MagicalRsq-X: A cross-cohort transferable genotype imputation quality metric.

Since genotype imputation was introduced, researchers have been relying on the estimated imputation quality from imputation software to perform post-imputation quality control (QC). However, this quality estimate (denoted as Rsq) performs less well for lower-frequency variants. We recently published MagicalRsq, a machine-learning-based imputation quality calibration, which leverages additional typed markers from the same cohort and outperforms Rsq as a QC metric. In this work, we extended the original MagicalRsq to allow cross-cohort model training and named the new model MagicalRsq-X. We removed the cohort-specific estimated minor allele frequency and included linkage disequilibrium scores and recombination rates as additional features. Leveraging whole-genome sequencing data from TOPMed, specifically participants in the BioMe, JHS, WHI, and MESA studies, we performed comprehensive cross-cohort evaluations for predominantly European and African ancestral individuals based on their inferred global ancestry with the 1000 Genomes and Human Genome Diversity Project data as reference. Our results suggest MagicalRsq-X outperforms Rsq in almost every setting, with 7.3%-14.4% improvement in squared Pearson correlation with true R2, corresponding to 85-218 K variant gains. We further developed a metric to quantify the genetic distances of a target cohort relative to a reference cohort and showed that such metric largely explained the performance of MagicalRsq-X models. Finally, we found MagicalRsq-X saved up to 53 known genome-wide significant variants in one of the largest blood cell trait GWASs that would be missed using the original Rsq for QC. In conclusion, MagicalRsq-X shows superiority for post-imputation QC and benefits genetic studies by distinguishing well and poorly imputed lower-frequency variants.

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

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

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.

Digital Connectedness in the Jackson Heart Study: Cross-sectional Study.

BACKGROUND: Although new approaches for data collection, such as mobile technology and teleresearch, have demonstrated new opportunities for the conduct of more timely and less costly surveys in community-based studies, literature on the feasibility of conducing cardiovascular disease research using mobile health (mHealth) platforms among middle-aged and older African Americans has been limited. OBJECTIVE: The purpose of this study was to contribute to the knowledge regarding the penetrance of internet and mobile technologies, such as cellphones or smartphones in existing large cohort studies of cardiovascular disease. METHODS: A digital connectedness survey was conducted in the Jackson Heart Study (JHS), a Mississippi-based African American cohort study, as part of the annual follow-up calls with participants from July 2017 to February 2019. RESULTS: Of the 4024 participants contacted, 2564 (63.7%) completed the survey. Among survey respondents, 2262 (88.2%) reported use of internet or cellphone, and 1593 (62.1%) had a smartphone. Compared to nonusers (n=302), internet or cellphone users (n=2262) were younger (mean age 80.1, SD 8.0 vs 68.2, SD 11.3 years), more likely to be affluent (n=778, 40.1% vs n=39, 15.4%), and had greater than high school education (n=1636, 72.5% vs n=85, 28.1%). Internet or cellphone users were less likely to have cardiovascular disease history compared to nonusers (136/2262, 6.6% vs 41/302, 15.8%). The prevalence of current smoking and average BMI were similar between internet or cellphone users and nonusers. Among internet or cellphone users, 1316 (58.3%) reported use of email, 504 (22.3%) reported use of apps to track or manage health, and 1269 (56.1%) expressed interest in using JHS-developed apps. CONCLUSIONS: Our findings suggest that it is feasible to use mHealth technologies to collect survey data among African Americans already enrolled in a longitudinal study. Our findings also highlight the need for more efforts to reduce the age and education divide in access and use of internet and smartphones for tracking health and research in African American communities.

TOP-LD: A tool to explore linkage disequilibrium with TOPMed whole-genome sequence data.

