Dysanapsis Genetic Risk Predicts Lung Function Across the Lifespan.

Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objective By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study (GWAS) of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate GWAS and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n=1,278) and adults from the UK Biobank (n=369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP, DSP, and NPNT as potential molecular targets based on colocalization of their expression. Higher dysanapsis genetic risk score was associated with obstructive spirometry among 5 year old children and among adults in the 5th, 6th and 7th decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endo-phenotype link between the genetic variations associated with lung function and COPD.

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 2,932 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 < .001), less likely to be Black or African American (14.8 % vs 38.1% P < .001), have higher rates of dysglycemia (31.9% vs 16.6%, P < .001) and triglycerides (140 [98.0, 199.0] vs 99.0 [72.0, 144.0] mg/dL, P > .001). These individuals had lower global longitudinal strain (-0.13 [-0.25, -0.02], P = .02), stroke volumes (-1.05 [-1.76, -0.33], P < .01), lateral e' velocity (-0.10 [-0.18, -0.02], P = .02), and 6-minute walk distances (-4.25 [-7.62 to -0.88], P = .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.

Racial and Ethnic Differences in All-Cause and Cardiovascular Disease Mortality: The MESA Study.

BACKGROUND: Despite improvements in population health, marked racial and ethnic disparities in longevity and cardiovascular disease (CVD) mortality persist. This study aimed to describe risks for all-cause and CVD mortality by race and ethnicity, before and after accounting for socioeconomic status (SES) and other factors, in the MESA study (Multi-Ethnic Study of Atherosclerosis). METHODS: MESA recruited 6814 US adults, 45 to 84 years of age, free of clinical CVD at baseline, including Black, White, Hispanic, and Chinese individuals (2000-2002). Using Cox proportional hazards modeling with time-updated covariates, we evaluated the association of self-reported race and ethnicity with all-cause and adjudicated CVD mortality, with progressive adjustments for age and sex, SES (neighborhood SES, income, education, and health insurance), lifestyle and psychosocial risk factors, clinical risk factors, and immigration history. RESULTS: During a median of 15.8 years of follow-up, 22.8% of participants (n=1552) died, of which 5.3% (n=364) died of CVD. After adjusting for age and sex, Black participants had a 34% higher mortality hazard (hazard ratio [HR], 1.34 [95% CI, 1.19-1.51]), Chinese participants had a 21% lower mortality hazard (HR, 0.79 [95% CI, 0.66-0.95]), and there was no mortality difference in Hispanic participants (HR, 0.99 [95% CI, 0.86-1.14]) compared with White participants. After adjusting for SES, the mortality HR for Black participants compared with White participants was reduced (HR, 1.16 [95% CI, 1.01-1.34]) but still statistically significant. With adjustment for SES, the mortality hazards for Chinese and Hispanic participants also decreased in comparison with White participants. After further adjustment for additional risk factors and immigration history, Hispanic participants (HR, 0.77 [95% CI, 0.63-0.94]) had a lower mortality risk than White participants, and hazard ratios for Black participants (HR, 1.08 [95% CI, 0.92-1.26]) and Chinese participants (HR, 0.81 [95% CI, 0.60-1.08]) were not significantly different from those of White participants. Similar trends were seen for CVD mortality, although the age- and sex-adjusted HR for CVD mortality for Black participants compared with White participants was greater than all-cause mortality (HR, 1.72 [95% CI, 1.34-2.21] compared with HR, 1.34 [95% CI, 1.19-1.51]). CONCLUSIONS: These results highlight persistent racial and ethnic differences in overall and CVD mortality, largely attributable to social determinants of health, and support the need to identify and act on systemic factors that shape differences in health across racial and ethnic groups.

