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Background Immigrants experience changes in cardiovascular risk factors and racial disparities in both cardiovascular health prevention and outcomes upon immigration. We aimed to examine cardiovascular risk factors and outcomes among Chinese American immigrants enrolled in the MESA (Multi‐Ethnic Study of Atherosclerosis) cohort. Methods and Results We analyzed data from 746 Chinese American immigrants in the MESA study with a median follow‐up period of 17.8 years. The mean age of the cohort was 62.3 years, with 52.7% being women. Kaplan–Meier curves and Cox proportional hazards models were used to assess the association of immigration history, geographic location, biomarkers, and cardiac imaging parameters with cardiovascular risk factors and cardiovascular outcomes. The Cox hazards models were adjusted for known family history of heart disease, education level, sex, diabetes, hypertension, age, and body mass index. Although immigration history categorized as earlier (

Introduction: Educational attainment, widely used in epidemiologic studies as a surrogate for socioeconomic status, is a predictor of cardiovascular health outcomes.Methods: A two-stage genome-wide meta-analysis of low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG) levels was performed while accounting for gene-educational attainment interactions in up to 226,315 individuals from five population groups. We considered two educational attainment variables: “Some College” (yes/no, for any education beyond high school) and “Graduated College” (yes/no, for completing a 4-year college degree). Genome-wide significant (p < 5 × 10−8) and suggestive (p < 1 × 10−6) variants were identified in Stage 1 (in up to 108,784 individuals) through genome-wide analysis, and those variants were followed up in Stage 2 studies (in up to 117,531 individuals).Results: In combined analysis of Stages 1 and 2, we identified 18 novel lipid loci (nine for LDL, seven for HDL, and two for TG) by two degree-of-freedom (2 DF) joint tests of main and interaction effects. Four loci showed significant interaction with educational attainment. Two loci were significant only in cross-population analyses. Several loci include genes with known or suggested roles in adipose (FOXP1, MBOAT4, SKP2, STIM1, STX4), brain (BRI3, FILIP1, FOXP1, LINC00290, LMTK2, MBOAT4, MYO6, SENP6, SRGAP3, STIM1, TMEM167A, TMEM30A), and liver (BRI3, FOXP1) biology, highlighting the potential importance of brain-adipose-liver communication in the regulation of lipid metabolism. An investigation of the potential druggability of genes in identified loci resulted in five gene targets shown to interact with drugs approved by the Food and Drug Administration, including genes with roles in adipose and brain tissue.Discussion: Genome-wide interaction analysis of educational attainment identified novel lipid loci not previously detected by analyses limited to main genetic effects.

Abstract Background The Pooled Cohort Equations (PCEs) are race- and sex-specific Cox proportional hazards (PH)-based models used for 10-year atherosclerotic cardiovascular disease (ASCVD) risk prediction with acceptable discrimination. In recent years, neural network models have gained increasing popularity with their success in image recognition and text classification. Various survival neural network models have been proposed by combining survival analysis and neural network architecture to take advantage of the strengths from both. However, the performance of these survival neural network models compared to each other and to PCEs in ASCVD prediction is unknown. Methods In this study, we used 6 cohorts from the Lifetime Risk Pooling Project (with 5 cohorts as training/internal validation and one cohort as external validation) and compared the performance of the PCEs in 10-year ASCVD risk prediction with an all two-way interactions Cox PH model (Cox PH-TWI) and three state-of-the-art neural network survival models including Nnet-survival, Deepsurv, and Cox-nnet. For all the models, we used the same 7 covariates as used in the PCEs. We fitted each of the aforementioned models in white females, white males, black females, and black males, respectively. We evaluated models’ internal and external discrimination power and calibration. Results The training/internal validation sample comprised 23216 individuals. The average age at baseline was 57.8 years old (SD = 9.6); 16% developed ASCVD during average follow-up of 10.50 (SD = 3.02) years. Based on 10 × 10 cross-validation, the method that had the highest C-statistics was Deepsurv (0.7371) for white males, Deepsurv and Cox PH-TWI (0.7972) for white females, PCE (0.6981) for black males, and Deepsurv (0.7886) for black females. In the external validation dataset, Deepsurv (0.7032), Cox-nnet (0.7282), PCE (0.6811), and Deepsurv (0.7316) had the highest C-statistics for white male, white female, black male, and black female population, respectively. Calibration plots showed that in 10 × 10 validation, all models had good calibration in all race and sex groups. In external validation, all models overestimated the risk for 10-year ASCVD. Conclusions We demonstrated the use of the state-of-the-art neural network survival models in ASCVD risk prediction. Neural network survival models had similar if not superior discrimination and calibration compared to PCEs.

