Primecuts – This Week In The Journals

March 19, 2014

By Anjali Mone, MD

Peer Reviewed

While the majority of media coverage is focusing on Crimea’s annexation and continued upheaval in the Middle East, also making the news this week was a high school teacher who lost weight while on an unconventional diet. John Cisna, a science teacher from Iowa, managed to lose 56 pounds and more shockingly saw an improvement in his cholesterol profile after eating only at McDonald’s for 6 months. [1] How could a diet of Quarter Pounders, salty fries, Chicken McNuggets, and McFlurries have led to improved health? There is no secret to Cisna’s success because at the end of the day, it’s simple mathematics; more calories expended than calories consumed equals weight loss. But this leads to another question; even if he lost weight, did he do it the “wrong” way? Does a diet so high in “bad fat” mean he’s at an increased risk for heart disease?

While Cisna was dieting at McDonald’s, researchers were investigating whether saturated fats are really to blame for heart disease. Their study, a large meta-analysis published in the Annals of Internal Medicine, collected data from 72 separate studies that included more than 650,000 people from 18 different countries. Their primary endpoint was to look at the association between fatty acids and coronary disease. To investigate their endpoint they looked for a relationship of three different measures with coronary disease: dietary fatty acid intake, biomarkers for circulating fatty acids, and fatty acid supplementation.

To start the authors analyzed trials that assessed the relationship between dietary fatty acid intake, through self-report as well as diet questionnaires, and coronary disease. There was no significant difference between total saturated fatty acids [RR 1.02 (95% CI 0.97-1.07) monounsaturated fatty acids [RR 0.99 (95% CI, 0.89-1.09)], total transfatty acids [RR 1.16 (95% CI, 1.06 -1.27). Nor was there a significant difference for risk in terms of polyunsaturated fatty acid intake including linolenic acid [RR 0.99 (95% CI, 0.86 - 1.14)], Omega 3 fatty acids [RR 0.93 (95% CI, 0.84- 1.02), and Omega 6 fatty acids [RR 1.01 (95% CI, 0.96 - 1.07)].

Next in the study, researchers looked at coronary risk in terms of circulating fatty acid composition. Studies to assess these fatty acid biomarkers employed a variety of methods including liquid chromatography, calorimetry, and enzymatic methods to measure fatty acids in the bloodstream. The relative risk for coronary outcomes when adjusted for other vascular risk factors was not statistically significant for any particular fatty acid subgroup: circulating total saturated fatty acids, total monounsaturated saturated fatty acids, linolenic acid , omega 3, omega 6, and total transfatty acids. Some of the individual polyunsaurated fats were also associated with lower risk: eicosapentaenoic [RR0.78 (95% CI 0.65-0.94)], docosahexaenoic [RR 0.79, 95%CI 0.67-0.93)], and arachidonic (0.83, CI 0.74-0.92).

Finally, authors assessed 27 randomized control trials looking at polyunsaturated fat supplementation and coronary outcomes. The relative risk for cardiovascular events over a range of 8 years did not differ significantly between the intervention group and the control group; linolenic acid [2.1% vs 2.3%, RR 0.97 (95%CI 0.69-1.36)], Omega 3 supplement [6.33% vs 6.65%, RR 0.94 (CI 0.86 to 1.03)] , Omega 6 supplement [4.82% vs 5.50%, RR 0.89 (CI 0.71 to 1.12)]

This study challenges the way we currently look at dietary fats. In fact the amount and specific type of fat (saturated or unsaturated) may not have as much to do with heart disease as we once thought. [2] This data contradicts the previously held theory that heart healthy diets are ones rich in polyunsaturated fats and low in saturated ones. Though this study and Cisna’s experiment could be misinterpreted as a green light to eat anything you like, the fact remains that diets with excessive amounts of fat are still more likely to lead to weight gain and ultimately heart disease. The take home point from these trials is that moderation is the key to a healthy diet.

Along with the theme of prevention and treatment of heart disease, the Lancet published an article this week looking at coronary stents and cardiac outcomes, challenging the traditional 1-yr primary endpoint to assess for major adverse cardiac events (MACE) after patients are treated with coronary drug eluting stents. Though there is still no established optimal timeline to assess for adverse outcomes after coronary stenting, data from a recent study suggests that 1-yr findings may not be sufficient to predict of long term outcomes. In the SORT OUT III trial, which this a comparison of 5-yr and 1-yr outcomes were made for patients that received two different types of drug-eluting stents.

The SORT OUT III study was initially a randomized controlled superiority trial comparing the safety and efficacy of zotarolimus-eluting and sirolimus-eluting coronary stents. In the original trial 1162 patients were randomized to receive zotarolimus stents and 1170 to sirolimus stents. Researchers looked at outcomes at 9 and 18 months and the results were notable for an increase in all cause mortality in patients who received zotarolimus stents compared to sirolimus stents [4% vs 3%; p=0.035] and an increase in MACE in patients with zotarolimus stents [8% vs 3.9%, OR 2-13, 95% CI 1.48-3.07; p<0.0001). [3] Surprisingly, however, the comparison of these end points is markedly different in a more recent publication from the study’s 5 year outcomes.

