
==== Front
BMC Cardiovasc Disord
BMC Cardiovasc Disord
BMC Cardiovascular Disorders
1471-2261
BioMed Central London

4118
10.1186/s12872-024-04118-0
Research
Abdominal obesity is associated with increased worsening renal function risk in patients with heart failure with preserved ejection fraction
Zhang Quan
Tai Shi
Zhou Shenghua zhoushenghua@csu.edu.cn

grid.216417.7 0000 0001 0379 7164 Department of Cardiovascular Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011 China
9 9 2024
9 9 2024
2024
24 47719 2 2024
13 8 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Background

Worsening renal function (WRF) is a frequent comorbidity of heart failure with preserved ejection fraction (HFpEF). However, its relationship with abdominal obesity in terms of HFpEF remains unclear. This study aimed to evaluate the value of waist circumference (WC) and body mass index (BMI) in predicting WRF and examine the correlation between abdominal obesity and the risk of WRF in the HFpEF population.

Methods

Data were obtained from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial. Abdominal obesity was defined as WC ≥ 102 cm for men and ≥ 88 cm for women. WRF was defined as doubling of serum creatinine concentration from baseline. Restricted cubic splines and receiver operating characteristic curves were used to evaluate the value of WC and BMI in predicting WRF. Cumulative incidence curves and cox proportional-hazards models were used to compare patients with and without abdominal obesity.

Results

We included 2,806 patients with HFpEF in our study (abdominal obesity, n: 2,065). Although baseline creatinine concentrations did not differ, patients with abdominal obesity had higher concentrations during a median follow-up time of 40.9 months. Unlike BMI, WC exhibited a steady linear association with WRF and was a superior WRF predictor. Patients with abdominal obesity exhibited a higher risk of WRF after multivariable adjustment (hazard ratio: 1.632; 95% confidence interval: 1.015–2.621; P: 0.043).

Conclusions

Abdominal obesity is associated with an increased risk of WRF in the HFpEF population.

Trial registration

URL: https://beta.clinicaltrials.gov. Unique identifier: NCT00094302.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12872-024-04118-0.

Keywords

HFpEF
Worsening renal function
Waist circumference
Body mass index
Abdominal obesity
Body fat distribution
National Natural Science Foundation of China82150006 issue-copyright-statement© BioMed Central Ltd., part of Springer Nature 2024
==== Body
pmcBackground

Heart failure with preserved ejection fraction (HFpEF) representing over 50% of the total heart failure population, which is continuously increasing in number [1]. Obesity is the most common comorbidity of HFpEF, and over 80% of patients were reported as being overweight or obese in the HFpEF population, which is double the rate observed in the general population [2, 3]. Patients with cardiometabolic phenotype significantly differ from non-affected patients in several ways, including greater plasma volume and epicardial fat tissue, more ventricular remodeling and dysfunction, and lower natriuretic peptide levels [4].

Worsening renal function (WRF) is one of the most clinically important complications of heart failure, occurring in approximately 25% of all cases [5]. It restricts the range of medications available for use in affected patients, complicates volume management, promotes the development of heart failure, and induces a heightened risk of subsequent mortality [5–8]. Therefore, the early identification of patients at elevated risk of WRF may be important.

As a classic anthropometric indicator, high body mass index (BMI) is correlated with the onset of worsening renal function in the population without kidney failure [9]. However, BMI has limitations in predicting risks in patients with HFpEF due to the challenge of distinguishing between central and subcutaneous fat. [10, 11]. As the importance of body fat distribution becomes more recognized, abdominal obesity, accessed by waist circumference (WC), has received more attention than general obesity. It is reported that abdominal obesity is associated with the elevated risk of all-cause mortality in the HFpEF population [12]. However, the longitudinal relationship between abdominal obesity and WRF in this population is unclear. Therefore, we conducted a study with the aim of reevaluating the anthropometric indicators and assessing their predictive potential for WRF in this population.

Methods

Patient population

Data were obtained from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, which is a randomized, double-blind phase III trial of spironolactone at 233 sites in six countries. The methodology of the trial has been previously described [13]. In short, patients aged ≥ 50 years who had a left ventricular ejection fraction ≥ 45% and a history of hospitalization for heart failure in the previous 12 months or an elevated level of brain natriuretic peptides (BNP) in the 60 days before randomization (BNP ≥ 100 pg/ml or N-terminal pro-BNP ≥ 360 pg/ml), systolic blood pressure < 140 mmHg, and a serum potassium concentration ≤ 5.0 mmol/L were included. Patients with a life expectancy < 3 years, estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2, or a serum creatinine concentration ≥ 2.5 mg/dL were excluded [13]. Since TOPCAT trial included patients with an LVEF > 45%, it recruited patients with mildly reduced as well as preserved ejection fraction, so we excluded patients whose LVEF on enrolment below 50%. Furthermore, we excluded patients with missing BMI and WC data in the current study. A WC of ≥ 102 cm for male patients and ≥ 88 cm for female patients was used as the criterion for abdominal obesity [14]. A final total of 2806 patients were suitable for inclusion. This study followed the Helsinki Declaration principles and ethical approval was granted by the Hunan Provincial Hospital ethics committee and all patients provided written informed consent.

Definition of worsening renal function

The optimal definition of WRF has not yet been established. In the TOPCAT trial, WRF was defined as doubling of serum creatinine levels from baseline on two determinations separated by ≥ 28 days and beyond the upper reference limit [15]. Follow-up laboratory tests were performed in weeks 1, 4, and 8, months 4, 8, and 12, and every 6 months thereafter. We used an eGFR-based definition of WRF for the sensitivity analyses, defined as a relative decrease of eGFR of > 25%, between baseline and month 4 [16], the calculation of eGFR during follow-up has been previously described [17].

