Statin Use for Patients with Normal Cholesterol and Triglyceride Levels

Ken Grauer, MD


June 07, 2001


Is there any evidence supporting the use of statin therapy for patients with normal cholesterol and triglyceride levels to further lower the risk of myocardial infarction?

Response from Ken Grauer, MD

Treatment of hyperlipidemia has clearly been shown to lower mortality from coronary artery disease (CAD) in both primary and secondary prevention trials. Although National Cholesterol Education Program (NCEP) Guidelines primarily target low-density lipoprotein (LDL) cholesterol levels, increasing evidence suggests that elevated triglyceride levels are an independent predictor of coronary mortality -- especially when associated with lower high-density lipoprotein levels (HDL) levels.[1,2]

Whether significant reductions in LDL cholesterol and serum triglyceride levels will lead to significant reductions in coronary mortality when starting lipid values are "normal" is a multifaceted question without a precise answer. An important issue relates to the definition of "normal" values. The AVERT Trial[3] showed that higher-than-usual doses of statin therapy (up to 80 mg of atorvastatin was used) achieved marked reduction of LDL levels, well below the target value of 100 mg/dL suggested for patients with diabetes or CAD. The participants with levels below target values demonstrated better clinical results, such as fewer hospitalizations and less need for a revascularization procedure, than a comparison group of patients treated with angioplasty. This degree of beneficial cardiovascular protection would probably not have been achieved if dosing increase of the statin drug had been stopped once LDL levels achieved a "normal" level.

The effect of statin use on primary prevention of coronary disease in subjects with normal baseline lipid values is even harder to define, especially when the cost-efficacy of long-term therapy in otherwise low-risk subjects is factored into the equation.[4] What is known is that elevated LDL levels identify fewer than 50% of those who will ultimately die from CAD.[5] Other factors in CAD that are often difficult to quantify, such as lipoprotein a, C-reactive protein, fibrinogen, plasma viscosity, and heredity, may alter the effect that a "high normal" lipid value may have in the atherogenic process.

Finally, other mechanisms besides the lipid-lowering are clearly operative in the statin cardioprotective effect.[6] Despite less than a 2% to 5% increase in coronary artery lumen diameter being achieved in most angiographic lipid-treatment and follow-up studies, coronary mortality is disproportionately improved.[7] Other benefits seem to accrue from related mechanisms, such as improved endothelial function, plaque stabilization, reduction in the inflammatory response, and modification of thrombogenesis. These changes probably begin very soon after starting statin therapy.

Based on the evidence available at this time, my answer to the question raised is, therefore, yes. Evidence suggests that statin therapy may provide a beneficial cardioprotective effect even in patients with seemingly "normal" lipid levels. Exciting implications of this suggestive evidence include the potential role of statin therapy in the treatment of acute coronary syndromes as an adjunct treatment to rapidly improve endothelial function/plaque stability. In addition, a rationale now exists for considering statin therapy as a secondary prevention measure for patients with significant CAD who have serum cholesterol levels that fall within the "normal" range.