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Objective: This study examined how cumulative BMI (cBMI) is associated with incident prediabetes in a biracial observational cohort study followed from young adulthood to middle age. Methods: Black and White men and women (n = 4190) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, ages 18 to 30 years in 1985 to 1986 and free of prediabetes or diabetes at baseline, were followed for 30 years. Cox regression was used to determine how cBMI was associated with incident prediabetes after controlling for traditional cardiovascular risk factors. Results: Over 30 years of follow‐up, 46.2% of the sample developed prediabetes. Mean cBMI was 801.4 BMI‐years for those with prediabetes and 658.3 BMI‐years for those without (p < 0.0001). After multivariable adjustment, the hazard rate ratio for the highest cBMI quartile was 2.064 (95% CI: 1.793‐2.377) relative to the lowest quartile. The second and third quartiles did not differ from the first quartile, consistent with a nonlinear trend. Conclusions: The cumulative burden of higher weight and longer duration was associated with incident prediabetes, but this association was statistically significant only after a higher threshold was reached. Strategies for prevention of prediabetes in middle age may focus on avoiding overweight in young adulthood to limit duration. [ABSTRACT FROM AUTHOR]

Background: The optimal coronary revascularization strategy to maximize the patient‐centered outcome of days alive and out of hospital (DAOH), in multimorbid older (≥65‐years) adults after an acute coronary syndrome (ACS) is incompletely understood. Methods: Using Kaiser Permanente Northern California Health Plan databases, we identified 3871 patients ≥65‐years presenting with ACS between 1/1/2010–3/1/2018 who underwent coronary revascularization with either coronary artery bypass grafting (CABG, N = 1575) or multivessel percutaneous coronary intervention (PCI, N = 2296). Selection bias was accounted for through propensity score modeling techniques and inverse probability of treatment weighting. Cox proportional hazards models were fit to evaluate the association of revascularization type with outcomes. Primary Outcomes: Absolute DAOH and the relative risk of achieving ≥90%DAOH during three time intervals. Secondary Outcomes: All‐cause mortality, recurrent MI, stroke, rehospitalization, repeat revascularization, and dialysis initiation. Results: CABG (compared to PCI) was associated with greater absolute number of DAOH, significant after the first year (mean difference at 1‐year: +5.8 days, 95% confidence interval [CI], −1.6 to 13 days; 3‐years: +56 days, 95%CI, +25 to +88 days; 5‐years: + 131 days, 95%CI, +57 to +205 days). The relative risk of achieving ≥90% DAOH significantly favored CABG after the first year (1‐year:1.02, 95%CI, 0.98–1.05; 3‐years:1.06, 95%CI 1.002–1.11, 5‐years:1.12, 95%CI, 1.03–1.22), and was related to lower incidences of all‐cause mortality, repeat revascularization, rehospitalization, incident dialysis, and nonfatal MI with CABG. Conclusions: In older adults with multivessel or left main coronary artery disease who presented with ACS, CABG, after the first year, was associated with a greater absolute number of DAOH—a geriatric and patient‐centered outcome, compared to PCI. CABG patients also had a higher probability of achieving ≥90%DAOH—with lower all‐cause mortality, recurrent MI, repeat revascularization, new dialysis, and rehospitalization rates. Future randomized trials should study the impact of optimal revascularization strategies on the quality of life of older adults with multimorbidity. See related editorial by Hanna et al. in this issue. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to assess short‐term outcomes among emergency department (ED) patients with acute heart failure (AHF) by preserved (≥50%) vs. reduced (<50%) ejection fraction (EF). Methods and results: We conducted a retrospective, multicentre study of adult ED patients with AHF from 2017 to 2018 in an integrated healthcare system with 21 hospitals. Among patients with known EF, our primary outcome was 30 day all‐cause mortality, comparing patients with heart failure with preserved EF (HFpEF) and heart failure with reduced EF (HFrEF), adjusted for known risk factors. We ran separate multivariate regression models to compare 30 day mortality between HFpEF and HFrEF patients stratified by ED disposition (admit, observe, and discharge). Our secondary outcomes were adjusted 30 day all‐cause return hospital admission and rates of non‐fatal serious adverse events, including new intra‐aorta balloon pump, endotracheal intubation, renal failure requiring dialysis, myocardial infarction, or coronary revascularization. We conducted a sensitivity analysis among patients with EF ≤ 40% and compared our primary and secondary outcomes among patients with EF ≤ 40% with those with EF ≥ 50%. Among the 26 050 total ED encounters for AHF, 15 275 (58.6%) had known EF and 62.4% had HFpEF. The mean age was 76, 49.6% were women, and 60.5% were white. We found that 62.4% of patients were admitted, 18.3% were observed, and 19.3% were