BackgroundThere are multiple predictive factors for cardiovascular (CV) mortality measured at, or after heart failure (HF) diagnosis. However, the predictive role of long-term exposure to these predictors prior to HF diagnosis is unknown.ObjectivesWe aim to identify predictive factors of CV mortality in participants with HF, using cumulative exposure to risk factors before HF development.MethodsParticipants of Multi-Ethnic Study of Atherosclerosis (MESA) with incident HF were included. We used stepwise Akaike Information Criterion to select CV mortality predictors among clinical, biochemical, and imaging markers collected prior to HF. Using the AUC of B-spline-corrected curves, we estimated cumulative exposure to predictive factors from baseline to the last exam before HF. The prognostic performance for CV mortality after HF was evaluated using competing risk regression with non-CV mortality as the competing risk.ResultsOverall, 375 participants had new HF events (42.9% female, mean age: 74). Over an average follow-up of 4.7 years, there was no difference in the hazard of CV death for HF with reduced versus preserved ejection fraction (HR = 1.27, p = 0.23). The selected predictors of CV mortality in models with the least prediction error were age, cardiac arrest, myocardial infarction, and diabetes, QRS duration, HDL, cumulative exposure to total cholesterol and glucose, NT-proBNP, left ventricular mass, and statin use. The AUC of the models were 0.72 when including the latest exposure to predictive factors and 0.79 when including cumulative prior exposure to predictive factors (p = 0.20).ConclusionIn HF patients, besides age and diagnosed diabetes or CVD, prior lipid profile, NT-proBNP, LV mass, and QRS duration available at the diagnosis time strongly predict CV mortality. Implementing cumulative exposure to cholesterol and glucose, instead of latest measures, improves predictive accuracy for HF mortality, though not reaching statistical significance.

The prevalence of physiological and pathological left ventricular hypertrophy (LVH) among young adults is about 5%. A use of electrocardiographic (ECG) voltage criteria and machine learning for the ECG parameters to identify the presence of LVH is estimated only 20-30% in the general population. The aim of this study is to develop an ECG system with anthropometric data using machine learning to increase the accuracy and sensitivity for a screen of LVH. In a large sample of 2,196 males, aged 17–45 years, the support vector machine (SVM) classifier is used as the machine learning method for 31 characteristics including age, body height and body weight in addition to 28 ECG parameters such as axes, intervals and voltages to link the output of LVH. The diagnosis of LVH is based on the echocardiographic criteria for young males to be 116 gram/meter2 (left ventricular mass (LVM)/body surface area) or 49 gram/meter2.7 (LVM/body height2.7). On the purpose of increasing sensitivity, the specificity is adjusted around 70-75% and all data tested in proposed model reveal high sensitivity to 86.7%. The area under curve (AUC) of the Precision-Recall (PR) curve is 0.308 in the proposed model which is better than 0.109 and 0.077 using Cornell and Sokolow-Lyon voltage criteria for LVH, respectively. Our system provides a novel screening tool using age, body height, body weight and ECG data to identify most of the LVH among young adults. It provides a fast, accurate and practical diagnosis tool to identify LVH.

Objective: Determine sex differences in hypertension control by age group in a diverse cohort of adults age 45–84 years at baseline followed for an average of 12 years. Methods: The Multi-Ethnic Study of Atherosclerosis enrolled 3213 men and 3601 women from six communities in the U.S. during years 2000–2002 with follow-up exams completed approximately every two years. At each exam, resting blood pressure (BP) was measured in triplicate, and the last two values were averaged. Hypertension was defined as a BP ≥ 140/90 mmHg and/or use of antihypertensive medications. Hypertension control was defined as a BP < 140/90 mmHg and in separate analyses as < 130/90 mmHg. Generalized linear mixed effects models with a binomial function were used to calculate the odds of hypertension control by age group (45–64,75–74, 75+) at a given exam and by sex, while accounting for the intra-individual correlation, and adjustment for demographics, co-morbidities, smoking, alcohol use, education and site among participants with hypertension at any of the first five exams. Results: At baseline, mean age was 64.1 (9.1 [SD]) years, 48.0% were men, and race/ethnicity was Non-Hispanic white in 34.1%, 10.1% Chinese, 35.1% Non-Hispanic Black and 20.7% Hispanic. Average SBP was lower while average DBP was higher among men vs. women at each exam. Adjusted odds ratios of hypertension control defined as BP < 140/90 mmHg among men vs. women was 0.89 (95% CI 0.67, 1.19) for age 45–64 years, 1.37 (95% CI 1.04, 1.81) for age 65–74 years and 2.08 (95% CI 1.43, 3.02) for age 75+ years. When defined as < 130/80 mmHg, adjusted odds of hypertension control among men vs. women was 0.60 (OR 0.60; 95% CI 0.46, 0.79) at age 45–64 years, 1.01 (OR 1.01; 95% CI 0.77, 1.31) at age 65–74 years and 1.71 (95% CI 1.19, 2.45) at age 75+ years. Conclusion: Sex disparities in hypertension control increase with advancing age and are greatest among adults age 75+ years.

