Family history of myocardial infarction with non-obstructive coronary arteries (MINOCA)

Abstract Introduction Genetic factors play an important role in the development of myocardial infarction (MI), and a positive family history is a risk factor for MI. The significance of family history among patients with a working diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is not known, and previous studies of family history in MI have not made a distinction between MINOCA and MI due to coronary artery disease (MI-CAD) based on angiographic findings. Purpose To investigate family history of MI with and without obstructive coronary arteries in patients with a working diagnosis of MINOCA. Methods A nationwide register-based case-control study of 15 462 MINOCA cases and 38 220 controls without MI with a non-obstructive coronary angiography due to chest pain, together with 204 424 MI-CAD cases, defined as MI with obstructive coronary arteries with a degree of stenosis >50%, between the years 1995-2020. Data from the Swedish coronary angiography and angioplasty register with information about angiographic findings was merged with information on first-degree relatives from the Swedish multi-generation register. Odds ratio (OR) was calculated with a 95% confidence interval (CI), to analyze the probability of MINOCA patients having first-degree relatives with 1) MINOCA, 2) MI-CAD, and 3) MI-CAD patients having first-degree relatives with MI-CAD. Logistic regression models adjusted for age, sex, hypertension, diabetes, hyperlipidemia and smoking status. Results A total of 161 MINOCA patients (1%) had ≥1 first-degree relative with MINOCA and the probability of having a positive family history of MINOCA did not differ compared to controls, with age and sex adjusted OR 1.08 (95% CI 0.89-1.31) and when adjusting for all covariates 1.08 (95% CI 0.87-1.34). Conversely, 1436 MINOCA patients (9%) had ≥1 first-degree relative with MI-CAD and the probability of having a positive family history of MI-CAD was higher compared to controls with age and sex adjusted OR 1.12 (95% CI 1.05-1.20) and when adjusting for all covariates OR 1.16 (95% CI 1.04-1.20). The sensitivity analysis showed that 24 972 MI-CAD (9%) patients had a positive family history of MI-CAD compared to controls, OR adjusted for age and sex 1.68 (95% CI 1.61-1.75), and OR adjusted for all covariates 1.68 (95% CI 1.60-1.75). Conclusions In this first study that examines family history of MINOCA, including data from over 250 000 coronary angiograms, a positive family history of MI-CAD was more common among patients with a working diagnosis of MINOCA compared to controls without MI and with non-obstructive coronary arteries. A family history of MINOCA was uncommon and was not associated with MINOCA. These results indicate that genetic factors and shared environmental factors within a family leading to CAD are important also for MINOCA, thus MI-CAD and MINOCA share underlying mechanisms.