Microvascular vasoregulatory dysfunction in African Americans - An enhanced opportunity for early prevention and treatment of atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease and its risk factors and precursors are a major driver of disparities in cardiovascular health. This review examines reported evidence that vascular endothelial dysfunction, and its manifestation as coronary microvascular dysfunction, underlies observed excess morbidity and mortality in African Americans. Advanced imaging insights that reveal patho-mechanisms, along with population evidence from the Jackson Heart Study, and the growing evidence emanating from national and international clinical trials and registries are presented. We examine a physiological framework that recognizes insulin-resistant cardiometabolic underpinnings of the conditions of the American Heart Associations' Life's Essential Eight construct of cardiovascular health as a unifying basis that affords early prevention. Mechanistic-based therapeutic approaches, can subsequently be implemented to interrupt progression to adverse outcomes employing layered, or personalized, treatment strategies of a well-defined set of conditions or diseases. Remaining knowledge gaps are acknowledged.

Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Subclinical Atherosclerosis Across the Menopausal Transition in Women With and Without HIV.

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.

Midlife body mass index, central adiposity and neuropsychological performance over 10 years in women living with and without HIV.

Background and objective: Observations of overweight and obesity in association with neuropsychological performance (NP) vary over the adult life course depending on baseline levels, biological sex, age, race, temporality of measurements, and other factors. Therefore, similar published analyses across cohorts are inconsistent. In our sample of women living with HIV (WLWH) and women without HIV (WWOH), we conducted comparable analyses as those published in men with and without HIV. We examined cross-sectional and longitudinal associations between body mass index (BMI) and waist circumference (WC) and NP. Methods: Four hundred thirty two 432 virologically-suppressed WLWH and 367 WWOH, ≥40 years in the Women's Interagency HIV Study (WIHS) with anthropometry and NP assessments every two years from 2009-2019 were included in the study. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear regression models stratified by HIV status were used to examine cross-sectional associations of BMI and WC by NP domain; repeated measures analyses assessed baseline BMI and WC in association with longitudinal change in NP. Covariates included sociodemographic, behavioral, and HIV-related characteristics. Results: At baseline among all women, the median age was 45 years, 65% were Non-Latinx Black women, and 45% were obese women. Obese WLWH (BMI≥30.0 kg/m2) had poorer executive function (ß=-2.27, 95%CI [-4.46, -0.07]) versus WLWH with healthy BMI (18.5-24.9 kg/m2). Longitudinally over ~8 years, obese versus overweight WWOH improved on memory (ß=2.19, 95%CI [0.13, 4.26]), however overweight versus healthy WWOH experienced declining memory (ß= -2.67, 95%CI [-5.40, -0.07]). Increasing WC was associated with declining executive, processing speed, and motor function (p's<0.05); an at-risk WC was associated with improved memory (ß=1.81, 95%CI [0.19, 3.44]) among WWOH. Among WLWH, increasing BMI was associated with improved learning (ß=0.07, 95%CI [0.00, 0.15]. Conclusion: Our cross-sectional and longitudinal analyses evaluating the associations of BMI and WC and NP were mixed compared to previous reports. This illustrates the importance of sociodemographic characteristics, baseline levels of exposures and outcomes, HIV status, temporality of measurements, and other factors when evaluating aging HIV epidemiology study results.

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.

Neighborhood characteristics and arterial stiffness among Black adults - Results from the Jackson Heart Study and Morehouse-Emory Cardiovascular Center for Health Equity.

