Ridker
PM, Stampfer MJ, Rifai N
JAMA 2001; 285:2481-5 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. |
