April P. Carson

Comparison of A1C and fasting glucose criteria to diagnose diabetes among U.S. adults.

OBJECTIVE To compare A1C and fasting glucose for the diagnosis of diabetes among U.S. adults. RESEARCH DESIGN AND METHODS This study included 6,890 adults (≥20 years of age) from the 1999–2006 National Health and Nutrition Examination Survey without a self-reported history of diabetes who had fasted ≥9 h. A1C ≥6.5% and fasting glucose ≥126 mg/dl were used, separately, to define diabetes. RESULTS Overall, 1.8% of U.S. adults had A1C ≥6.5% and fasting glucose ≥126 mg/dl, 0.5% had A1C ≥6.5% and fasting glucose <126 mg/dl, and 1.8% had A1C <6.5% and fasting glucose ≥126 mg/dl. Compared with individuals with A1C <6.5% and fasting glucose ≥126 mg/dl, individuals with A1C ≥6.5% and fasting glucose <126 mg/dl were younger, more likely to be non-Hispanic black, had lower Hb levels, and had higher C-reactive protein. CONCLUSIONS A1C ≥6.5% demonstrates reasonable agreement with fasting glucose for diagnosing diabetes among U.S. adults.

Ethnic Differences in Hypertension Incidence Among Middle-Aged and Older Adults The Multi-Ethnic Study of Atherosclerosis

The prevalence of hypertension is higher among blacks than whites. However, inconsistent findings have been reported on the incidence of hypertension among middle-aged and older blacks and whites, and limited data are available on the incidence of hypertension among Hispanics and Asians in the United States. Therefore, this study investigated the age-specific incidence of hypertension by ethnicity for 3146 participants from the Multi-Ethnic Study of Atherosclerosis. Participants, age 45 to 84 years at baseline, were followed for a median of 4.8 years for incident hypertension, defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or the initiation of antihypertensive medications. The crude incidence rate of hypertension, per 1000 person-years, was 56.8 for whites, 84.9 for blacks, 65.7 for Hispanics, and 52.2 for Chinese. After adjustment for age, sex, and study site, the incidence rate ratio (IRR) for hypertension was increased for blacks age 45 to 54 (IRR: 2.05 [95%CI: 1.47 to 2.85]), 55 to 64 (IRR: 1.63 [95% CI: 1.20 to 2.23]), and 65 to 74 years (IRR: 1.67 [95% CI: 1.21 to 2.30]) compared with whites but not for those 75 to 84 years of age (IRR: 0.97 [95% CI: 0.56 to 1.66]). Additional adjustment for health characteristics attenuated these associations. Hispanic participants also had a higher incidence of hypertension compared with whites; however, hypertension incidence did not differ for Chinese and white participants. In summary, hypertension incidence was higher for blacks compared with whites between 45 and 74 years of age but not after age 75 years. Public health prevention programs tailored to middle-aged and older adults are needed to eliminate ethnic disparities in incident hypertension.

Impact of A1C screening criterion on the diagnosis of pre-diabetes among U.S. adults.

OBJECTIVE New clinical practice recommendations include A1C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Survey 1999–2006 (n = 7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7–6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100–125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated. RESULTS The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7% of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respectively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with IFG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassified). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value. CONCLUSIONS Using A1C as the pre-diabetes criterion would reclassify the pre-diabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes.

Low Hemoglobin A1c and Risk of All-Cause Mortality Among US Adults Without Diabetes

Background—Among individuals without diabetes, elevated hemoglobin A1c (HbA1c) has been associated with increased morbidity and mortality, but the literature is sparse regarding the prognostic importance of low HbA1c. Methods and Results—National Health and Nutrition Examination Survey III (NHANES III) participants, 20 years and older, were followed up to 12 years (median follow-up, 8.8 years) for all-cause mortality. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between HbA1c levels and all-cause mortality for 14 099 participants without diabetes. There were 1825 deaths during the follow-up period. Participants with a low HbA1c (<4.0%) had the highest levels of mean red blood cell volume, ferritin, and liver enzymes and the lowest levels of mean total cholesterol and diastolic blood pressure compared with their counterparts with HbA1c levels between 4.0% and 6.4%. An HbA1c <4.0% versus 5.0% to 5.4% was associated with an increased risk of all-cause mortality (HR, 3.73; 95% CI, 1.45 to 9.63) after adjustment for age, race-ethnicity, and sex. This association was attenuated but remained statistically significant after further multivariable adjustment for lifestyle, cardiovascular factors, metabolic factors, red blood cell indices, iron storage indices, and liver function indices (HR, 2.90; 95% CI, 1.25 to 6.76). Conclusions—In this nationally representative cohort, low HbA1c was associated with increased all-cause mortality among US adults without diabetes. Additional research is needed to confirm these results and identify potential mechanisms that may be underlying this association.

Association of the Metabolic Syndrome With Atrial Fibrillation Among United States Adults (from the REasons for Geographic and Racial Differences in Stroke [REGARDS] Study)

Metabolic syndrome (MS) and atrial fibrillation (AF) are associated with increased cardiovascular disease morbidity and mortality. This analysis evaluated the association between MS and AF in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. MS was defined using criteria recommended in the joint interim statement from several international societies. AF was defined by electrocardiogram (ECG) and/or self-report and by ECG alone. In patients with 0, 1, 2, 3, 4, and 5 MS components, prevalences of AF by ECG and/or self-report were 5.5%, 7.7%, 8.2%, 9.2%, 9.6%, and 11.5%, respectively (p for trend <0.001). After multivariable adjustment, each MS component except serum triglycerides was significantly associated with AF. The multivariable-adjusted odds ratio for AF, defined by ECG and/or or self-reported history, comparing those with to those without MS was 1.20 (95% confidence interval 1.10 to 1.29). Results were consistent when AF was defined by ECG alone (odds ratio 1.15, 95% confidence interval 0.92 to 1.39). In conclusion, MS is associated with an increased prevalence of AF. Further studies investigating a potential mechanism for this excess risk are warranted.

Racial Differences in Abnormal Ambulatory Blood Pressure Monitoring Measures: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study

BACKGROUND Several ambulatory blood pressure monitoring (ABPM) measures have been associated with increased cardiovascular disease risk independent of clinic blood pressure (BP). African Americans have higher clinic BP compared with Whites but few data are available on racial differences in ABPM measures. METHODS We compared ABPM measures between African American (n = 178) and White (n = 103) participants at the Year 5 Coronary Artery Risk Development in Young Adults study visit. BP was measured during a study visit and the second and third measurements were averaged. ABPM was conducted over the following 24 hours. RESULTS Mean ± SD age of participants was 29.8 ± 3.8 years and 30.8 ± 3.5 years for African Americans and Whites, respectively. Mean daytime systolic BP (SBP) was 3.90 (SD 1.18) mm Hg higher among African Americans compared with Whites (P < 0.001) after age-gender adjustment and 1.71 (SD 1.03) mm Hg higher after multivariable adjustment including mean clinic SBP (P = 0.10). After multivariable adjustment including mean clinic SBP, nighttime SBP was 4.83 (SD 1.11) mm Hg higher among African Americans compared with Whites (P < 0.001). After multivariable adjustment, the African Americans were more likely than Whites to have nocturnal hypertension (prevalence ratio: 2.44, 95% CI: 0.99-6.05) and nondipping (prevalence ratio: 2.50, 95% CI: 1.39-4.48). The prevalence of masked hypertension among African Americans and Whites was 4.4% and 2.1%, respectively, (P = 0.49) and white coat hypertension was 3.3% and 3.9%, respectively (P = 0.99). Twenty-four hour BP variability on ABPM was higher among African Americans compared with Whites. CONCLUSIONS These data suggest racial differences in several ABPM measures exist.

Depressive symptoms and cardiovascular health by the American Heart Association's definition in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Background Depressive symptoms are associated with increased incident and recurrent cardiovascular events. In 2010, the American Heart Association published the Life’s Simple 7, a metric for assessing cardiovascular health as measured by 4 health behaviors (smoking, physical activity, body mass index, diet) and 3 biological measures (cholesterol, blood pressure, glucose). The association between depressive symptoms and the Life’s Simple 7 has not yet been explored. Methods Data from 20,093 participants ≥45 years of age who enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 and who had complete data available on Life’s Simple 7 components were used for these analyses. The prevalence of ideal, intermediate, and poor health on each Life’s Simple 7 component and total Life’s Simple 7 scores were compared between participants with and without depressive symptoms. Depressive symptoms were measured using the 4-item Centers for Epidemiologic Studies of Depression scale. Results Participants with depressive symptoms were more likely to have poor levels on each of the Life’s Simple 7 components other than cholesterol [adjusted prevalence ratios (95% CI): smoking 1.41 (1.29–1.55); physical activity 1.38 (1.31–1.46); body mass index 1.09 (1.04–1.15); diet 1.08 (1.06–1.10); blood pressure 1.11 (1.02–1.21); glucose 1.24 (1.09–1.41)]. There was a graded association between increasing depressive symptoms and lower total Life’s Simple 7 score. Conclusion Depressive symptoms are associated with worse cardiovascular health on the overall Life’s Simple 7 and on individual components representing both health behaviors and biological factors.

Comparison of the Framingham Heart Study Hypertension Model With Blood Pressure Alone in the Prediction of Risk of Hypertension The Multi-Ethnic Study of Atherosclerosis

A prediction model, developed in the Framingham Heart Study (FHS), has been proposed for use in estimating a given individuals risk of hypertension. We compared this model with systolic blood pressure (SBP) alone and age-specific diastolic blood pressure categories for the prediction of hypertension. Participants in the Multi-Ethnic Study of Atherosclerosis, without hypertension or diabetes mellitus (n=3013), were followed for the incidence of hypertension (SBP ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg and/or the initiation of antihypertensive medication). The predicted probability of developing hypertension among 4 adjacent study examinations, with a median of 1.6 years between examinations, was determined. The mean (SD) age of participants was 58.5 (9.7) years, and 53% were women. During follow-up, 849 incident cases of hypertension occurred. The c statistic for the FHS model was 0.788 (95% CI: 0.773 to 0.804) compared with 0.768 (95% CI: 0.751 to 0.785; P=0.096 compared with the FHS model) for SBP alone and 0.699 (95% CI: 0.681 to 0.717; P<0.001 compared with the FHS model) for age-specific diastolic blood pressure categories. The relative integrated discrimination improvement index for the FHS model versus SBP alone was 10.0% (95% CI: −1.7% to 22.7%) and versus age-specific diastolic blood pressure categories was 146.0% (95% CI: 116.0% to 181.0%). Using the FHS model, there were significant differences between observed and predicted hypertension risks (Hosmer-Lemeshow goodness of fit: P<0.001); recalibrated and best-fit models produced a better model fit (P=0.064 and 0.245, respectively). In this multiethnic cohort of US adults, the FHS model was not substantially better than SBP alone for predicting hypertension.

Hemoglobin A1c and the Progression of Coronary Artery Calcification Among Adults Without Diabetes

OBJECTIVE Higher levels of hemoglobin A1c (HbA1c) are associated with increased cardiovascular disease risk among individuals without diabetes and may also be positively associated with coronary artery calcification (CAC). This study investigated the association of HbA1c with CAC progression in the Coronary Artery Risk Development in Young Adults study. RESEARCH DESIGN AND METHODS We included 2,076 participants with HbA1c and noncontrast computed tomography (CT) assessed at baseline (2005–2006), and CT repeated 5 years later (2010–2011). CAC progression was defined as 1) incident CAC (increase >0 Agatston units among those with no CAC at baseline), 2) any CAC progression (increase >10 Agatston units between examinations), and 3) advanced CAC progression (increase >100 Agatston units between examinations). RESULTS During the 5-year follow-up period, 12.9% of participants without baseline CAC developed incident CAC; among all participants, 18.2% had any CAC progression and 5.4% had advanced CAC progression. Higher HbA1c was associated with incident CAC (risk ratio [RR] = 1.45; 95% CI 1.02, 2.06), any CAC progression (RR = 1.51; 95% CI 1.16, 1.96), and advanced CAC progression (RR = 2.42; 95% CI 1.47, 3.99) after adjustment for sociodemographic factors. Additional adjustment for cardiovascular risk factors attenuated the associations of HbA1c with incident CAC (RR = 1.05; 95% CI 0.74, 1.49) and any CAC progression (RR = 1.13; 95% CI 0.87, 1.47). In contrast, the association of HbA1c with advanced CAC progression persisted in multivariable adjusted models (RR = 1.78; 95% CI 1.08, 2.95). CONCLUSIONS Higher HbA1c was independently associated with advanced CAC progression among individuals without diabetes, while the associations with incident CAC and any CAC progression were accounted for by other established cardiovascular risk factors.

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.