Primecuts – This Week in the Journals

July 19, 2017

By Cesar Soria Jimenez, MD
Peer Reviewed

Obesity-waist_circumferenceIn this week’s Primecuts issue, we will be discussing topics related to obesity and its effects on the global population over the past quarter century (the effects are both surprising and worse than you likely imagine), a trial analyzing the potential for a blood serum biomarker to distinguish the infectious etiology of community acquired pneumonia and prevent unnecessary use of empiric antibiotics, and the characterization of a distinct phenotype of heart failure with ejection fraction, a condition that is becoming more common yet remains difficult to identify and treat.

1. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. [1]
Overweight and obesity prevalence continues to increase worldwide. Body mass index (BMI) has been identified as a risk factor for several chronic diseases, including but limited to cardiovascular diseases (CVD), diabetes mellitus (DM), chronic kidney disease (CKD), cancer, and musculoskeletal disorders. In order to develop treatments and prevention policies to ameliorate this trend and its sequelae, this article evaluated the trends in prevalence of overweight and obesity, including the patterns of death and disability-adjusted life-years related to high BMI, according to age and sex, in 195 countries.

Researchers used the comparative-risk-assessment approach from the Global Burden of Disease study to estimate the burden of disease related to high BMI from 1990 to 2015. To assess the global distribution of BMI, they searched Medline for studies providing nationally or subnationally representative estimates of BMI, overweight, obesity among adults and children. In addition, they estimated the effects of high BMI on health outcomes by using Bradford Hill’s criteria for causation and evidence-grading criteria of the World Cancer Research Fund to evaluate epidemiologic evidence supporting causal relationship between high BMI and several diseases. Finally, researchers used the most recent pooled analysis of prospective observational studies to determine the BMI associated with the lowest overall risk of death. The number of deaths and disability-adjusted life-years were computed in relation to high BMI for each country, according to age, sex, year and cause.

In 2015, 107.7 million children (uncertainty interval, 101.1-115.1) and 603.7 million adults (uncertainty interval, 592.9-615.6) were obese worldwide. Overall prevalence of obesity was 12.0% among adults and 5.0% among children. Notably, the prevalence of obesity was generally higher among women than men across all age brackets studied (5-year increment groups from 20 to 80+ years of age). There were no sex differences observed in obesity prevalence before the age of 20 years. Investigators also noted that in general, the prevalence of obesity among both men and women increased as socioeconomic index (SDI) – a measure of lag-distributed income per capita, average educational attainment among persons older than 15 years, and total fertility rate – increased. In children, the prevalence of obesity was greater in countries with higher SDI levels. At the national level, the prevalence of obesity among children and adults has doubled in 73 countries since 1980. Despite a lower prevalence of childhood obesity compared to adult obesity, the rate of increase in childhood obesity is outpacing that of adult obesity. Of note, the U.S. has the highest level of age-standardized childhood obesity (12.7%; 95% uncertainty interval, 12.2-13.2) and highest number of obese adults.

It was estimated that in 2015, a high BMI contributed to 4.0 million deaths (95% uncertainty interval, 2.7-5.3), and 120 million disability-adjusted life-years (95% uncertainty interval, 84-158). 70% of these deaths were related to CVD, sand 30% of deaths and 37% of disability-adjusted life-years occurred in adults with a BMI less than 30 (i.e. overweight). CVD was the leading cause of death and disability-adjusted life-years related to high BMI with 2.7 million deaths and 66.3 million disability-adjusted life-years. DM was the second leading cause of death with 0.6 million and 30.4 million disability-adjusted life-years. CKD was the second leading cause of disability-adjusted life-years; together with cancers, they accounted for less than 10% of all deaths. Globally, increases in BMI-related deaths and disability adjusted life-years were majorly offset by decreases in rates of death from CVD.

It is critical to note that the prevalence of obesity has increased despite national differences in income and wealth, pointing to changes in food environments and food systems as major drivers. Additionally, the rate of increase in BMI is outpacing the rate of related disease burden largely in part to improved clinical interventions that reduce this associated burden.