Background It is unclear if statin therapy in midlife can restore low cardiovascular risk in hypercholesterolemic individuals. Methods and Results At baseline, we grouped 5687 MESA (Multi‐Ethnic Study of Atherosclerosis) participants aged ≥50 years without clinical cardiovascular disease (CVD) by Adult Treatment Panel III statin treatment recommendation and statin treatment status. We used Cox regression to compare the risks for coronary heart disease and CVD between the untreated group with low‐density lipoprotein cholesterol (LDL‐C) 0 Agatston units), and statin status (untreated or treated) with the untreated LDL‐C 0 Agatston units, treated to LDL‐C 0 Agatston units have substantially higher risks despite lipid‐lowering therapy, suggesting that statin treatment in midlife may not restore a low‐risk state in primary prevention patients with established coronary atherosclerosis.

Background NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) is widely used to diagnose and manage patients with heart failure. We aimed to investigate associations between NT‐proBNP levels and development of global and regional myocardial impairment, dyssynchrony, and risk of developing myocardial scar over time. Methods and Results We included 2416 adults (45–84 years) without baseline clinical cardiovascular disease from MESA (Multi‐Ethnic Study of Atherosclerosis). NT‐proBNP was assessed at baseline (2000–2002). Cardiac magnetic resonance–measured left ventricular parameters were assessed at baseline and year 10 (2010–2012). Tagged cardiac magnetic resonance and myocardial dyssynchrony were assessed. We used linear and logistic regression models to study the relationships between quartiles of NT‐proBNP levels and outcome variables. Left ventricular parameters decreased over time. After 10‐year follow‐up and adjusting for cardiovascular disease risk factors, people in the highest quartile had significantly greater decline in left ventricular ejection fraction (−1.60%; 95% CI, −2.26 to −0.94; P

Introduction South Asians have a high prevalence of type 2 diabetes mellitus (T2DM). This may be associated with high rates of conversion through the natural history of disease. However, there is a paucity of data on prediabetes and T2DM incidence and related predictors in South Asians in the USA.Research design and methods We estimated prediabetes and T2DM incidence after 5 years of follow-up in the Mediators of Atherosclerosis in South Asians Living in America study (n=481) and examined the associated correlates. We defined T2DM and prediabetes using the American Diabetes Association criteria. Prediabetes included isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT) and combined IFG and IGT.Results Overall, 152 (32%, 95% CI: 27.6 to 35.9) individuals progressed either from normal glucose tolerance to prediabetes or T2DM, or from prediabetes to T2DM. In standardised logistic regression models controlling for age and sex, only hepatic fat attenuation (increased hepatic fat) (OR: 0.67 (95% CI: 0.55 to 0.87) per SD, visceral fat area (OR: 1.36 (95% CI: 1.06 to 1.74) per SD and hypertension (OR: 2.21 (95% CI: 1.44 to 3.40) were associated with any glycemic progression.Conclusions South Asians in the USA have a high incidence of dysglycemia. Hepatic and visceral fat may be factors in glycemic progression, and prevention efforts should target ectopic fat reduction.

