Barbara V Howard's research while affiliated with MedStar Health Research Institute and other places
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Publications (1,000)
Dyslipidemia has been associated with depression, but individual lipid species associated with depression remain largely unknown. The temporal relationship between lipid metabolism and the development of depression also remains to be determined. We studied 3721 fasting plasma samples from 1978 American Indians attending two exams (2001–2003, 2006–2...
Background
Insufficient data exist to conclude whether consumption of artificially sweetened beverages is associated with a higher risk of urinary tract cancers.
Objective
We sought to investigate whether urinary tract cancer incidence differed among women who consumed various amounts of artificially sweetened beverages.
Design, setting, and part...
Objective:
The aim of this study was to determine if higher artificially sweetened beverage intake is associated with higher prevalence of urinary incontinence symptoms.
Methods:
We conducted a secondary analysis of data from the Women's Health Initiative Observational Study. Our analytic cohort included 80,388 women. Participants who answered q...
American Indian (AI) communities experience persistent diabetes-related disparities, yet few nutrition interventions are designed for AI with type 2 diabetes or address socio-contextual barriers to healthy eating. We describe our process of adapting the evidence-based Cooking Matters® program for use by AI adults with type 2 diabetes in a rural and...
Background:
Previous studies report that obesity can be a risk and a protective factor for cognitive health. However, they have not examined whether white matter hyperintensities (WMH) mediate the association between mid- or late-life body mass index (BMI) and late-life cognitive performance. We examined this question in American Indians, a popula...
OBJECTIVE
A plant-based dietary pattern, the Portfolio Diet, has been shown to lower LDL cholesterol and other cardiovascular disease risk factors. However, no study has evaluated the association of this diet with incident type 2 diabetes.
RESEARCH DESIGN AND METHODS
This analysis included 145,299 postmenopausal women free of diabetes at baseline...
Background
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid that may impact atherosclerosis, and animal experimental studies suggest EETs protect cardiac function. Plasma EETs are mostly esterified to phospholipids and part of an active pool. To address the limited information about EETs and CVD in humans, we conducted a prospec...
Background
Plasma ceramides and sphingomyelins have been independently linked to diabetes risk, glucose and insulin levels, and the risk of several cardiovascular (CVD) outcomes. However, whether individual ceramide and sphingomyelin species contribute to CVD risk among people with type 2 diabetes is uncertain. Our goal was to evaluate associations...
Telomeres shorten with age and shorter leukocyte telomere length (LTL) has been associated with various age-related diseases. Thus, LTL has been considered a biomarker of biological aging. Dyslipidemia is an established risk factor for most age-related metabolic disorders. However, little is known about the relationship between LTL and dyslipidemia...
Dyslipidemia associates with and usually precedes the onset of chronic kidney disease (CKD), but a comprehensive assessment of molecular lipid species associated with risk of CKD is lacking. Here, we sought to identify fasting plasma lipids associated with risk of CKD among American Indians in the Strong Heart Family Study, a large-scale community-...
Purpose
Our study examined psychosocial risk and protective features affecting cardiovascular and mortality disparities in American Indians, including stress, anger, cynicism, trauma, depression, quality of life, and social support.
Methods
The Strong Heart Family Study cohort recruited American Indian adults from 12 communities over 3 regions in...
Background
Epigenetic dysregulation has been proposed as a key mechanism for arsenic-related cardiovascular disease (CVD). We evaluated differentially methylated positions (DMPs) as potential mediators on the association between arsenic and CVD.
Methods
Blood DNA methylation was measured in 2321 participants (mean age 56.2, 58.6% women) of the Str...
Background and Aims
Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its as...
Background: Plasma ceramides and sphingomyelins have been independently linked to diabetes risk, glucose and insulin levels, and the risk of several cardiovascular (CVD) outcomes. However, whether individual ceramide and sphingomyelin species contribute to CVD risk among people with type 2 diabetes is uncertain. Our goal was to evaluate association...
Background: Dyslipidemia is a major risk factor for CVD. Left ventricular mass (LVM) is an independent predictor of heart failure and other cardiovascular events. It is unclear whether and how altered plasma lipidome (all lipids in a plasma sample) affects LVM. The relationship between longitudinal change in plasma lipidome and change in LVM is als...
Background: Dyslipidemia is associated with and often precedes the onset of chronic kidney disease (CKD). However, standard lipid panels fail to describe the full spectrum of blood lipidome. A longitudinal profiling of the full spectrum of blood lipidome associated with the risk of CKD is still lacking in any racial/ethnic group, including American...
Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in % of total FAs in RBC), from samples of seven countries (USA,...
Background: Depression is an independent risk factor for CVD. Dyslipidemia, an established risk factor for CVD, has also been associated with depression, but a full spectrum of plasma lipidome for risk of depression is still lacking in any racial/ethnic groups.
Objective: To identify lipids associated with risk of depression, independent of known c...
Introduction: Dyslipidemia is characterized by high levels of total cholesterol (TC), LDL cholesterol (LDL-C), triglycerides (TG), or low levels of HDL cholesterol (HDL-C) and is an established risk factor for subclinical and clinical cardiovascular disease (CVD) among adults. Although several investigations exist in older American Indian (AI) adul...
Background
The association of social isolation or lack of social network ties in older adults is unknown. This knowledge gap is important since the risk of heart failure (HF) and social isolation increase with age. The study examines whether social isolation is associated with incident HF in older women, and examines depressive symptoms as a potent...
OBJECTIVE
Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis.
RESEARCH DESIGN AND METHODS
We included data from an in...
Introduction:
Research on factors associated with late-life cognitive performance in diverse racial/ethnic groups is increasingly important due to the growing size and racial diversity of the elder population.
Methods:
Using data on American Indians from the Strong Heart Study, we measured associations between mid-life physical activity (PA), as...
Background:
The apolipoprotein E (APOE) ε4 allele confers higher risk of neurodegeneration and Alzheimer's disease (AD), but differs by race/ethnicity. We examined this association in American Indians.
Methods:
The Strong Heart Study is a population-based cohort of American Indians who were 64 to 95 years of age in 2010 to 2013. APOE ε4 status,...
We recently presented associations of biomarker-calibrated protein, protein density, carbohydrate, and carbohydrate density with the incidence of cardiovascular diseases, cancers, and diabetes in Women’s Health Initiative cohorts (1993 to present, at 40 US clinical centers) of postmenopausal women. The biomarkers relied on serum and urine metabolom...
Background
We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, while protein density associations were mixed.
Objective...
Background:
Research on factors associated with late-life cognitive performance in diverse racial/ethnic groups is increasingly important due to the growing size and racial diversity of the elder population. American Indian elders suffer disproportionately from health conditions and behaviors that increase the risk of cognitive impairment, such as...
Introduction
Data on cigarette smoking prevalence among Alaska Native and American Indian (ANAI) people are limited to cross-sectional studies or specific subpopulations. Using data from the Alaska Education and Research toward Health (EARTH) Study 10-year follow-up, this study assessed patterns of smoking from baseline and factors associated with...
Introduction: Rates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Subclinical atherosclerosis is typically detected later in life and may develop into clinical CVD. Although investigators have established the association in older adults, the burden of subclinical atherosclerosis and its relation to CVD risk among...
Background: Dyslipidemia is an established risk factor for CVD. Standard lipid panel lacks description of the full spectrum of blood lipids. A longitudinal profiling of blood lipidome in relation to the risk of CVD is lacking in any racial/ethnic groups.
Objective: Identify novel lipid species associated with risk of CVD in American Indians, indepe...
Background: Dyslipidemia is an established risk factor for atherosclerotic CVD, but full identification of circulating molecular lipids associated with atherosclerosis is still lacking in any racial/ethnic group.
Objective: Prospectively identify lipid species associated with risk of atherosclerosis in American Indians.
Methods: Using an untargeted...
Background: Dyslipidemia is an important risk factor for hypertension (HTN). Routine clinical tests cannot capture all molecular lipid species in blood (i.e., lipidome). Moreover, a longitudinal lipidomic profiling of risk for HTN is still lacking in any racial/ethnic groups.
Objective: Identify novel lipid species and lipidomic signatures associat...
Objective:
Comprehensive assessment of alterations in lipid species preceding type 2 diabetes (T2D) is largely unknown. We aimed to identify plasma molecular lipids associated with risk of T2D in American Indians.
Research design and methods:
Using untargeted liquid chromatography-mass spectrometry, we repeatedly measured 3,907 fasting plasma sa...
Background
Cancer mortality among American Indian (AI) people varies widely, but factors associated with cancer mortality are infrequently assessed.
Methods
Cancer deaths were identified from death certificate data for 3516 participants of the Strong Heart Study, a population-based cohort study of AI adults ages 45–74 years in Arizona, Oklahoma, a...
