Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease

• Published in: Atherosclerosis 2015-04, Vol.239 (2), p.451-458
• Main Authors: Weijmans, Maaike, de Bakker, Paul I.W, van der Graaf, Yolanda, Asselbergs, Folkert W, Algra, Ale, Jan de Borst, Gert, Spiering, Wilko, Visseren, Frank L.J
• Format: Article
• Language: English
• Subjects: Aged; Cardiovascular; Coronary Artery Disease - diagnosis; Coronary Artery Disease - genetics; Coronary Artery Disease - mortality; Decision Support Techniques; Disease Progression; Disease-Free Survival; Female; Genetic Markers; Genetic Predisposition to Disease; Genetic risk score; Genetic Testing; Humans; Incremental value; Male; Middle Aged; Myocardial Infarction - diagnosis; Myocardial Infarction - genetics; Myocardial Infarction - mortality; Netherlands; Phenotype; Polymorphism, Single Nucleotide; Prediction score; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Stroke - diagnosis; Stroke - genetics; Stroke - mortality; Time Factors; Vascular events
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2015.02.008

Abstract Background Several genetic markers are related to incidence of cardiovascular events. We evaluated whether a genetic risk score (GRS) based on 30 single-nucleotide-polymorphisms associated with coronary artery disease (CAD) can improve prediction of 10-year risk of new cardiovascular events in patients with clinical manifest vascular disease. Methods In 5742 patients with symptomatic vascular disease enrolled in the SMART study, we developed Cox regression models based on the SMART Risk Score (SRS) and based on the SRS plus the GRS in all patients, in patients with a history of acute arterial thrombotic events and in patients with a history of more stable atherosclerosis and without CAD. The discriminatory ability was expressed by the c-statistic. Model calibration was evaluated by calibration plots. The incremental value of adding the GRS was assessed by net reclassification index (NRI) and decision curve analysis. Results During a median follow-up of 6.5 years (IQR4.0–9.5), the composite outcome of myocardial infarction, stroke, or vascular death occurred in 933 patients. Hazard ratios of GRS ranging from 0.86 to 1.35 were observed. The discriminatory capacity of the SRS for prediction of 10-year risk of cardiovascular events was fairly good (c-statistic 0.70, 95%CI 0.68–0.72), similar to the model based on the SRS plus the GRS. Calibration of the models based on SRS and SRS plus GRS was adequate. No increase in c-statistics, categorical NRIs and decision curves was observed when adding the GRS. The continuous NRI improved only in patients with stable atherosclerosis (0.14, 95%CI 0.03–0.25), increasing further excluding patients with a history of CAD (0.21, 95%CI 0.06–0.36). Conclusions In patients with symptomatic vascular disease, a GRS did not improve risk prediction of 10-year risk of cardiovascular events beyond clinical characteristics. The GRS might improve risk prediction of first vascular events in the subgroup of patients with a history of stable atherosclerosis.