Thomas K. Welty

Mitral Ratio of Peak Early to Late Diastolic Filling Velocity as a Predictor of Mortality in Middle-Aged and Elderly Adults: The Strong Heart Study

Background—With aging, left ventricular filling tends to decrease in early diastole, reducing the mitral ratio of peak early to late diastolic filling velocity (E/A). However, the prognostic significance of low or high E/A in older adults remains to be elucidated in population-based samples. Methods and Results—Doppler echocardiograms were analyzed in 3008 American Indian participants in the second Strong Heart Study examination who had no more than mild mitral or aortic regurgitation. Participants were followed for a mean of 3 years after Doppler echocardiography to assess risks of all-cause and cardiac death associated with E/A <0.6 or >1.5; 2429 (81%) participants had normal E/A ratio, 490 (16%) had E/A <0.6, and 89 (3%) had E/A >1.5. All-cause mortality was higher with E/A <0.6 or E/A >1.5 (12% and 13% versus 6%), as was cardiac mortality (4.5% and 6.5% versus 1.6%; both P <0.001). Adjusting for age, sex, body mass index, systolic blood pressure, HDL and LDL cholesterol, smoking, hypertension, diabetes, coronary heart disease, left ventricular hypertrophy, and low ejection fraction (<40%), the relative risk of all-cause death with E/A >1.5 was 1.73 (95% CI, 0.99 to 3.03;P =0.05); the relative risk of cardiac death was 2.8 (95% CI, 1.19 to 6.75;P <0.05). E/A <0.6 was not independently associated with increased all-cause or cardiac mortality (P =0.19 and 0.31, respectively) after adjusting for covariates. Conclusions—In a population-based sample of middle-aged and elderly adults, mitral E/A >1.5 at baseline Doppler echocardiography is associated with 2-fold increased all-cause and 3-fold increased cardiac mortality independent of covariates; mitral E/A <0.6 was also associated with 2-fold increased all-cause and cardiac mortality but not independent of covariates.

Adverse Effects of Diabetes on Multiple Cardiovascular Disease Risk Factors in Women: The Strong Heart Study

OBJECTIVE Many studies have shown that diabetes increases the risk of cardiovascular disease (CVD) in women to a greater extent than in men. One explanation could be that diabetes has more adverse effects on CVD risk factors in women than in men. We compared diabetes-associated differences in CVD risk factors in men and women in the Strong Heart Study, a population-based study of CVD and its risk factors in American Indians. RESEARCH DESIGN AND METHODS A total of 1,846 men and 2,703 women between the ages of 45 and 74 years from 13 American Indian communities in three geographic areas underwent an examination that included a medical history; an electrocardiogram; anthropometric and blood pressure measurements; an oral glucose tolerance test; and measurements of fasting plasma lipoproteins, fibrinogen, insulin, HbA1c, and urinary albumin. RESULTS Statistically significantly greater adverse differences in those with diabetes versus those without diabetes were observed in women than in men for waist-to-hip ratio, HDL cholesterol, apolipoprotein (apo)B, apoA1, fibrinogen, and LDL size. In multiple linear regression models adjusting for age, center, sex, and diabetes, the diabetes by sex interaction terms were statistically significant for waist-to-hip ratio, LDL cholesterol, HDL cholesterol, apoB, apoA1, fibrinogen, and LDL size. CONCLUSIONS Compared with diabetes-associated differences in men, diabetes in women was related to greater adverse differences in levels of several CVD risk factors. Although the magnitude of the individual diabetes-related differences between men and women was not large, the combined effects of these risk factor differences in diabetic women may be substantial. The apparent greater negative impact of diabetes on CVD risk factors in women may explain, in part, the greater risk for CVD in diabetic women.

Relations of Left Ventricular Mass to Fat-Free and Adipose Body Mass The Strong Heart Study

BACKGROUNDnIt is unclear whether increased left ventricular (LV) mass in overweight individuals is related to their adiposity or to greater fat-free mass (FFM).nnnMETHODS AND RESULTSnWe compared echocardiographic LV mass to FFM and adipose body mass by bioelectric impedance and to anthropometric measurements in 3107 American Indian participants in the Strong Heart Study. In men and women, the relations of LV mass and FFM (r=0.37 and 0.38, P<0.001) were closer (P<0.05 to <0.001) than they were with adipose mass, waist/hip ratio, body mass index, systolic blood pressure, height, or height2.7. Regression analyses showed that in men LV mass had the strongest independent relation with FFM, followed by systolic blood pressure and age (all P<0.001); in women, LV mass was related to FFM more strongly than it was to systolic blood pressure, age (all P<0. 001), and diabetes (P=0.012). Adipose mass had no independent relation to LV mass. When waist/hip ratio or body mass index were substituted for adipose mass, LV mass was independently related to FFM (P<0.001) and body mass index (P=0.02) but not to waist/hip ratio in men and was independently related to FFM and waist/hip ratio (both P<0.001) but not to body mass index in women. Using 97.5 percentile gender-specific partitions for LV mass/FFM in reference individuals, we found that LV hypertrophy occurred in 20.8% of Strong Heart Study participants with hypertension, overweight, or diabetes compared with 10.5% and 16.7% by LV mass indexed for body surface area or height2.7.nnnCONCLUSIONSnLV mass is more strongly related to FFM than to adipose mass, waist/hip ratio, body mass index, or height-based surrogates for lean body weight; LV mass/FFM criteria may increase sensitivity to detect LV hypertrophy.

