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Secondhand tobacco smoke (SHS) exposure may reduce heart rate variability and lead to atrial fibrillation (AF); however prior study findings have not been confirmed using objective measures for both SHS and AF events.We prospectively examined the association between SHS exposure and incident AF in 5731 participants, ages of 45-84 years and free of known AF and other cardiovascular diseases (CVD) at baseline (2000-2002), who were followed through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). SHS weekly exposure time was identified by self-report. Urine cotinine was collected in a cohort subset of 3237 current non-smoking cohort participants. AF events were identified using Medicare claims, hospital records, and 12‑lead electrocardiographic findings. A multivariable Cox proportional hazards regression analysis was used with simultaneous adjustment for demographic factors, educational level, health insurance status, active smoking status, tobacco pack-years, traditional CVD risk factors, depressive symptoms and medications.During a median follow-up of 14.0 years, 856 and 452 AF events were identified in the overall and the cohort subset, respectively. No association of SHS exposure time or urine cotinine with incident AF was observed. However, a higher AF risk with greater urine cotinine (8.53-442.0 ng/mL) compared with lower urine cotinine (≤7.07 ng/mL) was observed in never smokers [hazard ratios (HR) and 95% confidence intervals: 1.60 (1.16, 2.19)], but not in former smokers [HR: 0.88 (0.63, 1.23)] (p-value for multiplicative interaction: 0.009 and for additive interaction: 0.017, respectively).Objectively measured greater SHS exposure expressed by urine cotinine might be associated with 1.6-fold higher risk of incident AF in never smokers.

Purpose Microvascular diseases may contribute to the occurrence of atrial fibrillation (AF). Retinal microvascular signs that are similar to other microvasculature in the body and can be visualized directly via ophthalmoscopy may provide insights into such a relationship. Design Prospective, longitudinal, multiethnic study. Participants We examined the association between retinal microvascular signs and incident AF in 4994 participants 47 to 86 years of age and free of prior AF who underwent fundus photography from 2002 through 2004 and were followed up through 2015 in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods Retinal microvascular signs evaluated include central retinal arteriolar equivalent and central retinal venular equivalent (CRVE) and presence of any retinopathy signs (e.g., retinal microaneurysms or hemorrhages). A multivariate Cox regression analysis was used to determine the relationship while adjusting for traditional risk factors, alcohol intake, body mass index, diabetes status, chronic kidney disease status, hemoglobin A1c level, C-reactive protein level, medications, and prevalent cardiovascular diseases or heart failure. Main Outcome and Measures Incident AF events were identified using 12-lead electrocardiographic findings, hospital discharge records, and Medicare claims data. Results During a median follow-up of 14.1 years, 643 AF events were identified. No association was found between any retinal microvascular signs and incident AF except for retinal focal arteriolar narrowing (hazard ratio, 1.75; 95% confidence interval, 1.06–2.87) in the overall population. However, in the subgroup analyses by gender, wider CRVE was associated with a higher risk of incident AF in women, but not in men (hazard ratio for every 10-μm increase in CRVE, 1.08 [95% confidence interval, 1.01–1.15] and 0.97 [95% confidence interval, 0.92–1.03], respectively; P = 0.041 for interaction). Conclusions No consistent pattern of association was found between retinal microvascular signs and incident AF. We observed an association in women, but not in men, of wider retinal venular calibers with incidence of AF. The reasons for a possible interaction are incompletely understood.

Incident cardiovascular disease (CVD) increases with increasing low-density lipoprotein cholesterol (LDL-C) concentration and exposure duration. Area under the LDL-C versus age curve is a possible risk parameter. Data-based demonstration of this metric is unavailable and whether the time course of area accumulation modulates risk is unknown.Using CARDIA (Coronary Artery Risk Development in Young Adults) study data, we assessed the relationship of area under LDL-C versus age curve to incident CVD event risk and modulation of risk by time course of area accumulation-whether risk increase for the same area increment is different at different ages.This prospective study included 4,958 asymptomatic adults age 18 to 30 years enrolled from 1985 to 1986. The outcome was a composite of nonfatal coronary heart disease, stroke, transient ischemic attack, heart failure hospitalization, cardiac revascularization, peripheral arterial disease intervention, or cardiovascular death.During a median 16-year follow-up after age 40 years, 275 participants had an incident CVD event. After adjustment for sex, race, and traditional risk factors, both area under LDL-C versus age curve and time course of area accumulation (slope of LDL-C curve) were significantly associated with CVD event risk (hazard ratio: 1.053; p 0.0001 per 100 mg/dl × years; hazard ratio: 0.797 per mg/dl/year; p = 0.045, respectively).Incident CVD event risk depends on cumulative prior exposure to LDL-C and, independently, time course of area accumulation. The same area accumulated at a younger age, compared with older age, resulted in a greater risk increase, emphasizing the importance of optimal LDL-C control starting early in life.

INTRODUCTION: Depression is associated with increased risk of incident and recurrent cardiovascular disease, while the association between depression and cardiovascular health (CVH) remains unknown. Because the natural course of depression varies widely, different patterns of depression, as well as co-occurring factors such as cigarette smoking, may influence this relationship. We examined potential interactions between longitudinal patterns of depression and smoking with CVH. METHODS: Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, we modeled trajectories of depression (Center for Epidemiologic Studies Depression Scale scores; Years 5, 10, 15, 20) and smoking (cigarettes/day; Years 0, 2, 5, 7, 10, 15, 20). We calculated a modified American Heart Association (AHA) CVH Score (weight, blood glucose, cholesterol, blood pressure, physical activity, and diet; Year 20); higher scores indicate better CVH. Generalized linear models evaluated associations between depression trajectories, smoking trajectories, and their interaction with CVH Score. RESULTS: The depression trajectory x smoking trajectory interaction was not associated with CVH Score, but main effects of depression trajectory (p

It is unclear how long-term medical utilization and costs from diverse care settings and their age-related patterns may differ by cardiovascular health (CVH) status earlier in adulthood. We followed 17,195 participants of the Chicago Heart Association Detection Project Industry (1967–1973) with linked Medicare claims (1992 to 2010). Baseline CVH is a composite measure of blood pressure, body mass index, diabetes, cholesterol, and smoking and includes four mutually exclusive strata: all factors were favorable (5.5%), one or more factors were elevated but none high (20.3%), one factor was high (40.9%), and two or more factors were high (33.2%). We assessed differences in the quantities (using negative binomial models) of and costs (using quantile regressions) for inpatient admissions, ambulatory care, home health care, and others between less favorable and all favorable CVH. All analyses adjusted for baseline age, race, sex, education, age at follow-up, year, state of residence, and death. We found that all favorable CVH in earlier adulthood was associated with lower long-term utilization and costs in all settings and the gap widened with age. Compared to all favorable CVH, the annual number of acute inpatient admissions per person was 79% greater (p-value < 0.001) for poor CVH, the median annual Medicare payment per person was $640 greater (41%, p-value < 0.001), and the mean was $4,628 greater (67%, p-value < 0.001). The cost differences were greatest for acute inpatient, followed by ambulatory, post-acute inpatient, home health, and other. Early prevention efforts may potentially result in compressed all-cause morbidity in later years of age, along with reductions in resource use and health care costs for associated conditions.

