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The clinical use of N-terminal pro-brain natriuretic peptide (NT-proBNP) and blood concentrations of heart-type fatty acid-binding protein (HFABP) is well-established in diagnosing heart conditions. However, their applicability in forensics is controversial due to postmortem changes. NT-proBNP and HFABP are excreted in the urine due to their small molecular weights and may be found in postmortem urine samples; however, their correlation has not been evaluated. In this study, we compared the concentrations of urinary NT-proBNP and HFABP in 386 forensic autopsy cases. The urinary NT-proBNP levels were significantly higher in acute myocardial infarction (AMI), congestive heart failure (CHF), sepsis, and hyperthermia cases, with the highest levels in CHF cases. Similarly, HFABP concentration was significantly higher in CHF, sepsis, and hyperthermia cases, with the highest level observed in hyperthermia cases. However, the difference in urinary HFABP levels between the AMI and control cases was not significant. Our analysis revealed a correlation between postmortem urine NT-proBNP and HFABP levels, and the NT-proBNP/HFABP ratio was high in patients with CHF and sepsis cases and low in those with hyperthermia. The difference between the ratios was possibly due to the combined release of ventricular myocardial cells in response to ventricular wall stress and myocardial injury for NT-proBNP, as well as myocardial and skeletal muscle injuries for HFABP. This study, for the first time, demonstrates the utility of postmortem measurements of urinary NT-proBNP and HFABP levels, offering valuable insights for improving the accuracy of postmortem diagnosis in forensic medicine., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To screen biomarkers for forensic identification of acute myocardial infarction (AMI) by non-targeted metabolomic studies on changes of urine metabolites in rats with AMI., Methods: The rat models of the sham surgery group, AMI group and hyperlipidemia + acute myocardial infarction (HAMI) group were established. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to analyze the changes of urine metabolic spectrometry in AMI rats. Principal component analysis, partial least squares-discriminant analysis, and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. The MetaboAnalyst database was used to analyze the metabolic pathway enrichment and access the predictive ability of differential metabolites., Results: A total of 40 and 61 differential metabolites associated with AMI and HAMI were screened, respectively. Among them, 22 metabolites were common in both rat models. These small metabolites were mainly concentrated in the niacin and nicotinamide metabolic pathways. Within the 95% confidence interval, the area under the curve (AUC) values of receiver operator characteristic curve for N8-acetylspermidine, 3-methylhistamine, and thymine were greater than 0.95., Conclusions: N8-acetylspermidine, 3-methylhistamine, and thymine can be used as potential biomarkers for AMI diagnosis, and abnormal metabolism in niacin and nicotinamide may be the main causes of AMI. This study can provide reference for the mechanism and causes of AMI identification.

Rationale: Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic stem cell disease. Patients with PNH often experience a high incidence (14%-40%) of thrombotic events, which are mainly venous and rarely arterial thrombotic events. Because it is very rare, delay in diagnosis is common in patients with PNH, imposing a remarkable impact on patient's management and prognosis., Patient Concerns: We presented a 33-year-old female case with no medical history of any systemic illnesses who complained of approximately 1-month progressively worsening constant heartburn, and was also hospitalized twice due to acute myocardial infarction (AMI)., Diagnoses: In our case, AMI occurred twice, whereas there were no cardiovascular risk factors and abnormalities based on the angiography of the coronary artery. Flow cytometry analysis showed that 25% of CD55 and CD59 were lost on the surface of neutrophils, and 30% of CD55 and CD59 were lost on the surface of the blood cells. Thus, our diagnosis of this patient was AMI secondary to PNH., Interventions and Outcomes: For the first myocardial infarction, local hospitals used thrombolytic therapy to alleviate symptoms. After the patient's second myocardial infarction was treated in our hospital, we adopted coronary interventional therapy. Considering the patient's situation, eculizumab was given for treatment. The patient was gradually restored to achieve stability, and the follow-up observation showed that there was no arterial thrombosis., Lessons: This case report aimed to provide a reliable reference for the rare cause of AMI. In addition, PNH should be highly taken into consideration in young patients who have a rare cause of AMI.

Background In patients with myocardial infarction ( MI ), reduced kidney function is recognized as an important predictor of poor prognosis, but the impact of albuminuria, a representative measure of kidney damage, has not been extensively evaluated. Methods and Results In the SCREAM (Stockholm Creatinine Measurements) project (2006-2012), we identified 2469 patients with incident MI with dipstick proteinuria measured within a year before MI (427 patients also had urine albumin to creatinine ratio [ ACR ] measured concurrently) and obtained estimates for ACR with multiple imputation in participants with data solely on dipstick proteinuria. We quantified the association of ACR with the post- MI composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI , ischemic stroke, or heart failure using Cox models and then evaluated the improvement in C statistic. During a median follow-up of 1.0 year after MI , 1607 participants (65.1%) developed the post- MI composite outcome. Higher ACR levels were independently associated with all outcomes except for ischemic stroke. Per 8-fold higher ACR (eg, 40 versus 5 mg/g), the hazard ratio of composite outcome was 1.21 (95% CI , 1.08-1.35). The addition of the ACR improved the C statistic of the post- MI composite by 0.040 (95% CI, 0.030-0.051). Largely similar results were obtained regardless of diabetic status and when ACR or dipstick was separately analyzed without imputation. Conclusions In patients with MI , albuminuria was a potent predictor of subsequent outcomes, suggesting the importance of paying attention to the information on albuminuria, in addition to kidney function, in this high-risk population.

The purpose of the present study was to assess whether 6-week ranolazine application on top of guideline-based treatment impacts on the arginine/NO pathway and urinary isoprostane 8-iso-PGF 2α as marker of oxidative stress in patients directly after a myocardial infarction. 20 patients with unstable angina pectoris and proof of acute cardiac ischemia entered the study. 10 subjects received the study drug ranolazine in addition to standard treatment, the others received only standard treatment. Urine and venous blood were collected before and after treatment. At the end of the study and compared to baseline, homoarginine levels had increased in the control group. This was not the case in ranolazine-patients. Interestingly, in ranolazine-treated-patients arginine plasma levels were significantly higher at the end of the study than at baseline (difference +26 µmol/L, 95% CI 8.6 to 44 µmol/L). ADMA and SDMA levels were not different. Urine levels of the oxidative stress marker 8-iso-PGF 2α tended to be lower in ranolazine-treated patients (-144 pmol/mg creatinine). Findings of this hypothesis-driven study give evidence that ranolazine treatment enhances arginine plasma levels and lowers oxidative stress.