Statistical analysis

Baseline characteristics are reported as frequencies with corresponding percentages for categorical variables. Continuous variables are presented as mean ± standard deviation for normally distributed data, while for non-normally distributed data, median with interquartile range was used. Normality was assessed using normal quantile-quantile plots. The chi-square test was used to compare categorical variables, whereas Student’s t-test or the Mann–Whitney U test was used to compare normally and non-normally distributed continuous variables, respectively.

Cox proportional hazards regression models and cumulative incidence curves were utilized to explore the correlation between abdominal obesity and the development of WRF. We adjusted for different baseline covariates in two models to reduce the potential bias caused by multicollinearity. Model 1 included age, gender, race, hypertension, diabetes, smoking, drinking per week. Model 2 is adjusted for all variables that were significantly different between the category of interest in Table 1 and the logistic regression predictors of abdominal obesity in the HFpEF population (Supplement Table 1). For the sensitivity analyses, we further tested the effect of abdominal obesity on WRF in 8 subgroups in the univariate cox regression models (age, sex, American region, New York Heart Association functional class, eGFR, hypertension, diabetes, and use of spironolactone) and performed interaction analyses to assess potential interaction effect in these subgroups.

Table 1 Baseline characteristics of patients with and without abdominal obesity

	Total	Abdominal obesity	P value	
	n: 2806	(-) (n: 741)	(+) (n: 2,065)	
Age, years	68.95 ± 9.56	69.35 ± 9.97	68.80 ± 9.41	0.19	
Women	1513 (53.92)	268 (36.17)	1245 (60.29)	< 0.01	
Race and ethnicity				< 0.01	
White	2519 (89.77)	686 (92.58)	1833 (88.77)		
Black	217 (7.73)	29 (3.91)	188 (9.10)		
Other	70 (2.49)	26 (3.51)	44 (2.13)		
NYHA class III/IV	888 (31.65)	180 (24.29)	708 (34.29)	< 0.01	
BMI, kg/m2				< 0.01	
< 24.9	347 (12.37)	280 (37.79)	67 (3.24)		
25.0–29.9	879 (31.33)	370 (49.93)	509 (24.65)		
>=30	1580 (56.31)	91 (12.28)	1489 (72.11)		
HR, beats/min	68.72 ± 10.35	67.90 ± 9.63	69.01 ± 10.59	0.01	
SBP, mmHg	129.53 ± 13.93	127.51 ± 13.30	130.25 ± 14.08	< 0.01	
DBP, mmHg	75.68 ± 10.71	75.70 ± 10.37	75.67 ± 10.83	0.96	
LVEF	58.89 ± 6.51	58.06 ± 6.48	59.19 ± 6.49	< 0.01	
Medical history					
HF hospitalization	2042 (72.77)	535 (72.20)	1507 (72.98)	0.68	
MI	649 (23.13)	192 (25.91)	457 (22.13)	0.04	
CABG	341 (12.15)	96 (12.96)	245 (11.86)	0.44	
PCI	387 (13.79)	103 (13.90)	284 (13.75)	0.92	
Stroke	218 (7.77)	48 (6.48)	170 (8.23)	0.13	
Angina pectoris	1327 (47.29)	396 (53.44)	931 (45.08)	0.01	
COPD	313 (11.15)	66 (8.91)	247 (11.96)	0.02	
PAD	1695 (60.41)	405 (54.66)	1290 (62.47)	0.57	
Hypertension	2593 (92.41)	658 (88.80)	1935 (93.70)	< 0.01	
Dyslipidemia	1695 (60.41)	405 (54.66)	1290 (62.47)	< 0.01	
Diabetes	921 (32.82)	132 (17.81)	789 (38.21)	< 0.01	
Smoking status	273 (9.73)	113 (15.25)	160 (7.75)	< 0.01	
Alcohol drinks/week				< 0.01	
0	2205 (78.58)	546 (73.68)	1659 (80.34)		
1–5	461 (16.43)	149 (20.11)	312 (15.11)		
5–10	102 (3.64)	35 (4.72)	67 (3.24)		
11+	38 (1.35)	11 (1.48)	27 (1.31)		
Creatinine, mg/dL	1.08 ± 0.29	1.07 ± 0.29	1.09 ± 0.30	0.20	
eGFR, ml/min/1.73 m2	67.49 ± 20.10	71.42 ± 22.10	66.07 ± 19.15	< 0.01	
Sodium, mmol/L	141.26 ± 4.22	141.43 ± 4.57	141.19 ± 4.09	0.22	
Potassium, mmol/L	4.26 ± 0.44	4.29 ± 0.43	4.25 ± 0.44	0.04	
Hemoglobin, g/dL	13.28 ± 1.66	13.47 ± 1.69	13.21 ± 1.64	< 0.01	
Glucose, mmol/L	102.00

(90.91-121.82)

	98.18

(89.00-109.55)

	105.45

(92.73-127.14)

	< 0.01	
Albumin, g/L	4.10

(3.80–4.40)

	4.16

(3.90–4.47)

	4.10

(3.80–4.40)

