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Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non–HDL Cholesterol, Apolipoproteins A-I and B100, Standard Lipid Measures, Lipid Ratios, and CRP as Risk Factors for Cardiovascular Disease in Women. JAMA. 2005;294(3):326–333. doi:10.1001/jama.294.3.326
Author Affiliations: Donald W. Reynolds Center
for Cardiovascular Research (Drs Ridker, Cook, and Buring); the Leducq Center
for Molecular and Genetic Epidemiology (Drs Ridker and Cook); the Center for
Cardiovascular Disease Prevention and the Divisions of Preventive Medicine
(Drs Ridker, Cook, and Buring) and Cardiology (Dr Ridker), Brigham and Women’s
Hospital, and the Department of Laboratory Medicine, Children’s Hospital
(Dr Rifai and Mr Bradwin), Harvard Medical School, Boston, Mass; and the Department
of Epidemiology, Harvard School of Public Health, Boston, Mass (Drs Ridker,
Cook, and Buring).
Context 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).
Objective 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.
Results 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.
Conclusions 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.
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