BACKGROUND: 24-h urine collections are the suggested method to measure daily urinary potassium excretion (uK) but are costly and burdensome to implement. OBJECTIVE: This study tested how well existing equations with the use of spot urine samples can estimate 24-h uK and if accuracy varies by timing of spot urine collection, age, race, or sex. DESIGN: This cross-sectional study used data from 407 participants aged 18–39 y from the Washington, DC area in 2011 and 554 participants aged 45–79 y from Chicago in 2013. Spot urine samples were collected in individual containers for 24 h, and 1 for each timed period (morning, afternoon, evening, and overnight) was selected. For each selected timed spot urine, 24-h uK was predicted through the use of published equations. Difference (bias) between predicted and measured 24-h uK was calculated for each timed period and within age, race, and sex subgroups. Individual-level differences were assessed through the use of Bland-Altman plots and correlation tests. RESULTS: For all equations, regardless of the timing of spot urine, mean bias was usually significantly different than 0. No one prediction equation was unbiased across all sex, race, and age subgroups. With the use of the Kawasaki and Tanaka equations, 24-h uK was overestimated at low levels and underestimated at high levels, whereas observed differential bias with the Mage equation was in the opposite direction. Depending on prediction equation and timing of urine sample, 61–75% of individual 24-h uKs were misclassified among 500-mg incremental categories from

Objective To evaluate 25-year physical activity (PA) trajectories from young to middle age and assess associations with the prevalence of coronary artery calcification (CAC). Patients and Methods This study includes 3175 participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study who self-reported PA by questionnaire at 8 follow-up examinations over 25 years (from March 1985-June 1986 through June 2010-May 2011). The presence of CAC (CAC>0) at year 25 was measured using computed tomography. Group-based trajectory modeling was used to identify PA trajectories with increasing age. Results We identified 3 distinct PA trajectories: trajectory 1, below PA guidelines (n=1813; 57.1%); trajectory 2, meeting PA guidelines (n=1094; 34.5%); and trajectory 3, 3 times PA guidelines (n=268; 8.4%). Trajectory 3 participants had higher adjusted odds of CAC>0 (adjusted odds ratio [OR], 1.27; 95% CI, 0.95-1.70) vs those in trajectory 1. Stratification by race showed that white participants who engaged in PA 3 times the guidelines had higher odds of developing CAC>0 (OR, 1.80; 95% CI, 1.21-2.67). Further stratification by sex showed higher odds for white males (OR, 1.86; 95% CI, 1.16-2.98), and similar but nonsignificant trends were noted for white females (OR, 1.71; 95% CI, 0.79-3.71). However, no such higher odds of CAC>0 for trajectory 3 were observed for black participants. Conclusion White individuals who participated in 3 times the recommended PA guidelines over 25 years had higher odds of developing coronary subclinical atherosclerosis by middle age. These findings warrant further exploration, especially by race, into possible biological mechanisms for CAC risk at very high levels of PA.

Considering that estradiol (E2) and n-3 polyunsaturated fatty acids (PUFAs) have roles in neurogenesis and in neurotransmission, we examined whether the association of PUFAs with incident depressive symptoms in postmenopausal women is modified by hormone therapy (HT) use or estrogen status.Women (N=1616) free of depressive symptoms at baseline (2000-2002) in the Multi-Ethnic Study of Atherosclerosis were classified by HT usage and quartiles of dietary eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and the sum EPA+DHA. Women with serum E2 ≤0.073 nmol/L (sample median), were classified low on E2. Poisson regression was used to model incident depressive symptoms at examination 3 (2004-05), defined by the Center for Epidemiological Studies Depression Scale ≥16 or taking an antidepressant, first as a function of HT use and n-3 PUFA quartiles, and second, as a function of low E2 status and n-3 PUFA quartiles.Among HT non- users, positive, graded relationships (p-trends≤0.003) were found between PUFAs and incident depressive symptoms. Compared to the lowest quartile, the adjusted risk ratios (RRs) for the highest were 2.10, 2.39, and 2.04 for EPA, DHA, and EPA+DHA, respectively. For HT users, no associations were seen. When analyses were run for E2 status, the RRs over quartiles of the PUFAs were positive and graded for low E2 women, but were null for High E2 women.Higher intakes of DHA and EPA were associated with higher risk of depressive symptoms in nonusers of HT, contrary to hypothesis.

BACKGROUND A previous study indicated that 31% of the elderly in Taiwan have a vitamin D deficiency. Vitamin D adequacy has been associated with physical performance in the elderly. OBJECTIVES The first aim of the current study was to identify the determinants for vitamin D deficiency. The second aim was to evaluate the association between vitamin D status and physical performance. DESIGN A total of 5664 community-dwelling participants aged ≥55 y were recruited since 2008. Plasma total 25-hydroxyvitamin D concentrations were originally determined by ELISA and calibrated to a chemiluminescence measurement. Physical performance was assessed by handgrip strength, the Short Physical Performance Battery, timed up and go, a 6-min walk test, and single-leg stands. Multiple linear regression and logistic regression were used to estimate the cross-sectional associations. RESULTS Vitamin D inadequacy (

Background Several studies have demonstrated the tremendous potential of using coronary artery calcium (CAC) in addition to traditional risk factors for coronary heart disease (CHD) risk prediction. However, to date, no risk score incorporating CAC has been developed. Objectives The goal of this study was to derive and validate a novel risk score to estimate 10-year CHD risk using CAC and traditional risk factors. Methods Algorithm development was conducted in the MESA (Multi-Ethnic Study of Atherosclerosis), a prospective community-based cohort study of 6,814 participants age 45 to 84 years, who were free of clinical heart disease at baseline and followed for 10 years. MESA is sex balanced and included 39% non-Hispanic whites, 12% Chinese Americans, 28% African Americans, and 22% Hispanic Americans. External validation was conducted in the HNR (Heinz Nixdorf Recall Study) and the DHS (Dallas Heart Study). Results Inclusion of CAC in the MESA risk score offered significant improvements in risk prediction (C-statistic 0.80 vs. 0.75; p Conclusions An accurate estimate of 10-year CHD risk can be obtained using traditional risk factors and CAC. The MESA risk score, which is available online on the MESA web site for easy use, can be used to aid clinicians when communicating risk to patients and when determining risk-based treatment strategies.

Atrial fibrillation (AF) occurs frequently in patients with chronic obstructive pulmonary disease. Epidemiologic studies have found inconsistent associations between lung function and AF, and none have studied pulmonary emphysema, which overlaps only partially with chronic obstructive pulmonary disease in the general population. The aim of this study was to assess the relation among lung function measured by spirometry, the percentage of emphysema-like lung on computed tomography, and incident AF. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study following 6,814 subjects free of clinical cardiovascular disease, including AF, at baseline. Spirometry was performed in a subset of 3,965 participants. Percentage emphysema was defined on baseline computed tomographic scans as lung regions950 Hounsfield units. Incident AF was identified from hospital discharge diagnosis and Medicare claims data. Cox proportional hazards models were used to assess independent associations of lung volumes and percentage emphysema with AF. A total of 3,811 participants with valid spirometric results were included in this study. The mean age was 64.5 ± 9.8 years, and 49.4% were men. AF developed in 149 subjects (3.8%) over a mean follow-up period of 4.1 years after spirometry. Lower levels of forced expiratory volume at 1 second and forced vital capacity were associated with a higher risk for AF (hazard ratios 1.21 and 1.19 per 500 ml, respectively, p0.001) after adjustment for demographic and cardiovascular risk factors. Percentage emphysema was not significantly related to AF. In conclusion, in a multiethnic community-based sample of subjects free of cardiovascular disease at baseline, functional airflow limitation was related to a higher risk for AF.

Background Cumulative blood pressure (BP) exposure may adversely influence myocardial function, predisposing individuals to heart failure later in life. Objectives This study sought to investigate how cumulative exposure to higher BP influences left ventricular (LV) function during young to middle adulthood. Methods The CARDIA (Coronary Artery Risk Development in Young Adults) study prospectively enrolled 5,115 healthy African Americans and whites in 1985 and 1986 (baseline). At the year 25 examination, LV function was measured by 2-dimensional echocardiography; cardiac deformation was assessed in detail by speckle-tracking echocardiography. We used cumulative exposure of BP through baseline and up to the year 25 examination (millimeters of mercury × year) to represent long-term exposure to BP levels. Linear regression and logistic regression were used to quantify the association of BP measured repeatedly through early adulthood (18 to 30 years of age) up to middle age (43 to 55 years). Results Among 2,479 participants, cumulative BP measures were not related to LV ejection fraction; however, high cumulative exposure to systolic blood pressure (SBP) and diastolic blood pressure (DBP) were associated with lower longitudinal strain rate (both p Conclusions Higher cumulative exposure to BP over 25 years from young adulthood to middle age is associated with incipient LV systolic and diastolic dysfunction in middle age.

Background Isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) ≥140 mm Hg and diastolic blood pressure (DBP) Objective The aim of this study was to assess the risk for cardiovascular disease (CVD) with ISH in younger and middle-aged adults. Methods CVD risks were explored in 15,868 men and 11,213 women 18 to 49 years of age (mean age 34 years) at baseline, 85% non-Hispanic white, free of coronary heart disease (CHD) and antihypertensive therapy, from the Chicago Heart Association Detection Project in Industry study. Participant classifications were as follows: 1) optimal-normal blood pressure (BP) (SBP Results During a 31-year average follow-up period (842,600 person-years), there were 1,728 deaths from CVD, 1,168 from CHD, and 223 from stroke. Cox proportional hazards models were adjusted for age, race, education, body mass index, current smoking, total cholesterol, and diabetes. In men, with optimal-normal BP as the reference stratum, hazard ratios for CVD and CHD mortality risk for those with ISH were 1.23 (95% confidence interval [CI]: 1.03 to 1.46) and 1.28 (95% CI: 1.04 to 1.58), respectively. ISH risks were similar to those with high-normal BP and less than those associated with isolated diastolic hypertension and systolic diastolic hypertension. In women with ISH, hazard ratios for CVD and CHD mortality risk were 1.55 (95% CI: 1.18 to 2.05) and 2.12 (95% CI: 1.49 to 3.01), respectively. ISH risks were higher than in those with high-normal BP or isolated diastolic hypertension and less than those associated with systolic diastolic hypertension. Conclusions Over long-term follow-up, younger and middle-aged adults with ISH had higher relative risk for CVD and CHD mortality than those with optimal-normal BP.

Objectives The goal of this study was to investigate the relationship of body mass index (BMI) and its 25-year change to left ventricular (LV) structure and function. Background Longstanding obesity may be associated with clinical cardiac dysfunction and heart failure. Whether obesity relates to cardiac dysfunction during young adulthood and middle age has not been investigated. Methods The CARDIA (Coronary Artery Risk Development in Young Adult) study enrolled white and black adults ages 18 to 30 years in 1985 to 1986 (Year-0). At Year-25, cardiac function was assessed by conventional echocardiography, tissue Doppler imaging (TDI), and speckle tracking echocardiography (STE). Twenty-five–year change in BMI (classified as low: Results The mean BMI was 24.4 kg/m2 in 3,265 participants included at Year-0. Change in BMI adjusted for risk factors was directly associated with incipient myocardial systolic dysfunction assessed by STE (High-High: β-coefficient = 0.67; Low-High: β-coefficient = 0.35 for longitudinal peak systolic strain) and diastolic dysfunction assessed by TDI (High-High: β-coefficient = −074; Low-High: β-coefficient = −0.45 for e′) and STE (High-High: β-coefficient = −0.06 for circumferential early diastolic strain rate). Greater BMI was also significantly associated with increased LV mass/height (High-High: β-coefficient = 26.11; Low-High: β-coefficient = 11.87). Conclusions Longstanding obesity from young adulthood to middle age is associated with impaired LV systolic and diastolic function assessed by conventional echocardiography, TDI, and STE in a large biracial cohort of adults age 43 to 55 years.

Background and aim Short sleep duration and poor quality sleep are associated with coronary heart disease (CHD) mortality; however, the underlying pathophysiologic process remains unclear. Sleep apnea may confound the association because of its relationship with formation of thrombi, the vascular occlusive process in CHD. We tested whether sleep duration and quality were associated with prothrombotic biomarkers in adults with a low probability of apnea. Methods We included adults aged 35–64years recruited from the community and who had an apnea hypopnea index n =506). Sleep duration and maintenance were determined from 7days of wrist actigraphy; daytime sleepiness was estimated using the Epworth Sleepiness Scale. Factor VIII (FVIII), von Willebrand factor (vWF), thrombin antithrombin (TAT) complexes, and plasminogen activator inhibitor-1 (PAI-1) were measured in fasting blood. Results Sleep duration, maintenance, and daytime sleepiness were not associated with FVIII, vWf, or TAT. Sleep maintenance was modestly inversely associated with higher levels of log-transformed PAI-1 ( β =−0.07, standard error (SE)=0.03 per 4.8%, p =0.04) following adjustment for demographic characteristics, cardiovascular risk factors, and body mass index (BMI). Conclusions Mild impairment in sleep was modestly associated with activation of coagulation; further study is needed to evaluate the role of fibrinolytic factors in sleep-mediated coronary thrombosis.

Background Basic research suggests that rapid increases in circulating inflammatory and hemostatic blood markers may trigger or indicate impending plaque rupture and coronary thrombosis, resulting in acute ischemic heart disease (IHD) events. However, these associations are not established in humans. Methods and results The Biomarker Risk Assessment in Vulnerable Outpatients (BRAVO) Study will determine whether levels of inflammatory and hemostatic biomarkers rapidly increase during the weeks prior to an acute IHD event in people with lower extremity peripheral artery disease (PAD). The BRAVO Study will determine whether biomarker levels measured immediately prior to an IHD event are higher than levels not preceding an IHD event; whether participants who experience an IHD event (cases) have higher biomarker levels immediately prior to the event and higher biomarker levels at each time point leading up to the IHD event than participants without an IHD event (controls); and whether case participants have greater increases in biomarkers during the months leading up to the event than controls. BRAVO enrolled 595 patients with PAD, a population at high risk for acute IHD events. After a baseline visit, participants returned every two months for blood collection, underwent an electrocardiogram to identify new silent myocardial infarctions, and were queried about new hospitalizations since their prior study visit. Mortality data were also collected. Participants were followed prospectively for up to three years. Conclusions BRAVO results will provide important information about the pathophysiology of IHD events and may lead to improved therapies for preventing IHD events in high-risk patients.

Selenium is an essential trace element important to neurotransmission, but toxic at high levels. Some studies suggest beneficial effects on mood. We assessed the association of selenium exposure with presence of depressive symptoms. Selenium exposure was measured in toenail samples collected in 1987 from 3,735 US participants (age 20–32 years) and depressive symptoms assessed in 1990, 1995, 2000, 2005, and 2010 using the Center for Epidemiologic Studies Depression Scale (CES-D). Binary and polytomous logistic regression models were used to assess the relation of log2(selenium) and selenium quintiles with presence of depressive symptoms (CES-D score ≥ 27 or on antidepressant medication). Relative to selenium quintile 1, the adjusted odds ratio (OR) for having depressive symptoms in 1990 for quintile 5 was 1.59 (95% CI: 1.01, 2.51) and a unit increase in log2(selenium), which represents a doubling of the selenium level, was associated with an OR=2.03 (95% CI: 1.12, 3.70). When examining 1, 2 or 3+ exams vs no exams with symptoms, the OR for quintile 5 was 1.73 (1.04, 2.89) for 3+ exams and for one exam and two exams, there were no associations. In a generalized estimating equations longitudinal model, a doubling of the selenium level was associated with a 56% higher odds of having depressive symptoms at an exam. Contrary to previously reported findings related to mood, higher level of selenium exposure was associated with presence of elevated depressive symptoms. More research is needed to elucidate the role of selenium in depressive disorders.

BackgroundFramingham risk score (FRS) underestimates risk in young adults. Left ventricular mass (LVM) relates to cardiovascular disease (CVD), with unclear value in youth. In a young biracial cohort, we investigate how FRS predicts CVD over 20 years and the incremental value of LVM. We also explore the predictive ability of different cut-points for hypertrophy.MethodsWe assessed FRS and echocardiography-derived LVM (indexed by body surface area or height2.7) from 3980 African-American and white Coronary Artery Risk Development in Young Adults (CARDIA) participants (1990-1991); and followed over 20 years for a combined endpoint: cardiovascular death; nonfatal myocardial infarction, heart failure, cerebrovascular disease, and peripheral artery disease. We assessed the predictive ability of FRS for CVD and also calibration, discrimination, and net reclassification improvement for adding LVM to FRS.ResultsMean age was 30±4 years, 46% males, and 52% white. Event incidence (n=118) across FRS groups was, respectively, 1.3%, 5.4%, and 23.1% (p

Left ventricular (LV) mass and the LV ejection fraction (LVEF) are major independent predictors of future cardiovascular disease. The association of LV mass with the future LVEF in younger populations has not been studied. The aim of this study was to investigate the relation of LV mass index (LVMI) at ages 23 to 35 years to LV function after 20 years of follow-up in the Coronary Artery Risk Development in Young Adults (CARDIA) study. CARDIA is a longitudinal study that enrolled young adults in 1985 and 1986. In this study, participants with echocardiographic examinations at years 5 and 25 were included. LVMI and the LVEF were assessed using M-mode echocardiography at year 5 and using M-mode and 2-dimensional imaging at year 25. Statistical analytic models assessed the correlation between LVMI and LV functional parameters cross-sectionally and longitudinally. A total of 2,339 participants were included. The mean LVEF at year 25 was 62%. Although there was no cross-sectional correlation between LVMI and the LVEF at year 5, there was a small but statistically significant negative correlation between LVMI at year 5 and the LVEF 20 years later (r = -0.10, p0.0001); this inverse association persisted for LVMI in the multivariate model. High LVMI was an independent predictor of systolic dysfunction (LVEF50%) 20 years later (odds ratio 1.46, p = 0.0018). In conclusion, LVMI in young adulthood in association with chronic risk exposure affects systolic function in middle age; the antecedents of heart failure may occur at younger ages than previously thought.

