Does genetic information improve prediction of cardiovascular risk?

A single nucleotide polymorphism (SNP), or genetic variation, in the chromosome 9p21.3 region has recently been found to be strongly associated with coronary artery disease.  However, it is not known whether checking for this genetic variation would improve upon conventional ways of evaluating a person’s risk for coronary artery disease.  Fondation Leducq-supported investigators Paul M. Ridker and Julie E. Buring and their colleagues addressed this question in a study published in the January 20, 2009 issue of the Annals of Internal Medicine.

The study followed 22,129 white women enrolled in the Women’s Genome Health Study for 10 years.  Conventional risk factors that were assessed included clinical indices such as age, blood pressure, smoking history, and family history of premature heart disease, as well as laboratory indices such as cholesterol and C-reactive protein (CRP) levels.  Each woman also underwent genetic analysis to determine if she had 0, 1 or 2 copies of the high-risk SNP in 9p21.3.  Among the study population, 49.5% had 1 copy and 24.3% had 2 copies.

Consistent with previous studies in men, having 1 or 2 copies of the 9p21.3 SNP was associated with a higher risk of coronary artery disease.  In addition, the SNP was associated with stroke, abdominal aortic aneurysm, intracranial aneurysm and a family history of premature heart disease.  However, when the conventional risk factors were taken into account, knowledge of the SNP status did not add any incremental information about the risk for coronary artery disease.  Thus, although the SNP may be important in the pathophysiology of coronary artery disease, it is unlikely that screening for it will be useful in clinical practice.  It is possible that presence of the SNP did not override the low cardiovascular risk in this middle-aged female population, or that the SNP was so common that it no longer added incremental value to the other risk factors.  The results of this study may not apply in other populations.  Finally, while screening for this particular SNP is unlikely to be clinical useful in itself, evaluating multiple genetic locations, including 9p21.3, may be.

Drs. Buring and Ridker are members of the Leducq Transatlantic Network of Excellence on Atherothrombosis.  This research was also supported by the National Heart, Lung and Blood Institute, the National Cancer Institute, the Donald W. Reynolds Foundation, Celera, Roche Diagnostics, and Amgen.

Click on the title to access the article in the Annals of Internal Medicine:  Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3