Current vascular pharmacology最新文献

Background: Complex coronary lesions have been an understudied aspect of coronary artery disease in elderly patients. Oxidative stress and inflammation may be implicated in the pathogenesis of complex coronary lesions.

Objectives: The aim of this study is to investigate the complex interplay between pro-oxidative stress response, pro-inflammatory response, and complex coronary lesions in elderly patients.

Methods: Enzyme-linked immunosorbent assays for the detection of serum biomarkers [reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), superoxide dismutase (SOD) activity, total antioxidant capacity (TAC), transforming growth factor beta (TGF-β) and interleukin-4 (IL-4)] were performed in elderly patients with complex coronary lesions.

Results: The levels of pro-oxidative stress and pro-inflammatory markers (ROS, MDA, TNF-α and IFN-γ) were increased in the complex coronary lesion group when compared with the non-complex coronary lesion group (P < 0.01) in elderly patients. Anti-oxidative stress and anti-inflammatory markers (SOD activity, TAC, TGF-β, and IL-4) were decreased in the complex coronary lesion group when compared with the non-complex coronary lesion group (P < 0.01) in elderly patients.

Conclusion: Our findings suggest that the pathogenesis of complex coronary lesions may involve pro-oxidant/anti-oxidant and pro-inflammation/anti-inflammation imbalance, as well as the interplay between oxidative stress and inflammation in elderly patients.

Atrial fibrillation (AF) is the commonest cardiac arrhythmia, constituting a major cause of morbidity and mortality, with an age-dependent incidence and prevalence ranging from 1-2% in the general population to ~10% in persons aged >60 years. The global prevalence of AF is rapidly increasing, mostly due to the aging population. If not properly and timely managed, this arrhythmia adversely affects left ventricular function, increases the risk of stroke five-fold, impairs quality of life, and shortens longevity. There is a genetic, hence non-modifiable, predisposition to the arrhythmia, while several life-style and cardiometabolic inciting factors, such as hypertension, heart failure, coronary disease, metabolic syndrome, alcohol use, and thyroid disorders, can be addressed, attesting to the importance of a holistic approach to its management. Thromboembolism is a serious consequence of AF, which could lead to a disabling stroke or have a lethal outcome. The risk of a thromboembolic complication can be estimated as based on a scoring system that takes into consideration the patient's age, previous thromboembolic events, and clinical comorbidities. In addition, rapid AF could affect cardiac performance, leading to an elusive type of arrhythmia- induced cardiomyopathy and heart failure with grave consequences if undetected and untreated. Furthermore, AF may cause silent brain infarcts and/or its hemodynamic perturbations can account for a type of dementia that needs to be taken into account, emphasizing the need for AF screening and prevention strategies. All these issues are herein detailed, the causes of the arrhythmia are tabulated, and an algorithm illustrates our current approach to its management.

Purpose: The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical therapy (GDMT) in patients with HF, eventually impacting the patient's prognosis during the vulnerable phase.

Methods: This prospective, observational study enrolled consecutive patients admitted due to AHF. Propensity score matching (PSM) analysis has been used to homogenize differences between groups. In group 1 (G1), patients were treated with early 24-h Levosimendan infusion followed by in-hospital introduction/up-titration of GDMT. In group 2 (G2), patients were treated with alternative inotropes/ vasopressors followed by in-hospital introduction/up-titration of GDMT. The comparison between the two groups has been performed at the 6-month follow-up in terms of cardiovascular (CV) mortality and HF hospitalizations (HFH).

Results: 233 patients were included in the present study, and after propensity match adjustments, 176 patients were analysed, 88 patients for each group. No differences in the baseline characteristics have been reported between the groups. At 6 months follow-up, no statistically significant differences were shown in terms of the composite endpoint of CV death and HFH (p = 0.445) and CV death (p = 0.62). Statistically significant differences between the two groups were reported in terms of HFH (p = 0.02). The Kaplan-Meier survival analysis showed that patients in G1 were significantly less hospitalized compared to G2 during the 6 months after the index hospitalization (log-rank p = 0.03).

Conclusion: Early 24-hour infusion of Levosimendan followed by rapid optimization of HF diseasemodifying therapies results in a significant reduction of HFH in the vulnerable post-discharge phase.

Traditionally, arterial atherosclerosis (AA) and venous thromboembolic (VTE) diseases have been separated into two independent entities. However, a body of evidence suggests the link between arterial and venous disease. In this narrative review, the relationship between these two vascular diseases is discussed. Different risk factors are common in both diseases, such as dyslipidaemia, metabolic syndrome, and thrombophilia. Etiopathogenetic mechanisms of both diseases are similar. Inflammation, as a basic pathogenetic mechanism of arterial atherosclerosis, is also involved in the pathogenesis of VTE. Inflammation as a response to vessel wall injury promotes coagulation and inhibits endogenic fibrinolytic activity, which results in thromboembolic events in the arterial as well as in the venous system. A relationship has also been observed between preclinical or clinical arterial atherosclerosis and VTE. These findings indicate that atherosclerosis may induce VTE or that common risk factors simultaneously stimulate the development of both diseases. The relationship between arterial and venous disease is also supported by the efficacy of some drugs (antiplatelets, anticoagulants, statins) in the prevention of both diseases. In conclusion, arterial and venous diseases share similar pathophysiological mechanisms, often driven by common risk factors. This overlap suggests that a unified approach to prevention and treatment may be beneficial for both conditions, potentially improving patient outcomes by addressing the underlying shared pathways.

Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor- beta (TGF-β) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discussed several important advances in the past 10 years in understanding HHT disease mechanisms and in therapeutic development.

Objectives: To describe clinical factors predictive of warfarin response in atrial fibrillation (AF) patients and to evaluate its association with adverse outcomes.

Methods: Patients in the Middle Eastern JoFib study, a prospective, multicenter registry of AF patients, using warfarin with at least one international normalized ratio (INR) reading, were enrolled. We used the most recent INR as a measure of warfarin control.

Results: Out of the total 2020 patients, 544 (26.9%) were using warfarin. Multivariable logistic regression analysis demonstrated that heart failure (adjusted OR 0.55, 95%CI 0.36-0.86) and increasing HAS-BLED score (adjusted OR 0.73, 95%CI 0.58-0.92) decreased the odds of having a therapeutic INR. Chronic kidney disease (adjusted OR 3.11, 95%CI 1.46-6.62), heart failure (adjusted OR 2.37, 95%CI 1.4-4.01), and cancer (adjusted OR 2.48, 95%CI 1.03-6.01) were independently predictive of having INR less than 2.0. The first episode of AF was independently predictive of having INR above 3.0 (adjusted OR 2.48, 95%CI 1.39-4.42). Multivariable Cox regression analysis demonstrated that INR below the therapeutic range (aHR 4.36, 95%CI 2.19-8.68) and INR above the therapeutic range (aHR 3.03, 95%CI 1.33-6.92) were predictive of all-cause mortality. Below-range INR also predicted cardiovascular mortality (aHR 3.69, 95%CI 1.66-8.16).

Conclusion: Clinical factors predictive of sub-optimal INR in Middle Eastern AF patients using warfarin include chronic kidney disease, heart failure, cancer, high HAS-BLED score, and first episode of AF. Furthermore, sub-optimal INR is predictive of all-cause and cardiovascular mortality.

Background: Among the organ damage mediated by hypertension, cardiac lesions hold significant importance. Numerous authors focus on hypertensive heart disease (HHD) rather than exclusively on left ventricular hypertrophy (LVH).

Objectives: This narrative review aims to assess the incorporation of the concept of 'hypertensive heart disease' (HHD) in hypertension (HTN) guidelines. Furthermore, if HHD is not addressed, the review will evaluate the potential benefits of including this concept in future studies.

Methods: The following databases were searched: Scopus, Medline, Springer, Science Direct, Wiley, SAGE, Cambridge, Oxford Journals, and Google Scholar. Attention was given to the guidelines related to hypertension (HTN); the search items were "guidelines" and "hypertension." Within these guidelines, we specifically sought references to 'hypertensive heart disease.'.

Results: The concept of "HHD" is clearly advantageous compared to "HTN LVH," as it not only addresses LVH but also considers other structures of the heart that may be severely affected, which can significantly influence treatment. The concept of "hypertensive heart disease" is mentioned in only 8 out of 36 guidelines on HTN. The therapeutic implications and recommendations are absent in the guidelines.

Conclusion: The concept of HHD is reasonable and evidence-based, and there is no reason to focus only on LVH when considering HTN-induced damage to the heart. It is time to update our recommendations for heart treatment by using the phrase "Treatment of hypertensive heart disease" instead of "Treatment of hypertensive LVH." This update can enhance our awareness of the need to improve not only HTN LVH but the other parts of the heart as well.

Mendelian Randomization (MR) studies have emerged as a powerful tool for investigating causal relationships between modifiable risk factors and clinical outcomes, using genetic variants as instrumental variables. In the context of vitamin D research, MR is a promising approach to elucidate the effects of vitamin D on various health outcomes, including adverse cardiovascular events. However, the validity of MR analyses relies heavily on the strength of the genetic associations found. "Weak instrument bias", arising from instruments with low explanatory power for the exposure of interest, can lead to biased estimates and compromise causal inference. We have, herein, briefly reviewed the challenges posed by weak instrument bias in a large MR study on vitamin D [25(OH)D] and stroke, exploring implications for the study's validity and reliability of findings. We have then added an original meta-analysis stratified by 25(OH)D levels. By using aggregated data from a recent MR study, an original meta-analysis stratified by population mean levels of 25(OH)D has indicated that interventions based on vitamin D supplementations in population mean levels ranging from 50 to 70 nmol/L are likely to translate into a 13% reduction of stroke risk (pooled odds ratio=0.873, 95% CI: 0.764-0.997, p-value=0.04). MR studies are a valuable approach for discerning causal relationships between exposures, such as vitamin D, and health outcomes. However, the effectiveness of MR analyses depends on the robustness of the genetic instruments employed. By recognizing and addressing weak instrument bias in MR studies of vitamin D, researchers can enhance the credibility and utility of causal inference in understanding the health effects of this essential nutrient. A metaanalysis stratified by population mean levels of 25(OH)D has revealed the potential benefits of targeted interventions with vitamin D supplementations for stroke.