Veteran Program Research Articles

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.

Development and utility of a clinical research informatics application for participant recruitment and workflow management for a return of results pilot trial in familial hypercholesterolemia in the Million Veteran Program.

The development of clinical research informatics tools and workflow processes associated with re-engaging biobank participants has become necessary as genomic repositories increasingly consider the return of actionable research results. Here we describe the development and utility of an informatics application for participant recruitment and enrollment management for the Veterans Affairs Million Veteran Program Return Of Actionable Results Study, a randomized controlled pilot trial returning individual genetic results associated with familial hypercholesterolemia. The application is developed in Python-Flask and was placed into production in November 2021. The application includes modules for chart review, medication reconciliation, participant contact and biospecimen logging, survey recording, randomization, and documentation of genetic counseling and result disclosure. Three primary users, a genetic counselor and two research coordinators, and 326 Veteran participants have been integrated into the system as of February 23, 2023. The application has successfully handled 3367 task requests involving greater than 95000 structured data points. Specifically, application users have recorded 326 chart reviews, 867 recruitment telephone calls, 158 telephone-based surveys, and 61 return of results genetic counseling sessions, among other available study tasks. The development of usable, customizable, and secure informatics tools will become increasingly important as large genomic repositories begin to return research results at scale. Our work provides a proof-of-concept for developing and using such tools to aid in managing the return of results process within a national biobank.

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

BackgroundRed 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. ObjectivesTo prospectively examine the associations between red meat intake and incident CVD in an ongoing cohort study with diverse socioeconomic and racial or ethnic backgrounds. MethodsOur 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. ResultsComparing 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. ConclusionsRed 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.

ASSOCIATION BETWEEN MULTIPLE FRAILTY INDICES AND CVD MORTALITY

Abstract Introduction Frailty, a syndrome of physiologic vulnerability, increases cardiovascular disease (CVD) risk. Which frailty tool is ideal for risk stratification remains unclear. We calculated three frailty scores from the Million Veteran Program (MVP) and examined their association with mortality and CVD in older Veterans. Methods Participants were from MVP - a large, contemporary Veteran cohort study - and aged ≥50 years at baseline (2011-2018). The frailty scores used were: MVP-FI (36-item questionnaire deficit accumulation frailty index), VA-FI (31-item EHR index), and modified Study of Osteoporotic Fractures (mSOF; a physical frailty score). MVP-FI and VA-FI scores of ≤0.10 were robust, 0.11-0.20 pre-frail, and ≥0.21 frail; mSOF scores of 0 were robust, 1 pre-frail and ≥2 frail. Primary outcomes were all-cause and CVD mortality. Secondary outcomes were incident stroke, myocardial infarction (MI), and heart failure (HF). Cox regression was used to evaluate the association of frailty with outcomes. Results Among 190,688 participants, mean age was 69 ±9, 94% were male. By MVP-FI, 29% were robust, 42% pre-frail, and 29% frail. Hazard ratios (HR, 95% CI) for all-cause mortality were 1.66 (1.61-1.72) and 3.05 (2.95-3.16) for pre-frailty and frailty, respectively. For CVD mortality, HRs were 1.76 (1.65-1.88) and 3.65 (3.43-3.90) for pre-frailty and frailty. Hazards of stroke, MI, and HF also increased with greater frailty. VA-FI and mSOF yielded concordant results. Conclusion Irrespective of measure, frailty is associated with increased all-cause mortality and CVD event risk. Clinicians and researchers may consider the most convenient tool for available data to incorporate frailty into practice.

