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B V Howard

Publications and source records attributed to B V Howard.

At least 73 records · Page 4Linked to original sources

Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the Strong Heart Study.

Animal studies suggest that lipids are risk factors for kidney diseases. Some prospective studies and clinical trials have reported predictive effects of lipoproteins on different stages of diabetic nephropathy in humans. We examined lipoprotein abnormalities to determine if they predict abnormal urinary excretion of albumin (> or = 30 mg albumin/g creatinine), using logistic regression. We followed 671 American Indians (211 men, 460 women) with Type II diabetes for a mean of 3.9 years (range 1.7-6.2). Participants were aged 45-74 years. They had normal excretion of albumin and normal serum creatinine at baseline. 67 men and 144 women developed abnormal excretion of albumin. In models controlled for age, treatment with oral hypoglycaemic agents or insulin, HbA1c, study site, degree of Indian heritage, mean arterial blood pressure, albumin excretion at baseline and duration of diabetes, a high HDL cholesterol was a protector for abnormal excretion of albumin in women [odds ratio (OR) comparing the 90th with the 10th percentile = 0.56, 95% confidence interval (CI) = 0.32-0.98], but not in men (OR = 1.5, 95% CI = 0.66-3.4). Further adjustment for obesity, insulin concentration, alcohol consumption or physical activity did not change the results. There was a tendency for high values of VLDL and total triglyceride and small LDL size to predict abnormal excretion of albumin in women only. We conclude that low HDL cholesterol was a risk factor for abnormal excretion of albumin in women, but not in men. Sex hormones may be responsible for sex differences in the association between HDL cholesterol and abnormal excretion of albumin.

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Lowering fatty acids potentiates acute insulin response in first degree relatives of people with type II diabetes.

Studies have shown that a high plasma non-esterified fatty acid concentration may inhibit glucose induced insulin secretion in vitro and in vivo. The effect of lowering the fatty acid concentration on the acute insulin response was investigated in first degree relatives of people with Type II diabetes in a double-blind, randomised, placebo-controlled trial. Fifty first degree relatives of people with Type II diabetes volunteered for the study. Twenty five were given acipimox (250 mg/day, four times daily) and 25 placebo. The group treated with acipimox had a lower 2-h plasma glucose concentration (6.1 +/- 0.2 vs 7.7 +/- 0.3 vs mmol/l, p < 0.01); better insulin-mediated glucose uptake (35.4 +/- 0.5 vs 28.3 +/- 0.4 mumol/kg fat free mass per min, p < 0.01), acute insulin response (68 +/- 4.4 vs 46 +/- 7.3 mU/l, p < 0.01) and respiratory quotient (0.81 +/- 0.02 vs 0.77 +/- 0.03, p < 0.05); and a rise in the plasma glucagon (164 +/- 63 vs 134 +/- 72 ng/1, p < 0.05), growth hormone (1.31 +/- 0.13 vs 0.97 +/- 0.21 microgram/l, p < 0.03) and cortisol (325 +/- 41 vs 284 +/- 139 nmol/l, p < 0.05) concentrations. The difference in the acute insulin response persisted, even after adjustment for the 2-h plasma glucose concentration, insulin-mediated glucose uptake, the fasting plasma glucagon concentration and the growth hormone concentration (p < 0.05). In a subgroup of eight patients acipimox was compared with acipimox plus intralipid. The acute insulin response (44 +/- 5.1 vs 71 +/- 5.3 mU/l, p < 0.01) and the insulin-mediated glucose uptake (27.4 +/- 0.4 vs 36.7 +/- 0.5 mumol/kg fat free mass per min, p < 0.003) were lower with acipimox plus intralipid treatment than with acipimox alone. It is concluded that long term acipimox treatment lowers the plasma fasting free fatty acid concentration and improves the acute insulin response and the insulin mediated glucose uptake.

Adult↗

Relationships between insulin resistance and lipoproteins in nondiabetic African Americans, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study.

The study purpose was to explore the association between dyslipidemia and insulin resistance in three ethnic groups. The Insulin Resistance Atherosclerosis Study (IRAS) is a multicenter epidemiologic study conducted at four clinical centers in California, Texas, and Colorado. The study population for this analysis consisted of 931 non-Hispanic white, African American, and Hispanic men and women (aged 45 to 64 years) without diabetes. The IRAS clinical examinations included lipoprotein measures, a 75-g glucose tolerance test, and the frequently sampled intravenous glucose tolerance (FSIGT) test. The results show a consistent relationship between insulin-mediated glucose disposal and dyslipidemia in African American, Hispanic, and non-Hispanic white men and women. Further, LDL size was inversely associated with insulin resistance in all three ethnic groups. These findings indicate that dyslipidemia is a fundamental part of the insulin resistance syndrome in all of the ethnic groups studied.

