Socioeconomic Status, Antioxidant Micronutrients, and Correlates of Oxidative Damage: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

OBJECTIVE: To examine whether socioeconomic status (SES) (education, occupation, income), is associated both cross sectionally and prospectively with circulating concentrations of a) two correlates of oxidative damage, F(2)-isoprostanes (F(2)-IsoPs) and gamma-glutamyltransferase (GGT); and b) antioxidant nutrients (ascorbic acid and carotenoids). We also examine whether the proposed associations are mediated by smoking, alcohol consumption, and depression. Risk for chronic disease increases with decreasing SES. One pathway by which low SES might influence disease risk is by promoting oxidative stress. METHODS: Data from 1278 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the association of SES with oxidation correlates and antioxidant nutrients. Education, occupation, health behaviors, and body mass index (BMI) were assessed during Years 0, 10, and 15 of the study; income and depression were evaluated at Years 10 and 15. F(2)-isoprostanes were measured at Year 15, gamma-glutamyltransferase (GGT) at Years 0 and 10, carotenoids at Years 0 and 15, and ascorbic acid at Years 10 and 15. RESULTS: Cross sectionally, oxidation correlates decreased and antioxidant nutrients increased with increasing SES, estimated in several ways, independent of age, sex, race, and BMI. Prospectively, lower Year 0 education and occupation predicted greater increases in GGT and greater decreases in carotenoids over 10 to 15 years. Prospective associations of Year 0 SES with Year 15 carotenoids were independent of Year 15 SES. Smoking, drinking, and depression symptoms partially mediated these effects. CONCLUSIONS: Circulating oxidation correlates increase and antioxidant nutrients decrease with decreasing SES, both cross sectionally and prospectively.</p

Dose-response associations of plasma ascorbic acid (A) and the diet quality score (B) with incident hypertension.

<p>Linearity of the shape of the associations was evaluated with fractional polynomials, with P values for non-linearity being 0.02 for plasma ascorbic acid and 0.79 for the dietary quality score. Adjustments were according to multiple-adjustment model 2.</p

Serum Urate and Incident Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

<div><p>Objective</p><p>There is controversy about whether serum urate (sUA) predicts future cardiovascular disease (CVD) independently of classical risk factors, and the age at which any prediction starts. We studied the sUA-CVD association among generally healthy adults.</p><p>Methods</p><p>CARDIA recruited 5115 black and white individuals aged 18–30 years in 1985–1986 (year-0). Fatal and nonfatal CVD events by year 27 (n = 164) were ascertained during annual contacts and classified using medical records. The association with sUA (year-0, 10, 15 and 20) was modeled using Cox proportional hazards regression, pooling over gender-specific quartiles.</p><p>Results</p><p>Mean sUA concentration was higher in men than women, but increased over time in both genders. Those with elevated sUA had worse metabolic profiles that substantially deteriorated over time. Adjusting for demographic and lifestyle factors (the minimal model), baseline sUA concentration was positively associated with incident CVD (hazard ratio (HR) per mg/dL = 1.21; 95% confidence interval: 1.05, 1.39; P = 0.005). This positive association attenuated to nonsignificance in the full model accounting simultaneously for classical CVD risk factors (HR = 1.09; 0.94, 1.27; P = 0.24). Both the minimal and full models appeared to show stronger associations (than year-0 sUA) between year-10 sUA and incident CVD (HR = 1.27 and 1.12, respectively), but sUA was not statistically significant in the full model. Despite fewer events, year-15 sUA showed a significant sUA-CVD association pattern, with minimal model association magnitude comparable to year-10, and remained significant in the full model (HR = 1.19; 1.02, 1.40; P = 0.03). Hyperuricemia at year-15 strongly predicted CVD risk (HR = 2.11; 1.34, 3.33; P = 0.001), with some attenuation in the full model (HR = 1.68; P = 0.04).</p><p>Conclusions</p><p>sUA may be an early biomarker for CVD in adults entering middle age. The prediction of CVD by sUA appeared to strengthen with aging. The potential complex relation of sUA with deterioration of a cluster of metabolic abnormalities warrants future exploration.</p></div

Cubic spline of the association between glycated hemoglobin (HbA1c %) and self-reported incident diabetes, adjusted for age, gender, and dialect, The Singapore Chinese Health Study.

<p>The hazard ratio (HR) is per each absolute increase of 1 percentage point in the glycated hemoglobin value at baseline. The shaded area is the 95% confidence interval from the restricted-cubic-spline model. The HR scale is logarithmic, the model is centered at the mean/median (5.7%), and the plot was truncated at the 5th and 95th percentiles of glycated hemoglobin (4.9% and 6.5%, respectively). The hazard ratio was adjusted for age, gender, and dialect.</p

Timeline and assembly of sub-sample, The Singapore Chinese Health Study.

<p>Timeline and assembly of sub-sample, The Singapore Chinese Health Study.</p

Incidence rates and hazard ratios (HR) with 95% confidence intervals for incident type 2 diabetes according to category of glycated hemoglobin (HbA1c%), The Singapore Chinese Health Study.

<p>Crude incidence rate: per 100,000 person years</p><p>Standardized incidence rate: per 100,000 person years according to the gender, age and follow-up time distribution of the SCHS</p><p>Final adjusted model: Adjusted for age, gender, dialect, interview year, educational status, smoking status, average weekly alcohol intake BMI, and hypertensive status</p><p>Followed ≥ 3 years: analysis when excluding the first three years post blood-draw</p><p>Incidence rates and hazard ratios (HR) with 95% confidence intervals for incident type 2 diabetes according to category of glycated hemoglobin (HbA1c%), The Singapore Chinese Health Study.</p

Participant characteristics diabetes according to category of glycated hemoglobin (HbA1c%), The Singapore Chinese Health Study.

<p>¹Physical activity is the average min/week of combined moderate and strenuous activity</p><p>²Body mass index</p><p>NA: Not applicable to estimate due to missing data</p><p>Continuous variables are means (SD)</p><p>Categorical variables are % within column</p><p>P for trend is testing for a linear trend across HbA1c category</p><p>Participant characteristics diabetes according to category of glycated hemoglobin (HbA1c%), The Singapore Chinese Health Study.</p

Longitudinal association between sUA and the incidence of any fatal or nonfatal CVD endpoints by year 27.

<p>sUA, serum urate; CVD, cardiovascular disease; Y, year; Q, quartile; BMI, body mass index; CI, confidence interval.</p><p>^a Model 1: adjusted for year 0 age, sex, race, clinic, education level, smoking status, physical activity and intakes of total calories, alcohol and protein.</p><p>^b Model 1 + year 0 BMI, systolic and diastolic blood pressure, anti-hypertension medication use (excluding those taking diuretics), diuretics use, and glomerular filtration rate.</p><p>^c Model 2: adjusted for age, sex, race, clinic, education level, smoking status and physical activity at year 10, and average intakes of total calories, alcohol and protein at years 0 and 7.</p><p>^d Model 2 + year 10 BMI, systolic and diastolic blood pressure, anti-hypertension medication use (excluding those taking diuretics), diuretics use, and glomerular filtration rate.</p><p>^e Model 3: adjusted for age, sex, race, clinic, education level, smoking status and physical activity at year 15, and average intakes of total calories, alcohol and protein at years 0 and 7.</p><p>^f Model 3 + year 15 BMI, systolic and diastolic blood pressure, anti-hypertension medication use (excluding those taking diuretics), diuretics use, and glomerular filtration rate</p><p>^g Hazard ratio (95% CI) for the incidence of any fatal or nonfatal CVD endpoints by the end of 2012 (year 25) across sUA tertiles, reference group is participants in the lowest tertile of sUA concentrations.</p><p>^h Hazard ratio (95% CI) for the incidence of any fatal or nonfatal CVD endpoints per mg/dL sUA when using continuous sUA variable.</p><p>ⁱ<i>P</i>-values for the association between sUA and CVD when using continuous sUA variables.</p><p>^j Values are presented as “hyperuricemia group (reference group)”. Numbers in the reference group (participants without hyperuricaemia, i.e. sUA <6.8 mg/dL) are given in parentheses.</p><p>^kHazard ratio (95% CI) for the incidence of any fatal or nonfatal CVD endpoints by the end of 2012 (year 25) for the hyperuricemia group.</p><p>Longitudinal association between sUA and the incidence of any fatal or nonfatal CVD endpoints by year 27.</p

Unadjusted participant characteristics (mean±SD or percent) of participants across exam years.

<p>^a Prevalent CVD endpoints and missing data on sUA or covariates at the year of sUA measurement were excluded from the analyses.</p><p>^b HOMA-IR was calculated as (glucose × insulin) / 405 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0138067#pone.0138067.ref023" target="_blank">23</a>].</p><p>Unadjusted participant characteristics (mean±SD or percent) of participants across exam years.</p

QQ-plot of 55 T2D SNPs reported by GWAS-catalog.

<p>Observed distribution of −log <i>P</i>-values were compared to the expected (null) distribution.</p