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Angiotensin blockade for diabetes: Monitor microalbuminuria?
No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression (strength of recommendation: C, based on expert opinion).
It is unclear whether microalbuminuria tests in these cases is money well spent
Chris Vincent, MD
Swedish Family Medicine Residency, University of Washington, Seattle
At the residency where I teach, clinicians routinely try to get to the evidence behind the expert opinions, and faculty are discouraged from giving off the cuff or experiential answers. When asked whether to monitor microalbuminuria for patients with diabetes receiving ACE inhibitors or ARBs, it is frustrating to discover that no direct evidence supports the experts’ advice.
The screening test for urine microalbuminuria at our hospital costs $90. Since most patients with diabetes are being treated with ACE inhibitors or ARBs, it would be nice to know that the money for the testing is well spent. Unfortunately, in this instance, we can only continue to practice the “standard of care” and hope for future research to definitively answer this question.
Evidence Summary
Our comprehensive literature search found no studies that provide direct evidence for or against continuing to monitor microalbuminuria among patients with diabetes already on ACE inhibitor or ARB therapy. We reviewed and included indirect evidence and expert opinion to answer this clinical question.
Diabetes mellitus is the leading cause of end-stage renal disease in the Western world.1 The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy. One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine ≥2 mg/dL) from macroalbuminuria per year.2 Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled.
For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection.3,4 The American Diabetes Association (ADA) also recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs.1 There is also good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy.5
Recent studies have raised the possibility of further benefit in prevention and treatment of diabetic nephropathy by maximizing doses of ACE inhibitors or ARBs, and even from the dual blockade attained from using both. For example, during a 2-year trial—in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan—14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy.6 In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%.7
Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized.1,8 However, no direct evidence supports this recommendation.
Recommendations from others
The ADA suggests that clinicians perform a test each year for microalbuminuria among patients with type 1 diabetes of ≥5 years duration, and in all patients with type 2 diabetes at diagnosis and during pregnancy. They also recommend continued surveillance of proteinuria to assess both response to therapy and progression of disease.1
The National Kidney Foundation recommends continued surveillance of microalbuminuria to assess progression of chronic kidney disease and response to therapy.8
1. American Diabetes Association. Standards of Medical Care in Diabetes—2006. Diabetes Care 2006;29:S4-S42.
2. Adler AI, Stevens RJ, Manley SE. Development and progression of nephropathy in type 2 diabetes: The united Kingdom Prospective Diabetes study (UKPDS 64). Kidney Intl 2003;63:225-232.
3. Sferra L, Kelsberg G. Do ACE inhibitors prevent nephropathy in type 2 diabetes without proteinuria? J Fam Pract 2004;53:68-69.
4. Foreman BH, Chambliss ML. Are ARBs or ACE inhibitors preferred for nephropathy in diabetes? J Fam Pract 2004;53:241-242.
5. Hale WA, Nashelsky J. Does microalbuminuria screening in diabetes prevent complications? J Fam Pract 2003;52:229-230.
6. Parving HH, Lehnart H, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-878.
7. Rossing K, Jacobsen P, et al. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003;26:2268-2274.
8. Eknoyan G, Hostetter T, Bakris GL, et al. Proteinuria and other Markers of Chronic Kidney Disease: A Position statement of the National Kidney foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Am J Kidney Dis 2003;42:617-622.
No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression (strength of recommendation: C, based on expert opinion).
It is unclear whether microalbuminuria tests in these cases is money well spent
Chris Vincent, MD
Swedish Family Medicine Residency, University of Washington, Seattle
At the residency where I teach, clinicians routinely try to get to the evidence behind the expert opinions, and faculty are discouraged from giving off the cuff or experiential answers. When asked whether to monitor microalbuminuria for patients with diabetes receiving ACE inhibitors or ARBs, it is frustrating to discover that no direct evidence supports the experts’ advice.
The screening test for urine microalbuminuria at our hospital costs $90. Since most patients with diabetes are being treated with ACE inhibitors or ARBs, it would be nice to know that the money for the testing is well spent. Unfortunately, in this instance, we can only continue to practice the “standard of care” and hope for future research to definitively answer this question.