Objectives: No individual homocysteine (Hcy) metabolite has been studied as a risk marker for coronary artery disease (CAD). Our objective was to examine Hcy-thiolactone, a chemically reactive metabolite generated by methionyl-tRNA synthetase and cleared by the kidney, as a risk predictor of incident acute myocardial infarction (AMI) in the Western Norway B-Vitamin Intervention Trial., Design: Single centre, prospective double-blind clinical intervention study, randomized in a 2 × 2 factorial design., Subjects and Methods: Patients with suspected CAD (n = 2049, 69.8% men; 61.2-year-old) were randomized to groups receiving daily (i) folic acid (0.8 mg)/vitamin B 12 (0.4 mg)/vitamin B 6 (40 mg); (ii) folic acid/vitamin B 12 ; (iii) vitamin B 6 or (iv) placebo. Urinary Hcy-thiolactone was quantified at baseline, 12 and 38 months., Results: Baseline urinary Hcy-thiolactone/creatinine was significantly associated with plasma tHcy, ApoA1, glomerular filtration rate, potassium and pyridoxal 5'-phosphate (positively) and with age, hypertension, smoking, urinary creatinine, plasma bilirubin and kynurenine (negatively). During median 4.7-years, 183 patients (8.9%) suffered an AMI. In Cox regression analysis, Hcy-thiolactone/creatinine was associated with AMI risk (hazard ratio = 1.58, 95% confidence interval = 1.10-2.26, P = 0.012 for trend; adjusted for age, gender, tHcy). This association was confined to patients with pyridoxic acid below median (adjusted HR = 2.72, 95% CI = 1.47-5.03, P = 0.0001; P interaction = 0.020). B-vitamin/folate treatments did not affect Hcy-thiolactone/creatinine and its AMI risk association., Conclusions: Hcy-thiolactone/creatinine ratio is a novel AMI risk predictor in patients with suspected CAD, independent of traditional risk factors and tHcy, but modified by vitamin B 6 catabolism. These findings lend a support to the hypothesis that Hcy-thiolactone is mechanistically involved in cardiovascular disease., (© 2018 The Authors Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Oxidative stress contributes to endothelial dysfunction and is involved in the pathogenesis of cardiovascular diseases (CVD). However, large population-based cohort studies are sparse and biomarkers of oxidative stress have not been evaluated for CVD risk prediction so far., Methods: The associations of urinary oxidized guanine/guanosine (OxGua) levels (including 8-hydroxy-2'-deoxyguanosine (8-OHdGuo)) and 8-isoprostane levels with myocardial infarction, stroke and CVD mortality were examined in a population-based cohort of 9949 older adults from Germany with 14 years of follow-up in multivariable adjusted Cox proportional hazards models., Results: Both OxGua and 8-isoprostane levels were associated with CVD mortality independently from other risk factors (hazard ratio (HR) [95% confidence interval] of top vs. bottom tertile: 1.32 [1.06; 1.64] and 1.58 [1.27; 1.98], respectively). Moreover, CVD mortality risk prediction was significantly improved when adding the two biomarkers to the European Society of Cardiology's Systematic Coronary Risk Evaluation (ESC SCORE) tool. The area under the curve (AUC) increased from 0.739 to 0.752 (p = 0.001). In addition, OxGua levels were associated with stroke incidence (HR for 1 standard deviation increase: 1.07 [1.01; 1.13]) and 8-isoprostane levels were associated with fatal stroke incidence (HR of top vs. bottom tertile: 1.77 [1.09; 2.89]). With respect to myocardial infarction, associations were observed for both biomarkers in obese subjects (BMI ≥ 30 kg/m 2 )., Conclusions: These results from a large cohort study add evidence to the involvement of an imbalanced redox system to the etiology of CVD. In addition, 8-isoprostane and OxGua measurements were shown to be useful for an improved CVD mortality prediction., (Copyright © 2018 Elsevier B.V. All rights reserved.)

INTRODUCTION Leukotrienes (LTs) may be involved in atherosclerosis and may contribute to cardiovascular outcomes in CAD. OBJECTIVES    We aimed to compare the baseline LT production in patients with stable CAD (sCAD) and myocardial infarction (MI), and to assess whether an increased LT production is associated with major adverse cardiovascular events (MACEs) at 1 year after MI. PATIENTS AND METHODS    LTIMI (Leukotrienes and Thromboxane In Myocardial Infarction) was a single‑center, prospective, observational study of patients with stable sCAD and MI. Urinary leukotriene E4 (LTE4) levels were measured on admission, at 1 month, and at 1 year, using high‑performance liquid chromatography tandem mass spectrometry. RESULTS    Of the 404 patients screened, 289 were enrolled (110 with sCAD and 179 with MI; mean [SD] age, 63.9 [10.9] years). Patients with MI had higher median (interquartile range [IQR]) levels of log‑transformed LTE4 (logLTE4) than those with sCAD (4.74 pg/mg creatinine [4-5.45] vs 4.51 pg/mg creatinine [3.99 4.86], respectively; P <0.001). Median (IQR) logLTE4 levels in patients with MI significantly decreased at 1 month to 4.37 pg/mg creatinine (3.81-4.95), and at 1 year to 4.16 pg/mg creatinine (3.55-4.85). The baseline urinary logLTE4 levels were similar in patients with MACEs and those without MACEs (median [IQR], 4.78 pg/mg creatinine [4.01-5.56]) and 4.68 pg/mg creatinine [3.97-5.28], respectively; P >0.05). Multiple regression showed no relation between LTE4 levels and the incidence of MACEs. CONCLUSIONS    LT production assessed by urinary LTE4 excretion is higher in patients with MI than in those with sCAD; however, LTE4 levels at baseline do not differ between patients with and without MACEs at 1 year after MI.

Background: Systemic thromboxane generation, not suppressible by standard aspirin therapy and likely arising from nonplatelet sources, increases the risk of atherothrombosis and death in patients with cardiovascular disease. In the RIGOR (Reduction in Graft Occlusion Rates) study, greater nonplatelet thromboxane generation occurred early compared with late after coronary artery bypass graft surgery, although only the latter correlated with graft failure. We hypothesize that a similar differential association exists between nonplatelet thromboxane generation and long-term clinical outcome., Methods and Results: Five-year outcome data were analyzed for 290 RIGOR subjects taking aspirin with suppressed platelet thromboxane generation. Multivariable modeling was performed to define the relative predictive value of the urine thromboxane metabolite, 11-dehydrothromboxane B 2 (11-dhTXB 2 ), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11-dhTXB 2 measured 3 days after surgery did not independently predict outcome, whereas 11-dhTXB 2 >450 pg/mg creatinine measured 6 months after surgery predicted the composite end point (adjusted hazard ratio, 1.79; P =0.02) and death (adjusted hazard ratio, 2.90; P =0.01) at 5 years compared with lower values. Additional modeling revealed 11-dhTXB 2 measured early after surgery associated with several markers of inflammation, in contrast to 11-dhTXB 2 measured 6 months later, which highly associated with oxidative stress., Conclusions: Long-term nonplatelet thromboxane generation after coronary artery bypass graft surgery is a novel risk factor for 5-year adverse outcome, including death. In contrast, nonplatelet thromboxane generation in the early postoperative period appears to be driven predominantly by inflammation and did not independently predict long-term clinical outcome., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: To assess whether changes in proteinuria are associated with the incidence of myocardial infarction (MI) in patients with hypertension., Methods: The Kailuan study was a prospective longitudinal cohort study on cardiovascular risk factors and events. Hazard ratios with 95% confidence intervals (CIs) were calculated using Cox regression models., Results: A total of 24 926 hypertensive patients (mean age: 55.2 ± 10.9 years) without previous MI were included. After a mean follow-up of 6.8 years, 382 (1.5%) individuals developed MI. Participants with proteinuria at baseline had a 60% higher risk for developing MI as compared with participants without proteinuria at baseline (hazard ratio: 1.60, 95% CI: 1.12-2.29) after adjusting for dyslipidemia, diabetes mellitus and other cardiovascular risk factors. Compared with participants without proteinuria, individuals with incident proteinuria or persistent proteinuria during the follow-up had 54 and 141% higher risks for developing MI, respectively (hazard ratio: 1.54, 95% CI: 1.14-2.09 and hazard ratio: 2.41, 95% CI: 1.59-3.66; all P < 0.05)., Conclusion: Proteinuria is associated with an increased incidence of MI, but the association is likely to be underestimated if baseline measurements of proteinuria are used. Measures of changes in proteinuria, particular persistent proteinuria, are more likely to reflect the lifetime risk for MI.

