a possible role for hydrochlorothiazide hctz as enhancer of zofenopril activity at the tissue level

Background: Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic has proven to be effective in the treatment of hypertension with or without end-organ damage. Discussion: The mechanism of action of such a combination therapy may involve a opposite effect on the renin-angiotensinaldosterone system (RAAS) with possible "functional" synergistic effects. Indeed, while diuretics can initially reduce intravascular volume leading to an activation of the RAA system with consequent vasoconstriction and salt and water retention, the concomitant presence of an ACE inhibitor may prevent such a counterregulatory response on neurohumoral system. This creates the conditions for the achievement of a maximal antihypertensive effect for both the ACE inhibitor and the diuretic. In recent years, however, experimental evidence has suggested that in addition to the above described mechanism of action, which is common to all the combinations of ACE-inhibitors and diuretics, it can be possible to identify some additional and peculiar mechanisms involving some selected drugs. Such additional mechanisms would be essentially related to some differences in the pharmacokinetic profiles of ACE inhibitors. In particular, the extent of lipophilicity could play an important role in membrane penetration and tissue accumulation and has been correlated with the overall ACE-inibitory activity of various compounds, eg., tissue ACE inhibitory activity could increase with the increase of lipophilicity. For instance, in rats with myocardial infarction, volume depletion induced by concomitant administration of HCTZ can increase the tissue levels of zofenoprilat (the active metabolite of zofenopril, an highly lipophilic ACE inhibitor), but not those of the highly hydrophilic lisinopril. An interesting hypothesis is that associating HCTZ to a highly lipophilic ACE inhibitor translates into peculiar clinical profiles, therefore we suggest further studies on this matter. Conclusion: Experimental models have shown that hydrochlorothiazide (HCTZ) could act like a "tissue levels enhancer" of lipophilic ACE-inhibitors, eg., can increase tissue concentrations of zofenoprilat (active metabolite of zofenopril, an highly lipophilic compound), and consequently induce an enhancement of its tissue ACE inhibition. On the basis of available experimental data, we suggest a peculiar interaction between zofenopril and HCTZ, i.e., HCTZ could act as a "tissue levels enhancer" of zofenopril. This hypothesis, if confirmed, could imply a relevant therapeutic advantage for the treatment of arterial hypertension

Impact of trans-stent gradient on outcome after PCI: results from a HAWKEYE substudy

To test whether quantitative flow ratio (QFR)-based trans-stent gradient (TSG) is associated with adverse clinical events at follow-up. A post-hoc analysis of the multi-center HAWKEYE study was performed. Vessels post-PCI were divided into four groups (G) as follows: G1: QFR >= 0.90 TSG = 0 (n = 412, 54.8%); G2: QFR >= 0.90, TSG > 0 (n = 216, 28.7%); G3: QFR < 0.90, TSG = 0 (n = 37, 4.9%); G4: QFR < 0.90, TSG > 0 (n = 86, 11.4%). Cox proportional hazards regression model was used to analyze the effect of baseline and prognostic variables. The final reduced model was obtained by backward stepwise variable selection. Receiver operating characteristic (ROC) was plotted and area under the curve (AUC) was calculated and reported. Overall, 449 (59.8%) vessels had a TSG = 0 whereas (40.2%) had TSG > 0. Ten (2.2%) vessel-oriented composite endpoint (VOCE) occurred in vessels with TSG = 0, compared with 43 (14%) in vessels with TSG > 0 (p < 0.01). ROC analysis showed an AUC of 0.74 (95% CI: 0.67 to 0.80; p < 0.001). TSG > 0 was an independent predictor of the VOCE (HR 2.95 [95% CI 1.77-4.91]). The combination of higher TSG and lower final QFR (G4) showed the worst long-term outcome while low TSG and high QFR showed the best outcome (G1) while either high TSG or low QFR (G2, G3) showed intermediate and comparable outcomes. Higher trans-stent gradient was an independent predictor of adverse events and identified a subgroup of patients at higher risk for poor outcomes even when vessel QFR was optimal (> 0.90)

Acido urico e malattie cardiovascoalri: la realtà allo specchio?

Elevati livelli di acido urico sono stati corralati allo sviluppo di ipertensione arteriosa e malattie cardiovascolari con un incremento del rischio che si rende manifesto per livelli sieric di urato significativamente inferiori a quelli implicati nella precipitazione tessutale dello stesso composto

Hyperuricemia and cardiovascular disease risk

Uric acid (UA) is the final end product of purine catabolism and is formed from xanthines and hypoxanthines. Hyperuricemia can be secondary to either an exaggerated production of UA that follows high cellular turnover conditions or, most frequently, to a low renal excretion in patients with impaired renal function. Recent data suggest that serum UA (SUA) at high–normal level is associated with cardiovascular disease risk factors and cardiovascular disease, often being a predictor of incident events. Preliminary data suggest that the reduction of SUA level in subjects with normal–high SUA could prevent at least a part of target-organ damage related to high SUA, especially when xanthine oxidase is selectively inhibited

Procalcitonin Predicts Bacterial Infection, but Not Long-Term Occurrence of Adverse Events in Patients with Acute Coronary Syndrome

This study compiles data to determine if procalcitonin (PCT) values may predict both the risk of bacterial infection and potentially negative long-term outcomes in patients with acute coronary syndromes (ACS). All patients with a diagnosis of ACS that had PCT levels assessed during the first 24 h of hospitalization were enrolled in this study. The primary outcome was to detect the presence of bacterial infection defined as the occurrence of fever and at least one positive blood or urinary culture with clinical signs of infection. The secondary outcome was to monitor the occurrence after 1 year of the composite outcome of all-cause mortality, stroke and myocardial infarction. Overall, 569 patients were enrolled (mean age 69.37 ± 14 years, 30% females). Of these, 44 (8%) met the criteria for bacterial infection. After multivariate analysis, PCT and SBP were found to be independent predictors of bacterial infections (OR for PCT above the cut-off 2.67, 95% CI 1.09–6.53, p = 0.032 and OR for SBP 0.98, 95% CI 0.97–0.99, p = 0.043). After 1 year, the composite outcome of all-cause death, MI and stroke occurred in 104 patients (18%). PCT was not found to be an independent predictor of these outcomes. In conclusion, when assessing ACS, we found that testing for PCT levels during hospital admissions procedures was a good predictor of bacterial infections but not of all-cause mortality, stroke, or myocardial infarction. Clinicaltrial.org identifier: NCT02438085

Therapy for H. pylori: Current concepts

Helicobacter pylori plays an important role in the pathogenesis of chronic active gastritis, peptic ulcer and gastric mucosa-associated lymphoid tissue-lym- phoma, and is also involved in carcinogenesis of the stomach. Since now no current first-line therapy is able to cure the infection in all treated patients. We evaluated data on the most successful therapy regi- mens\u2014sequential, concomitant and quadruple thera- pies\u2014and on the standard therapy available for H. pylori eradication. When therapy fails several factors may be involved: we reviewed both bacterial and host factors that can affect the eradication and that can be involved in therapeutic management of the H. pylori infection

QFR-Based Virtual PCI or Conventional Angiography to Guide PCI: The AQVA Trial

BACKGROUND Post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) values $0.90 are associated with a low incidence of adverse events. OBJECTIVES The AQVA (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR) trial aims to test whether a QFR-based virtual percutaneous coronary intervention (PCI) is superior to a conventional angiography-based PCI at obtaining optimal post-PCI QFR results. METHODS The AQVA trial is an investigator-initiated, randomized, controlled, parallel-group clinical trial. A total of 300 patients (356 study vessels) undergoing PCI were randomized 1:1 to receive either QFR-based virtual PCI or angiography-based PCI (standard of care). The primary outcome was the rate of study vessels with a suboptimal post-PCI QFR value, which was defined as <0.90. Secondary outcomes were procedure duration, stent length/lesion, and stent number/patient. RESULTS Overall, 38 (10.7%) study vessels missed the prespecified optimal post-PCI QFR target. The primary outcome occurred significantly more frequently in the angiography-based group (n = 26, 15.1%) compared with the QFR-based virtual PCI group (n = 12 [6.6%]; absolute difference = 8.5%; relative difference = 57%; P = 0.009). The main cause of a suboptimal result in the angiography-based group is the underestimation of a diseased segment outside the stented one. There were no significant differences among secondary endpoints, although stent length/lesion and stent number/pa-tient were numerically lower in the virtual PCI group (P = 0.06 and P = 0.08, respectively), whereas procedure length was higher in the virtual PCI group (P = 0.06). CONCLUSIONS The AQVA trial demonstrated the superiority of QFR-based virtual PCI over angiography-based PCI with regard to post-PCI optimal physiological results. Future larger randomized clinical trials that demonstrate the superiority of this approach in terms of clinical outcomes are warranted. (Angio-based Quantitative Flow Ratio Virtual PCI Versus Conventional Angio-guided PCI in the Achievement of an Optimal Post-PCI QFR [AQVA]; NCT04664140) (J Am Coll Cardiol Intv 2023;16:783-794) (c) 2023 by the American College of Cardiology Foundation

Asthma in patients admitted to emergency department for COVID-19: prevalence and risk of hospitalization

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