Mary E. Lacy

High-Sensitivity C-Reactive Protein Is Associated With Incident Type 2 Diabetes Among African Americans: The Jackson Heart Study

OBJECTIVE Previous studies on the association between hs-CRP and incident type 2 diabetes among African Americans have been inconclusive. We examined the association between hs-CRP and incident diabetes in a large African American cohort (Jackson Heart Study). RESEARCH DESIGN AND METHODS hs-CRP was measured in 3,340 participants. Incident diabetes was defined by fasting glucose ≥126 mg/dL, physician diagnosis, use of diabetes drugs, or A1C ≥6.5% (48 mmol/mol) at follow-up. Cox regression was used to estimate hazard ratios (HRs) for incident diabetes, adjusting for age, sex, education, diabetes family history, alcohol, HDL, triglycerides, hypertension status, hypertension medications, physical activity, BMI, HOMA-insulin resistance (HOMAIR), and waist circumference. RESULTS Participants (63% women) were aged 53.3 ± 12.5 years. During a median follow-up of 7.5 years, 17.4% developed diabetes (23.1/1,000 person-years, 95% CI 21.3–25.1). After adjustment, the HR (hs-CRP third vs. first tertile) was 1.64 (95% CI 1.26–2.13). In separate models, further adjustment for BMI and waist circumference attenuated this association (HR 1.28 [95% CI 0.97–1.69] and 1.35 [95% CI 1.03–1.78, P < 0.05 for trend], respectively). Upon adding HOMAIR in the models, the association was no longer significant. In adjusted HOMAIR-stratified analysis, the hs-CRP–diabetes association appeared stronger in participants with HOMAIR <3.0 compared with HOMAIR ≥3.0 (P < 0.0001 for interaction). The association was also stronger among nonobese participants, although not significant when adjusted for HOMAIR. CONCLUSIONS Low-grade inflammation, as measured by hs-CRP level, may have an important role in the development of diabetes among African Americans with a lesser degree of insulin resistance.

Association of sickle cell trait with hemoglobin A1c in African Americans

Importance Hemoglobin A1c (HbA1c) reflects past glucose concentrations, but this relationship may differ between those with sickle cell trait (SCT) and those without it. Objective To evaluate the association between SCT and HbA1c for given levels of fasting or 2-hour glucose levels among African Americans. Design, Setting, and Participants Retrospective cohort study using data collected from 7938 participants in 2 community-based cohorts, the Coronary Artery Risk Development in Young Adults (CARDIA) study and the Jackson Heart Study (JHS). From the CARDIA study, 2637 patients contributed a maximum of 2 visits (2005-2011); from the JHS, 5301 participants contributed a maximum of 3 visits (2000-2013). All visits were scheduled at approximately 5-year intervals. Participants without SCT data, those without any concurrent HbA1c and glucose measurements, and those with hemoglobin variants HbSS, HbCC, or HbAC were excluded. Analysis of the primary outcome was conducted using generalized estimating equations (GEE) to examine the association of SCT with HbA1c levels, controlling for fasting or 2-hour glucose measures. Exposures Presence of SCT. Main Outcomes and Measures Hemoglobin A1c stratified by the presence or absence of SCT was the primary outcome measure. Results The analytic sample included 4620 participants (mean age, 52.3 [SD, 11.8] years; 2835 women [61.3%]; 367 [7.9%] with SCT) with 9062 concurrent measures of fasting glucose and HbA1c levels. In unadjusted GEE analyses, for a given fasting glucose, HbA1c values were statistically significantly lower in those with (5.72%) vs those without (6.01%) SCT (mean HbA1c difference, −0.29%; 95% CI, −0.35% to −0.23%). Findings were similar in models adjusted for key risk factors and in analyses using 2001 concurrent measures of 2-hour glucose and HbA1c concentration for those with SCT (mean, 5.35%) vs those without SCT (mean, 5.65%) for a mean HbA1c difference of −0.30% (95% CI, −0.39% to −0.21%). The HbA1c difference by SCT was greater at higher fasting (P = .02 for interaction) and 2-hour (P = .03) glucose concentrations. The prevalence of prediabetes and diabetes was statistically significantly lower among participants with SCT when defined using HbA1c values (29.2% vs 48.6% for prediabetes and 3.8% vs 7.3% for diabetes in 572 observations from participants with SCT and 6877 observations from participants without SCT; P<.001 for both comparisons). Conclusions and Relevance Among African Americans from 2 large, well-established cohorts, participants with SCT had lower levels of HbA1c at any given concentration of fasting or 2-hour glucose compared with participants without SCT. These findings suggest that HbA1c may systematically underestimate past glycemia in black patients with SCT and may require further evaluation.

