Impact of metabolic syndrome on clinical characteristics and one-year outcomes of patients undergoing primary percutaneous coronary intervention: a propensity score-matched comparison

Abstract

Background

Metabolic syndrome (MetS) is a set of symptoms, including insulin resistance, high blood sugar, and abdominal obesity, that increases the risk of cardiovascular diseases. This syndrome is prevalent in acute coronary syndrome (ACS), comprising patients with acute myocardial infarction (AMI). This study evaluated the prognosis of AMI patients who underwent primary PCI in two groups with and without MetS.

Methods

This retrospective study was performed on ST-segment elevation myocardial infarction (STEMI) patients referred to the emergency department of Tehran Heart Center from 2012 to 2020 who underwent primary PCI. Patients were divided into MetS and non-MetS according to the International Diabetes Federation (IDF) criteria. Clinical and laboratory characteristics were compared between the two groups.

Results

Two thousand, six hundred fifty-one patients were included, and 1850 patients (70%) had MetS. The mean age of patients with MetS compared to non-MetS showed no significant difference (60.16 vs 59.37 years, P-value = 0.053). In both groups, the majority were men. Forty-seven in-hospital deaths occurred, with no significant difference regarding the presence of MetS. Two hundred-six deaths happened during the one-year follow-up, without a significant difference between the two groups. Two hundred-sixteen MACEs were observed in one year, which was not significantly different between patients with and without MetS.

Conclusion

In-hospital mortality, one-year death, and one-year MACCE were not associated with MetS in this study.

Introduction

Metabolic syndrome (MetS) is defined as a combination of insulin resistance, hyperglycemia, abdominal obesity, hypertension, and dyslipidemia, which has a synergistic effect on the risk of cardiovascular disease. Previous research has demonstrated that MetS increases the risk of coronary heart disease, renal failure, peripheral vascular disease, and stroke [1, 2]. Therefore, the prime focus of the World Health Organization’s (WHO) Global Non-communicable Disease (NDC) Action Plan and Sustainable Development Goal 4 is to reduce NCD-related deaths by 25 percent in 2025 and by 30 percent in 2030 [3]. Indeed, MetS is one of the leading preventable causes of early mortality, affecting around one-quarter of the world’s population [2].

Prior studies have shown adverse outcomes related to MetS in patients with ST-segment elevation myocardial infarction (STEMI). These studies did not confirm a detrimental effect of this syndrome on clinical severity and the onset of new events during a brief follow-up period [4, 5].

Metabolic syndrome prevalence varies by gender and race. It is estimated that one-third of Iranian adults suffer from metabolic syndrome [6]. Therefore, in the present study, we aimed to examine the impact of MetS on the severity and one-year outcome of STEMI patients treated with primary PCI.

Methods

Study population and study design

This retrospective cohort study was conducted at Tehran Heart Center, a tertiary hospital in Iran, from 2012 to 2020. All the patients with STEMI treated with primary percutaneous coronary intervention (PPCI) were initially evaluated and enrolled in the study. STEMI was defined as an episode of chest pain in the last 24 h accompanying ST elevation in ≥ 2 contiguous leads (more than 0.2 mV in leads V1-V3 or 0.1 mV in other leads), or a new left bundle branch block on the admission electrocardiogram. All patients diagnosed with STEMI according to European Society of Cardiology guidelines and underwent PPCI were enrolled in the study if all the required data were available from the data bank registry [7]. Exclusion criteria were unsuccessful PPCI, planned CABG less than 3 months after PPCI, Plain Old Balloon Angioplasty (POBA), and loss of follow-up. The summary of patient allocation is provided in Fig. 1. Trained research assistants collected data through interviews and exams on recruited patients using standardized methods and tools. The medical records were reviewed by investigators unaware of the study’s objectives and outcomes. The data collected included demographic information, anthropometric measures, cardiovascular risk factors, medical history, and baseline clinical data obtained during hospital admission. Major adverse cardiac and cerebrovascular events (MACCE) were evaluated at one-year clinical follow-up after index PPCI. They were defined as the composite of cardiovascular death, stroke, revascularization, and re-infarction. This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki, and the research protocol has been verified and approved by the Ethics Committee of Tehran University of Medical Sciences (No: IR.TUMS.REC.1400.066). Given the study’s retrospective nature, an informed consent waiver was obtained from the ethics committee.

Fig. 1

Summary of the study process and patients’ allocation. Pts: patients, POBA: Plain Old Balloon Angioplasty

Definition of metabolic syndrome

International Diabetes Federation (IDF) criteria [8] were used for the diagnosis of MetS at baseline as the presence of central obesity (defined as waist circumference > 94 cm in men or > 80 cm in women) and at least two of the four following parameters:

• 1. High triglycerides (TG) level (TG ≥ 150 mg/dl [1.7 mmol/l], or taking medication for elevated TG)

• 2. Low high-density lipoprotein (HDL) cholesterol (HDL < 40 mg/dl [1.04 mmol/l] in men or HDL < 50 mg/dl [1.29 mmol/l] in women)

• 3. High blood pressure (systolic ≥ 130 mmHg or diastolic ≥ 85 mmHg or taking antihypertensive medication)

• 4. High fasting plasma glucose (≥ 100 mg/dl [5.5 mmol/l], or taking medication for hyperglycemia)

Statistical analysis

The mean and standard deviation (SD) for continuous variables and the median and interquartile range (IQR) boundaries for categorical variables were calculated. Frequencies and percentages were also computed for categorical data. Comparisons of variables in MetS and non-MetS groups were made using either an independent t-test or Mann–Whitney test for continuous variables and Pearson’s Chi-squared test or Fisher’s exact test for categorical variables, depending on the appropriateness of the test. The stabilized Inverse Probability Weighting (sIPW) technique was used to adjust the effects of potential confounders, including age, history of COPD, history of CVA, LVEF multi-vessel disease, stent diameter, Hb, creatinine (Cr), and LDL on MetS. The standardized mean difference was used to assess the covariate balance graphically (Fig. 2). Stent diameter was assigned instead of lesion length, resulting in the best-balanced model. To find a concise, balanced model, current smoking and history of opium use were added to ascertain their confounding roles. Adding smoking and opium did not change the balanced models. Therefore, only “COPD” was kept in the model to prevent having crowded models.

Fig. 2

The standardized mean differences (SMD) plot before (Original) and after weighting (Weighted), given as absolute values, for all covariates included in the model. The standardized difference compares the difference in means between groups in standard deviation units. After weighting, the differences between groups were < 10% (dashed line), showing good covariate balance. Inverse Probability Weighting (IPW) analysis was applied using the following variables: LDL, Hb, LVEF, age, creatinine, history of COPD, CV/TIA, number of vessel diseases, and stent diameter

To examine the impact of MetS on MACCE and mortality, a Cox proportional hazards (Cox-PH) regression model incorporating sIPWs was employed. Additionally, logistic regression and linear regression models considering sIPWs were utilized to evaluate the association between MetS and in-hospital mortality and the log-LOS (length of stay). The findings are reported as hazard ratios (HRs) and odds ratios (ORs), along with their corresponding 95% confidence intervals (CIs). Analyses were conducted using the R Statistical language (version 4.3.0; R Core Team, 2023), using the packages WeightIt (version 0.14.2; Greifer N, 2023), ggsurvfit (version 1.0.0; Sjoberg Det al., 2023) and survival (version 3.5.7; Therneau T, 2023). The level of P-value for statistical significance was set as ≤ 0.05.

Results

The study included 2651 STEMI patients. According to the IDF criteria, patients were divided into two groups: 1850 patients (70%) were in the MetS group, and 801 patients (30%) were in the non-MetS group.

The characteristics of the study population of MetS and non-MetS groups and their clinical and laboratory data are presented in Table 1. The mean age of the patients in the MetS group and the non-MetS group were 60.19 ± 11.79 and 59.37 ± 12.36, respectively (p = 0.053). Men constituted most of both groups; 70.5% of the Mets group and 95.6% of the non-MetS group were male. Mean blood pressure, history of diabetes, hypertension, hyperlipidemia, and serum levels of LDL, TG, total Cholesterol, and FBS were significantly higher in the MetS group than in the non-MetS group (P-value < 0.001). However, the non-MetS patients used cigarettes and opium significantly more than the Mets group (P-value < 0.001).

