Background: The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to increase the risk of atherosclerotic cardiovascular disease, type 2 diabetes mellitus, and possibly some cancers. Animal studies and observational clinical data in humans suggest that supplemental melatonin may ameliorate a number of components of the metabolic syndrome, including elevated glucose, elevated blood pressure, dyslipidemia, and obesity. The primary objective of this clinical trial was to determine the feasibility, efficacy, and safety of melatonin supplementation in men and women with the metabolic syndrome. Methods: Thirty-nine men and women of mixed race/ethnicity were enrolled into a randomized, double-blind, placebo-controlled clinical trial with two arms: placebo for 10 weeks followed by melatonin for 10 weeks, or vice versa, with an interval 6-week washout period, in a crossover trial design. Outcome measures include metabolic syndrome components (blood pressure, glucose, triglycerides, high-density lipoprotein cholesterol, waist circumference), oxidative stress, and inflammation biomarkers. These biomarkers, along with sleep duration and quality and pretreatment endogenous melatonin levels, were measured to explore possible underlying biologic mechanisms. Discussion: This trial will provide knowledge of the effects of melatonin in metabolic syndrome subjects, and lay the groundwork for future clinical trials of melatonin in metabolic syndrome subjects.

Background-Previous studies suggest that among patients with stable coronary artery disease, patients with diabetes mellitus (DM) have less angina and more silent ischemia when compared with those without DM. However, the burden of angina in diabetic versus nondiabetic patients after elective percutaneous coronary intervention (PCI) has not been recently examined. Methods and Results-In a 10-site US PCI registry, we assessed angina before and at 1, 6, and 12 months after elective PCI with the Seattle Angina Questionnaire angina frequency score (range, 0-100, higher=better). We also examined the rates of antianginal medication prescriptions at discharge. A multivariable, repeated-measures Poisson model was used to examine the independent association of DM with angina over the year after treatment. Among 1080 elective PCI patients (mean age, 65 years; 74.7% men), 34.0% had DM. At baseline and at each follow-up, patients with DM had similar angina prevalence and severity as those without DM. Patients with DM were more commonly prescribed calcium channel blockers and long-Acting nitrates at discharge (DM versus not: 27.9% versus 20.9% [P=0.01] and 32.8% versus 25.5% [P=0.01], respectively), whereas β-blockers and ranolazine were prescribed at similar rates. In the multivariable, repeated-measures model, the risk of angina was similar over the year after PCI in patients with versus without DM (relative risk, 1.04; range, 0.80-1.36). Conclusions-Patients with stable coronary artery disease and DM exhibit a burden of angina that is at least as high as those without DM despite more antianginal prescriptions at discharge. These findings contradict the conventional teachings that patients with DM experience less angina because of silent ischemia.

Background This study describes the patterns and socioeconomic influences of tobacco use among adults in tobacco-cultivating regions of rural southwest China. Methods A cross-sectional survey was conducted in 8681 adults aged ≥18 years in rural areas of Yunnan Province, China from 2010 to 2011. A standardized questionnaire was administered to obtain data about participants’ demographic characteristics, individual socioeconomic status, ethnicity, self-reported smoking habits, and exposure to secondhand smoke (SHS). The socioeconomic predictors of current smoking, nicotine addiction, and SHS exposure were analyzed using multivariate logistic regression. Results The prevalence rates of tobacco use were much higher in men compared with women (current smoking 68.5% vs. 1.3%; and nicotine dependence 85.2% vs. 72.7%). However, the rate of SHS exposure was higher in women compared with men (76.6% vs. 70.5%). Tobacco farmers had higher prevalence rates of current smoking, nicotine dependence, and SHS exposure compared with participants not engaged in tobacco farming (P<0.01). Most tobacco users (84.5%) reported initiating smoking during adolescence. A total of 81.1% of smokers smoked in public places, and 77.6% smoked in workplaces. Individuals belonging to an ethnic minority had a lower probability of SHS exposure and nicotine dependence. Individual educational level was found to be inversely associated with the prevalence of current smoking, exposure to SHS, and nicotine dependence. Higher annual household income was associated with a greater risk of nicotine dependence. Conclusions This study suggests that tobacco control efforts in rural southwest China must be tailored to address tobacco-cultivating status and socioeconomic factors.

The 1245.29 Trial recently showed that empaglifozin improved both blood pressure and glucose control in African American (AA) patients with type 2 diabetes (T2D) and hypertension. Using the Diabetes Collaborative Registry, a large-scale US registry of outpatients with diabetes recruited from primary care, cardiology and endocrinology practices, we sought to understand the potential impact of these observations in routine clinical practice. Among 74 290 AA patients with T2D from 368 US clinics, 60.4% had hypertension, of whom 34.5% had systolic blood pressure ≥ 140 mm Hg (20.8% of the total AA T2D population). Only 1.7% of this eligible population had been prescribed a sodium-glucose co-transporter two inhibitor. The mean estimated 5-year risk of cardiovascular death was 7.7%, which could be reduced to 6.2% when modelling the antihypertensive effect of empagliflozin across the eligible population (based on an 8-mm Hg blood pressure reduction). These findings may represent a potential opportunity for better management of cardiovascular risk factors and improved outcomes in this vulnerable cohort.

