A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk

Item does not contain fulltextBACKGROUND: Whether apolipoprotein B (apoB) or non-high-density lipoprotein cholesterol (HDL-C) adds to the predictive power of low-density lipoprotein cholesterol (LDL-C) for cardiovascular risk remains controversial. METHODS AND RESULTS: This meta-analysis is based on all the published epidemiological studies that contained estimates of the relative risks of non-HDL-C and apoB of fatal or nonfatal ischemic cardiovascular events. Twelve independent reports, including 233 455 subjects and 22 950 events, were analyzed. All published risk estimates were converted to standardized relative risk ratios (RRRs) and analyzed by quantitative meta-analysis using a random-effects model. Whether analyzed individually or in head-to-head comparisons, apoB was the most potent marker of cardiovascular risk (RRR, 1.43; 95% CI, 1.35 to 1.51), LDL-C was the least (RRR, 1.25; 95% CI, 1.18 to 1.33), and non-HDL-C was intermediate (RRR, 1.34; 95% CI, 1.24 to 1.44). The overall comparisons of the within-study differences showed that apoB RRR was 5.7%>non-HDL-C (PLDL-C (PLDL-C (P=0.017). Only HDL-C accounted for any substantial portion of the variance of the results among the studies. We calculated the number of clinical events prevented by a high-risk treatment regimen of all those >70th percentile of the US adult population using each of the 3 markers. Over a 10-year period, a non-HDL-C strategy would prevent 300 000 more events than an LDL-C strategy, whereas an apoB strategy would prevent 500 000 more events than a non-HDL-C strategy. CONCLUSIONS: These results further validate the value of apoB in clinical care

Surrogate end points, health outcomes, and the drug-approval process for the treatment of risk factors for cardiovascular disease

Data on surrogate end points such as blood pressure or body weight have often been used to support the approval of new pharmacologic treatments for cardiovascular risk factors. In small, short-term studies, a new drug reduces the level of a risk factor, and the changes in risk factor levels are interpreted as if the health benefits expected on the basis of those changes will necessarily follow. An editorial on the pharmacotherapy of obesity illustrates the argument1: in the context of discussing the association between appetite suppressant drugs and primary pulmonary hypertension,2 the editorialists used observational evidence on the association of body mass index with mortality and translated data on weight loss in a small, short-term trial of dexfenfluramine3 into an estimate of lives that could be saved by long-term drug therapy for obesity. The US Food and Drug Administration (FDA) approved dexfenfluramine on the basis of this same surrogate end point argument4: "the potential health benefits of anorectic drugs outweigh their risk when considered against the health hazards of obesity."5 When, after the drug was approved, the adverse effects were found to be greater than estimated on the basis of preapproval trials,6,7 the drug was withdrawn. Is this an example of the drug-approval process working well, or does it point to a fundamental flaw in the way drugs are approved