Publications by authors named "Fawn Yeh"

35 Publications

Cancer mortality in a population-based cohort of American Indians - The strong heart study.

Cancer Epidemiol 2021 Oct 19;74:101978. Epub 2021 Jul 19.

MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD, 20782, USA; Georgetown, Howard Universities Center for Clinical and Translational Research, Washington, DC, 2000, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.canep.2021.101978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455435PMC
October 2021

Correction to: Low-moderate arsenic exposure and respiratory health in American Indian communities in the Strong Heart Study.

Environ Health 2020 Feb 26;19(1):24. Epub 2020 Feb 26.

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, USA.

The original version of this article [1], published on 28 November 2019, contained incorrect title. In this Correction the affected part of the article is shown.
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http://dx.doi.org/10.1186/s12940-020-00576-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7043028PMC
February 2020

Low-moderate arsenic exposure and respiratory in American Indian communities in the Strong Heart Study.

Environ Health 2019 11 28;18(1):104. Epub 2019 Nov 28.

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe St, Baltimore, MD, USA.

Background: Arsenic exposure through drinking water is an established lung carcinogen. Evidence on non-malignant lung outcomes is less conclusive and suggests arsenic is associated with lower lung function. Studies examining low-moderate arsenic (< 50 μg/L), the level relevant for most populations, are limited. We evaluated the association of arsenic exposure with respiratory health in American Indians from the Northern Plains, the Southern Plains and the Southwest United States, communities with environmental exposure to inorganic arsenic through drinking water.

Methods: The Strong Heart Study is a prospective study of American Indian adults. This analysis used urinary arsenic measurements at baseline (1989-1991) and spirometry at Visit 2 (1993-1995) from 2132 participants to evaluate associations of arsenic exposure with airflow obstruction, restrictive pattern, self-reported respiratory disease, and symptoms.

Results: Airflow obstruction was present in 21.5% and restrictive pattern was present in 14.4%. The odds ratio (95% confidence interval) for obstruction and restrictive patterns, based on the fixed ratio definition, comparing the 75th to 25th percentile of arsenic, was 1.17 (0.99, 1.38) and 1.27 (1.01, 1.60), respectively, after adjustments, and 1.28 (1.02, 1.60) and 1.33 (0.90, 1.50), respectively, based on the lower limit of normal definition. Arsenic was associated with lower percent predicted FEV1 and FVC, self-reported emphysema and stopping for breath.

Conclusion: Low-moderate arsenic exposure was positively associated with restrictive pattern, airflow obstruction, lower lung function, self-reported emphysema and stopping for breath, independent of smoking and other lung disease risk factors. Findings suggest that low-moderate arsenic exposure may contribute to restrictive lung disease.
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http://dx.doi.org/10.1186/s12940-019-0539-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883619PMC
November 2019

Lung Function and Respiratory Symptoms after Tuberculosis in an American Indian Population. The Strong Heart Study.

Ann Am Thorac Soc 2020 01;17(1):38-48

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Permanent lung function impairment after active tuberculosis infection is relatively common. It remains unclear which spirometric pattern is most prevalent after tuberculosis. Our objective was to elucidate the impact of active tuberculosis survival on lung health in the Strong Heart Study (SHS), a population of American Indians historically highly impacted by tuberculosis. As arsenic exposure has also been related to lung function in the SHS, we also assessed the joint effect between arsenic exposure and past active tuberculosis. The SHS is an ongoing population-based, prospective study of cardiovascular disease and its risk factors in American Indian adults. This study uses tuberculosis data and spirometry data from the Visit 2 examination (1993-1995). Prior active tuberculosis was ascertained by a review of medical records. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV), and FEV/FVC were measured by spirometry. An additional analysis was conducted to evaluate the potential association between active tuberculosis and arsenic exposure. A history of active tuberculosis was associated with reduced percent predicted FVC and FEV, an increased odds of airflow obstruction (odds ratio = 1.45, 95% confidence interval = 1.08-1.95), and spirometric restrictive pattern (odds ratio = 1.73, 95% confidence interval = 1.24-2.40). These associations persisted after adjustment for diabetes and other risk factors, including smoking. We also observed the presence of cough, phlegm, and exertional dyspnea after a history of active tuberculosis. In the additional analysis, increasing urinary arsenic concentrations were associated with decreasing lung function in those with a history of active tuberculosis, but a reduced odds of active tuberculosis was found with elevated arsenic. Our findings support existing knowledge that a history of active tuberculosis is a risk factor for long-term respiratory impairment. Arsenic exposure, although inversely associated with prior active tuberculosis, was associated with a further decrease in lung function among those with a prior active tuberculosis history. The possible interaction between arsenic and tuberculosis, as well as the reduced odds of tuberculosis associated with arsenic exposure, warrants further investigation, as many populations at risk of developing active tuberculosis are also exposed to arsenic-contaminated water.
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http://dx.doi.org/10.1513/AnnalsATS.201904-281OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944345PMC
January 2020

Associations of diet soda and non-caloric artificial sweetener use with markers of glucose and insulin homeostasis and incident diabetes: the Strong Heart Family Study.

Eur J Clin Nutr 2020 02 28;74(2):322-327. Epub 2019 Jun 28.

Department of Epidemiology, University of Washington, Seattle, WA, USA.

Background/objectives: 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.

Subjects/methods: 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).

Results: 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.

Conclusions: Although reported consumption of diet soda and NAS were high, neither were associated with diabetes risk.
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http://dx.doi.org/10.1038/s41430-019-0461-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934923PMC
February 2020

Telomere length and cancer mortality in American Indians: the Strong Heart Study.

Geroscience 2019 06 22;41(3):351-361. Epub 2019 Jun 22.

Department of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida, 2004 Mowry Road, Gainesville, FL, 32610, USA.

The objective of this study was to investigate whether leukocyte telomere length (LTL) predicts the risk for cancer mortality among American Indians participating in the Strong Heart Study (1989-1991). Participants (aged 45-74 years) were followed annually until December 2015 to collect information on morbidity/mortality. LTL was measured by qPCR using genomic DNA isolated from peripheral blood. The association between LTL and risk for cancer mortality was examined using a multivariable Cox proportional hazard model, adjusting for age, gender, education, study site, smoking, alcohol use, physical activity, systolic blood pressure, fasting blood glucose, obesity, and low- and high-density lipoprotein. Of 1945 participants (mean age 56.10 ± 8.17 at baseline, 57% women) followed for an average 20.5 years, 220 died of cancer. Results showed that longer LTL at baseline significantly predicts an increased risk of cancer death among females (HR 1.57, 95% CI 1.08-2.30), but not males (HR 0.74, 95% CI 0.49-1.12) (p for interaction 0.009). Specifically, compared with the women with the longest LTL (fourth quartile), those in the third, second, and first quartiles showed 53%, 41%, and 44% reduced risk for cancer death, respectively. The findings highlight the importance of sex-specific analysis in future telomere research.
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http://dx.doi.org/10.1007/s11357-019-00080-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702505PMC
June 2019

Harmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.

Am J Epidemiol 2018 11;187(11):2265-2278

Division of General Medicine, Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.
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http://dx.doi.org/10.1093/aje/kwy139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211239PMC
November 2018

Target organ damage and incident type 2 diabetes mellitus: the Strong Heart Study.

Cardiovasc Diabetol 2017 05 12;16(1):64. Epub 2017 May 12.

Weill Cornell Medicine, New York, NY, USA.

Background: Recent analyses in a registry of hypertensive patients suggested that preceding left ventricular (LV) hypertrophy (LVH) and/or carotid atherosclerosis are associated with incident type 2 diabetes, independent of confounders. We assess the relation between prevalent cardio-renal target organ damage (TOD) and subsequent incident type 2 diabetes in a population-based study with high prevalence of obesity.

Methods: We selected 2887 non-diabetic participants from two cohorts of the Strong Heart Study (SHS). Clinical exam, laboratory tests and echocardiograms were performed. Adjudicated TODs were LVH, left atrium (LA) dilatation, and high urine albumin/creatinine ratio (UACR). Multivariable logistic regression models were used to identify variables responsible for the association between initial TODs and incident diabetes at 4-year follow-up (FU).

Results: After 4 years, 297 new cases of diabetes (10%) were identified, 216 of whom exhibited baseline impaired fasting glucose (IFG, 73%, p < 0.0001). Participants developing type 2 diabetes exhibited higher inflammatory markers, fat-free mass and adipose mass and higher prevalence of initial LVH and LA dilatation than those without (both p < 0.04). In multivariable logistic regression, controlling for age, sex, family relatedness, presence of arterial hypertension and IFG, all three indicators of TOD predicted incident diabetes (all p < 0.01). However, the effects of TOD was offset when body fat and inflammatory markers were introduced into the model.

Conclusions: In this population-based study with high prevalence of obesity, TOD precedes clinical appearance of type 2 diabetes and is related to the preceding metabolic status, body composition and inflammatory status. Trial registration Trial registration number: NCT00005134, Name of registry: Strong Heart Study, URL of registry: https://clinicaltrials.gov/ct2/show/NCT00005134, Date of registration: May 25, 2000, Date of enrolment of the first participant to the trial: September 1988.
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http://dx.doi.org/10.1186/s12933-017-0542-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5427627PMC
May 2017

The Relationship between Environmental Tobacco Smoke Exposure and Cardiovascular Disease and the Potential Modifying Effect of Diet in a Prospective Cohort among American Indians: The Strong Heart Study.

Int J Environ Res Public Health 2017 05 9;14(5). Epub 2017 May 9.

Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, USA.

American Indians experience high rates of cardiovascular diseases (CVD). Environmental tobacco smoke (ETS) has been linked to CVD, possibly due to pro-inflammatory and oxidative stress pathways. We examined the relationship between self-reported exposure to ETS and fatal and nonfatal CVD incidence using Cox proportional hazards models among 1843 non-smoking American Indians participating in the Strong Heart Study. We also evaluated potential modifying effects of several dietary nutrients high in anti-inflammatory and anti-oxidant properties with ETS exposure on fatal and nonfatal CVD by creating interaction terms between ETS exposure and the dietary variable. Participants exposed to ETS had a higher hazard (hazard ratio: 1.22; 95% confidence interval, 1.03 to 1.44) for developing CVD compared to persons not exposed. Interaction analyses suggested stronger effects of ETS on CVD incidence among those consuming diets lower in vitamin E as compared to those consuming higher amounts, particularly on the additive scale. Additional research is recommended to clarify whether public health prevention strategies should simultaneously target reductions in ETS exposures and improvements in diets that may exceed the expected benefits of targeting these risk factors separately.
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http://dx.doi.org/10.3390/ijerph14050504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5451955PMC
May 2017

Relationship between plasma plasminogen activator inhibitor-1 and hypertension in American Indians: findings from the Strong Heart Study.

J Hypertens 2017 09;35(9):1787-1793

aDepartment of Epidemiology, College of Public Health and Health Professions, College of Medicine, University of Florida, Gainesville, Florida bCenter for American Indian Health Research, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA cDepartment of Clinical and Experimental Medicine, Federico II University, Naples, Italy dEagle Butte Industries Research Inc, Timber Lake, South Dakota eMedStar Health Research Institute, Hyattsville, Maryland, USA.

Objectives: Deficient plasminogen activator inhibitor-1 (PAI-1) prevented hypertension in mice. Plasma PAI-1 was associated with hypertension in cross-sectional analyses, but the prospective association of PAI-1 with incident hypertension in large epidemiological studies is scarce.

