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Renal sympathetic denervation (RDN) reduces blood pressure (BP). This single-arm open-label study enrolled patients with resistant hypertension (RH) and treat them by CT-guided ozone mediated lumbar-renal sympathetic denervation (L-RDN). The primary endpoint was to assess the changes of BP over 24-h ambulatory BP monitoring (ABPM) and to evaluate the anti-hypertensive medication burden (AHMB) at 3-month follow-up. This study was registered in Chictr.org.cn (ChiCTR2300071375). 17 patients (mean age 65.12 ± 10.77 years) with AHMB of 4.12 ± 1.11 were enrolled. After the procedure, 7 patients (46.7 %) matched the criteria for antihypertensive medication reduction. The AHMB decreased to 3.87 ± 0.96 for the whole objectives and from 3.87 ± 0.96 to 3.55 ± 0.78 for patients with normal baseline renal function. On top of the lessened AHMB, L-RDN further reduced morning systolic BP (SBP) by −8.6 ± 4.0 mmHg (p = 0.034) and diastolic BP (DBP) by −4.6 ± 2.1 mmHg (p = 0.032) for all participants and morning SBP by −13.2 ± 3.6 mmHg (p < 0.001), morning DBP by −6.2 ± 2.4 mmHg (p = 0.011) and daytime SBP by −4.1 ± 1.6 mmHg (p = 0.009) for those with normal baseline renal function at 3-month of follow-up. No adverse events were reported intra- and post operation. CT-guided ozone-mediated L-RDN might be an innovative approach of RDN for treating RH. Confirmatory studies are warranted. Patients with RH was placed on the CT table in a prone position. Under local anesthesia, a 21G needle was punctured and targeted the pre-vertebral ganglia adjacent to the anteromedial area of the psoas muscle and the dorsolateral side of the abdominal aorta, where the left renal artery originated. A 10 mL gas mixture containing 30 % ozone and 70 % oxygen was then injected. After the procedure, the patent's antihypertensive medication burden and BP significantly reduced compared with baseline. The home BP control rate was optimal 12 weeks after the procedure. RH: resistant hypertension; BP: blood pressure. [Display omitted] • Lumbar-Renal denervation (L-RDN) emerged as an effective, safe, cheap, and easy to perform approach of renal denervation (RDN) to treat resistant hypertension (RH). • L-RDN works especially well for patients with normal renal function. • By denervating both the upstream components of the renal sympathetic nervous system and the renal nerve fibers that directly contact the renal artery surface, L-RDN could potentially provide more benefits compared with other RDN methods. [ABSTRACT FROM AUTHOR]

• BP is uncontrolled despite the use of three drugs at optimal or best tolerated doses. • The estimated prevalence of true RH is 5 % when strict criteria are applied. • Rule out pseudo-resistance before diagnosing true drug resistance. • Consider mineralocorticoid receptor antagonists as drug number four. • Renal denervation can be considered as a treatment option in some patients. The term RH describes a subgroup of hypertensive patients whose BP is uncontrolled despite the use of at least three antihypertensive drugs in an appropriate combination at optimal or best tolerated doses. True RH is considered when appropriate lifestyle measures and treatment with optimal or best tolerated doses of three or more drugs (a thiazide/thiazide-like diuretic, plus renin-angiotensin system -RAS- blocker and a calcium channel blocker -CCB-) fail to lower office BP to <140/90 mmHg; besides the inadequate BP control should be confirmed by home blood pressure monitoring (HBPM) or 24-hour ambulatory; and evidence of adherence to therapy and exclusion of secondary causes of hypertension are required. RH patients are at a high risk of cardiovascular events and death. RH is associated with a higher prevalence of end-organ damage. When stricter criteria are applied, a reasonable estimate of the prevalence of true RH is 5 % of the total hypertensive population. The predominant hemodynamic pattern appears to be increased systemic vascular resistance and plasma volume with normal or even low cardiac output. We must rule out pseudo-resistance before diagnosing true drug resistance. RH is a therapeutic challenge, and its management includes lifestyle interventions, avoiding nonadherence to treatment, avoiding inertia, appropriate use of antihypertensive drugs based on current evidence, especially long-acting diuretics, and the addition of mineralocorticoid receptor antagonists. RCTs to identify the most protective medical therapy in RH are needed. A series of drugs in different stages of investigation could significantly impact RH treatment in the future. [ABSTRACT FROM AUTHOR]

• Mineralocorticoid receptor antagonists lower blood pressure in resistant hypertension. • Renal denervation is not efficacious for treatment of resistant hypertension. • Endothelin receptor antagonists warrant further investigation for resistant hypertension. • Individual factors that impact treatment response in resistant hypertension warrant further investigation. There is a lack of consensus regarding the best add on therapy for treatment of resistant hypertension (RH). This is likely secondary to a paucity of data on the comparative effectiveness of proposed therapies for RH. Placebo-controlled and sham-controlled randomized clinical trials testing therapies for the treatment of RH were included in this meta-analysis. Therapies with two or more studies were included as subgroups in this meta-analysis. The primary outcomes being tested were 24-hr systolic blood pressure (SBP) and office SBP. Eight studies were identified that tested mineralocorticoid receptor antagonist (MRA) including 1,414 participants. The raw mean difference (RMD) between MRA and placebo control was statistically significant for 24-hour SBP (-10.56 mmHg; 95% confidence interval (CI) -12.82 to -8.30), 24-hour diastolic (DBP) (-5.48 mmHg; 95% CI -8.48 to -2.58), office SBP (-11.97 mmHg; 95% CI -16.41 to -7.54), and office DBP (-4.14 mmHg; 95% CI -5.62 to -2.65). Six studies were identified that tested renal denervation (RD) including 989 participants. The RMD between RD and sham control was not statistically significant for 24-hour SBP (-1.84 mmHg; 95% CI -3.92 to 0.24), 24-hour DBP (-0.66 mmHg; 95% CI -1.85 to 0.54), office SBP (-1.57 mmHg; 95% CI -6.04 to 2.89), and office DBP (-1.49 mmHg; 95% CI -3.52 to 0.55). Four studies were identified that tested endothelin receptor antagonists (ERA) including 1,193 participants. The raw mean difference (RMD) between ERA and placebo control was statistically significant for 24-hr systolic (SBP) (-7.02 mmHg; 95% CI -9.15 to -4.90, 24-hr diastolic (DBP) (-6.22 mmHg; 95% CI -7.61 to -4.82), office SBP (-5.84 mmHg; 95% CI -10.08 to -1.60), and office DBP (-3.73 mmHg; 95% CI -5.87 to -1.59). MRA lowers BP in patients with RH more than RD, which seems to have little to no effect in RH. ERAs lead to a statistically significant reduction in BP but the confidence in efficacy is limited due to the low number of studies and differences in trial population. Individual factors and their impact on treatment response in RH should be investigated in future research. [ABSTRACT FROM AUTHOR]

