Multi-Omic Profiling in Black and White Populations Reveals Novel Candidate Pathways in Left Ventricular Hypertrophy and Incident Heart Failure Specific to Black Adults

Abstract

Background - Increased left ventricular (LV) mass is associated with adverse cardiovascular events including heart failure (HF). Both increased LV mass and HF disproportionately affect Black individuals. To understand underlying mechanisms, we undertook a proteomic screen in a Black cohort and compared the findings to results from a white cohort. Methods - We measured 1305 plasma proteins using the SomaScan® platform in 1772 Black participants (mean age 56 years, 62% women) in the Jackson Heart Study (JHS) with LV mass assessed by 2D echocardiography. Incident HF was assessed in 1600 participants. We then compared protein associations in JHS to those observed in white participants from the Framingham Heart Study (FHS, mean age 54 years, 56% women). Results - In JHS, there were 110 proteins associated with LV mass and 13 proteins associated with incident HF hospitalization with false discovery rate <5% after multivariable adjustment. Several proteins showed expected associations with both LV mass and HF, including N-terminal pro-BNP (β = 0.04, p = 2 × 10 -8 ; HR = 1.48, p = 0.0001). The strongest association with LV mass was novel: Leukotriene A-4 hydrolase (LKHA4) (β = 0.05, p = 5 × 10 -15 ). This association was confirmed on an alternate proteomics platform and further supported by related metabolomic data. Fractalkine/CX3CL1 showed a novel association with incident HF (HR = 1.32, p = 0.0002). While established biomarkers such as cystatin C and N-terminal pro-BNP showed consistent associations in Black and white individuals, LKHA4 and fractalkine were significantly different between the two groups. Conclusions - We identified several novel biological pathways specific to Black adults hypothesized to contribute to the pathophysiologic cascade of LV hypertrophy and incident HF including LKHA4 and fractalkine.