Current publicly available tools that allow rapid exploration of linkage disequilibrium (LD) between markers (e.g., HaploReg and LDlink) are based on whole-genome sequence (WGS) data from 2,504 individuals in the 1000 Genomes Project. Here, we present TOP-LD, an online tool to explore LD inferred with high-coverage (∼30×) WGS data from 15,578 individuals in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. TOP-LD provides a significant upgrade compared to current LD tools, as the TOPMed WGS data provide a more comprehensive representation of genetic variation than the 1000 Genomes data, particularly for rare variants and in the specific populations that we analyzed. For example, TOP-LD encompasses LD information for 150.3, 62.2, and 36.7 million variants for European, African, and East Asian ancestral samples, respectively, offering 2.6- to 9.1-fold increase in variant coverage compared to HaploReg 4.0 or LDlink. In addition, TOP-LD includes tens of thousands of structural variants (SVs). We demonstrate the value of TOP-LD in fine-mapping at the GGT1 locus associated with gamma glutamyltransferase in the African ancestry participants in UK Biobank. Beyond fine-mapping, TOP-LD can facilitate a wide range of applications that are based on summary statistics and estimates of LD. TOP-LD is freely available online.

Monogenic and Polygenic Contributions to QTc Prolongation in the Population.

BACKGROUND: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequence data enables examination of the joint contribution of rare and common variations to the QT interval in the population. METHODS: We performed a genome-wide association study of the QTc in 84 630 UK Biobank participants and created a polygenic risk score (PRS). Among 26 976 participants with whole-genome sequencing and ECG data in the TOPMed (Trans-Omics for Precision Medicine) program, we identified 160 carriers of putative pathogenic rare variants in 10 genes known to be associated with the QT interval. We examined QTc associations with the PRS and with rare variants in TOPMed. RESULTS: Fifty-four independent loci were identified by genome-wide association study in the UK Biobank. Twenty-one loci were novel, of which 12 were replicated in TOPMed. The PRS composed of 1 110 494 common variants was significantly associated with the QTc in TOPMed (ΔQTc/decile of PRS=1.4 ms [95% CI, 1.3 to 1.5]; P=1.1×10-196). Carriers of putative pathogenic rare variants had longer QTc than noncarriers (ΔQTc=10.9 ms [95% CI, 7.4 to 14.4]). Of individuals with QTc>480 ms, 23.7% carried either a monogenic rare variant or had a PRS in the top decile (3.4% monogenic, 21% top decile of PRS). CONCLUSIONS: QTc duration in the population is influenced by both rare variants in genes underlying cardiac repolarization and polygenic risk, with a sizeable contribution from polygenic risk. Comprehensive assessment of the genetic determinants of QTc prolongation includes incorporation of both polygenic and monogenic risk.

Whole genome sequence analysis of platelet traits in the NHLBI Trans-Omics for Precision Medicine (TOPMed) initiative.

Platelets play a key role in thrombosis and hemostasis. Platelet count (PLT) and mean platelet volume (MPV) are highly heritable quantitative traits, with hundreds of genetic signals previously identified, mostly in European ancestry populations. We here utilize whole genome sequencing (WGS) from NHLBI's Trans-Omics for Precision Medicine initiative (TOPMed) in a large multi-ethnic sample to further explore common and rare variation contributing to PLT (n = 61 200) and MPV (n = 23 485). We identified and replicated secondary signals at MPL (rs532784633) and PECAM1 (rs73345162), both more common in African ancestry populations. We also observed rare variation in Mendelian platelet-related disorder genes influencing variation in platelet traits in TOPMed cohorts (not enriched for blood disorders). For example, association of GP9 with lower PLT and higher MPV was partly driven by a pathogenic Bernard-Soulier syndrome variant (rs5030764, p.Asn61Ser), and the signals at TUBB1 and CD36 were partly driven by loss of function variants not annotated as pathogenic in ClinVar (rs199948010 and rs571975065). However, residual signal remained for these gene-based signals after adjusting for lead variants, suggesting that additional variants in Mendelian genes with impacts in general population cohorts remain to be identified. Gene-based signals were also identified at several genome-wide association study identified loci for genes not annotated for Mendelian platelet disorders (PTPRH, TET2, CHEK2), with somatic variation driving the result at TET2. These results highlight the value of WGS in populations of diverse genetic ancestry to identify novel regulatory and coding signals, even for well-studied traits like platelet traits.

