Abdullah Bhuiyan, Muhammad Afridi, Khadijeh Shamsi, Mina Hmimas, Mohammadamin M Esfahani, Noushin Mohammadifard, Ehsan Zarepur, Nizal Sarrafzadegan
Introduction Premature coronary artery disease (PCAD) is highly prevalent in many low- and middle-income countries, including Iran. Women remain underdiagnosed in clinical practice and underrepresented in PCAD research, particularly across ethnically diverse populations. Iran comprises multiple major ethnic groups with distinct cultural, dietary, and lifestyle characteristics that may differentially shape cardiometabolic risk, providing a compelling rationale for ethnicity-stratified investigation of PCAD in women. Methods We analyzed data from the multicenter Iran Premature Coronary Artery Disease (IPAD) case-control study. Cases were women with angiographically confirmed obstructive coronary artery disease occurring at or before 70 years of age, whereas controls had normal coronary arteries on angiography. Although PCAD is commonly defined as CAD occurring before 65 years of age in women, the IPAD study extended the upper age limit to 70 years to reflect the later average age of CAD onset in Iranian women compared with Western populations and to capture a broader at-risk demographic in the context of Iran's epidemiological profile. This age criterion is consistent with the published IPAD study protocol. Results A total of 1,609 Iranian women aged ≤70 years were included, comprising 789 PCAD cases and 820 controls across eight ethnic groups from 15 cities. Across ethnicities, women with PCAD were consistently older than controls and were characterized by lower educational attainment, predominantly low socioeconomic status, very low smoking prevalence, and higher adiposity. Cardiometabolic risk factors varied by ethnicity: hypertension and diabetes were more common among cases in most groups, low high-density lipoprotein cholesterol (HDL-C) levels were highly prevalent in both cases and controls, and family history of cardiovascular disease (CVD) was more frequent among cases in several ethnicities. Ethnicity-stratified analyses revealed distinct risk factor profiles across groups. Among Fars women, hypertension, diabetes, low HDL-C, and family history of CVD were associated with higher odds of PCAD. Among Arab women, hypertension and diabetes were the dominant risk factors. Hypertriglyceridemia was the primary lipid-related predictor among Gilak women, while family history of CVD was the most prominent risk factor among Kurd and Bakhtiari women. Conclusions Traditional cardiometabolic risk factors are associated with PCAD among Iranian women, but their magnitudes vary across ethnic groups, supporting ethnicity-informed risk assessment and tailored prevention strategies.