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Primary open-angle glaucoma (POAG) is a degenerative eye disease for which early treatment is critical to mitigate visual impairment and irreversible blindness. POAG-associated loci individually confer incremental risk. Genetic risk score(s) (GRS) could enable POAG risk stratification. Despite significantly higher POAG burden among individuals of African ancestry (AFR), GRS are limited in this population. A recent large-scale, multi-ancestry meta-analysis identified 127 POAG-associated loci and calculated cross-ancestry and ancestry-specific effect estimates, including in European ancestry (EUR) and AFR individuals. We assessed the utility of the 127-variant GRS for POAG risk stratification in EUR and AFR Veterans in the Million Veteran Program (MVP). We also explored the association between GRS and documented invasive glaucoma surgery (IGS).Cross-sectional study.MVP Veterans with imputed genetic data, including 5830 POAG cases (445 with IGS documented in the electronic health record) and 64 476 controls.We tested unweighted and weighted GRS of 127 published risk variants in EUR (3382 cases and 58 811 controls) and AFR (2448 cases and 5665 controls) Veterans in the MVP. Weighted GRS were calculated using effect estimates from the most recently published report of cross-ancestry and ancestry-specific meta-analyses. We also evaluated GRS in POAG cases with documented IGS.Performance of 127-variant GRS in EUR and AFR Veterans for POAG risk stratification and association with documented IGS.GRS were significantly associated with POAG (Plt; 5 × 10sup-5/sup) in both groups; a higher proportion of EUR compared with AFR were consistently categorized in the top GRS decile (21.9%-23.6% and 12.9%-14.5%, respectively). Only GRS weighted by ancestry-specific effect estimates were associated with IGS documentation in AFR cases; all GRS types were associated with IGS in EUR cases.Varied performance of the GRS for POAG risk stratification and documented IGS association in EUR and AFR Veterans highlights (1) the complex risk architecture of POAG, (2) the importance of diverse representation in genomics studies that inform GRS construction and evaluation, and (3) the necessity of expanding diverse POAG-related genomic data so that GRS can equitably aid in screening individuals at high risk of POAG and who may require more aggressive treatment.

In this retrospective cohort study of 94 595 severe acute respiratory syndrome coronavirus 2–positive cases, we developed and validated an algorithm to assess the association between coronavirus disease 2019 (COVID-19) severity and long-term complications (stroke, myocardial infarction, pulmonary embolism/deep vein thrombosis, heart failure, and mortality). COVID-19 severity was associated with a greater risk of experiencing a long-term complication 31–120 days postinfection. Most incident events occurred 31–60 days postinfection and diminished after day 91, except heart failure for severe patients and death for moderate patients, which peaked on days 91–120. Understanding the differential impact of COVID-19 severity on long-term events provides insight into possible intervention modalities and critical prevention strategies.

Background: The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by recent studies that observed a U-shaped relation between cholesterol and mortality. The effect of low cholesterol and CHD risk among Veterans is unclear. Methods: This prospective cohort study included Veterans greater than 18 years of age with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018 in the Veterans Health Administration electronic health record system. Veterans were followed to assess CHD mortality risk in relation to outpatient blood cholesterol levels. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CHD mortality associated with total cholesterol (TC). Results: Among 4,467,942 Veterans, 381,871 CHD deaths were recorded. We observed a V-shaped relation between TC and age-, sex, race and smoking-adjusted risk of CHD mortality. The association became U-shaped after adjustment for statin use, body mass index, hypertension, and diabetes. When further adjusted for high-density lipoprotein level, 11 baseline diseases, and applying a 2-year lag analysis, the relation to CHD mortality was J-shaped--flat for TC Conclusions: Based on prospective data for almost 4.5 million adult Veterans, CHD mortality risk steadily increased for TC ≥200mg/dL after adjustment for a range of health conditions. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD risk and lower prevalence of multimorbidity, mental health disorders, nutritional deficits, and other risk factors for CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication. The changes in risk for CHD mortality by TC groups observed in our study (L- to U- to J-shape) highlights the importance of fully adjusting for the presence of multimorbidity and HDL-C to avoid misleading conclusions.

Background: Although recent large randomized clinical trials showed an increased risk of atrial fibrillation (AF) with marine omega-3 fatty acids supplements, it is unclear whether dietary marine omega-3 fatty acids assessed through food frequency questionnaires are associated with AF risk. Hence, we sought to test the hypothesis that dietary eicosapentaenoic acid/docosahexaenoic acid/docosapentaecnoic acid (EPA/DHA/DPA) is associated with a higher risk of AF in a large prospective cohort of US Veterans. Methods: We analyzed data from Million Veteran Program participants who completed self-reported food frequency questionnaires. We used multivariable Cox regression to estimate hazard ratios of AF across quintiles of omega-3 fatty acids consumption and a cubic spline analysis to assess the dose-response relationship between omega-3 fatty acids and AF. Results: Of the 301,294 Veterans studied, the mean intake of omega-3 fatty acids (EPA/DHA/DPA) was 0.39 g/day (SD 0.38), the mean age was 64.9 (SD 12.0) years; 91.2% (274,881 of 301,294) male and 84.0% (253,144 of 301,294) White. Consumption of EPA/DHA/DPA exhibited a non-linear inverse relation with incident AF characterized by an initial decline to 11% at 0.75 g/day of marine omega-3 fatty acids intake followed by a plateau. Conclusions: Contrary to our hypothesis, dietary EPA/DHA/DPA was not associated with a higher risk of AF but was inversely related to AF risk in a non-linear manner.

Aims Frailty is associated with an increased risk of all-cause mortality and cardiovascular (CV) events. Limited data exist from the modern era of CV prevention on the relationship between frailty and CV mortality. We hypothesized that frailty is associated with an increased risk of CV mortality. Methods and results All US Veterans aged ≥65 years who were regular users of Veteran Affairs care from 2002 to 2017 were included. Frailty was defined using a 31-item previously validated frailty index, ranging from 0 to 1. The primary outcome was CV mortality with secondary analyses examining the relationship between frailty and CV events (myocardial infarction, stroke, revascularization). Survival analysis models were adjusted for age, sex, ethnicity, geographic region, smoking, hyperlipidaemia, statin use, and blood pressure medication use. There were 3 068 439 US Veterans included in the analysis. Mean age was 74.1 ± 5.8 years in 2002, 76.0 ± 8.3 years in 2014, 98% male, and 87.5% White. In 2002, the median (interquartile range) frailty score was 0.16 (0.10–0.23). This increased and stabilized to 0.19 (0.10–0.32) for 2006–14. The presence of frailty was associated with an increased risk of CV mortality at every stage of frailty. Frailty was associated with an increased risk of myocardial infarction and stroke, but not revascularization. Conclusion In this population, both the presence and severity of frailty are tightly correlated with CV death, independent of underlying CV disease. This study is the largest and most contemporary evaluation of the relationship between frailty and CV mortality to date. Further work is needed to understand how this risk can be diminished. Key Question Can an electronic frailty index identify adults aged 65 and older who are at risk of CV mortality and major CV events? Key Finding Among 3 068 439 US Veterans aged 65 and older, frailty was associated with an increased risk of CV mortality at every level of frailty. Frailty was also associated with an increased risk of myocardial infarction and stroke, but not revascularization. Take Home Message Both the presence and severity of frailty are associated with CV mortality and major CV events, independent of underlying CV disease.