Background South Asians have a relatively high prevalence of coronary artery calcium (CAC) compared with other race/ethnic groups. We determined CAC incidence and progression among South Asians, and compared them with 4 race/ethnic groups. Methods and Results Data from the MASALA (Mediators of Atherosclerosis in South Asians Living in America) study were used to calculate CAC incidence and progression rates and any CAC change. Data from the MESA (Multi‐Ethnic Study of Atherosclerosis) were used to compare the CAC incidence and progression rates. A total of 698 South Asians had repeat CAC measurements after 4.8±0.8 years. Among those with no CAC at baseline, the age‐adjusted CAC incidence was 8.8% (95% CI, 6.8–10.8%) in men and 3.6% (2.5–4.8%) in women. The median annual CAC progression was 26 (interquartile range, 11–62) for men and 13 (interquartile range, 4–34) for women. Compared with MESA, age‐adjusted CAC incidence was similar in South Asian men compared with white, black, and Latino men, but significantly higher than Chinese men (11.1% versus 5.7%, P=0.008). After adjusting for age, diabetes mellitus, hypertension, and statin medication use, Chinese, black, and Latino men had significantly less CAC change compared with South Asian men, but there were no differences between South Asian and white men. There was no difference in CAC incidence or progression between South Asian women and women in MESA. Conclusions South Asian men had greater CAC change than Chinese, black, and Latino men but similar change to that of whites after adjusting for traditional risk factors.

Background Data are sparse on the association of cardiovascular health (CVH) in younger/middle age with the incidence of dementia later in life. Methods and Results We linked the CHA (Chicago Heart Association Detection Project in Industry) study data, assessed in 1967 to 1973, with 1991 to 2010 Medicare and National Death Index data. Favorable CVH was defined as untreated systolic blood pressure/diastolic blood pressure ≤120/≤80 mm Hg, untreated serum total cholesterol

Background Diminished peak lung function in young adulthood is a risk factor for future chronic obstructive pulmonary disease. The association between lung disease and cardiovascular disease later in life is well documented. Whether peak lung function measured in young adulthood is associated with risk of future cardiovascular events is unknown. Methods and Results CARDIA (The Coronary Artery Risk Development in Young Adults) study is a prospective, multicenter, community‐based, longitudinal cohort study including 4761 participants aged 18 to 30 years with lung function testing we investigated the association between lung health in young adulthood and risk of subsequent cardiovascular events. We performed Cox proportional hazards regression to test the association between baseline and years 10 and 20 pulmonary function with incident cardiovascular events. Linear and logistic regression was performed to explore the associations of lung function with development of risk factors for cardiovascular disease as well as carotid intima‐media thickness and coronary artery calcified plaque. At baseline, mean age (±SD) was 24.9±3.6 years. Baseline forced expiratory volume in 1 second (hazard ratio) per −10‐unit decrement in percent predicted forced expiratory volume in 1 second (hazard ratio, 1.18; 95% CI, 1.06–1.31 [P=0.002]) and FVC per −10‐unit decrement in percent predicted FVC (hazard ratio, 1.19; 95% CI, 1.06–1.33 [P=0.003]) were associated with future cardiovascular events independent of traditional cardiovascular risk factors. Baseline lung function was associated with heart failure and cerebrovascular events but not coronary artery disease events. Conclusions Lung function in young adulthood is independently associated with cardiovascular events into middle age. This association appears to be driven by heart failure and cerebrovascular events rather than coronary heart disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005130.

Abstract Background The objective of this study was to evaluate a pilot program that allowed Chicago field center participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study to submit follow-up information electronically (eCARDIA). Methods Chicago field center participants who provided email addresses were invited to complete contact information and follow-up questionnaires on medical conditions electronically in 2012–2013. Sociodemographic characteristics were compared between those who did and did not complete follow-up electronically. The number of participant contacts by CARDIA staff needed before follow-up was completed was also evaluated. Results Blacks and low socioeconomic position individuals were less likely to complete follow-up using the electronic questionnaire. Participants who used the electronic questionnaire for follow-up needed fewer contacts (e.g., median 1 contact compared with 3for contact information follow-up), but they also needed fewer contacts prior to eCARDIA (median 1 before and after eCARDIA). Conclusions Findings suggest other approaches will be needed to maintain contact and elicit follow-up information from harder-to-reach individuals.

[This corrects the article DOI: 10.1371/journal.pgen.1006728.].

