Coronary Artery Risk Development In Young Adults Year Research Articles

Migraines, vasomotor symptoms, and cardiovascular disease in the Coronary Artery Risk Development in Young Adults study.

To examine whether vasomotor symptoms (VMS) and migraine headaches, hypothesized to be vasoactive conditions, are associated with greater risk for cardiovascular disease (CVD) events including strokes. We performed a secondary data analysis of a subset of women (n = 1,954) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based cohort, which began data collection at 18 to 30 y of age. We examined whether migraine headaches and VMS trajectories (characterized as minimal, increasing, and persistent) at CARDIA year 15 examination were associated with higher risk of CVD events and stroke (both ischemic and hemorrhagic) using Cox proportional hazards regression models and adjustment for traditional CVD risk factors (age, cigarette use, and levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides) and reproductive factors. Among women with minimal VMS (n = 835), increasing VMS (n = 521), and persistent VMS (n = 598), there were 81 incident CVD events including 42 strokes. Women with histories of migraine and persistent VMS had greater risk of CVD (hazard ratio [HR], 2.25; 95% CI, 1.15-4.38) after adjustment for age, race, estrogen use, oophorectomy, and hysterectomy compared with women without migraine histories and with minimal/increasing VMS. After adjustment for CVD risk factors, these associations were attenuated (HR, 1.51; 95% CI, 0.73-3.10). Similarly, women with histories of migraine and persistent VMS had greater risk of stroke (HR, 3.15; 95% CI, 1.35-7.34), but these associations were attenuated after adjustment for CVD risk factors (HR, 1.70; 95% CI, 0.66-4.38). Migraines and persistent VMS jointly associate with greater risk for CVD and stroke, although risk is attenuated with adjustment for traditional CVD risk factors.

Abstract 15643: Social Determinants of Health, Epigenetic Aging, and Subclinical Cardiovascular Disease: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Associations of social determinants of health (SDOH) with subclinical cardiovascular disease (CVD), such as left ventricular mass index (LVMI) and coronary artery calcification (CAC), are poorly described. Mechanisms of such associations may involve epigenetic changes like DNA methylation. We sought to examine associations between selected SDOH measures and subclinical CVD, and potential mediation by GrimAge acceleration (GrimAA), a measure of epigenetic aging. Methods: We included 2932 Black and White adults from the CARDIA year 20 (Y20) exam (mean age 45y, 48% Black, 57% female). Associations between SDOH measures at Y20 (or cumulative up to Y20) and Y25 ln(CAC score +1) or LVMI (in g/m 2.7 ) were examined using linear regression. Statistical mediation analysis was used to estimate the proportion of associations attributable to GrimAA among 880 participants in whom it was measured. Results: All selected SDOH measures at Y20 - residential racial segregation (G* Score); census tract poverty; food insecurity; difficulty paying for basics, medications, or healthcare; and maximum years of participant or parental education - were associated with LVMI at Y25 (Table). For example, each 1% higher census tract poverty was associated with an average 0.95 g/m 2.7 higher LVMI. Several SDOH measures were also associated with CAC score at Y25. Similar associations were observed between cumulative SDOH exposures from Y0-Y20 and Y25 subclinical CVD. GrimAA mediated >30% of the statistical association between participant education and LVMI or CAC (Table), and >20% of the associations of residential segregation and census tract poverty with LVMI. Conclusions: SDOH metrics were significantly and longitudinally associated with subclinical CVD in midlife. DNA methylation, as represented by GrimAge acceleration, appears to statistically mediate these associations, suggesting possible molecular mechanisms by which SDOH may accelerate CVD risk.

