Genetic Predisposition to Higher Blood Pressure Increases Coronary Artery Disease Risk HYPERTENSION Lieb, W., Jansen, H., Loley, C., Pencina, M. J., Nelson, C. P., Newton-Cheh, C., Kathiresan, S., Reilly, M. P., Assimes, T. L., Boerwinkle, E., Hall, A. S., Hengstenberg, C., Laaksonen, R., McPherson, R., Thorsteinsdottir, U., Ziegler, A., Peters, A., Thompson, J. R., Koenig, I. R., Erdmann, J., Samani, N. J., Vasan, R. S., Schunkert, H. 2013; 61 (5): 995-?


Hypertension is a risk factor for coronary artery disease. Recent genome-wide association studies have identified 30 genetic variants associated with higher blood pressure at genome-wide significance (P<5 × 10(-8)). If elevated blood pressure is a causative factor for coronary artery disease, these variants should also increase coronary artery disease risk. Analyzing genome-wide association data from 22 233 coronary artery disease cases and 64 762 controls, we observed in the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) consortium that 88% of these blood pressure-associated polymorphisms were likewise positively associated with coronary artery disease, that is, they had an odds ratio >1 for coronary artery disease, a proportion much higher than expected by chance (P=4 × 10(-5)). The average relative coronary artery disease risk increase per each of the multiple blood pressure-raising alleles observed in the consortium was 3.0% for systolic blood pressure-associated polymorphisms (95% confidence interval, 1.8%-4.3%) and 2.9% for diastolic blood pressure-associated polymorphisms (95% confidence interval, 1.7%-4.1%). In substudies, individuals carrying most systolic blood pressure- and diastolic blood pressure-related risk alleles (top quintile of a genetic risk score distribution) had 70% (95% confidence interval, 50%-94%) and 59% (95% confidence interval, 40%-81%) higher odds of having coronary artery disease, respectively, as compared with individuals in the bottom quintile. In conclusion, most blood pressure-associated polymorphisms also confer an increased risk for coronary artery disease. These findings are consistent with a causal relationship of increasing blood pressure to coronary artery disease. Genetic variants primarily affecting blood pressure contribute to the genetic basis of coronary artery disease.

View details for DOI 10.1161/HYPERTENSIONAHA.111.00275

View details for Web of Science ID 000317718200025