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CLINICAL RESEARCH: CORONARY ARTERY DISEASE AND CARDIAC METABOLISM

The Relative Strength of C-Reactive Protein and Lipid Levels as Determinants of Ischemic Stroke Compared With Coronary Heart Disease in Women

Brendan M. Everett, MD^_*,,,,_*, Tobias Kurth, MD, ScD^_*,||,¶, Julie E. Buring, ScD^_*,,,|| and Paul M. Ridker, MD, MPH, FACC^_*,,,||

^_* Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
Donald W. Reynolds Cardiovascular Clinical Research Center on Atherosclerosis at Brigham and Women’s Hospital and the Harvard Medical School, Boston, Massachusetts
^|| Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
^¶ Division of Aging, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts

Manuscript received June 20, 2006; revised manuscript received September 6, 2006, accepted September 11, 2006.

^_* Reprint requests and correspondence: Dr. Brendan M. Everett, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Avenue East, Boston, Massachusetts 02215. (Email: beverett{at}partners.org).

OBJECTIVES: We sought to determine the relative strength of high-sensitivity C-reactive protein (hs-CRP) and lipid levels as markers for future ischemic stroke compared with coronary heart disease (CHD) in women.

BACKGROUND: Although hs-CRP and lipid levels are established risk determinants for vascular disease, the relative strength of these biomarkers for ischemic stroke compared with CHD is uncertain.

METHODS: Among 15,632 initially healthy women who were followed for a 10-year period, we compared hs-CRP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoproteins A-I and B100, and lipid ratios as determinants of ischemic stroke compared with CHD.

RESULTS: After adjustment for age, smoking status, blood pressure, diabetes, and obesity, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the third versus the first tertile for future ischemic stroke compared with CHD were, respectively, 1.91 (95% CI 1.13 to 3.21) and 2.26 (95% CI 1.64 to 3.12) for TC, 1.29 (95% CI 0.83 to 2.02) and 2.09 (95% CI 1.53 to 2.85) for LDL-C, 0.57 (95% CI 0.36 to 0.92) and 0.38 (95% CI 0.27 to 0.52) for HDL-C, 1.72 (95% CI 1.03 to 2.86) and 2.93 (95% CI 2.04 to 4.21) for non–HDL-C, and 2.76 (95% CI 1.51 to 5.05) and 1.66 (95% CI 1.17 to 2.34) for hs-CRP. Of the lipid ratios, that of TC to HDL-C had the largest HR for both future ischemic stroke and CHD (HR 1.95 [95% CI 1.16 to 3.26] and 4.20 [95% CI 2.79 to 6.32], respectively).

CONCLUSIONS: In this large prospective cohort of initially healthy women, lipid levels are significant risk determinants for ischemic stroke, but with a magnitude of effect smaller than that observed for CHD. High-sensitiviy CRP associates more closely with ischemic stroke than with CHD. Concomitant evaluation of lipid levels and hs-CRP may improve risk assessment for stroke as well as CHD. (The Women’s Health Study; http://www.clinicaltrials.gov/ct/show/NCT00000479/; NCT00000479 [ClinicalTrials.gov] )

Abbreviations and Acronyms   ARIC = Atherosclerosis Risk in Communities   CHD = coronary heart disease   CI = confidence interval   HDL-C = high-density lipoprotein cholesterol   HR = hazard ratio   hs-CRP = high-sensitivity C-reactive protein   LDL-C = low-density lipoprotein cholesterol   LR = likelihood ratio   TC = total cholesterol   WHS = Women’s Health Study

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