Current vascular pharmacology最新文献

Introduction: People on a ketogenic diet may develop an increase in low-density lipoprotein cholesterol (LDL-C), known as the lean mass hyper-responder (LMHR) phenotype. However, this increase does not necessarily correspond to a heightened cardiovascular (CV) risk, and optimal treatment strategies for high-risk individuals within this group remain uncertain.

Case presentation: A 61-year-old man with type 1 diabetes developed the LMHR phenotype after adopting a ketogenic diet. An atherosclerotic plaque was discovered in the bulb of his left common carotid artery, reclassifying him into the secondary prevention category of CV disease. After the introduction of rosuvastatin 20 mg daily, his LDL-C subfraction profile changed from a more atherogenic type B phenotype to a less atherogenic type A phenotype without significantly decreasing overall LDL-C levels. This suggests that rosuvastatin provided a beneficial effect, complementing the metabolic improvements associated with the ketogenic diet, including better blood glucose and insulin control, potential prior reductions in small dense LDL-C and triglycerides, and an increase in high-density lipoprotein cholesterol (HDL-C).In this case, no trend toward a lower threshold was observed for the development of diabetic ketoacidosis.

Conclusion: Assessing LDL-C subfractions before and after the initiation of lipid-lowering therapy is essential in individuals who develop the lean mass hyper-responder (LMHR) phenotype, particularly in the presence of confirmed atherosclerosis. Given the markedly elevated LDL-C levels often observed in this population, it may be difficult to accurately evaluate the burden of atherogenic cholesterol and the extent of its reduction without subfraction analysis. In such cases, statin therapy appears to be a reasonable and potentially beneficial intervention, even among LMHR individuals.

Aims: The present analysis of the ARCANGELO study aims to investigate the effect of switching to different oral P2Y12 inhibitors when using cangrelor during PCIs in patients with ACS.

Methods: Out of the 995 patients meeting the criteria for this investigation, 138 transitioned to Clopidogrel (CLO), 127 to rasugrel (PRA), and 730 to Ticagrelor (TICA). Compared to the patients on PRA or TICA, users of CLO were older (median (Q1-Q3) 74(64-81) years CLO, 59(54-65) years PRA, 65(56-73) TICA; p<0.0001), had more comorbidities (37.0% CLO, 17.3% PRA, 18.9% TICA, p<0.0001), and had more frequently an NSTEMI diagnosis (68.1% CLO vs 33.1% PRA vs 35.9% TICA, p<0.0001).

Results: Five moderate bleeds were recorded without any severe episodes. There were no significant differences in the bleeding rate when switching to the different oral P2Y12 inhibitors (2.2% CLO, 5.3% TICA, 7.9% PRA, p = 0.0705) while different incidences of MACEs (4.3% CLO, 1.1% TICA, 0% PRA, p = 0.0113) and NACEs (4.3% CLO, 1.8% TICA, 0% PRA, p=0.0321) were observed during the 30 days of the study.

Conclusion: The use of cangrelor and the switch to any oral P2Y12 inhibitor in compliance with the EU SmPC is safe, with a low risk of ischemic events in routine clinical practice.

Drug-eluting angioplasty balloons are a highly effective treatment for neointimal hyperplasia post-balloon angioplasty and in-stent restenosis. Current drug-eluting angioplasty balloons have restenosis rates approximating 20%, and both paclitaxel, the current drug coating of choice, and sirolimus, an alternative coating being evaluated in early clinical studies, delay re-endothelialisation, potentially predisposing to thrombosis. There remains a paucity of efficacious alternatives to these coatings. Research into alternative drug-eluting balloon coatings is the source of intense investigation in attempts to improve on efficacy and safety of this highly effective therapeutic intervention. We discuss recent clinical developments with regard to sirolimus drug-coated balloons, demonstrating efficacy in early studies in relation to coronary, peripheral arterial, and renal access applications. However, limited comparator studies with paclitaxel currently exist. In addition, we explore novel drug-eluting angioplasty balloon coatings currently under evaluation in the preclinical space, together with associated molecular mechanisms of action. Further in vivo evaluation of these potential alternative coatings is required, and an algorithm to support the rational evaluation of novel coatings and their subsequent clinical development has been provided.

Background: The prevalence and clinical outcomes of statin therapy in patients with acute heart failure [AHF] stratified by left ventricular ejection fraction [EF] in the Middle East are unknown.

