Therapy-resistant Hypertension Research Articles

Retrospective cohort study to characterise the blood pressure response to spironolactone in patients with apparent therapy-resistant hypertension using electronic medical record data

ObjectiveIdentify blood pressure (BP) response to spironolactone in patients with apparent therapy-resistant hypertension (aTRH) using electronic medical records (EMRs) in order to estimate response in a real-world clinical setting.DesignDeveloped an...

Effect of exercise and physical activity on blood pressure in adults with resistant hypertension: a protocol for a systematic review

Background: Hypertension is highly prevalent globally but controlling hypertension with medication alone is challenging. Resistant hypertension, a special hypertension phenotype, is even more challenging to manage. Use of aerobic exercise is supported by high grade evidence as a therapeutic modality to reduce blood pressure in hypertension thereby reducing cardiovascular risk. Further, the new hypertension guidelines strongly recommend exercise to reduce blood pressure. However publications of trials investigating effectiveness of exercise in resistant hypertension are limited and no systematic review has been published to date.Objectives: To identify the level of evidence for the effectiveness of exercise and physical activity in managing blood pressure in adults with resistant hypertension.Methods: Studies published in Scopus, MEDLINE, CINHAL, Web of Science, Embase and SPORTDiscus databases; and unpublished studies in Open Grey, Current Control Trials, ClinicalTrials.gov, Cos Conference Papers Index and the WHO International Clinical Trials Registry Platform will be searched. Two reviewers will independently review the studies.Results: The following will be reported: methodological quality of the selected full texts assessed using Cochrane risk of bias tools (RoB-2 and ROBINS-I) for randomised and non-randomised trials; clinical heterogeneity and sensitivity analysed using Review Manager (RevMan) software; outcomes of detected and/orAQ2 correct reporting and publication bias described in Funnel plots and Begg’s rank correlation/Edgar’s regression tests; and results of quality of the evidence described using the Recommendation Assessment, Development and Evaluation (GRADE) tool. Types of exercise will be described in sub-groupings.Conclusions: Strength of the literature for exercise therapy for resistant hypertension will be identified.

Apparent therapy-resistant hypertension as risk factor for the development of type 2 diabetes mellitus.

To evaluate whether the relationship between hypertension and type 2 diabetes mellitus (T2DM) is different for patients with uncontrolled hypertension, controlled hypertension or patients with apparent therapy-resistant hypertension (aTRH), compared with patients without hypertension. Using Cox proportional hazard models we evaluated the risk of new-onset T2DM in 8756 patients, at high risk for vascular disease. Hypertensive patients were subdivided according to blood pressure (BP) and use of BP-lowering drugs. BP ≥ 140/90 mmHg was defined as uncontrolled BP. aTRH was defined as uncontrolled BP despite being treated with at least three BP-lowering drugs including a diuretic, or the use at least four BP-lowering drugs irrespective of BP levels. Further analysis evaluated the risk of new-onset T2DM for patients with uncontrolled hypertension and for patients with aTRH, compared with patients with controlled hypertension and without hypertension, respectively. Forty-five percent had controlled hypertension, 20% had uncontrolled hypertension, 5.7% had aTRH, and 29% were nonhypertensive. During a follow-up of 7.0 (interquartile range: 0-14) years there were 705 new cases of T2DM. Patients with hypertension had a 1.48 (95% confidence interval 1.22-1.80) times higher risk of new-onset T2DM than nonhypertensive patients. There was no significant difference in risk among different hypertension groups. Patients at high risk for cardiovascular disease with hypertension have a 1.48 times higher risk of new-onset T2DM than nonhypertensive counterparts. The risk did not differ between patients with controlled hypertension, uncontrolled hypertension, or aTRH.

Interpreting stimulated plasma renin and aldosterone to select physiologically individualized therapy for resistant hypertension: importance of the class of stimulating drugs.

