Co-inheritance of α-thalassemia has a significant protective effect on the severity of complications of sickle cell disease (SCD), including stroke. However, little information exists on the ...association and interactions for the common African ancestral α-thalassemia mutation (-α3.7 deletion) and β-globin traits (HbS trait SCT and HbC trait) on important clinical phenotypes such as red blood cell parameters, anemia, and chronic kidney disease (CKD). In a community-based cohort of 2,916 African Americans from the Jackson Heart Study, we confirmed the expected associations between SCT, HbC trait, and the -α3.7 deletion with lower mean corpuscular volume/mean corpuscular hemoglobin and higher red blood cell count and red cell distribution width. In addition to the recently recognized association of SCT with lower estimated glomerular filtration rate and glycated hemoglobin (HbA1c), we observed a novel association of the -α3.7 deletion with higher HbA1c levels. Co-inheritance of each additional copy of the -α3.7 deletion significantly lowered the risk of anemia and chronic kidney disease among individuals with SCT (P-interaction = 0.031 and 0.019, respectively). Furthermore, co-inheritance of a novel α-globin regulatory variant was associated with normalization of red cell parameters in individuals with the -α3.7 deletion and significantly negated the protective effect of α-thalassemia on stroke in 1,139 patients with sickle cell anemia from the Cooperative Study of Sickle Cell Disease (CSSCD) (P-interaction = 0.0049). Functional assays determined that rs11865131, located in the major alpha-globin enhancer MCS-R2, was the most likely causal variant. These findings suggest that common α- and β-globin variants interact to influence hematologic and clinical phenotypes in African Americans, with potential implications for risk-stratification and counseling of individuals with SCD and SCT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardiovascular prognosis related to type 2 diabetes may not be adequately captured by information on comorbid conditions such as obesity and hypertension. To inform the cardiovascular prognosis among ...diabetic individuals, we conducted phenotyping using a clustering approach based on clinical data, echocardiographic indices and biomarkers.
We performed a cluster analysis on clinical, biochemical and echocardiographic variables from 529 Blacks with diabetes in the Jackson Heart Study. An association between identified clusters and major adverse cardiovascular events (MACE- composite of coronary heart disease, stroke, heart failure and atrial fibrillation) was assessed using Cox proportional hazards modeling.
Cluster analysis separated individuals with diabetes (68% women, mean age 60 ± 10 years) into three distinct clusters (Clusters 1,2 &3 - with Cluster 3 being a hypertrophic cluster characterized by highest LV mass, levels of brain natriuretic peptide BNP and high-sensitivity cardiac troponin-I hs-cTnI). After a median 12.1 years, there were 141 cardiovascular events. Compared to Cluster1, Clusters 3 had an increased risk of cardiovascular disease (hazard ratio HR 1.60; 95% confidence interval CI 1.08, 2.37), while Cluster 2 had a similar risk of outcome (HR 1.11; 95% CI 0.73, 168).
Among Blacks with diabetes, cluster analysis identified three distinct echocardiographic and biomarkers phenotypes, with cluster 3 (high LV mass, high cardiac biomarkers) associated with worse outcomes, thus highlighting the prognostic value of subclinical myocardial dysfunction.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Characterizing associations of sleep characteristics with blood-glucose-level factors among blacks may clarify the underlying mechanisms of impaired glucose metabolism and help identify ...treatment targets to prevent diabetes mellitus in blacks. Methods and Results Cross-sectional analyses were conducted in 789 blacks who completed home sleep apnea testing and 7-day wrist actigraphy in 2012-2016. Sleep-disordered breathing measurements included respiratory event index associated with 4% oxygen desaturation and minimum oxygen saturation. Sleep patterns on actigraphy included fragmented sleep indices. Associations between sleep characteristics (8 exposures) and measures of glucose metabolism (3 outcomes) were determined using multivariable linear regression. Mean (SD) age of the participants was 63 (11) years; 581 (74%) were women; 198 (25%) were diabetes mellitus, and 158 (20%) were taking antihyperglycemic medication. After multivariable adjustment, including antihyperglycemic medication use, the betas (95% CI) for fasting glucose and hemoglobin A1c, respectively, for each SD higher level were 0.13 (0.02, 0.24) mmol/L and 1.11 (0.42, 1.79) mmol/mol for respiratory event index associated with 4% oxygen desaturation and 0.16 (0.05, 0.27) mmol/L and 0.77 (0.10, 1.43) mmol/mol for fragmented sleep indices. Among 589 participants without diabetes mellitus, the betas (95% CI) for homeostatic model assessment of insulin resistance for each SD higher level were 1.09 (1.03, 1.16) for respiratory event index associated with 4% oxygen desaturation, 0.90 (0.85, 0.96) for minimum oxygen saturation, and 1.07 (1.01, 1.13) for fragmented sleep indices. Conclusions Sleep-disordered breathing, overnight hypoxemia, and sleep fragmentation were associated with higher blood glucose levels among blacks.
