Aims: Family history is a known risk factor for early-onset myocardial infarction (EOMI). However, the role of modifiable lifestyle and metabolic factors in EOMI risk is unclear.

Methods: This case-control study included MI-patients aged ≤45 years from a German EOMI registry and age-sex matched controls randomly selected from the general population at the same geographical region. Multiple logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the individual and combined associations of lifestyle and metabolic factors with EOMI risk, overall and according to family history for premature MI.  

Results: A total of 522 cases and 1,191 controls were included. A very strong association between lifestyle and metabolic factors and EOMI risk was found. In an adjusted model, the strongest predictor of EOMI risk was hypertension (OR: 84.5, 95%CI: 31.4-226.9), followed by current smoking (OR: 11.8, 95%CI: 7.9-17.4), waist-to-hip ratio (top vs bottom tertile; OR: 6.3, 95%CI: 3.4-11.5), and diabetes mellitus (OR: 5.3, 95%CI: 2.4-11.7). By contrast, higher frequency of alcohol consumption was associated with decreased EOMI risk. In a combined analysis of current smoking, hypertension, diabetes mellitus, and BMI ≥25.0kg/sqm, participants having one (OR=5.4, 95%CI=2.9-10.1) and two or more risk factors (OR=42.3, 95%CI=22.3-80.4) had substantially higher odds of EOMI compared to those with none of these risk factors, regardless of their family history (Figure 1).

Conclusion: Lifestyle and metabolic factors are strongly associated with EOMI risk irrespective of family history. These findings suggest that the risk of EOMI goes beyond just family history and demonstrate that lifestyle modifications and prevention of metabolic syndrome could potentially reduce EOMI risk, even among those with a family history of premature MI.