Red Meat Intake and the Risk of Cardiovascular Diseases: A Prospective Cohort Study in the Million Veteran Program.

BACKGROUND: Red meat consumption was associated with an increased risk of cardiovascular disease (CVD) in prospective cohort studies and a profile of biomarkers favoring high CVD risk in short-term controlled trials. However, several recent systematic reviews and meta-analyses concluded with no or weak evidence for limiting red meat intake. OBJECTIVES: To prospectively examine the associations between red meat intake and incident CVD in an ongoing cohort study with diverse socioeconomic and racial or ethnic backgrounds. METHODS: Our study included 148,506 participants [17,804 female (12.0%)] who were free of cancer, diabetes, and CVD at baseline from the Million Veteran Program. A food frequency questionnaire measured red meat intakes at baseline. Nonfatal myocardial infarction and acute ischemic stroke were identified through a high-throughput phenotyping algorithm, and fatal CVD events were identified by searching the National Death Index. RESULTS: Comparing the extreme categories of intake, the multivariate-adjusted relative risks of CVD was 1.18 (95% CI: 1.01, 1.38; P-trend < 0.0001) for total red meat, 1.14 (95% CI: 0.96, 1.36; P-trend = 0.01) for unprocessed red meat, and 1.29 (95% CI: 1.04, 1.60; P-trend = 0.003) for processed red meat. We observed a more pronounced positive association between red meat intake and CVD in African American participants than in White participants (P-interaction = 0.01). Replacing 0.5 servings/d of red meat with 0.5 servings/d of nuts, whole grains, and skimmed milk was associated with 14% (RR: 0.86; 95% CI: 0.83, 0.90), 7% (RR: 0.93; 95% CI: 0.89, 0.96), and 4% (RR: 0.96; 95% CI: 0.94, 0.99) lower risks of CVD, respectively. CONCLUSIONS: Red meat consumption is associated with an increased risk of CVD. Our findings support lowering red meat intake and replacing red meat with plant-based protein sources or low-fat dairy foods as a key dietary recommendation for the prevention of CVD.

Epidemiology of Craniomaxillofacial Fractures Over a 5-year Period at a Midwestern Level 1 Trauma Center Serving a Large Rural Population.

BACKGROUND: Though the epidemiology of craniomaxillofacial (CMF) fractures has been well documented at urban hospitals, the characteristics of these fractures in rural hospitals have not been well studied. PURPOSE: The purpose of this study is to report on the epidemiology of CMF fractures at a regional Level 1 trauma center serving a large rural population in central Illinois. STUDY DESIGN, SETTING, SAMPLE: This is a retrospective cohort study at a community-based regional tertiary referral center that serves a predominantly rural population. Inclusion criteria comprised patients with radiologically confirmed CMF fractures between 2015 and 2019. Patients with incomplete medical records were excluded. PREDICTOR VARIABLE: Predictor variables included demographics (age, admission source, race, and sex) and etiology of CMF fracture (assault/domestic violence, all-terrain vehicle/off-road, falls, farm-related, motor vehicle collisions, gunshot wound, and others). MAIN OUTCOME VARIABLE: The primary outcome variable was the CMF anatomic location including nasal bone, orbit, mandible, malar/maxillary, and other CMF fractures. COVARIATES: The covariates are not applicable. ANALYSES: Descriptive statistics were used to summarize a sample of the population characteristics. Wilcoxon ranked sign tests and χ2 tests of independence were used to assess for statistically significant associations between select variables of interest. Statistical significance was defined as P < .05. RESULTS: Between 2015 and 2019, a total of 2,334 patients presented to the emergency department with a CMF fracture. After applying the inclusion/exclusion criteria, the final sample was composed of 1,844 patients for the management of 2,405 CMF fractures. The majority of patients were male(62.0%) and young adults (aged 18-39) had the highest number of CMF fractures (819) relative to all other age groups. The most common fracture etiology was fall(37.3%), and nasal bone fractures represented the most common fracture location(41.6%). χ2 analyses revealed statistically significant associations between the anatomic location of CMF fracture incurred, and differing categories of age, admission source, race, sex, and etiology. CONCLUSION AND RELEVANCE: Our study shows that patients seen at our Midwestern Level 1 trauma center are more likely to present with nasal bone and malar/maxillary fractures due to falls. In studies based in urban centers, patients are likely to present with orbital and mandibular fractures due to falls and assault.

