Current guidelines for cardiovascular risk detection are controversial
with regard to the clinical utility of different lipid measures, non–high-density
lipoprotein cholesterol (non–HDL-C), lipid ratios, apolipoproteins,
and C-reactive protein (CRP).
To directly compare the clinical utility of total cholesterol, low-density
lipoprotein cholesterol (LDL-C), HDL-C, non–HDL-C, apolipoproteins A-I
and B100, high-sensitivity CRP, and the ratios of total cholesterol
to HDL-C, LDL-C to HDL-C, apolipoprotein B100 to apolipoprotein
A-I, and apolipoprotein B100 to HDL-C as predictors of future cardiovascular
events in women.
Design, Setting, and Participants
Prospective cohort study of 15 632 initially healthy US women aged
45 years or older (interquartile range, 48-59 years) who were enrolled between
November 1992 and July 1995. All participants were followed up over a 10-year
period for the occurrence of future cardiovascular events.
Main Outcome Measure
Hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever
major cardiovascular events (N = 464) according to baseline levels
of each biomarker.
After adjustment for age, smoking status, blood pressure, diabetes,
and body mass index, the HRs for future cardiovascular events for those in
the extreme quintiles were 1.62 (95% CI, 1.17-2.25) for LDL-C, 1.75 (95% CI,
1.30-2.38) for apolipoprotein A-I, 2.08 (95% CI, 1.45-2.97) for total cholesterol,
2.32 (95% CI, 1.64-3.33) for HDL-C, 2.50 (95% CI, 1.68-3.72) for apolipoprotein
B100, 2.51 (95% CI, 1.69-3.72) for non–HDL-C, and 2.98 (95%
CI, 1.90-4.67) for high-sensitivity CRP (P<.001
for trend across all quintiles). The HRs for the lipid ratios were 3.01 (95%
CI, 2.01-4.50) for apolipoprotein B100 to apolipoprotein A-I, 3.18
(95% CI, 2.12-4.75) for LDL-C to HDL-C, 3.56 (95% CI, 2.31-5.47) for apolipoprotein
B100 to HDL-C, and 3.81 (95% CI, 2.47-5.86) for the total cholesterol
to HDL-C (P<.001 for trend across all quintiles).
The correlation coefficients between high-sensitivity CRP and the lipid parameters
ranged from −0.33 to 0.15, and the clinical cut points for CRP of less
than 1, 1 to 3, and higher than 3 mg/L provided prognostic information on
risk across increasing levels of each lipid measure and lipid ratio.
Non–HDL-C and the ratio of total cholesterol to HDL-C were as
good as or better than apolipoprotein fractions in the prediction of future
cardiovascular events. After adjustment for age, blood pressure, smoking,
diabetes, and obesity, high-sensitivity CRP added prognostic information beyond
that conveyed by all lipid measures.