Customize your JAMA Network experience by selecting one or more topics from the list below.
Pradhan AD, Manson JE, Rossouw JE, et al. Inflammatory Biomarkers, Hormone Replacement Therapy, and Incident Coronary Heart Disease: Prospective Analysis From the Women's Health Initiative Observational Study. JAMA. 2002;288(8):980–987. doi:10.1001/jama.288.8.980
Author Affiliations: Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine (Drs Pradhan, Manson, and Ridker) and Cardiology (Drs Pradhan and Ridker), and the Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders (Dr Ridker), Brigham and Women's Hospital and Harvard Medical School, Boston, Mass; National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Rossouw); Departments of Epidemiology and Medicine, University of Washington, Seattle (Dr Siscovick); Division of Community Geriatrics, Department of Family and Community Medicine, University of Texas Health Science Center, San Antonio (Dr Mouton); Department of Pathology, Children's Hospital Medical Center, and Harvard Medical School, Boston, Mass (Dr Rifai); Department of Epidemiology, University of Iowa College of Public Health, Iowa City (Dr Wallace); Division of Endocrinology, Diabetes, and Metabolism, Ohio State University, Columbus (Dr Jackson); and Women's Health Initiative Clinical Coordinating Center, Fred Hutchinson Cancer Research Center, Seattle, Wash (Ms Pettinger).
Context Postmenopausal hormone replacement therapy (HRT) has been shown to elevate
C-reactive protein (CRP) levels. Several inflammatory biomarkers, including
CRP, are associated with increased cardiovascular risk. However, whether the
effect of HRT on CRP represents a clinical hazard is unknown.
Objectives To assess the association between baseline levels of CRP and interleukin
6 (IL-6) and incident coronary heart disease (CHD) and to examine the relationship
between baseline use of HRT, CRP, and IL-6 levels as they relate to subsequent
Design, Setting, and Participants Prospective, nested case-control study of postmenopausal women, forming
part of the Women's Health Initiative, a large, nationwide, observational
study. Among 75 343 women with no history of cardiovascular disease or
cancer, 304 women who developed incident CHD were defined as cases and matched
by age, smoking status, ethnicity, and follow-up time with 304 study participants
who remained event free during a median observation period of 2.9 years.
Main Outcome Measure Incidence of first myocardial infarction or death from CHD.
Results Median baseline levels of CRP (0.33 vs 0.25 mg/dL; interquartile range
[IQR], 0.14-0.71 vs 0.10-0.47; P<.001) and IL-6
(1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001)
were significantly higher among cases compared with controls. In matched analyses,
the odds ratio (OR) for incident CHD in the highest vs lowest quartile was
2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P
for trend = .002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P
for trend <.001). After additional adjustment for lipid and nonlipid risk
factors, both inflammatory markers were significantly associated with a 2-fold
increase in odds for CHD events. As anticipated, current use of HRT was associated
with significantly elevated median CRP levels. However, there was no association
between HRT and IL-6. In analyses comparing individuals with comparable baseline
levels of either CRP or IL-6, those taking or not taking HRT had similar CHD
ORs. In analyses stratified by HRT, we observed a positively graded relationship
between plasma CRP levels and the OR for CHD among both users and nonusers
of HRT across the full spectrum of baseline CRP.
Conclusions These prospective findings indicate that CRP and IL-6 independently
predict vascular events among apparently healthy postmenopausal women and
that HRT increases CRP. However, use or nonuse of HRT had less importance
as a predictor of cardiovascular risk than did baseline levels of either CRP
Create a personal account or sign in to: