Graded association between lipoprotein(a) levels and left ventricular diastolic dysfunction in preclinical heart failure

Background Lipoprotein(a) [Lp(a)] and low-density lipoprotein cholesterol (LDL-C) are established independent and additive risk factors for atherosclerotic cardiovascular disease (ASCVD). In addition to its pro-atherogenic and pro-inflammatory properties, elevated Lp(a) has been linked to incident heart failure and adverse cardiovascular outcomes. However, whether Lp(a) is associated with early myocardial functional impairment, particularly left ventricular (LV) diastolic dysfunction in the preclinical stages of heart failure, remains uncertain. Purpose To investigate the association between circulating Lp(a) levels and LV diastolic dysfunction in patients with heart failure stage A or B and no prior heart failure hospitalization. Methods Among 624 consecutive patients with established or at-risk ASCVD who underwent Lp(a) measurement between March 2024 and December 2025, 406 patients with heart failure stage A or B were included after excluding those with prior heart failure hospitalization, atrial fibrillation, or unavailable echocardiographic assessment. Patients were categorized into low and high Lp(a) groups according to the median value (9.7 mg/dL). LV diastolic function was assessed according to the 2016 ASE/EACVI recommendations. Diastolic dysfunction was defined as ≥2 abnormal parameters among septal or lateral e′ velocity, average E/e′ ratio, left atrial volume index, and tricuspid regurgitation velocity. Quartile analyses were performed to assess dose–response relationships. Multivariable logistic regression using log-transformed Lp(a) was conducted after adjustment for age, LDL-C, and HbA1c. Results The mean age was higher in the high Lp(a) group than in the low Lp(a) group (70±13 vs 67±13 years, P=0.003), whereas LDL-C and HbA1c levels did not differ. Left ventricular ejection fraction and septal and lateral e′ velocities were similar between groups. In contrast, average E/e′ ratio and left atrial volume index were significantly higher in the high Lp(a) group (11.7±5.2 vs 10.5±3.8, P=0.012; 32.4±12.4 vs 29.1±10.2 mL/m², P=0.003). The prevalence of LV diastolic dysfunction was significantly greater in the high Lp(a) group than in the low Lp(a) group (15.8% vs 4.4%, P<0.001). Quartile analyses demonstrated a graded increase in diastolic dysfunction prevalence across increasing Lp(a) quartiles (3.0%, 5.8%, 13.0%, and 18.5%; P for trend <0.01). In multivariable analysis, log-transformed Lp(a) remained independently associated with LV diastolic dysfunction (OR 1.48, 95% CI 1.04–2.13; P=0.028), independent of age, LDL-C, and HbA1c. Conclusions Elevated Lp(a) levels were independently associated with LV diastolic dysfunction in patients without prior heart failure hospitalization. These findings suggest that Lp(a) may contribute to early myocardial functional impairment and could serve as a biomarker for early heart failure risk stratification in high-risk populations.