Family history of premature coronary artery disease (pCAD) is a risk factor for coronary artery disease (CAD), reflecting the genetic and environmental interplay. However, positive family history of pCAD frequently reflects presence of conventional cardiovascular risk factors. Its precise clinical value in risk prediction of mortality in addition to other risk factors remains uncertain. 

This studies aim was to evaluate the effect of positive family history of pCAD on long-term survival in patients suffering from significant CAD following percutaneous coronary intervention (PCI). 

The present analysis is based on the ECAD registry of patients undergoing invasive coronary angiography at the Department of Cardiology and Vascular Medicine at the University Clinic Essen between 2004 and 2019. Positive family history of pCAD was defined as having a first-degree male relative who had been diagnose with CAD by age 55, or a first-degree female relative by age 65.  Baseline characteristics and long-term survival of patients who underwent PCI due to significant CAD during baseline hospitalization with and without a self-reported positive family history of pCAD were compared. Cox regression analysis was used to evaluate the association of positive family history and survival, controlling for traditional risk factors and medication. 

Overall, data from 7176 patient admissions (mean age 66.5±11.3 years, 74.7% male) were included in our analysis. Comparison of baseline characteristics showed that patients with a positive family history of pCAD were significantly younger (63.7±11.2 vs. 67.5±11.2 years; p<0.001) and reported a higher rate of smoking (60.2% vs. 36.5%; p<0.001). Additionally, the rate of patients recommended to taking ACE-Inhibitors (62.7% vs. 56.8%; p<0.001), and ß-blockers (78.8% vs. 71.2%; p<0.001) was higher among patients with positive family history.

Analysis of survival by univariate Cox regression analysis showed that positive family history as compared to no family history of pCAD was significantly associated with better long-term survival (hazard ratio (HR) [95% confidence interval (CI)]: 0.65 [0.59-0.70]; p<0.001). Effect sizes remained stable after controlling for traditional cardiovascular risk factory in multivariable Cox regression analysis (HR [95% CI]: 0.61 [0.53-0.72; p<0.001). However, when ancillary adjusting for medication, link between positive family history of pCAD and lower mortality rate was no longer present (HR [95% CI]: 0.88 [0.75-1.03]; p=0.11). 

Patients with a positive family history of premature CAD undergoing PCI due to significant CAD are younger and display a higher cardiovascular risk profile, but, contradictorily, possess a better long-term survival. This effect is – at least in parts – explained by an intensified medical strategy in patients with positive family history of premature CAD.