Methods: We analysed 5005 patients admitted to 47 hospitals in seven Middle Eastern countries [Saudi Arabia, Oman, Yemen, Kuwait, United Arab Emirates, Qatar, and Bahrain] with AHF from February to November 2012 with AHF who were enrolled in Gulf CARE, a multinational registry of patients with heart failure [HF]. AHF patients were stratified into three groups: HF patients with reduced [EF] [HFrEF] [<40%], HF with mildly reduced EF [HFmrEF] [40-49%], and HF patients with preserved EF [HFpEF] [≥50%].

Results: The mean age of the cohort was 59.3±14.9 years, 62.6% [n=3131.0] of the patients were males. A total of 2555 [51%] AHF patients had used statins prior to hospital admission. The mean EF was 36.9±14%. HFrEF was observed in 2683 patients [53%], whereas 961 patients [19.2%] had HFmrEF, and 932 patients [18.6%] had HFpEF. Multivariate logistic regression analysis revealed that prior statin use was significantly associated with reduced in-hospital mortality risk [OR=1.43, 95% CI: 1.10-1.86, p=0.007] and hospitalization rates for heart failure [OR=0.71, 95% CI: 0.60-0.83, p<0.001]. However, when examining rates of survival, there were no significant disparities between the two groups; at 3 months follow-up: aOR, 1.22; 95% Cl: 0.95-1.57; P=0.111; and 12-months follow-up: aOR, 1.07; 95% Cl: 1.07 0.87-1.31; P=0.553. Regarding rehospitalization rates, no significant difference was observed at a 3- month follow-up: aOR, 1.22; 95% Cl: 1.03-1.42; P=0.015. Interestingly, patients admitted with statin therapy were significantly associated with higher odds of hospitalization during the 12-month follow-up period: aOR, 1.42; 95% Cl: 1.21-1.66; P<0.001.

Conclusion: Prior statin use was associated with a lower risk of in-hospital mortality and rehospitalization. However, there were no significant differences in all-cause mortality between the two groups at both 3- and 12-month follow-ups. While rehospitalization rates at the 3-month follow-up showed higher odds of rehospitalization at the 12-month follow-up. Prior statin therapy appears to influence both in-hospital mortality and long-term rehospitalization outcomes in a Middle Eastern patient population.

Background: Several scores have been developed to facilitate risk stratification and early discharge following primary angioplasty, particularly the Zwolle Risk Score (ZRS). However, validation in large-sized studies is still lacking. Therefore, the aim of the current study was to validate the use of the ZRS in a contemporary global population, including patients who were treated during the SARS-CoV-2 pandemic and enrolled in a large intercontinental observational study.

Methods: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving primary PCI centers from Europe, Latin America, South-East Asia, and NorthAfrica, including patients treated from March 1st until June 30th, in 2019 and 2020]. ZRS was calculated for each patient. The patients were additionally categorized according to the following values of the ZRS [≤3; 4-6; 7-9; ≥10]. Our study outcomes were in-hospital and 30-day mortality. The discriminatory capacity of the ZRS was assessed by the area under the ROC curve [c statistic] as an index of model performance.

Results: Our population is represented by 16084 STEMI patients undergoing mechanical reperfusion enrolled in 109 centers. The score showed a very good performance in the predicting mortality both in-hospital [AUC=0.83 [0.82-0.85], p<0.0001] and at 30- day follow-up [AUC=0.82 [0.81-0.84, p<0.0001]. The results were confirmed when the ZRS was separately applied to patients treated in 2019 and 2020, with good stability across time. ZRS was able to identify a large cohort [n=10672, 66.3%] of low-risk patients [score ≤3] with a very low mortality rate at 2 days [1%] and between 3 and 10 days [0.7%], with a very good negative predictive value for in-hospital [98.3%] and 30-day mortality [97.7%], with similar results in 2019 and 2020.

Conclusion: This study is the first to demonstrate the good prognostic performance of the ZRS in a large-scale contemporary global multicenter validation set. Similar results were obtained both in the pre-pandemic and the COVID-19 era. ZRS ≤3 identified a very low-risk population that could be discharged early, even during the COVID-19 pandemic, with expected advantages in the availability of hospital beds and nursing staff, costs of medical care, and in-hospital risk of contagion.

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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with multiorgan and system involvement, including the Cardiovascular (CV) system. Cardiac involvement in these patients is frequent and most often asymptomatic, at least in the early stages. It includes accelerated atherosclerosis, premature Coronary Artery Disease (CAD), and a high risk of CV complications. The risk of developing CV Disease (CVD) in SLE is linked not only with classical CV risk factors but also with disease-specific factors, like the degree of activity, autoantibodies, organ damage, and type of therapy. Clinical presentation comprises several clinical manifestations ranging from angina to acute Myocardial Infarction (MI) and Sudden Cardiac Death (SCD). The leading cause of death in SLE patients is from CVD due to accelerated atherosclerosis, which often has a more rapid progression compared with the general population. The CV risk in SLE is greater when antiphospholipid antibodies are present. Regarding diagnosis, apart from relevant blood tests, the simplest and readily available diagnostic test, echocardiography, with its contemporary techniques that include global longitudinal strain, is needed to provide a more thorough cardiac evaluation and allow for early management. These aspects of the disease, together with issues regarding phenotypes, biomarkers, neonatal lupus, heart block, SLE-related CV ailments such as coronary artery disease, myocarditis, valvular heart disease, and the antiphospholipid syndrome, as well as diagnostic modalities, drug and interventional therapies, and current relevant guidelines are all thoroughly reviewed and discussed in this article.

Aims: Our study was to investigate the association between statin use and the prevalence of abdominal aortic calcification (AAC).

Methods: The population was enrolled in the 2013-2014 cycle of the National Health and Nutrition Examination Survey (NHANES). The statin use was determined from the questionnaire inquiring the medications taken in the past month. The presence of AAC and severe AAC were assessed based on the AAC score measured by abdominal dual-energy X-ray absorptiometry (DXA). Logistic regression analysis was performed to evaluate the association between statin treatment and AAC after adjustment for potential confounders.

Results: The study included a total of 2074 individuals; the average age 61.6±11.8 years old and 922 (44.5%) were male. AAC (AAC score >0) was present in 35.4% of the population and 12.0% had severe AAC. There were 836 (40.3%) statin users. After adjustment for demographics, lifestyles, comorbidities, and laboratory examinations, statin use was associated with higher odds of AAC (OR 1.28, 95%CI 1.02-1.62; P=0.034) and severe AAC (OR 1.78, 95%CI 1.24-2.55; P=0.002), respectively. Subgroup analysis revealed that the association was stronger in male, non-diabetic participants and those aged >60 years old.

Conclusion: Stain use was associated with a greater presence of AAC and severe AAC. This association was stronger for male, non-diabetic participants and those aged >60 years.

Background: Hepatic fibrosis, a chronic pathological condition, is associated with adverse outcomes in stroke patients. Cardioembolism (CE) is a common etiology of stroke, yet the association between hepatic fibrosis and CE remains understudied.

Aim: This study aims to investigate the association between hepatic fibrosis and CE-induced stroke, as well as its impact on stroke patient prognosis.

Methods: This retrospective study included 344 acute ischemic stroke (AIS) patients who underwent thrombolytic therapy. Hepatic fibrosis was assessed using the Fibrosis-4 (FIB-4) index and the Aspartate Aminotransferase-Platelet Ratio Index (APRI). Mediation analysis examined the role of CE in the association between hepatic fibrosis and 3-month functional outcomes.

Results: Among 344 patients, 319 were classified using the Trial of Org 10172 in Acute Stroke Treatment criteria. Severe fibrosis (FIB-4 ≥ 2.01) was observed in 131 patients (38.08%), and CE was identified in 79 patients. FIB-4 was an independent predictor of CE (OR: 2.038, 95%CI: 1.507- 2.757, p < 0.001) and poor 3-month functional outcome (OR: 1.477, 95%CI: 1.103-1.978, p = 0.009) after adjusting for confounders. The effect of FIB-4 on poor 3-month functional outcomes was partially mediated by CE, with a mediation proportion of 30.63%.

Conclusions: Hepatic fibrosis is a significant predictor of short-term functional outcomes in AIS, particularly cardioembolic stroke. The association between hepatic fibrosis and stroke outcomes is partially mediated through CE. These findings highlight the importance of assessing hepatic fibrosis in stroke patients, particularly those with CE etiology.