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Biomedical subjects

B V Howard

Publications and source records attributed to B V Howard.

At least 19 recordsLinked to original sources

Coronary heart disease prevalence and its relation to risk factors in American Indians. The Strong Heart Study.

Although coronary heart disease (CHD) is currently the leading cause of death among American Indians, information on the prevalence of CHD and its association with known cardiovascular risk factors is limited. The Strong Heart Study was initiated in 1988 to quantify cardiovascular disease and its risk factors among three geographically diverse groups of American Indians. Members of 13 Indian communities in Arizona, Oklahoma, and South and North Dakota between 45 and 74 years of age underwent a physical examination that included medical history; an electrocardiogram; anthropometric and blood pressure measurements; an oral glucose tolerance test; and measurements of fasting plasma lipoproteins, fibrinogen, insulin, hemoglobin A1c, and urinary albumin. Prevalence rates of definite myocardial infarction and definite CHD were higher in men than in women at all three centers (p < 0.0001) and higher in those with diabetes mellitus (p = 0.002 in men and p = 0.0003 in women). Diabetes was associated with relatively higher prevalence rates of myocardial infarction (diabetic:nondiabetic prevalence ratio = 3.8 vs. 1.9) and CHD (prevalence ratio = 4.6 vs. 1.8) in women than in men. Prevalence rates of heart disease were lowest in the communities in Arizona; prevalence rates were similar in Oklahoma and South Dakota/North Dakota and were two- to threefold higher than those in Arizona. By logistic regression, prevalent CHD among American Indians was significantly and independently related to age, diabetes, hypertension, albuminuria, percentage of body fat, smoking, high concentrations of plasma insulin, and low concentrations of high density lipoprotein cholesterol. In contrast to reports from other non-Indian populations, diabetes was the strongest risk factor. The lower prevalence of CHD among Indians in Arizona is distinctive in view of their higher rates of diabetes, obesity, hypertension, and albuminuria, but it may be partly related to their low frequency of smoking and their low concentrations of total and low density lipoprotein cholesterol. These findings from the initial Strong Heart Study examination emphasize the importance of diabetes and its associated variables as risk factors for CHD in Native American populations.

Aged

Cardiovascular disease risk factors among American Indians. The Strong Heart Study.

The Strong Heart Study, a study of cardiovascular disease among American Indians, was conducted to determine cardiovascular disease rates and the prevalence of risk factors among members of 13 tribal groups in South Dakota/North Dakota (SD/ND), southeastern Oklahoma, and Arizona. From 1989 to 1992, 4,549 tribal members aged 45-74 years (62% of eligible participants) were surveyed and examined for cardiovascular disease and its risk factors. Mean total cholesterol concentrations were over 20 mg/dl lower among the men and 27 mg/dl lower among the women than national mean levels for the same age groups. Cholesterol levels varied by tribal group; Arizona Indians had mean levels more than 20 mg/dl lower than those of SD/ND Indians. The prevalence of hypercholesterolemia was almost twice as high among SD/ND Indians as among Arizona Indians, but the rates for all three groups were much lower than total US rates (all races). Mean levels of high density lipoprotein cholesterol were lower among Indian men and women than in the US population as a whole. The prevalence of hypertension among Arizona and Oklahoma Indians was higher than that for the entire United States. SD/ND Indians had significantly lower mean blood pressures and prevalence rates of hypertension than Oklahoma and Arizona Indians and the United States as a whole. The prevalence of cigarette smoking was higher for all Indian groups except Arizona women in comparison with US rates. Smoking rates were highest in SD/ND and lowest in Arizona. Indian smokers smoked fewer cigarettes per day than the average US smoker. Arizona Indians had the highest prevalence of diabetes mellitus; over 60% of those participants were diabetic. In Oklahoma and SD/ND, one third of the men and over 40% of the women were diabetic. In addition, 13-20% of the participants had impaired glucose tolerance. Proteinuria was also a common problem; almost half of the Arizona Indians had micro- or macroalbuminuria, and 20% of Oklahoma and SD/ND Indians had significant proteinuria. The prevalence of obesity was high in all three groups, with Arizona Indians having the highest rates and the highest mean body mass indices. The prevalence of current alcohol use was lower among Indians than in the nation as a whole, but binge drinking was common among those who used alcohol. These results indicate that cardiovascular disease risk factors vary significantly among tribal groups. Prevention programs tailored toward decreasing the prevalence of risk factors are recommended for long-term reduction of cardiovascular disease rates in American Indian communities.