Methods: Leveraging two longitudinal cohorts of American Indians in the Strong Heart Study (SHS, N = 1019) and the Strong Heart Family Study (SHFS, N = 1502), we examined the prospective association of plasma PAI-1 with incident hypertension by multivariate logistic regression, adjusting for age, sex, study site, smoking, drinking, dietary sodium, obesity, lipids, fasting glucose, kidney function, inflammation, and follow-up years. Family relatedness in the SHFS was accounted for using the GLIMMIX procedure. Plasma PAI-1 level at baseline was measured by immunoassay. All participants were free of hypertension, cardiovascular diseases, and chronic kidney disease at baseline.

Results: A total of 305 and 258 participants, respectively, from the SHS (57 ± 7 years) and the SHFS (33 ± 13 years) developed incident hypertension during follow-up. In the SHS, higher level of log-transformed PAI-1 was associated with 1.35-fold increased risk of hypertension [odds ratio (OR) (95% confidence interval): 1.35 (1.06-1.72)]. Analysis using categorical PAI-1 (in tertiles) showed that participants in the highest tertile (≥58 ng/ml) had 63% increased risk for hypertension [OR = 1.63 (1.12-2.37)] compared with those in the lowest tertile (<33 ng/ml). This association was confirmed in the SHFS with similar effect sizes [OR = 1.41 (1.11-1.81) for log-transformed PAI-1; OR = 1.64 (1.08-2.50) for categorical PAI-1: ≥58 vs. <33 ng/ml].

Conclusion: A higher level of plasma PAI-1 is significantly associated with hypertension in American Indians, independent of established risk factors. The potential causality warrants further investigation.
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http://dx.doi.org/10.1097/HJH.0000000000001375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5615403PMC
September 2017

Dietary determinants of cadmium exposure in the Strong Heart Family Study.

Food Chem Toxicol 2017 Feb 22;100:239-246. Epub 2016 Dec 22.

Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

Urinary cadmium (Cd) concentrations in the Strong Heart Family Study (SHFS) participants are higher than in the general US population. This difference is unlikely to be related to tobacco smoking. We evaluated the association of consumption of processed meats and other dietary products with urinary Cd concentrations in the SHFS, a family-based study conducted in American Indian communities. We included 1725 participants with urine Cd concentrations (standardized to urine creatinine) and food frequency questionnaire data grouped in 24 categories, including processed meat. Median (IQR) urinary Cd concentrations were 0.42 (0.20-0.85) μg/g creatinine. The age, sex, smoking, education, center, body mass index, and total kcal adjusted geometric mean ratio (GMR) (95%CI) of urinary cadmium concentrations per IQR increase in each dietary category was 1.16 (1.04-1.29) for processed meat, 1.10 (1.00-1.21) for fries and chips, 0.87 (0.80-0.95) for dairy products, and 0.89 (0.82-0.97) for fruit juices. The results remained similar after further adjustment for the dietary categories associated with urinary Cd in the previous model except for fries and chips, which was no longer statistically significant. These findings revealed the potential importance of processed meat products as a dietary source of cadmium.
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http://dx.doi.org/10.1016/j.fct.2016.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373690PMC
February 2017

Depressive symptoms are associated with leukocyte telomere length in American Indians: findings from the Strong Heart Family Study.

Aging (Albany NY) 2016 11;8(11):2961-2970

Department of Epidemiology, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32611, USA.

Patients with depression have an increased risk for many aging-related disorders, but the biological mechanisms underlying this link remain to be determined. Here we examined the association between depressive symptoms and leukocyte telomere length (LTL), a marker of biological aging, among 2,175 American Indians participating in the Strong Heart Family Study. Depressive symptoms were assessed by the Center for Epidemiologic Studies of Depression Scale (CES-D), which was categorized into four levels: none (< 10), mild (10-15), moderate (16 -24), and severe (> 24). LTL (T/S ratio) was quantified by qPCR. The association between depressive symptoms and LTL was examined by multivariate generalized estimating equation models, adjusting for sociodemographic factors, lifestyle factors, and chronic conditions. Results showed that individuals with a higher level of depressive symptoms had shorter LTL. Specifically, LTL in participants reporting none, mild, moderate, and severe depressive symptoms were 1.000, 0.999, 0.988, and 0.966, respectively ( for trend = 0.0278). Moreover, gender appears to modulate the effect of reported depressive symptoms that fall in the severe range (CES-D > 24) on LTL ( for interaction = 0.0346). Our results suggest that depressive symptoms may accelerate biological aging through pathways beyond traditional risk factors in American Indians.
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http://dx.doi.org/10.18632/aging.101104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5191880PMC
November 2016

Impact of biological aging on arterial aging in American Indians: findings from the Strong Heart Family Study.

Aging (Albany NY) 2016 08;8(8):1583-92

Department of Epidemiology, Tulane University School of Public Health, New Orleans, LA 70112, USA.

Telomere length, a marker of biological aging, has been associated with cardiovascular disease (CVD). Increased arterial stiffness, an indicator of arterial aging, predicts adverse CVD outcomes. However, the relationship between telomere length and arterial stiffness is less well studied. Here we examined the cross-sectional association between leukocyte telomere length (LTL) and arterial stiffness in 2,165 American Indians in the Strong Heart Family Study (SHFS). LTL was measured by qPCR. Arterial stiffness was assessed by stiffness index β. The association between LTL and arterial stiffness was assessed by generalized estimating equation model, adjusting for sociodemographics (age, sex, education level), study site, metabolic factors (fasting glucose, lipids, systolic blood pressure, and kidney function), lifestyle (BMI, smoking, drinking, and physical activity), and prevalent CVD. Results showed that longer LTL was significantly associated with a decreased arterial stiffness (β=-0.070, P=0.007). This association did not attenuate after further adjustment for hsCRP (β=-0.071, P=0.005) or excluding participants with overt CVD (β=-0.068, P=0.012), diabetes (β=-0.070, P=0.005), or chronic kidney disease (β=-0.090, P=0.001). In summary, shorter LTL was significantly associated with an increased arterial stiffness, independent of known risk factors. This finding may shed light on the potential role of biological aging in arterial aging in American Indians.
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http://dx.doi.org/10.18632/aging.101013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5032684PMC
August 2016

Association of diabetes and cancer mortality in American Indians: the Strong Heart Study.

