Implementation of Obesity Science Into Clinical Practice: A Scientific Statement From the American Heart Association.

Obesity is a recognized public health epidemic with a prevalence that continues to increase dramatically in nearly all populations, impeding progress in reducing incidence rates of cardiovascular disease. Over the past decade, obesity science has evolved to improve knowledge of its multifactorial causes, identifying important biological causes and sociological determinants of obesity. Treatments for obesity have also continued to develop, with more evidence-based programs for lifestyle modification, new pharmacotherapies, and robust data to support bariatric surgery. Despite these advancements, there continues to be a substantial gap between the scientific evidence and the implementation of research into clinical practice for effective obesity management. Addressing barriers to obesity science implementation requires adopting feasible methodologies and targeting multiple levels (eg, clinician, community, system, policy) to facilitate the delivery of obesity-targeted therapies and maximize the effectiveness of guideline-driven care to at-need patient populations. This scientific statement (1) describes strategies shown to be effective or promising for enhancing translation and clinical application of obesity-based research; (2) identifies key gaps in the implementation of obesity science into clinical practice; and (3) provides guidance and resources for health care professionals, health care systems, and other stakeholders to promote broader implementation and uptake of obesity science for improved population-level obesity management. In addition, advances in implementation science that hold promise to bridge the know-do gap in obesity prevention and treatment are discussed. Last, this scientific statement highlights implications for health research policy and future research to improve patient care models and optimize the delivery and sustainability of equitable obesity-related care.

Evaluation of weight change and cardiometabolic risk factors in a real-world population of US adults with overweight or obesity.

Whether individuals in real-world settings are able to lose weight and improve cardiometabolic risk factors over time is unclear. We aimed to determine the management of and degree of body weight change over 2 years among individuals with overweight or obesity, and to assess associated changes in cardiometabolic risk factors and clinical outcomes. Using data from 11 large health systems within the Patient-Centered Outcomes Research Network in the U.S., we collected the following data on adults with a recorded BMI ≥25 kg/m2 between January 1, 2016 and December 31, 2016: body-mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDLC), triglycerides and glycated hemoglobin (HbA1c). We found that among 882,712 individuals with BMI ≥25 kg/m2 (median age 59 years; 56% female), 52% maintained stable weight over 2 years and 1.3% utilized weight loss pharmacotherapy. Weight loss of 10% was associated with small but significant lowering of mean SBP (-2.69 mmHg [95% CI -2.88, -2.50]), DBP (-1.26 mmHg [95% CI -1.35, -1.18]), LDL-C (-2.60 mg/dL [95% CI -3.14, -2.05]), and HbA1c (-0.27% [95% CI -0.35, -0.19]) in the same 12 months. However, these changes were not sustained over the following year. In this study of adults with BMI ≥25 kg/m2, the majority had stable weight over 2 years, pharmacotherapies for weight loss were under-used, and small changes in cardiometabolic risk factors with weight loss were not sustained, possibly due to failure to maintain weight loss.

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.

Association Between Social Determinants of Health and Glycemic Control Among African American People with Type 2 diabetes: The Jackson Heart Study.

BACKGROUND: Social determinants of health have a significant impact on health outcomes. However, the complexity and interaction of multiple factors influencing glycemic control remain understudied. PURPOSE: This study examined associations of socioeconomic position (income, education, and occupation), environmental (physical activity facilities, neighborhood social cohesion, neighborhood problem, and violence), behavioral (physical activity, nutrition, and smoking), and psychological factors (depressive symptoms, stress, and discrimination) with glycemic control (hemoglobin A1c [A1c]) using the World Health Organization Social Determinants of Health framework in African American adults with type 2 diabetes. METHODS: A secondary data analysis was conducted using a longitudinal cohort of 1,240 African American adults with type 2 diabetes who participated in the community-based Jackson Heart Study. Socioeconomic position, environmental, behavioral, and psychological factors were measured using validated instruments in the Jackson Heart Study. Longitudinal structural equation modeling was used with glycemic control (A1c) collected over time (Exams 1-3) as the study outcome. RESULTS: Our study presents the complex interplay of socioeconomic determinants of health and glycemic control over time. Higher socioeconomic position (higher income, higher level of education, and professional occupation) was directly associated with improvement in glycemic control over time. An association of socioeconomic position on glycemic control mediated through health behavior factors was also observed. CONCLUSIONS: In this analysis, socioeconomic position components were determinants of glycemic control in African American adults with type 2 diabetes. Future studies aimed at reducing health disparities and achieving equality of outcomes in this population will benefit from embedding socioeconomic position components into their design.

