The following is a summary of “Proteomics and Precise Exercise Phenotypes in Heart Failure With Preserved Ejection Fraction: A Pilot Study,” published in the November 2023 issue of Cardiology by Shah et al.
Heart failure with preserved ejection fraction (HFpEF) involves impaired exercise capacity, yet previous research on HFpEF biomarkers has predominantly concentrated on resting states. Researchers conducted a study combining precise exercise phenotypes with cardiovascular proteomics to better understand HFpEF’s exercise responses and identify potential therapeutic targets.
Their analysis involved examining 277 proteins (Olink) in 151 individuals, comprising 103 with HFpEF and 48 controls, with an average age of 62 years, among whom 56% were women. The investigators utilized ridge regression adjusted for age and sex to establish proteomic signatures associated with five key exercise-related variables relevant to HFpEF: peak oxygen uptake, peak cardiac output, pulmonary capillary wedge pressure/cardiac output slope, peak pulmonary vascular resistance, and peak peripheral O2 extraction. Each exercise phenotype exhibited a multiprotein signature that significantly captured the respective variance in exercise responses. Specific proteins identified within these signatures included those associated with HFpEF pathophysiology (such as inflammatory and profibrotic proteins) and novel proteins linked to diverse physiological aspects (e.g., kidney, liver, muscle, adipose health) implicated in impaired O2 extraction. In an independent sample (n=522, with 261 HF events), proteomic signatures related to peak oxygen uptake and pulmonary capillary wedge pressure/cardiac output slope were linked to incident HFpEF, with adjusted odds ratios of 0.67 (95% CI, 0.50–0.90) and 1.43 (95% CI, 1.11–1.85), respectively, after accounting for clinical factors and B-type natriuretic peptides.
Their study demonstrates an association between the cardiovascular proteome and precise exercise phenotypes in HFpEF, offering insights into potential mechanistic targets and strategies for early risk stratification to prevent the onset of HFpEF.
Source: ahajournals.org/doi/10.1161/JAHA.122.029980
