Myocardial infarction (MI) continues to be a major cause of mortality, contributing to the burden on individuals and society through its acute onset, relatively high mortality, unfavorable prognosis, and considerable medical costs (1). Metabolic abnormalities, including dyslipidemia, hypertension (HTN), glucose intolerance, and abdominal obesity, have been recognized as important risk factors for MI and its associated mortality (2,3). In the Middle East and North Africa (MENA) region, systolic blood pressure (SBP) with a cut-off of ≥120 mmHg and diabetes mellitus (DM) appear to be important contributors to cardiovascular disease (CVD) burden among both men and women, in terms of population-attributable fraction (PAF) (3), with PAFs of 26.1% and 33.9% for SBP in men and women, respectively, and 19.3% and 25.4% for DM in men and women, respectively.

Metabolic syndrome (MetS), as a surrogate of insulin resistance, is a cluster of metabolic risk factors, including elevated blood pressure, impaired fasting glucose, dyslipidemia, and central adiposity (4). According to the International Diabetes Federation (IDF) criteria, the Eastern Mediterranean region had the highest global prevalence of MetS at 34.6%, whereas, based on the Joint Interim Statement (JIS) definition, it reported the second highest rate at 35.9% (5). Previous studies have consistently demonstrated a significant association between the presence of MetS and an increased risk of CVD and CVD-related mortality, supporting its prognostic significance for adverse cardiovascular outcomes (6, 7, 8, 9). Among patients with acute coronary syndrome (ACS), the prevalence of MetS based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria has been reported to range from approximately 37.1% to 58.9% (10, 11, 12, 13, 14). Moreover, the prevalence of MetS among patients with MI was 22.1% using the World Health Organization (WHO) criteria and 28.1% using the IDF criteria (15).

We previously demonstrated the role of MetS in the development of CVD among Iranian adults (16, 17, 18). The association between MetS and MI was demonstrated in 52 countries, including Middle Eastern populations, using IDF and WHO criteria, with MetS conferring a risk comparable to DM or HTN alone (15). However, whether MetS in the absence of DM and HTN confers an elevated risk of MI remains less studied. There appears to be substantial heterogeneity in the risk conferred by MetS, depending on its accompanying metabolic abnormalities such as obesity, HTN, and DM (19, 20, 21, 22, 23, 24). For all-cause and cardiovascular mortality, previous community-based evidence has shown that MetS in the absence of both HTN and DM is not associated with an increased risk (25). Elevated triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), and excess adiposity, the prominent MetS components in individuals who do not have HTN or DM, have been shown to be associated with higher risk of CVD (26, 27, 28). However, it is unclear whether clustering these traits as MetS identifies individuals at higher risk of incident MI among those free of HTN and DM. Accordingly, we used data from the Tehran Lipid and Glucose Study (TLGS), a large-scale prospective Iranian cohort, to examine the association of MetS and its subgroups, defined by the presence or absence of HTN and DM, with incident MI. As a secondary aim, we evaluated the associations of individual MetS components with the risk of incident MI, both continuously and in a dichotomized fashion.