Association of Disproportionate Liver Fat with Markers of Heart Failure: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) has been linked to heart failure with preserved ejection fraction (HFpEF). We sought to understand association between individuals with amounts of liver adiposity greater than would be predicted by their body mass index (BMI) in order to understand whether this disproportionate liver fat (DLF) represents a proxy of metabolic risk shared between liver and heart disease. METHODS: We studied 2932 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who received computed tomography (CT) measurements of hepatic attenuation. Quartiles of DLF were compared and multivariable linear regression was performed to evaluate the association of DLF with clinical, echocardiographic, and quality of life metrics. RESULTS: Compared to the lowest quartile of DLF, individuals in the highest quartile of DLF were more likely to be male (52.0% vs 47.1%, p < 0.001), less likely to be Black or African American (14.8 % vs 38.1% p <0.001), have higher rates of dysglycemia (31.9% vs 16.6%, p < 0.001) and triglycerides (140 [98.0, 199.0] vs 99.0 [72.0, 144.0] mg/dL, p > 0.001). These individuals had lower global longitudinal strain (-0.13 [-0.25, -0.02], p = 0.02), stroke volumes (-1.05 [-1.76, -0.33], p < 0.01), lateral e' velocity (-0.10 [-0.18, -0.02], p = 0.02), and 6-minute walk distances (-4.25 [-7.62 to -0.88], p = 0.01). CONCLUSION: DLF is associated with abnormal metabolic profiles and ventricular functional changes known to be associated with HFpEF and may serve as an early metric to assess for those that may progress to clinical HFpEF.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Understanding uptake of COVID-19 testing, vaccination, and boosters among Spanish-speaking Latines in the United States: Qualitative insights from Spanish speakers and key informants.

BACKGROUND: Latine communities in the United States have been disproportionately affected by COVID-19. It is critical to gain a better understanding of the sociocultural determinants that challenge and facilitate COVID-19 testing, vaccination, and booster uptake within these vulnerable communities to inform culturally congruent strategies and interventions. METHODS: In summer 2022, our community-based participatory research partnership conducted 30 key informant interviews and 7 focus groups with 64 Spanish-speaking Latine participants in North Carolina. Interviewees consisted of representatives from health and service organizations, most of whom were engaged with direct service to Spanish speakers. Interviews were conducted in either English or Spanish, depending on the preference of the participant; all focus groups were conducted in Spanish. Interviews and focus groups were conducted in person or by videoconference. RESULTS: Twenty themes emerged that we organize into four domains: general perceptions about COVID-19; barriers to COVID-19 testing, vaccination, and booster uptake; facilitators to COVID-19 testing, vaccination, and booster uptake; and recommendations to promote testing, vaccination, and booster uptake. DISCUSSION: Results underscore important sociocultural determinants of ongoing COVID-19 testing, vaccination, and booster uptake to consider in developing interventions for Spanish-speaking Latines in the United States. Based on this formative work, our partnership developed Nuestra Comunidad Saludable (Our Healthy Community). We are implementing the intervention to test whether trained peer navigators can increase COVID-19 testing, vaccination, and booster uptake among Spanish-speaking Latines through blending in-person interactions and mHealth (mobile health) strategies using social media.

Multi-Ethnic Study of Atherosclerosis Early Heart Failure Study: Rationale, Design, and Baseline Characteristics.

