Cellular Adhesion Molecules in Young Adulthood and Cardiac Function in Later Life.

Background: E-selectin and intercellular adhesion molecule (ICAM)-1 are biomarkers of endothelial activation, which has been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFpEF). However, the temporal associations between E-selectin and ICAM-1 with subclinical cardiac dysfunction are unclear.

Objectives: This study sought to assess the longitudinal associations of E-selectin and ICAM-1 with subclinical alterations in cardiac function.

Methods: In the Coronary Artery Disease Risk Development in Young Adults study, a cohort of black and white young adults, we evaluated the associations of E-selectin and ICAM-1, obtained at year (Y) 7 (Y7) and Y15 examinations, with cardiac function assessed at Y30 after adjustment for key covariates.

Results: Higher E-selectin (n = 1,810) and ICAM-1 (n = 1,548) at Y7 were associated with black race, smoking, hypertension, and higher body mass index. After multivariable adjustment, higher E-selectin at Y7 (β coefficient per 1 SD higher: 0.22; SE: 0.06; p < 0.001) and Y15 (β coefficient per 1 SD higher: 0.19; SE: 0.06; p = 0.002) was associated with worse left ventricular (LV) global longitudinal strain (GLS). Additionally, higher Y15 ICAM-1 (β coefficient per 1 SD higher: 0.18; SE: 0.06; p = 0.004) and its increase from Y7 to Y15 (β coefficient per 1 SD higher: 0.16; SE: 0.07; p = 0.03) were also independently associated with worse LV GLS. E-selectin and ICAM-1 partially mediated the associations between higher body mass index and black race with worse GLS. Neither E-selectin nor ICAM-1 was associated with measures of LV diastolic function after multivariable adjustment.

Conclusion: Circulating levels of E-selectin and ICAM-1 and increases in ICAM-1 over the course of young adulthood are associated with worse indices of LV systolic function in midlife. These findings suggest associations of endothelial activation with subclinical HF with preserved ejection fraction.