Opium as a risk factor for early-onset coronary artery disease: Results from the Milano-Iran (MIran) study.

The spreading of opium use poses new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between non-medical opium use and CAD. We set up a case-control analysis, i.e., the Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2004 and 2011. Incident cases with CAD were contrasted with controls for opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4-6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9-31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that non-medical opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.

Factor V Leiden but not the factor II 20210G>A mutation is a risk factor for premature coronary artery disease: a case-control study in Iran.

Background: Factor V Leiden (FVL) and factor II c.∗97G>A (rs1799963) are genetic risk factors for venous thromboembolism. Their contribution to coronary artery disease (CAD) is less clear. Objectives: This study aimed to investigate the association between FVL, rs1799963, and premature CAD in Iranians. Methods: We performed a genetic case-control study of 944 cases and 1081 controls from the premature CAD Milano-Iran study, including patients aged 18-55 (female) and 18-45 years (male) who underwent coronary angiography at the Tehran Heart Centre (Iran) in 2004-2011. Cases had luminal stenosis ≥50% in at least 1 main coronary artery or branch. Controls were age- and sex-matched with no CAD history. FVL and rs1799963 were genotyped using TaqMan SNP genotyping assays. Association was tested by logistic regression adjusted for matching factors and ethnicity. Effect modification by sex and cardiovascular risk factors (metabolic [obesity, hypertension, hyperlipidemia, and diabetes], and smoking) was assessed. Results: The risk of premature CAD was increased by 50% in FVL carriers (adjusted odds ratio [adjOR] 1.54 [95% CI, 0.95-2.48]) and slightly reduced in rs1799963 carriers (adjOR 0.71 [95% CI, 0.40-1.27]). These effects were more pronounced in women than men (FVL, adjOR 1.66 vs 1.25; rs1799963, adjOR 0.60 vs 1.07). The risk of premature CAD was substantially increased in carriers of FVL with at least 1 metabolic risk factor compared with noncarriers without metabolic risk factors (adjOR 25.14 [95% CI, 12.51-50.52]). Conclusion: FVL but not FII rs1799963 was associated with an increased risk of CAD in young Iranians. This risk increased considerably when combined with metabolic cardiovascular risk factors.

Mortality from Acute Coronary Syndrome: Does Place of Residence Matter?

Background : Current evidence shows inequality in the outcomes of rural and urban patients treated at their place of residence. This study compared in-hospital mortality between rural and urban patients with acute coronary syndrome (ACS) to find whether there were differences in the outcome and received treatment. Methods : Between May 2007 and January 2018, patients admitted with ACS were included. The patients' demographic, clinical, and laboratory data, as well as their in-hospital medical courses, were recorded. The association between place of residence (rural/urban) and in-hospital mortality due to ACS was evaluated using logistic regression adjusted for potential confounders. Results: Of 9088 recruited patients (mean age =61.30±12.25 y; 5557 men [61.1%]), 838 were rural residents. A positive family history of coronary artery disease (P=0.003), smoking (P=0.002), and hyperlipidemia (P=0.026), as well as a higher body mass index (P=0.013), was seen more frequently in the urban patients, while the rural patients had lower education levels (P<0.001) and higher unemployment rates (P=0.009). In-hospital mortality occurred in 135 patients (1.5%): 10 rural (1.2%) and 125 urban (1.5%) patients (P=0.465). The Firth regression model, used to adjust the effects of possible confounders, showed no significant difference concerning in-hospital mortality between the rural and urban patients (OR, 1.57; 95% CI, 0.376 to 7.450; P=0.585). Conclusion : This study found no significant differences in receiving proper treatment and in-hospital mortality between rural and urban patients with ACS.

Combined Aortic and Mitral Valve Stenosis in Mucopolysaccharidosis Syndrome Type I-S: A Report of a Rare Case.

Mucopolysaccharidosis (MPS) syndrome is an inherited metabolic disorder. In more than half of the patients with MPS syndrome, heart valve involvement is reported; however, combined aortic and mitral valve stenosis in MPS syndrome type I-S is very rare. We describe a 39-year-old man with severe mitral and aortic valve stenosis due to MPS syndrome type I-S. Transthoracic and transesophageal echocardiography revealed severe thickening and calcification in the aortic and mitral valves with severe left ventricular hypertrophy. The coronary arteries were normal in angiography.

