Introduction

With the progress of society and living standards, obesity has become an increasingly critical concern. It is recognized as a substantial risk factor for cardiovascular diseases (CVD) and poses a significant challenge to global public health1. The World Health Organization (WHO) estimates that at least 2.6 billion adults worldwide are overweight, with around 1 billion of them being obese2. Obesity has recently been confirmed to be intimately linked with various CVD, such as coronary heart disease, hypertension, and diabetes3, indicating that it can significantly influence the onset, development, and prognosis of CVD4. Therefore, in-depth research on the relationship between obesity and CVD is crucial for clinical and public health.

Nevertheless, some studies have identified an unanticipated phenomenon, namely the obesity paradox5,6, which means that obese individuals display better prognoses than normal-weight individuals for specific CVD7, such as heart failure and chronic kidney disease8. Although the obesity paradox is controversial, an increasing number of studies indicate that obesity may not only negatively affect the prognosis of patients having some CVD9. ST-segment elevation myocardial infarction (STEMI) is a severe CVD that significantly affects the quality of life and survival rate of patients10,11,12,13. However, the role of obesity paradox in STEMI patients remains unclear14,15. Therefore, this research aims to examine the impact of mild obesity on the prognosis of STEMI patients to offer novel insights for clinical management and preventive measures for such cases.

Methods

Study design and participants

This retrospective cohort study enrolled 664 STEMI patients who underwent percutaneous coronary intervention (PCI) at Xiangtan Central Hospital between January 1, 2020 and July 31, 2022 (Fig. 1). The inclusion criteria were as follows: (1) Patients with first-episode STEMI based on the 2017 ESC Guidelines for the management of acute myocardial infarction16; and (2) patients receiving emergent PCI. The exclusion criteria included: (1) Age < 18 years; (2) lack of essential data; (3) deaths during hospitalization; (4) patients who did not undergo PCI; (5) patients with a body mass index (BMI) ≥ 35 kg/m2; and (6) patients with an expected survival time of fewer than 6 months due to malignant tumors or other non-cardiac diseases. Based on the WHO criteria2, patients were classified into the mildly obese group (BMI, 30–35 kg/m2) and the non-obese group (BMI < 30 kg/m2). We further stratified the study population by sex.

Figure 1
figure 1

Flow diagram for participant screening, eligibility and analysis.

Full size image

Data collection and variable definitions

The patient’s records were retrieved from the hospital’s electronic medical record system and the national chest pain platform. These records comprised demographic information, past history, biochemical indicators at admission, medication usage, and PCI treatment-related details. During the specified study period, all eligible patients with STEMI and mild obesity in our center were consecutively included to ensure a systematic and fair selection of participants.

Follow-up and outcome measures

We followed up with study participants until January 31, 2023. A specialized team consisting of five experienced cardiovascular physicians and two nurses collected information on outcome events through outpatient, telephone follow-up, and community registration. The primary composite endpoint was death and several cardiovascular events, including non-fatal myocardial infarction, ischemic stroke, and readmission due to angina, heart failure, bleeding, and revascularization.

Ethics and informed consent

This study was approved by the Ethics Committee of Xiangtan Central Hospital (Xiangtan, China) (Ethics Approval No. 2023-02-001) and adhered to the Declaration of Helsinki. The requirement for individual informed consent was waived because the study was retrospective in nature and simply collected anonymous data without intervening in the patient’s treatment.

Statistical analysis

The continuous variables were compared with the t-test or Mann–Whitney U test. The categorical variables were compared using the chi-square test. Kaplan–Meier survival curves were estimated and compared with the log-rank test. A Cox proportional hazards model was used for multivariable analysis to ascertain the independent effect of mild obesity on the prognosis of STEMI. Results were presented as the hazard ratio (HR) and 95% confidence interval (CI). P-values were obtained using the Kruskal–Wallis rank sum test or Fisher exact probability test. Results were considered significant when a P value < 0.05. Statistical analyses were performed using R version 4.2.0 (http://www.R-project.org) and EmpowerStats software (www.empowerstats.com, X&Y Solutions, Inc. Boston, MA).

Results

Baseline characteristics

This study enrolled 664 STEMI patients, including 515 males and 149 females. In the male patient cohort, the mildly obese group exhibited a younger mean age (57.3 ± 11.3 vs. 61.9 ± 12.3 years, P < 0.001) and a lower prevalence of renal dysfunction (9.2% vs. 17.1%, P = 0.022), atrial fibrillation (3.3% vs. 9.9%, P = 0.011), and chronic obstructive pulmonary disease (COPD) (9.2% vs. 17.6%, P = 0.015) than the non-obese group. Nevertheless, the mildly obese group showed a higher incidence of hyperlipidemia (48.7% vs. 35.8%, P = 0.006). In the female patient cohort, the mildly obese group displayed a younger mean age (64.6 ± 10.3 vs. 69.7 ± 9.0 years, P = 0.006) and a higher incidence of hyperlipidemia (50.0% vs. 28.2%, P = 0.02) than the non-obese group. Significant differences in the composite endpoints between the two groups were observed among male patients (22.4% vs. 41.3%, P < 0.001) but not among female patients (43.8% vs. 43.6%, P = 0.987) (Table 1).

