Impact of metabolic syndrome on clinical characteristics and one-year outcomes of patients undergoing primary percutaneous coronary intervention

doi:10.21203/rs.3.rs-3217222/v1

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Research Article

Impact of metabolic syndrome on clinical characteristics and one-year outcomes of patients undergoing primary percutaneous coronary intervention

https://doi.org/10.21203/rs.3.rs-3217222/v1

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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 International Diabetes Federation (IDF) criteria. Clinical and laboratory characteristics were compared between the two groups.

Results

3103 patients were included, and 2144 patients (69%) had MetS. The mean age of both groups was approximately 62 years. In both groups, the majority were men. Sixty-six in-hospital deaths occurred, with no significant difference regarding the presence of MetS. One hundred fifty-two deaths happened during the one-year follow-up, without a significant difference between the two groups. Four hundred twenty-one MACE were observed in one year, which was not significantly different between patients with and without MetS. Analysis of patients with a BMI less than 25 kg/m² revealed significantly higher MACE in MetS compared to the non-MetS group.

Conclusion

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

Metabolic Syndrome

STEMI

Primary PCI

Metabolic syndrome (MetS) defines 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.

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 hours 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 enrolled in the study if all the required data were available from the data bank registry(7). Trained research assistants conducted the data collection process through interviews and exams on recruited patients using standardized methods and tools. The medical records were reviewed by investigators who were unaware of the study's objectives and outcomes. The data collected included demographic information, anthropometric measures, cardiovascular risk factors, and medical history, as well as baseline clinical data obtained at the time of hospital admission. Major adverse cardiac and cerebrovascular events (MACE) were evaluated at one-year clinical follow-up and were defined as the composite of cardiovascular death, stroke, revascularization and re-infarction. The research protocol has been verified and approved by the Ethics Committee of Tehran University of Medical Sciences (No: IR.TUMS.REC.1400.066). Informed consent was obtained from patients upon admission to use their clinical data would be used anonymously for research purposes.

Definition of MS

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 :

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

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)

High blood pressure (systolic ≥ 130 mm Hg or diastolic ≥ 85 mm Hg or taking antihypertensive medication)

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

Statistical analysis

Statistical analysis was performed using SPSS (version 26). Mean (± standard deviation) and number (with percentage) are used to demonstrate quantitative and qualitative measurements, respectively. For the comparison of values, the Paired T-test was used for the quantitative values, and the Chi-square test was used for qualitative values. Mann-Whitney test was used to compare quantitative variables between the MetS and non-MetS. Univariate logistic regression analysis was performed to determine the relationship between MetS and outcomes. The Cox regression model was used to measure the effect of MetS on MACE and one-year mortality. The covariates included in the multivariable model were as follows: age, gender, history of COPD, history of CVA, LVEF, multi-vessel disease, Cr, LDL and. The level of P-value for statistical significance was set as ≤ 0.05.

A total of 3103 STEMI patients were included in the study. According to the IDF criteria, patients were divided into two groups, 2144 patients (69%) were in the MetS group, and 959 patients (31%) 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 62.54 ± 11.77 and 62.2 ± 12.37, respectively (p = 0.457). The majority of patients in the non-MetS group were male (95.4%) which were significantly higher than patients in the MetS group (70.8%, p < 0.001). Mean blood pressure, history of diabetes, hypertension, and hyperlipidemia, and the serum levels of LDL, TG, total Cholesterol, and FBS were significantly higher in the MetS group than in the non-MetS group (p < 0.001). However, the non-MetS patients used cigarettes and opium significantly more than the Mets group (p < 0.001).

