The role of cholesterol in cardiovascular disease (CVD) and especially coronary heart disease (CHD) is well established. Epidemiological studies show consistent relationships between total cholesterol, low-density lipoprotein cholesterol (LDL-C) and CHD risk. These same studies show a strong inverse relationship for levels of high-density lipoprotein cholesterol (HDL-C) and CHD risk and a possible relationship for triglycerides.
The metabolic syndrome is a common syndrome affecting 20—25% of the population whose features include abdominal obesity, low-HDL-C, elevated triglycerides, hypertension, hyperglycaemia, hyperinsulinaemia, elevated inflammatory markers, renal dysfunction and microalbuminuria. In the UKPDS study in type 2 diabetes that compared the effects of improved glycaemic and blood pressure control, though some benefit was seen on cardiovascular end points with tighter control, the critical factors predisposing to later macrovascular disease were LDL-C and HDL-C.
There is extensive trial evidence for the benefits of statins in secondary and primary prevention. All guidelines state these are first-line agents for the treatment of cardiovascular risk. Statins have undoubted benefits in the treatment of patients with type 2 diabetes. Statins are also effective in reducing CVD in patients with metabolic syndrome. However, the focus on the benefits of statin therapy has limited discussion of their limitations. In all statin trials to date they reduce CVD events by 25—30% with the largest reduction in the GREACE study being 50%. Only high-dose statin therapy prevents progression of atherosclerosis. Thus, a single minded concentration on LDL-C may underestimate the benefits of a more integrated approach to the management of hyperlipidaemia.
Keys A., Menotti A., Aravanis C. et al. The seven countries study: 2,289 deaths in 15 years. Prev Med1984;13:141-54.
2.
Menotti A., Keys A., Aravanis C. et al. Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries. Ann Med1989;21: 175-9.
3.
The multiple risk factor intervention trial (MRFIT).A national study of primary prevention of coronary heart disease. JAMA1976;235:825-7.
4.
Bucher HC, Griffith LE, Guyatt GHSystematic review on the risk and benefit of different cholesterol-lowering interventions. Arterioscler Thromb Vasc Biol1999;19:187-95.
5.
Wierzbicki AS , Poston R., Ferro A.The lipid and non-lipid effects of statins . Pharmacol Ther2003;99:95-112.
6.
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.
Joint British recommendations on prevention of coronary heart disease in clinical practice. British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society, endorsed by the British Diabetic Association. Heart1998;80(suppl 2):S1-S29.
8.
Pyorala K., Wood D.Prevention of coronary heart disease in clinical practice. European recommendations revised and reinforced. Eur Heart J1998;19:1413-15.
9.
Athyros VG, Mikhailidis DP, Papageorgiou AA et al. Prevalence of atherosclerotic vascular disease among subjects with the metabolic syndrome with or without diabetes mellitus: the METS-GREECE Multicentre Study. Curr Med Res Opin2004;20:1691-701.
10.
Athyros VG, Papageorgiou AA, Mercouris BR et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus 'usual' care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study . Curr Med Res Opin2002;18:220-8.
Stallones RAThe rise and fall of ischemic heart disease . Sci Am1980;243:53-9.
14.
Sijbrands EJ, Westendorp RG, Defesche JC et al. Mortality over two centuries in large pedigree with familial hypercholesterolaemia: family tree mortality study. BMJ2001;322:1019-23.
15.
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.
16.
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. JAMA1998;279:1615-22.
17.
Sacks FM, Tonkin AM, Craven T. et al. Coronary heart disease in patients with low LDL-cholesterol: benefit of pravastatin in diabetics and enhanced role for HDL-cholesterol and triglycerides as risk factors. Circulation2002;105:1424-8.
18.
Sattar N., Gaw A., Scherbakova O. et al. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland Coronary Prevention Study. Circulation2003;108:414-19.
19.
Haffner SM, Lehto S., Ronnemaa T. et al. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction . N Engl J Med1998;339: 229-34.
20.
Nishtar S., Wierzbicki AS, Lumb PJ et al. Waist-hip ratio and low HDL predict the risk of coronary artery disease in Pakistanis. Curr Med Res Opin2004 ;20:55-62.
21.
Wierzbicki AS, Nishtar S., Lumb PJ et al. Metabolic syndrome and risk of coronary heart disease in a Pakistani cohort. Heart2005;91:1003-07.
22.
Jaber LA, Brown MB, Hammad A. et al. The prevalence of the metabolic syndrome among arab Americans . Diabetes Care2004;27:234-8.
23.