Predictive Inflammation-related microRNAs for Cardiovascular Events Following Early-Onset Coronary Artery Disease.

BACKGROUND: Early-onset coronary artery disease (EOCAD) increases the risk of major cardiac adverse events (MACE) at the level of safety/effectiveness-related events. Since adverse events affect the quality of life of young patients with EOCAD, MACE prediction is of great importance for improving medical decision-making. AIMS OF THE STUDY: We sought to determine whether the most important inflammation-related microRNAs in atherogenesis could predict MACE among patients with EOCAD. METHODS: This nested case-control study recruited 143 young patients (males ≤45 and females ≤55 years old), selected from a cohort of patients with premature coronary atherosclerosis at a median follow-up period of 64.1 months. Total RNAs were extracted from their peripheral blood mononuclear cells. The expression levels of 18 miRNAs, which are involved in inflammation and atherogenesis, were analyzed via quantitative reverse transcription PCR. RESULTS: A scoring model based on the upregulation of miR-146a_1 and miR-342_1, along with a history of myocardial infarction and the chronic usage of antithrombotic drugs, was able to predict MI/death at the level of safety-related events (higher vs lower risk scores: sHR: 4.61, 95% CI: 1.57-13.57, and p = 0.005). Another prediction model based on the downregulation of miR-145_1, age, and a history of unstable angina was also able to predict revascularization at the level of effectiveness-related events (higher vs lower risk scores: sHR: 2.90, 95% CI: 1.49-5.66, and p = 0.002). CONCLUSIONS: Our results highlighted the role of miRNAs in adverse cardiac events and suggest that miR-146a_1, miR-342_1, and miR-145_1 may be useful biomarkers in predictive and preventive cardiology.

Relationship between the Severity of Coronary Artery Disease and Cardiovascular Risk Factors in Acute Coronary Syndrome: Based on Tehran Heart Center's Data Registry.

BACKGROUND: Acute coronary syndrome (ACS) is one of the main causes of mortality worldwide. We sought to evaluate the correlation between the severity of coronary artery disease (CAD) and conventional coronary artery risk factors in a large cohort of patients with ACS. METHODS: This study included all patients admitted to the coronary care unit with a diagnosis of ACS between 2003 and 2017. The patients were divided into 2 groups: 1) unstable angina and 2) myocardial infarction. The aims of this study were to evaluate the effects of the risk factors and extension of coronary artery stenosis in patients with ACS according to the Gensini score. RESULTS: Of a total 40 319 patients who presented with ACS, 18 862 patients (mean age =60.4±11.14 y, male: 67.2%) underwent conventional coronary angiography and met our criteria to enter the final analysis. The median of the Gensini score was 50 (25-88) in the study population. The multivariable analysis showed that age, sex, diabetes mellitus, hypertension, dyslipidemia, family history, cigarette smoking, opium consumption, and myocardial infarction increased the risk of positive Gensini scores. All the aforementioned risk factors, except cigarette smoking and opium consumption, increased the severity of stenosis in those with positive Gensini scores. The strongest relationship was seen vis-à-vis myocardial infarction, sex, and diabetes mellitus. CONCLUSION: Our findings suggest that age, sex, diabetes mellitus, dyslipidemia, hypertension, family history, and myocardial infarction have significant effects on the severity of CAD. The obesity paradox in relation to CAD should be taken into consideration and needs further investigation in patients with ACS.

Nanoscale Technologies for Prevention and Treatment of Heart Failure: Challenges and Opportunities.

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.

Association between illness perception and health-related quality of life in patients with preexisting premature coronary artery disease.