Introduction: Impaired renal function, reflected by estimated glomerular filtration rate (eGFR) or cystatin C, is a strong risk predictor in the presence of acute myocardial infarction (AMI). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of acute kidney injury. uNGAL might also be a good predictor of outcome in patients with cardiovascular disease. Aim of the present study was to evaluate the prognostic value of uNGAL compared to eGFR and cystatin C in patients with suspected AMI., Methods: 1818 patients were enrolled with suspected AMI. Follow-up information on the combined endpoint of death or non-fatal myocardial infarction was obtained 6months after enrolment and was available in 1804 patients. 63 events (3.5%) were registered., Results: While cystatin C and eGFR were strong risk predictors for the primary endpoint even adjusted for several variables, uNGAL was not independently associated with outcome: When applied continuously uNGAL was associated with outcome but did not remain a statistically significant predictor after several adjustments (i.e. eGFR). By adding cystatin C or uNGAL to GRACE risk score variables, only cystatin C could improve the predictive value while uNGAL showed no improvement., Conclusion: We could show that cystatin C is an independent risk predictor in patients with suspected AMI and cystatin C can add improvement to the commonly used GRACE risk score. In contrast uNGAL is not independently associated with outcome and seems not to add further prognostic information to GRACE risk score., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The relationship between changes in proteinuria and myocardial infarction (MI) remains unclear in people with diabetes or pre-diabetes. We aimed to evaluate the predictive value and independent role of changes in proteinuria over a 2-year period in the incidence of MI in people with diabetes or pre-diabetes., Methods: Based on the baseline and 2-year dipstick screening results from the Kailuan prospective cohort study, participants were divided into four categories: no proteinuria, remittent proteinuria, incident proteinuria, and persistent proteinuria. Four multivariable Cox proportional hazard models were built to adjust for the effects of different confounding covariates., Results: Among the 17,625 participants in this study, there were a total of 238 incidents of MI during a median follow-up of 6.69 years. After adjusting for demography factors and laboratory indices, the association between persistent proteinuria and MI incidence was maintained (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.48-4.22). Every decrease of proteinuria from 2006 to 2008 was observed to be responsible for a 21% decline of MI incidence (HR 0.79, 95% CI 0.68-0.90). The interaction between changes in proteinuria and diabetes was confirmed with no effect on MI (P = 0.3371)., Conclusions: Persistent proteinuria is an independent risk factor for MI incidence in the pre-diabetic and diabetic population. These findings may help clinicians to interpret proteinuria changes in the outpatient setting and provide possible preventive approaches for people with pre-diabetes or diabetes.

Objectives: Low nocturnal melatonin secretion is associated with cardiovascular risk factors, diabetes and hypertension, while individuals with prevalent cardiovascular disease have lower nocturnal melatonin levels. However, the prospective association of melatonin secretion with myocardial infarction (MI) has not been studied. We aimed to study the association between melatonin secretion and the risk of developing MI., Methods: We performed a prospective nested case-control study of participants from the Nurses' Health Study cohorts I and II. A total of 209 incident cases of fatal and non-fatal MI were identified among women who provided first morning voided urine specimens at baseline and were matched to 209 controls. Nocturnal melatonin secretion was assessed using 6-sulfatoxymelatonin concentrations in morning urines normalised to the urines' creatinine concentration. Multivariable conditional logistic regression was used to analyse associations independent of important risk factors., Results: Lower melatonin secretion was significantly associated with a higher risk of MI. After conditioning on matching variables, the OR for every one unit lower log-transformed sulfatoxymelatonin/creatinine ratio was 1.51 (95% CI 1.16 to 1.96). In multivariable models controlling for factors included in the American Heart Association Cardiovascular Risk Score plus circadian factors, every one unit lower in the ratio was associated with a significantly increased risk of MI (OR, 1.40; 95% CI 1.02 to 1.93). Women in the highest category had an estimated absolute risk of MI of 84 cases per 100 000 person-years compared with 197 cases per 100 000 person-years in the lowest category. The association was strongly modified by body mass index (BMI) (p value for interaction=0.02)., Conclusions: Lower melatonin secretion was significantly associated with a greater risk of incident MI in women with increased BMI. Melatonin may be a novel and modifiable risk factor for MI among such women., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Links between environmental chemicals and human health have emerged over the last few decades, but the effects from polyaromatic hydrocarbons were less studied, compared to other commonly known environmental chemicals such as heavy metals, phthalates, arsenic, phenols and pesticides. Therefore, it was aimed to study the relationships of urinary polyaromatic hydrocarbons and adult cardiovascular disease and cancer using human sample in a national and population-based study in recent years. Data was retrieved from US National Health and Nutrition Examination Surveys, 2011-2012, including demographics, self-reported health conditions and urinary polyaromatic hydrocarbons. Statistical analyses included chi-square test, t test, survey-weighted logistic regression modeling and population attributable risk (PAR) estimation. Of 5560 American adults aged 20-80 and included in the statistical analysis, urinary polyaromatic hydrocarbons (representatively in one-third sample) were observed to be higher in people with cardiovascular disease and total cancer. In particular, urinary 4-hydroxyphenanthrene was associated with hypertension (odds ratio (OR) 1.33, 95% confidence interval (CI) 1.00-1.76, P = 0.048, PAR 5.1%), urinary 1-hydroxypyrene was significantly associated with heart attack (OR 1.47, 95%CI 1.05-2.06, P = 0.027, PAR 1.7%), and urinary 2-hydroxynapthalene (2-naphthol) was associated with cancer (OR 1.46, 95%CI 1.12-1.90, P = 0.008, PAR 3.9%). Urinary polyaromatic hydrocarbons were associated with adult hypertension, heart attack and cancer, although the causality cannot be established. From the research perspective, future studies with a longitudinal or experimental approach would be suggested. From the law and public health perspectives, regulation on minimizing exposure to polyaromatic hydrocarbons might need to be considered in future health and environmental policies and intervention programs.

The prevalence of type 1 cardiorenal syndrome (CRS) is increasing and strongly associated with long-term mortality. However, lack of reliable animal models and well-defined measures of renoprotection, made early diagnosis and therapy difficult. We previously successfully established the swine acute myocardial infarction (AMI) model of ischemia-reperfusion by blocking left anterior descending branch (LAD). Reperfusion was performed after 90-minute occlusion of the LAD. AMI was confirmed by ECG and left ventricular angiography (LVG). Then those 52 survived AMI reperfusion swine, including ventricular fibrillation-cardiac arrest after restoration of blood flow, were randomly divided into four groups (four/group) according to different interventions: resuscitation in room temperature, resuscitation with 500 ml saline in room temperature, resuscitation with 4°C 500 ml saline and normal control (with no intervention of resuscitation). Each group was further observed in four groups according to different time of resuscitation after ventricular arrhythmias: 1, 3, 5, 10-minute reperfusion after ventricular arrhythmias. Plasma and random urine were collected to evaluate renal function and test renal biomarkers of acute kidney injury (AKI). Our swine AMI model of ischemia-reperfusion provoked subclinical AKI with the elevation of the tubular damage biomarker, NGAL, IL-18 and L-FABP. Renal damage rapidly observed after hemodynamic instability, rather than observation after several hours as previously reported. The increasing rate of biological markers declined after interventions, however, its impact on the long-term prognosis remains to be further studied. These data show that elevation of tubular damage biomarkers without glomerular function loss may indicate appropriate timing for effective renoprotections like hypothermia resuscitation in type 1 CRS.

Leukotrienes (LTs), highly bioactive lipid mediators play a major role in inflammation, wound healing and in the development of atherosclerosis. LTs biosynthesis have been suggested to be increased in myocardial infarction (MI) and in surgical patients with abdominal aortic aneurysms. Among LTs, Cysteinyl-LTs have the most potent biological properties and their production is well reflected by LTE4 concentration in urine (uLTE4). Aim of the study was to evaluate perioperative biosynthesis of uLTE4 in noncardiac vascular surgery patients, and its impact on patients' outcomes. Twenty eight consecutive patients aged 61.5 (59.0-72.5) that undergone an elective surgery for abdominal aortic aneurysm (AAA; n=6) or peripheral artery disease (PAD; n=22) were studied. uLTE4 was measured in urine samples using ELISA: before surgery (LT0), 6 hours postoperatively (LT1), and on three following days (LT2-LT4), and the results were adjusted for the urinary creatinine concentration. Patients were followed-up for 30-days for cardio-vascular complications including myocardial infarction (MI) with active post-surgery troponin T screening. One way analysis of variance (ANOVA) for repeated measurements and logistic regression tests were used to analyse the data with P<05 considered significant. Excretion of uLTE4 raised in the first two urine sample (LT1 and LT2) after surgery as compared to preoperative baseline value (LT0) (P=0.008) and returned to normal values on the second day (LT3). Patients that suffered MI during postoperative period had increased uLTE4 levels when compared to the no-MI patients (P=0.006). In conclusion we state that uLTE4 biosynthesis is increased shortly after surgery and returns to the preoperative level on the second day. The increase in uLTE4 biosynthesis is higher in patients that suffer MI after surgery, however this warrants further investigations.

