Polygenic Risk Score Assessment for Coronary Artery Disease in Asian Indians.

We evaluated the performance of various polygenic risk score (PRS) models derived from European (EU), South Asian (SA), and Punjabi Asian Indians (AI) studies on 13,974 subjects from AI ancestry. While all models successfully predicted Coronary artery disease (CAD) risk, the AI, SA, and EU + AI were superior predictors and more transportable than the EU model; the predictive performance in training and test sets was 18% and 22% higher in AI and EU + AI models, respectively than in EU. Comparing individuals with extreme PRS quartiles, the AI and EU + AI captured individuals with high CAD risk showed 2.6 to 4.6 times higher efficiency than the EU. Interestingly, including the clinical risk score did not significantly change the performance of any genetic model. The enrichment of diversity variants in EU PRS improves risk prediction and transportability. Establishing population-specific normative and risk factors and inclusion into genetic models would refine the risk stratification and improve the clinical utility of CAD PRS.

Replication study identified EFEMP1 association with varicose vein predisposition among Indians.

BACKGROUND: Varicose vein is a chronic condition that affects the lower extremities of the human body. Several factors have been implicated in the development of this disease, viz age, gender, weight, height and prolonged standing. Recently, genome-wide studies have identified genetic biomarkers that are associated with varicose veins in different ethnic groups. Such genetic studies are lacking in South Asians specifically in Indians where the prevalence of varicose veins is high, and it is important to replicate these variants in the stated population. The study aimed to replicate the association of genetic variants associated with varicose veins in this target population, which were found to be associated with the other ethnic groups. METHODOLOGY: The studied cohort is of the Indian population comprising unrelated 104 varicose veins cases and 448 non-varicose vein controls. The samples were genotyped using the Illumina Global Screening Array. Using the genomic data from UK BioBank and 23andMe studied cohorts; eight genetic variants were selected to replicate in our dataset. The allelic association was performed to identify the effective allele and risk was estimated using odds ratio and p-value as level of significance. Multifactor Dimensionality Reduction was used to estimate the cumulative effect of variants in Indians. RESULT: Variant rs3791679 of EFEMP1 was found to be associated with varicose veins in Indians. After observing the association of the EFEMP1 with varicose veins, we further ensued to identify all genetic variants within EFEMP1 to uncover the additional variants associated with this trait. Interestingly, we identified six new variants of EFEMP1 gene that have shown association. Moreover, the cumulative effect of all associated variations was estimated and the risk was 2.7 times higher in cases than controls whereas independently their effect ranges from 0.37-1.58. CONCLUSION: This study identifies EFEMP1 as a potential gene related to the risk of varicose veins in Indians. It also highlights that evaluating the maximum number of variants of a gene rather than focusing solely on replicating single variations offers a more comprehensive and nuanced understanding of the genetic factors contributing to a complex trait like varicose veins.

Association between ApoE ε4 genotype and attentional function in non-demented, middle-aged, and older adults from rural India.

Objectives: Several genetic factors have been associated with cognitive decline in aging. Apolipoprotein E (ApoE) ε4 has been widely studied in the risk for pathological cognitive decline, including dementia. However, the association between ApoE ε4 and cognitive functioning in the healthy aging Indian population has been understudied, and the results are ambiguous. Materials and Methods: This study aims to examine the role of the ApoE genotype with attentional function in aging adults (≥45 years) in a rural Indian population. Cross-sectional (baseline) data (n = 2100) was utilized from an ongoing longitudinal cohort study on aging (Srinivaspura Aging, Neurosenescence, and Cognition study). Participants hailed from villages of Srinivaspura in Karnataka, southern India. Participants were categorized based on ApoE-ε4 status into three categories: No ε4, heterozygous ε4, and homozygous ε4. Attentional function was assessed using the auditory and visual attention subtests from a computerized neurocognitive test battery. Linear regression was performed adjusting for age, gender, and education. Results: In model 1 (unadjusted), we did not find an association between ApoE and attention function. In the partially adjusted model 2 (adjusting for age), ApoE ε4 with age was significantly associated with the attention function. Further, with increasing age, there was a decline in attention among homozygous ε4 individuals. Model 3 (model 2 + gender) found that ApoE ε4, age, and gender explained a significant variance in attention function. In addition, with increasing age, males had poor attention in the homozygous as compared to heterozygous group. Model 4 (model 3+ education) explained a significant variance in attention and also revealed that with increasing age, attention declined in the illiterate and low literacy groups in both homozygous and heterozygous groups among both genders. Conclusion: Although ApoE ε4 alone was not associated, it interacted with age, gender, and education to affect attention function in this rural Indian population. Longitudinal cognitive monitoring will yield insights into understanding whether the ApoE ε4 genotype influences the rate of cognitive decline in this rural, aging population.

