Determinants Of Myocardial Infarction Research Articles

The Particular Expression Profiles of Circular RNA in Peripheral Blood of Myocardial Infarction Patients by RNA Sequencing.

Myocardial infarction (MI) is one of the most common illnesses seriously harmful to human health. Notwithstanding, the systems of its pathogenesis are as yet not totally demonstrated. CircRNA is one sort of non-coding RNA, and late distributed information proposes that circRNAs assume a significant part in heart diseases; however, their expression profiles in the peripheral blood of patients with MI are not yet totally characterized. Therefore, RNAs from peripheral blood were recruited for high-throughput RNA-seq analysis. A total of 3,862 circRNAs were distinguished to be remarkably different, including 2,738 circRNAs being upregulated and 1,124 circRNAs being downregulated. circTMEM165, circUBAC2, circZNF609, circANKRD12, and circSLC8A1 were reconfirmed by RT-qPCR in the cell model. ROC curves uncovered that they have great sensitivity and specificity in the determination of MI. Besides, circRNAs are associated with cell metabolism and function by directing complex networks among circular RNAs, microRNAs, and messenger RNAs. In outline, our study portrayed the specific articulation profiles of circular RNA in patients with MI. The outcomes showed that circRNAs might fill in as a sort of ideal biomarkers for MI diagnosis. Further exploration of these circRNAs may enrich our understanding of MI etiology and progression.

Investigating Genetic and Other Determinants of First-Onset Myocardial Infarction in Malaysia: Protocol for the Malaysian Acute Vascular Events Risk Study.

BackgroundAlthough the burden of premature myocardial infarction (MI) is high in Malaysia, direct evidence on the determinants of MI in this multi-ethnic population remains sparse.ObjectiveThe Malaysian Acute Vascular Events Risk (MAVERIK) study is a retrospective case-control study established to investigate the genomic, lipid-related, and other determinants of acute MI in Malaysia. In this paper, we report the study protocol and early results.MethodsBy June 2019, we had enrolled approximately 2500 patients with their first MI and 2500 controls without cardiovascular disease, who were frequency-matched by age, sex, and ethnicity, from 17 hospitals in Malaysia. For each participant, serum and whole blood have been collected and stored. Clinical, demographic, and behavioral information has been obtained using a 200-item questionnaire.ResultsTobacco consumption, a history of diabetes, hypertension, markers of visceral adiposity, indicators of lower socioeconomic status, and a family history of coronary disease were more prevalent in cases than in controls. Adjusted (age and sex) logistic regression models for traditional risk factors indicated that current smoking (odds ratio [OR] 4.11, 95% CI 3.56-4.75; P<.001), previous smoking (OR 1.34, 95% CI 1.12-1.60; P=.001), a history of high blood pressure (OR 2.13, 95% CI 1.86-2.44; P<.001), a history of diabetes mellitus (OR 2.72, 95% CI 2.34-3.17; P<.001), a family history of coronary heart disease (OR 1.28, 95% CI 1.07-1.55; P=.009), and obesity (BMI >30 kg/m2; OR 1.19, 95% CI 1.05-1.34; P=.009) were associated with MI in age- and sex-adjusted models.ConclusionsThe MAVERIK study can serve as a useful platform to investigate genetic and other risk factors for MI in an understudied Southeast Asian population. It should help to hasten the discovery of disease-causing pathways and inform regionally appropriate strategies that optimize public health action.International Registered Report Identifier (IRRID)RR1-10.2196/31885

Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. We carried out a genome-wide association study for MI in the UK Biobank (n∼472000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165000) and 16 independent angiography-based cohorts (n∼27000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. A large-scale analysis comprising ∼831000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

Determinants of Myocardial Infarction in Saurashtra Region, Gujarat: A Case-control Study.