Cardiometabolic Abnormalities Among Normal-Weight Persons From Five Racial/Ethnic Groups in the United States: A Cross-sectional Analysis of Two Cohort Studies.

BACKGROUND: The relationship between body weight and cardiometabolic disease may vary substantially by race/ethnicity. OBJECTIVE: To determine the prevalence and correlates of the phenotype of metabolic abnormality but normal weight (MAN) for 5 racial/ethnic groups. DESIGN: Cross-sectional analysis. SETTING: 2 community-based cohorts. PARTICIPANTS: 2622 white, 803 Chinese American, 1893 African American, and 1496 Hispanic persons from MESA (Multi-Ethnic Study of Atherosclerosis) and 803 South Asian participants in the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study. MEASUREMENTS: Prevalence of 2 or more cardiometabolic abnormalities (high fasting glucose, low high-density lipoprotein cholesterol, and high triglyceride levels and hypertension) among normal-weight participants was estimated. Correlates of MAN were assessed by using log-binomial models. RESULTS: Among normal-weight participants (n = 846 whites, 323 Chinese Americans, 334 African Americans, 252 Hispanics, and 195 South Asians), the prevalence of MAN was 21.0% (95% CI, 18.4% to 23.9%) in whites, 32.2% (CI, 27.3% to 37.4%) in Chinese Americans, 31.1% (CI, 26.3% to 36.3%) in African Americans, 38.5% (CI, 32.6% to 44.6%) in Hispanics, and 43.6% (CI, 36.8% to 50.6%) in South Asians. Adjustment for demographic, behavioral, and ectopic body fat measures did not explain racial/ethnic differences. After adjustment for age, sex, and race/ethnicity-body mass index (BMI) interaction, for the equivalent MAN prevalence at a BMI of 25.0 kg/m2 in whites, the corresponding BMI values were 22.9 kg/m2 (CI, 19.5 to 26.3 kg/m2) in African Americans, 21.5 kg/m2 (CI, 18.5 to 24.5 kg/m2) in Hispanics, 20.9 kg/m2 (CI, 19.7 to 22.1 kg/m2) in Chinese Americans, and 19.6 kg/m2 (CI, 17.2 to 22.0 kg/m2) in South Asians. LIMITATION: Cross-sectional study design and lack of harmonized dietary data between studies. CONCLUSION: Compared with whites, all racial/ethnic minority groups had a statistically significantly higher prevalence of MAN, which was not explained by demographic, behavioral, or ectopic fat measures. Using a BMI criterion for overweight to screen for cardiometabolic risk may result in a large proportion of racial/ethnic minority groups being overlooked. PRIMARY FUNDING SOURCE: National Institutes of Health.

The relationship between anthropometry and body composition from computed tomography: The Mediators of Atherosclerosis in South Asians Living in America Study.

OBJECTIVE: Few studies examine the relationships between anthropometry and the body composition measures they approximate, or whether they differ by sex, and no studies have examined these relationships in South Asians living in the US. DESIGN: We conducted a cross-sectional study of 871 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study who had BMI < 40 kg/m2 and underwent abdominal CT scans for measurement of visceral and subcutaneous fat. Linear regression was used to model the associations between anthropometric measures and naturally log-transformed body composition measures. RESULTS: All measures of anthropometry, except height, were significantly associated with visceral fat and had a significant non-linear component (p < .05). The only associations for visceral fat that exhibited significant heterogeneity by sex were waist circumference (% difference in visceral fat slope: women 1.92, men 2.74, p = .007 for interaction) and waist-to-hip ratio (women 25.9, men 717.4, p < .001). Except for height, all measures of anthropometry were significantly associated with subcutaneous fat, had a significant quadratic component, and significant heterogeneity by sex (weight (kg): 2.74 for women, 4.08 for men; BMI (kg/m2): 10.3, 14.0; waist circumference (cm): 1.51, 3.36; hip circumference (cm): 2.53, 4.50) with p < .001 for each. CONCLUSIONS: In MASALA participants, the relationships of anthropometric measures with visceral and subcutaneous fat appear similar to other race/ethnic groups, but with weaker non-linearity and heterogeneity by sex. Given these results, researchers should consider separate models by sex for US South Asians when approximating subcutaneous fat or when using waist circumference to approximate visceral fat.