Evidence Summary
Our comprehensive literature search found no studies that provide direct evidence for or against continuing to monitor microalbuminuria among patients with diabetes already on ACE inhibitor or ARB therapy. We reviewed and included indirect evidence and expert opinion to answer this clinical question.
Diabetes mellitus is the leading cause of end-stage renal disease in the Western world.1 The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy. One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine ≥2 mg/dL) from macroalbuminuria per year.2 Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled.
For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection.3,4 The American Diabetes Association (ADA) also recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs.1 There is also good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy.5
Recent studies have raised the possibility of further benefit in prevention and treatment of diabetic nephropathy by maximizing doses of ACE inhibitors or ARBs, and even from the dual blockade attained from using both. For example, during a 2-year trial—in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan—14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy.6 In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%.7
Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized.1,8 However, no direct evidence supports this recommendation.
Recommendations from others
The ADA suggests that clinicians perform a test each year for microalbuminuria among patients with type 1 diabetes of ≥5 years duration, and in all patients with type 2 diabetes at diagnosis and during pregnancy. They also recommend continued surveillance of proteinuria to assess both response to therapy and progression of disease.1
The National Kidney Foundation recommends continued surveillance of microalbuminuria to assess progression of chronic kidney disease and response to therapy.8
No studies address whether continued screening for microalbuminuria once a patient is taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-2 receptor blocker (ARB) improves outcomes. Indirect evidence and expert opinion suggest that it may be beneficial to continue microalbuminuria surveillance to assess response to therapy and monitor disease progression (strength of recommendation: C, based on expert opinion).
It is unclear whether microalbuminuria tests in these cases is money well spent
Chris Vincent, MD
Swedish Family Medicine Residency, University of Washington, Seattle
At the residency where I teach, clinicians routinely try to get to the evidence behind the expert opinions, and faculty are discouraged from giving off the cuff or experiential answers. When asked whether to monitor microalbuminuria for patients with diabetes receiving ACE inhibitors or ARBs, it is frustrating to discover that no direct evidence supports the experts’ advice.
The screening test for urine microalbuminuria at our hospital costs $90. Since most patients with diabetes are being treated with ACE inhibitors or ARBs, it would be nice to know that the money for the testing is well spent. Unfortunately, in this instance, we can only continue to practice the “standard of care” and hope for future research to definitively answer this question.
Evidence Summary
Our comprehensive literature search found no studies that provide direct evidence for or against continuing to monitor microalbuminuria among patients with diabetes already on ACE inhibitor or ARB therapy. We reviewed and included indirect evidence and expert opinion to answer this clinical question.
Diabetes mellitus is the leading cause of end-stage renal disease in the Western world.1 The prevalence of diabetic nephropathy continues to rise along with the rapidly rising prevalence of obesity and diabetes, with 40% of patients with diabetes at risk of developing nephropathy. One study that followed 5097 patients with type 2 diabetes over a median of 10.4 years found that 2% of patients progressed from normal levels of urinary protein to microalbuminuria; 2.8% changed from microalbuminuria to macroalbuminuria (urine albumin >300 mg in a 24-hour period); and 2.3% progressed to chronic renal disease (creatinine ≥2 mg/dL) from macroalbuminuria per year.2 Chronic renal disease is more likely to occur in those patients whose hypertension or hyperglycemia is poorly controlled.
For patients with diabetes who develop microalbuminuria, the evidence is good for starting ACE inhibitors or ARBs for renal protection.3,4 The American Diabetes Association (ADA) also recommends that patients with diabetes and hypertension and those aged >55 years with other cardiovascular risk factors (history of cardiovascular disease, dyslipidemia, or tobacco use) be started on ACE inhibitors or ARBs.1 There is also good evidence that screening for microalbuminuria can identify those who might benefit from treatments that delay the onset of nephropathy.5
Recent studies have raised the possibility of further benefit in prevention and treatment of diabetic nephropathy by maximizing doses of ACE inhibitors or ARBs, and even from the dual blockade attained from using both. For example, during a 2-year trial—in which 590 patients with diabetes and microalbuminuria were randomized to receive placebo, 150 mg irbesartan, or 300 mg irbesartan—14.9% of the placebo group, 9.7% of the 150-mg group, and only 5.2% of the 300-mg group progressed to overt nephropathy.6 In very small randomized trial of 20 patients with type 2 diabetes, adding 16 mg of candesartan to the maximal dose of an ACE inhibitor decreased albuminuria an additional 28%.7
Experts argue that it may benefit patients to continue regular surveillance for the presence or progression of microalbuminuria even if they are already taking an ACE inhibitor or ARB so that therapy can be maximized.1,8 However, no direct evidence supports this recommendation.