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Physical activity and lipids and lipoproteins in American Indians ages 45-74.

PURPOSE: The Strong Heart Study is a study of cardiovascular disease and its risk factors among American Indian men and women aged 45-74 yr representative of 13 communities from Arizona (AZ), Oklahoma (OK), and North/South Dakota (N/SD). This investigation sought to characterize the amount and type of physical activity and to determine the association between activity and lipids in this population. METHODS: Total physical activity (occupational plus leisure) was assessed with a validated questionnaire. RESULTS: Men and women from OK (21 +/- 19 and 16 +/- 15 h.wk-1; respectively) and N/SD (23 +/- 21 and 17 +/- 17 h.wk-1; respectively) had activity levels that were similar if not lower than the U.S. population with the AZ communities (17 +/- 21 and 10 +/- 14 h.wk-1; respectively) being substantially lower than the other two communities. Total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), and low density lipoprotein cholesterol (LDL-c) levels were lower than the U.S. population. CONCLUSIONS: For most of the population (diabetic men and nondiabetic men and women), activity was significantly associated (P < 0.05) with apolipoprotein (apo) AI after controlling for covariates. With levels of activity as low if not lower than the general U.S. population coupled with high prevalence of obesity and diabetes, efforts to increase physical activity in American Indians are warranted. Hopefully these increases in activity will result in favorable lipid changes as well as decreasing the risk of diabetes which is epidemic in these populations.

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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.

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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.

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High fat, high cholesterol diets alter low density lipoprotein size and binding affinity in monkeys.

The purpose of this study was to examine the effects of various dietary fats on low density lipoprotein (LDL) binding in an in vitro system where receptor number is not regulated. Cynomolgus monkeys were fed diets containing 37% of energy from fat, with various degrees of saturation, and 0.4 mg/kcal cholesterol or low-fat (13% of energy), low cholesterol (0.03 mg/kcal) chow. Plasma LDL was isolated after 16 weeks. The fatty acid composition of LDL showed enrichment corresponding to the dietary fats consumed, and the high fat, high cholesterol diets produced marked hypercholesterolemia compared to chow feeding. Of those fed the high fat diets, monkeys fed the fish oil diet had the highest LDL cholesterol concentrations, 13.25 +/- 0.77 mmol/l, while those fed the safflower oil diet had the lowest, 7.51 +/- 3.31. LDL from chow fed monkeys had the lowest binding affinity; the Kd was 26.2 +/- 8.7 microg/ml, nearly twice that of the high fat diets (P = 0.003). No significant differences in binding were found between the different high fat diets, although there was a trend toward lower affinity in the diets enriched in polyunsaturated fat. LDL size was affected by diet with chow fed monkeys having the smallest average LDL, 259.3 +/- 1.7 A compared to the other groups (P = 0.03). Monkeys fed the fish oil diet tended to have smaller LDL, but this was not significantly different from the other high fat diets. Binding affinity was correlated with LDL size, r = 0.54, P < 0.01. LDL composition, as measured by apo B/cholesterol ratio, was altered by feeding a high fat, high cholesterol diet. The ratio was reduced in the LDL samples from monkeys fed the high fat diets compared to those fed chow, but this ratio was not significantly correlated with binding. Thus, it appears that increasing dietary fat and cholesterol intake increases LDL size and binding affinity, such that LDL metabolism may be altered independently from effects on receptor number; the type of dietary fat does not seem to influence this process when fat and cholesterol content is very high.

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Plasma lipoproteins and incidence of non-insulin-dependent diabetes mellitus in Pima Indians: protective effect of HDL cholesterol in women.

The role of plasma lipoproteins in the development of non-insulin-dependent diabetes mellitus (NIDDM) was studied in 787 non-diabetic (2-h glucose < 11.1 mmol/l) Pima Indians (265 men and 522 women). Subjects were followed for a mean of 9.8 (range: 1.8-16.4) years, during which 261 (76 men and 185 women) developed NIDDM. In men and women, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, low-density lipoprotein triglyceride and total triglyceride, controlled for age, predicted NIDDM (P < 0.01 for each). These effects diminished when controlled for age, sex, body mass index, systolic blood pressure and 2-h glucose. However, high-density lipoprotein (HDL) cholesterol, controlled for age, body mass index, systolic blood pressure and 2-h glucose, was a significant protective factor for NIDDM in women (hazard rate ratio (HRR) = 0.35, 95% CI (0.23-0.54), P < 0.001, 90th compared with 10th percentile) but not in men (HRR = 1.04, 95% CI (0.53-2.05), P = 0.915). This association remained significant in women when controlled for fasting or 2-h plasma insulin concentrations, other estimates of insulin resistance or alcohol consumption. The protective effect of HDL cholesterol was similar among women with normal (2-h glucose < 7.8 mmol/1) or impaired (7.8 mmol/l < or = 2-h glucose < 11.1 mmol/l) glucose tolerance at baseline. These results indicate that lipoprotein disorders are an early accompaniment of the abnormalities that lead to NIDDM.