Objectives: Examine associations of favorable levels of all cardiovascular disease (CVD) risk factors (RFs) [i.e., low risk (LR)] at younger ages with high sensitivity C-reactive protein (hs-CRP) at older ages. Methods: There were 1324 participants ages 65–84 years with hs-CRP ≤ 10 mg/L from the Chicago Healthy Aging Study (2007–2010), and CVD RFs assessed at baseline (1967–73) and 39 years later. LR was defined as untreated blood pressure (BP) ≤120/≤80 mm Hg, untreated serum total cholesterol

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10-8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

Background Few adults have ideal cardiovascular health (CVH). We studied associations of an overall CVH score with subclinical cardiovascular disease and events. We assessed whether associations varied by race/ethnicity. Methods and Results Among 5961 participants in the Multi‐Ethnic Study of Atherosclerosis, components of CVH were measured at baseline, 2000‐2002: systolic blood pressure, total cholesterol, fasting glucose, smoking, physical activity, diet, and body mass index. Levels were classified as ideal (2 points), intermediate (1 point), and poor (0 points) according to American Heart Association definitions. Points were summed to produce a CVH score (0‐7 low, 8‐11 moderate, 12‐14 high). Coronary artery calcium, carotid intima‐media thickness, and left ventricular mass were measured at baseline. Cardiovascular disease was defined as myocardial infarction, coronary heart disease death, resuscitated cardiac arrest, stroke, heart failure, or peripheral artery disease. Follow‐up was 10.3 years. Regression models were used to examine associations of the CVH score with subclinical disease and events, adjusting for age, sex, and education. Analyses were stratified by race/ethnicity. Adults with high or moderate CVH scores had significantly lower odds of coronary artery calcium and lower carotid intima‐media thickness and left ventricular mass than adults with low CVH scores. Adults with high or moderate CVH scores were 67% (95%CI 41% to 82%) and 37% (95%CI 22% to 49%) less likely, respectively, to experience a cardiovascular disease event than adults with low scores. There was no interaction with race/ethnicity. Conclusions There is a graded inverse association between CVH scores and measures of subclinical and overt cardiovascular disease that is similar across race/ethnic groups.

BackgroundSouth Asians have a low body mass index and high prevalence of cardiovascular disease (CVD) relative to other racial/ethnic groups. Radiographically detected ectopic fat distribution is better associated with CVD than body mass index. We assessed whether differences in ectopic fat depots explained differences in the prevalence/severity of coronary artery calcium (CAC), a predictor of incident CVD events, among South Asians compared with other racial/ethnic groups. Methods and ResultsWe examined the associations of radiographically detected visceral, intermuscular, intrahepatic, and pericardial fat with CAC among adults without baseline CVD. We compared 803 South Asians in the Mediators of Atherosclerosis in South Asians Living in America to 4 racial/ethnic groups in the Multi‐Ethnic Study of Atherosclerosis: 2622 whites, 1893 blacks, 1496 Latinos, and 803 Chinese Americans. We adjusted for body mass index and known CVD risk factors. South Asians had the highest intrahepatic fat and lowest pericardial fat volume (PFV). There was a positive graded association between ectopic fat and higher CAC scores in all the groups with the strongest associations observed with PFV. PFV was independently associated with CAC severity in South Asians (P=0.01) and blacks (P=0.05) and borderline in whites (P=0.06). PFV partially explained the higher CAC burden in South Asians compared with blacks, but not the other racial/ethnic groups. ConclusionsDifferences in PFV explain a small fraction of the higher CAC burden in South Asians. Our findings suggest that ectopic fat depots may not explain the elevated CAC risk in South Asians.

BackgroundObstructive sleep apnea (OSA) is a common condition affecting more men than women. The relationship of OSA with microvascular disease is unclear, complicated by possible sex difference. Assessment of the relationship of OSA with retinal microvascular signs in men and women may provide insights into such a relationship. Methods and ResultsWe examined the sex‐specific cross‐sectional association of OSA severity with retinal vascular calibers in 1808 participants, and with specific retinopathy signs in 1831 participants from a sample of 2060 participants aged 54 to 93 years who underwent successful polysomnography in the Multi‐Ethnic Study of Atherosclerosis, 2010–2012. OSA severity was defined by the apnea–hypopnea index (events/h) as none (

