Sex-related differences in the associations between plasma free fatty acid levels and clinical features in patients with hypertrophic cardiomyopathy

BACKGROUND: Previous studies have indicated that inefficient energy utilization may play a pivotal role in hypertrophic cardiomyopathy (HCM). However, whether plasma free fatty acid (FFA), a main energy substrate of heart, has an effect on HCM remains unclear. Besides, several studies have suggested sex-related differences in HCM features and FFA metabolism. Here, we aimed to explore the association between plasma FFA levels and HCM and potential effects of sex on this relation. METHODS: A total of 412 patients (age 47.8 ± 12.7 years, 243 males (59.0%)) with HCM were recruited. Complete medical history was collected. Echocardiography and cardiovascular magnetic resonance imaging (CMRI) were performed. Fasting plasma FFA was determined by clinical laboratory. Left ventricular mass (LVM), maximum wall thickness (MWT), and left atrium diameter (LAD) were assessed with CMRI. RESULTS: The median FFA levels were 0.38 (interquartile range (IQR) 0.27–0.52) mmol/L in men and 0.40 (IQR 0.30–0.59) mmol/L in women. The FFA levels were significantly lower in men compared with those in women (p = 0.005). Compared with women, men had greater LVM index (LVMI) (96.8 ± 37.6 vs. 78.6 ± 31.5 g/m(2), p < 0.001). FFA levels in male patients correlated positively with LVM, LVMI, LAD, cholesterol levels, high-density lipoprotein-cholesterol (HDL-C) levels, heart rate, and systolic blood pressure (SBP). However, none of these variables were significantly associated with sqrt (FFA) in female patients except a borderline correlation of LAD (p = 0.050). Multiple linear regression analysis was performed in male patients and revealed that HDL-C (β = 0.191, p = 0.002), heart rate (β = 0.182, p = 0.004), SBP (β = 0.167, p = 0.007), LVMI (β = 0.132, p = 0.032), and LAD (β = 0.165, p = 0.009) were independently associated with increasing FFA levels. CONCLUSIONS: In patients with HCM, LVMI, LAD, HDL-C, SBP, and heart rate were independently associated with increasing plasma FFA levels in males, whereas not in females. These results suggest that sex may affect the pathogenesis of HCM through influencing FFA metabolism. And these sex-related differences should be taken into account in therapeutic approaches to influence myocardial FFA metabolism in HCM.