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Blood Pressure Dec 2023The current review is to describe the definition and prevalence of resistant arterial hypertension (RAH), the difference between refractory hypertension, patient... (Review)
Review
PURPOSE
The current review is to describe the definition and prevalence of resistant arterial hypertension (RAH), the difference between refractory hypertension, patient characteristics and major risk factors for RAH, how RAH is diagnosed, prognosis and outcomes for patients.
MATERIALS AND METHODS
According to the WHO, approximately 1.28 billion adults aged 30-79 worldwide have arterial hypertension, and over 80% of them do not have blood pressure (BP) under control. RAH is defined as above-goal elevated BP despite the concurrent use of 3 or more classes of antihypertensive drugs, commonly including a long-acting calcium channel blocker, an inhibitor of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a thiazide diuretic administered at maximum or maximally tolerated doses and at appropriate dosing frequency. RAH occurs in nearly 1 of 6 hypertensive patients. It often remains unrecognised mainly because patients are not prescribed ≥3 drugs at maximal doses despite uncontrolled BP.
CONCLUSION
RAH distinctly increases the risk of developing coronary artery disease, heart failure, stroke and chronic kidney disease and confers higher rates of major adverse cardiovascular events as well as increased all-cause mortality. Timely diagnosis and treatment of RAH may mitigate the associated risks and improve short and long-term prognosis.
Topics: Adult; Humans; Hypertension; Antihypertensive Agents; Angiotensin-Converting Enzyme Inhibitors; Calcium Channel Blockers; Blood Pressure
PubMed: 36891929
DOI: 10.1080/08037051.2023.2185457 -
Cardiovascular Drugs and Therapy Aug 2023Cardiovascular disease is the leading cause of mortality worldwide, affecting a wide range of patients at different stages across the cardiovascular continuum.... (Review)
Review
Cardiovascular disease is the leading cause of mortality worldwide, affecting a wide range of patients at different stages across the cardiovascular continuum. Hypertension is one of the earliest risk factors in this continuum and can be controlled in most patients with currently available antihypertensive agents. However, goals are often not met because treatments are not optimized in terms of tailoring therapy to individual patients based on their hypertension subclass and cardiovascular risk profile and initiating early use of adapted-dose, single-pill combinations. In this context, beta-blockers in combination with angiotensin-converting enzyme (ACE) inhibitors are of special interest as a result of their complementary actions on the sympathetic nervous system and renin-angiotensin-aldosterone system, two interlinked pathways that influence cardiovascular risk and disease outcomes. In addition to their antihypertensive actions, beta-blockers are used to manage arrhythmias and treat angina pectoris and heart failure, while ACE inhibitors provide cardioprotection in patients with acute coronary syndromes and treat congestive heart failure. A broad range of patients may therefore receive the combination in routine clinical practice. This paper examines the supporting evidence for beta-blockers and ACE inhibitors in each of the above indications and considers the rationale for combining these agents into a single pill, using data from bisoprolol and perindopril randomized controlled trials as supporting evidence. Combining these established antihypertensive agents into a single pill continues to provide effective blood pressure lowering and improved cardiovascular outcomes while allowing a greater proportion of patients to rapidly achieve treatment targets.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Cardiovascular Diseases; Hypertension; Adrenergic beta-Antagonists; Renin-Angiotensin System; Heart Failure
PubMed: 34533690
DOI: 10.1007/s10557-021-07248-1 -
Biomolecules Aug 2023Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the gene, including Duchenne and Becker muscular dystrophy, and dilated... (Review)
Review
Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoids therapy. Procedures for diagnosing dystrophinopathies include creatine kinase assay, haplotype analysis, Southern blot analysis, immunological analysis, multiplex PCR, multiplex ligation-dependent probe amplification, Sanger DNA sequencing, and next generation DNA sequencing. Pharmacological therapy for dystrophinopathies comprises glucocorticoids (prednisone, prednisolone, and deflazacort), vamorolone, and ataluren. However, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers are the first-line to prevent dilated cardiomyopathy in dystrophinopathy patients. Duchenne muscular dystrophy gene therapy strategies involve gene transfer, exon skipping, exon reframing, and CRISPR gene editing. Eteplirsen, an antisense-oligonucleotide drug for skipping exon 51 from the gene, is available on the market, which may help up to 14% of Duchenne muscular dystrophy patients. There are various FDA-approved exon skipping drugs including ExonDys-51 for exon 51, VyonDys-53 and Viltolarsen for exon 53 and AmonDys-45 for exon 45 skipping. Other antisense oligonucleotide drugs in the pipeline include casimersen for exon 45, suvodirsen for exon 51, and golodirsen for exon 53 skipping. Advances in the diagnosis and therapy of dystrophinopathies offer new perspectives for their early discovery and care.