Cancer Causes Control 2015 Nov 7;26(11):1551-60. Epub 2015 Aug 7.

Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.

Purpose: The metabolic abnormalities that accompany diabetes mellitus are associated with an increased risk of many cancers. These associations, however, have not been well studied in American Indian populations, which experience a high prevalence of diabetes. The Strong Heart Study is a population-based, prospective cohort study with extensive characterization of diabetes status.

Methods: Among a total cohort of 4,419 participants who were followed for up to 20 years, 430 cancer deaths were identified.

Results: After adjusting for sex, age, education, smoking status, drinking status, and body mass index, participants with diabetes at baseline showed an increased risk of gastric (HR 4.09; 95% CI 1.42-11.79), hepatocellular (HR 2.94; 95% CI 1.17-7.40), and prostate cancer mortality (HR 3.10; 95% CI 1.22-7.94). Further adjustment for arsenic exposure showed a significantly increased risk of all-cause cancer mortality with diabetes (HR 1.27; 95% CI 1.03-1.58). Insulin resistance among participants without diabetes at baseline was associated with hepatocellular cancer mortality (HR 4.70; 95% CI 1.55-14.26).

Conclusions: Diabetes mellitus, and/or insulin resistance among those without diabetes, is a risk factor for gastric, hepatocellular, and prostate cancer in these American Indian communities, although relatively small sample size suggests cautious interpretation. Additional research is needed to evaluate the role of diabetes and obesity on cancer incidence in American Indian communities as well as the importance of diabetes prevention and control in reducing the burden of cancer incidence and mortality in the study population.
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http://dx.doi.org/10.1007/s10552-015-0648-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596901PMC
November 2015

Smoking-attributable mortality in American Indians: findings from the Strong Heart Study.

Eur J Epidemiol 2015 Jul 13;30(7):553-61. Epub 2015 May 13.

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St. Suite 2000 SL-18, New Orleans, LA, 70112, USA.

Cigarette smoking is the leading preventable cause of death worldwide. American Indians have the highest proportion of smoking in the United States. However, few studies have examined the impact of cigarette smoking on disease mortality in this ethnically important but traditionally understudied minority population. Here we estimated the association of cigarette smoking with cardiovascular disease (CVD), cancer and all-cause mortality in American Indians participating in the Strong Heart Study, a large community-based prospective cohort study comprising of 4549 American Indians (aged 45-74 years) followed for about 20 years (1989-2008). Hazard ratio and population attributable risk (PAR) associated with cigarette smoking were estimated by Cox proportional hazard model, adjusting for sex, study site, age, educational level, alcohol consumption, physical activity, BMI, lipids, renal function, hypertension or diabetes status at baseline, and interaction between current smoker and study site. We found that current smoking was significantly associated with cancer mortality (HR 5.0, [1.9-13.4]) in men, (HR 3.9 [1.6-9.7] in women) and all-cause mortality (HR 1.8, [1.2-2.6] in men, HR 1.6, [1.1-2.4] in women). PAR for cancer and all-cause mortality in men were 41.0 and 18.4 %, respectively, whereas the corresponding numbers in women were 24.9 and 10.9 %, respectively. Current smoking also significantly increases the risk of CVD deaths in women (HR 2.2 [1.1, 4.4]), but not men (HR 1.2 [0.6-2.4]). PAR for CVD mortality in women was 14.9 %. In summary, current smoking significantly increases the risk of CVD (in women), cancer and all-cause mortality in American Indians, independent of known risk factors. Culturally specific smoking cessation programs are urgently needed to reduce smoking-related premature deaths.
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http://dx.doi.org/10.1007/s10654-015-0031-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519414PMC
July 2015

The association of urine arsenic with prevalent and incident chronic kidney disease: evidence from the Strong Heart Study.

Epidemiology 2015 Jul;26(4):601-12

From the aDepartment of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; bMedStar Health Research Institute, Hyattsville, MD; cGeorgetown-Howard Universities Center for Clinical and Translational Science, Washington, DC; dCollege of Public Health, University of Oklahoma, Oklahoma City, OK; eInstitute of Chemistry-Analytical Chemistry, Karl-Franzens University, Graz, Austria; fDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD. gDepartment of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; hWelch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD; iArea of Epidemiology and Population Genetics, National Center for Cardiovascular Research (CNIC), Madrid, Spain; and jDepartment of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD.

Background: Few studies have evaluated associations between low to moderate arsenic levels and chronic kidney disease (CKD). The objective was to evaluate the associations of inorganic arsenic exposure with prevalent and incident CKD in American Indian adults.

Methods: We evaluated the associations of inorganic arsenic exposure with CKD in American Indians who participated in the Strong Heart Study in 3,851 adults ages 45-74 years in a cross-sectional analysis, and 3,119 adults with follow-up data in a prospective analysis. Inorganic arsenic, monomethylarsonate, and dimethylarsinate were measured in urine at baseline. CKD was defined as estimated glomerular filtration rate ≤ 60 ml/min/1.73 m, kidney transplant or dialysis.

