Long-term Effects of Phosphodiesterase-5 Inhibitors on Cardiovascular Outcomes and Death: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Phosphodiesterase 5 inhibitors (PDE-5i), which are widely used for the treatment of erectile dysfunction (ED), have been found to exhibit systemic vascular benefits by improving endothelial function. In this context, we sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality. METHODS: A comprehensive search of electronic databases was conducted up to May 30, 2023. Cohort studies comparing PDE5i treatment at any dose with other ED treatment, placebo or no treatment and minimum follow-up duration of 6 months were considered eligible. The primary endpoints were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. RESULTS: Sixteen studies were included (1,257,759 subjects - 10.5% treated with PDE5i). The majority of patients (99.4%) were men[median age 61.5 years (range 30 - 72.8)]. The median follow-up duration was 4.3 years (range 6 months - 7.5 years). PDE5i use was associated with a significant reduction in the composite of MACE (RR 0.78, 95% CI 0.69-0.89). Moreover, the analysis of pooled data from 13 studies, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.56-0.87). CONCLUSIONS: The use of PDE5i primarily in men with or without known coronary artery disease was associated with a lower risk for cardiovascular events and overall mortality. This information underlines that PDE5i could provide clinical benefit beyond ED treatment and could instigate the conduction of further, large-scale randomized clinical trials.

Effect of DASH vs. mediterranean diet accompanied by a salt restriction on metabolic syndrome and cardiometabolic risk factors in adults with high normal blood pressure or grade 1 hypertension: secondary analyses of a randomized controlled trial.

OBJECTIVE: Lifestyle interventions are recommended as the first-line treatment to control metabolic syndrome components and improve cardiometabolic risk factors. However, studies directly comparing the cardiometabolic effects of the Dietary Approaches to Stop Hypertension (DASH) vs. the Mediterranean diet (MedDiet) accompanied by salt restriction are currently lacking. Thus, with the present secondary analyses of a randomized trial, we aimed to assess the cardiometabolic effects of a 3-month intensive dietary intervention implementing salt restriction alone or on top of the DASH and MedDiet compared to no/minimal intervention in never drug-treated adults with high normal blood pressure (BP) or grade 1 hypertension. METHODS: We randomly assigned individuals to the control group (CG, n = 60), salt restriction group (SRG, n = 60), DASH diet with salt restriction group (DDG, n = 60), or MedDiet with salt restriction group (MDG, n = 60). RESULTS: According to the intention-to-treat analysis, the DDG and the MDG had lower odds ratio (OR) (95% CI) of metabolic syndrome [0.29 (0.12, 0.72), and 0.15 (0.06, 0.41), respectively] compared to the CG. Moreover, the MDG had lower odds of metabolic syndrome compared to the SRG and lower odds of elevated BP levels than the DDG and the SRG. Moreover, total and LDL-cholesterol, fasting glucose, HbA1c, and systolic/diastolic BP were reduced in all three intervention groups compared to the CG. CONCLUSION: On a background of salt restriction, the MedDiet was superior in BP reduction, but the DASH and MedDiet reduced the prevalence of metabolic syndrome to the same extent.

Current Management of Hypertension in Older Adults.

Hypertension is a major global health issue and it accounts for a big proportion of disability and mortality worldwide even in adults aged 65 years and above. Moreover, advanced age per se is an independent risk factor for adverse cardiovascular events and there is abundant scientific evidence supporting the beneficial effects of blood pressure lowering, within certain limits, in this subset of hypertensive patients. The aim of this review article is to summarize the available evidence regarding the appropriate management of hypertension in this specific subgroup, in an era of a constantly increasing aging population.

Cardiometabolic Care: Assessing Patients with Diabetes Mellitus with No Overt Cardiovascular Disease in the Light of Heart Failure Development Risk.

The mechanisms leading to the development of heart failure (HF) in diabetes mellitus (DM) patients are multifactorial. Assessing the risk of HF development in patients with DM is valuable not only for the identification of a high-risk subgroup, but also equally important for defining low-risk subpopulations. Nowadays, DM and HF have been recognized as sharing similar metabolic pathways. Moreover, the clinical manifestation of HF can be independent of LVEF classification. Consequently, approaching HF should be through structural, hemodynamic and functional evaluation. Thus, both imaging parameters and biomarkers are important tools for the recognition of diabetic patients at risk of HF manifestation and HF phenotypes, and arrhythmogenic risk, and eventually for prognosis, aiming to improve patients' outcomes utilizing drugs and non-pharmaceutical cardioprotective tools such as diet modification.

Sex-related cardiovascular prognosis in patients with hypertensive emergencies: a 12-month study.

