Current vascular pharmacology最新文献

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.

Objective: 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: 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.

Aim: This study aimed to evaluate clinical outcomes, including recurrent acute coronary syndrome (ACS) and mortality, in ACS patients with varying HbA1c levels, addressing the controversy over optimal targets in those with newly diagnosed and pre-existing diabetes mellitus (DM).

Methods: From January 2005 to December 2019, a total of 33,990 patients were identified with ACS in the Chang Gung Research Database based on their medical history. After excluding patients without DM and baseline or subsequent HbA1C data, a cohort of 11,870 DM patients was divided into two groups: one consisting of 6,089 patients with newly diagnosed DM and the other comprising 5,781 patients with pre-existing DM.

Results: During the three-year follow-up, the pre-existing DM group experienced worse clinical outcomes, such as increased rates of re-ACS, major bleeding, cardiovascular (CV) events, and all-cause mortality. Optimal HbA1c levels for mitigating re-ACS and/or CV mortality and all-cause mortality appeared to differ between the two DM cohorts. Re-ACS and CV mortality reached their highest at an HbA1c of 6.8% for all DM patients, 6.6% for newly diagnosed, and 6.7% for pre-existing cases. The greatest all-cause mortality risk was at an HbA1c of 7.4% for all DM patients, 7.0% in newly diagnosed, and 8.2% in pre-existing patients.

Conclusion: Upon comparing newly diagnosed DM patients with those with pre-existing DM, a poorer prognosis was observed in the latter group, attributed to older age and a higher burden of comorbidities. Throughout the follow-up period, maintaining consistently low HbA1c levels did not reduce the incidence of re-ACS nor enhance survival rates.

Introduction: The global COVID-19 vaccination campaign has significantly reduced severe illness and mortality; however, emerging evidence raises concerns regarding its potential cardiovascular effects, particularly myocardial infarction (MI).

Method: This study investigates the relationship between COVID-19 vaccination and MI incidence among first-time MI patients in Saudi Arabia. Post-COVID-19 vaccination within six months postvaccination accounted for potential confounding factors, such as pre-existing health conditions, age, and lifestyle. A total of 102 MI patients, with a male predominance of 60.8% and a significant correlation with middle age, were analysed. A+ blood group patients were the most prevalent (33.3%), followed by B+ (29.4%), while Rh-negative patients constituted only 7.8%. Elevated mean BNP (761.98 pg/ml), pulse rate (87.72 bpm), and systolic blood pressure (139.98 mmHg) indicated heightened cardiac stress (p < 0.01).

Results: Significant elevations in AST (121.65 U/L) and ALT (133.63 U/L) levels suggested liver stress post-Covid-19 vaccination (p < 0.01). Males had higher AST, ALT, and bilirubin levels than females, with p-values of 0.02, 0.01, and 0.04, respectively, indicating hepatic differences. Elevated biomarkers like CK-MB (58.05 IU/L) and CPK (313.86 mcg/L) further affirmed significant myocardial damage post-vaccination (p < 0.05).

Conclusion: These findings suggest a link between vaccination and cardiovascular events and highlight the importance of considering individual health profiles in evaluating vaccine safety, cardiovascular health, and hepatic implications.

Pericytes, also known as mural cells, are cells embedded between endothelial cells and the basement membrane of capillaries, where they orchestrate the morphological and functional homeostasis of blood vessels. Within the tumor microenvironment, pericytes interact closely with various cellular components, including tumor cells, stromal cells, and immune cells. Through these dynamic interactions, pericytes are activated and subsequently transform into tumor-associated pericytes (TPCs). The origin of TPCs varies depending on the tissue and tumor type, contributing to their phenotypic and functional heterogeneity. TPCs play pivotal roles in facilitating tumor progression, metastasis, immune evasion, and therapeutic resistance by promoting angiogenesis, engaging in reciprocal interactions with tumor cells, remodeling the extracellular matrix, and fostering an immunosuppressive microenvironment. This review synthesizes the latest significant advancements in targeted therapies against TPCs. It underscores the challenges inherent in developing effective anti-TPC therapies, which include the heterogeneity and pluripotency of TPCs, the absence of specific markers for precise TPC targeting, and the limited understanding of how current anti-tumor therapies affect TPCs and vice versa. This review furnishes a comprehensive understanding of the origins, markers, and functions of TPCs, and their interplays within the tumor microenvironment, providing prospective strategies for more effective anti-tumor therapy.

Traditionally, arterial atherosclerotic (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 atherosclerotic disease, 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 atherosclerotic disease 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.

Background: Diabetic nephropathy, a major contributor to chronic kidney disease, is closely associated with inflammatory responses.

Objective: This study aimed to evaluate the effectiveness of combination therapy with dapagliflozin and telmisartan in treating diabetic nephropathy and its effect on patient's albuminuria levels.

Material and methods: We conducted a 12-week prospective observational study to assess diabetic nephropathy. Patients with diabetic nephropathy were treated with either dapagliflozin and telmisartan (n=92) or telmisartan alone (n=92). Measurements of waist-to-hip ratio, fasting blood glucose, hemoglobin A1c (HbA1c), blood pressure, urinary albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), uric acid, blood urea nitrogen, lipid profile, and inflammatory biomarkers, including C-C motif chemokine ligand 21 messenger RNA (CCL21 mRNA) and monocyte chemoattractant protein-1 (MCP-1), were obtained at baseline and following 12-weeks of treatment.

Results: Dapagliflozin and telmisartan combination therapy demonstrated a significant decrease in UACR compared with baseline levels (p<0.001). After treatment, the dapagliflozin and telmisartan group had significantly lower waist-to-hip ratio, fasting blood glucose, HbA1c, uric acid, total cholesterol, and low-density lipoprotein compared with the monotherapy group (p<0.05). Additionally, inflammatory biomarkers, including CCL21 mRNA and MCP-1, were substantially lower in the combination therapy group than in the monotherapy group (p<0.05).

Conclusion: In comparison to monotherapy, combination therapy demonstrated more significant clinical effects in treating diabetic nephropathy. This combination therapy effectively controls blood glucose levels and UACR, reduces inflammatory responses, and improves kidney function recovery in diabetic nephropathy patients, thereby enhancing the overall clinical treatment outcomes for these patients.

Introduction: Current guidelines and consensus statements advise caution in using direct oral anticoagulants (DOACs) for morbidly obese patients with body mass index (BMI) >40 kg/m2, indicating warfarin as the most studied treatment.

Methods: We systematically searched databases from their inception to January 4, 2024, to identify studies that evaluated the effectiveness and safety of DOACs compared to warfarin in patients with BMI >40 kg/m2 and atrial fibrillation (AF) or venous thromboembolism (VTE). The outcomes of allcause mortality, major and minor bleeding, stroke/systematic embolism (SE), VTE, and their composite endpoint were analyzed using a random-effects model.

Results: This meta-analysis included 24 studies and 119,960 morbidly obese patients with AF or VTE on oral anticoagulation therapy: 51,363 on DOACs (43%) vs. (57%) 68,597 on warfarin. DOAC use was significantly associated with lower all-cause mortality and major bleeding risk compared to warfarin. Although the risk of composite endpoint, stroke/SE, and VTE was lower in the DOAC group, no statistically significant difference was observed, indicating no superiority of warfarin compared to DOAC use. The risk of minor bleeding events, hemorrhagic stroke, and ischemic stroke was lower in the DOAC compared to the warfarin group. The same trend favoring DOACs over warfarin in all assessed endpoints was observed in the subgroup analysis based on anticoagulation indication (AF or VTE).

Conclusion: Our findings have documented a potentially more effective and safer profile of DOACs compared to warfarin in morbidly obese patients regardless of the indication for anticoagulation.

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.

Objective: 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.