Table 1 Baseline characteristics of mild obesity stratification after sex grouping.
Full size table

Clinical outcomes

The unadjusted analysis (Table 2, Model I) showed that the risk ratio of mildly obese patients to non-obese patients was 0.51 for the male cohort (95% CI 0.35–0.74; P = 0.0004) (Fig. 2A), 0.94 for the female cohort (95% CI 0.52–1.69; P = 0.8275) (Fig. 2B), and 0.59 for the overall population (95% CI 0.43–0.81; P = 0.0011).

Table 2 Impact of mild obesity on clinical outcomes.
Full size table
Figure 2
figure 2

Trend plot of the composite endpoint for the mildly obese and non-obese groups. (A) Cumulative incidence of the composite endpoint in male. (B) Cumulative incidence of the composite endpoint in female.

Full size image

After adjusting for age (Table 2, Model II), the risk ratio of mildly obese patients to non-obese patients was 0.53 for the male cohort (95% CI 0.36–0.77; P = 0.0008), 0.97 for the female cohort (95% CI 0.53–1.79; P = 0.9277), and 0.62 for the overall population (95% CI 0.45–0.85; P = 0.0030).

After adjusting for demographic characteristics, cardiac risk factors, and comorbidities (Table 2, Model III), the risk ratio of mildly obese patients to non-obese patients was 0.51 for the male cohort (95% CI 0.35–0.74; P = 0.0005), 1.02 for the female cohort (95% CI 0.51–2.03; P = 0.9585), and 0.61 for the overall population (95% CI 0.44–0.85; P = 0.0031).

After adjusting for demographic characteristics, cardiac risk factors, comorbidities, and treatment strategies (Table 2, Model IV), the risk ratio of mildly obese patients to non-obese patients was 0.47 for the male cohort (95% CI 0.32–0.69; P = 0.0001), 0.96 for the female cohort (95% CI 0.47–1.94; P = 0.9003), and 0.59 for the overall population (95% CI 0.43–0.82; P = 0.0017).

Independent risk factors associated with outcome events

We initially conducted univariate and multivariate analyses to investigate risk factors associated with outcome events. The findings are summarized below (Table 3).

Table 3 Cox proportional hazards regression model analysis for risk of composite endpoint.
Full size table

Antiplatelet agents

The univariate analysis showed that administering antiplatelet agents significantly reduced the risk of outcome events (HR 0.04; 95% CI 0.01–0.09; P < 0.0001). The multivariate analysis confirmed that it remained an independent protective factor (HR 0.03; 95% CI 0.01–0.10; P < 0.0001).

Killip classification

The univariate analysis indicated a significant relationship between Killip classification and an elevated risk of outcome events (HR 1.66; 95% CI 1.29–2.13; P < 0.0001). The multivariate analysis showed that Killip classification was an independent risk factor (HR 1.53; 95% CI 1.18–1.98; P = 0.0013).

Mild obesity

The univariate analysis revealed that mild obesity could significantly decrease the risk of outcome events (HR 0.58; 95% CI 0.43–0.80; P, 0.0008). In the multivariate analysis, it remained an independent protective factor (HR 0.61; 95% CI 0.44–0.84; P = 0.0027).

Cardiomyopathy

The univariate analysis demonstrated a significant relationship between cardiomyopathy and an elevated risk of outcome events (HR 2.03; 95% CI 1.28–3.20; P = 0.0025). The multivariate analysis further established it as an independent risk factor (HR 1.78; 95% CI 1.12–2.84; P = 0.015).

Other factors, such as age, valvular heart disease, stroke, atrial fibrillation, and hypertension, emerged as risk factors for outcome events in the univariate analysis. However, their impacts were not statistically significant in the multivariate analysis. Besides, lipid-lowering drugs, ARBs, smoking, hyperlipidemia, alcohol consumption, COPD, hyperthyroidism, and ACEIs exhibited no significant association with outcome events in the univariate and multivariate analyses.