Current evidence on the prognosis of patients with a hypertensive crisis and predisposing factors is limited. We registered the clinical phenotype of patients with HC admitted to the emergency department, while those with a hypertensive emergency (HE) were hospitalized. One-year outcomes, i.e., composite of death or cardiovascular hospitalizations, were determined in patients with HE after hospital discharge. Out of 38,589 patients assessed in the emergency department, 256 hypertensive urgencies and 97 HE was registered. After stratification of the HE by sex, 48 men and 46 women completed the one-year follow-up. Men had more events than women (27 vs. 13, Ηazard Ratio 2.2, 95% Confidence Interval 1.03-4.7, p = 0.042) after adjustment for age, cardiovascular or chronic kidney disease, and diabetes mellitus. Our study raises the hypothesis that the male sex is an independent risk factor for cardiovascular outcomes in HE patients. CV Cardiovascular, BP blood pressure. The diagram presents the groups of comparison, men versus women in hypertensive emergencies that completed the 1-year follow-up for outcomes, in terms of hospitalizations or deaths.

Twenty-Four-Hour Pulsatile Hemodynamics Predict Brachial Blood Pressure Response to Renal Denervation in the SPYRAL HTN-OFF MED Trial.

BACKGROUND: Renal denervation (RDN) lowers blood pressure (BP), but BP response is variable in individual patients. We investigated whether measures of pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, predict BP drop following RDN. METHODS: From the randomized, sham-controlled SPYRAL HTN-OFF MED Pivotal trial, we performed a post hoc analysis of BP waveforms from 111 RDN patients and 111 sham controls, obtained with a brachial cuff-based sphygmomanometer. Waveforms were acquired during ambulatory BP monitoring at diastolic BP level and processed with validated ARCSolver algorithms to derive hemodynamic parameters (augmentation index; augmentation pressure; backward and forward wave amplitude; estimated aortic pulse wave velocity). We investigated the relationship between averaged 24-hour values at baseline and the change in 24-hour BP at 3 months in RDN patients, corrected for observed trends in the sham group. RESULTS: There was a consistent inverse relationship between baseline augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity and BP response to RDN: the decrease in 24-hour systolic BP/diastolic BP was 7.8/5.9 (augmentation index), 8.0/6.3 (augmentation pressure), 6.7/5.4 (backward wave amplitude), 5.7/4.7 (forward wave amplitude), and 7.8/5.2 (estimated aortic pulse wave velocity) mm Hg greater for patients below versus above the respective median value (P<0.001 for all comparisons, respectively). Taking augmentation index/augmentation pressure/backward wave amplitude/forward wave amplitude/estimated aortic pulse wave velocity into account, a favorable BP response following RDN, defined as a drop in 24-hour systolic blood pressure of ≥5 mm Hg, could be predicted with an area under the curve of 0.70/0.74/0.70/0.65/0.62 (P<0.001 for all, respectively). CONCLUSIONS: These results suggest that pulsatile hemodynamics, obtained during 24-hour ambulatory BP monitoring, may predict BP response to RDN.

Profile and management of hypertensive urgencies and emergencies in the emergency cardiology department of a tertiary hospital: a 12-month registry.

AIMS: Currently there are scarce epidemiological data regarding prevalence, clinical phenotype, and therapy of hypertensive urgencies (HU) and emergencies (HE). The aim of this article was to record the prevalence, clinical characteristics, and management of patients with HU and HE assessed in an emergency department (ED) of a tertiary hospital. METHODS AND RESULTS: The population consisted of patients presenting with HE and HU in the ED (acute increase in systolic blood pressure (BP) ≥ 180 mmHg and/or diastolic BP ≥120 mmHg with and without acute target organ damage, respectively). Of the 38 589 patients assessed in the ED during a 12-month period, 353 (0.91%) had HU and HE. There were 256 (72.5%) cases presented as HU and 97 (27.5%) as HE. Primary causes for both HU and HE were stress/anxiety (44.9%), increased salt intake (33.9%), and non-adherence to medication (16.2%). Patients with HU reported mainly dizziness/headache (46.8%) and chest pain (27.4%), whereas those with HE presented dyspnoea (67%), chest pain (30.2%), dizziness/headache (10.3%), and neurological disorders (8.2%). In HE, the underlying associated conditions were pulmonary oedema (58%), acute coronary syndrome (22.6%), and neurological disorders/stroke (7.2%). All HE cases were hospitalized and received intensive healthcare, including dialysis. CONCLUSION: This 1-year single-centre registry demonstrates a reasonable prevalence of HU and HE contributing to the high volume of visits to the ED. Stress, increased salt intake and non-adherence were main triggers of HE and HU. Dizziness and headache were the prevalent symptoms of HU patients while heart failure was the most common underlying disease in patients with HE.

Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease.

During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.

COVID-19 pandemic and cardiovascular disease: where do we stand?

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19) which recently has been characterized as a pandemic by the World Health Organization (WHO) having killed almost 250,000 people worldwide as of May 4th, 2020. Despite the fact that SARS-CoV-2 seems to predominantly affect the respiratory system leading to pneumonia and acute respiratory distress syndrome, it is now evident that it may also affect the cardiovascular system in multiple ways. The current paper is a review of the most recent literature regarding SARS-CoV-2 infection and its associated main cardiovascular clinical manifestations. Cardiovascular disease represents a prevalent underlying comorbidity associated with increased mortality rates among COVID-19 affected individuals. In addition, various cardiovascular manifestations have been linked to the viral insult, including among others acute coronary syndromes, myocarditis, acute heart failure, cardiac injury, arrhythmias and acute pulmonary embolism. Further studies are required in order to establish the complicated association between SARS-CoV-2 infection and its effects on the cardiovascular system. Our knowledge regarding diagnostic approaches, therapeutic management and preventive measures is constantly enriched throughout an abundance of ongoing research in the respective fields.

Renal Denervation for Treating Hypertension: Current Scientific and Clinical Evidence.

Initial studies of catheter-based renal denervation (RDN) for uncontrolled HTN using radiofrequency ablation in the main renal arteries showed that RDN was effective in lowering office blood pressure (BP). However, the first randomized sham-controlled trial, SYMPLICITY-HTN-3, did not show significantly lower office or 24-h ambulatory systolic BP compared with sham treatment. Subsequent studies in both animals and humans demonstrated the potential importance of more distal and branch renal artery radiofrequency ablation, and a second-generation multielectrode system became available. Two recent randomized sham-controlled trials in patients not taking antihypertensive drugs (SPYRAL HTN-OFF MED) or continuing to take drugs (SPYRAL HTN-ON MED) performed RDN with the second-generation radiofrequency ablation system using an ablation protocol that included treatment of the distal renal artery as well as the branch renal arteries. These studies showed that RDN significantly reduced office and 24-h ambulatory BP compared with sham treatment. Another recent randomized sham-controlled trial in patients not receiving medications showed that RDN with catheter-based ultrasound (RADIANCE-HTN SOLO) applied in just the main renal arteries significantly lowered daytime ambulatory and office BP compared with sham treatment. These trials have renewed clinical and scientific interest in defining the appropriate role of RDN in hypertension treatment. In addition, other important issues will need to be addressed in the future such as the development of tests to determine the extent of RDN at the time of the procedure and the potential of renal nerve fibers to regain their patency at some later stage following the ablation procedure.

Management of supine hypertension in patients with neurogenic orthostatic hypotension: scientific statement of the American Autonomic Society, European Federation of Autonomic Societies, and the European Society of Hypertension.

: Supine hypertension commonly occurs in patients with neurogenic orthostatic hypotension due to autonomic failure. Supine hypertension promotes nocturnal sodium excretion and orthostatic hypotension, thus, interfering with quality of life. Perusal of the literature on essential hypertension and smaller scale investigations in autonomic failure patients also suggest that supine hypertension may predispose to cardiovascular and renal disease. These reasons provide a rationale for treating supine hypertension. Yet, treatment of supine hypertension, be it through nonpharmacological or pharmacological approaches, may exacerbate orthostatic hypotension when patients get up during the night. Fall-related complications may occur. More research is needed to define the magnitude of the deleterious effects of supine hypertension on cardiovascular, cerebrovascular, and renal morbidity and mortality. Integration of more precise cardiovascular risk assessment, efficacy, and safety data, and the prognosis of the underlying condition causing autonomic failure is required for individualized management recommendations.

Safety and performance of diagnostic electrical mapping of renal nerves in hypertensive patients.

AIMS: The aim of this study was to evaluate the safety and performance of renal nerve stimulation (RNS) for diagnostic mapping of the renal nerves. METHODS AND RESULTS: In this first-in-man study, twenty hypertensive patients underwent RNS using the ConfidenHT system. Bilateral stimulations were performed at three to four sites per artery at 2 and 4 mA. The primary endpoint was change in systolic blood pressure (SBP). Mean office blood pressure was 156/89 mmHg. No periprocedural adverse events occurred. Stimulation with 2 mA resulted in a maximum change of 8.3±6.3 mmHg in SBP (based on 119 stimulations; p<0.001), while stimulating with 4 mA resulted in a maximum change of 10.1±7.8 mmHg (based on 61 stimulations; p<0.001). The mean change in SBP did not vary between mid, distal or branch sites when stimulating at 2 mA but was significantly higher at ostial (23±14 mmHg) than at non-ostial locations (9±7 mmHg) when stimulating at 4 mA (p=0.003). CONCLUSIONS: RNS can be performed safely and effectively along the renal artery and results in a large variation in temporary BP changes per patient and per anatomic location. RNS might help in optimising treatment effect and selecting potential responders to renal sympathetic denervation.

Consensus statement on the definition of neurogenic supine hypertension in cardiovascular autonomic failure by the American Autonomic Society (AAS) and the European Federation of Autonomic Societies (EFAS) : Endorsed by the European Academy of Neurology (EAN) and the European Society of Hypertension (ESH).

PURPOSE: Patients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright position owing to impaired autonomic regulation. A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure. METHODS: As a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed. Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017. Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here. The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension. RESULTS: In patients with neurogenic orthostatic hypotension, nSH is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position. Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytime BP values. Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management. CONCLUSIONS: The establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.