Sex-specific impact of left atrial remodelling on heart failure with preserved ejection fraction: a study in arterial hypertensive patients with and without left ventricular hypertrophy

Background Left atrial (LA) remodelling has been associated with increased HFpEF risk in patients with arterial hypertension (AH), particularly in those with left ventricular hypertrophy (LVH). However, whether this structural pattern extends to AH individuals without LVH or differs according to sex remains unclear. The H2FPEF score estimates HFpEF probability but does not incorporate structural cardiac remodelling parameters, such as septal wall thickness (SWT) or LA size. Purpose To evaluate sex-specific associations of LA diameter and SWT with HFpEF risk estimated by the H2FPEF score in AH patients. Methods A total of 8.729 medical records were screened, and 164 AH patients aged >35 years with Teicholz ejection fraction≥55% were included. HFpEF risk was classified using the H2FPEF score (<6: low-risk; ≥6 high-risk). Additional analyses were performed according to LA diameter (≤40 mm: control group; >40 mm: enlarged group) and SWT (≤11 mm: control group; >11 mm: hypertrophy group). Univariate and multivariable logistic regression analyses, including sex-stratified models, and receiver operating characteristic curve analyses were performed. Results Age (73.6±10.2 vs. 69.8±12.0 years, p=0.067), SWT (11.0±1.3 vs. 10.0±2.1 mm, p=0.733), and sex distribution (p=0.601) did not differ between risk groups. In contrast, body mass index (BMI) (32.5±6.6 vs. 27.1±5.8 kg/m²; p<0.001) and LA diameter (46.0±5.4 vs. 42.6±6.0 mm, p=0.003) were significantly higher in the high-risk group. In multivariable analysis, age (OR 1.05, 95% CI 1.01–1.10; p=0.024), BMI (OR 1.16, 95% CI 1.08–1.25; p<0.001), and LA diameter (OR 1.08, 95% CI 1.01–1.17; p=0.035) were independently associated with high HFpEF risk, whereas SWT was not. LA enlargement was associated with higher H2FPEF scores in both women (4.46±1.50 vs. 3.18±1.33; p<0.001) and men (4.45±1.63 vs. 2.93±1.14; p=0.001), remaining independently associated in sex-stratified models (women: OR 2.05, 95% CI 1.38–3.05; p<0.001; men: OR 2.39, 95% CI 1.28–4.47; p=0.006), with good discriminative performance (women: AUC 0.739; p<0.001; men: AUC 0.764; p=0.003). Among women, LVH was associated with higher H2FPEF score (p=0.019) and larger LA diameter (p=0.048), with SWT remaining independently associated with HFpEF risk (OR 1.35; 95% 1.04-1.76; p=0.027). In contrast, no significant associations between SWT, LA diameter, and HFpEF risk were observed in men. Conclusion LA remodelling, rather than SWT, appears to be the predominant echocardiographic determinant of HFpEF risk in AH patients. LA enlargement was independently associated with higher HFpEF risk in both sexes, whereas SWT showed independent significance only in women. These findings suggest an atrial-centred, sex-specific HFpEF risk profile and highlight the potential incremental value of integrating LA remodelling into HFpEF risk assessment beyond the H2FPEF score