PrimeCuts: This Week in the Journals

January 26, 2009

bellevue.jpgCommentary by Michael Tees MD, MPH , PGY-1

The journals this week were not where the eyes of the nation or the world were fixed. All were focused upon a turning point, a new beginning, a change. The inauguration of America’s first African-American president and what that represented was where our attention was fixed. Policies before or after a leadership change can always be debated. But what happened on this special day in American history can be considered a birth of a new era, born from a collective abolishment of old thought. This era is embracing unconventionality and emphasizing unification of people and ideas. Will this era carry into the field of medicine? Will we see a turning point in research where unconventional thought produces novel therapies? Will we remember anything at all? Let’s take a look at the news this week to see if we can predict.

One of the most significant news, published in the New England Journal of Medicine this week, involves how we are treating those with coronary disease using clopidogrel. Previously known was the variability in the efficacy of the antiplatelet activity. Certain variants of genes that affect absorption, activation, and activity of the drug were assessed in relationship to risk of death, nonfatal stroke, or a myocardial infarction over 1 year.  This study found that in patients with an acute myocardial infarction who were starting clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events. This was especially true of those undergoing percutaneous coronary intervention (1). CYP2C19 is normally involved in activation of the drug. Lancet also published a study this week showing this genetic variant is particularly detrimental in younger patients (< 45 years) starting on clopidogrel after an acute myocardial infarction (2).

Since clopidogrel is known to dramatically reduce the rate of adverse cardiac events on the whole, how would the cardiologist know who should and who should not start drug therapy? New methods may be in the pipeline. Circulation published a study this week showing a particular assay used in patients receiving clopidogrel after stenting could detect acute coronary syndrome patients at risk of cardiovascular death or myocardial infarction. This assay detected high residual platelet reactivity, which has been associated with increased risk of events in those with dual-antiplatelet therapy (3). While no new therapies have been produced from this information, we are better learning to tailor our current regimen for decreased side effects.

However, the gene might not always reveal useful information. In a study published in the Annals of Internal Medicine, screening for a chromosome variant associated with incident CVD risk was shown to predict incident cardiovascular disease in a large cohort of white women. However, having this information was not any more effective at classifying those at risk compared to currently used risk factors (like ATP III) or knowing a family history of premature myocardial infarction (4). Perhaps this screening tool may be ahead of its time.

One interesting article in Circulation showed a potential future therapy. Renal artery stenosis induces ischemic nephropathy, an important cause of hypertension and end-stage renal disease. The researchers hypothesized that endothelial progenitor cells, which promote neovascularization and endothelial repair, may help protect the kidney in this disease. A single infusion was found to preserve the microvasculature and function and decrease microvascular remodeling (5). While this was studied in pigs on experimentally induced renal disease, further research may eventually lead to new therapies in humans.

The genotype is beginning to offer more information, but can do little to address the environment we interact with. A study published in the New England Journal of Medicine and highlighted in the New York Times compiled data on fine-particulate air pollution in 51 U.S. metropolitan areas from the late 1970’s and late 1990’s. Researchers gathered information on life expectancy, socioeconomic status, and demographic characteristics, and found that a decrease of 10 micrograms per cubic centimeter of fine-particulate matter caused an increase in the mean life expectancy of 0.6 years (6). Some good news from this is that none of the metropolitan areas studied had an increase in air pollution between the two periods of time.

But let’s not get stressed out about all this. Featured in the New York Times and cnn.com, a cohort study published in Neurology found that elderly patients who were less anxious and more extroverted had a significant decrease in risk for developing dementia. Low anxiety was also associated with a decreased risk of dementia in those in an inactive or socially isolated lifestyle (7).

Perhaps the physician community should reflect on this news and help advance a new era in medicine. A perspective piece in JAMA this week examined the recent Institute of Medicine report recommending that medical residents should work no more than 16 hours without sleep (8). Designed to reduce fatigue for the young doctor, this may improve patient care at the same time. Combined with more direct supervision, increased time off between shifts and more days off per month are highly recommended. More time away from the hospital or practice may conflict with the sense of responsibility to always be available to the patient. In an essay by Danielle Ofri, MD, PhD, DLitt, in JAMA, she writes of her career in part-time medicine. She discusses the realities and limitations of medicine today and reflects on not being available 24/7 for her patients. The extra time, however, provided her the opportunity to explore a literary passion. When offered a full-time academic position with the associated increase in pay, she thought about “…the one thing that I could not buy with money – time. So I ‘bought’ myself the time to continue writing by turning down the full time offer” (9).

Modern medicine will continue to be led by break-through findings, such as those being discovered by unraveling the DNA strand. But perhaps a new era of medicine will come not by novel therapies or breakthrough research, but by the delivery of care. The modern physician, fostered by more stringent work-hour regulations enforced early in the career, may have a second passion outside of medicine. Maybe the profession will move away from old thoughts and encourage time away from the hospital or science bench. Or not. Pagers are still in use today, and will likely still be in the future.

1. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. New Engl J Med. 2009;360:363-75.
2. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009;373:309-317.
3. Marcucci R, Gori AM, Paniccia R, et al. Cardiovascular death and nonfatal myocardial infarction in acute coronary syndrome patients receiving coronary stentng are predicted by residual platelet reactivity to ADP detected by a point-of-care assay: a 12-month follow-up. Circulation. 2009;119:237-242.
4. Paynter NP, Chasman DI, Buring JE, Shiffman D, Cook NR, Ridker PM. Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Ann Intern Med. 2009;150(2):65-72.
5. Chade AR, Zhu X, Lavi R, et al. Endothelial progenitor cells restore renal function in chronic experimental renovascular disease. Circulation. 2009;119:547-557.
6. Pope CA, Ezzati M, Dockery DW. Fine-particulate air pollution and life expectancy in the United States. New Engl J Med. 2009;360:376-386.
7. Wang HX, Karp A, Herlitz A, et al. Personality and lifestyle in relation to dementia incidence. Neurology. 2009;72:253-259.
8. Khuen BM. IOM: Shorten residents’ work shifts to reduce fatigue, improve patient safety. JAMA. 2009;301(3):259-261.
9. Ofri D. Part-time medicine. JAMA. 2009;301(3):254-255.

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