	0.90	
Spironolactone	1411 (50.29)	378 (51.01)	1033 (50.02)	0.64	
ACEI	1823 (64.97)	523 (70.58)	1300 (62.95)	< 0.01	
ARB	575 (20.49)	85 (11.47)	490 (23.73)	< 0.01	
Beta blockers	2182 (77.76)	578 (78.00)	1604 (77.68)	0.85	
CCB	1091 (38.88)	245 (33.06)	846 (40.97)	< 0.01	
Diuretics	2314 (82.47)	539 (72.74)	1775 (85.96)	< 0.01	
Statins	1451 (51.71)	348 (46.96)	1103 (53.41)	< 0.01	
Aspirin	1835 (65.40)	496 (66.94)	1339 (64.84)	0.30	
Baseline characteristics are summarized as frequencies (percentages) for categorical variables and as means ± standard deviations or medians (interquartile ranges) for continuous variables. ACEI: angiotensin-converting enzyme inhibitor, ARB: angiotensin receptor blocker, BMI: body mass index, CABG: coronary artery bypass grafting, CCB: calcium channel blockers, COPD: chronic obstructive pulmonary disease, DBP: Diastolic blood pressure, eGFR: estimated glomerular filtration rate, HR: heart rate, LVEF: left ventricular ejection fraction, MI: myocardial infarction, NYHA: New York Heart Association, PAD: Peripheral Arterial Disease, PCI: percutaneous coronary intervention, SBP: Systolic blood pressure

A multivariable cox proportional hazards model with restricted cubic splines was used to model the nonlinear correlation between BMI/WC and WRF. The potential of WC and BMI in predicting WRF was evaluated by receiver operating characteristic (ROC) curves and pairwise comparisons of ROC curves were conducted by Delong-test. A P-value < 0.05 was considered statistically significant. All analyses were conducted using R (v4.2.2, www.R-project.org) and IBM SPSS Statistics (v22.0, IBM Corp., Armonk, NY, USA).

Results

Clinical characteristics

Patients with abdominal obesity were more prone to be female and black and to have higher baseline heart rate, systolic blood pressure, BMI, and New York Heart Association functional class than those without abdominal obesity. Patients with abdominal obesity more often had a history of chronic obstructive pulmonary disease, hypertension, diabetes, and dyslipidemia and took ARBs, CCBs, statins and diuretics. A smaller number of patients with abdominal obesity had previously experienced myocardial infarction and angina pectoris, were current smokers (Table 1). Following randomization, patients experienced a short-term elevation in creatinine levels in both spironolactone and placebo arms, but patients with abdominal obesity demonstrated a tendency towards elevated serum creatinine concentration during follow-up visits, despite no significant differences in baseline creatinine concentration (P: 0.200) (Fig. 1).

Fig. 1 Serum creatinine concentration at the follow-up visits. During the entire follow-up period, serum creatinine concentration was lower in patients without abdominal obesity than that in those with abdominal obesity. Cr: creatinine

Abdominal obesity and the risk of WRF

After a median of 40.9 months’ follow-up period, 205 participants had developed WRF. Abdominal obesity significantly increased the risk of WRF in patients with HFpEF (unadjusted hazard ratio [HR]: 1.967; 95% confidence interval [CI]: 1.355–2.855; P < 0.001) when using the creatinine-based definition (Fig. 2A). Similar outcomes were observed with the eGFR-based definition (unadjusted HR: 1.275; 95% CI: 1.050–1.548; P: 0.014) (Fig. 2B).

Fig. 2 Cumulative incidence curves for worsening renal function. Abdominal obesity is associated with higher risk of WRF in patients with HFpEF. Similar results were obtained when using an eGFR-based definition of WRF. eGFR: estimated glomerular filtration rate

After adjusting for age, sex, and race, hypertension, diabetes, smoking, drinking per week, patients with abdominal obesity had a 60.1% higher risk of WRF. The increased risk remained significant after adjusting for all other confounding variables, with a 63.2% higher risk (Table 2). The results of subgroup analysis showed in Fig. 3, abdominal obesity was associated with an increased risk of WRF in all subgroups. Although the female subgroup, higher New York Heart Association functional class subgroup, hypertensive subgroup, diabetic subgroup, and both American and non-American subgroup didn’t exhibit statistically significant results, no interaction effects were discovered in any of the 8 subgroups, which enhance the credibility of the result.

Table 2 Risk of worsening renal function in HFpEF with and without abdominal obesity

	Abdominal obesity (–)	Abdominal obesity (+)	P value	
Unadjusted HR (95% CI)	1 (Ref)	1.967 (1.355–2.855)	< 0.001	
Model 1: HR (95% CI)	1 (Ref)	1.601 (1.086–2.361)	0.018	
Model 2: HR (95% CI)	1 (Ref)	1.632 (1.015–2.621)	0.043	
Model 1 included age, gender, race, hypertension, diabetes, smoking, drinking per week

Model 2 included age, gender, race, hypertension, diabetes, smoking, drinking per week, BMI, HR,

SBP, LVEF, MI, angina pectoris, COPD, dyslipidemia, eGFR, potassium, hemoglobin, glucose, ACEIs, ARBs, CCBs, diuretics, statins. CI: confidence interval, HFpEF: heart failure with preserved ejection fraction, HR: hazard ratio

Fig. 3 Subgroup analyses for worsening renal function. Abdominal obesity was associated with an increased risk of WRF in all subgroups, no interaction effects were discovered in all 8 subgroups. CI: confidence interval, eGFR: estimated glomerular filtration rate, NYHA: New York Heart Association

As illustrated in Fig. 4, BMI exhibited a nonlinear correlation with WRF in univariate model, patients with a mildly elevated BMI faced a lower risk of WRF, while excessively high or low BMIs led to an increased risk of WRF in univariate model, this relationship disappears when multivariable adjusted, while WC and WRF had a linear association in univariate and multivariate model. The ROC curves indicated that WC was superior to BMI for prediction of WRF (Fig. 5; Table 3).

