Jeunliang Yeh

Relations of Left Ventricular Mass to Demographic and Hemodynamic Variables in American Indians The Strong Heart Study

BACKGROUND Previous studies have identified associations of left ventricular (LV) mass with demographic (body habitus and sex) and hemodynamic variables (blood pressure, stroke volume [SV], and myocardial contractility), but the relative strength and independence of these associations remain unknown. METHODS AND RESULTS We examined the relations of echocardiographically determined LV mass to demographic variables, blood pressure, Doppler SV, and measures of contractility (end-systolic stress [ESS]/end-systolic volume index and midwall fractional shortening [MFS] as a percentage of predicted for circumferential end-systolic stress [stress-independent shortening]) in 1935 American Indian participants in the Strong Heart Study phase 2 examination without mitral regurgitation or segmental wall motion abnormalities. Weak positive relations of LV mass with systolic and diastolic pressures (r=.22 and r=.20) were exceeded by positive relations with height (r=.30), weight (r=.47), body mass index (r=.31), body surface area (r=.49), and Doppler SV (r=.50) and negative relations with ESS/volume index ratios (r= -.33 and -.29) and stress-independent MFS (r= -.26, all P<.0001). In multivariate analyses that included blood pressure, SV, and a different contractility measure in each model, systolic pressure, stroke volume, and the contractility measure were independent correlates of LV mass (multiple R=.60 to .66, all P<.0001). When demographic variables were added, LV mass was more strongly predicted by higher SV and lower afterload-independent MFS than by greater systolic pressure, height, and body mass index (each P<.00001, multiple R=.71). CONCLUSIONS Additional characterization of volume load and contractile efficiency improves hemodynamic prediction of LV mass (R(2)=.30 to .44) over the use of systolic blood pressure alone (R(2)=.05), with a further increase in R(2) to .51 when demographic variables are also considered. However, nearly half of the ventricular mass variability remains unexplained.

Prehypertension, Diabetes, and Cardiovascular Disease Risk in a Population-Based Sample. The Strong Heart Study

There are few data about the impact of the recently-defined category of prehypertension (systolic blood pressure 120 to 139 mm Hg or diastolic blood pressure 80 to 89 mm Hg) on cardiovascular disease incidence. It is also unknown whether this association differs between individuals with or without diabetes. A total of 2629 Strong Heart Study participants free from hypertension and cardiovascular disease at baseline examination were followed for 12 years to observe incident cardiovascular disease. Approximately 42% of the 2629 participants had diabetes. We assessed the prevalence of prehypertension and the hazard ratios of incident cardiovascular disease associated with prehypertension. Prehypertension was more prevalent in diabetic than nondiabetic participants (59.4% versus 48.2%, P<0.001 adjusted for age). Compared with nondiabetic participants with normal blood pressure, the hazard ratios of cardiovascular disease were 3.70 (95% confidence interval: 2.66, 5.15) for those with both prehypertension and diabetes, 1.80 (1.28, 2.54) for those with prehypertension alone and 2.90 (2.03, 4.16) for those with diabetes alone. Impaired glucose tolerance or impaired fasting glucose also greatly increased the cardiovascular disease risk in prehypertensive people. Clinical investigation of more aggressive interventions, such as drug treatment for blood pressure control for prehypertensive individuals with impaired fasting glucose, impaired glucose tolerance, or diabetes is warranted.

Diabetes and Impaired Glucose Tolerance in Three American Indian Populations Aged 45-74 Years: The Strong Heart Study

OBJECTIVE To estimate prevalence rates of diabetes and impaired glucose tolerance (IGT) in three American Indian populations, using standardized diagnostic criteria, and to assess the association of diabetes with the following selected possible risk factors: age, obesity, family history of diabetes, and amount of Indian ancestry. RESEARCH DESIGN AND METHODS This cross-sectional study involved enrolled members, men and women aged 45-74 years, of 13 American Indian tribes or communities in Arizona, Oklahoma, and South and North Dakota. Eligible participants were invited to the clinic for a personal interview and a physical examination. Diabetes and IGT status were defined by the World Health Organization criteria and were based on fasting plasma glucose and oral glucose tolerance test results. Data on age, family history of diabetes, and amount of Indian ancestry were obtained from the personal interview, and measures of obesity included body mass index, percentage body fat, and waist-to-hip ratio. RESULTS A total of 4,549 eligible participants were examined, and diabetes status was determined for4,304(1,446 in Arizona, 1,449 in Oklahoma, and 1,409 in the Dakotas). In all three centers, diabetes was more prevalent in women than in men. Arizona had the highest age-adjusted rates of diabetes: 65% in men and 72% in women. Diabetes rates in Oklahoma (38% in men and 42% in women) and South and North Dakota (33% in men and 40% in women), although considerably lower than in Arizona, were several times higher than those reported for the U.S. population. Rates of IGT among the three populations (14-17%) were similar to those in the U.S. population. Diabetes rates were positively associated with age, level of obesity, amount of Indian ancestry, and parental diabetes status. CONCLUSIONS Diabetes is found in epidemic proportions in Native American populations. Prevention programs and periodic screening should be implemented among American Indians. Standards of care and intervention have been developed by the Indian Health Service for individuals in whom diabetes is diagnosed. These programs shoula be expanded to include those with IGT to improve glycemie control or to reduce the risk of development of diabetes as well as to reduce the risk of diabetic complications.

Incidence and Risk Factors for Stroke in American Indians The Strong Heart Study

Background— There are few published data on the incidence of fatal and nonfatal stroke in American Indians. The aims of this observational study were to determine the incidence of stroke and to elucidate stroke risk factors among American Indians. Methods and Results— This report is based on 4549 participants aged 45 to 74 years at enrollment in the Strong Heart Study, the largest longitudinal, population-based study of cardiovascular disease and its risk factors in a diverse group of American Indians. At baseline examination in 1989 to 1992, 42 participants (age- and sex-adjusted prevalence proportion 1132/100 000, adjusted to the age and sex distribution of the US adult population in 1990) had prevalent stroke. Through December 2004, 306 (6.8%) of 4507 participants without prior stroke suffered a first stroke at a mean age of 66.5 years. The age- and sex-adjusted incidence was 679/100 000 person-years. Nonhemorrhagic cerebral infarction occurred in 86% of participants with incident strokes; 14% had hemorrhagic stroke. The overall age-adjusted 30-day case-fatality rate from first stroke was 18%, with a 1-year case-fatality rate of 32%. Age, diastolic blood pressure, fasting glucose, hemoglobin A1c, smoking, albuminuria, hypertension, prehypertension, and diabetes mellitus were risk factors for incident stroke. Conclusions— Compared with US white and black populations, American Indians have a higher incidence of stroke. The case-fatality rate for first stroke is also higher in American Indians than in the US white or black population in the same age range. Our findings suggest that blood pressure and glucose control and smoking avoidance may be important avenues for stroke prevention in this population.

Risk Factors for Coronary Heart Disease in Diabetic and Nondiabetic Native Americans: The Strong Heart Study

The Strong Heart Study is a study of cardiovascular disease and its risk factors among diabetic and nondiabetic Native Americans. The study includes 12 tribes in Arizona, Oklahoma, and North and South Dakota. Phase I, initiated in October 1988, included a mortality survey to determine CVD death rates in individuals 35–74 yr old between 1984 and 1988, and a medical record review to determine rates of myocardial infarction and stroke for individuals ages 45–74 during the same time. In addition, a physical examination was performed on persons 45–74 yr old to measure the prevalence of cardiovascular and peripheral vascular diseases and known and suspected risk factors, in Phase II, CVD mortality and morbidity rates will be determined in the examined cohort by surveillance. CVD risk factors, changes in risk factors over time, and the relationship between risk factors and CVD incidence will be assessed longitudinally. This study provides data on the relative importance of cardiovascular risk factors in nondiabetic and diabetic Native Americans and will provide insight into possible variations in the quantitative or qualitative importance of CVD risk factors among diverse population groups.

Diabetes and impaired glucose tolerance in three Alaskan Eskimo populations. The Alaska-Siberia Project.

OBJECTIVE The objectives of this study were to determine the prevalence of diabetes and impaired glucose tolerance (IGT) in three Alaskan Eskimo populations, using standardized diagnostic criteria, and to evaluate family history and obesity as risk factors. RESEARCH DESIGN AND METHODS This cross-sectional study involved men and women ≥25 years of age from three Eskimo ethnic groups (Siberian Yupik, Central Yupik, and Inupiat) residing in northwestern Alaska. Glucose tolerance status was denned by World Health Organization criteria and was based on a 75-g oral glucose tolerance test. Data on age, family history of diabetes, and degree of Eskimo ancestry were obtained from a personal interview. Obesity was assessed using BMI. RESULTS A total of 454 of 899 (50.5%) eligible participants were examined for diabetic status (239 Siberian Yupik, 106 Central Yupik, and 109 Inupiat participants). The prevalence of diabetes was more than twice as high among the Siberian Yupik (9.6%) as among the Central Yupik (2.8%) and Inupiat participants (3.7%). Diabetes was more prevalent in women than men (8.8 vs. 4.2%). IGT was found in an additional 11.7% of the women and 4.7% of the men. The combined prevalence of diabetes and IGT in the population ≥55 years of age was 30.4% (diabetes 12.0%, IGT 18.4%). Of the people identified with diabetes, 47% had not been previously diagnosed. Age-specific prevalences were similar to those found in U.S. whites in the National Health and Nutrition Examination Survey II. After adjustment for age, family history of diabetes was associated with diabetes in study participants with an odds ratio of 4.4, while obesity was associated with diabetes with an odds ratio of 2.6. CONCLUSIONS These prevalences of diabetes are the highest yet reported among Eskimo populations. Obesity and family history of diabetes are associated with increased odds of developing diabetes. These data underscore the need to further examine risk factors and to design effective interventions.

Prediction of Coronary Heart Disease in a Population With High Prevalence of Diabetes and Albuminuria The Strong Heart Study

Background— The present article presents equations for the prediction of coronary heart disease (CHD) in a population with high rates of diabetes and albuminuria, derived from data collected in the Strong Heart Study, a longitudinal study of cardiovascular disease in 13 American Indian tribes and communities in Arizona, North and South Dakota, and Oklahoma. Methods and Results— Participants of the Strong Heart Study were examined initially in 1989–1991 and were monitored with additional examinations and mortality and morbidity surveillance. CHD outcome data through December 2001 showed that age, gender, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, smoking, diabetes, hypertension, and albuminuria were significant CHD risk factors. Hazard ratios for ages 65 to 75 years, hypertension, LDL cholesterol ≥160 mg/dL, diabetes, and macroalbuminuria were 2.58, 2.01, 2.44, 1.66, and 2.11 in men and 2.03, 1.69, 2.17, 2.26, and 2.69 in women, compared with ages 45 to 54 years, normal blood pressure, LDL cholesterol <100 mg/dL, no diabetes, and no albuminuria. Prediction equations for CHD and a risk calculator were derived by gender with the use of Cox proportional hazards model and the significant risk factors. The equations provided good discrimination ability, as indicated by a c statistic of 0.70 for men and 0.73 for women. Results from bootstrapping methods indicated good internal validation and calibration. Conclusions— A “risk calculator” has been developed and placed on the Strong Heart Study Web site, which provides predicted risk of CHD in 10 years with input of these risk factors. This may be valuable for diverse populations with high rates of diabetes and albuminuria.

Cadmium Exposure and Cancer Mortality in a Prospective Cohort: The Strong Heart Study

Background: Cadmium (Cd) is a toxic metal classified as a human carcinogen by the International Agency for Research on Cancer. Objective: We evaluated the association of long-term Cd exposure, as measured in urine, with cancer mortality in American Indians from Arizona, Oklahoma, and North and South Dakota who participated in the Strong Heart Study during 1989–1991. Methods: The Strong Heart Study was a prospective cohort study of 3,792 men and women 45–74 years of age who were followed for up to 20 years. Baseline urinary Cd (U-Cd) was measured using inductively coupled plasma mass spectrometry. We assessed cancer events by annual mortality surveillance. Results: The median (interquintile range) U-Cd concentration was 0.93 (0.55, 1.63) μg/g creatinine. After adjusting for sex, age, smoking status, cigarette pack-years, and body mass index, the adjusted hazard ratios (HRs) comparing the 80th versus the 20th percentiles of U-Cd were 1.30 (95% CI: 1.09, 1.55) for total cancer, 2.27 (95% CI: 1.58, 3.27) for lung cancer, and 2.40 (95% CI: 1.39, 4.17) for pancreatic cancer mortality. For all smoking-related cancers combined, the corresponding HR was 1.56 (95% CI: 1.24, 1.96). Cd was not significantly associated with liver, esophagus and stomach, colon and rectum, breast, prostate, kidney, or lymphatic and hematopoietic cancer mortality. On the basis of mediation analysis, we estimated that the percentage of lung cancer deaths due to tobacco smoking that could be attributed to Cd exposure was 9.0% (95% CI: 2.8, 21.8). Conclusions: Low-to-moderate Cd exposure was prospectively associated with total cancer mortality and with mortality from cancers of the lung and pancreas. The implementation of population-based preventive measures to decrease Cd exposure could contribute to reducing the burden of cancer. Citation: García-Esquinas E, Pollan M, Tellez-Plaza M, Francesconi KA, Goessler W, Guallar E, Umans JG, Yeh J, Best LG, Navas-Acien A. 2014. Cadmium exposure and cancer mortality in a prospective cohort: the Strong Heart Study. Environ Health Perspect 122:363–370; http://dx.doi.org/10.1289/ehp.1306587