Lead (Pb), cadmium (Cd) and mercury (Hg) are toxic trace elements that represent a public health problem as risk factors for cardiovascular disease and hypertension (HT) and could also contribute to the development of resistant hypertension (rHT) To compare the blood concentrations of Pb, Cd and Hg in subjects with resistant and non-resistant HT and to define whether there is a relationship between its levels and rHT. Cross-sectional study. Subjects aged ≥ 21 to ≤ 80 years with a body mass index < 40 kg/m2 were recruited on a discretionary basis from October 2001 to October 2004 in a hypertension unit of a tertiary hospital amongst those sent to the hypertension unit by their family physician. Resistant hypertension was defined according to the American Heart Association (AHA) criteria. Whole blood concentrations of Cd, Pb and Hg were measured by electrothermal atomic absorption spectrometry. 46 out of 73 included subjects (63%) suffered from rHT. Blood Pb median: HT 3.9 (IQR 2.7–5.2) vs. rHT 3.6 (IQR 2.8–6.0) µg/dL (p=0.941). Blood Cd median: HT 0.07 (IQR 0.07–0.80) vs. rHT 0.30 (IQR 0.07–0.65) µg/L (p=0.681). Blood Hg median: HT 7.9 (IQR 5.8–12.9) vs. rHT 7.3 (IQR 4.6–13.3) µg/L (p=0.611). Considering the 75th percentile of each element (Pb: 5.55 µg/dL, Cd: 0.75 µg/L, Hg: 13.15 µg/L), a multiple logistic regression analysis (adjusted for age, BMI, diabetes mellitus, clearance of creatinine and only for Cd the smoking habit) showed an OR = 3.44 (0.84–14.10, p=0.086) for Pb, OR = 1.80 (0.39–8.24, p=0.451), for Cd and OR = 2.31 (0.59–9.14, p=0.232) for Hg. Moreover, the stratified analyses showed that men with Pb ≥5.55 µg/dL have a 14 times higher risk of suffering from rHT (p=0.026). Interestingly, a 9-fold increased risk was found for non-obese subjects with elevated Pb levels, above 5.55 µg/dL (p=0.029). Also in men, the probability of suffering from rHT was more than 7 times higher if Cd levels were ≥ 0.75 µg/L (p=0.076). Most smokers had higher Cd levels, with a high risk of suffering from rHT (ORa 12.6 (0.8–200.2), p=0.072). A higher blood Pb levels, defined by the 75th percentile (Pb ≥ 5.55 µg/dL), is associated with a greater risk of suffering from rHT and to a lesser extent in the case of Cd and Hg. [ABSTRACT FROM AUTHOR]

Background: Physical activity is associated with reduced arterial stiffness, although such a relationship has not been reported in those with resistant hypertension. Therefore, this study aimed to determine the association between daily physical activity and arterial stiffness in patients with resistant hypertension.Methods: Fifty-seven (57) patients with resistant hypertension (50.9% men), aged 58.8±9.4 years, were consecutively recruited. Arterial stiffness was evaluated using carotid-femoral pulse wave velocity (cf-PWV). Daily physical activity was objectively assessed with accelerometers during 7 consecutive days.Results: Patients had a body mass index of 29.0±4.0 kg/m2 (84.3% overweight/obese) and were taking an average 4.5 antihypertensive medications. Overall, the cf-PWV was 9.2±2.4 m/s and the majority of participants (n=41, 71.9%) presented a cf-PWV <10 m/s. The cf-PWV showed an inverse correlation with light-intensity physical activity (r = -0.290, p=0.029) and total daily physical activity (r = -0.287, p=0.030). The correlation between light physical activity and cf-PWV remained significant after adjustment for systolic and diastolic blood pressure, but lost significance when further adjusted for age.Conclusions: Higher daily levels of light-intensity and total physical activity were associated with lower arterial stiffness. Nonetheless, this association is weak and attenuated or abolished when adjusted for blood pressure and age. These results suggest that physical activity may play an important role as a lifestyle intervention for patients with resistant hypertension. Future studies with larger samples sizes are necessary to confirm this preliminary data. [ABSTRACT FROM AUTHOR]

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Resistant hypertension (RH) induces higher morbidity and mortality due to cardiovascular disease and stroke than hypertension without treatment resistance. New guidelines define RH as blood pressure (BP) ≥130/80 mmHg in a patient taking ≥3 antihypertensive agents of different classes or BP <130/80 mmHg in a patient taking ≥4 antihypertensive drugs. According to the new definition, pseudo-resistance due to error in BP measurement, white coat effect and medication nonadherence must be excluded to make the diagnosis of RH. This 2020 update focuses on the lifestyle and antihypertensive drug management of RH and includes recent proof-of-principle trials of renal nerve ablation in hypertension. Stepwise evidence-based pharmacologic treatment of RH includes optimization of the 3-drug regimen, substitution of a thiazide-like for a thiazide diuretic and addition of a mineralocorticoid receptor antagonist as the fourth drug. Non-evidence-based recommendations include addition of a β-blocker as the fifth drug and switching to a minoxidil-based regimen as the final step in achieving BP control. [ABSTRACT FROM AUTHOR]