Table 1 Descriptive Statistics of Study Participants’ Characteristics with Comparison Between MetS- and MetS + Groups

In this observational data, sIPW analysis was used to assess the net effect of metabolic syndrome on MACCE and mortality, balancing LDL, Hb, LVEF, age, creatinine, history of COPD, CV/TIA, number of vessel diseases, and stent diameter between the two groups (Fig. 2).

A total of 47 in-hospital deaths occurred in follow-up, of which 16 (2.0%) were in the non-MetS group, and 31 (1.7%) were in the MetS group (OR = 0.84, 95% CI: 0.46–1.57, P-value = 0.565). After adjusting for confounding factors, no significant association was found between MetS and in-hospital mortality (OR = 0.94, 95%CI: 0.45–2.06, P-value = 0.86) (Table 2). In addition, we examined the effect of the Mets on one-year mortality in patients with and without metabolic syndrome. A total of 206 deaths were recorded during one-year follow-up, of which 65 occurred in the non-MetS group and 141 in the MetS group. According to the analysis, the Mets had no significant effect on one-year mortality before and after adjustment for confounding factors. (adjusted HR = 0.91, 95%CI: 0.66–1.26, P-value = 0.571) (Table 2, Fig. 3). Finally, the adjusted and unadjusted effects of Mets on one-year MACCE (155 in Mets and 61 in the non-Mets group) were evaluated, none of which had a significant relationship with one-year MACCE. (adjusted HR = 1.08, 95%CI: 0.78–1.50, P-value = 0.635). The duration of hospitalization (expressed as a logarithm of length of stay) was also evaluated. Both groups showed no statistically significant difference (Table 2, Fig. 3). Meanwhile, we found no gender difference in MACCE and mortality in the presence of MetS.

Table 2 Unadjusted and adjusted effects of MetS on length of stay and in-hospital mortality using linear and logistic regression and one-year mortality and MACCE using Cox-PH regression (by applying the weights calculated from the IPW method)

Fig. 3

A Kaplan–Meier survival curves of MACCE before and after weighting between MetS groups, B Kaplan–Meier survival curves of one-year mortality before and after weighting between MetS groups

A total of 216 MACCEs occurred during the one-year follow-up, of which 61 cases (28.2%) occurred in the non-MetS group and 155 (71.8%) in the MetS group. The frequency of MACCE components, including re-MI, revascularization, death, and stroke, is also shown in Table 3.

Table 3 Prevalence of one-year MACCE components regarding the presence of MetS

Finally, in-hospital mortality, one-year mortality, and MACCE were evaluated in four different BMI subgroups (< 25, 25–29.9, 30–35, and > 35). There is no significant relationship between BMI subgroups and risk of in-hospital mortality, one-year mortality, and MACCE.

Discussion

This observation data analysis with sIPW analysis aimed to check the net effect of metabolic syndrome on MACCE and mortality. With sIPW, the two groups will be balanced regarding the possible contributing factors to the outcomes. The present study suggests that although there is a high prevalence of metabolic Syndrome in patients with STEMI, the presence of MetS does not appear to increase the risk of adverse cardiovascular events in this population. There was no significant relationship between MetS and in-hospital mortality, one-year mortality, or length of hospital stay.

This study showed a high prevalence of MetS (70%) among patients with STEMI. This prevalence was higher than the 37.6% to 54.5% observed in previous studies, which may have derived from the difference in the criteria used to define MetS, race, and age of the study population [4, 9,10,11]. In this study, we used the IDF criterion to divide patients into two groups of MetS and non-MetS because, according to previous studies, this criterion is more compatible with the Iranian race, while Zeller et al., Jelavic et al., and Kumar et al. used the ATP3 criterion [4, 9, 10]. A study by Jelavic et al. [4] examined the importance of dual criteria for diagnosing MetS in predicting the severity and prognosis of heart disease. This study showed that the risk of MACE in patients with MetS, based on the ATP3 definition, is significantly higher.

Additionally, it showed that MetS based on ATP3 definition and central obesity is superior to BMI in predicting the severity of acute myocardial infarction; however, according to the IDF definition, waist circumference and MetS do not affect MACE. In our study, none of the above affects the prognosis. We defined MetS based on IDF, and no association was found between MetS and MACCE.

