Life Course Socioeconomic Status and Hypertension in African American Adults: The Jackson Heart Study.

BACKGROUND: Limited research has examined the association of life-course socioeconomic status (SES) with hypertension prevalence and incidence in a large cohort of African Americans. METHODS: Among 4,761 participants from the Jackson Heart Study (JHS), we examined the association of SES indicators with prevalent and incident hypertension. We used multivariable Poisson regression to estimate prevalence ratios (PR, 95% confidence interval-CI) of baseline (2000-2004) hypertension by adult (education, income, occupation, wealth) and childhood (mother's education) SES. Cox proportional hazards regression was used to estimate hazard ratios (HR, 95% CI) of incident hypertension by adult and childhood SES (2005-2013; 7.21 median years of follow-up). We also examined the association of childhood-to-adult SES mobility (parent-to-adult education) with prevalent and incident hypertension. Model 1 adjusted for age and sex. Model 2 added waist circumference, behaviors (smoking, alcohol, physical activity, diet), and diabetes prevalence. RESULTS: High (vs. low) adult SES measures were associated with a lower prevalence of hypertension, with the exception of having a college degree and upper-middle income (PR: 1.04, 95% CI: 1.01, 1.07; PR: 1.05, 95% CI: 1.01, 1.09, respectively). Higher childhood SES was associated with a lower prevalence and risk of hypertension (PR: 0.83, 95%: CI 0.75, 0.91; HR: 0.76, 95% CI: 0.65, 0.89, respectively). Upward mobility and consistent high SES (vs. consistent low SES) from childhood to adulthood was associated with a greater prevalence, but lower incidence of hypertension. CONCLUSION: Efforts to prevent hypertension among African Americans should consider childhood and current SES status.

Associations of smoking indicators and cotinine levels with telomere length: National Health and Nutrition Examination Survey.

The influence of smoking exposure on telomere length with a focus on the impact of race has rarely been discussed. We performed a cross sectional analysis into the associations of smoking indicators with leukocyte telomere length (LTL) by race among 5864 nationally representative sample of US adults (≥20 years). Data from 1999 to 2002 National Health and Nutrition Examination Survey was used for the analysis. Smoking indicators were assessed by interviews and serum cotinine levels. LTL was quantified by polymerase chain reaction. Multiple linear regressions were used to assess the association with adjustment for covariates, sample weights and design effects separately for Whites, Blacks and Mexican Americans. The intensity of smoking, measured by the average number of cigarettes consumed per day, was negatively associated with LTL among Whites (ß: -3.87, 95% CI: -5.98 to -1.21) and among Blacks (ß: -15.46, 95% CI: -29.79 to -2.12) participants. Compared with cotinine level < 0.05 ng/ml, cotinine level ≥3 ng/ml was associated with shorter LTL (ß: -77.92, 95% CI = -143.05 to -11.70) among Whites, but not among Blacks. We found increased number of cigarette consumption to be associated with shorter LTL in both Blacks and Whites, indicating that the impact of smoking on life-shortening diseases could partly be explained by telomere biology. Increased cotinine concentration however, was associated with shorter LTL only among Whites, not among Blacks. This differential relationship that we observed may have implications in interpreting cotinine as an objective biomarker of smoking exposure across races and warrant additional prospective investigation.

Circadian CLOCK gene polymorphisms in relation to sleep patterns and obesity in African Americans: findings from the Jackson heart study.

BACKGROUND: Circadian rhythms regulate key biological processes and the dysregulation of the intrinsic clock mechanism affects sleep patterns and obesity onset. The CLOCK (circadian locomotor output cycles protein kaput) gene encodes a core transcription factor of the molecular circadian clock influencing diverse metabolic pathways, including glucose and lipid homeostasis. The primary objective of this study was to evaluate the associations between CLOCK single nucleotide polymorphisms (SNPs) and body mass index (BMI). We also evaluated the association of SNPs with BMI related factors such as sleep duration and quality, adiponectin and leptin, in 2962 participants (1116 men and 1810 women) from the Jackson Heart Study. Genotype data for the selected 23 CLOCK gene SNPS was obtained by imputation with IMPUTE2 software and reference phase data from the 1000 genome project. Genetic analyses were conducted with PLINK RESULTS: We found a significant association between the CLOCK SNP rs2070062 and sleep duration, participants carriers of the T allele showed significantly shorter sleep duration compared to non-carriers after the adjustment for individual proportions of European ancestry (PEA), socio economic status (SES), body mass index (BMI), alcohol consumption and smoking status that reach the significance threshold after multiple testing correction. In addition, we found nominal associations of the CLOCK SNP rs6853192 with longer sleep duration and the rs6820823, rs3792603 and rs11726609 with BMI. However, these associations did not reach the significance threshold after correction for multiple testing. CONCLUSIONS: In this work, CLOCK gene variants were associated with sleep duration and BMI suggesting that the effects of these polymorphisms on circadian rhythmicity may affect sleep duration and body weight regulation in Africans Americans.

