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Published in: Current Atherosclerosis Reports 1/2012

01-02-2012 | Statin Drugs (M Clearfield, Section Editor)

Residual Cardiovascular Risk Despite Optimal LDL Cholesterol Reduction with Statins: The Evidence, Etiology, and Therapeutic Challenges

Authors: Uchechukwu K. Sampson, Sergio Fazio, MacRae F. Linton

Published in: Current Atherosclerosis Reports | Issue 1/2012

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Abstract

This review captures the existence, cause, and treatment challenges of residual cardiovascular risk (CVR) after aggressive low-density lipoprotein cholesterol (LDL-C) reduction. Scientific evidence implicates low high-density lipoprotein cholesterol (HDL-C) and high triglycerides (TG) in the CVR observed after LDL-C lowering. However, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial with fenofibrate, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) study with torcetrapib, and the recently terminated Atherothrombosis Intervention in Metabolic Syndrome with Low HDL Cholesterol/High Triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study with niacin, do not clearly attribute risk reduction value to HDL-C/TG modulation. The optimum approach to long-term lipid-modifying therapies for CVR reduction remains uncertain. Consequently, absolute risk modulation via lifestyle changes remains the centerpiece of a strategy addressing the physiologic drivers of CVR associated with HDL-C/TG, especially in the context of diabetes/metabolic syndrome.
Literature
1.
go back to reference •• Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. This is the strongest available meta-analysis on the value of intensive LDL-C lowering in reducing cardiovascular risk.PubMedCrossRef •• Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81. This is the strongest available meta-analysis on the value of intensive LDL-C lowering in reducing cardiovascular risk.PubMedCrossRef
2.
go back to reference Smith Jr SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006;47:2130–9.PubMedCrossRef Smith Jr SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update endorsed by the National Heart, Lung, and Blood Institute. J Am Coll Cardiol. 2006;47:2130–9.PubMedCrossRef
3.
go back to reference Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–39.PubMedCrossRef Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–39.PubMedCrossRef
4.
go back to reference Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.
5.
go back to reference Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J. 2007;28:2375–414.PubMedCrossRef Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (Constituted by representatives of nine societies and by invited experts). Eur Heart J. 2007;28:2375–414.PubMedCrossRef
6.
go back to reference Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9.
7.
go back to reference Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349–57. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349–57.
8.
go back to reference MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.
9.
go back to reference Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615–22.PubMedCrossRef Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615–22.PubMedCrossRef
10.
go back to reference Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001–9.PubMedCrossRef Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators. N Engl J Med. 1996;335:1001–9.PubMedCrossRef
11.
go back to reference Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–7.PubMedCrossRef Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301–7.PubMedCrossRef
12.
go back to reference Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46:1225–8.PubMedCrossRef Libby P. The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol. 2005;46:1225–8.PubMedCrossRef
13.
go back to reference Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.PubMedCrossRef Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.PubMedCrossRef
14.
go back to reference LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–35.PubMedCrossRef LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–35.PubMedCrossRef
15.
go back to reference Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437–45.PubMedCrossRef Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437–45.PubMedCrossRef
16.
go back to reference de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307–16.PubMedCrossRef de Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307–16.PubMedCrossRef
17.
go back to reference Cannon CP, Steinberg BA, Murphy SA, et al. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006;48:438–45.PubMedCrossRef Cannon CP, Steinberg BA, Murphy SA, et al. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006;48:438–45.PubMedCrossRef
18.
go back to reference Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.PubMedCrossRef Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.PubMedCrossRef
19.
go back to reference • Sazonov V, Beetsch J, Phatak H, et al. Association between dyslipidemia and vascular events in patients treated with statins: report from the UK General Practice Research Database. Atherosclerosis. 2010;208:210–6. This is a retrospective cohort study that demonstrated the association between low HDL-C and/or elevated TG and cardiovascular events despite statin treatment for LDL-C reduction.CrossRef • Sazonov V, Beetsch J, Phatak H, et al. Association between dyslipidemia and vascular events in patients treated with statins: report from the UK General Practice Research Database. Atherosclerosis. 2010;208:210–6. This is a retrospective cohort study that demonstrated the association between low HDL-C and/or elevated TG and cardiovascular events despite statin treatment for LDL-C reduction.CrossRef
20.
