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Previous studies have failed to show a cardioprotective benefit of beta-blockers in patients with stable coronary artery disease (CAD). This study sought to determine the association between beta-blockers and cardiovascular events in patients with stable CAD using a new user design. All patients aged >66 years undergoing elective coronary angiography in Ontario, Canada, from 2009 to 2019 with diagnosed obstructive CAD were included. Exclusion criteria included heart failure or a recent myocardial infarction, as well as having a beta-blocker prescription claim in the previous year. Beta-blocker use was defined as having at least 1 beta-blocker prescription claim in the 90 days preceding or after the index coronary angiography. The main outcome was a composite of all-cause mortality and hospitalization for heart failure or myocardial infarction. Inverse probability of treatment weighting using the propensity score was used to account for confounding. This study included 28,039 patients (mean age: 73.0 ± 5.6 years; 66.2% male), and 12,695 of those (45.3%) were newly prescribed beta-blockers. The 5-year risks of the primary outcome were 14.3% in the beta-blocker group and 16.1% in the no beta-blocker group (absolute risk reduction: −1.8%; 95% CI: −2.8 to −0.8; HR: 0.92; 95% CI: 0.86-0.98 ; P = 0.006). This result was driven by reductions in myocardial infarction hospitalization (cause-specific HR: 0.87; 95% CI: 0.77-0.99 ; P = 0.031), whereas no differences were observed in all-cause death or heart failure hospitalization. In patients with angiographically documented stable CAD without heart failure or a recent myocardial infarction, beta-blockers were associated with a small but significant reduction in cardiovascular events at 5 years. [Display omitted] [ABSTRACT FROM AUTHOR]

Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction. The goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction. The T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe. There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts. The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome [High-STEACS]; NCT01852123) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Understanding trends in cardiovascular (CV) risk factors and CV disease according to age, sex, race, and ethnicity is important for policy planning and public health interventions.Objectives: The goal of this study was to project the number of people with CV risk factors and disease and further explore sex, race, and ethnical disparities.Methods: The prevalence of CV risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) and CV disease (ischemic heart disease, heart failure, myocardial infarction, and stroke) according to age, sex, race, and ethnicity was estimated by using logistic regression models based on 2013-2018 National Health and Nutrition Examination Survey data and further combining them with 2020 U.S. Census projection counts for years 2025-2060.Results: By the year 2060, compared with the year 2025, the number of people with diabetes mellitus will increase by 39.3% (39.2 million [M] to 54.6M), hypertension by 27.2% (127.8M to 162.5M), dyslipidemia by 27.5% (98.6M to 125.7M), and obesity by 18.3% (106.3M to 125.7M). Concurrently, projected prevalence will similarly increase compared with 2025 for ischemic heart disease by 31.1% (21.9M to 28.7M), heart failure by 33.0% (9.7M to 12.9M), myocardial infarction by 30.1% (12.3M to 16.0M), and stroke by 34.3% (10.8M to 14.5M). Among White individuals, the prevalence of CV risk factors and disease is projected to decrease, whereas significant increases are projected in racial and ethnic minorities.Conclusions: Large future increases in CV risk factors and CV disease prevalence are projected, disproportionately affecting racial and ethnic minorities. Future health policies and public health efforts should take these results into account to provide quality, affordable, and accessible health care. [ABSTRACT FROM AUTHOR]

Ischemic heart disease (IHD) is a condition where the heart muscle does not receive enough blood flow, leading to cardiac dysfunction. Restoring blood flow to the coronary artery is an effective clinical therapy for myocardial ischemia. This strategy helps lower the size of the myocardial infarction and improves the prognosis of patients. Nevertheless, if the disrupted blood flow to the heart muscle is restored within a specific timeframe, it leads to more severe harm to the previously deprived heart tissue. This condition is referred to as myocardial ischemia/reperfusion injury (MIRI). Until now, there is a dearth of efficacious strategies to prevent and manage MIRI. Hormones are specialized substances that are produced directly into the circulation by endocrine organs or tissues in humans and animals, and they have particular effects on the body. Hormonal medications utilize human or animal hormones as their active components, encompassing sex hormones, adrenaline medications, thyroid hormone medications, and others. While several studies have examined the preventive properties of different endocrine hormones, such as estrogen and hormone analogs, on myocardial injury caused by ischemia-reperfusion, there are other hormone analogs whose mechanisms of action remain unexplained and whose safety cannot be assured. The current study is on hormones and hormone medications, elucidating the mechanism of hormone pharmaceuticals and emphasizing the cardioprotective effects of different endocrine hormones. It aims to provide guidance for the therapeutic use of drugs and offer direction for the examination of MIRI in clinical therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field. [Display omitted] • Ferroptosis is crucial in numerous cardiovascular diseases (CVDs). • Ferroptosis interacts with other cell death modes in CVDs. • Modulating iron, lipid metabolism, and antioxidants can inhibit ferroptosis in CVDs. • Ferroptosis inhibitor development brings new hope for CVD treatment. • Ferroptosis mechanisms in various CVDs must be further revealed. [ABSTRACT FROM AUTHOR]

Background: Elevated remnant cholesterol causes ischemic heart disease.Objectives: We tested the hypothesis that the inclusion of elevated remnant cholesterol will lead to appropriate reclassification of individuals who later experience myocardial infarction and ischemic heart disease.Methods: For >10 years we followed up 41,928 white Danish individuals from the Copenhagen General Population Study without a history of ischemic cardiovascular disease, diabetes, and statin use. Using predefined cut points for elevated remnant cholesterol, we calculated net reclassification index (NRI) from below to above 5%, 7.5%, and/or 10% 10-year occurrence of myocardial infarction and ischemic heart disease defined as a composite of death from ischemic heart disease, myocardial infarction, and coronary revascularization.Results: For individuals with remnant cholesterol levels ≥95th percentile (≥1.6 mmol/L, 61 mg/dL), 23% (P < 0.001) of myocardial infarction and 21% (P < 0.001) of ischemic heart disease were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Consequently, the addition of remnant cholesterol levels yielded NRI of 10% (95% CI: 1%-20%) for myocardial infarction and 5% (95% CI: -3% to 13%) for ischemic heart disease. Correspondingly, when reclassifications were combined from below to above 5%, 7.5%, and 10% risk of events, 42% (P < 0.001) of individuals with myocardial infarction and 41% (P < 0.001) with ischemic heart disease were reclassified appropriately, leading to NRI of respectively 20% (95% CI: 9%-31%) and 11% (95% CI: 2%-21%).Conclusions: Elevated remnant cholesterol levels considerably improve myocardial infarction and ischemic heart disease risk prediction. [ABSTRACT FROM AUTHOR]

