Promoting Cardiovascular Health in the Community: Training the Next Generation of Scientists in the Jackson Heart Study.

PURPOSE: The aim of this article is to show the impact of the use of National Institutes of Health (NIH) research supplements in the training of African American students affiliated with the Jackson Heart Study (JHS). RECENT FINDINGS: The JHS Undergraduate Training and Education Center (UTEC) at Tougaloo College has had 19 students to be awarded research supplements. The awardees gained invaluable skills while working on the research supplements. Additionally, research supplement awards inspired these students to not only consider working in health-related fields, but to continue to engage in research activities and to mentor.

Thinking Ahead to the Next Generation of Cardiometabolic Investigators: What It Takes to Successfully Engage Underrepresented Minorities in Biomedical and Public Health Careers.

PURPOSE OF REVIEW: The purpose of this review is to examine the existing information regarding cardiometabolic syndrome (CMS) manifestations among underrepresented minority populations, underrepresented minorities' representation in the cardiometabolic workforce, and the models that successfully recruit and retain underrepresented minorities in the field. RECENT FINDINGS: The scientific literature is replete with information on methods to recruit and train URM in research careers. However, there are few programs that are specifically designed to train URM to become diabetes researchers, or more specifically cardiometabolic researchers. The CMS scientific community leaders do not have to design a new learning program to engage URM in research. They only have to follow the prototypes by other organizations and make applicable to cardiometabolic research.

Pooled Cohort Probability Score for Subclinical Airflow Obstruction.

Rationale: Early detection of chronic obstructive pulmonary disease (COPD) is a public health priority. Airflow obstruction is the single most important risk factor for adverse COPD outcomes, but spirometry is not routinely recommended for screening. Objectives: To describe the burden of subclinical airflow obstruction (SAO) and to develop a probability score for SAO to inform potential detection and prevention programs. Methods: Lung function and clinical data were harmonized and pooled across nine U.S. general population cohorts. Adults with respiratory symptoms, inhaler use, or prior diagnosis of COPD or asthma were excluded. A probability score for prevalent SAO (forced expiratory volume in 1 second/forced vital capacity < 0.70) was developed via hierarchical group-lasso regularization from clinical variables in strata of sex and smoking status, and its discriminative accuracy for SAO was assessed in the pooled cohort as well as in an external validation cohort (NHANES [National Health and Nutrition Examination Survey] 2011-2012). Incident hospitalizations and deaths due to COPD (respiratory events) were defined by adjudication or administrative criteria in four of nine cohorts. Results: Of 33,546 participants (mean age 52 yr, 54% female, 44% non-Hispanic White), 4,424 (13.2%) had prevalent SAO. The incidence of respiratory events (Nat-risk = 14,024) was threefold higher in participants with SAO versus those without (152 vs. 39 events/10,000 person-years). The probability score, which was based on six commonly available variables (age, sex, race and/or ethnicity, body mass index, smoking status, and smoking pack-years) was well calibrated and showed excellent discrimination in both the testing sample (C-statistic, 0.81; 95% confidence interval [CI], 0.80-0.82) and in NHANES (C-statistic, 0.83; 95% CI, 0.80-0.86). Among participants with predicted probabilities ⩾ 15%, 3.2 would need to undergo spirometry to detect one case of SAO. Conclusions: Adults with SAO demonstrate excess respiratory hospitalization and mortality. A probability score for SAO using commonly available clinical risk factors may be suitable for targeting screening and primary prevention strategies.

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

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

Cigarette Smoking and Incident Stroke in Blacks of the Jackson Heart Study.

Background Blacks are disproportionately affected by stroke compared with whites; however, less is known about the relationship between stroke and cigarette smoking in blacks. Therefore, we evaluated the relationship between cigarette smoking and all incident stroke in the JHS (Jackson Heart Study). Methods and Results JHS participants without a history of stroke (n=4410) were classified by self-reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers at baseline (2000-2004). Current smokers were further classified by smoking intensity (number of cigarettes smoked per day [1-19 and ≥20]) and followed up for incident stroke (through 2015). Hazard ratios (HRs) for incident stroke for current and past smoking compared with never smoking were estimated with adjusted Cox proportional hazard regression models. After adjusting for cardiovascular risk factors, the risk for stroke in current smokers was significantly higher compared with never smokers (HR, 2.48; 95% CI, 1.60-3.83) but there was no significant difference between past smokers and never smokers (HR, 1.10; 95% CI, 0.74-1.64). There was a dose-dependent increased risk of stroke with smoking intensity (HR, 2.28 [95% CI, 1.38-3.86] and HR, 2.78 [95% CI, 1.47-5.28] for current smokers smoking 1-19 and ≥20 cigarettes/day, respectively). Conclusions In a large cohort of blacks, current cigarette smoking was associated with a dose-dependent higher risk of all stroke. In addition, past smokers did not have a significantly increased risk of all stroke compared with never smokers, which suggests that smoking cessation may have potential benefits in reducing the incidence of stroke in blacks.

A Dyadic Growth Modeling Approach for Examining Associations Between Weight Gain and Lung Function Decline.

The relationship between body weight and lung function is complex. Using a dyadic multilevel linear modeling approach, treating body mass index (BMI; weight (kg)/height (m)2) and lung function as paired, within-person outcomes, we tested the hypothesis that persons with more rapid increase in BMI exhibit more rapid decline in lung function, as measured by forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and their ratio (FEV1:FVC). Models included random intercepts and slopes and adjusted for sociodemographic and smoking-related factors. A sample of 9,115 adults with paired measurements of BMI and lung function taken at ≥3 visits were selected from a pooled set of 5 US population-based cohort studies (1983-2018; mean age at baseline = 46 years; median follow-up, 19 years). At age 46 years, average annual rates of change in BMI, FEV1, FVC, and FEV1:FVC ratio were 0.22 kg/m2/year, -25.50 mL/year, -21.99 mL/year, and -0.24%/year, respectively. Persons with steeper BMI increases had faster declines in FEV1 (r = -0.16) and FVC (r = -0.26) and slower declines in FEV1:FVC ratio (r = 0.11) (all P values < 0.0001). Results were similar in subgroup analyses. Residual correlations were negative (P < 0.0001), suggesting additional interdependence between BMI and lung function. Results show that greater rates of weight gain are associated with greater rates of lung function loss.

Association of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults.

Importance: Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain. Objective: To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers. Design, Setting, and Participants: This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018. Exposures: Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years. Main Outcomes and Measures: Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis. Results: Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes. Conclusions and Relevance: The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.

The Jackson Heart Study: Preparing African American High School Students for Health Careers and Research.

In 1999, Tougaloo College (TC), located in Jackson, Mississippi, was charged, as a part of its role in the Jackson Heart Study (JHS), with creating a pool of well-trained high school students who, upon entering college, could successfully complete undergraduate and graduate or professional degrees in the health professions, biomedical research, and public health. TC identified the following educational challenges experienced by Mississippi high school students: inadequate exposure to reading, writing, logic, and quantitative skills; inadequate course work in science and mathematics; lack of mentors and role models in science-related fields as well as for exploration and identification of career options in the health professions and biomedical research. To this end, the JHS Undergraduate Training and Education Center (JHS UTEC) developed three four-week summer workshops in Science, Language Arts, and Mathematics (SLAM) for high school students in grades 9 through 11. Since SLAM's inception, more than 900 students have completed the program, and more than 90% have enrolled in college. In addition, according to National Student Clearinghouse and participant-reported data, many of the SLAM participants have earned not only undergraduate degrees in science, but also graduate degrees in a health-related and STEM fields. This article details the SLAM curricula and strategies for recruiting, selecting, training, and retaining high school students; we also present data to illustrate the success of the SLAM program.

The Role of Public Health Partnerships in the Success of the Jackson Heart Study Undergraduate Training and Education Center.

Background: The Jackson Heart Study (JHS) is a single-site prospective epidemiologic investigation of cardiovascular disease (CVD) among African Americans from the central Jackson, Mississippi area. The study is a collaboration between Jackson State University (JSU), University of Mississippi Medical Center (UMMC), Tougaloo College (TC), and the Mississippi State Department of Health (MSDH). The JHS Undergraduate Training and Education Center (JHSUTEC) at TC was developed to increase the numbers of college-aged African American students entering public health and health-related fields. To achieve this goal, the UTEC designed the Jackson Heart Study (JHS) Scholars program. Methods: JHS Scholars are required to take additional classes and participate in public health and/or biomedical research. The scholars engage in research locally during the academic year. However, many scholars participate in research outside of the Jackson Metropolitan area during the summer. Because of this, national collaborators were needed to act as mentors and hosts. Results: Since the inception of the JHSUTEC, more than 15 collaborations have been formed that have shared resources and student successes. As of May 2018, more than150 students have successfully completed the JHS Scholars program and many have continued into careers in public health, biomedical research, and medicine. Since 2004, JHS scholars have published 29 papers and 15 scholars have received diversity supplements. Conclusion: Collaborative activities and public health partnerships have contributed to the success of the JHSUTEC program and have served as a pathway of entry into STEM fields for minority students.

Lung function decline in former smokers and low-intensity current smokers: a secondary data analysis of the NHLBI Pooled Cohorts Study.

BACKGROUND: Former smokers now outnumber current smokers in many developed countries, and current smokers are smoking fewer cigarettes per day. Some data suggest that lung function decline normalises with smoking cessation; however, mechanistic studies suggest that lung function decline could continue. We hypothesised that former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers, including among those without prevalent lung disease. METHODS: We used data on six US population-based cohorts included in the NHLBI Pooled Cohort Study. We restricted the sample to participants with valid spirometry at two or more exams. Two cohorts recruited younger adults (≥17 years), two recruited middle-aged and older adults (≥45 years), and two recruited only elderly adults (≥65 years) with examinations done between 1983 and 2014. FEV1 decline in sustained former smokers and current smokers was compared to that of never-smokers by use of mixed models adjusted for sociodemographic and anthropometric factors. Differential FEV1 decline was also evaluated according to duration of smoking cessation and cumulative (number of pack-years) and current (number of cigarettes per day) cigarette consumption. FINDINGS: 25 352 participants (ages 17-93 years) completed 70 228 valid spirometry exams. Over a median follow-up of 7 years (IQR 3-20), FEV1 decline at the median age (57 years) was 31·01 mL per year (95% CI 30·66-31·37) in sustained never-smokers, 34·97 mL per year (34·36-35·57) in former smokers, and 39·92 mL per year (38·92-40·92) in current smokers. With adjustment, former smokers showed an accelerated FEV1 decline of 1·82 mL per year (95% CI 1·24-2·40) compared to never-smokers, which was approximately 20% of the effect estimate for current smokers (9·21 mL per year; 95% CI 8·35-10·08). Compared to never-smokers, accelerated FEV1 decline was observed in former smokers for decades after smoking cessation and in current smokers with low cumulative cigarette consumption (<10 pack-years). With respect to current cigarette consumption, the effect estimate for FEV1 decline in current smokers consuming less than five cigarettes per day (7·65 mL per year; 95% CI 6·21-9·09) was 68% of that in current smokers consuming 30 or more cigarettes per day (11·24 mL per year; 9·86-12·62), and around five times greater than in former smokers (1·57 mL per year; 1·00-2·14). Among participants without prevalent lung disease, associations were attenuated but were consistent with the main results. INTERPRETATION: Former smokers and low-intensity current smokers have accelerated lung function decline compared with never-smokers. These results suggest that all levels of smoking exposure are likely to be associated with lasting and progressive lung damage. FUNDING: National Institutes of Health, National Heart Lung and Blood Institute, and US Environmental Protection Agency.

Refining the Association Between Body Mass Index and Atrial Fibrillation: G-Formula and Restricted Mean Survival Times.

Background Previous studies assessing the association between body mass index (BMI) and atrial fibrillation (AF) did not account for time-varying covariates, which may be affected by previous BMI. We illustrate how the g-formula can account for time-varying confounding. Methods and Results We included 4392 participants from the Framingham Heart Study who were AF free at ages 45 to 55 years, and followed them for up to 20 years. We estimated hazard ratios (HRs) comparing time-varying nonobese versus obese with Cox models. We used the g-formula to compare nonobese versus obese and 10% annual decrease in BMI (until normal weight is reached) versus natural course. We estimated HRs and differences in restricted mean survival times, the mean difference in time alive and AF free. We adjusted for sex, age, and time-varying risk factors. Cox models indicated that nonobese participants had a decreased rate of AF versus obese participants (HR, 0.83; 95% CI, 0.72-0.97). G-formula analyses comparing everyone had they been nonobese versus obese yielded stronger associations (HR, 0.73; 95% CI, 0.58-0.91). The restricted mean survival time was 19.22 years had everyone been nonobese and 19.03 years had everyone been obese (difference, 2.25 months; 95% CI, -0.66 to 5.16). When assessing a 10% annual decrease in BMI, the association was weaker (HR 0.96; 95% CI, 0.86-1.08). Conclusions Decreased BMI was associated with a lower rate of AF after accounting for time-varying covariates that depend on previous exposure using the g-formula, which Cox models cannot accommodate. Absolute measures like the restricted mean survival time difference offer context to relative measures of association.

Discriminative Accuracy of FEV1:FVC Thresholds for COPD-Related Hospitalization and Mortality.

Importance: According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV1:FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. Objective: To determine the discriminative accuracy of various FEV1:FVC fixed thresholds for predicting COPD-related hospitalization and mortality. Design, Setting, and Participants: The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016. Exposures: Presence of airflow obstruction, which was defined by a baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN). Main Outcomes and Measures: The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV1:FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach. Results: Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, -0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models. Conclusions and Relevance: Defining airflow obstruction as FEV1:FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV1:FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

Cigarette Smoking and Subclinical Peripheral Arterial Disease in Blacks of the Jackson Heart Study.

Background Prevalence of peripheral artery disease ( PAD ) is significantly higher among blacks as compared with non-Hispanic whites, but the role of cigarette smoking in PAD is understudied in blacks. We aimed to evaluate the relationship between cigarette smoking and PAD in blacks in the (JHS) Jackson Heart Study. Methods and Results JHS participants (n=5306) were classified by self-reported baseline smoking status into current, past (smoked at least 400 cigarettes/life), or never smokers. We examined multivariable logistic and robust linear regression models to estimate the associations between baseline smoking status, smoking intensity, and measures of subclinical PAD (ankle-brachial index [visit 1] and aortic calcium by computed tomography [visit 2]) to yield odds ratios and ß-coefficients (estimated adjusted difference) to compare each smoking status with never smokers (reference group). There were 3579 (68%) never smokers, 986 (19%) past smokers, and 693 (13%) current smokers self-identified at baseline. After adjustment for covariates, current smokers had increased risk of ankle-brachial index <1 (odds ratio, 2.2, 95% CI, 1.5-3.3) and increased risk of abdominal aortic (odds ratio, 8.4, 95% CI, 5.8-12.0) and aortoiliac calcium (odds ratio, 9.6, 95% CI, 6.7-13.7). When stratifying by smoking intensity, those smoking more than 20 cigarettes daily (1 pack) had higher likelihood of subclinical PAD by all of these measures compared with lower-intensity use, suggesting a dose-dependent relationship. Conclusions In a large black cohort, cigarette smoking was associated with measures of subclinical PAD in a dose-dependent manner. These findings highlight the association between smoking and PAD in blacks and support further research exploring the impact of interventions on smoking cessation to reduce PAD in this population.

Harmonization of Respiratory Data From 9 US Population-Based Cohorts: The NHLBI Pooled Cohorts Study.

Chronic lower respiratory diseases (CLRDs) are the fourth leading cause of death in the United States. To support investigations into CLRD risk determinants and new approaches to primary prevention, we aimed to harmonize and pool respiratory data from US general population-based cohorts. Data were obtained from prospective cohorts that performed prebronchodilator spirometry and were harmonized following 2005 ATS/ERS standards. In cohorts conducting follow-up for noncardiovascular events, CLRD events were defined as hospitalizations/deaths adjudicated as CLRD-related or assigned relevant administrative codes. Coding and variable names were applied uniformly. The pooled sample included 65,251 adults in 9 cohorts followed-up for CLRD-related mortality over 653,380 person-years during 1983-2016. Average baseline age was 52 years; 56% were female; 49% were never-smokers; and racial/ethnic composition was 44% white, 22% black, 28% Hispanic/Latino, and 5% American Indian. Over 96% had complete data on smoking, clinical CLRD diagnoses, and dyspnea. After excluding invalid spirometry examinations (13%), there were 105,696 valid examinations (median, 2 per participant). Of 29,351 participants followed for CLRD hospitalizations, median follow-up was 14 years; only 5% were lost to follow-up at 10 years. The NHLBI Pooled Cohorts Study provides a harmonization standard applied to a large, US population-based sample that may be used to advance epidemiologic research on CLRD.

Cigarette Smoking and Incident Heart Failure: Insights From the Jackson Heart Study.

BACKGROUND: Cigarette smoking has been linked with several factors associated with cardiac dysfunction. We hypothesized that cigarette smoking is associated with left ventricular (LV) structure and function, and incident heart failure (HF) hospitalization. METHODS: We investigated 4129 (never smoker n=2884, current smoker n=503, and former smoker n=742) black participants (mean age, 54 years; 63% women) without a history of HF or coronary heart disease at baseline in the Jackson Heart Study. We examined the relationships between cigarette smoking and LV structure and function by using cardiac magnetic resonance imaging among 1092 participants, cigarette smoking and brain natriuretic peptide levels among 3325 participants, and incident HF hospitalization among 3633 participants with complete data. RESULTS: After adjustment for confounding factors, current smoking was associated with higher mean LV mass index and lower mean LV circumferential strain (P<0.05, for both) in comparison with never smoking. Smoking status, intensity, and burden were associated with higher mean brain natriuretic peptide levels (all P<0.05). Over 8.0 years (7.7-8.0) median follow-up, there were 147 incident HF hospitalizations. After adjustment for traditional risk factors and incident coronary heart disease, current smoking (hazard ratio, 2.82; 95% confidence interval, 1.71-4.64), smoking intensity among current smokers (≥20 cigarettes/d: hazard ratio, 3.48; 95% confidence interval, 1.65-7.32), and smoking burden among ever smokers (≥15 pack-years: hazard ratio, 2.06; 95% confidence interval, 1.29-3.3) were significantly associated with incident HF hospitalization in comparison with never smoking. CONCLUSIONS: In blacks, cigarette smoking is an important risk factor for LV hypertrophy, systolic dysfunction, and incident HF hospitalization even after adjusting for effects on coronary heart disease.

High-Intensity Cigarette Smoking Is Associated With Incident Diabetes Mellitus In Black Adults: The Jackson Heart Study.

BACKGROUND: Previous reports on whether smoking is associated with insulin resistance and diabetes mellitus have yielded inconsistent findings. We aimed to evaluate the relationship between cigarette smoking and incident diabetes mellitus in the Jackson Heart Study. METHODS AND RESULTS: Jackson Heart Study participants enrolled at baseline without prevalent diabetes mellitus (n=2991) were classified by self-report as current smokers, past smokers (smoked ≥400 cigarettes/life and no longer smoking), or never smokers. We quantified smoking intensity by number of cigarettes smoked daily; we considered ≥20 cigarettes per day (1 pack) "high-intensity." We defined diabetes mellitus as fasting glucose ≥126 mg/dL, hemoglobin A1c ≥6.5% or International Federation of Clinical Chemistry units HbA1c 48 mmol/mol, or use of diabetes mellitus medication. We estimated the adjusted associations of smoking status, intensity, and dose (pack-years) with incident diabetes mellitus using Poisson regression models. At baseline there were 361 baseline current (1-10 cigarettes per day [n=242]; ≥20 [n=119]), 502 past, and 2128 never smokers. From Visit 1 to Visit 3 (mean 8.0±0.9 years), 479 participants developed incident diabetes mellitus. After adjustment for covariates, baseline current smokers who smoked less than a pack/d and past smokers had similar rates of incident diabetes mellitus compared with never smokers (incidence rate ratios 1.04, 95% confidence interval, 0.69-1.58 and 1.08, 95% confidence interval, 0.82-1.42, respectively). Baseline current high-intensity smokers had a 79% (95% confidence interval, 1.14-2.81) higher incidence of diabetes mellitus compared with never smokers. Smoking dose (per 10 pack-years) was also associated with a higher incidence of diabetes mellitus (incidence rate ratios 1.10, 95% confidence interval, 1.03-1.19) in adjusted models. CONCLUSIONS: High-intensity cigarette smoking and smoking pack-years are associated with an increased risk of developing diabetes mellitus in blacks.

The association between cigarette smoking and inflammation: The Genetic Epidemiology Network of Arteriopathy (GENOA) study.

To inform the study and regulation of emerging tobacco products, we sought to identify sensitive biomarkers of tobacco-induced subclinical cardiovascular damage by testing the cross-sectional associations of smoking with 17 biomarkers of inflammation in 2,702 GENOA study participants belonging to sibships ascertained on the basis of hypertension. Cigarette smoking was assessed by status, intensity (number of cigarettes per day), burden (pack-years of smoking), and time since quitting. We modeled biomarkers as geometric mean (GM) ratios using generalized estimating equations (GEE). The mean age of participants was 61 ±10 years; 64.5% were women and 54.4% African American. The prevalence of smoking was 12.2%. After adjusting for potential confounders, 6 of 17 biomarkers were significantly higher among current smokers at a Bonferroni adjusted p-value threshold (p<0.003). High sensitivity C-reactive protein was the most elevated biomarker among current smokers when compared to never smokers [GM ratio = 1.39 (95% CI: 1.23, 1.57); p <0.001]. Among former smokers, each pack-year of cigarettes smoked was associated with a 0.4% higher serum level of hsCRP [GM ratio = 1.004 (95% CI: 1.001, 1.006); p = 0.002] and each 5-year lapsed since quitting was associated with a 4% lower serum level of hsCRP [GM ratio = 0.96 (95% CI: 0.93, 0.99); p = 0.006]. However, we found no significant association of smoking intensity or burden with biomarkers of inflammation among current smokers. HsCRP appears to be the most sensitive biomarker of inflammation associated with cigarette smoking of those investigated, and could be a useful biomarker of smoking-related injury for the study and regulation of emerging tobacco products.

Replication and fine mapping of asthma-associated loci in individuals of African ancestry.

Asthma originates from genetic and environmental factors with about half the risk of disease attributable to heritable causes. Genome-wide association studies, mostly in populations of European ancestry, have identified numerous asthma-associated single nucleotide polymorphisms (SNPs). Studies in populations with diverse ancestries allow both for identification of robust associations that replicate across ethnic groups and for improved resolution of associated loci due to different patterns of linkage disequilibrium between ethnic groups. Here we report on an analysis of 745 African-American subjects with asthma and 3,238 African-American control subjects from the Candidate Gene Association Resource (CARe) Consortium, including analysis of SNPs imputed using 1,000 Genomes reference panels and adjustment for local ancestry. We show strong evidence that variation near RAD50/IL13, implicated in studies of European ancestry individuals, replicates in individuals largely of African ancestry. Fine mapping in African ancestry populations also refined the variants of interest for this association. We also provide strong or nominal evidence of replication at loci near ORMDL3/GSDMB, IL1RL1/IL18R1, and 10p14, all previously associated with asthma in European or Japanese populations, but not at the PYHIN1 locus previously reported in studies of African-American samples. These results improve the understanding of asthma genetics and further demonstrate the utility of genetic studies in populations other than those of largely European ancestry.

Diabetes, impaired glucose tolerance, and metabolic biomarkers in individuals with normal glucose tolerance are inversely associated with lung function: the Jackson Heart Study.

The objectives of this study were to test the hypothesis that diabetes and impaired glucose tolerance (IGT), diabetes control and diabetes duration, and metabolic biomarkers in adults with normal glucose tolerance (NGT) are inversely associated with spirometry-measured lung function. We conducted a cross-sectional observational cohort study that included nonsmoking African American adults (n = 2,945; mean age = 52.5 ± 12.6 years; 69.2% female), who were free of cardiovascular disease, from the Jackson Heart Study. The interventions were diabetes, metabolic biomarkers and lung function. We measured the associations of glycemia with forced expiratory volume (FEV) in 1 s, FEV in 6 s, and vital capacity. Multivariable adjusted mean lung function values were lower among adults with diabetes and IGT (in women only, but not after adjustment for waist circumference) than adults with NGT. Among adults with diabetes, no associations were observed between lung function and diabetes control or duration. In women with NGT, lower lung function was consistently associated with higher glucose levels and less consistently with higher insulin levels and insulin resistance. Lower lung function was consistently associated with higher insulin levels and insulin resistance and less consistently associated with insulin and hemoglobin A1c in men with NGT. Overall, our findings generally support the hypothesis that diabetes, IGT, and increased levels of metabolic biomarkers in individuals with NGT are inversely associated with lung function in African Americans, independent of adiposity.

Genetic variability of smoking persistence in African Americans.

To date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, that is, cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis by using a genotyping array that includes 2,100 genes to analyze smoking persistence in unrelated African American participants from the Atherosclerosis Risk in Communities study. A locus located approximately 4 kb downstream from the 3'-UTR of the brain-derived neurotrophic factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5-CHRNA3-CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population, as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions.