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.