Missense Genetic Variation of ICAM1 and Incident Heart Failure.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is a cell surface protein that participates in endothelial activation and is hypothesized to play a central role in heart failure (HF). We evaluated associations of ICAM1 missense genetic variants with circulating ICAM-1 levels and with incident HF. METHODS AND RESULTS: We identified 3 missense variants within ICAM1 (rs5491, rs5498 and rs1799969) and evaluated their associations with ICAM-1 levels in the Coronary Artery Risk Development in Young Adults Study and the Multi-Ethnic Study of Atherosclerosis (MESA). We determined the association among these 3 variants and incident HF in MESA. We separately evaluated significant associations in the Atherosclerosis Risk in Communities (ARIC) study. Of the 3 missense variants, rs5491 was common in Black participants (minor allele frequency [MAF] > 20%) and rare in other race/ethnic groups (MAF < 5%). In Black participants, the presence of rs5491 was associated with higher levels of circulating ICAM-1 at 2 timepoints separated by 8 years. Among Black participants in MESA (n = 1600), the presence of rs5491 was associated with an increased risk of incident HF with preserved ejection fraction (HFpEF; HR = 2.30; [95% CI 1.25-4.21; P = 0.007]). The other ICAM1 missense variants (rs5498 and rs1799969) were associated with ICAM-1 levels, but there were no associations with HF. In ARIC, rs5491 was significantly associated with incident HF (HR = 1.24 [95% CI 1.02 - 1.51]; P = 0.03), with a similar direction of effect for HFpEF that was not statistically significant. CONCLUSIONS: A common ICAM1 missense variant among Black individuals may be associated with increased risk of HF, which may be HFpEF-specific.

Race/Ethnicity, Spirometry Reference Equations, and Prediction of Incident Clinical Events: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study.

Rationale: Normal values for FEV1 and FVC are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. Objectives: To determine whether race/ethnicity-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared with race/ethnicity-neutral equations. Methods: The MESA Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry from 2004 to 2006. Predicted values for spirometry were calculated using race/ethnicity-based equations following guidelines and, alternatively, race/ethnicity-neutral equations without terms for race/ethnicity. Participants were followed for events through 2019. Measurements and Main Results: The mean age of 3,344 participants was 65 years, and self-reported race/ethnicity was 36% White, 25% Black, 23% Hispanic, and 17% Asian. There were 181 incident CLRD-related events and 547 deaths over a median of 11.6 years. There was no evidence that percentage predicted FEV1 or FVC calculated using race/ethnicity-based equations improved the prediction of CLRD-related events compared with those calculated using race/ethnicity-neutral equations (difference in C statistics for FEV1, -0.005; 95% confidence interval [CI], -0.013 to 0.003; difference in C statistic for FVC, -0.008; 95% CI, -0.016 to -0.0006). Findings were similar for mortality (difference in C statistics for FEV1, -0.002; 95% CI, -0.008 to 0.003; difference in C statistics for FVC, -0.004; 95% CI, -0.009 to 0.001). Conclusions: There was no evidence that race/ethnicity-based spirometry reference equations improved the prediction of clinical events compared with race/ethnicity-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.

Lung function impairment and risk of incident heart failure: the NHLBI Pooled Cohorts Study.

AIMS: The aim is to evaluate associations of lung function impairment with risk of incident heart failure (HF). METHODS AND RESULTS: Data were pooled across eight US population-based cohorts that enrolled participants from 1987 to 2004. Participants with self-reported baseline cardiovascular disease were excluded. Spirometry was used to define obstructive [forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) <0.70] or restrictive (FEV1/FVC ≥0.70, FVC <80%) lung physiology. The incident HF was defined as hospitalization or death caused by HF. In a sub-set, HF events were sub-classified as HF with reduced ejection fraction (HFrEF; EF <50%) or preserved EF (HFpEF; EF ≥50%). The Fine-Gray proportional sub-distribution hazards models were adjusted for sociodemographic factors, smoking, and cardiovascular risk factors. In models of incident HF sub-types, HFrEF, HFpEF, and non-HF mortality were treated as competing risks. Among 31 677 adults, there were 3344 incident HF events over a median follow-up of 21.0 years. Of 2066 classifiable HF events, 1030 were classified as HFrEF and 1036 as HFpEF. Obstructive [adjusted hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.07-1.27] and restrictive physiology (adjusted HR 1.43, 95% CI 1.27-1.62) were associated with incident HF. Obstructive and restrictive ventilatory defects were associated with HFpEF but not HFrEF. The magnitude of the association between restrictive physiology and HFpEF was similar to associations with hypertension, diabetes, and smoking. CONCLUSION: Lung function impairment was associated with increased risk of incident HF, and particularly incident HFpEF, independent of and to a similar extent as major known cardiovascular risk factors.