Regional Adiposity and Risk of Heart Failure and Mortality: The Jackson Heart Study.

Background Visceral adipose tissue (VAT) is associated with incident heart failure (HF) and HF with preserved ejection fraction, yet it is unknown how pericardial and abdominal adiposity affect HF and mortality risks in Black individuals. We examined the associations of pericardial adipose tissue (PAT), VAT, and subcutaneous adipose tissue (SAT) with incident HF hospitalization and all-cause mortality in a large community cohort of Black participants. Methods and Results Among the 2882 Jackson Heart Study Exam 2 participants without prevalent HF who underwent body computed tomography, we used Cox proportional hazards models to examine associations between computed tomography-derived regional adiposity and incident HF hospitalization and all-cause mortality. Fully adjusted models included demographics and cardiovascular disease risk factors. Median follow-up was 10.6 years among participants with available VAT (n=2844), SAT (n=2843), and PAT (n=1386). Fully adjusted hazard ratios (95% CIs) of distinct computed tomography-derived adiposity measures (PAT per 10 cm3, VAT or SAT per 100 cm3) were as follows: for incident HF, PAT 1.08 (95% CI, 1.02-1.14) and VAT 1.04 (95% CI, 1.01-1.08); for HF with preserved ejection fraction, PAT 1.13 (95% CI, 1.04-1.21) and VAT 1.07 (95% CI, 1.01-1.13); for mortality, PAT 1.07 (95% CI, 1.03-1.12) and VAT 1.01 (95% CI, 0.98-1.04). SAT was not associated with either outcome. Conclusions High PAT and VAT, but not SAT, were associated with incident HF and HF with preserved ejection fraction, and only PAT was associated with mortality in the fully adjusted models in a longitudinal community cohort of Black participants. Future studies may help understand whether changes in regional adiposity improves HF, particularly HF with preserved ejection fraction, risk predictions. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005485.

Application of a Lifestyle-Based Score to Predict Cardiovascular Risk in African Americans: The Jackson Heart Study.

Cardiovascular disease (CVD) primordial prevention tools applicable to diverse populations are scarce. Our aim was to assess the performance of a lifestyle-based tool to estimate CVD risk in an African American population. The Jackson Heart Study is a prospective cohort including 5306 African American participants in Jackson, Mississippi (2000-2004), with a mean follow up of 12 years. The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on nine components: body mass index (BMI), physical activity, smoking, and a 5-component diet score. Gender-specific beta coefficients from its derivation cohorts were used to assess the performance of the Healthy Heart Score. Model discrimination was assessed using Harrell's C-Index for survival data and time dependent Area Under the Curve. Model calibration was evaluated through calibration plots. A total of 189 CVD events occurred. The Healthy Heart Score showed high-moderate discrimination for CVD events (C-statistic 0.75 [95% CI, 0.71-0.78]) but with little improvement over the age-only model. Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline and showed good calibration. In African Americans, the Healthy Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.

Association Between Cardiometabolic Factors and Dizziness in African Americans: The Jackson Heart Study.