Results: CKD prevalence was 10.3%. The median (IQR) concentration of inorganic plus methylated arsenic species (total arsenic) in urine was 9.7 (5.8, 15.7) μg/L. The adjusted odds ratio (OR; 95% confidence interval) of prevalent CKD for an interquartile range in total arsenic was 0.7 (0.6, 0.8), mostly due to an inverse association with inorganic arsenic (OR: 0.4 [0.3, 0.4]). Monomethylarsonate and dimethylarsinate were positively associated with prevalent CKD after adjustment for inorganic arsenic (OR: 3.8 and 1.8). The adjusted hazard ratio of incident CKD for an IQR in sum of inorganic and methylated arsenic was 1.2 (1.03, 1.41). The corresponding HRs for inorganic arsenic, monomethylarsonate, and dimethylarsinate were 1.0 (0.9, 1.2), 1.2 (1.00, 1.3), and 1.2 (1.0, 1.4).

Conclusions: The inverse association of urine inorganic arsenic with prevalent CKD suggests that kidney disease affects excretion of inorganic arsenic. Arsenic species were positively associated with incident CKD. Studies with repeated measures are needed to further characterize the relation between arsenic and kidney disease development.
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http://dx.doi.org/10.1097/EDE.0000000000000313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844343PMC
July 2015

Joint association of nicotinic acetylcholine receptor variants with abdominal obesity in American Indians: the Strong Heart Family Study.

PLoS One 2014 18;9(7):e102220. Epub 2014 Jul 18.

Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States of America.

Cigarette smoke is a strong risk factor for obesity and cardiovascular disease. The effect of genetic variants involved in nicotine metabolism on obesity or body composition has not been well studied. Though many genetic variants have previously been associated with adiposity or body fat distribution, a single variant usually confers a minimal individual risk. The goal of this study is to evaluate the joint association of multiple variants involved in cigarette smoke or nicotine dependence with obesity-related phenotypes in American Indians. To achieve this goal, we genotyped 61 tagSNPs in seven genes encoding nicotine acetylcholine receptors (nAChRs) in 3,665 American Indians participating in the Strong Heart Family Study. Single SNP association with obesity-related traits was tested using family-based association, adjusting for traditional risk factors including smoking. Joint association of all SNPs in the seven nAChRs genes were examined by gene-family analysis based on weighted truncated product method (TPM). Multiple testing was controlled by false discovery rate (FDR). Results demonstrate that multiple SNPs showed weak individual association with one or more measures of obesity, but none survived correction for multiple testing. However, gene-family analysis revealed significant associations with waist circumference (p = 0.0001) and waist-to-hip ratio (p = 0.0001), but not body mass index (p = 0.20) and percent body fat (p = 0.29), indicating that genetic variants are jointly associated with abdominal, but not general, obesity among American Indians. The observed combined genetic effect is independent of cigarette smoking per se. In conclusion, multiple variants in the nAChR gene family are jointly associated with abdominal obesity in American Indians, independent of general obesity and cigarette smoking per se.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0102220PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103845PMC
March 2015

Short leukocyte telomere length predicts incidence and progression of carotid atherosclerosis in American Indians: the Strong Heart Family Study.

Aging (Albany NY) 2014 May;6(5):414-27

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA;

Short leukocyte telomere length (LTL) has been associated with atherosclerosis in cross-sectional studies, but the prospective relationship between telomere shortening and risk of developing carotid atherosclerosis has not been well-established. This study examines whether LTL at baseline predicts incidence and progression of carotid atherosclerosis in American Indians in the Strong Heart Study. The analysis included 2,819 participants who were free of overt cardiovascular disease at baseline (2001-2003) and were followed through the end of 2006-2009 (average 5.5-yr follow-up). Discrete atherosclerotic plaque was defined as focal protrusion with an arterial wall thickness ≥50% the surrounding wall. Carotid progression was defined as having a higher plaque score at the end of study follow-up compared to baseline. Associations of LTL with incidence and progression of carotid plaque were examined using Cox proportional hazard regression, adjusting for standard coronary risk factors. Compared to participants in the highest LTL tertile, those in the lowest tertile had significantly elevated risk for both incident plaque (HR, 1.49; 95% CI, 1.09-2.03) and plaque progression (HR, 1.61; 95% CI, 1.26-2.07). Our results provide initial evidence for a potential prognostic utility of LTL in risk prediction for atherosclerosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069268PMC
http://dx.doi.org/10.18632/aging.100671DOI Listing
May 2014

Lung function and heart disease in American Indian adults with high frequency of metabolic abnormalities (from the Strong Heart Study).

Am J Cardiol 2014 Jul 2;114(2):312-9. Epub 2014 May 2.

Weill Cornell Medical College, New York, New York.

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, p<0.05). 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.
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http://dx.doi.org/10.1016/j.amjcard.2014.04.042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4093833PMC
July 2014

Short leukocyte telomere length is associated with obesity in American Indians: the Strong Heart Family study.

Aging (Albany NY) 2014 May;6(5):380-9

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA 70112, USA.

Shorter leukocyte telomere length (LTL) has been associated with a wide range of age-related disorders including cardiovascular disease (CVD) and diabetes. Obesity is an important risk factor for CVD and diabetes. The association of LTL with obesity is not well understood. This study for the first time examines the association of LTL with obesity indices including body mass index, waist circumference, percent body fat, waist-to-hip ratio, and waist-to-height ratio in 3,256 American Indians (14-93 years old, 60% women) participating in the Strong Heart Family Study. Association of LTL with each adiposity index was examined using multivariate generalized linear mixed model, adjusting for chronological age, sex, study center, education, lifestyle (smoking, alcohol consumption, and total energy intake), high-sensitivity C-reactive protein, hypertension and diabetes. Results show that obese participants had significantly shorter LTL than non-obese individuals (age-adjusted P=0.0002). Multivariate analyses demonstrate that LTL was significantly and inversely associated with all of the studied obesity parameters. Our results may shed light on the potential role of biological aging in pathogenesis of obesity and its comorbidities.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4069265PMC
http://dx.doi.org/10.18632/aging.100664DOI Listing
May 2014

Leukotriene haplotype × diet interaction on carotid artery hypertrophy and atherosclerosis in American Indians: the Strong Heart Family Study.

