Sex differences in resting sympathetic activity and systemic inflammation in heart failure with preserved ejection fraction

Background: The prevalence of heart failure with preserved ejection fraction (HFpEF) is higher in older women than in older men, with worse clinical outcomes for older women. The underlying mechanisms are unclear, but aberrant sympathetic neural control may in part contribute. Notably, >80% of patients with HFpEF, particularly women, are overweight or obese. This observation is important because obesity can augment chronic inflammation, which may lead to sympathetic overactivity. Therefore, we hypothesized that older women with HFpEF would have augmented sympathetic activity at rest compared to older men with HFpEF and similarly aged non-HFpEF controls, which would be associated with chronic inflammation. Methods: We studied 24 women with HFpEF [mean±SD; 70±7 yrs, body mass index (BMI) 39±7 kg/m2], 17 men with HFpEF (71±8 yrs, 35±6 kg/m2), 41 control women (70±7 yrs, 27±5 kg/m2), and 26 control men (71±6 yrs, 27±3 kg/m2). Mean arterial pressure (MAP), heart rate (HR), and muscle sympathetic nerve activity (MSNA, peroneal nerve microneurography) were measured during 10 minutes of supine rest. Blood samples were drawn for the measurement of C-reactive protein (CRP). Results: BMI was greater in patients with HFpEF compared with controls (p<0.001). There were no differences in resting MAP between groups and sexes (87±12 and 91±16 mmHg in men and women with HFpEF vs. 94±9 and 91±10 mmHg in control men and women, Pinteraction=0.130). Patients had higher HR compared to controls (p<0.001), but there were no differences between sexes (Pinteraction=0.108). Women with HFpEF had greater resting MSNA burst frequency (BF) compared to men with HFpEF (41±15 vs. 31±11 bursts/min, P=0.047) and control women (28±13 bursts/min, P=0.001); however, MSNA BF was not different between men with HFpEF and control men (31±13 bursts/min, P=0.940). All results were similar for MSNA burst incidence (Pinteraction=0.012). CRP was higher in patients than controls (P=0.002), but there were no differences between sexes (Pinteraction=0.148). However, a mediation analysis indicated that resting MSNA BF was associated with BMI rather than CRP in women. On the other hand, we did not observe any relationships between these variables in men. Conclusions: Women, but not men, with HFpEF have augmented sympathetic activity at rest, which seems to be linked to obesity rather than systemic inflammation. This sustained sympathetic overactivity may contribute to the poor clinical outcomes in women with HFpEF. Supported by the National Institutes of Health (P01HL137630) and Harry S Moss Heart Trust, Bank of America, N.A., Trustee. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.