Relative weight, often characterized as body mass index (BMI), is a factor associated with left ventricular (LV) mass and geometry. Cross-sectional studies in middle-aged adults showed higher BMI was associated with higher LV mass and volumes [(1)][1]. Longitudinal data in another middle-aged cohort

Whether autonomic dysfunction predates the development of symptomatic heart failure (HF) or is simply a consequence of severe HF is unknown. We hypothesized that reduced heart rate variability (a marker of abnormal autonomic function) at baseline is associated with incident HF in subjects free of clinically recognized cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical cardiovascular disease in adults aged 45 to 84 years, we measured the heart rate variability using a standard 30-second, 12-lead electrocardiogram to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). During a median follow-up of 7.6 years, 95 participants developed HF (incidence rate 2.7/1,000 person-years). After adjusting for age, gender, and ethnicity, the hazard ratio for incident HF stratified by the RMSSD tertile was 2.4 (95% confidence interval 1.4 to 4.2) for the lowest tertile and 1.7 (95% confidence interval 1.0 to 3.2) for the middle tertile (highest tertile was the referent group; p for trend

Because of the logistic complexity, excessive respondent burden, and high cost of conducting 24-h urine collections in a national survey, alternative strategies to monitor sodium intake at the population level need to be evaluated. We conducted a calibration study to assess the ability to characterize sodium intake from timed-spot urine samples calibrated to a 24-h urine collection. In this report, we described the overall design and basic results of the study. Adults aged 18–39 y were recruited to collect urine for a 24-h period, placing each void in a separate container. Four timed-spot specimens (morning, afternoon, evening, and overnight) and the 24-h collection were analyzed for sodium, potassium, chloride, creatinine, and iodine. Of 481 eligible persons, 407 (54% female, 48% black) completed a 24-h urine collection. A subsample (n = 133) collected a second 24-h urine 4–11 d later. Mean sodium excretion was 3.54 6 1.51 g/d for males and 3.09 6 1.26 g/d for females. Sensitivity analysis excluding those who did not meet the expected creatinine excretion criterion showed the same results. Day-to-day variability for sodium, potassium, chloride, and iodine was observed among those collecting two 24-h urine samples (CV = 16–29% for 24-h urine samples and 21–41% for timed-spot specimens). Among all race-gender groups, overnight specimens had larger volumes (P < 0.01) and lower sodium (P < 0.01 to P 5 0.26), potassium (P < 0.01), and chloride (P < 0.01) concentrations compared with other timed-spot urine samples, although the differences were not always significant. Urine creatinine and iodine concentrations did not differ by the timing of collection. The observed day-to-day and diurnal variations in sodium excretion illustrate the importance of accounting for these factors when developing calibration equations from this study. J. Nutr. 143: 1276–1282, 2013.

Background: Increasing dietary sodium drives the thirst response. Because sugar-sweetened beverages (SSBs) are frequently consumed by children, sodium intake may drive greater consumption of SSBs and contribute to obesity risk. Objective: We examined the association between dietary sodium, total fluid, and SSB consumption in a nationally representative sample of US children and adolescents aged 2–18 y. Design: We analyzed cross-sectional data from NHANES 2005–2008. Dietary sodium, fluid, and SSB intakes were assessed with a 24-h dietary recall. Multiple regression analysis was used to assess associations between sodium, fluid, and SSBs adjusted for age, sex, race-ethnic group, body mass index (BMI), socioeconomic status (SES), and energy intake. Results: Of 6400 participants, 51.3% (n = 3230) were males, and the average (±SEM) age was 10.1 ± 0.1 y. The average sodium intake was 3056 ± 48 mg/d (equivalent to 7.8 ± 0.1 g salt/d). Dietary sodium intake was positively associated with fluid consumption (r = 0.42, P < 0.001). After adjustment for age, sex, race-ethnic group, SES, and BMI, each additional 390 mg Na/d (1 g salt/d) was associated with a 74-g/d greater intake of fluid (P < 0.001). In consumers of SSBs (n = 4443; 64%), each additional 390 mg Na/d (1 g salt/d) was associated with a 32-g/d higher intake of SSBs (P < 0.001) adjusted for age, sex, race-ethnic group, SES, and energy intake. Conclusions: Dietary sodium is positively associated with fluid consumption and predicted SSB consumption in consumers of SSBs. The high dietary sodium intake of US children and adolescents may contribute to a greater consumption of SSBs, identifying a possible link between dietary sodium intake and excess energy intake.

We studied associations of magnetic resonance imaging (MRI)-measured superficial femoral artery (SFA) occlusions with functional performance, leg symptoms, and collateral vessel number in peripheral artery disease (PAD). We studied associations of collateral vessel number with functional performance in PAD.Associations of MRI-detected SFA occlusion and collateral vessel number with functional performance among individuals with PAD have not been reported.A total of 457 participants with an ankle brachial index (ABI)1.00 had MRI measurement of the proximal SFA with 12 consecutive 2.5-μm cross-sectional images. An occluded SFA was defined as an SFA in which at least 1 segment was occluded. A nonoccluded SFA was defined as absence of any occluded slices. Collateral vessels were visualized with magnetic resonance angiography. Lower extremity functional performance was measured with the 6-min walk, 4-m walking velocity at usual and fastest pace, and the Short Physical Performance Battery (SPPB) (0 to 12 scale, 12 = best).Adjusting for age, sex, race, comorbidities, and other confounders, the presence of an SFA occlusion was associated with poorer 6-min walk performance (1,031 vs. 1,169 feet, p = 0.006), slower fast-paced walking velocity (1.15 vs. 1.22 m/s, p = 0.042), and lower SPPB score (9.07 vs. 9.75, p = 0.038) compared with the absence of an SFA occlusion. More numerous collateral vessels were associated with better 6-min walk performance (0 to 3 collaterals-1,064 feet, 4 to 7 collaterals-1,165 feet, ≥8 collaterals-1,246 feet, p trend = 0.007), faster usual-paced walking speed (0 to 3 collaterals-0.84 m/s, 4 to 7 collaterals-0.88 m/s, ≥8 collaterals-0.91 m/s, p trend = 0.029), and faster rapid-paced walking speed (0 to 3 collaterals-1.17 m/s, 4 to 7 collaterals-1.22 m/s, ≥8 collaterals-1.29 m/s, p trend = 0.002), adjusting for age, sex, race, comorbidities, ABI, and other confounders.Among PAD participants, MRI-visualized occlusions in the proximal SFA are associated with poorer functional performance, whereas more numerous collaterals are associated with better functional performance. (Magnetic Resonance Imaging to Identify Characteristics of Plaque Build-Up in People With Peripheral Arterial Disease; NCT00520312).

Objectives This study determined whether greater 2-year declines in Walking Impairment Questionnaire (WIQ) stair climbing, distance, or speed scores were associated with higher all-cause and cardiovascular disease (CVD) mortality among men and women with lower extremity peripheral artery disease (PAD). Background Associations of decline in the WIQ with mortality among people with PAD are unknown. Methods Participants were 442 men and women with PAD identified from Chicago area medical centers. The WIQ was completed at baseline and at 2-year follow-up. Cox proportional hazard models were used to assess associations across categories of 2-year changes in WIQ stair climbing, WIQ distance, and WIQ speed scores with subsequent all-cause and CVD mortality, adjusting for age, sex, race, ankle-brachial index, body mass index, smoking, comorbidities, and other covariates. Results One hundred twenty-three participants (27.8%) died during a median follow-up of 4.7 years after the 2-year change in WIQ score measurements. Forty-five participants died from CVD. Adjusting for covariates, participants with WIQ score declines ≥20.0 points had higher all-cause mortality (hazard ratio [HR]: 1.93, 95% confidence interval [CI]: 1.01 to 3.68 for WIQ stair climbing; HR: 2.34, 95% CI: 1.15 to 4.75 for WIQ distance; and HR: 3.55, 95% CI: 1.57 to 8.04 for WIQ speed, respectively) compared with participants with ≥20.0 point improvement in each of the corresponding WIQ categories. Participants with ≥20.0 point declines in the WIQ distance score had higher CVD mortality (HR: 4.56, 95% CI: 1.30 to 16.01) compared with those with ≥20.0 point improvement in the WIQ distance score. Conclusions Patients with PAD who experienced ≥20.0 point declines in the WIQ stair climbing, distance, and speed scores had a higher rate of all-cause mortality compared with those with less declines in each WIQ score.