Some limitations of the study include: Using self-reported and measured data on height and weight; excluding studies that used the WHO definition of childhood overweight and obesity in order to apply a consistent definition from the International Obesity Task Force; limited availability of data for some locations; and not using other measures of adiposity such as waist circumference and wait-to-hip ratio. Nevertheless, this study addressed major limitations of previous studies by including more data sources and quantifying the prevalence of childhood obesity. Together, these results highlight the need for implementing multiple interventions to reduce the prevalence and disease burden of high BMI.

2. Procalcitonin as a Marker of Etiology in Adults Hospitalized With Community-Acquired Pneumonia. Clinical infectious Diseases. [2]

Pneumonia continues to be a major cause of morbidity and mortality in the country, with an estimated 63,000 deaths, 1.2 hospitalizations and 2.3 million emergency department visits a year. Management of community acquired pneumonia (CAP) includes empiric treatment with antibiotics targeting the most likely bacterial pathogen, however, recent studies suggest that viruses account for a large proportion of CAP cases in adults and children. If a viral etiology for CAP could be reliably distinguished from bacterial and mixed viral/bacterial infections, overuse of antibiotics could be prevented. Nevertheless, there is no available test that can rapidly and accurately differentiate between viral and bacterial respiratory infections. To this end, pro-calcitonin (PCT) has shown promise in discriminating between viral and bacterial infections.

In this study of 1735 adults hospitalized with CAP across 5 hospitals (3 academic, 1 county, and 1 community hospital), investigators evaluated the relationship between serum PCT concentration with etiology of pneumonia by performing systematic testing for viruses and bacteria, which included cultures, serology, urine antigen tests, and molecular detection.
Most notably, during the 2.5 years study period, pathogens were found in 645 (37%) of patients, of which 409 (24%) were viral, 67 (4%) atypical bacteria, 169 (10%) typical bacterial and 1% mycobacterial/fungal infections. The most common pathogens were rhinorvirus, M. pneumoniae, and S. pneumonia. Median PCT was lower in the viral group (0.09 ng/mL) compared to the typical (2.5 ng/mL) and atypical (0.20 ng/mL) bacterial group.

In distinguishing between 1) any bacterial CAP from viral CAP, a PCT threshold of ≥0.1 ng/mL resulted in a sensitivity of 80.9% and specificity of 51.6%; 2) a typical bacterial CAP from a viral/atypical CAP, this same PCT threshold had sensitivity of 87.6% and specificity of 49.3%; and 3) any bacterial CAP from a nonbacterial CAP, this threshold had a sensitivity of 80.9% and specificity of 46.2 %. As the PCT cut-point increased, sensitivity increased with a concomitant reduction in specificity.

Although there is limited applicability of this marker (no PCT threshold allowed for perfect discrimination between viral and bacterial etiologies, there were 62% of patients with no pathology detected, and no outpatient subjects were included) this study demonstrated that higher levels of serum PCT at hospital admission were strongly associated with increased probability of bacterial pathogen detection. This data suggest that serum PCT could be a helpful adjunct in assessing the etiology of patients’ CAP in the inpatient setting.

3. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure with Preserved Ejection Fraction. [3]

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder caused or exacerbated by a variety of co-morbidities linked to both cardiac and extracardiac abnormalities. There have been no treatments identified that can improve the prognosis of patients with HFpEF, but phenotyping patients into pathophysioligcally homogenous groups may provide a better way of targeting treatments in the future. As the prevalence of obesity continues to increase (see Health Effects of Overweight and Obesity in 195 Countries over 25 Years above), HFpEF has become more common.

As it is known that obesity has several deleterious cardiovascular effect, this study hypothesized that obesity-related HFpEF may be a distinct clinical phenotype. To test this hypothesis, detailed characterization of cardiovascular structure, function, and reserve capacity in patients with HFpEF and class II or greater obesity was compared with nonobese HFpEF and control patients without HF by undergoing detailed clinical assessment, echocardiography, and invasive hemodynamic exercise testing. This was a single center, restrospective study analyzing consecutive patients with HFpEF undergoing invasive hemodynamic exercise testing between 2000 and 2014.

