Primecuts – This Week In The Journals

March 21, 2011

By Ben Wu, MD

Faculty Peer Reviewed

As the long winter gives way to a tumultuous spring, we find our attention torn between budding revolutions in North Africa and the Middle East and the worsening environmental catastrophe in Japan. In the midst of these political and public health crises, news of an emerging disease is coming out of China, Severe Fever with Thrombocytopenia Syndrome (SFTS).  Doctors there have identified a novel bunyavirus as the cause of SFTS. [1] The syndrome is associated with fatigue, conjunctival congestion, abdominal pain, proteinuria, hematuria, leukocytopenia, and diarrhea, with progression to multi-organ failure.    There have been 171 confirmed cases and 21 deaths, with a case-fatality rate of 12%.  The authors suggested that not all of the deaths may be due to SFTS.  Furthermore, they hypothesized that the virus must have a vector since bunyavirus RNA was found in some ticks of the Ixodidae family, namely Haemaphysalis longicornis, the same species that transmits Lyme disease and Ehrlichiosis.

In matters a little closer to home, a recent randomized control trial attempted to answer the question, “How much clopidogrel is enough?” This week JAMA published the results of the GRAVITAS trial (Gauging Responsiveness with A VerifyNow assay – Impact on Thrombosis and Safety). The GRAVITAS trial studied high-dose clopidogrel (loading dose of 600mg, followed by 150mg daily) or standard of care (loading dose of 300mg, followed by 75mg daily) in patients who had high on-treatment platelet reactivity after recent percutaneous coronary intervention with drug-eluting stents. [2] Patients who had elevated on-treatment platelet reactivity were thought to have higher rates of cardiovascular events, including in-stent thrombosis. The trial examined 2,214 patients with the primary end points of death from cardiovascular disease, nonfatal myocardial infarction, or stent thrombosis. The GRAVITAS study found similar primary endpoints across the two groups (hazard ratio 1.01, CI, 0.58-1.76). The authors also explained that several patients in the trial had high-risk acute coronary syndromes so the study results may not apply to those patients. Notably, the researchers did not attempt to normalize platelet reactivity; rather, they followed reactivity after dosing clopidogrel. And finally, the authors acknowledge that platelet reactivity alone cannot predict an individual’s thrombotic risk.

Moving from the micro to the macro, analysis of human body shape gives us interesting new conclusions about cardiovascular risks. In the recent issue of The Lancet, the Emerging Risk Factors Collaboration study group examined the value of the body-mass index (BMI), waist circumference, and waist-to-hip ratio in the prediction of cardiovascular disease risk in combination with information on diabetes, lipids, and blood pressure is available to a physician. [3] The group examined 221,934 patient records from 17 countries, with 14,297 cardiovascular events. A thorough analysis showed that when biomedical data on serum glucose, lipids, and blood pressure were available, physical measurements of adiposity added little to the estimation of a patient’s cardiovascular risk.  According to researchers, the combination of BMI and waist-hip ratio only added approximately 25% of the extra predictive information that a physician may gleam from a lipid panel. The authors suggest that patients would benefit more from diagnostic tests for diabetes and hyperlipidemia than simply estimating their cardiovascular risks from physical indicators of adiposity.

The Annals of Medicine published the results of a single-center, randomized controlled trial of patients who, after cardiac surgery, required mechanical ventilation for four or more days, then either immediately received a tracheotomy or prolonged intubation followed by a tracheotomy. [4] The primary end point was the number of days alive and without assistance (mechanical ventilation or noninvasive ventilation) during the first 60 days post-randomization. Surprisingly, in their study population of 216 patients, the number of ventilator-free days was similar between the two groups. The early tracheotomy group had a mean number of vent-free days of 30.4 (SD-22.4) compared to the prolonged intubation group with a mean of 28.4 days (SD-23.7). The absolute difference was 2.1 days, but the confidence interval included 0 (-4.1 to 8.3). The researchers concluded that early tracheotomy in these cardiac patients provided no benefit in terms of duration of mechanical ventilation, length of hospital stay, mortality rate, or frequency of complications. The researchers did mention that early tracheotomy was associated with less sedation, better comfort, fewer unscheduled extubations and reintubations, and earlier oral nutrition and bed-to-chair transfers, all of which are patient care goals in the ICU.

