Gut Microbiota Dysbiosis and Sleep Disorders: Culprit in Cardiovascular Diseases.

Background: Over the past decade, the gut microbiome (GM) has progressively demonstrated to have a central role in human metabolism, immunity, and cardiometabolic risk. Likewise, sleep disorders showed an impact on individual health and cardiometabolic risk. Recent studies seem to suggest multi-directional relations among GM, diet, sleep, and cardiometabolic risk, though specific interactions are not fully elucidated. We conducted a systematic review to synthesize the currently available evidence on the potential interactions between sleep and GM and their possible implications on cardiometabolic risk. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses, including articles from January 2016 until November 2022. Narrative syntheses were employed to describe the results. Results: A total of 8 studies were selected according to these criteria. Our findings indicated that the sleep disorder and/or the acute circadian rhythm disturbance caused by sleep-wake shifts affected the human GM, mainly throughout microbial functionality. Conclusions: Sleep disorders should be viewed as cardiovascular risk factors and targeted for preventive intervention. More research and well-designed studies are needed to completely assess the role of sleep deprivation in the multi-directional relationship between GM and cardiometabolic risk.

Systematic Review Article: New Drug Strategies for Treating Resistant Hypertension-the Importance of a Mechanistic, Personalized Approach.

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2-3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs  as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article.

Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study.

BACKGROUND AND AIMS: Trehalose, spermidine, nicotinamide, and polyphenols are natural substances that exert pro-autophagic and antioxidant properties. Their role in blood pressure (BP) regulation and preservation of vascular function in essential hypertension is unknown. The aim of this study was to evaluate the effect of a mixture of these agents on BP level, markers of oxidative stress, autophagy, endothelial function, and vascular stiffness in outpatients with grade 1 uncomplicated essential hypertension. METHODS AND RESULTS: A single-centre, open-label, case-control, pilot study was conducted in adult outpatients (aged ≥18 years) receiving or not the mixture for two months along with the standard therapies. Both at baseline and at the end of the treatment the following clinical parameters were evaluated: brachial seated office BP level, central aortic pressure, pulse wave velocity, augmentation index (AI@75). Both at baseline and at the end of the treatment, a blood sample was drawn for the measurement of: H2O2, HBA%, levels of sNOX2-dp, Atg 5, P62, endothelin 1, and NO bioavailability. The mixture of nutraceuticals did not influence BP levels. Patients receiving the mixture showed a significant decrease of oxidative stress, stimulation of autophagy, increased NO bioavailability and no increase of the AI@75, in contrast to what observed in hypertensive patients not receiving the mixture. CONCLUSIONS: The supplementation of the trehalose, spermidine, nicotinamide, and polyphenols mixture counteracted hypertension-related arterial stiffness through mechanisms likely dependent on oxidative stress downregulation and autophagy stimulation. These natural activators of autophagy may represent favourable adjuvants for prevention of the hypertensive cardiovascular damage.

Current applications and limitations of European guidelines on blood pressure measurement: implications for clinical practice.

Hypertension is the most common cardiovascular (CV) risk factor, strongly and independently associated with an increased risk of major CV outcomes, including myocardial infarction, stroke, congestive heart failure, renal disease and death due to CV causes. Effective control of hypertension is of key importance for reducing the risk of hypertension-related CV complications, as well as for reducing the global burden of CV mortality. However, several studies reported relatively poor rates of control of high blood pressure (BP) in a setting of real-life practice. To improve hypertension management and control, national and international scientific societies proposed several educational and therapeutic interventions, among which the systematic implementation of out-of-office BP measurements represents a key element. Indeed, proper assessment of individual BP profile, including home, clinic and 24-h ambulatory BP levels, may improve awareness of the disease, ensure high level of adherence to prescribed medications in treated hypertensive patients, and thus contribute to ameliorate BP control in treated hypertensive outpatients. In line with these purposes, recent European guidelines have released practical recommendations and clear indications on how, when and how properly measuring BP levels in different clinical settings, with different techniques and different methods. This review aimed at discussing current applications and potential limitations of European guidelines on how to measure BP in office and out-of-office conditions, and their potential implications in the daily clinical management of hypertension.