Social support factors and cognitive outcomes in mid‐life

AbstractBackgroundA growing body of evidence suggests that social support is associated with cognitive outcomes including dementia in late‐life. Yet few studies have examined the association between social support and cognition in mid‐life, a critical time of transition to aging. Furthermore, little is known about the effects of other aspects of social function such as emotional support, social strain and loneliness on cognition. Our goal was to investigate the association between several social support factors and cognitive performance in mid‐life.MethodWe studied 2,732 Black and White adults from the Coronary Artery Risk Development in Young Adults (CARDIA) Study who completed a social support questionnaire at baseline (CARDIA Year 20, mean age 45.2 years, 57% female, 45% Black) which assessed aspects of emotional support, social strain, and loneliness. At the 10‐year follow‐up, cognitive performance was evaluated with a battery of five tests: Digit Symbol Substitution Test (DSST), Rey Auditory Verbal Learning Test (RAVLT), Stroop Test, Verbal Fluency (category and letter fluency), and the Montreal Cognitive Assessment (MOCA) and standardized to z‐scores. We used linear regression to determine the association between emotional support, social strain, and loneliness, categorized as tertiles (comparing high to low), with mid‐life cognition.ResultIn unadjusted models, all three social support factors were associated with cognition 10 years later. After adjusting for age, sex, race, education, marital status, income, and depression, participants reporting higher levels of emotional support performed better on all cognitive tests (DSST High vs. Low (z‐score)=0.13 [95%CI 0.03, 0.23]; RAVLT=0.17 [95%CI 0.07, 0.27]; reverse Stroop=0.15 [95%CI 0.05, 0.26]; Verbal Fluency=0.12 [95%CI 0.01, 0.23]; MOCA=0.19 [95%CI 0.09, 0.28]). Less social strain was associated with higher scores on most tests (DSST Low vs. High=0.16 [95%CI 0.06, 0.26]; RAVLT=0.11 [95%CI 0.01, 0.21]; and MOCA=0.13 [95%CI 0.04, 0.23]). Loneliness was not associated with mid‐life cognition.ConclusionGreater level of social support, particularly emotional support, was associated with better mid‐life cognitive outcomes 10 years later. To better inform risk and prevention efforts, more research should be conducted to investigate the associations between various dimensions of social support and cognitive outcomes across the life course.

Abstract 12995: Sex and Race Differences in Ventricular-Arterial Coupling in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Coupling between the left ventricle and arterial system can be quantified as the ventricular-arterial coupling (VAC) ratio with 1.00 reflecting optimal physiology. VAC has been most studied in heart failure, with higher values associating with worse prognosis, but its correlates among individuals without heart failure are less characterized. Thus, in the Coronary Artery Risk Development in Young Adults (CARDIA) study we tested the hypothesis that VAC ratio differs by sex and race. Methods: We studied VAC in 2,812 (42% male, 47% black, median age 50 years) CARDIA year 25 exam participants with transthoracic echocardiogram data available and no history of heart failure, myocardial infarction, peripheral vascular disease, or valvular disease. VAC was calculated as arterial elastance (Ea) divided by LV end systolic elastance (Ees). Ea and Ees were calculated as end systolic pressure/stroke volume and by the modified Chen single beat method, respectively. Associations between sex and race with VAC were tested in multivariable-adjusted linear regression. Results: VAC ratio differed by both sex and race with higher unadjusted values in men (median 1.14 [25 th -75 th percentile 1.08-1.20]) compared with women (1.11 [1.05-1.17]), p < 0.001, and white (1.12 [1.07-1.18]) compared with black (1.11 [1.06-1.18]) individuals, p = 0.004. In adjusted models, male sex (beta 0.027 [95% CI 0.021 to 0.037], p <0.001) and white race (0.007 [0.002 to 0.012], p = 0.009) remained associated with higher VAC ratio (Figure 1). Sex, LV ejection fraction (beta -0.096 [95% CI -0.099 to -0.093], and total arterial compliance (-0.045 [-0.049 to -0.041]) were the most strongly associated correlates of VAC. Systolic blood pressure, creatinine, heart rate, LDL, and triglycerides inversely associated with VAC. Age and LV remodeling index positively associated with VAC. Conclusions: In community dwelling middle-aged adults, male sex and white race independently associated with higher VAC.

Questionnaire-based problematic relationship to eating and food is associated with 25 year body mass index trajectories during midlife: The Coronary Artery Risk Development In Young Adults (CARDIA) Study.

