Current Vascular Pharmacology - Volume 20, Issue 2, 2022

Vascular calcification (VC) is highly prevalent in Chronic Kidney Disease (CKD) patients, progresses gradually with deterioration of kidney function and is a strong, independent predictor of cardiovascular (CV) mortality. Matrix Gla Protein (MGP), the most potent inhibitor of VC, requires vitamin K as a co-factor to become biologically active. Accumulating epidemiological data have associated vitamin K depletion with VC progression and CV outcomes. CKD patients are characterized by poor vitamin K status and at the same time, pronounced CV calcification. In early and advanced CKD, including end-stage kidney disease, exogenous supplementation of vitamin K (especially with menaquinone 7, its most bioavailable form) might decrease the inactive form of MGP (dephosphorylated, uncarboxylated MGP) and probably retard the progression or even reverse VC. Here, we focus and discuss the interventional human studies of vitamin K supplementation in CKD patients and suggest future directions in this area of interest.

Background: The number of patients with hypertension urgencies (HTN-Us) and emergencies (HTN-Es) in the emergency department is relatively constant despite improved detection, awareness and control of arterial hypertension. Objective: This study analyses the precision of the often-used definition of HTN-E, particularly the phrase ‘with the evidence of impending or progressive hypertension-mediated organ damage (HMOD)’. We then provide a rationale for the concept of impending HMOD. Methods: The databases PubMed, Science Direct, Springer, Oxford Press, Wiley, SAGE and Google Scholar were searched and the relevant definition has been analyzed. Results: The definition of HTN-E is suboptimal and requires a consensus on whether to include the phrase ‘impending hypertensive HMOD’ in the definition. Conclusion: A consensus on the principles of treating the ‘impending hypertensive HMOD’ does not exist, making its use inconsistent in emergency departments worldwide. In this paper, we present a rationale for the concept of ‘impending HMOD’.

Stroke is the second most common cause of death worldwide. The rates of stroke are increasing in less affluent countries predominantly because of a high prevalence of modifiable risk factors. The Lipid Association of India (LAI) has provided a risk stratification algorithm for patients with ischaemic stroke and recommended low density lipoprotein cholesterol (LDL-C) goals for those in very high risk group and extreme risk group (category A) of <50 mg/dl (1.3 mmol/l) while the LDL-C goal for extreme risk group (category B) is ≤30 mg/dl (0.8 mmol/l). High intensity statins are the first-line lipid lowering therapy. Nonstatin therapy like ezetimibe and proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors may be added as an adjunct to statins in patients who do not achieve LDL-C goals with statins alone. In acute ischaemic stroke, high intensity statin therapy improves neurological and functional outcomes regardless of thrombolytic therapy. Although conflicting data exist regarding increased risk of intracerebral haemorrhage (ICH) with statin use, the overall benefit risk ratio favors long-term statin therapy necessitating detailed discussion with the patient. Patients who have statins withdrawn while being on prior statin therapy at the time of acute ischaemic stroke have worse functional outcomes and increased mortality. LAI recommends that statins be continued in such patients. In patients presenting with ICH, statins should not be started in the acute phase but should be continued in patients who are already taking statins. ICH patients, once stable, need risk stratification for atherosclerotic cardiovascular disease (ASCVD).

Stress echocardiography (SE) was initially used for assessing patients with known or suspected coronary heart disease by detecting and evaluating myocardial ischemia and viability. The implementation of SE has gradually been extended to several cardiovascular diseases beyond coronary artery disease, and SE protocols have been modified and adapted for the detection of coronary artery disease (CAD) or other cardiovascular diseases in specific patient populations. This review attempts to summarize current data concerning SE implementation and clinical value in these specific and diverse populations: patients with an intramural course of a coronary artery, known as a myocardial bridge, chronic severe or end-stage hepatic disease, chronic severe or end-stage kidney disease, cardiac allograft vasculopathy, patients scheduled for solid-organ transplantation and other intermediate and high-risk surgery and, finally, patients treated with anticancer drugs or radiotherapy.

The role of vitamin D in maintaining a healthy cardiovascular (CV) and the renal system has received increasing attention. Low vitamin D levels are associated with the incidence of hypertension, cardiac remodeling, and chronic congestive heart failure. Low vitamin D levels also influence renal disease progression and albuminuria deterioration. Moreover, recent research indicates that vitamin D deficiency can be a potential risk factor for coronavirus disease-19 (COVID-19) infection and poorer outcomes. Data are inconclusive as to whether supplementation with vitamin D agents reduces CV disease risk or COVID-19 severity. Conversely, in patients with kidney disease, vitamin D supplementation is associated with an improvement in kidney function and albuminuria. This narrative review considers recent data on the effects of vitamin D on the CV and renal system, as well as its possible role regarding COVID-19 complications.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have changed the clinical landscape of diabetes mellitus (DM) therapy through their favourable effects on cardiovascular outcomes. Notably, the use of SGLT2i has been linked to cardiovascular benefits regardless of DM status, while their pleiotropic actions remain to be fully elucidated. What we do know is that SGLT2i exert beneficial effects even at the level of the myocardial cell and that these are linked to an improvement in the energy substrate, resulting in less inflammation and fibrosis. SGLT2i ameliorates myocardial extracellular matrix remodeling, cardiomyocyte stiffness and concentric hypertrophy, achieving beneficial remodeling of the left ventricle with significant implications for the pathogenesis and outcome of heart failure. Most studies show a significant improvement in markers of diastolic dysfunction along with a reduction in left ventricular hypertrophy. In addition to these effects, there is electrophysiological remodeling, which explains initial data suggesting that SGLT2i have an antiarrhythmic action against both atrial and ventricular arrhythmias. However, future studies need to clarify not only the exact mechanisms of this beneficial functional, structural, and electrophysiological cardiac remodeling but also its magnitude to determine whether this is a class or a drug effect.

Background: Given its close anatomical location to the heart and its endocrine properties, attention on epicardial adipose tissue (EAT) has increased. Objective: This study investigated the expression profiles of long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in EAT derived from patients with coronary artery disease (CAD). Methods: EAT samples from 8 CAD, and 8 non-CAD patients were obtained during open-heart surgery, respectively. The expression of lncRNAs and mRNAs in each EAT sample was investigated using microarray analysis and further verified using reverse transcription-quantitative polymerase chain reaction. Results: Overall, 1,093 differentially expressed mRNAs and 2,282 differentially expressed lncRNAs were identified in EAT from CAD vs. non-CAD patients. Analysis using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes showed that these differentially expressed genes were mainly enriched in various inflammatory, immune, and metabolic processes. They were also involved in osteoclast differentiation, B cell receptor and adipocytokine signaling, and insulin resistance pathways. Additionally, lncRNA-mRNA and lncRNA-target pathway networks were built to identify potential core genes (e.g., Lnc-CCDC68-2:1, AC010148.1, NONHSAT104810) involved in atherosclerotic pathogenesis. Conclusion: In summary, lncRNA and mRNA profiles in EAT were markedly different between CAD and non-CAD patients. Our study identifies several potential key genes and pathways that may participate in atherosclerosis development.