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Relations of Doppler stroke volume and its components to left ventricular stroke volume in normotensive and hypertensive American Indians: the Strong Heart Study.

Doppler echocardiographic measurement of time-velocity integral of blood flow across the aortic annulus ("stroke distance") or of stroke volume (SV) have been proposed as noninvasive measures of cardiac pump performance that could elucidate the hemodynamics of hypertension. To evaluate the performance of these measures of hemodynamic volume load in a population with a wide range of body build and other characteristics, we obtained technically adequate imaging and Doppler echocardiograms in 1,935 of 2,212 (87%) American Indian Strong Heart Study participants, without mitral regurgitation or segmental left ventricular (LV) dysfunction, in Arizona, Oklahoma, and South/North Dakota. The subjects ranged widely in age (48 to 81 years) and body mass index (17.0 to 62.6 kg/m2); 65% were women; 1,161 were normotensive and 774 were hypertensive. As a reference standard, LV and stroke volumes were calculated from LV internal dimensions by the Teichholz method. Doppler SVs were moderately related to LV SVs (r = 0.63), but Doppler SV was slightly lower in both normotensive (mean = 69.8 and 72.9 mL, respectively) and hypertensive subjects (71.1 v 73.6 mL). Aortic stroke distance was less closely related than was aortic annular area to LV SV (r = 0.34 v 0.40, P < .001). Aortic annular area (r = 0.44) but not stroke distance (r = 0.04) was moderately correlated with body surface area. Stroke distance was inversely related to annular area (r = -0.29) and in subjects stratified by aortic annular diameter 1.6 to 1.9, 2.0 to 2.1, and 2.3 to 2.9 cm, mean LV SV increased from 67 to 74 to 80 mL, but average stroke distance fell from 22.8 to 21.6 to 20.1 cm. Stroke distance also failed to identify gender differences in LV SV but did identify that due to obesity. Thus Doppler SV closely parallels independently measured LV SV but slightly underestimates SV in both normotensive and hypertensive adults, whereas aortic stroke distance yields misleading comparisons between genders or individuals of different body sizes.

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The relationship between weight and response to cholesterol-lowering diets in women.

OBJECTIVE: To determine whether factors related to body weight might influence the cholesterol lowering response to diet. DESIGN: Run-In diet followed by crossover to low fat diets; average response is reported. SUBJECTS: Sixty-three subjects (30 men and 33 women) with moderately elevated plasma cholesterol levels. MEASUREMENTS: Lipid and anthropometric measurements. Data were analyzed as a repeated measures analysis of variance with lipid lowering response in all combined cholesterol lowering diets compared to baseline. RESULTS: LDL cholesterol lowering was significantly affected by BMI in women (P = 0.01) but not in men (P = 0.54). There was also a weak effect of waist-hip (W/H) ratio on response (P = 0.127) in women, with the lower responders having a higher W/H ratio but there was no effect of W/H ratio in men (P = 0.86). CONCLUSION: These results suggest that overweight women with elevated plasma cholesterol may be less responsive to reducing their cholesterol levels with diet.

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Parity, postmenopausal estrogen use, and cardiovascular disease risk factors in American Indian women: the Strong Heart Study.

Studies have suggested that high parity is related to an increased risk of cardiovascular disease (CVD). Reasons for an increased risk are unclear but may include influences of child-bearing on levels of CVD risk factors. The present study examined the associations of parity and CVD risk factors in American Indian women, among whom large families are common. Estrogen use and CVD risk factors also were assessed. The study included 1982 ever-married, postmenopausal women aged 45 through 74 years who participated in the Strong Heart Study (SHS), a large study of American Indians in three geographic areas of the United States. Information was obtained during a physical examination and interview. Parity ranged from 0 to 18 (median 5). Current estrogen use varied from 5% in Arizona to 21% in Oklahoma. Multivariable analyses found a statistically significant, inverse association between parity and high-density lipoprotein (HDL) cholesterol, although the difference with increasing parity was small (-0.26 mg/dl per additional live birth). Estrogen users had significantly lower levels of low-density lipoprotein cholesterol (-6.4 mg/dl) and fibrinogen (-26.2 mg/dl) and a lower waist/hip ratio (-0.02), and higher values of HDL (5 mg/dl) and logarithm (ln) triglyceride (0.13 mg/dl). Current users were slightly more likely to be hypertensive (prevalence odds ratio, 1.56). Relations between parity and CVD risk factors in American Indian women with high parity suggested only small differences with increasing parity. Associations with estrogen use are much stronger and are similar to those observed in other groups of women.