Less Than Ideal Cardiovascular Health Is Associated With Shorter Leukocyte Telomere Length: The National Health and Nutrition Examination Surveys, 1999-2002.

BACKGROUND: The associations between individual cardiovascular disease risk factors and leukocyte telomere length (LTL) have been inconclusive. We investigated the association between LTL and overall cardiovascular health (CVH) as defined by the American Heart Association and whether the association is modified by sex and race/ethnicity. METHODS AND RESULTS: We included 5194 adults (aged ≥20) from the National Health and Nutrition Examination Survey 1999-2002. CVH was defined as a composite score of the 7 metrics (smoking, physical activity, diet, body mass index, blood pressure, total cholesterol, and fasting blood glucose) and categorized as "poor," "intermediate," and "ideal." LTL was assayed from whole blood using the quantitative polymerase chain reaction method relative to standard reference DNA. Multivariable linear regression models were used to estimate the association between CVH and log-transformed LTL. We found strong graded association between CVH and LTL in the overall sample, with evidence of dose-response relationship (P for trend=0.013). Individuals with poor and intermediate CVH had significantly shorter LTL than individuals with ideal CVH (-3.4% [95% CI=-6.0%, -0.8%] and -2.4% [-4.4%, -0.3%], respectively), after adjustment for demographic variables, socioeconomic status, and C-reactive protein. The association was stronger in women (-6.6% [-10.2%, -2.9%] for poor vs ideal CVH) and non-Hispanic whites (-4.3% [-7.1%, -1.4%] for poor vs ideal CVH). CONCLUSIONS: The findings suggest that less-than-ideal CVH is associated with shorter LTL, but this association varies by sex and race/ethnicity. Future longitudinal research is needed to elucidate the mechanisms that underlie the association between CVH and LTL.

Obstructive sleep apnea risk and leukocyte telomere length in African Americans from the MH-GRID study.

PURPOSE: Shorter telomere length and obstructive sleep apnea are associated with increased oxidative stress and chronic inflammation, which are both considered leading causes of age-related diseases. Different forms of sleep disordered breathing have been linked to telomere length although their relationship remains uncertain. The purpose of this study was to explore the associations between the risk of obstructive sleep apnea and telomere length in African Americans. METHODS: The analysis included 184 women and 122 men aged 30-55 years from the Morehouse School of Medicine Study. Relative TL (T/S ratio) was measured from peripheral blood leukocytes using quantitative real-time polymerase chain reaction. The Berlin questionnaire was used for OSA risk assessments. Multivariable linear regression models were used to examine the associations between OSA risk and LTL. RESULTS: We observed that LTL varied by OSA risk in women (0.532 ± 0.006 vs. 0.569 ± 0.008) (p = 0.04). Multiple linear regression analysis confirmed that women at higher risk for OSA presented shorter LTL compared to those at lower risk, independent of age, income, education, obesity, smoking, alcohol consumption, and hypertension. These differences were not observed in men. CONCLUSIONS: Our findings suggest that OSA risk may contribute to the acceleration of cellular aging processes through telomere shortening.

Vitamin D Receptor Gene Polymorphisms Are Associated with Abdominal Visceral Adipose Tissue Volume and Serum Adipokine Concentrations but Not with Body Mass Index or Waist Circumference in African Americans: The Jackson Heart Study.

