Putative Biomarkers of Environmental Enteric Disease Fail to Correlate in a Cross-Sectional Study in Two Study Sites in Sub-Saharan Africa.

Environmental enteric dysfunction (EED) is an elusive, inflammatory syndrome of the small intestine thought to be associated with enterocyte loss and gut leakiness and lead to stunted child growth. To date, the gold standard for diagnosis is small intestine biopsy followed by histology. Several putative biomarkers for EED have been proposed and are widely used in the field. Here, we assessed in a cross-sectional study of children aged 2-5 years for a large set of biomarkers including markers of protein exudation (duodenal and fecal alpha-1-antitrypsin (AAT)), inflammation (duodenal and fecal calprotectin, duodenal, fecal and blood immunoglobulins, blood cytokines, C-reactive protein (CRP)), gut permeability (endocab, lactulose-mannitol ratio), enterocyte mass (citrulline) and general nutritional status (branched-chain amino acids (BCAA), insulin-like growth factor) in a group of 804 children in two Sub-Saharan countries. We correlated these markers with each other and with anemia in stunted and non-stunted children. AAT and calprotectin, CRP and citrulline and citrulline and BCAA correlated with each other. Furthermore, BCAA, citrulline, ferritin, fecal calprotectin and CRP levels were correlated with hemoglobin levels. Our results show that while several of the biomarkers are associated with anemia, there is little correlation between the different biomarkers. Better biomarkers and a better definition of EED are thus urgently needed.

Cardiovascular mortality associated with 5 leading risk factors: national and state preventable fractions estimated from survey data.

BACKGROUND: Impressive decreases in cardiovascular mortality have been achieved through risk factor reduction and clinical intervention, yet cardiovascular disease remains a leading cause of death nationally. OBJECTIVE: To estimate up-to-date preventable fractions of cardiovascular mortality associated with elimination and reduction of 5 leading risk factors nationally and by state in the United States. DESIGN: Cross-sectional and cohort studies. SETTING: Nationally representative and state-representative samples of the U.S. population. PARTICIPANTS: Adults aged 45 to 79 years. MEASUREMENTS: Self-reported risk factor status in the BRFSS (Behavioral Risk Factor Surveillance System) 2009-2010 was corrected to approximate clinical definitions. The relative hazards of cardiovascular death (International Classification of Diseases, 10th Revision, codes I00 to I99) associated with risk factors were estimated using data from NHANES (National Health and Nutrition Examination Survey) (1988-1994 and 1999-2004, followed through 2006). RESULTS: The preventable fraction of cardiovascular mortality associated with complete elimination of elevated cholesterol levels, diabetes, hypertension, obesity, and smoking was 54.0% for men and 49.6% for women in 2009 to 2010. When the more feasible target of reducing risk factors to the best achieved levels in the states was considered, diabetes (1.7% and 4.1%), hypertension (3.8% and 7.3%), and smoking (5.1% and 4.4%) were independently associated with the largest preventable fractions among men and women, respectively. With both targets, southern states had the largest preventable fractions, and western states had the smallest. LIMITATION: Self-reported state data; mortality hazards relied on baseline risk factor status. CONCLUSION: Major modifiable cardiovascular risk factors collectively accounted for half of cardiovascular deaths in U.S. adults aged 45 to 79 years in 2009 to 2010. Fewer than 10% of cardiovascular deaths nationally could be prevented if all states were to achieve risk factor levels observed in the best-performing states. PRIMARY FUNDING SOURCE: Robert Wood Johnson Foundation.