Upper Extremity Functional Outcomes After Breast Cancer Treatment: An Analysis of DASH Score in Breast Reconstruction Patients.

BACKGROUND: Patients undergoing postoncologic breast reconstruction can experience upper extremity (UE) functional deficits. OBJECTIVES: In this study, we utilized the disabilities of the arm, shoulder, and hand (DASH) questionnaire to identify patient factors that impacted UE functional recovery. METHODS: Patients who underwent oncologic followed by reconstructive surgery by a single surgeon from 2014 to 2019 and completed the DASH survey were included. A DASH score was calculated for each patient, with values ranging from 0 (no impairment) to 100 (severe impairment). Regression analysis was conducted to identify significant predictors for DASH score with a significance level for entry and stay set at P = .15. RESULTS: Among 289 patients who underwent breast reconstruction, 157 completed the questionnaire. The average patient age was 52.6yrs ± 8.6 at the time of reconstruction. A total of 111 had implant-based reconstruction, 15 had autologous reconstruction, and 24 had a combination of both. Average DASH score was 7.7 (range 0.0-52.5), with 74.1% of patients having a score greater than 0. Regression analysis showed 5 variables associated with significantly higher DASH scores: age between 50 and 60 years (P = .13), history of radiation (P = .01), placement of a subpectoral implant (P = .06), postoperative complications (P = .10), and lymphedema (P < .01). Autologous breast reconstruction (P = .04) was associated with a significantly lower DASH score. CONCLUSIONS: Implant-based reconstruction, radiation history, postoperative complications, and age at reconstruction were associated with increased UE functional impairment in patients who underwent breast reconstructive surgery. Identification of these factors can inform areas for potential practice changes and improve patient counseling regarding postoperative expectations.

Frailty and cardiovascular mortality in more than 3 million US Veterans.

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.

Impact of Coronavirus Disease 2019 (COVID-19) Severity on Long-term Events in United States Veterans Using the Veterans Affairs Severity Index for COVID-19 (VASIC).

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.

Degree of Adherence to Based Diet and Total and Cause-Specific Mortality: Prospective Cohort Study in the Million Veteran Program.

OBJECTIVE: To examine the associations 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 separate the healthy plant foods from less-healthy plant foods. SETTING: the VA Million Veteran Program. PARTICIPANTS: 315,919 men and women aged 19 to 104 years who completed a food frequency questionnaire 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% confidence interval (CI): 0.71 to 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 to 0.68, Ptrend <0.001), whereas uPDI was positively associated with total mortality (HR comparing extreme deciles =1.41, 95% CI: 1.33 to 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 plant-based diet indices 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.

Impact of 8 lifestyle factors on mortality and life expectancy among United States veterans: The Million Veteran Program.

