Inflammation and the Long-Term Incidence of Hypertension in Women

Abstract Aims Chronic inflammation associates with prevalent and short-term incident hypertension. The aim of this study is to determine whether baseline high-sensitivity C-reactive protein (hsCRP) independently associates with incident hypertension over three decades in women. Methods Normotensive Women’s Health Study participants with a baseline hsCRP measurement were followed for incident hypertension for up to 30.9 years. Cause-specific Cox proportional hazards models estimated hazard ratios for incident hypertension across hsCRP quintiles and per SD log(hsCRP). Models were adjusted for a minimally sufficient set of covariates derived from a directed acyclic graph, including age, study arm, BMI, smoking, exercise, dietary factors, alcohol use, eGFR, and hormone replacement therapy (HRT). Stratified analyses were performed across categories of age, SBP, DBP, BMI, and HRT use. Landmark analyses estimated separate hazard ratios for each decade. Results 14,234 of 20,224 (70%) women developed hypertension during follow-up. Baseline hsCRP was associated with time-to-incident hypertension, with a time-averaged multivariable hazard ratio of 1.33 (95% CI 1.25-1.41) comparing the top and bottom quintiles, and 1.10 (95% CI 1.08-1.12) per SD log(hsCRP). There was no effect modification by age, SBP, DBP, BMI, or HRT use. In landmark analyses, hsCRP was associated with incident hypertension in the first two decades, but not beyond 20 years. Conclusions A single measure of low-grade inflammation independently associated with time-to-incident hypertension over the near- to intermediate-term, with limited prognostic value beyond 20 years. These data suggest that inflammation may be a primordial risk factor for hypertension in women.