BACKGROUND: Current prevalence estimates of heart failure (HF) are primarily based on self-report or HF hospitalizations. There is an unmet need to define the prevalence and pathogenesis of early symptomatic HF, which may be undiagnosed and precedes HF hospitalization. METHODS: The MESA (Multi-Ethnic Study of Atherosclerosis) Early HF study was conducted during MESA exam 6 to determine the prevalence of early HF and investigate the transition from risk factors to early HF in a diverse population-based cohort of older adults. Between 2016 and 2018, 3285 MESA participants from 6 field centers underwent comprehensive speckle-tracking echocardiography with passive leg raise maneuver, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test, arterial stiffness assessment, and proteomics (including NT-proBNP [N-terminal pro-B-type natriuretic peptide]). RESULTS: Median age was 73 (25th-75th percentile 67-81) years, 53.2% were female, 25.6% were Black, 12.8% were Chinese, and 40.0% were White. The prevalence of HF risk factors was high: hypertension, 61.9%; former or current smoking, 53.7%; obesity 34.8%; diabetes; 24.7%; and chronic kidney disease; 22%. Overt cardiovascular disease, which ranged from 2.1% (HF) to 13.6% (atrial fibrillation), was less common. Of the 3285 participants, 96% underwent proteomics, 94% Kansas City Cardiomyopathy Questionnaire, 93% speckle-tracking echocardiography with passive leg raise, 82% arterial stiffness exam, and 77% 6-minute walk test. Feasibility of resting speckle-tracking echocardiography (87%-99% across cardiac chambers) and passive leg raise Doppler/speckle-tracking echocardiography (>84%) measurements was high. A total of 120 unique echocardiographic indices were measured. CONCLUSIONS: The MESA Early HF study is a key resource for cardiovascular researchers who are interested in improving the epidemiological and phenotypic characterization of early HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.

Retinal vessel caliber and cognitive performance: the multi-ethnic study of atherosclerosis (MESA).

Retinal vessel calibers share anatomic and physiologic characteristics with the cerebral vasculature and can be visualized noninvasively. In light of the known microvascular contributions to brain health and cognitive function, we aimed to determine if, in a community based-study, retinal vessel calibers and change in caliber over 8 years are associated with cognitive function or trajectory. Participants in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort who completed cognitive testing at Exam 5 (2010-2012) and had retinal vascular caliber measurements (Central Retinal Artery and Vein Equivalents; CRAE and CRVE) at Exam 2 (2002-2004) and Exam 5 were included. Using multivariable linear regression, we evaluated the association of CRAE and CRVE from Exam 2 and Exam 5 and their change between the two exams with scores on tests of global cognitive function (Cognitive Abilities Screening Instrument; CASI), processing speed (Digit Symbol Coding; DSC) and working memory (Digit Span; DS) at Exam 5 and with subsequent change in cognitive scores between Exam 5 and Exam 6 (2016-2018).The main effects are reported as the difference in cognitive test score per SD increment in retinal vascular caliber with 95% confidence intervals (CI). A total of 4334 participants (aged 61.6 ± 9.2 years; 53% female; 41% White) completed cognitive testing and at least one retinal assessment. On multivariable analysis, a 1 SD larger CRAE at exam 5 was associated with a lower concomitant CASI score (- 0.24, 95% CI - 0.46, - 0.02). A 1 SD larger CRVE at exam 2 was associated with a lower subsequent CASI score (- 0.23, 95%CI - 0.45, - 0.01). A 1 SD larger CRVE at exam 2 or 5 was associated with a lower DSC score [(- 0.56, 95% CI - 1.02, - 0.09) and - 0.55 (95% CI - 1.03, - 0.07) respectively]. The magnitude of the associations was relatively small (2.8-3.1% of SD). No significant associations were found between retinal vessel calibers at Exam 2 and 5 with the subsequent score trajectory of cognitive tests performance over an average of 6 years. Wider retinal venular caliber was associated with concomitant and future measures of slower processing speed but not with later cognitive trajectory. Future studies should evaluate the utility of these measures in risk stratification models from a clinical perspective as well as for screening on a population level.

Increased Plasma Branched Short-Chain Fatty Acids and Improved Glucose Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of BSCFAs, with 25 individuals having high levels (H-BSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared with the L-BSCFA group (16% vs. 49%; P = 0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFAs. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose levels were lower and the disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial C-peptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes.