In fact, at 5 years the same study showed no significant difference in MACE between the two types of stents [197/1162 (17%) zotarolimus vs 182/1170 (15.6%) sirolimus, OR 1.10, 95% CI 0.88-1.37; p=0.4]. Furthermore, when looking at stent thrombosis, comparatively worse outcomes were noted for the sirolimus-eluting stents after 5 years, even though it appeared to be superior at the 1 year time mark. These new data challenge the traditional use of a 1-yr endpoint for assessment of MACE after coronary drug-eluting stents and suggest such a short follow-up period may not be useful in predicting long-term outcomes. [4]

Also publishing about heart disease prevention and treatment, a Canadian journal published an article about gender disparities in treating patients with chest pain. Given that acute coronary syndrome (ACS) rates are higher among men than women and that women are more likely to present with atypical symptoms for chest pain, it is not surprising that a recent study published in the Canadian Medical Association Journal (CMAJ) found that there are gender differences in ACS triage and treatment. Men, and very interestingly all individuals with masculine traits, are more likely to receive timely care and more invasive interventions. [5]

In this trial, 1123 patients ages 18-55 admitted to hospitals for ACS were recruited from 24 centers throughout Canada, 1 in the US, and 1 in Switzerland as part of GENESIS-PRAXY cohort study. Primary endpoints of the study focused on sex differences in time to procedure as well as sex differences in invasive procedures. The measures used to quantify these differences included door to EKG time, door to needle time (time to fibrinolytic administration), and door to balloon time, as well as cardiac catheterization, and reperfusion techniques.

Of the study population 362 (32%) were women and 761 (68%) were men, both groups of similar age. There was no significant difference in the amount of time to presenting to emergency room after the onset of chest pain between the two sexes with 4 hours and 3.5 hours for women and men respectively.

Men were more likely to receive EKGs and fibrinolytics more quickly than women based on measured door to EKG time [15 min (men) and 21 min (women); p<0.001] and door to needle time [28 min (men) and 36 min (women); p=0.02]. There was no significant difference in the time to primary percutaneous intervention (PCI) [93 min (men) and 106 min (women); p=0.7], however, women were less likely to have invasive procedures done than men for NSTEMI and unstable angina with rates of PCI at 48% in women and 66% in men (p<0.001).

The authors hypothesize that an increased incidence of concomitant anxiety and absence of a typical chest pain syndrome at presentation may contribute to the differences between the gender groups in this study. [5] This study clearly demonstrates that there is a disparity in the effectiveness of care delivery for men and women in the assessment of acute coronary syndrome, and practitioners should be further educated to help resolve this inequality.

Staying within the realm of emergency medicine, the Academic Emergency Medicine Journal published a paper on the dilemma of adequately treating patients for their pain. In the midst of a prescription opiate abuse epidemic, concerns about the over prescription of opioids are escalating. According to the Centers for Disease Control and Prevention, deaths related to prescription opioids have increased by nearly four-fold from 4030 in 1999 to 16,651 in 2010. Many are concerned about the recently FDA approved medication zohydro scheduled to hit the drug market this spring. Zohydro is pharmacologically five times more potent than current opiates and raise concerns for amplified abuse potential. [6] These concerns are validated by this recent study investigating opiate prescription trends in United States emergency rooms, which indicates there has been a significant increase over the past decade out of proportion to the moderate increase in pain-related visits.

Between 2001 and 2010 opioid prescriptions during ED visits increased from a frequency of 20.8% to 31% (95% CI=7 -13.4) while the percentage of visits for ‘painful conditions’ increased by only 4% [47.1% in 2001 to 51.1% in 2010; CI =2.3 - 5.8%].

The absolute increase in DEA schedule II drugs prescriptions was 6.9% during this period of time [95% CI =5.2 - 8.5], out of proportion to the increase in prescriptions for DEA schedules III and V, which was only 3.0% [95% CI = 2.0% to 5.7%]. Of note, the greatest increases were identified in the utilization of hydromorphone [0.9% in 2001 to 6.8% in 2010; CI=4.9-6.8] and morphine [1.6% in 2001 to 6.7 in 2010; CI=4.1 -6.1], while no significant changes were observed in non-opioid painkillers such as acetaminophen and NSAIDs. [7]

Experts attribute this upward trend to reimbursement strategies that now include patient satisfaction as part of the algorithm. Patients for whom pain is not adequately treated may report such in satisfaction surveys, subsequently leading to decreased hospital reimbursement. This is certainly an interesting phenomenon to monitor, especially with potential conflict of opiate misuse and overuse, and new standards for hospital payment.