Aim: A genetic variant (rs20417) of the PTGS2 gene, encoding for COX-2, has been associated with decreased COX-2 activity and a decreased risk of cardiovascular disease (CVD). However, this genetic association and the role of COX-2 in CVD remain controversial., Methods and Results: The association of rs20417 with CVD was prospectively explored in 49 232 subjects (ACTIVE-A, CURE, epiDREAM/DREAM, ONTARGET, RE-LY, and WGHS) and the effect of potentially modifiable risk factors on the genetic association was further explored in 9363 INTERHEART participants. The effect of rs20417 on urinary thromboxane and prostacyclin metabolite concentrations was measured in 117 healthy individuals. Carriage of the rs20417 minor allele was associated with a decreased risk of major CVD outcomes (OR = 0.78, 95% CI: 0.70-0.87; P = 1.2 × 10(-5)). The genetic effect was significantly stronger in aspirin users (OR: 0.74, 95% CI: 0.64-0.84; P = 1.20 × 10(-5)) than non-users (OR: 0.87, 95% CI: 0.72-1.06; P = 0.16) (interaction P-value: 0.0041). Among patients with previous coronary artery disease (CAD), rs20417 carriers had a stronger protective effect on risk of major adverse events when compared with individuals without previous CAD (interaction P-value: 0.015). Carriers had significantly lower urinary levels of thromboxane (P = 0.01) and prostacyclin (P = 0.01) metabolites when compared with non-carriers., Conclusion: The rs20417 polymorphism is associated with a reduced risk of major cardiovascular events and lower levels of thromboxane and prostacyclin. Our results suggest that a genetic decrease in COX-2 activity may be beneficial with respect to CVD risk, especially, in higher risk patients on aspirin., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

It has been speculated that trace elements may a play role in the pathogenesis of heart diseases. In the present study, we aimed to assess the levels of selenium (Se) and mercury (Hg) in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both genders (age range 45-60 years) at the first, second, and third heart attack (n = 130), hospitalized in a cardiac ward of a civil hospital of Hyderabad City (Pakistan). For comparison, healthy age-matched referent subjects (n = 61) of both genders were also selected. Se and Hg in biological samples were measured by electrothermal atomic absorption spectrometry and cold vapor atomic absorption spectrometry, prior to microwave acid digestion, respectively. The validity of the methodology was checked by biological certified reference materials. During this study, 78 % of the 32 registered patients of third MI attack (aged >50 years) died. The concentration of Se was decreased in scalp hair and blood samples of MI patients, while Hg was higher in all biological samples as compared to referent subjects. Se concentration was inversely associated with the risk of MI attacks in both genders. These results add to an increasing body of evidence that Se is a protective element for cardiovascular health.

Biomarkers play a critical role in the diagnosis of acute myocardial infarction (AMI), especially in patients with atypical clinical and/or electrocardiographic presentation or co-morbidities, like the elderly. High-sensitivity assays based on specific biomarkers (e.g. cardiac troponins) enabling earlier AMI diagnosis have recently become available in clinical practice. Although no single biomarker of myocardial necrosis is ever likely to afford AMI diagnosis, a combination including different biomarkers for necrosis and ischemia, like new circulating molecules (microRNAs), could enhance diagnostic specificity. We review the recent literature on conventional and novel AMI biomarkers, with special emphasis on circulating microRNAs.

Albuminuria has been shown to be associated with mortality and cardiovascular events, independent of traditional cardiovascular risk factors. This suggests that albuminuria may not just represent glomerular damage, but may be a marker of more diffuse endothelial dysfunction. We investigated the relationship between urinary albumin levels after an acute coronary syndrome and cardiovascular outcomes in statin treated subjects after acute coronary syndromes (ACS). Furthermore we assessed the effect of intensive statin treatment on albuminuria among patients in the PROVE IT-TIMI 22 trial, in which patients who had been hospitalized with ACS were randomized to pravastatin 40 mg (standard therapy) or atorvastatin 80 mg daily (intensive therapy). In univariate analyses, increasing urine albumin concentration was associated with increased risk of myocardial infarction, stroke, heart failure, and composite of death, myocardial infarction and stroke at 2 years. However, in a multivariable model containing traditional cardiovascular risk factors, albuminuria was not an independent predictor of the primary PROVE IT endpoint of death, myocardial infarction, unstable angina, revascularization and stroke, and was only an independent predictor of all-cause mortality at urinary albumin concentration >300 mcg/ml. There was no significant change in urinary albumin concentration from enrolment to end of study in either the standard or intensive statin therapy groups, and no significant difference between treatment groups. Our results suggest that after an acute coronary syndrome in statin treated patients, microalbuminuria may reflect traditional cardiovascular risk factor burden and offer little prognostic information independent of those factors.

Aims: Kynurenine is a potent endothelium-derived vasodilator. Its synthesis from tryptophan is stimulated by interferon γ and may represent an important compensatory pathway for the regulation of vascular function in inflammatory conditions. We assessed associations of urine kynurenine to tryptophan ratio (KTR) levels to incident major coronary events (MCEs), acute myocardial infarction (AMI), and ischaemic stroke and mortality in patients with suspected stable coronary artery disease (CAD)., Methods and Results: A total of 3224 patients (mean age 62 years, 69% men) underwent urine and blood sampling prior to elective coronary angiography and were subsequently followed up for median 55 months. A total of 8.4% experienced an MCE, 7.8% suffered an AMI, and 7.6% died. In age- and gender-adjusted analyses, the hazard ratios [HRs; 95% confidence intervals (CI)] of MCE, AMI, and all-cause mortality were 1.43 (1.29-1.59), 1.44 (1.29-1.59), and 1.38 (1.23-1.54) per standard deviation increment of the (log-transformed) urinary KTR, respectively. These estimates were only minimally attenuated after adjustment for potential confounders. The addition of the urine KTR to a model of conventional risk factors significantly improved goodness of fit, discrimination, and risk classification for these clinical endpoints. No association was seen between the urine KTR and the risk of incident ischaemic stroke., Conclusion: A novel urinary inflammation marker, KTR, is strongly associated with adverse prognosis in patients with suspected stable CAD. Underlying pathomechanisms should be further elucidated.

Background: Aspirin's therapeutic action is via inhibition of platelet cyclooxygenase 1 (COX-1) thromboxane A2 (TxA2) production. The aim of this study was to evaluate TxA2 production, in the absence of platelet COX-1 activity, in coronary atherosclerotic heart disease patients with and without atherothrombotic myocardial infarction (MI)., Methods and Results: TxA2 production, in the absence of platelet COX-1 activity, was evaluated in 44 patients taking aspirin on 3 commercially available assays that detect metabolites of TxA2 in the urine. Two assays measure urine 11-dehydro-thromboxane B2 (TxB2) alone and 1 measures urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2. Platelet COX-1 inhibition was confirmed on <10% platelet aggregation in response to ≥1 mmol/L arachidonic acid. Median urine 11-dehydro-TxB2 was no different in those with and without a diagnosis of atherothrombotic MI (325 vs. 311 pg/mg creatinine, P=0.59 via polyclonal ELISA) and (312 vs. 244 pg/mg creatinine, P=0.11 via LC-MS/MS). Median urine 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2, however, was higher in those with vs. those without a diagnosis of atherothrombotic MI (1,035 vs. 606 pg/mg creatinine, P=0.03 via monoclonal ELISA)., Conclusions: Differences in TxA2 production, in the absence of platelet COX-1 activity, between those with vs. without atherothrombotic MI were not observed when TxA2 generation was assessed on 11-dehydro-TxB2 production alone (polyclonal ELISA or LC-MS/MS), but differences were observed when TxA2 generation was assessed using 11-dehydro-TxB2 plus 11-dehydro-2,3-dinor-TxB2 (monoclonal ELISA). These findings highlight important differences between different commercially available assays for TxA2 generation and suggest that 11-dehydro-2,3-dinor-TxB2 may be critical to the biology of atherothrombosis.