Landscape of pharmacogenetic variants associated with non-insulin antidiabetic drugs in the Indian population.

INTRODUCTION: Genetic variants contribute to differential responses to non-insulin antidiabetic drugs (NIADs), and consequently to variable plasma glucose control. Optimal control of plasma glucose is paramount to minimizing type 2 diabetes-related long-term complications. India's distinct genetic architecture and its exploding burden of type 2 diabetes warrants a population-specific survey of NIAD-associated pharmacogenetic (PGx) variants. The recent availability of large-scale whole genomes from the Indian population provides a unique opportunity to generate a population-specific map of NIAD-associated PGx variants. RESEARCH DESIGN AND METHODS: We mined 1029 Indian whole genomes for PGx variants, drug-drug interaction (DDI) and drug-drug-gene interactions (DDGI) associated with 44 NIADs. Population-wise allele frequencies were estimated and compared using Fisher's exact test. RESULTS: Overall, we found 76 known and 52 predicted deleterious common PGx variants associated with response to type 2 diabetes therapy among Indians. We report remarkable interethnic differences in the relative cumulative counts of decreased and increased response-associated alleles across NIAD classes. Indians and South Asians showed a significant excess of decreased metformin response-associated alleles compared with other global populations. Network analysis of shared PGx genes predicts high DDI risk during coadministration of NIADs with other metabolic disease drugs. We also predict an increased CYP2C19-mediated DDGI risk for CYP3A4/3A5-metabolized NIADs, saxagliptin, linagliptin and glyburide when coadministered with proton-pump inhibitors (PPIs). CONCLUSIONS: Indians and South Asians have a distinct PGx profile for antidiabetes drugs, marked by an excess of poor treatment response-associated alleles for various NIAD classes. This suggests the possibility of a population-specific reduced drug response in atleast some NIADs. In addition, our findings provide an actionable resource for accelerating future diabetes PGx studies in Indians and South Asians and reconsidering NIAD dosing guidelines to ensure maximum efficacy and safety in the population.

The Báa nnilah Program: Results of a Chronic-Illness Self-Management Cluster Randomized Trial with the Apsáalooke Nation.

Indigenous people in Montana are disproportionately affected by chronic illness (CI), a legacy of settler colonialism. Existing programs addressing CI self-management are not appropriate because they are not consonant with Indigenous cultures in general and the Apsáalooke culture specifically. A research partnership between the Apsáalooke (Crow Nation) non-profit organization Messengers for Health and Montana State University co-developed, implemented, and evaluated a CI self-management program for community members. This article examines qualitative and quantitative program impacts using a pragmatic cluster randomized clinical trial design with intervention and waitlist control arms. The quantitative and qualitative data resulted in different stories on the impact of the Báa nnilah program. Neither of the quantitative hypotheses were supported with one exception. The qualitative data showed substantial positive outcomes across multiple areas. We examine why the data sets led to two very different stories, and provide study strengths and limitations, recommendations, and future directions.

Association of Achievement of the American Heart Association's Life's Essential 8 Goals With Incident Cardiovascular Diseases in the SHFS.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in American Indian people. In 2022, the American Heart Association developed the Life's Essential 8 goals to promote cardiovascular health (CVH) for Americans, composed of diet, physical activity, nicotine exposure, sleep, body mass index, blood lipids, blood pressure, and blood glucose. We examined whether achievement of Life's Essential 8 goals was associated with incident CVD among SHFS (Strong Heart Family Study) participants. METHODS AND RESULTS: A total of 2139 SHFS participants without CVD at baseline were included in analyses. We created a composite CVH score based on achievement of Life's Essential 8 goals, excluding sleep. Scores of 0 to 49 represented low CVH, 50 to 69 represented moderate CVH, and 70 to 100 represented high CVH. Incident CVD was defined as incident myocardial infarction, coronary heart disease, congestive heart failure, or stroke. Cox proportional hazard models were used to examine the relationship of CVH and incident CVD. The incidence rate of CVD at the 20-year follow-up was 7.43 per 1000 person-years. Compared with participants with low CVH, participants with moderate and high CVH had a lower risk of incident CVD; the hazard ratios and 95% CIs for incident CVD for moderate and high CVH were 0.52 (95% CI, 0.40-0.68) and 0.25 (95% CI, 0.14-0.44), respectively, after adjustment for age, sex, education, and study site. CONCLUSIONS: Better CVH was associated with lower CVD risk which highlights the need for comprehensive public health interventions targeting CVH promotion to reduce CVD risk in American Indian communities.

