A considerable amount of data supports a 1.8-7.4-fold increased mortality associated with Cushing’s syndrome (CS). This is attributed to a high occurrence of several cardiovascular disease (CVD) risk factors in CS [e.g. adiposity, arterial hypertension (AHT), dyslipidaemia and type 2 diabetes mellitus (T2DM)]. Therefore, practically all patients with CS have the metabolic syndrome (MetS), which represents a high CVD risk. Characteristically, despite a relatively young average age, numerous patients with CS display a 'high' or 'very high' CVD risk (i.e. risk of a major CVD event >20% in the following 10 years). Although T2DM is listed as a condition with a high CVD risk, CS is not, despite the fact that a considerable proportion of the CS population will develop T2DM or impaired glucose tolerance. CS is also regarded as a risk factor for aortic dissection in current guidelines. This review considers the evidence supporting listing CS among high CVD risk conditions.
Introduction: Beta blockers (BBs) are an important class of drugs, with numerous indications in cardiology, emergency and general medicine. The indications include heart failure (HF), acute myocardial infarction (AMI), post-MI [1], supraventricular and ventricular arrhythmias, chronic coronary syndrome, systemic arterial hypertension (HTN), hypertrophic cardiomyopathy and aortic aneurysm or dissection. All BBs decrease heart rate (HR) and blood pressure (BP), the major determinants of myocardial oxygen consumption; therefore, myocardial anti-ischemic action is a class effect. On the other hand, it is very important that not all BBs decrease all-cause mortality and sudden death; therefore, their crucial characteristics are not the class effect [2]. Literature overview: Importantly, not all indications and contraindications are valid for each BB because there is only some degree of uniformity among BBs as a class of drugs [3-5]. Despite their common mechanism of action, BBs show several distinctions regarding specific activities [6]. To start with basic characteristic of BBs, the effect on HR is stronger for e.g. bisoprolol vs nebivolol (in the average doses), while the opposite is true for the action on BP. BBs differ in the degree of preferential affinity for β-adrenergic receptors (β-ARs) that is, in their β1 selectivity (cardioselectivity), the degree of antagonist activity towards β-ARs, pharmacokinetic properties [7] (e.g. half-life, lipophilicity, excretion), as well as additional pharmacodynamic properties e.g. vasodilating properties [8] (α-receptor blocking property or capability to stimulate nitric oxide production), intrinsic sympathomimetic activity (ISA), membrane stabilizing activities (MSA), inverse agonist [9] and biased agonist activity [10] and evidence-based indication in HF [11]. These specific properties of BBs additionally determine not only their indications [12], but the distinctions in their side effects and contraindications [7]. Administration of an appropriate BB is of importance, according to the main indication (which is supported by evidence and recommended in current guidelines), as well as according to patient’s comorbidities as additional indications [13]. For example, not all BBs have acute myocardial infarction (AMI) as an evidence-based indication [14]. Moreover, only a few of numerous BBs are recommended for HF with reduced left ventricular ejection fraction (LVEF) [15, 16]. Furthermore, the effect of various BBs on central (aortic) BP is different: vasodilatory BBs (such as carvedilol and nebivolol) decrease it, while the first and the second generation of BBs do not. Therefore, vasodilatory BBs (by decreasing aortic BP) can be expected to better prevent aortic complications (dissection and aneurysm) in patients with Marfan syndrome [17]. Administration of an appropriate BB regarding the specific indication expectedly results in improvement of the patient’s condition, which progresses to better adherence, and consequently reduces the chance for BB rebound [13]. Compelling indications for antihypertensives are listed in guidelines [18, 19] and they are very useful to help optimize antihypertensive treatment [19-21]. Having in mind how many differences there are among BBs, it seems logical and practical not to refer to them always as a group, but to individualize the choice for specific indications. The first suggestion is to improve classification of BBs, by incorporating indications for individual BB. For example, for bisoprolol, the numerous indications could include HF, AMI, post-MI, chronic coronary syndrome, supraventricular and ventricular arrhythmias, HTN, aortic aneurysm or dissection, hypertrophic cardiomyopathy, etc. The second suggestion is to improve (some of) the current reports on a specific indication (disease) by listing exactly which BB is indicated. For example, for HF (both with and without preserved LVEF), only 3 BBs (carvedilol, bisoprolol, metoprolol succinate) should be listed according to some guidelines [16] or 4 BBs (the 3 BBs already mentioned plus nebivolol) as recommended by other guidelines [15]. The third suggestion is to explain how strong the evidence is for each BB. For example, evidence-based indication (derived from several randomised clinical trials) for a particular BB can be marked as level of evidence A (LOE-A). Similarly, LOE-C can be