Aged

In vitro regulation of low-density lipoprotein receptor interaction by fatty acids.

Low-density lipoprotein (LDL) receptor binding is the initial step in receptor-mediated clearance. Dietary fat composition is known to affect LDL clearance, but the mechanism of the effect is unknown. We have examined the effects of altered membrane fatty acid composition, as might occur when specific dietary fats are consumed, on LDL binding using a Chinese hamster ovary (CHO) line that constitutively expresses the human LDL receptor. Binding of pooled human LDL to its receptor was compared in cells enriched with various fatty acids. Binding affinity was greater (lower Kd) for cells grown in 16:0-, 18:0-, or 18:1-enriched media than for those grown in 18:2 (P < .0001). The apparent receptor number (Bmax) was lower for cells enriched in saturated fatty acids and 18:1. Fluidity was assessed by measuring diphenylhexatriene (DPH) fluorescence anisotropy (rs). Cells enriched in 18:1 or 18:2 were the most fluid (P < .003). The correlation between binding and fluidity (r = .24, P = .27) was weak and did not appear to explain the effects of fatty acid modification on LDL receptor binding. Thus, it appears that cellular enrichment in 16:0, 18:0, and 18:1 increases binding affinity by affecting properties other than membrane fluidity. Changes in Bmax may also contribute to the observed differences in LDL binding.

Animals

Polyunsaturated fatty acids result in greater cholesterol lowering and less triacylglycerol elevation than do monounsaturated fatty acids in a dose-response comparison in a multiracial study group.

Cholesterol-lowering effects of polyunsaturated and monounsaturated fatty acids were compared as they were varied in a reciprocal dose-dependent fashion in the context of a National Cholesterol Education Program (NCEP) Step 1 diet. The study population comprised 63 moderately hypercholesterolemic African American and white men and women. After a 6-wk baseline diet containing 37% of energy from total fat and 15% from saturated fat, participants consumed four diets for 6 wk each, in random order, containing 10% of energy as saturated fatty acids; 3%, 6%, 10%, and 14% of energy as polyunsaturated fatty acids; and 17%, 14%, 10%, and 6% of energy as monounsaturated fatty acids. Dietary cholesterol, fiber, plant sterol, and squalene contents were constant with all four diets. There was a progressive decrease in total (P = 0.028) and low-density-lipoprotein cholesterol (P = 0.184) across the four diets, with the greatest decrease observed in the diet with the highest content of polyunsaturated fatty acids; a small but significant decrease in high-density-lipoprotein (HDL) cholesterol that did not show a trend between the polyunsaturated and monounsaturated diets; and a trend between the four diets in triacylglycerol elevations (P = 0.029), with the smallest increment occurring in the diets highest in polyunsaturates. The magnitude of the cholesterol-lowering response was greater in those with higher baseline cholesterol and less in those who were more obese. The dietary response was similar in both ethnic groups and in both sexes. In conclusion, in an NCEP Step 1 diet containing 30% total fat, with all other known cholesterol-influencing dietary factors held constant, the substitution of polyunsaturated fatty acid for monounsaturated fatty acid from 3% to 14% resulted in a progressive decline in total cholesterol and less triacylglycerol elevations, without effect on HDL cholesterol.

Adult

Effects of sex and ethnicity on responses to a low-fat diet: a study of African Americans and whites.

The effects of sex and ethnicity on plasma lipoprotein changes that occur with low-fat diets were studied in 34 African American subjects (20 women, 14 men) and 29 white subjects (13 women, 16 men) aged 25-62 y with moderate hypercholesterolemia. A baseline diet containing 37% fat (15% saturated) was compared with four experimental diets containing 30% fat (10% saturated) with reciprocally varying contents of polyunsaturated and monounsaturated fatty acids. Diets were fed for 6 wk each, and all food and beverages provided and compliance were intensively monitored. Body weight and physical activity were held constant. Lowering of total and low-density-lipoprotein cholesterol were similar between women and men and between African Americans and whites. Small differences were observed between women and men in the extent of high-density lipoprotein lowering and triacylglycerol elevations. Additionally, African American subjects had slightly higher triacylglycerol elevations than did white subjects. Results suggest that men and women of varied ethnic backgrounds should respond similarly to cholesterol-lowering diets. Studies are required to develop strategies for achieving dietary changes that consider diverse eating patterns and cultural barriers to dietary adherence.