Recommendations from others
The ADA suggests that clinicians perform a test each year for microalbuminuria among patients with type 1 diabetes of ≥5 years duration, and in all patients with type 2 diabetes at diagnosis and during pregnancy. They also recommend continued surveillance of proteinuria to assess both response to therapy and progression of disease.1
The National Kidney Foundation recommends continued surveillance of microalbuminuria to assess progression of chronic kidney disease and response to therapy.8
1. American Diabetes Association. Standards of Medical Care in Diabetes—2006. Diabetes Care 2006;29:S4-S42.
2. Adler AI, Stevens RJ, Manley SE. Development and progression of nephropathy in type 2 diabetes: The united Kingdom Prospective Diabetes study (UKPDS 64). Kidney Intl 2003;63:225-232.
3. Sferra L, Kelsberg G. Do ACE inhibitors prevent nephropathy in type 2 diabetes without proteinuria? J Fam Pract 2004;53:68-69.
4. Foreman BH, Chambliss ML. Are ARBs or ACE inhibitors preferred for nephropathy in diabetes? J Fam Pract 2004;53:241-242.
5. Hale WA, Nashelsky J. Does microalbuminuria screening in diabetes prevent complications? J Fam Pract 2003;52:229-230.
6. Parving HH, Lehnart H, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-878.
7. Rossing K, Jacobsen P, et al. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003;26:2268-2274.
8. Eknoyan G, Hostetter T, Bakris GL, et al. Proteinuria and other Markers of Chronic Kidney Disease: A Position statement of the National Kidney foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Am J Kidney Dis 2003;42:617-622.
1. American Diabetes Association. Standards of Medical Care in Diabetes—2006. Diabetes Care 2006;29:S4-S42.
2. Adler AI, Stevens RJ, Manley SE. Development and progression of nephropathy in type 2 diabetes: The united Kingdom Prospective Diabetes study (UKPDS 64). Kidney Intl 2003;63:225-232.
3. Sferra L, Kelsberg G. Do ACE inhibitors prevent nephropathy in type 2 diabetes without proteinuria? J Fam Pract 2004;53:68-69.
4. Foreman BH, Chambliss ML. Are ARBs or ACE inhibitors preferred for nephropathy in diabetes? J Fam Pract 2004;53:241-242.
5. Hale WA, Nashelsky J. Does microalbuminuria screening in diabetes prevent complications? J Fam Pract 2003;52:229-230.
6. Parving HH, Lehnart H, et al. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001;345:870-878.
7. Rossing K, Jacobsen P, et al. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial. Diabetes Care 2003;26:2268-2274.
8. Eknoyan G, Hostetter T, Bakris GL, et al. Proteinuria and other Markers of Chronic Kidney Disease: A Position statement of the National Kidney foundation (NKF) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Am J Kidney Dis 2003;42:617-622.
Evidence-based answers from the Family Physicians Inquiries Network
How effective are dietary interventions in lowering lipids in adults with dyslipidemia?
Diets lower in fat, higher in soy protein, or higher in fiber reduce serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. More restrictive low-fat diets also lower high-density lipoprotein (HDL), while soy protein increases HDL. Average decreases in LDL range from 6.96 to 25.14 mg/dL, depending on the particular intervention and participants’ baseline characteristics (strength of recommendation [SOR]: C, based on meta-analyses of randomized controlled trials [RCTs] measuring intermediate endpoints). A “portfolio diet” that includes cholesterol-lowering “functional foods” can reduce total cholesterol and LDL; a Mediterranean-type diet can lower LDL (SOR: C, based on fair-quality RCTs, measuring intermediate endpoints). We do not yet know whether the these diets will also help patients live longer and more healthy lives or just improve their lipid profiles.
