Current Vascular Pharmacology - Volume 20, Issue 6, 2022

Telomeres represent the ends of chromosomes, and they are composed of an extensive number of – TTAGGG nucleotide sequence repeats in humans. Telomeres prevent chromosome degradation, participate in stabilization, and regulate the DNA repair system. Inflammation and oxidative stress have been identified as important processes causing cardiovascular disease and accelerating telomere shortening rate. This review investigates the link between telomere length and pathological vascular conditions from experimental and human studies. Also, we discuss pharmacological treatments affecting telomeres and telomerase activity.

Polyvascular disease (PolyvascDis) with atherosclerosis occurring in >2 vascular beds (coronary, carotid, aortic, visceral and/or peripheral arteries) is encountered in 15-30% of patients who experience greater rates of major adverse cardiovascular (CV) events. Every patient with multiple CV risk factors or presenting with CV disease in one arterial bed should be assessed for PolyvascDis clinically and noninvasively prior to invasive angiography. Peripheral arterial disease (PAD) can be readily diagnosed in routine practice by measuring the ankle-brachial index. Carotid disease can be diagnosed by duplex ultrasound showing % stenosis and/or presence of plaques. Coronary artery disease (CAD) can be screened by determining coronary artery calcium score using coronary computed tomography angiography; further, non-invasive testing includes exercise stress and/or myocardial perfusion imaging or dobutamine stress test, prior to coronary angiography. Abdominal ultrasound can reveal an abdominal aortic aneurysm. Computed tomography angiography will be needed in patients with suspected mesenteric ischemia to assess the mesenteric arteries. Patients with the acute coronary syndrome and concomitant other arterial diseases have more extensive CAD and poorer CV outcomes. Similarly, PolyvascDis in patients with carotid disease and/or other PAD is independently associated with an increased risk for all-cause and CV mortality during long-term follow-up. Treatment of patients with PolyvascDis should include aggressive management of all modifiable risk factors by lifestyle changes and drug therapy, with particular attention to patients who are commonly undertreated, such as those with PAD. Revascularization should be reserved for symptomatic vascular beds, using the least aggressive strategy in a multidisciplinary vascular team approach.

Objective: The objective of this study is to compare the efficacy and safety of thrombolysis plus anticoagulant therapy vs. anticoagulant therapy alone in acute submassive pulmonary embolism (PE). Materials and Methods: The PubMed, Embase, and Cochrane Library databases were searched for randomized clinical trials comparing thrombolytic therapy and anticoagulation vs. anticoagulation alone in acute submassive PE patients from 1 Jan 1980 to 20 Jan 2021, with no drug or dose restrictions. Data on upgraded treatment of clinical deterioration, all-cause mortality, PE recurrence and bleeding events were extracted and analyzed using Revman 5.3 software. Results: A total of 10 randomized controlled trials involving 1871 patients were included in the study after screening. In terms of efficacy, thrombolysis combined with anticoagulant therapy reduced the need for upgrading treatment (3.6 vs. 10.9%, risk ratio (RR) 0.36, 95% confidence interval (CI) 0.24- 0.54, p<0.00001) and PE recurrence (0.8 vs. 2.9%, RR 0.33, 95% CI 0.16-0.69, p=0.003) in patients with acute submassive PE. Compared with anticoagulant therapy alone, the concomitant use of thrombolysis was associated with lower all-cause mortality (1.3 vs. 3.0%, RR 0.47, 95% CI 0.26-0.87, p=0.02), but it increased minor bleeding rate (31.4 vs. 8.4%, RR 3.71, 95% CI 2.82-4.88, p<0.0001) and major bleeding rate (8.8 vs. 2.6%, RR 3.35, 95%CI 2.03-5.54, p<0.0001). Conclusion: The use of thrombolysis plus anticoagulant therapy in acute submassive PE was negatively associated with patients requiring escalation of treatment, PE recurrence, and all-cause mortality, but it was positively associated with bleeding.

Background: A higher red blood cell distribution width (RDW) predicts major adverse cardiac events in patients with coronary artery disease (CAD). However, there are only a few studies regarding the relationship between RDW and vulnerable plaques. Thus, the purpose of the present study is to retrospectively explore the predictive value of the association between RDW and plaque vulnerability assessed by optical coherence tomography (OCT) in patients with cardiovascular (CV) diseases. Methods: This study included 35 patients with stable angina pectoris (SAP) and 70 patients with the acute coronary syndrome (ACS). We documented clinical features as well as peripheral RDW. Plaque vulnerability was determined by OCT. We defined thin-cap fibroatheroma (TCFA) as a lipid-rich plaque (fibrous cap <65 μm thick). Results: Plaque rupture was detected more frequently in patients with ACS compared with patients with SAP (62.9 vs. 2.9%, p<0.001, and the corresponding TCFA were 50.69±15.68 vs. 80.03±21.60 μm, p<0.001, respectively). A higher RDW was found in patients with ACS than in patients with SAP (p<0.001). A cut-off value of RDW >13.85% could detect ruptured plaque with a sensitivity of 72.3% and a specificity of 62%. Conclusion: TCFA and plaque rupture were detected more frequently in patients with ACS compared with SAP. Elevated RDW was positively the predictive value of the association between plaque vulnerability.

