A Discrepancy: Calcium Channel Blockers Are Effective for the Treatment of Hypertensive Left Ventricular Hypertrophy but Not as Effective for Prevention of Heart Failure.

Arterial hypertension (HTN) is important due to its high prevalence, morbidity, and mortality rates. Calcium channel blockers (CCBs) are the first-line antihypertensive drugs. HTN can lead to heart failure (HF) by causing hypertensive left ventricular hypertrophy (HTN LVH). CCBs are recommended for the treatment of HTN LVH. The aim of this study was to analyze the status of CCBs regarding (1) HTN LVH treatment and (2) capability to prevent HTN-induced HF in the guidelines. For this narrative review, the following databases were searched: Medline, Scopus, Science Direct, Springer, SAGE, Wiley, Oxford Journals, Cambridge, and Google Scholar. CCBs are effective antihypertensive drugs and a very good therapeutic option for HTN LVH as they can cause reverse LVH remodeling. Consequently, we may expect that CCBs would prevent HF. However, evidence suggests that CCBs confer less protection from HF than other first-line antihypertensive drugs. A negative inotropic action of nondihydropyridine CCBs may contribute to suboptimal protection against HF. This discrepancy is clinically relevant because CCBs are in one of the two recommended (single pill) combinations for the initial treatment of HTN. LVH is a strong risk factor for HF in HTN patients. When LVH arises, the risk of HF increases dramatically. CCBs are inferior to renin-angiotensin-aldosterone system blockers but still very effective in bringing about regression of HTN LVH; consequently, CCBs are expected to protect from HF. On the contrary, CCBs protect from HF less effectively than other first-line antihypertensive drugs. This discrepancy needs to be investigated further to improve clinical practice.

Blood pressure cut-offs to diagnose impending hypertensive emergency depend on previous hypertension-mediated organ damage and comorbid conditions.

Background Hypertensive emergencies (HTN-E) are important due to a high risk of mortality. However, a sudden increase in blood pressure (BP) can damage target organs before the BP reaches cut-offs to diagnose HTN-E. We (i) analyse HTN guidelines for recommendations of treatment individualization, such as adjusting BP cut-offs for hypertensive urgency or impending HTN-E according to patient's susceptibility to complications (because of previous hypertension-mediated organ damage [HMOD], cardiovascular events and comorbid conditions), and (ii) provide a rationale for the inclusion of patient's susceptibility in protocols for treatment of acute HTN-E. Methods We searched PubMed, SCOPUS, Science Direct, Springer, Oxford Press, Wiley, SAGE and Google Scholar for the following terms: arterial hypertension, impending, emergency, target organ damage, hypertension-mediated organ damage, and comorbidity. Results The available guidelines do not recommend that when we estimate the probability of HTN-E in a patient with very high BP, we take into account not only the 'aggressive factor' (i.e. history of HTN, absolute BP values and rate of its increase), but also the 'vulnerability of the patient' due to previous major adverse cardio-vascular events, HMOD and comorbid conditions. Conclusion The risk does not depend only on the aggressiveness of the health threat but also on the strength of the host's defence. It is, therefore, surprising that one side of the natural interaction (i.e. susceptibility of a patient) is overlooked in almost all available guidelines on HTN.

Rationale for the Concept of Impending Hypertension-Mediated Organ Damage.

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'.

Beta Blockers can Mask not only Hypoglycemia but also Hypotension.

BACKGROUND: Beta-adrenergic (ß-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects that 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 ß-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.

Less Known but Clinically Relevant Comorbidities of Atrial Fibrillation: A Narrative Review.

BACKGROUND: The important risk factors for atrial fibrillation (AF) in the general population are not always equally important in specific and relatively prevalent diseases. OBJECTIVE: The main goal of this narrative review is to focus attention on the presence and the relationship of AF with several important diseases, such as cancer or sepsis, in order to: 1) stimulate further research in the field, and 2) draw attention to this relationship and search for AF in clinical practice. METHODS: We searched PubMed, SCOPUS, Elsevier, Wiley, Springer, Oxford Journals, Cambridge, SAGE, and Google Scholar for less-known comorbidities of AF. The search was limited to publications in English. No time limits were applied. RESULTS: AF is widely represented in cardiovascular and other important diseases, even in those in which AF is rarely mentioned. In some specific clinical subsets of AF patients (e.g., patients with sepsis or cancer), the general risk factors for AF may not be so important. Patients with new-onset AF have a several-fold increase in relative risk of cancer, deep vein thrombosis, and pulmonary thromboembolism (PTE) during the follow-up. CONCLUSION: AF presence, prognosis, and optimal therapeutic approach are insufficiently recognised in several prevalent diseases, including life-threatening ones. There is a need for a better search for AF in PTE, pulmonary oedema, aortic dissection, sepsis, cancer and several gastrointestinal diseases. Improved AF detection would influence treatment and improve outcomes.