Type 2 Diabetes Modifies the Association of CAD Genomic Risk Variants With Subclinical Atherosclerosis.

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D. METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 T2D cases leveraging whole-genome sequencing data from the Trans-Omics for Precision Medicine program. We included first-order T2D interaction terms in each model to determine whether CAD loci were modified by T2D. The genetic main and interaction effects were assessed using a joint test to determine whether a CAD variant, or gene-based rare variant set, was associated with the respective subclinical atherosclerosis measures and then further determined whether these loci had a significant interaction test. RESULTS: Using a Bonferroni-corrected significance threshold of P<1.6×10-4, we identified 3 genes (ATP1B1, ARVCF, and LIPG) associated with CAC and 2 genes (ABCG8 and EIF2B2) associated with carotid intima-media thickness and carotid plaque, respectively, through gene-based rare variant set analysis. Both ATP1B1 and ARVCF also had significantly different associations for CAC in T2D cases versus controls. No significant interaction tests were identified through the candidate single-variant analysis. CONCLUSIONS: These results highlight T2D as an important modifier of rare variant associations in CAD loci with CAC.

Relationship of Race With Functional and Clinical Outcomes With the REHAB-HF Multidomain Physical Rehabilitation Intervention for Older Patients With Acute Heart Failure.

Background The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3-month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health-related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown. Methods and Results In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6-Minute Walk Distance), cognition, depression, frailty, health-related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5-Dimension-5-Level Questionnaire) and at 6 months for hospitalizations and death. Significance level for interactions was P≤0.1. Participants (N=337, 97% of trial population) self-identified in near equal proportions as either Black (48%) or White (52%). The Short Physical Performance Battery intervention effect size was large, with values of 1.3 (95% CI, 0.4-2.1; P=0.003]) and 1.6 (95% CI, 0.8-2.4; P<0.001) in Black and White participants, respectively, and without significant interaction by race (P=0.56). Beneficial effects were also demonstrated in 6-Minute Walk Distance, gait speed, and health-related quality of life scores without significant interactions by race. There was an association between intervention and reduced all-cause rehospitalizations in White participants (rate ratio, 0.73 [95% CI, 0.55-0.98]; P=0.034) that appears attenuated in Black participants (rate ratio, 1.06 [95% CI, 0.81-1.41]; P=0.66; interaction P=0.067). Conclusions The intervention produced similarly large improvements in physical function and health-related quality of life in both older Black and White patients with acute decompensated heart failure. A future study powered to determine how the intervention impacts clinical events is required. REGISTRATION URL: https://www.clinicaltrials.gov. Identifier: NCT02196038.

Sepsis Prediction Model for Determining Sepsis vs SIRS, qSOFA, and SOFA.

