Novel biomarkers of inflammation in heart failure with preserved ejection fraction: analysis from a large prospective cohort study

Abstract

Background Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous cluster of causes, including non-resolving inflammation, endothelial dysfunction, and multi-organ defects. The present study’s objective was to identify novel predictors of HFpEF. Methods The study analyzed the Multi-Ethnic Study of Atherosclerosis (MESA) to assess the association of specific markers of inflammation with new onset of HFpEF (interleukin-2 [IL-2], matrix metalloproteinase 3 [MMP3], large low-density lipoprotein cholesterol [LDL-C], and medium high-density lipoprotein cholesterol [HDL-C]). The study included men and women 45 to 84 years of age without cardiovascular disease at baseline. The primary outcome was the multivariate association of the hypothesized markers of inflammation with new-onset of HFpEF versus participants without new-onset heart failure. Participants with missing data were excluded. Results The present analysis included 6814 participants, 53% female, with a mean age of 62 years. Among the entire cohort, HFpEF was diagnosed in 151 (2.2%) participants and heart failure with reduced ejection fraction (HFrEF) was diagnosed in 146 (2.1%) participants. Participants were followed for the outcome of heart failure for a median 13.9 years. Baseline IL-2 was available for 2861 participants. The multivariate analysis included 2792 participants. Of these, 2668 did not develop heart failure, 62 developed HFpEF, 47 developed HFrEF, and 15 developed unclassified heart failure. In the multivariate regression model, IL-2 was associated with new-onset HFpEF (OR, 1.00058; 95% confidence interval, 1.00014 to 1.00102, p = 0.009) but not new-onset HFrEF. In multivariate analysis, MMP3, large LDL-C, and medium HDL-C were not associated with HFpEF or HFrEF. Conclusion These findings portend IL-2 as an important component of suboptimal inflammation in the pathogenesis of HFpEF.

Heart failure with preserved ejection fraction and non‐alcoholic fatty liver disease: new insights from bioinformatics

“…Adiponectin is an adipocyte‐derived cytokine that prevents progression of aldosterone‐induced HFpEF, and its mechanism may be associated with the reduction of oxidative stress and regulation of intracellular calcium‐processing regulatory proteins 45 . Analysis of 6814 participants in the multi‐ethnic study of atherosclerosis showed that IL‐2 is an important component of suboptimal inflammation in the pathogenesis of HFpEF 46 . On the other hand, the PREVEND (Prevention of Renal and Vascular End‐Stage Disease) study showed a significant association between IL‐6 levels and HFpEF development 47 .…”

“…45 Analysis of 6814 participants in the multi-ethnic study of atherosclerosis showed that IL-2 is an important component of suboptimal inflammation in the pathogenesis of HFpEF. 46 On the other hand, the PREVEND (Prevention of Renal and Vascular End-Stage Disease) study showed a significant association between IL-6 levels and HFpEF development. 47 Elevated plasma levels of growth differentiation factor 15 (GDF15) are another significant independent predictor of complex outcomes in HFpEF patients.…”

Plasma Proteomic Patterns Show Sex Differences in Early Concentric Left Ventricular Remodeling

“…Our protein pathway analysis findings have not yet been validated, and the prognostic value of IFNA5 for cRM and HFpEF in women needs further investigation. 50 We are not able to provide reference values for IFNA5 levels, since our data were transformed to be comparable between proteins. Data on infiltrative or restrictive cardiomyopathy were not captured in a standardized manner.…”