Non-high-density lipoprotein cholesterol (non-HDL-C) was more strongly associated with future cardiovascular risk than low-density lipoprotein cholesterol (LDL-C) in patients taking statins, suggesting that the former may be a better target for statin treatment, according to a study published March 28 in the Journal of the American Medical Association.

S. Matthiajs Boekholdt, MD, PhD, of the department of cardiology at the Academic Medical Center in Amsterdam, the Netherlands, and colleagues noted that recent evidence shows apolipoprotein B (apoB) plays a role in the progression of atherosclerotic plaque and that apoB and non-HDL-C are markers of atherogenic lipoproteins. They designed their meta-analysis to assess whether, compared with LDL-C, apoB and non-HDL-C were more strongly associated with the risk of future cardiovascular events. Secondarily, they wanted to explore whether apoB and non-HDL-C accounted for a greater proportion of the atheroprotective effect of statin therapy than did LDL-C.

They devised a meta-analysis based on eight randomized clinical trials for statins and contacted the investigators to obtain individual patient data. To be eligible, trials had to have data on total cholesterol, LDL-C, HDL-C, triglycerides and apolipoproteins measured at baseline and during statin therapy. In all, they collected data on 62,154 patients who were enrolled in trials between 1994 and 2008.

Patient data included characteristics such as sex, age, smoking status, diabetes, blood measures and patient history of stable coronary disease, MI, PCI or CABG. Outcomes data included fatal and nonfatal MI, other fatal coronary artery disease, hospitalization for unstable angina, fatal and nonfatal stroke, peripheral artery disease, and congestive heart failure.

Because all the trials used a one-year time point for follow-up, they obtained lipid and apolipoprotein levels at baseline and one year. They used Cox proportional hazard models, adjusted Cox regression models and other statistical methods in their analyses.

They identified 38,153 patients treated with statins. Among that group, 158 had a fatal MI, 1,678 had a nonfatal MI, 615 had fatal events from other coronary artery disease, 2,806 were hospitalized for unstable angina and 1,029 had fatal or nonfatal strokes during follow-up. The adjusted hazard ratios for major cardiovascular events were 1.13 for LDL-C, 1.16 for non–HDL-C and 1.14 for apoB. They found that the proportion of treatment effect explained by non–HDL-C was larger (64 percent) than by LDL-C (50 percent) and by apoB (54 percent).

“The main finding of this study is that among statin-treated patients, non–HDL-C had a stronger association with risk of major cardiovascular events than LDL-C and apoB,” Boekholdt and colleagues wrote. “Changes in non–HDL-C also explained a larger proportion of the atheroprotective effect of statin intervention than did LDL-C and apoB.”

The authors noted that differences among the trials, including inclusion criteria and distribution levels for baseline characteristics and lipid levels, may have affected results. The trials also differed in their outcomes and their patient populations may not have been representative of the general population.

Methods for measuring non-HDL-C and other logistical and financial issues will affect the clinical utility of their findings, they pointed out. But, “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 concluded.