Background: Pericardial Effusion (PEf) can occur with Acute Heart Failure (AHF). Objective: To evaluate the effect of PEf size on the prognosis of patients with AHF. Methods: According to the maximum size of PEf, all patients were divided into five groups. The primary outcome was in-hospital mortality. The independent effect of PEf size was determined by binary logistic regression analysis. The curve in line with the overall trend was drawn by local weighted regression (Lowess). Results: We included 192 patients with AHF complicated by PEf. As PEf size increased, in-hospital mortality increased significantly (Group 5 vs. Group 1: 34.8 vs. 8.9% p=0.042). After adjusting for confounders, there was no significant association between PEf groups and in-hospital mortality (Group 5 vs. Group 1: odd ratio (OR), 95% confidence interval (CI): 2.72, 0.41-18.22, p=0.298). However, when PEf size was analysed as a continuous variable, an independent association between increased risk of inhospital mortality and PEf size was observed (OR, 95% CI: 1.08, 1.00-1.16, p=0.037). The Lowess curve showed a positive relationship between PEf size and in-hospital mortality. Furthermore, as PEf groups increased, the length of hospital stay (Group 5 vs. Group 1 median and interquartile range: 16, 14-21 vs. 13, 8-17 days, p<0.001) was significantly prolonged. An association between PEf size with acute kidney injury (AKI) was not observed. Conclusion: The PEf size was independently associated with the increased risk of in-hospital mortality in patients with AHF.

Aims: To explore treatment with Direct Oral Anticoagulants (DOACs) in left ventricular thrombus (LVT) after ST-segment elevation myocardial infarction (STEMI) in patients who underwent percutaneous coronary intervention (PCI). Background: Contemporary data regarding using DOACs for LVT after STEMI patients who underwent PCI is limited. Objectives: To investigate the efficacy and safety of DOACs on the treatment of LVT post STEMI and PCI. Methods: This retrospective study enrolled patients with LVT post STEMI and PCI within 1month from onset who received warfarin or DOACs at discharge. The primary endpoint was LVT resolution. Secondary endpoints were major adverse cardiovascular events (MACEs), including death, stroke, systemic embolism (SE), myocardial infarction (MI) and major or minor bleeding. Results: A total of 128 consecutive patients were recruited, of which 72 received warfarin and 56 DOACs [48 on rivaroxaban and 8 on dabigatran]. The rate of LVT resolution was higher within 1 month in the DOACs group than warfarin (26.8% vs. 11.1%; p = 0.022) (Kaplan-Meier estimates, p = 0.002). No significant differences were found at 3 months (p = 0.246), 6 months (p = 0.201), 9 months (p = 0.171) and 12 months (p = 0.442). No patients treated with DOACs had major bleeding, while two patients with warfarin had upper gastrointestinal bleeding (0 vs. 2 (2.8%); p = 0.209). No death or SE occurred. No significant differences on secondary endpoints were found in both the groups, including stroke, MI, minor bleeding and all bleeding events. Conclusion: DOACs appear to be a suitable alternative to warfarin for the management of LVT post STEMI, especially in patients who are intolerant to warfarin.

Objective: Obesity, a major health issue worldwide, is associated with increased cardiovascular risk, endothelial dysfunction, and arterial stiffness. Tadalafil has been demonstrated to improve vascular parameters. Aim: To evaluate the effect of a single 20 mg dose of tadalafil on flow-mediated dilation and hemodynamic and arterial stiffness markers. Methods: A randomized, double-blind, placebo-controlled study was conducted on 80 participants (41 assigned to placebo and 39 to tadalafil) with grade 1 obesity, to evaluate the acute effect of a single dose of 20 mg of tadalafil on flow-mediated dilation and hemodynamic and arterial stiffness markers. Results: Tadalafil did not modify flow-mediated dilation. However, it significantly lowered systolic blood pressure (SBP) (130.6±17.1 vs. 125.0±12.7 mmHg, p=0.011), diastolic blood pressure (82.7±18.2 vs. 76.5±11.8 mmHg, p≤0.001), central systolic blood pressure (116.33±19.16 vs. 109.90±15.05 mmHg, p=0.001), the augmentation index (69.1±17.1 vs. 65.7±14.4, p=0.012), and brachial-ankle pulse wave velocity (1229.7±218.4 vs. 1164.0±181.7, p=0.001). Conclusion: A single dose of tadalafil did not modify flow-mediated dilation in patients with grade 1 obesity but improved blood pressure and brachial-ankle pulse wave velocity.