Primecuts – This Week In The Journals

January 23, 2012

By David Hormozdi, MD

Faculty Peer Reviewed

With snow blanketing much of the Northeast it feels like winter has finally reared its ugly head here in New York City. While the hassle of shoveling snow and icy sidewalks may put a damper on your weekday plans, PrimeCuts is here to offer you a bit of respite with this week’s leading medical news. So sit back, pour yourself a warm beverage, and enjoy this week’s edition of Primecuts!

This week, controversy surrounding screening tests continues to make headlines. As every healthcare dollar is scrutinized and examined, policy makers are striving to ensure that we have rational screening recommendations based on the best available evidence. While new data surrounding breast and prostate screening tests have fueled debate about over-testing and over-treatment, a new study published in the New England Journal of Medicine may add testing for osteoporosis to the discussion [1]. The current U.S. Preventive Services Task Force (USPSTF) guidelines recommend screening for osteoporosis in women aged 65 or older and younger women at increased risk for fracture [2]. While the task force cites convincing evidence that drug therapies reduce the risk of fractures in older women and justify such screening recommendations, there is limited evidence regarding optimal screening intervals in women with normal bone mineral density (BMD). Clinicians are often left to decide on screening intervals based on their own clinical judgment. Researchers from the multi-centered Study of Osteoporotic Fracture Research Group attempted to help guide clinical practice with the results of their longitudinal cohort study examining BMD screening and transition rates to osteoporosis in older women. Following five thousand women over a fifteen year period, investigators stratified participants according to baseline T-score obtained from DEXA scans, and defined the testing interval as the estimated time during which osteoporosis occurred in 10% of each group. Transition to osteoporosis occurred much sooner in patients in the lowest T-score range, reaching a 10% transition to osteoporosis in just 1.1 years (95% CI 1.0-1.3) compared to approximately 17 years is patients with normal BMD or mild osteopenia (16.9 and 17.3 years, 95% CI 11.5-24.6 and 13.9-21.5, respectively). This data suggests that during a 15-year period less than 1% of women with a normal baseline BMD and 5% of those with mild osteopenia will develop osteoporosis. For these women longer repeat screening intervals may be appropriate and help focus screening efforts to populations that will derive the most benefit.

Also in the news is a new study out of the United Kingdom suggesting the choice of anti-hypertensive may affect the incident rate of gout [3]. While diuretics are the most commonly implicated antihypertensive in the development of hyperuricemia and gout, beta-blockers have also been implicated in short-term increases in uric acid levels. Conversely, angiotensin receptor blockers (ARBs) and calcium-channel blockers have been shown to decrease serum uric acid levels. Published in the British Medical Journal, this case-control study followed over 75,000 patients seen in general practice clinics. After adjusting for alcohol intake, age, sex, and co-morbidities, the authors report the relative risk of incident gout was lowest in patients taking losartan, 0.81 (95% CI 0.70 to 0.94) or calcium channel blockers, 0.87 (0.82 to 0.93) and highest in patients taking diuretics, 1.48 (1.40 to 1.57), beta-blockers, 1.48 (1.40 to 1.57), and angiotensin-converting enzyme (ACE) inhibitors, 1.24 (1.17 to 1.32). Interestingly, patients taking non-losartan ARBs also had a higher relative risk of incident gout, 1.29 (1.16 to 1.43). The proposed mechanism of losartan’s uric-acid lowering properties lies in the parent molecule blocking uric acid reabsorption in the kidney. Because over 70% of people with gout have concomitant hypertension, medication choice can have broad implications on morbidity in a large number of patients.