The goal of this study was to review recent clinical studies of azilsartan medoxomil (AZL-M) and chlorthalidone (CLD), a combined angiotensin receptor blocker and thiazide-like diuretic, and its role in recently published guidelines. This review explores the role of AZL-M/CLD in treating patients with hypertension. A systematic review of literature published from 1990 to 2018 was performed by using the following key words: Edarbyclor, azilsartan, chlorthalidone, pharmacokinetic, and hypertension. Available English-language data from reviews, abstracts, presentations, and clinical trials regarding the use of AZL-M/CLD therapy specifically detailing effects of lowering blood pressure (BP) and outcomes on cardiovascular disease in humans and rats were reviewed. One study compared a single–pill combination of AZL-M/CLD with co-administration of AZL-M and hydrochlorothiazide and found a greater reduction in clinic systolic BP with AZL-M/CLD (−35.1 mm Hg vs −29.5 mm Hg) than for AZL-M and hydrochlorothiazide. Another study of 153 patients with chronic kidney disease who received AZL-M/CLD or other single–pill combination agents found that AZL-M/CLD was more effective in lowering BP, achieving superior adherence. According to new guidelines, an increase in the prevalence of resistant hypertension can occur as a result of trying to lower target BP. A powerful and effective medication that can increase patient compliance is essential to reduce the incidence of resistant hypertension. AZL-M/CLD is a powerful and safe antihypertensive medication that has been thoroughly studied in patients with hypertension. [ABSTRACT FROM AUTHOR]

Introduction: Sympathetic renal denervation (RD) can potentially reduce blood pressure (BP) in people with resistant hypertension (RH) and uncontrolled hypertension (UH). While a large sham-controlled trial (SCT) showed similar outcomes of RD vs. sham control, in the recent trials, RD was effective in reducing BP in hypertensive people. We performed a meta-analysis of SCTs of RD vs. sham in hypertensive patients.Methods: Multiple electronic databases were searched since inception through September 2018 for SCTs that compared RD vs. sham. Change in 24-hour, daytime and nighttime ambulatory and office BP were efficacy outcomes. Various adverse events were safety outcomes.Results: A total of 7 SCTs were included in the analysis. RD vs. sham significantly reduced 24-hour ambulatory SBP by 3.45 mmHg [95% CI (-5.01, -1.88); P < 0.0001] and DBP by 1.87 mmHg [(-3.59, -0.15); P = 0.01], office DBP by 2.97 mmHg [(-4.76, -1.18); P = 0.001] and daytime ambulatory SBP by 4.03 mmHg [(-6.37, -1.68); P = 0.0008] and DBP by 1.53 mmHg [(-2.69, -0.37); P = 0.01]. RD vs. sham caused non-significant reduction in office SBP by 3.99 mmHg [(-8.10, 0.11); P = 0.06] and nighttime ambulatory SBP by 3.05 mmHg [(-6.86, 0.75), P = 0.12] and DBP by 1.03 mmHg [(-3.01, 0.96); P = 0.31]. There was no difference in the risk of hypertensive crisis/emergency [0.62; 0.24-1.60; P = 0.33] between the two strategies.Conclusions: Current meta-analysis shows that RD reduces ambulatory BP and office DBP in patients with hypertension. Future trials with longer follow-up should confirm these findings. [ABSTRACT FROM AUTHOR]

Despite the availability of numerous approved antihypertensive drugs, difficult-to-control and resistant hypertension are persistent and are major risk factors for cardiovascular disease. Emerging and investigational treatments that are currently being explored to target hypertension include firibrastat, empagliflozin and interventional procedures, including improved approaches to renal artery denervation and a novel baroreceptor device implantation. Firibrastat is an investigational drug that specifically and selectively inhibits aminopeptidase A leading to decreased formation of angiotensin III in the brain, resulting in decreased blood pressure. Sodium-glucose cotransporter-2 inhibitors, such as empagliflozin used to treat type 2 diabetes, may be beneficial as antihypertensive agents. Empagliflozin in a recent study demonstrated significant reductions in high blood pressure in an African American population. Advances in renal artery denervation and an investigational baroreceptor device implantation also show promise as potential interventions in patients with difficult-to-control and resistant hypertension. [ABSTRACT FROM AUTHOR]

