Six-year change in high-sensitivity C-reactive protein and risk of diabetes, cardiovascular disease, and mortality

BACKGROUND: Single measurements of elevated high-sensitivity C-reactive protein (hs-CRP) are associated with increased risk of diabetes, cardiovascular disease, and mortality. Large increases or sustained elevations in hs-CRP may be associated with even greater risk of these outcomes. The objective of this study was to characterize the association of 6-year change in hs-CRP with incident diabetes, incident cardiovascular events (heart disease, stroke, and heart failure), and mortality.

METHODS: We included 10,160 ARIC participants with hs-CRP measured at visits 2 (1990-1992) and 4 (1996-1998). Change in hs-CRP was categorized as sustained low/moderate (<3 mg/L at both visits), decreased (≥3 mg/L at visit 2 and <3 mg/L at visit 4), increased (<3 mg/L at visit 2 and ≥3 mg/L at visit 4), and sustained elevated (≥3 mg/L at both visits). Cox proportional hazards models were used to assess the association of 6-year change in hs-CRP with incident diabetes, cardiovascular events, and death during ~15 years after visit 4.

RESULTS: Compared with persons with sustained low/moderate hs-CRP, those with increased or sustained elevated hs-CRP had an increased risk of incident diabetes (hazard ratios [95% CIs] 1.56 [1.38-1.76] and 1.39 [1.25-1.56], respectively), whereas those with deceased hs-CRP did not. Persons with sustained elevated hs-CRP had an increased risk of coronary heart disease, ischemic stroke, heart failure, and mortality (hazard ratios [95% CIs] 1.51 [1.23-1.85], 1.70 [1.32-2.20], 1.60 [1.35-1.89], and 1.52 [1.37-1.69], respectively) compared with those with sustained low/moderate hs-CRP. Associations for sustained elevated hs-CRP were greater than for those with increased hs-CRP over 6 years.

CONCLUSIONS: Large increases or sustained elevations in hs-CRP over a 6-year period were associated with a subsequent increased risk of diabetes, and persons with sustained elevations in hs-CRP were at the highest risk for cardiovascular disease and mortality. Two measurements of hs-CRP are better than one for characterizing risk, and large increases are particularly prognostic.