Topics: Humans; Dystrophin; Muscular Dystrophy, Duchenne; Cardiomyopathy, Dilated; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Oligonucleotides, Antisense
PubMed: 37759719
DOI: 10.3390/biom13091319 -
Redox Biology Dec 2023Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health....
Non-alcoholic fatty liver disease (NAFLD) is a potentially serious disease that affects 30 % of the global population and poses a significant risk to human health. However, to date, no safe, effective and appropriate treatment modalities are available. In recent years, ferroptosis has emerged as a significant mode of cell death and has been found to play a key regulatory role in the development of NAFLD. In this study, we found that arbutin (ARB), a natural antioxidant derived from Arctostaphylos uva-ursi (L.), inhibits the onset of ferroptosis and ameliorates high-fat diet-induced NAFLD in vivo and in vitro. Using reverse docking, we identified the demethylase fat mass and obesity-related protein (FTO) as a potential target of ARB. Subsequent mechanistic studies revealed that ARB plays a role in controlling methylation of the SLC7A11 gene through inhibition of FTO. In addition, we demonstrated that SLC7A11 could alleviate the development of NAFLD in vivo and in vitro. Our findings identify the FTO/SLC7A11 axis as a potential therapeutic target for the treatment of NAFLD. Specifically, we show that ARB alleviates NAFLD by acting on the FTO/SLC7A11 pathway to inhibit ferroptosis.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Arbutin; Angiotensin Receptor Antagonists; Ferroptosis; Angiotensin-Converting Enzyme Inhibitors; Amino Acid Transport System y+; Alpha-Ketoglutarate-Dependent Dioxygenase FTO
PubMed: 37984229
DOI: 10.1016/j.redox.2023.102963 -
Cells Jul 2023Diabetes is the most frequent cause of kidney disease that progresses to end-stage renal disease worldwide, and diabetic kidney disease is significantly related to... (Review)
Review
Diabetes is the most frequent cause of kidney disease that progresses to end-stage renal disease worldwide, and diabetic kidney disease is significantly related to unfavorable cardiovascular outcomes. Since the 1990s, specific therapies have emerged and been approved to slow the progression of diabetic kidney disease, namely, renin-angiotensin-aldosterone system blockers (including angiotensin-converting enzyme inhibitors (ACEi) angiotensin receptor blockers (ARBs), the non-steroidal mineralocorticoid receptor antagonist (NS-MRA), finerenone, and sodium-glucose cotransporter-2 (SGLT2) inhibitors). Mechanistically, these different classes of agents bring different anti-inflammatory, anti-fibrotic, and complementary hemodynamic effects to patients with diabetic kidney disease such that they have additive benefits on slowing disease progression. Within the coming year, there will be data on renal outcomes using the glucagon-like peptide-1 receptor agonist, semaglutide. All the aforementioned medications have also been shown to improve cardiovascular outcomes. Thus, all three classes (maximally dosed ACEi or ARB, low-dose SGLT-2 inhibitors, and the NS-MRA, finerenone) form the "pillars of therapy" such that, when used together, they maximally slow diabetic kidney disease progression. Ongoing studies aim to expand these pillars with additional medications to potentially normalize the decline in kidney function and reduce associated cardiovascular mortality.
Topics: Humans; Diabetic Nephropathies; Angiotensin-Converting Enzyme Inhibitors; Angiotensin Receptor Antagonists; Renin-Angiotensin System; Kidney Failure, Chronic; Mineralocorticoid Receptor Antagonists; Diabetes Mellitus
PubMed: 37566054
DOI: 10.3390/cells12151975