Simple interventions, like reducing fast food and increasing fruit and vegetable intake, are a good starting place
Rade N. Pejic, MD
Department of Family Medicine, Tulane University School of Medicine, New Orleans, La
Dietary modifications are necessary for the successful long-term treatment of lipid disorders, as well as many other chronic medical conditions. Patients are often encouraged when they learn they can reverse a disease process without taking a medication. We should take every opportunity to educate our patients and promote healthy lifestyles. Simple interventions, such as eating less fast food and more fresh fruits and vegetables, are often a good starting place. Other simple interventions to reduce cholesterol levels are taking fiber supplements and substituting commercially available margarines with plant sterols for butter.
Dietary counseling or referral to a medical nutritionist should be part of our overall treatment plan for patients with lipid disorders. regularly scheduled follow-up visits help promote adherence to therapeutic lifestyle changes and encourage a therapeutic alliance.
Evidence summary
Dietary changes are recommended as first-line treatment for mild to moderate dyslipidemia. We examined evidence on 5 common dietary interventions for adults with dyslipidemia. The average effects on lipid levels are reported in the TABLE.
TABLE
Average effect of dietary interventions on serum lipid levels
| DIETARY INTERVENTION | AVERAGE CHANGE IN MG/DL OF LIPID LEVELS (% CHANGE) | ||||
|---|---|---|---|---|---|
| TOTAL CHOLESTEROL | LDL | HDL | TRIGLYCERIDES | ||
| Low fat | NCEP Step I | –24.36* (–10%) | –18.95* (–12%) | –1.55 (–1.5%) | –15.10* (–8%) |
| NCEP Step II | –31.32* (–7%) | –25.14* (–13%) | –3.48* (–16%) | –16.83* (–8%) | |
| Soy | All | –8.51* (–3.77%) | –8.12* (–5.25%) | –1.55* + (+ 3.03%) | –8.86* (–7.27%) |
| Hypercholesterolemia | –9.67* | –6.96* | + 3.87* | –7.97* | |
| Fiber (per g/d) | –1.74* | –2.20* | –0.12 | + 0.27 | |
| “Portfolio” | –58.39* (–22.34%) | –51.82* (–29.71%) | 3.09 (–6.50%) | 18.60 (9.33%) | |
| Mediterranean | –15.47 (–6.06%) | –19.34* (–11.37%) | 0 (–12.50%) | –17.71 (0%) | |
| * Statistically significant at P≤.05 | |||||
Low-fat
A meta-analysis of 37 mostly good-quality controlled trials evaluated the former National Cholesterol Education Program (NCEP) Step I and Step II diets in 11,586 participants.1 The Step I diet restricted in-take of total fat (≤30% of total calories), saturated fat (≤10% of total calories), and cholesterol (≤300 mg/d). Step II goals were lower for saturated fat (<7%) and cholesterol (<200 mg/d). Mean baseline lipid values (mg/dL) were total cholesterol, 233.57; LDL, 155.10; HDL, 47.95; and triglycerides, 147.91. Both of these low-fat diets significantly reduced total cholesterol, LDL, and triglycerides. The Step II diet also reduced HDL.
Soy
A meta-analysis of 23 good-quality controlled trials with 1381 participants reported that soy protein with naturally occurring isoflavones significantly reduced total cholesterol, LDL, and triglycerides while significantly increasing HDL.2 The amount of soy isoflavone consumed varied across studies. One subgroup analysis showed that consumption of >80 mg/d was associated with a better effect on lipids. In subjects with baseline hypercholesterolemia (total cholesterol >240 mg/dL), greater reductions in total cholesterol, and greater increases in HDL were reported, with comparable changes in LDL and triglycerides.
Soluble fiber
A meta-analysis of 67 good-quality RCTs evaluated the effects of soluble dietary fiber in 2990 subjects (mean baseline lipid values [mg/dL]: total cholesterol, 240.9; LDL, 164.4).3 Diets high in soluble fiber (average dose of 9.5 g/d) were associated with a statistically significant decrease in total cholesterol and LDL and no significant change in HDL or triglycerides. Type of fiber (oat, psyllium, or pectin) was not influential after controlling for initial lipid level.
“Portfolio” diet
A fair-quality randomized crossover study with 34 participants found that a “portfolio diet,” which combines the fat intake of the NCEP Step II diet with cholesterol-lowering “functional foods” (including plant sterols, nuts, soluble fibers, and soy protein), markedly reduced total cholesterol and LDL.4 Mean baseline lipid values (mg/dL) were: total cholesterol, 261.41; LDL, 174.40; HDL, 47.56; triglycerides, 199.28.
Mediterranean diet
A fair-quality RCT with 88 participants reported reduced LDL among subjects assigned to a Mediterranean-type diet.5 Mean baseline lipid values (mg/dL) were total cholesterol, 255.22; LDL, 170.15; HDL, 58.01; triglycerides, 141.71.
Recommendations from others
The NCEP Adult Treatment Panel III and the American Heart Association recommend the Therapeutic Lifestyle Changes diet.6,7 The first stage of this diet emphasizes reduction in dietary saturated fat and cholesterol at the levels of the former NCEP Step II diet (≤7% of energy as saturated fat and ≤200 mg dietary cholesterol). If the LDL goal is not achieved, the second stage emphasizes the addition of functional foods and soluble fiber.
1. Yu-Poth S, Zhao G, Etherton T, et al. Effects of the National Cholesterol Education Program’s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr 1999;69:632-646.
2. Zhan S, HO SC. Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 2005;81:397-408.
3. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999;69:30-42.
4. Jenkins DJA, Kendall CWC, Marchie A, et al. Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am J Clin Nutr 2005;81:380-387.
5. Vincent-Baudry S, Defoort C, Gerber M, et al. The Medi-RIVAGE study: reduction of cardiovascular risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet. Am J Clin Nutr 2005;82:964-971.
6. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
7. Krauss RM, Eckel RH, Howard B, et al. AHA dietary guidelines revision 2000: a statement for health-care professionals from the Nutrition Committee of the American Heart Association. Circulation 2000;102:2284-2299.
Diets lower in fat, higher in soy protein, or higher in fiber reduce serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. More restrictive low-fat diets also lower high-density lipoprotein (HDL), while soy protein increases HDL. Average decreases in LDL range from 6.96 to 25.14 mg/dL, depending on the particular intervention and participants’ baseline characteristics (strength of recommendation [SOR]: C, based on meta-analyses of randomized controlled trials [RCTs] measuring intermediate endpoints). A “portfolio diet” that includes cholesterol-lowering “functional foods” can reduce total cholesterol and LDL; a Mediterranean-type diet can lower LDL (SOR: C, based on fair-quality RCTs, measuring intermediate endpoints). We do not yet know whether the these diets will also help patients live longer and more healthy lives or just improve their lipid profiles.
Simple interventions, like reducing fast food and increasing fruit and vegetable intake, are a good starting place
Rade N. Pejic, MD
Department of Family Medicine, Tulane University School of Medicine, New Orleans, La
Dietary modifications are necessary for the successful long-term treatment of lipid disorders, as well as many other chronic medical conditions. Patients are often encouraged when they learn they can reverse a disease process without taking a medication. We should take every opportunity to educate our patients and promote healthy lifestyles. Simple interventions, such as eating less fast food and more fresh fruits and vegetables, are often a good starting place. Other simple interventions to reduce cholesterol levels are taking fiber supplements and substituting commercially available margarines with plant sterols for butter.
Dietary counseling or referral to a medical nutritionist should be part of our overall treatment plan for patients with lipid disorders. regularly scheduled follow-up visits help promote adherence to therapeutic lifestyle changes and encourage a therapeutic alliance.
Evidence summary
Dietary changes are recommended as first-line treatment for mild to moderate dyslipidemia. We examined evidence on 5 common dietary interventions for adults with dyslipidemia. The average effects on lipid levels are reported in the TABLE.