Assessment of sociodemographic factors associated with time to self-reported COVID-19 infection among a large multi-center prospective cohort population in the southeastern United States.

OBJECTIVE: We aimed to investigate sociodemographic factors associated with self-reported COVID-19 infection. METHODS: The study population was a prospective multicenter cohort of adult volunteers recruited from healthcare systems located in the mid-Atlantic and southern United States. Between April 2020 and October 2021, participants completed daily online questionnaires about symptoms, exposures, and risk behaviors related to COVID-19, including self-reports of positive SARS CoV-2 detection tests and COVID-19 vaccination. Analysis of time from study enrollment to self-reported COVID-19 infection used a time-varying mixed effects Cox-proportional hazards framework. RESULTS: Overall, 1,603 of 27,214 study participants (5.9%) reported a positive COVID-19 test during the study period. The adjusted hazard ratio demonstrated lower risk for women, those with a graduate level degree, and smokers. A higher risk was observed for healthcare workers, those aged 18-34, those in rural areas, those from households where a member attends school or interacts with the public, and those who visited a health provider in the last year. CONCLUSIONS: We identified subgroups within healthcare network populations defined by age, occupational exposure, and rural location reporting higher than average rates of COVID-19 infection for our surveillance population. These subgroups should be monitored closely in future epidemics of respiratory viral diseases.

The association of plasma lactate with incident cardiovascular outcomes: the ARIC Study.

We examined the association of plasma lactate at rest, a marker of oxidative capacity, with incident cardiovascular outcomes in 10,006 participants in the Atherosclerosis Risk in Communities (ARIC) Study visit 4 (1996-1998). We used Cox proportional-hazards models to estimate hazard ratios of incident coronary heart disease, stroke, heart failure, and all-cause mortality by quartiles of plasma lactate (Q1, ≤5.3 mg/dL; Q2, 5.4-6.6; Q3, 6.7-8.6; and Q4 ≥8.7). During a median follow-up time of 10.7 years, there were 1,105 coronary heart disease cases, 379 stroke cases, 820 heart failure cases, and 1,408 deaths. A significant graded relation between lactate level and cardiovascular events was observed in the demographically adjusted model (all P for trend < 0.001). After further adjustment for traditional and other potential confounders, the association remained significant for heart failure (Q4 vs. Q1: hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.07, 1.71) and all-cause mortality (HR = 1.27, 95% CI: 1.07, 1.51) (P for trend < 0.02 for these outcomes) but not for coronary heart disease (HR = 1.02, 95% CI: 0.84, 1.24) and stroke (HR = 1.26, 95% CI: 0.91, 1.75). The results for heart failure were robust across multiple subgroups, after further adjustment for N-terminal pro-B-type natriuretic peptide and after exclusion of participants with incident heart failure within 3 years. The independent associations of plasma lactate with heart failure and all-cause mortality suggest an important role for low resting oxidative capacity.

Associations of Slow-Wave Sleep With Prevalent and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis.

CONTEXT: N3 sleep (i.e., slow-wave sleep), a marker of deep restorative sleep, is implicated in hormonal and blood pressure regulation and may impact cardiometabolic health. OBJECTIVE: We conducted cross-sectional and prospective analyses to test whether a higher proportion and longer duration of N3 sleep are associated with reduced type 2 diabetes risk. METHODS: A subsample of participants from the Multi-Ethnic Study of Atherosclerosis completed 1-night polysomnography at Exam 5 (2010-2013) and were prospectively followed until Exam 6 (2016-2018). We used modified Poisson regression to examine the cross-sectional associations of N3 proportion and duration with prevalent diabetes and Cox proportional hazards models to estimate risk of diabetes according to N3 measures. RESULTS: In cross-sectional analyses (n = 2026, mean age: 69 years), diabetes prevalence was 28% (n = 572). Compared with the first quartile (Q1) of the N3 proportion (<2.0%), participants in Q4 (≥15.4%) were 29% (95% CI 0.58, 0.87) less likely to have prevalent diabetes (P trend = .0016). The association attenuated after adjustment for demographics, lifestyles, and sleep-related factors (P trend = .3322). In prospective analyses of 1251 participants and 129 incident cases over 6346 person-years of follow-up, a curvilinear relationship was observed between N3 proportion and incident diabetes risk. In the fully adjusted model, the hazard ratio (95% CI) of developing diabetes vs Q1 was 0.47 (0.26, 0.87) for Q2, 0.34 (0.15, 0.77) for Q3, and 0.32 (0.10, 0.97) for Q4 (P nonlinearity = .0213). The results were similar for N3 duration. CONCLUSION: Higher N3 proportion and longer N3 duration were prospectively associated with lower type 2 diabetes risk in a nonlinear fashion among older American adults.