Sodium glucose cotransporter-2 (SGLT2) inhibitors improve cardiorenal outcomes in patients with type 2 diabetes mellitus, chronic kidney disease, and chronic heart failure. SGLT2 inhibitors also reduce the risk of cardiovascular mortality and hospitalization for heart failure among patients with type 2 diabetes mellitus and a remote history of myocardial infarction (MI). As a result of the growing body of evidence in diverse disease states, and the hypothesized mechanisms of action, it is reasonable to consider the potential of SGLT2 inhibition to improve outcomes in patients with acute MI as well if initiated early after presentation. Whether these therapies are efficacious and safe to use early in the course of acute coronary heart disease remains relatively unexplored. Here, we describe the contemporary data and continuing evidence gap for considering the use of SGLT2 inhibitors early following an acute MI to reduce cardiovascular morbidity and mortality. [ABSTRACT FROM AUTHOR]

[Display omitted] • Type 2 diabetes (T2DM) increases the risk of recurrence in myocardial infarction patients. • A gut microbiota profile is associated to the further T2DM development. • Microbiome data improved the prediction of T2DM development when added to clinical parameters. • A risk score including the most predictive genera was associated with the probability of T2DM. • A high risk score was associated with a higher hepatic insulin resistance and β-cell dysfunction. A distinctive gut microbiome have been linked to type 2 diabetes mellitus (T2DM). We aimed to evaluate whether gut microbiota composition, in addition to clinical biomarkers, could improve the prediction of new incident cases of diabetes in patients with coronary heart disease. All the patients from the CORDIOPREV (Clinical Trials.gov.Identifier: NCT00924937) study without T2DM at baseline were included (n = 462). Overall, 107 patients developed it after a median of 60 months. The gut microbiota composition was determined by 16S rRNA gene sequencing and predictive models were created using hold-out method. A gut microbiota profile associated with T2DM development was determined through a microbiome-based predictive model. The addition of microbiome data to clinical parameters (variables included in FINDRISC risk score and the diabetes risk score of the American Diabetes Association, HDL, triglycerides and HbA1c) improved the prediction increasing the area under the curve from 0.632 to 0.946. Furthermore, a microbiome-based risk score including the ten most discriminant genera, was associated with the probability of develop T2DM. These results suggest that a microbiota profile is associated to the T2DM development. An integrate predictive model of microbiome and clinical data that can improve the prediction of T2DM is also proposed, if is validated in independent populations to prevent this disease. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is rarely reported in people with cystic fibrosis (PwCF) despite multiple potential risk factors. Here we report two cases of ST elevation myocardial infarction (STEMI), both in young women with cystic fibrosis (CF) and cystic fibrosis related diabetes (CFRD). These cases illustrate the importance of considering myocardial injury/infarction in the differential diagnosis of patients with CF and chest pain or shortness of breath, and addressing the growing risk of cardiovascular disease (CVD). [ABSTRACT FROM AUTHOR]

Background: Evidence regarding lignan consumption in relation to coronary heart disease (CHD) risk remains limited and mixed.Objectives: The aim of this study was to prospectively examine associations between lignan intake and CHD risk in U.S. men and women.Methods: We prospectively followed 214,108 men and women in 3 cohorts who did not have cardiovascular disease or cancer at baseline. Diet was repeatedly assessed using a validated food frequency questionnaire every 2-4 years since baseline.Results: During 5,517,225 person-years of follow-up, we documented 10,244 CHD cases, including 6,283 nonfatal myocardial infarction and 3,961 fatal CHD cases. In multivariable-adjusted analyses, comparing extreme quintiles, the pooled hazard ratios of CHD were 0.85 (95% CI: 0.79-0.92) for total lignans, 0.76 (95% CI: 0.71-0.82) for matairesinol, 0.87 (95% CI: 0.81-0.93) for secoisolariciresinol, 0.89 (95% CI: 0.83-0.95) for pinoresinol, and 0.89 (95% CI: 0.83-0.95) for lariciresinol (all P values for trend ≤0.003). Nonlinear relationships were found for total lignan, matairesinol, and secoisolariciresinol: the risk reduction plateaued at intakes above approximately 300 μg/d, 10 μg/d, and 100 μg/d, respectively (P < 0.01 for all nonlinearity). The inverse associations for total lignan intake appeared to be more apparent among participants with higher total fiber intake (P = 0.04 for interaction). In addition, lignan intake was more strongly associated with plasma concentrations of enterolactone when fiber intake was higher.Conclusions: Increased long-term intake of lignans was associated with a significantly lower risk of total CHD in both men and women. Possible synergistic effects may exist between lignan and fiber intake in relation to CHD risk reduction, possibly through enhancing the production of enterolignans. [ABSTRACT FROM AUTHOR]

ARIC (Atherosclerosis Risk In Communities) initiated community-based surveillance in 1987 for myocardial infarction and coronary heart disease (CHD) incidence and mortality and created a prospective cohort of 15,792 Black and White adults ages 45 to 64 years. The primary aims were to improve understanding of the decline in CHD mortality and identify determinants of subclinical atherosclerosis and CHD in Black and White middle-age adults. ARIC has examined areas including health disparities, genomics, heart failure, and prevention, producing more than 2,300 publications. Results have had strong clinical impact and demonstrate the importance of population-based research in the spectrum of biomedical research to improve health. [ABSTRACT FROM AUTHOR]

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Background: Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response.Objectives: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI.Methods: The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days.Results: We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups.Conclusions: Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703). [ABSTRACT FROM AUTHOR]