Objectives The study examined whether progression of coronary artery calcium (CAC) is a predictor of future coronary heart disease (CHD) events. Background CAC predicts CHD events and serial measurement of CAC has been proposed to evaluate atherosclerosis progression. Methods We studied 6,778 persons (52.8% female) aged 45 to 84 years from the MESA (Multi-Ethnic Study of Atherosclerosis) study. A total of 5,682 persons had baseline and follow-up CAC scans approximately 2.5 ± 0.8 years apart; multiple imputation was used to account for the remainder (n = 1,096) missing follow-up scans. Median follow-up duration from the baseline was 7.6 (max = 9.0) years. CAC change was assessed by absolute change between baseline and follow-up CAC. Cox proportional hazards regression providing hazard ratios (HRs) examined the relation of change in CAC with CHD events, adjusting for age, gender, ethnicity, baseline calcium score, and other risk factors. Results A total of 343 and 206 hard CHD events occurred. The annual change in CAC averaged 24.9 ± 65.3 Agatston units. Among persons without CAC at baseline (n = 3,396), a 5-unit annual change in CAC was associated with an adjusted HR (95% Confidence Interval) of 1.4 (1.0 to 1.9) for total and 1.5 (1.1 to 2.1) for hard CHD. Among those with CAC >0 at baseline, HRs (per 100 unit annual change) were 1.2 (1.1 to 1.4) and 1.3 (1.1 to 1.5), respectively. Among participants with baseline CAC, those with annual progression of ≥300 units had adjusted HRs of 3.8 (1.5 to 9.6) for total and 6.3 (1.9 to 21.5) for hard CHD compared to those without progression. Conclusions Progression of CAC is associated with an increased risk for future hard and total CHD events.

Objectives The objective of this analysis was to determine the natural history and prospective association of cardiovascular risk factors with early repolarization (ER). Background ER is common and has been suggested to increase risk for cardiovascular mortality in middle-aged adults. Data are sparse regarding the natural history of ER from young adulthood to middle age. Methods We examined 5,069 participants (mean age 25 years at baseline; 40% black) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort over 20 years. Electrocardiograms were recorded at years 0 (Y0), 7 (Y7), and 20 (Y20) and coded as either definite, probable, possible, or no ER. Logistic regression was used to determine the association of cardiovascular risk factors with the presence of ER cross-sectionally and prospectively. Results A total of 941 of the 5,069 participants (18.6%) had definite ER at baseline, and only 119 of 2,505 participants (4.8%) at the Y20 examination still demonstrated the presence of ER. Younger age, black race, male sex, longer exercise duration and QRS duration, and lower body mass index (BMI), heart rate, QT index, and Cornell voltage were associated cross-sectionally with the presence of ER. Predictors of maintenance of ER from Y0 to Y20 were black race (odds ratio [OR]: 2.62; 95% CI; 1.61 to 4.25), BMI (OR: 0.62 per 1 SD; 95% CI: 0.40 to 0.94), serum triglyceride levels (OR: 0.66 per 1 SD; 95% CI: 0.45 to 0.98), and QRS duration (OR: 1.68 per 1 SD; 95% CI: 1.37 to 2.06) at baseline. Conclusions The prevalence of ER was significantly higher than previous estimates among asymptomatic young adults, and the majority of ER regressed by middle age. Black race, lower BMI, lower serum triglyceride levels, and longer QRS duration were independently associated with maintenance of ER over time.

Cross-sectional and prospective studies have linked cardiovascular events and traditional risk factors (TRFs) with higher plasma fibrinogen levels. In a young cohort, we sought to determine longitudinal associations between changes in/development of TRFs and fibrinogen levels over 13 years.We included 2525 adults from the CARDIA study, aged 25-37 with fibrinogen and TRFs measured at year 7 (study baseline; 1992-1993); and year 20 (follow-up). Multiple linear regressions were used to compare mean changes in fibrinogen to TRFs.Mean fibrinogen increased by 71 mg/dL vs. 70 mg/dL (p = NS) in black vs. white men, and 78 mg/dL vs. 68 mg/dL (p 0.05) in black vs. white women, respectively over 13 years. After multivariable adjustments, fibrinogen generally rose with increasing BMI (p 0.001; all sex/race groups), LDL cholesterol, log triglycerides and diastolic blood pressure; and fell with increasing HDL cholesterol and physical activity. 13-year increase in fibrinogen for persons who quit smoking or became non-obese were comparable (p = NS) to that of never-smokers and never-obese persons.Among young black and white men and women with few baseline cardiovascular risk factors, fibrinogen tracked longitudinally with changes in TRFs over 13 years through middle age. There was a strong inverse longitudinal relationship between modifiable risk factors (weight loss/smoking cessation) and 13-year change in fibrinogen. Our study helps provide some insight into the role of fibrinogen as a disease marker in the associations between fibrinogen and CVD.

Background Systemic inflammation has been linked to the development of heart failure in population studies including Multi-Ethnic Study of Atherosclerosis (MESA), but little evidence exists regarding potential mechanism of this relationship. In this study, we used longitudinal magnetic resonance imaging follow-up analysis to examine whether C-reactive protein (CRP) levels relate to progressive myocardial functional deterioration as a potential mechanism of incident heart failure. Methods Regional myocardial functional data from MESA participants who had baseline CRP measurement and also underwent tagged cardiac magnetic resonance imaging both at baseline and at 5-year follow-up were analyzed. Left ventricular midwall and midslice peak circumferential strain (Ecc), of which a more negative value denotes stronger regional myocardial function, was measured. Circumferential strain change was calculated as the difference between baseline and follow-up Ecc. Results During the follow-up period, participants (n = 785) with elevated CRP experienced a decrease in strain, independent of age, gender, and ethnicity (B = 0.081, ΔEcc change per 1 mg/L CRP change, 95% CI 0.036-0.126, P b .001, model 1) and, additionally, beyond systolic blood pressure, heart rate, diabetes, smoking status, body mass index, current medication, and glomerular filtration rate (B = 0.099, 0.052-0.145, P b .001, model 2). The relationship remained statistically significant after further adjustment for left ventricular mass, coronary calcium score, and interim clinical coronary events (B = 0.098, 0.049-0.147, P b .001, model 3). Conclusion Higher CRP levels are related to progressive myocardial functional deterioration independent of subclinical atherosclerosis and clinical coronary events in asymptomatic individuals without previous history of heart disease. (Am Heart J

Objectives This study sought to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM) versus those with neither condition. Background MetS and DM are associated with subclinical atherosclerosis as evidenced by CAC. Methods The MESA (Multiethnic Study of Atherosclerosis) included 6,814 African American, Asian, Caucasian, and Hispanic adults 45 to 84 years of age, who were free of cardiovascular disease at baseline. Of these, 5,662 subjects (51% women, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac computed tomography scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%) to incidence and progression in subjects with neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years. Results Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals [CI]) for incident CAC were 1.7 (95% CI: 1.4 to 2.0), 1.9 (95% CI: 1.4 to 2.4), and 1.8 (95% CI: 1.4 to 2.2) (all p Conclusions Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared with individuals without these conditions, with progression also predicting coronary heart disease events in those with MetS and DM.