Association Between Alcohol Consumption and Ectopic Fat in the Multi-Ethnic Study of Atherosclerosis.

Background The relationship between alcohol consumption and ectopic fat distribution, both known factors for cardiovascular disease, remains understudied. Therefore, we aimed to examine the association between alcohol consumption and ectopic adiposity in adults at risk for cardiovascular disease. Methods and Results In this cross-sectional analysis, we categorized alcohol intake among participants in MESA (Multi-Ethnic Study of Atherosclerosis) as follows (drinks/day): <1 (light drinking), 1 to 2 (moderate drinking), >2 (heavy drinking), former drinking, and lifetime abstention. Binge drinking was defined as consuming ≥5 drinks on 1 occasion in the past month. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Using multivariable linear regression, we examined the associations between categories of alcohol consumption and natural log-transformed fat in ectopic depots. We included 6756 MESA participants (62.1±10.2 years; 47.2% women), of whom 6734 and 1934 had chest computed tomography (pericardial and hepatic fat) and abdominal computed tomography (subcutaneous, intermuscular, and visceral fat), respectively. In adjusted analysis, heavy drinking, relative to lifetime abstention, was associated with a higher (relative percent difference) pericardial 15.1 [95% CI, 7.1-27.7], hepatic 3.4 [95% CI, 0.1-6.8], visceral 2.5 [95% CI, -10.4 to 17.2], and intermuscular 5.2 [95% CI, -6.6 to 18.4] fat but lower subcutaneous fat -3.5 [95% CI, -15.5 to 10.2]). The associations between alcohol consumption and ectopic adiposity exhibited a J-shaped pattern. Binge drinking, relative to light-to-moderate drinking, was also associated with higher ectopic fat. Conclusions Alcohol consumption had a J-shaped association with ectopic adiposity. Both heavy alcohol intake and binge alcohol drinking were associated with higher ectopic fat.

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.

Association between COVID-19 and consistent mask wearing during contact with others outside the household-A nested case-control analysis, November 2020-October 2021.

BACKGROUND: Face masks have been recommended to reduce SARS-CoV-2 transmission. However, evidence of the individual benefit of face masks remains limited, including by vaccination status. METHODS: As part of the COVID-19 Community Research Partnership cohort study, we performed a nested case-control analysis to assess the association between self-reported consistent mask use during contact with others outside the household and subsequent odds of symptomatic SARS-CoV-2 infection (COVID-19) during November 2020-October 2021. Using conditional logistic regression, we compared 359 case-participants to 3544 control-participants who were matched by date, adjusting for enrollment site, age group, sex, race/ethnicity, urban/rural county classification, and healthcare worker occupation. RESULTS: COVID-19 was associated with not consistently wearing a mask (adjusted odds ratio [aOR] 1.49; 95% confidence interval [CI] [1.14, 1.95]). Compared with persons ≥14 days after mRNA vaccination who also reported always wearing a mask, COVID-19 was associated with being unvaccinated (aOR 5.94; 95% CI [3.04, 11.62]), not wearing a mask (aOR 1.62; 95% CI [1.07, 2.47]), or both unvaccinated and not wearing a mask (aOR 9.07; 95% CI [4.81, 17.09]). CONCLUSIONS: Our findings indicate that consistent mask wearing can complement vaccination to reduce the risk of COVID-19.

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.

The role of aldosterone and ideal cardiovascular health in incident diabetes: The Jackson Heart Study.