In comparison to nonobese patients with HFpEF and control patients, obese patients with HFpEF had larger plasma volume expansion (3907 mL vs 2772 mL and 2680 mL), more biventricular remodeling, grater right ventricular dilatation and dysfunctions, worse exercise capacity and hemodynamic restraints with exercise (peak oxygen consumption, 7.7±2.3 vs 10.0±3.4 and 12.9±4.0 mL/min•kg), and impaired pulmonary vasodilation.

Although this was a single-center study from a tertiary hospital and by nature is subject to selection and referral bial, this study provides a myriad of analytical evidence suggesting that obese patients with HFpEF have display a distinct phenotype and pathophysiology from nonobese HFpEF, opening the door for better targeting by novel treatments, and encourages other investigators to elucidate the cellular pathophysiology of this distinct phenotype.

Minicuts:

1. Immunochemical Faecal Occult Blood Testing to Screen for Colorectal Cancer: Can the Screening Interval be Extended? [4]

In a recently published article in BMJ, investigators explored alternative faecal immunochemical testing (FIT) strategies to screen for colorectal cancer. Since FIT is a quantitative test (in comparison to qualitative guaic-based faecal occult blood testing, gFOBT), it offers flexibility in selecting specific cut-off levels and screening intervals. The results found that alternative FIT strategies using a lower cut-off level and a longer screening interval were estimated to provide similar diagnostic ability compared to conventional FIT screening.

2. Effects of Physician-targeted Pay for Performance on Use of Spontaneous Breathing Trials in Mechanically Ventilated Patients. [5]

This study published in AJRCCM analyzes the effects of pay for performance, a common quality improvement strategy, on the rate of completion of daily spontaneous breathing trials (SBTs) in mechanically-ventilated patients. The results showed that paying physicians in this manner was associated with increasing trial completion rates in low-performing ICUs, however, improvements in patients outcomes were inconsistent.

3. Declining Risk of Sudden Death in Heart Failure. [6]

In this article published by NEJM, the change in risk of sudden death among patients with symptomatic heart failure with reduced ejection fraction (HFrEF) was analyzed. Investigators found that approx. 40,000 patients with HFrEF enrolled in 12 clinical trials spanning from 1995 to 2014 saw a 44% reduction in the rate of sudden death, attributed to the benefits of new pharmacotherapies over the last two decades.

Dr. Cesar Soria Jimenez is a 1st year resident at NYU Langone Medical Center

Peer reviewed by Kevin Hauck, associate editor, Clinical Correlations

Image Courtesy of Wikimedia Commons

References

1. Afshin, A. et al. Health Effects of Overweight and Obesity in 195 Countries over 25 Years. N Engl J Med 377, 13–27 (2017). http://www.nejm.org/doi/full/10.1056/NEJMoa1614362#t=article

2. Self, W. H. et al. Procalcitonin as a Marker of Etiology in Adults Hospitalized with Community-Acquired Pneumonia. Clin Infect Dis (2017). doi:10.1093/cid/cix317 https://www.ncbi.nlm.nih.gov/pubmed/28407054

3. Obokata, M., Reddy, Y. N. V., Pislaru, S. V., Melenovsky, V. & Borlaug, B. A. Evidence Supporting the Existence of a Distinct Obese Phenotype of Heart Failure With Preserved Ejection Fraction. Circulation 136, 6–19 (2017). http://paper.medlive.cn/literature/2449967

4. Haug, U., Grobbee, E. J., Lansdorp-Vogelaar, I., Spaander, M. C. W. & Kuipers, E. J. Immunochemical faecal occult blood testing to screen for colorectal cancer: can the screening interval be extended? Gut 66, 1262–1267 (2017). https://repub.eur.nl/pub/88904/

5. Barbash, I. J., Pike, F., Gunn, S. R., Seymour, C. W. & Kahn, J. M. Effects of Physician-targeted Pay for Performance on Use of Spontaneous Breathing Trials in Mechanically Ventilated Patients. Am J Respir Crit Care Med 196, 56–63 (2017). http://www.atsjournals.org/doi/abs/10.1164/rccm.201607-1505OC

6. Shen, L. et al. Declining Risk of Sudden Death in Heart Failure. N Engl J Med 377, 41–51 (2017). http://www.nejm.org/doi/full/10.1056/NEJMoa1609758

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