go back to reference Arsenault BJ, Barter P, DeMicco DA, et al. Prediction of cardiovascular events in statin-treated stable coronary patients by lipid and nonlipid biomarkers. J Am Coll Cardiol. 2011;57:63–9.PubMedCrossRef Arsenault BJ, Barter P, DeMicco DA, et al. Prediction of cardiovascular events in statin-treated stable coronary patients by lipid and nonlipid biomarkers. J Am Coll Cardiol. 2011;57:63–9.PubMedCrossRef
21.
go back to reference Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583–92.PubMedCrossRef Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583–92.PubMedCrossRef
22.
go back to reference Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid- lowering therapy in men with high levels of apolipoprotein B [see comments]. N Engl J Med. 1990;323:1289–98.PubMedCrossRef Brown G, Albers JJ, Fisher LD, et al. Regression of coronary artery disease as a result of intensive lipid- lowering therapy in men with high levels of apolipoprotein B [see comments]. N Engl J Med. 1990;323:1289–98.PubMedCrossRef
23.
go back to reference Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341:410–8.PubMedCrossRef Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341:410–8.PubMedCrossRef
24.
go back to reference Chen Z, Peto R, Collins R, et al. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. BMJ. 1991;303:276–82.PubMedCrossRef Chen Z, Peto R, Collins R, et al. Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations. BMJ. 1991;303:276–82.PubMedCrossRef
25.
go back to reference Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434–44.PubMedCrossRef Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16:434–44.PubMedCrossRef
26.
go back to reference Sacks FM, Tonkin AM, Shepherd J, et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation. 2000;102:1893–900.PubMed Sacks FM, Tonkin AM, Shepherd J, et al. Effect of pravastatin on coronary disease events in subgroups defined by coronary risk factors: the Prospective Pravastatin Pooling Project. Circulation. 2000;102:1893–900.PubMed
27.
go back to reference Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62:707–14.PubMedCrossRef Gordon T, Castelli WP, Hjortland MC, et al. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. 1977;62:707–14.PubMedCrossRef
28.
go back to reference Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79:8–15.PubMedCrossRef Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79:8–15.PubMedCrossRef
29.
go back to reference Genest Jr JJ, Martin-Munley SS, McNamara JR, et al. Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation. 1992;85:2025–33.PubMed Genest Jr JJ, Martin-Munley SS, McNamara JR, et al. Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation. 1992;85:2025–33.PubMed
30.
go back to reference Genest JJ, McNamara JR, Salem DN, Schaefer EJ. Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol. 1991;67:1185–9.PubMedCrossRef Genest JJ, McNamara JR, Salem DN, Schaefer EJ. Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol. 1991;67:1185–9.PubMedCrossRef
31.
go back to reference Assmann G, Schulte H, von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis. 1996;124(Suppl):S11–20.PubMedCrossRef Assmann G, Schulte H, von Eckardstein A, Huang Y. High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis. 1996;124(Suppl):S11–20.PubMedCrossRef
32.
go back to reference Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;104:1108–13.PubMedCrossRef Sharrett AR, Ballantyne CM, Coady SA, et al. Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;104:1108–13.PubMedCrossRef
33.
go back to reference Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–421.
