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Showing papers by "Barbara V. Howard published in 2010"


Journal ArticleDOI
TL;DR: Left ventricular hypertrophy is more strongly related to systolic pressure than to pulse pressure, and central pressures are more stronglyrelated than brachial pressures to concentric left ventricular geometry, which suggest that absolute (systolic) pressure is more important in stimulatingleft ventricularhypertrophy and remodeling, whereas pulsatile stress (pulse pressure) is moreImportant in causing vascular hyperTrophy and atherosclerosis.
Abstract: ObjectiveWe previously demonstrated stronger relations of central vs. brachial blood pressure, particularly pulse pressure, to carotid artery hypertrophy and extent of atherosclerosis. Data regarding the relative impacts of central and brachial pressures on left ventricular hypertrophy and geometry

233 citations


Journal ArticleDOI
TL;DR: Type 2 diabetes is a potent, independent risk factor for heart failure in diabetic patients and Mechanisms directly related to diabetes and impairing cardiac function should be studied and identified.
Abstract: OBJECTIVES Type 2 diabetes is accepted as a cause of heart failure, but direct cause-effect evidence independent of incident myocardial infarction (MI), hypertension and other coexisting risk factors is less well studied. We tested the hypothesis that diabetes predisposes to heart failure independently of hypertension and intercurrent MI. METHODS We evaluated 12-year incident heart failure in 2740 participants (1781 women) without prevalent cardiovascular or severe kidney disease, at the time of the first exam of the Strong Heart Study cohort. Intercurrent MI was censored as a competing risk event. RESULTS Diabetes was present in 1206 individuals (44%), and impaired fasting glucose (IFG) in 391 (14%). Diabetic participants more frequently had hypertension and/or central obesity (both P < 0.0001). Incident heart failure was ascertained in 64 participants with normal fasting glucose (NFG; 6%), 26 (7%) with IFG and 201 with diabetes (17%, hazard ratio = 4.04 vs. NFG, P < 0.0001). In Cox analysis adjusting for age, sex, obesity, central fat distribution, hypertension, antihypertensive medications, prevalent atrial fibrillation, glomerular filtration rate, urinary albumin/creatinine ratio, plasma cholesterol, Hb1Ac, smoking habit, alcohol use, educational level and physical activity, diabetes was associated with a two-fold greater risk of incident heart failure than NFG (hazard ratio = 2.45, P < 0.0001). Diabetes maintained 1.5-fold greater risk of heart failure than NFG (P < 0.03) even when intercurrent MI (n = 221) was censored as a competing risk event, similar to the adjusted hazard ratio for heart failure in hypertension. CONCLUSION Type 2 diabetes is a potent, independent risk factor for heart failure. Risk of heart failure in diabetic patients cannot be fully explained by incident MI and coexisting cardiovascular risk factors. Mechanisms directly related to diabetes and impairing cardiac function should be studied and identified.

124 citations


Journal ArticleDOI
TL;DR: Diabetes risk factors and incidence rates in American Indians (AI) with prediabetes are examined.
Abstract: Background The association between prediabetes as currently defined and incident diabetes in populations with widespread obesity, insulin resistance syndrome, and diabetes is not well defined. In this article, diabetes risk factors and incidence rates in American Indians (AI) with prediabetes are examined.

79 citations


Journal ArticleDOI
TL;DR: The replacement of 7-8% of fat intake with complex carbohydrates over 6 y was not associated with clinically adverse effects on triglycerides, HDL cholesterol, or lipoprotein subclasses, and diabetic white women with higher triglyceride concentrations may have greater increases in triglycerides.