Background:Myocardial infarction (MI) is a multifactorial noncommunicable disease. The study was conducted with an objective to assess the role of various sociodemographic and clinicoepidemiological determinants of MI.Materials and Methods:The cases and controls were selected in the ratio of 1:1 and were group matched for age, sex, and type of residence. Cases of MI were selected from the intensive coronary care unit of the medicine department at a tertiary care hospital, Rajkot, for 1 year. Controls were selected from the general population of Rajkot district. Information was collected in pretested pro forma using the interview technique.Results:A total of 406 cases and equal number of controls were enrolled in the study. Several risk factors identified for MI included illiteracy, upper socioeconomic class, family history of MI, Type A personality, hypertension, diabetes mellitus, obese or overweight, high waist–hip ratio, low intake of leafy vegetables, low intake of fruits, and history of acute life event for the past 1 year. On applying logistic regression model, these factors were also identified as independent determinants for MI.Conclusion:The findings confirm the role of conventional risk factors for MI and also highlight the role of sociodemographic factors such as illiteracy, higher social class, low intake of leafy vegetables and fruits, and history of acute life event.

MYOCARDIAL INFARCTION AND STROKE: 16-YEAR RISK AND STRESS AT WORK IN OPEN POPULATION OF 25–64-YEAR-OLD WOMEN IN RUSSIA/SIBERIA (WHO MONICA–PSYCHOSOCIAL PROGRAM)

Aim. To determine the effects of stress at workplace on the risks (HR: hazard ratio) of development of myocardial infarction and stroke in open population of 25-64-yearold women in Russia/Siberia (Novosibirsk). Material and methods. Random representative sample of 25-64-year-old women (n=870) was examined in a framework of WHO MONICA-Psychosocial program in one of Novosibirsk districts. Stress at workplace was studied by using the Karasek scale; attitudes to work and prophylactic exams were studied by using the scale of “Knowledge and attitude towards one’s own health” of WHO MONICA-Psychosocial program. During 16 years (1994-2010), all first-time cases of myocardial infarction and stroke were studied in the cohort based on the WHO program of Register of Acute Myocardial Infarction and all available documentation. Cox regression model was used for determination of myocardial infarction and stroke risk over 16 years of follow-up. Results. Prevalence rate of high level of stress in open population of 25-64-yearold women was 31,6%. High levels of stress at work were associated with high levels of responsibility, inability to get rest at the end of workday, frequent professional dissatisfaction, and decreased working ability. For 16 years, HR was by 3,22 times higher for myocardial infarction (p<0,05) and 1,96 times higher for stroke (p<0,05) in women with stress at work. Rates of myocardial infarction and stroke were higher in married women who experienced stress at work, belonged to categories of managers and physical labor, and had high and low level of education. Conclusion. Prevalence of high level of stress at workplace is significant in open population of 25–64-year-old women in Russia/Siberia (Novosibirsk). In the presence of stress at workplace, HR of myocardial infarction and stroke were 2 to 3 times higher than without it. Social gradient affected HR of infarct and stroke.

Abstract 12117: The Cardioprotection of Trimetazidine Against Ischemic Injury is Mediated by AMPK and ERK Signaling Pathway

Introduction: Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. Hypothesis: AMP-activated protein kinase (AMPK) is an energy sensor that control ATP supply from substrate metabolism and protect heart from energy stress. TMZ changes the cardiac AMP/ATP ratio via modulating fatty acid oxidation, thereby it may trigger AMPK signaling cascade that contribute to protection heart from ischemia/reperfusion (I/R) injury. Methods: The mouse in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) were used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results: TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p&lt;0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p&lt;0.05). Intriguingly, the administration of ERK inhibitor, PD 98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Conclusions: Both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

Abstract 210: Determining In-Hospital Myocardial Infarction Rate from Administrative Data in a Large Tertiary-Care Hospital

