Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study

PLoS One. 2021 May 4;16(5):e0251148. doi: 10.1371/journal.pone.0251148. eCollection 2021.

Abstract

Background: This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex.

Methods: Biomarkers and echocardiographic measures were measured at both baseline and follow-up in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders.

Results: Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %.

Conclusion: Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Cohort Studies
  • E-Selectin / metabolism
  • Echocardiography / methods
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Inflammation / metabolism
  • Inflammation / physiopathology*
  • Male
  • Prospective Studies
  • Sex Characteristics
  • Stroke Volume / physiology
  • Tumor Necrosis Factor-alpha / metabolism
  • Ventricular Function, Left / physiology

Substances

  • Biomarkers
  • E-Selectin
  • Tumor Necrosis Factor-alpha

Grants and funding

This work was supported by the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2016-Early HFPEF and CVON2017- She-Predicts). SR and AJvB are supported by a ZonMw grant (849500008). JWJB is supported by a ZonMw VIDI grant (91718304). SRBH received support of the ERA-Net-CVD project MacroERA (01KL1706) and IMI-2CARDIATEAM (821508). Furthermore, we acknowledge the support of FWO (Belgium; G091018N & G0B5930N) to SRBH. The NPA Alliance for the Promotion of Preventive Medicine (APPREMED), Mechelen, Belgium received a non-binding grant from OMRON Healthcare Co. Ltd., Kyoto, Japan.