WHOLE HEALTH(Y) AGING WITH GEROFIT: THE DEVELOPMENT OF A PILOT WELLNESS PROGRAM FOR OLDER VETERANS

Abstract The Veterans Health Administration (VHA) services over 9 million Veterans; approximately half are older than 65 years of age. Veterans are at a higher risk of comorbidities, including obesity and related chronic diseases, which contributes to higher health care costs, mobility disability, poor quality of life and even death. Gerofit is a VA Best Practice and Whole Health clinical exercise program for Veterans &amp;gt;65yrs that has positively impacted physical functioning, mental health symptoms, medication burden and 10-year mortality. This project describes the development of a comprehensive wellness and health promotion program incorporated into Gerofit, called Whole Healthy Aging Gerofit (WHAG). This novel program implemented wellness components to supplement the Gerofit in-person or virtual exercise options, including health education seminars, mindfulness classes, yoga classes, nutrition education classes, produce pick up service, and the Companion Dog Fostering program. WHAG deliverables included class attendance, individual Personal Health Inventories, observed physical function, self-reported physical activity levels, diet quality, perceived mental health, and Veteran satisfaction. The average Gerofit participant is approximately 73 years old, with obesity and multiple comorbid conditions (n=16), takes 10 medications, and is functionally impaired as assessed by gait speed (1.04 m/s). Programs that target healthy aging are needed to ensure the health of the population as it ages. This pilot program, WHAG, is one example of a comprehensive, patient centered wellness program that supports participants in setting their own goals and definitions of wellness to promote healthy aging.

Tribal Perspectives on Patient Navigation for Rural Native Veterans Using Veteran Health Administration Services.

American Indian and Alaska Native (Native) Veterans enrolled in theU.S. Department of Veterans Affairs(VA) benefits program are far less likely to access health care compared to other racial/ethnic groups, in part driven by challenges posed by often distant, complex, and culturally unresponsive health care that does not easily interface with the Indian Health Service (IHS) and local Tribal Health Care. To address this disparity, in 2020 the Veteran's Health Administration's (VHA) Office of Rural Health (ORH) initiated the development of a patient navigation program designed specifically for rural Native Veterans. There are no navigation programs for rural Native Veterans to guide development of such a program. Hence, the project team sought perspectives from rural Native Veterans, their families, and community advocates, (n = 34), via video and phone interviews about the role and functions of a Veteran patient navigator and personal characteristics best be suited for such a position. Participants believed a navigator program would be useful in assisting rural Native Veterans to access VHA care. They emphasized the importance of empathy, support, knowledge of local culture, and of Veteran experience within tribal communities, adeptness with VHA systems, and personnel consistency. These insights are critical to create a program capable of increasing rural Native Veteran access to VHA services.

Moderate alcohol consumption on the risk of stroke in the Million Veteran Program

BackgroundThere is inconsistent evidence on the association of moderate alcohol consumption and stroke risk in the general population and is not well studied among U.S. Veterans. Furthermore, it is unclear whether primarily drinking beer, wine, or liquor is associated with a difference in stroke risk.MethodsThe study included 185,323 Million Veteran Program participants who self-reported alcohol consumption on the Lifestyle Survey. Moderate consumption was defined as 1–2 drinks/day and beverage preference of beer, wine or liquor was defined if ≥ 50% of total drinks consumed were from a single type of beverage. Strokes were defined using ICD-9 and ICD-10 codes from the participants’ electronic health record.ResultsThe mean (sd) age of the sample was 64 (13) years and 11% were women. We observed 4,339 (94% ischemic; 6% hemorrhagic) strokes over a median follow-up of 5.2 years. In Cox models adjusted for age, sex, race, education, income, body mass index, smoking, exercise, diet, cholesterol, prevalent diabetes, prevalent hypertension, lipid-lowering medication, antihypertensive medication, and diabetes medication, moderate alcohol consumption (1–2 drinks/day) was associated with a 22% lower risk of total stroke compared with never drinking [Hazards ratio (HR) 95% confidence interval (CI): 0.78 (0.67, 0.92)]. When stratifying by stroke type, we observed a similar protective association with moderate consumption and ischemic stroke [HR (95% CI): 0.76 (0.65, 0.90)], but a non-statistically significant higher risk of hemorrhagic stroke [HR (95% CI): 1.29 (0.64, 2.61)]. We did not observe a difference in ischemic or hemorrhagic stroke risk among those who preferred beer, liquor or wine vs. no beverage preference. When stratifying by prior number of hospital visits (≤ 15, 16–33, 34–64, ≥ 65) as a proxy for health status, we observed attenuation of the protective association with greater number of visits [HR (95% CI): 0.87 (0.63, 1.19) for ≥ 65 visits vs. 0.80 (0.59, 1.08) for ≤ 15 visits].ConclusionsWe observed a lower risk of ischemic stroke, but not hemorrhagic stroke with moderate alcohol consumption and did not observe substantial differences in risk by beverage preference among a sample of U.S. Veterans. Healthy user bias of moderate alcohol consumption may be driving some of the observed protective association.