Background: Although practice guidelines stress individualization of glucose management in patients with type 2 diabetes (T2D), the extent to which providers take patient factors into account when selecting medications is not well known. Methods: Diabetes Collaborative Registry (DCR) is an outpatient diabetes registry including primary care, cardiology, and endocrinology practices. T2D medications were grouped as those which may be suboptimal for key patient subgroups, and we examined patient factors associated with use of these agents using hierarchical, multivariable Poisson models. Results: In DCR, 157,551 patients from 374 US practices were prescribed a glucose-lowering medication. Patients with morbid obesity were more likely treated with medications prone to cause weight gain (relative rate [RR] 1.09, 95% CI 1.07–1.11). Older patients were more likely to be treated with medications with increased risk of hypoglycemia (RR 1.04 per 5 years, 95% CI 1.04–1.05). Patients with CKD 4/5 were less likely to be treated with agents with known risk in patients with advanced CKD (RR 0.74, 95% CI 0.71–0.77). Patients with coronary artery disease were no more or less likely to be treated with medications with potential cardiovascular safety issues (RR 0.99, 95% CI 0.96–1.01). Conclusions: We observed some targeted use of glucose-lowering therapies in certain subgroups but also identified potential opportunities for better personalization of treatment. Data sources such as the DCR can highlight potential areas for improving targeted approaches to pharmacologic therapy in order to optimize selection of patients most likely to benefit (and least likely to be harmed) from treatments.

Background-We sought to determine temporal trends in use of evidence-based therapies and clinical outcomes among myocardial infarction (MI) patients with chronic kidney disease (CKD). Methods and Results-MI patients from the NCDR (National Cardiovascular Data Registry) Chest Pain-MI Registry between January 2007 and December 2015 were categorized into 3 groups by degree of CKD (end-stage renal disease on dialysis, CKD [glomerular filtration rate <60 mL/min per 1.73 m 2 ] not requiring dialysis, and no CKD [glomerular filtration rate ≥60 mL/min per 1.73 m 2 ]). Logistic regression modeling was used to determine the association between calendar years (2014-2015 versus 2007- 2008) and each outcome by degree of CKD. Among 325 396 patients with ST-segment-elevation MI, 1.0% had end-stage renal disease requiring dialysis, and 26.1% had CKD not requiring dialysis. Use of primary percutaneous coronary intervention increased over time regardless of the presence or degree of CKD (P=0.40 for interaction). In-hospital mortality was temporally higher among patients with preserved renal function (odds ratio: 1.25; 95% confidence interval, 1.13-1.39; P<0.001) but not among patients with CKD (P=0.035 for interaction). Among 506 876 non-ST-segment-elevation MI patients, 3.4% had end-stage renal disease requiring dialysis, and 34.4% had CKD not requiring dialysis. P2Y 12 inhibitor use within 24 hours increased over time only among dialysis patients (P for interaction <0.001). Use of coronary angiography and percutaneous coronary intervention also increased, with the greatest increase among dialysis patients (P for interaction <0.001 and <0.001, respectively). In-hospital mortality was lower, regardless of the presence or degree of CKD (P=0.64 for interaction). Conclusions-Uptake of evidence-based medical and invasive therapies has increased over the past decade among MI patients with CKD, particularly dialysis patients, with improvement of in-hospital mortality observed among patients with non-ST-segment- elevation MI, but not ST-segment-elevation MI, and CKD.

BACKGROUND: Patients with obstructive (≥50% stenosis) left main (LM) coronary artery disease (CAD) are at high risk for adverse events; prior studies have also documented worse outcomes among women than men with severe multivessel/LM CAD. However, the prognostic significance of nonobstructive (1%-49% stenosis) LM CAD, including sex-specific differences, has not been previously examined.METHODS AND RESULTS: In the long-term CONFIRM (Coronary CT Angiography Evaluation For Clinical Outcomes: An International Multicenter) registry, patients underwent elective coronary computed tomographic angiography for suspected CAD and were followed for 5 years. After excluding those with obstructive LM CAD, 5166 patients were categorized as having normal LM or nonobstructive LM (18% of cohort). Cumulative 5-year incidence of death, myocardial infarction, or revascularization was higher among patients with nonobstructive LM than normal LM in both women and men: women (34.3% versus 15.4%; P<0.0001); men (24.6% versus 18.2%; P<0.0001). A significant interaction existed between sex and LM status for the composite outcome (P=0.001). In multivariable Cox regression, the presence of nonobstructive LM plaque increased the risk for the composite outcome in women (adjusted hazard ratio, 1.48; P=0.005) but not in men (adjusted hazard ratio, 0.98, P=0.806). In subgroup analysis, women with nonobstructive LM CAD had a nearly 80% higher risk for events than men with nonobstructive LM CAD (adjusted hazard ratio, 1.78; P=0.017); sex-specific interactions were not observed across other patterns (eg, location or extent) of nonobstructive plaque.CONCLUSION: Nonobstructive LM CAD was frequently detected on coronary computed tomographic angiography and strongly associated with adverse events among women. Recognizing the sex-specific prognostic significance of nonobstructive LM plaque may augment risk stratification efforts.