Switching over to the world of sports, a new study published in the New England Journal of Medicine confirms that the risk of cardiac arrest and sudden death is relatively low during long distance races [4]. As interest in health and exercise have grown over the past decade, the number of participants in long-distance running races has doubled to nearly 2 million participants in 2010. Due to the explosive growth of competitive running, researchers set out to address concerns over sudden death and cardiac arrest events occurring during marathon and half-marathon races. Using a database of 10.9 million registered race participants from 2000 to 2010, investigators identified 59 cardiac arrests during or immediately after long distance races (0.54 per 100,000 participants; 95% CI 0.41-0.70). The average age of runners who suffered a cardiac arrest was 42 years. Cardiac arrest occurred more frequently among men and during full-length marathons, and the overall mortality of people who had a cardiac arrest was 71%. While cardiovascular disease was responsible for most episodes of cardiac arrest, a significant portion of individuals had hypertrophic caridomyopathy. Not surprisingly, bystander-administered cardiopulmonary resuscitation was a predictor of survival among those who had a cardiac arrest. Overall, the cardiac arrest (1 per 184,000 participants) and sudden death rate (1 per 259,000 participants) from this study were low compared to other fit populations, including collegiate athletes (1 death per 43,770 participants per year), previously healthy middle-aged joggers (1 death per 7,620 participants) and triatheletes (1 death per 52,630 participants). While the overall risk of death during long-distance races remains low, consulting a physician prior to starting a vigorous training program is always advisable.

And finally, a recent publication in the Annals of Internal Medicine may deal another blow to vitamin-D supplementation as an additional agent to combat some of the most common diseases. Low vitamin D levels have been linked to a myriad of common disease—from diabetes to depression—and observational studies showing lower levels of this fat-soluble vitamin in certain patient populations have piqued the interest of researchers in a variety of fields. While recent studies, using vitamin D as a therapeutic in multiple sclerosis, influenza, and diabetes have yielded disappointing results, this recent study examined high-dose vitamin D supplementation in patients with chronic obstructive pulmonary disease (COPD) [5]. Prior studies had demonstrated vitamin D deficiency in over 60% of patients with severe COPD [6]; whether this finding was a consequence or cause of the disease remained unclear. In this context the authors randomly assigned 182 individuals with moderate to severe COPD to high dose vitamin D (100,000 IU every four weeks) or placebo. At enrollment the mean vitamin D level was similar between both groups (20 ng/mL each group, p-value=0.9). The primary endpoint was time to first exacerbation, while secondary outcomes were FEV1, time to second exacerbation, a quality of life score, and death. After one year of follow-up the treatment arm exhibited a significant increase in mean serum vitamin D level (mean between-group difference, 20 ng/mL, 95% CI 27-44 ng/mL) however there were no difference in any primary or secondary outcomes. A post hoc analysis of 30 patients with severe vitamin D deficiency at baseline (mean level < 10 ng/mL) did show less exacerbations in the treatment group (1.84 vs. 3.45, p-value=0.042). While vitamin D supplementation did not reduce COPD exacerbations, this study may guide future intervention studies of possible sub-groups who may benefit from high-dose vitamin supplementation.

That wraps up this weeks edition of Primecuts—stay warm out there!

Dr. David Hormozdi is a 3rd-year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Michael Poles, MD, section editor (GI), Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Gourlay ML, Fine JP, Preisser JS, Mary RC, Li C, et. al. Bone-Density testing interval and transition to osteoporosis in older women. N Engl J Med 2010; 366:255-233. url: http://www.nejm.org/doi/full/10.1056/NEJMoa1107142

2. Screening for osteoporosis: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2011; 154:3556-64. url: http://www.uspreventiveservicestaskforce.org/uspstf10/osteoporosis/osteors.htm

3. Choi HK, Soriano LC, Zhang Y, Rodriquez LA. Antihypertensive drugs and risk of incident gout among patients with hypertension: population based case-control study. BMJ 2012; 344:d8190. url: http://www.bmj.com/content/344/bmj.d8190

4. Kim JH, Malhorta R, Chiampas G, d’Hemecourt P, Troyanos C, et al. Cardiac arrest during long-distance running races. N Engl J Med 2012;366:130-40. url: http://www.nejm.org/doi/full/10.1056/NEJMoa1106468

5. Lehouck, A, Mathieu C, Carremans C, Baeke F, Verhaegen J, et al. High dose vitamin D to reduce exacerbations in chronic obstructive pulmonary disease. Ann Intern Med 2012;156:105-114. url: http://www.annals.org/content/156/2/105.abstract

6. Janssens W, Bouillon R, Claes B, Carremans C, Lehouck A, et al. Vitamin D deficiency is highly prevalent in COPD and correlates withvariants in the vitamin D-binding gene. Thorax. 2010;65:215-20. url: http://thorax.bmj.com/content/early/2009/12/08/thx.2009.120659

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