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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.

Background: The effect of physical activity (PA) on incidence of atrial fibrillation (AF) is unclear in African Americans (AA). This study aimed to determine if higher levels of PA are associated with decreased incidence of AF in the Jackson Heart Study (JHS). Methods: Participants of the JHS with PA assessment and without previous AF at baseline were included in the study. PA was categorized based on the American Heart Association physical activity levels. Incident AF was defined as having 12 lead electrocardiogram evidence at a subsequent follow up, or a documented diagnosis code at the time of hospital discharge from 2000 to 2016. Cox proportional hazards models were used to evaluate for the association between baseline PA and incidence of AF. Given significant correlation between PA and baseline cardiovascular disease (CVD), stratified analysis was performed based on CVD status. Results: Of the 4,477 participants followed for a median of 12.5 years, 398 developed AF (7.13 cases per 1,000 person-years). Ideal and intermediate PA were associated with a reduced risk of incident AF compared with poor PA (unadjusted HRs with 95% CIs 0.47 [0.34 - 0.64] and 0.72 [0.58 - 0.90], respectively) (Table). After adjustment for traditional cardiovascular risk factors, the associations attenuated and became no longer significant (0.73 [0.53 - 1.00] and 1.00 [0.80 - 1.25], respectively). In stratified analysis based on baseline CVD status, in participants without baseline CVD, ideal PA was significantly associated with a reduced risk of AF while intermediate PA was not (0.68 [0.47 - 0.98] and 1.00 [0.78-1.29], respectively). In participants with baseline CVD, ideal PA or intermediate PA was not associated with incident AF. Conclusion: Ideal PA was associated with a reduced risk of AF in participants without baseline CVD in this AA community cohort. Our findings show intertwined relationship among PA, CVD, and incident AF. Physical activity could be a possible therapeutic target to reduce AF incidence in the AA general population without CVD.

High blood pressure (BP) based on measurements obtained in the office setting has been associated with the presence and level of coronary artery calcification (CAC)—a measure of subclinical atherosclerosis. We studied the association between out-of-office BP and CAC among 557 participants who underwent 24-hour ambulatory BP monitoring at visit 1 in 2000–2004 and a computed tomography scan at visit 2 in 2005–2008 as part of the JHS (Jackson Heart Study)—a community-based cohort of African American adults. Mean awake, asleep, and 24-hour BP were calculated for each participant. Among participants included in this analysis, 279 (50%) had any CAC defined by an Agatston score >0. After multivariable adjustment including office systolic BP (SBP), the prevalence ratios for any CAC comparing the highest versus the lowest quartiles of SBP on ambulatory BP monitoring were 1.08 (95% CI, 0.84–1.39) for awake SBP, 1.32 (95% CI, 1.01–1.74) for asleep SBP, and 1.19 (95% CI, 0.91–1.55) for 24-hour SBP. After multivariable adjustment including office diastolic BP, the prevalence ratios for any CAC comparing the highest versus the lowest quartiles of awake, asleep, and 24-hour diastolic BP were 1.27 (95% CI, 1.02–1.59), 1.29 (95% CI, 1.02–1.64), and 1.25 (95% CI, 0.99–1.59), respectively. The current results suggest that higher asleep SBP and higher awake and asleep diastolic BP may be risk factors for subclinical atherosclerosis and underscore the potential role of ambulatory BP monitoring in identifying individuals at high risk for coronary artery disease.

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 2 ) 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.

BACKGROUND Although new approaches for data collection such as mobile technology and tele-research have demonstrated new opportunities for the conduct of more timely and less costly surveys in community-based studies, literature on the feasibility of conducing mHealth research among African Americans has been limited. OBJECTIVE - 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/cellphone and 1593 (62.1%) had a smartphone. Compared to non-users, internet/cellphone users were younger (68.2 vs. 80.1 years), more likely to be affluent (40.1% vs. 15.4%), and had greater than high school education (72.5% vs. 28.1%). Internet/cellphone users were less likely to have cardiovascular disease history than non-users (6.6% vs. 15.8%). The prevalence of current smoking and average body mass index were similar between internet/cellphone users and non-users. Among internet/cellphone users, 1316 (58.3%) reported use of email, 504 (22.3%) reported use of apps to track/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.

Background– Based on body mass index (BMI), the prevalence of obesity has been shown to vary by age and sex. However, age- or sex-related variations in obesity defined by anthropometric measures of central adiposity, which may be better proxies for obesity-related risk, is unclear.Methods– Using data from 4063 African American (AA) participants in the Jackson Heart Study, linear and Poisson regression model analyses were conducted to estimate mean difference of standardized anthropometric measures and prevalence ratios of obesity based on body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) by age cohort and sex.Results– We found sex- and age-variations in the prevalence of obesity for all measures; however, these patterns varied. In cross-sectional analyses at Visit 2, older cohorts showed a lower prevalence of obesity based on BMI but a higher prevalence of obesity based on WHtR and WHR. In longitudinal analyses, for BMI, and WC, and WHtR, the mean and the prevalence of obesity from Visit 2 to Visit 3 increased only among younger cohorts; however, for WHR, the mean and the prevalence of obesity increased consistently from Visit 2 to 3 across all age cohorts for both sexes. Conclusions–WHR appeared to be a more consistent anthropometric measure for monitoring the prevalence of obesity particularly among elderly AAs. Instead of BMI, WHR would be used to monitor the prevalence of obesity among elderly AAs in clinic.

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.

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

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.

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 cm 3 , VAT or SAT per 100 cm 3 ) 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.