Background &amp; Objective: The PULSE Trial is a 5-year multisite randomized clinical trial to evaluate implementation of American Heart Association Practice Standards for Electrocardiographic Monitoring on nurses' knowledge, quality of care, and patient outcomes. The primary intervention was an online ECG monitoring education program for nurses. A key indicator in assessing patient outcomes is the incidence of myocardial infarction (MI) while on a monitored unit. Determination of MI while in hospital can be challenging, requiring time-consuming medical record review. We propose a method of reducing the number of medical records necessary for review to determine occurrence of an in-hospital MI by using an algorithm that incorporates administrative and laboratory data. Methods: Administrative data from a large tertiary-care hospital in the US were obtained for a 6-month period. Fields included patient identifier, admission identifier, demographic data, unit transfers, length of stay, procedural codes, and diagnostic codes. Troponin and CK-MB levels were matched with administrative data. Step 1: We deleted all patient encounters where there were no troponin or CK-MB values above the upper reference limit (URL). We then deleted all encounters where all values occurred &lt;24 hours after admission and the patient did not have coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). Finally, we deleted all patient encounters for which all values &gt;24 hours after admission were either decreasing or below the URL and the patient did not have CABG or PCI. This allowed us to exclude all those who did not have a MI, or had one prior to being admitted to a unit. Step 2: If patients had an elevated biomarker &lt;24 hours after admission, we examined if there was an increase of &gt;20% in value following the index event or CABG or PCI procedure. If yes, they were considered to have an MI. If patients had an elevated biomarker &gt;24 hours after admission, we determined if the values were 3x and 5x the URL for PCI and CABG, respectively. If yes, they were considered to have an MI; those who did not required further record review. Results: We had 7,691 admissions. In step 1 we were able to rule out MI in 6,849 admissions. In step 2 we determined 596 had elevated biomarkers within 24 hours of admission. We determined 193 had an MI. The remaining 403 required further review. We determined that 245 had elevated biomarkers &gt;24 hours after admission. Of those, 21 had an elective PCI or CABG, 4 of whom had 3x or 5x the URL of biomarkers and were consider to have a MI. The 224 who did not have an elective PCI or CABG required further review. Conclusions: This algorithm reduced the number of medical record reviews from 7,691 to 627 and allowed for determination of an outcome that is not easily assessed, thereby precluding the need for lengthy medical record reviews. The algorithm can be adjusted to reflect changing criteria for MI.

Attenuation of Inflammatory Response and Reduction in Infarct Size by Postconditioning Are Associated With Downregulation of Early Growth Response 1 During Reperfusion in Rat Heart

Early growth response 1 (EGR-1) works as a master regulator that plays a key role in triggering inflammation-induced tissue injury after ischemia and reperfusion. This study tested the hypothesis that postconditioning (Postcon) or anti-inflammatory compound, curcumin, ameliorates inflammatory responses and further reduces infarct size by normalizing EGR-1 expression during reperfusion. In the control group, male Sprague-Dawley rats were subjected to 30-min ischemia and 180-min reperfusion. Postcon with four cycles of 10-s/10-s reperfusion/ischemia was applied at the onset of reperfusion. Curcumin (150 mg/kg per day) was fed 5 days before ischemia. Relative to the control, Postcon reduced expression of EGR-1 mRNA and protein, as further identified by less EGR-1 immunoreactivity in myocardial nuclei and microvessels during reperfusion. Along with EGR-1 downregulation, levels of plasma and myocardial tumor necrosis factor α and interleukin 6 (IL-6) were significantly decreased. Upregulated P-selectin and intercellular adhesion molecule 1 mRNA and protein as well as their immunoreactivity at area at risk myocardium were significantly attenuated. Neutrophil extravasation identified by myeloperoxidase immunohistochemical staining was inhibited. Infarct size, determined with triphenyltetrazolium chloride staining, was smaller in the Postcon group than that in the control. The protection achieved with pretreatment with curcumin was comparable to the benefits gained by Postcon in all end points measured. In H9C2 rat cardiomyoblast cell line, EGR-1 siRNA downregulated hydrogen peroxide-induced EGR-1 mRNA expression and subsequently reduced tumor necrosis factor α mRNA level. These results suggest that EGR-1 seems to play a critical role in myocardial reperfusion injury because downregulation of EGR-1 either by Postcon or the use of pharmacological intervention reduces infarct size, most likely through an inhibition of inflammation-mediated processes.

Elektrokardiografsko utvrđivanje infarkta miokarda sa elevacijom ST segmenta

Elektrokardiografsko utvrđivanje infarkta miokarda sa elevacijom ST segmenta

Apolipoprotein B/Apolipoprotein A-I Ratio and Apolipoprotein B

We investigated whether serum concentrations of apolipoprotein (apo) B and apoA-I and the apoB/apoA-I ratio provided predictive information on myocardial infarction (MI) and ischemic stroke during 13 years of follow-up in a group of initially clinically healthy 58-year-old men, free from previous cardiovascular disease, diabetes, other established disease, or treatment with cardiovascular drugs. Multivariate logistic regression analysis showed that the apoB/apoA-I ratio and apoB were significant and independent determinants of MI (exponentiation of the B coefficient [Exp(β)] 3.1, 95% confidence interval [CI] 1.6-6.3, P=.001, Exp(β) 2.8, 95% CI 1.1-7.7, P=.045, respectively). The area under the receiver-operating characteristics curve as a relative measure of test efficiency was highest and significant for both apoB/apoA-I ratio and apoB (area under the curve=0.75, P<.001). In conclusion, the apoB/apoA-I ratio and apoB are independent risk factors for MI and has the highest efficiencies for predicting MI in initially healthy middle-aged men.

Abstract MP020: Long-term, Visit-to-visit Blood Pressure Variability and the Risk of Total Mortality, MI, and Stroke in the Cardiovascular Health Study

Introduction: Recent reports have linked visit-to-visit blood pressure (BP) variability to risk of mortality and stroke, independent of the effect of mean BP level. We sought to confirm these findings in the Cardiovascular Health Study (CHS), a cohort study of cardiovascular risk factors. Hypothesis: Variability in visit-to-visit SBP, defined as intraindividual SBP SD, is directly associated with risk of mortality, myocardial infarction (MI), and stroke, independent of intraindividual SBP mean and trend over time. Methods: Participants from CHS were eligible if they attended their first five annual clinic visits and did not have stroke, MI, or death by the 5th visit (N=3513). Follow-up started at the 5th visit and extended through June 2008. Analyses were further restricted to subjects who used no antihypertensive medications during the entire 5-year baseline period (non-users, n=1570) and subjects who used the same antihypertensive regimen during that time (users, n=978). Intraindividual SBP variables were defined using each subject’s 5-visit BPs. Cox proportional hazards models estimated adjusted hazard ratios (HR) per standard deviation (SD) increase in intraindividual SD (iSD) SBP or intraindividual mean (iMean) SBP. Results were stratified on medication use or non-use. Results: Participants’ mean age was 71 years, 42% were men, and 95% were white. Mean(SD) of iSD SBP was 9.8(4.6) mmHg for anti-hypertensive medications non-users and 12.0(6.0) mmHg for users. iMean SBP was significantly associated with all 3 outcomes among non-users and with stroke among users (table). iSD SBP was significantly associated with mortality in all participants and with MI among non-users; associations for stroke were not significant. Conclusion: Long-term visit-to-visit SBP variability may be an important determinant of MI and mortality risk in the elderly. Results for stroke are not consistent with other, previous reports. More research is needed to determine the clinical implications.

Stress ECG utilization in the evaluation of patients with chest pain: The real practice in Hungary with 10 million inhabitants

temperature on the incidence ofmyocardial infarction. Heart 2009;95(21):1760–9. [4] Buskirk ER, Kollias J, Akers RF, Prokop EK, Reategui EP.Maximal performance at altitude and on return fromaltitude in conditioned runners. J Appl Physiol 1967;23(2):259–66. [5] Tofler GH, Muller JE. Triggering of acute cardiovascular disease and potential preventive strategies. Circulation 2006;114(17):1863–72. [6] Mittleman MA, Maclure M, Sherwood JB, Mulry RP, Tofler GH, Jacobs SC, et al. Triggering of acute myocardial infarction onset by episodes of anger. Determinants ofMyocardial Infarction Onset Study Investigators. Circulation 1995;92(7):1720–5. [7] D'Agostino Sr RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation 2008;117(6):743–53. [8] Graham I, Atar D, Borch-Johnsen K, Boysen G, Burell G, Cifkova R, et al. European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur J Cardiovasc Prev Rehabil 2007;14(Suppl 2):S1–S113. [9] Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med 1993;329(23):1677–83. [10] Schmid JP, Noveanu M, Gaillet R, Hellige G, Wahl A, Saner H. Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease. Heart 2006;92(7):921–5. [11] Klug G, Zwick RH, Frick M, Wolf C, Schocke MF, Conci E, et al. Impact of exercise capacity onmyocardial high-energy phosphate metabolism. Int J Sports Med 2007;28(8):667–72. [12] Burtscher M, Faulhaber M, Flatz M, Likar R, Nachbauer W. Effects of short-term acclimatization to altitude (3200 m) on aerobic and anaerobic exercise performance. Int J Sports Med 2006;27(8):629–35. [13] Cold exposure and winter mortality from ischaemic heart disease, cerebrovascular disease, respiratory disease, and all causes inwarm and cold regions of Europe. The Eurowinter Group. Lancet 1997;349(9062):1341–6. [14] Shewan L, Coats A. Ethics in the authorship and publishing of scientific articles. Int J Cardiol 2010;144:1–2.

