Harms and Benefits of Using Aspirin for Primary Prevention of Cardiovascular Disease: A Narrative Overview

AbstractAspirin is one of the most often used drugs for prevention and treatment of a variety of thrombotic disorders. This narrative review aims to provide an overview of evidence highlighting potential benefits and relative harms of aspirin in primary prevention of cardiovascular disease. The authors summarize key findings of the ASPirin in Reducing Events in the Elderly (ASPREE) Investigator Group randomized trial and also provide a comparative overview of recent meta-analyses. Overall, all-cause mortality was largely heterogeneous, with some meta-analyses showing a modestly decreased risk in patients taking aspirin, with others reporting no effects, but the ASPREE Investigator Group trial evidencing 14% higher risk. Regarding cardiovascular disease, the most favorable impact could be noted for major adverse cardiovascular events, with most meta-analyses reporting a decreased risk in people receiving aspirin. Conversely, the ASPREE Investigator Group trial demonstrated no significant impact of aspirin on risk of cardiovascular mortality or ischemic stroke. A modest favorable effect of aspirin in decreasing the risk of myocardial infarction was noted in two meta-analyses, but not in other reports or in the ASPREE Investigator Group trial. Furthermore, one meta-analysis reported a lower risk of future cancer, others failed to report a significant effect, and the ASPREE Investigator Group trial reported a 31% increased risk. Unlike these conflicting outcomes, the bleeding risk of patients receiving aspirin was found to be consistently enhanced in all reports reviewed. These recent findings would lead us to conclude that the harms of aspirin in primary prevention of cardiovascular disease may be larger than the benefits, especially in the elderly general population

Transvaginal ligation of descending branch of uterine artery: could be the first surgical attempt to control post-partum haemorrhage?

Post-partum haemorrhage is the major cause of maternal death worldwide. This severe clinical condition can cause also physical morbidity and psychological distress (anemia, coagulopathy, blood transfusion, anterior pituitary ischemia with delay or failure of lactation, myocardial ischemia, postpartum depression). To date several efforts have been made to prevent and treat this severe condition mainly in three ways: medical, surgical, and interventional radiology even in combination. The surgical approach, needs the knowledge of anatomy of vascular distribution of the uterus. According to Palacios-Jaraquemada the feeding vessels of the body of the uterus is defined S1 area and the lower segment, uterine cervix and upper part of the vagina, S2 area. We report three cases in which the ligation of the descending branch of uterine artery (S2 area) helped the surgeon in the treatment of severe primary post-partum haemorrhage causing a significant reduction in blood loss

Urinary free cortisol assessment by liquid chromatography tandem mass spectrometry: a case study of ion suppression due to unacquainted administration of piperacillin

Introduction: Liquid chromatography coupled to atmospheric pressure ionization tandem mass spectrometry (LC-ESI-MS/MS) is currently considered the reference method for quantitative determination of urinary free cortisol (UFC). One of the major drawbacks of this measurement is a particular form of matrix effect, conventionally known as ion suppression. Materials and methods: We describe here the case of a 66-year-old-patient referred to the daily service of general medicine for intravenous antibiotic administration due to a generalized Staphylococcus aureus infection and for routine 24 hours UFC monitoring in the setting of glucocorticoid replacement therapy. Results: The observation of 10-fold decrease of internal standard of cortisol signal led us to hypothesize the presence of an ion suppression effect due to a co-eluting endogenous compound. Screening analysis of tandem mass spectrometry (MS/MS) spectra of the interfering molecule, along with in vitro confirmation analyses, were suggestive of the presence of high concentration of piperacillin. The problem was then easily solved with minor modifications of the chromatographic technique. Conclusions: According to our findings, antibiotic therapy with piperacillin/tazobactam should be regarded as an important interference in UFC assessment, which may potentially affect detection capability, precision and accuracy of this measurement. This case report emphasizes that accurate anamnesis and standardization of all phases of urine collection are essential aspects for preventing potential interference in laboratory testing. \ua9 Croatian Society of Medical Biochemistry and Laboratory Medicine

Impact of experimental hypercalcemia on routine haemostasis testing

The blood to anticoagulant ratio is standardized according to the physiological calcium concentration in blood samples conventionally used for hemostasis testing. Specifically, one fixed volume of 0.109 mmol/L sodium citrate is added to 9 volumes of blood. Since little is known about the impact of hypercalcemia on the calcium-binding capacity of citrate, this study was planned to investigate the effect of experimental hypercalcemia on routine hemostasis testing

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene—gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients’ data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7–10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived

Patient posture for blood collection by venipuncture: recall for standardization after 28 years

Although data about the effect of posture on routine hematological testing were published 28 years ago, this pre-analytical issue has not been standardized so far. This study was planned to evaluate whether postural changes influence the results of hematology testing. METHODS: A complete blood count was performed in 19 healthy volunteers after 25min in the supine position, 20min in a sitting position and 20min stationary standing in an upright position. RESULTS: The change from supine to sitting position caused clinically significant increases in the hemoglobin, hematocrit and red blood cell count. Furthermore, the change from supine to standing caused clinically significant increases in the hemoglobin, hematocrit, red blood cell, leukocyte, neutrophil, lymphocyte, basophil and platelet counts, and mean platelet volume, and that from sitting to standing caused clinically significant increases in hemoglobin, hematocrit, and red blood cell, leukocyte, neutrophil and lymphocyte counts. CONCLUSION: The results of this investigation provide further support to the notion that effort should be made to achieve widespread standardization in the practice of phlebotomy, including patient posture. Copyright \ua9 2017 Associa\ue7\ue3o Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved

Comparison of plasma lipids changes after middle-distance running in euglycemic and diabetic subjects

Background: Although regular performance of aerobic physical exercise is pivotal for preserving or improving health and fitness, scarce information is available on plasma lipids changes after middle-distance running in euglycemic and diabetic subjects. Methods: Eleven male euglycemic amateur runners (mean age 41\ub16 years) and 9 male diabetic amateur runners (4 with type 1 and 5 with type 2 diabetes; mean age 55\ub114 years) participated to a 21.1-km running trial. All subjects belonged to an amateur running team, regularly engaged in amateur running. Blood was collected before the start of the trial and immediately after. The lipid profile, encompassing measurement of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), was assayed with Roche Cobas 6000. Results: All athletes successfully completed the 21.1-km running trial, with running pace comprised between 9.6\u201312.8 km/h. In both categories of subjects the values of LDL-C significantly decreased by approximately 6% after the run, whilst HDL-C and triglycerides significantly increased by 6\u20139% and 30\u201336%, respectively. The post-run variations of all lipoprotein fractions after the running trial were virtually identical in diabetic and euglycemic subjects. Conclusions: The results of this study show for the first time that middle-distance running elicits acute favorable changes of lipid profile both in euglycemic and diabetic subjects. This form of endurance exercise shall hence be further fostered for purposes of public health promotion and improvement

Ezetimibe prevents ischemia/reperfusion-induced oxidative stress and up-regulates Nrf2/ARE and UPR signaling pathways

BACKGROUND: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). METHODS: Cultured cells were subjected to simulated IR with or without Ezetimibe. RESULTS: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. CONCLUSIONS: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation

Plasma bile acid profile in patients with and without Type 2 Diabetes

A paucity of information currently exists on plasma bile acid (BA) profiles in patients with and without type 2 diabetes mellitus (T2DM). We assayed 14 plasma BA species in 224 patients with T2DM and in 102 nondiabetic individuals with metabolic syndrome. Plasma BA levels were measured with ultra-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) technique. Multivariable linear regression analyses were undertaken to assess associations between measured plasma BA species and T2DM status after adjustment for confounding factors. The presence of T2DM was significantly associated with higher plasma concentrations of both primary BAs (adjusted-standardized beta coefficient: 0.279, p = 0.005) and secondary BAs (standardized beta coefficient: 0.508, p < 0.001) after adjustment for age, sex, adiposity measures, serum alanine aminotransferase and use of statins or metformin. More specifically, the presence of T2DM was significantly associated with higher levels of plasma taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid, hyodeoxycholic acid, glycodeoxycholic acid, glycolithocholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurodeoxycholic acid, glycochenodeoxycholic acid and glycodeoxycholic acid (adjusted-standardized beta coefficients ranging from 0.315 to 0.600; p < 0.01 or less), as well as with lower plasma levels of cholic acid (adjusted-standardized beta coefficient: -0.250, p = 0.013) and taurocholic acid (adjusted-standardized beta coefficient: -0.309, p = 0.001). This study shows that there are marked differences in plasma BA profiles between patients with and without T2DM. Further research will be needed to better understand how these differences in plasma BA profiles may interplay with the pathophysiology of T2DM

The Renalase Asp37Glu polymorphism is not associated with hypertension and cardiovascular events in an urban-based prospective cohort: the Malmo Diet and cancer study

Background: Renalase (gene name RNLS), a recently discovered enzyme with monoamine oxidase activity, is implicated in the degradation of catecholamines. Recent studies delineate a possible role of this enzyme in blood pressure (BP) maintenance and cardiac protection and two single nucleotide polymorphisms, RNLS rs2576178 A > G and rs2296545 C > G have been associated with hypertension. The latter SNP leads to a non synonymous Asp to Glu substitution deleting a flavin adenine dinucleotide (FAD) binding site with possible impaired functionality. We tested the hypothesis that these polymorphisms could affect BP levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes. Methods: The polymorphisms were genotyped in 5696 participants of the population-based Cardiovascular Cohort of the "Malmo Diet and Cancer" (MDC-CC). The incidence of cardiovascular events (coronary events [n = 408], strokes [n = 330], heart failure [n = 190] and atrial fibrillation/flutter [n = 406]) was monitored for an average of approximately 15 years of follow-up. Results: Both before and after adjustment for sex, age and BMI the polymorphisms did not show any effect on BP level and hypertension prevalence. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for cardiac and cerebrovascular events was not significantly different in carriers of different genotypes. A significant interaction was found between the rs2296545 C > G and age with respect to BP/hypertension. Conclusions: Our data do not support a major role for these RNLS polymorphisms in determining BP level and incident events at population level. The positive interaction with age suggest that the effect of the rs2296545 C > G polymorphism, if any, could vary between different ages