Omega-3 Red Blood Cell Content Is Associated with Fat Mass Index and Leptin in Subjects with Obesity and Heart Failure with Preserved Ejection Fraction (P21-001-19)

Overweight and obesity affect 80% of patients with heart failure and preserved ejection fraction (HFpEF). Exercise intolerance is a cardinal manifestation of HFpEF and is associated with excess fat mass (FM). Dietary polyunsaturated fatty acids (PUFA) have been associated with lower FM. However, the relationship between Omega-3 (N-3) PUFA and FM in HFpEF remains unclear. Red blood cell membrane (RBC) N-3 and omega-6 (N-6) PUFA content may serve as better objective measures of intake than subject-reported data. We hypothesized that increased RBC omega-3 (N-3) content is associated with lower FM and leptin in subjects with obesity and HFpEF. Twenty-four consecutive subjects with HFpEF underwent body composition measurement with bioelectrical impedance analysis to obtain FM Index (FMI; kg/m²) and venipuncture to obtain RBC total percentage of N-3 PUFA content (RBC N-3%) as well as the ratio of N-6 to N-3 PUFA (N-6/N-3 ratio). Fourteen subjects were female (58%) with a median age of 53 (interquartile range [IQR] 48–63). Median BMI was 42.4 kg/m² (38.1–47.4) and FMI was 18.7 kg/m² (14.2–22.7). Median leptin was 82.5 ng/mL (63.5–116.5), RBC N-3% was 7.4% (6.6–8.9), and N-6/N-3 ratio was 5.00 (4.03–5.70). RBC N-3% was inversely associated with FMI (r = −0.406, P = 0.049), while N-6/N-3 ratio was positively associated with FMI (r = +0.472, P = 0.020) (Figure 1A and B). N-6/N-3 ratio was also associated with leptin (r = +0.462, P = 0.023), while RBC N-3% presented an inverse trend with leptin (r = −0.388, r = 0.061) (Figure 1C and D). Higher percentage of N-3 PUFA in RBC membranes is associated with lower FMI and leptin in subjects with obesity and HFpEF. These findings suggest that increasing dietary N-3 intake and reducing N-6/N-3 ratio may protect against adiposity in HFpEF. This cross-sectional analysis was performed from baseline data of the DHART2 clinical trial (NCT02173548) and was funded by the NIH (1R34HL11348-01A1).