In most developed and developing countries, the proportion of the population aged 60 years or more is growing faster than any other age group. Given that the vast majority of cardiovascular events occur in older individuals, new thinking is needed to reduce their risk. Epidemiological studies have shown an increasing prevalence of the metabolic syndrome with age, driven by nutrition inappropriate for a modern sedentary lifestyle. A low level of high-density lipoprotein (HDL)-cholesterol, a component of the atherogenic dyslipidaemia of the metabolic syndrome, has been shown to be an important determinant of coronary risk, which rises in prevalence with increasing age. Thus, raising HDL-cholesterol, in addition to lowering the level of low-density lipoprotein (LDL)-cholesterol, seems a plausible approach to reduce cardiovascular risk in an ageing population.
Clinical studies have shown that adding nicotinic acid, which raises HDL-cholesterol by 20-25%, to a statin enhances the reduction in progression of atherosclerosis. Results of the ongoing Atherothrombosis Intervention in Metabolic syndrome with low HDL/High triglyceride and Impact on Global Health Outcomes (AIM-HIGH) study are awaited with interest to see whether such theoretical benefit translates into clinical outcome.
1. Active Ageing. A policy framework. World Health Organization. Geneva, Switzerland: Document WHO/NMH/NPH/02.8.
2.
2. 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. Lancet2004;364:937–52.
3.
3. Ménard J, Colombet I, Chatellier G, Jougla E.Cardiovascular management of the elderly. Eur Heart J2002;2(suppl D):D11–D12.
4.
4. Zyriax B-Chr, Boeing H, Windler E.Nutrition is a powerful independent risk factor for coronary heart disease in women - The CORA study: a population-based case-control study. Eur J Clin Nutr2005;59:1201–07.
5.
5. Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH.Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med2006;354:1264–72.
6.
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 (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA2001;285:2486–97.
7.
7. International Atherosclerosis Society. Harmonized clinical guidelines on prevention of atherosclerotic vascular disease. Available from http://www.athero.org [Accessed 10 June 2006].
8.
8. Guidelines of the International Task Force for Prevention of Coronary Heart Disease. Available from http://www.chd-taskforce.de/guide-lines/toc.htm [Accessed 10 June 2006].
9.
9. De Backer G, Ambrosioni E, Borch-Johnsen K et al. Executive summary. European guidelines on cardiovascular disease prevention in clinical practice. Third Joint Task Force of European and other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J2003;24:1601–10.
10.
10. 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. Lancet2005;366:1267–78.
11.
11. Malik S, Wong ND, Franklin SS. et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation2004;110:1245–50.
12.
12. Lakka HM, Laaksonen DE, Lakka TA. et al. The metabolic syndrome and total and cardiovascular mortality in middle-aged men. JAMA2002;288:2709–16.
13.
13. Isomaa B, Almgren P, Tuomi T. et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care2001;24:683–9.
14.
14. Ford ES, Giles WH, Dietz WH.Prevalence of the metabolic syndrome among US adults. Findings from the Third National Health and Nutrition Examination Survey. JAMA2002;287:356–9.
16. The IDF consensus worldwide definition of the metabolic syndrome. Available from http://www.idf.org [Accessed 10 June 2006].
17.
17. Andrawes WF, Bussy C, Belmin J.Prevention of cardiovascular events in elderly people. Drugs Aging2005;22:859–76.
18.
18. UK Prospective Diabetes Study (UKPDS) Group.Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 Diabetes (UKPDS 33). Lancet1998;352:837–53.
19.
19. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.The Diabetes Control and Complications Trial Research Group. N Engl J Med1993;329:977–86.
20.
20. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group.Sustained effect of intensive treatment of type 1 Diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study. JAMA2003;290:2159–67.
21.
21. UKPDS Group.Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet1998;352:854–65.
22.
22. Dormandy JA, Charbonnel B, Eckland DJ. et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular Events): a randomised controlled trial. Lancet2005;366:1279–89.
23.
23. Lamarche B, Tchernof A, Moorjani S. et al. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Circulation1997;95:69–76.
24.
24. Kannel WB.High-density lipoproteins: epidemiologic profile and risks of coronary artery disease. Am J Cardiol1983;52:9B–12B.
25.
25. Castelli WP.Cardiovascular disease and multifactorial risk: challenge of the 1980s. Am Heart J1983;106:1191–200.
26.
26. Assmann G, Cullen P, Schulte H.The Münster Heart Study (PROCAM). Results of follow-up at eight years. Eur Heart J1998;19(suppl A):A2–A11.
27.
27. Cremer P, Nagel D, Mann H. et al. Ten-year follow-up results from the Goettingen Risk, Incidence and Prevalence Study (GRIPS). I. Risk factors for myocardial infarction in a cohort of 5790 men. Atherosclerosis1997;129:221–30.
29. Carr MC.The emergence of the metabolic syndrome with menopause. J Clin Endocrinol Metab2003;88:2404–11.
30.
30. Matthews KA, Meilahn E, Kuller LH. et al. Menopause and risk factors for coronary heart disease. N Engl J Med1989;321:641–6.
31.
31. Matthews KA, Kuller LH, Sutton-Tyrrell K, Chang Y-F.Changes in cardiovascular risk factors during the perimenopause and postmenopause and carotid artery atherosclerosis in healthy women. Stroke2001;32:1104–11.
32.
32. Shai I, Rimm EB, Hankinson SE. et al. Multivariate assessment of lipid parameters as predictors of coronary heart disease among post-menopausal women: the potential implications for clinical guidelines. Circulation2004;110:2824–30.
