Abstract
Background: Obesity and adiposity are associated with risk of heart failure with preserved ejection fraction (HFpEF), yet the role of adipokines and other obesity related pathways as contributors to HFpEF remains unclear. Objectives: We sought to examine the association of obesity and obesity related biomarkers including adipokines, inflammatory markers, and insulin resistance with HFpEF and specific cardiac and extracardiac organ reserve measures among patients who underwent CPET. Methods: We studied 509 consecutive patients with LVEF ≥ 50% and NYHA class II - III symptoms, who underwent clinically indicated CPET with invasive hemodynamic monitoring. Fasting blood samples at the time of CPET were used to assay obesity-related biomarkers, including leptin, adiponectin, resistin, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), glucose and insulin to estimate insulin resistance (HOMA-IR). We examined the association of biomarkers with physiologic HFpEF and exercise traits using multivariable regression models. Results: Among 509 patients (mean age 55 years, 61% women, 38% obese), 223 met hemodynamic criteria for HFpEF. Obesity was associated with more than 2-fold higher odds of HFpEF (OR 2.08, 95% CI 1.38-3.14). We found that higher levels of leptin, hsCRP and HOMA-IR were associated with greater odds of HFpEF (P ≤ 0.01, Figure 1). By contrast, resistin and adiponectin were not associated with HFpEF (P>0.05). In secondary analyses, we observed associations of obesity related biomarkers with measures of impaired exercise capacity, such as lower peak VO 2 (P<0.05), higher blood pressure response (leptin, HOMA-IR), and impaired heart rate response (hsCRP, HOMA-IR, IL-6, resistin). Conclusions: Obesity related biomarkers were associated with HFpEF and impaired exercise capacity. These findings highlight potential pathways underlying the association of obesity and cardiometabolic disease with development of HFpEF.
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