Differences in Immune Cell Mitochondrial Function in Black and White Patients with Heart Failure with Preserved Ejection Fraction

Abstract

BACKGROUNDHeart failure with preserved ejection fraction (HFpEF) affects patients of all races and ethnicities. However, Black/African American patients are historically underrepresented in clinical research of HFpEF and have been reported to have unfavorable outcomes, yet the underlying mechanisms are not entirely understood. Excess proinflammatory cytokine and reactive oxygen species production from immune cells contributes to increased cardiovascular risk and may be a cause or consequence of alterations in immune cell metabolism. The aim of this study was to describe the immune cell bioenergetic profile in Black and White patients with HFpEF.METHODSWe studied 20 patients with HFpEF. 13 patients self‐reported as Black or African‐American (11 female; Median [IQR]: Age: 55 [50, 66] yrs; BMI 39 [36, 43] kg/m2; hsCRP 5.3 [3.5, 9.3] mg/dL; BNP 50 [50, 200] pg/mL) and 7 self‐reported as White (7 female; Age: 68 [43, 72] yrs; BMI 34 [33, 40] kg/m2; hsCRP 3 [1, 4.9] mg/dL; BNP 109 [50, 168] pg/mL). The mitochondrial bioenergetic profile was assessed in isolated peripheral blood mononuclear cells by a Seahorse XFp Analyzer. Respirometry coupled with modulators of cellular respiration were used to obtain basal respiration, ATP‐linked respiration, maximal respiration, proton linked respiration, spare respiratory capacity, and non‐mitochondrial respiration. The Mann Whitney U test was used to compare variables between groups.RESULTSProton leak respiration (Median [IQR]: 29 [4, 66] vs. 2.5 [1, 3] pmol/min, p=0.013), basal respiration 93 [60, 138] vs. 57 [53, 69] pmol/min, p = 0.008), maximal respiration (323 [191, 432] vs. 185 [162, 238] pmol/min, p = 0.0370) were higher in Black versus White patients. Raw spare respiratory capacity (232 [128, 293] vs. 125 [105, 145] pmol/min, p = 0.037) was also higher in Black versus White patients, whereas relative spare respiratory capacity (293% [276, 378] vs. 307% [259, 357] pmol/min, p=0.87) was not different between groups. There was a trend for lower coupling efficiency (94% [55, 95] vs. 97% [94, 99] pmol/min, p = 0.08) in Black vs White patients.CONCLUSIONIn an unselected cohort of patients with HFpEF, immune cell mitochondria basal respiration and respiratory reserve, as indicated by maximal respiration and spare respiratory capacity, are higher in Black versus White patients. Future studies are warranted to better understand the potential pathophysiological consequences of the observed differences.