discharged from the ED. The 30 day all‐cause mortality rate was lowest among discharged patients (3.9%), intermediate among observed patients (5.9%), and highest among admitted patients (13.9%). Overall, the adjusted 30 day mortality rate was significantly higher among HFpEF patients compared with HFrEF patients (10.2% vs. 8.4%, P = 0.0004). HFpEF patients had higher mortality regardless of ED disposition, although the difference was only significant among admitted patients. The adjusted 30 day return hospital admission rates were not significantly different between HFpEF and HFrEF patients (17.9% vs. 17.8%, P = 0.89). The adjusted 30 day non‐fatal serious adverse event rates were significantly higher among HFrEF patients compared with HFpEF patients (13.7% vs. 11.1%, P < 0.0001), driven by myocardial infarction and coronary revascularization. We found that 3692 patients had EF ≤ 40%. Patients with EF ≥ 50% had significantly higher adjusted 30 day mortality rates compared with those with EF ≤ 40% (10.2% vs. 8.4%, P < 0.05). Conclusion: In a contemporary population, almost three quarters of ED patients with AHF and known EF have HFpEF. These patients have higher 30 day adjusted mortality compared with those with HFrEF. Further studies might evaluate the underlying factors associated with this difference and target interventions to improve outcomes. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the prevalence of electrocardiogram (ECG) abnormalities in marijuana users as an indirect measure of subclinical cardiovascular disease (CVD). Design Longitudinal and cross‐sectional secondary data analysis from the CARDIA (Coronary Artery Risk Development in Young Adults) study. Setting: Four communities in the United States. Participants: A total of 2585 participants from the 5115 black and white men and women recruited at age 18–30 years in 1985 to 1986 in CARDIA. Measurements ECG abnormalities coded as minor and major abnormalities with the Minnesota code of electrocardiographic findings at year 20. Self‐reported current (past 30 days) and computed cumulative life‐time marijuana use (one 'marijuana‐year' corresponds to 365 days of use) through assessments every 2–5 years. We fitted logistic regression models adjusting for sex, race, center, education, age, tobacco smoking, physical activity, alcohol use and body mass index. Findings Among the 2585 participants with an ECG at year 20, mean age was 46, 57% were women, 45% were black; 83% had past exposure to marijuana and 11% were using marijuana currently. One hundred and seventy‐three participants (7%) had major abnormalities and 944 (37%) had minor abnormalities. Comparing current with never use in multivariable‐adjusted models, the odds ratio (OR) for major ECG abnormalities was 0.60 [95% confidence interval (CI) = 0.32–1.15] and for minor ECG abnormalities 1.21 (95% CI = 0.87–1.68). Results did not change after stratifying by sex and race. Cumulative marijuana use was not associated with ECG abnormalities. Conclusion: In a middle‐aged US population, life‐time cumulative and occasional current marijuana use were not associated with increases in electrocardiogram abnormalities. This adds to the growing body of evidence that occasional marijuana use and cardiovascular disease events and markers of subclinical atherosclerosis are not associated. [ABSTRACT FROM AUTHOR]

Abstract: Aims: We investigated the association between cumulative lifetime and current marijuana use with total abdominal adipose tissue (AT), visceral AT, subcutaneous AT, intermuscular AT, and mean liver attenuation (LA) at mid‐life. Design: Longitudinal and cross‐sectional secondary data analysis of participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Setting: CARDIA field centers in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA, USA. Participants: CARDIA participants, aged 18–30 years in 1985–1986, who were present at the clinic examination in 2010–2011 (n = 2902). Measurements: Marijuana use was assessed from responses to self‐administered questionnaires at 8 CARDIA examinations over 25 years, determined as cumulative marijuana‐years and current use status. Non‐contrast computed tomography imaging of the abdomen was obtained in 2010–2011. Findings: In 2010–2011, 84% of participants reported a history of marijuana use with 11% reporting use within the past 30 days. Before adjustment, we observed greater cumulative marijuana use was associated with lower total abdominal and subcutaneous AT volume and lower LA and current marijuana use was associated with lower subcutaneous AT. However, after adjustment for age, sex, race, field center, cigarette pack‐years and current use, regular alcohol consumption, cumulative drink‐years, and physical activity, neither cumulative marijuana use nor current use showed an association with any abdominal adipose depot. Our estimates did not differ by age, sex, or race nor after accounting for cohort attrition. Conclusion: Neither cumulative marijuana use nor current marijuana use is associated with total abdominal, visceral, subcutaneous, or intermuscular adipose tissue, or liver attenuation in mid‐life. [ABSTRACT FROM AUTHOR]