BACKGROUND: Lifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs. OBJECTIVE: This study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy. METHODS: Age- and sex-specific mortality rates were calculated on the basis of 719,147 veterans aged 40-99 y enrolled in the Veteran Affairs Million Veteran Program (2011-2019). Hazard ratios and estimated increase in life expectancy were examined among a subgroup of 276,132 veterans with complete data on 8 lifestyle factors at baseline. The 8 lifestyle factors included never smoking, physical activity, no excessive alcohol consumption, restorative sleep, nutrition, stress management, social connections, and no opioid use disorder. RESULTS: On the basis of 1.12 million person-years of follow-up, 34,247 deaths were recorded. Among veterans who adopted 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, the adjusted hazard ratios for mortality were 0.74 (0.60-0.90), 0.60 (95% CI: 0.49, 0.73), 0.50 (95% CI: 0.41, 0.61), 0.43 (95% CI: 0.35, 0.52), 0.35 (95% CI: 0.29, 0.43), 0.27 (95% CI: 0.22, 0.33), 0.21 (95% CI: 0.17, 0.26), and 0.13 (95% CI: 0.10, 0.16), respectively, as compared with veterans with no adopted lifestyle factors. The estimated life expectancy at age 40 y was 23.0, 26.5, 28.8, 30.8, 32.7, 35.1, 38.3, 41.3, and 47.0 y among males and 27.0, 28.8, 33.1, 38.0, 39.2, 41.4, 43.8, 46.3, and 47.5 y for females who adopted 0, 1, 2, 3, 4, 5, 6, 7, and 8 lifestyle factors, respectively. The difference in life expectancy at age 40 y was 24.0 y for male veterans and 20.5 y for female veterans when comparing adoption of 8-9 lifestyle factors. CONCLUSIONS: A combination of 8 lifestyle factors is associated with a significantly lower risk of premature mortality and an estimated prolonged life expectancy.

The Million Veteran Program 1990-1991 Gulf War Era Survey: An Evaluation of Veteran Response, Characteristics, and Representativeness of the Gulf War Era Veteran Population.

To address gaps in understanding the pathophysiology of Gulf War Illness (GWI), the VA Million Veteran Program (MVP) developed and implemented a survey to MVP enrollees who served in the U.S. military during the 1990-1991 Persian Gulf War (GW). Eligible Veterans were invited via mail to complete a survey assessing health conditions as well as GW-specific deployment characteristics and exposures. We evaluated the representativeness of this GW-era cohort relative to the broader population by comparing demographic, military, and health characteristics between respondents and non-respondents, as well as with all GW-era Veterans who have used Veterans Health Administration (VHA) services and the full population of U.S. GW-deployed Veterans. A total of 109,976 MVP GW-era Veterans were invited to participate and 45,270 (41%) returned a completed survey. Respondents were 84% male, 72% White, 8% Hispanic, with a mean age of 61.6 years (SD = 8.5). Respondents were more likely to be older, White, married, better educated, slightly healthier, and have higher socioeconomic status than non-respondents, but reported similar medical conditions and comparable health status. Although generally similar to all GW-era Veterans using VHA services and the full population of U.S. GW Veterans, respondents included higher proportions of women and military officers, and were slightly older. In conclusion, sample characteristics of the MVP GW-era cohort can be considered generally representative of the broader GW-era Veteran population. The sample represents the largest research cohort of GW-era Veterans established to date and provides a uniquely valuable resource for conducting in-depth studies to evaluate health conditions affecting 1990-1991 GW-era Veterans.

Dietary ω-3 fatty acids and the incidence of atrial fibrillation in the Million Veteran Program.

BACKGROUND: Although recent large randomized clinical trials have reported an increased risk of atrial fibrillation (AF) with marine ω-3 fatty acid supplements, it is unclear whether dietary marine ω-3 fatty acids assessed through food frequency questionnaires are associated with AF risk. OBJECTIVES: 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 the HRs of AF across quintiles of ω-3 fatty acid consumption and a cubic spline analysis to assess the dose-response relations between ω-3 fatty acids and AF. RESULTS: Of the 301,294 veterans studied, the median intake of ω-3 fatty acids (EPA/DHA/DPA) was 219 mg/d (IQR: 144-575), and the mean age was 64.9 y (SD: 12.0); 91% were men, and 84% were White. Consumption of EPA/DHA/DPA exhibited a nonlinear inverse relation with incident AF characterized by an initial decline to 11% at 750 mg/d of marine ω-3 fatty acid 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 nonlinear manner.

Data resource profile: nutrition data in the VA million veteran program.

