AIMS: Understanding sex-related cardiovascular differences in those with pre-HFpEF (asymptomatic with normal ejection fraction, elevated natriuretic peptides and structural or functional heart disease) could help explain why females are more likely to develop symptomatic HFpEF compared with males. This study analyses sex-related cardiovascular differences in pre-HFpEF, including measures of cardiovascular stiffness and vascular resistance derived from cardiac magnetic resonance imaging (CMR) and Doppler echocardiography. METHODS AND RESULTS: This post hoc analysis of the PARABLE trial enrolled 250 patients with pre-HFpEF. CMR and Doppler echocardiography were used to estimate baseline markers of cardiovascular stiffness and resistance, including effective arterial elastance (EAE), systemic vascular resistance (SVR), total arterial compliance (TAC), left ventricular end diastolic pressure (LVEDP) and left ventricular end diastolic chamber stiffness index (LVSId). The population median age was 72.0 [IQR 68.0
77.0] years and 38.4% were female. Both sexes had a similar age, blood pressure, HbA1c, renal function and H2FPEF score. Fewer female participants had a diagnosis of diabetes and coronary artery disease. When adjusted for age, hypertension, diabetes, obesity and vascular disease, female participants had higher pulse pressures (62.1 (SD 15.3) vs. 60.1 (SD 12.5) mmHg, P <
0.002) as well as higher median [IQR] levels of LDL-cholesterol (2.50 [2.10
3.25] vs. 2.00 [1.60
2.40] mmol/L, P <
0.002), EAE (1.55 [1.26
1.84] vs. 1.26 [1.05
1.51] mmHg/mL/m CONCLUSIONS: Markers of elevated cardiovascular stiffness and vascular resistance are seen in female versus male participants with pre-HFpEF, suggesting that sex-related pathophysiological mechanisms are present before symptoms of HF develop.