INTRODUCTION: Poor quality neighborhood environments are independent risk factors for cardiovascular disease (CVD) but are understudied in Black adults, who face large CVD health disparities. Arterial stiffness, a marker of early vascular aging, precedes development of hypertension and adverse CVD events but the effect of neighborhood on arterial stiffness among Black adults remains unknown. OBJECTIVE: We compared the association between neighborhood environment and arterial stiffness among Black adults in Jackson, MS and Atlanta, GA. METHODS: We studied 1582 Black adults (mean age 53 ± 10, 35% male) living in Jackson, MS from the Jackson Heart Study (JHS) and 451 Black adults (mean age 53 ± 10, 39% male) living in Atlanta, GA from the Morehouse-Emory Cardiovascular Center for Health Equity (MECA) study, without known CVD. Neighborhood problems (includes measures of aesthetic quality, walking environment, food access), social cohesion (includes activity with neighbors), and violence/safety were assessed using validated questionnaires. Arterial stiffness was measured as pulse wave velocity (PWV) using magnetic resonance imaging in JHS and as PWV and augmentation index (AIx) using applanation tonometry (SphygmoCor, Inc.) in MECA. Multivariable linear regression models were used to examine the association between neighborhood characteristics and arterial stiffness, adjusting for potential confounders. RESULTS: Improved social characteristics, measured as social cohesion in JHS (ß = -0.32 [-0.63, -0.02], p = 0.04) and activity with neighbors (ß = -0.23 [-0.40, -0.05], p = 0.01) in MECA, were associated with lower PWV in both cohorts and lower AIx (ß = -1.74 [-2.92, - 0.56], p = 0.004) in MECA, after adjustment for CVD risk factors and income. Additionally, in MECA, better food access (ß = -1.18 [-2.35, - 0.01], p = 0.05) was associated with lower AIx and, in JHS, lower neighborhood problems (ß = -0.33 [-0.64, - 0.02], p = 0.04) and lower violence (ß = -0.30 [-0.61, 0.002], p = 0.05) were associated with lower PWV. CONCLUSION: Neighborhood social characteristics show an independent association with the vascular health of Black adults, findings that were reproducible in two distinct American cities.

Vitamin D Levels in Black Americans and the Association With Left Ventricular Remodeling and Incident Heart Failure With Preserved Ejectin Fraction: The Jackson Heart Study.

BACKGROUND: In observational studies, a lower serum vitamin D3 concentration has been associated with an increased risk of cardiovascular disease. However, the associations between serum vitamin D3 levels and left ventricular (LV) structure and heart failure with preserved ejection fraction (HFpEF) have not been well-characterized among Black Americans. The prevalence of vitamin D3 deficiency is higher among Black Americans than in other race/ethnicity groups. We hypothesized that serum vitamin D3 levels are associated with LV concentric remodeling and incident HFpEF in Black Americans. METHODS AND RESULTS: Among 5306 Black Americans in the Jackson Heart Study cohort, we investigated the relationships between serum vitamin D3 levels and LV structure and function, evaluated with echocardiography, and incident HF hospitalization, categorized as either HF with reduced EF (HFrEF; an EF of <50%) or HFpEF (an EF of ≥50%). After adjustment for possible confounding factors, lower vitamin D3 levels were associated with greater relative wall thickness (ß for 1 standard deviation [SD] increase -0.003, 95% confidence interval -0.005 to -0.000). Over a median follow-up period of 11 years (range 10.2-11.0 years), 340 participants developed incident HF (7.88 cases per 1000 person-years), including 146 (43%) HFrEF and 194 (57%) HFpEF cases. After adjustment, higher serum vitamin D3 levels were associated with decreased hazard for HF overall (hazard ratio for 1 SD increase 0.88, 95% confidence interval 0.78-0.99) driven by a significant association with HFpEF (hazard ratio for 1 SD increase 0.84, 95% confidence interval 0.71-0.99). CONCLUSIONS: In this community-based Black American cohort, lower serum vitamin D3 levels were associated with LV concentric remodeling and an increased hazard for HF, mainly HFpEF. Further investigation is required to examine whether supplementation with vitamin D3 can prevent LV concentric remodeling and incident HFpEF in Black Americans.

Insights From a Large-Scale Whole-Genome Sequencing Study of Systolic Blood Pressure, Diastolic Blood Pressure, and Hypertension.

BACKGROUND: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure. METHODS: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants. RESULTS: Two blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P<5×10-8). Among them, a rare intergenic variant at novel locus, LOC100506274, was associated with lower systolic blood pressure in stage-1 (beta [SE]=-32.6 [6.0]; P=4.99×10-8) but not stage-2 analysis (P=0.11). Furthermore, a novel common variant at the known INSR locus was suggestively associated with diastolic blood pressure in stage-1 (beta [SE]=-0.36 [0.07]; P=4.18×10-7) and attained genome-wide significance in stage-2 (beta [SE]=-0.29 [0.03]; P=7.28×10-23). Nineteen additional signals suggestively associated with blood pressure in meta-analysis of single and aggregate rare variant findings (P<1×10-6 and P<1×10-4, respectively). DISCUSSION: We report one promising but unconfirmed rare variant for blood pressure and, more importantly, contribute insights for future blood pressure sequencing studies. Our findings suggest promise of aggregate analyses to complement single variant analysis strategies and the need for larger, diverse samples, and family studies to enable robust rare variant identification.