BackgroundWe compared the incidence of depression, defined by a Geriatric Depression Score (GDS) ≥6, between people with versus without peripheral artery disease (PAD). We determined whether depressive symptoms were associated with increased mortality in people with and without PAD. Methods and ResultsNine hundred and fifty‐one PAD patients and 478 non‐PAD patients were recruited from Chicago medical centers and followed prospectively. At baseline and annually, participants completed the GDS (0–15 scale, score ≥6=depression) and 6‐minute walk. Cause of death was confirmed with death certificates. The prevalence of a GDS ≥6 at baseline was 186/951 (19.6%) among PAD versus 63/478 (13.2%) among non‐PAD participants (P=0.003). During a mean follow‐up of 2.7±1.2 years, 122/712 (17.1%) of participants with PAD versus 51/403 (12.7%) without PAD developed a GDS ≥6 (P=0.047). Adjusting for age, sex, race, comorbidities, and other confounders, PAD participants had an increased rate of developing a GDS ≥6 compared to non‐PAD participants (hazard ratio=1.54 (95% CI=1.05–2.25, P=0.026). This association was not statistically significant after adjusting for 6‐minute walk (P=0.258). Among PAD participants, a baseline GDS ≥6 was associated with increased all‐cause mortality, adjusting for confounders (hazard ratio=1.57, 95% CI=1.12–2.21, P=0.009). This association was not significant after adjusting for 6‐minute walk (P=0.224). ConclusionsPeople with PAD have a higher incidence of depressive symptoms than people without PAD. In PAD, depressive symptoms are associated with increased all‐cause and cardiovascular mortality. These associations are explained in part by poorer 6‐minute walk among people with PAD and among depressed people with PAD, respectively.

BackgroundThe classic view of blood pressure (BP) reactivity to psychological stress in relation to cardiovascular risks assumes that excess reactivity is worse and lower reactivity is better. Evidence addressing how stress‐induced BP reactivity in young adults is associated with midlife cognitive function is sparse. Methods and ResultsWe assessed BP reactivity during a star tracing task and a video game in adults aged 20 to 32 years. Twenty‐three years later, cognitive function was assessed with use of the Digit Symbol Substitution Test (a psychomotor speed test), the Rey Auditory Verbal Learning Test (a verbal memory test), and the modified Stroop test (an executive function test). At the time of follow‐up, participants (n=3021) had a mean age of 50.2 years; 56% were women, and 44% were black. In linear regression models adjusted for demographic and clinical characteristics including baseline and follow‐up resting BP, lower systolic BP (SBP) reactivity during the star tracing and video game was associated with worse Digit Symbol Substitution Test scores (β [SE]: 0.11 [0.02] and 0.05 [0.02], respectively) and worse performance on the Stroop test (β [SE]: −0.06 [0.02] and −0.05 [0.02]; all P

Background Few medical therapies improve lower extremity functioning in people with lower extremity peripheral artery disease (PAD). Among people with PAD, we studied whether a group‐mediated cognitive behavioral intervention promoting home‐based unsupervised exercise prevented mobility loss and improved functional performance compared to control. Methods and Results One hundred ninety‐four PAD participants were randomized. During months 1 to 6, the intervention group met weekly with other PAD participants and a facilitator. Group support and self‐regulatory skills were used to help participants adhere to walking exercise. Ninety‐percent of exercise was conducted at or near home. The control group attended weekly lectures. During months 6 to 12, each group received telephone contact only. Primary outcomes have been reported. Here we compare changes in exploratory outcomes of mobility loss (the inability to climb a flight of stairs or walk one‐quarter mile without assistance), walking velocity, and the Short Physical Performance Battery. Compared to controls, fewer participants randomized to the intervention experienced mobility loss at 6‐month follow‐up: 6.3% versus 26.5%, P=0.002, odds ratio=0.19 (95% CI=0.06 to 0.58) and at 12‐month follow‐up: 5.2% versus 18.5%, P=0.029, odds ratio=0.24 (95% CI=0.06 to 0.97). The intervention improved fast‐paced 4‐m walking velocity at 6‐month follow‐up (P=0.005) and the Short Physical Performance Battery at 12‐month follow‐up (P=0.027), compared to controls. Conclusions In exploratory analyses, a group‐mediated cognitive behavioral intervention promoting unsupervised walking exercise prevented mobility loss and improved functioning at 6‐ and 12‐month follow‐up in PAD patients. Clinical Trial Registration URL: http://clinicaltrials.gov. Unique identifier: NCT00693940.