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

BackgroundLifestyle medicine has been proposed as a way to address the root causes of chronic disease and their associated health care costs. ObjectiveThis study aimed to estimate mortality risk and longevity associated with individual lifestyle factors and comprehensive lifestyle therapy. MethodsAge- 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. ResultsOn 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. ConclusionsA combination of 8 lifestyle factors is associated with a significantly lower risk of premature mortality and an estimated prolonged life expectancy.

VA Home Telehealth Program for Initiating and Optimizing Heart Failure Guideline-Directed Medical Therapy.

Heart failure (HF) is a chronic, progressive medical condition. Evidence suggests that guideline-directed medical therapy improves both morbidity and mortality in patients with HF with reduced ejection fraction when properly optimized. Unfortunately, many patients do not receive optimized therapy, highlighting the need to optimize clinicians' methods to more effectively and efficiently initiate and titrate medical therapy. This single-center, retrospective study evaluated the rates of drug interventions prompted by the home telehealth monitoring program for veterans with HF with reduced ejection fraction. Rates of drug interventions were evaluated among those who enrolled and those who did not enroll in the program. There were 20 drug-related interventions in the home telehealth group compared with 11 interventions for the control group. One HF-related hospitalization occurred in the home telehealth program group compared with 6 in the control group. This study demonstrates the potential of home telehealth to optimize veterans' medication regimens and to reduce HF-related hospitalizations. It also provides an additional catalyst to further develop home telehealth services specifically targeted at drug therapy initiation and optimization in patients with HF with reduced ejection fraction.

Genome-Wide Association Study of Chronic Dizziness in the Elderly Identifies Loci Implicating MLLT10, BPTF, LINC01224, and ROS1.

Chronic age-related imbalance is a common cause of falls and subsequent death in the elderly and can arise from dysfunction of the vestibular system, an elegant neuroanatomical group of pathways that mediates human perception of acceleration, gravity, and angular head motion. Studies indicate that 27-46% of the risk of age-related chronic imbalance is genetic; nevertheless, the underlying genes remain unknown. The cohort consisted of 50,339 cases and 366,900 controls in the Million Veteran Program. The phenotype comprised cases with two ICD diagnoses of vertigo or dizziness at least 6months apart, excluding acute or recurrent vertiginous syndromes and other non-vestibular disorders. Genome-wide association studies were performed as individual logistic regressions on European, African American, and Hispanic ancestries followed by trans-ancestry meta-analysis. Downstream analysis included case-case-GWAS, fine mapping, probabilistic colocalization of significant variants and genes with eQTLs, and functional analysis of significant hits. Two significant loci were identified in Europeans, another in the Hispanic population, and two additional in trans-ancestry meta-analysis, including three novel loci. Fine mapping revealed credible sets of intronic single nucleotide polymorphisms (SNPs) in MLLT10- a histone methyl transferase cofactor, BPTF- a subunit of a nucleosome remodeling complex implicated in neurodevelopment, and LINC01224- a proto-oncogene receptor tyrosine kinase. Despite the difficulties of phenotyping the nature of chronic imbalance, we replicated two loci from previous vertigo GWAS studies and identified three novel loci. Findings suggest candidates for further study and ultimate treatment of this common elderly disorder.

