May 16, 2001JAMA1,304 citations
View Full PaperNovel Risk Factors for Systemic Atherosclerosis
Key Result
Elevated total cholesterol-HDL-C ratio and CRP strongly predicted incident peripheral arterial disease (RR 3.9, 95% CI 1.7-8.6 and RR 2.8, 95% CI 1.3-5.9 for highest vs lowest quartiles).
Key Points
- To compare the predictive value of lipid and nonlipid biomarkers for symptomatic peripheral arterial disease.
- Nested case-control study using plasma samples from a cohort of 14,916 healthy male physicians aged 40 to 84 years.
- 140 cases of symptomatic peripheral arterial disease matched with 140 controls on age and smoking status.
- Multivariable analyses to assess the predictive power of 11 biomarkers including cholesterol and C-reactive protein.
- Total cholesterol-HDL-C ratio (RR 3.9, 95% CI 1.7-8.6) was the strongest lipid predictor for PAD risk.
- C-reactive protein was the strongest nonlipid predictor (RR 2.8, 95% CI 1.3-5.9).
- Adding C-reactive protein to lipid screening significantly enhanced risk prediction models (P<.001).
Study Design
Type
Case-Control (n=280)
Structured PICO
Do elevated levels of novel atherothrombotic biomarkers predict the development of symptomatic peripheral arterial disease in initially healthy men?
P
Population
280 men (140 cases of incident symptomatic PAD and 140 age- and smoking status-matched controls) drawn from a prospective cohort of 14,916 initially healthy US male physicians aged 40 to 84 years.
I
Intervention
Measurement of 11 lipid and nonlipid biomarkers (total cholesterol, HDL-C, LDL-C, total cholesterol-HDL-C ratio, triglycerides, homocysteine, CRP, lipoprotein(a), fibrinogen, apo A-I, and apo B-100)
C
Comparator
Lower levels (lowest quartile) of the respective biomarkers
O
Outcome
Incident symptomatic peripheral arterial disease (PAD) over an average 9-year follow-uphard clinical
The total cholesterol-HDL-C ratio and CRP are strong, independent predictors of incident peripheral arterial disease in initially healthy men, with CRP adding prognostic value to standard lipid screening.
Main Result
Effect estimate: RR 3.9 (95% CI 1.7-8.6)
p-value: p=<.001
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.