Objective:To examine the association between adherence to plant-based diets and mortality.Design:Prospective study. We calculated a plant-based diet index (PDI) by assigning positive scores to plant foods and reverse scores to animal foods. We also created a healthful PDI (hPDI) and an unhealthful PDI (uPDI) by further separating the healthy plant foods from less-healthy plant foods.Setting:The VA Million Veteran Program.Participants:315 919 men and women aged 19–104 years who completed a FFQ at the baseline.Results:We documented 31 136 deaths during the follow-up. A higher PDI was significantly associated with lower total mortality (hazard ratio (HR) comparing extreme deciles = 0·75, 95 % CI: 0·71, 0·79, Ptrend < 0·001]. We observed an inverse association between hPDI and total mortality (HR comparing extreme deciles = 0·64, 95 % CI: 0·61, 0·68, Ptrend < 0·001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles = 1·41, 95 % CI: 1·33, 1·49, Ptrend < 0·001). Similar significant associations of PDI, hPDI and uPDI were also observed for CVD and cancer mortality. The associations between the PDI and total mortality were consistent among African and European American participants, and participants free from CVD and cancer and those who were diagnosed with major chronic disease at baseline.Conclusions:A greater adherence to a plant-based diet was associated with substantially lower total mortality in this large population of veterans. These findings support recommending plant-rich dietary patterns for the prevention of major chronic diseases.

Objective: To examine the association between intakes of sodium and potassium and the ratio of sodium to potassium and incident myocardial infarction and stroke. Design, Setting and Participants: Prospective cohort study of 180,156 Veterans aged 19 to 107 years with plausible dietary intake measured by food frequency questionnaire (FFQ) who were free of cardiovascular disease (CVD) and cancer at baseline in the VA Million Veteran Program (MVP). Main outcome measures: CVD defined as non-fatal myocardial infarction (MI) or acute ischemic stroke (AIS) ascertained using high-throughput phenotyping algorithms applied to electronic health records. Results: During up to 8 years of follow-up, we documented 4090 CVD cases (2499 MI and 1712 AIS). After adjustment for confounding factors, a higher sodium intake was associated with a higher risk of CVD, whereas potassium intake was inversely associated with the risk of CVD [hazard ratio (HR) comparing extreme quintiles, 95% confidence interval (CI): 1.09 (95% CI: 0.99–1.21, p trend = 0.01) for sodium and 0.87 (95% CI: 0.79–0.96, p trend = 0.005) for potassium]. In addition, the ratio of sodium to potassium (Na/K ratio) was positively associated with the risk of CVD (HR comparing extreme quintiles = 1.26, 95% CI: 1.14–1.39, p trend < 0.0001). The associations of Na/K ratio were consistent for two subtypes of CVD; one standard deviation increment in the ratio was associated with HRs (95% CI) of 1.12 (1.06–1.19) for MI and 1.11 (1.03–1.19) for AIS. In secondary analyses, the observed associations were consistent across race and status for diabetes, hypertension, and high cholesterol at baseline. Associations appeared to be more pronounced among participants with poor dietary quality. Conclusions: A high sodium intake and a low potassium intake were associated with a higher risk of CVD in this large population of US veterans.

Supplemental Digital Content is available in the text., Background: Abdominal aortic aneurysm (AAA) is an important cause of cardiovascular mortality; however, its genetic determinants remain incompletely defined. In total, 10 previously identified risk loci explain a small fraction of AAA heritability. Methods: We performed a genome-wide association study in the Million Veteran Program testing ≈18 million DNA sequence variants with AAA (7642 cases and 172 172 controls) in veterans of European ancestry with independent replication in up to 4972 cases and 99 858 controls. We then used mendelian randomization to examine the causal effects of blood pressure on AAA. We examined the association of AAA risk variants with aneurysms in the lower extremity, cerebral, and iliac arterial beds, and derived a genome-wide polygenic risk score (PRS) to identify a subset of the population at greater risk for disease. Results: Through a genome-wide association study, we identified 14 novel loci, bringing the total number of known significant AAA loci to 24. In our mendelian randomization analysis, we demonstrate that a genetic increase of 10 mm Hg in diastolic blood pressure (odds ratio, 1.43 [95% CI, 1.24–1.66]; P=1.6×10−6), as opposed to systolic blood pressure (odds ratio, 1.06 [95% CI, 0.97–1.15]; P=0.2), likely has a causal relationship with AAA development. We observed that 19 of 24 AAA risk variants associate with aneurysms in at least 1 other vascular territory. A 29-variant PRS was strongly associated with AAA (odds ratioPRS, 1.26 [95% CI, 1.18–1.36]; PPRS=2.7×10−11 per SD increase in PRS), independent of family history and smoking risk factors (odds ratioPRS+family history+smoking, 1.24 [95% CI, 1.14–1.35]; PPRS=1.27×10−6). Using this PRS, we identified a subset of the population with AAA prevalence greater than that observed in screening trials informing current guidelines. Conclusions: We identify novel AAA genetic associations with therapeutic implications and identify a subset of the population at significantly increased genetic risk of AAA independent of family history. Our data suggest that extending current screening guidelines to include testing to identify those with high polygenic AAA risk, once the cost of genotyping becomes comparable with that of screening ultrasound, would significantly increase the yield of current screening at reasonable cost.

BACKGROUND AND AIMS: Limited and inconsistent data are available on the relation between egg consumption and risk of myocardial infarction (MI) and it is unclear if adiposity or type 2 diabetes modifies egg-MI relation. We tested the primary hypothesis that egg consumption is positively associated with incidence of MI among veterans. In secondary analyses, we examined potential effect modification of egg-MI relation by adiposity and type 2 diabetes. METHODS: We analyzed data collected on 188,267 US veterans who were enrolled in the Million Veteran Program (MVP) from 2011 to 2018. Information on egg consumption was obtained via self-administered food frequency questionnaire and we used electronic health records to identify incident MI. RESULTS: The mean age was 64.4 (SD=12.0) years and 9.9% of the population were female. We ascertained 10,260 new cases of non-fatal MI during an average follow up of 3.24 years (range: 0.002 to 7.49 y). Hazard ratio (95% CI) for non-fatal MI were 1.00 (ref), 0.93 (0.85–0.1.02), 0.96 (0.87–1.05), 0.98 (0.89–1.07), 1.08 (0.98–1.19), 1.11 (1.00–1.24), and 1.13 (1.00–1.28) for egg consumption of

BACKGROUND AND AIMS: Observational and clinical trial evidence suggests an inverse association of omega-3 polyunsaturated fatty acid with coronary artery disease (CAD) mortality, although relationships with non-fatal CAD and stroke are less clear. We investigated whether omega-3 fatty acid supplement use and fish intake were associated with incident non-fatal CAD and ischemic stroke among US Veterans. METHODS: The Million Veteran Program (MVP) is an ongoing nation-wide longitudinal cohort study of US Veterans with self-reported survey, biospecimen, and electronic health record data. Regular use of omega-3 supplements (yes/no) and frequency of fish intake within the past year were assessed using a food frequency questionnaire. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of omega-3 supplement use and fish intake with incident non-fatal CAD and ischemic stroke, defined from electronic health records using validated algorithms. Multivariable models included demographics, body mass index, education, smoking status, alcohol intake, and exercise frequency. RESULTS: Among 197,761 participants with food frequency data (mean age: 66 ± 12 years, 92% men), 21% regularly took omega-3 supplements and median fish intake was 1 (3–5 ounce) serving/week. Over a median follow-up of 2.9 years for non-fatal CAD and 3.3 years for non-fatal ischemic stroke, we observed 6,265 and 4,042 incident cases of non-fatal CAD and non-fatal ischemic stroke, respectively. Omega-3 fatty acid supplement use was independently associated with a lower risk of non-fatal ischemic stroke [HR (95% CI): 0.88 (0.81, 0.95)] but not non-fatal CAD [0.99 (0.93, 1.06)]. Fish intake was not independently associated with non-fatal CAD [1.01 (0.94, 1.09) for 1–3 servings/month, 1.03 (0.98, 1.11) for 1 serving/week, 1.02 (0.93, 1.11) for 2–4 servings/week, and 1.15 (0.98, 1.35) for ≥5 servings/week, reference =

