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Longitudinal data are needed to investigate chronic disease causation and improve prevention efforts for Alaska Native and American Indian (ANAI) people. This paper describes the methods used to conduct follow-up data collection of a longitudinal cohort that enrolled ANAI adults between 2004 and 2006 in south central Alaska. The follow-up study re-examined ANAI participants in a large, urban centre in south central Alaska between 2015 and 2017. Computerized surveys were used to collect self-reported health, lifestyle, physical activity, and diet data. Clinical measurements included blood pressure, fasting blood glucose and lipid panel, urine albumin/creatinine, height, weight, and waist and hip circumference. Participants were provided individual results at the conclusion of their visit. A total of 1320 south central Alaska study participants completed the baseline visit. Study staff attempted to contact all living cohort members for inclusion in the follow-up study. More than 11,000 attempted contacts were made. Of the 637 available for participation, 388 completed the follow-up visit. The proportion of women increased from baseline to follow-up examinations (67 vs. 72%, p < 0.01). Self-reported health status of being married or living as married (46% vs. 39%, p < 0.01), and those reporting being employed or self-employed (55% vs. 47%, p < 0.01) were higher at follow-up when compared to baseline. Almost all participants at follow-up (97%) agreed to long-term storage of biological specimens for future study. Despite demographic differences between the follow-up and baseline cohorts, longitudinal data collected will provide novel insight on chronic disease development and prevention for ANAI people as well as other populations. [ABSTRACT FROM AUTHOR]

American Indian and Alaska Native women had approximately twice the incidence of cervical cancer as white women. Preventive measures for cervical cancer rely on screening and HPV vaccination. However, vaccine series completion and catch-up vaccinations for eligible adults are low across all racial/ethnic groups. Therefore, the aim of this study was to identify gaps in knowledge and evaluate the attitudes toward HPV and the vaccine among AIANs with various levels of training in the STEM and health-related fields. A survey was used to collect data from audience members at two national conferences geared towards American Indian and Alaska Natives in health and STEM fields in September 2017. A vignette study was administered via a live electronic poll to test knowledge (true/false questions), attitudes, and to collect demographic information. Respondents self-identified as primarily American Indian and Alaska Native (74%), pursuing or completed a graduate degree (67%), and female (85%). Most respondents (86%) were aware of HPV-associated cancer in men. However, most (48-90%) answered incorrectly to detailed true/false statements about HPV and available vaccines. After educational information was provided, opinions collected via vignettes highlighted mainly positive attitudes toward vaccination; specifically, that vaccines are safe and all eligible community members should be vaccinated (75% and 84%, respectively). We observed that our respondents with higher educational attainment still lacked accurate knowledge pertaining to HPV and the vaccine. Overall, continued education about HPV and the vaccine is needed across all levels of education including American Indian and Alaska Native community members and health professionals. [ABSTRACT FROM AUTHOR]

Objective: A common nonsense mutation in TBC1D4 was recently found to substantially increase the odds of type 2 diabetes in Greenlandic Inuit, leading to exclusively increased postprandial glucose. We investigated the frequency and effect of the TBC1D4 mutation on glucose metabolism and type 2 diabetes diagnosis among Canadian and Alaskan Inuit.Research Design and Methods: Exome sequencing of the TBC1D4 variant was performed in 114 Inuit from Nunavik, Canada, and Sanger sequencing was undertaken in 1,027 Alaskan Inuit from the Genetics of Coronary Artery Disease in Alaskan Natives (GOCADAN) Study. Association testing evaluated the effect of the TBC1D4 variant on diabetes-related metabolic traits and diagnosis.Results: The TBC1D4 mutation was present in 27% of Canadian and Alaskan Inuit. It was strongly associated with higher glucose (effect size +3.3 mmol/L; P = 2.5 x 10-6) and insulin (effect size +175 pmol/L; P = 0.04) 2 h after an oral glucose load in homozygote carriers. TBC1D4 carriers with prediabetes and type 2 diabetes had an increased risk of remaining undiagnosed unless postprandial glucose values were tested (odds ratio 5.4 [95% CI 2.5-12]) compared with noncarriers. Of carriers with prediabetes or type 2 diabetes, 32% would remain undiagnosed without an oral glucose tolerance test (OGTT).Conclusions: Disruption of TBC1D4 is common among North American Inuit, resulting in exclusively elevated postprandial glucose. This leads to underdiagnosis of type 2 diabetes, unless an OGTT is performed. Accounting for genetic factors in the care of Inuit with diabetes provides an opportunity to implement precision medicine in this population. [ABSTRACT FROM AUTHOR]