Race and Place Matter: Inequity in Prenatal Care for Reservation-Dwelling American Indian People.

Early initiation and consistent use of prenatal care is linked with improved health outcomes. American Indian birthing people have higher rates of inadequate prenatal care (IPNC), but limited research has examined IPNC among people living on American Indian reservations. The current study uses birth certificate data from the state of Montana (n = 57,006) to examine predictors of IPNC. Data on the community context is integrated to examine the role of community health in mediating the associations between reservation status and IPNC. Results suggest that reservation-dwelling birthers are more likely to have IPNC, an association partially mediated by community health. Odds of IPNC are higher for reservation-dwelling American Indian people compared to reservation-dwelling White birthers, highlighting intersecting inequalities of race and place.

Circulatory levels of lysophosphatidylcholine species in obese adolescents: Findings from cross-sectional and prospective lipidomics analyses.

BACKGROUND AND AIMS: Obesity has reached epidemic proportions, emphasizing the importance of reliable biomarkers for detecting early metabolic alterations and enabling early preventative interventions. However, our understanding of the molecular mechanisms and specific lipid species associated with childhood obesity remains limited. Therefore, the aim of this study was to investigate plasma lipidomic signatures as potential biomarkers for adolescent obesity. METHODS AND RESULTS: A total of 103 individuals comprising overweight/obese (n = 46) and normal weight (n = 57) were randomly chosen from the baseline ORANGE (Obesity Reduction and Noncommunicable Disease Awareness through Group Education) cohort, having been followed up for a median of 7.1 years. Plasma lipidomic profiling was performed using the UHPLC-HRMS method. We used three different models adjusted for clinical covariates to analyze the data. Clustering methods were used to define metabotypes, which allowed for the stratification of subjects into subgroups with similar clinical and metabolic profiles. We observed that lysophosphatidylcholine (LPC) species like LPC.16.0, LPC.18.3, LPC.18.1, and LPC.20.3 were significantly (p < 0.05) associated with baseline and follow-up BMI in adolescent obesity. The association of LPC species with BMI remained consistently significant even after adjusting for potential confounders. Moreover, applying metabotyping using hierarchical clustering provided insights into the metabolic heterogeneity within the normal and obese groups, distinguishing metabolically healthy individuals from those with unhealthy metabolic profiles. CONCLUSION: The specific LPC levels were found to be altered and increased in childhood obesity, particularly during the follow-up. These findings suggest that LPC species hold promise as potential biomarkers of obesity in adolescents, including healthy and unhealthy metabolic profiles.

Religiosity, Aging in the Homeland, and Growing Old in the Diaspora: A Longitudinal Study of Two Cohorts of Indian Older Adults.

This article reports a longitudinal study comparing religiosity among two cohorts of Indian older adults-those who age in the homeland of India (AIH cohort) and immigrants (to the USA) or diaspora older adults (DOA). Results indicated that AIH and DOA cohorts' religiosity outcomes were comparable at baseline but there was a statistically significant increase in all outcomes of the DOA cohort at subsequent time points. Women and single older adults in both the cohorts had higher religiosity scores at baseline. Religiosity scores were higher among those in the DOA cohort who migrated following marital disruption (widowhood, divorce) or grandchild birth and lived with adult immigrant children and their families. The immigration process can have an impact on religious orientation of older adults and place is a significant variable impacting religiosity possibly for augmenting the sense of self, acquire social capital and preserve cultural identity in the foreign land.

Cultural Considerations in Healthcare for Older Asian Indian US Adults.

Approximately 4.8 million Asian Indians were documented by the US Census Bureau in 2023. Members of this population follow different religious practices, speak a multitude of languages, and belong to different socioeconomic classes. Asian Indians immigrated to this country in different waves, leading to transgenerational diversity. Immigration, financial, religious, and cultural factors uniquely impact how Asian Indians interact with their healthcare providers. Asian Indians have settled throughout the country, and it is important that clinicians familiarize themselves with the specific health concerns that affect this rapidly growing population.