Table 1

Characteristic features and their associations with MetS.
Variable	MetS- N = 959	MetS+ N = 2144	P value
Age(yr), mean ± SD	62.20 ± 12.37	62.54 ± 11.77	0.457
Male	915(95.4%)	1519(70.8%)	< 0.001
Smoking	471(49.1%)	761(35.5%)	< 0.001
Opium	259(27.0%)	346(16.1%)	< 0.001
HLP	350(36.5%)	1324(61.6%)	< 0.001
HTN	295(30.8%)	1317(61.4%)	< 0.001
DM	237(24.7%)	1041(48.6%)	< 0.001
Renal Failure	21(2.2%)	34(1.6%)	0.230
COPD	39(4.1%)	108(5.0%)	0.240
CVA	41(4.3%)	98(4.6%)	0.713
History Of PCI	99(10.3%)	288(13.4%)	0.015
History Of CABG	43(4.5%)	119(5.6%)	0.217
Positive Family History	140(14.6%)	346(16.1%)	0.276
SBP	132.73 ± 25.98	143.23 ± 25.27	< 0.001
DBP	83.31 ± 1837	89.08 ± 17.61	< 0.001
Killip class No CHF S3 gallop or basal rale Acute pulmonary edema Cardiogenic shock	671(98.4%) 6(0.9%) 1(0.1%) 4(0.6%)	1583(97.9%) 18(1.1%) 4(0.3%) 11(0.7%)	0.960
BMI	24.71 ± 3.46	29.10 ± 4.21	< 0.001
Waist circumferene (cm)	91.5 ± 11.5	106.1 ± 11.4	< 0.001
Total CHO	152.62 ± 36.38	160.64 ± 40.93	< 0.001
LDL	98.80 ± 32.49	104.71 ± 35.37	< 0.001
TG	103(77,137.5)	131(95,179)	< 0.001
FBS	101(90.50,126)	120(101,167)	< 0.001
Hb	15.11 ± 1.83	14.92 ± 1.96	0.01
Cr	0.9(0.8,1.07)	0.9(0.8,1.08)	0.052
EF	40.59 ± 8.43	41.42 ± 8.25	0.120
Stent Diameter	3.02 ± 0.47	2.98 ± 0.48	0.057
Stent Length	30.07 ± 12.75	30.79 ± 13.1	0.179
Vessel Disease SVD 2VD 3VD	243(25.3%) 336(35.0%) 380(39.6%)	589(27.5%) 752(35.1%) 803(37.5%)	0.378
LM	5(.05%)	15(0.7%)	0.566
LAD Territory	512(53.4%)	1088(50.7%)	0.173
LCX Territory	183(19.1%)	449(20.9%)	0.235
RCA Territory	302(31.5%)	706(32.9%)	0.429

Data are means ± SD or count (%).HLP, Hyperlipidemia; HTN, high blood pressure; DM, diabetes mellitus; COPD, chronic obstructive pulmonary disease; CVD, Cardiovascular Accident; CABG, coronary artery bypass graft; SBP, Systolic Blood Pressure; DBP: Diastolic Blood Pressure, BMI, body mass index; LDL-c, low-density lipoprotein cholesterol; HDL-c, high-density lipoprotein cholesterol; PCI, percutaneous coronary intervention; CHO, Cholesterol; TG, Total Glycerides; FBS, Fast Blood Glucose; LAD, left anterior descending artery; LCX, left circumflex artery; LM, Left Main; RCA, Right coronary artery.

A total of 66 in-hospital deaths occurred in follow up, of which 28 (2.9%) were in the non-MetS group and 38 (1.8%) were in the MetS group (OR = 0.60, 95% CI: 0.366–0.883, p = 0.043). However after adjustment for cofounding factors, no significant association was found between MetS and in-hospital mortality (OR = 0.737, 95%CI: 0.371–1.464, p = 0.383). In addition, we examined the effect of the MetS on one-year mortality in patients with and without metabolic syndrome. A total of 152 deaths were recorded during one year follow-up, of which 56 occurred in the non-MetS group and 96 in the MetS group. According to the analysis, the MetS had no significant effect on one-year mortality after adjustment for cofounding factors. (HR = 0.757, 95%CI: 0.503–1.139, p = 0.182). (Fig. 1) And finally, the adjusted and unadjusted effects of MetS on one-year MACE evaluated and none of which had a significant relationship with one-year MACE. (HR = 0.824, 95%CI: 0.665–1.022, p = 0.078). (Table 2) (Fig. 2 )

We found that MetS was a robust factor across different genders, and the prognostic value was more evident for patients who have the following: age of > 60 (HR 1.633, 95% CI 1.182–2.256, p = 0.003), LVEF of ≤ 40% (HR 2.922, 95% CI 1.668–5.119, p < 0.001), GRACE of > 140 (HR1.633, 95% CI 1.118–2.385, p = 0.011), MVD (HR 1.744, 95% CI 1.251–2.432, p = 0.001), or hsTNT of > 0.1 ng/ml (HR 1.689, 95% CI 1.237–2.307, p = 0.001).

Table 2

Cox Proportional Hazard Regression of effect of MetS on in-hospital mortality, one-year mortality and one-year MACE.
Unadjusted	In hospital mortality OR(95%CI)	P-value	One-year mortality OR(95% CI)	P-value	MACE OR(95% CI)	P-value
MetS	0.600 (0.366,0.883)	0.043	0.752 (0.541,1.046)	0.091	0.844 (0.690,1.032)	0.099
Adjusted
MetS	0.737 (0.371,1.464)	0.383	0.757 (0.503,1.139)	0.182	0.824 (0.665,1.022)	0.078
age	1.042 (1.015,1.071)	0.002	0.033 (1.016,1.050)	< 0.001	1.008 (0.999,1.018)	0.87
LDL	0.990 (0.981,1.00)	0.052	0.995 (0.990,1.001)	0.081	0.999 (0.996,1.002)	0.500
Cr	1.203 (0.915,1.581)	0.186	1.161 (0.958,1.407)	0.127	1.133 (1.013,1.268)	0.029
Hb	0.824 (0.704,0.964)	0.016	0.902 (0.819,0.993)	0.036	0.940 (0.890,0.993)	0.026
EF	0.914 (0.881,0.949)	< 0.001	0.912 (0.891,0.934)	< 0.001	0.968 (0.956,0.981)	< 0.001
Hx COPD	2.135 (0.931,4.894)	0.073	1.534 (0.916,2.569)	0.104	1.163 (0.779,1.737)	0.460
Hx CVA	1.084 (0.360,3.091)	0.880	1.492 (0.850,2.620)	0.164	0.934 (0.596,1.463)	0.764
SVD	1	0.154	1	0.001	1	< 0.001
2VD	0.922 (0.405,2.100)	0.847	0.903 (0.546,1.492)	0.690	1.243 (0.928,1.665)	0.145
3VD	1.750 (0.844,3.627)	0.133	1.963 (1.251,3.078)	0.003	3.045 (2.325,3.988)	< 0.001

A total of 421 cases of MACE occurred during the year, of which 144 cases (15%) occurred in the non-MetS group, and 277 (12.9%) cases occurred in the MetS group. The frequency of MACE types by MetS, including re-MI, revascularization, death and stroke is also shown in Table 3.

Table 3

Different types of one-year MACE and its association with MetS.
MACE TYPE	MetS(-)	MetS(+)	Total
MI	18	54	72
Death	52	92	144
Revascularization	74	156	230
Stroke	0	3	3

Finally, one-year MACE was evaluated in four different BMI subgroups according to Table 4. Only in patients with BMI < 25 was there a significant relationship between MetS and higher risk of one-year MACE (p = 0.025). The duration of hospitalization was also evaluated. The median hospitalization of both groups was approximately four days, showing no statistically significant difference (p = 0.415).

