Title : Associations of infectious disease and polygenic risk score with heart failure and cardiac remodeling: Findings from UK biobank and ARIC study
Abstract:
Background: Infectious disease (ID) has been reported to exacerbate heart failure (HF); however, a comprehensive evaluation of ID in relation to incident HF is limited.
Purpose: We aim to assess the association of ID and ID-polygenetic risk score (PRS) with incident HF and cardiac remodeling.
Methods: We ascertained over 900 IDs in participants from the UK Biobank (UKB) and the Atherosclerosis Risk in Communities (ARIC) study to assess the associations of ID with incident HF and HF subtypes (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]). Cardiac morphology was evaluated through cardiac MRI and echocardiography. Fibro-inflammatory pathway-specific ID-PRS was calculated.
Results: In the UKB, 6,484 HF cases occurred during a median of 13.5 years, and ARIC recorded 2,062 cases over 22.4 years. IDs were associated with a higher HF risk in UKB (HR: 1.54, 95% CI 1.46-1.63) and ARIC (1.84, 1.68-2.00). The risk was consistent across pathogens (P for difference >0.05) and HF subtypes, more pronounced in those with atrial fibrillation (P for interaction <0.001), highest within 180 days after infection (HR: 5.88, 95% CI 4.49-7.71), and remained elevated after one year (1.45, 1.37-1.54). IDs were associated with reduced cardiac pumping and filling capacity, cardiac hypertrophy, and elevated left ventricular filling pressures. In ID-free individuals, a higher ID-PRS correlated with adverse cardiac status, with the involvement of TGF-β and inflammation pathways.
Conclusions: ID was associated with higher HF risk regardless of pathogen type and was related to cardiac remodeling. ID-PRS also had an adverse cardiac impact, even in the population in the absence of overt infection