BACKGROUND: The biological actions of vitamin D are mediated through the vitamin D receptor (VDR). Single-nucleotide polymorphisms (SNPs) in the VDR gene have been previously associated with adiposity traits. However, to our knowledge, few studies have included direct measures of adiposity and adipokine concentrations. OBJECTIVE: We examined the association of tagging SNPs in the VDR gene with multiple adiposity measures, including waist circumference (WC), body mass index (BMI), body fat percentage, subcutaneous and visceral adipose tissue (VAT) volume, and serum adipokine (adiponectin and leptin) concentrations in adult African Americans (AAs). METHODS: Data from 3020 participants (61.9% women; mean age, 54.6 y) from the Jackson Heart Study were used for this analysis. Forty-five tag SNPs were chosen with the use of genotype data from the International HapMap project. We used linear regression to test the associations of imputed VDR SNPs with each of the traits, adjusted for age, sex, educational status, physical activity, smoking, alcohol intake, serum vitamin D concentration, European ancestry, and multiple testing. RESULTS: The G allele of the SNP rs4328262 remained associated with increased VAT volume after multiple testing correction (ß = 45.7; P < 0.001). The A allele of another SNP (rs11574070) was nominally associated with body fat percentage (ß = 0.96; P = 0.002). None of the VDR SNPs analyzed showed any link with WC or BMI. The A allele of rs2228570 (ß = 0.08; P = 0.001) for men and the T allele of rs2853563 (ß = 0.04; P < 0.001) for women remained positively associated with serum adiponectin concentrations after multiple testing correction. CONCLUSION: Although we did not find any association for anthropometric measures, we did observe associations of VDR variants with serum adipokines and with the more metabolically active fat, VAT. Therefore, our findings demonstrate a possible role of VDR variants in regulating adipose tissue activity and adiposity among AAs.

Perceived discrimination is associated with health behaviours among African-Americans in the Jackson Heart Study.

BACKGROUND: Using Jackson Heart Study data, we examined associations of multiple measures of perceived discrimination with health behaviours among African-Americans (AA). METHODS: The cross-sectional associations of everyday, lifetime and burden of discrimination with odds of smoking and mean differences in physical activity, dietary fat and sleep were examined among 4925 participants aged 35-84 years after adjustment for age and socioeconomic status (SES). RESULTS: Men reported slightly higher levels of everyday and lifetime discrimination than women and similar levels of burden of discrimination as women. After adjustment for age and SES, everyday discrimination was associated with more smoking and a greater percentage of dietary fat in men and women (OR for smoking: 1.13, 95% CI 1.00 to 1.28 and 1.19, 95% CI 1.05 to 1.34; mean difference in dietary fat: 0.37, p<0.05 and 0.43, p<0.01, in men and women, respectively). Everyday and lifetime discrimination were associated with fewer hours of sleep in men and women (mean difference for everyday discrimination: -0.08, p<0.05 and -0.18, p<0.001, respectively; and mean difference for lifetime discrimination: -0.08, p<0.05 and -0.24, p<0.001, respectively). Burden of discrimination was associated with more smoking and fewer hours of sleep in women only. CONCLUSIONS: Higher levels of perceived discrimination were associated with select health behaviours among men and women. Health behaviours offer a potential mechanism through which perceived discrimination affects health in AA.

Prevalence, associated factors and heritabilities of metabolic syndrome and its individual components in African Americans: the Jackson Heart Study.

OBJECTIVE: Both environmental and genetic factors play important roles in the development of metabolic syndrome (MetS). Studies about its associated factors and genetic contribution in African Americans (AA) are sparse. Our aim was to report the prevalence, associated factors and heritability estimates of MetS and its components in AA men and women. PARTICIPANTS AND SETTING: Data of this cross-sectional study come from a large community-based Jackson Heart Study (JHS). We analysed a total of 5227 participants, of whom 1636 from 281 families were part of a family study subset of JHS. METHODS: Participants were classified as having MetS according to the Adult Treatment Panel III criteria. Multiple logistic regression analysis was performed to isolate independently associated factors of MetS (n=5227). Heritability was estimated from the family study subset using variance component methods (n=1636). RESULTS: About 27% of men and 40% of women had MetS. For men, associated factors with having MetS were older age, lower physical activity, higher body mass index, and higher homocysteine and adiponectin levels (p<0.05 for all). For women, in addition to all these, lower education, current smoking and higher stress were also significant (p<0.05 for all). After adjusting for covariates, the heritability of MetS was 32% (p<0.001). Heritability ranged from 14 to 45% among its individual components. Relatively higher heritability was estimated for waist circumference (45%), high density lipoprotein-cholesterol (43%) and triglycerides (42%). Heritability of systolic blood pressure (BP), diastolic BP and fasting blood glucose was 16%, 15% and 14%, respectively. CONCLUSIONS: Stress and low education were associated with having MetS in AA women, but not in men. Higher heritability estimates for lipids and waist circumference support the hypothesis of lipid metabolism playing a central role in the development of MetS and encourage additional efforts to identify the underlying susceptibility genes for this syndrome in AA.