Background: Cardiovascular disease (CVD) imparts a heavy economic burden on the U.S. health care system. Evidence regarding the long-term costs after comprehensive CVD screening is limited. Objectives: This study calculated 10-year health care costs for 6,814 asymptomatic participants enrolled in MESA (Multi-Ethnic Study of Atherosclerosis), a registry sponsored by the National Heart, Lung, and Blood Institute, National Institutes of Health. Methods: Cumulative 10-year costs for CVD medications, office visits, diagnostic procedures, coronary revascularization, and hospitalizations were calculated from detailed follow-up data. Costs were derived by using Medicare nationwide and zip code–specific costs, inflation corrected, discounted at 3% per year, and presented in 2014 U.S. dollars. Results: Risk factor prevalence increased dramatically and, by 10 years, diabetes, hypertension, and dyslipidemia was reported in 19%, 57%, and 53%, respectively. Self-reported symptoms (i.e., chest pain or shortness of breath) were common (approximately 40% of enrollees). At 10 years, approximately one-third of enrollees reported having an echocardiogram or exercise test, whereas 7% underwent invasive coronary angiography. These utilization patterns resulted in 10-year health care costs of $23,142. The largest proportion of costs was associated with CVD medication use (78%). Approximately $2 of every $10 were spent for outpatient visits and diagnostic testing among the elderly, obese, those with a high-sensitivity C-reactive protein level >3 mg/l, or coronary artery calcium score (CACS) ≥400. Costs varied widely from <$7,700 for low-risk (Framingham risk score <6%, 0 CACS, and normal glucose measurements at baseline) to >$35,800 for high-risk (persons with diabetes, Framingham risk score ≥20%, or CACS ≥400) subgroups. Among high-risk enrollees, CVD costs accounted for $74 million of the $155 million consumed by MESA participants. Conclusions: Longitudinal patterns of health care resource use after screening revealed new evidence on the economic burden of treatment and testing patterns not previously reported. Maintenance of a healthy population has the potential to markedly reduce the economic burden of CVD among asymptomatic individuals.

Background--With the recent implementation of the Medicare Quality Payment Program, providers face increasing accountability for delivering high-quality care. Such pay-for-performance programs aim to leverage systematic data captured by electronic health record (EHR) systems to measure performance; however, the fidelity of EHR query for assessing performance has not been validated compared with manual chart review. We sought to determine whether our institution's methodology of EHR query could accurately identify cases in which providers failed to prescribe statins for eligible patients with coronary artery disease. Methods and Results--A total of 9459 patients with coronary artery disease were seen at least twice at the Emory Clinic between July 2014 and June 2015, of whom 1338 (14.1%, 95% confidence interval 13.5-14.9%) had no statin prescription or exemption per EHR query. A total of 120 patient cases were randomly selected and reviewed by 2 physicians for further adjudication. Of the 120 cases initially classified as statin prescription failures, only 21 (17.5%; 95% confidence interval, 11.7-25.3%) represented true failure following physician review. Conclusions--Sole reliance on EHR data query to measure quality metrics may lead to significant errors in assessing provider performance. Institutions should be cognizant of these potential sources of error, provide support to medical providers, and form collaborative data management teams to promote and improve meaningful use of EHRs. We propose actionable steps to improve the accuracy of EHR data query that require hypothesis testing and prospective validation in future studies.

The efficacy of implantable cardioverter-defibrillators (ICD) for primary prevention of sudden cardiac death (SCD) has not been studied in patients with end-stage renal disease (ESRD) and left ventricular dysfunction. We sought to identify predictors of long-term survival among ICD recipients with and without ESRD. Methods Patients implanted with an ICD at our institution from January 2006 to March 2014 were retrospectively identified. Clinical and demographic characteristics were collected. Patients were stratified by the presence of ESRD at the time of ICD implant. Mortality data were collected from the Social Security Death Index (SSDI). Results A total of 3453 patients received an ICD at our institution in the pre-specified time period, 184 (5.3%) of whom had ESRD. In general, ESRD patients were sicker and had more comorbidities. Kaplan Meier survival curve showed that ESRD patients had worse survival as compared with non-dialysis patients (p < 0.001). Following adjustment for differences in baseline characteristics, patients with ESRD remained at increased long-term mortality in the Cox model. The one-year mortality in the ESRD patients was 18.1%, as compared with 7.7% in the non-dialysis cohort (p < 0.001). The three-year mortality in ESRD patients was 43%, as compared with 21% in the non-dialysis cohort (p < 0.001). Conclusion ESRD patients are at significantly increased risk of mortality as compared with a non-dialysis cohort. While the majority of these patients survive more than one year post-diagnosis, the three-year mortality is high (43%). Randomized studies addressing the benefits of ICDs in ESRD patients are needed to better define their value for primary prevention of SCD.