Nutrients that regulate methylation processes may modify susceptibility to the effects of air pollutants. Data from the National Birth Defects Prevention Study (United States, 1997-2006) were used to ...estimate associations between maternal exposure to nitrogen dioxide (NO2), dietary intake of methyl nutrients, and the odds of congenital heart defects in offspring. NO2 concentrations, a marker of traffic-related air pollution, averaged across postconception weeks 2-8, were assigned to 6,160 nondiabetic mothers of cases and controls using inverse distance-squared weighting of air monitors within 50 km of maternal residences. Intakes of choline, folate, methionine, and vitamins B6 and B12 were assessed using a food frequency questionnaire. Hierarchical regression models, which accounted for similarities across defects, were constructed, and relative excess risks due to interaction were calculated. Relative to women with the lowest NO2 exposure and high methionine intake, women with the highest NO2 exposure and lowest methionine intake had the greatest odds of offspring with a perimembranous ventricular septal defect (odds ratio = 3.23, 95% confidence interval: 1.74, 6.01; relative excess risk due to interaction = 2.15, 95% confidence interval: 0.39, 3.92). Considerable departure from additivity was not observed for other defects. These results provide modest evidence of interaction between nutrition and NO2 exposure during pregnancy.
Although maternal age has been associated with a number of birth defects in several reports, the literature on the association of maternal age with isolated congenital heart defect (CHD) phenotypes ...has been limited. We evaluated CHD prevalence based on a cohort of 5,289 infants and fetuses with isolated CHDs born during the period 1968–2005 and ascertained by the Metropolitan Atlanta Congenital Defects Program (MACDP) among residents of five central counties in Atlanta. For our denominator, we obtained information on births to residents of the same counties from vital records (n = 1,301,143). We calculated prevalence ratios for 23 CHD phenotypes by several maternal age categories, using the group 25–29 years of age as a reference group. We used Poisson regression models to estimate adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), controlling for maternal race, infant sex, and birth cohort. A maternal age of 35 years or older was associated with an increased prevalence for several CHD phenotypes: laterality defects (aPR = 2.06; CI 1.22–3.48), all conotruncal defects (aPR = 1.30; CI 1.03–1.65), and specifically for dextro‐transposition of the great arteries (aPR = 1.65; CI 1.10–2.48), coarctation of the aorta (aPR = 1.54; CI 1.10–2.16), ventricular septal defects (aPR = 1.20; CI 1.06–1.36), and atrial septal defects (aPR = 1.36; CI 1.05–1.77). Our findings suggest that the birth prevalence of specific isolated CHDs varies with maternal age. Further studies are warranted to corroborate these observations, taking into account potential confounding by known modifiable risk factors. Published 2011 Wiley‐Liss, Inc.
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.