Stratified analysis

We conducted a comprehensive stratified analysis for multiple binary variables. Forest plots (Fig. 3) illustrated the relationship between mild obesity (independent variable) and composite endpoint events (dependent variable). The stratified analysis showed that mild obesity exerted a protective effect on the patient’s prognosis in most subgroups, particularly under the following conditions: age ≥ 70 or < 70 years, smoker or non-smoker, non-drinker, with or without hyperlipidemia, with or without hypertension, without atrial fibrillation, with or without diabetes, without hyperthyroidism, with or without stroke, with or without valvular heart disease, without cardiomyopathy, without COPD, with or without renal insufficiency, and Killip classification ≥ 2 (all P < 0.05). In contrast, the association between mild obesity and composite endpoint events did not achieve statistical significance in subgroups of females, alcohol consumers, patients with atrial fibrillation, hyperthyroidism, cardiomyopathy, COPD, and Killip class I (all P values > 0.05).

Figure 3
figure 3

Forest plot: Relationship between mild obesity and composite endpoint events, stratified by multiple dichotomous variables based on obesity grouping.

Full size image

We carefully considered and analyzed numerous significant factors that might affect the prognosis of STEMI patients. To provide a comprehensive overview, we compared other important prognostic indicators between the mildly obese and non-obese groups (Supplementary Table 1).

Ethics approval and consent to participate

The study protocol was approved by the Ethics Committee of Xiangtan Central Hospital (Xiangtan, China, No. 2023-02-001) and conformed to the principles outlined in the Declaration of Helsinki. The need for informed consent was waived by the ethics committee Review Board of Xiangtan Central Hospital, because of the retrospective nature of the study.

Discussion

The study revealed that mild obesity functioned as an independent protective factor for the composite endpoint in male STEMI patients after adjusting for confounding variables. However, no association was identified between mild obesity and composite endpoint among female STEMI patients. Additionally, the administration of antiplatelet agents emerged as an independent protective factor for the incidence of the composite endpoint. In contrast, a Killip class ≥ 2 and a history of cardiomyopathy were established as independent risk factors.

The fundamental similarity between this study and prior research validated the “obesity paradox” in obese patients, suggesting that obesity was correlated with a more favorable prognosis in particular CVD. Numerous investigations have demonstrated obesity as a significant risk factor for CVD, while obese patients exhibited a better prognosis than non-obese patients under specific circumstances, such as acute myocardial infarction and heart failure1,5,14,17,18. This phenomenon was known as the “obesity paradox”.

The uniqueness of this study was that we further examined the influence of sex on the mild obesity paradox and revealed differences in the association of mild obesity with the prognosis of STEMI between male and female patients. Previous research has primarily concentrated on the mild obesity paradox, with less attention paid to the role of the sex factor19,20. In research focused on gender disparities in Acute Coronary Syndrome (ACS), there has been no observed trend supporting the obesity paradox21. Our investigation discovered a protective effect of mild obesity on male STEMI patients; however, this effect was not observed in female patients. This finding emphasized the importance of gender difference when assessing the impact of mild obesity on the prognosis of CVD and provided an innovative perspective for developing future interventions to address these differences.

This study suggested that the protective effect of mild obesity on the prognosis of male STEMI patients might be attributed to the following factors: (1) Obese patients were younger at onset and possessed a lower risk of CVD6,22; (2) obese patients demonstrated excellent myocardial reserve function and resistance to myocardial ischemia23; and (3) inflammatory factors and metabolic hormones in obese patients could have a protective effect on the myocardium24. In contrast, this protective effect was not present in female patients, possibly due to differences in the physiology, metabolism, diagnosis and treatment of coronary artery disease, characteristics of acute myocardial infarction, and coronary microvascular function associated with diabetes between male and female patients25,26,27,28,29.

Study limitations

The main limitations of this study included the following aspects: (1) The retrospective design of the study might lead to the bias of final results; (2) the sample size was relatively small, with a particularly limited number of females and patients with BMI ≥ 35 kg/m2; (3) other metabolic indicators and hormone levels were not considered; (4) The limited racial diversity of the study cohort might affect the generalizability of our findings in other populations. To address these issues, future research should adopt a prospective design, increase the sample size, particularly the number of female patients, and further evaluate the impact of other metabolic indicators and hormone levels.

Clinical implications

To tackle the above limitations, we suggest future research directions as follows: (1) Conduct prospective studies to minimize potential omissions and biases; (2) expand the research scope by increasing the sample size of female patients for a more comprehensive exploration of the impact of gender on the obesity paradox and incorporating patients with BMI ≥ 35 kg/m2 to determine the cut-off value of BMI associated with the obesity paradox; (3) investigate the biological mechanisms of the impact of mild obesity on the prognosis of STEMI by taking into account factors like inflammation, metabolic hormones, and hormone levels; (4) Examine other interventions, including lifestyle change and medication treatments, to improve the prognosis of obese patients with CVD.

Conclusion

In conclusion, our study demonstrates that mild obesity is an independent protective factor for clinical outcomes in male patients with STEMI. Conversely, this protective effect was not observed in female patients. Further research is warranted to elucidate the underlying mechanism of our finding and develop potential sex-specific interventions to improve the prognosis of STEMI patients.