Lipids, lipid modifying agents and cardiovascular risk: a review of the evidence.

It is well-established that serum total-cholesterol, LDL-cholesterol, low HDL-cholesterol and calculated indices such as total cholesterol:HDL-cholesterol ratio or less commonly used indices such as non-HDL cholesterol are strongly predictive of cardiovascular events. Serum triglycerides, by contrast, are only modestly associated with coronary heart disease (CHD) in multivariate analysis and incorporation of triglycerides into prediction algorithms is therefore unlikely to improve their prediction capability. Meta-analysis of studies including > 90,000 subjects has provided robust evidence that statins reduce important clinical end-points. These included a 12% fall in all-cause mortality, 19% fall in CHD mortality and 23% fall in CHD mortality or myocardial infarction. Furthermore there are high quality data showing additional benefit of intensive statin therapy over standard statin therapy for secondary prevention of cardiovascular disease. However, meta-analysis of 10 fibrate trials has shown inconsistent evidence of vascular benefit and non-cardiovascular mortality has been slightly but consistently elevated in most fibrate trials and in meta-analysis. The general use of fibrates for cardiovascular risk reduction can therefore not be supported at present. Other second line agents such as bile acid sequestrants, nicotinic acid and omega-3 fatty acid supplements have been evaluated in a few randomized controlled studies in which cardiovascular benefit has been found but clearly further data are required to properly establish their use in clinical practice. Ongoing studies such as ACCORD, IMPROVE-IT, ASCEND, ORIGIN and HPS2-THRIVE should assist in answering outstanding questions over the next 5 years.