Background: Greater attainment of ideal cardiovascular health (ICH) and lower serum aldosterone are associated with lower diabetes risk. Higher levels of ICH are associated with lower aldosterone. The mediational role of aldosterone in the association of ICH with incident diabetes remains unexplored. Thus, we examined the mediational role of aldosterone in the association of 5 ICH components (smoking, diet, physical activity, body mass index [BMI], and cholesterol) with incident diabetes. Additionally, we investigated the mediational role of glucose and blood pressure (BP) in the association of aldosterone with incident diabetes in an African American (AA) cohort. Methods: We conducted a prospective cohort analysis among AA adults, aged 21-94 years, in the Jackson Heart Study. Data on ICH, aldosterone, and cardiometabolic risk factors were collected at exam 1 (2000-2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at exams 1 through 3 (2009-2012). ICH metrics were defined by American Heart Association 2020 goals for smoking, dietary intake, physical activity, BMI, total cholesterol, BP and glucose. The number of ICH metrics attained at exam 1, excluding BP and fasting glucose, were summed (0-2, vs. 3+). R Package Mediation was used to examine: 1) The mediational role of aldosterone in the association of ICH with incident diabetes; and 2) the mediational role of BP and glucose in the association of aldosterone with incident diabetes. Results: Among 2,791 participants (mean age: 53±12, 65% female) over a median of 7.5 years, there were 497 incident diabetes cases. Risk of incident diabetes was 37% (HR: 0.63, 95%CI: 0.47, 0.84) lower in 3+ ICH category compared to 0-2 ICH category. Aldosterone mediated 6.98% (95% CI: 1.8%, 18.0%) of the direct effect of ICH on incident diabetes. A 1-unit increase in log-aldosterone was associated with a 44% higher risk of diabetes (HR 1.44, 95%CI 1.25-1.64). BP and glucose mediated 16.3% (95% CI: 7.0%, 31.0%) and 19.7% (95% CI: 6.5%, 34.0%) of the association of aldosterone with incident diabetes, respectively. Conclusion: Aldosterone is a mediator of the association of ICH with incident diabetes, whereas BP and glucose are mediators of the association of aldosterone with incident diabetes, emphasizing the importance of the renin-angiotensin-aldosterone system and ICH in lowering risk of diabetes in AA populations.

The role of aldosterone and ideal cardiovascular health in incident cardiovascular disease: The Jackson heart study.

Background: Higher levels of ideal cardiovascular health (ICH) are associated with lower levels of aldosterone and incidence of cardiovascular disease (CVD). However, the degree to which aldosterone mediates the association between ICH and CVD incidence has not been explored. Thus, we investigated the mediational role of aldosterone in the association of 5 components of ICH (cholesterol, body mass index (BMI), physical activity, diet and smoking) with incident CVD and the mediational role of blood pressure (BP) and glucose in the association of aldosterone with incident CVD in a cohort of African Americans (AA). Methods: The Jackson Heart Study is a prospective cohort of AAs adults with data on CVD outcomes. Aldosterone, ICH metrics and baseline characteristics were collected at exam 1 (2000-2004). ICH score was developed by summing 5 ICH metrics (smoking, dietary intake, physical activity, BMI, and total cholesterol) and grouped into two categories (0-2 and ≥3 metrics). Incident CVD was defined as stroke, coronary heart disease, or heart failure. Cox proportional hazard regression models were used to model the association of categorical ICH score with incident CVD. The R Package Mediation was utilized to examine: 1) The mediational role of aldosterone in the association of ICH with incident CVD and 2) The mediational role of blood pressure and glucose in the association of aldosterone with incident CVD. Results: Among 3,274 individuals (mean age: 54±12.4 years, 65% female), there were 368 cases of incident CVD over a median of 12.7 years. The risk of incident CVD was 46% lower (HR: 0.54; 95%CI 0.36, 0.80) in those with ≥3 ICH metrics at baseline compared to 0-2. Aldosterone mediated 5.4% (p = 0.006) of the effect of ICH on incident CVD. A 1-unit increase in log-aldosterone was associated with a 38% higher risk of incident CVD (HR 1.38, 95%CI: 1.19, 1.61) with BP and glucose mediating 25.6% (p<0.001) and 4.8% (p = 0.048), respectively. Conclusion: Aldosterone partially mediates the association of ICH with incident CVD and both blood pressure and glucose partially mediate the association of aldosterone with incident CVD, emphasizing the potential importance of aldosterone and ICH in risk of CVD among AAs.

Factors associated with COVID-19 vaccination during June-October 2021: A multi-site prospective study.