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Differences in insulin suppression of free fatty acid levels by gender and glucose tolerance status. Relation to plasma triglyceride and apolipoprotein B concentrations. Insulin Resistance Atherosclerosis Study (IRAS) Investigators.

Most discussions of relations of insulin resistance to coronary heart disease risk factors have focused on insulin-stimulated glucose uptake, but insulin suppression of plasma free fatty acid (FFA) levels is also important in lipid and lipoprotein metabolism. To identify groups with impaired insulin suppression of FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non-insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load adjusted for fasting FFAs was used as the measure of insulin suppression. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were significantly higher in men than women and in persons with impaired glucose tolerance and non-insulin-dependent diabetes mellitus versus normal glucose tolerance. The gender difference was largely accounted for by differences in central obesity as measured by waist-hip ratio; the difference by glucose tolerance status was not affected by central obesity, suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and apoB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB and triglyceride concentrations associated with male gender and with glucose intolerance are partly accounted for by differences in the ability of insulin to suppress FFA concentrations.

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Relation of LDL size to the insulin resistance syndrome and coronary heart disease in American Indians. The Strong Heart Study.

Small, dense LDL has been shown to be associated with the insulin resistance syndrome and coronary heart disease (CHD). We examined the distribution of LDL size and phenotype within a population-based sample of American Indians to determine the relationships with prevalent CHD and to examine associations with hyperinsulinemia and other components of the insulin resistance syndrome. Data were available for 4505 men and women between 45 and 74 years of age who are members of 13 American Indian communities in three geographic areas. Diabetes, CHD, and CHD risk factors were assessed by standardized techniques, and LDL size was measured by gradient gel electrophoresis. LDL size was smaller in men than in women and in individuals with diabetes than in those without diabetes. In multivariate analysis, LDL size was significantly related to several components of the insulin resistance syndrome, including triglycerides (inversely) and HDL cholesterol (positively). Although univariate relations were positive, LDL size was not significantly related to fasting insulin concentrations or body mass index in the multivariate model. LDL size also showed no relationship to apolipoprotein E phenotype. When LDL size was compared in individuals with and without CHD, no significant differences were observed, either in nondiabetic or diabetic individuals. We conclude that LDL size is most strongly related to lipoprotein components of the insulin resistance syndrome, especially plasma triglycerides. However, in this population with low LDL, it is not related to cardiovascular disease.

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Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

OBJECTIVE: Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. RESEARCH DESIGN AND METHODS: In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. RESULTS: The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P < 0.05). When analyzed by clinic, each of the active intervention groups differed significantly from the control clinics (P < 0.05). The relative decrease in rate of development of diabetes in the active treatment groups was similar when subjects were stratified as lean or overweight (BMI < or > or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. CONCLUSIONS: Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

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The Sleep Heart Health Study: design, rationale, and methods.

The Sleep Heart Health Study (SHHS) is a prospective cohort study designed to investigate obstructive sleep apnea (OSA) and other sleep-disordered breathing (SDB) as risk factors for the development of cardiovascular disease. The study is designed to enroll 6,600 adult participants aged 40 years and older who will undergo a home polysomnogram to assess the presence of OSA and other SDB. Participants in SHHS have been recruited from cohort studies in progress. Therefore, SHHS adds the assessment of OSA to the protocols of these studies and will use already collected data on the principal risk factors for cardiovascular disease as well as follow-up and outcome information pertaining to cardiovascular disease. Parent cohort studies and recruitment targets for these cohorts are the following: Atherosclerosis Risk in Communities Study (1,750 participants), Cardiovascular Health Study (1,350 participants), Framingham Heart Study (1,000 participants), Strong Heart Study (600 participants), New York Hypertension Cohorts (1,000 participants), and Tucson Epidemiologic Study of Airways Obstructive Diseases and the Health and Environment Study (900 participants). As part of the parent study follow-up procedures, participants will be surveyed at periodic intervals for the incidence and recurrence of cardiovascular disease events. The study provides sufficient statistical power for assessing OSA and other SDB as risk factors for major cardiovascular events, including myocardial infarction and stroke.

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