BACKGROUND: Although previous studies have suggested cocoa products may promote cardiovascular health in the general population, no public data are available from patients receiving care in a national integrated health care system. OBJECTIVES: We tested the hypothesis that regular chocolate consumption is associated with a lower risk of coronary artery disease (CAD) events among participants of the Million Veteran Program (MVP). Secondary analysis examined if the main hypothesis was observed among participants with type 2 diabetes. METHODS: We analyzed data from MVP participants who completed the food frequency section of the MVP Lifestyle Survey and were free of CAD at the time of survey completion. CAD events during follow-up (International Statistical Classification of Diseases Ninth Revision codes 410–411 and 413–414, and Tenth Revision codes I20–I25 except I25.2) were assessed using electronic health records. We fitted a Cox proportional hazard model to estimate the RR of CAD. RESULTS: Of 188,447 MVP enrollees with survey data, mean ± SD age was 64 ± 12.0 y and 90% were men. For regular chocolate (28.3 g/serving) consumption of

Cardiovascular disease (CVD), including stroke and coronary artery disease (CAD), is the major cause of mortality for Americans. Nuts have been shown to improve a variety of cardiovascular disease risk factors. This study aimed to test the hypothesis that nut consumption is inversely associated with risk of incidence of stroke, CAD, and CVD mortality in the prospective Million Veterans Program (MVP). A total of 179,827 MVP participants enrolled between 2011 and 2018 were free of CVD prior to assessment of nut consumption via the food frequency questionnaire. Incident stroke and CVD events were ascertained from the Veterans Affairs electronic medical health records and the National Death Index. We used the Cox regression model to compute multivariable adjusted hazard ratios. Over the 3.5-year median follow-up, 3362 new cases of ischemic stroke were identified. When compared with participants who rarely or never consumed nuts, those consuming nuts ≥ 5 times per week were 19% less likely to experience a stroke (95% CI: 8% to 28%), 22% less likely to suffer from CAD (95% CI: 16% to 28%), and 24% less likely to die from CVD (95% CI: 7% to 37%). Consumption of peanut butter was not associated with risk of stroke. Increased dietary intake of nuts, but not peanut butter, was associated with a lower risk of stroke, CAD, and CVD death.

In response to the novel Coronavirus Disease 2019 (COVID-19) pandemic, the Department of Veterans Affairs (VA) Million Veteran Program (MVP) organized efforts to better understand the impact of COVID-19 on Veterans by developing and deploying a self-reported survey.The MVP COVID-19 Survey was developed to collect COVID-19 specific elements including symptoms, diagnosis, hospitalization, behavioral and psychosocial factors and to augment existing MVP data with longitudinal collection of key domains in physical and mental health. Due to the rapidly evolving nature of the pandemic, a multipronged strategy was implemented to widely disseminate the COVID-19 Survey and capture data using both the online platform and mailings.We limited the findings of this paper to the initial phase of survey dissemination which began in May 2020. A total of 729,625 eligible MVP Veterans were invited to complete version 1 of the COVID-19 Survey. As of October 31, 2020, 58,159 surveys have been returned. The mean and standard deviation (SD) age of responders was 71 (11) years, 8.6% were female, 8.2% were Black, 5.6% were Hispanic, and 446 (0.8%) self-reported a COVID-19 diagnosis. Over 90% of responders reported wearing masks, practicing social distancing, and frequent hand washing.The MVP COVID-19 Survey provides a systematic collection of data regarding COVID-19 behaviors among Veterans and represents one of the first large-scale, national surveillance efforts of COVID-19 in the Veteran population. Continued work will examine the overall response to the survey with comparison to available VA health record data.

Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.

The exposome represents the array of dietary, lifestyle, and demographic factors to which an individual is exposed. Individual components of the exposome, or groups of components, are recognized as influencing many aspects of human physiology, including cardiometabolic health. However, the influence of the whole exposome on health outcomes is poorly understood and may differ substantially from the sum of its individual components. As such, studies of the complete exposome are more biologically representative than fragmented models based on subsets of factors. This study aimed to model the system of relationships underlying the way in which the diet, lifestyle, and demographic components of the overall exposome shapes the cardiometabolic risk profile. The current study included 36,496 US Veterans enrolled in the VA Million Veteran Program (MVP) who had complete assessments of their diet, lifestyle, demography, and markers of cardiometabolic health, including serum lipids, blood pressure, and glycemic control. The cohort was randomly divided into training and validation datasets. In the training dataset, we conducted two separate exploratory factor analyses (EFA) to identify common factors among exposures (diet, demographics, and physical activity) and laboratory measures (lipids, blood pressure, and glycemic control), respectively. In the validation dataset, we used multiple normal regression to examine the combined effects of exposure factors on the clinical factors representing cardiometabolic health. The mean ± SD age of participants was 62.4 ± 13.4 years for both the training and validation datasets. The EFA revealed 19 Exposure Common Factors and 5 Physiology Common Factors that explained the observed (measured) data. Multivariate regression in the validation dataset revealed the structure of associations between the Exposure Common Factors and the Physiology Common Factors. For example, we found that the factor for fruit consumption was inversely associated with the factor summarizing total cholesterol and low-density lipoprotein cholesterol (LDLC, p = 0.008), and the latent construct describing light levels of physical activity was inversely associated with the blood pressure latent construct (p &lt, 0.0001). We also found that a factor summarizing that participants who frequently consume whole milk are less likely to frequently consume skim milk, was positively associated with the latent constructs representing total cholesterol and LDLC as well as systolic and diastolic blood pressure (p = 0.0006 and &lt, 0.0001, respectively). Multiple multivariable-adjusted regression analyses of exposome factors allowed us to model the influence of the exposome as a whole. In this metadata-rich, prospective cohort of US Veterans, there was evidence of structural relationships between diet, lifestyle, and demographic exposures and subsequent markers of cardiometabolic health. This methodology could be applied to answer a variety of research questions about human health exposures that utilize electronic health record data and can accommodate continuous, ordinal, and binary data derived from questionnaires. Further work to explore the potential utility of including genetic risk scores and time-varying covariates is warranted.

Racial/ethnic health disparities persist among veterans despite comparable access and quality of care. We describe racial/ethnic differences in self-reported health characteristics among 437,413 men and women (mean age (SD) = 64.5 (12.6), 91% men, 79% White) within the Million Veteran Program. The Cochran–Mantel–Haenszel test and linear mixed models were used to compare age-standardized frequencies and means across race/ethnicity groups, stratified by gender. Black, Hispanic, and Other race men and women reported worse self-rated health, greater VA healthcare utilization, and more combat exposure than Whites. Compared to White men, Black and Other men reported more circulatory, musculoskeletal, mental health, and infectious disease conditions while Hispanic men reported fewer circulatory and more mental health, infectious disease, kidney, and neurological conditions. Compared to White women, Black women reported more circulatory and infectious disease conditions and Other women reported more infectious disease conditions. Smoking rates were higher among Black men, but lower for other minority groups compared to Whites. Minority groups were less likely to drink alcohol and had lower physical fitness than Whites. By identifying differences in burden of various health conditions and risk factors across different racial/ethnic groups, our findings can inform future studies and ultimately interventions addressing disparities.

Summary Background & aims Dyslipidemia is a major cardiovascular disease risk factor. Research has proposed mechanisms whereby yogurt may improve circulating lipid concentrations. However, at the population level, the association of yogurt, as distinct from other dairy foods, with these important risk factors is poorly understood. This study aimed to determine whether the circulating lipid profile associated with yogurt is different to the circulating lipid profile that is associated with non-yogurt dairy products, specifically milk and cheese. Methods The current study included the 192,564 US Veterans enrolled in the Million Veteran Program who reported frequency of yogurt consumption (assessed via food frequency questionnaire) and had lipid concentrations assessed. Trends were evaluated with linear regression. Mean age was 65 (SD = 11) years [20, 100 years]. Results A one serve/day higher yogurt consumption was positively associated (coefficient ± SE) with the concentration of high-density lipoprotein cholesterol (HDLC) in individuals who were not (0.26 ± 0.12 mg/dL, P value = 0.025), and who were (0.25 ± 0.09, P value = 0.004), using antilipemic agents. Furthermore, higher yogurt consumption was inversely associated with the concentration of triglycerides, but only in individuals who were not using antilipemic agents (−1.46 ± 0.58, P value = 0.012). Conclusion These apparent beneficial associations of yogurt with HDLC and triglycerides were independent of consumption of non-yogurt dairy foods and were not observed for consumption of either milk or cheese. In this prospective cohort study of U.S. Veterans, we found a beneficial relationship between higher frequency of yogurt consumption with circulating HDLC and triglyceride concentrations that was distinct from non-yogurt dairy foods.

Introduction: Frailty has been associated with an increased risk of all-cause mortality and CV events. There are limited data from the modern era of CV prevention to examine the relationship between frailty and CV mortality. We hypothesized that frailty would be associated with with increased risk of CV mortality. Methods: All Veterans ≥65 who were regular users of VA care from 2002–2014 were included. Index date was the last visit date in the year of cohort entry. Data were queried biennially, with frailty & outcomes queried each period. Frailty was defined using a 31-item previously validated frailty index, ranging from 0-1. Degrees of frailty were defined as: not frail (FI 0.1-≤0.2), mild frailty (FI >0.2-≤0.3), moderate frailty (FI >0.3-≤0.4), and severe frailty (FI >0.4). Variables were extracted from national VA administrative data linked to Medicare and Medicaid. The primary outcome was CV mortality. Survival analysis was performed. Models were adjusted for age, sex, race/ethnicity, geographic region, smoking status, hyperlipidemia, statin use, and blood-pressure medication use. Results: There were 2,837,152 Veterans included in the analysis. In 2002 mean age was 74+/- 5.8 years and in 2012 was 76+/- 8.1 years, 98% were male, 88.8% were white. In 2002, the median frailty score was 0.16 (IQR= 0.13). This increased and then stabilized to 0.19 for 2006 to 2012 (IQR= ranging 0.19 to 0.23). Overall frailty became more prevalent over time (prevalence increased from 31.9% in 2002 to 46.5% in 2012). The presence of frailty was associated with increased risk of CVD mortality at every degree of frailty and year, as shown in the Table. Discussion: Frailty is highly prevalent in the VA population, and both the presence and severity of frailty are tightly correlated with CV death. This study is the largest and most contemporary evaluation of the relationship between frailty and CV mortality to date. Further work is needed to understand how this risk can be diminished.

Aim Million Veteran Program (MVP) is the largest ongoing mega-cohort biobank program in the US with 570,131 enrollees as of May 2017. The primary aim is to describe demographics, military service, and major diseases and comorbidities of the MVP cohort. Our secondary aim is to examine body mass index (BMI), a proxy for general health, among enrollees. Materials and Method The study population consists of Veterans who actively use the Veterans Health Administration in the US. Data evaluated in this paper combine health information from multiple sources to provide the most comprehensive demographic profile and information on height and weight of MVP enrollees. A standardized cleaning algorithm was used to curate the demographic variables for each participant in MVP. For height and weight, we derived a final data point for each participant to evaluate BMI. Statistical Analysis Used Multivariable logistic regression was used to compare the differences in BMI categories across enrollment years adjusting for gender, race, and age. P < 0.05 was considered statistically significant. All analyses were conducted using Statistical Analysis System 9.2. Results The MVP cohort consists of 90.4% of males with an average age of 61.9 years (standard deviation [SD] = 13.9). MVP is the largest multiethnic biobank cohort within the Veteran population with 73.9% White, 19.0% Black, and 6.5% Hispanic. The most common self-reported disease was hypertension (62.6%) for males and depression (47.5%) for females. Mean BMI was 29.7 kg/m2 (SD = 5.8) with 38.2% obese and 42.3% overweight. Conclusions Our findings suggest that demographic representation in MVP is similar to the Veterans Health Administration population and contrasts with the overall National Health and Nutrition Examination Survey US population. The prevalence of overweight and obese is high among US Veterans, and future studies will examine the role of BMI and disease risk in the Veteran population.

Moderate alcohol consumption has been associated with a lower risk of coronary artery disease (CAD) in the general population but has not been well studied in US veterans. We obtained self-reported alcohol consumption from Million Veteran Program participants. Using electronic health records, CAD events were defined as 1 inpatient or 2 outpatient diagnosis codes for CAD, or 1 code for a coronary procedure. We excluded participants with prevalent CAD (n = 69,995) or incomplete alcohol information (n = 8,449). We used a Cox proportional hazards model to estimate hazard ratios and 95% confidence intervals for CAD, adjusting for age, gender, body mass index, race, smoking, education, and exercise. Among 156,728 participants, the mean age was 65.3 years (standard deviation = 12.1) and 91% were men. There were 6,153 CAD events during a mean follow-up of 2.9 years. Adjusted hazard ratios (95% confidence intervals) for CAD were 1.00 (reference), 1.02 (0.92 to 1.13), 0.83 (0.74 to 0.93), 0.77 (0.67 to 0.87), 0.71 (0.62 to 0.81), 0.62 (0.51 to 0.76), 0.58 (0.46 to 0.74), and 0.95 (0.85 to 1.06) for categories of never drinker; former drinker; current drinkers of ≤0.5 drink/day, >0.5 to 1 drink/day, >1 to 2 drinks/day, >2 to 3 drinks/day, and >3 to 4 drinks/day; and heavy drinkers (>4 drinks/day) or alcohol use disorder, respectively. For a fixed amount of ethanol, intake at ≥3 days/week was associated with lower CAD risk compared with ≤1 day/week. Beverage preference (beer, wine, or liquor) did not influence the alcohol-CAD relation. Our data show a lower risk of CAD with light-to-moderate alcohol consumption among US veterans, and drinking frequency may provide a further reduction in risk.