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.

Association of Mild Valvular Lesions With Long-term Cardiovascular Outcomes Among Black Adults.

Importance: Little is known about the long-term outcomes of mild valvular lesions. Objective: To examine the associations of 3 major types of valvular lesions (aortic stenosis, trace or mild aortic regurgitation, and trace or mild mitral regurgitation) with risk of cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, and atrial fibrillation. Design, Setting, and Participants: This cohort study analyzed data from the ongoing Atherosclerosis Risk in Communities study and focused on Black participants in the Jackson, Mississippi, site who underwent echocardiography at visit 3 from 1993 to 1995. Data analysis was conducted between April 2021 and February 2022. Exposures: Three valvular lesions were analyzed: aortic sclerosis, aortic regurgitation (trace or mild), and mitral regurgitation (trace or mild). Main Outcomes and Measures: The outcomes were cardiovascular mortality, coronary heart disease, heart failure, stroke, and atrial fibrillation. Multivariable Cox proportional hazards regression models were used to examine the independent associations between the 3 valvular lesions and these outcomes. Results: A total of 2106 Black participants were included, with a mean (SD) age of 59.1 (5.6) years and 1354 women (64.3%). The baseline prevalence was 7.7% for aortic sclerosis, 15.1% for aortic regurgitation (6.1% with trace, and 9.0% with mild), and 43.0% for mitral regurgitation (29.4% with trace, and 13.6% with mild). During a median (interquartile interval) follow-up of 22.5 (15.6-23.5) years, 890 participants developed at least 1 cardiovascular outcome. Each valvular lesion was significantly associated with at least 1 cardiovascular outcome: aortic sclerosis was associated with cardiovascular mortality (adjusted hazard ratio [HR], 1.54; 95% CI, 1.06-2.22), mild mitral regurgitation was associated with atrial fibrillation (HR, 1.47; 95% CI, 1.09-1.99), and trace or mild aortic regurgitation was associated with all outcomes (HRs ranging from 1.45 [95% CI, 1.17-1.81] to 1.75 [95% CI, 1.29-2.37]) except stroke. The total number of valvular lesions had graded associations with all cardiovascular outcomes except stroke: the HR of cardiovascular mortality was 1.77 (95% CI, 1.18-2.65) for those with 2 to 3 lesions and was 1.44 (95% CI, 1.05-1.96) for those with 1 lesion vs no lesions. Conclusions and Relevance: Results of this study indicate an association between valvular lesions, even at mild stage, and a long-term risk of cardiovascular events, suggesting the importance of recognizing and monitoring these valvular conditions.

Rare coding variants in RCN3 are associated with blood pressure.

BACKGROUND: While large genome-wide association studies have identified nearly one thousand loci associated with variation in blood pressure, rare variant identification is still a challenge. In family-based cohorts, genome-wide linkage scans have been successful in identifying rare genetic variants for blood pressure. This study aims to identify low frequency and rare genetic variants within previously reported linkage regions on chromosomes 1 and 19 in African American families from the Trans-Omics for Precision Medicine (TOPMed) program. Genetic association analyses weighted by linkage evidence were completed with whole genome sequencing data within and across TOPMed ancestral groups consisting of 60,388 individuals of European, African, East Asian, Hispanic, and Samoan ancestries. RESULTS: Associations of low frequency and rare variants in RCN3 and multiple other genes were observed for blood pressure traits in TOPMed samples. The association of low frequency and rare coding variants in RCN3 was further replicated in UK Biobank samples (N = 403,522), and reached genome-wide significance for diastolic blood pressure (p = 2.01 × 10- 7). CONCLUSIONS: Low frequency and rare variants in RCN3 contributes blood pressure variation. This study demonstrates that focusing association analyses in linkage regions greatly reduces multiple-testing burden and improves power to identify novel rare variants associated with blood pressure traits.