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.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

Association of plasma endothelin-1 with blood pressure progression among Blacks: The Jackson Heart Study.

BACKGROUND: Despite pathophysiological links between endothelin (ET)-1 and hypertension in Black adults, there is no population-based data appraising the association of plasma ET-1 with longitudinal blood pressure (BP) changes in Blacks. METHODS: We analyzed data from 1197 Jackson Heart Study participants without hypertension (mean age 47.8 years [SD: 12.0]; 64.2% women), with plasma ET-1 available at the baseline examination (2000-2004). Poisson regression with robust variance was used to generate risk ratios (RRs) and 95% confidence intervals (CIs) of BP progression (an increase by ≥1 BP category based on the 2017 American College of Cardiology/American Heart Association classification) and incident hypertension (BP ≥ 130/80 mm Hg or use of antihypertensive medication) at follow-up (2005-2008 or 2009-2013). RESULTS: Over a median follow-up of 7 years (range: 4-11), 71.2% (n = 854) progressed to a higher BP stage and 64.6% (n = 773) developed hypertension. After adjusting for possible confounders, each unit increment in baseline log (ET-1) was associated with higher risks of BP progression (RR 1.15 [95% CI 1.03-1.29], P = .016) and incident hypertension (RR 1.15 [95% CI 1.01-1.31], P = .032). Compared to those in the lowest ET-1 quartile, participants in the highest quartile had significantly higher risks of BP progression (RR 1.20 [95% CI 1.05-1.37], P = .007) and incident hypertension (RR 1.16 [95% CI 1.00-1.36], P = .052). CONCLUSIONS: In a large, community-based sample of African Americans, higher plasma ET-1 concentrations were associated with higher risks of BP progression and incident hypertension.

Dysglycemia and incident heart failure among blacks: The jackson heart study.

BACKGROUND: We aimed to investigate the associations of glycemic markers (hemoglobin A1C [HbA1C], fasting plasma glucose [FPG] and glycemic status [normoglycemia, prediabetes and diabetes]) with incident heart failure (HF) and its subtypes, among Blacks. METHODS: We included 2,290 community-dwelling Blacks (64% women, mean age 58 years) without prevalent HF from the Jackson Heart Study who attended the second exam (2005 - 2008). The associations between glycemic markers and incident HF (and subtypes including HF with preserved ejection fraction [HFpEF] and reduced ejection fraction [HFrEF]) were evaluated using Cox proportional hazards regression models, adjusting for risk factors and coronary heart disease. RESULTS: There were 119 incident HF events (48 HFpEF, 58 HFrEF, and 13 unclassified HF events) over a median follow-up of 10.5 years. Higher levels of HbA1C (HR per SD increment, 1.30; 95% CI 1.12, 1.51) and FPG (HR per SD increment FPG: 1.32; 95% CI: 1.17, 1.48) were associated with a higher risk of incident HF. Compared to normal glycemia, diabetes status was associated with a higher risk of incident HF (HR: 1.24; 95%CI: 1.02, 2.05). HbA1C was significantly associated with higher risks of HFpEF (HR per SD increment: 1.41, 95% CI: 1.18, 1.69) and HFrEF (HR per SD increment: 1.32; 95% CI: 1.12, 1.56). FPG was significantly associated with higher risk of HFpEF (HR per SD increment: 1.35, 95% CI: 1.14, 1.62) but not HFrEF (HR per SD increment: 1.12; 95% CI: 0.53, 2.35). CONCLUSIONS: Among community-dwelling Blacks, higher levels of glycemic markers were associated with higher risk of HF subtypes.

Glycemic Markers and Heart Failure Subtypes: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: Although diabetes increases heart failure (HF) risk, it is unclear how various dysglycemia markers (hemoglobin A1C [HbA1C], fasting plasma glucose [FPG], homeostasis model assessment of insulin resistance, and fasting insulin) are associated with HF subtypes (HF with preserved ejection fraction [HFpEF] and HF with reduced ejection fraction [HFrEF]). We assessed the relation of markers of dysglycemia and risks of HFpEF and HFrEF. METHODS AND RESULTS: We included 6688 adults without prevalent cardiovascular disease who attended the first MESA visit (2000-2002) and were followed for incident hospitalized HF (HFpEF or HFrEF). Association of glycemic markers and status (normoglycemia, prediabetes, diabetes) with HFpEF and HFrEF were evaluated using adjusted Cox models. Over a median follow-up of 14.9 years, there were 356 HF events (145 HFpEF, 173 HFrEF, and 38 indeterminate HF events). Diabetes status conferred higher risks of HFpEF (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.57-2.68) and HFrEF (HR 2.02, 95% CI 1.38-2.97) compared with normoglycemia. Higher levels of FPG (≥126 mg/dL) and HbA1C (≥6.5%) were associated with similarly higher risks of HFpEF (HR for FPG 1.96, 95% CI 1.21-3.17; HR for HbA1C 2.00, 95% CI 1.20-3.31) and HFrEF (HR for FPG 1.84, 95% CI 1.18-2.88; HR for HbA1C 1.99, 95% CI 1.28-3.09) compared with reference values. Prediabetic range HbA1C (5.7%-6.4%) or FPG (100%-125 mg/dL), homeostasis model assessment of insulin resistance, and fasting insulin were not significantly associated with HFpEF or HFrEF. CONCLUSIONS: Among community-dwelling individuals, HbA1C and FPG in the diabetes range were each associated with higher risks of HFpEF and HFrEF, with similar magnitudes of their associations. LAY ABSTRACT: Heart failure (HF) has 2 major subtypes (the heart's inability to pump or to fill up). Diabetes is known to increase HF risk, but its effects and that of markers of high glucose levels (fasting blood glucose and hemoglobin A1C) on the occurrence of HF subtypes remains unknown. Among 6688 adults without known cardiovascular disease followed for nearly 15 years, diabetes conferred significantly higher risks of both HF types, compared with those with normal blood glucose levels. Higher levels of fasting blood glucose and hemoglobin A1C were similarly associated with higher risks of both types of HF.

Patients phenotypes and cardiovascular risk in type 2 diabetes: the Jackson Heart Study.

BACKGROUND: Cardiovascular prognosis related to type 2 diabetes may not be adequately captured by information on comorbid conditions such as obesity and hypertension. To inform the cardiovascular prognosis among diabetic individuals, we conducted phenotyping using a clustering approach based on clinical data, echocardiographic indices and biomarkers. METHODS: We performed a cluster analysis on clinical, biochemical and echocardiographic variables from 529 Blacks with diabetes in the Jackson Heart Study. An association between identified clusters and major adverse cardiovascular events (MACE- composite of coronary heart disease, stroke, heart failure and atrial fibrillation) was assessed using Cox proportional hazards modeling. RESULTS: Cluster analysis separated individuals with diabetes (68% women, mean age 60 ± 10 years) into three distinct clusters (Clusters 1,2 &3 - with Cluster 3 being a hypertrophic cluster characterized by highest LV mass, levels of brain natriuretic peptide [BNP] and high-sensitivity cardiac troponin-I [hs-cTnI]). After a median 12.1 years, there were 141 cardiovascular events. Compared to Cluster1, Clusters 3 had an increased risk of cardiovascular disease (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.08, 2.37), while Cluster 2 had a similar risk of outcome (HR 1.11; 95% CI 0.73, 168). CONCLUSIONS: Among Blacks with diabetes, cluster analysis identified three distinct echocardiographic and biomarkers phenotypes, with cluster 3 (high LV mass, high cardiac biomarkers) associated with worse outcomes, thus highlighting the prognostic value of subclinical myocardial dysfunction.

Variability of adiposity indices and incident heart failure among adults with type 2 diabetes.

BACKGROUND: It remains unclear how the variability of adiposity indices relates to incident HF. This study evaluated the associations of the variability in several adiposity indices with incident heart failure (HF) in individuals with type 2 diabetes (T2DM). METHODS: We included 4073 participants from the Look AHEAD (Action for Health in Diabetes) study. We assessed variability of body mass index (BMI), waist circumference (WC), and body weight across four annual visits using three variability metrics, the variability independent of the mean (VIM), coefficient of variation (CV), and intraindividual standard deviation (SD). Multivariable Cox regression models were used to generate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for incident HF. RESULTS: Over a median of 6.7 years, 120 participants developed incident HF. After adjusting for relevant confounders including baseline adiposity levels, the aHR for the highest (Q4) versus lowest quartile (Q1) of VIM of BMI was 3.61 (95% CI 1.91-6.80). The corresponding aHRs for CV and SD of BMI were 2.48 (95% CI 1.36-4.53) and 2.88 (1.52-5.46), respectively. Regarding WC variability, the equivalent aHRs were 1.90 (95% CI 1.11-3.26), 1.79 (95% CI 1.07-3.01), and 1.73 (1.01-2.95) for Q4 versus Q1 of VIM, CV and SD of WC, respectively. CONCLUSIONS: In a large sample of adults with T2DM, a greater variability of adiposity indices was associated with higher risks of incident HF, independently of traditional risk factors and baseline adiposity levels. Registration-URL: https://clinicaltrials.gov/ct2/show/NCT00000620 .

High-density lipoprotein-cholesterol and incident type 2 diabetes mellitus among African Americans: The Jackson Heart Study.

AIMS: Accruing evidence suggests an association between high-density lipoprotein cholesterol (HDL-C) and incident diabetes. However, there is a paucity of data on the link between HDL-C and diabetes, especially among African Americans (AAs). We aimed to assess the association of HDL-C and its fractions with incident type 2 diabetes among AAs. METHODS: We included Jackson Heart Study participants who attended visit 1 (2001-2004), were free from diabetes and were not treated with lipid-modifying medications. Incident diabetes was assessed at two subsequent-yearly visits (2 and 3). We cross-sectionally assessed the association of HDL-C and insulin resistance (IR) using multivariable linear models. We prospectively assessed the association of HDL-C and its fractions with incident diabetes using multivariable Cox regression models. RESULTS: Among 2829 participants (mean age: 51.9 ± 12.4 years, 63.9% female), 487 participants (17%) developed new-onset diabetes, over a median follow-up of 8 years. In adjusted models, a higher HDL-C concentration was associated with a lower odds of IR (odds ratio [OR] per standard deviation [SD] increment: OR 0.56 [95% confidence interval, CI 0.50-0.63], p < 0.001). In adjusted models, a higher HDL-C concentration was associated with a lower risk of diabetes (HR per SD increment: 0.78 [95% CI 0.71, 0.87], p < 0.001; HR for highest vs. the lowest tertile of HDL-C was 0.56 [95% CI: 0.44, 0.71], p < 0.001). CONCLUSION: In a sample of African-American adults not on any lipid-modifying therapy, high HDL-C concentrations were inversely associated with the risk of new-onset diabetes. These findings suggest a strong link between HDL-C metabolism and glucose regulation.

Glycemic status, non-traditional risk and left ventricular structure and function in the Jackson Heart Study.

BACKGROUND: Left ventricular structure and function abnormalities may be an early marker of cardiomyopathy among African Americans with diabetes (DM) even in the absence of coronary artery disease (CAD), arrhythmia, valvular heart disease and end-stage renal disease (ESRD). This study examined the association of prediabetes (PDM), DM and HbA1c with left ventricular structure and function among Jackson Heart Study (JHS) participants without traditional risk factors. METHODS: Retrospective cross-sectional analyses of the association of PDM, DM and HbA1c with, left ventricular ejection fraction (LV EF), fractional shortening (LV FS), stroke volume index (SVI), cardiac index (CI), left ventricular end diastolic volume index (LVEDVI), left ventricular end systolic volume index (LVESVI), relative wall thickness (RWT), myocardial contraction fraction (MCF) and left ventricular mass index (LVMI). The study was conducted in 2234 adult JHS participants without preexisting CAD, arrhythmia, valvular heart disease or ESRD. Statistical analyses included descriptive, univariate and covariate adjusted linear regression analyses. Sensitivity analyses to explore the impact of hypertension on study outcomes were also carried out. RESULTS: DM compared with no DM was associated with lower, SVI (- 0.96 ml/m2, p = 0.029), LVEDVI (- 1.44 ml/m2 p = 0.015), and MCF (- 1.90% p = 0.007) but higher CI (0.14 L/min/m2, p < 0.001), RWT (0.01 cm, p = 0.002) and LVMI (2.29 g/m2, p = 0.009). After further control for DM duration, only CI remaining significantly higher for DM compared with no DM participants (0.12 L/min/m2, p = 0.009). PDM compared with no PDM was associated with lower, SVI (- 0.87 ml/m2, P = 0.024), LVEDVI (- 1.15 ml/m2 p = 0.003) and LVESVI (- 0.62 ml/m2 p = 0.025). HbA1c ≥ 8.0% compared with HbA1c < 5.7% was associated with lower SVI (- 2.09 ml/m2, p = 0.004), LVEDVI (- 2.11 ml/m2 p = 0.032) and MCF (- 2.94% p = 0.011) but higher CI (0.11 L/min/m2, p = 0.043) and RWT (0.01 cm, p = 0.035). CONCLUSIONS: Glycemic status is associated with important left ventricular structure and function changes among African Americans without prior CAD, arrhythmia, valvular heart disease and ESRD. Longitudinal studies may further elucidate these relationships.

Neighborhood greenspace and risk of type 2 diabetes in a prospective cohort: the Multi-Ethncity Study of Atherosclerosis.

BACKGROUND: Neighborhood greenspaces provide opportunities for increased physical activity and social interaction, and thus may reduce the risk of Type 2 diabetes. However, there is little robust research on greenspace and diabetes. In this study, we examine the longitudinal association between neighborhood greenspace and incident diabetes in the Multi-Ethnic Study of Atherosclerosis. METHODS: A prospective cohort study (N = 6814; 2000-2018) was conducted to examine the association between greenspace, measured as annual and high vegetation season median greenness determined by satellite (Normalized Difference Vegetation Index) within 1000 m of participant homes, and incident diabetes assessed at clinician visits, defined as a fasting glucose level of at least 126 mg/dL, use of insulin or use of hypoglycemic medication, controlling for covariates in stages. Five thousand five hundred seventy-four participants free of prevalent diabetes at baseline were included in our analysis. RESULTS: Over the study period, 886 (15.9%) participants developed diabetes. Adjusting for individual characteristics, individual and neighborhood-scale SES, additional neighborhood factors, and diabetes risk factors, we found a 21% decrease in the risk of developing diabetes per IQR increase in greenspace (HR: 0.79; 95% CI: 0.63, 0.99). CONCLUSIONS: Overall, neighborhood greenspace provides a protective influence in the development of diabetes, suggesting that neighborhood-level urban planning that supports access to greenspace--along with healthy behaviors--may aid in diabetes prevention. Additional research is needed to better understand how an area's greenness influences diabetes risk, how to better characterize greenspace exposure and usage, and future studies should focus on robust adjustment for neighborhood-level confounders.

Associations between adherence to the dietary approaches to stop hypertension (DASH) diet and six glucose homeostasis traits in the Microbiome and Insulin Longitudinal Evaluation Study (MILES).

BACKGROUND AND AIMS: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components. METHODS AND RESULTS: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) yielded fasting plasma glucose, insulin, C-peptide, and insulin secretion, sensitivity, and disposition index. Habitual dietary intake was assessed by food frequency questionnaire (FFQ). Associations between DASH components and glucose homeostasis traits were examined, controlling for demographics, body mass index (BMI), physical activity, and energy intake. For significant associations, the models were repeated with scores for DASH-P and DASH-NP as predictors in the same model. DASH and DASH-P scores were inversely associated with fasting plasma glucose (DASH:ß = -0.036 ± 0.012,P = 0.005; DASH-P: ß = -0.04 ± 0.017,P = 0.002), and positively associated with insulin sensitivity (DASH:ß = 0.022 ± 0.012,P = 0.042; DASH-P: = 0.036 ± 0.015,P = 0.014). The DASH score was also associated with disposition index (ß = 0.026 ± 0.013,P = 0.038), but this association did not reach significance with DASH-P (ß = 0.035 ± 0.018,P = 0.051). No associations were observed with DASH-NP score (all P > 0.05). CONCLUSIONS: DASH diet is associated with improvement in specific glucose homeostasis traits, likely arising from increased plant-based foods. Such research may help tailor future dietary advice to specific metabolic risk, and to food groups most effective at improving these.

