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J Am Coll Cardiol, 2006; 48:2235-2242, doi:10.1016/j.jacc.2006.09.030 (Published online 9 November 2006).
© 2006 by the American College of Cardiology Foundation
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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*,{dagger},{ddagger},§,*, Tobias Kurth, MD, ScD*,||, Julie E. Buring, ScD*,{dagger},§,|| and Paul M. Ridker, MD, MPH, FACC*,{dagger},§,||

* Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
{dagger} Center for Cardiovascular Disease Prevention, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
{ddagger} 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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