54 citations


Journal ArticleDOI
TL;DR: The hypothesis that saturated fatty acids are associated with insulin resistance and glucose intolerance and that saturated fat acids are significant risk factors for type 2 diabetes are strongly supported.
Abstract: Objectives. Type 2 diabetes and the consumption of saturated fatty acids (FAs) are on the rise among Alaska Inuits. This analysis, based on a cross-sectional study, explores the possible associations of saturated FA content in red blood cells (RBCs) and parameters of glucose metabolism in a sample of Alaska Natives. Study design and methods. The sample included 343 women and 282 men aged 35–74. Statistical analyses explored the associations of selected RBC (myristic, palmitic and stearic acids) FAs with fasting glucose (plasma), fasting insulin (plasma), 2h glucose (2-hour glucose tolerance test), 2h insulin and homeostasis model assessment (HOMA) index. The models included sex and glucose metabolism status as fixed factors and age, body mass index (BMI), waist circumference, physical activity (METS) and FA content in RBCs as covariates. Measures of insulin, glucose and HOMA index were used as dependent variables. Results. Myristic acid was positively associated with fasting insulin (β=0.47, p<0.001), 2h insulin (β=0.53, p=0.02) and HOMA index (β=0.455, p<0.001). Palmitic acid was associated with 2h glucose (β=2.3×10-2, p<0.001) and 2h insulin (β=5.6×10-2, p=0.002) and stearic acid was associated with fasting glucose (β=4.8×10-3, p=0.006). Conclusions. These results strongly support the hypothesis that saturated fatty acids are associated with insulin resistance and glucose intolerance and that saturated fatty acids are significant risk factors for type 2 diabetes. (Int J Circumpolar Health 2010; 69(4):344–351) Keywords: myristic acid, palmitic acid, stearic acid, Inuit, Alaska Natives, diabetes, saturated fat

54 citations


Journal ArticleDOI
TL;DR: Estrogen therapy increases the risk of nephrolithiasis in healthy postmenopausal women, and the mechanisms underlying this higher susceptibility remain to be determined.
Abstract: Background Observational studies examining the role of estrogen in the risk of kidney stone formation have shown conflicting results. However, randomized trial evidence on nephrolithiasis risk with estrogen therapy in postmenopausal women is lacking. Methods We reviewed the incidence of nephrolithiasis in the Women's Health Initiative estrogen-alone and estrogen plus progestin trials conducted at 40 US clinical centers. A total of 10 739 postmenopausal women with hysterectomy were randomized to receive 0.625 mg/d of conjugated equine estrogens (CEE) or placebo, and 16 608 postmenopausal women without hysterectomy were randomized to receive placebo or estrogen plus progestin given as CEE plus medroxyprogesterone acetate (2.5 mg/d). The incidence of nephrolithiasis was determined for an average follow-up of 7.1 years for the CEE trial and 5.6 years for the estrogen plus progestin trial. Results Baseline demographic characteristics and risk factors for nephrolithiasis were similar in the placebo and treatment arms. Estrogen therapy was associated with a significant increase in nephrolithiasis risk from 34 to 39 cases per 10 000 person-years (hazard ratio, 1.21; 95% confidence interval, 1.03-1.44). Censoring data from women when they ceased to adhere to study medication increased the hazard ratio to 1.39 (95% confidence interval, 1.08-1.78). The increased nephrolithiasis risk was independent of progestin coadministration, and effects did not vary significantly according to prerandomization history of nephrolithiasis. Conclusions These data suggest that estrogen therapy increases the risk of nephrolithiasis in healthy postmenopausal women. These findings should be considered in decision making regarding postmenopausal estrogen use. The mechanisms underlying this higher susceptibility remain to be determined. Trial Registration clinicaltrials.gov Identifier:NCT0000611

52 citations


Journal ArticleDOI
TL;DR: Findings in independent populations support that KIAA1797 genetic variation may be associated with HR but elucidation of a functional relationship requires additional study.
Abstract: Heart rate (HR) has been identified as a risk factor for cardiovascular disease (CVD), yet little is known regarding genetic factors influencing this phenotype. Previous research in American Indians (AIs) from the Strong Heart Family Study (SHFS) identified a significant quantitative trait locus (QTL) for HR on chromosome 9p21. Genetic association on HR was conducted in the SHFS. HR was measured from electrocardiogram (ECG) and echocardiograph (Echo) Doppler recordings. We examined 2248 single-nucleotide polymorphisms (SNPs) on chromosome 9p21 for association using a gene-centric statistical test. We replicated the aforementioned QTL [logarithm of odds (LOD) 5 4.83; genome-wide P 5 0.0003] on chromosome 9p21 in one SHFS population using joint linkage of ECG and Echo HR. After correcting for effective number of SNPs using a gene-centric test, six SNPs (rs7875153, rs7848524, rs4446809, rs10964759, rs1125488 and rs7853123) remained significant. We applied a novel bivariate association method, which was a joint test of association of a single locus to two traits using a standard additive genetic model. The SNP, rs7875153, provided the strongest evidence for association (P 5 7.14 3 1026 ). This SNP (rs7875153) is rare (minor allele frequency 5 0.02) in AIs and is located within intron 9 of the gene KIAA1797. To support this association, we applied lymphocyte RNA expression data from the San Antonio Family Heart Study, a longitudinal study of CVD in Mexican Americans. Expression levels of KIAA1797 were significantly associated (P 5 0.012) with HR. These findings in independent populations support that KIAA1797 genetic variation may be associated with HR but elucidation of a functional relationship requires additional study.