In the treatment of resistant hypertension, physiologically individualized therapy based on phenotyping with plasma renin activity (PRA) and plasma aldosterone significantly improves blood pressure control. Patients with a low-renin/low aldosterone (Liddle) phenotype respond best to amiloride, while those with low-renin/high aldosterone respond best to aldosterone antagonists, and those with high renin/high aldosterone (renal phenotype) respond best to angiotensin receptor blockers (ARB). However, it is important to measure PRA in a stimulated condition to distinguish between low levels due to high salt intake, licorice or nonsteroidal inflammatory drugs and low levels due to suppression by excess aldosterone secretion or renal tubular genetic variants causing retention of salt and water (Liddle phenotype). In the past, both diuretics and angiotensin converting inhibitors (ACEi) have been used for this purpose, and it has been assumed that these classes of drugs are equivalent. In this study of 2896 patients with hypertension, we evaluated that assumption. We found important differences among diuretics alone, ACEi/ARB alone, and ACEi/ARB + diuretics, which all stimulated PRA. However, ACEi/ARB lowers plasma aldosterone, and beta blockers lower PRA. Among patients with systolic pressure ≥ 180 mmHg ± diastolic pressure ≥ 100 mmHg stimulated only by diuretics, the phenotypes were 25% Liddle, 38% IA, 8.7% renal, and 28.3% mixed. In choosing physiologically individualized therapy based on PRA and aldosterone, it is important to consider the classes of stimulating drugs. Phenotypes are best distinguished by taking into account the aldosterone/PRA ratio in addition to the levels of PRA and aldosterone.

RESISTANCE TO ANTIHYPERTENSIVE THERAPY

Objective:To determine possible causes of resistance to antihypertensive therapy.Design and method:The study included 101 patients with resistant hypertension (RH) (1-st gr.). In 129 patients after administration of a standardized 3-component therapy RH was excluded (2-nd gr. with pseudoRH). Plasma

Eplerenone Versus Spironolactone in Resistant Hypertension: an Efficacy and/or Cost or Just a Men's Issue?

To review comparative efficacy and tolerability data between the two main mineralocorticoid receptor antagonists (MRAs), spironolactone and eplerenone, in patients with resistant hypertension (HTN). The focus was whether spironolactone, being the classical non-selective agent that has been used for years, albeit with several anti-androgenic side effects, can be rivaled by eplerenone, an apparently weaker, but better tolerated, more selective MRA. Evidence has accumulated that resistant HTN is generally volume-dependent, attributable to varying degrees of aldosterone excess with its attendant renal effects of sodium and fluid retention. Such aldosteronism may be due to an underestimated occurrence of primary aldosteronism; however, it more commonly occurs separately from it and independent from angiotensin II. The aldosterone-induced volume excess placed at the root of the development of resistant HTN in a large number of patients, together with the extrarenal deleterious effects of aldosterone, such as endothelial dysfunction, vascular remodeling and increased arterial stiffness, cardiac hypertrophy, and fibrosis can all be counterbalanced by the administration of MRAs. In the absence of a direct comparison between spironolactone and eplerenone, and in light of compelling evidence provided by the recently reported results of the PATHWAY-2 and ReHOT studies, spironolactone has been established as the most effective add-on anti-aldosterone therapy in resistant HTN. The data on use of eplerenone continue to emerge and are quite encouraging. Despite the lack of direct comparative data, the weight of evidence regarding efficacy is currently in favor of spironolactone. However, the data on the efficacy of eplerenone are promising but still being accumulated suggesting this agent as an alternative to spironolactone and certainly as the preferred choice for those not tolerating spironolactone, especially for patients developing anti-androgenic side effects like breast tenderness, gynecomastia/mastodynia, and/or sexual dysfunction. Both these agents appear to have several other pleiotropic effects that confer cardioprotection and renoprotection beyond their antihypertensive effect. Potassium levels and renal function need to be closely monitored during administration of these therapies. Future comparative studies may shed more light on these issues, while emerging newer agents may offer better and safer therapeutic options.

The prevalence of therapy resistant hypertension

The prevalence of therapy resistant hypertension

Baroreflex activation therapy : Indication and evidence in resistant hypertension and heart failure

Baroreflex activation therapy (BAT) is asympathoinhibitory procedure for treatment of therapy-resistant hypertension (rsHTN) and severe heart failure with reduced ejection fraction (HFrEF) that been available for several years. The double-blind, randomized Rheos Pivotal Trial demonstrated ablood pressure lowering effect in patients with rsHTN for the first-generation BAT device. Asmaller randomized study in heart failure showed that the Barostim Neo system is safe and can improve heart failure symptoms and decrease neuroendocrine activation. However, for this unilateral system, which is currently in clinical use, no data from large randomized trials exist. Despite existing data for BAT in rsHTN and HFrEF, large randomized trials, showing reduction of blood pressure and cardiovascular events are still lacking. Therefore, BAT's efficacy and safety cannot be conclusively assessed.