Applying RE-AIM to examine the impact of an implementation facilitation package to scale up a program for Veterans with chronic obstructive pulmonary disease

BackgroundUS Veterans are four times more likely to be diagnosed with chronic obstructive pulmonary disease (COPD) compared to the civilian population with no care model that consistently improves Veteran outcomes when scaled. COPD Coordinated Access to Reduce Exacerbations (CARE) is a care bundle intended to improve the delivery of evidence-based practices to Veterans. To address challenges to scaling this program in the Veterans’ Health Administration (VA), the COPD CARE Academy (Academy), an implementation facilitation package comprised of five implementation strategies was designed and implemented.MethodsThis evaluation utilized a mixed-methods approach to assess the impact of the Academy’s implementation strategies on the RE-AIM framework implementation outcomes and the extent to which they were effective at increasing clinicians’ perceived capability to implement COPD CARE. A survey was administered one week after Academy participation and a semi-structured interview conducted 8 to 12 months later. Descriptive statistics were calculated for quantitative items and thematic analysis was used to analyze open-ended items.ResultsThirty-six clinicians from 13 VA medical centers (VAMCs) participated in the Academy in 2020 and 2021 and 264 front-line clinicians completed COPD CARE training. Adoption of the Academy was indicated by high rates of Academy session attendance (90%) and high utilization of Academy resources. Clinicians reported the Academy to be acceptable and appropriate as an implementation package and clinicians from 92% of VAMCs reported long-term utilization of Academy resources. Effectiveness of the Academy was represented by clinicians’ significant increases (p < 0.05) in their capability to complete ten implementation tasks after Academy participation.ConclusionsThis evaluation found that the use of implementation facilitation paired with additional strategies enhanced the capacity of clinicians to implement COPD CARE. Future assessments are needed to explore post-academy resources that would help VAMCs to strategize localized approaches to overcome barriers.

Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking.

Brainwide Mendelian Randomization Study of Anxiety Disorders and Symptoms

BackgroundTo gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from the UK Biobank (n = 380,379), the FinnGen Program (n = 290,361), and the Million Veteran Program (n = 175,163) together with UK Biobank genome-wide data (n = 33,224) related to 3935 brain imaging–derived phenotypes (IDPs). MethodsA genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX–brain associations, a 2-sample Mendelian randomization was performed considering multiple methods and sensitivity analyses. A subsequent multivariable Mendelian randomization was conducted to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms. ResultsAfter false discovery rate correction (q < .05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UK Biobank, FinnGen, and Million Veteran Program). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent multivariable Mendelian randomization analysis, reduced area of the right posterior middle cingulate gyrus (β = −0.09, p = 8.01 × 10−4) and reduced gray matter volume of the right anterior superior temporal gyrus (β = −0.09, p = 1.55 × 10−3) had direct effects on ANX. In the ANX symptom-level analysis, the right posterior middle cingulate gyrus was negatively associated with "tense, sore, or aching muscles during the worst period of anxiety" (β = −0.13, p = 8.26 × 10−6). ConclusionsThis study identified genetically inferred effects that are generalizable across large cohorts, thereby contributing to our understanding of how changes in brain structure and function can lead to ANX.

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk

Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones. To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones. This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics. Genetic proxies of thiazide diuretics were derived from the International Consortium for Blood Pressure. Kidney stone cases and controls were derived from the Million Veteran Program, UK Biobank, and the FinnGen study. These cross-sectional designs do not report a duration of follow-up. Data analysis was performed in May 2023. Genetic proxies of thiazide diuretics were genetic variants in the thiazide-sensitive sodium chloride cotransporter gene associated with systolic blood pressure. Genetic proxies of β-blockers and systolic blood pressure served as negative controls. The main outcome was the odds of kidney stones. The secondary outcomes were serum laboratory values relevant to the treatment of kidney stones. The main analysis included up to 1 079 657 individuals, including 50 832 kidney stone cases and 1 028 825 controls. In a meta-analysis of all cohorts, genetic proxies of thiazide diuretics were associated with a lower odds of kidney stones (OR, 0.85; 95% CI, 0.81-0.89; P < .001). Genetic proxies of β-blockers (OR, 1.02; 95% CI, 0.96-1.07; P = .52) and systolic blood pressure (OR, 1.00; 95% CI, 1.00-1.01; P = .49) were not associated with kidney stones. Genetic proxies of thiazide diuretics were associated with higher serum calcium (β [SE], 0.051 [0.0092]; P < .001) and total cholesterol (β [SE], 0.065 [0.015]; P < .001), but lower serum potassium (β [SE], -0.073 [0.022]; P < .001). In this genetic association study, genetic proxies of thiazide diuretics were associated with reduced kidney stone risk. This finding reflects a drug effect over the course of a lifetime, unconstrained by the limited follow-up period of clinical trials.