OBJECTIVES: Illness perception in younger age differs from that in older age. We aimed to examine the association between illness perception and health-related quality of life (HRQoL) in patients with premature coronary artery disease (CAD). METHODS: In a cross-sectional design, between November 2016 and September 2017, a total of 779 adults (52.5% female) with premature CAD (diagnosed in men aged ≤ 45 y and women aged ≤ 55 y) completed the Beck Depression Inventory-II, the Beck Anxiety Inventory, the Brief Illness Perception, and the Short-Form Health Survey 36 questionnaires in an outpatient clinic 8 years after the diagnosis. RESULTS: The patients were treated with coronary artery bypass graft surgery (24.6%), percutaneous coronary intervention (39.5%), and medical treatment (35.8%). The cognitive, emotional, and comprehension aspects of illness perception had significant associations with both physical and mental health in univariable analysis (all Ps < 0.001). After adjustments for potential confounding factors, higher cognitive perception was independently associated with greater physical health [OR = 4.13, Confidence interval (CI): 3.53-4.72] and mental health (OR = 3.17, CI: 2.57-3.77). Additionally, emotional perception was also directly associated with higher physical (OR = 1.62, CI: 1.17-2.06) and mental (OR = 1.52, CI: 1.07-1.96) health; all Ps < 0.001. CONCLUSIONS: Of the 3 different aspects of illness perception, cognitive perception appeared to have the greatest influence on HRQoL, either physical or mental health. Further studies are needed to investigate whether cognitive interventions can improve HRQoL in premature CAD patients and, thus, their outcome.

Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial.

BACKGROUND: Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS: We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 µmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS: Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION: Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388.

Illness Perceptions in Patients with Premature Coronary Artery Disease: A Sex-Based Analysis 8 Years After the Diagnosis.

To assess illness perceptions in patients with premature atherosclerotic coronary artery disease (CAD), 717 adults with premature CAD (diagnosis of CAD in men age < 45 years and women age < 55 years) completed sociodemographic indices, the Beck's Depression Inventory-II, Beck Anxiety Inventory and the Brief Illness Perceptions 8 years after the diagnosis. Mean age was 49.59 ± 3.57 years for men and 57.72 ± 4.90 years for women at the time of study. Both sexes were treated through coronary artery bypass graft surgery, percutaneous coronary intervention, or medical treatment. Depressive and anxiety symptoms were significantly more prevalent among women. Generally, the patients believed that their disease was chronic and well controlled and that it had no considerable negative impact on their routine life. Overall, patients had a low concern about their illness. Women had a more negative perception of their disease than did men which may indicate their need for higher psychological support.

Novel Scoring System for Prediction of Cardiac Syndrome X in Women with Typical Angina and a Positive Exercise Tolerance Test.

A major diagnostic challenge for cardiologists is to distinguish cardiac syndrome X (CSX) from obstructive coronary artery disease in women with typical angina and a positive exercise tolerance test (ETT). We performed this study to develop a scoring system that more accurately predicts CSX in this patient population. Data on 976 women with typical angina and a positive ETT who underwent coronary angiography at our center were randomly divided into derivation and validation datasets. We developed a backward stepwise logistic regression model that predicted the presence of CSX, and a scoring system was derived from it. The derivation dataset (809 patients) was calibrated by uing a Hosmer-Lemeshow goodness-of-fit test (8 degrees of freedom; χ2=12.9; P=0.115), and the area under the curve was 0.758. The validation dataset (167 patients) was calibrated in the same way (8 degrees of freedom; χ2=9.0; P=0.339), and the area under the curve was 0.782. Independent predictors of CSX were age <55 years; negative histories of smoking, diabetes mellitus, hyperlipidemia, hypertension, or familial premature coronary artery disease; and highly positive ETTs. A total score >9.5 was the optimal cutoff point for differentiating CSX from obstructive coronary artery disease. Our proposed scoring system is a simple, objective, and accurate system for distinguishing CSX from obstructive coronary artery disease in women with typical angina and positive ETTs. It may help determine which of these patients need invasive coronary angiograms or noninvasive tests like computed tomographic coronary angiography.

Ethnic Differences in the Risk Factors and Severity of Coronary Artery Disease: a Patient-Based Study in Iran.