Atherosclerosis 2014 Mar 10;233(1):165-71. Epub 2014 Jan 10.

MedStar Health Research Institute Hyattsville, MD and Georgetown and Howard Universities Centers for Translational Sciences, Washington, DC, USA.

Objective: Gene × diet interaction plays an important role in atherosclerosis, an inflammatory disorder. Leukotrienes are the most potent inflammatory mediators, and genetic variants encoding leukotriene genes have been implicated in atherosclerosis. This study tests nutrigenetic interaction of a previously defined leukotriene haplotype on carotid artery hypertrophy and atherosclerosis in American Indians.

Methods: This study included 3402 American Indians participating in the Strong Heart Family Study (SHFS). Carotid artery measurements, including intima-media thickness (IMT), vascular mass, and plaque, were assessed using ultrasound. Eleven tagSNPs in the leukotriene A4 hydrolase (LTA4H) gene were genotyped in all subjects. Main haplotype effect and haplotype × diet interaction were examined by generalized estimating equation, adjusting for known risk factors.

Results: There was no significant main effect of haplotype or diet on any of the carotid artery measures. However, a previously defined LTA4H haplotype, called HapE, significantly interacted with dietary intake of n-3 and n-6 fatty acids on both IMT (P(HapE × n3) = 0.018, P(HapE × n6) = 0.040) and vascular mass (P(HapE × n3) = 0.012, P(HapE × n6) = 0.018), but not plaque. The direction of this nutrigenetic interaction on IMT was consistent with that reported in a recent study of Caucasian twins.

Conclusion: Dietary intake of polyunsaturated fatty acids significantly modifies the effect of a leukotriene haplotype on carotid artery hypertrophy but not atherosclerosis in American Indians, independent of established cardiovascular risk factors. Replication of nutrigenetic interaction in two distinct ethnic groups suggests the robustness and generalizability of our findings to diverse populations.
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http://dx.doi.org/10.1016/j.atherosclerosis.2013.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3932307PMC
March 2014

Insulin resistance, incident cardiovascular diseases, and decreased kidney function among nondiabetic American Indians: the Strong Heart Study.

Diabetes Care 2013 Oct 4;36(10):3195-200. Epub 2013 Jun 4.

Corresponding author: Ying Zhang,

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.
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http://dx.doi.org/10.2337/dc12-2368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3781520PMC
October 2013

Urine arsenic and prevalent albuminuria: evidence from a population-based study.

Am J Kidney Dis 2013 Mar 9;61(3):385-94. Epub 2012 Nov 9.

Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.

Background: Long-term arsenic exposure is a major global health problem. However, few epidemiologic studies have evaluated the association of arsenic with kidney measures. Our objective was to evaluate the cross-sectional association between inorganic arsenic exposure and albuminuria in American Indian adults from rural areas of Arizona, Oklahoma, and North and South Dakota.

Study Design: Cross-sectional. SETTING & PARTIPANTS: Strong Heart Study locations in Arizona, Oklahoma, and North and South Dakota. 3,821 American Indian men and women aged 45-74 years with urine arsenic and albumin measurements.

Predictor: Urine arsenic.

Outcomes: Urine albumin-creatinine ratio and albuminuria status.

Measurements: Arsenic exposure was estimated by measuring total urine arsenic and urine arsenic species using inductively coupled plasma mass spectrometry (ICPMS) and high-performance liquid chromatography-ICPMS, respectively. Urine albumin was measured by automated nephelometric immunochemistry.

Results: The prevalence of albuminuria (albumin-creatinine ratio ≥30 mg/g) was 30%. Median value for the sum of inorganic and methylated arsenic species was 9.7 (IQR, 5.8-15.6) μg per gram of creatinine. Multivariable-adjusted prevalence ratios of albuminuria (albumin-creatinine ratio ≥30 mg/g) comparing the 3 highest to lowest quartiles of the sum of inorganic and methylated arsenic species were 1.16 (95% CI, 1.00-1.34), 1.24 (95% CI, 1.07-1.43), and 1.55 (95% CI, 1.35-1.78), respectively (P for trend <0.001). The association between urine arsenic and albuminuria was observed across all participant subgroups evaluated and was evident for both micro- and macroalbuminuria.

Limitations: The cross-sectional design cannot rule out reverse causation.

Conclusions: Increasing urine arsenic concentrations were cross-sectionally associated with increased albuminuria in a rural US population with a high burden of diabetes and obesity. Prospective epidemiologic and mechanistic evidence is needed to understand the role of arsenic as a kidney disease risk factor.
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http://dx.doi.org/10.1053/j.ajkd.2012.09.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578134PMC
March 2013

Obesity in adults is associated with reduced lung function in metabolic syndrome and diabetes: the Strong Heart Study.

Diabetes Care 2011 Oct 18;34(10):2306-13. Epub 2011 Aug 18.

College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.

Objective: The purposes of this study were to investigate whether reduced lung function is associated with metabolic syndrome (MS) and diabetes (DM) in American Indians (AIs) and to determine whether lower pulmonary function presents before the development of DM or MS.

Research Design And Methods: The Strong Heart Study (SHS) is a multicenter, prospective study of cardiovascular disease (CVD) and its risk factors among AI adults. The present analysis used lung function assessment by standard spirometry at the SHS second examination (1993-1995) in 2,396 adults free of overt lung disease or CVD, with or without DM or MS. Among MS-free/DM-free participants, the development of MS/DM at the SHS third examination (1996-1999) was investigated.