BACKGROUND: Balance dysfunction is a complex, disabling health condition that can present with multiple phenotypes and etiologies. Data regarding prevalence, characterization of dizziness, or associated factors is limited, especially in an African American population. PURPOSE: The aim of the study is to characterize balance dysfunction presentation and prevalence in an African American cohort, and balance dysfunction relationship to cardiometabolic factors. RESEARCH DESIGN: The study design is descriptive, cross sectional analysis. STUDY SAMPLE: The study sample consist of N = 1,314, participants in the Jackson Heart Study (JHS). DATA COLLECTION AND ANALYSIS: JHS participants were presented an initial Hearing health screening questionnaire (N = 1,314). Of these, 317 participants reported dizziness and completed a follow-up Dizziness History Questionnaire. Descriptive analysis was used to compare differences in the cohorts' social-demographic characteristics and cardiometabolic variables to the 997 participants who did not report dizziness on the initial screening questionnaire. Based on questionnaire responses, participants were grouped into dizziness profiles (orthostatic, migraine, and vestibular) to further examine differences in cardiometabolic markers as related to different profiles of dizziness. Logistical regression models were adjusted for age, sex, education, reported noise exposure, and hearing sensitivity. RESULTS: Participants that reported any dizziness were slightly older and predominantly women. Other significant complaints in the dizzy versus nondizzy cohort included hearing loss, tinnitus, and a history of noise exposure (p < 0.001). Participants that reported any dizziness had significantly higher prevalence of hypertension, blood pressure medication use, and higher body mass index (BMI). Individuals with symptoms alluding to an orthostatic or migraine etiology had significant differences in prevalence of hypertension, blood pressure medication use, and BMI (p < 0.001). Alternatively, cardiometabolic variables were not significantly related to the report of dizziness symptoms consistent with vestibular profiles. CONCLUSION: Dizziness among African Americans is comparable to the general population with regards to age and sex distribution, accordingly to previously published estimates. Participants with dizziness symptoms appear to have significant differences in BMI and blood pressure regulation, especially with associated orthostatic or migraine type profiles; this relationship does not appear to be conserved in participants who present with vestibular etiology symptoms.

Association Between Ambulatory Blood Pressure and Coronary Artery Calcification: The JHS.

[Figure: see text].

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

Obesity and overall mortality: findings from the Jackson Heart Study.

BACKGROUND: Overall mortality has been reported to be lower among individuals classified as overweight/obese when compared with their normal weight counterparts ("obesity paradox") when obesity classification is based on the body mass index (BMI). One possible reason for this apparent paradox is that BMI is not a reliable measure of obesity-related risk as it does not differentiate fat mass from lean muscle mass or fat mass phenotypes. Waist circumference (WC), as a measure of central adiposity, may be a better indicator of obesity-related risk. We examined the association of overall mortality with BMI and with WC measures, including WC, waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR). METHODS: Data from 3976 African American participants (551 deaths) in the Jackson Heart Study (JHS) were analyzed. Cox regression models were used to perform survival analysis. Obesity measures were analyzed as dichotomous (obese/non-obese) and continuous variables. Baseline covariates included age, sex and smoking status. RESULTS: Comparing obese to non-obese participants, adjusted hazard ratios (95% CI) for overall mortality were 1.14 (0.96, 1.35), 1.30 (1.07, 1.59), 1.02 (0.73, 1.41) and 1.45 (1.18, 1.79) when using BMI, WC, WHtR and WHR, respectively. For BMI, WC and WHtR, a J-shaped relationship was observed with overall mortality. For WHR, a monotonic increasing relationship was observed with overall mortality. CONCLUSIONS: In the JHS, we found that obesity as defined by WC and WHR was associated with an increased risk of overall and CVD mortality, while obesity defined by BMI was associated only with an increased risk of CVD mortality. WHR was the only obesity measure that showed a monotonic increasing relationship with overall and CVD mortality.

Recovery From Mobility Limitation in Middle-Aged African Americans: The Jackson Heart Study.

BACKGROUND: Despite evidence that African Americans shoulder a high burden of mobility limitation, little is known about factors associated with recovery. METHOD: Participants from the Jackson Heart Study underwent 3 in-person exams from 2000 to 2013. Mobility limitations were assessed over this period by self-reported limitations in walking half a mile or climbing stairs during annual phone calls. The outcome of interest, recovery from mobility limitation, was defined as no mobility limitation the year following an incident event. Candidate predictor variables were assessed in logistic regression models, including sociodemographic, psychosocial, and health measures. Inverse probability weights were used to address missing data in the outcome. RESULTS: Among 4526 participants (mean [SD] age = 54.5 (12.8) years) without a mobility limitation at baseline, 1445 (32%) had an incident mobility limitation over 12 years of follow-up, and 709 (49%) reported recovery from mobility limitation by 1 year later. Low income and daily discrimination were associated with a lower likelihood of recovery even after adjustment for covariates. In adjusted models, greater comorbidity was associated with a lower likelihood of recovering (p-value for trend = .05). History of heart failure and cancer were associated with a lower likelihood of recovering from mobility limitation (OR: 0.52, 95% CI: 0.29, 0.94 and OR: 0.74, 95% CI: 0.55, 1.00). Adiposity, smoking status, and physical activity were not associated with recovery from mobility limitation. CONCLUSION: Half of incident mobility limitations in this population of middle-aged African Americans were transient. Adverse sociodemographic factors and comorbidities were associated with lower likelihood of recovery.