Hypertension affects millions of Americans and has adverse long-term consequences increasing morbidity and mortality. Resistant hypertension (RH) continues to be difficult to treat with medications alone which may be associated with significant side effects. Alternate therapies have been evaluated for treating RH and renal denervation has been investigated extensively. We review the data from renal denervation trials and other novel technologies which are not FDA approved to date. [ABSTRACT FROM AUTHOR]

The updated scientific statement by the American Heart Association has defined resistant hypertension (HTN;RH) as uncontrolled blood pressure (BP) ≥ 130/80 mmHg, despite concurrent use of 3 anti-HTN drug classes comprising a calcium channel blocker, a blocker of renin-angiotensin system, and a thiazide diuretic, preferably chlorthalidone. Using the updated BP criteria, the prevalence of RH in the United States is found to be modestly increased by approximately 3-4% among treated population. Meta-analysis of observational studies have demonstrated that pseudo-RH from white coat HTN or medication nonadherence is as much common as the truly RH. Thus, screening for pseudo-resistance in the evaluation of all apparent RH is of utmost importance as diagnosis of white-coat HTN requires no treatment, while medication nonadherence would benefit from identifying and targeting barriers to adherence. [ABSTRACT FROM AUTHOR]

Renal artery stenosis (RAS) is a common cause of secondary hypertension (HTN) and may lead to resistant (refractory) HTN despite guideline directed medical therapy. Although randomized controlled trials comparing medical therapy to medical therapy and renal artery stenting have shown no benefit with renal artery stenting, according to comparative effectiveness reviews by the Agency for Healthcare Research and Quality, the trials did not enroll patients with the most severe RAS who would be more likely to benefit from renal stenting. Because of limitations of conventional angiography, it is important to assess the hemodynamic severity of moderate (50%-70%) RAS lesions with a hemodynamic measurement. We review techniques to optimize patient selection, to minimize procedural complications, and to facilitate durable patency of renal stenting. We also review the current ACC/AHA Guidelines and SCAI Appropriate Use Criteria as they relate to renal stenting. [ABSTRACT FROM AUTHOR]

Hypertensive individuals are at an increased risk of developing heart disease and stroke. Adopting healthy lifestyles, such as being active on ≥4 days per week, weight-loss in the presence of obesity, consuming a diet rich in fruits and vegetables, and sodium below the recommended threshold, avoiding high alcohol consumption and refraining from smoking have been effective lifestyle therapies to prevent or control stage 1 hypertension (HTN). Among the 1 in 3 Americans who have HTN (systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg), 16% are diagnosed with resistant HTN (RHT). Although there are comparatively fewer studies examining the blood pressure lowering effects of therapeutic lifestyle interventions in patients with resistant HTN, the available literature appears promising. This paper reviews key studies that quantify the blood pressure lowering effects of certain therapeutic lifestyles in patients with RHT and highlights areas needing more attention. [ABSTRACT FROM AUTHOR]

Resistant hypertension is a condition in which blood pressure remains elevated despite using 3 or more antihypertensive medications. Though contemporary antihypertensive drug therapies have been essential in treating hypertension, in recent years different studies have explored renal denervation (RDN) as an adjunctive or a replacement modality. Here we summarize an open-label, Symplicity HTN 2 trial and 7 randomized, sham-controlled clinical trials: Spyral-HTN OFF MEDS (Spyral Pivotal), Spyral-HTN ON MEDS, RADIANCE-HTN SOLO, RADIANCE-HTN TRIO, RADIANCE II, SYMPLICITY-HTN 1, and SYMPLICITY-HTN 3, which evaluated safety and efficacy of multiple renal denervation systems (RDN) at lowering blood pressure from baseline, and in comparison, to control group. Prior systematic reviews and meta-analyses evinced a modest reduction of ambulatory and office blood; however, these trials and analyses were limited by short-term follow-up. In our updated comprehensive literature review we summarize the short-term, and long-term effects of RDN, based on the latest randomized clinical trials. Our conclusions based on each summary are unanimous with previous literature findings. [ABSTRACT FROM AUTHOR]

