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Abstract

Introduction: A marker of inflammation, elevated high-sensitivity C-reactive protein (hsCRP) is associated with increased risk of cardiovascular disease, stroke and all-cause mortality. Similar to acute vascular events, while CRP increases during acute sepsis, the association between hsCRP at a stable phase of health and future sepsis events is unknown. Hypothesis: Individuals with elevated hsCRP are at increased risk for future sepsis events. Methods: We conducted a population-based longitudinal cohort study using the national REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Baseline hsCRP was measured at the start of the study. We identified sepsis events over an 8-year maximum observation period, defining sepsis as hospitalization for a serious infection with the presence of?2 systemic inflammatory response syndrome criteria. Using Cox regression, we evaluated the association between elevated baseline hsCRP (>3.0 mg/L) and the risk of subsequent sepsis events, adjusted for sociodemographic factors (age, sex, race, region, education, income), health behaviors (tobacco and alcohol use), and chronic medical conditions (hypertension dyslipidemia, coronary artery disease, chronic kidney disease, chronic lung disease and diabetes). Results: Among 30,239 study participants, median hsCRP was 2.2 mg/L (IQR 1.0, 5.0); 11,447 (37.9%) had hsCRP >3.0 mg/L. Elevated hsCRP was more likely in younger, female, black, low income and low education subjects and those reporting tobacco use or chronic medical conditions (all p<0.001). Over a mean observation period of 4.6 ± 1.6 years, there were 820 first sepsis events. After adjustment for age, sex, race and geographic region, elevated hsCRP was independently associated with subsequent sepsis episodes (HR 1.76; 95% CI 1.53-2.03). After adjustment for all confounders, elevated hsCRP remained independently associated with future sepsis events (HR 1.44; 95% CI 1.24-1.67). Conclusions: Elevated hsCRP at a stable phase of health was associated with increased risk of future sepsis events over 4.6 years of follow-up. Heightened inflammation may predispose to sepsis. Measurement of hsCRP may provide an option for sepsis risk prediction, mitigation or prevention.