Sustainment of the TeleSleep program for rural veterans.

In fiscal year 2021, the Veterans Health Administration (VHA) provided care for sleep disorders to 599,966 Veterans, including 189,932 rural Veterans. To further improve rural access, the VA Office of Rural Health developed the TeleSleep Enterprise-Wide Initiative (EWI). TeleSleep's telemedicine strategies include tests for sleep apnea at the Veteran's home rather than in a sleep lab; Clinical Video Telehealth applications; and other forms of virtual care. In 2017 and 2020, VHA provided 3-year start-up funding to launch new TeleSleep programs at rural-serving VA medical facilities. In early 2022, we surveyed leaders of 24 sites that received TeleSleep funding to identify successes, failures, facilitators, and barriers relevant to sustaining TeleSleep implementations upon expiration of startup funding. We tabulated frequencies on the multiple choice questions in the survey, and, using the survey's critical incident framework, summarized the responses to open-ended questions. TeleSleep program leaders discussed the responses and synthesized recommendations for improvement. 18 sites reported sustainment, while six were "on track." Sustainment involved medical centers or regional entities incorporating TeleSleep into their budgets. Facilitators included: demonstrating value; aligning with local priorities; and collaborating with spoke sites serving rural Veterans. Barriers included: misalignment with local priorities; and hiring delays. COVID was a facilitator, as it stimulated adoption of telehealth practices; and also a barrier, as it consumed attention and resources. Recommendations included: longer startup funding; dedicated funding for human resources to accelerate hiring; funders communicating with local facility leaders regarding how TeleSleep aligns with organizational priorities; hiring into job classifications aligned with market pay; and obtaining, from finance departments, projections and outcomes for the return on investment in TeleSleep.

Seventeen-Year National Pain Prevalence Trends Among U.S. Military Veterans

U.S. military veterans experience higher pain prevalence than nonveterans. However, it is unclear how the disparities in pain prevalence have changed over time because previous trend studies are limited to veterans using the Veterans Health Administration. This repeated cross-sectional study aimed to characterize pain prevalence trends in the overall population of U.S. veterans compared to nonveterans, using nationally representative data. We analyzed 17 years of data from the National Health Interview Survey (2002–2018), with a mean annual unweighted sample of 29,802 U.S. adults (total unweighted n = 506,639) and mean annual weighted population of 229.7 million noninstitutionalized adults. The weighted proportion of veterans ranged from 11.48% in 2002 (highest) to 8.41% in 2017 (lowest). We found that veterans experience a similar or higher prevalence of pain than nonveterans across the study period, except for severe headaches or migraine and facial pain. Pain prevalence among veterans increased over time, with a higher rate of increase compared to nonveterans for all pain variables. From 2002 to 2018, there was an absolute increase (95% confidence interval) in pain prevalence among veterans (severe headache or migraine: 2.0% [1.6–2.4%]; facial pain: 1.9% [1.4–2.4%]; neck pain: 4.7% [4.1–5.2%]; joint pain: 11.4% [10.8–11.9%]; low back pain: 10.3% [9.5–11.1%]; any pain: 10.0% [9.6–10.4%]; and multiple pains: 9.9% [9.2–10.6%]). The continued pain prevalence increase among veterans may have implications for health care utilization, highlighting the need for improved pain prevention and care programs for this population with a disproportionate pain burden. PerspectiveThis article uses routinely-collected cross-sectional data that are nationally representative of U.S. adults to present changes in pain prevalence among military veterans compared to nonveterans. The findings underscore the need for improved prevention and pain care programs for veterans, who experienced a widening disproportionate pain burden from 2002 to 2018.

