Body mass index extremes association with worsened disease and clinical outcomes in patients with hypertrophic cardiomyopathy

Background Hypertrophic cardiomyopathy (HCM) is a primary myocardial disease that may be associated with worsened prognosis in the presence of other comorbidities. Body mass index (BMI) has been linked to major outcomes in heart hailure – the so-called obesity paradox. However, whether a similar pattern of association is observed in HCM remains uncertain. Objective To assess whether BMI is linked to disease severity and adverse outcomes in HCM. Methods Retrospective analysis of patients with HCM diagnosis followed at a tertiary center. Patients were categorized according to BMI class into 6 groups: underweight (BMI < 20 kg/m²), normal weight (BMI 20-24,9 kg/m²), pre-obesity (BMI 25-29,9 kg/m²), class I (BMI 30-34,9 kg/m²), class II(BMI 35-39,9 kg/m²) and class III obesity (BMI >40 kg/m²). Patients aged over 16 years and with at least 1 year of follow-up were included. The primary endpoint was a composite of appropriate implantable cardioverter-defibrillator shocks, heart transplantation and all-cause death. Survival analysis was assessed by Kaplan–Meier curves. Results A total of 545 HCM patients were included (mean age 66 ± 15 years; 57% male; mean BMI 27.4 ± 4.7 Kg/m2). Patients were distributed across BMI categories as follows: underweight (17 [3%]); normal weight (153 [28%]); pre-obesity (235 [43%]); class I(107 [20%]); class II(22 [4%]) and class III obesity (11 [2%]). BMI extremes were associated with more syncope (11.8 vs 15.7 vs 6.0 vs 6.5 vs 13.6 vs 9.1%; p= 0.045); higher median NT proBNP levels (2864 vs 1488 vs 540 vs 1371 vs 1090 vs 1691 pg/mL; p= 0.006); greater mean maximum left ventricular wall thickness (18.5 vs 17.5 vs 17.3 vs17.4 vs 18.3 vs 18 mm; p= 0.049); and more frequent apical aneurysm (0% vs 1.3% vs 4.3% vs 1.9% vs 13.6% vs 27.3%; p<0.001), respectively (central figure). No significant differences on other clinical or ecocardiographic markers were noted. Over a median follow-up of 4 (2-8) years, 91 (17%) patients reached the primary composite endpoint. Underweight and severe obesity were significantly associated with a higher risk of the composite outcome (41.2 vs 20.3 vs 14.0 vs 13.1 vs 18.2 vs 18.2%; p=0.031; respectively), mainly due a higher risk of death (29.4 vs. 13.7 vs. 11.1 vs. 10.3 vs. 9.1 vs. 18.2%, p=0.031). Conclusions In a contemporary HCM cohort, BMI extremes were associated with a worsened clinical profile and a higher risk of major cardiovascular outcomes. We observed a "U-shaped" risk pattern across BMI categories, suggesting that targeted weight management interventions in underweight and moderate-to-severe obese patients could confer HCM-related benefits.