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Pathophysiologic importance of visceral adipose tissue in women with heart failure and preserved ejection fraction

Sorimachi, Hidemi, Obokata, Masaru, Takahashi, Naoki, Reddy, Yogesh N V, Jain, Christopher C, Verbrugge, Frederik H, Koepp, Katlyn E, Khosla, Sundeep, Jensen, Michael D, Borlaug, Barry A·2021·European Heart Journal
DOI 10.1093/eurheartj/ehaa823
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Abstract

Aims: Central obesity is a major risk factor for heart failure with preserved ejection fraction (HFpEF), particularly in women, but the mechanisms remain unclear. We hypothesized that sex-specific differences in visceral adipose tissue (VAT) content would differentially relate to haemodynamic severity of HFpEF in women and men. Methods and results: Abdominal computed tomography (CT) and invasive haemodynamic exercise testing were performed in 105 subjects with HFpEF (63 women) and 105 age-, sex-, and body mass index-matched controls. Visceral adipose tissue area was quantified by CT. As compared with control women, VAT area was 34% higher in women with HFpEF (186 ± 112 vs. 139 ± 72 cm2, P = 0.006), while VAT area was not significantly different in men with or without HFpEF (294 ± 158 vs. 252 ± 92 cm2, P = 0.1). During exercise, pulmonary capillary wedge pressure (PCWP) increased markedly and to similar extent in both men and women with HFpEF. Women with increased VAT area displayed 33% higher PCWP during exercise compared with women with normal VAT area (28 ± 10 vs. 21 ± 10 mmHg, P = 0.001), whereas exercise PCWP was similar in men with or without excess VAT (24 ± 9 vs. 25 ± 6, P = 0.89). In women, each 100 cm2 increase in VAT area was associated with a 4.0 mmHg higher PCWP (95% CI 2.1, 6.0 mmHg; P < 0.0001), but there was no such relationship in men (interaction P = 0.009). Conclusions: These data suggest that accumulation of excess VAT plays a distinct and important role in the pathophysiology of HFpEF preferentially in women. Further research is needed to better understand the mechanisms and treatment implications for visceral fat in HFpEF.

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  • As compared with nonobese HFpEF, patients with obesity-related HFpEF display distinct pathophysiologic features, including greater volume expansion, more severe inflammation, increases in visceral and paracardiac adipose tissue and more severe myocardial injury.

    “As compared with nonobese HFpEF, patients with obesity-related HFpEF display distinct pathophysiologic features, including greater volume expansion5,17, more severe inflammation6,7, increases in visceral and paracardiac adipose tissue5,15,18,19 and more severe myocardial injury15.”

    From Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial (2025) · cites this paper as [19]

    The Sex-stratified differences in fat distribution section reports greater visceral adipose tissue in women with HFpEF than in BMI-matched women without heart failure. That is not a comparison of obesity-related with nonobese HFpEF. The Subject characteristics section says epicardial fat thickness was similar between groups, and the passages found do not establish more severe myocardial injury. (LLM, conf=0.87)

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  • Sensitivity analyses were performed using eGFR calculated with the 2021 creatinine-based CKD-EPI formula and separately with the combined creatinine-cystatin C CKD-EPI formula.

    “Sensitivity analyses were also performed using eGFR calculated determined using the 2021 creatinine-based CKD-EPI formula43, and separately using the combined creatinine-cystatin C CKD-EPI formula (Supplementary Appendix 2)19.”

    From Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial (2025) · cites this paper as [19]

    The cited paper’s baseline-characteristics table (labeled Conclusions; page unavailable) reports estimated GFR, but does not identify the formula used. Searches for the combined creatinine–cystatin C CKD-EPI formula and cystatin C sensitivity analyses found no passage addressing them. The 2021 creatinine-based formula has a separate citation in the citing sentence. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Citations

Cites

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Research works printed but not linked: 40

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Metadata

Authors
Sorimachi, H., Obokata, M., Takahashi, N., Reddy, Y. N. V., Jain, C. C., Verbrugge, F. H., Koepp, K. E., Khosla, S., Jensen, M. D., & Borlaug, B. A.
Venue
European Heart Journal
Publisher
Oxford University Press (OUP)
Published
2020-11-23
Volume
42
Issue
16
Pages
1595-1605
ISSN
  • 0195-668X
  • 1522-9645
DOI
10.1093/eurheartj/ehaa823
Cited by
183
References
7
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Funders
  • NIH (RO1 HL128526, U10 HL110262, AR027065, UL1 TR002377)
  • Belgian American Educational Foundation
  • Special Research Fund
  • Hasselt University (BOF19PD04)

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