Transthyretin V142I Genetic Variant and Cardiac Remodeling, Injury, and Heart Failure Risk in Black Adults.

OBJECTIVES: This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults. BACKGROUND: The valine-to-isoleucine substitution in the TTR protein is prevalent in Black individuals and causes cardiac amyloidosis. METHODS: Jackson Heart Study participants without HF at baseline who had available data on the TTR V142I variant were included. The association of the TTR V142I variant with baseline echocardiographic parameters and repeated measures of high-sensitivity cardiac troponin-I (hs-cTnI) was assessed using adjusted linear regression models and linear mixed models, respectively. Adjusted Cox models, restricted mean survival time analysis, and Anderson-Gill models were constructed to determine the association of TTR V142I variant with the risk of incident HF, survival free of HF, and total HF hospitalizations. RESULTS: A total of 119 of 2,960 participants (4%) were heterozygous carriers of the TTR V142I variant. The TTR V142I variant was not associated with measures of cardiac parameters at baseline but was associated with a greater increase in high-sensitivity troponin I (hs-TnI) levels over time. In adjusted Cox models, TTR V142I variant carriers had significantly higher risk of incident HF (HR: 1.80; 95% CI: 1.07-3.05; P = 0.03), lower survival free of HF (mean difference: 4.0 year; 95% CI: 0.6-6.2 years); P = 0.02), and higher risk of overall HF hospitalizations (HR: 2.12; 95% CI: 1.23-3.63; P = 0.007). CONCLUSIONS: The TTR V142I variant in middle-aged Black adults is not associated with adverse cardiac remodeling but was associated with a significantly higher burden of chronic myocardial injury, and greater risk of incident HF and overall HF hospitalizations.

Cardiovascular risk score associations with frailty in men and women with or at risk for HIV.

OBJECTIVE: To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV. DESIGN: We considered 10-year coronary heart disease and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). METHODS: FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/µl, antiretroviral therapy, and HIV viral load. RESULTS: There were 5554 participants (1265 HIV seronegative/1396 MWH; 768 seronegative/1924 WWH) included. Among men, high-risk FRS was associated with increased risk of incident frailty among seronegative [adjusted hazard ratio (aHR)) = 2.12, 95% confidence interval (CI):1.22-3.69] and MWH (aHR = 2.19, 95% CI: 1.33-3.61). Similar associations were seen with high-risk PCE and incident frailty among SN (aHR = 1.88, 95% CI: 1.48-2.39) and MWH (aHR = 1.59, 95% CI: 1.26-2.00). Among women, high-risk PCE was associated with frailty in SN [adjusted odds ratio (aOR) = 1.43, 95% CI: 1.02-2.00] and WWH (aOR = 1.36, 95% CI: 1.08-1.71); however, high-risk FRS was not (seronegative: aOR = 1.03, 95% CI: 0.30-3.49; WWH: aOR = 0.86, 95% CI: 0.23-3.20). CONCLUSION: Higher CVD risk was associated with increased frailty regardless of HIV serostatus among men and women. These findings may inform clinical practices of screening for frailty.

Hypertensive Diseases in Pregnancy and Kidney Function Later in Life: The Genetic Epidemiology Network of Arteriopathy (GENOA) Study.

OBJECTIVE: To evaluate the relationship between hypertensive diseases in pregnancy and kidney function later in life. METHODS: We evaluated measured glomerular filtration rate (mGFR) using iothalamate urinary clearance in 725 women of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. Women were classified by self-report as nulliparous (n=62), a history of normotensive pregnancies (n=544), a history of hypertensive pregnancies (n=102), or a history of pre-eclampsia (n=17). We compared adjusted associations among these four groups with mGFR using generalized estimating equations to account for familial clustering. Chronic kidney disease (CKD) was defined as mGFR of less than 60 mL/min per 1.73 m2 or urinary albumin-creatinine ratio (UACR) greater than or equal to 30 mg/g. RESULTS: Among women with kidney function measurements (mean age, 59±9 years, 52.9% African American), those with a history of hypertensive pregnancy had lower mGFR (-4.66 ml/min per 1.73 m2; 95% CI, -9.12 to -0.20) compared with women with a history of normotensive pregnancies. Compared with women with a history of normotensive pregnancies, women with a history of hypertensive pregnancy also had higher odds of mGFR less than 60 ml/min per 1.73 m2 (odds ratio, 2.09; 95% CI, 1.21 to 3.60). Additionally, women with a history of hypertensive pregnancy had greater odds for chronic kidney disease (odds ratio, 4.89; 95% CI, 1.55 to 15.44), after adjusting for age, race, education, smoking history, hypertension, body mass index, and diabetes. CONCLUSION: A history of hypertension in pregnancy is an important prognostic risk factor for kidney disease. To our knowledge, this is the first and largest investigation showing the association between hypertensive diseases in pregnancy and subsequent kidney disease using mGFR in a large biracial cohort.