Introduction: The Department of Veterans Affairs (VA) Million Veteran Program (MVP) nutrition data is derived from dietary food/beverage intake information collected through a semiquantitative food frequency questionnaire (SFFQ). Methods: Estimates of dietary energy, nutrient, and non-nutritive food components intakes data were derived from an extensively validated SFFQ, which assessed the habitual frequency of consumption of 61 food items, added sugar, fried food frequency, and 21 nutritional supplements over the 12 months preceding questionnaire administration. Results: Complete nutrition data was available for 353,418 MVP participants as of 30th September 2021. Overall, 91.5% of MVP participants with nutrition data were male with an average age of 65.7 years at enrollment. Participants who completed the SFFQ were primarily White (82.5%), and Blacks accounted for 13.2% of the responders. Mean ± SD energy intake for 353, 418 MVP participants was 1428 ± 616 kcal/day, which was 1434 ± 617 kcal/day for males and 1364 ± 601 kcal/day for females. Energy intake and information on 322 nutrients and non-nutritive food components is available through contact with MVP for research collaborations at www.research.va.gov/mvp. Conclusions: The energy and nutrient data derived from MVP SFFQ are an invaluable resource for Veteran health and research. In conjunction with the MVP Lifestyle Survey, electronic health records, and genomic data, MVP nutrition data may be used to assess nutritional status and related risk factors, disease prevalence, and determinants of health that can provide scientific support for the development of evidence-based public health policy and health promotion programs and services for Veterans and general population.

Association of dietary fatty acids with the risk of atherosclerotic cardiovascular disease in a prospective cohort of United States veterans.

BACKGROUND: Atherosclerotic cardiovascular diseases (ASCVDs) are the leading cause of worldwide adult mortality. Although broad classes of dietary fats have been shown to alter ASCVD risk, the roles that individual dietary fatty acids play in influencing ASCVD risk are unclear. OBJECTIVES: The aim of this prospective cohort study was to examine the relationships of the total fat classes and individual fatty acids with the risk of ASCVD. METHODS: The Million Veteran Program is a prospective cohort whereby dietary intake of fatty acids was assessed in 158,198 participants that had enrolled between January 2011 and November 2018 and were free of ASCVD at baseline. Incident ASCVD was ascertained from the Veterans Affairs electronic health records and the National Death Index. Multivariable-adjusted hazard ratios (HRs) for the relationship between fat intake and ASCVD risk were computed using Cox regression models. RESULTS: The mean age was 61 years, 88% were males. A total of 11,771 ASCVD events were identified during the follow-up. When compared with the lowest quintile, participants in the highest quintile of dietary trans-monounsaturated fats and conjugated linoleic acids had an increased risk (HR [95% CI]) of ASCVD events: 1.10 (1.04, 1.17) and 1.11 (1.05, 1.18), respectively. When compared with low consumers, participants in the highest quintile of total cis-polyunsaturated fatty acid intake had a lower risk of experiencing an ASCVD event 0.93 (0.87, 0.99). CONCLUSION: Although higher intakes of specific trans-fatty acids and conjugated linoleic were associated with an increased risk of ASCVD, the same cannot be said for all other fat classes. This work suggests that care must be taken when drawing general conclusions regarding the health effects of dietary individual fatty acids.

Overview of Efforts to Increase Women Enrollment in the Veterans Affairs Million Veteran Program.

Background: Ensuring enhanced delivery of care to women Veterans is a top Veterans Affairs (VA) priority; however, women are historically underrepresented in research that informs evidence-based health care. A primary barrier to women's participation is the inability to engage with research in person due to a number of documented challenges. The VA Million Veteran Program (MVP) is committed to increasing access for women Veterans to participate in research, thereby better understanding conditions specific to this population and how disease manifests differently in women compared to men. The goal of this work is to describe the results of the MVP Women's Campaign, an effort designed to increase outreach to and awareness of remote enrollment options for women Veterans. Materials and Methods: The MVP Women's Campaign launched two phases between March 2021 and April 2022: the Multimedia Phase leveraged a variety of strategic multichannel communication tactics and the Email Phase focused on direct email communication to women Veterans. The effect of the Multimedia Phase was determined using t-tests and chi-square tests, as well as logistic regression models to compare demographic subgroups. The Email Phase was evaluated using comparisons of the enrollment rate across demographic groups through a multivariate adjusted logistic regression model. Results: Overall, 4694 women Veterans enrolled during the MVP Women's Campaign (54% during the Multimedia Phase and 46% during the Email Phase). For the Multimedia Phase, the percentage of older women online enrollees increased, along with women from the southwest and western regions of the United States. Differences for women Veteran online enrollment across different ethnicity and race groups were not observed. During the Email Phase, the enrollment rate increased with age. Compared to White women Veterans, Blacks, Asians, and Native Americans were significantly less likely to enroll while Veterans with multiple races were more likely to enroll. Conclusion: The MVP Women's Campaign is the first large-scale outreach effort focusing on recruitment of women Veterans into MVP. The combination of print and digital outreach tactics and direct email recruitment resulted in over a fivefold increase in women Veteran enrollees during a 7-month period. Attention to messaging and communication channels, combined with a better understanding of effective recruitment methods for certain Veteran populations, allows MVP the opportunity to advance health and health care not only for women Veterans, but beyond. Lessons learned will be applied to increase other populations in MVP such as Blacks, Hispanics, Asians, Native Americans, younger Veterans, and Veterans with certain health conditions.

Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans.

Background The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by reports of a U-shaped relation between cholesterol and death in recent studies. We sought to examine whether the U-shaped relationship is true and to assess the impact of age on this association. Method and Results We conducted a prospective cohort study of 4 467 942 veterans aged >18 years, with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018, in the Veterans Health Administration electronic health record system. We observed a J-shaped relation between total cholesterol (TC) and CHD mortality after a comprehensive adjustment of confounding factors: flat for TC <180 mg/dL, and greater risk was present at higher cholesterol levels. Compared with veterans with TC between 180 and 199 mg/dL, the multiadjusted hazard ratios (HRs) for CHD death were 1.03 (95% CI, 1.02-1.04), 1.07 (95% CI, 1.06-1.09), 1.15 (95% CI, 1.13-1.18), 1.25 (95% CI, 1.22-1.28), and 1.45 (95% CI, 1.42-1.49) times greater among veterans with TC (mg/dL) of 200 to 219, 220 to 239, 140 to 259, 260 to 279 and ≥280, respectively. Similar J-shaped TC-CHD mortality patterns were observed among veterans with and without statin use at or before baseline. Conclusions The cholesterol paradox, for example, higher CHD death in patients with a low cholesterol level, was a reflection of reverse causality, especially among older participants. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication.

Plant-based diets and the incidence of cardiovascular disease: the Million Veteran Program.

Background: A healthful plant-based diet was associated with lower risks of coronary heart disease and type 2 diabetes, and a favourable profile of adiposity-associated biomarkers, while an unhealthful plant-based diet was associated with elevated risk of cardiometabolic disease in health professional populations. However, little is known about the associations between plant-based dietary patterns and risk of cardiovascular disease (CVD) in US veterans. Methods: The study population consisted of 148 506 participants who were free of diabetes, CVD and cancer at baseline in the Veterans Affairs (VA) Million Veteran Program. Diet was assessed using a Food Frequency Questionnaire at baseline. We calculated an overall Plant-Based Diet Index (PDI), a healthful PDI (hPDI) and an unhealthful PDI (uPDI). The CVD endpoints included non-fatal myocardial infarction (MI) and acute ischaemic stroke (AIS) identified through high-throughput phenotyping algorithms approach and fatal CVD events identified by searching the National Death Index. Results: With up to 8 years of follow-up, we documented 5025 CVD cases. After adjustment for confounding factors, a higher PDI was significantly associated with a lower risk of CVD (HR comparing extreme quintiles=0.75, 95% CI 0.68 to 0.82, P trend<0.0001). We observed an inverse association between hPDI and the risk of CVD (HR comparing extreme quintiles=0.71, 95% CI 0.64 to 0.78, P trend<0.001), whereas uPDI was positively associated with the risk of CVD (HR comparing extreme quintiles=1.12, 95% CI 1.02 to 1.24, P trend<0.001). We found similar associations of hPDI with subtypes of CVD; a 10-unit increment in hPDI was associated with HRs (95% CI) of 0.81 (0.75 to 0.87) for fatal CVD, 0.86 (0.79 to 0.94) for non-fatal MI and 0.86 (0.78 to 0.95) for non-fatal AIS. Conclusions: Plant-based dietary pattern enriched with healthier plant foods was associated with a substantially lower CVD risk in US veterans.

