Benecol - Healthcare Professionals

Dyslipidaemia and Risk of CHD

High Cholesterol and CHD Risk Confirmed

Genetic, pathological, laboratory as well as observational and interventional epidemiological studies have clearly established the primary role of plasma lipoproteins in the development of atherosclerotic CHD. Observational epidemiological data linking elevated TC or LDL-C to an increased incidence of CHD come from between-population as well as within-population studies. There is a remarkable consistency amongst cohort studies, and CHD risk has usually been considered to be 2-3% lower for each 1% decrement in TC concentration. However, in a meta-analysis of international studies, Law et al. (BMJ. 1994;308:367-72) found a 10% difference in TC to be associated with a difference of about 38% in the CHD mortality rate. In a 25-year follow-up study of the classical Seven Countries Study, differences in serum cholesterol during the early phase of the study accounted for most of the late CHD death rates (Menotti et al. Eur Heart J. 1997;18:566-71). Such data are corroborated by animals trials where typical atherosclerosis develops when plasma LDL-C concentrations are increased by a high-fat diet.

Lipids, Lipoproteins and CHD Risk Assessment

The genetic "model" of severe, premature atherosclerosis in humans is homozygous familial hypercholesterolaemia where the LDL-C concentration exceeds 600 mg/dl (16 mmol/l) and symptomatic CHD typically occurs by the age of 20 years. Furthermore, clinical trails using lipid-lowering drugs have unequivocally shown that lowering LDL-C results in a significant reduction in both morbidity and mortality from CHD in patients with or without established CHD, including in patients with only average cholesterol values in Western(ised) societies. Moreover, LDL-C reduction as secondary prevention significantly increases survival, and it is likely that the general population would benefit from a reduction in cholesterol. In the Framingham and several other studies, the TC:HDL-C ratio was found to be a better predictor of CHD events than TC, LDL-C, HDL-C or TG. The TC:HDL-C ratio implicitly incorporates information on both LDL-C and TG. It appears that a high CHD risk results when elevated TG and low HDL-C occur together with elevated TC or LDL-C, or the TC:HDL-C or LDL-C:HDL-C ratio is high and TG is elevated (Castelli. Am Heart J. 1986;112:432-7).

Clinical Endpoint Trials

With the availability of statins, the question of whether lowering cholesterol is beneficial has been answered very clearly. In the 5-year West of Scotland Coronary Prevention Study (WOSCOPS), with a 26% reduction in LDL-C, statin therapy doubled the efficacy of cholesterol reduction seen in earlier trials, and achieved substantial reductions in both CHD event rates (31% in CHD death or non-fatal MI, and 37% in requiring CABG or PTCA) and the all-cause mortality rate (22%) (Shepherd et al. N Engl J Med. 1995;333:1301-7). Similar lipid changes and CHD risk reduction were achieved in the 5-year Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS; Down et al. JAMA. 1998;279:1615-22).

Patients Who Stand to Benefit

The AFCAPS/TexCAPS study differed from previous primary prevention trials of cholesterol-lowering pharmacotherapy in that not only middle-aged men were enrolled, but also postmenopausal women and elderly patients. Moreover, the patients had only average cholesterol levels (mean baseline TC and LDL-C: 221 resp. 150 mg/dl, or 5.7 resp. 3.9 mmol/l). Treatment benefits on the first major coronary event applied equally to both younger and older patients, and CHD incidence was reduced amongst women. Benefits were also seen in other predefined subgroups such as hypertensive patients and smokers. Results of large, long-term clinical endpoint statin trials leave no doubt that elevated LDL-C must be lowered in patients with established atherosclerotic disease. A meta-analysis of non-statin secondary prevention trials found a 10% reduction in TC to yield 19%, and 15% reductions in rates of non-fatal, fatal and all MIs (Rossouw et al. N Engl J Med. 1990;323:112-9). There has been a number of studies on cholesterol lowering through dietary therapy. In the 5-year, non-blinded, randomised Oslo Diet-Heart Study, the recurrent MI rate was significantly reduced (by 33%), and the CHD death rate non-significantly (by 26%) in MI survivors (Leren. Acta Med Scand Suppl. 1966;466:1-92). Nevertheless, dietary modification is the cornerstone of lipid management, and can play an important role in lowering cholesterol and reducing CHD death and disability.