Abdul-Ghani MA, Sabbah M., Muati B. et al. High frequency of pre-diabetes, undiagnosed diabetes and metabolic syndrome among overweight Arabs in Israel. Isr Med Assoc J2005;7:143-7.
24.
Onat A., Ceyhan K., Basar O. et al. Metabolic syndrome: major impact on coronary risk in a population with low cholesterol levels -a prospective and cross-sectional evaluation . Atherosclerosis2002;165: 285-92.
25.
Castelli WP , Garrison RJ, Wilson PW et al. Incidence of coronary heart disease and lipoprotein cholesterol levels. Framingham study. JAMA1986;256:2835-8.
26.
Abbott RD, Wilson PW, Kannel WB et al. High density lipoprotein cholesterol, total cholesterol screening, and myocardial infarction. The Framingham Study. Arterioclerosis1988;8:207-11.
27.
Assmann G., Schulte H.Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Munster study. Am J Cardiol1992;70:733-7.
28.
Goldbourt U. , Yaari S., Medalie JHIsolated low HDL cholesterol as a risk factor for coronary heart disease mortality. A 21-year follow-up of 8000 men. Arterioscler Thromb Vasc Biol1997;17:107-13.
29.
Gordon DJ, Probstfield JL, Garrison RJ et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation1989;79:8-15.
30.
Sacks FMThe role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations. Am J Cardiol2002;90:139-43.
31.
Austin MA, Hokanson JE, Edwards KLHypertriglyceridemia as a cardiovascular risk factor. Am J Cardiol1998;81:7B-12B.
32.
Hokanson JE , Austin MAPlasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies. J Cardiovasc Risk1996;3:213-19.
33.
Assmann G., Schulte H., Funke H. et al. The emergence of triglycerides as a significant independent risk factor in coronary artery disease. Eur Heart J1998;19 (suppl M):M8-M14.
34.
Austin MATriglyceride, small, dense low-density lipoprotein, and the atherogenic lipoprotein phenotype. Curr Atheroscler Rep2000;2:200-07.
35.
Haim M., Benderly M., Brunner D. et al. Elevated serum triglyceride levels and long-term mortality in patients with coronary heart disease: the Bezafibrate Infarction Prevention (BIP) Registry. Circulation1999; 100:475-82.
36.
Turner RC, Millns H., Neil HA et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ1998;316:823-8.
37.
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. Lancet2004;364:685-96.
38.
Caro J., Klittich W., McGuire A. et al. The West of Scotland coronary prevention study: economic benefit analysis of primary prevention with pravastatin. BMJ1997;315:1577-82.
39.
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.
40.
Canner PL, Furberg CD, Terrin ML et al. Benefits of niacin by glycemic status in patients with healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol2005;95:254-7.
41.
The need for a large-scale trial of fibrate therapy in diabetes: the rationale and design of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. [ISRCTN64783481]. Cardiovasc Diabetol2004;
42.
Laing SP, Swerdlow AJ, Slater SD et al. Mortality from heart disease in a cohort of 23,000 patients with insulin-treated diabetes. Diabetologia2003;46:760-5.
43.
Lipid and lipoprotein levels in patients with IDDM diabetes control and complication.Trial experience. The DCCT Research Group. Diabetes Care1992 ;15:886-94.
44.
Nathan DM, Lachin J., Cleary P. et al. Intensive diabetes therapy and carotid intima-media thickness in type 1 diabetes mellitus. N Engl J Med2003;348:2294-303.
45.
Collins R., Armitage J., Parish S. et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet2003;361:2005-16.
46.
Walldius G. , Jungner I., Holme I. et al. High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study. Lancet2001;358:2026-33.
47.
Cromwell WC , Otvos JDLow-density lipoprotein particle number and risk for cardiovascular disease. Curr Atheroscler Rep2004;6:381-7.
48.
Sacks FM, Alaupovic P., Moye LA et al. VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial. Circulation2000;102:1886-92.
49.
Onat A., Hergenc G., Sansoy V. et al. Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis2003;168:81-9.
50.
Olsson AG, Holmquist L., Walldius G. et al. Serum apolipoproteins, lipoproteins and fatty acids in relation to ischaemic heart disease in northern and southern European males. Acta Med Scand1988;223:3-13.
51.
Bjorkegren J., Boquist S., Samnegard A. et al. Accumulation of apolipoprotein C-I-rich and cholesterol-rich VLDL remnants during exaggerated postprandial triglyceridemia in normolipidemic patients with coronary artery disease. Circulation2000;101:227-30.
52.
Wierzbicki ASHave we forgotten the pivotal role of high-density lipoprotein cholesterol in atherosclerosis prevention?Curr Med Res Opin2005;21:299-306.
