Results of the trycort: Cohort study of add-on antihypertensives for treatment of resistant hypertension.

Although true treatment resistant hypertension is relatively rare (about 7.3% of all patients with hypertension), optimal control of blood pressure is not achieved in every other patient due to suboptimal treatment or nonadherence. The aim of this study was to compare effectiveness, safety and tolerability of various add-on treatment options in adult patients with treatment resistant hypertension The study was designed as multi-center, prospective observational cohort study, which compared effectiveness and safety of various add-on treatment options in adult patients with treatment resistant hypertension. Both office and home blood pressure measures were recorded at baseline and then every month for 6 visits. The study cohort was composed of 515 patients (268 females and 247 males), with average age of 64.7 ± 10.8 years. The patients were switched from initial add-on therapy to more effective ones at each study visit. The blood pressure measured both at office and home below 140/90 mm Hg was achieved in 80% of patients with add-on spironolactone, while 88% of patients taking this drug also achieved decrease of systolic blood pressure for more than 10 mm Hg from baseline, and diastolic blood pressure for more than 5 mm Hg from baseline. Effectiveness of centrally acting antihypertensives as add-on therapy was inferior, achieving the study endpoints in <70% of patients. Adverse drug reactions were reported in 9 patients (1.7%), none of them serious. Incidence rate of hyperkalemia with spironolactone was 0.44%, and gynecomastia was found in 1 patient (0.22%). In conclusion, the most effective and safe add-on therapy of resistant hypertension were spironolactone alone and combination of spironolactone and a centrally acting antihypertensive drug.

A review of the risk and precipitating factors for spontaneous coronary artery dissection.

Introduction: Spontaneous coronary artery dissection (SCAD) accounts for 1%-4% of cases of acute coronary syndrome (ACS). SCAD is caused by separation occurring within or between any of the three tunics of the coronary artery wall. This leads to intramural hematoma and/or formation of false lumen in the artery, which leads to ischemic changes or infarction of the myocardium. The incidence of SCAD is higher in women than in men, with a ratio of approximately 9:1. It is estimated that SCAD is responsible for 35% of ACS cases in women under the age of 60. The high frequency is particularly observed during pregnancy and in the peripartum period (first week). Traditional risk factors are rare in patients with SCAD, except for hypertension. Patients diagnosed with SCAD have different combinations of risk factors compared with patients who have atherosclerotic changes in their coronary arteries. We presented the most common so-called "non-traditional" risk factors associated with SCAD patients. Risk factors and precipitating disorders which are associated with SCAD: In the literature, there are few diseases frequently associated with SCAD, and they are identified as predisposing factors. The predominant cause is fibromuscular dysplasia, followed by inherited connective tissue disorders, systemic inflammatory diseases, pregnancy, use of sex hormones or steroids, use of cocaine or amphetamines, thyroid disorders, migraine, and tinnitus. In recent years, the genetic predisposition for SCAD is also recognized as a predisposing factor. The precipitating factors are also different in women (emotional stress) compared with those in men (physical stress). Women experiencing SCAD frequently describe symptoms of anxiety and depression. These conditions could increase shear stress on the arterial wall and dissection of the coronary artery wall. Despite the advancement of SCAD, we can find significant differences in the clinical presentation between women and men. Conclusion: When evaluating patients with chest pain or other ACS symptoms who have a low cardiovascular risk, particularly female patients, it is important to consider the possibility of ACS due to SCAD, particularly in conditions often associated with SCAD. This will increase the recognition of SCAD and the timely treatment of affected patients.

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats.

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

Predictive potential of biomarkers and risk scores for major adverse cardiac events in elderly patients undergoing major elective vascular surgery.

Elderly patients scheduled for major elective vascular surgery are at high risk for a major adverse cardiac events (MACE). The objectives of the study were: (1) To determine the individual discriminatory ability of four risk prediction models and four biomarkers in predicting MACEs in elderly patients undergoing major elective vascular surgery; (2) to find a prognostic model with the best characteristics; (3) to examine the significance of all preoperative parameters; and (4) to determine optimal cut-off values for biomarkers with best predictor capabilities. We enrolled 144 geriatric patients, aged 69.97 ± 3.73 years, with a 2:1 male to female ratio. Essential inclusion criteria were open major vascular surgery and age >65 years. The primary outcome was the appearance of MACEs within 6 months. These were noted in 33 (22.9%) patients. The most frequent cardiac event was decompensated heart failure, which occurred in 22 patients (15.3%). New onset atrial fibrillation was registered in 13 patients (9%), and both myocardial infarction and ventricular arrhythmias occurred in eight patients each (5.5%). Excellent discriminatory ability (AUC >0.8) was observed for all biomarker combinations that included the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP). The most predictive two-variable combination was the Geriatric-Sensitive Cardiac Risk Index (GSCRI) + NT-proBNP (AUC of 0.830 with a 95% confidence interval). Female gender, previous coronary artery disease, and NT-proBNP were three independent predictors in a multivariate model of binary logistic regression. The Cox regression multivariate model identified high-sensitivity C-reactive protein and NT-proBNP as the only two independent predictors.

Preoperative Levels of the Soluble Urokinase-Type Plasminogen Activator Receptor as Predictor for New Episodes of Atrial Fibrillation After Vascular Surgery.

INTRODUCTION: The soluble urokinase-type plasminogen activator receptor (suPAR) in uPAR soluble form is produced when the uPAR is cleaved from the cell membrane during the inflammatory process. Postoperative atrial fibrillation (AF) is the most common perioperative cardiac arrhythmia. It is speculated that elevated suPAR has a role in the development of AF. The aim of our study was to investigate the predictive role of preoperative suPAR in the occurrence of AF during the first 6 months after major vascular surgery. METHODS: We included 119 male and 63 female patients with an average age of 67.19 ± 6.02 years, without permanent/persistent AF. Basic predictive model (BASIC) included traditional risk factors for AF: age, gender, body mass index-BMI, smoking status, presence of arterial hypertension, diabetes mellitus and dyslipidemia. RESULTS: Over the 6-month period, 19 (10.4%) patients had one new episode of atrial fibrillation and 2 patients (1.1%) had 2 episodes of paroxysmal atrial fibrillation. Paroxysms of AF were significantly more frequent in patients who had a resection of an abdominal aneurysm than in patients with other types of major vascular surgery. BASIC had good discriminatory ability in the prediction of AF paroxysms during the first 6 months after surgery (AUC = 0.715, 95%CI 0.590-0.840). Adding suPAR to the basic model significantly improved the discriminative ability of the predictive model for AF episodes (ΔAUC = 0.238, p < 0.001). The predictive performance of the model BASIC+CRP+suPAR, measured using AUC, NRI and IDI statistics, was very similar to the model BASIC+suPAR. CONCLUSION: AF is a common complication in surgical patients with high mortality and morbidity. suPAR could improve the ability of traditional risk factors to predict its occurrence up to 6 months after major vascular surgery.

Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride - involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism.

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg-1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4 to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.

Renal dysfunction as intrahospital prognostic indicator in acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE), due to hemodynamic disturbances, may lead to multi-organ damage, including acute renal dysfunction. The aim of our study was to investigate the predictive role of renal dysfunction at admission regarding the short-term mortality and bleeding risk in hospitalized PE patients. METHODS: The retrospective cohort study included 1330 consecutive patients with PE. The glomerular filtration rate (GFR) was calculated using the serum creatinine value and Cocroft-Gault formula, at hospital admission. Primary outcomes were all-cause mortality and PE-related mortality in the 30 days following admission, as well as major bleeding events. RESULTS: Based on the estimated GFR, patients were divided into three groups: the first with GFR < 30 mL/min, the second with GFR 30-60 mL/min, and the third group with GFR > 60 mL/min. A multivariable analysis showed that GFR at admission was strongly associated with all-cause death, as well as with death due to PE. Patients in the first and second group had a significantly higher risk of 30-day all-cause mortality (HR 7.109, 95% CI 4.243-11.911, p < 0.001; HR 2.554, 95% CI 1.598-4.081, p < 0.001). Fatal bleeding was recorded in 1.6%, 0.5% and 0.8% of patients in the first, second and in the third group (p < 0.05). There were no significant differences regarding major bleeding rates among the groups. CONCLUSION: Renal dysfunction at admission in patients with acute pulmonary embolism is strongly associated with overall PE mortality.

A Risk Stratification Model for Cardiovascular Complications during the 3-Month Period after Major Elective Vascular Surgery.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is an extensively used simple risk stratification tool advocated by the European Society of Cardiology and European Society of Anesthesiology (ESC/ESA). PURPOSE: The aim of this study was to find the best model for predicting 3-month cardiovascular complications in elective major vascular surgical patients using preoperative clinical assessment, calculation of the RCRI and Vascular Physiological and Operative Severity Score for the enumeration of mortality and morbidity (V-POSSUM) scores, and the preoperative levels of N-terminal brain natriuretic peptide (NT pro-BNP), high-sensitivity troponin I (hs TnI), and high-sensitivity C-reactive protein (hs CRP). MATERIALS AND METHODS: We included 122 participants in a prospective, single-center, observational study. The levels of NT pro-BNP, hs CRP, and hs TnI were measured 48 hours prior to surgery. During the perioperative period and 90 days after surgery the following adverse cardiac events were recorded: myocardial infarction, arrhythmias, pulmonary edema, acute decompensated heart failure, and cardiac arrest. RESULTS: During the first 3 months after surgery 29 participants (23.8%) had 50 cardiac complications. There was a statistically significant difference in the RCRI score between participants with and without cardiac complications. ROC analysis showed that a combination of RCRI with hs TnI has good discriminatory power (AUC 0.909, p<0,001). By adding NT pro-BNP concentrations to the RCRI+hs TnI+V-POSSSUM combination we obtained the model with the best predictive power for 3-month cardiac complications (AUC 0.963, p<0,001). CONCLUSION: We need to improve preoperative risk assessment in participants scheduled for major vascular surgery by combining their clinical scores with biomarkers. Therefore, it is possible to identify patients at risk of cardiovascular complications who need adequate preoperative diagnosis and treatment.

Preoperative Midregional Pro-Adrenomedullin and High-Sensitivity Troponin T Predict Perioperative Cardiovascular Events in Noncardiac Surgery.

OBJECTIVE: We evaluated the utility of preoperative midregional (MR) pro-adrenomedullin (proADM) and cardiac troponin T (TnT) for improved detection of patients at high risk for perioperative cardiac events and mortality after major noncardiac surgery. SUBJECTS AND METHODS: This prospective, single-center, observational study enrolled 79 patients undergoing major noncardiac surgery. After initial clinical assessment (clinical history, physical examination, echocardiogram, blood tests, and chest X-ray), MR-proADM and high-sensitivity TnT (hsTnT) were measured within 48 h prior to surgery by immunoluminometric and electrochemiluminescence immunoassay. Patients were followed by the consulting physician until discharge or up to 14 days in the hospital after surgery. Perioperative cardiac events included myocardial infarction and development or aggravation of congestive heart failure. Data were compared between patients who developed target events and event-free patients. RESULTS: Within 14 days of monitoring, 14 patients (17.72%) developed target events: 9 (11.39%) died and 5 (6.33%) developed cardiovascular events. The average age of the patients was 71.29 ± 6.62 years (range: 55-87). Sex, age, and hsTnT did not significantly differ between groups. MR- proADM concentration was higher in deceased patients (p = 0.01). The upper quartile of MR-proADM was associated with a fatal outcome (66.7 vs. 20.0%, p < 0.01) and with cardiovascular events (64.3 vs. 16.9%, p < 0.01). MR-proADM above the cutoff value (≥0.85) was associated with a fatal outcome (88.9 vs. 20.0%, p < 0.01) and cardiovascular events (71.4 vs. 28.6%, p < 0.01); this association was not observed for hsTnT. CONCLUSION: Preoperative measurement of MR-proADM provides useful information for perioperative cardiac events in high-risk patients scheduled for noncardiac surgery.

Amlodipine as an antiischemic drug is superior to long acting nitrates.

European Society of Cardiology Guidelines cite results of meta-analysis that the use of calcium channel blockers results in fewer angina episodes per week vs. long-acting nitrates. Moreover, we listed 12 reasons more to prefer amlodipine over long-acting nitrates, especially in stable angina pectoris patients with arterial hypertension. It may be the way to decrease polypharmacy without loosing efficacy. Some important advantages of amlodipine versus long-acting nitrate(s) are: amlodipine also treats hypertension, it helps reducing hypertensive target organ damages (e.g. left ventricular hypertrophy) and prevents morning blood pressure surge. Moreover, amlodipine can be given once daily (which improves adherence), it produces neither tolerance nor rebound, it has less side effects.