The British Medical Journal recently examined the use of statins to prevent atrial fibrillation. Scientists Laufs and Liao described the pleiotropic effects of statins, including improvement of endothelial function, enhancing stability of atherosclerotic plaques, reducing oxidative stress and inflammation, thereby lowering the body’s thrombogenic response. [5] Rahimi et al. conducted a meta-analysis of both published and unpublished data regarding statin treatment and its effects on atrial fibrillation. From 13 short-term studies, statins seem to reduce the frequency of atrial fibrillation with an odds ratio of 0.61 (CI 0.51 to 0.74); however, there was significant heterogeneity between the trials. [6] When they examined the 22 long-term trials, the effect of statins on atrial fibrillation was lost (OR-0.95, CI 0.88 to 1.03). Findings held true even for high-dose statin use.

From Science Magazine, researchers have discovered a novel molecule that may play a role in the treatment of systolic heart failure. Malik et al. identified a molecule, omecamtiv mecarbil, which directly activates the contractility of the cardiac sarcomere. [7] In a prior study done in canines, they found that omecamtiv mecarbil improved cardiac systolic function without increasing myocardial oxygen consumption, likely by lowering the energy needed to transition from the weak binding site state in actomyosin to its strong binding site. Furthermore, the molecule increased contractility in the presence of carvedilol and without affecting calcium transport in myocytes. The authors suggest this molecule may be a new therapeutic approach to heart failure.

Finally, an article in the Archives of Ophthalmology gives us insight into the adage that eating fish is good for your eyes.  A large group of female health professionals (n= 39,876) were followed for 10 years and the incidence of age-related macular degeneration (AMD) and their intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were measured. [8] The researchers showed that consumption of DHA and EPA lowered the risk of visually-significant AMD by 35% and 45%, respectively. This article presents the strongest evidence to date regarding the ocular benefits of omega-3 fatty acids, so now you have an excuse to eat more sushi.

Thus, with warmer weather headed our way, our thoughts turn to matters of the heart, both metaphorically and literally. New York City may not seem as dark and dreary now that spring is here, but for the people of North Africa and the Middle East on the verge of democratic change and the Japanese who are coping with the aftermath of a possible radiological disaster, spring may seem a long way off indeed. If you have a chance, make a donation to your favorite charity to help with the humanitarian crises across the globe.

Ben Wu is a first year resident at NYU School of Medicine

Peer reviewed by Ishmeal Bradley, Section Editor, Clinical Correlations.

Image courtesy of Wikimedia Commons.


1. Yu XJ, Liang MF, Zhang SY, et al.  Fever with Thrombocytopenia Associated with a Novel Bunyavirus in China. N Engl J Med 2011 Mar 16, online edition.

2. Price MJ, Berger PB, Teirstein PS et al.; GRAVITAS Investigators. Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA 2011;305(11):1097-105.

3. The Emerging Risk Factors Collaboration. Separate and combined associations of body-mass index and abdominal adiposity with cardiovascular disease: collaborative analysis of 58 prospective studies. Lancet 2011 Mar 10, online edition.

4. Trouillet JL, Luyt CE, Guiguet M et al. Early percutaneous tracheotomy versus prolonged intubation of mechanically ventilated patients after cardiac surgery: a randomized trial. Ann Intern Med 2011;154(6):373-83.

5.  Liao, James K. and Laufs, Ulrich. Pleiotropic Effect of Statins. Annu Rev Pharmacol Toxicol 2005; 45: 89–118.

6. Rahimi K, Emberson J, McGale P et al.  Effect of statins on atrial fibrillation: collaborative meta-analysis of published and unpublished evidence from randomised controlled trials.” BMJ 2011;342:d1250.

7. Malik FI, Hartman JJ, Elias KA et al. Cardiac myosin activation: a potential therapeutic approach for systolic heart failure. Science 2011;331(6023):1439-43.

8. Christen WG, Schaumberg DA, Glynn RJ, Buring JE. Dietary {omega}-3 Fatty Acid and Fish Intake and Incident Age-Related Macular Degeneration in Women. Arch Ophthalmol 2011 Mar 14, online edition.