Fig. 4 Restricted cubic splines for the relationship between BMI/WC and worsening renal function. Unlike BMI, WC shows a steady linear association with WRF in male and female patients. Full-adjusted model included age, gender, race, hypertension, diabetes, smoking, drinking per week, BMI, HR, SBP, LVEF, myocardial infarction history, angina pectoris history, COPD history, dyslipidemia history, eGFR, serum potassium, hemoglobin, glucose, use of ACEIs, ARBs, CCBs, diuretics, and statins. BMI: body mass index, CI: confidence interval, HR: hazard ratio, WC: waist circumference, WRF: worsening renal function

Table 3 Predictive capacity of BMI/WC in worsening renal function in HFpEF

Variable	AUC (95% CI)	Sensitivity	Specificity	Youden index	P-values	
Un-adjusted					0.002	
BMI	0.594 (0.550–0.638)	0.405	0.776	0.181		
WC	0.632 (0.591–0.673)	0.512	0.696	0.208		
Full-adjusted					0.005	
BMI + other factors	0.759 (0.727–0.792)	0.600	0.778	0.378		
WC + other factors	0.770 (0.739–0.801)	0.780	0.623	0.403		
Full-adjusted model included age, gender, race, hypertension, diabetes, smoking, drinking per week, BMI, HR, SBP, LVEF, MI, angina pectoris, COPD, dyslipidemia, eGFR, potassium, hemoglobin, glucose, ACEIs, ARBs, CCBs, diuretics, statins. AUC: area under the receiver operating characteristic curve, BMI: body mass index, CI: confidence interval, HFpEF: heart failure with preserved ejection fraction, WC: waist circumference

Fig. 5 Receiver operating characteristic curves for worsening renal function. WC was superior to BMI for prediction of WRF. BMI: body mass index, WC: waist circumference, WRF: worsening renal function. Other factors included age, gender, race, hypertension, diabetes, smoking, drinking per week, BMI, HR, SBP, LVEF, myocardial infarction history, angina pectoris history, COPD history, dyslipidemia history, eGFR, serum potassium, hemoglobin, glucose, use of ACEIs, ARBs, CCBs, diuretics, and statins

Discussion

Two main conclusions can be drawn from our study. First, abdominal obesity is associated with the elevated risk of WRF in the HFpEF population. Second, WC exhibited a greater capacity for predicting WRF than BMI.

Following randomization, patients experienced a short-term elevation in creatinine levels in both spironolactone and placebo arms, and those with abdominal obesity maintaining higher levels. However, previous study suggested that the beneficial effect on cardiovascular mortality is pronounced despite the incidence of WRF [16]. Similar results were observed in trials of diuretics and angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) [18, 19]. Those results led us to reevaluate the relationship between WRF and clinical outcomes, the prevalence of WRF may be overestimated owing to the phenomenon of “pseudo-WRF”, in this condition, a patient’s clinical status improves or remains constant despite an elevated serum creatinine concentration [20].

The relationship between visceral adipose tissue deposition and poor nephritic outcomes has gained attention in recent years. Studies showed that in obese, overweight, average-weight, and even lean people, a central pattern of fat distribution is an important factor in new-onset renal impairment [21, 22]. Possible reasons for the superiority of abdominal obesity in predicting WRF include the following. First, perirenal and renal sinus fat mechanically compress the thin loop of Henle and vasa recta of the renal medulla, resulting in reduced tubular flow and increased sodium reabsorption, which activates tubular glomerular feedback and exacerbates renal hyperfiltration [23]. Second, epicardial adipose tissue in HFpEF correlates with worsening hemodynamic parameters, which exacerbate the decreased effective renal perfusion pressure [24]. Third, visceral adipose tissue exhibits lower oxygen tension and more abundant macrophages, regulatory and natural killer T cells, and eosinophils, all of which secrete inflammatory cytokines and induce systemic inflammation, [25] together with increased oxidative stress, this type of inflammation causes wide-ranging endothelial dysfunction that eventually results in fibrosis of the heart and kidneys [26, 27].Fourth, lipolysis of visceral adipose tissue contributes 5–10% (normal-weight) and up to 25% (abdominal-obese) to hepatic free fatty acid delivery. This stimulates very-low-density lipoprotein production and ectopic fat accumulation in the kidneys, resulting in glomerulosclerosis, tubular injury, and fibrosis [28].

The subgroup analysis revealed differences in incidence rates across various subgroups, aligning with our expectations that patients with poorer health status and more comorbidities would have a higher incidence of WRF. For example, patients with NYHA class III-IV had a higher incidence of WRF (10.81% vs. 9.18%), and elderly patients also exhibited a higher incidence (7.79% vs. 6.40%). Notably, the results from the American region are significant, with patients in this region experiencing a dramatically higher incidence of WRF. However, neither the American nor the non-American subgroups showed statistically significant results, which may be attributed to the limited sample size of the TOPCAT trial and the substantial differences in baseline characteristics between regions [29]. Although there was no significant interaction effect of regions on the relationship between abdominal obesity and WRF, our findings warrant further confirmation in large-scale studies.

