Urine Metabolites Changes in Acute Myocardial Infarction Rats via Metabolomic Analysis.

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.

Relationship between N-terminal pro-brain natriuretic peptide concentration and heart-type fatty acid-binding protein in postmortem urine.

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.

Acute myocardial infarction in a Chinese patient with paroxysmal nocturnal hemoglobinuria: A case report.

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.

Effect of ranolazine on plasma arginine derivatives and urinary isoprostane 8-iso-PGF2α in patients with myocardial infarction in the randomized RIMINI-Trial.

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-PGF2α 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-PGF2α 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.

Albuminuria as a Predictor of Cardiovascular Outcomes in Patients With Acute Myocardial Infarction.

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.

Urinary excretion of homocysteine thiolactone and the risk of acute myocardial infarction in coronary artery disease patients: the WENBIT trial.

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 B12 (0.4 mg)/vitamin B6 (40 mg); (ii) folic acid/vitamin B12 ; (iii) vitamin B6 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; Pinteraction = 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 B6 catabolism. These findings lend a support to the hypothesis that Hcy-thiolactone is mechanistically involved in cardiovascular disease.

Prediction of myocardial infarction, stroke and cardiovascular mortality with urinary biomarkers of oxidative stress: Results from a large cohort study.

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/m2). 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.

Leukotriene biosynthesis in coronary artery disease. Results of the Leukotrienes and Thromboxane In Myocardial Infarction (LTIMI) study.

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 single­center, 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 high­performance 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 log­transformed 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.

Differential Impact of Serial Measurement of Nonplatelet Thromboxane Generation on Long-Term Outcome After Cardiac Surgery.

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 B2 (11-dhTXB2), measured 3 days versus 6 months after surgery on the composite end point of death, myocardial infarction, revascularization or stroke, and death alone. 11-dhTXB2 measured 3 days after surgery did not independently predict outcome, whereas 11-dhTXB2 >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-dhTXB2 measured early after surgery associated with several markers of inflammation, in contrast to 11-dhTXB2 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.

Changes in proteinuria and the risk of myocardial infarction in people with diabetes or pre-diabetes: a prospective cohort study.

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.

Urinary neutrophil gelatinase-associated lipocalin and cystatin C compared to the estimated glomerular filtration rate to predict risk in patients with suspected acute myocardial infarction.

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.

Two-year changes in proteinuria and risk for myocardial infarction in patients with hypertension: a prospective cohort study.

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 ±â€Š10.9 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.

A nested case-control study of the association between melatonin secretion and incident myocardial infarction.

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.

Detection and evaluation of renal biomarkers in a swine model of acute myocardial infarction and reperfusion.

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.

Are urinary polyaromatic hydrocarbons associated with adult hypertension, heart attack, and cancer? USA NHANES, 2011-2012.

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.

Leukotrienes biosynthesis in vascular surgery patients during perioperative period.

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.

Association of cyclooxygenase-2 genetic variant with cardiovascular disease.

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.

Interaction between selenium and mercury in biological samples of Pakistani myocardial infarction patients at different stages as related to controls.

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.

Conventional and novel diagnostic biomarkers of acute myocardial infarction: a promising role for circulating microRNAs.

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.