The following is a summary of “Intercellular Adhesion Molecule-1 Missense Variant rs5491, High-Sensitivity C-reactive Protein, and Heart Failure With Preserved Ejection Fraction Risk,” published in the November 2023 issue of Cardiology by Giro et al.

The intercellular adhesion molecule-1 (ICAM-1) variant rs5491, more common in Black individuals, raises heart failure with preserved ejection fraction (HFpEF) risk, but the underlying mechanisms remain unclear.

Researchers launched a retrospective study to test if the ICAM-1 variant rs5491, prevalent in Black individuals, fuels hsCRP.

They examined the association of rs5491 with hsCRP at Exam 1 and conducted a formal mediation analysis of hsCRP on the association between rs5491 and incident HFpEF among Black individuals in the Multi-Ethnic Study of Atherosclerosis.

The results showed 1,558 black participants (average age 62±10 years, 47% female); those with at least one instance of rs5491 (N=580) displayed higher hsCRP levels in unadjusted analysis (2.78 mg/L [IQR: 1.11-6.25] compared to 2.25 mg/L [IQR: 0.99-4.82], P=0.009). Following adjustment for covariates, each additional rs5491 allele was significantly linked to an increase in hsCRP (β: 0.15, SE: 0.07, P=0.02). Each other rs5491 allele remained linked considerably to incident HFpEF after adjusting for hsCRP, clinical factors, and ancestry components 1-10 (HR 1.86, 95% CI: 1.15-3.01, P=0.01). In the mediation analysis, hsCRP did not emerge as a significant mediator in the relationship between rs5491 and HFpEF (percent mediated: 0%, 95% CI: 0-31%, P= 0.08).

They concluded that Rs5491 in Black individuals boosts HFpEF risk beyond inflammation, suggesting other inflammatory paths.

Source: ahajournals.org/doi/10.1161/circ.148.suppl_1.12132