Spotlight Commentary:What's new with the old drug aspirin in older adults?

The benefit‐to‐harm balance of aspirin has been further questioned

Platelet-Derived Extracellular Vesicles as Target of Antiplatelet Agents. What Is the Evidence?

Platelet-derived large extracellular vesicles (often referred to as microparticles in the field of cardiovascular disease) have been identified as effector in the atherothrombotic process, therefore representing a target of pharmacological intervention of potential interest. Despite that, limited evidence is so far available concerning the effects of antiplatelet agents on the release of platelet-derived extracellular vesicles. In the present narrative review, the mechanisms leading to vesiculation in platelets and the pathophysiological processes implicated will be discussed. This will be followed by a summary of the present evidence concerning the effects of antiplatelet agents under experimental conditions and in clinical settings

Hypertension, cardiovascular risk and polymorphisms in genes controlling the cytochrome P450 pathway of arachidonic acid: A sex-specific relation?

Hypertension is a multifactorial disease in which the interplay of genetic and environmental factors that maintain blood pressure stable throughout life is altered. Cytochrome P450 (CYP)-derived metabolites of arachidonic acid such as epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), active on vascular tone, endothelial function and renal sodium reapportion, have been identified as candidate mediators in the development of hypertension in several animal models, with remarkable sex-specific effect. Several SNPs, some recognized as functional, in human genes implicated in EETs/20-HETE biosynthesis and metabolism, such as CYP2J2 and CYP4A11, have been tested for association with blood pressure, hypertension and its long-term cardiovascular consequences in different populations, with conflicting results. A sex-specific effect, related to CYP4F2 polymorphisms and expression, has been observed in association studies. This finding indicates that altered 20-HETE bioactivity underlay the excess of hypertension and associated vascular events observed in men with respect to women and is consistent with the results from experimental models. Further epidemiological and mechanistic studies are required to confirm the effect of lipid mediators on blood pressure in humans and define the mechanisms of a putative sex-specific effect

Platelets in Non-alcoholic Fatty Liver Disease

Non alcoholic steatohepatitis (NASH) is the inflammatory reaction of the liver to excessive accumulation of lipids in the hepatocytes. NASH can progress to cirrhosis and hepatocellular carcinoma (HCC). Fatty liver is the hepatic manifestation of metabolic syndrome. A subclinical inflammatory state is present in patients with metabolic alterations like insulin resistance, type-2 diabetes, obesity, hyperlipidemia, and hypertension. Platelets participate in immune cells recruitment and cytokines-induced liver damage. It is hypothesized that lipid toxicity cause accumulation of platelets in the liver, platelet adhesion and activation, which primes the immunoinflammatory reaction and activation of stellate cells. Recent data suggest that antiplatelet drugs may interrupt this cascade and prevent/improve NASH. They may also improve some metabolic alterations. The pathophysiology of inflammatory liver disease and the implication of platelets are discussed in details

Succinate dehydrogenase gene mutation with cardiac paraganglioma: multimodality imaging and pathological correlation.

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Plant cystine-knot peptides: pharmacological perspectives.

The cystine-knot peptides are well represented in several plant species. The pharmacological interest for plant cystine-knot peptides derived from their broad biological activities. The mechanisms of action of plant cystine-knot peptides are still largely undiscovered, although eveidences indicate that they interfere with plasma membranes. In some cases, as tomato TCMPs, the cystine-knot peptides target human growth factor receptors either by acting as growth factor antagonist or by altering their signal transduction pathway. The possibility to identify specific molecular targets of plant cystine-knot peptides in human cells opens novel possibilities for the pharmacological use of these peptides besides their use as scaffold to develop stable disease molecular markers and therapeutic agent

Hypertension, uncontrolled hypertension and resistant hypertension: prevalence, comorbidities and prescribed medications in 228,406 adults resident in urban areas. A population-based observational study

Although hypertension is the leading cause of cardiovascular disease and premature death worldwide, it remains difficult to control. The prevalence of uncontrolled and resistant hypertension (RH) may be underestimated and can reach up to 50% of all hypertensive patients. The aim of this observational study was to analyze the prevalence of hypertension, uncontrolled hypertension and RH, and their associations with risk factors or diseases in a large cohort of patients referred to primary care physician. In a population of 228406 adults, we only collected data from people with a diagnosis of arterial hypertension for a total of 43,526 patients. For this purpose, we used the MySQL database, run by Azalea.NET, built on the medical records of 150 General Practitioners (GPs). Patient data included sex, age, blood pressure (BP) values, number of antihypertensive drugs and presence of major cardiovascular comorbidities. We classified patients with RH as those treated with 3 different antihypertensive agents, with recorded BP & GE; 140/90 mmHg, or patients taking & GE; 4 medications. The prevalence of hypertension was 19.06%, that of resistant hypertension was 2.46% of the whole population and 20.85% of the hypertensive group. Thirteen thousand hundred, forty-six patients (30.20% of the hypertensive group) had uncontrolled BP (& GE; 140/90 mmHg), whereas 16,577 patients did not have BP measurements done in the last 2 years (38.09% of the hypertensive group). Patients with uncontrolled BP were mainly female, used less drugs and showed a lower prevalence of all major cardiovascular comorbidities, except for diabetes. Instead, patients with RH had a significantly higher prevalence of all considered comorbidities compared to those without RH. Our results evidence that a broad number of patients with hypertension, especially those without comorbidities or with a low number of antihypertensive drugs, do not achieve adequate BP control. To improve the clinical management of these patients it is very important to increase the collaboration between GPs and clinical specialists of hypertension

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

Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes.

Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmö Preventive Project, investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (β±SEM, 0.968±0.102 mm Hg and 0.585±0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β±SEM, 1.333±0.161 mm Hg and 0.724±0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio [95% CI], 1.192 [1.140-1.245] and 1.144 [1.107-1.183]; P<1E-15 for both). The GRS was positively associated with change (Δ) in BP (β±SEM, 0.033±0.008 mm Hg/y and 0.023±0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio [95% CI], 1.110 [1.065-1.156]; P=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension

The management of clinical risk in a sample of hospital wards and in the service centers for the elderly the Region of Veneto [La gestione del rischio clinico in un campione di reparti ospedalieri e nei centri di servizi per anziani della Regione del Veneto]

Negli ultimi decenni \ue8 cresciuta la cultura del rischio correlato agli errori di terapia farmacologica quale causa di eventi potenzialmente dannosi per i pazienti. Il Progetto \u201cLa gestione del rischio clinico in un campione di reparti ospedalieri e nei Centri di Servizi per anziani della Regione del Veneto\u201d \ue8 stato condotto con l\u2019obiettivo di rilevare lo stato di applicazione delle indicazioni ritenute pi\uf9 rilevanti tra quelle contenute nelle Raccomandazioni Ministeriali n. 1-7-12 presso un campione di Reparti ospedalieri e di Centri di Servizi per anziani non autosufficienti del territorio regionale. La rilevazione ha coinvolto tutte le aziende pubbliche (21 Aziende ULSS, 2 Aziende Ospedaliere, 2 IRCCS) e 16 strutture private; i Centri di Servizi per Anziani sono stati selezionati dalle Aziende ULSS. La rilevazione \ue8 stata effettuata dal farmacista locale, direttamente in reparto attraverso interviste di audit al personale medico/infer- mieristico, osservazione diretta e controlli a campione. Il progetto ha mostrato, sia nei reparti che nei Centri di Servizi per anziani, alcune criticit\ue0 tra cui la bassa ado- zione di procedure sulla Ricognizione e Riconciliazione terapeutica (rispettivamente 34% e 30%), la non com- pleta attenzione alla registrazione in cartella clinica delle allergie dei pazienti (74% e 69%), una bassa segnalazione delle reazioni avverse a farmaci