Hypertension in Adult American Indians: The Strong Heart Study

Hypertension is a primary risk factor for cardiovascular disease in the United States. Although cardiovascular disease is the leading cause of death among American Indians, the prevalence of hypertension, its awareness and control, and its association with other cardiovascular disease risk factors and physiological variables have not been well studied in this population. The Strong Heart Study is a longitudinal study of cardiovascular disease and its risk factors in American Indians. Participants (2703 women and 1846 men) were members of 13 tribes in central Arizona, southwestern Oklahoma, and regions of South and North Dakota. At least 1500 individuals between 45 and 74 years of age participated from each center in a baseline clinical examination conducted between July 1989 and January 1992. The examination consisted of a personal interview and physical examination that included an oral glucose tolerance test and three consecutive blood pressure measurements. This study reports data from the baseline examination on the prevalence of hypertension and correlates of blood pressure. Results indicated that despite the high frequency of diabetes and obesity, prevalence rates of hypertension in Arizona and Oklahoma were similar to those in the US population in the Third National Health and Nutrition Examination Survey (NHANES III), and rates among South/North Dakota participants were significantly lower (P < .0001). Blood pressure was higher in individuals with diabetes (P < .0001) and was significantly correlated with age (P < .0001) and albuminuria (P < .0001) but only weakly related to obesity. There was no independent relation between blood pressure and insulin. Blood pressure seems to be less affected by obesity and hyperinsulinemia in American Indians compared with other populations. Nevertheless, hypertension should be aggressively treated and controlled in American Indians because it is a known precursor to morbidity and mortality associated with diabetes and cardiovascular disease.

Type II Diabetes and Cognitive Function: A population-based study of Native Americans

OBJECTIVE To explore the relationship between type II diabetes and cognitive function in older Native Americans and to assess the effects of other selected risk factors for cognitive dysfunction on this relationship. RESEARCH DESIGN AND METHODS Cognitive function was assessed in 80 diabetic and 81 nondiabetic Native Americans who were 45–76 years of age in a cross-sectional population-based sub-study of the Strong Heart Study. Thirteen cognitive function tests were administered during a personal interview. Information about six other risk factors for cognitive dysfunction, including depressive symptoms, physical function, alcoholism, current alcohol use, hypertension, and myocardial infarction, was ascertained from interviews andfrom abstraction of medical records. RESULTS Diabetes was associated with impairment on only two tests of cognitive function: verbal fluency (P = 0.004) and similarities (P = 0.010). Depressive symptoms were related to verbal fluency (P = 0.004), but did not explain thediabetes-related difference in performance. The effects of hypertension, depressive symptoms, and current alcohol use explained the diabetes-related performance difference on similarities. Cognitive function was not related to metabolic control (HbA1c level). CONCLUSIONS We found little evidence that type II diabetes in this population of Native Americans is associated with decrement in cognitive function. Some of the cognitive impairment previously attributed to diabetes may be related, at least in part, to the influence of other risk factors. This should be considered in the design of future studies in other populations.

Apolipoprotein E Polymorphism in American Indians and Its Relation to Plasma Lipoproteins and Diabetes The Strong Heart Study

Apo E is an important genetic factor in the development of cardiovascular disease, which is the leading cause of death among American Indians. We investigated the occurrence of the apo E alleles and the relation between apo E polymorphism and blood lipoproteins and apoproteins in members of 13 American Indian communities in three geographic areas. The frequencies of the epsilon 2 alleles in American Indians are significantly lower than those in white Americans, with the lowest frequencies of epsilon 2 in American Indians who reside in Arizona. Levels of LDL cholesterol and apo B were highest in those with epsilon 4 and lowest in those with epsilon 2. Concentrations of HDL cholesterol and apo A-I, however, tended to be lowest in epsilon 4 and highest in epsilon 2. Concentrations of total and VLDL triglycerides were lowest in the epsilon 3 group and higher in groups epsilon 2 and epsilon 4. Differences in concentrations of LDL cholesterol, HDL cholesterol, apo B, and apo A-I with apo E polymorphism were greater in women than in men, and differences in total and VLDL triglyceride concentrations by apo E phenotype were greater in men. Relations of total and VLDL triglycerides with apo E phenotype were stronger in women after menopause. In addition, differences in nearly all lipid and apoprotein concentrations between postmenopausal women and premenopausal women were greater if they had epsilon 2. Relations between apo E phenotype and lipoproteins were seen in individuals with diabetes mellitus as well as in nondiabetics. Apo E was significantly related to glucose control in diabetic women; those with epsilon 3 had higher glucose and hemoglobin A1C concentrations. Our findings show that (1) American Indians have low frequencies of apo epsilon 2; (2) apo E phenotype can influence levels of VLDL, LDL, HDL, apo B, and apo A-I; (3) the associations of apo E polymorphisms with lipid parameters differ between men and women; and (4) the associations in women of apo E polymorphisms with lipid parameters are modified by menopausal status.