Association between systemic lupus erythematosus and myasthenia gravis: A population-based National Study

BackgroundSystemic lupus erythematosus (SLE) and myasthenia gravis (MG) are autoimmune diseases. Previous case reports and case series suggest an association may exist between these diseases, as well as an increased risk of SLE after thymectomy for MG. We undertook this study to determine whether SLE and MG were associated in large cohorts. MethodsWe searched the IBM Watson Health Explorys platform and the Department of Veterans Affairs Million Veteran Program (MVP) database for diagnoses of SLE and MG. In addition, we examined subjects enrolled in the Lupus Family Registry and Repository (LFRR) as well as controls for a diagnosis of MG. ResultsAmong 59,780,210 individuals captured in Explorys, there were 25,750 with MG and 65,370 with SLE. 370 subjects had both. Those with MG were >10 times more likely to have SLE than those without MG. Those with both diseases were more likely to be women, African American, and at a younger age than MG subjects without SLE. In addition, the MG patients who underwent thymectomy had an increased risk of SLE compared to MG patients who had not undergone thymectomy (OR 3.11, 95% CI: 2.12 to 4.55). Autoimmune diseases such as pernicious anemia and miscellaneous comorbidities such as chronic kidney disease were significantly more common in MG patients who developed SLE. In the MVP, SLE and MG were also significantly associated. Association of SLE and MG in a large SLE cohort with rigorous SLE classification confirmed the association of SLE with MG at a similar level. ConclusionWhile the number of patients with both MG and SLE is small, SLE and MG are strongly associated together in very large databases and a large SLE cohort.

Correlates of Risk for Disinhibited Behaviors in the Million Veteran Program Cohort

Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs). To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP). A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the African, European, and Hispanic or Latin American ancestries. Next, a conditional PheWAS, covarying for PGSs of comorbid psychiatric problems (depression, schizophrenia, and suicide attempt; European ancestries only), was performed. Lastly, to adjust for unmeasured confounders, a within-family analysis of significant associations from the main PheWAS was performed in full siblings (European ancestries only). This study included the electronic health record data from US veterans from VA health care centers enrolled in MVP. Analyses took place from February 2022 to August 2023 covering a period from October 1999 to January 2020. PGSs for EXT, depression, schizophrenia, and suicide attempt. Phecodes for diagnoses derived from the International Statistical Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification, codes from electronic health records. Within the MVP (560 824 patients; mean [SD] age, 67.9 [14.3] years; 512 593 male [91.4%]), the EXT PGS was associated with 619 outcomes, of which 188 were independent of risk for comorbid problems or PGSs (from odds ratio [OR], 1.02; 95% CI, 1.01-1.03 for overweight/obesity to OR, 1.44; 95% CI, 1.42-1.47 for viral hepatitis C). Of the significant outcomes, 73 (11.9%) were significant in the African results and 26 (4.5%) were significant in the Hispanic or Latin American results. Within-family analyses uncovered robust associations between EXT PGS and consequences of SUDs, including liver disease, chronic airway obstruction, and viral hepatitis C. Results of this cohort study suggest a shared polygenic basis of EXT disorders, independent of risk for other psychiatric problems. In addition, this study found associations between EXT PGS and diagnoses related to SUDs and their sequelae. Overall, this study highlighted the potential negative consequences of EXT disorders for health and functioning in the US veteran population.

