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This study aimed to compare the 2-year cardio-cerebrovascular adverse outcomes of patients with influenza with and without preexisting cardiovascular disease (preCVD) treated with oral antiviral agents in the outpatient clinic. Oral antiviral agents are routinely prescribed to treat influenza infection with a positive rapid-antigen test in the outpatient clinic; however, influenza-associated cardio-cerebrovascular outcomes have not yet been characterized in patients with preCVD treated with oral antiviral agents. Data between 2006 and 2016 were extracted from the National Health Database of South Korea. A total of 865,522 patients with influenza treated with oral antiviral agents were selected in South Korea and classified as preexisting ischemic heart disease (IHD), heart failure (HF), or atrial fibrillation (AF), and 2-year cardio-cerebrovascular outcomes were analyzed using a Cox proportional hazard regression model. Among the participants, 96,433 had preCVD (11.1%; mean age, 46 years) including IHD (86.4%), HF (23.1%), and AF (12.5%). The incidence of new-onset IHD, AF, HF, and death was similar between patients with influenza with and without preCVD. The incidences of IHD and stroke were 0.489 and 0.047 per 100-person year in the preCVD group, respectively. The incidence of cardiovascular mortality was 0.489 per 100-person year in the preCVD group, and the hazard ratio for cardiovascular mortality in the preCVD group was not significantly different from that in patients without preCVD. Based on the national health data, 2-year cardio-cerebrovascular adverse outcomes were not significantly different between patients with and without preCVD treated with oral antiviral agents., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Thyroid dysfunction is associated with the risk of cardiovascular disease; however, whether plasma thyroid-stimulating hormone (TSH) levels in subjects with euthyroidism affect the risk of cardiovascular disease remains unclear. This study aimed to investigate the causal association between plasma TSH levels and cardiovascular diseases, particularly ischemic heart disease and heart failure (HF). Summary statistics from the Integrative Epidemiology Unit Open genome-wide association studies Project and FinnGen consortium were used to investigate the causal relationship between plasma TSH levels and the risk of cardiovascular diseases. Two-sample Mendelian randomization analysis using inverse-variance weighting as the primary method was performed. The MR Pleiotropy RESidual Sum and Outlier and leave-one-out methods were used to ensure the robustness of our findings. Genetically determined plasma TSH levels were associated with major coronary heart disease events (OR 1.0557, 95% CI 1.0141-1.0991), all-cause HF (OR 0.9587, 95% CI 0.9231-0.9956), and HF + non-ischemic cardiomyopathy (OR 0.9318, 95% CI 0.8786-0.9882). After the Bonferroni correction, the causation described above disappeared. In the secondary analysis, genetically determined higher TSH levels were associated with a higher risk for unstable angina pectoris (OR 1.0913, 95% CI 1.0350-1.1507), but were associated with a lower risk for HF + overweight (OR 0.9265, 95% CI 0.8821-0.9731). These results were further validated using sensitivity analysis. Our findings show that increased plasma TSH levels in patients with euthyroidism may increase the risk of unstable angina pectoris but reduce the risk of HF in overweight patients. This evidence indicates that plasma TSH levels may need to be carefully controlled in specific patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Study Objectives: Fibromyalgia (FM) is one of the most common causes of chronic widespread musculoskeletal pain, but also sleep disturbances, cognitive and psychological disorders. It has been suggested that FM may have a correlation with cardiovascular events. In this study, we aimed to assess the association between FM and ischemic heart disease (IHD)., Methods: A population-based cross-sectional study was conducted utilizing data retrieved from the largest medical records database in Israel, Clalit Health Services. Patients were defined as having FM or IHD when there were at least two such documented diagnoses in their medical records. The occurrence of IHD was compared between FM and age- and sex-frequency-matched healthy controls. A logistic regression model was used to estimate this association following an adjustment for conventional cardiovascular risk factors and depression., Results: An overall population of 18 598 FM patients and 36 985 age- and gender-matched controls were included in the study. The proportion of IHD amongst FM patients was increased in comparison to controls (9.2% and 6.2%, respectively; P  < 0.001). Furthermore, FM demonstrated an independent association with IHD on multivariate analysis (odds ratio [OR], 1.43; 95% confidence intervals [CI], 1.33-1.54; P  < 0.0001). Finally, IHD was also found to be independently associated with the diagnosis of FM (OR, 1.40; CI, 1.31-1.51; P  < 0.0001)., Conclusion: Our data suggest a bidirectional link between FM and IHD even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Oxidative stress plays an important role in the health impacts of both outdoor fine particulate air pollution (PM 2.5 ) and thermal stress. However, it is not clear how the oxidative potential of PM 2.5 may influence the acute cardiovascular effects of temperature., Methods: We conducted a case-crossover study of hospitalization for cardiovascular events in 35 cities across Canada during the summer months (July-September) between 2016 and 2018. We collected three different metrics of PM 2.5 oxidative potential each month in each location. We estimated associations between lag-0 daily temperature (per 5ºC) and hospitalization for all cardiovascular (n = 44,876) and ischemic heart disease (n = 14,034) events across strata of monthly PM 2.5 oxidative potential using conditional logistical models adjusting for potential time-varying confounders., Results: Overall, associations between lag-0 temperature and acute cardiovascular events tended to be stronger when outdoor PM 2.5 oxidative potential was higher. For example, when glutathione-related oxidative potential (OP GSH ) was in the highest tertile, the odds ratio (OR) for all cardiovascular events was 1.040 (95% confidence intervals [CI] = 1.004, 1.074) compared with 0.980 (95% CI = 0.943, 1.018) when OP GSH was in the lowest tertile. We observed a greater difference for ischemic heart disease events, particularly for older subjects (age >70 years)., Conclusions: The acute cardiovascular health impacts of summer temperature variations may be greater when outdoor PM 2.5 oxidative potential is elevated. This may be particularly important for ischemic heart disease events., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Contemporary cardiovascular disease (CVD) risk prediction models are rarely applied in routine clinical practice in China due to substantial regional differences in absolute risks of major CVD types within China. Moreover, the inclusion of blood lipids in most risk prediction models also limits their use in the Chinese population. We developed 10-year CVD risk prediction models excluding blood lipids that may be applicable to diverse regions of China., Methods: We derived sex-specific models separately for ischemic heart disease (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS) in addition to total CVD in the China Kadoorie Biobank. Participants were age 30-79 years without CVD at baseline. Predictors included age, systolic and diastolic blood pressure, use of blood pressure-lowering treatment, current daily smoking, diabetes, and waist circumference. Total CVD risks were combined in terms of conditional probability using the predicted risks of 3 submodels. Risk models were recalibrated in each region by 2 methods (practical and ideal) and risk prediction was estimated before and after recalibration., Results: Model derivation involved 489,596 individuals, including 45,947 IHD, 43,647 IS, and 11,168 HS cases during 11 years of follow-up. In women, the Harrell C was 0.732 (95% CI 0.706-0.758), 0.759 (0.738-0.779), and 0.803 (0.778-0.827) for IHD, IS, and HS, respectively. The Harrell C for total CVD was 0.734 (0.732-0.736), 0.754 (0.752-0.756), and 0.774 (0.772-0.776) for models before recalibration, after practical recalibration, and after ideal recalibration. The calibration performances improved after recalibration, with models after ideal recalibration showing the best model performances. The results for men were comparable to those for women., Discussion: Our CVD risk prediction models yielded good discrimination of IHD and stroke subtypes in addition to total CVD without including blood lipids. Flexible recalibration of our models for different regions could enable more widespread use using resident health records covering the overall Chinese population., Classification of Evidence: This study provides Class I evidence that a prediction model incorporating accessible clinical variables predicts 10-year risk of IHD, IS, and HS in the Chinese population age 30-79 years., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Cardiac ischemia during daily life is associated with an increased risk of adverse outcomes. Mental stress is known to provoke cardiac ischemia and is related to psychological variables. In this multicenter cohort study, we assessed whether psychological characteristics were associated with ischemia in daily life., Methods: This study examined patients with clinically stable coronary artery disease (CAD) with documented cardiac ischemia during treadmill exercise (n = 196, mean [standard deviation] age = 62.64 [8.31] years; 13% women). Daily life ischemia (DLI) was assessed by 48-hour ambulatory electrocardiophic monitoring. Psychological characteristics were assessed using validated instruments to identify characteristics associated with ischemia occurring in daily life stress., Results: High scores on anger and hostility were common in this sample of patients with CAD, and DLI was documented in 83 (42%) patients. However, the presence of DLI was associated with lower anger scores (odds ratio [OR] = 2.03; 95% confidence interval [CI] = 1.12-3.69), reduced anger expressiveness (OR = 2.04; 95% CI = 1.10-3.75), and increased ratio of anger control to total anger (OR = 2.33; 95% CI = 1.27-4.17). Increased risk of DLI was also associated with lower hostile attribution (OR = 2.22; 95% CI = 1.21-4.09), hostile affect (OR = 1.92; 95% CI = 1.03-3.58), and aggressive responding (OR = 2.26; 95% CI = 1.25-4.08). We observed weak inverse correlations between DLI episode frequency and anger expressiveness, total anger, and hostility scores. DLI was not associated with depression or anxiety measures. The combination of the constructs low anger expressiveness and low hostile attribution was independently associated with DLI (OR = = 2.59; 95% CI = 1.42-4.72)., Conclusions: In clinically stable patients with CAD, the tendency to suppress angry and hostile feelings, particularly openly aggressive behavior, was associated with DLI. These findings warrant a study in larger cohorts, and intervention studies are needed to ascertain whether management strategies that modify these psychological characteristics improve outcomes., (Copyright © 2022 by the American Psychosomatic Society.)

