Current Vascular Pharmacology - Volume 20, Issue 4, 2022

Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome Coronavirus- 2 (SARS-CoV-2), has caused a global pandemic with high morbidity and mortality. The presence of several comorbidities has been associated with a worse prognosis, with chronic kidney disease being a critical risk factor. Regarding COVID-19 complications, other than classical pneumonia and thromboembolism, acute kidney injury (AKI) is highly prevalent and represents a poor prognostic indicator linked to increased disease severity and mortality. Its pathophysiology is multifactorial, revolving around inflammation, endothelial dysfunction, and activation of coagulation, while the direct viral insult of the kidney remains a matter of controversy. Indirectly, COVID-19 AKI may stem from sepsis, volume depletion, and administration of nephrotoxic agents, among others. Several markers have been proposed for the early detection of COVID-19 AKI, including blood and urinary inflammatory and kidney injury biomarkers, while urinary SARS-CoV-2 load may also be an early prognostic sign. Concerning renal replacement therapy (RRT), general principles apply to COVID-19 AKI, but sudden RRT surges may mandate adjustments in resources. Following an episode of COVID-19 AKI, there is a gradual recovery of kidney function, with pre-existing renal impairment and high serum creatinine at discharge being associated with kidney disease progression and long-term dialysis dependence. Finally, kidney transplant recipients represent a special patient category with increased susceptibility to COVID- 19 and subsequent high risk of severe disease progression. Rates of mortality, AKI, and graft rejection are significantly elevated in the presence of COVID-19, highlighting the need for prevention and careful management of the disease in this subgroup.

Coronavirus disease-2019 (COVID-19) causes mild illness to serious infection with lung involvement, thrombosis, and other complications potentially resulting in fatal outcomes. Recognised inflammatory biomarkers play important roles in managing patients with COVID-19; for example, diagnosis, follow-up, assessment of treatment response, and risk stratification. Inflammatory markers in COVID-19 disease were analysed in two categories. Well-known inflammatory markers include complete blood count, C-reactive protein, albumin, cytokines, and erythrocyte sedimentation rate. Asymmetric dimethylarginine, endocan, pentraxin 3, serum amyloid A, soluble urokinase plasminogen activator receptor, total oxidant status and total antioxidant status, and galectin-3 are considered among the emerging inflammatory markers. This brief narrative review assesses the relationship between these inflammatory markers and COVID-19 infection.

The neurological complications of Coronavirus 2019 (COVID-19) including stroke have been documented in the recent literature. COVID-19-related inflammation is suggested to contribute to both a hypercoagulable state and haemorrhagic transformation, including in younger individuals. COVID-19 is associated with a heightened risk of ischaemic stroke. Haemorrhagic stroke in COVID-19 patients is associated with increased morbidity and mortality. Cerebral venous sinus thrombosis (CVST) accounts for <1% of stroke cases in the general population but has come to heightened public attention due to the increased risk associated with adenoviral COVID-19 vaccines. However, recent evidence suggests the prevalence of stroke is less in vaccinated individuals than in unvaccinated COVID-19 patients. This review evaluates the current evidence of COVID-19-related ischaemic and haemorrhagic stroke, with a focus on current epidemiology and inflammatory-linked pathophysiology in the field of vascular neurology and stroke medicine.

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease leading to right heart failure and death if untreated. Medical therapies for PAH have evolved substantially over the last decades and are associated with improvements in functional class, quality of life, and survival. PAH-targeted therapies now consist of multiple inhaled, oral, subcutaneous, and intravenous therapies targeting the phosphodiesterase, guanylate cyclase, endothelin and prostacyclin pathways. Patients with congenital heart disease (CHD) are at high risk of developing PAH and growing evidence exists that PAH-targeted therapy can be beneficial in PAH-CHD. However, the PAH-CHD patient population is challenging to treat due to the heterogeneity and complexity of their cardiac lesions and associated comorbidities. Furthermore, most high-quality randomized placebo-controlled trials investigating the effects of PAH-targeted therapies only included a minority of PAH-CHD patients. Few randomized, controlled trials have investigated the effects of PAH-targeted therapy in pre-specified PAH-CHD populations. Consequently, the results of these clinical trials cannot be extrapolated broadly to the PAH-CHD population. This review summarizes the data from high-quality clinical PAH treatment trials with a specific focus on the PAH-CHD population.

Background: Familial hypercholesterolemia (FH) is a common illness mainly caused by variants occurring in the low-density lipoprotein receptor (LDLR) gene. FH is a leading cause of coronary artery disease. Objective: This study aims to determine genetic defect(s) in homozygous and heterozygous FH index patients and their first-degree blood relatives and understand the genotype-phenotype correlation. Methods: This study employed the genetic screening of FH-related genes by next-generation sequencing and cascade screening by capillary sequencing. Results: We identified the presence of a novel frameshift variant [c.335_336insCGAG, p.(F114Rfs*17)] and three known missense variants [c.622G>A, p.(E208K)], [c.1474G>A, p.(D492N)], [c.1429G>A, p.(D477N)] in the LDLR gene of four unrelated Saudi families with FH. In proband 1, a nonsense variant c.1421C>G, p.(S474*) was also detected at exon 9 of the lipoprotein lipase gene. The segregation arrangement of the identified variants corresponded with the clinical characteristics. In this study, all the detected variants were confined in the ligand-binding domain and epidermal growth factor (EGF)-precursor homology domain of the LDLR protein, which portrayed severe clinical phenotypes of FH. Moreover, these LDLR variants were in a highly conserved residue of the proteins. Conclusion: In addition to the finding of the novel variant in the LDLR gene that extends the spectrum of variants causing FH, the results of this study also support the need for diagnostic screening and cascade genetic testing of this high-risk condition and to understand the genotype-phenotype correlation, which could lead to better prevention of coronary artery disease.

Background: There is limited data on moderate-dose with slow-infusion thrombolytic regimen by ultrasound-asssisted-thrombolysis (USAT) in patients with acute pulmonary embolism (PE). Aims: In this study, our eight-year experience on USAT with moderate-dose, slow-infusion tissue-type plasminogen activator (t-PA) regimen in patients with PE at intermediate-high- and high-risk was presented, and short-, and long-term effectiveness and safety outcomes were evaluated. Methods: Our study is based on the retrospective evaluation of 225 patients with PE having multiple comorbidities who underwent USAT. Results: High- and intermediate-high-risk were noted in 14.7% and in 85.3% of patients, respectively. Mean t-PA dosage was 35.4±13.3 mg, and the infusion duration was 26.6±7.7 h. Measures of pulmonary artery (PA) obstruction and right ventricle (RV) dysfunction were improved within days (p<0.0001 for all). During the hospital stay, major and minor bleeding and mortality rates were 6.2%, 12.4%, and 6.2%, respectively. Bleeding and unresolved PE accounted for 50% and 42.8% of in-hospital mortality, respectively. Age, rate, and duration of t-PA were not associated with in-hospital major bleeding and mortality. Oxygen saturation exceeded 90% in 91.2% of patients at discharge. During follow-up of median 962 (610-1894) days, high-risk status related to 30-day mortality, whereas age >65 years was associated with long-term mortality. Conclusion: Our real-life experience with USAT with moderate-dose, slow-infusion t-PA regimen in patients with PE at high-and intermediate-high risk demonstrated clinically relevant improvements in PA obstructive burden and RV dysfunction. Age, rate or infusion duration of t-PA was not related to major bleeding or mortality risk, whereas unresolved obstruction remained as a lethal issue.