TABLE
Average effect of dietary interventions on serum lipid levels
| DIETARY INTERVENTION | AVERAGE CHANGE IN MG/DL OF LIPID LEVELS (% CHANGE) | ||||
|---|---|---|---|---|---|
| TOTAL CHOLESTEROL | LDL | HDL | TRIGLYCERIDES | ||
| Low fat | NCEP Step I | –24.36* (–10%) | –18.95* (–12%) | –1.55 (–1.5%) | –15.10* (–8%) |
| NCEP Step II | –31.32* (–7%) | –25.14* (–13%) | –3.48* (–16%) | –16.83* (–8%) | |
| Soy | All | –8.51* (–3.77%) | –8.12* (–5.25%) | –1.55* + (+ 3.03%) | –8.86* (–7.27%) |
| Hypercholesterolemia | –9.67* | –6.96* | + 3.87* | –7.97* | |
| Fiber (per g/d) | –1.74* | –2.20* | –0.12 | + 0.27 | |
| “Portfolio” | –58.39* (–22.34%) | –51.82* (–29.71%) | 3.09 (–6.50%) | 18.60 (9.33%) | |
| Mediterranean | –15.47 (–6.06%) | –19.34* (–11.37%) | 0 (–12.50%) | –17.71 (0%) | |
| * Statistically significant at P≤.05 | |||||
Low-fat
A meta-analysis of 37 mostly good-quality controlled trials evaluated the former National Cholesterol Education Program (NCEP) Step I and Step II diets in 11,586 participants.1 The Step I diet restricted in-take of total fat (≤30% of total calories), saturated fat (≤10% of total calories), and cholesterol (≤300 mg/d). Step II goals were lower for saturated fat (<7%) and cholesterol (<200 mg/d). Mean baseline lipid values (mg/dL) were total cholesterol, 233.57; LDL, 155.10; HDL, 47.95; and triglycerides, 147.91. Both of these low-fat diets significantly reduced total cholesterol, LDL, and triglycerides. The Step II diet also reduced HDL.
Soy
A meta-analysis of 23 good-quality controlled trials with 1381 participants reported that soy protein with naturally occurring isoflavones significantly reduced total cholesterol, LDL, and triglycerides while significantly increasing HDL.2 The amount of soy isoflavone consumed varied across studies. One subgroup analysis showed that consumption of >80 mg/d was associated with a better effect on lipids. In subjects with baseline hypercholesterolemia (total cholesterol >240 mg/dL), greater reductions in total cholesterol, and greater increases in HDL were reported, with comparable changes in LDL and triglycerides.
Soluble fiber
A meta-analysis of 67 good-quality RCTs evaluated the effects of soluble dietary fiber in 2990 subjects (mean baseline lipid values [mg/dL]: total cholesterol, 240.9; LDL, 164.4).3 Diets high in soluble fiber (average dose of 9.5 g/d) were associated with a statistically significant decrease in total cholesterol and LDL and no significant change in HDL or triglycerides. Type of fiber (oat, psyllium, or pectin) was not influential after controlling for initial lipid level.
“Portfolio” diet
A fair-quality randomized crossover study with 34 participants found that a “portfolio diet,” which combines the fat intake of the NCEP Step II diet with cholesterol-lowering “functional foods” (including plant sterols, nuts, soluble fibers, and soy protein), markedly reduced total cholesterol and LDL.4 Mean baseline lipid values (mg/dL) were: total cholesterol, 261.41; LDL, 174.40; HDL, 47.56; triglycerides, 199.28.
Mediterranean diet
A fair-quality RCT with 88 participants reported reduced LDL among subjects assigned to a Mediterranean-type diet.5 Mean baseline lipid values (mg/dL) were total cholesterol, 255.22; LDL, 170.15; HDL, 58.01; triglycerides, 141.71.
Recommendations from others
The NCEP Adult Treatment Panel III and the American Heart Association recommend the Therapeutic Lifestyle Changes diet.6,7 The first stage of this diet emphasizes reduction in dietary saturated fat and cholesterol at the levels of the former NCEP Step II diet (≤7% of energy as saturated fat and ≤200 mg dietary cholesterol). If the LDL goal is not achieved, the second stage emphasizes the addition of functional foods and soluble fiber.