Iliac vein stenosis after implantation of a central arteriovenous coupler device in the treatment of therapy resistant arterial hypertension

Iliac vein stenosis after implantation of a central arteriovenous coupler device in the treatment of therapy resistant arterial hypertension

RENAL DENERVATION ON BLOOD PRESSURE VARIABILITY AND BLOOD PRESSURE LEVELS

Objective: Therapy-resistant hypertension (RHTN) is associated with major adverse cardiovascular events. Increased sympathetic drive is considered to be one of mechanisms of resistance to antihypertensive treatment and associated with high blood pressure level. Sympathetic hyperactivity is also linked to increased blood pressure variability (BPV) resulting in worse prognosis. Renal denervation (RDN) reduces sympathetic activity and BP in some patients with RHTN, however data on the impact of the procedure on BPV are lacking. Aim of the present study was to assess effect of RDN on blood pressure levels and BPV during 2-years follow-up. Design and method: The study enrolled 22 consecutive patients (mean age 56 ± 10.2 years, 9 males) with confirmed true RHTN (mean of 4.2 ± 1.4 antihypertensive drugs intake) who underwent bilateral RDN procedure (Symplicity RDN System, Medtronic, USA). BP and BPV (by means of average real variability) were assessed by ABPM (BPLab, Petr Telegin, Russia) at baseline, 12-month and 24 month after procedure. Results: In overall population there was a decrease of both office and 24-hour SBP at 12 months after RDN (−26 ± 20.2 mmHg; −17.4 ± 10.8 mmHg; respectively, p < 0.05 for all), however further reduction at 24-month follow-up was only for “office” SBP (−22.8 ± 23 mmHg; p < 0.02 and −22.6 ± 17.6 mmHg; p = 0.3 respectively). 24-hour BPV decreased from 18.8 ± 4.4 mmHg to 17 ± 4.2 mmHg (−2.6 ± 3.7 mmHg, p < 0.0001) after 12 months and continued to decline to 15.36 ± 2.9 mmHg (−3.3 ± 2.5 mmHg, p < 0.001) two years after procedure. In 15 patients RDN provided decrease of BP level > 20 mm Hg, in 7 patients resulted in 10 mm Hg decrease. Both groups had a significant reduction of BPV in 24-month (−5.0 and −1.3 mmHg respectively;p < 0.001). There was a positive correlation between change of SBP, 24-h SBP and 24-h BPV at 24-month visit compared to baseline (r = 0.654 for office SBP/BPV; p = 0.02 and r = 0.628 for 24-h SBP/BPV; p = 0.02). Conclusions: RDN resulted in significant reduction of 24-BPV in patients with both marked and moderate decrease of blood pressure level indicating additional positive impact on adverse prognostic features of hypertension.

Therapy-resistant and therapy-refractory arterial hypertension

Therapy-resistant and therapy-refractory arterial hypertension differ in prevalence, pathogenesis, prognosis and therapy. In both cases, astructured approach is required, with the exclusion of pseudoresistance and, subsequently, secondary hypertension. Resistant hypertension has been reported to be more responsive to intensified diuretic therapy, whereas refractory hypertension is presumed to require sympathoinhibitory therapy. Once the general measures and the drug-based step-up therapy have been exhausted, interventional procedures are available.

Long-term outcome of stenting for atherosclerotic renal artery stenosis and the effect of angiographic restenosis

Symptomatic renal artery stenosis (RAS) is mainly treated with pharmacological blood pressure control, sometimes with percutaneous transluminal renal angioplasty (PTRA). It is unclear if PTRA benefits these patients over time. To determine long-term renal function, morbidity, and mortality in patients with symptomatic RAS treated with PTRA, and whether long-term outcomes are associated with angiographic restenosis. Retrospective single-center, long-term follow-up of 57 patients with atherosclerotic RAS treated with PTRA with stent during 1995-2004 and investigated for restenosis with angiography after one year. Outcomes were retrieved from medical records and from mandatory healthcare registries. Mortality rates were related to expected survival in an age- and gender-matched population, using a life-table database. Surviving patients were assessed with blood pressures, laboratory tests, duplex ultrasonography, and radioisotope renography. Median follow-up was 11 years 7 months. Major indications for PTRA were therapy-resistant hypertension and declining renal function. Angiographic restenosis at one year was found in 21 of 57 patients (37%). Thirty-six patients (60%) died during follow-up. Main cause of death was cardiovascular events (54%). Mortality was significantly increased, and morbidity and healthcare utilization were high. Hypertension control during follow-up was stable with persistent need for anti-hypertensive medication, and renal function remained moderately reduced with no long-term difference between patients with vs. without restenosis. Long-term prognosis after PTRA for atherosclerotic RAS is dismal, with high mortality and morbidity and reduced renal function, despite maintained hypertension control. Restenosis does not appear to affect late outcome.

A novel integrated care concept (NICC) versus standard care in the treatment of chronic cardiovascular diseases: protocol for the randomized controlled trial CardioCare MV

BackgroundCardiovascular diseases are the major cause of death globally and represent a major economic burden on health care systems. Positive effects of disease management programs have been shown for patients with heart failure (HF). Remote monitoring and telemonitoring with active intervention are beneficial in atrial fibrillation (AF) and therapy-resistant hypertension (TRH), respectively. For these patients, we have developed a novel integrated care concept (NICC) which combines telemedicine with intensive support by a care center, including a call center, an integrated care network including inpatient and outpatient care providers and guideline therapy for patients.MethodsThe aim of the study is to demonstrate the superiority of NICC over guideline therapy alone. The trial is designed as open-label, bi-center, parallel-group design with two groups and a blinded observer. Patients will be included if they are either inpatients or if they are referred to the outpatient clinic of the hospitals by their treating physician. Randomization will be done individually with stratification by cardiovascular disease (AF, HF, TRH), center and admission type. Primary endpoints are based on the 1-year observation period after randomization. The first primary endpoint is the composite endpoint consisting of mortality, stroke and myocardial infarction. The number of hospitalizations form the second primary endpoint. The third primary endpoint is identical to the first primary endpoint plus cardiac decompensation. Adjustments for multiple testing are done using a fall-back strategy. Secondary endpoints include patient adherence, health care costs, quality of life, and safety. A sample size of 2930 gives 80% power at the two-sided 2.5% test level for the first primary endpoint. The power for the second primary endpoint is 99.8% at this sample size, and it is 80% with 1086 patients.DiscussionThis study will inform care providers whether quality of care can be improved by an integrated care concept providing telemedicine through a round-the-clock call center approach. We expect that cost of the NICC will be lower than standard care because of reduced hospitalizations. If the study has a positive result, NICC is planned to be immediately rolled out in the federal state of Mecklenburg-West Pomerania and other federal states in Germany. The trial will also guide additional research to disentangle the effects of this complex intervention.Trial registrationDRKS, ID: DRKS00013124. Registered on 5 October 2017;ClinicalTrials.gov, ID: NCT03317951. Registered on 17 October 2017.

Renal sympathetic nerve activity after catheter-based renal denervation

BackgroundCatheter-based renal sympathetic denervation (RDN) has been considered a potential treatment for therapy resistant hypertension (RHT). However, in a randomized placebo-controlled trial, RDN did not lead to a substantial blood pressure (BP) reduction. We hypothesized that variation in the reported RDN efficacy might be explained by incomplete nerve disruption as assessed by renal 123I–meta-iodobenzylguanidine (123I–mIBG) scintigraphy.MethodsIn 21 RHT patients (median age 60 years), we performed 123I–mIBG scintigraphy before and 6 weeks after RDN. Additionally, we assessed changes in BP (24 h day, night, and average), plasma- and urinary-catecholamines and plasma renin activity (PRA) before and after RDN. Planar scintigraphy was performed at 15 min and 4 h after 123I–mIBG administration. The ratio of the mean renal (specific) counts vs. muscle (non-specific) counts represented 123I–mIBG uptake. Renal 123I–mIBG washout was calculated between 15 min and 4 h.ResultsAfter RDN office-based systolic BP decreased from 172 to 153 mmHg (p = 0.036), while diastolic office BP (p = 0.531), mean 24 h systolic and diastolic BP (p = 0.602, p = 0.369, respectively), PRA (p = 0.409) and plasma catecholamines (p = 0.324) did not significantly change post-RDN. Following RDN, 123I–mIBG renal uptake at 15 min was 3.47 (IQR 2.26–5.53) compared to 3.08 (IQR 2.79–4.95) before RDN (p = 0.289). Renal 123I–mIBG washout did not change post-RDN (p = 0.230). In addition, there was no significant correlation between the number of denervations and the renal 123I–mIBG parameters.ConclusionsNo changes were observed in renal 123I–mIBG uptake or washout at 6 weeks post-RDN. These observations support incomplete renal denervation as a possible explanation for the lack of RDN efficacy.