Objectives This study analyzed whether lower calf muscle density and poorer upper and lower extremity strength are associated with higher mortality rates in men and women with peripheral arterial disease (PAD). Background Men and women with lower extremity PAD have lower calf muscle density and reduced lower extremity strength compared with individuals without PAD. Methods At baseline, participants underwent measurement of calf muscle density with computed tomography in addition to knee extension power and isometric knee extension, plantar flexion, and hand grip strength measures. Participants were followed up annually for up to 4 years. Results were adjusted for age, sex, race, body mass index, ankle-brachial index, smoking, physical activity, and comorbidities. Results Among 434 PAD participants, 103 (24%) died during a mean follow-up of 47.6 months. Lower calf muscle density was associated with higher all-cause mortality (lowest density tertile hazard ratio [HR]: 1.80 [95% confidence interval (CI): 1.07 to 3.03], second tertile HR: 0.91 (95% CI: 0.51 to 1.62); highest density tertile HR: 1.00; p trend = 0.020) and higher cardiovascular disease mortality (lowest density tertile HR: 2.39 [95% CI: 0.90 to 6.30], second tertile HR: 0.85 [95% CI: 0.27 to 2.71]; highest density tertile HR: 1.00; p trend = 0.047). Poorer plantar flexion strength (p trend = 0.004), lower baseline leg power (p trend = 0.046), and poorer handgrip (p trend = 0.005) were associated with higher all-cause mortality. Conclusions These data demonstrate that lower calf muscle density and weaker plantar flexion strength, knee extension power, and hand grip were associated with increased mortality in these participants with PAD, independently of the ankle-brachial index and other confounders.

Background Data describing factors associated with the development of a prolonged QRS duration (QRSd) from young adulthood to middle age are sparse. Methods We analyzed 12-lead electrocardiograms (ECGs) from the Coronary Artery Risk Development in Young Adults study over 20 years. We performed logistic regression to examine the associations of baseline (year 0) or average (years 0-20) risk factors with incident prolonged QRSd (QRS >100 milliseconds). Results We included 2537 participants (57.2% women, 44.7% black; mean age, 25 years); 292 (11.5%) developed incident QRSd greater than 100 milliseconds by year 20. In univariate analyses, baseline covariates associated with incident QRSd prolongation included white race, male sex, ECG–left ventricular mass index, and baseline QRSd. Similar results were observed after multivariable adjustment. Conclusion We found no long-term associations of modifiable risk factors with incident QRSd >100 milliseconds. Men, whites, and those with higher ECG–left ventricular mass index and QRSd in young adulthood are at an increased risk for incident prolonged QRSd by middle age.

Religious involvement has been associated with improved health outcomes but greater obesity in older adults. No longitudinal study of young adults has examined the prospective association of religious involvement with incident cardiovascular risk factors (RFs) and subclinical disease (subCVD).We included 2433 participants of the CARDIA study, aged 20 to 32 in 1987 when religiosity was assessed, who were followed for 18 years. Multivariable-adjusted regression models were fitted to assess prospective associations of frequency of religious participation at baseline with incidence of RFs and prevalence of subCVD after 18 years' follow up.The high frequency of religious participation was associated with a significantly greater incidence of obesity in unadjusted models (RR 1.57, 95% CI 1.14-1.73) and demographic-adjusted models (RR 1.34, 95% CI 1.09-1.65) but not after additional adjustment for baseline RFs (RR 1.17, 95% CI .97-1.41). When religious participation was treated dichotomously, any religious participation, compared with none, was associated with significantly lower subCVD.Frequent religious participants are more likely to become obese between young adulthood and middle age; this association is confounded by demographic and other factors. Nonetheless, young adults with frequent participation may represent an opportunity for obesity prevention.

Objectives We studied associations of magnetic resonance imaging measurements of plaque area and relative percent lumen reduction in the proximal superficial femoral artery with functional performance among participants with peripheral arterial disease. Background The clinical significance of directly imaged plaque characteristics in lower extremity arteries is not well established. Methods A total of 454 participants with an ankle brachial index Results Adjusting for age, sex, race, body mass index, smoking, statin use, comorbidities, and other covariates, higher mean plaque area (1st quintile [least plaque]: 394 m, 2nd quintile: 360 m, 3rd quintile: 359 m, 4th quintile: 329 m, 5th quintile [greatest plaque]: 311 m; p trend Conclusions Among participants with peripheral arterial disease, greater plaque burden and smaller lumen area in the proximal superficial femoral artery are associated independently with poorer functional performance, even after adjusting for the ankle brachial index and leg symptoms.

Objectives By examining the distribution of coronary artery calcium (CAC) levels across Framingham risk score (FRS) strata in a large, multiethnic, community-based sample of men and women, we sought to determine if lower-risk persons could benefit from CAC screening. Background The 10-year FRS and CAC levels are predictors of coronary heart disease. A CAC level of 300 or more is associated with the highest risk for coronary heart disease even in low-risk persons (FRS, Methods We included 5,660 Multi-Ethnic Study of Atherosclerosis participants. The number needed to screen (number of people that need to be screened to detect 1 person with CAC level above the specified cutoff point) was used to assess the yield of screening for CAC. CAC prevalence was compared across FRS strata using chi-square tests. Results CAC levels of more than 0, of 100 or more, and of 300 or more were present in 46.4%, 20.6%, and 10.1% of participants, respectively. The prevalence and amount of CAC increased with higher FRS. A CAC level of 300 or more was observed in 1.7% and 4.4% of those with FRS of 0% to 2.5% and of 2.6% to 5%, respectively (number needed to screen, 59.7 and 22.7, respectively). Likewise, a CAC level of 300 or more was observed in 24% and 30% of those with FRS of 15.1% to 20% and more than 20%, respectively (number needed to screen, 4.2 and 3.3, respectively). Trends were similar when stratified by age, sex, and race or ethnicity. Conclusions Our study suggests that in very low-risk individuals (FRS ≤5%), the yield of screening and probability of identifying persons with clinically significant levels of CAC is low, but becomes greater in low- and intermediate-risk persons (FRS 5.1% to 20%).

Objectives We sought to examine the prognostic value of subclinical left ventricular (LV) regional myocardial dysfunction (RMD) measured by magnetic resonance imaging (MRI) among asymptomatic individuals. Background LV RMD, defined as segmental impairment in systolic wall thickening, predicts adverse events in patients with established cardiovascular disease. MRI is highly accurate for detecting subtle RMD, of which the prognostic significance in a large multiethnic asymptomatic population is not known. Methods We used MRI to evaluate baseline regional LV myocardial function and prospectively followed a multiethnic (African American, Caucasian, Chinese, and Hispanic) population-based sample of 4,510 men and women without cardiovascular disease for a mean of 4.6 years. Regional myocardial dysfunction was defined as the presence of impaired systolic wall thickening ( Results Baseline prevalence of RMD was 25.6%. Heart failure developed in 34 (1.0%) and 30 (2.6%) participants without and with RMD, respectively (p Conclusions Among an asymptomatic multiethnic American cohort, RMD is an independent predictor beyond traditional risk factors and global LV assessment for incident heart failure and atherosclerotic cardiovascular events. The clinical utility of early recognition of this subclinical phenotype deserves further investigation. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487)

Even among asymptomatic persons at low risk (10%) according to the Framingham risk score, high coronary artery calcium (CAC) scores signify a greater predicted risk of coronary heart disease events. We sought to determine the noninvasive factors (without radiation exposure) significantly associated with CAC in low-risk, asymptomatic persons. In a cross-sectional analysis, we studied 3,046 participants from the Multi-Ethnic Study of Atherosclerosis at a low 10-year predicted risk (Framingham risk score10%) of coronary heart disease events. Multivariate logistic regression analysis was used to assess the association of novel markers with the presence of any CAC (CAC0) and advanced CAC (CAC ≥ 300). A CAC level of0 and of ≥ 300 was present in 30% and 3.5% of participants, respectively. Factor VIIIc, fibrinogen, and soluble intercellular adhesion molecule were each associated with the presence of CAC (p ≤ 0.02), and C-reactive protein, D-dimer, and the carotid intima-media thickness with advanced CAC (p ≤ 0.03). The base model combining the traditional risk factors had excellent discrimination for advanced CAC (C-statistic 0.808). The addition of the 2 best-fit models combining the biomarkers with or without carotid intima-media thickness improved the c-statistic to 0.822 and 0.820, respectively. All 3 models calibrated well but were similar in estimating the individual risk probabilities for advanced CAC (prevalence 9.97%, 10.63%, and 10.10% in the greatest quartiles of predicted probabilities vs 0.26%, 0.26%, and 0.26% in the lowest quartiles, respectively). In conclusion, in low-risk persons, the traditional risk factors alone predicted advanced CAC with high discrimination and calibration. The biomarker combinations with and without carotid intima-media thickness were also significantly associated with advanced CAC; however, the improvement in the prediction and estimation of the clinical risk were modest compared to the traditional risk factors alone.