Objective: Given the limited data available in the literature, the aim of this study was to examine the risk of resistant hypertension (RHT) associated with restless legs syndrome (RLS) and periodic limb movements during sleep (PLMS) in a large sample of treated hypertensive individuals.Methods: Demographic and polysomnographic (PSG) data from 673 treated hypertensive individuals recruited from the research database of the sleep laboratory of Erasme Hospital were analysed. After exclusion of the main causes of pseudo-resistance and secondary hypertension, RHT status was defined by the presence of an uncontrolled hypertension despite treatment with at least three antihypertensive agents (including a diuretic) from different classes in correct combination and at the highest tolerated doses or by the presence of controlled hypertension requiring the use of at least four antihypertensive agents. Logistic regression analyses were conducted to examine the risk of RHT associated with RLS and PLMS in treated hypertensive individuals.Results: After adjustment for major confounding factors associated with RHT, multivariate logistic regression analysis revealed that frequent RLS (≥2 episodes/week) combined with PLMS index ≥26/h [odds ratio (OR) 2.20; 95% confidence interval (CI) 1.35-3.61, p = 0.021] was a significant risk factor of RHT in treated hypertensive individuals.Conclusion: In treated hypertensive individuals, frequent RLS combined with PLMS index ≥26/h is associated with higher risk of RHT which suggests that this pathology may be a secondary cause of RHT (eg, obstructive sleep apnoea syndrome and insomnia with short sleep duration) justifying the establishment of effective treatments in this particular subpopulation. [ABSTRACT FROM AUTHOR]

L'objectif principal était d'estimer la proportion de non-adhérence aux médicaments antihypertenseurs chez des patients avec hypertension en apparence résistante malgré un traitement optimal. L'objectif secondaire était d'identifier les facteurs associés à une mauvaise adhérence. Étude monocentrique, observationnelle et prospective, ayant inclus des patients consécutifs suivis pour HTA résistante entre janvier 2014 et décembre 2017, ayant eu une mesure ambulatoire de la pression artérielle (MAPA) dans l'année précédente et un bilan étiologique exhaustif durant les deux dernières années. L'hypertension était considérée résistante si la MAPA de jour était ≥ 135/85 mmHg et/ou la mesure des 24 heures ≥ 130/80 mmHg, malgré 4 médicaments antihypertenseurs à doses optimales. L'adhérence au traitement a été évaluée par l'échelle à 8 items de Morisky (MMAS-8). Nous avons recruté 386 patients, d'âge moyen de 64,6 ans, dont 48,2 % d'hommes. Les pressions artérielles de consultation, des 24 heures et de jour étaient en moyenne de 178,6/101,3 mmHg, 164,4/97,2 mmHg et 170,5/99,7 mmHg respectivement. Les proportions d'adhérence faible, moyenne et élevée au traitement étaient de 24,5 %, 47,6 % et 27,9 % respectivement. Étaient associés à une mauvaise adhérence le sexe féminin, le niveau d'instruction faible, le célibat, la polymédication et l'absence de pratique de l'automesure tensionnelle. Plus de deux tiers des patients hypertendus apparemment résistants malgré un traitement optimal étaient partiellement ou complétement non adhérents au traitement dans notre étude. L'évaluation de l'adhérence devrait être systématique chez ces patients avant d'entreprendre des explorations complexes ou des thérapies non pharmacologiques invasives. The primary objective was to estimate the proportion of non-adherence to antihypertensive drugs in patients with an apparently resistant hypertension despite optimal medical treatment. The secondary objective was to identify related factors to poor adherence. Monocentric, prospective and observational study, including consecutive patients, managed for an apparently resistant hypertension between January 2014 and December 2017, with an ambulatory blood pressure measurement (ABP) in the past year and a thorough etiological work up in the 2 past years. Hypertension was considered resistant if the daytime ABP was ≥ 135/85 mmHg and/or the 24 hours ABP ≥ to 130/80 mmHg, despite 4 antihypertensive medications at optimal doses. Adherence to treatment was assessed by the eight-item Morisky Scale (MMAS-8). We enrolled 386 patients, with a mean age of 64.6 years, and 48.2% of men. The mean office blood pressure, 24 hours and daytime APB were 178.6/101.3 mmHg, 164.4/97.2 mmHg and 170.5/99.7 mmHg respectively. The proportions of low, medium and high adherence were 24.5%, 47.6% and 27.9% respectively. Associated-factors with poor adherence were female sex, low education level, celibacy, polypharmacy and lack of home self-blood pressure monitoring. Over two out of three patients with an apparently resistant hypertension under optimal treatment were partially or fully nonadherent to treatment in our study. Assessment of adherence would be systematic in these patients before implementing complex investigations or non-pharmacologic invasive procedures. [ABSTRACT FROM AUTHOR]