Importance: The Sepsis Prediction Model (SPM) is a proprietary decision support tool created by Epic Systems; it generates a predicting sepsis score (PSS). The model has not undergone validation against existing sepsis prediction tools, such as Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick Sepsis-Related Organ Failure Asessement (qSOFA). Objective: To assess the validity and timeliness of the SPM compared with SIRS, qSOFA, and SOFA. Design, Setting, and Participants: This retrospective cohort study included all adults admitted to 5 acute care hospitals in a single US health system between June 5, 2019, and December 31, 2020. Data analysis was conducted from March 2021 to February 2023. Main Outcomes and Measures: A sepsis event was defined as receipt of 4 or more days of antimicrobials, blood cultures collected within ±48 hours of initial antimicrobial, and at least 1 organ dysfunction as defined by the organ dysfunction criteria optimized for the electronic health record (eSOFA). Time zero was defined as 15 minutes prior to qualifying antimicrobial or blood culture order. Results: Of 60 507 total admissions, 1663 (2.7%) met sepsis criteria, with 1324 electronic health record-confirmed sepsis (699 [52.8%] male patients; 298 [22.5%] Black patients; 46 [3.5%] Hispanic/Latinx patients; 945 [71.4%] White patients), 339 COVID-19 sepsis (183 [54.0%] male patients; 98 [28.9%] Black patients; 36 [10.6%] Hispanic/Latinx patients; and 189 [55.8%] White patients), and 58 844 (97.3%; 26 632 [45.2%] male patients; 12 698 [21.6%] Black patients; 3367 [5.7%] Hispanic/Latinx patients; 40 491 White patients) did not meet sepsis criteria. The median (IQR) age was 63 (51 to 73) years for electronic health record-confirmed sepsis, 69 (60 to 77) years for COVID-19 sepsis, and 60 (42 to 72) years for nonsepsis admissions. Within the vendor recommended threshold PSS range of 5 to 8, PSS of 8 or greater had the highest balanced accuracy for classifying a sepsis admission at 0.79 (95% CI, 0.78 to 0.80). Change in SOFA score of 2 or more had the highest sensitivity, at 0.97 (95% CI, 0.97 to 0.98). At a PSS of 8 or greater, median (IQR) time to score positivity from time zero was 68.00 (6.75 to 605.75) minutes. For SIRS, qSOFA, and SOFA, median (IQR) time to score positivity was 7.00 (-105.00 to 08.00) minutes, 74.00 (-22.25 to 599.25) minutes, and 28.00 (-108.50 to 134.00) minutes, respectively. Conclusions and Relevance: In this cohort study of hospital admissions, balanced accuracy of the SPM outperformed other models at higher threshold PSS; however, application of the SPM in a clinical setting was limited by poor timeliness as a sepsis screening tool as compared to SIRS and SOFA.

Cross-sectional and longitudinal analyses of variations of anthropometric measures of obesity with age in the Jackson Heart Study.

OBJECTIVE: To explore how anthropometric measures of obesity vary with age among African American (AA) adults. PARTICIPANTS AND SETTING: 3634 AA adults participated in the Jackson Heart Study (Jackson, Mississippi, USA) from 2004 to 2013. OUTCOME MEASURES: Body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR). METHODS: Linear regression models were used to estimate the mean differences in anthropometric measures cross-sectionally by age group. Longitudinal changes in anthropometric measures over time (ie, the ageing effect) within each sex and age group were analysed using mixed effects models. All regression models were adjusted for education and lifestyle factors. RESULTS: In cross-sectional analysis, older age was associated with lower BMI, WC and WHtR, but higher WHR in both sexes. Compared with 25 to <44 years age group, the mean (95% CI) BMI, WC and WHtR was 0.80 (0.66 to 0.94), 0.27 (0.13 to 0.42) and 0.18 (0.03 to 0.32) standardised (SD) unit lower, while WHR was 0.48 (0.33 to 0.62) SD unit higher in the 75+ years age group. In longitudinal analysis, ageing was associated with increased BMI, WC and WHtR, among younger age groups but not in older age groups. However, WHR tended to increase with ageing across all age groups in both sexes. Among men 75+ years old, the mean change (95% CI) in BMI, WC and WHtR for every 5 years increase in age, was -0.20 (-0.29 to -0.11), -0.19 (-0.31 to -0.07), -0.15 (-0.27 to -0.02) SD unit, respectively, while it was 0.24 (0.05 to 0.44) SD unit for WHR. CONCLUSIONS: Among middle-aged AA adults, all four anthropometric measures of obesity examined increased with ageing. However, among elderly AA adults, only WHR showed continued increase with ageing. WHR may be a better anthropometric measure for monitoring obesity in older AA adults.

Association of Domains of Sedentary Behavior with Cardiovascular Disease Events in The Multi-Ethnic Study of Atherosclerosis.