Problematic eating behaviors and attitudes are of public health concern. Questionnaire-based assessment of these behaviors is important for large-scale research on eating behaviors. The questionnaire on eating and weight patterns-revised (QEWP-R) measures potential problematic behaviors and attitudes toward food (including anxieties, compensatory actions, overeating and loss of control, dieting, and shape concerns) that in aggregate may indicate diagnosable eating disorders. An important question regards the prevalence of these issues and their longitudinal associations with body mass index (BMI) in generally healthy middle aged adults. Based on eight constructs measured on QEWP-R, we created a new problematic relationship to eating and food (PREF) scale by assigning a point for each construct endorsed. Analyses were conducted in 3,892 black and white men and women participating in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) Study. The QEWP-R was administered in CARDIA year 10, when participants were aged 27-41 years. We used linear regression to model the relationship of individual constructs and the PREF scale to BMI over CARDIA follow-up. Fifty-five percent of participants had 1-5 points and 4% had 6-8 points on the PREF scale. Each separate construct was positively associated with BMI, except concern about weight and shape. Adjusting for age, race, sex, education, and study center, mean BMI at CARDIA year 10, the time of PREF assessment, was approximately 1.0-2.5 kg/m2 higher per PREF category. In middle age, problematic behaviors and attitudes toward food were common and associated with higher BMI.

Rapid decline in lung function is temporally associated with greater metabolically active adiposity in a longitudinal study of healthy adults

RationaleAdiposity is associated with low lung function, but the longitudinal relationship between lung function and adiposity is inadequately studied.ObjectiveTo examine the bidirectional longitudinal associations between rapid decline in lung function...

Circulating Cellular Adhesion Molecules and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study.

Higher circulating concentrations of cellular adhesion molecules (CAMs) can be used as markers of endothelial dysfunction. Given that the brain is highly vascularized, we assessed whether endothelial function is associated with cognitive performance. Within the Coronary Artery Risk Development in Young Adults (CARDIA) Study, excluding N = 54 with stroke before year 25, we studied CAMs among N = 2,690 black and white men and women in CARDIA year 7 (1992-1993, ages 25-37) and N = 2,848 in CARDIA year 15 (2000-2001, ages 33-45). We included subjects with levels of circulating soluble CAMs measured in year 7 or 15 and cognitive function testing in year 25 (2010-2011, ages 43-55). Using multiple regression analysis, we evaluated the association between CAMs and year 25 cognitive test scores: Rey Auditory Verbal Learning Test (RAVLT, memory), Digit Symbol Substitution Test (DSST, speed of processing), and the Stroop Test (executive function). All CAM concentrations were greater in year 15 vs. year 7. Adjusting for age, race, sex, education, smoking, alcohol, diet, physical activity, participants in the fourth vs. the first quartile of CARDIA year 7 of circulating intercellular adhesion molecule-1 (ICAM-1) scored worse on RAVLT, DSST, and Stroop Test (p ≤ 0.05) in CARDIA year 25. Other CAMs showed little association with cognitive test scores. Findings were similar for ICAM-1 assessed at year 15. Adjustment for possibly mediating physical factors attenuated the findings. Higher circulating ICAM-1 at average ages 32 and 40 was associated with lower cognitive skills at average age 50. The study is consistent with the hypothesis that endothelial dysfunction is associated with worse short-term memory, speed of processing, and executive function.

Prevalence and Predictors of Diastolic Dysfunction According to Different Classification Criteria: The Coronary Artery Risk Development in Young in Adults Study.

Heart failure with preserved ejection fraction is often preceded by diastolic dysfunction (DD). Of several published DD criteria, it is unclear which, if any, are applicable to data obtained in epidemiologic cohorts. We evaluated the prevalence of DD using previously published definitions in a population-based study, the Coronary Artery Risk Development in Young Adults (CARDIA) Study, using data gathered in 2010-2011. Echocardiography was performed on 3,474 individuals (mean age=50.2years) at the CARDIA year 25 examination. Four published definitions of DD were studied. We calculated DD prevalence for each definition and determined the overlap between definitions. We used logistic regression to assess the strength of associations between demographic and clinical factors and the definitions of DD. Prevalence of DD ranged from 2% to 32% across the 4 definitions, with a minority of cases identified by more than 1 definition. Two definitions classified 38%-39% of the study sample as indeterminate for DD. Associations of risk factors with DD varied considerably, with male sex being associated positively with DD for one definition (odds ratio=1.4, 95% confidence interval: 1.2, 1.6) and inversely for another (odds ratio=0.7, 95% confidence interval: 0.6, 0.8). Prevalence of DD varies markedly in CARDIA by the definition applied. A uniform, reliable, and accurate definition of DD for epidemiologic studies is needed.

Association of Insulin Resistance and Glycemic Metabolic Abnormalities With LV Structure and Function in Middle Age: The CARDIA Study

ObjectivesThis study sought to investigate how cumulative exposure to glycemic abnormalities and trajectories of insulin resistance (IR) relate to left ventricular (LV) remodeling and function during young to middle adulthood. BackgroundCumulative exposure to glycemic abnormalities and trajectories of IR may adversely influence LV remodeling and function over a 25-year period in subjects who were young adults, predisposing individuals to heart failure later in life. MethodsIn the CARDIA (Coronary Artery Risk Development in Young Adults) Year 25 examination, 3,179 participants were identified with information on glucose metabolism; these participants were stratified into 4 subgroups: group 1 normal glucose tolerance (NGT), group 2 impaired glucose tolerance (IGT) or impaired fasting glucose, group 3 late diabetes mellitus (DM) (DM diagnosed at year 15 or later), and group 4 early DM (DM diagnosed at year 0 to year 15). Among the subgroup without DM, 3 trajectory groups of change in the homeostasis model assessment of IR were identified: low IR, moderate IR, and high IR. LV mass, relative wall thickness, LV ejection fraction (LVEF), longitudinal systolic strain (Ell), and early diastolic strain rate (Ell_SRe) at year 25 were assessed by echocardiography. Clinically relevant systolic and diastolic dysfunction were defined as LVEF <50% for systolic dysfunction, and E/e′ ≥13 for diastolic dysfunction. ResultsThe early DM group had less favorable LV mass (coefficient = 11.04; p < 0.001), LVEF (coefficient = −2.72; p < 0.05), Ell (coefficient = 1.53; p < 0.001), and Ell_SRe (coefficient = −0.09; p < 0.05) than did the NGT group. Being in the early DM group and having high hemoglobin A1c were independently associated with greater odds of having systolic dysfunction (odds ratio = 5.44; p < 0.005) compared with the NGT group. High IR was associated with worse relative wall thickness (coefficient = 0.019; p < 0.0001) and worse Ell, E′, and Ell_SRe, depending on obesity level. ConclusionsCumulative exposure to DM or higher IR beginning in early adulthood adversely impacts LV remodeling and function at middle age.

Higher pericardial adiposity is associated with prevalent diabetes: The Coronary Artery Risk Development in Young Adults study

Background and aimsPericardial adipose tissue (PAT) is located on both sides of the pericardium. We tested whether PAT was associated with prevalent diabetes at the year 25 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Methods and resultsThe CARDIA Year 25 exam (2010–2011) included complete data for all covariates on 3107 participants. Prevalent diabetes (n = 436) was defined as high fasting (≥126 mg/dl) or 2-h postload glucose (≥200 mg/dl) or HbA1c (≥6.5%) or use of diabetes medications. Volume of PAT was measured from computed tomographic scans. Logistic regression was performed to examine the relationship between quartiles of PAT and diabetes. In regression models adjusted for field center, sex, race, age, systolic blood pressure, total cholesterol, log triglycerides, and treatment with blood pressure and cholesterol lowering medication, PAT volume in the 4th quartile was significantly associated with diabetes status after adjustment for BMI (OR 2.57, 95% CI 1.66, 3.98) or visceral adipose tissue (OR 2.08, 95% CI 1.32, 3.29). PAT volume in the 2nd and 3rd quartiles was not significantly associated with diabetes status relative to the first quartile. ConclusionsMetabolically active pericardial adipose tissue is associated with prevalent diabetes only at higher volumes independent of overall obesity.

Abstract 31: Prediction of coronary artery and abdominal aortic calcium in middle-aged adults using the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) risk score: the CARDIA study

Background: Risk scores to predict coronary and abdominal atherosclerosis have been developed from autopsy specimens from the right coronary artery and descending aorta and risk factors measured post-mortem in the Pathobiological Determinants of Atherosclerosis in Youth Study (PDAY), cohort aged 15-34 years. While the PDAY risk score predicts coronary artery calcium (CAC) up to 15 years before its assessment in Coronary Artery Risk Development in Young Adults (CARDIA), the clinical validity at 25 years follow up and of the abdominal score to predict abdominal aortic calcium (AAC) has not been tested. Objectives: To test the hypotheses: 1) PDAY risk scores at CARDIA baseline (cohort aged 18-30 years) predict CAC and abdominal aortic calcium (AAC) at year 25 better than PDAY risk scores measured at subsequent time points. 2) Change in risk over time will improve associations in Aim 1. Methods: The CARDIA study assessed CAC and AAC by computed tomography in young adults participating at year 25. The PDAY risk score was calculated from risk factors measured at the CARDIA examinations at years 0 (cohort aged 18-30 years), 5, 10, 15 and 25 (age 43-55 years). Results: Age and gender independent PDAY risk scores increased from CARDIA year 0 to year 25 (coronary from 1.80 to 4.95, abdomen from 1.88 to 3.18). Prevalence of any CAC was 28% and AAC was 53%. For a one point increase in risk score, baseline risk predicted CAC and AAC better than year 25 risk; change in risk improved the prediction further (Table). C-statistics for CAC prediction were higher at year 0 but similar at years 0 and 25 for AAC. Further analyses using PDAY scores calculated at 5 year intervals prior to the CT scan confirmed that CAC at baseline and AAC at year 5 had the highest Odds Ratios for a one point increase in score (AAC year 5 Odds Ratio 1.35 (1.30-1.41)). Conclusions: PDAY risk scores, applied to living adults in the CARDIA study, predicted CAC and AAC in 43-55 year old adults; including change in risk slightly improves model performance.

Longitudinal Determinants of Left Ventricular Mass and Geometry

Background— The purpose of this study was to identify determinants of 20-year change in left ventricular (LV) mass (LVM) and LV geometry in black and white young adults in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods and Results— We studied 2426 black and white men and women (54.7% white) aged 43 to 55 years with cardiovascular risk factor data and echocardiograms from CARDIA year 5 and 25 examinations. In regression models, year 25 LVM or relative wall thickness was the dependent variable and with year 5 echo values, age, sex, race, body mass index, change in body mass index, mean arterial blood pressure, change in mean blood pressure, heart rate, change in heart rate, tobacco use, presence of diabetes mellitus, alcohol use, and physical activity score as independent variables. LVM and relative wall thickness increased, whereas prevalence of normal geometry declined from 84.2% to 69.7%. Significant determinants of year 25 LVM/m 2.7 were year 5 LVM, year 5 and change in body mass index, year 5 and change in mean arterial pressure, year 5 and change in heart rate, baseline diabetes mellitus, and year 5 tobacco and alcohol use (overall r 2 =0.40). Significant determinants of year 25 relative LV wall thickness were year 5 value, black race, change in body mass index, year 5 and change in mean arterial pressure, starting smoking, and year 5 diabetes mellitus (overall r 2 =0.11). Conclusions— Prevalence of abnormal LV hypertrophy and geometry increased from young adulthood to middle age. Both young adult cardiovascular risk traits and change in these traits predicted change in LV mass/geometry.

Antiphospholipid antibodies and sub-clinical atherosclerosis in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort.

Antiphospholipid antibodies (APA) have been associated with clinical cardiovascular disease, but it remains unclear whether APA are associated with sub-clinical atherosclerosis. This study examined the relationship between APA and sub-clinical atherosclerosis, measured as coronary artery calcification (CAC), in participants from the prospective Coronary Artery Risk Development in Young Adults (CARDIA) Study. 2,203 black and white participants with sera available from the CARDIA year 7 examination and CAC measured by computed tomography at years 15 or 20 were selected. Anti-β2-glycoprotein I (anti-β2-GPI) immunoglobulin (Ig) M, IgG, and IgA were positive in 7.0, 1.4, and 1.8 % of participants, respectively; anti-cardiolipin (aCL) IgM and IgG were positive in 1.5 and 1.0 %, respectively. 9.5 % of participants had CAC score >0 at year 15. Anti-β2-GPI IgM, IgG, IgA, and aCL IgG positivity were associated with CAC >0 at year 15 after adjustment for traditional cardiovascular risk factors; [odds ratios (95 % confidence intervals) were 1.7 (1.0, 3.1), 6.4 (2.4, 16.8), 5.6 (2.3, 13.2), and 5.1 (1.4, 18.6), respectively]. Anti-β2-GPI IgG was associated with year 20 CAC >0, and anti-β2-GPI IgA and aCL IgG were marginally associated. These findings indicate that APA positivity during young adulthood is a risk factor for subsequent sub-clinical atherosclerosis and might play a role in the pathogenesis of atherosclerosis

Health-care access and weight change among young adults: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Health-care access is associated with improved control of multiple chronic diseases, but the association between health-care access and weight change is unclear. The present study aims to test the association between health-care access and weight change. The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a multicentre population-based prospective study. Weight change was calculated at 3 and 13 years after CARDIA year 7 (1992-1993). Health-care access was defined as no barriers or one or more barriers to access (health insurance gap, no usual source of care, not seeking care due to expense). Intermediary variables evaluated included history of dieting and use of diet pills, meal replacements or weight-control programmes. Four cities in the USA. Participants were aged 18-30 years at baseline (1985-1986). Analyses include 3922 black and white men and women with relevant data from CARDIA years 7, 10 and 20 (1992-1993, 1995-1996 and 2005-2006, respectively). Mean weight change was +2.22 kg (+4.9 lb) by 3 years and +8.48 kg (+18.7 lb) by 13 years, with no differences by health-care access. Being on a weight-reducing diet was not consistently associated with health-care access across examinations. Use of diet pills, meal replacements or organized weight-control programmes was low, and did not vary by health-care access. Weight gain was high irrespective of health-care access. Public health and clinical approaches are needed to address weight gain.

Low Serum Adiponectin Predicts Future Risk for Asthma in Women

Our previous cross-sectional study showed that serum adiponectin is inversely associated with asthma among women. However, it is not known if serum adiponectin predicts future development of asthma or if asthma affects subsequent serum adiponectin concentrations among women. To determine longitudinal association between serum adiponectin and incident asthma among women. We used data from examinations at Years 10, 15, and 20 of the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. In our primary analysis, the association of CARDIA Year 15 serum adiponectin concentration with Year 20 incident asthma was evaluated. In our secondary analysis, the converse direction, that is, the association of CARDIA Year 10 prevalent asthma with Year 15 serum adiponectin, was evaluated, using logistic regression techniques. Our primary analysis included 1,450 women, mostly premenopausal. Multivariable analyses demonstrated that the lowest tertile of Year 15 serum adiponectin concentration (<7 mg/L) predicted significantly higher risk for incident asthma at Year 20 among women (odds ratio, 2.07; 95% confidence interval, 1.05, 4.10), and particularly among current smokers (interaction P = 0.051). Further, low serum adiponectin was more important than body mass index in predicting the risk for incident asthma among women. We also showed that the converse relationship was not true; that is, Year 10 prevalent asthma did not predict Year 15 serum adiponectin concentrations in women. Serum adiponectin affects future risk for asthma in women and not vice versa. Measures that raise systemic adiponectin concentrations may lead to newer ways to prevent asthma among women, particularly among those who smoke.