Introduction: Cardiovascular disease (CVD) primordial prevention tools applicable to diverse populations are scarce. Hypothesis: We assessed the hypothesis that the Healthy Heart Score, a lifestyle-based tool to estimate CVD risk, will perform well in estimating CVD risk in an African American population. Methods: The Jackson Heart Study (JHS) is a prospective cohort, community-based study in Jackson, Mississippi that recruited participants between September 2000 and March 2004 (baseline), with a mean follow up of 12 years. A total of 5306 African American were recruited, 3041 individuals free of CVD at baseline were included for the current analysis. CVD incidence was defined as the first occurrence of fatal/non-fatal myocardial infarction (MI), stroke or fatal coronary heart disease (CHD). The Healthy Heart Score is a lifestyle-based CVD risk prediction model based on 9 components: body mass index (BMI), physical activity, cereal fiber, fruit and vegetables, red and processed meat, nuts, sugar and sweetened beverages and alcohol intake. 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 (AUC). Model calibration was evaluated through calibration plots. Results: A total of 189 CVD events occurred (111 in women and 78 in men, average age at baseline 53.1 (12.7) years). 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. The time dependent AUC analysis showed similar results for CVD events and improved performance in the first year with the complete model (age only: AUC 0.76 (95% CI, 0.65-0.88) vs. Healthy Heart Score 0.78 (95% CI 0.68-0.89)). Both the age-only and Healthy Heart Score models had better performance in participants without diabetes at baseline. The Healthy Heart Score model showed good calibration. Conclusions and Relevance . In African Americans with a high prevalence of clinical CVD risk factors, the Hearty Heart Score does not improve prediction of mid-life CVD events beyond what is obtained by age alone.

PURPOSE: Evidence suggests that snoring is associated with increased risk for cardiovascular disease (CVD) events such as myocardial infarction and stroke. Limited data exists pertaining to this association among African Americans. We therefore examined the association between self-reported habitual snoring and incident CVD in the Jackson Heart Study (JHS), a population-based cohort study of African Americans. METHODS: Self-reported data on snoring and risk factors for CVD were collected at baseline (2000-2004). Participants were followed prospectively for the development of incident CVD. Habitual snoring was defined as present if the participants reported it as “often” or “almost always” or absent if reported as “sometimes”, “never”, or “seldom”. A CVD event included stroke, myocardial infarction, coronary revascularization procedure or fatal CHD event. Cox proportional hazards models assessed the independent association between self-reported habitual snoring and incident CVD event adjusting for multiple covariates including age, sex, hypertension, body mass index, diabetes, hypercholesterolemia, smoking status. RESULTS: The snorer group consisted of 787 participants (mean age 52.1 years) and the non-snorer group consisted of 3708 participants (mean age 54.9 years). Frequency of incident CVD events in the snorer group was not significantly different from the non-snorer group. The fully adjusted hazard ratio for a CVD event in the snorer group was 1.01 (95% confidence interval [0.69, 1.47], p-value of 0.96). CONCLUSION: In conclusion, self-reported habitual snoring was not associated with incident CVD amongst this large African American cohort. Future studies providing objective data on snoring and sleep apnea may provide more information on the snoring-CVD association among African Americans.

AIM: To examine the association of psychosocial resources with prevalent type 2 diabetes (T2D) in 5,104 African American men and women. METHODS: Using data from the Jackson Heart Study (JHS), we evaluated the cross-sectional associations of four psychosocial resources (social support, optimism, religiosity, and social networks) with T2D [fasting glucose ≥126 mg/dL, or HbA1c ≥ 6.5%, or use of diabetic medication]. Multivariable Poisson regression estimated prevalence ratios (PR, 95% confidence interval-CI) of T2D by each psychosocial measure, adjusting for demographics, SES, waist circumference, health behaviors, and depressive symptoms. RESULTS: Women reported greater religiosity and had more social networks than men (p

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.

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.

Background Hypertension diagnosed by blood pressure (BP) measured in the clinic is associated with rapid kidney function decline (RKFD) and incident chronic kidney disease (CKD). The extent to which hypertension defined using out-of-clinic BP measurements is associated with these outcomes is unclear. Methods We evaluated the association of any masked hypertension (daytime SBP/DBP ≥ 135/85 mmHg, night-time SBP/DBP ≥ 120/70 mmHg or 24-h SBP/DBP ≥ 130/80 mmHg) with RKFD and incident CKD among 676 African-Americans in the Jackson Heart Study with clinic-measured SBP/DBP less than 140/90 mmHg who completed ambulatory BP monitoring in 2000-2004. RKFD was defined as a decline in estimated glomerular filtration rate (eGFR) at least 30% and incident CKD was defined as development of eGFR less than 60 ml/min per 1.73 m with an at least 25% decline in eGFR between 2000-2004 and 2009-2013. Results The mean age of participants was 57.6 years, 28.8% were men and 52.7% had any masked hypertension. After a median follow-up of 8 years, 13.8 and 8.6% of participants had RKFD and incident CKD, respectively. In unadjusted analyses, masked hypertension was associated with an increased odds for incident CKD [odds ratio (OR) 2.20, 95% confidence interval (CI) 1.22, 3.97]. This association remained statistically significant after adjustment for demographic characteristics, baseline eGFR and albumin-to-creatinine ratio (OR 1.95, 95% CI 1.04, 3.67) but was eliminated after propensity score adjustment (OR 1.62, 95% CI 0.87, 3.00). There was no association between masked hypertension and RKFD. Conclusion Masked hypertension may be associated with the development of CKD in African-Americans.

Objective We determined differences in the prevalence of blood pressure (BP) phenotypes and the association of these phenotypes with left ventricular hypertrophy (LVH) for individuals who fulfilled and did not fulfill various criteria used for defining a complete ambulatory blood pressure monitoring (ABPM) recording. Methods We analyzed data for 1141 participants from the Jackson Heart Study. Criteria evaluated included having greater than or equal to 80% of planned readings with more than or equal to one reading per hour (Spanish ABPM Registry criteria), more than or equal to 70% of planned readings with a minimum of 20 daytime and seven nighttime readings (2013 European Society of Hypertension criteria), greater than or equal to 14 daytime and greater than or equal to seven nighttime readings (2003 European Society of Hypertension criteria), more than or equal to 10 daytime and more than or equal to 5 nighttime readings (International Database of Ambulatory Blood Pressure in Relation to Cardiovascular Outcome criteria), and greater than or equal to 14 daytime readings (UK National Institute of Health and Clinical Excellence criteria). Results Between 45.0% (Spanish ABPM Registry) and 91.8% (UK National Institute of Health and Clinical Excellence) of the participants fulfilled the different criteria for a complete ABPM recording. Across the various criteria evaluated, 55.5-57.8% of participants had nocturnal hypertension and 62.8-66.8% had nondipping systolic BP. Among participants with clinic-measured systolic/diastolic BP of more than or equal to 140/90 mmHg, 22.9-26.5% had white-coat hypertension. The prevalence of daytime, 24-h, sustained, and masked hypertension differed by up to 2% for participants fulfilling each criterion. The association of BP phenotypes with LVH was similar for participants who fulfilled versus those who did not fulfill different criteria (each P>0.05). Conclusion Irrespective of the criteria used for defining a complete ABPM recording, the prevalence of BP phenotypes and their association with LVH were similar.

Cardiovascular disease (CVD) primordial prevention tools applicable to diverse popula-tions 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., This research was funded by the National Heart, Lung, and Blood Institute, and the National Institute on Minority Health and Health Disparities, contract numbers HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C. M.S.-P. holds a Ramón y Cajal contract (RYC-2018-025069-I) from the Ministry of Science, Innovation and Universities and FEDER/FSE and a FIS grant PI20/00896 (Instituto de Salud Carlos III, State Secretary of R+D+I and FEDER/FSE). Preparation of this manuscript was supported by The Robert Wood Johnson Foundation (Harold Amos Medical Faculty Development Program ID# 76236, J.J.J.) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23DK117041, J.J.J.) of the National Institutes of Health

BACKGROUND The Jackson Heart Study (JHS) assesses cardiovascular disease risk factors among African Americans in Jackson, Mississippi. Whether characteristics of JHS participants differ from those of a broader African American population are unknown. METHODS In a retrospective observational analysis, we compared characteristics and outcomes of JHS participants 65 years old and older and enrolled in Medicare (n = 1,105) to regional (n = 57,489) and national (n = 95,494) cohorts of African American Medicare beneficiaries. We weighted the regional and national cohorts to match the age and sex distributions of the JHS-Medicare cohort for pairwise baseline comparisons. Outcomes of interest included mortality and Medicare costs. We used Cox proportional hazards models to test associations between cohorts and outcomes. RESULTS The JHS-Medicare cohort was younger, included more women, and had fewer beneficiaries with dual Medicare-Medicaid eligibility, compared with regional and national Medicare cohorts. The cohort also had lower risks of stroke, lung disease, heart failure, diabetes, and renal disease. Mean Medicare costs were lower ($5,066 [SD = $11,932]) than in the regional ($7,419 [SD = $17,574]) and national ($8,013 [SD = $19,378]) cohorts. The regional and national cohorts had higher mortality (adjusted hazard ratios = 1.52; 95% confidence interval [CI] = 1.31, 1.76; and 1.49; 95% CI = 1.29, 1.73, respectively). Subgroup analysis for dual Medicare-Medicaid eligibility attenuated mortality differences. CONCLUSION JHS-Medicare participants had fewer comorbid conditions, better survival, and lower Medicare costs compared with regional and national cohorts. Observed differences may reflect healthy volunteer bias and higher socioeconomic status.See video abstract at, http://links.lww.com/EDE/B235.

We introduce and evaluate the oblique random survival forest (ORSF). The ORSF is an ensemble method for right-censored survival data that uses linear combinations of input variables to recursively partition a set of training data. Regularized Cox proportional hazard models are used to identify linear combinations of input variables in each recursive partitioning step. Benchmark results using simulated and real data indicate that the ORSF’s predicted risk function has high prognostic value in comparison to random survival forests, conditional inference forests, regression and boosting. In an application to data from the Jackson Heart Study, we demonstrate variable and partial dependence using the ORSF and highlight characteristics of its ten-year predicted risk function for atherosclerotic cardiovascular disease events (ASCVD; stroke, coronary heart disease). We present visualizations comparing variable and partial effect estimation according to the ORSF, the conditional inference forest, and the Pooled Cohort Risk equations. The obliqueRSF R package, which provides functions to fit the ORSF and create variable and partial dependence plots, is available on the comprehensive R archive network (CRAN).

Background There is limited evidence on the relationship between social support and renal outcomes in African Americans. We sought to determine the association of social support with prevalent chronic kidney disease (CKD) and kidney function decline in an African American cohort. We also examined whether age modifies the association between social support and kidney function decline. Methods We identified Jackson Heart Study (JHS) participants with baseline (Exam in 2000–2004) functional and structural social support data via the Interpersonal Support Evaluation List (ISEL) and social network size questions, respectively. With ISEL as our primary exposure variable, we performed multivariable regression models to evaluate the association between social support and prevalent CKD [estimated glomerular filtration rate (eGFR) 30% decrease in eGFR over approximately 10 years). All models were adjusted for baseline sociodemographics, diabetes, hypertension, smoking status, and body mass index; models for eGFR decline and RRFD were additionally adjusted for eGFR and ACR. In models for eGFR decline, we assessed for interaction between age and social support. For secondary analyses, we replaced ISEL with its individual domains (appraisal, belonging, self-esteem, and tangible) and social network size in separate models as exposure variables. Results Of 5301 JHS participants, 4015 (76%) completed the ISEL at baseline. 843 (21%) had low functional social support (ISEL score

Background: Mortality has been reported to be lower among individuals classified as overweight/obese (based on body mass index (BMI, kg/m 2 )) when compared with their normal weight counterparts (“obesity paradox”). One possible reason for this apparent paradox is that BMI includes the weight of lean muscle and fat mass, both of which vary with age, sex, and race/ethnicity, and variations in these individual mass measures may not be reflected by the BMI. We compared associations between all-cause mortality and BMI and other obesity measures that may better reflect central adiposity, including waist circumference (WC, cm), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR) in the Jackson Heart Study (JHS), a prospective cohort study of cardiovascular disease in African Americans. Methods: Data from 3,976 JHS participants (441 deaths) who attended Exam 2 (2005-2008) where various measures of obesity were collected, were analyzed. Cox regression models were used to evaluate the associations between obesity and all-cause mortality. “Time 0” for the survival analysis was the date of Exam 2 and the administrative censoring date was 12/31/2015. Obesity measures were analyzed as categories based on standard cut-points defining obesity and as quintiles. Covariates include age, sex and smoking. The predictive abilities of these obesity measures were assessed using c-index. Results: The age-sex-smoking adjusted mortality rates were the lowest among participants who were overweight (BMI 25-102 in men/>88 in women vs. ≤102 in men/≤88 in women; aHR 1.45 [1.16-1.82]) and by WHR (≥0.9 in men/≥0.85 in women vs. 65 vs. ≤65 years). Analyses using quintiles showed that the 5 th quintiles were associated with a significant increase in mortality compared with the 1 st quintiles for all obesity measures. The c-indexes were comparable for all obesity measures. Conclusions: The “obesity paradox” was suggested in the JHS based on BMI. However, only morbidly obese participants had a significantly higher mortality than normal weight participants. The recommended cut-points for defining obesity based on WC and WHR were significantly associated with increased mortality in this large cohort of African Americans.

Table S1. Comparison of characteristics of JHS participants with and without CKD. (DOCX 19 kb)

Diabetes mellitus (DM) and hypertension (HTN) have been associated with left ventricular (LV) remodeling. However, as DM and HTN often occur concurrently, the independent effects of DM on LV remodeling have not been adequately assessed. Jackson Heart Study participants (n=2950 African Americans)

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.

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.

Background: Data showing long term efficacy and sustained active lifestyle change are scant. Identifying social determinants for maintaining an active lifestyle overtime may help pinpoint barriers/facilitators for sustaining an active lifestyle change. Methods: We evaluated the associations between social determinants of health (SDH) and changes in physical activity (PA). The analysis dataset included 3,741 participants in the Jackson Heart Study (JHS) who completed the PA questionnaire at exams 1 and 3, approximately 8 years apart. Participants were classified into 3 PA groups-poor (0 minutes/week moderate/vigorous activity), intermediate (some moderate/vigorous activity), or ideal (≥75 minutes/week vigorous or ≥150 minutes/week moderate or ≥150 minutes/week combined moderate/vigorous activity). SDH evaluated were individual level socioeconomic status (SES), social support, perceived stress and neighborhood characteristics. Other covariates included age, sex and body mass index (BMI). Unadjusted analyses followed by multivariable logistic regression analyses with backward selection were performed to explore the most significant SDH associated with changes in PA. Results: Twenty-eight percent (28%) participants had poor PA at both exams; 35.5% had at least intermediate PA at both exams; 19.2% changed from poor to intermediate/ideal PA and 17.8% changed from intermediate/ideal to poor PA overtime. In unadjusted analyses, among participants with intermediate/ideal PA at exam 1, younger age, higher levels of SES and greater social support; as well as higher neighborhood SES, greater social cohesion, fewer neighborhood problems and violence were positively associated with maintaining intermediate/ideal PA at exam 3. Among those with poor PA at exam 1, the same factors other than social cohesion were associated with improved PA to moderate/ideal level at exam 3. Sex, perceived stress, number of PA facilities in the neighborhood or being overweight/obese at either exam was not associated with changes in physical activity levels. Exploratory multivariable logistic regression with backward selection suggested that all three individual SES indicators were important factors for maintaining moderate/ideal PA levels at exam 3; and younger age, higher education, and higher neighborhood SES were important factors for improving PA levels from poor to intermediate/ideal. Conclusions: Individual SES indicators were significantly associated with maintaining an intermediate/ideal PA overtime; whereas younger age, higher educational attainment and higher neighborhood SES were significantly associated with changes in PA from poor to intermediate/ideal. Targeting individual education and environmental factors (e.g., neighborhood problems, violence) associated with neighborhood SES may provide most benefit both in initiating and maintaining an active lifestyle.

Introduction: Compared to other racial and ethnic groups, African Americans experience greater negative psychosocial factors (depression, stress), which are related to increased risk of cardiovascular disease (CVD). Little research has examined the association of positive psychosocial factors (optimism) with cardiovascular health in this population. Using the Jackson Heart Study (JHS) data, we examined the association of optimism with the American Heart Association Life’s Simple 7 TM (LS7), a measure of seven metrics that assesses a person’s cardiovascular health. Hypothesis: Higher levels of optimism are positively associated with individual LS7 metrics, and positively associated with the total LS7 score. Methods: We evaluated cross-sectional associations of optimism with each LS7 metric [cigarette smoking, physical activity, diet, body mass index (BMI), blood pressure, cholesterol, glucose] and with a composite LS7 score among 4,761 participants, 21-95 years old (women=3,070; men=1,691) enrolled in the JHS, a single-site, community-based cohort of African Americans residing in Jackson, MS. Optimism was measured in tertiles (low, moderate, high) to examine threshold effects. Each LS7 metric was classified as poor, intermediate, and ideal. LS7 metrics were also summed to create a total continuous score (0-13) categorized in tertiles (low, moderate, high). Multinomial logistic regression estimated the odds ratios (OR, 95% confidence interval-CI) of intermediate (vs. poor) and ideal (vs. poor) LS7 metric by levels of optimism. Multinomial regression also estimated the odds of moderate (vs. low) or high (vs. low) total LS7 score by optimism. Models adjusted for demographics, SES, and depressive symptoms. Results: Descriptive findings showed that participants who reported high optimism had ideal physical activity, nutrition, smoking, blood pressure, glucose and high total LS7 score (all p Conclusion: Optimism is associated with ideal physical activity and ideal smoking, which is important for promoting cardiovascular health and reducing the risk of CVD among African Americans in this sample.

Introduction: African Americans (AAs) have among the highest prevalence of type 2 diabetes in the U.S. Research has shown that positive affect and supportive networks are associated with better health outcomes and may improve regulation of physiological processes. We examined the extent to which psychosocial resources were protective of diabetes outcomes among a sample of 5,306 AAs. Hypothesis: Psychosocial resource measures are inversely associated with prediabetes and diabetes [defined by hemoglobin (Hb)A1c categories] and prevalent diabetes (defined by self-report diabetes status and medication use). Methods: Using data from the Jackson Heart Study (JHS), we evaluated the cross-sectional associations of four psychosocial-resource indicators (social support, optimism, religiosity, social networks) with two diabetes outcomes [1) HbA1c categories: normal (HbA1c ≤ 5.7%), at risk/pre-diabetic (5.7% < HbA1c < 6.5%), diabetic (HbA1c ≥ 6.5%) and 2) prevalent diabetes (vs. no diabetes)]. For each psychosocial-resource measure, we created high vs. low categories (median split) and continuous standard deviation (SD) units. Associations with HbA1c categories were examined using multinomial logistic regression to estimate odds ratios (OR 95% confidence interval-CI) of pre-diabetes (vs. normal) and diabetes (vs. normal). Associations with prevalent diabetes were examined using Poisson regression to estimate prevalence ratios (PR 95% CI) of diabetes (vs. no diabetes). Models adjusted for demographics, SES, waist circumference, health behaviors, and depression. Results: Participants with diabetes reported fewer psychosocial resources than those with pre-diabetes and normal HbA1c ( p social support was associated with an 11% lower odds of pre-diabetes (vs. normal HbA1c) (OR 0.89, 95% CI 0.81-0.99). High (vs. low) religiosity was associated with an increased odds of diabetes (vs. normal Hba1c) (OR 1.29, 95% CI 1.01-1.64) after full adjustment. Optimism and social networks were only associated with lower diabetes prevalence after adjustment for demographics and education, respectively. Conclusion: With the exception of religiosity, psychosocial-resource measures were inversely associated with diabetes. Social support and social networks, especially, should be considered when addressing the reduction of diabetes burden among AAs.

INTRODUCTION: Using Jackson Heart Study (JHS) data, we assessed the association between perceived psychosocial stressors and metabolic syndrome (MetS) severity in African American adults. METHODS: Participants included 3,870 African American JHS participants aged 21 to 95 years (63.1% women; mean age 53.8± 13.0). Psychosocial stressors assessed included: major life events (MLEs); global stress; and weekly stress inventory. Each stress measure was classified into tertiles (low, medium, and high). Associations of psychosocial stressors with a sex- and race/ethnic-specific MetS severity Z-score were examined after adjustment for demographics and MetS risk factors (i.e., nutrition, physical activity, smoking status, and alcohol consumption). RESULTS: Independent of lifestyle factors, participants who reported high (versus low) perceived global stress and MLEs had significantly greater MetS severity (p=0.0207 and p=0.0105, respectively). Weekly stress was not associated with MetS severity. Compared to men, women reported significantly higher global stress and MLEs (p

Introduction: African Americans are disproportionately affected by hypertension (HTN) and cardiovascular disease (CVD). Determining the population attributable risk (PAR) for CVD associated with HTN and prehypertension in African Americans can help inform policymakers and prioritize public health interventions. Methods: Among 3770 participants in the Jackson Heart Study without prevalent CVD, we used Cox-proportional hazard analysis adjusted for traditional CVD risk factors to determine the association of HTN and prehypertension with incident CVD and its components including coronary heart disease, heart failure, and stroke. The PAR was calculated as pd*(HR-1)/HR; where pd is the prevalence of the exposure and HR is the hazard ratio for the outcome associated with the exposure. HTN was defined as a systolic blood pressure (SBP) ≥140 mmHg, diastolic blood pressure (DBP) ≥90 mmHg, or self-reported antihypertensive medication use and prehypertension as SBP of 120 to 139 mmHg or DBP of 80 to 89 mmHg. Results: At baseline, 52.4% of the cohort had HTN and 77.1% had prehypertension or HTN. Over a median of 9.9 years follow-up, 349 (9.3%) participants developed CVD. The HR for CVD and PAR associated with HTN was 2.17 (95% CI 1.63, 2.89) and 0.28 (95% CI 0.20, 0.35), respectively (Table). The HR for CVD and PAR associated with HTN and prehypertension pooled together was 2.21 (95% CI 1.41, 3.47) and 0.42 (95% CI 0.25, 0.56), respectively. In the pooled group there were significant associations with incident coronary heart disease, heart failure, and stroke. Sex-specific sensitivity analysis demonstrated PAR for CVD associated with HTN and prehypertension was 0.40 (95% CI 0.07, 0.62) in men and 0.43 (95% CI 0.19, 0.61) in women. Conclusions: Approximately 40% of incident CVD is attributable to HTN and prehypertension among African Americans in the southeastern United States. Preventing HTN and prehypertension in this population is a major public health priority.

Background Black persons have an excess burden of cardiovascular disease ( CVD ) compared with white persons. This burden persists after adjustment for socioeconomic status and other known CVD risk factors. This study evaluated the CVD burden and the socioeconomic gradient of CVD among black participants in the JHS (Jackson Heart Study). Methods and Results CVD burden was evaluated by comparing the observed prevalence of myocardial infarction, stroke, and hypertension in the JHS at baseline (2000–2004) with the expected prevalence according to US national surveys during a similar time period. The socioeconomic gradient of CVD was evaluated using logistic regression models. Compared with the national data, the JHS age‐ and sex‐standardized prevalence ratios for myocardial infarction, stroke, and hypertension were 1.07 (95% CI , 0.90–1.27), 1.46 (95% CI , 1.18–1.78), and 1.51 (95% CI , 1.42–1.60), respectively, in men and 1.50 (95% CI , 1.27–1.76), 1.33 (95% CI , 1.12–1.57), and 1.43 (95% CI , 1.37–1.50), respectively, in women. A significant and inverse relationship was observed between socioeconomic status and CVD within the JHS cohort. The strongest and most consistent socioeconomic correlate after adjusting for age and sex was income for myocardial infarction (odds ratio: 3.53; 95% CI , 2.31–5.40) and stroke (odds ratio: 3.73; 95% CI , 2.32–5.97), comparing the poor and affluent income categories. Conclusions Except for myocardial infarction in men, CVD burden in the JHS cohort was higher than expected. A strong inverse socioeconomic gradient of CVD was also observed within the JHS cohort.

Background— Among individuals without hypertension based on clinic blood pressure (BP), it is unclear who should be screened for masked hypertension, defined as having hypertension based on out-of-clinic BP. We hypothesized that individuals with a higher 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk, calculated using the pooled cohort risk equations, have a higher prevalence of masked hypertension. Methods and Results— We analyzed data from the Jackson Heart Study—a population-based cohort of blacks—to determine the association of predicted ASCVD risk with masked hypertension. The sample included 644 participants, 40 to 79 years of age, with clinic systolic/diastolic BP Conclusions— Higher ASCVD risk was associated with an increased prevalence of masked hypertension. Although the discrimination of ASCVD risk for masked hypertension was not superior to clinic BP, risk prediction equations may be useful for identifying the subgroup of individuals with both masked hypertension and high predicted ASCVD risk.

Background: Cardiovascular disease (CVD) risk assessment tools such as the Framingham Risk Score are useful to identify population high risk subgroups for targeted intervention. However, no CVD risk score specific for African Americans (AAs) were available until the Pooled Cohort Equations (PCE) was introduced in 2013 for calculating sex- and race-specific10-year predicted risk of atherosclerotic cardiovascular disease (ASCVD). This study evaluated the performance of PCE in the Jackson Heart Study (JHS), a prospective cohort study of CVD in AAs. Methods: The analytic sample included 2,191 JHS participants who were 40-79 years old without a history of CVD or CVD procedures at baseline (2000-2004) and who were not a shared participant in the Atherosclerosis Risk in Communities (ARIC) Study. ASCVD events (CHD and stroke) were ascertained by active surveillance with medical records abstraction. Because all participants were followed at least 8 years through 2012, validation of the PCE was based on 8-year observed and predicted risks of ASCVD. The PCE was evaluated for discrimination and calibration properties using c-index and Hosmer-Lemeshow (HL) x 2 statistic, respectively. Overall and subgroup analysis among participants (no diabetes, LDL between 70 and 189 mg/dL and not taking statins) for whom CVD risk assessment may be applied to guide treatment for high blood cholesterol were performed. Stratified analyses evaluating the performance of PCE by baseline characteristics, including sex, age ( Results: There were a total of 63 incident ASCVD events (29 CHD; 34 stroke). The PCE predicted total number of event was 130, with a c-index=0.78 (95% CI 0.54-0.96) and a HL x 2 =38.2 (p x 2 =21.9, p=0.005). In stratified analyses, PCE had better calibration in participants who were younger (n=831, HL x 2 =10.5, p=0.23), not affluent (n=1,120, HL x 2 =12.6, p=0.12), less educated (n=186, HL x 2 =6.6, p=0.58), those with lower BMI (n=833, HL x 2 =8.5, p=0.39), those with diabetes (n=287, HL x 2 =11.1, p=0.20), and statin users (n=159, HL x 2 =10.8, p=0.21). Conclusions: Overall, the PCE showed good discrimination but did not calibrate well and overestimated the risk of ASCVD. In the subset of participants for whom CVD risk assessment may be applied to guide treatment for high blood cholesterol, the PCE showed improved calibration but still overestimated risk. *Defined as 3 times above poverty level.

There are limited reports on the association of psychosocial factors with unhealthy behaviors, which are key mediators in the psychosocial-cardiovascular disease pathway. The Jackson Heart Study was used to examine the associations of multiple psychosocial factors with behaviors among African Americans.The Jackson Heart Study is a prospective, cohort study of cardiovascular disease among African Americans recruited from the Jackson, MS, metropolitan area between 2000 and 2004. Between 2015 and 2016, multivariable regression was used to analyze the cross-sectional associations of baseline negative affect (cynicism, anger-in, anger-out, and depressive symptoms) and stressors (global stress, Weekly Stress Inventory-event, Weekly Stress Inventory-impact, and major life events) with the odds of current smoking and mean differences in dietary fat intake, physical activity, and hours of sleep.Men were more likely to smoke than women (p0.001) and had higher physical activity scores (p0.001). Women reported more hours of sleep (p=0.001). In fully adjusted models, each negative affect and stress measure was significantly associated with an increased odds of current smoking. For example, the odds of smoking increased by 14% for each 1-SD increase in cynical distrust score (OR=1.14, 95% CI=1.01, 1.27) in the fully adjusted model. Further, each negative affect and stress measure (except anger-out) was significantly associated with fewer hours of sleep in fully adjusted models.Using a large sample of African Americans, this study found that multiple psychosocial risk factors were associated with unhealthy behaviors that are prevalent among this population.

Background: Research has found that socioeconomic status (SES) is associated with cardiovascular disease (CVD) risk. However, few studies have reported the SES correlates of CVD risk in African Americans (AA). Since low SES is over-represented in AA, our objective is to examine the socioeconomic correlates of CVD risk in this population, which may provide new insights on racial/ethnic disparities in CVD risk. Methods: A cross-sectional analysis of baseline data collected in the Jackson Heart Study (JHS), an entirely AA population, was performed. Multivariable logistic regression analysis estimated the age and sex-adjusted association of SES indicators (education, household income and occupation) with prevalent CVD (myocardial infarction (MI), stroke and hypertension). Stratified analyses by age ( Results: Baseline prevalence for MI, stroke and hypertension were 5.5%, 4.4% and 60.1%. About one-third (32.5%) of the participants had a bachelor’s degree, 35% held management or professional occupations and 30% were “affluent” (≥3.5 US Census poverty level). We observed an inverse relationship between prevalent CVD and SES indicators. The largest and most consistent SES correlate of prevalent CVD was observed with income on MI (odds ratio (OR) 3.5; 95% CI 2.3, 5.4) and stroke (OR 3.7; 95% CI 2.3, 6.0) comparing the poor (below US Census poverty level) to the affluent income categories. Stratified analyses suggested stronger SES gradients in individuals Conclusions: Inverse SES gradients on the prevalence of MI, stroke and hypertension were observed among AA in the JHS. The most important SES correlates were income for MI and stroke, and occupation for hypertension. These findings suggest SES, and income in particular, is an important factor contributing to health disparities in CVD among AA and possibly AA-White disparities in health outcomes.

Background: African Americans (AA) bear an excess burden of CVD compared to Whites. This burden persists when socioeconomic status (SES) and other known CVD risk factors are considered. One limitation to studies of Black-White disparities in CVD is that population subgroups with lower SES may be over-represented among AA compared to Whites. We aimed to quantify CVD burden in the Jackson Heart Study (JHS), an exclusively AA cohort with a balanced representation of SES. Methods: Baseline distributions of SES indicators in 5,301 JHS participants were compared to the US 2000 Census data. Baseline prevalence of myocardial infarction (MI), stroke and hypertension were compared to the National Health and Nutrition Examination Survey (NHANES) data collected during a comparable time period as the JHS baseline exam (2000-2004) (population reference including all races). Indirect standardization methods based on population age and sex specific prevalence were used to calculate the expected prevalence of MI, stroke and hypertension in the JHS. Standardized prevalence ratios (SPR) was calculated by dividing the observed by the expected prevalence. An SPR greater than 1 indicates excess burden. Results: Compared to national data, JHS participants were more likely to have some college education (61% vs. 52%) or a bachelor’s degree (32% vs. 24%), were more likely to hold management or professional occupations (36% vs. 34%), but had somewhat lower income, which could be in part due to a higher proportion (64%) of women in the JHS cohort. The observed baseline prevalence of MI, stroke and hypertension in JHS was 5.5%, 4.4% and 60.1%. The SPR for MI, stroke and hypertension were 1.05 (95% CI 0.88, 1.25), 1.39 (95% CI 1.12, 1.69) and 1.51 (1.42, 1.60) for men. The corresponding values for women were 1.61 (95% CI 1.37, 1.89), 1.33 (95% CI 1.12, 1.57) and 1.43 (95% CI 1.37, 1.50). Further analyses evaluating CVD risk factors (smoking, weight, physical activity, serum cholesterol, blood pressure and diabetes) found excess burden in overweight/obesity, physical inactivity, elevated blood pressure (≥140/90 mmHg), and diabetes among JHS participants compared to the population reference. Conclusions: We found an excess burden for stroke and hypertension in men, and an excess burden for MI, stroke and hypertension in women in the JHS. We also found an excess burden for CVD risk factors in the JHS cohort. Despite comparable SES between JHS and US population, we found an excess burden of CVD and CVD risk factors in this AA cohort.

The 2013 pooled cohort equations (PCEs) are central in prevention guidelines for cardiovascular disease (CVD) but can misestimate CVD risk.To improve the clinical accuracy of CVD risk prediction by revising the 2013 PCEs using newer data and statistical methods.Derivation and validation of risk equations.Population-based.26 689 adults aged 40 to 79 years without prior CVD from 6 U.S. cohorts.Nonfatal myocardial infarction, death from coronary heart disease, or fatal or nonfatal stroke.The 2013 PCEs overestimated 10-year risk for atherosclerotic CVD by an average of 20% across risk groups. Misestimation of risk was particularly prominent among black adults, of whom 3.9 million (33% of eligible black persons) had extreme risk estimates (70% or250% those of white adults with otherwise-identical risk factor values). Updating these equations improved accuracy among all race and sex subgroups. Approximately 11.8 million U.S. adults previously labeled high-risk (10-year risk ≥7.5%) by the 2013 PCEs would be relabeled lower-risk by the updated equations.Updating the 2013 PCEs with data from modern cohorts reduced the number of persons considered to be at high risk. Clinicians and patients should consider the potential benefits and harms of reducing the number of persons recommended aspirin, blood pressure, or statin therapy. Our findings also indicate that risk equations will generally become outdated over time and require routine updating.Revised PCEs can improve the accuracy of CVD risk estimates.National Institutes of Health.

Filgrastim, or granulocyte colony-stimulating factor, reverses neutropenia associated with human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) infections. During a trial of anti-CMV retinitis therapies coadministered with antiretroviral therapy, 2-4 plasma specimens of HIV-1 RNA were collected from 36 HIV-1-infected patients receiving filgrastim to prevent neutropenia and from 36 patients not receiving filgrastim. For both groups, the crude mean and mean rate of change of HIV-1 log(10) RNA levels were similar. Adjustment for covariates (CD4(+) T cell lymphocytes, virus load at enrollment, level of neutropenia and antiretroviral therapy [mainly non-highly active antiretroviral therapy], and anti-CMV therapy during follow-up) resulted in a mean log(10) HIV-1 RNA level for individuals receiving filgrastim versus those not receiving the drug of 5.11 versus 4.87 (P=.12) and respective log mean rates of change per month of -0.08 versus -0.21 (P=.08). This latter difference has borderline statistical significance, which suggests that filgrastim may reduce the decline of HIV-1 RNA loads.

Objective To refine and validate the Birmingham Vasculitis Activity Score (BVAS) as a disease-specific activity index for Wegener's granulomatosis (WG). Methods Sixteen members of the International Network for the Study of the Systemic Vasculitides (INSSYS) revised the BVAS, with 3 goals: to reduce the redundancy of some component items, to enhance its ability to capture important disease manifestations specific to WG, and to streamline the instrument for use in clinical research. We defined the items and weighted them empirically as either minor (e.g., nasal crusting = 1 point) or major (e.g., alveolar hemorrhage = 3 points). We then validated the new, disease-specific BVAS/WG in 2 simulation exercises and a clinical case series that involved 117 patients with WG. Results We removed 38 items from the original BVAS, revised 9 items, and added 7 new items. Correlations between the scores on the BVAS/WG and the physician's global assessment (PGA) of disease activity were high, even when patients in remission were excluded. In the clinical case series, Spearman's rank correlation coefficient between the BVAS/WG and the PGA was r = 0.81 (95% confidence interval 0.73–0.87). The interobserver reliability using intraclass (within-case) correlation coefficients in the 2 simulation exercises was r = 0.93 for the BVAS/WG and r = 0.88 for the PGA in the first and r = 0.91 for the BVAS/WG and r = 0.88 for the PGA in the second. There was no significant observer effect in the scoring of the BVAS/WG or the PGA. The discriminant validity of the BVAS/WG was good: r = 0.73 (95% confidence interval 0.43–0.83). Conclusion The BVAS/WG is a valid, disease-specific activity index for WG. Tested in simulation exercises and in actual patients, the BVAS/WG correlates well with the PGA, is sensitive to change, and has good inter- and intraobserver reliability. The INSSYS will use the BVAS/WG to assess the primary outcome in a phase II/III trial of etanercept in WG.

BACKGROUND: Industrial hygienists' assessments of prenatal occupational exposures based on parental job histories is a promising approach for population-based case-control studies of birth defects and other perinatal outcomes. However, evaluations of inter-rater agreement of such assessments have been limited. METHODS: We examined inter-rater agreement of occupational lead exposure assessments of maternal job reports by industrial hygienists in a population-based case-control study of parental occupational lead exposure and low birth weight. A total of 178 jobs with potential exposure to lead during the 6 months before pregnancy to the end of pregnancy were examined. Three industrial hygienists evaluated these jobs independently for exposure to lead including probability of exposure, type of exposure, route of entry, exposure frequency, duration, and intensity. Inter-rater agreement of these assessments beyond chance was evaluated using the kappa statistic (κ). RESULTS: In general, inter-rater agreement was greater for assessment of direct exposures than assessment of indirect exposures. However, inter-rater agreement varied with the lead exposure metric under consideration, being: 1) fair to good for type of direct exposure (i.e., inorganic or organic), respiratory exposure and frequency of exposure to direct inorganic lead, hours per day of direct (i.e., inorganic or organic), and intensity of direct inorganic exposure; 2) poor for probability and type of indirect exposure (inorganic or organic); and 3) indeterminate for frequency of direct organic exposure, frequency of indirect exposures (organic or inorganic), and intensity of direct exposures (organic or inorganic). CONCLUSION: Retrospective assessment of maternal prenatal exposures to lead by industrial hygienists can provide some reliable metrics of exposure for studies of perinatal outcomes. Reliability studies of such exposure assessments may be useful for: quantifying the reliability of derived exposure metrics; identifying exposure metrics for exposure-outcome analyses; and determining the reliability of prenatal occupational exposures to other agents of interest. Birth Defects Research (Part A), 2006. © 2006 Wiley-Liss, Inc.

Etanercept is a soluble fusion protein designed to inhibit tumor necrosis factor (TNF). During the Wegener's Granulomatosis Etanercept Trial (WGET), a placebo-controlled trial of etanercept given in addition to standard therapy for remission induction and maintenance, more solid malignancies were observed in the etanercept group than in the group treated with standard therapy alone. This study was undertaken to further explore the potential association between anti-TNF therapy and the development of malignancy in these patients.One hundred eighty patients with active WG were enrolled and followed up for a median of 27 months. At enrollment, disease characteristics, treatment history, specific medical history items, and information about previous WG treatments and risk factors for malignancy were recorded. During the trial, the occurrence of malignancies and other adverse events was recorded prospectively.All 6 solid malignancies observed during the WGET occurred in the etanercept group (P = 0.01 versus placebo group); based on a comparison of age- and sex-specific incidence rates, 1.92 solid malignancies would have been expected in this group. The solid malignancies included 2 cases of mucinous adenocarcinoma of the colon, 1 each of metastatic cholangiocarcinoma, renal cell carcinoma, and breast carcinoma, and 1 recurrent liposarcoma. There were no differences between the 2 treatment groups in sex distribution, disease severity, personal or family history of cancer, or tobacco and alcohol use. The etanercept group was older at baseline and less likely to be newly diagnosed with WG at the time of randomization. Patients who developed solid tumors were older than patients who did not. All etanercept-treated patients who developed solid tumors were also treated with cyclophosphamide during the trial. However, there were no differences between the groups in the amount of cyclophosphamide received during the trial or the percentage who had received cyclophosphamide before enrollment. There were also no differences in the mean duration of daily cyclophosphamide therapy or the maximum daily cyclophosphamide dosage before enrollment.Data from the WGET, the first substantial reported experience of the combined use of etanercept and cyclophosphamide in the treatment of WG, indicate that the combination of TNF inhibition and cyclophosphamide may heighten the risk of cancer beyond that observed with cyclophosphamide alone.