Pharmacogenetics of Cardiovascular Prevention in Diabetes: From Precision Medicine to Identification of Novel Targets.

Pharmacogenetics-a branch of precision medicine-holds the promise of becoming a novel tool to reduce the social and healthcare burdens of cardiovascular disease (CVD) and coronary artery disease (CAD) in diabetes. The improvement in cardiovascular risk stratification resulting from adding genetic characteristics to clinical data has moved from the modest results obtained with genetic risk scores based on few genetic variants, to the progressively better performances of polygenic risk scores based on hundreds to millions of variants (CAD-PGRS). Similarly, over the past few years, the number of studies investigating the use of CAD-PGRS to identify different responses to cardio-preventive treatment has progressively increased, yielding striking results for lipid-lowering drugs such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and statins. The use of CAD-PGRS to stratify patients based on their likely response to diabetes-specific interventions has been less successful, but promising results have been obtained with regard to specific genetic variants modulating the effects of interventions such as intensive glycemic control and fenofibrate. The finding of diabetes-specific CAD-loci, such as