Association of Long‐term Change in Waist Circumference With Insulin Resistance

Recent studies have shown that fat accumulation is associated with insulin resistance; however, the risks associated with long-term changes and fluctuations in central fatness are less clear. This study examined the longitudinal relationship between waist circumference (WC) and insulin resistance using three dimensions of WC: baseline WC, slope of linear changes in WC, and fluctuation of WC around the slope during 20 years of follow-up. Anthropometry, insulin resistance (homeostasis model assessment (HOMA(IR))), and lifestyle factors were obtained in a population-based, prospective observational study (Coronary Artery Risk Development in Young Adults (CARDIA)) during 1985-2006, excluding participants who had been diagnosed with diabetes at any examination. After adjusting for socio-demographic and lifestyle factors, the evolution of HOMA(IR) from CARDIA year 15 to 20 was 6.9% higher per standard deviation of year 0 WC (P trend <0.0001) and 6.3% higher per standard deviation increase in the change in WC over the long term (P trend <0.0001). However, WC fluctuations around the linear change were not associated with insulin resistance or its evolution. The level of HOMA(IR) increased substantially with steeper linear WC slope among initially thinner participants at baseline, whereas this association tended to be weaker in those with higher initial WC (P interaction <0.0001). We conclude that year 0 WC and long-term increment in WC are associated with worsening insulin resistance. However, the association of HOMA(IR) with slope of WC change may vary across the range of initial WC.

Prospective Association Between C-Reactive Protein and Fatigue in the Coronary Artery Risk Development in Young Adults Study

Fatigue is highly prevalent and causes serious disruption in quality of life. Although the underlying biological mechanism is unknown, increases in inflammation have been implicated. This prospective study examined the association between C-reactive protein (CRP), a biomarker of systemic inflammation, and fatigue 5 years later. The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based longitudinal study conducted in four U.S. cities. Highly sensitive CRP concentration and fatigue were measured in 2983 African American and white adults at both year 15 (2000-2001, ages 33-45 years) and year 20 (2005-2006) examinations. Fatigue was assessed using the vitality subscale of the 12-item Short Form Health Survey. Plasma CRP concentration at baseline (i.e., CARDIA year 15) was a significant predictor of fatigue level 5 years later (unadjusted beta = .126, p < .001). After adjustment for potential confounders, this association remained significant (adjusted beta = .044, p = .033). Additionally, baseline CRP independently predicted fatigue in the subgroup of participants without medical comorbidity (adjusted beta = .051, p = .039). Fatigue was associated with a persistent elevation of CRP at both examinations but not with a transient elevation of CRP at only one of the examinations. This is the first study to demonstrate a prospective association between an inflammatory marker and fatigue in a general population. Furthermore, the association between low-grade systemic inflammation and fatigue seems primarily driven by persistent immune activation and not explained by the presence or development of medical comorbidity.

Association between endothelial biomarkers and arterial elasticity in young adults: the CARDIA Study

Reduced arterial elasticity and endothelial dysfunction both may indicate early cardiovascular (CV) disease in young adults. Pulse waveform analysis estimates large (LAE) and small (SAE) artery elasticity noninvasively. We assessed the associations between LAE and SAE and markers of endothelial dysfunction and CV risk factors. The Coronary Artery Risk Development in Young Adults (CARDIA) assessed arterial elasticity and other characteristics cross-sectionally in 389 men and 381 women age 27 to 42 years in 1995 (CARDIA year 10) and circulating levels of P-selectin and soluble intercellular adhesion molecule 1 (sICAM1) in 2000. We adjusted for variables included in the estimation of arterial elasticity (year 10 height, body mass index, age, heart rate, and blood pressure) and other year 10 characteristics. Mean adjusted SAE was 8.5 vs. 7.6 mL/mm Hg × 100 in those with urine albumin/creatinine ratio ≤4 vs. microalbuminuria (ratio >25; P trend = .008). Mean LAE was 25.6 vs. 24.2 mL/mm Hg × 10 in the lowest vs. highest quintile of P-selectin ( P trend = .004). sICAM1 was unrelated to either LAE or SAE. Plasma triglycerides were inversely related to LAE ( P trend = .029). Cigarette smokers had lower SAE than nonsmokers ( P trend = .009). In addition to smoking and triglycerides, biomarkers for endothelial dysfunction were associated with impaired LAE and SAE in young adults.