BACKGROUND: Diverse ethnic groups may differ regarding the risk factors and severity of coronary artery disease (CAD). This study sought to assess the association between ethnicity and CAD risk and severity in six major Iranian ethnic groups. METHODS: In this study, 20,165 documented coronary artery disease patients who underwent coronary angiography at a tertiary referral heart center were recruited. The demographic, laboratory, clinical, and risk factor data of all the patients were retrieved. The Gensini score (an indicator of CAD severity) was calculated for all, and the risk factors and severity of CAD were compared between the ethnical groups, using adjusted standardized residuals, Kruskal-Wallis test, and multivariable regression analysis. RESULTS: The mean age of the participants (14,131 [70.1%] men and 6034 [29.9%] women) was 60.7 ± 10.8 years. The Fars (8.7%) and Gilak (8.6%) ethnic groups had the highest prevalence of ≥4 simultaneous risk factors. The mean Gensini score was the highest for the Gilaks (77.1 ± 55.9) and the lowest among the Lors (67.5 ± 52.8). The multivariable regression analysis showed that the Gilaks had the worst severity (ß 0.056, 95% CI 0.009 to 0.102; P = 0.018), followed by the Torks (ß 0.032, 95% CI 0.005 to 0.059; P = 0.020). Meanwhile, the Lors showed the lowest severity (ß -0.087, 95% CI -0.146 to -0.027; P = 0.004). CONCLUSIONS: This study found that there was heterogeneity in CAD severity and a diverse distribution in its well-known traditional risk factors among major Iranian ethnic groups.

Effects of Saffron on Cognition, Anxiety, and Depression in Patients Undergoing Coronary Artery Bypass Grafting: A Randomized Double-Blind Placebo-Controlled Trial.

OBJECTIVES: Cognitive decline, depression, and anxiety are among the major concerns in patients undergoing coronary artery bypass grafting (CABG). Crocus sativus L. (saffron) seems to be a promising candidate for treatment of these conditions. DESIGN: In this 12-week, randomized, double-blind, placebo-controlled clinical trial, men and women with on-pump CABG, who had Wechsler Memory Scale (WMS) score >70 and age <70 years, received either saffron capsules (15 mg/twice daily) or placebo. Patients were excluded if they had history of treatment with saffron or acetylcholinesterase inhibitors, comorbid neuropsychiatric disorders, serious medical conditions other than cardiovascular diseases, and hypersensitivity to herbal compounds. The primary outcome was defined as the difference in mean total score changes for WMS-Revised from the baseline to week 12 between the saffron and placebo groups. Secondary outcomes included difference in mean score changes from baseline to endpoint between the two treatment groups for Mini Mental Status Examination and subscales of Hospital Anxiety and Depression Scale ( www.irct.ir ; IRCT201408071556N63). RESULTS: No significant difference was detected in primary or secondary outcomes between the saffron and placebo groups. Also, no significant time × treatment interaction effect was found for any of the scales. CONCLUSIONS: The results of this trial do not support the hypothesis of potential benefits of saffron in treatment of CABG-related neuropsychiatric conditions.

C1019T Polymorphism in the Connexin 37 Gene and Myocardial Infarction Risk in Premature Coronary Artery Disease.

Background: The C1019T polymorphism of the connexin-37 (GJA4) gene is a single-nucleotide polymorphisms involved in atherosclerotic plaque rupture and atherosclerosis predisposition. We examined the association between the C1019T polymorphism of the GJA4 gene and the occurrence of myocardial infarction (MI) in patients with premature coronary artery disease (CAD). Methods: Our study recruited 1000 patients with the final diagnosis of premature CAD and classified them into 2 groups: with a history of MI (n = 461) and without it (n = 539). The polymorphism variants were determined via the PCR-RFLP, and then genotyping was conducted through the high-resolution melting method. From a total of 1000 patients, 554 patients, who had been previously followed-up with a median follow-up time of 45.74 months vis-à-vis long-term major adverse cardiac events, were enrolled in this retrospective cohort phase. Results: The frequencies of the wild, heterozygous, and mutant genotypes of the C1019T polymorphism were 54.0%, 40.6%, and 5.4% in the MI group and 49.2%, 43.2%, and 7.6% in the non-MI group (p value = 0.187). After adjustment for the baseline covariates, no difference was found between the MI and non-MI groups apropos the frequency of the heterozygous genotype (p value = 0.625) and the mutant genotype (p value = 0.452). Regarding the level of human connexin-37, the serum level of this marker was not different between the MI and non-MI groups. Conclusion: The C1019T polymorphism of the GJA4 gene may not be useful for predicting the occurrence of MI in patients with premature CAD. The presence of this polymorphism in such patients may also have a low value for predicting long-term CAD complications.