Abstract Young-onset hypertensives (YOHs) with resistant hypertension (RH) have a greater long-term cardiovascular risk. The present study examined whether a functional adiponectin T94G polymorphism (rs2241766) is associated with RH in YOHs. We analyzed data from the Academia Sinica Collaborative Study on Hypertension Genetics in Taiwanese subjects to compare rs2241766 between YOHs with and without RH (≤50 years of age). RH was defined as the need for at least 3 drugs, including a diuretic to control blood pressure. Genotyping of rs2241766 was performed using TaqMan allelic discrimination. A total of 861 YOHs were enrolled and 54 had RH in enrolled population. For the rs2241766 in the allelic model, the odds ratio (OR) of RH allele frequency was 2.45 (p = 0.008), and there was a linear relationship between allele numbers and the presence of RH (p = 0.005). In multivariate analysis, the rs2241766 (OR = 2.766, p = 0.002), age (OR = 1.103, p = 0.001), uric acid (OR = 1.322, p = 0.001), high-sensitivity C-reactive protein (OR = 2.769, p = 0.001) and aldosterone (OR = 1.004, p = 0.001) were independently associated with the presence of RH. In the Taiwanese population, the adiponectin T94G polymorphism (rs2241766) is associated with RH in YOHs. Highlights • YOHs with RH patients have a greater cardiovascular risk but the association of adiponectin T94G polymorphism is unknown. • Total 861 YOHs in Taiwanese subjects were collected to compare rs2241766 between YOHs with and without RH (≤50 year-old) • In this study, we found inflammation and hyperaldosteronism might play important roles in young-onset RH. • We also found the adiponectin T94G polymorphism (rs2241766) was independently associated with RH. • An increasing G allele frequency and heterozygous TG genotype of adiponectin gene showed a significant association with RH. [ABSTRACT FROM AUTHOR]