34.
go back to reference Bruckert E, Baccara-Dinet M, McCoy F, Chapman J. High prevalence of low HDL-cholesterol in a pan-European survey of 8545 dyslipidaemic patients. Curr Med Res Opin. 2005;21:1927–34.PubMedCrossRef Bruckert E, Baccara-Dinet M, McCoy F, Chapman J. High prevalence of low HDL-cholesterol in a pan-European survey of 8545 dyslipidaemic patients. Curr Med Res Opin. 2005;21:1927–34.PubMedCrossRef
35.
go back to reference Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–9.PubMedCrossRef Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–9.PubMedCrossRef
36.
go back to reference •• Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk. Ann Intern Med. 2010;153:800–8. This is the strongest available meta-analysis showing the persistent relationship between low HDL-C and cardiovascular risk despite statin therapy.PubMed •• Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk. Ann Intern Med. 2010;153:800–8. This is the strongest available meta-analysis showing the persistent relationship between low HDL-C and cardiovascular risk despite statin therapy.PubMed
37.
go back to reference Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–10.PubMedCrossRef Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–10.PubMedCrossRef
38.
go back to reference Ray KK, Cannon CP, Cairns R, et al. Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2009;29:424–30.PubMedCrossRef Ray KK, Cannon CP, Cairns R, et al. Prognostic utility of apoB/AI, total cholesterol/HDL, non-HDL cholesterol, or hs-CRP as predictors of clinical risk in patients receiving statin therapy after acute coronary syndromes: results from PROVE IT-TIMI 22. Arterioscler Thromb Vasc Biol. 2009;29:424–30.PubMedCrossRef
39.
go back to reference Ridker PM, Genest J, Boekholdt SM, et al. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet. 2010;376:333–9.PubMedCrossRef Ridker PM, Genest J, Boekholdt SM, et al. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial. Lancet. 2010;376:333–9.PubMedCrossRef
40.
go back to reference Garrison RJ, Kannel WB, Feinleib M, et al. Cigarette smoking and HDL cholesterol: the Framingham offspring study. Atherosclerosis. 1978;30:17–25.PubMedCrossRef Garrison RJ, Kannel WB, Feinleib M, et al. Cigarette smoking and HDL cholesterol: the Framingham offspring study. Atherosclerosis. 1978;30:17–25.PubMedCrossRef
41.
go back to reference Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med. 2003;37:283–90.PubMedCrossRef Maeda K, Noguchi Y, Fukui T. The effects of cessation from cigarette smoking on the lipid and lipoprotein profiles: a meta-analysis. Prev Med. 2003;37:283–90.PubMedCrossRef
42.
go back to reference Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid. J Intern Med. 1989;226:271–6.PubMedCrossRef Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein Lp(a) in hyperlipidaemic subjects treated with nicotinic acid. J Intern Med. 1989;226:271–6.PubMedCrossRef
43.
go back to reference Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320–8.PubMed Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320–8.PubMed
44.
go back to reference Ellison RC, Zhang Y, Qureshi MM, et al. Lifestyle determinants of high-density lipoprotein cholesterol: the National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J. 2004;147:529–35.PubMedCrossRef Ellison RC, Zhang Y, Qureshi MM, et al. Lifestyle determinants of high-density lipoprotein cholesterol: the National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J. 2004;147:529–35.PubMedCrossRef
45.
go back to reference James WP, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet. 2000;356:2119–25.PubMedCrossRef James WP, Astrup A, Finer N, et al. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. STORM Study Group. Sibutramine Trial of Obesity Reduction and Maintenance. Lancet. 2000;356:2119–25.PubMedCrossRef
46.
go back to reference Karpe F, Frayn KN. The nicotinic acid receptor–a new mechanism for an old drug. Lancet. 2004;363:1892–4.PubMedCrossRef Karpe F, Frayn KN. The nicotinic acid receptor–a new mechanism for an old drug. Lancet. 2004;363:1892–4.PubMedCrossRef
47.
go back to reference Lichtenstein AH. Dietary fat and cardiovascular disease risk: quantity or quality? J Womens Health (Larchmt). 2003;12:109–14.CrossRef Lichtenstein AH. Dietary fat and cardiovascular disease risk: quantity or quality? J Womens Health (Larchmt). 2003;12:109–14.CrossRef
48.
go back to reference Meksawan K, Pendergast DR, Leddy JJ, et al. Effect of low and high fat diets on nutrient intakes and selected cardiovascular risk factors in sedentary men and women. J Am Coll Nutr. 2004;23:131–40.PubMed Meksawan K, Pendergast DR, Leddy JJ, et al. Effect of low and high fat diets on nutrient intakes and selected cardiovascular risk factors in sedentary men and women. J Am Coll Nutr. 2004;23:131–40.PubMed
49.