Background and Purpose: Several prospective cohort studies and a randomized clinical trial have shown the beneficial effects of peanut consumption on cardiovascular disease and its risk factors. We examined the association between peanut consumption and risk of cardiovascular disease in Japanese men and women., Methods: We analyzed data of 74 793 participants aged 45 to 74 years who completed a lifestyle questionnaire including the validated food frequency questionnaire in the Japan Public Health Center–based Prospective Study. They were followed up from 1995 to 2009 for cohort I and from 1998 to 1999 to 2012 for cohort II. Peanut consumption was calculated from the food frequency questionnaire, and the end points were incidence of stroke, ischemic heart disease, and cardiovascular disease (stroke and ischemic heart disease)., Results: During a median follow-up of 14.8 years, 3,599 strokes and 849 ischemic heart diseases were reported. Higher peanut consumption was associated with reduced risks of total stroke, ischemic stroke, and cardiovascular disease among men and women. The multivariable hazard ratios (95% CIs) for the highest versus lowest quartiles of peanut consumption after adjustment for age, sex, public health center, smoking, alcohol consumption, perceived stress level, physical activity, vegetable, fruit, fish, soy, sodium and total energy intakes, body mass index, history of hypertension, history of diabetes, and cholesterol-lowering drug were 0.84 (0.77–0.93, P for trend=0.002) for total stroke, 0.80 (0.71–0.90, P for trend=0.002) for ischemic stroke, 0.93 (0.79–1.08, P for trend=0.27) for hemorrhagic stroke, 0.97 (0.80–1.17, P for trend=0.81) for ischemic heart disease and 0.87 (0.80–0.94, P for trend=0.004) for cardiovascular disease, and these associations were similarly observed in both sexes., Conclusions: Higher peanut consumption was associated with reduced risk of stroke, especially ischemic stroke, but not ischemic heart disease in Japanese men and women.

Abstract: There was a controversy for the electrocardiogram (ECG) changes and their relationship with disease severity in old patients with acute cerebral ischemic stroke (CIS). This study was aim to provide referential data for this topic.Totally 200 old patients with acute CIS in our hospital from January 2017 to December 2019 were included into this study. According to the ST-T segment changes in ECG, these patients were divided into 3 groups: persistent ischemic group (n = 38), transient ischemic group (n = 106) and non-ischemic group (n = 56). The characteristics and incidence of abnormal ECG and their relationship with disease severity, infarct size and prognosis were respectively analyzed under the severe, moderate and mild type of disease.The ECG changes of patients were mainly characterized by myocardial ischemic ST-T segment changes with a abnormal ECG incidence of 72.00%, the arrhythmia with a abnormal ECG incidence of 9.50%, which were the second most common in clinical features. There were statistically significant differences of myocardial ischemic ST-T segment changes among different disease severity, infarct size and prognosis of acute CIS patients (P < .05). The ischemic ST-T segment changes of ECG reflected that the disease severity, and more ECG abnormalities indicated more severe pathological conditions in CIS patients.The characteristics of ischemic ST-T segment changes have important reference value in the evaluation of severity and prognosis of acute CIS in old patients., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Mental stress-induced myocardial ischemia (MSIMI), a transient myocardial ischemic response to mental stress, is associated with poorer outcomes among patients with coronary heart disease and is more likely to occur among women. However, predictors of MSIMI are not well explored. The current study investigated the association between experiences of everyday discrimination and MSIMI among patients with recent myocardial ischemia and contrasted the results with conventional stress-induced myocardial ischemia (CSIMI). We examined sex differences in associations., Methods: We studied 295 post-MI patients (145 women, 150 men). Provocation of myocardial ischemia with mental stress (speech task) and conventional stress (exercise or pharmacologic) was assessed by myocardial perfusion imaging. Frequency of exposure to everyday discrimination was assessed via questionnaire using the Everyday Discrimination Scale (EDS)., Results: The mean age was 51 years in both women and men, and the EDS score ranged from 10 to 38 (mean [standard deviation] = 17 [6] years). After multivariable analysis, each standard deviation increase in the EDS score (more frequent exposure) was associated with an increased odds of MSIMI (odds ratio [OR] = 1.57 [1.10-2.23]). The EDS score was not associated with CSIMI (OR = 0.86 [0.64-1.17]). Women demonstrated a twofold increase (OR = 1.96 [1.13-3.38], p = .02) in the adjusted odds of MSIMI, with each standard deviation increase in the EDS score compared with a 1.4-fold increase (OR = 1.40 [0.80-2.44], p = .24) among men; however, interaction was not statistically significant., Conclusions: Among post-MI patients, everyday discrimination was positively associated with occurrence of MSIMI, but not with CSIMI; associations were more pronounced among women., (Copyright © 2021 by the American Psychosomatic Society.)

Abstract: Major adverse cardiac and cerebral events (MACCE) are common complications, which prolong hospitalization and increase mortality rate in end-stage renal disease (ESRD) patients who underwent continuous ambulatory peritoneal dialysis (CAPD). Therefore, this study aimed to investigate MACCE occurrence and its potential predictive factors in those patients.In this prospective cohort study, 196 diagnosis of ESRD patients who underwent CAPD treatment in our hospital were eligible, and their clinical data (including demographic data and biochemical indexes) were documented. Besides, their MACCE occurrence was assessed within 3-year follow-up period.In patients, 1-, 2-, and 3-year MACCE occurrence rates were 5.1%, 11.7%, and 14.8%, respectively. Meanwhile, the mean duration of accumulating MACCE occurrence was 33.1 (95% confidence interval: 32.0-34.2) months. Furthermore, age, peritoneal dialysis duration (PDD), C-reactive protein (CRP), fasting blood glucose (FBG) and total cholesterol high correlated with increased accumulating MACCE occurrence, while high-density lipoprotein cholesterol (HDL-C) high correlated with decreased accumulating MACCE occurrence. Notably, by further multivariate Cox's proportional hazard regression analysis, age, PDD, CRP, serum uric acid, and FBG high were independent predictive factors for raised accumulating MACCE occurrence, while HDL-C high was an independent predictive factor for attenuated accumulating MACCE occurrence.MACCE are common; besides, age, peritoneal dialysis duration, C-reactive protein, serum uric acid, fasting blood glucose, and high-density lipoprotein cholesterol serve as potential markers for indicating MACCE in ESRD patients who underwent CAPD., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To describe sex differences in the presentation, diagnosis, and revision of diagnosis after early brain MRI in patients who present with acute transient or minor neurologic events., Methods: We performed a secondary analysis of a prospective multicenter cohort study of patients referred to neurology between 2010 and 2016 with a possible cerebrovascular event and evaluated with brain MRI within 8 days of symptom onset. Investigators documented the characteristics of the event, initial diagnosis, and final diagnosis. We used multivariable logistic regression analyses to evaluate the association between sex and outcomes., Results: Among 1,028 patients (51% women, median age 63 years), more women than men reported headaches and fewer reported chest pain, but there were no sex differences in other accompanying symptoms. Women were more likely than men to be initially diagnosed with stroke mimic (54% of women vs 42% of men, adjusted odds ratio (OR) 1.60, 95% confidence interval [CI] 1.24-2.07), and women were overall less likely to have ischemia on MRI (10% vs 17%, OR 0.52, 95% CI 0.36-0.76). Among 496 patients initially diagnosed with mimic, women were less likely than men to have their diagnosis revised to minor stroke or TIA (13% vs 20%, OR 0.53, 95% CI 0.32-0.88) but were equally likely to have acute ischemia on MRI (5% vs 8%, OR 0.56, 95% CI 0.26-1.21)., Conclusions: Stroke mimic was more frequently diagnosed in women than men, but diagnostic revisions were common in both. Early brain MRI is a useful addition to clinical evaluation in diagnosing transient or minor neurologic events., (© 2020 American Academy of Neurology.)

