Current vascular pharmacology最新文献

Introduction/objective: Both fasting and postprandial hypertriglyceridemia are associated with atherosclerotic cardiovascular disease (ASCVD). The Hellenic Postprandial Lipemia Study (HPLS, NCT02163044) is the largest prospective cohort trial assessing the effects of statin therapy on postprandial lipemia.

Methods: Individuals at high or very high risk for ASCVD were evaluated, and their characteristics were recorded at baseline (Visit 1). At Visit 2 (2-4 weeks after Visit 1) and Visit 3 (3-4 months after Visit 2), serum triglyceride (TG) levels were measured after a 12-hour fast (fTG) as well as 4 hours after the ingestion of a commercially available oral fat tolerance test meal (pTG). After Visit 2, all individuals were treated with a statin.

Results and discussion: Among 900 participants, 699 completed all 3 visits, and of these, 209 (29.9%) had an abnormal pTG response. The mean (standard deviation, SD) total- and low-density lipoprotein cholesterol concentrations were 225 (50) and 148 (46) mg/dL at Visit 1, 231 (42) and 156 (40) mg/dL at Visit 2, and 171 (28) and 101 (27) mg/dL at Visit 3. At Visit 2, the mean fTG level was 127 (45) mg/dL and pTG was 188 (73) mg/dL with a mean difference of 58 mg/dL (P<0.001). At Visit 3, the mean fTG concentration was 110 (40) mg/dL, while pTG was 140 (54) mg/dL (mean difference: 29 mg/dL; P<0.001). Fasting glucose levels had no impact on pTG response in statin-treated individuals with abnormal postprandial lipemia.

Conclusion: Nearly 30% of individuals at high-/very high-risk for ASCVD had postprandial hypertriglyceridemia. Statin treatment normalized abnormal postprandial lipemia in 75.6% of participants, and decreased pTG concentration even in those with normal fTG levels.

Background: Patients with adult growth hormone deficiency (AGHD) show accelerated atherosclerosis. While growth hormone replacement therapy (GHRT) may help mitigate this process, the mechanisms driving atherosclerosis progression in GHRT-treated patients with AGHD remain unclear.

Methods: Thirty-one patients with AGHD on daily GHRT for ≥5 years were assessed in this crosssectional study. Carotid intima-media thickness (cIMT) was evaluated by ultrasound. Reactive hyperemia index (RHI) was measured using peripheral arterial tonometry. Associations between vascular measures and clinical, pituitary, treatment, body composition, and laboratory parameters were evaluated.

Results: cIMT correlated with body mass index (r=0.584, p=0.001) and visceral adipose tissue area (r=0.791, p<0.001), while demonstrating nominally significant associations with triglyceride levels, insulin resistance index, smoking history, and arterial hypertension. Neither the current nor the 5-year mean insulin-like growth factor 1 standard deviation score directly correlated with vascular parameters. Median cIMT was higher in adult-onset compared with child-onset AGHD (0.70 vs. 0.58 mm; p=0.020), while median RHI was lower in genetic than structural etiology (1.58 vs. 2.18; p=0.010); however, both associations were nominally significant.

Discussion: Several of the identified cardiovascular risk factors associated with cIMT are unlikely to be sufficiently controlled through GHRT. Pituitary disease characteristics may play a role in atherogenesis; however, the subgroups defined by disease onset timing and etiology were small and not fully comparable.

Conclusion: In long-term GHRT-treated patients, cIMT is linked to well-established cardiovascular risk factors rather than features of the pituitary disorder and its management, highlighting the need for targeted cardiovascular risk management alongside GHRT in AGHD.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) and peripheral arterial disease (PAD) are highly prevalent conditions that increase cardiovascular risk. This review aims to summarize current evidence on the association between MASLD and PAD, with a particular focus on clinical studies. A critical appraisal of this association will enhance understanding of MASLD as a multi-system disease and provide potential therapeutic implications.

Methods: A literature search was performed using the PubMed database.