INTRODUCTION: Vaccine hesitancy presents a challenge to COVID-19 control efforts. To identify beliefs associated with delayed vaccine uptake, we developed and implemented a vaccine hesitancy survey for the COVID-19 Community Research Partnership. METHODS: In June 2021, we assessed attitudes and beliefs associated with COVID-19 vaccination using an online survey. Self-reported vaccination data were requested daily through October 2021. We compared responses between vaccinated and unvaccinated respondents using absolute standardized mean differences (ASMD). We assessed validity and reliability using exploratory factor analysis and identified latent factors associated with a subset of survey items. Cox proportional hazards models and mediation analyses assessed predictors of subsequent vaccination among those initially unvaccinated. RESULTS: In June 2021, 29,522 vaccinated and 1,272 unvaccinated participants completed surveys. Among those unvaccinated in June 2021, 559 (43.9 %) became vaccinated by October 31, 2021. In June, unvaccinated participants were less likely to feel "very concerned" about getting COVID-19 than vaccinated participants (10.6 % vs. 43.3 %, ASMD 0.792). Among those initially unvaccinated, greater intent to become vaccinated was associated with getting vaccinated and shorter time to vaccination. However, even among participants who reported no intention to become vaccinated, 28.5 % reported vaccination before study end. Two latent factors predicted subsequent vaccination-being 'more receptive' was derived from motivation to protect one's own or others' health and resume usual activities; being 'less receptive' was derived from concerns about COVID-19 vaccines. In a Cox model, both factors were partially mediated by vaccination intention. CONCLUSION: This study characterizes vaccine hesitant individuals and identifies predictors of eventual COVID-19 vaccination through October 31, 2021. Even individuals with no intention to be vaccinated can shift to vaccine uptake. Our data suggest factors of perceived severity of COVID-19 disease, vaccine safety, and trust in the vaccine development process are predictive of vaccination and may be important opportunities for ongoing interventions.

Determinants of Metabolic Syndrome and Type 2 Diabetes in the Absence of Obesity: The Jackson Heart Study.

Context: Multiple studies suggest that adults who were normal weight at diabetes diagnosis are at higher risk for all-cause mortality than those who had overweight or obesity at diagnosis. Objective: While obesity is a known risk factor for cardiometabolic disease, differences in body fat distribution in those without obesity are understudied, especially in African Americans. Methods: In 1005 participants of the Jackson Heart Study, without cardiovascular disease at baseline, we used logistic regression to investigate the longitudinal association of body fat distribution by CT scan with metabolic syndrome (MetS) or type 2 diabetes (T2D). We used the harmonized International Diabetes Federation criteria to define MetS. We included only normal weight or overweight participants (BMI: 18.5 to < 30.0 kg/m2). We created separate models for MetS and T2D adjusted for a standard set of covariates. We excluded participants with prevalent MetS or T2D, respectively in sensitivity. Results: Higher visceral fat, subcutaneous fat, BMI, and insulin resistance (HOMA-IR) were significantly associated with MetS and T2D after adjustment. Visceral fat was strongly associated with both outcomes (MetS OR = 2.07 [1.66-2.68]; T2D OR = 1.51 [1.21-1.88]), and the association for MetS persisted in the normal weight only group. Estimates were robust to sensitivity analysis and were only modestly mediated by insulin resistance. Physical activity was not associated with MetS or T2D. Conclusion: Visceral fat is strongly associated with developing MetS, even in normal weight individuals, suggesting that excess visceral fat plays a role in cardiometabolic risk beyond that of overall adiposity and obesity in African Americans.

Association of Obesity and Diabetes with SARS-Cov-2 Infection and Symptoms in the COVID-19 Community Research Partnership.