Genetic Influences on Aortic Root Size in American Indians The Strong Heart Study

Aortic root dilatation is a major pathophysiological mechanism for aortic regurgitation and predisposes the aortic root to dissection or rupture. However, only a small proportion of the variance of aortic root size can be explained by its known clinical and demographic correlates. The present study was undertaken to determine the heritability of echocardiographically derived aortic root diameter in the American Indian participants in the second Strong Heart Study examination. Echocardiograms were analyzed in 1373 SHS participants who had ≥1 family member in the cohort. Heritability calculations were performed by using variance component analysis as implemented in SOLAR, a computer analysis program. In a polygenic model, the variables entered and identified as covariates of larger aortic root diameter were older age, male sex, and center (P <0.001), which accounted for 35% of the overall variability of aortic root diameter. After simultaneous adjustment was made for these significant covariates, the proportion of phenotypic variance due to additive genetic contribution or residual heritability (h2) was 0.51 (SE=0.08, P <0.001). Additionally, simultaneous adjustment for height, weight, and systolic and diastolic BPs yielded slightly lower residual h2 of aortic root diameter (h2=0.44, SE=0.08, P <0.001), which accounted for 26% of the overall variance of aortic root size. Because center effects were identified as significant covariates in the analyses, h2 analyses were performed separately in Arizona, Oklahoma, and North/South Dakota centers, which confirmed that a significant proportion of the phenotypic variance of aortic root diameter is due to additive genetic contribution. Heredity explains a substantial proportion of the variability of aortic root size that is not accounted for by age, sex, body size, and blood pressure. Echocardiographic screening of family members with aortic root dilatation may identify other individuals predisposed to aortic dissection or rupture.

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.

Relationship between glycemic control and depression among American Indians in the Strong Heart Study

OBJECTIVESnTo examine the relationship between depression and glycemic control in the Strong Heart Study (SHS), a longitudinal study of cardiovascular disease in American Indians.nnnMETHODSnThis cross-sectional analysis focused on the relationship between depression, diabetes and glycemic control among 2832 individuals aged > or =15 years. Depression was measured by the Center for Epidemiologic Studies of Depression Scale and diabetes by American Diabetes Association criteria. An ordered logit regression model was used to assess whether diabetes was related to level of depression (none, mild, moderate, severe). Multiple logistic regression was used to explore the relationship between A1c and severe depression in participants with diabetes.nnnRESULTSnRates of depression were higher in men and women with diabetes when compared to those without diabetes, respectively (P<.05). For every 1-U increase in A1c, the odds of severe depression increased by 22% (OR 1.22, 95% CI: 1.05-1.42). Female sex (OR 2.97, 95% CI: 1.32-6.69) and body mass index (BMI) (OR 1.04, 95% CI: 1.00-1.08) also were significantly associated with increased risk for severe depression. Although BMI appears to be significantly associated with increased risk for severe depression, the magnitude of this effect was small.nnnCONCLUSIONSnIndividuals with diabetes have higher rates of depression than those without diabetes, consistent with other populations. There is a positive relationship between severity of depression and A1c levels; men and women with severe depression have higher A1c levels than those with moderate-to-no depression.

Associations of postmenopausal hormone therapy with markers of hemostasis and inflammation and lipid profiles in diabetic and nondiabetic american Indian women: the strong heart study.

OBJECTIVESnTo examine the associations of postmenopausal hormone therapy (PHT) with indicators of hemostasis and inflammation and with lipid profiles in American Indian women and to determine if diabetes modifies these associations.nnnMETHODSnThis report is a cross-sectional analysis of data from 1446 postmenopausal women who were free from cardiovascular disease (CVD) at the second Strong Heart Study examination (1993-1995). Diabetes was diagnosed by WHO criteria. Postmenopausal hormone use was ascertained by review of the medications brought to the examination or by medical record review. Lipoproteins, plasminogen activator inhibitor type 1 (PAI-1), fibrinogen, and C-reactive protein (CRP) were measured in fasting plasma samples.nnnRESULTSnAmong nondiabetic women, current PHT users had lower mean fibrinogen, PAI1, and low-density lipoprotein cholesterol (LDLC) levels than those in never users (38.4 mg/dl, 8.68 ng/ml, and 14.16 mg/dl lower, respectively) but higher CRP and triglyceride levels (1.53 mg/l and 31.43 mg/dl higher, respectively). Multivariate adjustment did not alter any of these associations. In diabetic women, current PHT use was associated only with lower PAI-1 (5.48 ng/ml lower) and higher high-density lipoprotein cholesterol (HDLC) levels (3.33 mg/dl higher) compared with never users.nnnCONCLUSIONSnIn American Indian women without diabetes, PHT was associated with lower levels of hemostatic markers but higher levels of an inflammatory marker. Associations were less marked in women with diabetes. The relation of PHT with lipid profiles also differed in nondiabetic and diabetic women. These data provide an additional rationale for considering diabetes status when deciding whether or not to use PHT.