In this study, the majority of patients were men. Similarly, in other studies, men have always been more than women, so in the studies of Fanta et al., 62.5%; in the study of Babic et al., 70.3%; and in the study of Arbel et al., 72.5% of the study population were men. In general, the incidence of coronary artery disease in women is lower due to the presence of the sex hormones estrogen and progesterone, which modulate the lipid profile [12,13,14]. Although most patients were men, this percentage was significantly different in the two groups with MetS and non-MetS, and the rate of female patients in the MetS group was higher than in the non-metabolic group (29.5% to 4.4%). In the study of Lovic et al., 27.19% were female in the MetS group, and 18.62% were female in the non-metabolic group [15].

In the present study, 49.4% and 25.5% of the non-Mets group and 34.6% and 13.9% of the MetS group had a history of smoking and opium use, respectively, which showed there are other risk factors, such as smoking and opium in non-infected people. In the study of Lovic et al., the number of people with a history of smoking was higher in the group without the non-MetS (76.2%, 66.63%) [15].

The presence of a family history of heart disease was not different between the two groups. Similarly, in the studies of Zeller, Jelavic, and Lovic et al., no significant difference was found between the two groups [4, 9, 15]. Although in our research, Hemoglobin, creatinine, and LVEF significantly differed between MetS and non-MetS groups, this difference was not clinically significant. The observed difference was only due to the high sample volume and the resultant high power of the study to detect the differences. The procedural characteristics, including the presence of a proximal lesion, eccentric, calcified, or bifurcated lesion, stent diameter, AHA lesion type, pre- and post-procedural TIMI flow, thrombus burden, need to thrombosuction, multiple PCI in one session, multiple vessel involvement, LM involvement, vessel territory (LAD, LCX or RCA) was similar in MetS and non-MetS groups except for lesion length and need for staged PCI that was higher in the MetS group.

In contrast, in Lee et al.’s study, LVEF was lower in the group with MetS, but angiographic indices were not significantly different. In Lovic’s research, which is similar to ours, the disease severity and LVEF indices were the same in both groups. In Zeller’s study, LVEF was the same in both groups.

In a 2009 study by Lee et al., it was shown that the incidence of in-hospital mortality was significantly higher in the group with MetS. Low LVEF, old age, low HDL, and multi-vascular involvement were also seen as other predictors of in-hospital death. Lovic study showed no difference between hospital deaths in the two groups. Similar to the Lovic study, hospital mortality was not significantly different between the two groups in our study [15, 16].

Research has found a contradictory clinical impact of BMI on the results of PCI in patients who have experienced acute MI. The link between higher BMI and better survival rates has been named the “obesity paradox” [17]. In a study by Lee et al. [18], patients were divided into four groups based on the presence or absence of obesity and MetS to investigate the effect of MetS and obesity on the outcomes of patients with acute myocardial infarction who underwent PPCI. MetS was seen in normal-weight individuals as a risk factor for cardiac death and mortality for any reason. Still, this association was not observed in obese individuals with and without MetS. Moreover, in obese individuals with MetS, obesity had a protective effect. MACE levels also did not differ between groups, so MetS alone was not considered a risk factor in obese individuals. Our study showed no significant relationship between BMI subgroups and risk of in-hospital mortality, one-year mortality, and MACCE.

A 2018 study by Kim et al. [11] examined the effect of MetS on the outcomes of patients with acute MI who underwent PPCI in two age groups of fewer than 50 years and over 50 years. The highest incidence of MACE occurred in older people without MetS, and the highest recurrence of MI occurred in young individuals with MetS. Therefore, it was concluded that MetS in people under 50 years is an independent predictor of the recurrence of MACE and MI. Our study did not impose an age limit; instead, age was balanced using stabilized inverse probability weighting (sIPW), which precluded a direct assessment of the association between MACCE and metabolic syndrome in a specified age limit.

The presenting study has some limitations. A relatively short follow-up time (one year) might explain the absence of difference in the observed outcomes. All the patients received the appropriate guideline therapy for STEMI at the hospital. After discharge, the follow-up clinics routinely checked the continuation of guideline-directed therapies. Still, no objective methods for assessment of drug compliance with possible effects on the outcome and MACCE were used in the retrospective cohort.

Conclusion

Although the presence of MetS at the time of PCI was not related to an elevated risk of cardiac events in the year following the treatment, MetS was highly prevalent among patients with STEMI. Raising awareness and implementing preventative actions is crucial to improving these patients’ prognosis.