9p21. More than just three numbers and one letter, this stretch of DNA, which is present in 1 out of five Caucasians, results in a 64% increase in the risk of myocardial infarction. Two groups, performing genome-wide association studies, made this discovery, which would not have been possible before the work of the Human Genome Project. It should be noted that this mutation is not present in Africans and does not confer an increased risk in African Americans. This stretch of DNA is also linked to diabetes, though the patients studied did not have diabetes. I can only imagine that these studies will have enormous effects and may usher in the genomic age that we have been hearing about for so long. Perhaps we will be far better able to stratify patients according to their genetic risk and develop targeted gene therapies. Science #1 Link, Science #2 Link, New York Times Link
In the New England Journal of Medicine, this week, we have results from the HORIZON Pivotal Fracture Trial, which showed that A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. Given issues with compliance with daily oral therapies, it appears that use of a once-yearly infusion, that produces a sustained reduction in bone turnover and increased bone mineral density may result in a major impact on osteoporosis-related fractures in post-menopausal women. In fact, at 3 years, the incidence of vertebral fractures in this study were reduced by 70%, hip fractures by 41%, and nonvertebral fractures by 25%. As always, a caveat must be mentioned; the treatment group had an increased risk of atrial fibrillation, though no increased risk of death. NEJM Link
Two studies in this week’s Annals of Internal Medicine show that use of Infliximab (Remicaide) does not improve endpoints in the treatment of polymyalgia rheumatica or giant cell arteritis. Both trials examined the effectiveness of infliximab after tapering off steroids, which are known to have a therapeutic effect in these diseases, but with serious side effects. In neither trial did infliximab reduce the rate of relapse or recurrence. These results can be interpreted to suggest that TNF-a, which infliximab effectively blocks does not play a major role in the pathogenesis of these diseases. Perhaps other biologics, targeting other cytokines will be more effective.
Annals Link #1
Annals Link #2
-Michael Poles, MD Associate Editor Clinical Correlations
Image: one way street in Pompeji, Greece, by: Martin Herbst, courtesy Wikimedia Commons