Experiences of Discrimination Are Associated With Worse Metabolic Syndrome Severity Among African Americans in the Jackson Heart Study.

BACKGROUND: Metabolic syndrome (MetS) is a risk factor for the development of cardiovascular disease and type 2 diabetes. Although the development of MetS is attributed to known lifestyle factors, perceived discrimination may also contribute to MetS development and severity. PURPOSE: We examined the associations of perceived discrimination with MetS severity among African American adults at baseline and 8-year follow-up. METHODS: Three thousand eight hundred and seventy participants (mean age 53.8 ± 13.0; 63.1% female) without diabetes and no missing MetS severity scores at baseline were included. Each self-reported measure of discrimination at baseline (everyday, lifetime, and burden of lifetime) was classified into tertiles (low, medium, high). After adjustment for demographics and MetS risk factors, associations of discrimination were examined with a sex- and race/ethnicity-specific MetS severity Z-score. We employed a mixed model approach that allowed for the assessment of an overall association between reported discrimination at baseline and MetS severity, and for the possible change over time. RESULTS: Sex and age differences were observed in experiences with discrimination, such that men reported higher levels of all aspects of discrimination relative to women. Everyday discrimination decreased with age, whereas lifetime discrimination increased with age (p < .05). Independent of lifestyle and demographic factors, everyday and lifetime discrimination were significantly associated with MetS severity (p = .003 and p = .017, respectively) and the associations remained constant over the 8 years (i.e., no interaction with time). CONCLUSIONS: Our results suggest that, in a large community-based sample of African Americans, discrimination is a salient psychosocial risk factor for severity of MetS.

Joint modelling of longitudinal lipids and time to coronary heart disease in the Jackson Heart Study.

BACKGROUND: Multiple longitudinal responses together with time-to-event outcome are common in biomedical studies. There are several instances where the longitudinal responses are correlated with each other and at the same time each longitudinal response is associated with the survival outcome. The main purpose of this study is to present and explore a joint modeling approach for multiple correlated longitudinal responses and a survival outcome. The method will be illustrated using the Jackson Heart Study (JHS), which is one of the largest cardiovascular studies among African Americans. METHODS: Four longitudinal responses, i.e., total cholesterol (TC), high density lipoprotein (HDL) cholesterol, triglyceride (TG) and inflammation measured by high-sensitivity C-reactive protein (hsCRP); and time-to-coronary heart disease (CHD) were considered from the JHS. The repeated lipid and hsCRP measurements from a given subject overtime are likely correlated with each other and could influence the subject's risk for CHD. A joint modeling framework is considered. To deal with the high dimensionality due to the multiple longitudinal profiles, we use a pairwise bivariate model fitting approach that was developed in the context of multivariate Gaussian random effects models. The method is further explored through simulations. RESULTS: The proposed model performed well in terms of bias and relative efficiency. The JHS data analysis showed that lipid and hsCRP trajectories could exhibit interdependence in their joint evolution and have impact on CHD risk. CONCLUSIONS: We applied a unified and flexible joint modeling approach to analyze multiple correlated longitudinal responses and survival outcome. The method accounts for the correlation among the longitudinal responses as well as the association between each longitudinal response and the survival outcome at once. This helps to explore how the combination of multiple longitudinal trajectories could be related to the survival process.

Underutilization of Treatment for Black Adults With Apparent Treatment-Resistant Hypertension: JHS and the REGARDS Study.

