Journal
ATHEROSCLEROSIS
Volume 222, Issue 2, Pages 456-463Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2012.03.024
Keywords
Coronary artery disease; Cardiovascular disease; Genetic variants; Genetic risk; Polymorphisms; Risk assessment
Funding
- ACC1O [RD08-1-0024]
- European Funds for Development (ERDF-FEDER)
- Spanish Ministry of Science and Innovation through the Carlos III Health Institute [CIBER Epidemiologia y Salud Publica, Red HERACLES] [RD06/0009, PI061254, PI09/90506]
- Fundacio Marato TV3 [081810, 080431]
- Catalan Research and Technology Innovation Interdepartmental Commission [SGR 1195]
- Ministerio de Educacion [JCI-2009-04684]
- Comissionat per a Universitat I Recerca del Departament d'Innovacio, Universitats I Empresa de la Generalitat de Catalunya [2007-BP-B1-0068]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK075030]
- US Department of Agriculture Research [53-K06-5-10, 58-1950-9-001]
- Spanish National DNA Bank [2008/0012]
- National Heart, Lung, and Blood Institute (NHLBI) [HL-54776, N01-HC-25195, N02-HL-64278]
- Boston University [N01-HC-25195]
- [1534]
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Background: The American Heart Association has established criteria for the evaluation of novel markers of cardiovascular risk. In accordance with these criteria, we assessed the association between a multi-locus genetic risk score (GRS) and incident coronary heart disease (CHD), and evaluated whether this GRS improves the predictive capacity of the Framingham risk function. Methods and results: Using eight genetic variants associated with CHD but not with classical cardiovascular risk factors (CVRFs), we generated a multi-locus GRS, and found it to be linearly associated with CHD in two population based cohorts: The REGICOR Study (n = 2351) and The Framingham Heart Study (n = 3537) (meta-analyzed HR [95% CI]: similar to 1.13 [1.01-1.27], per unit). Inclusion of the GRS in the Framingham risk function improved its discriminative capacity in the Framingham sample (c-statistic: 72.81 vs. 72.37, p = 0.042) but not in the REGICOR sample. According to both the net reclassification improvement (NRI) index and the integrated discrimination index (IDI), the GRS improved re-classification among individuals with intermediate coronary risk (meta-analysis NRI [95% CI]: 17.44 [8.04; 26.83]), but not overall. Conclusions: A multi-locus GRS based on genetic variants unrelated to CVRFs was associated with a linear increase in risk of CHD events in two distinct populations. This GRS improves risk reclassification particularly in the population at intermediate coronary risk. These results indicate the potential value of the inclusion of genetic information in classical functions for risk assessment in the intermediate risk population group. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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