Objective To determine the influence of the total cumulative exposure to excess overall and abdominal adiposity on the incidence of cardiovascular disease (CVD). Methods Prospective study of 4,061 white and black adults without CVD at baseline in 1985-1986 (age 18-30 years) from the multicenter, community-based CARDIA study. Time-varying excess body mass index (BMI)- and waist circumference (WC)-years were calculated as products of the degree and duration of excess overall (BMI ≥ 25 kg/m2) and abdominal adiposity [WC >94 cm (men) and >80 cm (women)], respectively, collected at up to eight examinations. Results During a median of 24.8 years, there were 125 incident CVD, 62 coronary heart disease (CHD), and 33 heart failure (HF) events. Adjusted hazard ratios for CVD, CHD, and HF for each additional 50 excess BMI-years were 1.20 (1.08, 1.34), 1.25 (1.07, 1.46), and 1.45 (1.23, 1.72), respectively. For each 50 excess WC-years, these hazard ratios were 1.10 (1.04, 1.18), 1.13 (1.03, 1.24), and 1.22 (1.11, 1.34), respectively. Akaike information criterion values were lowest in models containing time-varying excess BMI- or WC-years compared to those including time-varying BMI or WC only. Conclusions Excess BMI- and WC-years are predictors of the risk of CVD and may provide a better indicator of the cumulative exposure to excess adiposity than BMI or WC only. [ABSTRACT FROM AUTHOR]

Background There is an ongoing debate about the performance of non-high-density lipoprotein cholesterol (non- HDL-C) compared with apolipoprotein B (apo B) in the prediction of coronary heart disease ( CHD) risk. Therefore, we compared the associations between non- HDL-C and apo B in regard to CHD among apparently healthy Western European individuals. Design In the European Prospective Investigation into Cancer and Nutrition ( EPIC)-Norfolk prospective population study, 25 639 men and women aged 45-79 years were followed for 11·4 ± 2·8 years. Those with diabetes or prevalent CHD at baseline were excluded. A total of 2066 (12·1%) participants developed CHD during 195 692 person-years follow-up. Results The multivariable-adjusted hazard ratio [ HR] of future CHD per one standard deviation increase was 1·22 [95% confidence interval ( CI): 1·17-1·27] for LDL-C, 1·26 (95% CI 1·20-1·31) for non- HDL-C and 1·19 (95% CI 1·14-1·24) for apo B, respectively. The multivariable-adjusted HR of future CHD in the highest quartile LDL-C was 1·67 (95% CI: 1·47-1·91). For non- HDL-C and apo B, these respective HRs were 1·87 (95% CI: 1·62-2·15) and 1·56 (95% CI: 1·36-1·78). Kaplan-Meier survival analyses showed that there was incremental and comparable increase in risk of CHD with increasing quartiles of both non- HDL-C and apo B. Conclusions In this prospective study, non- HDL-C and apo B were comparable in their ability to predict risk of future CHD. [ABSTRACT FROM AUTHOR]

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4±12.3 vs 65.6±11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction. Prev Cardiol. 2010;13:112–116.©2009 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

1. Cell transplantation has promise as a therapeutic option for restoring impaired heart function after acute myocardial infarction (AMI). However, the optimal cell type to use remains controversial. We investigated the therapeutic efficacy and feasibility of intramyocardial transplantation of human umbilical cord blood-derived endothelial progenitor cells (hUCB-EPC) in rats with AMI. 2. The Wistar rats myocardial infarction model was established by ligating the left anterior descending artery. The labelled hUCB-EPC were transplanted through intramyocardial injection. Left ventricular function was assessed using a pressure-volume catheter and echocardiogram. Anti-VIII immunohistochemistry staining was used to reflect the degree of angiogenesis in peri-infarcted areas by calculating the average capillary density. The fibrosis degree of infarcted myocardium was analysed by Masson staining and the collagen volume fraction was calculated. 3. The labelled donor endothelial progenitor cells were detected in the new microvessels in host myocardium by double-positive staining with CM-Dil and FITC-UEA-l. An increase in left ventricular ejection fraction, left ventricular fractional shortening, left ventricular end-systolic pressure, first derivative of left ventricular pressure (+dP/dtmax and −dP/dtmax), as well as a decrease in the left ventricular end-diastolic pressure in rats with cell therapy indicated a significant improvement in global heart function. The cell therapy group had increased microvessel formation and a decreased degree of myocardial fibrosis compared to the control group. Moreover, the degree of myocardial fibrosis was less than that of the control group. 4. The improved global heart function and decreased cardiac fibrosis in rats with AMI implies the potential benefit of hUCB-EPC transplantation. [ABSTRACT FROM AUTHOR]

The impact of obesity on cardiovascular disease (CVD) outcomes in patients with type 2 diabetes mellitus (T2DM) and established coronary artery disease (CAD) is controversial; whether BMI and/or waist circumference correlate with atherothrombotic risk factors in such patients is uncertain. We sought to evaluate whether higher BMI or waist circumference are associated with specific risk factors among 2,273 Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study participants with T2DM and documented CAD (baseline data, mean age 62 years, 66% non-Hispanic white, 71% men). Multiple linear regression models were constructed after adjusting for sex, age, race/ethnicity, US vs. non-US site, diabetes duration, exercise, smoking, alcohol, and relevant medication use. First-order partial correlations of BMI with risk factors after controlling for waist circumference and of waist circumference with risk factors after controlling for BMI were also evaluated. Ninety percent of the patients were overweight (BMI ≥25 kg/m2); 68% of men and 89% of women had high-risk waist circumference measures (≥102 and ≥88 cm, respectively). BMI and waist circumference, in separate models, explained significant variation in metabolic (insulin, lipids, blood pressure (BP)) and inflammatory/procoagulation (C-reactive protein, PAI-1 activity and antigen, and fibrinogen) risk factors. In partial correlation analyses BMI was independently associated with BP and inflammatory/procoagulation factors, waist circumference with lipids, and both BMI and waist circumference with insulin. We conclude that, in cross-sectional analyses, both BMI and waist circumference, independently, are associated with increased atherothrombotic risk in centrally obese cohorts such as the BARI 2D patients with T2DM and CAD. [ABSTRACT FROM AUTHOR]

In order to examine lipids, a major treatment parameter in those with diabetes and heart disease, the authors analyzed baseline data from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial. The study consisted of 2368 participants with type 2 diabetes and coronary artery disease from 49 sites in 6 countries (2295 provided lipid measurements). Fifty-nine percent of participants had a low-density lipoprotein (LDL) cholesterol level <100 mg/dL. Levels of total, LDL, and non–high-density lipoprotein (HDL) cholesterol and triglycerides differed by age group (younger than 55, 55–64, and 65 years and older); they were lowest in those aged 65 years. Women had higher total, LDL, and non-HDL cholesterol values. Education was associated with lower total, LDL, and non-HDL cholesterol levels. LDL cholesterol and triglyceride values were lower in the United States and Canada. Adjustment for age, sex, education level, randomization year, and medication did not eliminate these differences. Geographic variation was seen and was not fully accounted for by demographic or treatment characteristics (all P values <.05). [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis of myocardial infarction. Stem cells are able to regenerate infarcted myocardium. This study investigated whether TNF-α was able to induce migration of embryonic stem cells (ESCs) in vitro. We used a Transwell assay in which neonatal rat cardiomyocytes, with or without transfection of TNF-α cDNA, were plated in the lower compartments and mouse ESCs tagged with green fluorescent protein were added to the upper compartments. TNF-α level was significantly increased in the medium of the lower compartments seeded with TNF-α-transfected cardiomyocytes. Compared with the controls, overexpression of TNF-α significantly enhanced migration of ESCs to the lower compartments. This enhancement was attenuated by preincubation of ESCs with the antibody against the type II TNF-α receptor (TNF-RII), but not by the antibody against the type I TNF-α receptor (TNF-RI). Western blot analysis showed that the phosphorylated protein levels of p38 and c-Jun amino-terminal kinase (JNK) were significantly increased in TNF-α-treated ESCs. Inhibition of the activity of p38 or JNK significantly attenuated TNF-α-induced ESC migration. Our data demonstrate that excessive TNF-α stimulates TNF-RII and enhances migration of ESCs in vitro. Activation of p38 and JNK is required for TNF-α-enhanced ESC migration.--Chen, Y., Ke, Q., Yang, Y., Rana, J. S., Tang, J, Morgan, J. P., Xiao, Y.-F. Cardiomyocytes overexpressing TNF-α attract migration of embryonic stem cells via activation of p38 and c-Jun amino-terminal kinase. [ABSTRACT FROM AUTHOR]

Background The association between diets that focus on plant foods and restrict animal products and cardiovascular disease (CVD) is inconclusive. We investigated whether cumulative intake of a plant-centered diet and shifting toward such a diet are associated with incident CVD. Methods and Results Participants were 4946 adults in the CARDIA (Coronary Artery Risk Development in Young Adults) prospective study. They were initially 18 to 30 years old and free of CVD (1985-1986, exam year [year 0]) and followed until 2018. Diet was assessed by an interviewer-administered, validated diet history. Plant-centered diet quality was assessed using the A Priori Diet Quality Score (APDQS), in which higher scores indicate higher consumption of nutritionally rich plant foods and limited consumption of high-fat meat products and less healthy plant foods. Proportional hazards models estimated hazard ratios of CVD associated with both time-varying average APDQS and a 13-year change in APDQS score (difference between the year 7 and year 20 assessments). During the 32-year follow-up, 289 incident CVD cases were identified. Both long-term consumption and a change toward such a diet were associated with a lower risk of CVD. Multivariable-adjusted hazard ratio was 0.48 (95% CI, 0.28-0.81) when comparing the highest quintile of the time-varying average ADPQS with lowest quintiles. The 13-year change in APDQS was associated with a lower subsequent risk of CVD, with a hazard ratio of 0.39 (95% CI, 0.19-0.81) comparing the extreme quintiles. Similarly, strong inverse associations were found for coronary heart disease and hypertension-related CVD with either the time-varying average or change APDQS. Conclusions Consumption of a plant-centered, high-quality diet starting in young adulthood is associated with a lower risk of CVD by middle age.

Background and Aims: Unlike tobacco, the effect of marijuana smoke on subclinical atherosclerosis, a surrogate measure for cardiovascular disease, is not known. This study aimed to determine the association between lifetime exposure to marijuana and measures of subclinical atherosclerosis in mid-life., Design, Setting and Participants: We used data from the US-based Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of black and white men and women aged 18-30 years at baseline in 1985-86, with up to seven follow-up examinations over 25 years. A total of 3498 participants in the CARDIA study were included in this study., Measurements: Cumulative years of exposure to marijuana (expressed in 'marijuana-years', with 1 marijuana-year equivalent to 365 days of use) using repeated assessments every 2-5 years for 25 years. Abdominal artery calcium (AAC) and coronary artery calcium (CAC) scores were measured by computed tomography at year 25 examination., Results: Among 3117 participants with AAC and CAC measurements, 2627 (84%) reported past marijuana use and 1536 (49%) past daily tobacco smoking. Compared with tobacco smokers, 46% of whom reported 10 or more pack-years of use, only 12% of marijuana users reported 5 or more marijuana-years of use and only 6% reported having used marijuana daily. We found a significant interaction between never and ever tobacco users on the association between cumulative marijuana use and AAC (P = 0.05). Among those who never smoked tobacco, cumulative marijuana-years were not associated with AAC or CAC in models adjusted for demographics, cardiovascular risk factors, licit and illicit drug exposure and depression symptoms. However, among ever tobacco smokers, marijuana exposure was associated with AAC and CAC. At 5 marijuana-years of exposure, using AAC = 0 and CAC = 0 as a reference group, the odds ratio (OR) was 1.97 [95% confidence interval (CI) = 1.21-3.21, P = 0.007] for AAC > 0/CAC = 0 and 1.83 (95% CI = 1.02-3.31, P = 0.04) for CAC > 0), regardless of AAC. Tobacco smoking was associated strongly with both AAC and CAC., Conclusion: Marijuana use appears to be associated with subclinical atherosclerosis, but only among ever tobacco users., (© 2017 Society for the Study of Addiction.)