Genetic risk for myocardial infarction in Japanese individuals with or without chronic kidney disease

Although chronic kidney disease (CKD) is recognized as an important risk factor for myocardial infarction (MI), genetic factors underlying predisposition to MI in individuals with or without CKD remain largely unknown. The aim of the present study was to identify genetic variants that confer susceptibility to MI in individuals with or without CKD in order to allow prediction of genetic risk for such individuals separately. The study population comprised a total of 4344 individuals, including 1247 individuals with CKD (506 subjects with MI and 741 controls) and 3097 individuals without CKD (833 subjects with MI and 2264 controls). The 150 polymorphisms examined in this study were selected by genome-wide association studies of ischemic stroke and MI with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix) and determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. In individuals with CKD, no polymorphism was significantly related to MI. In individuals without CKD, an initial screen by the Chi-square test revealed that the Cyright curved arrow T polymorphism of CLEC16A (rs9925481) and the Aright curved arrow G polymorphism of LAMA3 (rs12373237) were significantly (false discovery rate for allele frequencies of <0.05) associated with MI. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the Cright curved arrow T polymorphism of CLEC16A (dominant model; P=0.0003; odds ratio, 0.66) and the Aright curved arrow G polymorphism of LAMA3 (recessive model; P=0.0087; odds ratio, 0.75) were significantly (P<0.05) associated with MI. A stepwise forward selection procedure also revealed that these polymorphisms were significant and independent determinants of MI. CLEC16A and LAMA3 may be susceptibility loci for MI in Japanese individuals without CKD. Determination of genotypes for CLEC16A and LAMA3 may prove informative for assessment of the genetic risk for MI in such individuals.

The Case-Crossover Study: A Novel Design in Evaluating Transient Fatigue as a Risk Factor for Road Traffic Accidents

The Case-Crossover Study: A Novel Design in Evaluating Transient Fatigue as a Risk Factor for Road Traffic Accidents

The Pakistan Risk of Myocardial Infarction Study: a resource for the study of genetic, lifestyle and other determinants of myocardial infarction in South Asia

The burden of coronary heart disease (CHD) is increasing at a greater rate in South Asia than in any other region globally, but there is little direct evidence about its determinants. The Pakistan Risk of Myocardial Infarction Study (PROMIS) is an epidemiological resource to enable reliable study of genetic, lifestyle and other determinants of CHD in South Asia. By March 2009, PROMIS had recruited over 5,000 cases of first-ever confirmed acute myocardial infarction (MI) and over 5,000 matched controls aged 30-80 years. For each participant, information has been recorded on demographic factors, lifestyle, medical and family history, anthropometry, and a 12-lead electrocardiogram. A range of biological samples has been collected and stored, including DNA, plasma, serum and whole blood. During its next stage, the study aims to expand recruitment to achieve a total of about 20,000 cases and about 20,000 controls, and, in subsets of participants, to enrich the resource by collection of monocytes, establishment of lymphoblastoid cell lines, and by resurveying participants. Measurements in progress include profiling of candidate biochemical factors, assay of 45,000 variants in 2,100 candidate genes, and a genomewide association scan of over 650,000 genetic markers. We have established a large epidemiological resource for CHD in South Asia. In parallel with its further expansion and enrichment, the PROMIS resource will be systematically harvested to help identify and evaluate genetic and other determinants of MI in South Asia. Findings from this study should advance scientific understanding and inform regionally appropriate disease prevention and control strategies.