Introduction. Few studies have examined the association between the PR interval (PRi) and subclinical cardiovascular disease measures. Methods and Results. The Multiethnic Study of Atherosclerosis (MESA) is a population-based study of 6814 men and women aged 45–84 years without clinical cardiovascular disease and 4962 had complete baseline data on cardiac magnetic resonance imaging measures of LV dimension and ejection fraction and surface electrocardiogram. Linear regression models were constructed to determine the adjusted association between the PRi and measures of LV stroke volume, LV mass, LV end-systolic and end-diastolic volumes, and ejection fraction. Overall, mean age was 61.5 years, and 47.6% were male and race/ethnicity was white in 39.1%, Chinese in 13.1%, African-American in 25.7%, and Hispanic in 22.2%. The PRi ranged from 88 to 308 ms with a median value of 162 ms. As a continuous variable, every standard deviation unit (25 ms) increment in PRi was associated with a 2.00 mL (95% CI 1.52, 2.48) higher stroke volume, a 3.08 g (95% CI 2.30, 3.86) higher LV mass, a 1.36 g/m2 (95% CI 0.96, 1.76) higher LV mass index, and 1.31 mL (95% CI 0.88, 1.73) higher end-systolic and 3.31 mL (95% CI 2.58, 4.03) higher end-diastolic volumes after adjustment for all covariates. No significant association was noted between the PRi and LV ejection fraction. Conclusions. A prolonged PRi is associated with LV measures and may in part explain the link between a prolonged PRi and cardiovascular outcomes.

Genetic variation in the apolipoprotein A-V gene (APOA5) has been associated with variation in plasma triglyceride (TG) levels in African American and white females and males older than 40 years and/or at increased risk of coronary artery disease. We have examined whether plasma TG levels are associated with 16 APOA5 polymorphisms in young (18–30 years) African American (1,075 females and 783 males) and white (1,041 females and 932 males) individuals of the Coronary Artery Risk Development in Young Adults (CARDIA) Study selected without regard to health. Plasma TG was significantly (P < 0.01) associated with markers 27376 and 28837 (−3A/G) in both white females and males, with 27709 (−1131T/C) and 29085 in white males, with 29009 (S19W) in African American females and white males, and with 30966 in African American females. No statistically significant associations were observed in African American males. These six single-nucleotide polymorphisms individually accounted for 0–0.78% of lnTG variation among white females, 0–2.46% among white males, and 0–0.69% among African American females.The results of our study suggest a small but replicable context-dependent influence of the APOA5 gene region on plasma TG levels in young, healthy individuals.

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

Objective. To examine the association between anxiety and weight change in a multiethnic cohort followed for approximately 10 years. Methods. The study population consisted of participants of the multiethnic study of atherosclerosis who met specified inclusion criteria (n = 5,799). Weight was measured at baseline and four subsequent follow-up exams. Anxiety was analyzed as sex-specific anxiety quartiles (QANX). The relationship between anxiety level and weight change was examined using a mixed-effect model with weight as the dependent variable, anxiety and time as the independent variables, and adjusted for covariates. Results. Average annual weight change (range) was −0.17 kg (−6.04 to 4.38 kg) for QANX 1 (lowest anxiety), −0.16 kg (−10.71 to 4.45 kg) for QANX 2, −0.15 kg (−8.69 to 6.39 kg) for QANX 3, and −0.20 kg (−7.12 to 3.95 kg) for QANX 4 (highest anxiety). No significant association was noted between QANX and weight change. However, the highest QANX was associated with a −2.48 kg (95% CI = −3.65, −1.31) lower baseline weight compared to the lowest QANX after adjustment for all covariates. Conclusions. Among adults, age 45–84, higher levels of anxiety, defined by the STPI trait anxiety scale, are associated with lower average baseline weight but not with weight change.

Hepatic lipase encoded by the hepatic lipase gene (LIPC) is involved in the metabolism of several lipoproteins. Four promoter polymorphisms in LIPC have been found to be in complete disequilibrium and associated with high density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo)A-I levels in both white and black populations. We investigated the association between the promoter polymorphism and lipid profiles as well as anthropometric phenotypes in African American men in the Coronary Artery Risk Development in Young Adults study. We performed serial cross-sectional analyses and longitudinal analyses of lipids from 578 subjects in five examinations over 10 years of follow-up. Results showed that the allele frequency (0.52) in our black population was consistent with that reported in black subjects but much higher than that reported (~0.2) in white populations. Analysis of covariance tests of the three genotypic means in each examination showed that the P values ranged from 0.01 to 0.08 for HDL-C (except P = 0.54 in the fourth examination), from 0.006 to 0.01 for HDL2-C, and from 0.06 to 0.07 for apoA-I. Mean HDL3-C levels were essentially identical among the three genotypes. Total cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, and apoB, which are mainly involved in the very low density lipoprotein-LDL pathway, were not significantly different according to the promoter polymorphism, except for triglycerides in the third examination (P = 0.01). No significant association was found between anthropometric phenotypes and the LIPC polymorphism in any of five examinations. The change of the anthropometric variables was not significantly associated with genotypes. In conclusion, our results indicated that the LIPC promoter polymorphism has exclusive effects on HDL2-C but not HDL3-C levels. —Juo, S-H. H., Z. Han, J. D. Smith, L. Colangelo, and K. Liu. Promoter polymorphisms of hepatic lipase gene influence HDL2 but not HDL3 in African American men: CARDIA study.

BACKGROUND: Physical performance is a major determinant of health in older adults, and is related to lifestyle factors. Dietary fiber has multiple health benefits. It remains unclear whether fiber intake is independently linked to superior physical performance. We aimed to assess the association between dietary fiber and physical performance in older adults. METHODS: This was a cross-sectional study conducted with community-dwelling adults aged 55 years and older (n=2680) from the ongoing Healthy Aging Longitudinal Study (HALST) in Taiwan 2008-2010. Daily dietary fiber intake was assessed using a validated food frequency questionnaire. Physical performance was determined objectively by measuring gait speed, 6-minute walk distance, timed "up and go" (TUG), summary performance score, hand grip strength. RESULTS: Adjusting for all potential confounders, participants with higher fiber intake had significantly faster gait speed, longer 6-minute walk distance, faster TUG, higher summary performance score, and higher hand grip strength (all P

BACKGROUND:Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities. METHODOLOGY/PRINCIPAL FINDINGS:We tested a set of ∼50,000 polymorphisms from ∼2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed. CONCLUSIONS/SIGNIFICANCE:We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans.

Smoking tobacco reduces lung function. African Americans have both lower lung function and decreased metabolism of tobacco smoke compared to European Americans. African ancestry is also associated with lower pulmonary function in African Americans. We aimed to determine whether African ancestry modifies the association between smoking and lung function and its rate of decline in African Americans.We evaluated a prospective ongoing cohort of 1,281 African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study initiated in 1997. We also examined an ongoing prospective cohort initiated in 1985 of 1,223 African Americans in the Coronary Artery Disease in Young Adults (CARDIA) Study. Pulmonary function and tobacco smoking exposure were measured at baseline and repeatedly over the follow-up period. Individual genetic ancestry proportions were estimated using ancestry informative markers selected to distinguish European and West African ancestry. African Americans with a high proportion of African ancestry had lower baseline forced expiratory volume in one second (FEV₁) per pack-year of smoking (-5.7 ml FEV₁/ smoking pack-year) compared with smokers with lower African ancestry (-4.6 ml in FEV₁/ smoking pack-year) (interaction P value = 0.17). Longitudinal analyses revealed a suggestive interaction between smoking, and African ancestry on the rate of FEV(1) decline in Health ABC and independently replicated in CARDIA.African American individuals with a high proportion of African ancestry are at greater risk for losing lung function while smoking.

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

Atherosclerosis is the leading cause of cardiovascular disease (CVD). Traditional risk factors can be used to identify individuals at high risk for developing CVD and are generally associated with the extent of atherosclerosis; however, substantial numbers of individuals at low or intermediate risk still develop atherosclerosis.A case-control study was performed using microarray gene expression profiling of peripheral blood from 119 healthy women in the Multi-Ethnic Study of Atherosclerosis cohort aged 50 or above. All participants had low (100 and carotid intima-media thickness (IMT) >1.0 mm, whereas controls (N = 71) had CAC

BACKGROUND:Systemic inflammation is associated with reduced lung function in both healthy individuals and those with chronic obstructive pulmonary disease (COPD). Whether systemic inflammation in healthy young adults is associated with future impairment in lung health is uncertain. METHODOLOGY/PRINCIPAL FINDINGS:We evaluated the association between plasma fibrinogen and C-reactive protein (CRP) in young adults and lung function in the Coronary Artery Risk Development in Young Adults cohort study. Higher year 7 fibrinogen was associated with greater loss of forced vital capacity (FVC) between years 5 and 20 (439 mL in quartile 4 vs. 398 mL in quartile 1, P