Radical cystectomy is considered the standard treatment for patients with muscle-invasive bladder tumors and has high postoperative complication rates among urological surgeries. High-risk patients, defined as those ≥45 years of age with history of coronary artery disease, stroke, or peripheral artery disease or those ≥65 years of age, can have a higher incidence of cardiac complications. Therefore, we evaluated the incidence, risk factors, and outcomes of myocardial injury after non-cardiac surgery (MINS) in high-risk patients who underwent radical cystectomy.This retrospective observational study analyzed 248 high-risk patients who underwent radical cystectomy. MINS was defined as serum troponin I concentration ≥0.04 mg/L within postoperative 3 days. The risk factors for MINS were evaluated by multivariate logistic regression analysis. Postoperative outcomes were evaluated. The 1-year survival after radical cystectomy was also compared between patients who developed MINS (MINS group) and those who did not (non-MINS group) by Kaplan-Meier analysis.MINS occurred in 35 patients (14.1%). Multivariate logistic regression analysis showed that early diastolic transmitral filling velocity (E)/early diastolic septal mitral annular velocity (E') ratio (odds ratio = 1.102, 95% confidence interval [1.009-1.203], P = .031) and large volume blood transfusion (odds ratio = 2.745, 95% confidence interval [1.131-6.664], P = .026) were significantly associated with MINS in high-risk patients who underwent radical cystectomy. Major adverse cardiac events and 1-year mortality were significantly higher in the MINS group than in the non-MINS group (17.1% vs 6.1%, P = .035; 28.6% vs 12.7%, P = .021, respectively). Kaplan-Meier analysis showed significantly lower 1-year survival in the MINS group than in the non-MINS group (P = .010).MINS occurred in 14.1% of patients. High E/E' ratio and large volume blood transfusion were risk factors for MINS in high-risk patients who underwent radical cystectomy. Postoperative major adverse cardiac events and 1-year mortality were significantly higher in the MINS group than in the non-MINS group. Preoperative evaluation of risk factors for MINS may provide useful information to detect cardiovascular complications after radical cystectomy in high-risk patients.

We evaluated the statewide burden of obesity and its complications among government and state funded programs (Medicare and Medicaid) and commercial insurance.We calculated the prevalence of obesity and the prevalence of relevant comorbidities among different demographic groups and based on health insurance, among adults (18-65 years old) who visited a statewide health network in the state of Rhode Island, in 2017.The overall prevalence of obesity among 74,089 individuals was 38.88% [Asians 16.77%, Whites 37.49%, Hispanics 44.23%, and Blacks 48.44%]. Medicare or Medicaid beneficiaries were 26% and 27%, respectively, more likely to have obesity than those who had commercial insurance (Odds Ratio:1.26, 95% confidence interval [CI]:1.20-1.32; Odds Ratio:1.27, 95%CI:1.22-1.32). Moreover, Medicaid and Medicare beneficiaries with obesity had a higher prevalence of diabetes compared with privately insured with obesity (10.58% and 10.44% vs 4.45%). Medicare beneficiaries with obesity had a statistically higher prevalence of ischemic heart disease (4.34%, 95%CI: 3.77-4.91) than privately insured (3.21%, 95%CI: 2.94-3.47).Based on statewide data among 18 to 65 years old adults, Medicare and Medicaid provide health coverage to 40% of individuals with obesity and 46% of those with the obesity-related comorbidities and complications. State and federal health care programs need to support and expand obesity-related services and coverage.

Background: Heart failure (HF) in patients with type 2 diabetes mellitus (T2D) has received growing attention. We examined the effect of HF development on prognosis compared with other cardiovascular or renal diagnoses in patients with T2D., Methods and Results: Patients with new T2D diagnosis patients were identified between 1998 and 2015 through Danish nationwide registers. At yearly landmark timepoints after T2D diagnosis, we estimated the 5-year risks of death, 5-year risk ratios, and decrease in lifespan within 5 years associated with the development of HF, ischemic heart disease, stroke, peripheral artery disease, and chronic kidney disease. A total of 153 403 patients with newly diagnosed T2D were followed for a median of 9.7 years (interquartile range, 5.8-13.9) during which 48 087 patients died. The 5-year risk ratio of death associated with HF development 5 years after T2D diagnosis was 3 times higher (CI, 2.9-3.1) than patients free of diagnoses (CI, 2.9-3.1). Five-year risk ratios were lower for ischemic heart disease (1.3 [1.3-1.4]), stroke (2.2 [2.1-2.2]), chronic kidney disease (1.7 [1.7-1.8]), and peripheral artery disease (2.3 [2.3-2.4]). The corresponding decrease in lifespan within 5 years when compared with patients free of diagnoses (in months) was HF 11.7 (11.6-11.8), ischemic heart disease 1.6 (1.5-1.7), stroke 6.4 (6.3-6.5), chronic kidney disease 4.4 (4.3-4.6), and peripheral artery disease 6.9 (6.8-7.0). HF in combination with any other diagnosis imposed the greatest risk of death and decrease in life span compared with other combinations. Supplemental analysis led to similar results when stratified according to age, sex, and comorbidity status, and inclusion period., Conclusions: HF development, at any year since T2D diagnosis, was associated with the highest 5-year absolute and relative risk of death, and decrease in lifespan within 5 years, when compared with development of other cardiovascular or renal diagnoses.

Background: Several studies have evaluated the long-term clinical outcomes of periprocedural myocardial injury for chronic total occlusions patients. However, the results of these studies were inconsistent. To determine whether the periprocedural myocardial injury has adverse effects on long-term clinical outcomes in chronic total occlusion patients undergoing percutaneous coronary intervention., Methods: We searched Cochrane Library, PubMed, and Embase for eligible articles from their date of inception up to March 2019. Long-term clinical outcomes included major adverse cardiac events, all-cause death, cardiac death, myocardial infarction, and target vessel revascularization. Odds ratios with 95% confidence intervals were calculated as summary statistics by using Review Manager software., Results: A total of 8 observational studies involving 5879 chronic total occlusions patients were included in this meta-analysis. These results of this meta-analysis indicated that periprocedural myocardial injury was associated with a higher risk of major adverse cardiac events (odds ratio, 1.94; 95% confidence interval, 1.22-3.08; P = 0.005), a higher risk of all-cause death (odds ratio, 1.30; 95% confidence interval, 1.02-1.64; P = 0.03), a higher risk of cardiac death (odds ratio, 2.59; 95% confidence interval, 1.41-4.78; P = 0.002), a higher risk of myocardial infarction (odds ratio, 3.07; 95% confidence interval, 1.90-4.98; P < 0.00001), and a higher risk of target vessel revascularization (odds ratio, 2.07; 95% confidence interval, 1.35-3.16; P=0.0008) than non-periprocedural myocardial injury., Conclusion: Periprocedural myocardial injury was associated with significantly increased risk of major adverse cardiac events, all-cause death, cardiac death, myocardial infarction, and target vessel revascularization in chronic total occlusion patients undergoing percutaneous coronary intervention at long-term follow-up.