Colicins and Microcins Produced by Enterobacteriaceae: Characterization, Mode of Action, and Putative Applications.

Enterobacteriaceae are widely present in many environments related to humans, including the human body and the food that they consume, from both plant or animal origin. Hence, they are considered relevant members of the gastrointestinal tract microbiota. On the other hand, these bacteria are also recognized as putative pathogens, able to impair human health and, in food, they are considered indicators for the microbiological quality and hygiene status of a production process. Nevertheless, beneficial properties have also been associated with Enterobacteriaceae, such as the ability to synthesize peptides and proteins, which can have a role in the structure of microbial communities. Among these antimicrobial molecules, those with higher molecular mass are called colicins, while those with lower molecular mass are named microcins. In recent years, some studies show an emphasis on molecules that can help control the development of pathogens. However, not enough data are available on this subject, especially related to microcins. Hence, this review gathers and summarizes current knowledge on colicins and microcins, potential usage in the treatment of pathogen-associated diseases and cancer, as well as putative applications in food biotechnology.

Contraindications Differ Widely Among Beta Blockers and Ought to be Cited for an Individual Drug, Not for the Entire Class.

Beta blockers (BBs) have important side effects that contribute to low adherence and persistence. Therefore, the optimal choice of BB is an important mode to prevent BB's side effects, leading to an increase in compliance, which can improve the outcomes in BBs' evidence-based indications, such as acute myocardial infarction, heart failure, etc. The aim of the paper is to suggest an improved method of reporting contraindications for BBs. We used a search of the following indexing databases: SCOPUS and PubMed, and web search engine Google Scholar to identify guidelines on arterial hypertension (HTN). HTN guidelines published during the last 2 decades were analyzed (from 2000 to 2020). Some of the contraindications (e.g., bradycardia, acute heart failure) are true for every BB. However, some contraindications do not belong to the whole BB class. For example, propranolol and carvedilol are contraindicated in chronic obstructive lung disease, but nebivolol and bisoprolol are not. We suggest that contraindications which are specific for some BBs (i.e., not for the whole class) ought to be listed with the exact name(s) of the individual BBs. In this way, we may decrease the number of wrong choices among BBs and consequently increase drug adherence (which is currently worse for the class of BBs than for most of the other antihypertensive drugs). To our knowledge, there is a lack of guidelines citing contraindications for individual BBs, because they vary a lot within-the-class of BBs. This is an approach to improve both basic medical education and guidelines.

Single prognostic cut-off value for admission glycemia in acute myocardial infarction has been used although high-risk stems from hyperglycemia as well as from hypoglycemia (a narrative review).

All original articles and meta-analysis use the single cut-off value to distinguish high-risk hyperglycemic from other acute myocardial infarction (AMI) patients. The mortality rate is 3.9 times higher in non-diabetic AMI patients with admission glycemia ≥6.1mmol compared to normoglycemic non-diabetic AMI patients. On the other hand, admission hypoglycemia in AMI is an important predictor of mortality. Because both admission hypo- and hyperglycemia correspond to higher in-hospital mortality, this graph is recognized as "J or U shaped curve". The review suggests two cut-off values for admission glycemia for risk assessment in AMI instead of single one because hypoglycemia as well as hyperglycemia represents a high-risk factor.

Should Cushing's Syndrome be Considered as a Disease with High Cardiovascular Risk in Relevant Guidelines?

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.

Beta blocker rebound phenomenon is important, but we do not know its definition, incidence or optimal prevention strategies.

The aim of this review is to analyze whether there is a need for scientific information about the beta blocker (BB) rebound phenomenon; whether such information is available; and, if it is, how detailed is the BB rebound phenomenon explained in the guidelines and papers? A narrative review is used due to the lack of valid randomized clinical trials (RCTs) on the topic, which are needed for a meta-analysis. The BB rebound phenomenon can have dangerous consequences. The discontinuation of a BB leads to a fourfold increased risk of events related to coronary artery disease in hypertensive patients; it increases in-hospital mortality in heart failure patients; it can precipitate angina pectoris attack; and it increases the risk for death and rehospitalization in patients who survive acute myocardial infarction. Consequently, being considered in the guidelines, the BB rebound phenomenon is believed to be clinically relevant (by experts in the field). This is in sharp contrast with the lack of any additional relevant information about the BB rebound phenomenon in the various important guidelines. For example, we lack a consensus about the precise definition. Moreover, data about the incidence and optimal prevention strategies are lacking for the phenomenon (which is sometimes life-threatening). The BB rebound phenomenon is an additional reason why it is very important to test the prognosis of patients following the cessation of long-term medicaments in RCTs, particularly for BBs.