Recent studies suggest that the type of saturated fatty acid bound to sphingolipids influences the biological activity of those sphingolipids. However, it is unknown whether associations of sphingolipids with diabetes may differ by the identity of bound lipid species. Here we investigated associations of 15 ceramide and sphingomyelin species (i.e.,...
Background:
Epidemiologic studies often use self-report as proxy for clinical history. However, whether self-report correctly identifies prevalence in minority populations with health disparities and poor health-care access is unknown. Furthermore, overlap of clinical vascular events with covert vascular brain injury (VBI), detected by imaging, is...
Importance
American Indian communities experience a high burden of coronary heart disease (CHD). Strategies are needed to identify individuals at risk and implement preventive interventions.
Objective
To investigate the association of blood DNA methylation (DNAm) with incident CHD using a large number of methylation sites (cytosine-phosphate-guani...
BACKGROUND
Heart failure (HF) is a leading cause of cardiac morbidity among women, whose risk factors differ from those in men. We used machine learning approaches to develop risk prediction models for incident HF in a cohort of postmenopausal women from the Women's Health Initiative (WHI).
METHODS AND RESULTS
We used two machine learning methods,...
Objectives
To assess the association of the plant-based cholesterol-lowering diet, the Portfolio Diet, with incident type 2 diabetes in women.
Methods
We followed 147,732 postmenopausal women initially free of diabetes in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 through 2017. Adherence to the Portfolio...
Objective: CHIP is an aging-related accumulation of somatic mutations in hematopoietic stem cells, leading to clonal expansion. CHIP presence has been implicated in elevated atherosclerotic heart disease (CHD) and all-cause mortality, but its association with incident T2D is unknown. We hypothesize CHIP is adversely associated with glycemic traits...
Background
/Objective: Insomnia is common in older women and is associated with higher cardiovascular disease risk (CVD). Nonbenzodiazepine GABA agonists (Z-drugs) are the most commonly prescribed sleep aids. The study objective was to determine whether the use of Z-drugs is associated with the risk of developing CVD and mortality in older women wi...
Background
Knowledge about macronutrient intake and chronic disease risk has been limited by the absence of objective macronutrient measures. Recently, we proposed novel biomarkers for protein, protein density, carbohydrate, and carbohydrate density, using established biomarkers and serum and urine metabolomics profiles in a human feeding study.
O...
The dietary modification (DM) clinical trial, within the Women's Health Initiative (WHI), studied a low-fat dietary pattern intervention that included guidance to increase vegetables, fruit, and grains. This study was motivated in part from uncertainty about the reliability of observational studies examining the association between dietary fat and...
Background
Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid with multiple biological functions. Rodent experiments suggest EETs play a role in insulin sensitivity and diabetes, but evidence in humans is limited. To address this knowledge gap, we conducted a case-cohort study in the Strong Heart Family Study, a prospective cohort...
Background
Obesity is associated with an increased risk of heart failure (HF); however, how metabolic weight groups relate to HF risk, especially in postmenopausal women, has not been demonstrated.
Methods
We included 19 412 postmenopausal women ages 50 to 79 without cardiovascular disease from the Women’s Health Initiative. Normal weight was defi...
Although many loci have been associated with height in European ancestry populations, very few have been identified in African ancestry individuals. Furthermore, many of the known loci have yet to be generalized to and fine-mapped within a large-scale African ancestry sample. We performed sex-combined and sex-stratified meta-analyses in up to 52,76...
Background
Dietary recommendations regarding protein intake have been focused on the amount of protein. However, such recommendations without considering specific protein sources may be simplistic and insufficient.
Methods and Results
We included 102 521 postmenopausal women enrolled in the Women’s Health Initiative between 1993 and 1998, and foll...
Background
The prevalence of poor diet quality and type 2 diabetes are exceedingly high in many rural American Indian (AI) communities. Because of limited resources and infrastructure in some communities, implementation of interventions to promote a healthy diet is challenging—which may exacerbate health disparities by region (urban/rural) and ethn...
Background
The potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.
Objectives
We aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.
Methods
We included 96,831 US postmenopausal women aged 50–79...
Carrying an APOE ε4 allele increases risk for Alzheimer’s disease and related dementias. However, risk effects and prevalence of risk alleles are not consistent across races/ethnicities. Prevalence of cognitive impairment or dementia and attributable risk from APOE ε4 genotype are unknown in American Indians (AI). This project evaluated association...
Background
Rapid kidney decline is associated with mortality and cardiovascular disease, even in the absence of CKD. American Indians (AI) have particularly high burden of kidney disease, cardiovascular disease, and stroke. This study aims to examine extreme loss in glomerular function in this population in association with clinical outcomes.
Meth...
Introduction: Leukocyte telomere length (LTL) is a potential biomarker of aging and associated with several age-related diseases. Current research on an association between LTL and incident stroke has had inconclusive results. We hypothesized that LTL is associated with incident stroke among American Indians (AI) in the Strong Heart Family Study (S...
Background
Heart failure (HF) and breast cancer are 2 of the leading causes of death in postmenopausal women. The temporal association between HF and breast cancer in postmenopausal women has not been described.
Objectives
This study sought to examine the temporal association between HF and breast cancer.
Methods
Postmenopausal women within the W...
Background and aims:
Alaska Native (AN) traditional lifestyle may be protective against chronic disease risk. Weight gain in adulthood has been linked to increases in chronic disease risk among other populations; yet, its impact among Alaska Native people has never been evaluated. We aimed to evaluate changes in obesity-related metrics over time,...
Background:
The smoking behavior of American Indians (AIs) differs from that of non-Hispanic whites (NHWs). Typically light smokers, cessation interventions for AIs are generally less effective. To improve cessation programs for AIs, clinicians, researchers and public health workers need a better understanding of the genetic factors involved in th...
American Indians (AI) have a high prevalence of diabetes, obesity, cardiovascular disease (CVD), and chronic kidney disease. Inclusion of kidney function and other population-specific characteristics in equations used to predict atherosclerotic CVD (ASCVD) risk may help define risk more accurately in populations with these chronic diseases. We used...
Previous studies consistently report that diet quality is inversely associated with risk of cardiovascular disease (CVD) and type 2 diabetes. However, few studies have assessed the association of diet quality with serum lipoproteins, an intermediate marker of cardio-metabolic health, or assessed whether type 2 diabetes modifies these associations....
Aims
This study estimates incidence of diabetes (DM) and pre-DM relative to DM risk factors among relatively healthy Alaska Native and American Indian (henceforth AN) adults living in urban south central Alaska.
Methods
Baseline (2004-2006) and follow-up (2014-2017) surveys, blood samples, and medical chart review data were collected from AN adults...
Objectives
Type 2 diabetes is a leading cause of morbidity among American Indians (AIs). Although healthy diet is a key component of diabetes management, many AIs face barriers to adopting a healthy diet. Preliminary work in an AI community in the north-central USA indicated that the most salient factors that influence healthy diet are: difficulty...
Background:
Cardiovascular disease (CVD) is the leading cause of death among American Indians and Alaska Natives. Over the past 50 years, the prevalence of CVD has been rising among American Indians and Alaska Natives. The objective of this statement is to summarize population-level risk factors and management techniques tailored for the American...
We conducted latent class analyses to identify women with homogeneous combinations of lifestyle and behavioral variables and tested whether latent classes were prospectively associated with diabetes incidence for women with or without baseline obesity. A total of 64,710 postmenopausal women aged 50–79 years without prevalent diabetes at baseline (y...
Background: Biological aging assessed by both leukocyte telomere length (LTL) and DNA methylation (DNAm) has been associated with CVD and its risk factors. Moreover, LTL is epigenetically regulated. We hypothesized that LTL-associated epigenetic changes are associated with risk of CVD in the community.
Objective: To test whether LTL-associated loci...
Introduction: About 30% of all U.S. adults and 70-80% of those with Type 2 diabetes mellitus (T2DM) have non-alcoholic fatty liver disease (NAFLD). Atherosclerotic cardiovascular disease (CVD) is more common among NAFLD patients, albeit with limited evidence from large prospective studies.
Hypothesis: American Indians (AI) with NAFLD would be more...
Background: American Indians (AIs) suffer disproportionately high rate of type 2 diabetes (T2D). Traditional biomarkers have limited value in predicting and tracking early onset and progression of T2D. There is an urgent need for early biomarkers in this high-risk but understudied minority population.
Objective: To identify novel lipids predictive...
Background: In the US, American Indians suffer a disproportionate burden of CHD compared to other racial/ethnic groups. Additional strategies are needed to identify individuals at risk.
Objectives: Investigate the association of blood DNA methylation (DNAm) with incident CHD in the Strong Heart Study and the prediction ability of DNAm beyond tradit...
Introduction: The association of egg or dietary cholesterol intake with risk of cardiovascular disease (CVD) and overall mortality remains a topic of active debate.
Hypothesis: Higher egg or dietary cholesterol intake is associated with elevated risk of CVD and all-cause mortality.
Methods: We analyzed data from 96,755 women aged 50-79 years who we...
Background: In postmenopausal women, use of hormone therapy is associated with a lower incidence of diabetes (DM). The association of adjuvant endocrine therapy (AET) with DM has not been well studied among women treated for early stage breast cancer. The objective of this study was to examine the association of AET with risk of developing DM among...
Background:
Women without cardiovascular disease (CVD) or hypertension at baseline assigned to intervention in the Women's Health Initiative Dietary Modification (DM) trial experienced 30% lower risk of coronary heart disease (CHD), whereas results in women with hypertension or prior CVD could have been confounded by postrandomization use of stati...
Experimental and prospective epidemiologic evidence suggest that arsenic exposure has diabetogenic effects. However, little is known about how family exposure to arsenic may affect risk for type 2 diabetes (T2D)-related outcomes in adulthood. We evaluated the association of both maternal and offspring arsenic exposure with fasting glucose and incid...
Background/objectives:
Non-caloric artificial sweeteners (NAS) are marketed as healthier alternatives to sugar, but the relationship between consumption of NAS and development of diabetes is unclear. This study assessed the associations of diet soda and NAS consumption with (1) early markers of insulin and glucose homeostasis (cross-sectionally) a...
Background
American Indians experience high rates of cardiovascular disease. We evaluated whether cardiovascular disease incidence, mortality, and prevalence changed over 25 years among American Indians aged 30 to 85.
Methods and Results
The SHS (Strong Heart Study) and SHFS (Strong Heart Family Study) are prospective studies of cardiovascular dis...
Background:
Few studies have assessed the associations of ceramides and sphingomyelins (SMs) with diabetes in humans.
Objective:
We assessed associations of 15 circulating ceramides and SM species with incident diabetes in 2 studies.
Methods:
The analysis included 435 American-Indian participants from the Strong Heart Study (nested case-contro...
![GWAS Catalog [115] and selected SNP associations with serum CRP from...](publication/336623518/figure/tbl1/AS:815158389641216@1571360313383/GWAS-Catalog-115-and-selected-SNP-associations-with-serum-CRP-from-the-literature_Q320.jpg)
Background:
Increased serum levels of C-reactive protein (CRP), an important component of the innate immune response, are associated with increased risk of cardiovascular disease (CVD). Multiple single nucleotide polymorphisms (SNP) have been identified which are associated with CRP levels, and Mendelian randomization studies have shown a positive...
Background:
Alaska Native (AN) traditional foods and associated harvesting activities are beneficial to human health.
Objective:
This study assessed longitudinal self-reported traditional food use and harvesting activities among Alaska Native and American Indian (AN/AI) participants in the Alaska Education and Research Towards Health (EARTH) stu...
Longitudinal data are needed to investigate chronic disease causation and improve prevention efforts for Alaska Native and American Indian (ANAI) people. This paper describes the methods used to conduct follow-up data collection of a longitudinal cohort that enrolled ANAI adults between 2004 and 2006 in south central Alaska. The follow-up study re-...
Background:
Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown.
Objective:
To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups.
Design:
Subgroup analyses of the randomized Women's Health Initiative Est...
Background
Epidemiologic studies regarding weight loss and subsequent cancer risk are sparse. The study aim was to evaluate the association between weight change by intentionality and obesity-related cancer incidence in the Women’s Health Initiative (WHI) Observational Study. Eleven cancers were considered obesity related: breast, ovary, endometriu...
Objective:
To examine associations of parental ages at childbirth with healthy survival to age 90 years among older women.
Study design:
This study included a racially and ethnically diverse sub-cohort of 8,983 postmenopausal women from the larger Women's Health Initiative population, recruited during 1993-1998 and followed for up to 25 years th...
Background and aims:
The association of fatty acids with coronary heart disease (CHD) has been examined, mainly through dietary measurements, and has generated inconsistent results due to measurement error. Large observational studies and randomized controlled trials have shown that plasma phospholipid fatty acids (PL-FA), especially those less li...