Background: Evidence from prospective studies has suggested that long working hours are associated with incident coronary heart disease (CHD) events. However, no previous study has examined whether long working hours are associated with an increased risk of recurrent CHD events among patients returning to work after a first myocardial infarction (MI).Objectives: The purpose of this study was to examine the effect of long working hours on the risk of recurrent CHD events.Methods: This is a prospective cohort study of 967 men and women age 35 to 59 years who returned to work after a first MI. Patients were recruited from 30 hospitals across the province of Quebec, Canada. The mean follow-up duration was 5.9 years. Long working hours were assessed on average 6 weeks after their return to work. Incident CHD events (fatal or nonfatal MI and unstable angina) occurring during follow-up were determined using patients' medical files. Hazard ratios were estimated using Cox proportional hazard regression models. Splines and fractional polynomial regressions were used for flexible exposure and time modeling.Results: Recurrent CHD events occurred among 205 patients. Participants working long hours (≥55 h/week) had a higher risk of recurrent CHD events after controlling for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors (hazard ratio vs. 35 to 40 h/week: 1.67; 95% confidence interval: 1.10 to 2.53). These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain.Conclusions: Among patients returning to work after a first MI, longer working hours per week is associated with an increased risk of recurrent CHD events. Secondary prevention interventions aiming to reduce the number of working hours among these patients may lower the risk of CHD recurrence. [ABSTRACT FROM AUTHOR]

Background: Phosphodiesterase 5 inhibitor (PDE5i) treatment is associated with reduced mortality compared with no treatment for erectile dysfunction after myocardial infarction (MI).Objectives: This study sought to investigate the association between treatment with PDE5i or alprostadil and outcomes in men with stable coronary artery disease.Methods: All Swedish men with a prior MI or revascularization who received PDE5i or alprostadil during 2006 through 2013 at >6 months after the event were included, using the Swedish Patient Register and the Swedish Prescribed Drug Register. Cox regression was used to estimate adjusted hazard ratios with 95% confidence intervals for all-cause mortality, MI, heart failure, cardiovascular mortality, noncardiovascular mortality, cardiac revascularization, peripheral arterial disease, and stroke in men treated with PDE5i versus alprostadil.Results: This study included 16,548 men treated with PDE5i and 1,994 treated with alprostadil. The mean follow-up was 5.8 years, with 2,261 deaths (14%) in the PDE5i group and 521 (26%) in the alprostadil group. PDE5i compared with alprostadil treatment was associated with lower mortality (hazard ratio: 0.88; 95% confidence interval: 0.79 to 0.98) and with similar associations for MI, heart failure, cardiovascular mortality, and revascularization. When quintiles (q) of filled PDE5i prescriptions were compared using q1 as reference, patients in q3, q4, and q5 had lower all-cause mortality. Among alprostadil users, those in q5 had a lower all-cause mortality compared to q1.Conclusions: In men with stable coronary artery disease, treatment with PDE5i is associated with lower risks of death, MI, heart failure, and revascularization compared with alprostadil treatment. Although the decrease in all-cause mortality was PDE5i dose dependent, the data do not permit the inference of causality or any clinical benefits of PDE5i because of the observational study design. [ABSTRACT FROM AUTHOR]

• This is the first Mendelian randomization analysis to comprehensively explore the causal relationship between cognitive impairment and cardiovascular disease. • Cognitive impairment may lead to an increased risk of atrial fibrillation, heart failure, hypertension, coronary heart disease, coronary atherosclerosis, and myocardial infarction, but not stroke. • In the reverse study, only hypertension and stroke may have contributed to the increased risk of cognitive impairment. • We validated our results with additional datasets to increase the credibility of our conclusions. • Neither heterogeneity nor pleiotropy were detected in this study. Growing evidence points to a connection between cardiovascular disease and cognitive impairment. These observational study findings, however, were not all uniform, and some did not discover a link like this. Investigating the causal link between cognitive impairment and cardiovascular disease is vital. Using publicly available genome-wide association study (GWAS) summary datasets and stringent screening instrumental variables, we carried out a bidirectional Mendelian randomization study. To investigate the causality between cardiovascular disease and cognitive impairment, three different MR techniques—inverse variance weighted (IVW), MR-Egger, and weighted median—as well as various sensitivity analyses—Cochran's Q, ivw_radial, leave-one-out (LOO), MR-Egger intercept, and MR-PRESSO—were used. The causal impact of genetically predicted cognitive performance on hypertension, atrial fibrillation, heart failure, coronary atherosclerosis, coronary artery disease, and myocardial infarction was detected in the forward MR analysis, but not stroke or any subtypes. We only discover the causal effects of hypertension, any stroke, and its subtypes (ischemic and small vessel stroke) on cognitive performance in the reverse MR analysis. This MR analysis offers proof of a causal link between cognitive impairment and elevated cardiovascular disease risk. Our research emphasizes the value of cognitively impaired patients being screened for cardiovascular disease, which may offer fresh perspectives on cardiovascular disease prevention. [ABSTRACT FROM AUTHOR]

Heart diseases are the primary cause of mortality and morbidity worldwide which inflict a heavy social and economic burden. Among heart diseases, most deaths are due to myocardial infarction (MI) or heart attack, which occurs when a decrement in blood flow to the heart causes injury to cardiac tissue. Despite several available diagnostic, therapeutic, and prognostic approaches, heart disease remains a significant concern. Exosomes are a kind of small extracellular vesicles released by different types of cells that play a part in intercellular communication by transferring bioactive molecules important in regenerative medicine. Many studies have reported the diagnostic, therapeutic, and prognostic role of exosomes in various heart diseases. Herein, we reviewed the roles of exosomes as new emerging agents in various types of heart diseases, including ischemic heart disease, cardiomyopathy, arrhythmia, and valvular disease, focusing on pathogenesis, therapeutic, diagnostic, and prognostic roles in different areas. We have also mentioned different routes of exosome delivery to target tissues, the effects of preconditioning and modification on exosome's capability, exosome production in compliance with good manufacturing practice (GMP), and their ongoing clinical applications in various medical contexts to shed light on possible clinical translation. [Display omitted] • Exosomes aid cardiac regeneration, beyond their intercellular communication function. • Exo-mi-RNAs induce cardiac regeneration by angiogenesis, anti-inflammation, and anti-apoptosis. • Exosomes can be injected intracardially, intraperitoneally, intravenously, or subcutaneously. • Ongoing clinical trials on exosomes in heart disease explore their biomarker and regenerative potential." [ABSTRACT FROM AUTHOR]

Background: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value.Objectives: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC).Methods: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease.Results: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD.Conclusions: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD. [ABSTRACT FROM AUTHOR]