Furthermore, our study confirmed the findings about sex-specific difference, it suggested that males appear to be more susceptible to the impact of central obesity and the development of WRF. Indeed, sex differences in body-fat distribution have garnered attention in recent decades. The findings of the current study suggest that there are variations in the proportion of visceral adipose tissue between sexes, with men accumulating a higher proportion of visceral adipose tissue compared to women [30]. This kind of sex difference in fat distribution leads to a poorer prognosis in men with abdominal obesity compared to women, which is reported in previous studies [31–33].

As a modifiable risk factor, reduction of visceral adipose tissue following bariatric surgery, as in the Roux-en-Y gastric bypass, is reported to yield significantly improved left ventricular diastolic function, ventricular remodeling, and pericardial restraint [34–37]; to reverse tissue fibrosis; and to reduce the incidence of WRF in patients with or without pre-existing kidney disease [38, 39]. The underlying mechanisms may be associated with inhibition of chronic inflammation and improvement of mitochondrial function [40].

While this study presents important findings and has notable strengths, several limitations should be acknowledged. First, more accurate indices for assessing visceral adipose distribution, such as the visceral adiposity index, and for WRF, such as the urinary concentration of Kidney Injury Molecule-1, were identified after the completion of the TOPCAT trial. Second, we cannot rule out the possibility of reverse causality due to changes in WC during the follow-up period. Third, the limited sample size of the TOPCAT trial may have introduced bias in the subgroup analysis. Therefore, our results require further validation in large-scale studies that incorporate these newer indices and include a broader range of patients.

Conclusions

Based on our study’s findings, WC exhibits a steady linear correlation with WRF and is a superior predictor of WRF than BMI in the HFpEF population. Abdominal obesity is associated with the elevated risk of WRF in the HFpEF population. Future research should aim to identify superior indicators for predicting WRF and examine the benefits of weight loss during follow-up in prospective studies.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Acknowledgements

Our study was completed using the TOPCAT data collected by the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. The views expressed by the authors in this article may not align with the perspectives of TOPCAT or NHLBI.

Author contributions

SZ and ST defined the study themes and methods; QZ and ST analyzed the data; QZ wrote the paper and SZ and ST edited the manuscript. All authors have read and approved the final manuscript.

Funding

Not applicable.

Data availability

Our study was completed using the TOPCAT data collected by the National Heart, Lung, and Blood Institute (NHLBI) Biologic Specimen and Data Repository Information Coordinating Center. (Trial registration: URL: https://beta.clinicaltrials.gov. Unique identifier: NCT00094302)

Declarations

Ethics approval and consent to participate

This study followed the Helsinki Declaration principles and ethical approval was granted by the Hunan Provincial Hospital ethics committee. All patients provided written informed consent for.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Abbreviations

