Table 4.

Pathophysiological mechanisms and clinical observations demonstrating that women may be at greater risk for inflammatory‐metabolic heart failure with a preserved ejection fraction than men

• Women predominate among community‐based cohorts of HFpEF

• Women exhibit higher pulmonary venous pressures with volume loading, possibly because women have a greater limitation of systemic venous capacitance

• Women show greater degree of arterial stiffness, more impaired ventricular–vascular coupling, and more striking LV concentric remodelling with pressure overload than men

• LV volumes are smaller in women than in men (even when accounting for differences in body surface area), and thus, women are more reliant on a higher ejection fraction to maintain stroke volume and cardiac output

• In patients with HFpEF, women show greater increases in pulmonary wedge pressure and abnormalities of diastolic filling dynamics at a given workload and manifest greater LV wall thickness than men. Women with HFpEF have greater symptoms and disability than men

• Systemic inflammatory and metabolic disorders that are linked to HFpEF are more common in women than men

• Women are more likely than men to experience systemic inflammation and show increases in proinflammatory cytokines in response to increases in body fat

• As compared to men, women are more likely to develop myocardial steatosis in response to metabolic derangements, and women have greater volumes of epicardial or intramyocardial fat than men, particularly as they age and particularly if they have HFpEF

• Epicardial fat is accompanied by evidence of systemic inflammation, coronary microcirculatory abnormalities, abnormalities of diastolic filling and increases in blood pressure in women, but not in men

• As compared with men, women are more likely to show adverse changes in cardiac structure and function in response to systemic inflammation and metabolic disorders. Obesity causes greater structural changes in the hearts of women, and obesity and diabetes increases the risk of HFpEF more in women than in men

• Women have higher levels of leptin and aldosterone than men, and they are more sensitive to the effects of agonists of aldosterone secretion. Obesity is more likely to be accompanied by hyperaldosteronism in women, and women show heightened leptin response to inflammation and visceral adiposity

• In states of adipose tissue inflammation and insulin resistance, circulating levels of natriuretic peptides are decreased more in women than men. As compared with men with HFpEF, women with HFpEF have lower levels of B‐type natriuretic peptide

• Women show greater increases in sympathetic activity in response to leptin than men, and leptin is correlated with blood pressure in women, but not in men

• Women with HFpEF may show a greater reduction in all‐cause mortality with mineralocorticoid receptor antagonism than men

• Women with HFpEF may show a greater reduction in hospitalizations for heart failure with neprilysin inhibition than men

HFpEF, heart failure with a preserved ejection fraction; LV, left ventricular.