Coronary artery tortuosity (CAT) is a prevalent angiographic finding commonly associated with aging, hypertension, atherosclerosis and other conditions. Preliminary evidence suggests that degradation of elastin, a key component of extracellular matrix in the vascular wall, may be responsible for the development of CAT. The clinical significance of CAT should be considered in several aspects. First, coronary flow alteration associated with CAT may result in myocardial ischemia owing to reduced perfusion pressure distal to the tortuous segment. Second, increased and oscillatory shear stress in the tortuous vessel may promote atherosclerotic plaque formation and acute coronary syndrome. Third, as one of the criteria for coronary lesion complexity, the presence of severe tortuosity proximal to the culprit lesion may pose a challenge to wiring and stent or balloon delivery, thereby increasing the risk of periprocedural complications. Last, the presence of CAT may serve as a diagnostic clue of concurrent vasculopathy such as fibromuscular dysplasia or spontaneous coronary artery dissection. In general, CAT represents a benign entity that does not require specific treatment or intervention. Further research is warranted to elucidate the pathogenesis and prognostic effect of coronary tortuosity.

Objective: Firefighting-related environmental and physiological factors associated with cardiovascular strain may promote arrhythmias and myocardial ischemia, which induce sudden cardiac events (SCE) in susceptible individuals. The present study evaluated electrocardiographic (ECG) changes that may reflect increased SCE risk following simulated live-firefighting., Methods: Using a repeated measures design, ECG tracings from 32 firefighters were recorded 12-hours post-firefighting in a residential structure and compared with a 12-hour control period., Results: Ventricular arrhythmias were present in 20%, and ST segment changes indicative of myocardial ischemia in 16%, of firefighters 12-hours post-firefighting that were not detected in the control period., Conclusion: Live-firefighting induces significant ECG changes that include ventricular arrhythmias and ST segment changes, which may reflect myocardial ischemia. The implications of such ECG changes explaining increased cardiovascular risk in firefighters warrants further research.

Myocardial injury after noncardiac surgery (MINS) is a common postoperative complication associated with adverse cardiovascular outcomes. The purpose of this systematic review was to determine the incidence, clinical features, pathogenesis, management, and outcomes of MINS. We searched PubMed, Embase, Central and Web of Science databases for studies reporting the incidence, clinical features, and prognosis of MINS. Data analysis was performed with a mixed-methods approach, with quantitative analysis of meta-analytic methods for incidence, management, and outcomes, and a qualitative synthesis of the literature to determine associated preoperative factors and MINS pathogenesis. A total of 195 studies met study inclusion criteria. Among 169 studies reporting outcomes of 530,867 surgeries, the pooled incidence of MINS was 17.9% [95% confidence interval (CI), 16.2-19.6%]. Patients with MINS were older, more frequently men, and more likely to have cardiovascular risk factors and known coronary artery disease. Postoperative mortality was higher among patients with MINS than those without MINS, both in-hospital (8.1%, 95% CI, 4.4-12.7% vs 0.4%, 95% CI, 0.2-0.7%; relative risk 8.3, 95% CI, 4.2-16.6, P < 0.001) and at 1-year after surgery (20.6%, 95% CI, 15.9-25.7% vs 5.1%, 95% CI, 3.2-7.4%; relative risk 4.1, 95% CI, 3.0-5.6, P < 0.001). Few studies reported mechanisms of MINS or the medical treatment provided. In conclusion, MINS occurs frequently in clinical practice, is most common in patients with cardiovascular disease and its risk factors, and is associated with increased short- and long-term mortality. Additional investigation is needed to define strategies to prevent MINS and treat patients with this diagnosis.

Background: Despite evidence suggesting that air pollution-related health effects differ by emissions source, epidemiologic studies on fine particulate matter (PM2.5) infrequently differentiate between particles from different sources. Those that do rarely account for the uncertainty of source apportionment methods., Methods: For each day in a 12-year period (1998-2010) in Atlanta, GA, we estimated daily PM2.5 source contributions from a Bayesian ensemble model that combined four source apportionment methods including chemical transport and receptor-based models. We fit Poisson generalized linear models to estimate associations between source-specific PM2.5 concentrations and cardiorespiratory emergency department visits (n = 1,598,117). We propagated uncertainty in the source contribution estimates through analyses using multiple imputation., Results: Respiratory emergency department visits were positively associated with biomass burning and secondary organic carbon. For a 1 µg/m increase in PM2.5 from biomass burning during the past 3 days, the rate of visits for all respiratory outcomes increased by 0.4% (95% CI 0.0%, 0.7%). There was less evidence for associations between PM2.5 sources and cardiovascular outcomes, with the exception of ischemic stroke, which was positively associated with most PM2.5 sources. Accounting for the uncertainty of source apportionment estimates resulted, on average, in an 18% increase in the standard error for rate ratio estimates for all respiratory and cardiovascular emergency department visits, but inflation varied across specific sources and outcomes, ranging from 2% to 39%., Conclusions: This study provides evidence of associations between PM2.5 sources and some cardiorespiratory outcomes and quantifies the impact of accounting for variability in source apportionment approaches.

Aims: Although the benefits of percutaneous coronary interventions (PCIs) in patients with stable chronic ischemic heart disease (SIHD) are controversial, a large number of PCIs are currently performed in SIHD patients, frequently after coronary angiography (ad-hoc procedures), without the use of fractional flow reserve (FFR) to identify patients most likely to benefit from PCI., Methods: Assessment of regional variations in PCI for SIHD performed in Italy in 2017 and correlation of the regional number of PCI per million inhabitants with the use of FFR were performed using the data reported in the registry of the Italian Society of Interventional Cardiology (SICI-GISE) registry for the year 2017., Results: PCI for SIHD accounted for 44.5% of all PCI performed in Italy with large variations among the Italian regions. There was a significant and inverse relationship between the use of FFR and the PCI number per million inhabitants performed for SIHD in the various Italian regions (P = 0.01). In the Veneto region, where local authorities mandated Heart Team reports to select the most appropriate treatment choice in multivessel disease patients, the rate of ad-hoc procedures was significantly lower than the national average., Conclusion: PCI for SIHD patients represent almost half of all procedures currently performed in Italy with regional variations inversely related to physiologic guidance use. The mandatory assessment by the Heart Team to select the most appropriate treatment choice in multivessel disease patients is associated with a significantly lower number of ad-hoc procedures.

Background: There is uncertainty about the relevance of animal foods to the pathogenesis of ischemic heart disease (IHD). We examined meat, fish, dairy products, and eggs and risk for IHD in the pan-European EPIC cohort (European Prospective Investigation Into Cancer and Nutrition)., Methods: In this prospective study of 409 885 men and women in 9 European countries, diet was assessed with validated questionnaires and calibrated with 24-hour recalls. Lipids and blood pressure were measured in a subsample. During a mean of 12.6 years of follow-up, 7198 participants had a myocardial infarction or died of IHD. The relationships of animal foods with risk were examined with Cox regression with adjustment for other animal foods and relevant covariates., Results: The hazard ratio (HR) for IHD was 1.19 (95% CI, 1.06-1.33) for a 100-g/d increment in intake of red and processed meat, and this remained significant after exclusion of the first 4 years of follow-up (HR, 1.25 [95% CI, 1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR, 0.93 [95% CI, 0.89-0.98] per 100-g/d increment), cheese (HR, 0.92 [95% CI, 0.86-0.98] per 30-g/d increment), and eggs (HR, 0.93 [95% CI, 0.88-0.99] per 20-g/d increment); the associations with yogurt and eggs were attenuated and nonsignificant after exclusion of the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish, or milk. In analyses modeling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese, or eggs was associated with ≈20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-high-density lipoprotein cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-high-density lipoprotein cholesterol., Conclusions: Risk for IHD was positively associated with consumption of red and processed meat and inversely associated with consumption of yogurt, cheese, and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It is not clear whether the associations with red and processed meat and cheese reflect causality, but they were consistent with the associations of these foods with plasma non-high-density lipoprotein cholesterol and for red and processed meat with systolic blood pressure, which could mediate such effects.