HFpEF Heart failure with preserved ejection fraction

BMI Body mass index

TOPCAT Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist

eGFR Estimated glomerular filtration rate

ACEI Angiotensin-converting enzyme inhibitor

ARB Angiotensin receptor blocker

WC Waist circumference

ROC Receiver operating characteristic

HR Hazard ratio

CI Confidence interval

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Shannon M Dunlay, Roger VL Redfield MM Epidemiology of heart failure with preserved ejection fraction Nat Rev Cardiol 2017 14 591 602 10.1038/nrcardio.2017.65 28492288
Shannon M, Dunlay, Roger VL, Redfield MM. Epidemiology of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2017;14:591–602.28492288 10.1038/nrcardio.2017.65
2. Kitzman DW Brubaker P Morgan T Haykowsky M Hundley G Kraus WE Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in obese older patients with heart failure with preserved ejection fraction: a Randomized Clinical Trial JAMA 2016 315 36 46 10.1001/jama.2015.17346 26746456
Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, et al. Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in obese older patients with heart failure with preserved ejection fraction: a Randomized Clinical Trial. JAMA. 2016;315:36–46.26746456 10.1001/jama.2015.17346
3. Upadhya B Amjad A Stacey RB Optimizing the management of obese HFpEF phenotype: can we mind both the Heart and the kidney? J Card Fail 2020 26 108 11 10.1016/j.cardfail.2019.11.018 31759161
Upadhya B, Amjad A, Stacey RB. Optimizing the management of obese HFpEF phenotype: can we mind both the Heart and the kidney? J Card Fail. 2020;26:108–11.31759161 10.1016/j.cardfail.2019.11.018
4. Obokata M Reddy YNV Pislaru SV Melenovsky V Borlaug BA Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction Circulation 2017 136 6 19 10.1161/CIRCULATIONAHA.116.026807 28381470
Obokata M, Reddy YNV, Pislaru SV, Melenovsky V, Borlaug BA. Evidence supporting the existence of a distinct obese phenotype of heart failure with preserved ejection fraction. Circulation. 2017;136:6–19.28381470 10.1161/CIRCULATIONAHA.116.026807
5. Damman K Valente MAE Voors AA O’Connor CM van Veldhuisen DJ Hillege HL Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis Eur Heart J 2014 35 455 69 10.1093/eurheartj/eht386 24164864
Damman K, Valente MAE, Voors AA, O’Connor CM, van Veldhuisen DJ, Hillege HL. Renal impairment, worsening renal function, and outcome in patients with heart failure: an updated meta-analysis. Eur Heart J. 2014;35:455–69.24164864 10.1093/eurheartj/eht386
6. Damman K Perez AC Anand IS Komajda M McKelvie RS Zile MR Worsening renal function and outcome in heart failure patients with preserved ejection fraction and the impact of angiotensin receptor blocker treatment J Am Coll Cardiol 2014 64 1106 13 10.1016/j.jacc.2014.01.087 25212644
Damman K, Perez AC, Anand IS, Komajda M, McKelvie RS, Zile MR, et al. Worsening renal function and outcome in heart failure patients with preserved ejection fraction and the impact of angiotensin receptor blocker treatment. J Am Coll Cardiol. 2014;64:1106–13.25212644 10.1016/j.jacc.2014.01.087
7. Damman K Solomon SD Pfeffer MA Swedberg K Yusuf S Young JB Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme: WRF in HFREF and HFPEF Eur J Heart Fail 2016 18 1508 17 10.1002/ejhf.609 27427441
Damman K, Solomon SD, Pfeffer MA, Swedberg K, Yusuf S, Young JB, et al. Worsening renal function and outcome in heart failure patients with reduced and preserved ejection fraction and the impact of angiotensin receptor blocker treatment: data from the CHARM-study programme: WRF in HFREF and HFPEF. Eur J Heart Fail. 2016;18:1508–17.27427441 10.1002/ejhf.609
8. Damman K Testani JM The kidney in heart failure: an update Eur Heart J 2015 36 1437 44 10.1093/eurheartj/ehv010 25838436
Damman K, Testani JM. The kidney in heart failure: an update. Eur Heart J. 2015;36:1437–44.25838436 10.1093/eurheartj/ehv010
9. Garofalo C Borrelli S Minutolo R Chiodini P De Nicola L Conte G A systematic review and meta-analysis suggests obesity predicts onset of chronic kidney disease in the general population Kidney Int 2017 91 1224 35 10.1016/j.kint.2016.12.013 28187985
Garofalo C, Borrelli S, Minutolo R, Chiodini P, De Nicola L, Conte G. A systematic review and meta-analysis suggests obesity predicts onset of chronic kidney disease in the general population. Kidney Int. 2017;91:1224–35.28187985 10.1016/j.kint.2016.12.013
10. Sharma A Lavie CJ Borer JS Vallakati A Goel S Lopez-Jimenez F Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure Am J Cardiol 2015 115 1428 34 10.1016/j.amjcard.2015.02.024 25772740
Sharma A, Lavie CJ, Borer JS, Vallakati A, Goel S, Lopez-Jimenez F, et al. Meta-analysis of the relation of body mass index to all-cause and cardiovascular mortality and hospitalization in patients with chronic heart failure. Am J Cardiol. 2015;115:1428–34.25772740 10.1016/j.amjcard.2015.02.024
11. Horwich TB Fonarow GC Clark AL Obesity and the obesity Paradox in Heart failure Prog Cardiovasc Dis 2018 61 151 6 10.1016/j.pcad.2018.05.005 29852198
Horwich TB, Fonarow GC, Clark AL. Obesity and the obesity Paradox in Heart failure. Prog Cardiovasc Dis. 2018;61:151–6.29852198 10.1016/j.pcad.2018.05.005
12. Tsujimoto T Kajio H Abdominal obesity is Associated with an increased risk of all-cause mortality in patients with HFpEF J Am Coll Cardiol 2017 70 2739 49 10.1016/j.jacc.2017.09.1111 29191321
Tsujimoto T, Kajio H. Abdominal obesity is Associated with an increased risk of all-cause mortality in patients with HFpEF. J Am Coll Cardiol. 2017;70:2739–49.29191321 10.1016/j.jacc.2017.09.1111
