Background and Aims: Assessment of cardiovascular risk using established risk scores such as ESC SCORE2 or the Prospective Cardiovascular Münster (PROCAM) score insufficiently emphasize the role of genetic factors. A number of commercially available assays for genetic polymorphisms associated with an increased risk of atherosclerotic and/or thromboembolic events may provide additional information on hereditary cardiovascular risk in a timely and cost-efficient manner. In this study, we aim to investigate whether the results of a genetic assay for selected polymorphisms implicated in cardiovascular disease may improve cardiovascular risk assessment in coronary artery disease patients. 

 

Methods: In a cohort of 51 patients treated for coronary artery disease (CAD) at University Hospital Heidelberg, Germany, a subgroup of patients with “unstable” CAD (i.e. recurrent acute coronary syndrome) was identified and compared to patients with “stable” disease (i.e. chronic coronary syndrome). Gene array analysis using a commercial assay for 15 potentially pathogenic polymorphisms was performed to evaluate genetic risk profile regarding atherosclerotic and/or thromboembolic events. Improvement of cardiovascular risk assessment based on established risk scores was analyzed using net reclassification, logistic regression and receiver operating characteristic (ROC) analysis.

 

Results: Discriminatory capacity of traditional risk scores such as SCORE2 or PROCAM with regard to “stable” and “unstable” CAD groups was found to be poor (ROC AUC <0.5). Patients in the “unstable” CAD group exhibited a significantly increased frequency of pathogenic eNOS 984 and MTHFR 1298 polymorphisms compared to “stable” CAD patients, and information on these polymorphisms significantly improved risk assessment based on SCORE2 or PROCAM scores (p<0.05, ROC AUC ≥0.75). Moreover, combinations of pathogenic polymorphisms included in the assay such as eNOS 984, MTHFR 1298, ACE d/d or PAI-1 mutations additionally optimized established risk prediction models, resulting in a marked improvement of discriminatory ability between the “unstable” and “stable” CAD groups in our cohort.

 

Conclusion: Commercially available assays for genetic polymorphisms may provide valuable information on individual genetic cardiovascular risk, and their standardized use in cardiologic baseline diagnostics could make genetic risk profile a hallmark of cardiovascular risk assessment in the future, potentially guiding primary and/or secondary preventative therapies for coronary artery disease.