Primecuts – This Week In The Journals

July 22, 2013

By Mark Adelman, MD

Faculty Peer Reviewed

In the wake of George Zimmerman’s acquittal this past week for the shooting death of Trayvon Martin, rallies and marches continue around the country to protest perceived racial inequalities in the criminal justice system. President Obama spoke on Friday in an unusually personal manner regarding the experiences of young African American men. Summing up his views by stating, “Trayvon Martin could have been me 35 years ago,” Obama urged more frank, open discussions about the history and future of race relations in America.

Racial disparities have also been well described in the realm of healthcare. The National Center for Health Statistics, a part of the CDC, recently released a report that described trends in causes of death and life expectancy that differ between white and black Americans (1). Comparing the years 1970 and 2010, the authors found an overall increase in life expectancy among the total US population from 70.8 years to 78.7 years. However, the average life expectancy remains higher for whites than blacks (78.9 years vs. 75.1 years in 2010). Encouragingly between 1970 and 2010, this gap in life expectancy has decreased from 7.6 years to 3.8 years, but the disparity is still present. In 2010, black Americans had higher mortality rates due to heart disease, cancer, homicide, diabetes mellitus and perinatal conditions, which collectively accounted for 60% of the black population disadvantage in life expectancy. These data should serve to remind clinicians and public health stakeholders that interventions targeting the management of cardiovascular risk factors, screening for preventable cancers, the epidemic of gun violence, and infant mortality could be of particularly high yield in further eliminating racial disparities in US life expectancy.

The actor Michael Douglas made headlines last month in an interview when he attributed his throat cancer diagnosis to human papillomavirus infection contracted by performing oral sex (2). HPV infection, particularly with serotype 16, is known to cause a subset of oropharyngeal cancers (3). Vaccinating adolescent females against oncogenic strains of HPV associated with cervical cancer has been shown to reduce the prevalence of infection with those strains (4). Investigators in Costa Rica working with the National Cancer Institute published their findings this week on the impact of vaccination with bivalent HPV16/18 vaccine on oral HPV infections. In this study, 7,466 sexually active 18-25 year old women in two areas of Costa Rica were randomized in a blinded fashion to receive HPV16/18 or hepatitis A vaccines. Subjects were given booster doses and followed for four years with annual pap smears and HPV DNA testing of cervical samples, and at the fourth-year visit gave oral specimens that were analyzed for HPV DNA. Among 5,834 women that completed follow-up, the investigators estimated a 93% type-specific (HPV16/18) vaccine efficacy rate; there was one infection with either of these strains in the vaccine group vs. 15 in the control group. A major limitation of the study was that it was initially designed primarily to study the vaccine’s effect on cervical HPV infection, so oral specimens were obtained only at the study’s conclusion, unlike cervical specimens which were collected at baseline and throughout the four years of follow-up. This made it impossible to measure the incidence of oral infections in the vaccine and control groups. However these results do add to the body of evidence that HPV vaccination effectively reduces the risk of infection with oncogenic strains of HPV at different body sites and will hopefully reduce the future burden of cervical, oropharyngeal and anal cancers.

Another study of interventions that may prevent cancer–in this case of the colon and rectum–was published in this week’s Annals of Internal Medicine (5). This was a long-term observational follow-up study of former participants in the Women’s Health Study, a large randomized controlled trial that investigated aspirin and vitamin E for the primary prevention of various cancers and cardiovascular disease that enrolled nearly 40,000 women between 1993 and 2004. About 34,000 women agreed to continue participating for a median follow-up of 18 years. Long-term low-dose aspirin use (100mg every other day) was associated with a reduced risk of developing colorectal cancer (HR 0.80; P=0.021) but not breast or lung cancers. Kaplan-Meier curves suggested that the difference between groups emerged after 10 years of treatment. Not surprisingly, aspirin users had higher rates of gastrointestinal bleeding (HR 1.14; P<0.001). We should consider aspirin use for women at higher risk of developing colorectal cancer but the risk of precipitating GI bleeds would likely limit its use among otherwise healthy women.

The increasing prevalence of obesity in the US has been labeled by many as an epidemic. The AMA went so far as to label obesity a disease during its annual meeting in Chicago last month, noting its relationship to hypertension and type 2 diabetes with their associated cardiovascular morbidity and mortality (6). This week in JAMA, further results of the CARDIA (Coronary Artery Risk Development in Young Adults) study were published (7). In this study, nearly 3300 non-obese adults aged 18 to 30 were followed for up to 25 years, with serial measurements of BMI and waist circumference every few years as well as measurement of coronary artery calcification by CT at either 15, 20 or 25 year follow-up visits. Longer duration of obesity was associated with increased presence and severity of coronary artery calcifications (P<0.001 for both). In addition, 38.2% and 39.3% of participants with more than 20 years of overall and abdominal obesity, respectively, had coronary artery calcifications, vs. 25% in participants who did not become obese. Although the study did not include any hard cardiovascular outcomes, coronary artery calcifications are associated with risk of coronary artery disease (8). The correlation found between duration of obesity and severity of coronary artery calcifications is especially concerning given the high rates of obesity among children in the US.

Other articles of note:

Mancia G, Bombeli M, Brambilla G. Long-Term Prognostic Value of White Coat Hypertension: An Insight From Diagnostic Use of Both Ambulatory and Home Blood Pressure Measurements. Hypertension. 2013;62:168-174.  http://hyper.ahajournals.org/content/62/1/168

2051 residents of a town in Italy each underwent three different forms of blood pressure measurement: in-office, self-measured at home, and 24 hour ambulatory monitoring. Participants were labeled as having white coat hypertension if their in-office BP was elevated but at least one out-of-office BP was normal. Those with normal BPs on both out-of-office measures were considered to have true white coat hypertension, while those with an elevated BP on one of the out-of-office measures had partial white coat hypertension. After an average 16 years of follow-up, cardiovascular and all-cause mortality were higher among patients with sustained hypertension and partial white coat hypertension, but not true white coat hypertension, when compared to normotensive participants.

Jamal SA, Vandermeer B, Raggi P et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis. Lancet. Early online publication. doi:10.1016/S0140-6736(13)60897-1.  http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960897-1/abstract

This systematic review included 11 randomized trials that compared mortality in chronic kidney disease patients taking calcium-based phosphate binders with those taking non-calcium based binders. Patients taking non-calcium based binders had a 22% relative reduction in all-cause mortality compared to those taking calcium-based binders.

Atar S, Wishniak A, Shturman A, Shtiwi S, Brezins M. Fatal Association of Mechanical Valve Thrombosis With Dabigatran: A Report of Two Cases. Chest. 2013;144(1):327-328.  http://journal.publications.chestnet.org/article.aspx?articleid=1699501

The authors present two cases of patients with mechanical mitral valves who were switched from warfarin to dabigatran and within 2-3 months both experienced severe thrombotic complications leading to their deaths. Cases like these should serve as a reminder that the novel oral anticoagulants are not FDA approved for thromboprophylaxis in patients with mechanical valves, and no randomized data have been published establishing their efficacy or safety in these patients.

Dr. Mark Adelman is a 3rd year resident (Medicine) at NYU Langone Medical Center

Peer reviewed by Matthew Vorsanger, MD, Associate Editor, Clinical Correlations

Image courtesy of Wikimedia Commons

References:

1. Kochanek KD, Arias E, Anderson RN. How did cause of death contribute to racial differences in life expectancy in the United States in 2010? NCHS data brief, no 125. Hyattsville, MD: National Center for Health Statistics. 2013.  http://www.cdc.gov/nchs/data/databriefs/db125.pdf

2. Brooks X. Michael Douglas on Liberace, Cannes, cancer and cunnilingus. The Guardian. June 10, 2013.  http://www.guardian.co.uk/film/2013/jun/02/michael-douglas-liberace-cancer-cunnilingus

3. Herrero R, Castellsague X, Pawlita M et al. (2003) Human papillomavirus and oral cancer: the International Agency for Research on Cancer multicenter study. J Natl Cancer Inst. 2003;95(23):1772–1783.  http://jnci.oxfordjournals.org/content/95/23/1772

4. Markowitz LE, Hariri S, Lin C et al. Reduction in HPV prevalence among young women following HPV vaccine introduction in the United States, National Health and Nutrition Examination Surveys, 2003-2010. J Infect Dis. Advance online publication. doi: 10.1093/infdis/jit192. http://jid.oxfordjournals.org/content/early/2013/06/18/infdis.jit192

5. Cook NR, Lee I-M, Zhang SM et al. Alternate-Day, Low-Dose Aspirin and Cancer Risk: Long-Term Observational Follow-up of a Randomized Trial. Ann Intern Med. 2013;159(2):77-85.  http://annals.org/article.aspx?articleid=1709803

6. Pollack A. AMA recognizes obesity as a disease. New York Times. June 18, 2013.  http://www.nytimes.com/2013/06/19/business/ama-recognizes-obesity-as-a-disease.html

7. Reis JP, Loria CM, Lewis CE et al. Association Between Duration of Overall and Abdominal Obesity Beginning in Young Adulthood and Coronary Artery Calcification in Middle Age. JAMA. 2013;310(3):280-288.  http://jama.jamanetwork.com/article.aspx?articleid=1713590

8. O’Rourke RA, Brundage BH, Froelicher VF et al. American College of Cardiology/American Heart Association Expert Consensus Document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol. 2000;36:326–340.  https://www.sciencedirect.com/science/article/pii/S0735109700008317

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