Aim: To study renal dysfunction in patients with myocardial infarction (MI)., Subjects and Methods: 670 case histories of patients diagnosed with acute coronary syndrome, including 369 (55.8%) men and 292 (44.2%) women at the age of 33 to 85 years (mean age 64.8 +/- 11.7 years), were retrospectively studied. The authors considered comorbidities and analyzed complaints, history data, and the results of physical examinations, biochemical blood tests for plasma glucose, troponin, MB fractions of creatine phosphokinase and creatinine, and cholesterol in all the patients. Instrumental studies involved electro- and echocardiography. Glomerular filtration rate (GFR) was estimated using the MDRD formula. The patients were divided into groups according to GFR values: 1) > 90 ml/min/1.73 m2; 2) 60 to 89 ml/min/1.73 m2; 3) 30 to 59 ml/min/1.73 m2; 4) less than 30 ml/min/1.73 m2., Results: Most patients were found to have a moderate or significant reduction in kidney function. Worsening renal function in patients with MI was associated with advanced patient age, the lower proportion of men in the patient structure, the higher prevalence of concomitant cardiovascular diseases, such as arterial hypertension, chronic heart failure, and prior MI, and diabetes mellitus., Conclusion: The findings suggest that kidney dysfunction is of essential value in developing the multiplicity of comorbidities in patients with MI. The wide introduction of a GFR calculating method in daily medical practice will be able to adequately and timely identify renal filtration function and to make a correction into a treatment regimen, thus decreasing the number of poor outcomes.

Objective: To observe the change of urine level of cardiac specific microRNA-1 (miR-1) in patients with ST segment elevation acute myocardial infarction (STEAMI) and investigate its potential applications., Methods: Urine samples were collected from 20 STEAMI patients within 12 hours after STEAMI and from 20 healthy volunteers as control. Urine miR-1 concentrations were measured with real-time quantity reverse transcription-polymerase chain reaction (qRT-PCR), at the same time serum cardiac troponin I (cTnI) and MB isoenzyme of creatine kinase (CK-MB) concentrations were measured., Results: Serum level of cTnI, CK-MB and urine level of miR-1 in STEAMI patients were obviously higher than those in healthy control group [cTnI in blood: 19.27±7.53 μg/L vs. 0.02±0.01 μg/L, CK-MB in blood: 93.82±12.30 μg/L vs. 0.86±0.63 μg/L, miR-1 in urine (Ct value): 45.50±4.21 vs. 52.63±4.41, P<0.05 or P<0.01]. The urine miR-1 level in patients with STEAMI had a strong correlation with serum CK-MB or cTnI when CK-MB < 300 μg/L and cTnI <50 μg/L (Ct value of urine miR-1 with blood CK-MB: r=-0.81, P<0.01; Ct value of urine miR-1 with blood cTnI: r=-0.63, P<0.05)., Conclusions: The results suggest that urine miR-1 could be a novel sensitive biomarker the early diagnosis of SETAMI.

The currently used biomarkers for acute myocardial infarction (AMI) are blood creatinine phosphokinase-muscle band (CPK-MB), troponin-T (TnT), and troponin I (TnI). However, no good biomarkers are identified in urine after AMI, because these blood protein biomarkers are difficult to be filtered into urine. In this study, the role of urine microRNAs in the diagnosis of AMI and the mechanism involved were determined. We found that urine miR-1 was quickly increased in rats after AMI with peak at 24h after AMI, in which an over 50-fold increase was demonstrated. At 7 days after AMI, the urine miR-1 level was returned to the basal level. No miR-208 was found in normal urine. In urine from rats with AMI, miR-208 was easily detected. To determine the mechanism involved, we determined the levels of heart-released miR-1 in the liver, spleen and kidney after AMI in rats and found that the kidney was an important metabolic organ. To determine the renal elimination of blood miRNAs, we isolated serum exosomes from rats after AMI and injected these exosomes into the circulating blood of normal rats. We found that the urine miR-1 was significantly increased in exosome-injected animals. Moreover, PKH67-labeled exosomes injected into circulating blood could enter into the kidney tissues and cells, as well as urine. Furthermore, the levels of urine miR-1 were significantly increased in patients with AMI. The results suggest that urine miRNAs such as miR-1 could be novel urine biomarkers for AMI., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Introduction: Previous studies have revealed that acute myocardial infarction (AMI) with acute kidney injury (AKI), about 17%, is strongly related to long-term mortality and heart failure. The dynamic changes in renal function during AMI are strongly related to long-term mortality and heart failure., Objectives: Our study used clinical parameters and AKI biomarkers including neutrophil gelatinase-associated lipocalin, interleukin (IL)-6, IL-18, and cystatin C to evaluate prognostic relevance of AKI in the setting of AMI., Methods: This prospective study was conducted from November 2009 to January 2011 and enrolled sequential 96 patients with catheter-proven AMI; it was approved by the institutional review board of Chang Gung Memorial Hospital, Taiwan (institutional review board no. 99-0140B) and conformed to the tenets of the Declaration of Helsinki. The definition of AKI is the elevation of serum creatinine of more than 0.3 mg/dL within 48 hours., Results: Our results show that the incidence of AKI after AMI is 17.7% (17 patients). The following could be statistically related to AKI after AMI: age (P = .012), cardiac functions (Killip stage and echocardiogram; P = .003 each), Thrombolysis in Myocardial Infarction (TIMI) flow grade (P < .001), stenting (P < .001), neutrophil gelatinase-associated lipocalin (P = .005), IL-6 (P = .01), IL-18 (P = .002), and cystatin C (P = .002) in serum. The TIMI flow grade and serum cystatin C were shown to be important predictors by using multivariate analysis. Both TIMI flow lower than grade 2 and serum cystatin C of more than 1364 mg/L could be used to predict AKI (both overall correctness, 0.78). Moreover, IL-6 in serum is also associated with the major cardiovascular events after AMI (P = .02), as demonstrated in our study., Conclusion: In conclusion, the worse TIMI flow and high plasma cystatin C can be used to predict AKI after AMI. Moreover, IL-6 can also be used as a 30-day major cardiovascular event indicator after AMI. A larger prospective and longitudinal study should follow the relationship between AKI predictors after AMI., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Recently, much attention has been focused on cardio-renal interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is produced in the proximal tubule by renal hypoxia and oxidative stress, has been identified as a useful marker for diagnosis of acute kidney disease and a predictor of future events in chronic kidney disease. However, the clinical significance of U-L-FABP measurements in patients with acute coronary syndrome (ACS) has not been completely evaluated., Methods and Results: This study included 50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and 13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other serum parameters were measured at admission and at 24 h after percutaneous coronary intervention., Results: U-L-FABP levels in patients with AMI were significantly higher (p=0.0019), than in control subjects, while patients with UAP did not exhibit such an increase. U-L-FABP levels at admission were positively correlated with brain natriuretic protein levels (p=0.001) and duration of hospitalization (p=0.025). At follow-up angiography, patients with restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels (p<0.0001) than those without restenosis. After a median follow-up of 42 months, U-L-FABP levels at second measurement in patients with major adverse cardiocerebrovascular events (MACCEs) were significantly higher than those in patients without MACCEs (p=0.028). After adjusting for confounding factors, high U-L-FABP levels at second measurement were found to be independent factors for MACCEs (p=0.019)., Conclusions: These data suggest that patients with ACS, especially those with AMI, have high U-L-FABP levels, and that U-L-FABP measurements may be useful in identifying high-risk patients for future cardiovascular events after ACS., (Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background: Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF., Method: In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI., Results: Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage., Conclusions: The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.

Background: Cardiac events are the main cause of death among patients with end-stage renal failure. Even a mild renal disease is currently considered a major risk factor for cardiovascular complications following myocardial infarction (MI). The aim of the present study was to detect histological, sera and urine characteristics of kidney injury in cardiorenal syndrome (CRS) compared to chronic kidney disease (CKD) with an intact cardiac function., Methods: We employed a rat model for CRS, in which an acute MI (AMI) was induced 4 weeks after establishment of subtotal nephrectomy. Four weeks later, left ventricular function was assessed by echocardiography and changes in renal performance were examined using histological and biochemical parameters., Results: Increased interstitial fibrosis as well as renal inflammation were observed in renal sections derived from CRS rats, compared to subtotal nephrectomy (CKD)-only animals. Moreover, we found that even though AMI on the background of CKD was not associated with a further decrease in creatinine clearance or a further increase in sera BUN levels compared to CKD only, a significant long-term elevation in urine neutrophil gelatinase-associated lipocalin (Ngal) levels was detectable post-MI induction., Conclusions: AMI in the CKD setting is associated with accelerated renal fibrosis and long-term elevated urine Ngal values, suggesting that cardiac dysfunction contributes to accelerated intrinsic kidney injury in CKD. The data indicate that elevated urine Ngal may potentially serve as an early non-invasive laboratory parameter for a left ventricular dysfunction-related renal injury., (Copyright © 2012 S. Karger AG, Basel.)

Background: In spite of great advances in target-oriented Western medicine for treating myocardial infarction (MI), it is still a leading cause of death in a worldwide epidemic. In contrast to Western medicine, Traditional Chinese medicine (TCM) uses a holistic and synergistic approach to restore the balance of Yin-Yang of body energy so the body's normal function can be restored. Sini decoction (SND) is a well-known formula of TCM which has been used to treat MI for many years. However, its holistic activity evaluation and mechanistic understanding are still lacking due to its complex components., Methodology/principal Findings: A urinary metabonomic method based on nuclear magnetic resonance and ultra high-performance liquid chromatography coupled to mass spectrometry was developed to characterize MI-related metabolic profiles and delineate the effect of SND on MI. With Elastic Net for classification and selection of biomarkers, nineteen potential biomarkers in rat urine were screened out, primarily related to myocardial energy metabolism, including the glycolysis, citrate cycle, amino acid metabolism, purine metabolism and pyrimidine metabolism. With the altered metabolism pathways as possible drug targets, we systematically analyze the therapeutic effect of SND, which demonstrated that SND administration could provide satisfactory effect on MI through partially regulating the perturbed myocardial energy metabolism., Conclusions/significance: Our results showed that metabonomic approach offers a useful tool to identify MI-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating MI.

Background: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients., Methods: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days., Principal Findings: The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002)., Conclusions: Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk.

Context: The precise relationship between sodium and potassium intake and cardiovascular (CV) risk remains uncertain, especially in patients with CV disease., Objective: To determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and CV events in patients with established CV disease or diabetes mellitus., Design, Setting, and Patients: Observational analyses of 2 cohorts (N = 28,880) included in the ONTARGET and TRANSCEND trials (November 2001-March 2008 from initial recruitment to final follow-up). We estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample (Kawasaki formula). We used restricted cubic spline plots to describe the association between sodium and potassium excretion and CV events and mortality, and to identify reference categories for sodium and potassium excretion. We used Cox proportional hazards multivariable models to determine the association of urinary sodium and potassium with CV events and mortality., Main Outcome Measures: CV death, myocardial infarction (MI), stroke, and hospitalization for congestive heart failure (CHF)., Results: At baseline, the mean (SD) estimated 24-hour excretion for sodium was 4.77 g (1.61); and for potassium was 2.19 g (0.57). After a median follow-up of 56 months, the composite outcome occurred in 4729 (16.4%) participants, including 2057 CV deaths, 1412 with MI, 1282 with stroke, and 1213 with hospitalization for CHF. Compared with the reference group with estimated baseline sodium excretion of 4 to 5.99 g per day (n = 14,156; 6.3% participants with CV death, 4.6% with MI, 4.2% with stroke, and 3.8% admitted to hospital with CHF), higher baseline sodium excretion was associated with an increased risk of CV death (9.7% for 7-8 g/day; hazard ratio [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for >8 g/day; HR, 1.66; 95% CI, 1.31-2.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for >8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for >8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.12-2.05 for >8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for <2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n = 2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for >3 g/day) on multivariable analysis., Conclusions: The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.

The exposure of toxic elements may directly or indirectly associate with different pathogenesis of heart diseases. In the present study, the association of arsenic (As), cadmium (Cd), cobalt (Co), lead (Pb), and nickel (Ni) in biological samples (whole blood and urine) and mortality from myocardial infarction (MI) patients at first, second, and third heart attacks was carried out. Both biological samples of 130 MI patients (77 male and 53 female), with ages ranging from 45 to 60 years, and 61 healthy persons (33 male and 28 female) of the same age group were collected. The elements in biological samples were assessed by electrothermal atomic absorption spectrophotometer, prior to microwave-assisted acid digestion. The validity of methodology was checked by the biological certified reference materials. During this study, 78% of 32 patients aged above 50 years, registered after third MI attack, died. In these subjects, the levels of As, Cd, Co, Ni, and Pb in blood samples were higher in MI patients as compared with referents (p < 0.05), while increased by 11.7%, 12.2%, 5.55%, and 7.2%, respectively, in the blood samples of those patients who tolerated the third MI attack (p = 0.12). The high level of understudied toxic elements may play a role in the mortality of MI patients.

A metabolomic method using reversed-phase liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS) was developed to obtain a systematic view of the development and progression of myocardial infarction (MI). By combining with partial least squares discriminant analysis (PLS-DA), 16 biomarkers in rat urine were identified and eight of them were related to the pathway of energy metabolism. Among the regulated pathways, the citric acid cycle related network was acutely perturbed. The metabolomic results not only supplied a systematic view of the development and progression of MI but also provided the theoretical basis for the prevention or treatment of MI. The developed method was also used to analyze the therapeutic effects of a traditional Chinese medicine (TCM) named Shexiang Baoxin Pill (SBP), a widely used anti-MI medicine in clinics. The results showed that SBP administration could provide satisfactory effects on MI through partially regulating the perturbed pathway of energy metabolism.

Background: Microalbuminuria has been reported to occur in patients with acute myocardial infarction (AMI) and associated with worse outcome. In our prospective analysis we included patients with AMI with the primary aim to examine whether urinary albumin excretion is increased in those patients and whether it is associated with worse in-hospital prognosis (major complications). The secondary objective was to examine the predictive power of microalbuminuria for 6-month mortality and re-hospitalization for cardiovascular disease., Methods: One hundred thirty patients admitted to the Coronary Care Unit were studied prospectively. The diagnosis of myocardial infarction was based on the latest criteria of the European Cardiac Society. Microalbuminuria was defined as a urinary albumin creatinine ratio (UACR) and was measured on the third day after admission in the first morning urine sample., Results: One hundred thirty patients were enrolled in this study--82 (63.03%) men and 48 (36.92%) women, age 62.48 +/- 12 years. A high proportion of study patients (27.7%) had microalbuminuria and 8.5% had overt albuminuria (UACR over 25 mg/mmol in men and over 35 mg/mmol in women) at the time of urine examination. During the hospital stay (average 7.6 +/- 3.0 days) 4 patients (3.1%) died from cardiovascular complications and all had microalbuminuria. In our study a high percentage of patients with in-hospital nonfatal complications had microalbuminuria but it did not have positive predictive association with the occurrence. During a 6-month follow-up period, 8 patients died from cardiovascular cause. In-hospital and total mortality (in-hospital and the during six-month follow-up) were significantly frequent in patients with microalbuminuria (p < 0.05). During a six-month follow-up period, 24 patients (18.5%) were re-hospitalized for cardiovascular disease and, among them, 54.2% had microalbuminuria. In univariant regression analysis microalbuminuria increased the risk for re-hospitalization, but multiple analysis didn't show the significance., Conclusions: We found that UACR measured during the first week after AMI is independently associated with increased long-term risk for in-hospital and six-month mortality. On the basis of these results, we suggest that this measurement should be included in the routine clinical work up of patients with AMI.

Objectives: Circulating microRNAs (miRNAs) are promising as biomarkers for various diseases. We examined the release patterns of cardiospecific miRNAs in a closed-chest, large animal ischemia-reperfusion model and in patients with ST elevation myocardial infarction (STEMI)., Methods: Six anesthetized pigs were subjected to coronary occlusion-reperfusion. Plasma, urine, and clinical parameters were collected from 25 STEMI patients undergoing primary percutaneous coronary intervention. miRNA was extracted and measured with qPCR., Results: In the pig reperfusion model miR-1, miR-133a, and miR-208b increased rapidly in plasma with a peak at 120 min, while miR-499-5p remained elevated longer. In patients with STEMI all 4 miRNAs increased abruptly from 70-fold to 3,000-fold in plasma, with a peak within 12 h (p < 0.01). miR-1 and miR-133a both correlated strongly with the glomerular filtration rate (GFR), indicating renal elimination. This was confirmed by detection of miR-1 and miR-133a, but not miR-208b or miR-499-5p, in urine. Peak values of miR-208b correlated with peak troponin and the ejection fraction., Conclusion: We demonstrate a distinct and rapid increase in levels of cardiospecific miRNA in the circulation after myocardial infarction. Release of miRNAs correlated with cardiomyocyte necrosis markers, the ejection fraction, and the GFR, indicating a possible role for these molecules as biomarkers for the diagnosis of STEMI as well as the prediction of long-term complications., (Copyright © 2011 S. Karger AG, Basel.)

A study was undertaken amog 80 non-diabetic patients of acute myocardial infarction (AMI) admitted within 24 hours of the onset of pain, to investigate the prevalence and significance of microalbuminuria (MA) as a predictor of in-hospital mortality, and also to correlate it with other well-established prognostic markers. Spot urinary albumin-to-creatinine ratio (ACR) was measured in first morning sample on day 1 (D1), day 4 (D4) and/or day 7 (D7). Haemodynamic status was assessed clinically by Killip's class and the ejection fraction was measured by echocardiography on D1, D4, and/or D7. Total 7 days mortality was recorded. MA (>30 microg/mg) was found in 95% of patients on 1,. In the group with higher value of MA (>100 microg/mg) on D1, there was significantly more deaths (p <0.01). Also there was significantly more deaths with static or increasing MA value from D1 to D4/D7 (p <0.01). Increasing or static MA had a positive correlation with deteriorating Killip's class in non-survivors, and also there was a correlation between decrease in left ventricular ejection fraction from D1 to D4/D7 and an increasing trend in MA over that period. Thus, MA was found to be a reliable predictor of short-term in-hospital mortality in AMI.

Objectives: Previous investigations on microalbuminuria in acute myocardial infarction have been performed in heterogeneous populations of hypetensive/nonhypertensive, diabetic/nondiabetic patients, submitted to either thrombolysis or mechanical revascularization or not revascularized. Therefore, the aim of our investigation was to assess, in 242 consecutive hypertensive patients with ST elevation myocardial infarction without previously known diabetes, all submitted to mechanical revascularization, whether microalbuminuria, in the early phase, has a prognostic role for in-hospital mortality or complications (acute pulmonary edema and arrhythmias)., Methods: The study population was divided into two groups according to microalbuminuria excretion: group A (microalbuminuria within the normal range); group B (microalbuminuria above the normal range)., Results: The incidence of microalbuminuria was 52.1% (126/242). No significant difference was detectable in the incidence of in-hospital mortality and complications between the two groups. Patients with microalbuminuria exhibit a larger infarct size as indicated by higher values of troponin I. Microalbuminuria was associated with higher values of glucose and a higher prevalence of insulin resistance., Conclusion: In ST elevation myocardial infarction hypertensive patients without previously known diabetes, all submitted to mechanical revascularization, microalbuminuria is a common finding but it does not yield prognostic information about in-hospital mortality or complications. Interestingly it was associated with acute glucose dysmetabolism (as inferred by hyperglycemia and the prevalence of insulin resistance), thus suggesting that it can be considered part of the acute metabolic response to the acute coronary event.

Background: C-reactive protein (CRP) is an established prognostic marker in the setting of acute coronary syndromes. Recently, albumin excretion rate also has been found to be associated with adverse outcomes in this clinical setting. Our aim was to compare the prognostic power of CRP and albumin excretion rate for long-term mortality following acute myocardial infarction (AMI)., Hypothesis: To determine whether albumin excretion rate is a better predictor of long-term outcome than CRP in post-AMI patients., Methods: We prospectively studied 220 unselected patients with definite AMI (median [interquartile] age 67 [60-74] y, female 26%, heart failure 39%). CRP and albumin-to-creatinine ratio (ACR) were measured on day 1, day 3, and day 7 after admission in 24-hour urine samples. Follow-up duration was 10 years for all patients., Results: At survival analysis, both CRP and ACR were associated with increased risk of 10-year all-cause mortality, also after adjusting for age, hypertension, diabetes mellitus, prehospital time delay, creatine kinase-MB isoenzyme peak, heart failure, and creatinine clearance. CRP and ACR were associated with nonsudden cardiovascular (non-SCV) mortality but not with sudden death (SD) or noncardiovascular (non-CV) death. CRP was not associated with long-term mortality, while ACR was independently associated with outcome both in short- and long-term analyses. At C-statistic analysis, CRP did not improve the baseline prediction model for all-cause mortality, while it did for short-term non-SCV mortality. ACR improved all-cause and non-SCV mortality prediction, both in the short and long term., Conclusions: ACR was a better predictor of long-term mortality after AMI than CRP.

Background: Urinary excretion of leukotriene (LT) E(4) is an index of LTC(4) biosynthesis and platelet-neutrophil interactions, which may occur in coronary heart disease and contribute to myocardial ischaemia. Enhanced LTC(4) biosynthesis may be a consequence of myocardial ischaemia or be linked to its pathogenetic substrate., Methods and Results: Overnight urine collections were obtained from 17 patients with chronic stable angina, three patients with Prinzmetal's angina, 16 patients with non ST-elevation acute coronary syndromes (NSTE-ACS) and six patients with acute ST-elevation myocardial infarction (STEMI). LTE(4) excretion was measured by enzyme immunoassay after HPLC separation. Compared with healthy controls (51.1 +/- 21.3 pg mg(-1) creatinine, mean +/- SD, n = 11) and with non-coronary cardiac controls (36.6 +/- 9.8 pg mg(-1) creatinine, n = 9), LTE(4) excretion was unchanged in stable angina (40.5 +/- 25.8 pg mg(-1) creatinine), but significantly (P < 0.01) increased in NSTE-ACS (122.7 +/- 137.2 pg mg(-1) creatinine) and STEMI (213.4 +/- 172.4 pg mg(-1) creatinine). In these patients, LTE(4) excretion rapidly dropped after day 1, consistent with effective coronary reperfusion. In patients with NSTE-ACS, the increase in LTE(4) excretion was entirely restricted to patients with recent (< 48 h) spontaneous anginal episodes. Myocardial ischaemia elicited by a positive exercise stress test was not accompanied by any detectable increase in LTE(4) excretion, while a significant (P < 0.01) increase was detected after a single-vessel percutaneous coronary interventions (PCI) procedure (n = 10), as compared with diagnostic angiography (n = 9)., Conclusions: In coronary heart disease, increased LTC(4) biosynthesis is restricted to ACS and not linked to myocardial ischaemia per se, but likely to the occurrence of plaque disruption.

Background: Many studies have examined the association between cardiovascular disease (CVD) mortality and the intake of essential micronutrients (potassium (K+), calcium (Ca(2+)), magnesium (Mg(2+)), and sodium (Na+)). They may separately reduce the CVD incidence to a small degree over the short term levels. The aim of the present study was to compare the levels of micronutrients in biological samples (whole blood, urine, and scalp hair) of myocardial infarction (MI) patients of both genders where ages ranged from 45 to 60 years at first, second and third heart attack (n = 232). For comparison purposes, healthy age-matched referent subjects (n = 103) and patients with cardiovascular without MI, of both genders were also selected., Methods: The elemental concentrations in scalp hair and whole blood were measured by flame atomic absorption spectrophotometer prior to microwave-induced acid digestion. The validity and accuracy was checked by means of certified reference materials., Results: The results of this study showed that the mean values of K+ and Mg(2+) were significantly reduced, while the Na+ level was higher in blood and scalp hair samples of MI patients as com-pared to control subjects of both genders (p < 0.05). The levels of Ca(2+) in the biological samples of MI patients were found to be higher than in referents, but the difference was not significant (p > 0.05). The urinary levels of these elements were found to be higher in MI patients than in the age-matched healthy controls., Conclusions: Although these data do not prove a causal relationship, these results are consistent with the hypothesis that deficiency and efficiency of some essential micronutrients may play a role in the development of heart disease. The micronutrient supplements containing K+ and Mg(2+) may be beneficial, but because of potential risks, use should be carefully monitored and restricted to men taking potassium-losing diuretics.

Chromium deficiency is associated with impaired glucose tolerance (IGT) and dyslipidemia. Hence, the objective of the current study was to investigate chromium status among Saudi men with and without established cardiovascular disease (CVD) and its relationship to glucose tolerance, lipid profile and other established CVD risk factors. We measured serum and urine chromium concentrations, fasted lipid profile, plasma glucose, and serum lipid peroxide in 130 Saudi men with an established history of myocardial infarction and 130 age-matched controls without established CVD. Patients with established CVD had higher serum triglycerides (p < 0.05) and plasma glucose (p < 0.0001) and lower serum and urinary chromium concentrations (p < 0.0001) than controls. Serum chromium was inversely correlated with plasma glucose among cases and controls (r = -0.189, p < 0.05 and r = -0.354, p < 0.00001, respectively). Plasma glucose (OR 1.127, CI 1.0-1.269, p < 0.05), serum chromium (OR 0.99, CI 0.985-0.995, p < 0.0001), and urinary chromium (OR 0.988, CI 0.981-0.995, p < 0.001) were independently associated with the presence of established coronary disease applying this model. While chromium metabolism appears to be altered in individuals with CVD, it is unclear whether chromium supplementation would be effective in CVD prevention among patients with IGT. This would need to be tested in long-term outcome trials.

Objective: To investigate urinary methylmalonic acid (uMMA) levels and their relationship with markers of myocyte necrosis and inflammation in patients with acute myocardial infarction (AMI)., Subjects and Methods: The study participants consisted of 80 consecutive patients with AMI and 72 age- and sex-matched consecutive controls. Of the patients, 38 had ST segment elevation myocardial infarction (STEMI) and 42 had non-ST segment elevation. All patients with STEMI underwent fibrinolytic therapy. Routine laboratory tests included troponin-I, creatinine phosphokinase MB (CK-MB), high-sensitivity C-reactive protein (hs-CRP), vitamin B(12), folate, homocysteine and methylmalonic acid analyses. uMMA measurements were made by a spectrophotometric method., Results: uMMA levels were significantly higher in patients with AMI than in controls (10.1 vs. 5.2 mmol/mol creatinine, p < 0.001) and higher in patients with anterior MI compared to those with non-anterior MI (18.9 vs. 8.7 mmol/mol creatinine, p < 0.001). In addition, uMMA levels were significantly higher in patients without successful reperfusion compared to those with successful reperfusion. In patients with STEMI, a strong positive association was found between urinary MMA and plasma hs-CRP levels (r = 0.81, p < 0.001), symptom duration (r = 0.91, p < 0.001) and wall motion score (r = 0.60, p = 0.006). More importantly, a strong positive association was observed between uMMA and the size of myocardial infarction in patients without successful reperfusion (for CK-MB r = 0.81, p = 0.013; for wall motion score r = 0.82, p = 0.012)., Conclusion: uMMA levels were elevated in patients with AMI and, as such, may be a candidate biochemical indicator of larger infarct size and enhanced inflammation in patients with AMI., (Copyright 2009 S. Karger AG, Basel.)

Background: Albumin excretion rate has been found to be associated with increased risk of mortality in several clinical settings. We assessed the relationship between urinary albumin and 7-year mortality in a cohort of patients with acute myocardial infarction (AMI)., Methods: In this prospective study, we examined 505 white patients admitted with AMI to the intensive care unit of 3 hospitals. Main end points were nonearly all-cause and cardiovascular (CV) mortality. Albumin-to-creatinine ratio (ACR) was measured by radioimmunoassay on the first, third, and seventh days after admission. Risk estimates were made using Cox proportional-hazard model and relative odds. Forty patients (7.9%) died early inhospital, and 175 (34.7%) died during the rest of the follow-up (nonearly mortality)., Results: The ACR measured on the third day predicted the occurrence of 7-year nonearly all-cause and CV mortality. Hazard ratios for ACR > or =0.97 mg/mmol were 3.0 (95% confidence limit 2.2-4.1), P < .0001, for nonearly all-cause mortality and 3.5 (95% confidence limit 2.5-5.0), P < .0001, for CV mortality. Correspondent fully adjusted hazard ratios were 1.9 (95% CI 1.4-2.6), P < .0001, and 2.2 (95% CI 1.5-3.2), P < .0001, respectively. By adding ACR to the 18-variable predictive model, ACR improved significantly both the goodness of fitting of the model for nonearly all-cause (P < .0001) and CV mortality (P < .0001) and the C-statistic value (P < .0001 and P = .002 for nonearly all-cause and CV mortality, respectively). Similar results were obtained for ACR measured on the first day or the seventh day., Conclusions: An early increase of urinary albumin in AMI is a strong independent predictor of long-term adverse clinical outcome. The ACR improved clinical prediction over and above baseline traditional multivariable risk models.

We conducted a cross-sectional analysis of individuals 45-79 years old in the National Health and Nutrition Examination Survey III (1988-1994) (NHANES III). Myocardial infarction was determined by electrocardiogram (ECG). Our sample included 4912 participants, which when weighted represented 52,234,055 Americans. We performed adjusted logistic regressions with the Framingham risk score, pack-years of smoking, race-ethnicity, and family history of heart attack, and diabetes as covariates. Urinary cadmium >or= 0.88 microg/g creatinine had an odds ratio of 1.86 (95% CI 1.26-2.75) compared to urinary cadmium <0.43 microg/g creatinine. This result supports the hypothesis that cadmium is associated with coronary heart disease. When logistic regressions were done by gender, women, but not men, showed a significant association of urinary cadmium with myocardial infarction. Women with urinary cadmium >or= 0.88 microg/g creatinine had an odds ratio of 1.80 (95% CI 1.06-3.04) compared to urinary cadmium <0.43 microg/g creatinine. When the analysis was restricted to never smokers (N=2187) urinary cadmium >or= 0.88 microg/g creatinine had an odds ratio of 1.85 (95% CI 1.10-3.14) compared to urinary cadmium <0.43 microg/g creatinine.