The Contribution of Declines in Blood Lead Levels to Reductions in Blood Pressure Levels: Longitudinal Evidence in the Strong Heart Family Study.

BACKGROUND: Chronic lead exposure is associated with both subclinical and clinical cardiovascular disease. We evaluated whether declines in blood lead were associated with changes in systolic and diastolic blood pressure in adult American Indian participants from the SHFS (Strong Heart Family Study). METHODS AND RESULTS: Lead in whole blood was measured in 285 SHFS participants in 1997 to 1999 and 2006 to 2009. Blood pressure and measures of cardiac geometry and function were obtained in 2001 to 2003 and 2006 to 2009. We used generalized estimating equations to evaluate the association of declines in blood lead with changes in blood pressure; cardiac function and geometry measures were considered secondary. Mean blood lead was 2.04 µg/dL at baseline. After ≈10 years, mean decline in blood lead was 0.67 µg/dL. In fully adjusted models, the mean difference in systolic blood pressure comparing the highest to lowest tertile of decline (>0.91 versus <0.27 µg/dL) in blood lead was -7.08 mm Hg (95% CI, -13.16 to -1.00). A significant nonlinear association between declines in blood lead and declines in systolic blood pressure was detected, with significant linear associations where blood lead decline was 0.1 µg/dL or higher. Declines in blood lead were nonsignificantly associated with declines in diastolic blood pressure and significantly associated with declines in interventricular septum thickness. CONCLUSIONS: Declines in blood lead levels in American Indian adults, even when small (0.1-1.0 µg/dL), were associated with reductions in systolic blood pressure. These findings suggest the need to further study the cardiovascular impacts of reducing lead exposures and the importance of lead exposure prevention.

Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.

Variations in the Prevalence of Childhood Anemia by Ethnicity Before and During the COVID-19 Pandemic in Peru.

We aimed to determine the variations in the prevalence of childhood anemia according to the ethnic group before and during the COVID-19 pandemic in Peru. Secondary analysis of the Demographic and Family Health Survey during 2016-2021. The outcome variable was anemia, and the exposure variable was maternal ethnicity. Also, we included sociodemographic and clinical confounding variables. We constructed generalized linear models of the Poisson family with a logarithmic link function. We evaluated 85,905 records; 30.34% had anemia, 50.83% were mestizo, 25.98% were Quechua, and 2% were Aymara. Compared with mestizos, Quechua children (PR: 1.11; 95% CI: 1.07-1.15; p < 0.001), Aymara (PR: 1.35; 95% CI: 1.27-1 .44; p < 0.001), natives of the Amazon (PR: 1.20; 95% CI: 1.12-1.28; p < 0.001) and those who belonged to other indigenous peoples (PR: 1.29; 95% CI: 1.05-1.57; p = 0.013) had a higher prevalence of childhood anemia. On the contrary, compared to mestizos, white children had a lower prevalence of anemia (PR: 0.93; 95% CI: 0.89-0.99; p = 0.019). During the COVID-19 pandemic, compared to mestizos, only Quechua (PR: 1.15; 95% CI: 1.08-1.23; p < 0.001) and Aymara (PR: 1.38; 95% CI: 1.23-1.55; p < 0.001) had a higher prevalence of childhood anemia. Except for Afro-descendants, children from 6 to 59 months of age who belong to an ethnic minority had a higher probability of having childhood anemia than mestizos. However, only Quechua and Aymara children had higher odds of anemia during the COVID-19 pandemic than mestizos.

"It Seems Like a Bad Thing": US South Asian Youths' Perspectives About the Use of Hospice Care.

BACKGROUND: South Asians are one of the fastest growing populations in the US. Family based decision making is common among this population. Little is known about their knowledge and attitudes towards hospice use. OBJECTIVE: This study explored US South Asian youths' knowledge of, and attitudes towards hospice care. DESIGN: Qualitative study, using focus group discussions. METHODS: Thirty-six university students of South Asian heritage participated in ten focus group discussions. Data were coded inductively and deductively. Thematic analysis was performed. Disagreements were resolved through discussion. RESULTS: Participants were in consensus that if patients had an incurable, fatal condition, keeping them comfortable was important. Several participants were unaware of the terms 'hospice' and 'palliative care'. After these terms were explained, most opposed hospice care for reasons of 'desire for a normal life', 'cultural incompatibility', 'concerns about the hospice environment' and 'preference for home as the place of death'. Some were opposed to even home hospice fearing that it would continuously remind the family and patient about impending death. Concerns were also expressed about having a 'stranger' in the home to provide hospice care. One participant said she would support hospice use if it aligned with the patient's values. Others cited financial reasons and quality of life as considerations in choosing hospice care. CONCLUSIONS: Research is needed on culturally-appropriate modes of palliative care education and advocacy for South Asian populations in the US, especially youth, that are often the decision makers for the care of older family members.

Outcomes following lung transplantation for American Indians/Alaska Natives in the United States.

Limited data is available for American Indians/Alaska Natives (AI/AN) undergoing lung transplant. The goal of our study was to assess outcomes for AI/AN lung transplant recipients (LTR). A retrospective review of data from the Organ Procurement and Transplant Network was performed comparing AI/AN (n = 88) and Caucasian (n = 22,767) LTRs between May 4, 2005 and October 31, 2019. AI/AN LTRs had worse functional parameters prior to transplantation but had similar post-transplant outcomes compared to Caucasians LTRs.

Posttraumatic Stress Disorder Symptoms and Sleep Disturbances Among Asian Indians: A Systematic Review.

Substantial comorbidity exists between posttraumatic stress disorder and sleep disturbances/disorders. Such comorbidities are understudied in minority groups, including Asian Indians residing in countries outside India. Thus, we synthesized the existing literature specific to this group of Asian Indians to determine (a) prevalence estimates of posttraumatic stress disorder (PTSD) and sleep disturbances/disorders; and (b) PTSD-sleep comorbidity estimates. For this systematic review, we searched four databases (PubMed, PsycInfo, PTSDpubs, Web of Science) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Of 3,796 screened articles, 9 articles (10 studies) met inclusion criteria. Study sample sizes ranged from 11 to 2,112 Asian Indians; studies were conducted in Singapore or Malaysia. No reviewed study examined PTSD. All studies examined sleep disturbances/disorders among Asian Indians; prevalence estimates were: 8.3% to 70.4% for short sleep duration, 2.0% to 22.9% for long sleep duration, 25.9% to 56.3% for poor sleep quality, 3.4% to 67.5% for insomnia diagnosis or probable insomnia, 7.7% for excessive daytime sleepiness, 3.8% to 54.6% for obstructive sleep apnea (OSA) diagnosis or high OSA risk, and 5.1% to 11.1% for sleep-disordered breathing. Specific to Asian Indians residing in countries outside India, this review advances PTSD-sleep literature by (a) suggesting substantial prevalence of sleep disturbances/disorders; (b) highlighting the need for culturally relevant sleep interventions; and (c) highlighting research gaps (e.g., no PTSD-focused research).

Arg4810Lys mutation in RNF213 among Eastern Indian non-MMD ischemic stroke patients: a genotype-phenotype correlation.

INTRODUCTION: RNF213 mutations have been reported mostly in moyamoya disease (MMD) with varying frequencies across different ethnicities. However, its prevalence in non-MMD adult-onset ischemic stroke is still not well explored. AIMS AND OBJECTIVES: This present study thus aims to screen the most common RNF213 variant (Arg4810Lys, among East Asians) in the Eastern Indian non-MMD ischemic stroke patients and correlate it with long-term progression and prognosis of the patients. The subjects were analyzed for this variant using PCR-RFLP and confirmed using Sanger sequencing method. RESULT AND CONCLUSION: We have identified Arg4810Lys variant among eleven young-onset familial ischemic stroke patients in heterozygous manner. A positive correlation of the variant with positive family history (P = 0.001), earlier age at onset (P = 0.002), and history of recurrent stroke (P = 0.015) was observed. However, the carriers showed better cognitive performances in memory (P = 0.042) and executive function (P = 0.004). Therefore, we can conclude that Arg4810Lys/RNF213 - a pathogenic variant for young-onset familial ischemic stroke with higher incidence of recurrent events unlike in MMD cases, have no additional impact on cognition among Eastern Indians.

Incidence of Stomach, Liver, and Colorectal Cancers by Geography and Social Vulnerability Among American Indian and Alaska Native Populations, 2010-2019.