Association of genetic variants with myocardial infarction in Japanese individuals with metabolic syndrome

Objective The purpose of the present study was to identify genetic variants that confer susceptibility to myocardial infarction (MI) in individuals with metabolic syndrome (MetS). Methods The study population comprised 1887 Japanese individuals with MetS, including 773 subjects with MI and 1114 controls. The genotypes for 136 polymorphisms of 97 candidate genes were determined. Results An initial screen by the chi-square test revealed that seven polymorphisms were significantly (false discovery rate < 0.05) associated with the prevalence of MI in individuals with MetS. Subsequent multivariable logistic regression analysis with adjustment for covariates revealed that the G→A (Ser89Asn) polymorphism of UTS2 [odds ratio (OR), 1.90; 95% confidence interval (CI), 1.18–3.08], the 2445G→A (Ala54Thr) polymorphism of FABP2 (OR, 1.72; 95% CI, 1.23–2.40), the −11377C→G polymorphism of ADIPOQ (OR, 1.43; 95% CI, 1.15–1.79), the −231A→G polymorphism of EDNRA (OR, 0.65; 95% CI, 0.48–0.89), and the −108/3G→4G polymorphism of PDX1 (OR, 0.64; 95% CI, 0.48–0.87) were significantly ( P < 0.05) associated with MI. The variant alleles of UTS2, FABP2, and ADIPOQ were risk factors for MI, whereas the variant alleles of EDNRA and PDX1 were protective against this condition. A stepwise forward selection procedure demonstrated that UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 genotypes were significant ( P < 0.05) and independent determinants of MI. Conclusions Determination of genotypes for these polymorphisms of UTS2, FABP2, ADIPOQ, EDNRA, and PDX1 may prove informative for assessment of the genetic risk for MI in Japanese individuals with MetS.

Incidence and determinants of myocardial infarction following percutaneous coronary interventions according to the revised Joint Task Force definition of troponin T elevation

Background Elevations in troponin T (TnT) occur frequently following percutaneous coronary intervention (PCI) and are associated with an adverse prognosis. The Joint ESC/ACC/AHA/WHF Task Force have released a proposal for a universal definition of myocardial infarction (MI), including diagnostic criteria for PCI associated MI. This is based on a TnT cut-point of more than three times the 99th percentile (0.03 ng/ml), which better reflects the precision of the assay. Our study investigated the incidence and predictive factors of a PCI associated MI, using the revised definition. Methods 325 patients were studied following PCI with stenting. TnT was collected at both 8 and 18 h following PCI in patients with either stable or unstable angina and normal baseline TnT levels. Comparison was made of both clinical and procedural characteristics of patients with and without a rise in TnT following intervention, using cut points of 0.01 and 0.03 ng/ml. Results TnT was elevated ≥ 0.03 ng/ml in 27% and ≥ 0.01 ng/ml in 39% of patients following PCI. Troponin elevation was significantly more likely in those patients who experienced peri-procedural ischemic symptoms or EKG changes, or in whom abciximab was used. The variables associated with a troponin rise showed a greater difference between TnT positive and negative patients when using 0.03 ng/ml compared to 0.01 ng/ml, suggesting that this may be a better definition of PCI-related MI. Conclusions Approximately one-quarter of low risk patients experience a procedural MI according to the revised definition. Rises in troponin were significantly associated with peri-procedural ischemic symptoms and EKG changes, and abciximab use, consistent with this level of TnT reflecting true myocardial necrosis.

Genetic Effects versus Bias for Candidate Polymorphisms in Myocardial Infarction: Case Study and Overview of Large-Scale Evidence

Several genetic polymorphisms have been proposed to be associated with myocardial infarction (MI). The authors examined the evidence and biases underlying such associations using a case-study meta-analysis and an overview of large-scale data. In a meta-analysis of 27 studies addressing the association of the angiotensin type 1 receptor (AT1R)+1166A/C polymorphism with MI (10,180 cases, 17,129 controls), the *C allele conferred an increase in MI risk (odds ratio = 1.13 per allele, p = 0.005). However, there was large between-study heterogeneity; the largest study showed no effect, contradicting smaller studies; and studies with blinded genotyping showed no effect. The authors conducted an overview of meta-analyses of genetic associations for MI or coronary artery disease, including at least three studies and 3,000 subjects. In their latest meta-analysis, another 14 polymorphisms were found to have formally significant associations. If true, these associations would already explain 42% of the MI risk for Caucasian populations. Significant between-study heterogeneity was common. Across the 32 largest studies, only two found formally significant results (nine would be expected if each meta-analysis showed a true association). Even with large-scale evidence from meta-analyses, significant associations for MI may be subject to bias. Large-scale single studies and prospective consortia should be used for detecting and validating the genetic determinants of MI.

Minor elevations in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values

Background: A consensus document developed by a joint committee of the European Society of Cardiology and the American College of Cardiology redefines myocardial infarction (MI) using an increase of troponin I or T as compared to a reference control population (i.e., troponin T (TnT) of 0.01 μg/l). A clinical problem arises when an arbitrary cut-off point is selected for determination of MI (i.e., TnT≥0.1 μg/l), as minor elevations of troponin are associated with increased cardiovascular risk in selected patients with acute coronary syndromes. Methods: We prospectively studied 420 unselected patients being evaluated for suspected myocardial ischemia in the emergency department (ED). We compared a 99th percentile MI cut-off limit for TnT, determined by constructing a standard receiver operator curve from our ED population in whom an acute coronary syndrome was excluded, to a standard MI cut-off limit of 0.1 μg/l in assessing cardiovascular risk. We also assessed the prognostic value of detectable TnT concentrations below this 99th percentile MI cut-off, but above the upper reference limit of healthy controls. Results: The diagnosis of acute coronary syndromes (ACS) was more frequent in groups with higher TnT concentrations: 16.8% with a normal TnT (<0.03 μg/l), 29.5% with detectable TnT below the 99th percentile MI limit (0.03–0.066 μg/l), 64.3% with detectable TnT between the 99th percentile and standard MI cut-offs (0.067–0.099 μg/l), and 85.4% with TnT≥0.1 μg/l ( p<0.001 for the trend). Thirty-day cardiovascular event rates increased for any detectable concentration of troponin: 1.3% with normal TnT, 4.8% with detectable TnT below the 99th percentile MI limit, 15.4% with TnT between the 99th percentile and standard MI cut-off limits, and 12.5% with TnT≥0.1 μg/l ( p<0.01 for the trend). Conclusion: Using an MI cut-off concentration for TnT from a “non-ACS reference” improves risk stratification, but fails to detect a positive TnT in 11.7% of subjects with an acute coronary syndrome.

Location as a Determinant of Myocardial Infarction in Rabbits

Determinants of infarct size in the rabbit heart include risk zone size, regional myocardial blood flow (RMBF), temperature and duration of ischemia. However, other factors might contribute, such as the location of the risk zone (apex to base), independent of known factors. Occlusion of a large marginal branch of the circumflex artery in the rabbit produces a risk region that typically comprises the entire apex of the left ventricle with decreasing area involvement from apex to base. In a retrospective study of 65 rabbit hearts (subjected to 30 min of coronary artery occlusion) which had been sliced into six to eight cross-sectional slices, average area at risk (AR) comprised 86±3% of the apical level, 68±2% of the middle level and 39±2% near the site of occlusion at the base of the heart. If necrosis were dependent on AR alone, then infarct size (area of necrosis/area at risk, AN/AR) would not vary by site. However, AN/AR in the apex was 54±3% while AN/AR near the base was 27±2%, P<0.0001. To test if this salvage of tissue at risk near the base was due to differences in regional myocardial blood flow, we measured RMBF during occlusion in additional rabbits (n=4). Average RMBF in the risk zone was 0.025 ml/min/g in the apex and 0.010 in the base,P =N.S. Nor was the salvage due to differences in temperature. During occlusion, temperature in the risk zone (n=5) was 38.1°C±0.3 in the apex and 38.4±0.2 in the base (P=N.S.). When we examined this phenomenon in hearts that received a non-pharmacological intervention that decreases overall infarct size (ischemic preconditioning) and in hearts that received a pharmacological intervention that decreases overall infarct size, a similar pattern of decreasing infarct size as a percentage of the area at risk from apex to base was observed. In conclusion, infarct size as a percentage of the AR depends on whether the AR is at the apex or base of the heart. A larger part of the AR undergoes necrosis toward the apex of the heart. This phenomenon is independent of collateral flow or temperature, and suggests that other as yet unknown factors contribute to infarct size.