Background: Sudden cardiac arrest is a serious complication of acute myocardial infarction (MI). Although in-hospital mortality from MI has decreased, the mortality of MI patients complicated with out-of-hospital cardiac arrest (OHCA) remains high. However, the features of acute MI patients with OHCA have not been well known.Objectives: We sought to characterize the clinical and angiographic features of acute MI patients with OHCA comparing with those without OHCA.Methods: We retrospectively analyzed 480 consecutive patients with acute MI undergoing percutaneous coronary intervention. Patients complicated with OHCA were compared with patients without OHCA.Results: Of the patients, 141 (29%) were complicated with OHCA. Multivariate analysis revealed that age (odds ratio [OR]: 0.8; 95% confidence interval [CI]: 0.7 to 0.9 per 5 years; p < 0.001), estimated glomerular filtration rate (OR: 0.8; 95% CI: 0.7 to 0.8 per 10 ml/min/1.73 m2; p < 0.001), peak creatine kinase-myocardial band (OR: 1.3; 95% CI: 1.2 to 1.4 per 102 U/l; p < 0.001), calcium-channel antagonists use (OR: 0.4; 95% CI: 0.2 to 0.7; p = 0.002), the culprit lesion at the left main coronary artery (OR: 5.3; 95% CI: 1.9 to 15.1; p = 0.002), and the presence of chronic total occlusion (OR: 2.9; 95% CI: 1.5 to 5.7; p = 0.001) were significantly associated with OHCA.Conclusions: Younger age, no use of calcium-channel antagonists, worse renal function, larger infarct size, culprit lesion in the left main coronary artery, and having chronic total occlusion were associated with OHCA. [ABSTRACT FROM AUTHOR]

Background: Varying definitions of procedural myocardial infarction (PMI) are in widespread use.Objectives: This study sought to determine the rates and clinical relevance of PMI using different definitions in patients with left main coronary artery disease randomized to percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) surgery in the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial.Methods: The pre-specified protocol definition of PMI (PMIProt) required a large elevation of creatine kinase-MB (CK-MB), with identical threshold for both procedures. The Third Universal Definition of MI (types 4a and 5) (PMIUD) required lesser biomarker elevations but with supporting evidence of myocardial ischemia, different after PCI and CABG. For the PMIUD, troponins were used preferentially (available in 49.5% of patients), CK-MB otherwise. The multivariable relationship between each PMI type and 5-year mortality was determined.Results: PMIProt occurred in 34 of 935 (3.6%) patients after PCI and 56 of 923 (6.1%) patients after CABG (difference -2.4%; 95% confidence interval [CI]: -4.4% to -0.5%; p = 0.015). The corresponding rates of PMIUD were 37 (4.0%) and 20 (2.2%), respectively (difference 1.8%; 95% CI: 0.2% to 3.4%; p = 0.025). Both PMIProt and PMIUD were associated with 5-year cardiovascular mortality (adjusted hazard ratio [HR]: 2.18 [95% CI: 1.13 to 4.23] and 2.87 [95% CI: 1.44 to 5.73], respectively). PMIProt was associated with a consistent hazard of cardiovascular mortality after both PCI and CABG (pinteraction = 0.86). Conversely, PMIUD was strongly associated with cardiovascular mortality after CABG (adjusted HR: 11.94; 95% CI: 4.84 to 29.47) but not after PCI (adjusted HR: 1.14; 95% CI: 0.35 to 3.67) (pinteraction = 0.004). Results were similar for all-cause mortality and with varying PMIUD biomarker definitions. Only large biomarker elevations (CK-MB ≥10× upper reference limit and troponin ≥70× upper reference limit) were associated with mortality.Conclusions: The rates of PMI after PCI and CABG vary greatly with different definitions. In the EXCEL trial, the pre-specified PMIProt was associated with similar hazard after PCI and CABG, whereas PMIUD was strongly associated with mortality after CABG but not after PCI. (EXCEL Clinical Trial [EXCEL]; NCT01205776). [ABSTRACT FROM AUTHOR]

The worldwide pandemic caused by the novel acute respiratory syndrome coronavirus 2 has resulted in a new and lethal disease termed coronavirus disease-2019 (COVID-19). Although there is an association between cardiovascular disease and COVID-19, the majority of patients who need cardiovascular care for the management of ischemic heart disease may not be infected with this novel coronavirus. The objective of this document is to provide recommendations for a systematic approach for the care of patients with an acute myocardial infarction (AMI) during the COVID-19 pandemic. There is a recognition of two major challenges in providing recommendations for AMI care in the COVID-19 era. Cardiovascular manifestations of COVID-19 are complex with patients presenting with AMI, myocarditis simulating an ST-elevation myocardial infarction (STEMI) presentation, stress cardiomyopathy, non-ischemic cardiomyopathy, coronary spasm, or nonspecific myocardial injury, and the prevalence of COVID-19 disease in the U.S. population remains unknown with risk of asymptomatic spread. This document addresses the care of these patients focusing on 1) the varied clinical presentations; 2) appropriate personal protection equipment (PPE) for health care workers; 3) role of the Emergency Department, Emergency Medical System and the Cardiac Catheterization Laboratory; and 4) Regional STEMI systems of care. During the COVID-19 pandemic, primary PCI remains the standard of care for STEMI patients at PCI capable hospitals when it can be provided in a timely fashion, with an expert team outfitted with PPE in a dedicated CCL room. A fibrinolysis-based strategy may be entertained at non-PCI capable referral hospitals or in specific situations where primary PCI cannot be executed or is not deemed the best option. [ABSTRACT FROM AUTHOR]

Background: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia.Objectives: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia.Methods: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE).Results: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE.Conclusions: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891). [ABSTRACT FROM AUTHOR]

Background: Food-based dietary guidelines recommend replacement of whole-fat dairy products with low-fat variants based on data suggesting that diets high in saturated fat are associated with a higher risk of ischemic heart disease. However, the health effects of saturated fat may depend on the source.Objectives: The aim was to investigate substitutions between different subgroups of dairy products and the risk of myocardial infarction (MI).Methods: Data were from the Danish Diet, Cancer and Health cohort and included 54,903 men and women aged 50-64 y at enrollment and without an MI diagnosis. Information about intake of dairy products was obtained by a semiquantitative food-frequency questionnaire. Incident MI cases were identified through nationwide registries. We used Cox proportional hazards regression to estimate associations between specified substitutions of dairy products and MI risk.Results: During a median follow-up of 15.9 y, 3033 cases were identified. Whole-fat yogurt products in place of low-fat or whole-fat milk were associated with a lower risk of MI (HR: 0.89; 95% CI: 0.80, 0.99 per 200 g/d replaced; and HR: 0.87; 95% CI: 0.78, 0.98 per 200 g/d replaced, respectively). Substitution of 20 g/d of cheese for 200 g/d of low-fat or whole-fat milk was also associated with a lower risk of MI (HR: 0.96; 95% CI: 0.92, 0.99; and HR: 0.95; 95% CI: 0.89, 0.99, respectively).Conclusions: Among middle-aged Danish men and women, intake of whole-fat yogurt products or cheese in place of milk, regardless of fat content, was associated with a lower risk of development of MI. [ABSTRACT FROM AUTHOR]