Social determinants of health and associated systems, policies, and practices are important drivers of health disparities. American Indian and Alaska Native (AI/AN) populations in the United States have elevated incidence rates of stomach, liver, and colorectal cancers compared with other racial/ethnic groups. In this study, we examined incidence rates of 3 types of gastrointestinal cancer among non-Hispanic AI/AN (NH-AI/AN) and non-Hispanic White (NHW) populations by geographic region and Social Vulnerability Index (SVI) score. Incident cases diagnosed during 2010-2019 were identified from population-based cancer registries linked with the Indian Health Service patient registration databases. Age-adjusted incidence rates (per 100,000 population) for stomach, liver, and colorectal cancers were compared within NH-AI/AN populations and between the NH-AI/AN and NHW populations by SVI score. Rates were higher among NH-AI/AN populations in moderate- and high-SVI-score counties in Alaska, the Southern Plains, and the East than in low-SVI counties. Incidence rates among NH-AI/AN populations were elevated when compared with NHW populations by SVI category. Results indicated that higher social vulnerability may drive elevated cancer incidence among NH-AI/AN populations. Additionally, disparities between NH-AI/AN and NHW populations persist even when accounting for SVI. Exploring social vulnerability can aid in designing more effective interventions to address root causes of cancer disparities among AI/AN populations.

Trends in Premature Mortality from Acute Myocardial Infarction in American Indians/Alaska Natives in the United States from 1999 to 2020.

Cardiovascular disease is the leading cause of mortality in American Indian and Alaska Native (AI/AN) groups. They are disproportionately found to have a higher rate of premature myocardial infarction (MI). The Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research were queried to identify premature MI deaths (female <65 years and male <55 years) occurring within the United States between 1999 and 2020. We investigated proportionate mortality trends related to premature MI in AI/ANs stratified by gender. Deaths attributed to acute MI (AMI) were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes I21 to I22. We compared the proportional mortality rate because of premature MI with that of a non-AI/AN racial group, which comprised all other races (Blacks, Whites, and Asian/Pacific Islander populations). In AI/ANs, we analyzed a total of 14,055 AMI deaths, of which 3,211 were premature MI deaths corresponding to a proportionate mortality rate of 22.8% (male 20.8%, female 26.2%). The non-AI/AN population had a lower proportionate mortality of 14.8% (male 13.7%, female 16%), p <0.01). On trend analysis, there was no significant improvement over time in the proportionate mortality of AI/ANs (19.8% in 1999 to 21.7% in 2020, p = 0.09). Upon comparison of gender, proportionate mortality of premature MI in women showed a statistically nonsignificant increase from 21.6% in 1999 to 27.3% in 2020 [average annual percent change of 0.7, p = 0.06)]. However, men had a statistically significant decrease in proportionate mortality of premature MI from 18.5% in 1999 to 18.2% in 2020 [average annual percent change of -0.8, p = 0.01)]. AI/ANs have an alarmingly higher rate of proportionate mortality of premature MI than that of other races, with no improvement in the proportionate mortality rates over 20 years, despite an overall downtrend in AMI mortality. Further research to address the reasons for the lack of improvement in premature MI is needed to improve outcomes in this patient population.

Fatal Firearm Violence Among American Indians and Alaska Natives.

There is a dearth of population-based studies regarding firearm-related deaths and years of potential life lost among American Indians and Alaska Natives (AI/AN). Using the Centers for Disease Control and Prevention's (CDC) We Based Injury Statistics Query and Reporting System (WISQARS) data for the three most recent years (2018-2020), we analyzed the demographic characteristics of AI/ANs who succumbed to firearm violence. AI/ANs averaged almost 500 firearm-related deaths per year. The majority of these deaths were observed among individuals 20-39 years of age (53%), males (84.4%), and in the West (55.3%). A plurality of these firearm-related deaths were suicides (48.9%) followed by homicides (43.5%). During the 3-year study period, the age-adjusted firearm death rate increased almost 5 times the growth of the AI/AN population. Also, a staggering 67,050 years of potential life were lost before the age of 80 years (YPLL80) during this period. Firearm suicides were responsible for the largest proportion of YPLL80s (48.5%). Traditional legal interventions [e.g., child access prevention (CAP) laws and extreme risk protection orders (ERPO)], if expanded to more states could potentially help reduce AI/AN firearm mortality. None of the 10 states with the highest firearm mortality of AI/AN have ERPOs and 8 of the 10 do not have CAP laws. Also, a renewed focus on cultural continuity and indigenous protective factors is essential to ameliorate the level of firearm violence in AI/ANs.