Arterial stiffness in heart failure with preserved ejection fraction: is this a new predisposing factor?

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome characterized by diastolic dysfunction (DD), impaired left ventricular relaxation and elevated left ventricular filling pressures (LVFP), with limited disease-modifying therapeutic options. Emerging evidence implicates the association between arterial stiffness and the development of HFpEF. This review aims to summarize current evidence on the relationship between arterial stiffness and HFpEF and to explore its potential implications for risk stratification and future therapies. Structural and functional vascular changes increase pulsatile afterload and disrupt ventricular-arterial coupling (VAC), leading to myocardial hypertrophy, fibrosis and DD. Arterial stiffening is closely associated with common HFpEF comorbidities including hypertension, diabetes mellitus, obesity and atrial fibrillation, reflecting shared mechanisms such as endothelial dysfunction and systemic inflammation. Several non-invasive indices of arterial stiffness correlate with DD, reduced exercise capacity and adverse clinical outcomes, underscoring their potential prognostic value. Additionally, emerging indices that integrate vascular and myocardial mechanics, providing a more comprehensive assessment of VAC, may offer incremental value in risk stratification. Although arterial stiffness represents a promising therapeutic target in HFpEF, it remains uncertain whether the reduction of arterial stiffness after pharmacological therapies translates into improved VAC and clinical outcomes. We need new insights into the interplay between arterial stiffness and HFpEF and novel therapeutic strategies should be tested.