Kidney Function and Aortic Stiffness, Pulsatility, and Endothelial Function in African Americans: The Jackson Heart Study.

RATIONALE & OBJECTIVE: The relation of vascular stiffness, endothelial function, and kidney function is incompletely elucidated in African Americans. Our hypothesis was that increased vascular stiffness and endothelial dysfunction are associated with low estimated glomerular filtration rate (eGFR) and albuminuria in African Americans. STUDY DESIGN: Cross-sectional cohort analysis of data from the Jackson Heart Study. SETTINGS & PATIENTS: 2,244 Jackson Heart Study participants (2012-2017 after Exam 3) who had undergone noninvasive hemodynamic assessment using arterial tonometry. PREDICTORS: Baseline carotid-femoral pulse wave velocity, pulsatile hemodynamics forward wave amplitude, and hyperemic brachial artery flow were measured. Reduced eGFR was defined as eGFR between 15 and 60 mL/min/1.73 m2. OUTCOMES: Prevalent albuminuria, urinary albumin-creatinine ratio. ANALYTICAL APPROACH: 2-sample t test for continuous variables and χ2 test for categorical variables in addition to logistic and linear regression models to assess the risk for chronic kidney disease with each proposed hemodynamic variable. RESULTS: Among 2,244 participants, mean age was 66 ± 11 years and 64% were women. Reduced eGFR was present in 233 (10.4%), and elevated urinary albumin-creatinine ratio, in 232 (10.4%). In multivariable-adjusted analyses, higher carotid-femoral pulse wave velocity was associated with the presence of reduced eGFR (OR, 1.37 [95% CI, 1.08-1.75] per SD; P = 0.01) and with prevalent albuminuria (OR, 1.66 [95% CI, 1.32-2.11]; P < 0.001). Higher forward wave amplitude was significantly associated with prevalent albuminuria (OR, 1.37 [95% CI, 1.14-1.65]; P = 0.001). LIMITATIONS: Cross-sectional analyses cannot inform causality. CONCLUSIONS: Higher arterial stiffness and pulsatility are associated with higher odds of reduced eGFR in African Americans. Future studies should focus on whether improving arterial stiffness contributes to kidney protection in African Americans.

Epidemiology of Heart Failure Stages in Middle-Aged Black People in the Community: Prevalence and Prognosis in the Atherosclerosis Risk in Communities Study.

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993-1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0: no risk factors; (2) Stage A: presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B: presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D: prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all-cause mortality on follow-up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow-up (median 19.0 years), 309 participants developed overt HF, 390 incurred new-onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person-years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5- to 2-fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community-based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.

Cigarette Smoking, Incident Coronary Heart Disease, and Coronary Artery Calcification in Black Adults: The Jackson Heart Study.

Background Although Black adults are more likely to die from coronary heart disease (CHD) compared with White adults, few studies have examined the relationship between cigarette smoking and CHD risk among Black adults. We evaluated the relationship between cigarette smoking, incident CHD, and coronary artery calcification in the JHS (Jackson Heart Study). Methods and Results We classified JHS participants without a history of CHD (n=4432) by self-reported baseline smoking status into current, former (smoked at least 400 cigarettes/life) or never smokers at baseline (2000-2004). We further classified current smokers by smoking intensity (number of cigarettes smoked per day [1-19 or ≥20]) and followed for incident CHD (through 2016). Hazard ratios (HR) for incident CHD for each smoking group compared with never smokers were estimated with adjusted Cox proportional hazard regression models. At baseline, there were 548 (12.4%) current, 782 (17.6%) former, and 3102 (70%) never smokers. During follow-up (median, 13.8 years), 254 participants developed CHD. After risk factor adjustment, CHD risk was significantly higher in current smokers compared with never smokers (HR, 2.11; 95% CI, 1.39-3.18); the difference between former smokers and never smokers (HR, 1.37; 95% CI, 1.0-1.90) did not achieve statistical significance. Among current smokers, we did not observe a dose-response effect for CHD risk. Additionally, in multivariable logistic regression models with a subset of our analytic cohort, current smokers had greater odds of coronary artery calcification score >0 compared with never smokers (odds ratio, 2.63; 95% CI, 1.88-3.68). Conclusions In a large prospective cohort of Black adults, current smoking was associated with a >2-fold increased risk of CHD over a median follow-up of greater than a decade.