go back to reference Couillard C, Despres JP, Lamarche B, et al. Effects of endurance exercise training on plasma HDL cholesterol levels depend on levels of triglycerides: evidence from men of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Arterioscler Thromb Vasc Biol. 2001;21:1226–32.PubMedCrossRef Couillard C, Despres JP, Lamarche B, et al. Effects of endurance exercise training on plasma HDL cholesterol levels depend on levels of triglycerides: evidence from men of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. Arterioscler Thromb Vasc Biol. 2001;21:1226–32.PubMedCrossRef
50.
go back to reference King AC, Haskell WL, Young DR, et al. Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation. 1995;91:2596–604.PubMed King AC, Haskell WL, Young DR, et al. Long-term effects of varying intensities and formats of physical activity on participation rates, fitness, and lipoproteins in men and women aged 50 to 65 years. Circulation. 1995;91:2596–604.PubMed
51.
52.
go back to reference Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102:21–7. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102:21–7.
53.
go back to reference Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet. 2001;357:905–10. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet. 2001;357:905–10.
54.
go back to reference Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61.PubMedCrossRef Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61.PubMedCrossRef
55.
go back to reference Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA. 1988;260:641–51.PubMedCrossRef Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA. 1988;260:641–51.PubMedCrossRef
56.
go back to reference Jacobson TA, Chin MM, Fromell GJ, et al. Fluvastatin with and without niacin for hypercholesterolemia. Am J Cardiol. 1994;74:149–54.PubMedCrossRef Jacobson TA, Chin MM, Fromell GJ, et al. Fluvastatin with and without niacin for hypercholesterolemia. Am J Cardiol. 1994;74:149–54.PubMedCrossRef
57.
go back to reference O’Keefe Jr JH, Harris WS, Nelson J, Windsor SL. Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol. 1995;76:480–4.PubMedCrossRef O’Keefe Jr JH, Harris WS, Nelson J, Windsor SL. Effects of pravastatin with niacin or magnesium on lipid levels and postprandial lipemia. Am J Cardiol. 1995;76:480–4.PubMedCrossRef
58.
go back to reference Gardner SF, Schneider EF, Granberry MC, Carter IR. Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin. Pharmacotherapy. 1996;16:419–23.PubMed Gardner SF, Schneider EF, Granberry MC, Carter IR. Combination therapy with low-dose lovastatin and niacin is as effective as higher-dose lovastatin. Pharmacotherapy. 1996;16:419–23.PubMed
59.
go back to reference Capuzzi DM, Morgan JM, Weiss RJ, et al. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol. 2003;91:1304–10.PubMedCrossRef Capuzzi DM, Morgan JM, Weiss RJ, et al. Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol. 2003;91:1304–10.PubMedCrossRef
60.
go back to reference Insull Jr W, McGovern ME, Schrott H, et al. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Arch Intern Med. 2004;164:1121–7.PubMedCrossRef Insull Jr W, McGovern ME, Schrott H, et al. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Arch Intern Med. 2004;164:1121–7.PubMedCrossRef
61.
go back to reference Hunninghake DB, McGovern ME, Koren M, et al. A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extended-release and lovastatin. Clin Cardiol. 2003;26:112–8.PubMedCrossRef Hunninghake DB, McGovern ME, Koren M, et al. A dose-ranging study of a new, once-daily, dual-component drug product containing niacin extended-release and lovastatin. Clin Cardiol. 2003;26:112–8.PubMedCrossRef
62.
go back to reference Taylor AJ, Sullenberger LE, Lee HJ, et al. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110:3512–7.PubMedCrossRef Taylor AJ, Sullenberger LE, Lee HJ, et al. Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins. Circulation. 2004;110:3512–7.PubMedCrossRef
63.
go back to reference Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin. 2006;22:2243–50.PubMedCrossRef Taylor AJ, Lee HJ, Sullenberger LE. The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3. Curr Med Res Opin. 2006;22:2243–50.PubMedCrossRef
64.
go back to reference Navab M, Anantharamaiah GM, Reddy ST, Fogelman AM. Apolipoprotein A-I mimetic peptides and their role in atherosclerosis prevention. Nat Clin Pract Cardiovasc Med. 2006;3:540–7.PubMedCrossRef Navab M, Anantharamaiah GM, Reddy ST, Fogelman AM. Apolipoprotein A-I mimetic peptides and their role in atherosclerosis prevention. Nat Clin Pract Cardiovasc Med. 2006;3:540–7.PubMedCrossRef
65.
go back to reference Navab M, Anantharamaiah GM, Reddy ST, et al. Oral D-4F causes formation of pre-beta high-density lipoprotein and improves high-density lipoprotein-mediated cholesterol efflux and reverse cholesterol transport from macrophages in apolipoprotein E-null mice. Circulation. 2004;109:3215–20.PubMedCrossRef Navab M, Anantharamaiah GM, Reddy ST, et al. Oral D-4F causes formation of pre-beta high-density lipoprotein and improves high-density lipoprotein-mediated cholesterol efflux and reverse cholesterol transport from macrophages in apolipoprotein E-null mice. Circulation. 2004;109:3215–20.PubMedCrossRef
66.
go back to reference Navab M, Anantharamaiah GM, Hama S, et al. Oral administration of an Apo A-I mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation. 2002;105:290–2.PubMedCrossRef Navab M, Anantharamaiah GM, Hama S, et al. Oral administration of an Apo A-I mimetic Peptide synthesized from D-amino acids dramatically reduces atherosclerosis in mice independent of plasma cholesterol. Circulation. 2002;105:290–2.PubMedCrossRef
67.
go back to reference Garber DW, Datta G, Chaddha M, et al. A new synthetic class A amphipathic peptide analogue protects mice from diet-induced atherosclerosis. J Lipid Res. 2001;42:545–52.PubMed Garber DW, Datta G, Chaddha M, et al. A new synthetic class A amphipathic peptide analogue protects mice from diet-induced atherosclerosis. J Lipid Res. 2001;42:545–52.PubMed
68.
go back to reference Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290:2292–300.PubMedCrossRef Nissen SE, Tsunoda T, Tuzcu EM, et al. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003;290:2292–300.PubMedCrossRef
69.
go back to reference Davidson MH. Apolipoprotein A-I therapy promise, challenges, and disappointment. J Am Coll Cardiol. 2011;57:1120–1.PubMedCrossRef Davidson MH. Apolipoprotein A-I therapy promise, challenges, and disappointment. J Am Coll Cardiol. 2011;57:1120–1.PubMedCrossRef
70.
go back to reference Schwartz GG, Olsson AG, Ballantyne CM, et al. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J. 2009;158:896–901 e3.PubMedCrossRef Schwartz GG, Olsson AG, Ballantyne CM, et al. Rationale and design of the dal-OUTCOMES trial: efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome. Am Heart J. 2009;158:896–901 e3.PubMedCrossRef
71.
go back to reference Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505–15.PubMedCrossRef Brousseau ME, Schaefer EJ, Wolfe ML, et al. Effects of an inhibitor of cholesteryl ester transfer protein on HDL cholesterol. N Engl J Med. 2004;350:1505–15.PubMedCrossRef
72.
go back to reference de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose–response study. Circulation. 2002;105:2159–65.PubMedCrossRef de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, et al. Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose–response study. Circulation. 2002;105:2159–65.PubMedCrossRef
73.
go back to reference Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.PubMedCrossRef Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.PubMedCrossRef
74.
go back to reference Vergeer M, Bots ML, van Leuven SI, et al. Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: a pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials. Circulation. 2008;118:2515–22.PubMedCrossRef Vergeer M, Bots ML, van Leuven SI, et al. Cholesteryl ester transfer protein inhibitor torcetrapib and off-target toxicity: a pooled analysis of the rating atherosclerotic disease change by imaging with a new CETP inhibitor (RADIANCE) trials. Circulation. 2008;118:2515–22.PubMedCrossRef
75.
