Inflammation
Lp(a) does not predict peripheral artery disease, unlike CRP and the cholesterol ratio, a study of 14,916 physicians (JAMA 2001)
Original title: Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease
This nested case-control study compared 11 lipid and nonlipid biomarkers, including Lp(a), as predictors of symptomatic peripheral arterial disease (PAD) in a cohort of 14,916 initially healthy US male physicians aged 40-84, with 140 who developed PAD compared to 140 matched controls over an average 9-year follow-up. Baseline Lp(a) was not significantly elevated in men who developed PAD (P=.40), unlike total cholesterol, LDL cholesterol, triglycerides, apoB-100, fibrinogen, CRP, and the total cholesterol-HDL ratio, all significantly higher in cases (P<=.02). In multivariable analysis, the total cholesterol-HDL ratio was the strongest lipid predictor (relative risk 3.9 for highest versus lowest quartile, 95% CI 1.7-8.6), and CRP the strongest nonlipid predictor (relative risk 2.8, 95% CI 1.3-5.9), with CRP significantly improving prediction beyond standard lipid screening (P<.001). The findings show Lp(a) was not a significant predictor of PAD in this cohort, whereas the total cholesterol-HDL ratio and CRP were the strongest independent predictors.
Original abstract
Context: Several novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers.
Objective: To compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD).
Design, Setting, And Participants: Nested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status-matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls.
Main Outcome Measure: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100.
Results: In univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P =.001), triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP (P =.006), and the total cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P =.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P =.40) and homocysteine (P =.90) were observed. In multivariable analyses, the total cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001).
Conclusions: Of 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.
epidemiologyinflammationrisk prediction
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.