PP.27.06] TO SEARCH...OR NOT TO SEARCH FOR THE CAUSE OF ARTERIAL HYPERTENSION

Objective: Primary hyperaldosteronism was initially considered a rarity, but has proven to be, according to more recent data, a more common cause of secondary hypertension (HTN). When sought, it may occur in greater percentages among patients with resistant HTN. More recent epidemiological work showed that most cases are usually associated with bilateral adrenal hyperplasia in the absence of the classically reported adenoma. Design and method: We present the case of 55 years old male diabetic patient, presenting to the emergency department with frequent hypertensive urgencies during the past year. He had been diagnosed 5 years prior with HTN and received treatment with an ACE inhibitor, a calcium channel blocker and a low-dose diuretic. Despite proper life style changes and appropriate adherence to therapy, the 24 h ambulatory blood pressure measurement showed significantly elevated blood pressure (BP) levels – mean systolic BP 175/94 mmHg with a non-dipping profile. In the course of investigations for secondary causes of hypertension we performed nocturnal polysomnography, duplex ultrasound of renal arteries and tested for cortisol levels – all with negative findings. Remarkable findings were a persistent moderate hypokalemia (∼ 3 mmol/L), mild hypernatremia (143 mmol/L) despite low-sodium diet and urinary potassium excretion increased at 37 mmol/24 h. Further, the abdominal CT scan showed bilateral adrenal hyperplasia, with no adenomas. The patient was switched to high-dose verapamil and high-dose doxazosin for 4 weeks, and the endocrinology profile showed high plasma aldosterone levels (suppressed after oral 50 mg of captopril), high plasma aldosterone/plasma renin activity ratio, with a negative postural test, thus confirming primary hyperaldosteronism. The patient was switched to initial antihypertensive therapy adding 50 mg spironolactone, which conferred a better BP control confirmed at 1-month re-evaluation. Results: The diagnostic of primary hyperaldosteronism is challenging, but it presence significantly affects BP control, especially in selected populations, such as resistant HTN patients. Considering recent trials (PATHWAY) showed that adding spironolactone to the triple therapy in resistant HTN achieves BP control in most patients, it may remain an open debate whether cases without evidence of adenoma actually benefit from performing the full diagnostic algorithm.

Prevalence and clinical characteristics of apparent therapy-resistant hypertension in patients with cardiovascular disease: a cross-sectional cohort study in secondary care

ObjectivesOur aim was to investigate the prevalence of apparent therapy-resistant hypertension (aTRH) in patients with clinical manifest cardiovascular disease (CVD), and to study clinical characteristics related to aTRH in this...

OP.7A.10] THE BLOOD PRESSURE LOWERING EFFECT OF THE MOBIUSHD DEVICE IS INDEPENDENT OF PULSE PRESSURE

Objective: The Framingham Heart Study showed an increased risk of cardiovascular disease with increasing pulse pressure (PP). Elevated PP is frequently observed with increasing age and may reflect the loss of elastic properties in large arteries. We investigated the effects of the MobiusHD-device on office systolic BP (SBP) and on 24-hour ambulatory BP (ABPM) in patients with high PP. Design and method: MobiusHD is designed to passively amplify pulsatile strain at the carotid sinus and reduce BP through increased baroreceptor activation, and consequently increase sympathoinhibition. A total of 40 patients were treated with MobiusHD for therapy-resistant hypertension and had BP measured at discharge, 1, 3, and 6 months. For analyses, patients were grouped according to baseline PP (high PP:>70 mmHg, n = 25; low PP:<70 mmHg, n = 15). Responsiveness at 6 months to MobiusHD treatment was defined as decrease in SBP of more than 10 mmHg, and also as decrease in ABPM of more than 5 mmHg. Linear mixed models were used to compare mean changes in BP over time between groups, chi-square tests were used to assess responsiveness. Results: Mean ± SD age was 53 ± 12 years and 50% were female. Baseline mean SBP, PP, and ABPM were 182 ± 17 mmHg, 74 ± 16 mmHg, and 165 ± 16 mmHg, respectively. Upon implantation of MobiusHD, SBP and PP were significantly reduced at 1,3,6 months by 21,29,25 mmHg (p<0.001) and by 13,16,12 mmHg (p < 0.001) in the high PP group and by 24,16,25 mmHg (p = 0.001) and by 11,6,11 mmHg (p = 0.009) in the low PP group, respectively. ABPM was significantly reduced at 3,6 months by 15,19 mmHg (p < 0.001) in the high PP group and by 14,22 mmHg (p = 0.001) in the low PP group. There were no significant differences in overall reductions in SBP, PP, ABPM between the high and low groups (p = 0.64, p = 0.28, and p = 0.90 respectively). No significant differences in SBP responsiveness were observed between high and low baseline PP groups (68%vs.80%, p = 0.41), as well as ABPM responsiveness between high and low baseline PP groups (76%vs.73%, p = 0.85). Conclusions: The MobiusHD-device effectively reduced SBP, PP, and ABPM in patients with therapy-resistant hypertension. The SBP and ABPM responses to MobiusHD were not different between patients with high or low PP.