42 citations


Journal ArticleDOI
TL;DR: Risk stratification as proposed in the 2007 AHA guideline is simple, accessible to patients and providers, and identifies cardiovascular risk with accuracy similar to that of the current Framingham algorithm.
Abstract: Background— The 2007 update to the American Heart Association (AHA) guidelines for cardiovascular disease prevention in women recommend a simplified approach to risk stratification. We assigned Women’s Health Initiative participants to risk categories as described in the guideline and evaluated clinical event rates within and between strata. Methods and Results— The Women’s Health Initiative enrolled 161 808 women ages 50 to 79 years and followed them prospectively for 7.8 years (mean). Applying the 2007 AHA guideline categories, 11% of women were high risk, 72% at-risk, and 4% at optimal risk; 13% of women did not fall into any category, that is, lacked risk factors but did not adhere to a healthy lifestyle (moderate intensity exercise for 30 minute most days and <7% of calories from saturated fat). Among high risk, at-risk, and optimal risk women, rates of myocardial infarction/coronary death were 12.5%, 3.1%, and 1.1% per 10 years (P for trend <0.0001); the event rate was 1.3% among women who could not...

41 citations


Journal ArticleDOI
TL;DR: Data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C; identifying these risk factors early and treating to target is recommended.
Abstract: Background and aims Although Eskimos were thought to be protected from cardiovascular disease (CVD), state health data show a large proportion of deaths from CVD, despite traditional lifestyles and high omega-3 fatty acid intake. This article explores CVD prevalence and its relation to risk factors in Alaska Eskimos. Methods and results A population-based cohort of 499 Alaska Eskimos > age 45 from the Norton Sound region was examined in 2000–2004 for CVD and associated risk factors as part of the Genetics of Coronary Artery Disease in Alaska Natives study. CVD and atherosclerosis were evaluated and adjudicated using standardized methods. Average age was 58 years; diabetes prevalence was low and high-density lipoprotein cholesterol (HDL-C) concentrations were high, but a large proportion smoked and had high pathogen burden. CVD was higher in men (12.6%) than in women (5.3%) (prevalence ratio 2.4, CI 1.3–4.4). Rates of stroke (6.1% in men, 1.8% in women) were similar to those for coronary heart disease (CHD) (6.1% men, 2.5% women). MI prevalence was low in both genders (1.9% and 0.7%). CVD was higher in men and in those >60 years. Hypertension, diabetes, high LDL-C, high apoB, and low HDL-C were all strong correlates ( Conclusion These data show high CHD and stroke prevalence in Alaska Eskimos, despite low average LDL-C and high HDL-C. Hypertension and high LDL-C were independent correlates; identifying these risk factors early and treating to target is recommended.

41 citations



Journal ArticleDOI
TL;DR: Individuals with diabetes have higher rates of depression than those without diabetes, consistent with other populations; men and women with severe depression have higher A1c levels than those with moderate-to-no depression.
Abstract: Objectives To examine the relationship between depression and glycemic control in the Strong Heart Study (SHS), a longitudinal study of cardiovascular disease in American Indians. Methods This cross-sectional analysis focused on the relationship between depression, diabetes and glycemic control among 2832 individuals aged ≥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. Results Rates of depression were higher in men and women with diabetes when compared to those without diabetes, respectively ( P Conclusions Individuals 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.

Journal ArticleDOI
TL;DR: Preliminary support for the utility of MI techniques in diabetes care among American Indians is provided, with significant improvements in participants' self-reported depressive symptoms, genetic/racial fatalism, treatment satisfaction, and social/vocational worry observed.
Abstract: A study was conducted to assess the utility of motivational interviewing techniques to improve management of type 2 diabetes among residents of an American Indian reservation. A convenience sample of participants was recruited at an Indian Health Service diabetes clinic (n = 26). Random blood glucose, A1C, and demographic variables for the 6 months before baseline were collected via chart review; data on random blood glucose, A1C, demographic variables, health-related behaviors, and psychological self-report instruments were collected at baseline and 3 months after intervention. The intervention consisted of two individual, 30-minute sessions of motivational interviewing (MI) delivered over 3 weeks. Significant improvements in participants9 self-reported depressive symptoms, genetic/racial fatalism, treatment satisfaction, and social/vocational worry were observed. Stepwise regression revealed seven predictors of change in A1C from baseline to study end: completion of the study, total blood quantum, change in A1C from 6 months before baseline to baseline, and change in provider trust, treatment acceptance, depression, and reported hours of exercise per week from baseline to study completion. The final analysis had an R2 value of 0.896, accounting for 89.6% of the variance in A1C change. This pilot study provides preliminary support for the utility of MI techniques in diabetes care among American Indians.

Journal ArticleDOI
TL;DR: Diabetes is a major determinant of CVD in this population and most of the CVD is occurring in those with diabetes, so strategies to prevent diabetes and manage blood pressure and lipids should reduce CVD rates in Native Hawaiians.


Journal ArticleDOI
TL;DR: Common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations because of the lack of replication of this gene in the population of American Indians.
Abstract: Chronic kidney disease (CKD) is an important public health problem in American Indian populations. Recent research has identified associations of polymorphisms in the myosin heavy chain type II isoform A (MYH9) gene with hypertensive CKD in African-Americans. Whether these associations are also present among American Indian individuals is unknown. To evaluate the role of genetic polymorphisms in the MYH9 gene on kidney disease in American Indians, we genotyped 25 SNPs in the MYH9 gene region in 1,119 comparatively unrelated individuals. Four SNPs failed, and one SNP was monomorphic. We inferred haplotypes using seven SNPs within the region of the previously described E haplotype using Phase v2.1. We studied the association between 20 MYH9 SNPs with kidney function (estimated glomerular filtration rate, eGFR) and CKD (eGFR < 60 ml/min/1.73 m2 or renal replacement therapy or kidney transplant) using age-, sex- and center-adjusted models and measured genotyped within the variance component models. MYH9 SNPs were not significantly associated with kidney traits in additive or recessive genetic adjusted models. MYH9 haplotypes were also not significantly associated with kidney outcomes. In conclusion, common variants in MYH9 polymorphisms may not confer an increased risk of CKD in American Indian populations. Identification of the actual functional genetic variation responsible for the associations seen in African-Americans will likely help to clarify the lack of replication of this gene in our population of American Indians.

Journal ArticleDOI
15 Sep 2010-BMJ
TL;DR: Bolland et al. as mentioned in this paper compared the results of their meta-analysis with those of the women's health initiative (WHI) randomised controlled trial of calcium/vitamin D supplementation with 254,000 subject years of follow-up.
Abstract: Bolland and colleagues contrast the results of their meta-analysis with those of the women’s health initiative (WHI) randomised controlled trial of calcium/vitamin D supplementation with 254 000 subject years of follow-up.1 2 Cardiovascular events in the WHI study were pre-specified end points …

Journal ArticleDOI
TL;DR: Standard and aggressive lipid targets can be safely maintained in diabetic patients and standardized algorithms, point-of-care lipid testing, and nonphysician providers facilitate care delivery.

Journal ArticleDOI
TL;DR: Arab Americans in the sample had a higher prevalence of high cholesterol and lower prevalence of diabetes and hypertension than the general population of the United States, and a high levels of smoking and a lack of physical activity.
Abstract: Cardiovascular disease (CVD) risk factor profiles of Arab Americans may differ from those of the majority ethnic groups in the United States on which clinical practice guidelines are based. Reasons for these differences include genetic homogeneity and both cultural and lifestyle factors that influence CVD risk. Therefore, appropriate therapeutic targets for effective CVD prevention in Arab Americans need to be designed. However, research on Arab American health is sparse. For the cross-sectional survey described in this article, a convenience sample of Arab Americans living in Washington, DC; Virginia; and Maryland was recruited. Arab Americans in our sample had a higher prevalence of high cholesterol and lower prevalence of diabetes and hypertension than the general population of the United States. High levels of smoking and a lack of physical activity were also reported. Most participants (71%) reported a score of 15 and below on the Center for Epidemiologic Studies Depression Scale, indicating no signs of clinical depression. Predictors of depression were compared in those born inside and outside the United States. With the results from this survey, we have designed a cross-sectional study to begin in early 2010 to determine the prevalence of CVD risk factors in Arab Americans which can be compared with the overall population of the United States.

Journal ArticleDOI
TL;DR: In this paper, the authors examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic BP ≤115 mmHg versus standard targets, and concluded that treatment to lower blood pressure below standard targets was not cost-effective because of the cost of the additional medications required to meet the lower targets.

Journal ArticleDOI
TL;DR: The aim of this paper is to propose models incorporating marginal models approaches with a covariance structure for assessing population-based associations of diseases with their risk factors/covariates and estimating population characteristics for epidemiological studies while adjusting for the complicated relatedness among outcomes collected from large extended families.
Abstract: Large studies of extended families usually collect valuable phenotypic data that may have scientific value for purposes other than testing genetic hypotheses if the families were not selected in a biased manner. These purposes include assessing population-based associations of diseases with risk factors/covariates and estimating population characteristics such as disease prevalence and incidence. Relatedness among participants however, violates the traditional assumption of independent observations in these classic analyses. The commonly used adjustment method for relatedness in population-based analyses is to use marginal models, in which clusters (families) are assumed to be independent (unrelated) with a simple and identical covariance (family) structure such as those called independent, exchangeable and unstructured covariance structures. However, using these simple covariance structures may not be optimally appropriate for outcomes collected from large extended families, and may under- or over-estimate the variances of estimators and thus lead to uncertainty in inferences. Moreover, the assumption that families are unrelated with an identical family structure in a marginal model may not be satisfied for family studies with large extended families. The aim of this paper is to propose models incorporating marginal models approaches with a covariance structure for assessing population-based associations of diseases with their risk factors/covariates and estimating population characteristics for epidemiological studies while adjusting for the complicated relatedness among outcomes (continuous/categorical, normally/non-normally distributed) collected from large extended families. We also discuss theoretical issues of the proposed models and show that the proposed models and covariance structure are appropriate for and capable of achieving the aim.


Journal ArticleDOI
TL;DR: The burden of albuminuria is low, and comprehensive programs and policies are important given the rise in diabetes and hypertension among Alaska Natives.
Abstract: Background: The prevalence and associated risk factors for albuminuria and low-grade albuminuria in Alaska Natives is not known. Methods: Cross-sectional analysis of the Genetics of Coronary Artery Disease in Alaska Natives Study. We included 1,026 individuals, who represent 85% of the study participants for whom complete data were available. Risk factors examined were age, sex, education, diabetes, hypertension, obesity, lipids, C-reactive protein, angiotensin-converting enzyme inhibitor use, and smoking status. Urine albumin excretion was estimated by the albumin/creatinine ratio measured from a single random morning urine sample. Albuminuria was defined as an albumin/creatinine ratio of ≧30 mg/g. Low-grade albuminuria was defined as an albumin/creatinine ratio of 10 to Results: The mean age was 42 years and over half were female. Diabetes prevalence was low at 3% and the prevalence of hypertension was 20%. The prevalence of albuminuria was 6%; the prevalence of low-grade albuminuria was 12%. Individuals with diabetes or hypertension were 3 times more likely to have albuminuria than those without these conditions [odd ratios: diabetes 3.0 (1.2–7.9) and hypertension 3.0 (1.2–7.3)]. Conclusions: The burden of albuminuria is low. Comprehensive programs and policies are important given the rise in diabetes and hypertension among Alaska Natives.