Lipoprotein(a) increased risk for premature coronary heart disease in men
ACP J Club. 1997 Jan-Feb;126:24. doi:10.7326/ACPJC-1997-126-1-024
Bostom AG, Cupples LA, Jenner JL, et al. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA. 1996 Aug 21; 276:544-8.
To analyze the association between elevated lipoprotein(a) (Lp[a]) level and premature coronary heart disease (CHD) in men.
Cohort analytic study of participants in the Framingham Offspring Study.
Community-based study in Framingham, Massachusetts, USA.
2191 men 20 to 54 years of age (mean age 37 y) who were free of cardiovascular disease at a baseline examination between 1971 and 1975.
Assessment of risk factors
A physical examination was done at baseline and every 3 to 4 years thereafter and included complete medical history, 12-lead electrocardiogram, fasting lipid profile, and other biochemical measurements. Elevated Lp(a) levels were detected as a sinking pre-β-lipoprotein band on electrophoresis of fresh plasma. Quantitative analysis of Lp(a) was done in a subset of 1250 participants using a validated enzyme-linked immunosorbent assay.
Main outcome measures
Incident CHD (myocardial infarction [MI], coronary insufficiency, angina pectoris, or sudden cardiac death) occurring by 55 years of age. Outcome events were identified through follow-up assessments and review of hospital records and other source documents.
Presence of a sinking pre-β-lipoprotein band was 43% sensitive and 93% specific for plasma Lp(a) levels ≥ 0.78 mmol/L and was found in 248 participants (prevalence 11.4%). Elevated Lp(a) was associated with increased risk for premature CHD on univariate analysis. On multivariate analysis (using a proportional hazards model that also included age, body mass index, hypertension, smoking, glucose intolerance, total cholesterol level ≥ 6.2 mmol/L or low-density lipoprotein [LDL] cholesterol ≥ 4.1 mmol/L, and high-density lipoprotein [HDL] cholesterol level < 0.9 mmol/L), elevated Lp(a) remained associated with increased risk for premature CHD (relative risk [RR] 1.9, 95% CI 1.2 to 2.9). The RR for premature CHD associated with total cholesterol level ≥ 6.2 mmol/L was 1.8 (CI 1.2 to 2.7); for HDL cholesterol < 0.9 mmol/L, 1.8 (CI 1.2 to 2.6); for hypertension, 1.2 (CI 0.8 to 1.8); for glucose intolerance, 2.7 (CI 1.4 to 5.3); and for smoking, 3.6 (CI 2.4 to 5.7). Smoking was not only strongly associated with risk for premature CHD but was also a very prevalent risk factor (46.7%), contributing substantially to the population-attributable risk (54.8%) in this study cohort.
Elevated plasma lipoprotein(a) level was an independent risk factor for premature coronary heart disease in men.
Sources of funding: In part, National Institutes of Health and U.S. Department of Agriculture.
For article reprint: Dr. A.G. Bostom, Vitamin Bioavailability Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts New England Medical Center, 711 Washington Street, Boston, MA 02111, USA. FAX 617-556-3344.
Results from several observational studies suggest that the level of Lp(a), a plasma particle closely related to LDL, is a predictor of CHD (1). Although this association has not been observed uniformly (2), most studies support this conclusion. The study by Bostom and colleagues concurs with published data that link Lp(a) level with CHD and is noteworthy because it found that high levels of Lp(a) were independently associated with incident premature CHD in men. Although the precise mechanisms that link Lp(a) level with risk for CHD are unknown, Lp(a) (which shares structural similarities with plasminogen) may be thrombogenic and may impair endothelium-dependent arterial dilatation and promote atherogenesis when oxidatively modified.
Measuring Lp(a) levels when screening a population for CHD risk factors has been proposed (1), but the case for screening is weak. Although high Lp(a) levels may be a relatively common inherited CHD risk factor, a standardized quantitative assay for the determination of Lp(a) levels is not available (3), and qualitative electrophoretic assays are not sensitive. Furthermore, there is no diet or drug therapy proven to lower Lp(a) levels consistently (3), and most important, it is unknown whether lowering Lp(a) levels reduces risk for CHD. Among persons who may have elevated Lp(a) levels (such as those with or at risk for premature CHD), prevention efforts should focus on traditional CHD risk reduction strategies, particularly smoking cessation and LDL cholesterol lowering. Lp(a) levels currently have limited clinical use but may eventually be useful for targeted stratification of CHD risk.
Joel A. Simon, MD, MPH
San Francisco Veterans Affairs Medical CenterUniversity of California, San FranciscoSan Francisco, California, USA