INTRODUCTION: Previous studies of the relationship between fried food consumption and coronary artery disease (CAD) have yielded conflicting results. We tested the hypothesis that frequent fried food consumption is associated with a higher risk of incident CAD events in Million Veteran Program (MVP) participants. METHODS: Veterans Health Administration electronic health record data were linked to questionnaires completed at MVP enrollment. Self-reported fried food consumption at baseline was categorized: (

Introduction: Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity in the U.S. We mapped ACC/AHA ASCVD risk in U.S. Veterans outpatients across U.S. geographic regions. Methods: We computed 10-year ASCVD risk using the 2013 ACC/AHA risk calculator with risk factor values derived from electronic health records and compared the estimates to observed ASCVD rates within Veterans Health Administration (VHA) population. We mapped the standardized differences in the observed and predicted risk at the county level using ArcGIS software. Results: There were 1.48 million VHA users between 2002-2007 aged 40 to 79 with median 10 years of follow-up. Mean age was 60 years, 96% were male, and 80% were white. The average 10-year predicted ASCVD risk after adjustment for true follow-up time at baseline was 13.8%, and the average observed risk was 6.6%, an overestimation of 7.2%. At baseline, 43.1% of patients were taking anti-hypertensive medications and 20.3% were taking statins. After updating risk factor statuses two years following baseline, 75.9% were taking anti-hypertensive medication, 42.6% were takings statins, and average predicted risk was dropped to 12.1%. In sex- and race-specific analyses the 2013 ACC/AHA risk calculator over-estimated 10-year ASCVD risk in white female, non-white female, white male, and non-white male by 2.0%, 2.0%, 8.1% and 4.8%, respectively. The greatest over-predictions in 10-year ASCVD risks were observed in western Arizona, southern California, southern Florida and Pennsylvania. These regions had higher percentages of white male VHA users compared to national averages. Conclusion: The 2013 ACC/AHA risk equation generally over-predicts ASCVD risk in the VHA population, particularly among white male Veterans. Increased anti-hypertensive and statin therapy with continual care at VHA was also associated with lower ASCVD risk. The mapping of these results allowed an overall visualization of the geographic variation across the U.S.

IMPORTANCE: Electronic health record (EHR) biobanks containing clinical and genomic data on large numbers of individuals have great potential to inform drug discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker profiles similar to those treated with IL6R blockers. This gene–drug pair provides an example to test whether associations of IL6R SNPs with a broad range of phenotypes can inform which diseases may benefit from treatment with IL6R blockade. OBJECTIVE: To determine whether screening for clinical associations with the IL6R SNP in a phenome-wide association study (PheWAS) using EHR biobank data can identify drug effects from IL6R clinical trials. DESIGN, SETTING, AND PARTICIPANTS: Diagnosis codes and routine laboratory measurements were extracted from the VA Million Veteran Program (MVP); diagnosis codes were mapped to phenotype groups using published PheWAS methods. A PheWAS was performed by fitting logistic regression models for testing associations of the IL6R SNPs with 1342 phenotype groups and by fitting linear regression models for testing associations of the IL6R SNP with 26 routine laboratory measurements. Significance was reported using a false discovery rate of 0.05 or less. Findings were replicated in 2 independent cohorts using UK Biobank and Vanderbilt University Biobank data. The Million Veteran Program included 332 799 US veterans; the UK Biobank, 408 455 individuals from the general population of the United Kingdom; and the Vanderbilt University Biobank, 13 835 patients from a tertiary care center. EXPOSURES: IL6R SNPs (rs2228145; rs4129267). MAIN OUTCOMES AND MEASURES: Phenotypes defined by International Classification of Diseases, Ninth Revision codes. RESULTS: Of the 332 799 veterans included in the main cohort, 305 228 (91.7%) were men, and the mean (SD) age was 66.1 (13.6) years. The IL6R SNP was most strongly associated with a reduced risk of aortic aneurysm phenotypes (odds ratio, 0.87-0.90; 95% CI, 0.84-0.93) in the MVP. We observed known off-target effects of IL6R blockade from clinical trials (eg, higher hemoglobin level). The reduced risk for aortic aneurysms among those with the IL6R SNP in the MVP was replicated in the Vanderbilt University Biobank, and the reduced risk for coronary heart disease was replicated in the UK Biobank. CONCLUSIONS AND RELEVANCE: In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.

Background The Department of Veterans Affairs Million Veteran Program (MVP) is the largest ongoing cohort program of its kind, with 654,903 enrollees as of June 2018. The objectives of this study were to examine gender differences in the MVP cohort with respect to response and enrollment rates; demographic, health, and health care characteristics; and prevalence of self-reported health conditions. Methods The MVP Baseline Survey was completed by 415,694 veterans (8% women), providing self-report measures of demographic characteristics, health status, and medical history. Results Relative to men, women demonstrated a higher positive responder rate (23.0% vs. 16.0%), slightly higher enrollment rate (13.5% vs. 12.9%), and, among enrollees, a lower survey completion rate (59.7% vs. 63.8%). Women were younger, more racially diverse, had higher educational attainment, and were less likely to be married or cohabitating with a partner than men. Women were more likely to report good to excellent health status but poorer physical fitness, and less likely to report lifetime smoking and drinking than men. Compared with men, women veterans showed an increased prevalence of musculoskeletal conditions, thyroid problems, gastrointestinal conditions, migraine headaches, and mental health disorders, as well as a decreased prevalence of gout, cardiovascular diseases, high cholesterol, diabetes, and hearing problems. Conclusions These results revealed some substantial gender differences in the research participation rates, demographic profile, health characteristics, and prevalence of health conditions for veterans in the MVP cohort. Findings highlight the need for tailoring recruitment efforts to ensure representation of the increasing women veteran population receiving care through the Veterans Health Administration.

Background While adherence to healthful dietary patterns has been associated with a lower risk of coronary artery disease (CAD) in the general population, limited data are available among US veterans. We tested the hypothesis that adherence to Dietary Approach to Stop Hypertension (DASH) food pattern is associated with a lower risk of developing CAD among veterans. Methods and Results We analyzed data on 153 802 participants of the Million Veteran Program enrolled between 2011 and 2016. Information on dietary habits was obtained using a food frequency questionnaire at enrollment. We used electronic health records to assess the development of CAD during follow‐up. Of the 153 802 veterans who provided information on diet and were free of CAD at baseline, the mean age was 64.0 (SD=11.8) years and 90.4% were men. During a mean follow‐up of 2.8 years, 5451 CAD cases occurred. The crude incidence rate of CAD was 14.0, 13.1, 12.6, 12.3, and 11.1 cases per 1000 person‐years across consecutive quintiles of Dietary Approach to Stop Hypertension score. Hazard ratios (95% confidence interval) for CAD were 1.0 (ref), 0.91 (0.84–0.99), 0.87 (0.80–0.95), 0.86 (0.79–0.94), and 0.80 (0.73–0.87) from the lowest to highest quintile of Dietary Approach to Stop Hypertension score controlling for age, sex, body mass index, race, smoking, exercise, alcohol intake, and statin use ( P linear trend, Conclusions Our data are consistent with an inverse association between Dietary Approach to Stop Hypertension diet score and incidence of CAD among US veterans.

No data exist on the prevalence of ideal cardiovascular health metrics in a national sample of U.S. veterans. We assessed the prevalence of ideal Life's Simple Seven (LSS) metrics in a cross-sectional study of 554,855 U.S. veterans enrolled in the Million Veteran Program (MVP) from 2011 to 2017. We used the American Heart Association's established criteria to categorize each LSS metric as either poor, intermediate, or ideal for a veteran at time of MVP enrollment. Information on adiposity/body mass index, smoking status, diet, and physical activity was obtained from self-reported survey data, and clinical measurements for total cholesterol, blood pressure, and plasma glucose were obtained from electronic health records. Complete data on all LSS health factors were available for 201,745 veterans. The prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal cardiovascular health metrics was 29.2%, 34.6%, 22.6%, 10.0%, 3.0%, 0.6%

Introduction: Prior studies have suggested a link between diet and Coronary Artery Disease (CAD), but there have been mixed findings on the risks and benefits of coffee and tea consumption. We assessed whether there is an association and dose response between coffee and tea intake on CAD incidence among Veterans. Methods: Million Veteran Program (MVP) is a national, representative longitudinal study of Veterans for genomic and non-genomic research that combines data from self-reported surveys, electronic health records, and biospecimens. Using food frequency data collected from 2011-2017 and CAD outcomes obtained from electronic health records, we used cox proportional hazard ratios (HR) to evaluate the association of coffee or tea intake with CAD incidence among Veterans with complete data. Follow-up began at the completion of the food frequency survey. Tea and coffee were evaluated separately, with intake categorized as never or less than one cup/month, 1-3 cups/month, one cup/week, 2-4 cups/week, 5-6 cups/week, one cup/day, 2-3 cups/day, 4-5 cups/day, or 6+ cups/day. For tea, the last two categories were combined to obtain stable estimates. Multivariate models were adjusted for known CAD risk factors (age, smoking status, physical activity, and education) and other caffeine use (e.g. tea for coffee). We plan to use restricted cubic splines to assess dose-response relationships. Results: Among 139,549 participants (90.3% male, mean age 64 ± 12 years), 74.2% consumed 1+ cups of coffee a month and 53.7% consumed 1+ cups of tea a month. During a median follow up of 3.2 years, we observed 4,715 new cases of CAD. Compared to those who drank less than one cup of coffee/month, adjusted HRs (95% CI) for CAD were 1.06 (0.92-1.22) for 1-3 cups/month, 1.09 (0.91-1.29) for one cup/week, 0.96 (0.84-1.10) for 2-4 cups/week, 0.92 (0.81-1.04) for 5-6 cups/week, 0.93 (0.85-1.01) for one cup/day, 0.99 (0.91-1.07) for 2-3 cups/day, 1.05 (0.93-1.19) for 4-5 cups/day, and 1.08 (0.92-1.28) for 6+ cups/day (p-linear trend=0.24). Compared to those who drank less than one cup of caffeinated tea/month, adjusted HRs (95% CI) for CAD were 1.08 (0.99-1.17) for 1-3 cups/month, 1.11 (0.99-1.23) for one cup/week, 1.01 (0.91-1.12) for 2-4 cups/week, 1.03 (0.89-1.17) for 5-6 cups/week, 1.04 (0.93-1.17) for one cup/day, 1.12 (0.98-1.28) for 2-3 cups/day, and 1.27 (1.04-1.58) for 4+ cups/day (p-linear trend=0.14). Conclusion: While coffee intake was not associated with incidence of CAD, there was an elevated risk of CAD restricted to Veterans consuming 4+ cups of caffeinated tea per day.

Background: While previous studies have reported the prevalence of Life’s Simple Seven (LSS) in the general population, no data exist in a national sample of US veterans. Objective: To assess the prevalence of ideal LSS in a cross-sectional study of 500,000 US Veterans participating in the Million Veteran Program (MVP) from 2011-2016. Methods: We assigned one of three possible values (0=poor, 1=intermediate, 2=ideal) for each of the seven LSS metrics (adiposity /BMI), smoking status, total cholesterol, blood pressure, plasma glucose, diet, physical activity) at baseline using self-reported data and electronic health records. A total score of 0 across all seven metrics indicated overall poor cardiovascular health and a score of 14 indicated ideal cardiovascular health. Results: Complete data on all LSS factors were available for 171,146 Veterans (92% men and mean age 65.5yrs ±11.5 SD). Average LSS score was 6.1 ±1.9. Ideal BMI, smoking status, total cholesterol, blood pressure and plasma glucose (fasting and non-fasting) was present in 23.8%, 30%, 22.2%, 22.5% and 42.9%, respectively, in the study population (Fig). Prevalence of ideal diet was 0.4%. Among dietary factors, recommendation for fruits and vegetables (at least 4.5cups/day) was the least likely to be achieved. Physical activity at the workplace, home or at leisure was reported among 25.6% of Veterans (21.8% intermediate and 3.8% ideal physical activity). Conclusions: Our data show a low prevalence of ideal LSS among Veterans in the MVP, especially diet (0.4%) and physical activity (3.8%). Compared to NHANES 2005-2006 unadjusted prevalence estimates for AHA 2020 goals, Veterans in MVP have a lower prevalence of all ideal LSS metrics except for diet: BMI (23.8 vs 33%), physical activity (3.8 vs 45%), smoking status (30 vs 73%), total cholesterol (22.2 vs 45%) blood pressure (22.5 vs 42%) and glucose (42.9 vs 58%). These findings underscore the need to improve adherence to modifiable lifestyle factors with subsequent reduction in CVD burden among Veterans.

Introduction: Moderate alcohol consumption has been shown to protect against coronary artery disease (CAD) in the general population, but this relationship has not been well studied among U.S. Veterans. Methods: 61,587 Million Veteran Program (MVP) participants completed a baseline and lifestyle survey that included questions about frequency and volume of alcohol consumption. We combined grams of ethanol in wine, beer, and spirits to create the exposure variable for this analysis. Using the VA electronical health record, incident CAD events included myocardial infarction, angina pectoris, other forms of chronic ischemic heart disease (ICD9 codes 410-414.9) or coronary procedures (ICD9 procedure codes 36.0-36.99). Participants with prevalent CAD (n=27,844) before the baseline survey date or alcohol abuse using ICD9 codes 303.0 and 305.0 (n=16,048) were excluded from the analysis. We used a Cox Proportional Hazard model to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CAD adjusting for age, sex, body mass index, and smoking status. Results: Among 59,288 participants analyzed, the mean age was 65y (SD=11.9), mean BMI was 28.9 kg/m 2 , 90% were men, 33% were never smokers, 86% self-reported as White, 11% Black, and 6% Hispanic. Participants were categorized into 6 alcohol consumption categories: Never, former, and current drinkers of half drink/d, >half to 1 drink/d, >1 to 2 drinks/d, >2 to 3 drinks/d, >3 to 4 drinks/d, and >4 drinks/d. During a mean follow up of 3.3 years, 3,670 CAD events were documented. Using current drinkers of ≤half a drink/d as the reference group, we found a 19% lower risk of CAD in drinkers of >1 to 2 drinks/d, a 25% lower risk of CAD with alcohol intake of >3 to 4 drinks/d, and 34% lower risk in the highest alcohol category in a multivariable adjusted model (Table 1). As expected, former drinkers had a slightly higher risk of CAD. We did not have enough data on women to conduct sex-specific analyses. Conclusion: Our data show a lower risk of CAD with moderate alcohol consumption among MVP participants.

Background: More than one-third of US adults are obese and the prevalence has remained stable since 2003. In the largest cohort of 515,912 men and women participating in the Million Veteran Program (MVP), we analyzed trends in baseline weight/obesity across the years of enrollment. Objective: The goal of this study is to examine prevalence and trends in baseline characteristics among US Veterans enrolled in MVP between 2011 and 2016. We highlight the trends in BMI over the enrollment period. Methods: BMI was computed for 479,521 Veterans who enrolled in MVP between 2011 to September 2016. Participants reported weight and height on the baseline survey. Missing survey data was supplemented with patient EMR data taken closest to enrollment date and stratified by year of enrollment. Results: Mean age was 61.2 (SD=13.8), 91.6% (391,124/427,187) were men, 73.8% (353,720/479,520) White, 18.8% (90,020/479,520) Black, and 7.4% (35,593/479,520) Hispanic. Overall, mean BMI was 29.7 [range 11.3 to 78.5]. Prevalence of underweight, normal weight, and overweight was 0.7% (3,164/479,521), 19.4% (93,318/479,521), 38.4% (184,625/479,521), respectively, in this cohort. While the prevalence of obesity increased with consecutive years of enrollment in men and overall, we did not observe such trend for other categories of adiposity (Fig). When stratified by race we did not observe any difference in prevalence of underweight and normal weight among White and Black participants. Prevalence of obesity was higher in Blacks, but the rate of obesity among Whites appears to be growing at a faster rate than in Blacks. Compared to the general VHA (Veterans Health Administration) population, prevalence of obesity and the distributions of race, gender, and ethnicity were similar among participants in MVP. Conclusion: Our data show that the prevalence of overweight/obesity is high among US Veterans. Across consecutive years of enrollment, prevalence of obesity but not overweight appears to increase across each ethnic group.

Background Laparoscopic adjustable gastric banding is gaining in popularity in the United States. Our objective was to examine the outcomes of laparoscopic adjustable gastric banding and the prevalence of band revision and explantation at academic medical centers. Methods Using the "International Classification of Diseases, 9th revision," diagnosis and procedure codes, data were obtained from the University Health System Consortium Clinical Database for all laparoscopic adjustable gastric banding procedures performed from 2006 to 2009. The outcome measures included demographics, length of hospital stay, perioperative morbidity, mortality, and the prevalence of band revision and explantation. Results A total of 10,151 laparoscopic gastric banding procedures were performed from January 2007 to December 2009. The mean length of stay was 1.2 days. The perioperative morbidity rate was 3.0%, and the in-hospital mortality rate was .03%. The prevalence of band revision was .76% and of band explantation was .87%. Compared with the outcome of primary gastric banding, gastric band revision or explantation was associated with a longer length of hospital stay, greater perioperative morbidity, and greater cost. Conclusion Within the context of the 3-year period of analysis, laparoscopic gastric banding was associated with low perioperative morbidity and mortality and a low prevalence of band revision and explantation.

Esophagectomy can be associated with significant morbidity such as leaks and strictures. Preoperative gastric ischemic conditioning is a concept aimed at inducing an ischemic insult to the gastric fundus and cardia prior to esophagectomy, thus leading to improvement of gastric perfusion.This retrospective study compared outcome data from 81 patients who underwent esophagectomy after laparoscopic gastric ischemic conditioning with that from 71 patients who underwent esophagectomy without conditioning. Gastric ischemic conditioning consisted of laparoscopic division of the left gastric vessels ± the short gastric vessels. The time interval from gastric ischemic conditioning to esophagectomy ranged from 2 to 75 days. Main outcome measures included demographics, mean time interval between staging and esophagectomy, and the rate of leaks and strictures following esophagectomy.The two groups were comparable with respect to gender and age. In the gastric ischemic conditioning procedures, there were no conversions; the mean operative time was 57 ± 15 min, the mean length of hospital stay was 1.0 ± 1.1 days, and the rate of postoperative complications was 3.7%. The mean time interval between gastric ischemic conditioning and esophagectomy was 6.0 ± 5.4 days. There were no significant differences in the leak rate (11.1% for conditioning vs. 8.5% without conditioning) or stricture rate (29.6% for conditioning vs. 25.3% without conditioning) between the two groups.Laparoscopic gastric ischemic conditioning is feasible and safe. However, the use of gastric ischemic conditioning in this study did not alter the clinical rate of postoperative leaks and strictures.

Transoral incisionless fundoplication is a new treatment for patients with gastroesophageal reflux disease. We present our initial experience with 10 patients undergoing this procedure with varying past surgical histories. All procedures were performed under general nasotracheal anesthesia. RAND-36 and Visual Analog Scale symptom scores were collected at pre and postoperative appointments for a mean of 9.2 months. The mean procedure time was 68 minutes. There were no intraoperative or postoperative complications. Patients with prior pancreaticoduodenectomy had observed reduced working space due to prior distal gastrectomy and required additional insufflation due to no pyloric resistance to insufflation of the small bowel. The patient with prior fundoplication required additional time and force for fastener penetration of the resultant scar from the partially disrupted fundoplication. All patients were discharged within 23 hours of the procedure. Throughout the follow-up period, patients reported gradual changes in medication requirements and symptom scores. There were no late complications. Transoral incisionless fundoplication is technically safe in well-selected patients including those with prior esophageal and gastric surgery.

Background Obesity is one of the most important modifiable risk factors for the prevention of type 2 diabetes. The aim of this study was to examine the prevalence of diabetes with increasing severity of obesity and the distribution of HbA1c levels in diabetics participating in the latest National Health and Nutrition Examination Survey (NHANES). Methods Data from a representative sample of adults with diabetes participating in the NHANES between 1999 and 2006 were reviewed. The prevalence of diabetes and levels of fasting glucose, insulin, c-peptide, and HbA1c were examined across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as body mass index (BMI) of 8.0%) in 23%. The mean fasting glucose and HbA1c levels were highest for diabetics with BMI

Pyloroplasty is performed during esophagectomy to avoid delayed gastric emptying. However, studies have shown that gastric function is minimally impaired even without a pyloroplasty when a gastric tube rather than the whole stomach is used for reconstruction. The aim of this study was to evaluate outcomes of minimally invasive esophagectomy without performance of a pyloroplasty. We performed a retrospective review of 145 patients who underwent a minimally invasive esophagectomy. The 30-day mortality was 2.1 per cent with an in-hospital mortality of 3.4 per cent. Of the 140 patients with more than 90 days follow-up, 31 patients had a pyloroplasty and 109 patients did not. One (3.2%) of 31 patients with pyloroplasty versus six (5.5%) of 109 patients without pyloroplasty developed delayed gastric emptying. There was no significant difference in the leak rate between the two groups (9.7% vs 9.6%, respectively). Total operative time was significantly shorter in the group without pyloroplasty (360 vs 222 minutes with a pyloroplasty, P < 0.01). Patients with delayed gastric emptying responded well to endoscopic pyloric dilation or Botox injection. The routine performance of a pyloroplasty during minimally invasive esophagectomy can be safely omitted with a reduction in operative time and minimal adverse effects on postoperative gastric function.

BACKGROUND Recent studies suggest that intraluminal pancreatic enzymes play a major role in the initiation of the inflammatory cascade by the gut after hemorrhagic shock. Previous animal models have shown that the inhibition of enteral pancreatic enzymes with a serine protease inhibitor, nafamostat mesilate (NM), decreases leukocyte activation and transfusion requirements after hemorrhagic shock. The objective of this study was to determine whether enteroclysis with NM would improve the clinical outcomes in swine after hemorrhagic shock and intestinal hypoperfusion. METHODS Thirty-three male Yucatan minipigs weighing 25 kg to 30 kg underwent a controlled hemorrhage of 25 mL/kg with mesenteric clamp for further gut ischemia. Animals were allocated to three groups: (1) shock only (n = 15), (2) shock + enteroclysis with 100 mL/kg GoLYTELY (GL) as a carrier (n = 11), and (3) shock + enteroclysis with GL + 0.37 mmol/L NM (GL+NM, n = 7). Animals were resuscitated, recovered from anesthesia, observed for 3 days, and graded on a daily 4-point clinical scoring system. A score of 0 indicated a moribund state or early death, and a score of 4 indicated normal behavior. RESULTS Pigs treated with GL + NM had significantly higher mean postoperative recovery scores (3.8 +/- 0.4, essentially normal behavior with no early deaths) compared with animals within the shock only and shock + GL groups (2.1 +/- 1 with one early death and 2.2 +/- 1.2 with two early deaths, respectively, analysis of variance p < 0.003). CONCLUSION The inhibition of intraluminal pancreatic enzymes using enteroclysis with the serine protease inhibitor, NM, after hemorrhagic shock significantly improves the clinical outcome.

Aim: Million Veteran Program (MVP) is the largest ongoing mega-cohort biobank program in the US with 570,131 enrollees as of May 2017. The primary aim is to describe demographics, military service, and major diseases and comorbidities of the MVP cohort. Our secondary aim is to examine body mass index (BMI), a proxy for general health, among enrollees. Materials and Method: The study population consists of Veterans who actively use the Veterans Health Administration in the US. Data evaluated in this paper combine health information from multiple sources to provide the most comprehensive demographic profile and information on height and weight of MVP enrollees. A standardized cleaning algorithm was used to curate the demographic variables for each participant in MVP. For height and weight, we derived a final data point for each participant to evaluate BMI. Statistical Analysis Used: Multivariable logistic regression was used to compare the differences in BMI categories across enrollment years adjusting for gender, race, and age. P < 0.05 was considered statistically significant. All analyses were conducted using Statistical Analysis System 9.2. Results: The MVP cohort consists of 90.4% of males with an average age of 61.9 years (standard deviation [SD] = 13.9). MVP is the largest multiethnic biobank cohort within the Veteran population with 73.9% White, 19.0% Black, and 6.5% Hispanic. The most common self-reported disease was hypertension (62.6%) for males and depression (47.5%) for females. Mean BMI was 29.7 kg/m2 (SD = 5.8) with 38.2% obese and 42.3% overweight. Conclusions: Our findings suggest that demographic representation in MVP is similar to the Veterans Health Administration population and contrasts with the overall National Health and Nutrition Examination Survey US population. The prevalence of overweight and obese is high among US Veterans, and future studies will examine the role of BMI and disease risk in the Veteran population.

Laparoscopic techniques in colon surgery reduce postoperative pain, length of hospital stay, and 30-day morbidity when compared with open surgery. The objective of this study was to determine the feasibility of a laparoscopic colectomy in patients who have previously undergone abdominal surgery. We performed a retrospective, single-institution review of laparoscopic colorectal procedures for benign or malignant pathology between October 2002 and September 2008. Our analysis included 55 patients who previously had laparoscopic, open, or a combination of procedures and subsequently underwent laparoscopic colorectal surgery. We observed a 14.5 per cent conversion rate (n = 8). Of the patients who had previous open procedures (n = 48 [87.3%]), the conversion rate was 16.7 per cent. Only one patient (12.5%) who had a history of only laparoscopic surgery required conversion. The highest conversion rate in our study was from patients who underwent a left colectomy (60%, n = 3/5), which was the only statistically significant factor found for conversion. Since the emergence of laparoscopy, use in colon and rectal surgery nationwide has been poor as a result of multiple factors, including a frequent history of abdominal surgery. Our experience shows that laparoscopic colorectal surgery in patients with prior intra-abdominal surgery can be completed with an acceptable conversion rate.

Twenty-five to 30 per cent of hypotensive trauma patients require an emergent surgery, however, we have no reliable means to quickly determine that need. Our goal was to determine, via retrospective review, parameters available within minutes of arrival that predict the need for emergent surgery to control hemorrhage in hypotensive trauma patients. Inclusion criterion was initial systolic blood pressure (SBP) < 90 mm Hg in the emergency department (ED). Patients who were dead on arrival or underwent ED thoracotomy were excluded. Emergent surgery was defined as sternotomy, thoracotomy, laparotomy, or major neck vascular repair on day of admission. Potential clinical predictors were analyzed in a binary logistic regression model. Six hundred and thirty-nine hypotensive patients were identified and 193 excluded, leaving 446 with a mean age of 33 ± 19 years and Injury Severity Score of 22 ± 17. Thirty-two per cent suffered penetrating trauma, 30 per cent needed emergent surgery, and 19 per cent died. Independent predictors were: prolonged extrication (odds ratio (OR) 2.3), no loss of consciousness (OR 2.8), intubation (OR 1.7), central line placement (OR 1.7), and blood transfusion (OR 2.1, all P < 0.05). We concluded that hypotensive trauma patients without head injuries who require prolonged extrication, intubation, central venous access, and blood transfusion in the ED are more likely to need emergent surgery.

Anastomotic stenosis is one of the most common delayed complications following Roux-en-Y gastric bypass. Stricture at the gastrojejunal anastomosis can lead to symptoms of progressive dysphagia, nausea, and emesis. Stricture diagnosis is typically made via endoscopy, and definitive treatment can usually be achieved with endoscopic methods of stricture dilation. This chapter reviews diagnosis and management of strictures in the bariatric patient.

Strategic laparoscopic surgery for improved cosmesis (SLIC) is a less invasive surgical approach than conventional laparoscopic surgery. The aim of this study was to examine the feasibility and safety of SLIC for general and bariatric surgical operations. Additionally, we compared the outcomes of laparoscopic sleeve gastrectomy with those performed by the SLIC technique.In an academic medical center, from April 2008 to December 2010, 127 patients underwent SLIC procedures: 38 SLIC cholecystectomy, 56 SLIC gastric banding, 26 SLIC sleeve gastrectomy, 1 SLIC gastrojejunostomy, and 6 SLIC appendectomy. SLIC sleeve gastrectomy was initially performed through a single 4.0-cm supraumbilical incision with extraction of the gastric specimen through the same incision. The technique evolved to laparoscopic incisions that were all placed within the umbilicus and suprapubic region.There were no 30-day or in-hospital mortalities or 30-day re-admissions or re-operations. For SLIC cholecystectomy, gastric banding, appendectomy, and gastrojejunostomy, conversion to conventional laparoscopy occurred in 5.3%, 5.4%, 0%, and 0%, respectively; there were no major or minor postoperative complications. For SLIC sleeve gastrectomy, there were no significant differences in mean operative time and length of hospital stay compared with laparoscopic sleeve gastrectomy; 1 (3.8%) of 26 SLIC patients required conversion to five-port laparoscopy. There were no major complications. Minor complications occurred in 7.7% in the SLIC sleeve group versus 8.3% in the laparoscopic sleeve group.SLIC in general and bariatric operations is technically feasible, safe, and associated with a low rate of conversion to conventional laparoscopy. Compared with laparoscopic sleeve gastrectomy, SLIC sleeve gastrectomy can be performed without a prolonged operative time with comparable perioperative outcomes.