Objective To identify the proportion of major structural noncardiac anomalies identified with congenital heart defects (CHDs). Study design Records of infants with CHDs in the Metropolitan Atlanta ...Congenital Defects Program who were born during the period 1968 through 2005 were classified as having isolated, syndromic, multiple CHD (ie, having an unrecognized pattern of multiple congenital anomalies or a recognized pattern of multiple congenital anomalies of unknown etiology), or laterality defects. Frequencies of associated noncardiac anomalies were obtained. Results We identified 7984 live-born and stillborn infants and fetuses with CHDs. Among them, 5695 (71.3%) had isolated, 1080 (13.5%) had multiple, 1048 (13.1%) had syndromic, and 161 (2.0%) had laterality defects. The percentage of multiple congenital anomalies was highest for case with atrial septal defects (18.5%), cardiac looping defects (17.2%), and conotruncal defects (16.0%), and cases with atrioventricular septal defects represented the highest percentages of those with syndromic CHDs (66.7%). Conclusions Including those with syndromes and laterality defects, 28.7% of case infants with CHDs had associated major noncardiac malformations. Thus, infants with CHDs warrant careful examination for the presence of noncardiac anomalies.
Growing evidence suggests that leptin is critical for glycemic control. Impaired leptin signaling may also contribute to low adiponectin expression in obese individuals. We assessed the association ...of leptin and adiponectin with incident type 2 diabetes (T2D), their interactions with sex and obesity status, and mediation by insulin resistance.
We included study participants from the Jackson Heart Study, a prospective cohort of adult African Americans in Jackson, Mississippi, that were free of T2D at the baseline Exam 1. Incident T2D was defined as new cases at Exam 2 or Exam 3. We created separate Cox regression models (hazard ratios per log-transformed ng/mL of leptin and adiponectin) with and without insulin resistance, HOMA-IR. Mediation by insulin resistance was analyzed. Several interactions were assessed, including by sex, HbA1c, and obesity.
Among our 3363 participants (mean age 53 years, 63% women), 584 developed incident T2D. Leptin was directly associated with incident T2D when modeled without HOMA-IR (HR = 1.29, 95% CI = 1.05-1.58). This direct association between leptin and T2D was significant among men (HR = 1.33, 95% CI = 1.05-1.69), but nonsignificant among women (HR = 1.24, 95% CI = 0.94-1.64); statistical interaction with sex was nonsignificant (p = 0.65). The associations in all participants and in men were nullified by HOMA-IR (HR = 0.99, 95% CI = 0.80-1.22; HR = 1.00, 95% CI = 0.78-1.28, respectively), indicating mediation through insulin resistance (proportion mediated: 1.04), and were not observed in abdominally obese participants. Adiponectin was inversely associated with T2D even after adjustment for HOMA-IR in women (HR = 0.68, 95% CI = 0.55-0.84), but not in men (HR = 0.80, 95% CI = 0.62-1.04). The inverse association was present only among abdominally obese participants, and persisted after adjustment for HOMA-IR.
Among African Americans in the Jackson Heart Study the association of leptin with incident type 2 diabetes was mediated by insulin resistance. This association was present only among abdominally non-obese participants. Differences by sex appeared: men showed a significant association mediated by insulin resistance. Among abdominally obese participants, adiponectin was inversely associated with incident T2D even after adjustment for HOMA-IR. Our results should inform future clinical trials that aim to reduce the burden of type 2 diabetes through the modification of serum levels of leptin and adiponectin.
Objectives. Orofacial clefts are common birth defects that often require multiple surgeries and medical treatments during childhood. We used health-care insurance claims data to estimate health-care ...expenditures for infants and children ≤10 years of age with an orofacial cleft. Methods. The data were derived from the 2000–2004 MarketScan® Commercial Claims and Encounters databases, which include person-specific information on health-care use, expenditures, and enrollment for approximately 50 large employers, health plans, and government and public organizations. Health insurance claims data from 821,619 children ≤10 years of age enrolled in employer-sponsored plans during 2004 were analyzed. Expenditures for inpatient admissions, outpatient services, and prescription drug claims were calculated for children with and those without an orofacial cleft. Results. The difference in annual mean costs (i.e., incremental costs) between children aged 0 through 10 years with an orofacial cleft and those without an orofacial cleft was $13,405. The mean and median costs for children ≤10 years of age with an orofacial cleft were eight times higher than for children of the same age without an orofacial cleft. Mean costs for infants with a cleft and another major, unrelated defect were 25 times higher than those for an infant without a cleft, and five times higher than for infants with an isolated cleft. Conclusion. These findings document substantially elevated medical care costs for privately insured children with an orofacial cleft. Additional study of the economic burden associated with this condition should include a broader range of economic costs.
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