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Objectives. To compare fine particulate matter (PM2.5) concentrations in American Indian (AI)-populated with those in non–AI-populated counties over time (2000–2018) in the contiguous United States. Methods. We used a multicriteria approach to classify counties as AI- or non--AI-populated. We ran linear mixed effects models to estimate the difference in countywide annual PM2.5 concentrations from well-validated prediction models and monitoring sites (modeled and measured PM2.5, respectively) in AI- versus non–AI-populated counties. Results. On average, adjusted modeled PM2.5 concentrations in AI-populated counties were 0.38 micrograms per cubic meter (95% confidence interval [CI] = 0.23, 0.54) lower than in non–AI-populated counties. However, this difference was not constant over time: in 2000, modeled concentrations in AI-populated counties were 1.46 micrograms per cubic meter (95% CI = 1.25, 1.68) lower, and by 2018, they were 0.66 micrograms per cubic meter (95% CI = 0.45, 0.87) higher. Over the study period, adjusted modeled PM2.5 mean concentrations decreased by 2.13 micrograms per cubic meter in AI-populated counties versus 4.26 micrograms per cubic meter in non–AI-populated counties. Results were similar for measured PM2.5. Conclusions. This study highlights disparities in PM2.5 trends between AI- and non–AI-populated counties over time, underscoring the need to strengthen air pollution regulations and prevention implementation in tribal territories and areas where AI populations live. (Am J Public Health. 2022;112(4): 615–623. https://doi.org/10.2105/AJPH.2021.306650 )

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults at risk for coronavirus disease 2019 (COVID-19) comprising 14 established United States (US) prospective cohort studies. For decades, C4R cohorts have collected extensive data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R will link this pre-COVID phenotyping to information on SARS-CoV-2 infection and acute and post-acute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and broadly reflects the racial, ethnic, socioeconomic, and geographic diversity of the US. C4R is ascertaining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations, and high-quality events surveillance. Extensive pre-pandemic data minimize referral, survival, and recall bias. Data are being harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these will be pooled and shared widely to expedite collaboration and scientific findings. This unique resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including post-acute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term trajectories of health and aging.

Introduction: Dyslipidemia is characterized by high levels of total cholesterol (TC), LDL cholesterol (LDL-C), triglycerides (TG), or low levels of HDL cholesterol (HDL-C) and is an established risk factor for subclinical and clinical cardiovascular disease (CVD) among adults. Although several investigations exist in older American Indian (AI) adults, the data on AI adolescents and young adults are scarce. Hypothesis: Dyslipidemia will be prevalent, and the incidence of subclinical and clinical CVD will be higher in young AI with than without baseline dyslipidemia. Methods: We evaluated AI participants from the SHFS, who were 14-39 years old at the baseline examination, 2001-2003 (n=1,436). To measure lipids, we drew blood after a 12-hour fast and defined dyslipidemia as any of the following: TC ≥ 200 mg/dL, LDL-C ≥ 100 mg/dL, TG ≥ 150 mg/dL, HDL-C < 40 mg/dL for men, HDL-C < 50mg/dL for women, non-HDL-C ≥ 130 mg/dL or taking lipid lowering medication. We used carotid ultrasound to detect atherosclerotic plaque at baseline and at the follow-up examination, 2006-2009. We identified CVD events through 2019 with a median follow-up of 17.8 years. We used log-rank tests to determine if the incidence of plaque or CVD events differed according to different categories of dyslipidemia. Results: Prevalence of dyslipidemia was 42%, 65%, and 73% for participants Conclusions: AI adolescents and young adults have an unexpectedly high prevalence of dyslipidemia, which leads to higher incident plaque and CVD events later in life. These data provide evidence for the benefits of lipid screening and intervention among this population.

Introduction: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Subclinical atherosclerosis is typically detected later in life and may develop into clinical CVD. Although investigators have established the association in older adults, the burden of subclinical atherosclerosis and its relation to CVD risk among AI youth is unclear. Hypothesis: Subclinical atherosclerosis will be prevalent and the risk of CVD will be higher in AI with atherosclerotic plaque in adolescence and early adulthood. Methods: We evaluated AI participants from the SHFS, who were 14-39 years old, CVD free, and had a carotid ultrasound at the baseline examination, 2001-2003 (n=1,376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified fatal and/or non-fatal CVD events through the end of 2019 with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between subclinical atherosclerosis and time to CVD events, while controlling for covariates. Results: Among 1,376 participants, 71 (5.2%) had atherosclerotic plaque at baseline. During follow-up, 120 (8.7%) participants had a fatal or non-fatal CVD event. CVD incidence was higher in participants with baseline plaque (13.51/1,000 person-years) than in those without (4.95/1,000 person-years, p=0.0003, Figure 1). Risk of CVD was higher in participants with baseline plaque compared to those without, while controlling for age and obesity (CVD HR=1.85, 95% CI=1.02-3.37, p=0.0420). Conclusions: AI adolescents and young adults have an unexpectedly high prevalence of atherosclerotic plaque, which is independently associated with incident CVD later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Broad health data sharing raises myriad ethical issues related to data protection and privacy. These issues are of particular relevance to Native Americans, who reserve distinct individual and collective rights to control data about their communities. We sought to gather input from tribal community leaders on how best to understand health data privacy and sharing preferences in this population. We conducted a workshop with 14 tribal leaders connected to the Strong Heart Study to codesign a research study to assess preferences concerning health data privacy for biomedical research. Workshop participants provided specific recommendations regarding who should be consulted, what questions should be posed, and what methods should be used, underscoring the importance of relationship-building between researchers and tribal communities. Biomedical researchers and informaticians who collect and analyze health information from Native communities have a unique responsibility to safeguard these data in ways that align to the preferences of specific communities.

Objective Valid neuropsychological assessment is critical to the accurate diagnosis and effective treatment of diverse populations. American Indians and Alaska Natives experience substantial health disparities relative to the general U.S. Population Given the dearth of studies on neuropsychological health in this population, we aimed to characterize neuropsychological performance among older American Indians with respect to age, sex, education, income, and language use. Method From 2010 to 2014, we recruited 818 American Indians aged 60 and older from the Cerebrovascular Disease and Its Consequences in American Indians Study, who comprised all of the surviving members of a cardiovascular study (Strong Heart Study). This cohort from 11 tribes resided on or near their home reservations in three geographic regions (Northern Plains, Southern Plains, and Southwest). Using a cross-sectional design investigating potential vascular brain injury, we administered a brief, targeted neuropsychological and motor function assessments. Results Higher scores on neuropsychological tests were associated with younger age, female sex, more education, higher income, and less Native American language use. Similar associations were found for the motor tests, although men had higher scores on both motor function tests. After accounting for other sociocultural and health factors, age, sex, education, income, and Native American language use all had significant associations to the test scores. Conclusions Our findings may be used to guide research and inform clinical practice. The development of future normative studies for older American Indians will be more culturally appropriate when sociocultural factors are included. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Non-caloric artificial sweeteners (NAS) are marketed as healthier alternatives to sugar, but the relationship between consumption of NAS and development of diabetes is unclear. This study assessed the associations of diet soda and NAS consumption with (1) early markers of insulin and glucose homeostasis (cross-sectionally) and (2) incident diabetes (over an average of 8 years of follow-up) among American Indians, a population with high rates of obesity. The study population included Strong Heart Family Study participants without cardiovascular disease or diabetes who participated in the 2007–2009 study exam (n = 1359). Diet soda and NAS consumption were assessed using a Block food frequency questionnaire and supplemental NAS questionnaire at the study exam. Fasting plasma glucose and insulin were measured during the study exam after a 12-h overnight fast. Participants were followed for incident diabetes through December 2017 using a single phone interview and medical record review; diabetes was identified by self-report and confirmed by documentation in medical records. Associations of diet soda and NAS consumption with fasting insulin, glucose, and incident diabetes were assessed using generalized estimating equations (fasting insulin and glucose analyses) and parametric survival models with Weibull distributions (incident diabetes analyses). Just under half of participants reported regularly consuming diet soda (40%) or using NAS to sweeten their beverages (41%). During an average 8 years of follow-up, we identified 98 cases of incident diabetes. After correction for multiple comparisons, there were no statistically significant associations of reported diet soda and NAS consumption with fasting insulin, fasting glucose, or incident diabetes. Although reported consumption of diet soda and NAS were high, neither were associated with diabetes risk.

Background: Clinical stroke is prevalent in American Indians, but the lifestyle risk factors for vascular brain injury have not been well-studied in this population. The purpose of this study was to correlate brain magnetic resonance imaging (MRI) findings with obesity, alcohol use, and smoking behaviors in elderly American Indians from the Strong Heart Study. Methods: Cranial MRI scans (n = 789) were analyzed for dichotomous measures of infarcts, hemorrhages, white matter hyperintensities (WMH), and cerebral atrophy and continuous measures of total brain, WMH, and hippocampal volume. Poisson regression was used to estimate prevalence ratios, and linear regression was used to estimate measures of association for continuous outcomes. Models were adjusted for the risk factors of interest as well as age, sex, study site, income, education, hypertension, diabetes, and low-density lipoprotein cholesterol. Results: Smoking was associated with increased hippocampal atrophy (p = 0.002) and increased prevalence of sulcal widening (p < 0.001). Relative to nonsmokers, smokers with more than 25 pack-years of smoking had a 27% (95% CI 7–47%) increased prevalence of high-grade sulci, p = 0.005. Body mass index was inversely associated with prevalence of nonlacunar infarcts and sulcal widening (all p = 0.004). Alcohol use was not significantly associated with any of the measured MRI findings. Conclusions: This study found similar associations between smoking and vascular brain injury among American Indians, as seen in other populations. In particular, these findings support the role of smoking as a key correlate for cerebral atrophy.

Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (SHFS). Methods: The SHFS is a population-based cohort study of cardiovascular disease (CVD) and its risk factors. Participants (n=2,769) recruited from regions in Arizona, Oklahoma and the Dakotas were assessed for LTL and CVD risk factors during a clinic visit between 2001 and 2003. Incident stroke events were identified through the end of 2018 (mean follow-up: 16.4 years). We assessed the association between LTL and incident stroke using frailty models based on the proportional hazards, accounting for family relatedness and established stroke risk factors that include sex, geographical location, education, smoking, atrial fibrillation, diabetes mellitus, and hypertension. Results: Among 2,769 participants, the mean age was 40.6±17.2 and 41.4% were male. During follow-up, there were 79 (2.9%) incident stroke cases. In the primary model, which adjusted for demographic variables (sex, location and education), the hazard ratios (HR) for stroke in participants in the first and second LTL quartiles were significantly higher than those in the highest (longest) LTL quartile, with HRs of 3.1 (95%CI: 1.4 - 6.6) and 3.5 (95%CI: 1.7 - 7.5), respectively. After adjusting for smoking, atrial fibrillation, diabetes mellitus, and hypertension, the association between LTL and stroke was attenuated, but remained significant when comparing the second shortest LTL quartile to the longest LTL quartile, HR: 2.3 (95% CI: 1.1 – 5.0). Conclusions: In summary, LTL was associated with incident stroke among SHFS participants. Those with shorter LTL have higher risk of stroke. Longer follow-up time may add more power to data analyses since the SHFS is relatively young, with an average baseline age of 40 years. If results are confirmed in other populations, LTL may serve as a biomarker identifying high risk individuals for the purpose of stroke prevention.

Tribal communities have legitimate reasons for being wary of research. The Strong Heart Study works to coordinate multi-disciplinary efforts towards bidirectional partnerships, with an ethos of respect and capacity development. Best practices are being developed through iterative processes including co-development of survey research through translating/communicating data analysis and applying CBPR practices. Information translation and CBPR throughout the research process also includes participating in community-based research symposia, developing site specific information through informational venues (e.g. Red Talks), formal reporting to Tribal councils and health committees, informal interaction by participating in local Native American community events, engaging Community Advisory groups, and supporting local students through hands-on internships. These activities also enhance transition of traditional public health research to a support a more autonomous, individualized system for the Tribal partners toward greater self-determining their own health. This approach encourages health literacy, promotes Institutional memory and automates longitudinal surveillance of local health issues to reduce disparities in Tribal nations.

Introduction: About 30% of all U.S. adults and 70-80% of those with Type 2 diabetes mellitus (T2DM) have non-alcoholic fatty liver disease (NAFLD). Atherosclerotic cardiovascular disease (CVD) is more common among NAFLD patients, albeit with limited evidence from large prospective studies. Hypothesis: American Indians (AI) with NAFLD would be more likely to develop carotid atherosclerosis given their high prevalence of obesity and T2DM. Methods: The Strong Heart Family Study (SHFS) is a population-based family study of CVD and its risk factors in AI. Participants (n=2786; 59.6% female, mean age 40.8 ±17.3 y) were recruited from 12 tribes in 3 regions: Arizona, North/South Dakota, and Oklahoma. Carotid ultrasound-assessed plaque and plaque score were obtained at the baseline examination in 2001-03, and again in surviving participants (n=2406) from 2006 to 2009. NAFLD prevalence was estimated using hepatic steatosis index (HSI). NAFLD fibrosis score was used to separate NAFLD patients with or without advanced fibrosis. HSI is calculated using serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), BMI, diabetes status, and sex, while the NAFLD fibrosis score is derived from age, BMI, diabetes status, ALT, AST, platelet count, and serum albumin. Plaque progression was defined as any increase in plaque score (0 to 8 carotid segments with plaque) from baseline to the second examination. Frailty model was used in data analyses to account for the relatedness among family members. Results: Mean BMI of participants was 31.3 ± 7.5 kg/m 2 , 19% had T2DM, 32.6% were hypertensive, and 36.3% were current smokers. NAFLD prevalence (HSI > 36) was 78%, while 6% did not have NAFLD (HSI < 30) and 16% participants were in an intermediate category (HSI 30-36). Among participants with NAFLD (n=2096), three fibrosis classes were defined by NAFLD fibrosis scores: 1 no to moderate fibrosis (61%, fibrosis score < -1.455), 2 indeterminate (31%, -1.455 ≤ fibrosis score ≤ 0.676), and 3 cirrhosis or severe cirrhosis (8%, fibrosis score > 0.676). About 31% of participants had carotid atherosclerosis (plaque score ≥ 1) at baseline. About 14% of the 2252 participants who had two carotid ultrasound evaluations had plaque progression and 19% of those without carotid atherosclerosis at baseline (n=1571) had incident plaque at the second visit. Compared to those with no to moderate fibrosis, those who had cirrhosis or severe cirrhosis had higher risks of plaque progression with a hazard ratio (HR, 95% CI) of 1.8 (1.1-2.9, P=0.026), and of incident plaque with a HR (95% CI) of 2.6 (1.5-4.6, P=0.0009), adjusted for sex, smoking, hypertension, albuminuria, LDL-C, and HDL-C. Similar results were found among participants with intermediate fibrosis scores. Conclusions: The prevalence of HSI-defined NAFLD is high in AI. NAFLD fibrosis score predicts both incident and progressive carotid atherosclerosis.

Background Cancer mortality among American Indian (AI) people varies widely, but factors associated with cancer mortality are infrequently assessed. Methods Cancer deaths were identified from death certificate data for 3516 participants of the Strong Heart Study, a population-based cohort study of AI adults ages 45–74 years in Arizona, Oklahoma, and North and South Dakota. Cancer mortality was calculated by age, sex and region. Cox proportional hazards model was used to assess independent associations between baseline factors in 1989 and cancer death by 2010. Results After a median follow-up of 15.3 years, the cancer death rate per 1000 person-years was 6.33 (95 % CI 5.67–7.04). Cancer mortality was highest among men in North/South Dakota (8.18; 95 % CI 6.46–10.23) and lowest among women in Arizona (4.57; 95 % CI 2.87–6.92). Factors independently associated with increased cancer mortality included age, current or former smoking, waist circumference, albuminuria, urinary cadmium, and prior cancer history. Factors associated with decreased cancer mortality included Oklahoma compared to Dakota residence, higher body mass index and total cholesterol. Sex was not associated with cancer mortality. Lung cancer was the leading cause of cancer mortality overall (1.56/1000 person-years), but no lung cancer deaths occurred among Arizona participants. Mortality from unspecified cancer was relatively high (0.48/100 person-years; 95 % CI 0.32−0.71). Conclusions Regional variation in AI cancer mortality persisted despite adjustment for individual risk factors. Mortality from unspecified cancer was high. Better understanding of regional differences in cancer mortality, and better classification of cancer deaths, will help healthcare programs address cancer in AI communities.

Left ventricular mass (LVM) has been shown to serve as a measure of target organ damage resulting from chronic exposure to several risk factors. Data on the association of midlife LVM with later cognitive performance are sparse. We studied 721 adults (mean age 56 years at baseline) enrolled in the Strong Heart Study (SHS, 1993–1995) and the ancillary CDCAI (Cerebrovascular Disease and Its Consequences in American Indians) Study (2010–2013), a study population with high prevalence of cardiovascular disease. LVM was assessed with transthoracic echocardiography at baseline in 1993 to 1995. Cranial magnetic resonance imaging and cognitive testing were undertaken between 2010 and 2013. Generalized estimating equations were used to model associations between LVM and later imaging and cognition outcomes. The mean follow-up period was 17 years. A difference of 25 g in higher LVM was associated with marginally lower hippocampal volume (0.01%; 95% confidence interval, 0.02–0.00; P =0.001) and higher white matter grade (0.10; 95% confidence interval, 0.02–0.18; P =0.014). Functionally, participants with higher LVM tended to have slightly lower scores on the modified mini-mental state examination (0.58; 95% confidence interval, 1.08–0.08; P =0.024). The main results persisted after adjusting for blood pressure levels or vascular disease. The small overall effect sizes are partly explained by survival bias because of the high prevalence of cardiovascular disease in our population. Our findings emphasize the role of cardiovascular health in midlife as a target for the prevention of deleterious cognitive and functional outcomes in later life.

Objective:American Indians experience substantial health disparities relative to the US population, including vascular brain aging. Poorer cognitive test performance has been associated with cranial magnetic resonance imaging findings in aging community populations, but no study has investigated these associations in elderly American Indians.Methods:We examined 786 American Indians aged 64 years and older from the Cerebrovascular Disease and its Consequences in American Indians study (2010–2013). Cranial magnetic resonance images were scored for cortical and subcortical infarcts, hemorrhages, severity of white matter disease, sulcal widening, ventricle enlargement, and volumetric estimates for white matter hyperintensities (WMHs), hippocampus, and brain. Participants completed demographic, medical history, and neuropsychological assessments including testing for general cognitive functioning, verbal learning and memory, processing speed, phonemic fluency, and executive function.Results:Processing speed was independently associated with the presence of any infarcts, white matter disease, and hippocampal and brain volumes, independent of socioeconomic, language, education, and clinical factors. Other significant associations included general cognitive functioning with hippocampal volume. Nonsignificant, marginal associations included general cognition with WMH and brain volume; verbal memory with hippocampal volume; verbal fluency and executive function with brain volume; and processing speed with ventricle enlargement.Conclusions:Brain-cognition associations found in this study of elderly American Indians are similar to those found in other racial/ethnic populations, with processing speed comprising an especially strong correlate of cerebrovascular disease. These findings may assist future efforts to define opportunities for disease prevention, to conduct research on diagnostic and normative standards, and to guide clinical evaluation of this underserved and overburdened population.

American Indians (AI) experience high rates of both liver disease and type 2 diabetes (T2D), yet few studies have investigated the contributions of T2D and other known risk factors to liver disease in AI. We used magnetic resonance imaging (MRI)-estimated proton density fat fraction (PDFF) and MR elastography (MRE)-estimated stiffness to assess hepatic fat and fibrosis, respectively, and assessed whether obesity, T2D, and heavy episodic alcohol (ETOH) consumption are associated with these liver measures in AI. The Strong Heart Family Study (SHFS) is a population-based family study of AI recruited from 12 communities located within Arizona (AZ), the Dakotas, and Oklahoma (OK). Metabolic measures were assessed during a clinic visit in 2006-2009. A re-exam including MRI and MRE has been conducted on 109 participants to date from AZ and OK (mean age 50.6 ± 11.3 years, 72% women, 71% obese (BMI ≥ 30 kg/m2), 57% had T2D, and 28% reported ETOH consumption). Median liver PDFF was 8.9% (1rst and 3rd quartiles: 4.3%, 14.6%), with 71% of participants having elevated liver fat (PDFF ≥ 5%). Median liver stiffness was 2.6 kPa, with 23% showing mild liver fibrosis (stiffness 2.8 - 3.63 kPa) and 8.3% advanced liver fibrosis (stiffness > 3.63 kPa). In cross-sectional analyses, liver PDFF was significantly higher in obese vs. non-obese participants (Wilcoxon rank sum test, p Disclosure S.A. Cole: None. W.C. Henderson: None. T. Ali: None. C. West: None. M.S. Middleton: Consultant; Self; Kowa Pharmaceutical Europe Co. Ltd., Median, Novo Nordisk Inc. Stock/Shareholder; Self; General Electric, Pfizer Inc. A. Silva: None. D.N. Batakis: None. A.L. Louie: None. B.V. Howard: None. J.D. Dvorak: None. R. Devereux: Consultant; Self; Acer. J.G. Umans: None. C. Sirlin: Advisory Panel; Self; AMRA Medical, Bristol-Myers Squibb Company, VirtualScopics. Consultant; Self; Fulcrum Therapeutics. Other Relationship; Self; Celgene Corporation, Enanta Pharmaceuticals, Inc., Genzyme, Gilead Sciences, Inc., Gilead Sciences, Inc., ICON plc., Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., NuSirt Biopharma, Inc., Shire, Synageva, Takeda Pharmaceutical Company Limited, VirtualScopics. Y. Zhang: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK110096)

Introduction: Non-alcoholic fatty liver disease has been associated with an increased risk of cardiovascular disease (CVD). Levels of the circulating hepatic enzymes aspartate amino transferase (AST) and alanine amino transferase (ALT) are used as non-invasive biomarkers of liver fat and fibrosis. A number of studies have investigated the potential for these biomarkers of liver function, as well as their ratio AST/ALT, to predict CVD risk, with equivocal results. We hypothesized that these measurements might be important biomarkers of CVD in American Indians (AI) who experience high rates of both liver disease and type 2 diabetes-related CVD. Methods: The Strong Heart Family Study (SHFS) is a population-based family study of heart disease and its risk factors in AI. Participants (n=2760) were recruited from 12 tribes located within 3 geographical regions in Arizona, North/South Dakota, and Oklahoma. Circulating biomarkers and metabolic measures were assessed during a clinic visit in 2001-2003. Participants were followed for morbidity and mortality events until the end of 2016. Median follow-up time was 14.5 years. Results: In this study, 59.8% were female, mean (± standard deviation) age was 40.8 ±17.2 years, mean BMI was 31.3 ± 7.5 kg/m 2 , 19% had type 2 diabetes (T2D), 32.6% were hypertensive, and 36.1% were current smokers. In univariate analyses, higher ALT and AST levels (IU/L) were associated with all components of the metabolic syndrome (MS), i.e., increased waist circumference, triglycerides, blood pressure, fasting glucose, and decreased HDL-C; all p Conclusions: In American Indians of the SHFS, liver function biomarkers are significantly associated with metabolic syndrome and its components, and predict all-cause and cardiovascular mortality, suggesting that common mechanisms impact MS-related CVD risk factors and liver disease biomarker levels in this high-risk population.

The Cerebrovascular Disease and Its Consequences in American Indians (CDCAI) Study recruited surviving members of a 20-year, longitudinal, population-based cohort of American Indians focused on cardiovascular disease, its risk factors, and its consequences. The goal of CDCAI Study is to characterize the burden, risk factors, and manifestations of vascular brain injury identified on cranial magnetic resonance imaging (MRI). CDCAI Study investigators enrolled 1,033 participants aged 60 years and older from 11 American Indian communities and tribes in the Northern Plains, Southern Plains, and Southwestern U.S. In addition to cranial MRI performed according to standardized protocols, participants underwent extensive medical interview, clinical examination, neurocognitive testing, physical function evaluation, electrocardiogram, and provided blood and urine specimens. Participants also self-administered questionnaires covering demographics, quality of life, and medical history. This report describes the design, implementation, and some of the unique challenges of this study and data collection.

Non-caloric artificial sweeteners (NAS) are marketed as healthier alternatives to sugar, but the relationship between consumption of NAS and development of diabetes is unclear. This study assessed the associations of diet soda and NAS consumption with (1) early markers of insulin and glucose homeostasis (cross-sectionally) and (2) incident diabetes (over an average of 8 years of follow-up) among American Indians, a population with high rates of obesity.The study population included Strong Heart Family Study participants without cardiovascular disease or diabetes who participated in the 2007-2009 study exam (n = 1359). Diet soda and NAS consumption were assessed using a Block food frequency questionnaire and supplemental NAS questionnaire at the study exam. Fasting plasma glucose and insulin were measured during the study exam after a 12-h overnight fast. Participants were followed for incident diabetes through December 2017 using a single phone interview and medical record review; diabetes was identified by self-report and confirmed by documentation in medical records. Associations of diet soda and NAS consumption with fasting insulin, glucose, and incident diabetes were assessed using generalized estimating equations (fasting insulin and glucose analyses) and parametric survival models with Weibull distributions (incident diabetes analyses).Just under half of participants reported regularly consuming diet soda (40%) or using NAS to sweeten their beverages (41%). During an average 8 years of follow-up, we identified 98 cases of incident diabetes. After correction for multiple comparisons, there were no statistically significant associations of reported diet soda and NAS consumption with fasting insulin, fasting glucose, or incident diabetes.Although reported consumption of diet soda and NAS were high, neither were associated with diabetes risk.

Background: Clinical stroke is prevalent in American Indians, but the risk factors for cerebrovascular pathology have not been well-studied in this population. The purpose of this study was to correlate abnormalities on brain magnetic resonance imaging (MRI) with clinical risk factors in a cohort of elderly American Indians. Methods: Brain MRI scans from 789 participants of the Strong Heart Study were analyzed for infarcts, hemorrhage, white matter disease, and measures of cerebral atrophy including ventricular and sulcal grade and total brain volume. Clinical risk factors included measures of hypertension, diabetes, and high levels of low-density lipoprotein (LDL) cholesterol. Regression models adjusted for potential confounders were used to estimate associations between risk factors and brain MRI outcomes. Results: ­Hypertension was associated with the presence of infarcts (p = 0.001), ventricle enlargement (p = 0.01), and increased white matter hyperintensity volume (p = 0.01). Diabetes was associated with increased prevalence of cerebral atrophy (p < 0.001), ventricular enlargement (p = 0.001), and sulcal widening (p = 0.001). High LDL was not significantly associated with any of the measured cranial imaging outcomes. Conclusions: This study found risk factors for cerebrovascular disease in American Indians similar to those seen in other populations and provides additional evidence for the important roles of hypertension and diabetes in promoting cerebral infarcts and brain atrophy, respectively.

The associations of pulmonary function with cardiovascular disease (CVD) independent of diabetes mellitus (DM) and metabolic syndrome have not been examined in a population-based setting. We examined prevalence and incidence CVD in relation to lower pulmonary function in the Strong Heart Study second examination (1993 to 1995) in 352 CVD and 2,873 non-CVD adults free of overt lung disease (mean age 60 years). Lung function was assessed by standard spirometry. Participants with metabolic syndrome or DM with or without CVD had lower pulmonary function than participants without these conditions after adjustment for hypertension, age, gender, abdominal obesity, smoking, physical activity index, and study field center. CVD participants with DM had significantly lower forced vital capacity than participants with CVD alone. Significant associations were observed between reduced pulmonary function, preclinical CVD, and prevalent CVD after adjustment for multiple CVD risk factors. During follow-up (median 13.3 years), pulmonary function did not predict CVD incidence, it predicted CVD mortality. Among 3,225 participants, 412 (298 without baseline CVD) died from CVD by the end of 2008. In models adjusted for multiple CVD risk factors, DM, metabolic syndrome, and baseline CVD, compared with highest quartile of lung function, lower lung function predicted CVD mortality (relative risk up to 1.5, 95% confidence interval 1.1 to 2.0, p0.05). In conclusion, a population with a high prevalence of DM and metabolic syndrome and lower lung function was independently associated with prevalent clinical and preclinical CVD, and its impairment predicted CVD mortality. Additional research is needed to identify mechanisms linking metabolic abnormalities, low lung function, and CVD.

OBJECTIVE Prevalence of insulin resistance is high in the American Indian population, likely as a result of the high prevalence of obesity. This condition may be influential for clinical outcomes such as cardiovascular disease (CVD) and decreased kidney function. RESEARCH DESIGN AND METHODS Normal glucose tolerant (NGT) participants free of hypertension and CVD at the baseline examination (1989–1992) (N = 964) of the Strong Heart Study were selected to explore the cross-sectional association between insulin resistance quantified by homeostasis model assessment (HOMA-IR) and demographic, behavioral, and cardiometabolic variables. The longitudinal association between baseline HOMA-IR and the development of CVD was also explored. The longitudinal association between baseline HOMA-IR and the development of high urinary albumin-to-creatinine ratio was explored among nondiabetic participants (N = 1,401). RESULTS Cross-sectionally, HOMA-IR was associated with sex, residence location, smoking, and high-risk cardiometabolic profile. Prospectively, insulin resistance is associated with the development of CVD and decreased kidney function in this population. CONCLUSIONS Insulin resistance may have an important role in the pathogenesis of CVD and chronic kidney disease. Since obesity contributes to the development of insulin resistance, intervention focusing on modifiable factors such as physical activity and weight control may reduce the development of these diseases.

The Balance Study is a randomized controlled trial designed to reduce cardiovascular disease (CVD) risk in 200 American Indian (AI) participants with metabolic syndrome who reside in southwestern Oklahoma. Major risk factors targeted include weight, diet, and physical activity. Participants are assigned randomly to one of two groups, a guided or a self-managed group. The guided group attends intervention meetings that comprise education and experience with the following components: diet, exercise, AI culture, and attention to emotional wellbeing. The self-managed group receives printed CVD prevention materials that are generally available. The duration of the intervention is 24 months. Several outcome variables will be compared between the two groups to assess the effectiveness of the intervention program.

Background: The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain. Methods: We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174 374 deaths or major non-fatal vascular outcomes recorded among 1 085 949 people in 121 prospective studies. Results: For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators. Conclusion: Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces atherosclerosis. LDL and high-density lipoprotein (HDL) are commonly measured by their cholesterol content, but non-HDL cholesterol, LDL particle number (LDL-P), or total apolipoprotein B (apoB) may better predict cardiovascular risk. Few studies have examined relations among lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C. OBJECTIVE: To measure changes in carotid artery intimal media thickness (CIMT) and lipid concentration and composition during 36 months of statin therapy. METHODS: Analyses were conducted on 418 diabetic individuals, with complete data and no prior cardiovascular events, who were randomized to aggressive (AG) versus standard (STD) treatment for LDL-C, non-HDL-C, and systolic blood pressure (SBP) as part of the Stop Atherosclerosis in Native Diabetics Study (SANDS). RESULTS: The AG group achieved average LDL-C and non-HDL-C of 71mg/dL and 100mg/dL and a decrease in CIMT. No significant interactions were observed between treatment effect and initial levels of LDL-C, non-HDL-C, HDL-C, triglycerides, apoB, or LDL-P. Decreases in LDL-C (p

American Indians have a very high prevalence of metabolic syndrome that increases their risk of developing cardiovascular disease and type 2 diabetes. Dietary habits are of central importance in the prevention and treatment of metabolic syndrome.The main objective of this article was to describe dietary intake among American Indians with metabolic syndrome and compare it to several dietary recommendations. A secondary objective was to identify certain barriers to dietary adherence experienced by this population.A total of 213 participants with metabolic syndrome were enrolled in the Balance Study, a randomized controlled trial with two intervention groups: Guided Group and Self-Managed Group. Dietary intake was assessed using the Block Food Frequency questionnaire. Dietary intakes were evaluated against the Dietary Guidelines for Americans.Intakes of saturated fats, cholesterol, and sodium were higher and intakes of dietary fiber, calcium, magnesium, potassium, vitamin A, vitamin D, and vitamin E were lower than recommended. Additionally, intake of many food groups was noticeably low. Economic factors seem to be related to low adherence to dietary recommendations.Results showed low adherence by the participants to dietary recommendations for key nutrients and food groups related to risk factors for metabolic syndrome, type 2 diabetes, and cardiovascular disease. Economic factors are related to this low adherence. These findings illustrate a need to develop innovative, focused, and perhaps individualized health promotion strategies that can improve dietary habits of American Indians with metabolic syndrome.

Rationale: Although obstructive sleep apnea is associated with physiological perturbations that increase risk of hypertension and are proatherogenic, it is uncertain whether sleep apnea is associated with increased stroke risk in the general population. Objectives: To quantify the incidence of ischemic stroke with sleep apnea in a community-based sample of men and women across a wide range of sleep apnea. Methods: Baseline polysomnography was performed between 1995 and 1998 in a longitudinal cohort study. The primary exposure was the obstructive apnea–hypopnea index (OAHI) and outcome was incident ischemic stroke. Measurements and Main Results: A total of 5,422 participants without a history of stroke at the baseline examination and untreated for sleep apnea were followed for a median of 8.7 years. One hundred ninety-three ischemic strokes were observed. In covariate-adjusted Cox proportional hazard models, a significant positive association between ischemic stroke and OAHI was observed in men (P value for linear trend: P = 0.016). Men in the highest OAHI quartile (>19) had an adjusted hazard ratio of 2.86 (95% confidence interval, 1.1–7.4). In the mild to moderate range (OAHI, 5–25), each one-unit increase in OAHI in men was estimated to increase stroke risk by 6% (95% confidence interval, 2–10%). In women, stroke was not significantly associated with OAHI quartiles, but increased risk was observed at an OAHI greater than 25. Conclusions: The strong adjusted association between ischemic stroke and OAHI in community-dwelling men with mild to moderate sleep apnea suggests that this is an appropriate target for future stroke prevention trials.

BACKGROUND: Lowering low-density lipoprotein cholesterol (LDL-C) with statins reduces atherosclerosis. LDL and high-density lipoprotein (HDL) are commonly measured by their cholesterol content, but non-HDL cholesterol, LDL particle number (LDL-P), or total apolipoprotein B (apoB) may better predict cardiovascular risk. Few studies have examined relations among lipoprotein levels and composition before and after interventions to lower LDL-C and non-HDL-C. OBJECTIVE: To measure changes in carotid artery intimal media thickness (CIMT) and lipid concentration and composition during 36 months of statin therapy. METHODS: Analyses were conducted on 418 diabetic individuals, with complete data and no prior cardiovascular events, who were randomized to aggressive (AG) versus standard (STD) treatment for LDL-C, non-HDL-C, and systolic blood pressure (SBP) as part of the Stop Atherosclerosis in Native Diabetics Study (SANDS). RESULTS: The AG group achieved average LDL-C and non-HDL-C of 71mg/dL and 100mg/dL and a decrease in CIMT. No significant interactions were observed between treatment effect and initial levels of LDL-C, non-HDL-C, HDL-C, triglycerides, apoB, or LDL-P. Decreases in LDL-C (p.005) and non-HDL-C (p.001) were independently correlated with CIMT regression in the AG group. Changes in apoB and LDL-P showed borderline correlations with CIMT regression (p=.07 and p=.09). CONCLUSIONS: In diabetic adults with no prior cardiovascular events, treatment to current targets for lipids and SBP reduces atherosclerosis progression and when more aggressive targets are met, atherosclerosis regresses. The aggressive targets for LDL-C and non-HDL-C appeared to be the main determinants of CIMT regression and were more predictive of this outcome than changes in LDL-P or apoB.

Brachial blood pressure is predictive of cardiovascular outcome; however central pressure may better represent the load imposed on the coronary and cerebral arteries and thereby bear a stronger relationship to vascular damage and prognosis. Relations of brachial and central pressures to carotid artery hypertrophy (intimal-medial thickness and vascular mass), extent of atherosclerosis (plaque score), and incident cardiovascular events were examined in the Strong Heart Study. Central pressures were calculated using radial applanation tonometry. Among 3520 participants, central and brachial pulse pressures were more strongly related to vascular hypertrophy and extent of atherosclerosis than were systolic pressures. Central pulse pressure was more strongly related to all 3 arterial measures than was brachial pulse pressure ( r =0.364 versus 0.309 for plaque score; P r =0.293 versus 0.249 for intimal-medial thickness; P r =0.320 versus 0.289 for vascular mass; P 2 =13.4, P 2 =6.9, P =0.008). In conclusion, noninvasively-determined central pulse pressure is more strongly related to vascular hypertrophy, extent of atherosclerosis, and cardiovascular events than is brachial blood pressure. These findings support prospective examination of use of central blood pressure as a treatment target in future trials.

Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2,737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI1.5 to 8.8 (4.8) in subjects with RDI/= 15 (p0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score/= 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults.