Showing papers by "Barbara V. Howard published in 2021"

Association of Major Dietary Protein Sources With All-Cause and Cause-Specific Mortality: Prospective Cohort Study.

Abstract: 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 ...

Blood DNA Methylation and Incident Coronary Heart Disease: Evidence From the Strong Heart Study.

Abstract: 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-guanine [CpG]) in a single model. Design, Setting, and Participants This prospective study, including a discovery cohort (the Strong Heart Study [SHS]) and 4 additional cohorts (the Women's Health Initiative [WHI], the Framingham Heart Study [FHS], the Atherosclerosis Risk in Communities Study ([ARIC]-Black, and ARIC-White), evaluated 12 American Indian communities in 4 US states; African American women, Hispanic women, and White women throughout the US; White men and White women from Massachusetts; and Black men and women and White men and women from 4 US communities. A total of 2321 men and women (mean [SD] follow-up, 19.1 [9.2] years) were included in the SHS, 1874 women (mean [SD] follow-up, 15.8 [5.9] years) in the WHI, 2128 men and women (mean [SD] follow-up, 7.7 [1.8] years) in the FHS, 2114 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-Black, and 931 men and women (mean [SD] follow-up, 20.9 [7.2] years) in the ARIC-White. Data were collected from May 1989 to December 2018 and analyzed from February 2019 to May 2021. Exposure Blood DNA methylation. Main Outcome and Measure Using a high-dimensional time-to-event elastic-net model for the association of 407 224 CpG sites with incident CHD in the SHS (749 events), this study selected the differentially methylated CpG positions (DMPs) selected in the SHS and evaluated them in the WHI (531 events), FHS (143 events), ARIC-Black (350 events), and ARIC-White (121 events) cohorts. Results The median (IQR) age of participants in SHS was 55 (49-62) years, and 1359 participants (58.6%) were women. Elastic-net models selected 505 DMPs associated with incident CHD in the SHS beyond established risk factors, center, blood cell counts, and genetic principal components. Among those DMPs, 33 were commonly selected in 3 or 4 of the other cohorts and the pooled hazard ratios from the standard Cox models were significant at P < .05 for 10 of the DMPs. For example, the hazard ratio (95% CI) for CHD comparing the 90th and 10th percentiles of differentially methylated CpGs was 0.86 (0.78-0.95) for cg16604233 (tagged to COL11A2) and 1.23 (1.08-1.39) for cg09926486 (tagged to FRMD5). Some of the DMPs were consistent in the direction of the association; others showed associations in opposite directions across cohorts. Untargeted independent elastic-net models of CHD showed distinct DMPs, genes, and network of genes in the 5 cohorts. Conclusions and Relevance In this multi-cohort study, blood-based DNAm findings supported an association between a complex blood epigenomic signature and CHD that was largely different across populations.

Discovery and fine-mapping of height loci via high-density imputation of GWASs in individuals of African ancestry

Abstract: 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 52,764 individuals with height and genome-wide genotyping data from the African Ancestry Anthropometry Genetics Consortium (AAAGC). We additionally combined our African ancestry meta-analysis results with published European genome-wide association study (GWAS) data. In the African ancestry analyses, we identified three novel loci (SLC4A3, NCOA2, ECD/FAM149B1) in sex-combined results and two loci (CRB1, KLF6) in women only. In the African plus European sex-combined GWAS, we identified an additional three novel loci (RCCD1, G6PC3, CEP95) which were equally driven by AAAGC and European results. Among 39 genome-wide significant signals at known loci, conditioning index SNPs from European studies identified 20 secondary signals. Two of the 20 new secondary signals and none of the 8 novel loci had minor allele frequencies (MAF) < 5%. Of 802 known European height signals, 643 displayed directionally consistent associations with height, of which 205 were nominally significant (p < 0.05) in the African ancestry sex-combined sample. Furthermore, 148 of 241 loci contained ≤20 variants in the credible sets that jointly account for 99% of the posterior probability of driving the associations. In summary, trans-ethnic meta-analyses revealed novel signals and further improved fine-mapping of putative causal variants in loci shared between African and European ancestry populations.

Comparing Vascular Brain Injury and Stroke by Cranial Magnetic Resonance Imaging, Physician-Adjudication, and Self-Report: Data from the Strong Heart Study.

Abstract: 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 largely unexamined. METHODS The Strong Heart Study recruited American Indians from 3 regions, with surveillance and adjudication of stroke events from 1989 to 2013. In 2010-2013, all 817 survivors, aged 65-95 years, underwent brain imaging, neurological history interview, and cognitive testing. VBI was defined as imaged infarct or hemorrhage. RESULTS Adjudicated stroke was prevalent in 4% of participants and separately collected, self-reported stroke in 8%. Imaging-defined VBI was detected in 51% and not associated with any stroke event in 47%. Compared with adjudication, self-report had 76% sensitivity and 95% specificity. Participants with adjudicated or self-reported stroke had the poorest performance on cognitive testing; those with imaging-only (covert) VBI had intermediate performance. CONCLUSION In this community-based cohort, self-report for prior stroke had good performance metrics. A majority of participants with VBI did not have overt, clinically recognized events but did have neurological or cognitive symptoms. Data collection methodology for studies in a resource-limited setting must balance practical limitations in costs, accuracy, feasibility, and research goals.

Glomerular filtration function decline, mortality, and cardiovascular events: data from the Strong Heart Study.

Abstract: BACKGROUND Rapid kidney decline is associated with mortality and cardiovascular disease, even in the absence of chronic kidney disease. 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. METHODS The Strong Heart Study, a large longitudinal cohort of adult AI participants, collected plasma creatinine at 3 examination visits between 1989-1999. Intraindividual regressions of estimated glomerular filtration rate (eGFR) provided linear estimates of change in kidney function over this time period. Surveillance with physician adjudication identified mortality and cardiovascular events between visit 3 through 2017. RESULTS Mean change in eGFR was loss 6.8 mL/min over the ten year baseline (range: -66.0 to +28.9 mL/min). The top 1 percentile lost approximately 5.7 mL/min/year. Participants with extreme eGFR loss were more likely to have diabetes (95% vs 71%), hypertension (49% vs 33%), or longer smoking history, among smokers (19 pack years vs 17 pack years). CKD (eGFR 20 mL/min over baseline period) was associated with mortality, independent of baseline eGFR: HR 3.5 (95% CI 2.7-4.4), and also independently associated with composite CVD events and CHF: HR 1.4 and 1.7 (95% CI 1.1-1.9 and 1.2-2.6), respectively. CONCLUSION This is the first examination of decline in eGFR in association with mortality and CVD among AIs. The implications of these findings are broad: clinical evaluation may benefit from evaluating change in eGFR over time in addition to dichotomous eGFR. Also, these findings suggest there may be aspects of renal function that are not well-marked by clinical CKD, but which may have particular relevance to long-term renal and vascular health.

Cooking for Health: a healthy food budgeting, purchasing, and cooking skills randomized controlled trial to improve diet among American Indians with type 2 diabetes.

Abstract: 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 ethnicity (AIs/other populations). It is critical to adapt existing evidence-based healthy food budgeting, purchasing, and cooking programs to be relevant to underserved populations with a high burden of diabetes and related complications. The Cooking for Health Study will work in partnership with an AI community in South Dakota to develop a culturally-adapted 12-month distance-learning-based healthy food budgeting, purchasing, and cooking intervention to improve diet among AI adults with type 2 diabetes. The study will enroll 165 AIs with physician-diagnosed type 2 diabetes who reside on the reservation. Participants will be randomized to an intervention or control arm. The intervention arm will receive a 12-month distance-learning curriculum adapted from Cooking Matters® that focuses on healthy food budgeting, purchasing, and cooking skills. In-person assessments at baseline, month 6 and month 12 will include completion of the Nutrition Assessment Shared Resources Food Frequency Questionnaire and a survey to assess frequency of healthy and unhealthy food purchases. Primary outcomes of interest are: (1) change in self-reported intake of sugar-sweetened beverages (SSBs); and (2) change in the frequency of healthy and unhealthy food purchases. Secondary outcomes include: (1) change in self-reported food budgeting skills; (2) change in self-reported cooking skills; and (3) a mixed-methods process evaluation to assess intervention reach, fidelity, satisfaction, and dose delivered/received. Targeted and sustainable interventions are needed to promote optimal health in rural AI communities. If effective, this intervention will reduce intake of SSBs and the purchase of unhealthy foods; increase the purchase of healthy foods; and improve healthy food budgeting and cooking skills among AIs with type 2 diabetes – a population at high risk of poor health outcomes. This work will help inform future health promotion efforts in resource-limited settings. This study was registered on ClinicalTrials.gov on October 9, 2018 with Identifier NCT03699709 .

Ten-year weight gain is not associated with multiple cardiometabolic measures in Alaska EARTH study participants.

Abstract: 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, and determine associations of changes with cardiometabolic markers of chronic disease risk among AN people. Methods and results Study participants enrolled in the southcentral Alaska Education and Research Towards Health Study in 2004–2006 were invited to participate in a follow-up study conducted 2015–2017. Of the original 1320 participants, 388 completed follow-up health assessments consisting of multiple health surveys, anthropometric measurements, and cardiometabolic measures including blood sugars, blood lipids, and blood pressure. Differences in measurements between visits were determined and associations of weight change with cardiometabolic measures evaluated. Body mass index increased by 3.7 kg/m2 among men and 4.8 kg/m2 among women. Hip circumference (1.1 cm, p Conclusions While weight increase over a 10-year period was not associated with substantive changes in cardiometabolic measures among AN men, there was a decrease in high density lipid cholesterol associated with weight gain among AN women.