Leukocyte telomere length and risk of heart failure with preserved ejection fraction in high-risk Chinese patients with hypertension under 65 years

Shorter leukocyte telomere length (LTL) is associated with aging-related cardiovascular diseases, but its relationship with heart failure with preserved ejection fraction (HFpEF) in high-risk Chinese patients with hypertension under 65 years remains unclear. In this observational prospective study, we investigated 646 patients with hypertension aged < 65 years with diabetes, coronary heart disease (CHD), or ≥ 3 cardiovascular risk factors. Baseline assessments included clinical evaluation, measurement of aging markers (LTL and mitochondrial DNA copy number) and echocardiography. Participants underwent scheduled quarterly follow-up for 5 years, with documentation of major adverse cardiovascular events (MACEs), including cardiovascular mortality, myocardial infarction, ischemia-driven revascularization, stroke and heart failure hospitalization. At the final follow-up visit, the evaluation for HFpEF was performed through echocardiography and plasma B-type natriuretic peptide (BNP) measurement. Participants were stratified by LTL tertiles: long (> 79.89; n = 216), mid (58.49-79.89; n = 214), and short (< 58.49; n = 216). Compared with the long and mid LTL groups, the short LTL group had a higher prevalence of male, smoking, hyperlipidemia, diabetes, and CHD, along with elevated blood pressure and fasting blood glucose, but lower mitochondrial DNA copy number (all P < 0.05). At 5-year follow-up, HFpEF prevalence increased with shorter LTL (15.7%,11.2% and 7.9% across LTL tertiles, p = 0.037). Multivariable logistic regression analysis identified shorter LTL as an independent predictor of HFpEF (adjusted OR 2.087, 95% CI: 1.017, 4.280, p = 0.045), in addition to CHD, uric acid, and C-reactive protein. Compared with the long LTL group, both the short (adjusted hazard ratio [HR] 1.953, 95% CI 1.259-3.028; P = 0.003) and mid LTL groups (adjusted HR 1.581, 95% CI: 1.015-2.464, P = 0.043) showed a significantly increased risk of 5-year MACE. In conclusion, shorter LTL independently predicts HFpEF development and adverse cardiovascular outcomes in high-risk Chinese patients with hypertension under 65 years, suggesting telomere biology may contribute to HFpEF pathogenesis and clinical outcomes in this population.