Resistant hypertension, defined as blood pressure levels above goal while taking ≥3 classes of antihypertensive medication or ≥4 classes regardless of blood pressure level, is associated with increased cardiovascular disease risk. The 2018 American Heart Association Scientific Statement on Resistant Hypertension recommends healthy lifestyle habits and thiazide-like diuretics and mineralocorticoid receptor antagonists for adults with resistant hypertension. The term apparent treatment-resistant hypertension (aTRH) is used when pseudoresistance cannot be excluded. We estimated the use of healthy lifestyle factors and recommended antihypertensive medication classes among US Black adults with aTRH. Data were pooled for Black participants in the JHS (Jackson Heart Study) in 2009 to 2013 (n=2496) and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) in 2013 to 2016 (n=3786). Outcomes included lifestyle factors (not smoking, not consuming alcohol, ≥75 minutes of vigorous-intensity or ≥150 minutes of moderate or vigorous physical activity per week, and body mass index <25 kg/m2) and recommended antihypertensive medications (thiazide-like diuretics and mineralocorticoid receptor antagonists). Overall, 28.3% of participants who reported taking antihypertensive medication had aTRH. Among participants with aTRH, 14.5% and 1.2% had ideal levels of 3 and 4 of the lifestyle factors, respectively. Also, 5.9% of participants with aTRH reported taking a thiazide-like diuretic, and 9.8% reported taking a mineralocorticoid receptor antagonist. In conclusion, evidence-based lifestyle factors and recommended pharmacological treatment are underutilized in Black adults with aTRH. Increased use of lifestyle recommendations and antihypertensive medication classes specifically recommended for aTRH may improve blood pressure control and reduce cardiovascular disease-related morbidity and mortality among US Black adults. Graphic Abstract A graphic abstract is available for this article.

Relationship of Overall Cardiovascular Health and Hearing Loss in The Jackson Heart Study Population.

OBJECTIVES: To evaluate the relationships among the overall cardiovascular health scoring tool, Life's Simple 7 (LS7), and hearing in an African-American cardiovascular study cohort. METHODS: Using the Jackson Heart Study's cohort of African Americans, the relationships between the LS7 scoring metric and hearing of 1314 individuals were assessed. Standard audiometric data was collected and hearing loss was defined as a four-frequency average of 500, 1000, 2000, and 4000 Hz greater than 25 dBHL (PTA4). Measures of reported tinnitus and dizziness were also collected. The LS7 scoring tool, which consists of seven individual categories (abstinence from smoking, body mass index, physical activity, healthy diet, total cholesterol <200 mg/dL, normotension, and absence of diabetes mellitus), was used as measure of overall cardiovascular health. Each category of the LS7 was broken down into poor, intermediate, and ideal subgroups as in accordance with the American Heart Association Strategic Planning Task Force and Statistics Committee. Unadjusted and adjusted gamma regression and logistic regression models were constructed for determining relationships between LS7 and hearing loss. RESULTS: Higher total LS7 scores (per 1-unit increase) were associated with lower PTA4 in gamma regression analyses (RR = 0.942, 95% CI, 0.926-0.958, P < .001). This held true even after adjustments for age, sex, education, and history of noise exposure. Using logistic regression analyses to compare LS7 scores to presence of hearing loss, tinnitus, and vertigo; only hearing loss showed a statically significant relationship after adjustments for age, sex, education, and history of noise exposure. CONCLUSIONS: This study shows a significant, graded association between higher life's simple seven scores and lower incidence of hearing loss. LEVEL OF EVIDENCE: 2b. Laryngoscope, 2019.

Population-Attributable Risk for Cardiovascular Disease Associated With Hypertension in Black Adults.