Results: Both MASLD and PAD are multifactorial diseases that share common risk factors and pathogenic mechanisms. Most relevant clinical studies support an association between MASLD and PAD, particularly in the context of hepatic steatosis. Data regarding steatohepatitis or hepatic fibrosis are limited, largely due to the scarcity of studies with biopsy-proven MASLD. Management strategies for MASLD and PAD overlap, emphasizing lifestyle modifications such as a balanced diet, regular exercise, and smoking cessation. Additionally, certain medications used for PAD (e.g., statins, aspirin) or under investigation for MASLD (e.g., glucagon-like peptide-1 receptor agonists, dual and triple peptide agonists) may have beneficial effects on both conditions.

Discussion: Until clinical trials specifically evaluate medications for patients with concomitant MASLD and PAD, priority should be given to lifestyle interventions and the management of shared comorbidities, including obesity, type 2 diabetes mellitus, arterial hypertension, and dyslipidemia, which may confer benefits for both diseases.

Conclusions: MASLD and PAD frequently coexist. Targeting both conditions is expected to reduce the elevated cardiovascular risk observed in patients affected by both MASLD and PAD.

Introduction: The interplay between lipid metabolism and renal injury in the context of metabolic kidney diseases has garnered growing scientific interest. Nevertheless, the majority of existing studies have primarily concentrated on the modulation of individual lipid parameters, with relatively limited emphasis on the potential role of PCSK9 as a crucial mediator linking lipid metabolism disturbances to kidney damage.

Methods: A comprehensive literature search was performed across databases such as PubMed and Web of Science, covering the period from 2003 to 2025. Search terms included "PCSK9," "metabolic kidney disease," and "chronic kidney disease", which were used to identify relevant Randomized Controlled Trials (RCTs), systematic reviews, and mechanistic studies. In addition, proteomics data were obtained from the iProX database and integrated into the analysis.

Results: PCSK9 exacerbates lipid metabolism dysregulation through LDLR degradation. Its inhibitors improve lipid metabolism and reduce proteinuria, thereby exerting renoprotective effects via downregulation of lipid-related proteins (e.g., Angptl3) and inhibition of TGF-β signaling components.

Discussion: PCSK9 as a therapeutic target, extending prior research by demonstrating dual lipidrenal protective effects. However, evidence for rare metabolic kidney diseases and long-term safety data is lacking.

Conclusion: PCSK9 inhibitors show promise in metabolic kidney diseases, but large-scale trials are needed to clarify their long-term efficacy and optimal application scope.

Over the last few decades, there has been noteworthy long-lasting stagnancy in the field of antiarrhythmic drugs (AAD), with the development of novel AAD notably declining over the years. Although ablation therapy has dominated, there remains an unmet need for effective and safe antiarrhythmic therapy in those choosing a conservative approach and those failing the ablation procedure( s). Also, in patients with life-threatening ventricular arrhythmias, in the era of the implantable cardioverter defibrillator dominance, many patients require effective and safe AAD therapy to mitigate the recurrence of arrhythmias and the delivery of painful and unpleasant device shocks. The repurposing and reformulation of current drugs in circulation for novel therapeutic uses may provide new avenues for developing antiarrhythmic treatments that can assist in curtailing cardiac arrhythmia- associated morbidity and mortality, and ameliorate the quality of life for millions of patients. Stressful factors may lead to endothelial dysfunction and a surge in blood pressure, contributing to the emergence of cardiac arrhythmogenic effects, including myocardial fibrosis and remodeling of structural, ion channels, and connexin 43 channels, with consequent dysfunction. Agents influencing this latter protein may have cardioprotective and potentially antiarrhythmic effects. In this review of new antiarrhythmic agents, the advantages of sodium-glucose co-transporter inhibitors, and also those of pirfenidone, ranolazine, sotatercept, mirabegron, nintedanib, and melatonin are discussed. Some of these agents have been approved for other indications and repurposed for use in managing arrhythmias. Finding novel antiarrhythmic therapeutic approaches may be challenging for further research.