used if the indication for another BB as suggested by experts. Additional (fourth) suggestion is that in large tables with numerous drugs (such as compelling indications for antihypertensive drugs), when BBs are mentioned, a couple of proper individual examples should be listed in parenthesis. This can help prevent inadequate choices from the BB class (as BBs are very different). Lists of compelling indications for BBs, or the other way round – list of diseases as indications for a particular BB can help physicians to select the most appropriate BB. Namely, in a paper about tremor, in the part about treatment, instead of (or in addition to) BB, should list “propranolol” (which blocks strongly β2-ARs) and not e.g. bisoprolol (because it is a β1-selective BB and therefore not indicated for tremor treatment). Similarly, if the topic is the chronic treatment of ventricular tachycardia in patients with chronic obstructive lung disease, potential mistakes in practice can be avoided if “bisoprolol” is stated instead of BB. Even a better example is the direct comparison between the first BB used (propranolol) and the latest one (nebivolol): propranolol is not β1-selective (“cardioselective”) and therefore is indicated for tremor, but not in chronic obstructive lung disease, etc. while nebivolol is very cardioselective (and has better metabolic profile as far as glycaemia and cholesterol are concerned) [20]. Moreover, propranolol is not vasodilatory but nebivolol is; propranolol has membrane stabilizing activity, but nebivolol does not [22]; propranolol is not indicated in congestive heart failure while nebivolol is recommended by the European Society of Cardiology (ESC) for heart failure, particularly with preserved ejection fraction (HFpEF) [15]. Indeed, such tables with individual BBs and their compelling indications (with the levels of evidence) are very important and ought to be created by international experts, in the form of position paper/guidelines. Table 1 illustrates the main proposal of the paper and it may serve as a material to initiate this process. Conclusions: BBs differ within the class in so many ways that it is not only logical but also practical for real-life clinical practice that experts in the field make a list of the compelling indications for individual BBs. Time has come to incorporate our knowledge about BBs into a new approach of presenting these useful and very individual drugs.
Background: There is a need to analyse the current approach to beta-blocker (BB) use in relation to exercise-based stress tests. Objective: We compared various guidelines regarding recommending abrupt vs gradual discontinuation of BB prior to exercise tests. We also analyse the shortcomings of the currently recommended approach and suggest a new approach to avoid BB rebound. Methods: A narrative review is used to analyse this topic due to lack of valid randomized clinical trials. Results: Omitting the BB therapy prior to exercise-based test has been recommended in guidelines for many years. Although reasonable, this approach has potential disadvantages since sudden BB withdrawal may induce a rebound phenomenon, which is, also, acknowledged in several guidelines. Conclusions: We observed inconsistency among relevant guidelines; there is no homogenous approach regarding BB use before exercise tests. Most guidelines recommend BB withdrawal for a couple of days before the test; they do not advise BB dose tapering. This approach is not standardised and raises the risk of BB rebound phenomenon both before and during the test. Therefore, we suggest using the half the prescribed BB dose at the usual time of administration (in the morning, prior to the exercise test).
Background: Beta-adrenergic (β-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects which decrease the compliance, adherence, and persistence of this very useful group of drugs. Objective: The paper aims to analyze the possibility that an unnoticed side effect may contribute to a less favorable pharmacologic profile of BBs, e.g., a diminished reaction to a sudden fall in BP. Methods: We searched two medical databases for abstracts and citations (Medline and SCOPUS). Moreover, we searched the internet for drug prescription leaflets (of the individual BBs). Results: Whichever cause of stress is considered, the somatic manifestations of stress will be (partially) masked if a patient takes BB. Stress–induced hypercatecholaminemia acts on β-AR of cardiomyocytes; it increases heart rate and contractility, effects suppressed by BBs. The answers of the organism to hypoglycemia and hypotension share the main mechanisms such as sympathetic nervous system activation and hypercatecholaminemia. Thus, there is a striking analogy: BBs can cover up symptoms of both hypoglycemia (which is widely known) and of hypotension (which is not recognized). It is widely known that BBs can cause hypotension. However, they can also complicate recovery by spoiling the defense mechanisms in hypotension as they interfere with the crucial compensatory reflex to increase blood pressure in hypotension. Conclusion: Beta blockers can cause hypotension, mask it, and make recovery more difficult. This is clinically important and deserves to be more investigated and probably to be stated as a warning.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.