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Gene polymorphism predicted CV events, mortality in white Europeans

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NEW YORK — People with the TT homozygote at position –665 on the eNOS gene had a higher risk for CV events, coronary events, CV mortality and all-cause mortality compared with those with the C allele, according to findings presented at the American Society of Hypertension 2014 Annual Scientific Meeting.

Previous research had identified the TT homozygote at that position as being associated with higher risk for hypertension. Laura Olivi, MD, of the Università degli Studi di Milano in Italy, and colleagues compared CV outcomes in people with the TT homozygote (n=32) or the C allele (n=2,787) in 2,819 white Europeans enrolled in the Flemish Study on Environment, Genes and Health Outcomes.

Participants were followed for a median of 15 years. The outcomes of interest were CV mortality, CV events and coronary events.

After accounting for family clusters, the researchers found that the HRs associated with having the TT homozygote were as follows:

• CV mortality, 4.11 (95% CI, 1.53-11.1).
• CV events, 2.75 (95% CI, 1.32-5.73).
• Coronary events, 3.1 (95% CI, 1.18-8.17).

After further adjustments for CV risk factors, Olivi, of the University of Milan, Italy, and colleagues found that the HRs associated with having the TT homozygote were as follows:

• CV mortality, 6.01 (95% CI, 2.26-16).
• CV events, 2.64 (95% CI, 1.27-5.46).
• Coronary events, 2.89 (95% CI, 1.28-6.5).

The results did not change when adjustments for BP and antihypertensive treatment were not made, Olivi said during a presentation.

For all CV events, the positive predictive value of having the TT homozygote was 21.9%, the attributable risk was 61.5% and the population-attributable risk was 2%, Olivi and colleagues found. In positive predictive value and attributable risk, having the TT homozygote was higher than smoking, Olivi said. It was lower than smoking in population-attributable risk because the prevalence of the TT homozygote is only about 1%, while the prevalence of smoking is much higher, she said.

The results “suggest that high BP and adverse outcomes are not necessarily causally linked, but they may be a result of a common pathophysiological process,” Olivi said. “For instance, in this case, an insufficient production of nitric oxide. Of course, the exact mechanism must be clarified in other studies.” – by Erik Swain

For more information:

Olivi L. Abstract LB-OR-03. Presented at: American Society of Hypertension 2014 Annual Scientific Meeting; May 16-20, 2014; New York City.

Disclosure: The researchers reported no relevant financial disclosures.