Objectives We hypothesized that a greater 2-year decline in office-based functional performance measures would be associated with greater mobility loss and mortality in people with peripheral arterial disease (PAD). Background Associations of decline in functional performance with clinically important outcomes in patients with PAD are unknown. Methods A total of 440 men and women with PAD completed the 6-min walk test and measures of walking velocity at baseline and annually for 2 years. Participants were categorized into tertiles according to their functional decline between baseline and 2-year follow-up and were followed annually after the functional change assessment. Cox proportional hazard models were used to assess relations between the 2-year change in functional performance with later mortality and mobility loss, with adjustments for age, sex, race, ankle brachial index, comorbidities, and other confounders. Results A total of 102 participants (23.2%) died during a median follow-up of 44.5 months after functional change was assessed. Of 319 participants without baseline mobility disability, 60 (18.8%) developed mobility loss after functional change was assessed. Participants in the tertile with the greatest 6-min walk decline had the highest subsequent mobility loss (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.56 to 7.85; p = 0.002), all-cause mortality (HR: 2.16; 95% CI: 1.28 to 3.64; p = 0.004), and cardiovascular disease mortality (HR: 2.45; 95% CI: 1.08 to 5.54; p = 0.031), compared with those with the smallest 6-min walk decline. Greater declines in fastest-paced 4-m walking velocity were associated with higher mobility loss (p trend = 0.018), all-cause mortality (p trend = 0.01), and cardiovascular mortality (p trend = 0.004). Conclusions Participants with PAD with declining functional performance are at increased risk for later mobility loss and mortality.

Background The association between measures of subclinical cardiovascular disease and progression of urine albumin-creatinine ratios (UACRs) over time is uncertain. Study Design Prospective cohort study. Setting & Participants The Multi-Ethnic Study of Atherosclerosis (MESA), a cohort of adults aged 45-84 years without baseline clinical cardiovascular disease. Examinations were completed approximately every 1.5 years, and UACR was measured during the first 3 examinations. Analysis was limited to 4,878 participants without baseline micro- or macroalbuminuria. Predictor 1–standard deviation (SD) unit difference in baseline maximum common and internal carotid intima-media thickness (CIMT) measured using ultrasonography. Outcomes & Measurements Baseline UACR was categorized as normal or high-normal. UACR progression was categorized as no progression (consistent UACR category across all 3 examinations or regression to a lower category) and definite progression (higher UACR category at examination 2 compared with baseline, then stabilizing or progressing at examination 3). UACR changes not consistent with definite or no UACR progression were classified as intermediate UACR progression. Change in log UACR also was examined. Results In the 4,878 participants, median baseline UACR was 4.6 mg/g (range, 0.4-24.6 mg/g). Definite and intermediate UACR progression was noted in 279 and 807, respectively. Every 1-SD unit difference in common CIMT was associated with a 22% increased adjusted odds of definite compared with no UACR progression (95% CI, 1.07-1.41). No significant association was noted between 1-SD unit difference in maximum internal CIMT and definite UACR progression after adjusting for covariates (OR, 1.08; 95% CI, 0.96-1.21). In the mixed-effects model, changes in log UACR were 0.029 (95% CI, 0.012-0.046) and 0.019 mg/g (95% CI, 0.001-0.037) per 1-SD difference in maximum common and internal CIMT after adjustment for covariates, respectively. Limitations UACR was measured in a single spot urine specimen at each exam. Conclusion Higher common CIMT is associated with UACR progression.

Echocardiographic measures of left ventricular (LV) mass and relative wall thickness and left atrial (LA) size predict future cardiovascular morbidity and mortality. The aim of this study was to compare young adults with low cardiovascular risk (body mass index, 18.5-24.9 kg/m(2); blood pressure120/80 mmHg; no tobacco use, no diabetes, and physical fitness) with those without these characteristics with regard to LV mass and relative wall thickness and LA size, to determine the protective effect of a healthy lifestyle on the development of these characteristics.Cross-sectional assessment of 4059 black and white men and women aged 23 to 35 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study at the year 5-examination, when risk factors were measured, and echocardiography to assess LV mass and relative wall thickness were performed. Physical fitness was measured at baseline using a symptom-limited maximal treadmill test. All other covariates were measured concurrently with echocardiography.Gender, body mass index, and systolic blood pressure were associated with LV mass and relative wall thickness and LA size in multivariate models. Additional correlates of LV mass/height(2.7) ratio were tobacco use, resting heart rate (inverse), self-reported physical activity, gender (male higher), and age. Age was associated with LV relative wall thickness but not other measures of LV size. Additional correlates of LA diameter/height ratio were tobacco use, resting heart rate (inverse), serum glucose, and self-reported physical activity. Seven hundred ninety of 4059 subjects (19%) were classified as having low risk; black race was less likely in the low-risk group. Those with low risk had lower LV mass/height(2.7) ratios (32.0 vs 34.6 g/m(2.7), P.0001), better LV relative wall thickness (0.33 vs 0.35, P.0001), and lower LA diameter/height ratios (2.02 vs 2.08 cm/m, P.01).A low cardiovascular risk profile in young adulthood is associated with more favorable LV mass, LV relative wall thickness, and LA size. This may be one mechanism of lifestyle protection against cardiovascular morbidity and mortality.

Purpose The Hispanic Community Health Study (HCHS)/Study of Latinos (SOL) is a multicenter, community-based cohort study of Hispanic/Latino adults in the United States. A diverse participant sample is required that is both representative of the target population and likely to remain engaged throughout follow-up. The choice of sample design, its rationale, and benefits and challenges of design decisions are described in this study. Methods The study design calls for recruitment and follow-up of a cohort of 16,000 Hispanics/Latinos 18–74 years of age, with 62.5% (10,000) over 44 years of age and adequate subgroup sample sizes to support inference by Hispanic/Latino background. Participants are recruited in community areas surrounding four field centers in the Bronx, Chicago, Miami, and San Diego. A two-stage area probability sample of households is selected with stratification and oversampling incorporated at each stage to provide a broadly diverse sample, offer efficiencies in field operations, and ensure that the target age distribution is obtained. Conclusions Embedding probability sampling within this traditional, multisite cohort study design enables competing research objectives to be met. However, the use of probability sampling requires developing solutions to some unique challenges in both sample selection and recruitment, as described here.

We determined whether statin use was associated with lower all-cause and cardiovascular disease (CVD) mortality in 579 participants with lower extremity peripheral arterial disease (PAD) according to the presence and absence of elevated C-reactive protein (CRP) and D-dimer levels. Statin use was determined at baseline and at each annual visit. The CRP and D-dimer levels were measured at baseline. The mean follow-up was 3.7 years. The analyses were adjusted for age, gender, race, co-morbidities, ankle brachial index, cholesterol, and other confounders. Of the 579 participants, 242 (42%) were taking a statin at baseline and 129 (22%) died during follow-up. Statin use was associated with lower all-cause mortality (hazard ratio 0.51, 95% confidence interval [CI] 0.30 to 0.86, p = 0.012) and CVD mortality (hazard ratio 0.36, 95% CI 0.14 to 0.89, p = 0.027) compared to statin nonuse. No statistically significant interaction was found for the baseline CRP or D-dimer level with the association of statin use and mortality. However, statin therapy was associated with significantly lower all-cause and total mortality only among participants with baseline CRP values greater than the median and not among those with CRP values less than the median (hazard ratio 0.44, 95% CI 0.23 to 0.88 vs hazard ratio 0.73, 95% CI 0.31 to 1.75 for all-cause mortality and hazard ratio 0.20, 95% CI 0.063 to 0.65 vs hazard ratio 0.59, 95% CI 0.093 to 3.79 for CVD mortality). In conclusion, among those with PAD, statin use was associated with lower all-cause and CVD mortality compared to no statin use. The favorable association of statin use with mortality was not influenced significantly by the baseline CRP or D-dimer level.

