said Dr. Howard. He and his coauthors cited a “rich literature” of effective approaches to primordial prevention of hypertension. The National Heart, Lung, and Blood Institute High Blood Pressure Education Program, for example, concluded that engaging in moderate physical activity; maintaining normal body weight; limiting alcohol consumption; reducing sodium intake; maintaining adequate intake of potassium; and consuming a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat are approaches with proven efficacy for the prevention of hypertension.

“Although there is randomized trial evidence for effective interventions to prevent (or delay) incident hypertension, there is less evidence that the prevention of hypertension will subsequently reduce stroke risk,” said Dr. Howard. “In addition, the challenges of implementing these lifestyle changes should not be understated. Much work on the science of implementing and disseminating behavior change, including potential policy changes that might nurture environments supportive of these behavior changes, is needed to effectively delay the development of hypertension at the population level.”

—Erik Greb

Successful treatment with antihypertensive medications does not reduce the risk of stroke to the level of a person who is normotensive without medication, according to research published in the June issue of Stroke. Furthermore, stroke risk increases with the number of medications required to normalize blood pressure. The study results suggest that preventing the development of cardiovascular risk factors is more beneficial than treating hypertension successfully, according to the researchers.

The Affordable Care Act and organizations such as the American Heart Association are focusing public attention on prevention as a key to maintaining health. The stroke literature and clinical practice related to stroke, however, emphasize blood pressure control for people with established hypertension, said George Howard, DrPH, Professor of Biostatistics at the University of Alabama at Birmingham School of Public Health. Because of the dearth of literature describing differences in risk between people receiving and not receiving antihypertensive drugs, Dr. Howard and colleagues examined data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether hypertensive people with well-controlled blood pressure have a residual increased risk of stroke. The researchers also sought to assess how the intensiveness of antihypertensive treatment affects risk.

Analyzing Data From REGARDS
In the REGARDS study, 30,239 community-dwelling black and white participants age 45 or older completed in-home medical assessments that included blood pressure measurement, fasting blood and urine collection, ECG, and an inventory of medications. Participants also underwent telephone interviews at six-month intervals. The investigators retrieved medical records for suspected strokes, and physicians adjudicated stroke end points using published methods.

The investigators categorized participants’ blood pressure as normal (ie, <120 mmHg), prehypertensive (ie, 120–139 mmHg), stage 1 hypertension (ie, 140–159 mmHg), or stage 2 hypertension (ie, ≥160 mmHg). Participants were similarly grouped according to whether they were taking no, one, two, or three or more antihypertensive medications. After excluding ineligible participants, Dr. Howard and colleagues restricted their analysis to 26,875 people. During 6.2 years of follow-up, 860 participants had a stroke.

Within strata defined by the number of medications, participants with higher blood pressure tended to be older and were more likely black. For each group defined by blood pressure, patients on more medications also tended to be older and were more likely black.

Stroke Risk Increased With Number of Medications
For patients who were normotensive, stroke risk increased with increasing medication use. Normotensive patients taking one, two, and three or more antihypertensive medication classes had a 42%, 60%, and 148% increased stroke risk, respectively. Each additional class of antihypertensive medication taken increased stroke risk by approximately 33%.

Similarly, stroke risk tended to be higher for patients in higher blood-pressure categories who took more classes of antihypertensive medications. Although the researchers found no evidence of a difference in the association of stroke risk associated with increasing numbers of antihypertensive medications across blood-pressure categories, the increase in stroke risk per category of medication use was numerically smaller for people with prehypertension, stage 1 hypertension, and stage 2 hypertension, compared with normotensive people. Among individuals receiving more medications, the increase in stroke risk was statistically significant for people with prehypertension and people with stage 1 hypertension.

Among patients who did not take antihypertensive medication, stroke risk increased with higher blood pressure. For people who took one or two antihypertensive medications, the data suggested that the increased stroke risk at higher blood-pressure levels was smaller than that for people on no medications. People on no medications had a 49% increase in risk per blood-pressure stratum, compared with a 16% increase in risk per blood-pressure stratum for people on one or two medications.

The Importance of Prevention
“These results suggest that successful pharmacologic treatment of hypertension reduces, but does not eliminate, the harmful effects of hypertension,” said Dr. Howard. “Even with normalization of systolic blood pressure, there is substantial residual increased stroke risk among those on antihypertensive treatment, and the stroke risk is higher if more aggressive treatment is required to achieve normal systolic blood pressure.”

Dr. Howard and his colleagues suggested several reasons why hypertensive people with normal blood pressure on medication may have increased stroke risk. These individuals’ hypertension may not always have been well controlled, they said, and they may have had periods of undetected hypertension. In addition, elevated blood pressure earlier in life may have caused vascular damage, such as atherosclerosis and accelerated vascular aging, that increased these participants’ stroke risk.

“There is a substantial lost opportunity from not focusing prevention efforts on primordial prevention of hypertension—that is, interventions to prevent individuals from developing prehypertension and hypertension,” said Dr. Howard. He and his coauthors cited a “rich literature” of effective approaches to primordial prevention of hypertension. The National Heart, Lung, and Blood Institute High Blood Pressure Education Program, for example, concluded that engaging in moderate physical activity; maintaining normal body weight; limiting alcohol consumption; reducing sodium intake; maintaining adequate intake of potassium; and consuming a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat are approaches with proven efficacy for the prevention of hypertension.