Cardiovascular disease and risk factors in three Alaskan Eskimo populations: the Alaska-Siberia project

Abstract Objectives. To determine the prevalence of CVD and to identify and characterize associated risk factors in three distinct Eskimo populations. Study Design. Cross-sectional. Methods. A slightly modified Strong Heart Study protocol was followed to examine 454 participants, aged 25–91, from four villages. Results. Overall, 6% of the participants under 55 years of age and 26% of those ≥ 55 years of age showed evidence of CHD by ECG, or in patient records. The prevalence of “definite coronary heart disease” (CHD) in women with glucose intolerance (GI) was 21.0%, compared to 2.4% in those with normal glucose tolerance (NGT). Men had comparable values of 26.7% and 6.3%. In addition, comparable values for “possible CHD” were 29.7% vs 6.0% for women and 21.4% vs 8.0% for men. GI was associated with relatively higher prevalences of CHD in women than in men (prevalence ratio = 8.5 vs 4.3). CHD was significantly related to age, glucose intolerance and insulin. Hypertension and obesity were significantly associated with CHD only in some ethnic groups. The prevalence of current smokers was 56%. Conclusions. Recent changes in lifestyle and diet of Alaskan Eskimos, leading to obesity, hypertension, insulin resistance and DM, contribute to an increased risk for cardiovascular disease. (Int J Circumpolar Health 2005; 64(4):365–386)

Lipoprotein(a) in American Indians is Low and Not Independently Associated with Cardiovascular Disease ☆: The Strong Heart Study

PURPOSE To evaluate the distribution of lipoprotein(a) (Lp(a)) and assess its association to cardiovascular disease (CVD) in American Indians. METHODS Lp(a) was measured in 3991 American Indians (aged 45-74 years with no prior history of CVD at baseline) from 13 communities in Arizona, Oklahoma, and South/North Dakota. They were followed prospectively from 1989 to 1997 for CVD. The distribution of Lp(a) was examined by center, sex, and diabetic status. Spearman correlation coefficients and Cox regression models were used to evaluate the association of Lp(a) to CVD. RESULTS A total of 388 participants subsequently developed CVD. Median Lp(a) concentration in American Indians was 3.0 mg/dl. This was almost half of that in whites and one sixth in blacks from the CARDIA study measured by the same method. Nondiabetic participants had significantly higher Lp(a) levels than diabetic participants for both genders. Lp(a) levels were higher in women than in men for nondiabetic participants, but there was no gender difference for diabetic participants. Correlation analysis showed Lp(a) was significantly negatively correlated with the degree of Indian heritage, insulin, triglycerides (TG), fasting plasma glucose (FPG), and 2-hour plasma glucose (2hPG), and positively with low-density lipoproteins (LDL), apoprotein B (apoB), and fibrinogen (FIB). In Cox regression models, adjusting for other risk factors, Lp(a) was no longer a significant predictor of CVD in either diabetic or nondiabetic participants. CONCLUSIONS The lower concentration of Lp(a) in American Indians and the high correlation with Indian heritage confirm the concept that Lp(a) concentration is in large part genetically determined. Lp(a) concentration is not an independent predictor of CVD among American Indians; it is higher in those who develop CVD because of its positive correlation with LDL, apoB, and FIB.