33.
33. Ferrara A, Barrett-Connor E, Shan J.Total, LDL, and HDL cholesterol decrease with age in older men and women. The Rancho Bernardo Study 1984-1994. Circulation1997;96:37–43.
34.
34. Shirai K.Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr Med Res Opin2004;20:295–304.
35.
35. Lichtenstein AH, Appel LJ, Brands M. et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation2006;114:82–96.
36.
36. Christ M, Iannello C, Iannello PG, Grimm W.Effects of a weight reduction program with and without aerobic exercise in the metabolic syndrome. Int J Cardiol2004;97:115–22.
37.
37. 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 J2004;147:529–35.
38.
38. Garrison RJ, Kannel WB, Feinleib M. et al. Cigarette smoking and HDL cholesterol: the Framingham offspring study. Atherosclerosis1978;30:17–25.
39.
39. Van Gaal LF, Wauters MA, De Leeuw IH.The beneficial effects of modest weight loss on cardiovascular risk factors. Int J Obes Relat Metab Disord1997;21(suppl 1):S5–S9.
40.
40. Zyriax BC, Windler E.Dietary fat in the prevention of cardiovascular disease. Eur J Lipid Sci Technol2000;102:355–65.
41.
41. Libby P.The forgotten majority: unfinished business in cardiovascular risk reduction. J Am Coll Cardiol2005;46:1225–8.
42.
42. Birjmohun RS, Hutten BA, Kastelein JJP, Stroes ESG.Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds. A meta-analysis of randomized controlled trials. J Am Coll Cardiol2005;45:185–97.
43.
43. McCormack PL, Keating GM.Prolonged-release nicotinic acid. A review of its use in the treatment of dyslipidaemia. Drugs2005;65:2719–40.
44.
44. McGovern ME.Use of nicotinic acid in patients with elevated fasting glucose, diabetes, or metabolic syndrome. Br J Diabetes Vasc Dis2004;4:78–85.
45.
45. Knopp RH, Alagona P, Davidson M. et al. Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia. Metabolism1998;47:1097–104.
46.
46. Garg A, Grundy SM.Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. JAMA1990;264:723–6.
47.
47. Shepherd J, Betteridge JVan Gaal L on behalf of a European Consensus Panel. 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 Opin2005;21:665–82.
48.
48. Elam MB, Hunninghake DB, Davis KB. et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease. The ADMIT study: a randomized trial. JAMA2000;284:1263–70.
49.
49. Grundy SM, Vega GL, McGovern ME. et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dyslipidemia associated with type 2 diabetes. Results of the Assessment of Diabetes Control and Evaluation of the Efficacy of Niaspan Trial. Arch Intern Med2002;162:1568–76.
50.
50. 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 Cardiol2005;95:254–7.
51.
51. Coronary Drug Project Research Group.Clofibrate and niacin in coronary heart disease. JAMA1975;231:360–81.
52.
52. Canner PL, Berge KG, Wenger NK. et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol1986;8:1245–55.
53.
53. Carlson LA, Rosenhamer G.Reduction of mortality in the Stockholm Ischaemic Heart Disease Secondary Prevention Study by combined treatment with clofibrate and nicotinic acid. Acta Med Scand1988;223:405–18.
54.
54. The FIELD study investigators.Effect of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet2005;366:1849–61.
55.
55. Ellen RL, McPherson R.Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. Am J Cardiol1998;81:60B–65B.
56.
56. Manninen V, Elo MO, Frick MH. et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA1988;260:641–51.
57.
57. 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 cholesteroli. N Engl J Med1999;341:410–18.
58.
58. Robins SJ, Collins D, Wittes JT. et al. Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial. JAMA2001;285:1585–91.
59.
59. Pedersen TR, Olsson AG, Faergeman O. et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation1998;97:1453–60.
60.
60. 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 Opin2005;21:1927–34.
61.
61. Nissen SE, Nicholls SJ, Sipahi I. et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis. The ASTEROID trial. JAMA2006;295:1556–65.
62.
62. Nissen SE, Tuzcu EM, Schoenhagen P. et al. REVERSAL Investigators. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA2004;291:1071–80.
63.
63. Bays HE, Dujovne CA, McGovern ME. et al. Comparison of once-daily niacin extended-release/lovastatin with standard doses of atorvastatin and simvastatin [the Advicor Versus Other Cholesterolmodulating Agents Trial Evaluation (ADVOCATE)]. Am J Cardiol2003;91:667–72.
64.
64. 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 Cardiol2003;91:1304–10.
65.
65. 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. Circulation2004;110:3512–17.
66.
66. 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 Opin2006;22:2243–50.
67.
67. 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. N Engl J Med1990;323:1289–98.
68.
68. 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 Med2001;345:1583–92.
69.
69. Clinical Trial: AIM HIGH: Niacin plus statin to prevent vascular events. Available from www.clinicaltrials.gov.ct/show/NCT00120289 [Accessed 10 June 2006].
70.
70. Clinical Trial: ACCORD: Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Available from http://www.clinicaltrials.gov/ct/show/NCT00000620 [Accessed 10 June 2006].
71.
71. Pedersen TR, Assmann G, Bassand J-P et al. Reducing cardiovascular risk: the relevance of raising high-density lipoprotein cholesterol in patients on cholesterol-lowering treatment. A position paper developed by A European Expert Panel. Diabetes Vasc Dis Res2006;3(suppl 2): S1–S12.