Gender-specific associations between ADIPOQ gene polymorphisms and adiponectin levels and obesity in the Jackson Heart Study cohort.

BACKGROUND: Despite the important role of adiponectin in regulating general metabolic homeostasis, analysis of genetic determinants of adiponectin and the related cardio-metabolic traits in African American population has been limited and inconsistent. Considering the high genetic admixture of African Americans and thus the important population stratification that may confound the genetic-trait associations, the objective of this work was to perform a comprehensive analysis of the associations between ADIPOQ variants and adiponectin levels and obesity phenotypes in a large African American population from the Jackson Heart Study (JHS) cohort. METHODS: Genotype data was available for 2968 JHS participants (1131men; 1837women). Single Nucleotide Polymorphisms (SNPs) were selected by a Tag-SNP Approach and literature review. The genotype imputation was performed using IMPUTE2 software and reference phased data from the 1000G project. PLINK software was used for the genetic analysis. Plasma specimens were analyzed by ELISA for adiponectin levels. All analyses were controlled for population stratification assessed by Individual Proportions of European Ancestry (PEA) estimates calculated in HAPMIX using ancestry informative markers (AIMs). RESULTS: We found a gender-dependent association of some ADIPOQ variants and adiponectin levels. In women four of the studied polymorphisms (rs6444174, rs16861205, rs1403697, rs7641507) were associated with adiponectin levels after Bonferroni correction and controlling for the percentage of PEA, age, annual household income and smoking. These results were consistent with the haplotype analysis. The association between the rs12495941 variant and obesity is modulated by the PEA, so that the relationship between the G allele and a higher incidence of obesity was present in those individuals within the lower PEA group. In addition we found an effect modification of obesity on the association between the ADIPOQ rs6444174 SNP and BMI so that the presence of the T allele was negatively and significantly associated with BMI only in participants with a normal weight. CONCLUSIONS: In this large African American cohort, ADIPOQ variants were associated with adiponectin levels in a gender-dependent manner and the relationship of some of these variants with obesity and BMI was modulated by the PEA and obesity status respectively. This suggests that the effects of these polymorphisms on adiponectin and obesity phenotypes are subject to a strong interaction with genetic and environmental factors in African American population.

Geographic variations in cardiovascular health in the United States: contributions of state- and individual-level factors.

BACKGROUND: Improving cardiovascular health (CVH) of all Americans by 2020 is a strategic goal of the American Heart Association. Understanding the sources of variation and identifying contextual factors associated with poor CVH may suggest important avenues for prevention. METHODS AND RESULTS: Cross-sectional data from the Behavioral Risk Factor Surveillance System for the year 2011 were linked to state-level coronary heart disease and stroke mortality data from the National Vital Statistics System and to state-level measures of median household income, income inequality, taxes on soda drinks and cigarettes, and food and physical activity environments from various administrative sources. Poor CVH was defined according to the American Heart Association definition using 7 self-reported CVH metrics (current smoking, physical inactivity, obesity, poor diet, hypertension, diabetes, and high cholesterol). Linked micromap plots and multilevel logistic models were used to examine state variation in poor CVH and to investigate the contributions of individual- and state-level factors to this variation. We found significant state-level variation in the prevalence of poor CVH (median odds ratio 1.32, P<0.001). Higher rates of poor CVH and cardiovascular disease mortality were clustered in the southern states. Minority and low socioeconomic groups were strongly associated with poor CVH and explained 44% of the state-level variation in poor CVH; state-level factors explained an additional 28%. State-level median household income (odds ratio 0.89; 95% CI 0.84-0.94), taxes on soda drinks (odds ratio 0.94; 95% CI 0.89-0.99), farmers markets (odds ratio 0.91; 95% CI 0.85-0.98), and convenience stores (odds ratio 1.09; 95% CI 1.01-1.17) were predictive of poor CVH even after accounting for individual-level factors. CONCLUSIONS: There is significant state-level variation in poor CVH that is partly explained by individual- and state-level factors. Additional longitudinal research is warranted to examine the influence of state-level policies and food and physical activity environments on poor CVH.