Table 4

Adjusted effect of MetS on one-year MACE in different BMIs subgroups.
BMI	Sig.	HR (95.0% CI)
< 25 + MetS	0.025	1.622 (1.062–2.476)
25–30 + MetS	0.592	1.104 (.769-1.586)
30–35 + MetS	0.413	1.395 (.629-3.094)
≥ 35 + MetsS	0.460	2.224 (.266-18.570)

Adjusted for age, LDL, Cr, Hb, EF, Smoking, COPD, CVA, PCI, SVD, 2VD, 3VD, LM, LAD territory, LCX terroir, RCA territory

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. BMI less than 25 in the group with MetS, was significantly associated with higher MACE than the non-MetS group.

This study showed a high prevalence of MetS (69%) among patients with STEMI. This prevalence was higher than 37.6–54.5% observed in previous studies, which may have drived from the difference in type of criteria used to define MetS, race, and age of the study population (4, 9–11). 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 the diagnosis of MetS in predicting the severity and prognosis of heart disease. This study showed that the risk of MACE in patients with MetS, based on 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 MACE.

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 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(12–14). Although the majority of patients were men, this percentage was significantly different in the two groups with MetS and non-MetS, and the percentage of female patients in the MetS group was higher than in the non-metabolic group (29.2–4.6%). 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, 49.1% and 27% of the non-Mets group and 35.5% and 16.1% 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). In our study, disease severity indices, including LVEF, stent diameter and length, number of vessels involved, LM involvement, and myocardial infarction, were not significantly different between MetS and non-MetS groups. In contrast, in Lee et al.'s study, LVEF was lower in the group with MetS, but angiographic indices were not significantly different. In the Lovic study 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. In the study of Lovic, there was 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. Older age, history of renal failure, lower blood pressure, history of COPD and CVA, higher class clip, higher blood sugar, coronary artery disease, lower LVEF and LM involvement were more common in cases where in-hospital death occurred(15, 16).

Research has found that there is 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, but in obese individuals with and without MetS, this association was not observed. 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. In our study, the definition of MetS based on IDF critria did not included the BMI, while BMI less than 25 was significantly associated with higher risk of MACE in patients with MetS. Hence, it can be concluded that the obesity paradox may be responsible for the lack of association between MACE and MetS in our analysis. In contrast to our findings, a similar study by Zhao et al(19) in non-ST-elevation myocardial infarction patients, reported higher occurrence of MACE in patients with BMI of higher than 28 kg/m2.

In a 2018 study, 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 the elderly without MetS, and the highest recurrence of MI occurred in young individuals with MetS. Therefore, it was concluded that the presence of MetS in people under 50 years is an independent predictor of the recurrence of MACE and MI. In our study, young and older people were studied in one group, and perhaps the lack of association between MACE and MetS is because people are not divided into young and old groups.

Despite the fact that the presence of MS at the time of PCI was not related to an elevated risk of cardiac events in the year following the treatment, MS was highly prevalent among patients with STEMI. In order to improve the prognosis for these patients, it is crucial to raise awareness and implement preventative actions.

Acknowledgment: Authors are thankful to all the participants.

Funding: Nil

Contribution: B.G. and A-M.H-Z. designed the study. M-J.Z. collaborated in conceptualization and wrote the first draft. E.S. and A.B. collaborated in data processing and statistical analysis. F.L. critically reviewed and edited the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate: The protocol of this study and written consents were approved by the ethics committee of the Tehran University of medical sciences (No: IR.TUMS.THC.REC.1400.066).

Consent for publication: Not applicable

Competing interests: The authors have declared that no competing interests exist.

Availability of data and materials: All data and the questionnaire are available upon request to the corresponding author.

ACKNOWLEDGEMENTS

We thank the esteemed staff of the Tehran Heart Center for their help.

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No competing interests reported.

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Impact of metabolic syndrome on clinical characteristics and one-year outcomes of patients undergoing primary percutaneous coronary intervention

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Introduction

Methods

Study population and study design

Definition of MS

Statistical analysis

Results

Discussion

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