Redo renal denervation using amulti-electrode radiofrequency system in patients with persistent therapy-resistant hypertension.

ObjectivesRenal sympathetic denervation has been studied as a potential therapeutic option for patients with therapy-resistant hypertension; however, a significant proportion of patients do not show a significant reduction in blood pressure and are classified as non-responders. The objective of the present study was to assess whether a redo renal denervation procedure increases response rates.MethodsWe present a case series of three consecutive renal denervation non-responders treated with the multi-electrode radiofrequency St. Jude EnligHTN catheter after an average of 22 months. Patients were followed for 6 months.ResultsMean age was 66 years and two patients were male. Patients were previously treated using either ReCor’s Paradise system, the Vessix V2 system or the Covidien OneShot system. Mean office blood pressure one year after the initial procedure was 187/102 mm Hg with a mean 24 h ambulatory blood pressure of 166/102 mm Hg. All patients underwent a successful redo procedure using the EnligHTN system because of persistent therapy-resistant hypertension. At 6 months a significant drop in both office and ambulatory blood pressure of −27/−6 mm Hg and −15/−13 mm Hg, respectively, was observed. No significant renal artery stenosis was observed at 6 months.ConclusionsIn patients with therapy-resistant hypertension who do not respond to an initial renal denervation procedure, a redo procedure using the St. Jude EnligHTN system may help to significantly improve blood pressure control.

Serial quantitative magnetic resonance angiography follow-up of renal artery dimensions following treatment by four different renal denervation systems.

Renal sympathetic denervation (RDN) is being studied as a therapeutic option for patients with therapy-resistant hypertension. It remains unclear if the procedure affects the renal arteries in such a way that luminal narrowing might occur at the mid to longer term. The aim of the present study was to assess renal artery integrity accurately at the medium to long term using recently validated quantitative magnetic resonance angiography software in patients treated with four different RDN devices. In a prospective cohort of 27 patients referred for RDN, quantitative magnetic resonance angiography (MRA) was used to assess 52 vessels at baseline, six, and 12 months post treatment with one of four different devices. No renal artery stenosis was seen at six or 12 months. The average mean lumen area was 26.6±7.3 mm2 at baseline versus 25.0±7.1 mm² and 25.0±6.1 mm² at six and 12 months, respectively, resulting in a late loss of 1.6 mm2 at six months and 1.9 mm2 at 12 months. No differences were observed in the arterial response to RDN with the four different systems used. There was no correlation between post-procedural dissections, oedema or thrombi as detected with invasive imaging, and luminal narrowing at follow-up. Quantitative MRA of patients treated with RDN revealed no significant change in renal artery dimensions up to 12-month follow-up. The lack of a change in renal artery luminal dimensions was irrespective of the arterial response to the individual devices used.

Hypertension up to date: SPRINT to SPYRAL

Hypertension is the most common chronic cardiovascular condition with increasing prevalence all over the world. Treatment of patients at risk requires a multimodal therapeutic concept to adjust blood pressure, including systematic identification of secondary causes of hypertension or pseudo-resistance, lifestyle modification, polypharmacy, and as well as accompanying risk factors and comorbidities. The present review discusses recent studies on patients with increased cardiovascular risk potentially influencing future treatment strategies. It covers blood pressure targets in patients at risk (SPRINT), novel treatment options such as angiotensin receptor neprilysin inhibitors, discusses the treatment of patients with impaired glucose tolerance, and appreciates novelties in controlling therapy-resistant hypertension by fourth-line pharmacotherapies (PATHWAY), as well as new interventional approaches.