Primary Aldosteronism and ARMC5 Variants.

CONTEXT: Primary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia. OBJECTIVE: We investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects. METHODS: Patients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods. RESULTS: We identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023). CONCLUSIONS: Germline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension.

Parent-offspring association of metabolic syndrome in the Framingham Heart Study.

BACKGROUND: Metabolic syndrome (MetS) is a clustering of five metabolic risk factors including abdominal obesity, elevated blood pressure, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), and impaired fasting glucose. Few studies have fully reported the strength of clustering of these risk factors in a parent-offspring relationship. This analysis describes the associations between parents and their adult offspring in regard to MetS. It also estimates the association between each risk factor in parents and the presence of MetS in their offspring. METHODS: We analyzed data for 1193 offspring (565 sons, and 628 daughters) from the Framingham Offspring Study who attended examinations 5, 6, and 7. Information about their parents was collected from examinations 13, 14 and 15 of the Framingham Original Cohort study. We used pedigree file to combine parental and offspring's data. Participants were classified as having the MetS according to the Adult Treatment Panel III criteria. Analyses were conducted separately for mothers and fathers. Logistic regression was used to estimate the associations. RESULTS: After adjusting for age, education, smoking, alcohol consumption and physical activity level of offspring, no significant association was found between father's and their offspring's MetS. Mother's MetS was significantly and positively associated with their daughter's MetS (adjusted odds ratio or adj OR: 1.63; 95% confidence Interval, CI:1.02-2.61), but not with their sons' MetS. When analyzed by individual components, maternal impaired glucose (adj OR: 2.03; 95% CI: 1.02- 9.31), abdominal obesity (adj OR: 1.56; 95% CI: 0.98- 2.55) and low HDL-C (adj OR: 2.12; 95% CI: 1.36-3.32) were associated daughter's MetS. Maternal low HDL-C and raised total cholesterol showed marginal association with son's MetS. For fathers, only impaired glucose (adj OR: 4.91; 95% CI: 2.07- 11.68) was associated with their daughter's MetS. CONCLUSIONS: Using the data from Framingham Heart Study, we demonstrate differential association of MetS and its components between parents and offspring. Mother's MetS was strongly related with daughter's MetS, but the association was inconsistent with son's MetS. No association was found between father's MetS and offspring's Mets. These results provide evidence that daughters with mother's MetS are in higher risk than daughters or sons with father's MetS.

Visualization and interpretation of birth defects data using linked micromap plots.

BACKGROUND: Many states have implemented birth defects surveillance systems to monitor and disseminate information regarding birth defects. However, many of these states rely on tabular methods to disseminate statistical birth defects summaries. An innovative presentation technique for birth defect data that portrays the information in a joint geographical and statistical context is the linked micromap (LM) plot. METHODS: LM plots were generated for oral cleft data at two geographical resolutions-USA states and counties of Utah. The LM plots also included demographic and behavioral risk data. RESULTS: A LM plot for the USA reveals spatial patterns indicating higher oral cleft occurrence in the southwest and the midwest and lower occurrence in the east. The LM plot also indicates relationships between oral cleft occurrence and maternal smoking rates and the proportion of American Indians and Alaskan Natives. In particular, the five states with the highest oral cleft occurrence had a higher proportion of American Indians and Alaskan Natives. Among the 15 states with the highest oral cleft occurrence, nine had a smoking rate of 16% or higher while among the 15 states with the lowest oral cleft occurrence only one state had a smoking rate greater than 16%. The LM plot for the state of Utah shows no clear geographic pattern, due perhaps to a relatively small number of cases in a limited geographic area. CONCLUSIONS: LM plots are effective in representing complex and large volume birth defects data. Integration to birth defects surveillance systems will improve both presentation and interpretation.