Background: Autopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes.Objectives: The purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents.Methods: In this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI4mm was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion-related, nonculprit (untreated) lesion-related, or indeterminate.Results: Among 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion-related, 10.7% were nonculprit lesion-related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion-related MACE was not significantly associated with maxLCBI4mm (hazard ratio of maxLCBI4mm per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors.Conclusions: Following PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid. [ABSTRACT FROM AUTHOR]

Background: Recurrent myocardial infarction (MI) is common in patients with coronary artery disease and is associated with high mortality. Long-term reprogramming of myeloid progenitors occurs in response to inflammatory stimuli and alters the organism's response to secondary inflammatory challenges.Objectives: This study examined the effect of recurrent MI on bone marrow response and cardiac inflammation.Methods: The investigators developed a surgical mouse model in which 2 subsequent MIs affected different left ventricular regions in the same mouse. Recurrent MI was induced by ligating the left circumflex artery followed by the left anterior descending coronary artery branch. The study characterized the resulting ischemia by whole-heart fluorescent coronary angiography after optical organ clearing and by cardiac magnetic resonance imaging.Results: A first MI-induced bone marrow "memory" via a circulating signal, reducing hematopoietic maintenance factor expression in bone marrow macrophages. This dampened the organism's reaction to subsequent events. Despite a similar extent of injury according to troponin levels, recurrent MI caused reduced emergency hematopoiesis and less leukocytosis than a first MI. Consequently, fewer leukocytes migrated to the ischemic myocardium. The hematopoietic response to lipopolysaccharide was also mitigated after a previous MI. The increase of white blood count in 28 patients was lower after recurrent MI compared with their first MI.Conclusions: The data suggested that hematopoietic and innate immune responses are shaped by a preceding MI. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C).Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE).Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina.Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081).Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402). [ABSTRACT FROM AUTHOR]

Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin–kexin type 9 inhibition in such patients is undetermined. This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: −2.4% to 6.2%), and 13.0% (95% CI: −2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: −0.1% to 1.0%), 1.3% (95% CI: −1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402) [ABSTRACT FROM AUTHOR]

Angiogenesis has been considered a pivotal strategy for treating ischemic heart disease. One possible approach, the Shexiang Baoxin Pill (MUSKARDIA), has been noted to promote angiogenesis, but its underlying mechanism is still largely unknown. We aimed to determine the effects of MUSKARDIA on acute myocardial infarction (AMI), as well as the underlying mechanistic bases. AMI was induced in rats, using left anterior descending coronary arterial occlusion, and either 6 (low) or 12 (high-dose) mg/kg/day of MUSKARDIA was administered for 56 days. We found that MUSKARDIA improved cardiac function and counteracted against adverse remodeling among AMI rats, which most likely is due to it promoting angiogenesis. Transcriptome analysis by RNA-sequencing found that MUSKARDIA up-regulated cardiac pro-angiogenic genes, particularly growth differentiation factor 15 (GDF15), which was confirmed by RT-qPCR. This up-regulation was also correlated with elevated serum GDF15 levels. In vitro analyses with human umbilical vein endothelial cells found that increased GDF15, stimulated by MUSKARDIA, resulted in enhanced cell migration, proliferation, and tubular formation, all of which were reversed after GDF15 knockdown using a lentiviral vector. Gene Ontology, as well as Kyoto Genes and Genomes enrichment analyses identified calcium signaling pathway as a major contributor to these outcomes, which was verified by Western blot and Cal-590 AM loading showing that transient receptor potential cation channel subfamily V member 4 protein (TRPV4) and intracellular Ca2+ levels increased in accordance with MUSKARDIA-induced GDF15 up-regulation, and decreased with GDF15 knock-down. Therefore, MUSKARDIA may exert its cardioprotective effects via stimulating the GDF15/TRPV4/calcium signaling/angiogenesis axis. [Display omitted] • MUSKARDIA exerts cardioprotective effects in acute myocardial infarction (AMI). • The underlying mechanism is the promotion of peri-infarct angiogenesis by MUSKARDIA. • MUSKARDIA up-regulates pro-angiogenic GDF15 and calcium ion channel TRPV4. • GDF15/TRPV4/calcium signal/angiogenesis axis underlies MUSKARDIA alleviating AMI. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that coronary heart disease (CHD) may be associated with accelerated cognitive decline. However, the temporal pattern of cognitive decline before and after incident CHD remains largely unknown.Objectives: The purpose of this study was to determine the cognitive trajectory before and after incident CHD diagnosis in a national representative cohort age ≥50 years.Methods: This study included 7,888 participants (mean age 62.1 ± 10.2 years) with no history of stroke or incident stroke during follow-up from the English Longitudinal Study of Ageing. Participants underwent a cognitive assessment at baseline (wave 1, 2002 to 2003), and at least 1 other time point (from wave 2 [2004 to 2005] to wave 8 [2016 to 2017]). Incident CHD was identified as a diagnosis of myocardial infarction and/or angina during follow-up.Results: Incident CHD was associated with accelerated cognitive decline during a median follow-up of 12 years. The annual rate of cognitive decline before CHD diagnosis among individuals who experienced incident CHD was similar to that of participants who remained CHD-free throughout follow-up. No short-term cognitive decline was observed in participants with CHD diagnosis after the event. In the years following CHD diagnosis, global cognition, verbal memory, and temporal orientation scores declined significantly faster than they did before the event, after multivariable adjustment. Sensitivity analyses yielded similar results.Conclusions: Incident CHD is associated with accelerated cognitive decline after, but not before, the event. Attention should be drawn to the long-term cognitive deterioration related to CHD. Careful monitoring of cognitive function is warranted in CHD patients in the years following the event. [ABSTRACT FROM AUTHOR]