Hypertension is a common chronic disease and a key risk factor in the development of cardiovascular disease. The Western Alaska Tribal Collaborative for Health study consolidates baseline data from four major cohorts residing in the Norton Sound and Yukon-Kuskokwim regions of western Alaska. This consolidated cohort affords an opportunity for a systematic analysis of high blood pressure and its correlates in a unique population with high stroke rates over a wide age range. While the prevalence of hypertension among western Alaska Native people (30%, age-standardized) is slightly less than that of the US general population (33%), cardiovascular disease is a leading cause of mortality in this rural population. The authors found that improvement is needed in hypertension awareness as about two thirds (64%) of patients reported awareness and only 39% with hypertension were controlled on medication. Future analyses assessing risk and protective factors for incident hypertension in this population are indicated. [ABSTRACT FROM AUTHOR]

Objectives. We determined all-cause, cardiovascular disease (CVD), and cancer mortality in western Alaska Native people and examined agreement between death certificate information and adjudicated cause of deaths. Methods. Data from 4 cohort studies were consolidated. Death certificates and medical records were reviewed and adjudicated according to standard criteria. We compared adjudicated CVD and cancer deaths with death certificates by calculating sensitivity, specificity, predictive values, and j statistics. Results. Men (n = 2116) and women (n = 2453), aged 18 to 95 years, were followed an average of 6.7 years. The major cause of death in men was trauma (25%), followed by CVD (19%) and cancer (13%). The major cause of death in women was CVD (24%), followed by cancer (19%) and trauma (8%). Stroke rates in both genders were higher than those of US Whites. Only 56% of deaths classified as CVD by death certificate were classified as CVD by standard criteria; discordance was higher among men (55%) than women (32%; κs = 0.4 and 0.7). Conclusions. We found lower rates for coronary heart disease death but high rates of stroke mortality. Death certificates overestimated CVD mortality; concordance between the 2 methods is better for cancer mortality. The results point to the importance of cohort studies in this population in providing data to assist in health care planning [ABSTRACT FROM AUTHOR]

Background. According to health status reports, chronic disease prevalence appears to be rising in western Alaska Native (AN) people, and accurate population-based data are needed. Four cohort studies of western AN people were conducted in the Norton Sound and Yukon-Kuskokwim regions, but none have been large enough to allow reliable estimates of rates of chronic diseases and evaluate their risk factors. Objective. In this article, the methods used to combine 4 major cohort studies of rural western AN people are described and the benefits and challenges encountered in combining data and standardizing surveillance methods for these studies are discussed. Design. Tribal permission was obtained for each cohort study and the consolidated study. Data from baseline exams were directly combined or harmonized into new variables. Common surveillance methods were developed and implemented to identify incidence and risk factors for cardiovascular disease (CVD) events and type 2 diabetes. Results. A cohort of 4,569 western AN participants (2,116 men and 2,453 women), aged 18-95 years, was established to study CVD and diabetes prevalence. Prospective surveillance data over an average 6.7-year follow-up can now be used to study CVD and diabetes incidence and associated risk factors in a subset of 2,754 western AN participants (1,218 men and 1,536 women) who consented to initial surveillance. Conclusions. The combined cohort provides statistical power to examine incidence rates and risk factors for CVD and diabetes and allows for analyses by geographic region. The data can be used to develop intervention programmes in these populations and others. [ABSTRACT FROM AUTHOR]

Background: Few studies have compared lipoprotein composition with dietary intake. Objective: The lipoprotein subfraction profile was evaluated in relation to diet in Alaska Eskimos at high cardiovascular risk but with a low frequency of hyperlipidemia and high intake of n-3 (omega- 3) fatty acids. Design: A population-based sample (n = 1214) from the Norton Sound Region of Alaska underwent a physical examination and blood sampling. Analyses were from 977 individuals who did not have diabetes or use lipid-lowering medications and had complete dietary information (food-frequency questionnaire) and a lipoprotein subfraction profile (nuclear magnetic resonance spectroscopy). Results: After adjustment for age, BMI, total energy intake, and percentage of energy from fat, the intake of n-3 fatty acids was significantly associated with fewer large VLDLs (P = 0.022 in women, P = 0.064 in men), a smaller VLDL size (P = 0.018 and P = 0.036), more large HDLs (P = 0.179 and P = 0.021), and a larger HDL size (P = 0.004 and P = 0.001). After adjustment for carbohydrate and sugar intakes, large VLDLs (P = 0.042 and 0.018) and VLDL size (P = 0.011 and 0.025) remained negatively associated with n-3 fatty acid intake in women and men, and large HDLs (P = 0.067 and 0.005) and HDL size (P = 0.001 in both) remained positively associated with n-3 fatty acid intake in women and men. In addition, large LDLs (P = 0.040 and P = 0.025) were positively associated in both sexes, and LDL size (P = 0.006) showed a positive association in women. There were no significant relations with total LDL particles in either model. Conclusions: Dietary n-3 fatty acids, independent of the reciprocal changes in carbohydrate and sugar intakes, are associated with an overall favorable lipoprotein profile in terms of cardiovascular risk. Because there are no relations with total LDL particles, the benefit may be related to cardiovascular processes other than atherosclerosis. [ABSTRACT FROM AUTHOR]

Aims: This study estimates incidence of diabetes (DM) and pre-DM relative to DM risk factors among relatively healthy Alaska Native and American Indian (henceforth AN) adults living in urban south central Alaska.Methods: Baseline (2004-2006) and follow-up (2014-2017) surveys, blood samples, and medical chart review data were collected from AN adults living in south central Alaska. We analyzed associations between prevalent risk factors and incident DM and pre-DM using Cox proportional hazards and used multivariable models to identify independent predictors for both DM and pre-DM.Results: Among 379 participants with follow-up data, overall DM incidence was 16.5/1,000 PY; overall pre-DM incidence was 77.6/1,000 PY, with marked differences between men and women. Prevalent cardiometabolic risk factors also varied with greater amounts of overweight in men and greater amounts of obesity in women. Controlling for age and sex, obesity, abdominal adiposity, pre-DM, and metabolic syndrome independently increased DM risk.Conclusion: Health care providers of AN populations must seize the opportunity to screen, refer, and treat individuals with pre-DM and other modifiable DM risk factors prior to DM diagnosis if we are to alter the epidemiologic course of disease progression in this urban AN population. [ABSTRACT FROM AUTHOR]

The article focuses on a study which characterised the population-based prevalence of type 2 diabetes (DM2) and associated risk factors in western AN people living in the Norton Sound and Yukon Kuskokwim regions. The study found that diabetes prevalence in western Alaska Native people remains lower than the U.S. national average.

Pre-diabetes (pre-DM) is a strong predictor of diabetes (DM) over time. This study investigated how much of the recent increase in pre-DM identified among Alaska Native (AN) peoples living in urban southcentral Alaska may be due to changes in diagnostic methods. We used clinical and demographic data collected at baseline between 2004 and 2006 and at follow-up collected between 2015 and 2017 from the urban southcentral Alaska Education and Research Towards Health (EARTH) cohort. We used descriptive statistics and logistic regression to explore differences in demographic and clinical variables among the identified pre-DM groups. Of 388 participants in the follow-up study, 243 had A1c levels indicating pre-DM with only 20 demonstrating pre-DM also by fasting blood glucose (FBG). Current smoking was the sole predictor for pre-DM by A1c alone while abdominal obesity and elevated FBG-predicted pre-DM by A1c+FBG. No participants had an elevated FBG without an A1c elevation. A substantial portion of the rise in pre-DM found among urban southcentral AN peoples in the EARTH follow-up study was due to the addition of A1c testing. Pre-DM by A1c alone should be used to motivate behavioural changes that address modifiable risk factors, including smoking cessation, physical activity and weight management.

Introduction: Data on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with current use., Aims and Methods: EARTH Study urban south central ANAI participants (N = 376; 73% women) provided questionnaire data on smoking at baseline and 10-year follow-up. Multivariable-adjusted logistic regression assessed whether gender, cultural factors (Tribal identity, language spoken in the home), depressive symptoms (PHQ-9), baseline smoking status, and baseline cigarettes per day (CPD) were associated with current smoking at follow-up., Results: Current smoking was 27% and 23% at baseline and follow-up, respectively. Of baseline smokers, 60% reported smoking at follow-up (77% men, 52% women). From multivariable-adjusted analyses, the odds of current smoking at follow-up were lower among women than men, those who never or formerly smoked versus currently smoked at baseline, and smoking <10 CPD compared with ≥10 CPD at baseline. PHQ-9 score or cultural variables were not associated with smoking at follow-up. Smoking fewer baseline CPD was associated with former smoking status (ie, quitting) at follow-up among women, but not men., Conclusions: Our project is among the first to longitudinally explore smoking within an ANAI cohort. While we observed persistent smoking during a 10-year period, there were important differences by gender and CPD in quitting. These differences may be important to enhance the reach and efficacy of cessation interventions for ANAI people., Implications: This study contributes novel longitudinal information on cigarette smoking prevalence during a 10-year period among Alaska Native and American Indian (ANAI) people. Prior data on smoking prevalence among ANAI people are limited to cross-sectional studies or specific subpopulations. Our project is among the first to longitudinally explore smoking prevalence within an ANAI cohort. We observed persistent smoking during a 10-year period. The study also contributes information on differences by gender and cigarettes smoked per day in quitting. These findings have implications for enhancing the reach and efficacy of cessation interventions for ANAI people., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Tobacco use prevalence among Alaska Native (AN) people living in Alaska is greater than the general population prevalence statewide and nationally. Better understanding of regional tobacco use is needed to improve cessation efforts and reduce prevalence. Using self-reported baseline data from the Western Alaska Tribal Collaborative for Health study, we describe tobacco use patterns among AN people in two western Alaska regions. Data were stratified by age group and sex. Dual- and multi-product use in the Yukon-Kuskokwim (Y-K) region was stratified by concurrent vs sequential use. Overall, 87% of the cohort reported having used tobacco. In Norton Sound, cigarette (98%) was the predominant tobacco type. In Y-K 71% smoked, 76% used smokeless tobacco (ST), with 47% reporting use of both products. ST use in Y-K consisted of commercial ST and homemade iqmik. Y-K women reported more ST product use, while men reported more cigarette use. Among dual- and multi-product users, the majority reported concurrent use, with no significant differences between men and women. Distinct regional differences include high smoking prevalence in Norton Sound and frequent use of smoking and ST products in Y-K. Findings support modification of cessation programmes to address regional variations in tobacco use patterns.

Objectives: We determined all-cause, cardiovascular disease (CVD), and cancer mortality in western Alaska Native people and examined agreement between death certificate information and adjudicated cause of deaths., Methods: Data from 4 cohort studies were consolidated. Death certificates and medical records were reviewed and adjudicated according to standard criteria. We compared adjudicated CVD and cancer deaths with death certificates by calculating sensitivity, specificity, predictive values, and κ statistics., Results: Men (n = 2116) and women (n = 2453), aged 18 to 95 years, were followed an average of 6.7 years. The major cause of death in men was trauma (25%), followed by CVD (19%) and cancer (13%). The major cause of death in women was CVD (24%), followed by cancer (19%) and trauma (8%). Stroke rates in both genders were higher than those of US Whites. Only 56% of deaths classified as CVD by death certificate were classified as CVD by standard criteria; discordance was higher among men (55%) than women (32%; κs = 0.4 and 0.7)., Conclusions: We found lower rates for coronary heart disease death but high rates of stroke mortality. Death certificates overestimated CVD mortality; concordance between the 2 methods is better for cancer mortality. The results point to the importance of cohort studies in this population in providing data to assist in health care planning.

This paper describes genetic investigations of seroreactivity to five common infectious pathogens in the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Antibody titers and seroprevalence were available for 495 to 782 (depending on the phenotype) family members at two time points, approximately 15 years apart, for Chlamydophila pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and herpes simplex virus 2 (HSV-2). Seroprevalence rates indicate that infections with most of these pathogens are common (≥20% for all of them, >80% for H. pylori, CMV, and HSV-1). Seropositive individuals typically remain seropositive over time, with seroreversion rates of <1% to 10% over ∼15 years. Antibody titers were significantly heritable for most pathogens, with the highest estimate being 0.61 for C. pneumoniae. Significant genome-wide linkage evidence was obtained for C. pneumoniae on chromosome 15 (logarithm of odds, LOD score of 3.13). These results demonstrate that individual host genetic differences influence antibody measures of common infections in this population, and further investigation may elucidate the underlying immunological processes and genes involved., (© 2013 WILEY PERIODICALS, INC.)

It is unknown what role uric acid (UA) may play in the increasing rates of cardiovascular disease (CVD) among Alaska Eskimos. UA is associated with both hypertension (HTN) and chronic kidney disease (CKD). The authors analyzed 1078 Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) participants. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine measures using the Modification of Diet in Renal Disease equation. CKD was defined by an eGFR of <60 mL/min/1.73 m(2) . The authors adjusted for age, sex, education, diabetes, hypertension (or eGFR), obesity, lipids, and smoking status; 7% (n=75) had prevalent CKD. eGFR decreased with increasing tertiles of serum UA (P<.001). UA was independently associated with prevalent CKD (adjusted odds ratio [OR] and 95% confidence interval [CI] of 2.04 (1.62-2.56), respectively). Twenty-one percent (n=230) had prevalent HTN and UA was independently associated with prevalent HTN (adjusted OR, 1.2; 95% CI, 1.1-1.5). UA is independently associated with prevalent CKD and HTN in this population., (© 2011 Wiley Periodicals, Inc.)

Variation in anthropometric measurements due to sexual dimorphism can be the result of genotype by sex interactions (G×S). The purpose of this study was to examine the sex-specific genetic architecture in anthropometric measurements in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Maximum likelihood-based variance components decomposition methods, implemented in SOLAR, were used for G×S analyses. Anthropometric measurements included BMI, waist circumference (WC), waist/height ratio, percent body fat (%BF), and subscapular and triceps skinfolds. Except for WC, mean values of all phenotypes were significantly different in men and women (P < 0.05). All anthropometric measures were significantly heritable (P < 0.001). In a preliminary analysis not allowing for G×S interaction, evidence of linkage was detected between markers D19S414 and D19S220 on chromosome 19 for WC (logarithm of odds (lod) = 3.5), %BF (lod = 1.7), BMI (lod = 2.4), waist/height ratio (lod = 2.5), subscapular (lod = 2.1), and triceps skinfolds (lod = 1.9). In subsequent analyses which allowed for G×S interaction, linkage was again found between these traits and the same two markers on chromosome 19 with significantly improved lod scores for: WC (lod = 4.5), %BF (lod = 3.8), BMI (lod = 3.5), waist/height ratio (lod = 3.2), subscapular (lod = 3.0), and triceps skinfolds (lod = 2.9). These results support the evidence of a G×S interaction in the expression of genetic effects resulting in sexual dimorphism in anthropometric phenotypes and identify the chromosome 19q12-13 region as important for adiposity-related traits in Alaskan Eskimos.

Objectives: To examine sex-specific associations of nutritional factors with prevalent hypertension (HTN) and systolic blood pressure (SBP) in Alaska Natives. Diet is known to affect SBP, a major risk factor for cardiovascular disease., Study Design: Cross-sectional analysis of participants without diabetes in the Genetics of Coronary Artery Disease in Alaska Natives study., Methods: Macronutrients such as fat, carbohydrate and protein and micronutrients such as sodium were investigated. HTN was defined as SBP≥140 mmHg, diastolic blood pressure≥90 mmHg and/or taking anti-HTN medication. Analyses were stratified by sex and covariates included age, body mass index (BMI), energy intake, smoking and physical activity., Results: Mean age was 42 years for men (n=456) and women (n=602). Men with HTN (n=106) compared to men without HTN consumed a higher proportion of calories from total (p=0.01), saturated (p<0.01) and trans fatty acid (p=0.03) fats. Women with HTN (n=99) compared to women without HTN consumed more total (p=0.03) and monounsaturated (p=0.04) fat, higher protein (p=0.02) and lower total (p<0.01) and simple (p<0.01) carbohydrates. After covariate adjustment, men not on anti-HTN medications (n=407) had significantly higher average SBP with increasing quartiles of trans fatty acid intake (p for linear trend=0.01) and sodium intake (p for linear trend=0.02). For women not on anti-HTN medications (n=528), after covariate adjustment, average SBP decreased with increasing quartiles of omega 3 fatty acid intake (p for linear trend <0.01)., Conclusions: Prospective evaluation of the sex-specific associations of nutritional factors with HTN and SBP on outcomes is needed along with novel interventions to lower the risk of cardiovascular disease.

Background and Aims: Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos., Methods and Results: A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000-2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58 years; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3-4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 years. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates (<.002) and albuminuria and CRP were also correlated with CVD (p<.05) after adjustment for age and gender. Carotid atherosclerosis was correlated with CVD (p=.0079) independent of other risk factors., Conclusion: These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended.

Background: The prevalence and associated risk factors for albuminuria and low-grade albuminuria in Alaska Natives is not known., Methods: Cross-sectional analysis of the Genetics of Coronary Artery Disease in Alaska Natives Study. We included 1,026 individuals, who represent 85% of the study participants for whom complete data were available. Risk factors examined were age, sex, education, diabetes, hypertension, obesity, lipids, C-reactive protein, angiotensin-converting enzyme inhibitor use, and smoking status. Urine albumin excretion was estimated by the albumin/creatinine ratio measured from a single random morning urine sample. Albuminuria was defined as an albumin/creatinine ratio of > or =30 mg/g. Low-grade albuminuria was defined as an albumin/creatinine ratio of 10 to <30 mg/g., Results: The mean age was 42 years and over half were female. Diabetes prevalence was low at 3% and the prevalence of hypertension was 20%. The prevalence of albuminuria was 6%; the prevalence of low-grade albuminuria was 12%. Individuals with diabetes or hypertension were 3 times more likely to have albuminuria than those without these conditions [odd ratios: diabetes 3.0 (1.2-7.9) and hypertension 3.0 (1.2-7.3)]., Conclusions: The burden of albuminuria is low. Comprehensive programs and policies are important given the rise in diabetes and hypertension among Alaska Natives., (Copyright 2010 S. Karger AG, Basel.)