Circulating Vascular Cell Adhesion Molecule-1 and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA)

J Am Heart Assoc. 2020 Nov 17;9(22):e019390. doi: 10.1161/JAHA.120.019390. Epub 2020 Nov 9.

Abstract

Background Serum levels of vascular cell adhesion molecule-1 (VCAM-1) are reflective of endothelial activation. Although VCAM-1 has been implicated in the pathogenesis of heart failure with preserved ejection fraction (HFpEF), the prospective association of VCAM-1 with development of clinically overt heart failure (HF) across ejection fraction categories is unclear. Methods and Results In MESA (the Multi-Ethnic Study of Atherosclerosis), we evaluated the association of VCAM-1 at examination 2 (2002-2004) with incident HF (HFpEF and HF with reduced ejection fraction) after adjustment for cardiovascular risk factors. Incident HF was independently adjudicated as first hospitalization for symptomatic HF. Among 2297 participants (mean age, 63 years; women, 53%), those with higher VCAM-1 were more likely to be White race, had higher blood pressure, and had lower kidney function. Over a median of 14.4 years, there were 102 HF events (HFpEF=65; HF with reduced ejection fraction=37). After covariate adjustment, each doubling of VCAM-1 was associated with incident HF (hazard ratio [HR], 1.94; 95% CI, 1.17-3.23; P=0.01). This association appeared stronger among current/former smokers compared with never smokers. On evaluation of HF subtypes, VCAM-1 was associated with incident HFpEF (HR, 1.97; 95% CI, 1.04-3.72; P=0.04) but not with incident HF with reduced ejection fraction, although risk estimates were consistent (HR, 1.82; 95% CI, 0.79-4.21; P=0.16). Conclusions In a multiethnic cohort, VCAM-1 was significantly associated with incident HF over long-term follow-up. These findings suggest a potential role for endothelial activation in driving clinical HF, and specifically HFpEF. Therapies that decrease endothelial activation may prevent the progression from cardiovascular risk factors to clinical HF.

Keywords: cellular adhesion molecule; endothelial activation; heart failure; heart failure with preserved ejection fraction; vascular cell adhesion molecule‐1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue
  • Aged
  • Atherosclerosis / blood*
  • Atherosclerosis / ethnology
  • Ethnicity / statistics & numerical data*
  • Female
  • Heart Failure / blood*
  • Heart Failure / epidemiology*
  • Hospitalization
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Stroke Volume
  • Vascular Cell Adhesion Molecule-1 / blood*
  • White People / statistics & numerical data*

Substances

  • Vascular Cell Adhesion Molecule-1