Diets lower in fat, higher in soy protein, or higher in fiber reduce serum total cholesterol, low-density lipoprotein (LDL), and triglycerides. More restrictive low-fat diets also lower high-density lipoprotein (HDL), while soy protein increases HDL. Average decreases in LDL range from 6.96 to 25.14 mg/dL, depending on the particular intervention and participants’ baseline characteristics (strength of recommendation [SOR]: C, based on meta-analyses of randomized controlled trials [RCTs] measuring intermediate endpoints). A “portfolio diet” that includes cholesterol-lowering “functional foods” can reduce total cholesterol and LDL; a Mediterranean-type diet can lower LDL (SOR: C, based on fair-quality RCTs, measuring intermediate endpoints). We do not yet know whether the these diets will also help patients live longer and more healthy lives or just improve their lipid profiles.
Simple interventions, like reducing fast food and increasing fruit and vegetable intake, are a good starting place
Rade N. Pejic, MD
Department of Family Medicine, Tulane University School of Medicine, New Orleans, La
Dietary modifications are necessary for the successful long-term treatment of lipid disorders, as well as many other chronic medical conditions. Patients are often encouraged when they learn they can reverse a disease process without taking a medication. We should take every opportunity to educate our patients and promote healthy lifestyles. Simple interventions, such as eating less fast food and more fresh fruits and vegetables, are often a good starting place. Other simple interventions to reduce cholesterol levels are taking fiber supplements and substituting commercially available margarines with plant sterols for butter.
Dietary counseling or referral to a medical nutritionist should be part of our overall treatment plan for patients with lipid disorders. regularly scheduled follow-up visits help promote adherence to therapeutic lifestyle changes and encourage a therapeutic alliance.
Evidence summary
Dietary changes are recommended as first-line treatment for mild to moderate dyslipidemia. We examined evidence on 5 common dietary interventions for adults with dyslipidemia. The average effects on lipid levels are reported in the TABLE.
TABLE
Average effect of dietary interventions on serum lipid levels
| DIETARY INTERVENTION | AVERAGE CHANGE IN MG/DL OF LIPID LEVELS (% CHANGE) | ||||
|---|---|---|---|---|---|
| TOTAL CHOLESTEROL | LDL | HDL | TRIGLYCERIDES | ||
| Low fat | NCEP Step I | –24.36* (–10%) | –18.95* (–12%) | –1.55 (–1.5%) | –15.10* (–8%) |
| NCEP Step II | –31.32* (–7%) | –25.14* (–13%) | –3.48* (–16%) | –16.83* (–8%) | |
| Soy | All | –8.51* (–3.77%) | –8.12* (–5.25%) | –1.55* + (+ 3.03%) | –8.86* (–7.27%) |
| Hypercholesterolemia | –9.67* | –6.96* | + 3.87* | –7.97* | |
| Fiber (per g/d) | –1.74* | –2.20* | –0.12 | + 0.27 | |
| “Portfolio” | –58.39* (–22.34%) | –51.82* (–29.71%) | 3.09 (–6.50%) | 18.60 (9.33%) | |
| Mediterranean | –15.47 (–6.06%) | –19.34* (–11.37%) | 0 (–12.50%) | –17.71 (0%) | |
| * Statistically significant at P≤.05 | |||||
Low-fat
A meta-analysis of 37 mostly good-quality controlled trials evaluated the former National Cholesterol Education Program (NCEP) Step I and Step II diets in 11,586 participants.1 The Step I diet restricted in-take of total fat (≤30% of total calories), saturated fat (≤10% of total calories), and cholesterol (≤300 mg/d). Step II goals were lower for saturated fat (<7%) and cholesterol (<200 mg/d). Mean baseline lipid values (mg/dL) were total cholesterol, 233.57; LDL, 155.10; HDL, 47.95; and triglycerides, 147.91. Both of these low-fat diets significantly reduced total cholesterol, LDL, and triglycerides. The Step II diet also reduced HDL.