To explore the prevalence and risk factors of silent myocardial ischemia (SMI) detected by using single photon emission computed tomography (SPECT) in Chinese asymptomatic patients with type 2 diabetes (T2D).In this hospital-based retrospective study, 821 T2D patients who were screened for SMI detected by stress myocardial perfusion imaging using SPECT between June 2014 and July 2016 were investigated. Clinical indicators were compared between the patients with SMI and controls without SMI. Risk factors for SMI were evaluated by univariate and multivariate analysis.In this study, there were 131 patients with SMI in asymptomatic diabetes and the prevalence of SMI was 21.3% of 614 individuals. Logistic regression analysis indicated that diabetic retinopathy (OR = 1.474, 95%CI: 1.113-1.951, P = .007), male gender (OR = 1.805, 95%CI: 1.183-2.747, P = .006), and low-density lipoprotein (LDL) cholesterol (OR = 1.298, 95%CI: 1.042-1.615, P = .02) were risk factors associated with SMI. Besides, the prevalence of SMI increased in associated with the progression of retinopathy (P = .041). The percentage of SMI diagnosed in patients with no diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) were 18.5% (75/405), 25.2% (37/147), and 30.6% (19/62), respectively. The percentage of SMI in male (24.5%, 85/347) was higher than that in female (17.2%, 46/267), P = .029.Physicians should be aware of these conditions when examining male patients with type 2 diabetes, especially with DR and/or high level of low-density lipoprotein cholesterol (LDL cholesterol), even if otherwise asymptomatic. A routine screening for SMI may thus be considered advisable in these patients.

Background and Purpose- Dietary sodium reduction with concurrent increase in potassium intake is a current public health priority to reduce risk of cardiovascular events. This study explored associations between the spot urine sodium-to-potassium ratio and cardiovascular events in the MESA (Multi-Ethnic Study of Atherosclerosis) longitudinal cohort. Methods- The MESA is a prospective cohort study of 6814 adults from 4 ethnic groups (European-, Asian-, African- and Hispanic-American) with a mean age of 62 (±10.2) years and an average of 11.7 (±2.2) years of follow-up. Participants were free of clinical cardiovascular disease at baseline. Spot urine sodium and potassium excretion, as a marker of dietary intake, was collected at baseline. The impact of urinary sodium-to-potassium ratio on adjudicated cardiovascular events was assessed using Cox proportional hazards models. Results- Only 39% of MESA participants had a urinary sodium-to-potassium ratio ≤1, and these participants experienced only 74 of the 236 strokes. A sodium-to-potassium ratio >1 was associated with a hazard ratio of 1.47 (95% CI,1.07-2.00) for risk of stroke, adjusting for age, sex, race, cardiovascular risk factors, socio-demographic characteristics, body size, and kidney function. Conclusions- The spot urine sodium-to-potassium ratio (measurable in routine care) is associated with stroke. A urine sodium-to-potassium ratio of ≤1, may be related to a clinically relevant reduction in stroke risk and is a feasible target for health interventions.

Background and Purpose- Cerebral microbleeds (CMBs) have been observed using magnetic resonance imaging in patients with cardiovascular risk factors, cognitive deterioration, small vessel disease, and dementia. They are a well-known consequence of cerebral amyloid angiopathy, chronic hypertension, and diffuse axonal injury, among other causes. However, the frequency and location of new CMBs postadult cardiac surgery, in association with cognition and perioperative risk factors, have yet to be studied. Methods- Pre- and postsurgery magnetic resonance susceptibility-weighted images and neuropsychological tests were analyzed from a total of 75 patients undergoing cardiac surgery (70 men; mean age, 63±10 years). CMBs were identified by a neuroradiologist blinded to clinical details who independently assessed the presence and location of CMBs using standardized criteria. Results- New CMBs were identified in 76% of patients after cardiac surgery. The majority of new CMBs were located in the frontal lobe (46%) followed by the parietal lobe (15%), cerebellum (13%), occipital lobe (12%), and temporal lobe (8%). Patients with new CMBs typically began with a higher prevalence of preexisting CMBs ( P=0.02). New CMBs were associated with longer cardiopulmonary bypass times ( P=0.003), and there was a borderline association with lower percentage hematocrit ( P=0.04). Logistic regression analysis suggested a ≈2% increase in the odds of acquiring new CMBs during cardiac surgery for every minute of bypass time (odds ratio, 1.02; 95% CI, 1.00-1.05; P=0.04). Postoperative neuropsychological decline was observed in 44% of patients and seemed to be unrelated to new CMBs. Conclusions- New CMBs identified using susceptibility-weighted images were found in 76% of patients who underwent cardiac surgery. CMBs were globally distributed with the highest numbers in the frontal and parietal lobes. Our regression analysis indicated that length of cardiopulmonary bypass time and lowered hematocrit may be significant predictors for new CMBs after cardiac surgery. Clinical Trial Registration- URL: http://www.isrctn.com . Unique identifier: 66022965.

Background: Balancing ischemic and bleeding risk is an evolving framework., Methods and Results: Our objectives were to simulate changes in risks for adverse events and event-driven costs with use of ticagrelor or prasugrel versus clopidogrel according to varying levels of ischemic and bleeding risk. Using the validated PARIS risk functions, we estimated 1-year ischemic (myocardial infarction or stent thrombosis) and bleeding (Bleeding Academic Research Consortium types 3 or 5) event rates among PARIS study participants who underwent percutaneous coronary intervention with drug-eluting stent implantation for an acute coronary syndrome and were discharged with aspirin and clopidogrel (n=1497). Simulated changes in adverse events with ticagrelor or prasugrel were calculated by applying treatment effects from randomized trials for a 1-year time horizon. Event costs were estimated using National Inpatient Sample data. Net costs were calculated between antiplatelet therapy groups according to level of ischemic and bleeding risk. After weighting events for quality-of-life impact, we calculated event rates and costs for risk-tailored treatment versus clopidogrel under multiple drug pricing assumptions. One-year rates (per 1000 person-years) for ischemic events were 12.6, 24.1, and 66.1, respectively, among those at low (n=630), intermediate (n=536), and high (n=331) ischemic risk. Analogous bleeding rates were 11.0, 23.9, and 66.2, respectively, among low (n=728), intermediate (n=634), and high (n=135) bleeding risk patients. Mean per event costs were $22 174 (ischemic) and $12 203 (bleeding). When risks for ischemia matched or exceeded bleeding, simulated utility-weighted event rates favored ticagrelor/prasugrel, whereas clopidogrel reduced utility-weighted events when bleeding exceeded ischemic risk. One-year costs were sensitive to drug pricing assumptions, and risk-tailored treatment with either agent progressed from cost incurring to cost saving with increasing generic market share., Conclusions: Tailoring antiplatelet therapy intensity to patient risk may improve health utility and could produce cost savings in the first year after percutaneous coronary intervention., Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00998127.

