Depressive Symptoms, Race, and Circulating C-Reactive Protein: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Objective: To examine the prospective association of depressive symptoms with circulating C-reactive protein (CRP) and to determine the direction of that association. Methods: Using data from 2,544 healthy participants in the Coronary Artery Risk Development in Young Adults study (ages, 33-45 years; 55% female; 42% black), we examined the prospective association of depressive symptoms, as measured by the Centers for Epidemiologic Studies Depression Scale, with circulating CRP 5 years later. Results: Depressive symptoms in the Coronary Artery Risk Development in Young Adults study Year 15 predicted CRP at Year 20, independent of demographic characteristics, biological and medical risk factors, health behaviors, and Year 15 CRP. This association, however, was conditional on race such that the increase in CRP with increasing depressive symptoms was present in blacks but not whites. In neither blacks nor whites did Year 15 CRP predict Year 20 depressive symptoms. Among black participants, when examined in separate analyses, higher scores on the depressed affect and somatic symptoms subscales of the Centers for Epidemiologic Studies Depression Scale and lower scores on the positive affect subscale were associated with greater Year 20 CRP. The interpersonal problems subscale was unrelated to CRP. When all four subscale scores were entered simultaneously in the same model, black participants' scores on the positive affect and somatic symptoms subscales emerged as independent predictors of Year 20 CRP, whereas the depressed affect and interpersonal problems subscales did not. Conclusions: Depressive symptoms may be linked more closely to inflammation in blacks than in whites.</p

Vascular Factors and Multiple Measures of Early Brain Health: CARDIA Brain MRI Study

<div><p>Objective</p><p>To identify early changes in brain structure and function that are associated with cardiovascular risk factors (CVRF).</p><p>Design</p><p>Cross-sectional brain Magnetic Resonance I (MRI) study.</p><p>Setting</p><p>Community based cohort in three U.S. sites.</p><p>Participants</p><p>A Caucasian and African-American sub-sample (n= 680; mean age 50.3 yrs) attending the 25 year follow-up exam of the Coronary Artery Risk Development in Young Adults Study.</p><p>Primary and Secondary Outcomes</p><p>3T brain MR images processed for quantitative estimates of: total brain (TBV) and abnormal white matter (AWM) volume; white matter fractional anisotropy (WM-FA); and gray matter cerebral blood flow (GM-CBF). Total intracranial volume is TBV plus cerebral spinal fluid (TICV). A Global Cognitive Function (GCF) score was derived from tests of speed, memory and executive function.</p><p>Results</p><p>Adjusting for TICV and demographic factors, current smoking was significantly associated with lower GM-CBF and TBV, and more AWM (all <0.05); SA with lower GM-CBF, WM-FA and TBV (p=0.01); increasing BMI with decreasing GM-CBF (p<0003); hypertension with lower GM-CBF, WM-FA, and TBV and higher AWM (all <0.05); and diabetes with lower TBV (p=0.007). The GCS was lower as TBV decreased, AWM increased, and WM-FA (all p<0.01).</p><p>Conclusion</p><p>In middle age adults, CVRF are associated with brain health, reflected in MRI measures of structure and perfusion, and cognitive functioning. These findings suggest markers of mid-life cardiovascular and brain health should be considered as indication for early intervention and future risk of late-life cerebrovascular disease and dementia.</p></div

Demographic, behavioral, clinical and brain characteristics in a bi-racial middle-age cohort:CARDIA BRAIN Sub-study.

<p>Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; DSST, Digit Symbol Substitution Test; AWM, abnormal white matter; GM-CBF, gray matter cerebral blood flow; WM-FA, white matter fractional anisotropy.</p><p>^a Includes Smoking, Sedentary activity (upper 75th p); BMI >30; Diabetes, and Hypertension.</p><p>^b Composite is the sum of Z-scores from the DSST, modified Stroop Test and Rey Auditory Verbal Learning Test.</p><p>^c median (25%, 75%).</p><p>Demographic, behavioral, clinical and brain characteristics in a bi-racial middle-age cohort:CARDIA BRAIN Sub-study.</p

Distribution of study characteristics by study and overall.

<p>Distribution of study characteristics by study and overall.</p

Association between SNPs in the <i>FTO</i> region and BMI for all studies combined.

<p><b>a</b>SNPposition based on build 37.</p><p><b>b</b>Coding = coding allele, Base = baseline allele (risk estimates provide the log additive effect per copy of the coding allele).</p><p><b>c</b>CAF = coding allele frequency.</p><p><b>d</b>Rsq = measurement of imputation accuracy, ranging from 0 (low) to 1 (high).</p

Association results (p-values) and correlation structure for all SNPs in the 16q12.2/<i>FTO</i> region and lnBMI among African Americans using rs56137030 to calculate correlation among SNPs (LocusZoom plots).

<p>The top half of each figure has physical position along the x axis, and the −log₁₀ of the meta-analysis p-value on the y-axis. Each dot on the plot represents the p-value of the association for one SNP with lnBMI across all studies. The most significant SNP (rs56137030) is marked as a purple diamond. The color scheme represents the pairwise correlation (r²) for the SNPs across the 16q12.2/<i>FTO</i> region with the most significant SNP (rs56137030). Gray squares indicate that correlation was missing for this p-value because the variant was monomorphic in EA. The bottom half of the figure shows the position of the genes across the region. A and B show the same region and results. The only difference between A and B is that in A correlation with the most significant SNP (rs56137030) was calculated based on EAs, specifically based on data from 65 European Americans (Utah residents with Northern and Western European ancestry from the CEPH collection, CEU) sequenced as part of the 1000 Genomes Project and B correlation was based on 61 African Americans from the South-west (ASW) and sequenced as part of the 1000 Genomes Project.</p

Novel SNVs/Genes associated with BP traits in Multi-ancestry meta-analysis in combined Stage 1 and Stage 2.

<p>Novel SNVs/Genes associated with BP traits in Multi-ancestry meta-analysis in combined Stage 1 and Stage 2.</p

Novel SNVs/Genes associated with BP traits from correlated meta-analysis in European ancestry in Stage 1.

<p>Novel SNVs/Genes associated with BP traits from correlated meta-analysis in European ancestry in Stage 1.</p

Potential novel SNVs/Genes associated with BP traits in African ancestry.

<p>Potential novel SNVs/Genes associated with BP traits in African ancestry.</p

Novel SNVs/Genes associated with BP traits in European ancestry.

<p>Novel SNVs/Genes associated with BP traits in European ancestry.</p