Adult

LDL size and subclass pattern in Mexico City residents and San Antonio Mexican Americans.

Recent studies suggest that a relative abundance of small dense LDL is a risk factor for coronary heart disease. We compared LDL size in Mexico City residents (n = 191) and San Antonio Mexican Americans (n = 282), two genetically similar populations that differ markedly in dietary behaviors: in Mexico City approximately 62% of calories are from carbohydrate and approximately 19% from fat, and in San Antonio approximately 40% of calories are from carbohydrate and approximately 40% from fat. Mean LDL size in Mexico City was 258.6 +/- 0.9 A, and in San Antonio, 255.9 +/- 0.6 A (P = .013). After adjustment for the higher triglyceride and lower HDL cholesterol levels (the two most important predictors of LDL size) in Mexico City, LDL size was significantly lower in San Antonio than in Mexico City by -8.33 +/- 0.84 A (P < .001). Our data suggest that the higher triglyceride concentrations in Mexico City residents that are associated with a higher carbohydrate diet may not be associated with atherogenic changes in LDL.

Adult

Apolipoprotein E polymorphism and insulin levels in a biethnic population.

OBJECTIVE: To study the association of apolipoprotein E (apoE) polymorphism with important cardiovascular risk factors other than cholesterol levels, such as insulinemia and insulin resistance. RESEARCH DESIGN AND METHODS: In this report, we study the association of three major apoE phenotypes (apoE 3/2, apoE 3/3, and apoE 4/3) with indicators of insulin resistance such as fasting insulin, glucose, and lipid levels in 320 nondiabetic Mexican-Americans and non-Hispanic whites from San Antonio, TX. RESULTS: The two ethnic groups differed in the frequencies of the three major apoE phenotypes. However, the associations of these phenotypes with lipid and insulin levels were similar in both ethnic groups and in both sexes. Compared with the other two major apoE phenotypes, the apoE 3/2 phenotype was associated with lower levels of total and low-density lipoprotein cholesterol and lower levels of fasting and 2-h postload insulin. CONCLUSIONS: In addition to the association with cholesterol levels, the variability at the apoE locus may be associated with a much broader set of metabolic factors that relate to insulin resistance.

Alleles

Concentrations of Lp(a) in black and white young adults: relations to risk factors for cardiovascular disease.

The purpose of this report is to compare the distribution of total lipoprotein(a) [Lp(a)] mass in a population-based sample of blacks and whites, and to investigate the association of Lp(a) with other cardiovascular risk factors. A cross-sectional study design was used. Black and white men and women (n = 4125), aged 23-35 from the Coronary Artery Risk Development in Young Adults Study had the following data collected: Lp(a), lipids and lipoproteins, other metabolic parameters, anthropometry, physical activity, dietary intake, cigarette use, and alcohol use. Blacks had concentrations of Lp(a) approximately three-fold higher than whites. Medians were: black men 21.5 mg/dL, black women 23.9 mg/dL, white men 6.1 mg/dL, and white women 6.4 mg/dL. Lp(a) concentrations were higher in women than in men. Lp(a) was not consistently associated with smoking, alcohol consumption, physical activity, dietary fat, or obesity. In stepwise regression analyses in both blacks and whites, Lp(a) was consistently associated with low-density lipoprotein (LDL) cholesterol, fibrinogen, and apoB; regression models explained about 7% of the variance in Lp(a). In whites, Lp(a) tended to be higher in those with a positive family history of myocardial infarction. The large differences in Lp(a) between blacks and whites, and the absence of association with many other variables are consistent with previous suggestions that Lp(a) concentration is in large part genetically determined. The association of Lp(a) with LDL and fibrinogen, two strong risk factors for cardiovascular disease (CVD), could represent part of the mechanism of the CVD risk associated with Lp(a) in other studies. Longitudinal data are needed to determine the extent to which Lp(a) will independently predict disease, especially in diverse ethnic groups.

Adult

Lipoprotein metabolism in diabetes.

An understanding of lipoprotein metabolism in diabetes is essential because dyslipidemia contributes to the atherosclerotic process in diabetic individuals. Current work has centered on elucidating the compositional changes and apolipoprotein alterations of plasma lipoproteins that occur in diabetic individuals. Studies of the mechanisms responsible for the altered concentrations and composition are reviewed. There is an urgent need for more studies of therapeutic approaches to diabetic dyslipidemia.