Background: Preclinical studies have demonstrated that high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion (sonothrombolysis) can restore epicardial and microvascular flow in acute ST-segment elevation myocardial infarction (STEMI).Objectives: This study tested the clinical effectiveness of sonothrombolysis in patients with STEMI.Methods: Patients with their first STEMI were prospectively randomized to either diagnostic ultrasound-guided high MI impulses during an intravenous Definity (Lantheus Medical Imaging, North Billerica, Massachusetts) infusion before, and following, emergent percutaneous coronary intervention (PCI), or to a control group that received PCI only (n = 50 in each group). A reference first STEMI group (n = 203) who arrived outside the randomization window was also analyzed. Angiographic recanalization before PCI, ST-segment resolution, infarct size by magnetic resonance imaging, and systolic function (LVEF) at 6 months were compared.Results: ST-segment resolution occurred in 16 (32%) high MI PCI versus 2 (4%) PCI-only patients before PCI, and angiographic recanalization was 48% in high MI/PCI versus 20% in PCI only and 21% in the reference group (p < 0.001). Infarct size was reduced (29 ± 22 g high MI/PCI vs. 40 ± 20 g PCI only; p = 0.026). LVEF was not different between groups before treatment (44 ± 11% vs. 43 ± 10%), but increased immediately after PCI in the high MI/PCI group (p = 0.03), and remained higher at 6 months (p = 0.015). Need for implantable defibrillator (LVEF ≤30%) was reduced in the high MI/PCI group (5% vs. 18% PCI only; p = 0.045).Conclusions: Sonothrombolysis added to PCI improves recanalization rates and reduces infarct size, resulting in sustained improvements in systolic function after STEMI. (Therapeutic Use of Ultrasound in Acute Coronary Artery Disease; NCT02410330). [ABSTRACT FROM AUTHOR]

Punicalagin has been found to exert cardiac protective effects against myocardial ischemia/reperfusion (MI/R) injury, although the detailed mechanisms remain largely unknown. This experiment was performed to explore the potential involvement of silent information regulator 1 (SIRT1)-NFE2-related factor 2 (NRF-2)-heme oxygenase-1 (HO-1) pathway in the cardiac protective actions of punicalagin. Sprague-Dawley (SD) rats were subjected to MI/R operation with or without punicalagin treatment (40 mg kg−1d−1). We showed that punicalagin-treated group exhibited enhanced cardiac function, reduced myocardial infarction and decreased cleaved caspase-3 level. Furthermore, myocardial oxidative/nitrosative stress was ameliorated by punicalagin as evidenced by suppressed superoxide generation, gp91 phox and iNOS expressions, NO metabolites as well as myocardial nitrotyrosine level. Additionally, punicalagin decreased myocardial IL-6, TNF-α and the levels of ICAM-1, VCAM-1 and IKK-β expressions as well as IκB-α phosphorylation and NF-κB nuclear translocation. However, these effects were abolished by EX527 (5 mg kg−1d−1, a selective SIRT1 inhibitor). We further found that punicalagin dose-dependently enhanced SIRT1 nuclear distribution and NRF-2-HO-1 signaling. While EX527 treatment not only reduced SIRT1 activity, but also reversed the activation of NRF-2-HO-1 pathway. Collectively, these results revealed that punicalagin reduced cardiac oxidative/nitrosative stress and inflammatory response induced by MI/R operation through SIRT1-mediated activation of NRF-2-HO-1 signaling. Image 1 • Oral treatment with punicalagin reduces MI/R injury. • Punicalagin protects against oxidative/nitrosative stress and inflammatory response. • Activation of myocardial SIRT1-NRF-2-HO-1 signaling participates in this process. [ABSTRACT FROM AUTHOR]

Background: Few data exist on the contemporary profiles and outcomes of patients with significant aortic regurgitation (AR).Objectives: This study sought to assess the benefits of aortic valve repair or replacement (AVR) and the prognostic value of left ventricular (LV) dimensions in significant AR.Methods: From 2006 to 2017, consecutive patients with ≥moderate-severe chronic AR without prior heart surgery, myocardial infarction, or overt coronary artery disease were included.Results: Of 748 participants (58 ± 17 years of age; 82% men), 387 (52%) were medically treated, and 361 (48%) had AVR. Of 361 patients having AVR, 334 (93%) met guideline criteria: Class I indications in 284 (79%) patients, which included symptoms in 236, and Class II indications in 50 (14%). The remaining 27 (7%) opted for surgery without Class I or II indications. At a median follow-up of 4.9 years (interquartile range: 2.3 to 8.3 years), 125 (17%) patients had died. Age, comorbidities, baseline symptoms, and higher LV end-systolic dimension index (LVESDi) were associated with all-cause mortality (all p ≤ 0.01). Compared with patients having LVESDi <20 mm/m2, those with LVESDi 20 to 25 mm/m2 (hazard ratio: 1.53; 95% confidence interval: 1.01 to 2.31) and ≥25 mm/m2 (HR: 2.23; 95% confidence interval: 1.32 to 3.77) had increased risks of death. AVR was associated with better survival (p < 0.0001). Patients with Class I indications for surgery had inferior post-operative survival (p < 0.003).Conclusions: Class I indications for surgery, mainly symptoms, are the most common triggers for AVR. Class II indications were associated with better post-operative outcome and thus merit more attention. LVESDi was the only LV parameter independently associated with all-cause mortality and the ideal cutoff seems to be lower than previously recommended. [ABSTRACT FROM AUTHOR]

Abstract Purpose Few previous studies have investigated the association between urban green space and cardiovascular disease (CVD) within Asian populations. We aimed to determine the relationship between amount of green space in the residential environment and CVD within a large general Asian population in this population-based longitudinal study. Methods The study population consisted of 351,409 participants aged over 20 years extracted from the National Health Insurance Service National Sample Cohort. Data on newly-occurred CVD events were collected from hospital admission records for the period 1 January 2006 to 31 December 2013. Cox proportional hazards regression analysis was used for determining the risk of developing CVD according to urban green space coverage (% area), adjusting for a number of relevant confounders. Results Compared to those within the lowest quartile of green space coverage, those within the highest quartile of urban space had a reduced risk of total CVD (hazard ratio, HR 0.85, 95% confidence interval, CI 0.81–0.89), coronary heart disease (HR 0.83, 95% CI 0.78–0.89), acute myocardial infarction (HR 0.77, 95% CI 0.68–0.88), total stroke (HR 0.87, 95% CI 0.82–0.93) and ischemic stroke (HR 0.86, 95% CI 0.80–0.94), but not hemorrhagic stroke (HR 0.98, 95% CI 0.86–1.12). The risk-reducing effect of green space coverage was preserved after stratification according to sex, household income, and Charlson comorbidity index. Conclusion Residing in urban regions with greater green space coverage may lead to a reduced risk of CVD. Urban planning intervention policies that increase urban green space coverage could help to reduce the risk of CVD. Highlights • Those living in areas with greater amounts of green space found to have lower risk of CVD. • The association was preserved regardless of income and sex groups of participants. • Residing in urban regions with greater green space coverage may lead to reduced risk of CVD. [ABSTRACT FROM AUTHOR]

Abstract Objective This study is performed to investigate the effect of long chain noncoding RNA myocardial infarction associated transcript 1 (MIRT1) on myocardial ischemia reperfusion (I/R) injury in aged diabetic rats. Methods The aged diabetic rat model and myocardial I/R injury model were established. Through injecting MIRT1 siRNA into caudal vein of rats, the cardiac function, myocardial pathological injury, myocardial fibrosis, cardiomyocytes apoptosis, oxidative stress and inflammatory injury of myocardial tissue of rats were measured. Results For diabetic I/R rats, the expression of MIRT1 in myocardial tissue was increased, the activation of nuclear factor kappa B (NF-κB) signaling pathway was increased, the degree of damage to cardiac function was aggravated, the area of myocardial pathological injury and myocardial fibrosis was enlarged, the degree of cardiomyocytes apoptosis was increased, the degree of oxidative stress and inflammatory injury was increased. After inhibiting the expression of MIRT1, the activation of NF-κB signaling pathway was inhibited, the damage of cardiac function and cardiomyopathy was alleviated, the area of myocardial fibrosis was decreased, the degree of myocardial apoptosis was decreased, the degree of oxidative stress and inflammatory injury was obviously improved. Conclusion Our study highlights that down-regulation of MIRT1 improves myocardial I/R injury in aged diabetic rats by inhibition of activation of NF-κB signaling pathway. Highlights • High expression of MIRT1 in myocardial tissue of aged diabetic I/R rats. • Diabetes can induce increased cardiac function damage in aged I/R rats. • Inhibition of MIRT1 reduces myocardial I/R injury in aged diabetic I/R rats. • Inhibition of MIRT1 inhibits NF-κB signaling pathway in aged diabetic I/R rats. • MIRT1 regulates myocardial I/R injury in aged diabetic rats by NF-κB pathway. [ABSTRACT FROM AUTHOR]

Abstract Hyperglycemia-induced impairment of angiogenesis contributes to the unfavorable prognosis of myocardial ischemia in long-standing diabetes mellitus. The underlying mechanism remains largely unknown and therapeutic strategies thereby limited. In the present study, we investigated the possible involvement of thioredoxin-interacting protein (TXNIP) and Wnt/β-catenin signaling in the context, and their possible relation was also explored. STZ induced diabetic mice were subjected to myocardial infarction (MI). Adenovirus expressing shTXNIP, shCtnnb1 (β-catenin) driven by VE-Cadherin promoter was administered intramyocardially immediately after MI. Cardiac function, histology, and molecular analyses were performed at predetermined time points. Increased endothelial expression of TXNIP was found in diabetic hearts, which correlated well with reduced nuclear β-catenin expression, insufficient angiogenesis, aggravated cardiac remodeling, and poor survival. Endothelial-specific knockdown of TXNIP significantly rescued β-catenin activity, together with increased angiogenesis, preserved cardiac function, and improved survival rate. Moreover, additional knockdown of β-catenin essentially reversed the beneficial effects of TXNIP downregulation. In vitro, high glucose treatment of human umbilical vein endothelial cells (HUVECs) increased TXNIP levels and ROS concentration, while it reduced β-catenin activity. Silencing TXNIP or ROS scavenger restored the high glucose induced reduction of Wnt/β-catenin activity in HUVECs. In addition, either reduction of TXNIP expression or supplementation of exogenous Wnt3a improved the HUVECs quantity and migration under high glucose conditions. Diabetes-induced increase of TXNIP expression in the endothelium contributes to impaired angiogenesis after MI, especially via the elevation of ROS and the impaired Wnt/β-catenin signaling. Targeting TXNIP-ROS-Wnt is a promising strategy in improving the prognosis. Highlights • Diabetes induced TXNIP increase in ECs was shown to be the key reason for impaired angiogenesis after myocardial infarction. • Knockdown of TXNIP improved the angiogenesis and prognosis via restoration of Wnt/b-catenin signaling. • Either targeting endothelial TXNIP or Wnt would be therapeutic strategy for myocardial infarction in diabetic subjects. [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of the study was to investigate the role of estrogen receptor type 2 gene (ESR2) variant G1730A in myocardial infarction (MI) in young age. Methods Genotyping was performed with restriction fragments length polymorphism method in 158 patients (79.1% men) with MI aged <50 years (studied group) and in control groups: 150 healthy individuals aged <50 years (63.3% men) and 202 patients (64.3% men) with MI aged ≥50 years. Results The AA genotype of ESR2 G1730A variant was significantly more frequent in men with MI aged <50 comparing to men with MI aged ≥50 (21.6% vs. 8.4%, P = 0.004) and to healthy young men (21.6% vs. 11.6%, P = 0.048). There was statistically significant difference between AA genotype and GA + GG genotypes male carriers with MI aged <50 in median triglyceride (TG) level (2.0 vs. 1.7 mmol/l respectively, p = 0.023). Conclusions Our findings suggest a possible role of ESR2 G1730A variant as the risk factor of MI in a young age not as an independent but a potential risk factor associated with TG level in men but not in women. Highlights • The AA genotype of ESR2 G1730A variant was significantly more frequent in men with MI aged <50 comparing to men with MI aged ≥50 (21.6% vs. 8.4%, p = 0.004) and to healthy young men (21.6% vs. 11.6%, p = 0.048). • Median triglyceride level was significantly higher in AA than in GA + GG male carriers with MI aged <50. • Our findings suggest a possible role of ESR2 G1730A variant as the risk factor of MI in young age not as an independent but a potential risk factor associated with TG level in men but not in women. [ABSTRACT FROM AUTHOR]

Corresponding Author [ABSTRACT FROM AUTHOR]

Background: Coronary lesions with low fractional flow reserve (FFR) that are treated medically are associated with higher revascularization rates. High wall shear stress (WSS) has been linked with increased plaque vulnerability.Objectives: This study investigated the prognostic value of WSS measured in the proximal segments of lesions (WSSprox) to predict myocardial infarction (MI) in patients with stable coronary artery disease (CAD) and hemodynamically significant lesions. The authors hypothesized that in patients with low FFR and stable CAD, higher WSSprox would predict MI.Methods: Among 441 patients in the FAME II (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation II) trial with FFR ≤0.80 who were randomized to medical therapy alone, 34 (8%) had subsequent MI within 3 years. Patients with vessel-related MI and adequate angiograms for 3-dimensional reconstruction (n = 29) were propensity matched to a control group with no MI (n = 29) by using demographic and clinical variables. Coronary lesions were divided into proximal, middle, and distal, along with 5-mm upstream and downstream segments. WSS was calculated for each segment.Results: Median age was 62 years, and 46 (79%) were male. In the marginal Cox model, whereas lower FFR showed a trend (hazard ratio: 0.084; p = 0.064), higher WSSprox (hazard ratio: 1.234; p = 0.002, C-index = 0.65) predicted MI. Adding WSSprox to FFR resulted in a significant increase in global chi-square for predicting MI (p = 0.045), a net reclassification improvement of 0.69 (p = 0.005), and an integrated discrimination index of 0.11 (p = 0.010).Conclusions: In patients with stable CAD and hemodynamically significant lesions, higher WSS in the proximal segments of atherosclerotic lesions is predictive of MI and has incremental prognostic value over FFR. [ABSTRACT FROM AUTHOR]

Background: Hypertensive disorders of pregnancy (HDP) affect 10% to 15% of women and are associated with a 2-fold increased risk of cardiovascular disease (CVD).Objectives: This study sought to determine whether inclusion of HDP in an established CVD risk score improves prediction of CVD events in women.Methods: The analysis comprised 106,230 ≤10-year observations contributed by 67,406 women, age ≥40 years, free of prior CVD, with data available on model covariates in the Nurses' Health Study II. Participants were followed up for confirmed myocardial infarction, fatal coronary heart disease, or stroke from 1989 to 2013. We fit an established CVD risk prediction model (Model A: age, total cholesterol and high-density lipoprotein cholesterol, systolic blood pressure, antihypertensive medication use, current smoking, diabetes mellitus) and compared it to the same model plus HDP and parity (Model B); Cox proportional hazards models were used to obtain predicted probabilities for 10-year CVD risk.Results: HDP and parity were associated with 10-year CVD risk independent of established CVD risk factors, overall and at ages 40 to 49 years. However, inclusion of HDP and parity in the risk prediction model did not improve discrimination (Model A: C-index = 0.691; Model B: C-index = 0.693; p value for difference = 0.31) or risk reclassification (net reclassification improvement = 0.4%; 95% confidence interval: -0.2 to 1.0%; p = 0.26).Conclusions: In this first test of the clinical utility of HDP and parity in CVD risk prediction, additional inclusion of HDP and parity in an established risk score did not improve discrimination or reclassification in this low-risk population; this might be because of the known associations between HDP and established CVD risk factors in the reference model. [ABSTRACT FROM AUTHOR]

Background: In patients with coronary artery disease (CAD), low diastolic blood pressure (DBP) is associated with increased risk of myocardial infarction, but its association with angina is unknown.Objectives: The goal of this study was to examine the association of low DBP and angina in patients with CAD.Methods: The study assessed the frequency of angina (measured by using the Seattle Angina Questionnaire-Angina Frequency score) according to DBP in patients with known CAD from 25 U.S. cardiology clinics. Hierarchical logistic regression was used to test the association between DBP and angina, with a spline term for DBP to assess nonlinearity.Results: Among 1,259 outpatients with CAD, 411 (33%) reported angina in the prior month, with higher rates in the lowest DBP quartile (40 to 64 mm Hg: 37%). In the unadjusted model, DBP was associated with angina with a J-shaped relationship (p = 0.017, p for nonlinearity = 0.027), with a progressive increase in odds of angina as DBP decreased below ∼70 to 80 mm Hg. This association remained significant after sequential adjustment for demographic characteristics (p = 0.002), comorbidities (p = 0.002), heart rate (p = 0.002), systolic blood pressure (p = 0.046), and antihypertensive antianginal medications (p = 0.045).Conclusions: In patients with chronic CAD, there seemed to be an association between lower DBP and increased odds of angina. If validated, these findings suggest that clinicians should consider less aggressive blood pressure control in patients with CAD and angina. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) is the leading cause of deaths worldwide, triggering widespread and irreversible damage to the heart. Currently, there are no drugs that can reverse ischemic damage to the myocardium and hence, finding novel therapeutic agents that can limit the extent of myocardial damage following MI is crucial. Liensinine (LSN) is a naturally derived bisbenzylisoquinoline alkaloid that is known to exhibit numerous antioxidative and cardiovascular beneficial effects. However, the role of LSN in MI-induced injury and its underlying mechanisms remain unexplored. Our study aims to evaluate the cardioprotective effects of LSN following MI and its underlying molecular mechanisms. We constructed murine models of MI in order to examine the potential cardioprotective effects and mechanisms of LSN in protecting against myocardial ischemic damage both in vivo and in vitro. Administration with LSN strongly protected against cardiac injuries following MI by decreasing the extent of ischemic damage and improving cardiac function. Additionally, LSN was found to be a potent inhibitor of Wnt/β‑catenin signaling pathway. Hence, the beneficial effects of LSN in preventing oxidative and DNA damage following ischemia was due to its ability to inhibit aberrant activation of Wnt/β‑catenin signaling. Our findings reveal for the first time a novel cardioprotective role of LSN during myocardial infarction and most notably, its ability to protect cardiomyocytes against oxidative stress-induced damage via inhibiting Wnt/β-catenin signaling. Our study therefore suggests new therapeutic potential of LSN or plants that contain the natural alkaloid LSN in ischemic heart diseases. [Display omitted] • Liensinine is a natural alkaloid that exhibits strong cardioprotective effects. • Liensinine robustly protects against ischemic injury after myocardial infarction. • Liensinine attenuates ischemia-induced oxidative and DNA damage. • Cardioprotective effects of Liensinine is via inhibiting Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]