OBJECTIVE: Obesity and diabetes are established risk factors for severe SARS-CoV-2 outcomes, but less is known about their impact on susceptibility to COVID-19 infection and general symptom severity. We hypothesized that those with obesity or diabetes would be more likely to self-report a positive SARS-CoV-2 test, and among those with a positive test, have greater symptom severity and duration. METHODS: Among 44,430 COVID-19 Community Research Partnership participants, we evaluated the association of self-reported and electronic health record obesity and diabetes with a self-reported positive COVID-19 test at any time. Among the 2,663 participants with a self-reported positive COVID-19 test during the study, we evaluated the association of obesity and diabetes with self-report of symptom severity, duration, and hospitalization. Logistic regression models were adjusted for age, sex, race/ethnicity, socioeconomic status, and healthcare worker status. RESULTS: We found a positive graded association between Body Mass Index (BMI) category and positive COVID-19 test (Overweight OR = 1.14 [1.05-1.25]; Obesity I OR = 1.29 [1.17-2.42]; Obesity II OR = 1.34 [1.19-1.50]; Obesity III OR = 1.53 [1.35-1.73]), and a similar but weaker association with COVID-19 symptoms and severity among those with a positive test. Diabetes was associated with COVID-19 infection but not symptoms after adjustment, with some evidence of an interaction between obesity and diabetes. CONCLUSIONS: While the limitations of this health system convenience sample include generalizability and selection around test-seeking, the strong graded association of BMI and diabetes with self-reported COVID-19 infection suggests that obesity and diabetes may play a role in risk for symptomatic SARS-CoV-2 beyond co-occurrence with socioeconomic factors.

Relationship of American Heart Association's Life Simple 7, Ectopic Fat, and Insulin Resistance in 5 Racial/Ethnic Groups.

BACKGROUND: The inverse association between ideal cardiovascular health (CVH) as measured by the American Heart Association's Life Simple 7 (LS7) and cardiovascular disease (CVD) incidence is well documented. However, research exploring the association between CVH and specific risk factors for cardiometabolic disease is sparse in diverse cohorts. METHODS: This study included 7717 participants from the Mediators of Atherosclerosis in South Asians Living in America and the Multi-Ethnic Study of Atherosclerosis cohorts. We assigned each LS7 component a 0, 1, and 2 and summed these scores to derive an overall CVH score. Visceral, subcutaneous, and intermuscular fat area, pericardial fat volume, and hepatic fat attenuation were measured using noncontrast computed tomography. Multivariable linear regression was used to examine associations between CVH categories and each log-transformed ectopic fat depot, as well as the homeostatic assessment for insulin resistance (HOMA-IR). RESULTS: In adjusted analysis, compared to those with ideal CVH, participants with poor CVH demonstrated 63.4% (95% CI, 54.3-73.0) higher visceral fat area, 84.0% (95% CI, 76.5-92.1) higher pericardial fat volume, 61.6% (95% CI, 50.7-73.2) higher subcutaneous fat area, and 40.6% (95% CI, 30.2-52.0) higher intermuscular fat area, and 15.1% (95% CI, 13.1-17.2) higher hepatic fat (all Ps < 0.001). Also, poor CVH was associated with 148.2% (95% CI, 131.1-166.7) higher HOMA-IR. We also found significant heterogeneity in the strengths of association by race/ethnicity for each ectopic fat depot. CONCLUSION: Poor and intermediate CVH, as defined by LS7 metrics, were associated with significantly higher measures of ectopic fat and insulin resistance among individuals from 5 racial/ethnic groups.

Association of Visceral Adipose Tissue and Insulin Resistance with Incident Metabolic Syndrome Independent of Obesity Status: The IRAS Family Study.

OBJECTIVE: Although increasing evidence suggests that visceral adipose tissue (VAT) is a major underlying cause of metabolic syndrome (MetS), few studies have measured VAT at multiple time points in diverse populations. VAT and insulin resistance were hypothesized to differ by MetS status within BMI category in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study and, further, that baseline VAT and insulin resistance and increases over time are associated with incident MetS. METHODS: Generalized estimating equations were used for differences in body fat distribution and insulin resistance by MetS status. Mixed effects logistic regression was used for the association of baseline and change in adiposity and insulin resistance with incident MetS across 5 years, adjusted for age, sex, race/ethnicity, and family correlation. RESULTS: VAT and insulin sensitivity differed significantly by MetS status and BMI category at baseline. VAT and homeostatic model assessment of insulin resistance (HOMA-IR) at baseline (VAT odds ratio [OR] = 1.16 [95% CI: 1.12-2.31]; HOMA-IR OR = 1.85 [95% CI: 1.32-2.58]) and increases over time (VAT OR = 1.55 [95% CI: 1.22-1.98]; HOMA-IR OR = 3.23 [95% CI: 2.20-4.73]) were associated with incident MetS independent of BMI category. CONCLUSIONS: Differing levels of VAT may be driving metabolic heterogeneity within BMI categories. Both overall and abdominal obesity (VAT) may play a role in the development of MetS. Increased VAT over time contributed additional risk.