Arteriosclerosis

Serum lipoproteins in African Americans and whites with non-insulin-dependent diabetes in the US population.

BACKGROUND: Despite the significant role that dyslipidemia is believed to play in the development of cardiovascular disease in diabetes, most studies examining diabetic dyslipidemia in the United States have not been population based, and very little data are available for African Americans with diabetes. We used data from a national survey to compare the effect of diabetes on lipid concentrations in African-American and white men and women. In addition, we examined other factors related to lipid concentrations and controlled for these factors in our analyses. METHODS AND RESULTS: The Second National Health and Nutrition Examination Survey included a representative sample of 4177 African Americans and whites in the US civilian noninstitutionalized population 20 to 74 years old. These persons were classified as having non-insulin-dependent diabetes mellitus (NIDDM) (n = 720) or as being nondiabetic (n = 3457) based on an oral glucose tolerance test and a medical history of diabetes. Subjects were given an interview and physical examination that included measurement of serum lipoproteins, body mass index, body fat distribution, dietary fat intake, alcohol consumption, frequency of smoking, and use of medications. By univariate analysis, a worse profile of mean cholesterol, triglycerides, and high-density lipoprotein cholesterol levels was generally apparent in NIDDM than in nondiabetic subjects, regardless of race or sex; a similar pattern was found for the prevalence of abnormal concentrations of these lipids. Lipid profiles appeared to be worse in whites with NIDDM than in African Americans. For mean total and low-density lipoprotein cholesterol, concentrations tended to be worse in women with NIDDM than in men. When other factors significantly affecting lipid levels were adjusted by multivariate analysis, we found that in all race/sex groups, total cholesterol was higher in NIDDM than in nondiabetic subjects but differences were not significant (P = 54), triglyceride concentrations were significantly higher in NIDDM subjects (P < .0001), and high-density lipoprotein cholesterol concentrations were lower in NIDDM subjects (P = .003). An interaction of diabetes with race was found for low-density lipoprotein cholesterol (P = .0001), where concentrations were substantially lower in NIDDM than in nondiabetic subjects among African Americans (P < .01) but slightly higher in NIDDM subjects among whites (P = .33). For other lipids, no differential effect of NIDDM was found by race or sex. CONCLUSIONS: In African-American and white men and women in the United States, NIDDM is associated with a pattern of dyslipidemia that may potentiate the atherosclerotic process. Diabetic treatment should include aggressive treatment of dyslipidemia to reduce this increased risk.

Adult

Greater effect of diabetes on LDL size in women than in men.

OBJECTIVE: Coronary heart disease (CHD) is increased two- to fourfold in subjects with NIDDM compared with normoglycemic subjects. This excess risk is only partially explained by conventional risk factors. We studied the effect of non-insulin-dependent diabetes mellitus (NIDDM) on the size of low-density lipoproteins (LDL). RESEARCH DESIGN AND METHODS: We examined the effect of NIDDM on LDL size and subclass pattern B (LDL size < 253.5 A) in 95 diabetic subjects and 371 nondiabetic subjects from the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. RESULTS: LDL size (A) was significantly lower in diabetic subjects (men: 252.2 +/- 1.8; women: 254.7 +/- 1.3) than in nondiabetic subjects (men: 256.1 +/- 0.8; women: 259.7 +/- 0.7) (P = 0.007). After the use of analysis of covariance to adjust for triglyceride and high-density lipoprotein cholesterol, LDL size was still significantly lower in diabetic women than in nondiabetic women. In men, however, diabetes was no longer significantly associated with LDL size after similar adjustments. Fasting glucose was more strongly correlated with LDL size in women (r = -0.30) than in men (r = -0.18). CONCLUSIONS: We conclude that LDL size is significantly lower in diabetic subjects of both sexes than in nondiabetic subjects, but that diabetic dyslipidemia accounts for the association in diabetic men. The stronger association between LDL size and diabetes in women than in men may partially explain the greater relative risk of CHD observed in women with NIDDM in some studies.

Adult

Dietary fats, insulin resistance, and diabetes.

Although population-based studies suggest that a high-fat diet may increase the incidence of diabetes, the mechanism of this association is not clear. Controlled metabolic studies indicate that changes in fat content of the diet within the range that people normally consume have little or no effect on insulin-mediated glucose disposal. Thus, the effects of a high-fat diet on the incidence of non-insulin-dependent diabetes mellitus (NIDDM) may be mediated by inducing obesity, a known cause of insulin resistance and a risk factor for NIDDM. More research is needed in this area.

Diabetes Mellitus, Type 2

Plasma fibrinogen: levels and correlates in young adults. The Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Sufficient evidence exists that plasma fibrinogen is a risk factor for cardiovascular disease to prompt a search for fibrinogen determinants. The authors measured fibrinogen in 4,193 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study with three objectives: to describe fibrinogen levels in young adults, to determine if correlates of fibrinogen in older adults apply to younger adults, and to examine several additional hypothesized correlates. Fibrinogen (overall mean +/- standard deviation = 263 +/- 57 mg/dl) was greater in women than in men and in blacks than in whites; it was associated positively with cigarette smoking, body mass index, low density lipoprotein cholesterol, triglycerides, and blood pressure, and negatively with physical activity, high density lipoprotein cholesterol, and ethanol intake. Socioeconomic stress indicators and negative personality traits hypothesized as being associated with fibrinogen, possibly through adrenergic mechanisms, proved weak correlates. Parental history of diabetes was correlated positively with fibrinogen, in part because those with a positive parental history had greater body mass. Diabetes mellitus, lipoprotein(a), left ventricular mass, and oral contraceptive use were also positively correlated with fibrinogen concentration. Thus, even in young adults, fibrinogen is associated positively with most risk factors for atherosclerotic cardiovascular disease. This has implications for the role of fibrinogen as a risk factor and, potentially, for cardiovascular disease prevention.

Adolescent

LDL size and subclass pattern in a biethnic population.

Recently, the presence of small, dense low-density lipoprotein (LDL) has been recognized as a risk factor for coronary heart disease. There has been little work on correlates of LDL size in population-based studies and none in Mexican Americans. We examined the relationship of LDL size and pattern to anthropometric and metabolic variables in 466 Mexican Americans and non-Hispanic whites in the San Antonio Heart Study. LDL size in Angstrom units was significantly lower in Mexican Americans (255.8 +/- 0.6) than in non-Hispanic whites (257.9 +/- 0.7) (P = 0.041) after adjustment for gender and age. The percentage of subjects with pattern B tended to be higher in Mexican Americans than in non-Hispanic whites (40.0% versus 34.4%, respectively), although this difference did not reach statistical significance. In univariate analysis, LDL size was significantly associated with glucose (r = -.20), insulin (r = -.19), male gender (r = -.20), total cholesterol (r = -.22), high-density lipoprotein cholesterol (HDL-C) (r = .53), and triglyceride concentrations (r = -.63). In multivariate analyses, higher triglyceride, insulin, and glucose concentrations, lower HDL-C, and male gender were independent correlates of smaller, denser LDL. Correlates of LDL size were similar in Mexican Americans and non-Hispanic whites. Our results confirm previous reports that triglyceride and HDL-C concentrations are the most important variables associated with LDL size. The additional findings of independent effects of male gender, glucose, and insulin concentrations suggest that sex hormones and the insulin resistance syndrome may also play an important role.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose

Increased receptor binding of low-density lipoprotein from individuals consuming a high-carbohydrate, low-saturated-fat diet.

The substitution of saturated fat by complex carbohydrate, according to current dietary recommendations, results in a decrease of plasma and low-density lipoprotein (LDL) cholesterol levels. To determine whether this decrease might result from structural and thus functional changes in LDL particles, the binding internalization and degradation of 125I-LDL were measured using TR715-19 cells, a mutant CHO line into which has been transfected the human LDL receptor, and in which measurements of binding are highly reproducible. Eleven nondiabetic subjects (35 +/- 4 years, 27% +/- 3% body fat) were studied after they had 15% protein, and 560 mg cholesterol/d and the other containing 21% fat (6% saturated), 65% carbohydrate, 14% protein, and 524 mg cholesterol/d.LDL cholesterol levels decreased form 125 +/- 6 to 108 +/- 5 mg/dl (P < .01) on the high-carbohydrate diet. There was an increase in the binding affinity of LDL (Kd 6.6 +/- 2.6 v 7.3 +/- 2.7 micrograms/mL +/- SD; P < .02), and internalization (P < .10), and degradation (P < .05) were also higher. The data suggest that decreasing dietary saturated fat may cause alterations in LDL composition that result in increased receptor clearance; this may partially explain the LDL-decreasing effect of this dietary change.

Adult

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.

Adult