Clinical Associations of Vascular Stiffness, Microvascular Dysfunction, and Prevalent Cardiovascular Disease in a Black Cohort: The Jackson Heart Study.

Background Measures of vascular dysfunction are related to adverse cardiovascular disease (CVD) outcomes in non-Hispanic, White populations; however, data from Black individuals are limited. We aimed to investigate the associations between novel hemodynamic measures and prevalent CVD in a sample of Black individuals. Methods and Results Among older Black participants of the Jackson Heart Study, we assessed noninvasive vascular hemodynamic measures using arterial tonometry and Doppler ultrasound. We assessed 5 measures of aortic stiffness and wave reflection (carotid-femoral pulse wave velocity, pulse wave velocity ratio, forward pressure wave amplitude, central pulse pressure, and augmentation index), and 2 measures of microvascular function (baseline and hyperemic brachial flow velocity). Using multivariable logistic regression models, we examined the relations between vascular hemodynamic measures and prevalent CVD. In models adjusted for traditional CVD risk factors, higher carotid-femoral pulse wave velocity (odds ratio [OR],1.25; 95% CI, 1.01-1.55; P=0.04), lower augmentation index (OR, 0.84; 95% CI, 0.70-0.99; P=0.05), and lower hyperemic brachial flow velocity (OR, 0.77; 95% CI, 0.65-0.90; P=0.001) were associated with higher odds of CVD. After further adjustment for hypertension treatment, lower augmentation index (OR, 0.84; 95% CI, 0.70-0.99; P=0.04) and hyperemic brachial flow velocity (OR, 0.79; 95% CI, 0.67-0.94; P=0.006), but not carotid-femoral pulse wave velocity (OR, 1.23; 95% CI, 0.99-1.051; P=0.06), were associated with higher odds of CVD. Conclusions In a sample of older Black individuals, more severe microvascular damage and aortic stiffness were associated with prevalent CVD. Further research on hemodynamic mechanisms that contribute to cardiovascular risk among older Black individuals is merited.

Relation of Low Normal Left Ventricular Ejection Fraction to Heart Failure Hospitalization in Blacks (From the Jackson Heart Study).

There is no clear consensus on a lower cutoff value for normal left ventricular ejection fraction (EF) and the prognostic implications of low normal EF (LNEF) are poorly understood, particularly in Blacks. Therefore, we investigated the association of LNEF and incident heart failure (HF) in a community-based cohort of Blacks. We studied 3,669 participants (mean age 54 years, 63% women) of the Jackson Heart Study without prevalent HF or coronary heart disease (CHD). Participants were divided into three groups: (1) Reduced EF (<50%), (2) LNEF (≥50%, <55%), and (3) Normal EF (≥55%). There were 197 cases of incident HF hospitalizations over a median follow-up of 10 years (interquartile range 9.4 to 10). After adjustment for conventional risk factors and incident CHD, the LNEF group had a higher rate of incident HF hospitalization than the Normal EF group (HR 1.58, 95% CI 1.04 to 2.38, p<0.05). Furthermore, this relation remained statistically significant after additionally adjusting for LV mass index but was not significant after adjusting for LV diastolic dysfunction grade. In participants with LNEF with incident HF, 63% developed HF with reduced EF and 37% developed HF with preserved EF. In conclusion, LNEF is associated with higher risk of incident HF hospitalization in comparison with normal EF in a community-based cohort of Blacks. In those with LNEF who went on to develop HF, most cases were HF with reduced EF. These findings suggest that strategies are needed for risk stratification and management to improve outcomes in patients with LNEF.