Abstract and Introduction
Background: Experimental studies have shown that the known biologic effects of proinflammatory cytokines could explain many aspects of the syndrome of heart failure. The inflammatory marker that presently seems most suitable to assess inflammation is C-reactive protein (CRP). This study was designed to investigate the association between serum CRP levels, as determined by high-sensitivity assay, and the occurrence of heart failure.
Methods: Serum CRP levels were available from 6437 men and women without heart failure, aged ≥55 years, from the prospective population-based Rotterdam Study. Cox proportional hazards analysis was used to determine risk of heart failure for sex-specific quartiles of CRP.
Results: C-reactive protein levels in the highest versus the lowest quartile showed increased hazard ratios of incident heart failure. The age- and sex-adjusted hazard ratio was 2 .64 (95% CI 2.04-3.43) for all participants. For men, the age adjusted hazard ratio was 4.37 (2.87-6.66), and for women, 1.86 (1.32-2.62). The interaction term of CRP with sex was highly significant. After additional adjustment for established cardiovascular risk factors, the association attenuated slightly in men and substantially in women, becoming 3.73 (2.40-5.78) and 1.42 (0.99-2.03), respectively. Excluding participants with prevalent coronary heart disease and accounting for incident coronary heart disease resulted in a further attenuation of the hazard ratios, which was proportionately larger in men than in women.
Conclusions: C-reactive protein is strongly and independently associated with occurrence of heart failure in men. In women, the association is weaker and does not persist after accounting for established cardiovascular risk factors.
Recently, inflammatory markers have been implicated as predictors of heart failure. Experimental studies have shown that the known biologic effects of proinflammatory cytokines could explain many aspects of the syndrome of heart failure, such as left ventricular dysfunction, pulmonary edema, and the process of left ventricular remodeling, including myocyte hypertrophy and progressive myocyte loss through apoptosis.
The inflammatory marker that presently seems most suitable to assess inflammation is C-reactive protein (CRP). Elevated CRP levels have been associated with an adverse prognosis in patients with heart failure,[3,4,5] and elevated CRP levels have shown to be predictive of the development of heart failure in high-risk participants.[6,7]
Few population-based studies have examined the association between CRP and heart failure. In the Cardiovascular Health Study, increased CRP was an independent predictor of heart failure, the association persisting after adjustment for clinically prevalent as well as subclinical atherosclerotic disease. The Framingham Heart Study demonstrated that participants with CRP serum levels of ≥5 mg/L experienced a significantly increased risk of heart failure, even after adjustment for prevalent cardiovascular disease and the occurrence of myocardial infarction during follow-up. This study was limited by the use of a low-sensitivity CRP assay. Finally, in the Health ABC study, high levels of CRP independently predicted the incidence of events of heart failure. In this study, incident heart failure was defined as any overnight hospitalization with this diagnosis, which does not account for all heart failure cases in a population.
These studies suggest that elevated levels of CRP precede heart failure. We sought to expand the evidence by examining the relation between CRP levels, as determined by high-sensitivity assay, and the occurrence of heart failure, in the Rotterdam Study, a prospective population-based cohort study in men and women aged ≥55 years.
Am Heart J. 2006;152(3):514-520. © 2006 Mosby, Inc.
Cite this: C-reactive Protein and Risk of Heart Failure. The Rotterdam Study - Medscape - Sep 01, 2006.