Racial Differences in the Performance of Existing Risk Prediction Models for Incident Type 2 Diabetes: The CARDIA Study

OBJECTIVE In 2010, the American Diabetes Association (ADA) added hemoglobin A1c (A1C) to the guidelines for diagnosing type 2 diabetes. However, existing models for predicting diabetes risk were developed prior to the widespread adoption of A1C. Thus, it remains unknown how well existing diabetes risk prediction models predict incident diabetes defined according to the ADA 2010 guidelines. Accordingly, we examined the performance of an existing diabetes prediction model applied to a cohort of African American (AA) and white adults from the Coronary Artery Risk Development Study in Young Adults (CARDIA). RESEARCH DESIGN AND METHODS We evaluated the performance of the Atherosclerosis Risk in Communities (ARIC) diabetes risk prediction model among 2,456 participants in CARDIA free of diabetes at the 2005–2006 exam and followed for 5 years. We evaluated model discrimination, calibration, and integrated discrimination improvement with incident diabetes defined by ADA 2010 guidelines before and after adding baseline A1C to the prediction model. RESULTS In the overall cohort, re-estimating the ARIC model in the CARDIA cohort resulted in good discrimination for the prediction of 5-year diabetes risk (area under the curve [AUC] 0.841). Adding baseline A1C as a predictor improved discrimination (AUC 0.841 vs. 0.863, P = 0.03). In race-stratified analyses, model discrimination was significantly higher in whites than AA (AUC AA 0.816 vs. whites 0.902; P = 0.008). CONCLUSIONS Addition of A1C to the ARIC diabetes risk prediction model improved performance overall and in racial subgroups. However, for all models examined, discrimination was better in whites than AA. Additional studies are needed to further improve diabetes risk prediction among AA.

Temporal Trends and Hospital Variation in Mineralocorticoid Receptor Antagonist Use in Veterans Discharged With Heart Failure

Background Despite concerns about mineralocorticoid receptor antagonist therapies (MRAs) underuse and misuse in patients with heart failure, temporal and institutional variations of MRA prescription have not been reported. Methods and Results We studied a national sample of veterans hospitalized for heart failure between 2003 and 2009 and left ventricular ejection fraction <40%. We identified ideal and non‐ideal candidates for MRA therapy based on American College of Cardiology/American Heart Association guidelines. We measured temporal trends and hospital variation of MRA prescriptions within 90 days after discharge. We determined the median odds ratio (MOR), a measure of the relative odds of an MRA prescription for 2 individuals with similar characteristics discharged at 2 randomly selected hospitals. From 37 126 patients (n=131 hospitals), 9355 were ideal‐MRA candidates, and 4056 were non‐ideal candidates. Among ideal candidates, 36% received an MRA, but there was a decline in use (41% in 2003 to 31% in 2009, P<0.001). Of non‐ideal candidates, 27% received an MRA with a decline in use (34% in 2003 to 22% in 2009, P<0.001). Hospital MRA prescription ranged from 0% to 71% for ideal candidates and 0% to 100% for non‐ideal candidates. The median odds ratios of MRA prescription for ideal and non‐ideal candidates were 1.44 and 1.36, respectively; a median odds ratio >1.2 indicates significant practice‐level variation. Conclusions There was decreasing MRA use between 2003 and 2009 with wide institutional variation in MRA prescription, which suggests opportunities for improvement to stimulate MRA use in ideal candidates while further reducing use in those with contraindications.