go back to reference Miyares MA. Anacetrapib and dalcetrapib: two novel cholesteryl ester transfer protein inhibitors. Ann Pharmacother. 2011;45:84–94.PubMedCrossRef Miyares MA. Anacetrapib and dalcetrapib: two novel cholesteryl ester transfer protein inhibitors. Ann Pharmacother. 2011;45:84–94.PubMedCrossRef
76.
go back to reference Canner PL, Furberg CD, Terrin ML, McGovern ME. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2005;95:254–7.PubMedCrossRef Canner PL, Furberg CD, Terrin ML, McGovern ME. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2005;95:254–7.PubMedCrossRef
77.
go back to reference •• Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210:353–61. This is the strongest available meta-analysis on the beneficial effects of nicotinic acid in reducing cardiovascular risk.PubMedCrossRef •• Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210:353–61. This is the strongest available meta-analysis on the beneficial effects of nicotinic acid in reducing cardiovascular risk.PubMedCrossRef
78.
go back to reference •• Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364:127–35. This article provides strong evidence that the functionality of HDL, independent of HDL-C level, has a strong inverse association with atherosclerotic cardiovascular disease.PubMedCrossRef •• Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364:127–35. This article provides strong evidence that the functionality of HDL, independent of HDL-C level, has a strong inverse association with atherosclerotic cardiovascular disease.PubMedCrossRef
79.
go back to reference Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115:450–8.PubMedCrossRef Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation. 2007;115:450–8.PubMedCrossRef
80.
go back to reference Miller M, Cannon CP, Murphy SA, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724–30.PubMedCrossRef Miller M, Cannon CP, Murphy SA, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51:724–30.PubMedCrossRef
81.
go back to reference Sacks FM. After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: implications for fenofibrate. Am J Cardiol. 2008;102:34L–40L.PubMedCrossRef Sacks FM. After the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: implications for fenofibrate. Am J Cardiol. 2008;102:34L–40L.PubMedCrossRef
82.
go back to reference Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–74.PubMedCrossRef Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362:1563–74.PubMedCrossRef
83.
go back to reference Barter PJ, Rye KA. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome? Arterioscler Thromb Vasc Biol. 2008;28:39–46.PubMedCrossRef Barter PJ, Rye KA. Is there a role for fibrates in the management of dyslipidemia in the metabolic syndrome? Arterioscler Thromb Vasc Biol. 2008;28:39–46.PubMedCrossRef
84.
go back to reference Elam M, Lovato LC, Ginsberg H. Role of fibrates in cardiovascular disease prevention, the ACCORD-Lipid perspective. Curr Opin Lipidol. 2011;22:55–61.PubMedCrossRef Elam M, Lovato LC, Ginsberg H. Role of fibrates in cardiovascular disease prevention, the ACCORD-Lipid perspective. Curr Opin Lipidol. 2011;22:55–61.PubMedCrossRef
85.
go back to reference Cui Y, Blumenthal RS, Flaws JA, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med. 2001;161:1413–9.PubMedCrossRef Cui Y, Blumenthal RS, Flaws JA, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med. 2001;161:1413–9.PubMedCrossRef
86.
go back to reference Jiang R, Schulze MB, Li T, et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care. 2004;27:1991–7.PubMedCrossRef Jiang R, Schulze MB, Li T, et al. Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. Diabetes Care. 2004;27:1991–7.PubMedCrossRef
87.
go back to reference Liu J, Sempos C, Donahue RP, et al. Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes. Diabetes Care. 2005;28:1916–21.PubMedCrossRef Liu J, Sempos C, Donahue RP, et al. Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes. Diabetes Care. 2005;28:1916–21.PubMedCrossRef
88.
go back to reference Ridker PM, Rifai N, Cook NR, et al. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005;294:326–33.PubMedCrossRef Ridker PM, Rifai N, Cook NR, et al. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005;294:326–33.PubMedCrossRef
89.
go back to reference Liu J, Sempos CT, Donahue RP, et al. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease. Am J Cardiol. 2006;98:1363–8.PubMedCrossRef Liu J, Sempos CT, Donahue RP, et al. Non-high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease. Am J Cardiol. 2006;98:1363–8.PubMedCrossRef
90.
go back to reference Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet. 2004;364:937–52.PubMedCrossRef Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case–control study. Lancet. 2004;364:937–52.PubMedCrossRef
91.
go back to reference Shepherd J, Betteridge J, Van Gaal L. Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel. Curr Med Res Opin. 2005;21:665–82.PubMedCrossRef Shepherd J, Betteridge J, Van Gaal L. Nicotinic acid in the management of dyslipidaemia associated with diabetes and metabolic syndrome: a position paper developed by a European Consensus Panel. Curr Med Res Opin. 2005;21:665–82.PubMedCrossRef
92.
go back to reference Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117–25.PubMedCrossRef Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117–25.PubMedCrossRef
93.
go back to reference Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRef Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRef
94.
go back to reference •• Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175–82. This article provides clinical trial evidence for the relationship between inflammation, LDL-C, and cardiovascular events in patients with low LDL-C but elevated hs-CRP.PubMedCrossRef •• Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;373:1175–82. This article provides clinical trial evidence for the relationship between inflammation, LDL-C, and cardiovascular events in patients with low LDL-C but elevated hs-CRP.PubMedCrossRef
95.
96.
go back to reference Ridker PM. Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J Thromb Haemost. 2009;7 Suppl 1:332–9.PubMedCrossRef Ridker PM. Testing the inflammatory hypothesis of atherothrombosis: scientific rationale for the cardiovascular inflammation reduction trial (CIRT). J Thromb Haemost. 2009;7 Suppl 1:332–9.PubMedCrossRef
97.
go back to reference Vollmer WM, Sacks FM, Ard J, et al. Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial. Ann Intern Med. 2001;135:1019–28.PubMed Vollmer WM, Sacks FM, Ard J, et al. Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial. Ann Intern Med. 2001;135:1019–28.PubMed
98.
go back to reference Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3–10.PubMedCrossRef Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3–10.PubMedCrossRef
99.
go back to reference Kelley GA, Kelley KS. Progressive resistance exercise and resting blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2000;35:838–43.PubMed Kelley GA, Kelley KS. Progressive resistance exercise and resting blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2000;35:838–43.PubMed
100.
go back to reference Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493–503.PubMed Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493–503.PubMed
101.
go back to reference Major outcomes in moderately hypercholesterolemic. hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288:2998–3007.CrossRef Major outcomes in moderately hypercholesterolemic. hypertensive patients randomized to pravastatin vs usual care: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288:2998–3007.CrossRef
102.
go back to reference Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled tria. Lancet. 2003;361:1149–58.PubMedCrossRef Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled tria. Lancet. 2003;361:1149–58.PubMedCrossRef
103.
go back to reference Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29:1478–85.PubMedCrossRef Knopp RH, d’Emden M, Smilde JG, Pocock SJ. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabetes mellitus (ASPEN). Diabetes Care. 2006;29:1478–85.PubMedCrossRef
104.
go back to reference Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685–96.PubMedCrossRef Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685–96.PubMedCrossRef
105.
go back to reference Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30.PubMedCrossRef Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30.PubMedCrossRef
Metadata
Title
Residual Cardiovascular Risk Despite Optimal LDL Cholesterol Reduction with Statins: The Evidence, Etiology, and Therapeutic Challenges
Authors
Uchechukwu K. Sampson
Sergio Fazio
MacRae F. Linton
Publication date
01-02-2012
Publisher
Current Science Inc.
Published in
Current Atherosclerosis Reports / Issue 1/2012
Print ISSN: 1523-3804
Electronic ISSN: 1534-6242
DOI
https://doi.org/10.1007/s11883-011-0219-7

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