Results: Significantly lower pulmonary function was observed for AIs with MS or DM. Impaired pulmonary function was associated with MS and DM after adjustment for age, sex, abdominal obesity, current smoking status, physical activity index, hypertension, and SHS field center. Both forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were negatively associated with insulin resistance or DM severity and with serum markers of inflammation (P < 0.05). FVC and FEV1-to-FVC ratio both predicted DM in unadjusted analyses but not when adjusted for covariates, including waist circumference. In the adjusted model, abdominal obesity predicted both MS and DM.

Conclusions: Reduced lung function is independently associated with MS and with DM, and impaired lung function presents before the development of MS or DM; these associations may result from the effects of obesity and inflammation.
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http://dx.doi.org/10.2337/dc11-0682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3177743PMC
October 2011

Achieving lipid targets in adults with type 2 diabetes: the Stop Atherosclerosis in Native Diabetics Study.

J Clin Lipidol 2010 Sep-Oct;4(5):435-43

Phoenix Indian Medical Center, Phoenix, AZ, USA.

Background: Although lipid management in diabetes is standard practice, goals often are neither met nor maintained. Strategies for achieving lower targets have not been explored. The Stop Atherosclerosis in Native Diabetics Study randomized patients with diabetes to standard versus aggressive lipid and blood pressure goals for 36 months.

Objective: To report strategies used to achieve and maintain lipid goals and to report adverse events (AEs).

Methods: Adults with type 2 diabetes and no history of cardiovascular disease (N = 499) were randomized to standard (low-density lipoprotein cholesterol [LDL-C] ≤ 100 mg/dL, non-high-density lipoprotein cholesterol [non-HDL-C] ≤ 130 mg/dL) or aggressive (LDL-C ≤ 70 mg/dL, non-HDL-C ≤ 100 mg/dL) targets. An algorithm was started with statin monotherapy, with intestinally acting agents added as required to reach LDL-C targets.Triglyceride [TG]-lowering agents were next used to reach non-HDL-C goals. Lipid management was performed by mid-level practitioners, with physician consultation, by the use of point-of-care lipid determinations.

Results: On average, both groups achieved the LDL-C and non-HDL-C goals within 12 months and maintained them throughout the study. At 36 months, mean (SD) LDL-C and non-HDL-C were 72 (24) and 102 (29) mg/dL in the aggressive group (AGG) and 104 (20) and 138 (26) mg/dL, respectively, in the standard group (STD); systolic blood pressure targets were 115 and 130 mmHg, respectively. A total of 68% of participants reached target LDL-C for greater than 50% of the visits and 46% for greater than 75% of visits. At 36 months, the AGG averaged 1.5 lipid lowering medications and the STD 1.2. Statins were used in 91% and 68% of the AGG and STD; ezetimibe by 31% and 10%; fibrates by 8% and 18%. No serious AEs were observed; AEs occurred in 18% of the AGG and 14% of the STD.

Conclusion: Standard and aggressive lipid targets can be safely maintained in diabetic patients. Standardized algorithms, point-of-care lipid testing, and nonphysician providers facilitate care delivery.
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http://dx.doi.org/10.1016/j.jacl.2010.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976563PMC
July 2011

Advantages of video questionnaire in estimating asthma prevalence and risk factors for school children: findings from an asthma survey in American Indian youth.

J Asthma 2010 Sep;47(7):711-7

Center for American Indian Health Research, University of Oklahoma Health Sciences Center, College of Public Health, 801 N.E. 13th Street, Oklahoma City, OK 73190, U.S.A.

Objectives: The aims of the present study were to estimate the prevalence and risk factors of asthma among a sample of American Indian youth and to evaluate survey instruments used in determining asthma prevalence and risk factors.

Methods: Three hundred and fifty-two adolescents aged 9 to 21 years enrolled in an Indian boarding school completed an asthma screening. The survey instruments were a written questionnaire and a video-illustrated questionnaire prepared from the International Study of Asthma and Allergies in Childhood (ISAAC), school health records, and a health questionnaire. Participants also underwent spirometry testing.

Results: The prevalence of self-reported asthma varied from 12.7% to 13.4% depending upon the instrument used and the questions asked. A history of hay fever, respiratory infections, and family history of asthma were found to be risk factors for asthma by all instruments. Female gender and living on a reservation were significantly associated with asthma by some, but not all, instruments. Airway obstruction was highly associated with one asthma symptom (wheeze) shown in the video questionnaire. Associations for most risk factors with asthma were strongest for the video questionnaire.

Conclusions: The prevalence of self-reported asthma among these American Indian youth was similar to rates reported for other ethnic groups. The video-based questionnaire may be the most sensitive tool for identifying individuals at risk for asthma.
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http://dx.doi.org/10.3109/02770903.2010.485663DOI Listing
September 2010

Cost-effectiveness of lower targets for blood pressure and low-density lipoprotein cholesterol in diabetes: the Stop Atherosclerosis in Native Diabetics Study (SANDS) .

J Clin Lipidol 2010 May-Jun;4(3):165-72

Phoenix Indian Medical Center, 4212 N 16th Street, Phoenix, AZ 85016, USA.

Background: The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals.

Objective: In this analysis, we examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic BP ≤115 mmHg versus standard targets of LDL-C ≤100 mg/dL and systolic BP ≤130 mmHg.

Design: Randomized, open label blinded-to-endpoint 3-year trial.

Data Sources: SANDS clinical trial database, Quality of Wellbeing survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices.

Target Population: American Indians ≥ age 40 years with type 2 diabetes and no previous cardiovascular events.

Time Horizon: April 2003 to July 2007.

Perspective: Health payer.

Interventions: Participants were randomized to aggressive versus standard groups with treatment algorithms defined for both.

Outcome Measures: Incremental cost-effectiveness.

Results Of Base-case Analysis: Compared with the standard group, the aggressive group had slightly lower costs of medical services (-$116) but a 54% greater cost for BP medication ($1,242) and a 116% greater cost for lipid-lowering medication ($2,863), resulting in an increased cost of $3,988 over 3 years. Those in the aggressively treated group gained 0.0480 quality-adjusted life-years (QALY) over the standard group. When a 3% discount rate for costs and outcomes was used, the resulting cost per QALY was $82,589.

Results Of Sensitivity Analysis: The use of a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61,329, $40,070, and $18,810, respectively.

Limitations: This study was limited by use of a single ethnic group and by its 3-year duration.

Conclusions: Within this 3-year study, treatment to lower BP and LDL-C below standard targets was not cost-effective because of the cost of the additional medications required to meet the lower targets. With the anticipated availability of generic versions of the BP and lipid-lowering drugs used in SANDS, the cost-effectiveness of this intervention should improve. Published by Elsevier Inc on behalf of the National Lipid Association.
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http://dx.doi.org/10.1016/j.jacl.2010.01.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885818PMC
May 2011

Safety and feasibility of achieving lower systolic blood pressure goals in persons with type 2 diabetes: the SANDS trial.

J Clin Hypertens (Greenwich) 2009 Oct;11(10):540-8

University of Maryland School of Medicine, Baltimore, MD 21201, USA.

The Stop Atherosclerosis in Native Diabetics Study (SANDS) was a randomized open-label clinical trial in type 2 diabetics designed to examine the effects of intensive reduction of blood pressure, aggressive vs standard goals (< or =115/75 mm Hg vs < or =130/80 mm Hg), and low-density lipoprotein (LDL) cholesterol on the composite outcome of change in carotid intimal-medial thickness and cardiovascular events. The study demonstrated that in conjunction with a lower LDL cholesterol target of 70 mg/dL, aggressive systolic blood pressure-lowering resulted in a reduction in carotid intimal-medial thickness and left ventricular mass without measurable differences in cardiovascular events. The blood pressure treatment algorithm included renin-angiotensin system blockade, with other agents added if necessary. The authors conclude that both standard and more aggressive systolic blood pressure reduction can be achieved with excellent safety and good tolerability in patients with type 2 diabetes mellitus.
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http://dx.doi.org/10.1111/j.1751-7176.2009.00121.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182961PMC
October 2009

Effect of lower targets for blood pressure and LDL cholesterol on atherosclerosis in diabetes: the SANDS randomized trial.

JAMA 2008 Apr;299(14):1678-89

MedStar Research Institute, 6495 New Hampshire Ave, Suite 201, Hyattsville, MD 20783, USA.

Context: Individuals with diabetes are at increased risk for cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested.

Objective: To compare progression of subclinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and systolic blood pressure (SBP) of 115 mm Hg or lower vs standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower.

Design, Setting, And Participants: A randomized, open-label, blinded-to-end point, 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma, Arizona, and South Dakota. Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events.

Interventions: Participants were randomized to aggressive (n=252) vs standard (n=247) treatment groups with stepped treatment algorithms defined for both.

Main Outcome Measures: Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness (IMT). Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events.

Results: Mean target LDL-C and SBP levels for both groups were reached and maintained. Mean (95% confidence interval) levels for LDL-C in the last 12 months were 72 (69-75) and 104 (101-106) mg/dL and SBP levels were 117 (115-118) and 129 (128-130) mm Hg in the aggressive vs standard groups, respectively. Compared with baseline, IMT regressed in the aggressive group and progressed in the standard group (-0.012 mm vs 0.038 mm; P < .001); carotid arterial cross-sectional area also regressed (-0.02 mm(2) vs 1.05 mm(2); P < .001); and there was greater decrease in left ventricular mass index (-2.4 g/m(2.7) vs -1.2 g/m(2.7); P = .03) in the aggressive group. Rates of adverse events (38.5% and 26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events (1.6/100 and 1.5/100 person-years; P = .87) did not differ significantly between groups.

Conclusions: Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events were lower than expected and did not differ significantly between groups. Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes.

Trial Registration: clinicaltrials.gov Identifier: NCT00047424.
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http://dx.doi.org/10.1001/jama.299.14.1678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243925PMC
April 2008

Asthma in American Indian adults: the Strong Heart Study.

Chest 2007 May 30;131(5):1323-30. Epub 2007 Mar 30.

University of Vermont College of Medicine, 111 Colchester Ave, Burlington, VT 05401, USA.

Background: Despite growing recognition that asthma is an important cause of morbidity among American Indians, there has been no systematic study of this disease in older adults who are likely to be at high risk of complications related to asthma. Characterization of the impact of asthma among American Indian adults is necessary in order to design appropriate clinical and preventive measures.

Methods: A sample of participants in the third examination of the Strong Heart Study, a multicenter, population-based, prospective study of cardiovascular disease in American Indians, completed a standardized respiratory questionnaire, performed spirometry, and underwent allergen skin testing. Participants were > or = 50 years old.

Results: Of 3,197 participants in the third examination, 6.3% had physician-diagnosed asthma and 4.3% had probable asthma. Women had a higher prevalence of physician-diagnosed asthma than men (8.2% vs 3.2%). Of the 435 participants reported in the asthma substudy, morbidity related to asthma was high: among those with physician-diagnosed asthma: 97% reported trouble breathing and 52% had severe persistent disease. The mean FEV(1) in those with physician-diagnosed asthma was 61.3% of predicted, and 67.2% reported a history of emergency department visits and/or hospitalizations in the last year, yet only 3% were receiving regular inhaled corticosteroids.

Conclusions: The prevalence of asthma among older American Indians residing in three separate geographic areas of the United States was similar to rates in other ethnic groups. Asthma was associated with low lung function, significant morbidity and health-care utilization, yet medications for pulmonary disease were underutilized by this population.
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http://dx.doi.org/10.1378/chest.06-1968DOI Listing
May 2007
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