Abstract 18062: Association of Leisure Time Physical Activity With Incidence of Heart Failure With Preserved and Reduced Ejection Fraction in the Million Veteran Program

Introduction: Heart failure (HF) continues to be the leading cause of hospitalization in older men in the United States. While previous studies have reported beneficial effects of leisure time physical activity (LTPA) on cardiovascular disease, it is unclear whether LTPA is associated with incidence of HF with reduced or preserved ejection fraction (EF). The current study examined the association of LTPA with incidence of HF in US Veterans in the Million Veteran program. Methods: The MVP is a nationally representative, prospective cohort study of Veterans which started in 2011 and has currently enrolled over 900,000 participants. Self-reported vigorous, moderate, and light activity was collected at baseline and converted into hours of metabolic equivalent of task per week (MET-h/week). HF was ascertained using ICD-9 code of 428.x or ICD-10 code of I50.x. We defined incident HFpEF using ejection fraction ≥ 50% and HFrEF using ejection fraction ≤ 40%. Cox proportional hazard model was used to compute multivariable adjusted hazard ratio (HR) and 95% confidence intervals (95%). Results: Among 461,267 Veterans analyzed, the mean age was 63.9 years (SD 12.7) and 95% were men. Participants were followed for 5 years, with 25,192 new cases of HF (12,226 HFrEF and 10,422 HFpEF) occurred. In a multivariable adjusted model, LPTA was inversely associated with incident HF with HR (95% CI) of 1.00 (ref), 0.82 (0.79-0.86); 0.67 (0.63-0.71); 0.65 (0.62-0.69); and 0.50 (0.48-0.53), from the lowest to the highest quintile of LTPA, respectively, p for linear trend &lt;0.00001. Similar inverse associations were observed for HFpEF as well as HFrEF (p&lt;0.0001 each). Conclusion: Our data are consistent with inverse association of LTPA with incidence of HF including HFpEF and HFrEF.

Abstract 14410: Hemoglobin A1c and Major Adverse Cardiovascular Events in the VA Million Veteran Program: Evidence-Based Recommendation for Life’s Essential Eight Improvement

Background: The American Heart Association (AHA) recently proposed the Life’s Essential 8 (LE8) score as an enhanced measurement tool for cardiovascular health. For the blood glucose metric in LE8, persons with diabetes mellitus (DM) and a hemoglobin A1c (HbA1c) &lt;7% receive higher points (40 out of 100) and successively fewer with increasing HbA1c. However, some studies have found that having a HbA1c &lt;6% in DM patients was associated with a higher risk of mortality, especially cardiovascular (CVD) death. Aim: We sought to categorize DM with HbA1c &lt;7% into two groups (&lt;6% vs . 6-6.9%) and compare their associations with risk for a major adverse cardiovascular event (MACE) to better inform DM HbA1c cut points and LE8 scoring. Methods: Prospective cohort study of 213,760 Veterans enrolled in the VA Million Veteran Program (MVP) (2011-2021) who had a HbA1c measurement and were free of 5 point-MACE (fatal CVD, non-fatal myocardial infarction [MI], non-fatal stroke, non-fatal heart failure and non-fatal atrial fibrillation [Afib]) at baseline. Results: During a mean follow-up of 4.9 years, we identified 38,151 instances of MACE, including 9,665 MI, 2,837 stroke, 5,523 fatal CVD, 16,543 heart failure, and 18,114 Afib. Compared to diabetic patients with HbA1c of 6-6.9%, diabetic patients with a very low HbA1c level (&lt;6%) had significantly higher risk of MACE [Hazard Ratio (HR): 1.15; 95%CI: 1.09-1.21], which was comparable to diabetic patients with HbA1c of 7-7.9% [HR: 1.14 (95%CI: 1.09-1.18)]. Similar results were observed for the associations between HbA1c and risk for stroke, heart failure, Afib and fatal CVD (Figure 1). Conclusions: Our results confirm previous findings that a very low HbA1c level among diabetic patients was associated with a higher risk for MACE. Based on our findings, we suggest further categorization of diabetic patients with HbA1c below 7% (i.e., &lt;6% and 6-6.9%) and subsequent adjustment in LE8 scoring (i.e., from 40 to 30 points) for HbA1c.