Mid- to Late-Life Systemic Inflammation and Late-Life Cardiac Structure and Function: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction Systemic inflammation has been implicated in the development of heart failure with preserved ejection fraction (HFpEF) through left ventricular (LV) systolic and diastolic dysfunction via impairments in nitric oxide generation, reduced cyclic GMP, and altered titan phosphorylation. However, few studies have examined the association of systemic inflammation with cardiac structure and function. Hypothesis Greater systemic inflammation from mid- to late-life is associated with worse LV systolic and diastolic function in late-life. Methods We conducted a prospective cohort analysis of 4,011 participants in the ARIC Study who underwent hs-CRP measurements at visits 2 (1990-92), 4 (1996-98), and 5 (2011-13). Echocardiography was conducted at Visit 5. We calculated the time-weighted mean hs-CRP concentration as the sum of the mean hs-CRP values at 3 consecutive visits multiplied by the time between visits. Participants were categorized as hs-CRP Results Mean age at Visit 2 was 54.6±5.0 and at Visit 5 was 75.3±5.1, 64% were female, and 21% were black. Covariates at visit 5 associated with higher hs-CRP were female sex, black race, presence of diabetes (DM), obesity, and CKD. Greater time averaged hs-CRP predicted higher LV mass index related to both greater LV dimension and wall thickness, worse longitudinal strain, and higher E/e’ ratio in models adjusted for demographics (Figure). After further adjustment for SBP, DM, smoking, BMI, heart rate, and eGFR, higher hs-CRP remained associated with worse longitudinal strain (p=0.009). Conclusions Higher time averaged hs-CRP exposure from mid- to late-life predicts greater LV mass, and worse LV systolic and diastolic function in late life. These associations were attenuated after accounting for clinical comorbidities associated with systemic inflammation.