Importance: The prevalence of hypertension and the risk for hypertension-related cardiovascular disease (CVD) are high among black adults. The population-attributable risk (PAR) accounts for both prevalence and excess risk of disease associated with a risk factor. Objective: To examine the PAR for CVD associated with hypertension among black adults. Design, Setting, and Participants: This prospective cohort study used data on 12 497 black participants older than 21 years without CVD at baseline who were enrolled in the Jackson Heart Study (JHS) from September 26, 2000, through March 31, 2004, and cardiovascular events were adjudicated through December 31, 2015. The Reasons for Geographic and Racial Differences in Stroke (REGARDS) study participants were enrolled from July 1, 2003, through September 12, 2007, and cardiovascular events were adjudicated through March 31, 2016. Data analysis was performed from March 26, 2018, through July 10, 2019. Exposures: Normal blood pressure and hypertension were defined using the 2017 American College of Cardiology/American Heart Association blood pressure guideline thresholds. Main Outcomes and Measures: The PAR for CVD associated with hypertension, calculated using multivariable-adjusted hazard ratios (HRs) for CVD, coronary heart disease, heart failure, and stroke associated with hypertension vs normal blood pressure. Prevalence of hypertension among non-Hispanic black US adults 21 years and older without CVD was calculated using data from the National Health and Nutrition Examination Survey, 2011-2014. Results: Of 12 497 participants, 1935 had normal blood pressure (638 [33.0%] male; mean [SD] age, 53.5 [12.4] years), 929 had elevated blood pressure (382 [41.1%] male; mean [SD] age, 58.6 [11.8] years), and 9633 had hypertension (3492 [36.3%] male; mean [SD] age, 62.0 [10.3] years). For a maximum 14.3 years of follow-up, 1235 JHS and REGARDS study participants (9.9%) experienced a CVD event. The multivariable-adjusted HR associated with hypertension was 1.91 (95% CI, 1.48-2.46) for CVD, 2.41 (95% CI, 1.59-3.66) for coronary heart disease, 1.52 (95% CI, 1.01-2.30) for heart failure, and 2.20 (95% CI, 1.44-3.36) for stroke. The prevalence of hypertension was 53.2% among non-Hispanic black individuals. The PAR associated with hypertension was 32.5% (95% CI, 20.5%-43.6%) for CVD, 42.7% (95% CI, 24.0%-58.4%) for coronary heart disease, 21.6% (95% CI, 0.6%-40.8%) for heart failure, and 38.9% (95% CI, 19.4%-55.6%) for stroke. The PAR was higher among those younger than 60 years (54.6% [95% CI, 37.2%-68.7%]) compared with those 60 years or older (32.0% [95% CI, 11.9%-48.1%]). No differences were present in subgroup analyses. Conclusions and Relevance: These findings suggest that a substantial proportion of CVD cases among black individuals are associated with hypertension. Interventions to maintain normal blood pressure throughout the life course may reduce the incidence of CVD in this population.

Optimism and cardiovascular health among African Americans in the Jackson Heart Study.

Little research has examined associations of positive psychosocial factors with the American Heart Association Life's Simple 7™ (LS7) among African Americans. This study examined the associations between positive optimistic orientation and LS7 among African Americans. Using exam 1 data (2000-2004) from the Jackson Heart Study, we examined cross-sectional associations of optimism (in tertiles) with LS7 components [smoking, physical activity, diet, body mass index, blood pressure, cholesterol, glucose] and a composite LS7 score (classified as poor, intermediate, ideal) among 4734 African Americans free of cardiovascular disease. Multivariable prevalence regression was used to estimate prevalence ratios (PR, 95% confidence interval-CI) of intermediate and ideal (vs. poor) individual LS7 components and composite LS7 score by optimism levels, adjusting for demographics, socioeconomic status, and depressive symptoms. For LS7 components with low prevalence, we estimated odds ratios. A greater percentage of participants with high vs. low optimism were younger, female, high SES, and not depressed. After full covariate adjustment, the prevalence ratio of ideal (vs. poor) composite LS7 score was 1.24 for participants who reported high (vs. low) optimism (95% CI 1.09-1.42) at exam 1. Higher levels of optimism were also associated with greater prevalence of ideal (vs. poor) physical activity and smoking. Promoting positive optimistic orientation may be an important step toward increasing the likelihood of achieving optimal cardiovascular health among African Americans.