The 2 most prevalent risk factors for the development of heart failure and a preserved ejection fraction (HFpEF) are hypertension and obesity, but their relative importance in driving the evolution and progression of HFpEF has not been critically evaluated. The role of excess adiposity in HFpEF has been substantially underappreciated, largely because of reliance on body mass index (rather than waist-to-height ratio) to identify an expanded fat mass and on a meaningful elevation of natriuretic peptides to identify HFpEF. In the general population, changes in central obesity and visceral adiposity are observed years before HFpEF becomes clinically manifest, and central obesity is present in >80% to 90% of patients with established HFpEF, with the degree of adiposity being strongly related to the hemodynamic and clinical severity of HFpEF. Therapeutic amelioration of excess adiposity by bariatric surgery or incretin-based drugs appears to have substantial effects on the evolution and progression of HFpEF, with reported reductions of 40% to 60% in the risk of heart failure hospitalizations. Hypertension also increases the risk of heart failure, but in Mendelian randomization studies, HFpEF is more strongly linked to obesity than to hypertension. Furthermore, the available evidence from clinical trials does not support a consistent link between blood pressure lowering and a reduced risk of HFpEF, particularly in patients with coexisting obesity. Although a history of hypertension is exceptionally prevalent among patients with established HFpEF, in trials of patients with established HFpEF, drugs that lowered systolic blood pressure by 3 to 7 mm Hg yielded a heart failure event risk reduction of only 5% to 18%. Furthermore, the magnitude of the observed benefit on heart failure events was not related to the elevation of baseline systolic blood pressure or the magnitude of the drug-related decreases in blood pressure. Adiposity causes hypertension, and if excess adiposity is not alleviated, blood pressure lowering with many antihypertensive drugs may not be able to alleviate left ventricular systolic and diastolic and vascular stiffness. Taken together, the totality of evidence suggests that-in the current era-central adiposity appears to be more important than hypertension as a determinant of the evolution and progression of HFpEF.