13. Pitt B Pfeffer MA Assmann SF Boineau R Anand IS Claggett B Spironolactone for heart failure with preserved ejection fraction N Engl J Med 2014 370 1383 92 10.1056/NEJMoa1313731 24716680
Pitt B, Pfeffer MA, Assmann SF, Boineau R, Anand IS, Claggett B, et al. Spironolactone for heart failure with preserved ejection fraction. N Engl J Med. 2014;370:1383–92.24716680 10.1056/NEJMoa1313731
14. Grundy SM Cleeman JI Daniels SR Donato KA Eckel RH Franklin BA Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: executive Summary Crit Pathw Cardiol 2005 4 198 203 10.1097/00132577-200512000-00018 18340209
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement: executive Summary. Crit Pathw Cardiol. 2005;4:198–203.18340209 10.1097/00132577-200512000-00018
15. Desai AS Lewis EF Li R Solomon SD Assmann SF Boineau R Rationale and design of the treatment of preserved cardiac function heart failure with an Aldosterone Antagonist Trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction Am Heart J 2011 162 966 e97210 10.1016/j.ahj.2011.09.007 22137068
Desai AS, Lewis EF, Li R, Solomon SD, Assmann SF, Boineau R, et al. Rationale and design of the treatment of preserved cardiac function heart failure with an Aldosterone Antagonist Trial: a randomized, controlled study of spironolactone in patients with symptomatic heart failure and preserved ejection fraction. Am Heart J. 2011;162:966–e97210.22137068 10.1016/j.ahj.2011.09.007
16. Beldhuis IE Myhre PL Bristow M Claggett B Damman K Fang JC Spironolactone in patients with heart failure, preserved ejection fraction, and worsening renal function J Am Coll Cardiol 2021 77 1211 21 10.1016/j.jacc.2020.12.057 33663739
Beldhuis IE, Myhre PL, Bristow M, Claggett B, Damman K, Fang JC, et al. Spironolactone in patients with heart failure, preserved ejection fraction, and worsening renal function. J Am Coll Cardiol. 2021;77:1211–21.33663739 10.1016/j.jacc.2020.12.057
17. Levey AS Coresh J Greene T Marsh J Stevens LA Kusek JW Expressing the modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values Clin Chem 2007 53 766 72 10.1373/clinchem.2006.077180 17332152
Levey AS, Coresh J, Greene T, Marsh J, Stevens LA, Kusek JW, et al. Expressing the modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem. 2007;53:766–72.17332152 10.1373/clinchem.2006.077180
18. Valente MAE Voors AA Damman K Van Veldhuisen DJ Massie BM O’Connor CM Diuretic response in acute heart failure: clinical characteristics and prognostic significance Eur Heart J 2014 35 1284 93 10.1093/eurheartj/ehu065 24585267
Valente MAE, Voors AA, Damman K, Van Veldhuisen DJ, Massie BM, O’Connor CM, et al. Diuretic response in acute heart failure: clinical characteristics and prognostic significance. Eur Heart J. 2014;35:1284–93.24585267 10.1093/eurheartj/ehu065
19. Beldhuis IE, Streng KW, Ter Maaten JM, Voors AA, van der Meer P, Rossignol P, et al. Renin–angiotensin system inhibition, worsening renal function, and Outcome in Heart failure patients with reduced and preserved ejection fraction: a Meta-analysis of published Study Data. Circ: Heart Fail. 2017;10:e003588.
20. Damman K Tang WHW Testani JM McMurray JJV Terminology and definition of changes renal function in heart failure Eur Heart J 2014 35 3413 6 10.1093/eurheartj/ehu320 25157110
Damman K, Tang WHW, Testani JM, McMurray JJV. Terminology and definition of changes renal function in heart failure. Eur Heart J. 2014;35:3413–6.25157110 10.1093/eurheartj/ehu320
21. Mulyadi L Stevens C Munro S Lingard J Bermingham M Body fat distribution and total body fat as risk factors for microalbuminuria in the obese Ann Nutr Metab 2001 45 67 71 10.1159/000046708 11359031
Mulyadi L, Stevens C, Munro S, Lingard J, Bermingham M. Body fat distribution and total body fat as risk factors for microalbuminuria in the obese. Ann Nutr Metab. 2001;45:67–71.11359031 10.1159/000046708
22. Pinto-Sietsma S-J Navis G Janssen WMT de Zeeuw D Gans ROB de Jong PE A central body fat distribution is related to renal function impairment, even in lean subjects Am J Kidney Dis 2003 41 733 41 10.1016/S0272-6386(03)00020-9 12666059
Pinto-Sietsma S-J, Navis G, Janssen WMT, de Zeeuw D, Gans ROB, de Jong PE, et al. A central body fat distribution is related to renal function impairment, even in lean subjects. Am J Kidney Dis. 2003;41:733–41.12666059 10.1016/S0272-6386(03)00020-9
23. Hall JE do Carmo JM da Silva AA Wang Z Hall ME Obesity, kidney dysfunction and hypertension: mechanistic links Nat Rev Nephrol 2019 15 367 85 10.1038/s41581-019-0145-4 31015582
Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity, kidney dysfunction and hypertension: mechanistic links. Nat Rev Nephrol. 2019;15:367–85.31015582 10.1038/s41581-019-0145-4
24. Koepp KE Obokata M Reddy YNV Olson TP Borlaug BA Hemodynamic and functional impact of Epicardial Adipose tissue in heart failure with preserved ejection fraction JACC: Heart Fail 2020 8 657 66 32653449
Koepp KE, Obokata M, Reddy YNV, Olson TP, Borlaug BA. Hemodynamic and functional impact of Epicardial Adipose tissue in heart failure with preserved ejection fraction. JACC: Heart Fail. 2020;8:657–66.32653449
25. Koenen M Hill MA Cohen P Sowers JR Obesity, adipose tissue and vascular dysfunction Circ Res 2021 128 951 68 10.1161/CIRCRESAHA.121.318093 33793327
Koenen M, Hill MA, Cohen P, Sowers JR. Obesity, adipose tissue and vascular dysfunction. Circ Res. 2021;128:951–68.33793327 10.1161/CIRCRESAHA.121.318093
26. Paulus WJ Tschöpe C A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation J Am Coll Cardiol 2013 62 263 71 10.1016/j.jacc.2013.02.092 23684677
Paulus WJ, Tschöpe C. A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. J Am Coll Cardiol. 2013;62:263–71.23684677 10.1016/j.jacc.2013.02.092
