The dyslipidaemic profile of diabetes greatly contributes to the increased cardiovascular risk associated with the disorder, and evidence from many intervention trials using
statins,
fibrates,
nicotinic acid or a
nicotinic acid-
statin combination, indicates the substantial cardiovascular risk reduction to be gained from
lipid modification. Several large
statin trials have demonstrated the efficacy of
cholesterol-lowering in individuals with
coronary heart disease and raised
low-density lipoprotein-cholesterol (
LDL-C) (>or=130 mg/dL; >or=3.4 mmol/L), but for the 40% of patients whose
LDL-C is within recommended limits, many of whom have low
high-density lipoprotein-cholesterol (HDL-C), an alternative strategy is necessary if excess risk is to be minimized. The veterans affairs
high-density lipoprotein cholesterol intervention trial (VA-HIT) proved the efficacy of the
fibric acid derivative,
gemfibrozil, to elevate HDL-C and reduce
triglycerides, with a resulting 22% relative risk reduction for cardiovascular death or non-fatal
myocardial infarction, and even greater reductions in individuals with
insulin resistance and diabetes. Increased HDL-C was independently predictive of reduction in
coronary heart disease. In the Coronary
Drug Project, individuals with diabetes or
insulin resistance derived as much as 70% cardiovascular risk reduction from the HDL-C elevations achieved with
nicotinic acid therapy. The effects of lowering
LDL-C and raising HDL-C are additive and predictive of total cardiovascular event reduction, and by using
statin-
nicotinic acid combination
therapy, cardiovascular risk reductions as great as 90% are possible. Such combination strategies offer patients the greatest opportunity for improved cardiovascular health and are likely to become the treatment strategy of the future.