Soy
A meta-analysis of 23 good-quality controlled trials with 1381 participants reported that soy protein with naturally occurring isoflavones significantly reduced total cholesterol, LDL, and triglycerides while significantly increasing HDL.2 The amount of soy isoflavone consumed varied across studies. One subgroup analysis showed that consumption of >80 mg/d was associated with a better effect on lipids. In subjects with baseline hypercholesterolemia (total cholesterol >240 mg/dL), greater reductions in total cholesterol, and greater increases in HDL were reported, with comparable changes in LDL and triglycerides.
Soluble fiber
A meta-analysis of 67 good-quality RCTs evaluated the effects of soluble dietary fiber in 2990 subjects (mean baseline lipid values [mg/dL]: total cholesterol, 240.9; LDL, 164.4).3 Diets high in soluble fiber (average dose of 9.5 g/d) were associated with a statistically significant decrease in total cholesterol and LDL and no significant change in HDL or triglycerides. Type of fiber (oat, psyllium, or pectin) was not influential after controlling for initial lipid level.
“Portfolio” diet
A fair-quality randomized crossover study with 34 participants found that a “portfolio diet,” which combines the fat intake of the NCEP Step II diet with cholesterol-lowering “functional foods” (including plant sterols, nuts, soluble fibers, and soy protein), markedly reduced total cholesterol and LDL.4 Mean baseline lipid values (mg/dL) were: total cholesterol, 261.41; LDL, 174.40; HDL, 47.56; triglycerides, 199.28.
Mediterranean diet
A fair-quality RCT with 88 participants reported reduced LDL among subjects assigned to a Mediterranean-type diet.5 Mean baseline lipid values (mg/dL) were total cholesterol, 255.22; LDL, 170.15; HDL, 58.01; triglycerides, 141.71.
Recommendations from others
The NCEP Adult Treatment Panel III and the American Heart Association recommend the Therapeutic Lifestyle Changes diet.6,7 The first stage of this diet emphasizes reduction in dietary saturated fat and cholesterol at the levels of the former NCEP Step II diet (≤7% of energy as saturated fat and ≤200 mg dietary cholesterol). If the LDL goal is not achieved, the second stage emphasizes the addition of functional foods and soluble fiber.
1. Yu-Poth S, Zhao G, Etherton T, et al. Effects of the National Cholesterol Education Program’s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr 1999;69:632-646.
2. Zhan S, HO SC. Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 2005;81:397-408.
3. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999;69:30-42.
4. Jenkins DJA, Kendall CWC, Marchie A, et al. Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am J Clin Nutr 2005;81:380-387.
5. Vincent-Baudry S, Defoort C, Gerber M, et al. The Medi-RIVAGE study: reduction of cardiovascular risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet. Am J Clin Nutr 2005;82:964-971.
6. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
7. Krauss RM, Eckel RH, Howard B, et al. AHA dietary guidelines revision 2000: a statement for health-care professionals from the Nutrition Committee of the American Heart Association. Circulation 2000;102:2284-2299.
1. Yu-Poth S, Zhao G, Etherton T, et al. Effects of the National Cholesterol Education Program’s Step I and Step II dietary intervention programs on cardiovascular disease risk factors: a meta-analysis. Am J Clin Nutr 1999;69:632-646.
2. Zhan S, HO SC. Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr 2005;81:397-408.
3. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999;69:30-42.
4. Jenkins DJA, Kendall CWC, Marchie A, et al. Direct comparison of a dietary portfolio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am J Clin Nutr 2005;81:380-387.
5. Vincent-Baudry S, Defoort C, Gerber M, et al. The Medi-RIVAGE study: reduction of cardiovascular risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet. Am J Clin Nutr 2005;82:964-971.
6. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults. Executive Summary of the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-2497.
7. Krauss RM, Eckel RH, Howard B, et al. AHA dietary guidelines revision 2000: a statement for health-care professionals from the Nutrition Committee of the American Heart Association. Circulation 2000;102:2284-2299.
Evidence-based answers from the Family Physicians Inquiries Network