Factors Associated with Anxiety in Premature Coronary Artery Disease Patients: THC-PAC Study.

Anxiety may negatively affect the course of coronary artery disease (CAD). The aim of this study was to assess which factors are associated with anxiety in young adults with CAD. A cohort of individuals with premature coronary artery disease was formed between 2004-2011, as the Tehran Heart Center's Premature Coronary Atherosclerosis Cohort (THC-PAC) study. Patients (men≤45-year-old, and women≤55-year-old) were visited between March 2013 and February 2014. All participants were examined, and their demographic, clinical, and laboratory data were collected. Then, all participants filled in the Beck Anxiety Inventory. Logistic regression models were used to identifying factors related to anxiety in both sexes. During the study, 708 patients (mean [SD] age: 45.3 [5.8] y, men:48.2%) were visited. Anxiety was present in 53.0% of participants (66.0% of women and 39.0% of men). The logistic regressions model showed that the associated factors for anxiety in men were opium usage (OR=1.89, 95% CI: 1.09-3.27), positive family history (OR=1.49, 95% CI:0.94-2.35), and creatinine serum level (OR=1.17, 95% CI:1.05-1.303); and in women were major adverse cardiac events (MACE) during follow-up (OR=2.30, 95% CI:1.25-4.23), hypertension (OR=1.71, 95% CI:1.07-2.73) and the duration of CAD (OR=0.99, 95% CI:0.98-1.00). In premature CAD patients, the determinants of anxiety seem to be different in each sex. Opium usage, positive family history of CAD, and creatinine serum levels in men, and MACE, hypertension, and duration of CAD in women appear the relevant factors in this regard.

Factors Associated with Depressive Symptoms in Young Adults with Coronary Artery Disease: Tehran Heart Center's Premature Coronary Atherosclerosis Cohort (THC-PAC) Study.

Objective: Depressed coronary artery disease (CAD) patients may experience a poorer prognosis than non-depressed patients. The aim of this study was to find the associated factors for depressive symptoms in young adults with CAD. Method: This was a cross-sectional study within Tehran Heart Center's Premature Coronary Atherosclerosis Cohort (THC-PAC) study. Young adult CAD patients (men ≤ 45 year-old and women ≤ 55 year-old) were visited from March 2013 to February 2014. Demographic, clinical and laboratory data were collected and all patients were asked to fill in the Beck Depression Inventory II. Informed consent was obtained from all participants. A logistic regression model was used to find multiple associated factors of depressive symptoms. Results: Seven hundred seventy patients (mean ±SD age: 45.34 ±5.75 y, men: 47.7%) were visited. The point prevalence of depressive symptoms was 46.9% in women and 30.2% in men (p < 0.001). Logistic regressions model revealed that the most important associated factors for depressive symptoms in the male premature CAD patients were opium usage (OR: 2.4, 95% CI: 1.33-4.43), major adverse cardiac events (MACE) (OR: 2.2, 95% CI: 1.17-3.93), initial coronary artery bypass grafting (CABG) treatment (OR: 2.1, 95% CI: 1.07-4.06), positive family history for CAD (OR: 1.8, 95% CI: 1.11-3.01) and cigarette smoking (OR: 1.7, 95% CI: 0.97-2.98). Hypertension showed a protective role in this group of patients (OR = 0.5, CI = 0.29-0.92). In the female patients, hypertension (OR = 1.5, CI = 0.96-2.22) and body mass index (BMI) (OR = 1.1, CI = 1.02-1.10) were associated with depressive symptoms. Conclusion: In premature CAD male patients, opium usage, MACE, initial CABG treatment, positive family history for CAD and cigarette smoking were associated with depressive symptoms; and hypertension and BMI were associated with depressive symptoms in women.

Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Cardiopulmonary bypass initiates a systemic inflammatory response syndrome that is associated with postoperative morbidity and mortality. Steroids suppress inflammatory responses and might improve outcomes in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. We aimed to assess the effects of steroids in patients at high risk of morbidity and mortality undergoing cardiopulmonary bypass. METHODS: The Steroids In caRdiac Surgery (SIRS) study is a double-blind, randomised, controlled trial. We used a central computerised phone or interactive web system to randomly assign (1:1) patients at high risk of morbidity and mortality from 80 hospital or cardiac surgery centres in 18 countries undergoing cardiac surgery with the use of cardiopulmonary bypass to receive either methylprednisolone (250 mg at anaesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients were assigned with block randomisation with random block sizes of 2, 4, or 6 and stratified by centre. Patients aged 18 years or older were eligible if they had a European System for Cardiac Operative Risk Evaluation of at least 6. Patients were excluded if they were taking or expected to receive systemic steroids in the immediate postoperative period or had a history of bacterial or fungal infection in the preceding 30 days. Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcomes were 30-day mortality and a composite of death and major morbidity (ie, myocardial injury, stroke, renal failure, or respiratory failure) within 30 days, both analysed by intention to treat. Safety outcomes were also analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00427388. FINDINGS: Patients were recruited between June 21, 2007, and Dec 19, 2013. Complete 30-day data was available for all 7507 patients randomly assigned to methylprednisolone (n=3755) and to placebo (n=3752). Methylprednisolone, compared with placebo, did not reduce the risk of death at 30 days (154 [4%] vs 177 [5%] patients; relative risk [RR] 0·87, 95% CI 0·70-1·07, p=0·19) or the risk of death or major morbidity (909 [24%] vs 885 [24%]; RR 1·03, 95% CI 0·95-1·11, p=0·52). The most common safety outcomes in the methylprednisolone and placebo group were infection (465 [12%] vs 493 [13%]), surgical site infection (151 [4%] vs 151 [4%]), and delirium (295 [8%] vs 289 [8%]). INTERPRETATION: Methylprednisolone did not have a significant effect on mortality or major morbidity after cardiac surgery with cardiopulmonary bypass. The SIRS trial does not support the routine use of methylprednisolone for patients undergoing cardiopulmonary bypass. FUNDING: Canadian Institutes of Health Research.

Introducing the Tehran Heart Center's Premature Coronary Atherosclerosis Cohort: THC-PAC Study.

BACKGROUND: Data on premature coronary artery disease (CAD) are scarce. The Tehran Heart Center's Premature Coronary Atherosclerosis Cohort Study (THC-PAC) is the first study of its kind in the Middle East to assess major adverse cardiac events (MACE) in young CAD patients. METHODS: The cohort consists of CAD patients, males ≤ 45 years old and females ≤ 55 years old. The participants are residents of Tehran or its suburbs and underwent coronary angiography between June 2004 and July 2011. A 10-year follow-up, via either clinical visits or telephone calls at least once a year, was commenced in August 2012. The end point is considered MACE, encompassing death, myocardial infarction, stroke, new coronary involvement, percutaneous coronary intervention, and coronary artery bypass grafting. RESULTS: The cohort comprises 1232 eligible patients (613 [49.8%] males) at a mean age of 45.1 years (SD = 5.8). High frequencies of conventional risk factors, including hyperlipidemia (884 [71.8%]), hypertension (575 [46.7%]), positive family history (539 [43.8%]), cigarette smoking (479 [38.8%]), and diabetes mellitus (390 [31.7%]), were seen in the participants. The mean body mass index (BMI) of the enrolled patients was high (29.2 ± 4.8 kg/m(2)), and 532 (43.3%) and 440 (35.8%) of them were overweight and obese, respectively. The females' BMI was higher (30.4 ± 5.3 vs. 28.0 ± 3.9 kg/m2; P < 0.001) and they had a greater mean abdominal circumference (99.9 ± 13.5 vs. 98.1 ± 9.3 cm; P = 0.035). Between August 2012 and August 2013, follow-up was successful in 1173 (95.2%) patients (median follow-up duration = 55.3 months, 95%CI: 53.5-57.0 months). CONCLUSION: Our younger patients with CAD had a high frequency of risk factors compared to the same-age general population and all-age CAD patients, which may predispose them to higher incidence of recurrent MACE.