Other noteworthy articles in the literature:

The American Cancer Society has released more evidence that colorectal cancer screening saves lives. Over the past 10 years, increased screening has resulted in a 30% reduction in colorectal cancer incidence. [8]

Another advisory board, the USPSTF, has also been promoting routine screening. In the new lung cancer screening guidelines, patients considered at high-risk (55-80 years with 30 pack-year smoking history that are still smoking or quit less than 15 years ago) are recommended to get screening low-dose spiral CT scans. [9]

Related to lung cancer screening guidelines, a timely study published in the European Heart Journal demonstrated that passive second hand smoke can cause irreversible damage to children’s arterial vasculature, putting them at increased risk for future heart attacks and strokes. [10]

Furthermore not only is second hand smoking bad, but third hand smoke has been shown to be a carcinogen as was discussed during a recent American Chemical Society meeting. Tobacco-specific nitrosamines, a byproduct of third hand smoke, are now proven DNA-damaging substances. [11]

Another recent study also looking at DNA found that specific DNA modifications are related to weight gain. DNA methylation has been linked to increased BMI and these findings may be a big step towards uncovering the genetic basis for obesity. [12]

Dr. Anjali Mone is a 1st year internal medicine resident at NYU Langone Medical Center

Peer reviewed by Gregory Schrank, MD, 3rd year resident, NYU Langone Medical Center

Image courtesy of Wikimedia Commons

References:

1) Pawlowski, A. Man loses 56 pounds after eating only McDonald’s for six months. Today.com. Accessed March 18, 2014. http://www.today.com/health/3-mistakes-youre-making-bathroom-how-fix-them-2D79396546

2) Chowdhury R, Warnakula S, Kunutsor S, et al. Association of dietary, circulating, and supplemental fatty acids with coronary risk: a systemic review and metaanalysis. Annals of Internal Medicine, 2014; 160(6): 398-406. DOI:10.7326/M13-1788 http://annals.org.ezproxy.med.nyu.edu/article.aspx?articleid=1846638

3) Rasmussen K, Maeng M Kaltoft A, et al. Efficacy and safety of zotarolimus-eluting and sirolimus-eluting coronary stents in routine clinical care (SORT OUT III): a randomized controlled superiority trial. Lancet, 2014; 375 (9720): 1090-1099. DOI: 10.1016/S0140-6736(10)60208-5. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60208-5/fulltext

4) Maeng, M, Tilsted HH, Jensen LO, et al. Differential clinical outcomes after 1 year versus 5 years in a randomized comparison of zotarolimus-eluting and sirolimus-eluting coronary stents (the SORT OUT III study): a multicentre, open-label, randomized superiority trial. Lancet 2014. doi:10.1016/S0140-6736(14)60405-0.  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60405-0/fulltext

5) Roxanne Pelletier, Karin H. Humphries, Avi Simony, Simon L. Bacon, Kim L. Lavoie, Doreen Rabi, Igor Karp, Meytal Avgil Tsadok, Louise Pilote. Sex-related difference in access to Care Among patients with Premature Acute Coronary syndrome. CMAJ 2014 doi:10.1503/cmaj.131450 http://www.cmaj.ca/content/early/2014/03/17/cmaj.131450

6) Perrone, Matthew. FDA Chief Defends Zohydro as Criticism Intensifies. Abcnews.go.com. Accessed March 18, 2014. http://abcnews.go.com/US/wireStory/fda-chief-defends-zohydro-criticism-intensifies-22904943

7) Mazer-Amirshahi M, Mullins MA, Rasooly I, et al. Rising Opioid Prescribing in Adult U.S. Emergency Department Visits: 2001-2010. Academic Emergency Medicine, 2014; 21 (3):236-243. DOI: 10.1111/acem.12328 http://onlinelibrary.wiley.com.ezproxy.med.nyu.edu/doi/10.1111/acem.12328/full

8) Siegel, R., DeSantis, C. and Jemal, A. (2014), Colorectal cancer Statistics, 2014. CA: A Cancer Journal for Clinicians, 64: 104-117. DOI: 10.3322/caac.21220 http://onlinelibrary.wiley.com/doi/10.3322/caac.21220/full

9) Virginia A. Moyer, on behalf of the U.S. Preventive Services Task force. Screening for lung cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 2014 Mar; 160(5): 330-338. doi:10.7326/M13-2771 http://annals.org/article.aspx?articleid=1809422

10) Gall S, Huynh QL, Magnussen CG, et al. Exposure to parental smoking in childhood or adolescence is associated with increased carotid intima-media thickness in young adults: evidence from the Cardiovascular Risk in Young Finns study and the Childhood determinants of Adult Health Study. European Heart Journal, 2014. DOI: 10.1093/eurheartj/ehu049 http://www.sciencedaily.com/releases/2014/03/140304215425.htm

11) Hang B, Sarker AH, Havel C, Saha S et al. Thirdhand smoke causes DNA damage in human cells. Mutagenesis. 2014. doi:10.1093/mutage/get013  http://mutage.oxfordjournals.org/content/early/2013/03/04/mutage.get013.full

12) Dick KJ, Nelson CP, Tsaprouni L, et al. DNA methylation and body-mass index: a genome-wide analysis. Lancet 2014. DOI: 10.1016/S0140-6736(13)62674-4. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(13)62674-4/fulltext

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