Background: Sedentary behavior is associated with an increased risk for adverse health outcomes, including cardiovascular disease (CVD), independent of physical activity status. Little is known about this relationship in an ethnically diverse population. The objective of our study is to assess the effects of leisure time and occupational sedentary behavior on multiple cardiovascular outcomes in a multi-ethnic cohort. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) includes 2619 Caucasian, 1495 Hispanic, 1891 Black, and 804 Chinese-American adults aged 45-84 years and free of clinical CVD at enrollment, Sedentary behavior was self-reported at baseline. Participants were followed for an average of 13.6 years, and 14 types of cardiovascular outcomes were ascertained. Hazards of each cardiovascular outcome were modeled with adjustment for potential confounders, including physical activity. Results: Every one hour per day increase in leisure time sedentary behavior predicts a 6% increase in the adjusted hazards for CVD death ( P < 0.05). Every one hour increase in occupational sedentary time predicts a 21% and 20% decrease in the hazard for PVD and other revascularization, respectively ( P < 0.05). Conclusions: Leisure time sedentary behavior was associated with increased hazards for CVD death, but occupational sedentary time appears to be protective of peripheral vascular disease and other revascularization. Condensed Abstract: Sedentary behavior has been consistently associated with an increased risk for adverse health outcomes, including cardiovascular disease (CVD), independent of physical activity status. The Multi-Ethnic Study of Atherosclerosis (MESA) consists of a racially and ethnically diverse cohort of adults age 45-84, free from CVD at baseline. Greater levels of leisure time sedentary behavior predicted increased hazards for PVD and CVD death after an average follow up of 13.6 years whereas occupational sedentary behaviors predicted reduced PVD. These results underscore the importance of reducing time spent sitting in addition to advocating for meeting physical activity targets across ethnicities.

Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis.

CONTEXT: Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline. OBJECTIVE: Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D. METHODS: We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period. RESULTS: Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (-1.7 [95% CI: -3.1, -0.3] and -2.1 [-3.7, -0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D. CONCLUSION: Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.

Association of brain microbleeds with risk factors, cognition, and MRI markers in MESA.

INTRODUCTION: Little is known about the epidemiology of brain microbleeds in racially/ethnically diverse populations. METHODS: In the Multi-Ethnic Study of Atherosclerosis, brain microbleeds were identified from 3T magnetic resonance imaging susceptibility-weighted imaging sequences using deep learning models followed by radiologist review. RESULTS: Among 1016 participants without prior stroke (25% Black, 15% Chinese, 19% Hispanic, 41% White, mean age 72), microbleed prevalence was 20% at age 60 to 64.9 and 45% at ≥85 years. Deep microbleeds were associated with older age, hypertension, higher body mass index, and atrial fibrillation, and lobar microbleeds with male sex and atrial fibrillation. Overall, microbleeds were associated with greater white matter hyperintensity volume and lower total white matter fractional anisotropy. DISCUSSION: Results suggest differing associations for lobar versus deep locations. Sensitive microbleed quantification will facilitate future longitudinal studies of their potential role as an early indicator of vascular pathology.

Evaluating a Telephone and Home Blood Pressure Monitoring Intervention to Improve Blood Pressure Control and Self-Care Behaviors in Adults with Low-Socioeconomic Status.

Hypertension (HTN) affects nearly 75 million in the United States, and percentages increase with low socioeconomic status (SES) due to poor access to, and quality of, care, and poor self-care behaviors. Federally Qualified Health Centers (FQHCs) employ evidence-based strategies, such as telehealth interventions, to improve blood pressure (BP) control in under-resourced communities, yet a southeastern FQHC could achieve a BP control rate of only 27.6%, well below the Health People 2020 goal of 61.2%. This pilot project used a pre/post, matched-cohort design to evaluate the effect of a telehealth intervention on BP control and self-care behaviors. Secondary outcomes included self-efficacy and perceived stress. Frequency and percentage, Wilcoxon signed-rank, and McNemar tests were used for statistical analysis of results from a convenience sample of 27 participants. Baseline HTN management guidance that incorporated home blood pressure monitoring (HBPM) was reinforced through telephone counseling every two weeks. Although BP control was not achieved, average scores for systolic and diastolic blood pressures decreased significantly: 13 mm Hg (p = 0.0136) and 5 mm Hg (p = 0.0095), respectively. Statistically significant differences were also seen in select self-care behaviors. Greater BP reduction aligned with higher self-efficacy scores and call engagement. Overall, telephone counseling and HBPM were feasible and effective in reducing BP and increasing self-care behaviors. The inability to control BP may be attributable to under-recognition of stress, lack of medication adherence/reconciliation, and underutilization of guideline-based prescribing recommendations. Findings elucidate the potential effectiveness of a sustainable telehealth intervention to improve BP in low-SES populations.

Impact of Diabetes and Hypertension on Left Ventricular Structure and Function: The Jackson Heart Study.

Background Diabetes and hypertension have been associated with adverse left ventricular (LV) remodeling. While they often occur concurrently, their individual effects are understudied. We aimed to assess the independent effects of diabetes and hypertension on LV remodeling in Black adults. Methods and Results The JHS (Jackson Heart Study) participants (n=4143 Black adults) with echocardiographic measures from baseline exam were stratified into 4 groups: neither diabetes nor hypertension (n=1643), only diabetes (n=152), only hypertension (n=1669), or both diabetes and hypertension (n=679). Echocardiographic measures of LV structure and function among these groups were evaluated by multivariable regression adjusting for covariates. Mean age of the participants was 52±1 years, and 63.7% were women. LV mass index was not different in participants with only diabetes compared with participants with neither diabetes nor hypertension (P=0.8). LV mass index was 7.9% (6.0 g/m2) higher in participants with only hypertension and 10.8% (8.1 g/m2) higher in participants with both diabetes and hypertension compared with those with neither (P<0.001). LV wall thickness (relative, posterior, and septal) and brain natriuretic peptide levels in participants with only diabetes were not significantly higher than participants with neither (P>0.05). However, participants with both diabetes and hypertension demonstrated higher LV wall thickness and brain natriuretic peptide levels than participants with neither (P<0.05). Conclusions In this cross-sectional analysis, diabetes was not associated with altered LV structure or function in Black adults unless participants also had hypertension. Our findings suggest hypertension is the main contributor to cardiac structural and functional changes in Black adults with diabetes.

Investigating Gene-Diet Interactions Impacting the Association Between Macronutrient Intake and Glycemic Traits.

Few studies have demonstrated reproducible gene-diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient-glycemia relationship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We fit cohort-specific, multivariable-adjusted linear mixed models for the effect of diet, modeled as an isocaloric substitution of carbohydrate for fat, and its interactions with common and rare variants genome-wide. In main effect meta-analyses, participants consuming more carbohydrate had modestly lower glycemic trait values (e.g., for glycated hemoglobin [HbA1c], -0.013% HbA1c/250 kcal substitution). In GDI meta-analyses, a common African ancestry-enriched variant (rs79762542) reached study-wide significance and replicated in the UK Biobank cohort, indicating a negative carbohydrate-HbA1c association among major allele homozygotes only. Simulations revealed that >150,000 samples may be necessary to identify similar macronutrient GDIs under realistic assumptions about effect size and measurement error. These results generate hypotheses for further exploration of modifiable metabolic disease risk in additional cohorts with African ancestry. ARTICLE HIGHLIGHTS: We aimed to identify genetic modifiers of the dietary macronutrient-glycemia relationship using whole-genome sequence data from 10 Trans-Omics for Precision Medicine program cohorts. Substitution models indicated a modest reduction in glycemia associated with an increase in dietary carbohydrate at the expense of fat. Genome-wide interaction analysis identified one African ancestry-enriched variant near the FRAS1 gene that may interact with macronutrient intake to influence hemoglobin A1c. Simulation-based power calculations accounting for measurement error suggested that substantially larger sample sizes may be necessary to discover further gene-macronutrient interactions.

Mixed meal tolerance testing highlights in diabetes altered branched-chain ketoacid metabolism and pathways associated with all-cause mortality.

BACKGROUND: Elevated BCAA levels are strongly associated with diabetes, but how diabetes affects BCAA, branched-chain ketoacids (BCKAs), and the broader metabolome after a meal is not well known. OBJECTIVE: To compare quantitative BCAA and BCKA levels in a multiracial cohort with and without diabetes after a mixed meal tolerance test (MMTT) as well as to explore the kinetics of additional metabolites and their associations with mortality in self-identified African Americans. METHODS: We administered an MMTT to 11 participants without obesity or diabetes and 13 participants with diabetes (treated with metformin only) and measured the levels of BCKAs, BCAAs, and 194 other metabolites at 8 time points across 5 h. We used mixed models for repeated measurements to compare between group metabolite differences at each timepoint with adjustment for baseline. We then evaluated the association of top metabolites with different kinetics with all-cause mortality in the Jackson Heart Study (JHS) (N = 2441). RESULTS: BCAA levels, after adjustment for baseline, were similar at all timepoints between groups, but adjusted BCKA kinetics were different between groups for α-ketoisocaproate (P = 0.022) and α-ketoisovalerate (P = 0.021), most notably diverging at 120 min post-MMTT. An additional 20 metabolites had significantly different kinetics across timepoints between groups, and 9 of these metabolites-including several acylcarnitines-were significantly associated with mortality in JHS, irrespective of diabetes status. The highest quartile of a composite metabolite risk score was associated with higher mortality (HR:1.57; 1.20, 2.05, P = 0.00094) than the lowest quartile. CONCLUSIONS: BCKA levels remained elevated after an MMTT among participants with diabetes, suggesting that BCKA catabolism may be a key dysregulated process in the interaction of BCAA and diabetes. Metabolites with different kinetics after an MMTT may be markers of dysmetabolism and associated with increased mortality in self-identified African Americans.

Racial Differences in Trends and Prognosis of Guideline-Directed Medical Therapy for Heart Failure with Reduced Ejection Fraction: the Atherosclerosis Risk in Communities (ARIC) Surveillance Study.

BACKGROUND: Racial disparities in guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) have not been fully documented in a community setting. METHODS: In the ARIC Surveillance Study (2005-2014), we examined racial differences in GDMT at discharge, its temporal trends, and the prognostic impact among individuals with hospitalized HFrEF, using weighted regression models to account for sampling design. Optimal GDMT was defined as beta blockers (BB), mineralocorticoid receptor antagonist (MRA) and ACE inhibitors (ACEI) or angiotensin II receptor blockers (ARB). Acceptable GDMT included either one of BB, MRA, ACEI/ARB or hydralazine plus nitrates (H-N). RESULTS: Of 16,455 (unweighted n = 3,669) HFrEF cases, 47% were Black. Only ~ 10% were discharged with optimal GDMT with higher proportion in Black than White individuals (11.1% vs. 8.6%, p < 0.001). BB use was > 80% in both racial groups while Black individuals were more likely to receive ACEI/ARB (62.0% vs. 54.6%) and MRA (18.0% vs. 13.8%) than Whites, with a similar pattern for H-N (21.8% vs. 10.1%). There was a trend of decreasing use of optimal GDMT in both groups, with significant decline of ACEI/ARB use in Whites (- 2.8% p < 0.01) but increasing H-N use in both groups (+ 6.5% and + 9.2%, p < 0.01). Only ACEI/ARB and BB were associated with lower 1-year mortality. CONCLUSIONS: Optimal GDMT was prescribed in only ~ 10% of HFrEF patients at discharge but was more so in Black than White individuals. ACEI/ARB use declined in Whites while H-N use increased in both races. GDMT utilization, particularly ACEI/ARB, should be improved in Black and Whites individuals with HFrEF.