Impact of the COVID-19 Pandemic on Diabetes Care Among a North Carolina Patient Population.

In this study, researchers reviewed electronic health record data to assess whether the coronavirus disease 2019 pandemic was associated with disruptions in diabetes care processes of A1C testing, retinal screening, and nephropathy evaluation among patients receiving care with Wake Forest Baptist Health in North Carolina. Compared with the pre-pandemic period, they found an increase of 13-21 percentage points in the proportion of patients delaying diabetes care for each measure during the pandemic. Alarmingly, delays in A1C testing were greatest for individuals with the most severe disease and may portend an increase in diabetes complications.

Associations among vascular risk factors, neuroimaging biomarkers, and cognition: Preliminary analyses from the Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Little is known about how antecedent vascular risk factor (VRF) profiles impact late-life brain health. METHODS: We examined baseline VRFs, and cognitive testing and neuroimaging measures (ß-amyloid [Aß] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African-American, 50% White) from Wake Forest's Multi-Ethnic Study of Atherosclerosis Core. RESULTS: African-Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aß positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aß. Aß was cross-sectionally associated with cognition, and all imaging biomarkers were associated with greater 6-year cognitive decline. DISCUSSION: Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.

Association of T-wave abnormalities with major cardiovascular events in diabetes: the ACCORD trial.

AIMS/HYPOTHESIS: T-wave abnormalities (TWA) are often found on ECG and signify abnormal ventricular repolarisation. While TWA have been shown to be associated with subclinical atherosclerosis, the relationship between TWA and hard cardiovascular endpoints is less clear and may differ in the presence of diabetes, so we sought to explore these associations in participants from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. METHODS: TWA were operationally defined as the presence of any Minnesota Codes 5-1 through 5-4 in any lead distribution. Multivariable Cox proportional hazards models were constructed to examine relationships between TWA and clinical cardiovascular events. Secondary analyses explored the risks conferred by major vs minor TWA, differential effects of TWA by anatomic localisation (anterolateral, inferior or anterior lead distributions), and differing associations in those with or without prevalent CVD. RESULTS: Among 8176 eligible participants (mean 62.1 ± 6.3 SD years, 61.4% male), there were 3759 cardiovascular events, including 1430 deaths (473 of a cardiovascular aetiology), 474 heart failure events, 1452 major CHD events and 403 strokes. Participants with TWA had increased risks of all-cause mortality (HR 1.45 [95% CI 1.30, 1.62], p < 0.0001), cardiovascular mortality (HR 1.93 [1.59, 2.34], p = 0.0001), congestive heart failure (HR 2.04 [1.69, 2.48], p < 0.0001) and major CHD (HR 1.40 [1.26, 1.57], p < 0.0001), but no increased risk of stroke (HR 0.99 [0.80, 1.23], p = 0.95). Major TWA conferred a higher risk than minor TWA. When TWA were added to the UK Prospective Diabetes Study risk engine, there was improved discrimination for incident CHD events, but only for those with prevalent CVD (area under the receiver operating characteristic curve 0.5744 and 0.6030 with p = 0.0067). Adding TWA to the risk engine yielded improvements in reclassification that were of greater magnitude in those with prevalent CVD (net reclassification improvement [NRI] 0.24 [95% CI 0.16, 0.32] in those with prevalent CVD, NRI 0.14 [95% CI 0.07, 0.22] in those without prevalent CVD). CONCLUSIONS/INTERPRETATION: The presence and magnitude of TWA are associated with increased risk of clinical cardiovascular events and mortality in individuals with diabetes and may have value in refining risk, particularly in those with prevalent CVD. Graphical abstract.