Epidemiological Study Designs: Traditional and Novel Approaches to Advance Life Course Health Development Research

The central focus of life course epidemiology and life course approaches to health development is on the complex processes underlying the occurrence and accrual of risks at multiple levels and their impact on the developing individual. Reflecting the multilevel and integrated features of human health development that are at the centre of life course health-development (LCHD) principles, study designs seek better understanding of social, familial, and genetic contributions to the aetiology of health conditions, exploring the timing and interactions of different experiences and risks in relationship to the natural course of disorders in different populations and examining the time-specific and cumulative impacts of social and environmental factors. Many different study designs can advance a life course health-development framework. In this chapter we review common epidemiologic study designs including (i) cohort studies (general prospective cohort studies, perinatal/birth cohorts, twin studies, and high-risk cohort studies); (ii) case–control studies, including nested case–control studies within larger cohorts; (iii) cross-sectional studies; (iv) quasi-experimental designs; and (v) randomized controlled trials (RCTs). Although certain design strategies, namely, cohort studies, lend themselves more readily to the life course approach—examining the process of health development and its emphasis on emergent, person-context relations, and plasticity across the lifespan—we also describe other study designs that can be used to further our understanding of health and the development of different disorders and diseases from the life course perspective. The benefits and limitations of alternative design approaches are discussed using one study question as an example—investigating the relationship between traumatic experience and the development of a substance use disorder.

Prediction of Incident Diabetes in the Jackson Heart Study Using High-Dimensional Machine Learning

Statistical models to predict incident diabetes are often based on limited variables. Here we pursued two main goals: 1) investigate the relative performance of a machine learning method such as Random Forests (RF) for detecting incident diabetes in a high-dimensional setting defined by a large set of observational data, and 2) uncover potential predictors of diabetes. The Jackson Heart Study collected data at baseline and in two follow-up visits from 5,301 African Americans. We excluded those with baseline diabetes and no follow-up, leaving 3,633 individuals for analyses. Over a mean 8-year follow-up, 584 participants developed diabetes. The full RF model evaluated 93 variables including demographic, anthropometric, blood biomarker, medical history, and echocardiogram data. We also used RF metrics of variable importance to rank variables according to their contribution to diabetes prediction. We implemented other models based on logistic regression and RF where features were preselected. The RF full model performance was similar (AUC = 0.82) to those more parsimonious models. The top-ranked variables according to RF included hemoglobin A1C, fasting plasma glucose, waist circumference, adiponectin, c-reactive protein, triglycerides, leptin, left ventricular mass, high-density lipoprotein cholesterol, and aldosterone. This work shows the potential of RF for incident diabetes prediction while dealing with high-dimensional data.

Measurement of Hemoglobin A1c in Patients With Sickle Cell Trait—Reply

Author Contributions: Mr Kahn and Ms Gardin had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: All authors. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: All authors. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: All authors. Administrative, technical, or material support: Gardin.

Inflammatory Obesity Phenotypes, Gender Effects, and Subclinical Atherosclerosis in African Americans: The Jackson Heart Study.

Objective—Reasons for variations in atherosclerotic burden among individuals with similar levels of obesity are poorly understood, especially in African Americans. This study examines whether high-sensitivity C-reactive protein (hsCRP) is useful for discriminating between benign and high-risk obesity phenotypes for subclinical atherosclerosis in African Americans. Approach and Results—Participants from the Jackson Heart Study (n=4682) were stratified into 4 phenotypes based on the presence of National Heart and Lung and Blood Institute definition of obesity or obesity-equivalent (body mass index ≥30 or body mass index 25–30 with waist circumference >102 cm in men and >88 cm in women) and inflammation by hsCRP ≥2 mg/L. Using multivariate regression models, we conducted cross-sectional analyses of the association between inflammatory obesity phenotypes and subclinical atherosclerosis determined by carotid intima–media thickness or coronary artery calcium scores. Sex-specific analyses were conducted given significant interaction for gender (P=0.03). The prevalence of obesity or equivalent was 65%, of which 30% did not have inflammation. Conversely, 37% of nonobese individuals had inflammation. Among nonobese men, hsCRP ≥2 mg/L identified a subset of individuals with higher carotid intima–media thickness (adjusted mean difference =0.05, 95% confidence interval 0.02, 0.08 mm) compared with their noninflammatory counterparts. Among obese men, hsCRP <2 mg/L identified a subset of individuals with lower coronary artery calcium compared with their inflammatory counterparts. Among women, associations between hsCRP and carotid intima–media thickness or coronary artery calcium were not found. Conclusions—In the largest African American population-based cohort to date, hsCRP was useful in identifying a subset of nonobese men with higher carotid intima–media thickness, but not in women. hsCRP did not identify a subset of obese individuals with less subclinical atherosclerosis.