Self-reported family history, however, was significantly associated with cardiovascular disease in Caucasian women.
Use of genetic risk scores comprising single nucleotide polymorphisms (SNPs) was unable to improve the prediction of incident cardiovascular disease in Caucasian women, according to a study published in the February 17 JAMA.
Nina P. Paynter, PhD, of Brigham and Women’s Hospital in Boston, and colleagues sought to determine the effectiveness of genetic risk scores in predicting incident myocardial infarction, ischemic stroke, coronary revascularization, and cardiovascular death. They created two such scores and applied them to a cohort of 19,313 participants from the Women’s Genome Health Study, which includes over 25,000 women who provided blood samples and extensive survey data. The researchers said that they limited their cohort to Caucasian women “to avoid population stratification and because many of the published genetic associations have been explored in white populations only.”
Both risk scores were created using the National Human Genome Research Institute’s catalogue of associations between SNPs and human disease phenotypes that were published between 2005 and June 5, 2009. The researchers’ primary risk score was the sum of cardiovascular disease risk alleles from all 101 SNPs that had a published association with cardiovascular disease or at least one intermediate phenotype. Their secondary risk score was the sum of cardiovascular disease risk alleles from all 12 SNPs that had a published association with cardiovascular disease.
The study participants experienced 777 cardiovascular disease events during a median follow-up of 12.3 years. The primary risk score’s highest tertile had a significant hazard ratio of 1.22 in comparison with its lowest tertile, which corresponded to an absolute cardiovascular disease risk of 3.7% over 10 years in the highest tertile and 3% in the lowest tertile. After adjustment for traditional cardiovascular disease risk factors, however, the investigators found that neither of the scores was associated with increased risk for incident cardiovascular disease. In addition, the scores did not improve discrimination or reclassification when added to the covariates of existing risk scores. Self-reported family history of premature myocardial infarction, in contrast, remained associated with incident cardiovascular disease in multivariate models.
The researchers concluded that known genetic markers cannot yet be used to improve cardiovascular disease risk prediction. They noted, however, that their findings “confirm the importance of family history of cardiovascular disease, which integrates shared genetics, shared behaviors, and environmental factors.” The “substantial risk component due to genes and shared environment,” they added, “may be elucidated by future genetic research.”
—Jack Baney