“Although there is randomized trial evidence for effective interventions to prevent (or delay) incident hypertension, there is less evidence that the prevention of hypertension will subsequently reduce stroke risk,” said Dr. Howard. “In addition, the challenges of implementing these lifestyle changes should not be understated. Much work on the science of implementing and disseminating behavior change, including potential policy changes that might nurture environments supportive of these behavior changes, is needed to effectively delay the development of hypertension at the population level.”

—Erik Greb

Successful treatment with antihypertensive medications does not reduce the risk of stroke to the level of a person who is normotensive without medication, according to research published in the June issue of Stroke. Furthermore, stroke risk increases with the number of medications required to normalize blood pressure. The study results suggest that preventing the development of cardiovascular risk factors is more beneficial than treating hypertension successfully, according to the researchers.

The Affordable Care Act and organizations such as the American Heart Association are focusing public attention on prevention as a key to maintaining health. The stroke literature and clinical practice related to stroke, however, emphasize blood pressure control for people with established hypertension, said George Howard, DrPH, Professor of Biostatistics at the University of Alabama at Birmingham School of Public Health. Because of the dearth of literature describing differences in risk between people receiving and not receiving antihypertensive drugs, Dr. Howard and colleagues examined data from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study to determine whether hypertensive people with well-controlled blood pressure have a residual increased risk of stroke. The researchers also sought to assess how the intensiveness of antihypertensive treatment affects risk.

Analyzing Data From REGARDS
In the REGARDS study, 30,239 community-dwelling black and white participants age 45 or older completed in-home medical assessments that included blood pressure measurement, fasting blood and urine collection, ECG, and an inventory of medications. Participants also underwent telephone interviews at six-month intervals. The investigators retrieved medical records for suspected strokes, and physicians adjudicated stroke end points using published methods.

The investigators categorized participants’ blood pressure as normal (ie, <120 mmHg), prehypertensive (ie, 120–139 mmHg), stage 1 hypertension (ie, 140–159 mmHg), or stage 2 hypertension (ie, ≥160 mmHg). Participants were similarly grouped according to whether they were taking no, one, two, or three or more antihypertensive medications. After excluding ineligible participants, Dr. Howard and colleagues restricted their analysis to 26,875 people. During 6.2 years of follow-up, 860 participants had a stroke.

Within strata defined by the number of medications, participants with higher blood pressure tended to be older and were more likely black. For each group defined by blood pressure, patients on more medications also tended to be older and were more likely black.

Stroke Risk Increased With Number of Medications
For patients who were normotensive, stroke risk increased with increasing medication use. Normotensive patients taking one, two, and three or more antihypertensive medication classes had a 42%, 60%, and 148% increased stroke risk, respectively. Each additional class of antihypertensive medication taken increased stroke risk by approximately 33%.

Similarly, stroke risk tended to be higher for patients in higher blood-pressure categories who took more classes of antihypertensive medications. Although the researchers found no evidence of a difference in the association of stroke risk associated with increasing numbers of antihypertensive medications across blood-pressure categories, the increase in stroke risk per category of medication use was numerically smaller for people with prehypertension, stage 1 hypertension, and stage 2 hypertension, compared with normotensive people. Among individuals receiving more medications, the increase in stroke risk was statistically significant for people with prehypertension and people with stage 1 hypertension.

Among patients who did not take antihypertensive medication, stroke risk increased with higher blood pressure. For people who took one or two antihypertensive medications, the data suggested that the increased stroke risk at higher blood-pressure levels was smaller than that for people on no medications. People on no medications had a 49% increase in risk per blood-pressure stratum, compared with a 16% increase in risk per blood-pressure stratum for people on one or two medications.

The Importance of Prevention
“These results suggest that successful pharmacologic treatment of hypertension reduces, but does not eliminate, the harmful effects of hypertension,” said Dr. Howard. “Even with normalization of systolic blood pressure, there is substantial residual increased stroke risk among those on antihypertensive treatment, and the stroke risk is higher if more aggressive treatment is required to achieve normal systolic blood pressure.”

Dr. Howard and his colleagues suggested several reasons why hypertensive people with normal blood pressure on medication may have increased stroke risk. These individuals’ hypertension may not always have been well controlled, they said, and they may have had periods of undetected hypertension. In addition, elevated blood pressure earlier in life may have caused vascular damage, such as atherosclerosis and accelerated vascular aging, that increased these participants’ stroke risk.

“There is a substantial lost opportunity from not focusing prevention efforts on primordial prevention of hypertension—that is, interventions to prevent individuals from developing prehypertension and hypertension,” said Dr. Howard. He and his coauthors cited a “rich literature” of effective approaches to primordial prevention of hypertension. The National Heart, Lung, and Blood Institute High Blood Pressure Education Program, for example, concluded that engaging in moderate physical activity; maintaining normal body weight; limiting alcohol consumption; reducing sodium intake; maintaining adequate intake of potassium; and consuming a diet rich in fruits, vegetables, and low-fat dairy products and reduced in saturated and total fat are approaches with proven efficacy for the prevention of hypertension.

“Although there is randomized trial evidence for effective interventions to prevent (or delay) incident hypertension, there is less evidence that the prevention of hypertension will subsequently reduce stroke risk,” said Dr. Howard. “In addition, the challenges of implementing these lifestyle changes should not be understated. Much work on the science of implementing and disseminating behavior change, including potential policy changes that might nurture environments supportive of these behavior changes, is needed to effectively delay the development of hypertension at the population level.”

—Erik Greb