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Introduction: In 2010, the American Heart Association (AHA) established “Life’s Simple 7” a composite of metrics aimed at defining cardiovascular health (CVH). Seven positive health factors (blood cholesterol, blood pressure, and fasting plasma glucose) and behaviors (diet quality, physical activity, smoking, and body mass index) are emphasized within the construct, each being scored into ideal, intermediate, or poor categories. While multiple studies have explored the association between the individual components of CVH and markers of inflammation and atherogenesis, none have examined total CVH score as a predictor of elevated C-reactive protein (CRP) levels.Purpose: To assess the hypothesis that CVH score is inversely associated with future elevated CRP levels.Methods: Black and White men and women (N=1096) from the Coronary Artery Risk Development in young Adults (CARDIA) study were examined at 4 different examinations across 18 years (1992, 2000, 2005,2010). At each examination, CRP and the components of CVH were measured. A 14-point CVH score was determined by summing points for each CVH metric at ideal (2 points), intermediate (1 point), and poor (0 points) levels. Three categories of CVH score were created: low (0-7), moderate (8-11), and high (12-14). Multivariable Cox proportional hazards regression models were used to test the association of both categorical and continuous CVH score with incidence of elevated CRP (>3.0 mg/L) over up to 18 years of follow-up. All models were adjusted for sex and race, and the following time-varying covariates: age, and current level of education.Results: Over the 18-year period, the incidence of elevated CRP was 33.6 per 1000 person years. Baseline CVH was associated with lower risk (hazard ratio (HR): 0.83; 95% CI: 0.80 to 0.86) of elevated CRP per 1point increment in CVH. When compared to the high CVH group at baseline, both low (HR: 2.80; 95% CI: 2.16 to 3.65) and moderate (HR: 1.63; 95%CI: 1.35 to 1.96) CVH groups had elevated risk of elevated CRP. Time-varying CVH was associated with a lower risk (HR: 0.88; 95% CI: 0.85 to 0.91) of elevated CRP per increment in CVH score. In models that entered CVH category as a time-varying covariate, both low (HR: 2.84; 95% CI: 2.08 to 3.87) and moderate (HR: 2.09; 95% CI: 1.56 to 2.79) CVH categories were associated with over twice the risk of elevated CRP compared to the optimal CVH group.Conclusions: Lower CVH is associated with elevated risk of elevated CRP during the transition from young adulthood to middle age.