ShortCuts-This Week in the Journals

May 6, 2008

island.jpgCommentary by Sean Cavanaugh MD, Associate Editor, Clinical Correlations

More strong evidence is popping up in the journals indicating that genes might actually be important in determining disease. Who knew? Now that we are well into the dawning age of genetically determined diagnosis and therapy, this week features a few interesting articles on recently discovered genetic associations with particular disease. Other than that – it’s all about global hypertension…

The Lancet features a type of research increasingly seen in the major journals: combing the genome for single nucleotide polymorphisms (or SNPs) associated with disease, in this case osteoporosis. Association studies identified two suspect SNPs from an initial cohort of 2094 women in the United Kingdom with osteoporosis and then “validated” the Odds Ratios in other cohorts derived from western Europe. The Odds Ratio for the combination of these alleles was independent of bone mineral density but wasn’t too impressive (1.3); however it does compare with known environmental risk factors for fractures and could very likely have a role in the near future as the era of genetic analysis continues to unfold.

The New England Journal of Medicine features a publication on shared genetic causes of cardiac hypertrophy. Taking a group of 84 children who were diagnosed with idiopathic cardiac hypertrophy before the age of 15 (33 of whom had positive family histories for cardiomyopathy and 51 of whom had no such history and were presumed to be sporadic cases), analyses were run to determine the presence of genetic mutations known to be associated with cardiac hypertrophy. Nucleotide sequences encoding eight sarcomere-protein genes and two metabolic genes were determined in each proband. Tested mutations were found in 21 of 33 children with apparent family history and in 25 of the 51 children without a family history (4 of whom demonstrated new mutations and 7 of whom had inherited mutations that simply didn’t manifest in their parents). There was a clear trend toward mutations in 2 of the 8 sarcomere protein genes that were tested and significantly more of a particular mutation (a missense mutation in MYBPC3) was found in this group of children as compared to adults with inherited cardiac hypertrophy. The bigger clinical implications of this will be told in the future when specific therapies will be designed, but for now this research provides further evidence for specific testing of children with cardiac hypertrophy and their families.

Interestingly, both The Lancet and NEJM also feature articles on hypertension. The Lancet published a terrific article on the global burden of blood pressure related disease. Analysis suggests that about 80% of the burden occurred in low-income and middle-income economies, and over half occurred in people aged 45–69 years. About half this burden was in people with hypertension; the remainder was in those with lesser degrees of high blood pressure. The obvious implication of this is that the need for preventative care (treating patients with “pre-hypertension”) in resource-poor countries is and will be of imminent importance as the population continues to grow older. On the heels of that, and suggesting that it is never too late, the NEJM published a study looking at the effects of treating hypertension in the over-80 age group. 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. Perhaps not surprisingly, treating hypertension in this cohort was associated with a lower risk of stroke, cardiac events, CHF, adverse events and all cause mortality. Although this study had some obvious limitations (conclusive evidence for cause of death was not routinely available and there was no reporting on associated effects of treating blood pressure in patients with co-morbid conditions), this is one of the few trials that provide firm evidence in this group specifically. The thiazides are inexpensive and seemingly very effective medicines – if the above two articles are taken in hand, we are a small step away from proving to ourselves the need for and even financial intelligence of treating chronic medical conditions like hypertension in resource-poor countries.

To finish it up, JAMA features an original article suggesting that cost-related nonadherence to prescribed medical regimens in the elderly has decreased slightly (but significantly) since the introduction of Medicare Part D – although this did not seem to hold true for the sickest of the beneficiaries. An interesting and context-providing editorial accompanies this article. For other new reading on the topic of health care in America, flip back to NEJM which has a nicely written Perspectives piece about the all-too-familiar situation we presently find ourselves in.