Major cardio event risk among statin users associated with non-HDL-C level

Findings from a newly published meta-analysis suggests that levels of non-high-density lipoprotein cholesterol (non-HDL-C) among statin users is associated with risk of developing a major cardiovascular event, such as a heart attack or stroke, as are levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B.

The meta-analysis was published in the March 28 issue of JAMA.

As background, the authors noted, “Statin therapy is the cornerstone of pharmacological therapy for the primary and secondary prevention of cardiovascular disease. All currently available guidelines state that LDL-C levels should be used as the primary target to initiate and titrate lipid-lowering therapy. However, trials investigating the efficacy of statin therapy have shown that the cardiovascular benefits of statins may go beyond their influence on LDL-C levels. Thus, LDL-C may not be the best lipid parameter to predict cardiovascular risk or to quantify the atheroprotective effect of statin therapy.”

Matthijs Boekholdt, M.D., Ph.D., of the Academic Medical Center, Amsterdam, the Netherlands, and colleagues conducted the meta-analysis. They assessed the data to see if, among patients on statins, non-HDL-C and apoB were more strongly associated with the risk of future cardiovascular events than LDL-C.

The study included controlled statin-trial data, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up.

The investigators found 8 trials, published between 1994 and 2008, that met criteria for inclusion in the meta-analysis, with individual patient data for 62,154 subjects. And 38,153 subjects had been randomized to a statin group, with an ensuing complete set of lipid and apolipoprotein levels during statin treatment.

Of these 38,153 subjects, 158 (0.4 percent) developed a fatal heart attack, and 1,678 (4.4 percent) developed a non-fatal heart attack during follow-up. The researchers found fatal other coronary artery disease in 615 subjects (1.6 percent) and fatal or nonfatal stroke occurred in 1,029 subjects (2.7 percent). A total of 2,806 subjects (7.4 percent) were hospitalized for unstable angina.

A total of 6,286 major cardiovascular events occurred in 5,387 study participants (event rate 14.1 percent).

Among statin-treated subjects, levels of LDL-C, non-HDL-C, and apoB were each strongly associated with the risk of major cardiovascular events, but non-HDL-C was more strongly associated than LDL-C and apoB. Notably, changes in non-HDL-C explained a larger proportion of the atheroprotective effect of statin intervention than did LDL-C and apoB.

“Given the fact that many other arguments for the clinical applicability of non-HDL-C and LDL-C are identical, non-HDL-C may be a more appropriate target for statin therapy than LDL-C,” the authors wrote.