Cumulative Exposure to High‐Sensitivity C‐Reactive Protein Predicts the Risk of Cardiovascular Disease

BACKGROUND One measurement of hs-CRP (high-sensitivity C-reactive protein) is associated with increased risk of cardiovascular disease (CVD). The objective of this study was to characterize the association of cumulative exposure to increased hs-CRP with incident cardiovascular events. METHODS AND RESULTS We included 53 065 participants with hs-CRP measured at 3 examinations in 2006, 2008, and 2010. Cumulative exposure to hs-CRP was calculated as the weighted sum of the average hs-CRP level for each time interval (level×time). Participants were classified into nonexposed group (hs-CRP<3.0 mg/L in all 3 examinations), 1-exposed group (hs-CRP≥3.0 mg/L in 1 of the 3 examinations), 2-exposed group (hs-CRP≥3.0 mg/L in 2 of the 3 examinations), and 3-exposed group (hs-CRP≥3.0 mg/L in 3 examinations). Cox proportional hazards models were used to assess the association of cumulative hs-CRP with incident CVD. The study showed a dose-response pattern with risk of CVD and myocardial infarction as the number of years of exposure to hs-CRP increases. Participants in the 3-exposed group had significantly increased CVD risk with hazard ratio (95% confidence interval) of 1.38 (1.11-1.72), in comparison with 1.28 (1.07-1.52) for participants in the 2-exposed group and 1.13 (0.97-1.31) for those in the 1-exposed group (P<0.05); meanwhile, the similar and significant associations were also observed for myocardial infarction with respective hazard ratio (95% confidence interval) of 2.13 (1.42-3.18), 1.60 (1.12-2.27), and 1.57 (1.17-2.10). The associations between stroke and cumulative hs-CRP were not statistically significant (P=0.360). CONCLUSIONS Cumulative exposure to hs-CRP was dose dependently associated with a subsequent increased risk of CVD and myocardial infarction. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov/. Unique identifier: ChiCTR-TNC-11001489.