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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

Rationale: Permanent lung function impairment after active tuberculosis infection is relatively common. It remains unclear which spirometric pattern is most prevalent after tuberculosis.Objectives: 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.Methods: 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 (FEV1), and FEV1/FVC were measured by spirometry. An additional analysis was conducted to evaluate the potential association between active tuberculosis and arsenic exposure.Results: A history of active tuberculosis was associated with reduced percent predicted FVC and FEV1, 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.Conclusions: 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.

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.

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.

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

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.

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

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.

Asthma in American Indian adults: the Strong Heart Study.

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.

Aging and the prevalence of cardiovascular disease risk factors in older American Indians: the Strong Heart Study.

OBJECTIVES: To describe longitudinal changes in the prevalence of major cardiovascular disease (CVD) risk factors in aging American Indians. DESIGN: Population-based ongoing epidemiological study. SETTING: The Strong Heart Study is a study of CVD and its risk factors. Standardized examinations were repeated in 1993 to 1995 and again in 1997 to 1999. PARTICIPANTS: A diverse cohort of 4,549 American Indians aged 45 to 74 at the initial examinations in 1989 to 1991. MEASUREMENTS: Changes in the prevalence of hypertension, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), current smoking, and type 2 diabetes mellitus. RESULTS: The prevalence of hypertension rose rapidly and steadily with aging. A nonsignificant decrease in LDL-C was seen in men, and men and women initially had rapid increases in the prevalence of low HDL-C. The prevalence of smoking decreased, but the prevalence of diabetes mellitus continued to rise for men and women. CONCLUSION: Overall, unfavorable changes in CVD risk factors were seen in the aging participants and will likely be reflected in worsening morbidity and mortality.

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.

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.

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

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 ±â€Š7 years) and the SHFS (33 ±â€Š13 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.

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

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.

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

Diabetes incidence is increasing rapidly in the United States. Diabetes increases the risk for cardiovascular disease, the major cause of death in diabetic individuals. The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease. Treatment targets for low-density lipoprotein cholesterol (LDL-C) and blood pressure in diabetic individuals are being debated. The SANDS is a randomized, open-label, 3-year trial to examine the effects of aggressive LDL-C (goal <70 mg/dL) and blood pressure (BP) (goal <115/75 mm Hg) reduction versus the standard goals of <100 mg/dL for LDL-C and <130/85 mm Hg for BP. Five hundred forty-nine American-Indian men and women >40 years old with type 2 diabetes were randomized to 1 of 2 groups. Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach. The presence and progression of atherosclerosis are evaluated by carotid ultrasonography; echocardiography assesses cardiac function. The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events. These outcomes are combined by using a ranked analysis for carotid thickness and assigning a "worst rank" for a cardiovascular event. Secondary end points include carotid plaque score, left ventricular geometry and function, serum C-reactive protein, and safety measures. Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the standard of care. Study results will further understanding of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US populations and will help determine optimal LDL-C and BP treatment goals for diabetic patients.