Experimental and clinical trial data have suggested an association between fish oil intake and atrial fibrillation (AF). However, previous observational studies have reported conflicting results regarding this association. Thus, we sought to compare the association between dietary fish intake and incident AF in a large sample of older, postmenopausal women. We included 44,720 participants from the Women's Health Initiative clinical trials who were not enrolled in the dietary modification intervention arm and without AF at baseline. The dietary intake of nonfried fish and omega-3 fatty acid intake was estimated from a Food Frequency Questionnaire at study entry. Incident AF was determined by follow-up electrocardiography at years 3 and 6. The baseline characteristics and rates of incident AF were compared across the quartiles of fish intake. Adjusted logistic regression models were used to evaluate the association between dietary nonfried fish intake and incident AF. A total of 378 incident cases of AF occurred during the follow-up period. In the age-adjusted models, no association was found between dietary nonfried fish intake and incident AF (odds ratio 1.17, 95% confidence interval 0.88 to 1.57 for quartile 4 vs quartile 1 of dietary fish intake). Similar findings were observed in the multivariate models and in the subgroup analyses. In conclusion, in a large cohort of healthy women, we found no evidence of an association between fish or omega-3 fatty acid intake and incident AF.

Animal and human studies suggest that C-reactive protein (CRP) may be inversely associated with serum insulin-like growth factor-I (IGF-I) concentrations. However, most human studies have not controlled adequately for confounding factors, particularly nutritional intake. This population-based study examined whether CRP is inversely associated with IGF-I and IGFBP-3 concentrations.In cross-sectional analysis, multivariable linear regression with adjustment for age, BMI, smoking status, alcohol intake, and nutritional factors was used to relate log CRP, the independent variable, to IGF-I and IGFBP-3 in a sample of black (n=364) and white men (n=486) separately by race.Only black men had positive findings: log CRP was significantly associated with IGF-I (beta=-13.1 ng/ml, p=0.02) and the difference in mean IGF-I concentrations between the highest and lowest quartiles of CRP was 26 ng/ml. There was a statistically significant interaction between log CRP and smoking status (p=0.02); the regression coefficient for IGF-I predicted from log CRP was significant in smokers (beta=-39.8 ng/ml, p=0.0001), but not in non-smokers. The difference in mean IGF-I concentrations between highest and lowest quartiles of CRP was 100 ng/ml for black smokers. There were no associations for IGFBP-3.In our study, CRP levels are inversely associated with IGF-I concentrations in black male smokers; however, the causal nature of the association is unclear and should be studied further.

Objective Experimental and observational data suggest that a higher dietary intake of long-chain ω-3 polyunsaturated acids may lead to a decreased risk of depressive disorders. We assessed multivariable-adjusted associations of fish consumption and dietary intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) with depressive symptoms in a population-based sample of 3317 African-American and Caucasian men and women from the Coronary Artery Risk Development in Young Adults study. Methods Diet was assessed in year 7 (1992–1993) and depressive symptoms were measured in years 10 (1995–1996), 15 (2000–2001), and 20 (2005–2006) by the 20-item Center for Epidemiological Studies Depression Scale. Depressive symptoms were defined as a Center for Epidemiological Studies Depression Scale score ≥16 or self-reported use of antidepressant medication. Results In the entire cohort, the highest quintiles of intakes of EPA (≥0.03% energy), DHA (≥0.05% energy), and EPA + DHA (≥0.08% energy) were associated with a lower risk of depressive symptoms at year 10 ( P for trends = 0.16, 0.10, and 0.03, respectively). The observed inverse associations were more pronounced in women. For the total number of occasions with depressive symptoms, the multivariable adjusted odds ratios (95% confidence interval) in women were 0.75 (0.55–1.01) for fish intake, 0.66 (0.50–0.89) for EPA, 0.66 (0.49–0.89) for DHA, and 0.71 (0.52–0.95) for EPA + DHA when comparing the highest with the lowest quintiles. Analyses of continuous Center for Epidemiological Studies Depression Scale scores revealed inverse associations with fourth-root–transformed ω-3 variables in women. Conclusion Our findings suggest that dietary intakes of fish and long-chain ω-3 fatty acids may be inversely associated with chronic depressive symptoms in women.

Isolated minor nonspecific ST-segment and T-wave abnormalities (NSSTAs), minor and major electrocardiographic (ECG) abnormalities are established, independent risk markers for incident cardiovascular events. Their association with subclinical atherosclerosis has been postulated but is not clearly defined. The aim of this study was to define the association between ECG abnormalities and measurements of subclinical atherosclerosis. We studied participants from MESA, a multiethnic sample of men and women 45 to 84 years of age and free of clinical cardiovascular disease at enrollment. Baseline examination included measurement of traditional risk factors, 12-lead electrocardiograms at rest, coronary artery calcium (CAC) measurement, and common carotid intima-media thickness (CC-IMT). Electrocardiograms were coded using Novacode criteria and were defined as having minor abnormalities (e.g., minor NSSTTAs, first-degree atrioventricular block, and QRS-axis deviations) or major abnormalities (e.g., pathologic Q waves, major STTAs, significant dysrhythmias, and conduction system delays). Multivariable logistic and linear regressions were used to determine cross-sectional associations of ECG abnormalities with CAC and CC-IMT. Of 6,710 participants, 52.7% were women, with a mean age of 62 years. After multivariable adjustment, isolated minor STTAs and minor and major ECG abnormalities were not associated with presence of CAC (>0) in men (odds ratio 1.04, 95% confidence interval 0.81 to 1.33; 1.10, 0.91 to 1.32; and 1.03, 0.81 to 1.31, respectively) or women (1.01, 0.82 to 1.24; 1.04, 0.87 to 1.23; and 0.94, 0.73 to 1.22, respectively). Lack of association remained consistent when using log CAC and CC-IMT as continuous variables. In conclusion, ECG abnormalities are not associated with markers of subclinical atherosclerosis in a large multiethnic cohort.

Objectives: The purpose of this study was to assess coronary arterial remodeling as a marker of subclinical atherosclerosis using coronary wall magnetic resonance imaging (MRI) in an asymptomatic p...

The cardioprotective effects of long-chain n-3 polyunsaturated fatty acids (PUFAs) and fish consumption have been observed. However, data on the specific associations of these dietary factors with inflammation and endothelial activation are sparse. A cross-sectional study was conducted of 5,677 men and women from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, including African Americans, Caucasians, Chinese, and Hispanics aged 45 to 84 years and free of clinical cardiovascular disease. Dietary information was collected using a self-administered food frequency questionnaire. Multivariate linear regression analyses were used to examine relations between the intake of long-chain n-3 PUFAs, nonfried fish, and fried fish and biomarkers of inflammation and endothelial activation. Long-chain n-3 PUFA intake was inversely associated with plasma concentrations of interleukin-6 (p = 0.01) and matrix metalloproteinase-3 (p = 0.03) independent of age, body mass index, physical activity, smoking, alcohol consumption, and dietary variables. Nonfried fish consumption was inversely related to C-reactive protein (p = 0.045) and interleukin-6 (p

Background Previous studies have suggested an inverse relationship between physical activity and markers of inflammation such as high-sensitivity C-reactive protein (hs-CRP). However, these were inconsistent, and few examined whether race and gender influenced the relationship. This study determined a cross-sectional association between physical activity and hs-CRP level in 6142 middle-aged white, Chinese, black, and Hispanic participants enrolled in the Multi-Ethnic Study of Atherosclerosis in 2000–2002. Methods Combined moderate and vigorous physical activity was measured by self-reported leisure, conditioning, occupational, and household activities. ANCOVA was used to assess the association between moderate/vigorous physical activity and hs-CRP by gender and race. Results Hs-CRP was higher in women. Blacks had the highest hs-CRP, and Chinese participants had the lowest. Hs-CRP decreased across tertiles of moderate/vigorous physical activity in Hispanic men in models adjusted for age, education, study site, and physical activity questionnaire mode of administration ( p =0.005) and further adjusted for smoking, infection, and aspirin use ( p =0.020). The trend remained significant after further adjustment for BMI; blood pressure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol; diabetes; and the use of antihypertensive, statin, and diabetes medication ( p =0.044). There was a downward trend in hs-CRP across tertiles of physical activity in black and white men, but the association was weaker. No clear trend was observed in any female racial/ethnic groups. Conclusions These findings suggest that the association between moderate/vigorous physical activity and hs-CRP differs by race and gender. Further studies are needed to confirm this and to examine the mechanisms for these race and gender differences.