Objective: It is unclear whether mental stress-induced myocardial ischemia (MSIMI) is related to obstructive coronary artery disease (CAD). We examined this question and contrasted results with ischemia induced by conventional stress testing (CSIMI). Because women are more susceptible to ischemia without coronary obstruction than men, we examined sex differences., Methods: We studied 276 patients 61 years and younger with recent myocardial infarction. CAD severity was quantified using the log-transformed Gensini Score (lnGS) and the Sullivan Stenosis Score. Patients underwent myocardial perfusion imaging with mental stress (public speaking) and conventional (exercise or pharmacological) stress testing. MSIMI and CSIMI were defined as a new or worsening perfusion defect., Results: The prevalence of MSIMI was 15% in men and 20% in women. The median GS for patients with MSIMI was 65.0 in men and 28.5 in women. In logistic regression models adjusted for demographic and cardiovascular risk factors, CAD severity was associated with CSIMI in the full sample (odds ratio [OR] = 1.49, 95% [CI], 1.14-1.95, per 1-unit increase in lnGS), with no significant difference by sex. Although CAD severity was not associated with MSIMI in the entire sample, results differed by sex. CAD severity was associated with MSIMI among men (OR = 1.95, 95% CI, 1.13-3.36, per 1-unit increase in lnGS), but not among women (OR = 1.02, 95% CI, 0.74-1.42, p = .042 for interaction). Analysis using Sullivan Stenosis Score yielded similar results., Conclusions: Findings suggest that CAD severity is related to MSIMI in men but not women. MSIMI in women may therefore be driven by alternative mechanisms such as coronary microvascular disease.

Objective: To determine the prognostic relevance, clinical characteristics, and 30-day outcomes associated with myocardial injury after noncardiac surgery (MINS) in vascular surgical patients., Background: MINS has been independently associated with 30-day mortality after noncardiac surgery. The characteristics and prognostic importance of MINS in vascular surgery patients are poorly described., Methods: This was an international prospective cohort study of 15,102 noncardiac surgery patients 45 years or older, of whom 502 patients underwent vascular surgery. All patients had fourth-generation plasma troponin T (TnT) concentrations measured during the first 3 postoperative days. MINS was defined as a TnT of 0.03 ng/mL of higher secondary to ischemia. The objectives of the present study were to determine (i) if MINS is prognostically important in vascular surgical patients, (ii) the clinical characteristics of vascular surgery patients with and without MINS, (iii) the 30-day outcomes for vascular surgery patients with and without MINS, and (iv) the proportion of MINS that probably would have gone undetected without routine troponin monitoring., Results: The incidence of MINS in the vascular surgery patients was 19.1% (95% confidence interval (CI), 15.7%-22.6%). 30-day all-cause mortality in the vascular cohort was 12.5% (95% CI 7.3%-20.6%) in patients with MINS compared with 1.5% (95% CI 0.7%-3.2%) in patients without MINS (P < 0.001). MINS was independently associated with 30-day mortality in vascular patients (odds ratio, 9.48; 95% CI, 3.46-25.96). The 30-day mortality was similar in MINS patients with (15.0%; 95% CI, 7.1-29.1) and without an ischemic feature (12.2%; 95% CI, 5.3-25.5, P = 0.76). The proportion of vascular surgery patients who suffered MINS without overt evidence of myocardial ischemia was 74.1% (95% CI, 63.6-82.4)., Conclusions: Approximately 1 in 5 patients experienced MINS after vascular surgery. MINS was independently associated with 30-day mortality. The majority of patients with MINS were asymptomatic and would have gone undetected without routine postoperative troponin measurement.

Background: Randomized, clinical trials in selected acute ischemic stroke patients reported that for every hour delay of endovascular treatment (EVT), chances of functional independence diminish by up to 3.4%. These findings may not be fully generalizable to clinical practice because of strict in- and exclusion criteria in these trials. Therefore, we aim to assess the association of time to EVT with functional outcome in current, everyday clinical practice., Methods: The MR CLEAN Registry (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in The Netherlands) is an ongoing, prospective, observational study in all centers that perform EVT in The Netherlands. Data were analyzed from patients treated between March 2014 and June 2016. In the primary analysis we assessed the association of time from stroke onset to start of EVT and time from stroke onset to successful reperfusion with functional outcome (measured with the modified Rankin Scale), by means of ordinal logistic regression., Results: We analyzed 1488 patients with acute ischemic stroke who underwent EVT. An increased time to start of EVT was associated with worse functional outcome (adjusted common odds ratio, 0.83 per hour; 95% confidence interval, 0.77-0.89) and a 2.2% increase in mortality. Every hour increase from stroke onset to EVT start resulted in a 5.3% decreased probability of functional independence (modified Rankin Scale, 0-2). In the 742 patients with successful reperfusion, every hour increase from stroke onset to reperfusion was associated with a 7.7% decreased probability of functional independence., Conclusions: Time to EVT for acute ischemic stroke in current clinical practice is strongly associated with functional outcome. Our data suggest that this association might be even stronger than previously suggested in reports on more selected patient populations from randomized, controlled trials. These findings emphasize that functional outcome of EVT patients can be greatly improved by shortening onset to treatment times., (© 2018 American Heart Association, Inc.)

This retrospective cohort study investigated the outcomes of patients with unplanned intensive care unit (ICU) readmission.All of the patients readmitted to ICU within 48 hours between 2010 and 2016 were enrolled.A total of 99 patients early readmitted to ICU were identified and their mean age of the patients was 68.8 ± 14.8 years. Respiratory failure was the most common cause of ICU readmission (n = 48, 48.5%), followed by acute myocardial ischemia or worsening heart failure (n = 25, 25.3%), sepsis (n = 22, 22.2%), gastrointestinal disease (n = 16, 16.2%), and neurologic disease (n = 11, 11.1%). The median length of stay in the ICU and hospital was 7 (IQR, 4-11.5) and 32 (IQR, 15.5-48.5) days, respectively. A total of 34 patients died during the hospital stay and the rate of in-hospital mortality was 34.3%. Patients with higher APACHE II scores (adjusted odds ratio [OR], 1.17; 95% CI, 1.02-1.33), underlying malignancy (adjusted OR, 4.70; 95% CI, 1.19-18.57), and cardiovascular organ dysfunction (adjusted OR, 5.14; 95% CI, 1.24-21.38) were more likely to die.The mortality rate of ICU readmission patients was high, especially for those with higher APACHE II score, underlying malignancy and cardiovascular organ dysfunction.

Background: Because specialty care accounts for half of Medicare expenditures, improving its value is critical to the success of Medicare accountable care organizations (ACOs) in curbing spending growth. However, whether ACOs have reduced low-value specialty care without compromising use of high-value services remains unknown., Methods and Results: Using national Medicare data, we identified 2 cohorts: beneficiaries for whom the value of coronary revascularization is lower (those with ischemic heart disease without angina, congestive heart failure, or recent admission for acute myocardial infarction) and beneficiaries for whom its value is higher (those with recent acute myocardial infarction admission). We then determined the provider groups who cared for the cohorts, distinguishing between those participating (n=298) and those not participating in a Medicare ACO (1329). After measuring the provider groups' use of coronary artery bypass grafting and percutaneous coronary intervention among the 2 cohorts, we fit multivariable models to test the statistical significance of rates of change in low- and high-value revascularization after ACO participation. During the pre-ACO period, participating and nonparticipating provider groups had similar rates of low- and high-value revascularization. Our multivariable model results show that rates of change for low- and high-value coronary revascularization were not altered by a provider group's participation in a Medicare ACO (lower value: difference, -0.04 per year; 95% confidence interval, -0.11 to 0.03; higher value: difference, 0.96 per year; 95% confidence interval, -0.46 to 2.4)., Conclusions: We found no association between provider group participation in a Medicare ACO and use of low- or high-value coronary revascularization., (© 2018 American Heart Association, Inc.)

Background: Postoperative myocardial injury (PMI) is a strong predictor of mortality after noncardiac surgery. PMI is believed to be attributable to coronary artery disease (CAD), yet its etiology is largely unclear. We aimed to quantify the prevalence of significant CAD in patients with and without PMI using coronary computed tomography angiography (CCTA)., Methods: This prospective cohort study included patients of 60 years or older without a history of cardiac disease and with and without PMI after intermediate- to high-risk noncardiac surgery. PMI was defined as any serum troponin I level ≥60 ng/L on the first 3 postoperative days. Main exclusion criteria were known cardiac disease and postoperative ischemic symptoms or electrocardiography abnormalities. Noninvasive imaging consisted of a postoperative CCTA. Main outcome was CAD defined as >50% coronary stenosis on CCTA., Results: The analysis included 66 patients. Median peak troponin levels in the PMI (n = 46) and control group (n = 20) were 150 (interquartile range, 120-298) vs 15 (interquartile range, 10-31) ng/L (P < .01). CAD was found in 23 patients with PMI (50%) vs 3 without PMI (15%; relative risk, 3.3; 95% confidence interval, 1.1-9.8). Remarkably, pulmonary embolism was present in 15 patients with PMI (33%) versus in 4 without PMI (20%; relative risk, 1.6; 95% confidence interval, 0.6-4.3). None of the patients died within 30 days., Conclusions: In patients without a history of cardiac disease, PMI after noncardiac surgery was associated with CAD. In addition, a clinically silent pulmonary embolism was found in one-third of patients with PMI. This urges further research to improve clinical workup using imaging and may have important clinical implications.