27. Fontana L Eagon JC Trujillo ME Scherer PE Klein S Visceral fat adipokine secretion is associated with systemic inflammation in obese humans Diabetes 2007 56 1010 3 10.2337/db06-1656 17287468
Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010–3.17287468 10.2337/db06-1656
28. Jung UJ Choi M-S Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease Int J Mol Sci 2014 15 6184 223 10.3390/ijms15046184 24733068
Jung UJ, Choi M-S. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15:6184–223.24733068 10.3390/ijms15046184
29. Pfeffer MA Claggett B Behind the scenes of TOPCAT — bending to inform NEJM Evid 2022 10.1056/EVIDctcs2100007 37645407
Pfeffer MA, Claggett B. Behind the scenes of TOPCAT — bending to inform. NEJM Evid. 2022. 10.1056/EVIDctcs2100007.37645407 10.1056/EVIDctcs2100007
30. Lemieux S Prud’homme D Bouchard C Tremblay A Després JP Sex differences in the relation of visceral adipose tissue accumulation to total body fatness Am J Clin Nutr 1993 58 463 7 10.1093/ajcn/58.4.463 8379501
Lemieux S, Prud’homme D, Bouchard C, Tremblay A, Després JP. Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am J Clin Nutr. 1993;58:463–7.8379501 10.1093/ajcn/58.4.463
31. Fu L Zhou Y Sun J Zhu Z Tai S Abdominal obesity is Associated with an increased risk of all-cause mortality in males but not in females with HFpEF Cardiovasc Ther 2022 2022 1 11 10.1155/2022/2950055
Fu L, Zhou Y, Sun J, Zhu Z, Tai S. Abdominal obesity is Associated with an increased risk of all-cause mortality in males but not in females with HFpEF. Cardiovasc Ther. 2022;2022:1–11.10.1155/2022/2950055
32. Roriz AKC Passos LCS de Oliveira CC Eickemberg M Moreira P de Sampaio A Evaluation of the Accuracy of Anthropometric Clinical indicators of Visceral Fat in adults and Elderly PLoS ONE 2014 9 e103499 10.1371/journal.pone.0103499 25078454
Roriz AKC, Passos LCS, de Oliveira CC, Eickemberg M, Moreira P, de Sampaio A. Evaluation of the Accuracy of Anthropometric Clinical indicators of Visceral Fat in adults and Elderly. PLoS ONE. 2014;9:e103499.25078454 10.1371/journal.pone.0103499
33. Barzin M Hosseinpanah F Serahati S Salehpour M Nassiri AA Azizi F Changes in waist circumference and incidence of chronic kidney disease Eur J Clin Invest 2014 44 470 6 10.1111/eci.12253 24580088
Barzin M, Hosseinpanah F, Serahati S, Salehpour M, Nassiri AA, Azizi F. Changes in waist circumference and incidence of chronic kidney disease. Eur J Clin Invest. 2014;44:470–6.24580088 10.1111/eci.12253
34. Kurnicka K Domienik-Karłowicz J Lichodziejewska B Bielecki M Kozłowska M Goliszek S Improvement of left ventricular diastolic function and left heart morphology in young women with morbid obesity six months after bariatric surgery Cardiol J 2018 25 97 105 10.5603/CJ.a2017.0059 28541599
Kurnicka K, Domienik-Karłowicz J, Lichodziejewska B, Bielecki M, Kozłowska M, Goliszek S, et al. Improvement of left ventricular diastolic function and left heart morphology in young women with morbid obesity six months after bariatric surgery. Cardiol J. 2018;25:97–105.28541599 10.5603/CJ.a2017.0059
35. Fenk S Fischer M Strack C Schmitz G Loew T Lahmann C Successful weight reduction improves left ventricular diastolic function and physical performance in severe obesity Int Heart J 2015 56 196 202 10.1536/ihj.14-261 25740581
Fenk S, Fischer M, Strack C, Schmitz G, Loew T, Lahmann C, et al. Successful weight reduction improves left ventricular diastolic function and physical performance in severe obesity. Int Heart J. 2015;56:196–202.25740581 10.1536/ihj.14-261
36. Sorimachi H Obokata M Omote K Reddy YNV Takahashi N Koepp KE Long-term changes in Cardiac structure and function following bariatric surgery J Am Coll Cardiol 2022 80 1501 12 10.1016/j.jacc.2022.08.738 36229085
Sorimachi H, Obokata M, Omote K, Reddy YNV, Takahashi N, Koepp KE, et al. Long-term changes in Cardiac structure and function following bariatric surgery. J Am Coll Cardiol. 2022;80:1501–12.36229085 10.1016/j.jacc.2022.08.738
37. Henry JA Abdesselam I Deal O Lewis AJ Rayner J Bernard M Changes in epicardial and visceral adipose tissue depots following bariatric surgery and their effect on cardiac geometry Front Endocrinol 2023 14 1092777 10.3389/fendo.2023.1092777
Henry JA, Abdesselam I, Deal O, Lewis AJ, Rayner J, Bernard M, et al. Changes in epicardial and visceral adipose tissue depots following bariatric surgery and their effect on cardiac geometry. Front Endocrinol. 2023;14:1092777.10.3389/fendo.2023.1092777
38. O’Brien R Johnson E Haneuse S Coleman KJ O’Connor PJ Fisher DP Microvascular outcomes in patients with diabetes after bariatric surgery Versus Usual Care: a matched cohort study Ann Intern Med 2018 169 300 10 10.7326/M17-2383 30083761
O’Brien R, Johnson E, Haneuse S, Coleman KJ, O’Connor PJ, Fisher DP, et al. Microvascular outcomes in patients with diabetes after bariatric surgery Versus Usual Care: a matched cohort study. Ann Intern Med. 2018;169:300–10.30083761 10.7326/M17-2383
39. Imam TH Fischer H Jing B Burchette R Henry S DeRose SF Estimated GFR before and after bariatric surgery in CKD Am J Kidney Dis 2017 69 380 8 10.1053/j.ajkd.2016.09.020 27927587
Imam TH, Fischer H, Jing B, Burchette R, Henry S, DeRose SF, et al. Estimated GFR before and after bariatric surgery in CKD. Am J Kidney Dis. 2017;69:380–8.27927587 10.1053/j.ajkd.2016.09.020
40. Ding H Zhang Y Ma X Zhang Z Xu Q Liu C Bariatric surgery for diabetic comorbidities: a focus on hepatic, cardiac and renal fibrosis Front Pharmacol 2022 13 1016635 10.3389/fphar.2022.1016635 36339532
Ding H, Zhang Y, Ma X, Zhang Z, Xu Q, Liu C, et al. Bariatric surgery for diabetic comorbidities: a focus on hepatic, cardiac and renal fibrosis. Front Pharmacol. 2022;13:1016635.36339532 10.3389/fphar.2022.1016635