Minimally invasive esophagectomy with and without gastric ischemic conditioning.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Dietary Sodium and Potassium Intake and Risk of Non-Fatal Cardiovascular Diseases: The Million Veteran Program.

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.

Million Veteran Program's response to COVID-19: Survey development and preliminary findings.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Genome-wide and phenome-wide analysis of ideal cardiovascular health in the VA Million Veteran Program.

BACKGROUND: Genetic studies may help identify causal pathways; therefore, we sought to identify genetic determinants of ideal CVH and their association with CVD outcomes in the multi-population Veteran Administration Million Veteran Program. METHODS: An ideal health score (IHS) was calculated from 3 clinical factors (blood pressure, total cholesterol, and blood glucose levels) and 3 behavioral factors (smoking status, physical activity, and BMI), ascertained at baseline. Multi-population genome-wide association study (GWAS) was performed on IHS and binary ideal health using linear and logistic regression, respectively. Using the genome-wide significant SNPs from the IHS GWAS, we created a weighted IHS polygenic risk score (PRSIHS) which was used (i) to conduct a phenome-wide association study (PheWAS) of associations between PRSIHS and ICD-9 phenotypes and (ii) to further test for associations with mortality and selected CVD outcomes using logistic and Cox regression and, as an instrumental variable, in Mendelian Randomization. RESULTS: The discovery and replication cohorts consisted of 142,404 (119,129 European American (EUR); 16,495 African American (AFR)), and 45,766 (37,646 EUR; 5,366 AFR) participants, respectively. The mean age was 65.8 years (SD = 11.2) and 92.7% were male. Overall, 4.2% exhibited ideal CVH based on the clinical and behavioral factors. In the multi-population meta-analysis, variants at 17 loci were associated with IHS and each had known GWAS associations with multiple components of the IHS. PheWAS analysis in 456,026 participants showed that increased PRSIHS was associated with a lower odds ratio for many CVD outcomes and risk factors. Both IHS and PRSIHS measures of ideal CVH were associated with significantly less CVD outcomes and CVD mortality. CONCLUSION: A set of high interest genetic variants contribute to the presence of ideal CVH in a multi-ethnic cohort of US Veterans. Genetically influenced ideal CVH is associated with lower odds of CVD outcomes and mortality.

Genomics and phenomics of body mass index reveals a complex disease network.

Elevated body mass index (BMI) is heritable and associated with many health conditions that impact morbidity and mortality. The study of the genetic association of BMI across a broad range of common disease conditions offers the opportunity to extend current knowledge regarding the breadth and depth of adiposity-related diseases. We identify 906 (364 novel) and 41 (6 novel) genome-wide significant loci for BMI among participants of European (N~1.1 million) and African (N~100,000) ancestry, respectively. Using a BMI genetic risk score including 2446 variants, 316 diagnoses are associated in the Million Veteran Program, with 96.5% showing increased risk. A co-morbidity network analysis reveals seven disease communities containing multiple interconnected diseases associated with BMI as well as extensive connections across communities. Mendelian randomization analysis confirms numerous phenotypes across a breadth of organ systems, including conditions of the circulatory (heart failure, ischemic heart disease, atrial fibrillation), genitourinary (chronic renal failure), respiratory (respiratory failure, asthma), musculoskeletal and dermatologic systems that are deeply interconnected within and across the disease communities. This work shows that the complex genetic architecture of BMI associates with a broad range of major health conditions, supporting the need for comprehensive approaches to prevent and treat obesity.

Association of Nut Consumption with Risk of Stroke and Cardiovascular Disease: The Million Veteran Program.

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.