Background: Current guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study-based meta-analysis of published randomized controlled trials., Methods: A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis., Results: This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67-0.91; vascular death: HR, 0.85; 95% CI, 0.76-0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69-1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26-0.56)., Conclusions: This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy., (© 2017 American Heart Association, Inc.)

Background: Difficulty directly visualizing the coronary microvasculature as opposed to the epicardial coronary artery makes its assessment challenging. The goal of this study is to measure the index of microcirculatory resistance (IMR) in all 3 major coronary vessels to identify the clinical and angiographic predictors of an abnormal IMR., Methods and Results: Ninety-three patients who underwent coronary physiological assessment in all 3 major coronary vessels were prospectively enrolled (59.8±9.4 years with 77.4% men). IMR was corrected using Yong's formula and coronary microvascular dysfunction (CMD) was defined using vessel-specific cutoffs. A global IMR was calculated as the sum of the IMR in all 3 major epicardial vessels. Angiographic epicardial disease severity was assessed with vessel-specific and overall SYNTAX score. Median IMR and fractional flow reserve was 17.2 (Q1-Q3: 13.3-22.9) and 0.92 (0.85-0.97). The majority of patients (59.1%) had no CMD, 23.7% had 1-vessel CMD, 14.0% had 2-vessel CMD, and 3.2% had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery 28.0%, left circumflex artery 19.4%, and right coronary artery 23.7%; P =0.39). Fractional flow reserve had a weak, positive correlation with IMR (ρ=0.16; P <0.01). The SYNTAX score had no significant correlation with IMR, both at a patient level (ρ=-0.002; P =0.99) and a vessel-specific level (ρ=-0.06; P =0.36). By multivariable ordinal logistic regression analysis, no variable was left as an independent predictor of an abnormal IMR., Conclusions: Clinical factors and epicardial coronary disease severity are not predictors of the extent of CMD., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01621438., (© 2017 American Heart Association, Inc.)

Purpose of Review: The purpose of this review is to summarize and synthesize recent data on the risk of ischemic heart disease (IHD) in HIV-infected individuals., Recent Findings: Recent studies in the field demonstrate an increasing impact of cardiovascular disease (CVD) on morbidity and mortality in HIV relative to AIDS-related diagnoses. Studies continue to support an approximately 1.5 to two-fold increased risk of IHD conferred by HIV, with specific risk varying by sex and virologic/immunologic status. Risk factors include both traditional CVD risk factors and novel, HIV-specific factors including inflammation and immune activation. Specific antiretroviral therapy (ART) drugs may increase CVD risk, yet the net effect of ART with viral suppression is beneficial with regard to CVD risk. Management of cardiovascular risk and prevention of CVD is complex, because current general population strategies target traditional CVD risk factors only. Extensive investigation is being directed at developing tailored CVD risk prediction algorithms and interventions to reduce CVD risk in HIV., Summary: Increased IHD risk is a significant clinical and public health challenge in HIV. The development and application of HIV-specific interventions to manage CVD risk factors and reduce CVD risk will improve the long-term health of this ageing population.

Purpose of Review: To summarize recent findings in the pathogenesis of ischemic heart disease (IHD) in people living with HIV (PLWH)., Recent Findings: PLWH have an elevated risk of IHD. Although incidence is declining, this condition still represents a major cause of non-AIDS-related mortality. The cause is likely multifactorial: traditional risk factors play an important role and IHD risk might be reduced with greater emphasis on primary prevention. The contribution of specific antiretroviral agents to IHD risk is changing as antiretroviral coverage increases globally and as safer agents have replaced drugs with well-described metabolic toxicities. The beneficial impact of virological suppression on antiretroviral therapy (ART) in reducing IHD is particularly evident in participants with advanced HIV infection and high baseline cardiovascular risk. The association between current abacavir use and myocardial infarction is still unexplained and indicates that mechanisms other than metabolic alterations may underlie IHD in PLWH. Consequently, the contributions of inflammation, subclinical atherosclerosis and endothelial dysfunction are receiving greater attention., Summary: Modern ART coupled with intensified efforts towards primary prevention is the cornerstone of IHD risk management in PLWH. The role of chronic inflammation and its optimal management need to be defined.

Alcoholic beverages have been consumed for thousands of years, attracting great human interest for social, personal, and religious occasions. In addition, they have long been debated to confer cardioprotective benefits. The French Paradox is an observation of a low prevalence of ischemic heart disease, with high intakes of saturated fat, a phenomenon accredited to the consumption of red wine. Although many epidemiological investigations have supported this view, others have attributed it to beer or spirits, with many suggesting that the drink type is not important. Although excessive consumption of alcoholic beverages is commonly regarded to be detrimental to cardiovascular health, there is a debate as to whether light-to-moderate intake is cardioprotective. Although there is extensive epidemiological support for this drinking pattern, a consensus has not been reached. On the basis of published work, we describe the composition of wine and the effects of constituent polyphenols on chronic cardiovascular diseases., (© 2017 American Heart Association, Inc.)

Background: The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF <40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%-50%) and preserved EF (HFpEF; EF ≥50%) has been much less explored., Methods and Results: We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89-0.93] versus HFmrEF and risk ratio, 0.90 [0.88-0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84-0.95] versus HFmrEF and hazard ratio, 0.84 [0.80-0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time., Conclusions: HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types., (© 2017 American Heart Association, Inc.)

Background: Survivors of a myocardial infarction (MI) are at a considerable risk of developing further cardiovascular events, including recurrent MI, heart failure, stroke, and death. Patients with type 2 diabetes mellitus and stable ischemic heart disease (SIHD) have worse outcomes than their nondiabetic counterparts, and those with previous MI may be at particularly high risk. Yet, little is known about the effect of adding prompt revascularization to intensive medical therapy in this high-risk group., Patients and Methods: We carried out a post-hoc analysis of the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, which randomized patients with type 2 diabetes mellitus and SIHD to prompt revascularization with percutaneous coronary intervention or coronary artery bypass grafting in addition to intensive medical therapy or intensive medical therapy alone. Previous MI status was defined by a history of MI or pathologic Q-waves. The primary endpoints were death, nonfatal or fatal MI, nonfatal or fatal stroke, congestive heart failure, and a composite of death/MI/stroke., Results: Of the 2280 patients with evaluable data, 936 had previous MI. In these patients, there were no differences in the 5-year event-free rates of all-cause death, MI, stroke, congestive heart failure, or death/MI/stroke between those who were randomized to prompt revascularization in addition to intensive medical therapy and those who were randomized to intensive medical therapy alone., Conclusion: In diabetic patients with SIHD and previous MI, adding prompt revascularization to intensive medical therapy yielded no benefit compared with intensive medical therapy alone. These findings underscore the importance of intensive medical therapy in mitigating further ischemic events.

Objective: Mental stress-induced myocardial ischemia (MSIMI) is a common phenomenon in patients with coronary artery disease (CAD), but contemporary studies of its prognostic significance and its underlying pathophysiology are limited., Methods: We prospectively enrolled patients with confirmed CAD in the Mental Stress Ischemia Prognosis Study (MIPS) between 2011 and 2014. All patients underwent mental stress testing using a standardized public speaking task, and ischemia was detected by Tc-sestamibi myocardial perfusion imaging. Patients also underwent conventional stress testing for myocardial ischemia (CSIMI) using exercise or pharmacological stress testing. Furthermore, digital microvascular flow, endothelial function, arterial stiffness, and blood sample collections were performed before, during, and after mental stress. Two-year adverse clinical outcomes are being assessed., Results: Six-hundred ninety-five patients completed baseline enrollment in the MIPS. Their mean (standard deviation) age was 62.9 (9.1) years, 72% were men, 30% were African American, and 32% had a history myocardial infarction. The prevalence of MSIMI and CSIMI is 16.1% and 34.7%, respectively. A total of 151 patients (22.9%) had only CSIMI, 28 (4.2%) had only MSIMI, and 78 (11.8%) had both MSIMI and CSIMI. Patients with ischemia had a lower ejection fraction and higher prevalence of previous coronary artery bypass grafting compared with those without inducible ischemia (p < .050). The prevalence of obstructive CAD was not statistically different between patients with and without MSIMI (p = .426); in contrast, it was higher in patients with CSIMI (p < .001)., Conclusions: The MIPS data will provide useful information to assess the prognostic significance and underlying mechanisms of MSIMI.

Background: Continued reductions in morbidity and mortality attributable to ischemic heart disease (IHD) require an understanding of the changing epidemiology of this disease. We hypothesized that we could use genetic correlations, which quantify the shared genetic architectures of phenotype pairs and extant risk factors from a historical prospective study to define the risk profile of a contemporary IHD phenotype., Methods and Results: We used 37 phenotypes measured in the ARIC study (Atherosclerosis Risk in Communities; n=7716, European ancestry subjects) and clinical diagnoses from an electronic health record (EHR) data set (n=19 093). All subjects had genome-wide single-nucleotide polymorphism genotyping. We measured pairwise genetic correlations (rG) between the ARIC and EHR phenotypes using linear mixed models. The genetic correlation estimates between the ARIC risk factors and the EHR IHD were modestly linearly correlated with hazards ratio estimates for incident IHD in ARIC (Pearson correlation [r]=0.62), indicating that the 2 IHD phenotypes had differing risk profiles. For comparison, this correlation was 0.80 when comparing EHR and ARIC type 2 diabetes mellitus phenotypes. The EHR IHD phenotype was most strongly correlated with ARIC metabolic phenotypes, including total:high-density lipoprotein cholesterol ratio (rG=-0.44, P=0.005), high-density lipoprotein (rG=-0.48, P=0.005), systolic blood pressure (rG=0.44, P=0.02), and triglycerides (rG=0.38, P=0.02). EHR phenotypes related to type 2 diabetes mellitus, atherosclerotic, and hypertensive diseases were also genetically correlated with these ARIC risk factors., Conclusions: The EHR IHD risk profile differed from ARIC and indicates that treatment and prevention efforts in this population should target hypertensive and metabolic disease., (© 2016 American Heart Association, Inc.)

Previous studies have examined water quality and its association with all-cause and cardiovascular mortality. However, there is a lack of data regarding association between the amount of water consumption and risk of mortality. We used the third National Health and Nutrition Examination Survey (NHANES III) database and its subsequent follow-up data. Only patients older than 45 years who reported amount of average water consumption and for whom follow-up mortality data were available were included in the study. Patients were stratified into following groups of average daily raw water consumption: (1) no water consumption, (2) ≤2 cups, (3) >2 to ≤ 4 cups, (4) >4 to ≤6 cups, (5) >6 to ≤8 cups, and (6) ≥8 cups. End points studied were all-cause mortality, ischemia-related mortality, congestive heart failure-related mortality, and stroke-related mortality. Baseline characteristics were compared using t tests and Mann-Whitney U tests. Odds ratios, 95% confidence intervals, and P values were calculated for univariate analysis using >6 cups to ≤8 cups of water a day group as reference. Multivariate analysis was then performed adjusting for various factors. P values of less than 0.05 were considered statistically significant. A total of 7666 patients were ultimately included in the study. Multivariate analysis demonstrated no significant differences in all-cause, ischemia-related, heart failure-related, or stroke-related mortality among various raw water intake groups when compared with the reference group. The significance noted for all-cause mortality in >2 glasses to ≤4 glasses a day group in the univariate analysis was not seen with multivariate analysis (odds ratio: 0.747; 95% confidence interval: 0.437-1.276; P = 0.285). Daily raw water consumption does not seem to impact all-cause mortality or cause-specific cardiovascular mortality.

Aim: This survey study was performed to provide an overall picture on the incidence of symptoms, with or without typical angina, in the real-life clinical practice and to identify clinical factors associated with atypical presentations in an unselected population of consecutive outpatients with chronic coronary artery disease (CAD)., Methods: Thirty-six cardiology units located in different geographic areas of Italy enrolled a total of 1475 outpatients (73.6% men and 26.3% women; mean age 71 ± 10 and 67 ± 9 years in men and women, respectively) with a documented diagnosis of chronic CAD. Each patient underwent a medical history, with a detailed investigation as to the presence of typical angina or ischemic equivalents defined as sensation of chest pressure, or arm, neck, or jaw pain., Results: At admission, symptoms suggesting ischemic episodes were reported by 24.4% of patients. After an in-depth medical history collection by the specialist, the prevalence of combined typical or atypical myocardial ischemic episodes was ascertained in 39.3% of the overall population.Typical angina was reported by 13.6% of men and 22.7% of women (P < 0.0001), whereas ischemic equivalents were present in 7.3 and 12.9% of male and female patients, respectively (P < 0.001). Previous coronary artery bypass grafting (CABG; P < 0.001) and fewer medical visits by cardiologists (P = 0.02) were independent predictors of atypical presentations., Conclusion: The ISPICA study shows that in an Italian population of real-world patients with chronic CAD, ischemic episodes, with both typical and atypical presentation, are still present in nearly 50% of patients, despite optimal medical therapy, and that atypical presentations of angina are linked to fewer visits by specialists and previous CABG. These findings would suggest to encourage patients with chronic CAD and general practitioners to consider more frequent cardiology specialist visits and to take into account the possibility of atypical presentations, particularly in patients with previous CABG.

Objective: To assess the burden of mortality and hospitalized morbidity in newly treated epilepsy patients., Methods: We extracted relevant data of patients with newly treated epilepsy between September 16, 2005, and September 15, 2010, from the data repository covering all public hospitals in Hong Kong. Patients were followed up until September 15, 2011. Mortality and hospitalized morbidity were assessed, stratified by baseline comorbidities, number of antiepileptic drugs (AEDs) used, and treatment with enzyme-inducing AEDs (EIAEDs). Mortality was compared to the age- and sex-specific general population in Hong Kong., Results: Of the 7,461 newly treated epilepsy patients (55% male; median age 60 years), 2,166 (29%) died during the study period. The standardized mortality ratio was 5.09 (95% confidence interval [CI] 4.88-5.31), and was higher among those with physical or psychiatric baseline comorbidity (5.46; 95% CI 5.22-5.71) than those without (3.28; 95% CI 2.87-3.73). Standardized hospitalization ratio was 6.76 (95% CI 6.70-6.82). Baseline physical comorbidity-free patients (n = 3,514) exhibited higher risk of developing stroke (standardized incidence ratio [SIR] 4.96; 95% CI 4.19-5.84) and ischemic heart disease (SIR 4.18; 95% CI 3.54-4.91), and male patients had elevated risk of developing cancer (SIR 2.30; 95% CI 1.75-2.97). Patients treated with EIAEDs had higher risk of being subsequently recorded with new physical comorbidities than those with non-EIAEDs (relative risk [RR] 1.48; 95% CI 1.19-1.85), especially for cerebrovascular disease (RR 1.78; 95% CI 1.14-2.77)., Conclusions: Newly treated epilepsy patients bear excess mortality and hospitalization risks. They have higher risk of developing stroke, ischemic heart disease, and cancer. Treatment with EIAEDs was associated with increased overall morbidity., (© 2016 American Academy of Neurology.)

Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease., (© 2016 American Heart Association, Inc.)