Abstract Background The aim of the present study was to evaluate endothelial status by measuring the concentration of novel markers of endothelial dysfunction (ED): a number of circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs) and their ratio (CEPCs/CECs) as well as a traditional parameter - soluble thrombomodulin (sTM) in patients with resistant (RH) and mild hypertension (MH). Materials and methods Thirty patients with MH and thirty subjects with RH were involved in the study. The control group included thirty-three age and sex-matched normotensive volunteers. We used multicolor flow cytometry for CECs and CEPCs analysis and the commercial human sTM ELISA kit to measure plasma sTM concentration. Results An elevated CECs number and a decreased CEPCs/CECs ratio was found in MH as well as in RH patients in comparison with normotensive volunteers. CECs correlated positively with an increased triglycerides in MH patients and an elevated LDL-cholesterol and hsCRP in RH group. Positive correlation between CEPCs and LDL-cholesterol level was observed in both types of hypertension. Conclusions The results of the present study suggest that an endothelial alteration accompanies hypertension. The number of CECs reflecting the extent of endothelial damage does not appear to be related to the severity of disease. The drastically decreased ratio between CEPCs and CECs observed in both groups of patients suggests an inadequate process of endothelial regeneration. Among analyzed factors inflammation and lipid abnormalities may have significant contribution in endothelial pathology in hypertension. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Objectives: We assessed a novel approach to percutaneous renal denervation for uncontrolled hypertension consisting of ablation beyond the proximal main renal artery (Y-pattern), including the primary branches, and compared it to the standard procedure applied only within the main vessel. We also assessed the safety and practicality of a brachial access approach.Methods and Results: Renal denervation was performed on 119 consecutive patients (60 ± 13 years). In 68 of the patients, femoral arterial vascular approach was used and in 51 brachial. In 80 patients treated with the standard ablation, 12.0 ± 3.0 total ablations (both sides) were applied while 20.4 ± 3.9 total ablations were delivered for the group of 39 patients with Y-pattern denervation (P < 0.001). Technically successful renal denervation was achieved in all patients. Office blood-pressure levels at baseline were 170 ± 17/93 ± 10 mm Hg for the standard group and 169 ± 13/96 ± 9 mm Hg for the Y-pattern group. No major adverse events occurred during the procedure or in the postprocedural in-hospital period. Renal denervation was associated with significant decreases in both office and ambulatory systolic and diastolic blood pressure in both groups. The reduction in 24-hour mean ambulatory systolic blood pressure at 6 months was significantly greater (P = 0.002) for the Y-Pattern group (-22.1 ± 15.4 mm Hg) compared to the Standard group (-11.8 ± 16.2 mm Hg). Changes in diastolic office and ambulatory pressure were also significantly greater at 6 months in the Y-pattern ablation group. Indices of blood pressure variability improved in both groups.Conclusion: Renal denervation using a Y-pattern ablation strategy combined with a greater number of lesions is safe and resulted in significant greater decreases in mean 24-hour ambulatory systolic and diastolic blood pressure compared to the conventional approach in this single-centre matched cohort study. Brachial artery access was shown to be feasible and safe for renal denervation. [ABSTRACT FROM AUTHOR]

• Endothelin-1 (ET-1) is one of the most potent vasoconstrictory proteins that regulate vascular tone, remodeling and blood pressure. • Aprocitentan is a first-in-class dual antagonist of ET A and ET B receptors. • Aprocitentan is well tolerated and lowers blood pressure in patients with resistant hypertension. Hypertension is reaching epidemic proportions worldwide and is a significant public health concern. However, ∼15% of patients with hypertension continue to experience elevated blood pressure, even after taking antihypertensive medications [such as angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine calcium channel blockers (CCBs) and thiazide diuretics], a condition referred to as resistant hypertension (RH). Within the complex realm of blood pressure regulation and vascular function, endothelin-1 (ET-1), a potent vasoconstrictor, plays a pivotal role. Recent research, particularly a Phase III clinical trial (NCT03541174), has shed light on the potential of aprocitentan, a dual ET-1 receptor antagonist, in significantly lowering blood pressure in individuals with RH. In this review, we summarize the mechanism of action and therapeutic potential of aprocitentan as an innovative approach for treating RH. [ABSTRACT FROM AUTHOR]

Resistant hypertension is commonly defined as office blood pressure above recommended target despite the use of optimal doses of at least three antihypertensive drugs including a diuretic. Australian guidelines recommend combination of blockers of the renin-angiotensin system, either ACE inhibitors or angiotensin receptor blockers, with calcium channel blockers and diuretics as the preferred triple therapy. A substantial proportion of hypertensive patients will require additional pharmacotherapy to achieve or get close to target blood pressure levels. Here we briefly review the evidence currently available to provide guidance on the most appropriate choice for additional antihypertensive pharmacotherapy and touch on interventional approaches that may be considered in some patients. [ABSTRACT FROM AUTHOR]

Objective The aim of the present study was to investigate the association of I/D polymorphisms of ACE gene is associated with resistant hypertension and essential controlled hypertension. Results Our results show that the homozygous mutant genotype DD was more represented among resistant than controlled (58.1% vs 41.9% respectively), however the homozygote wild was more represented among controlled than resistant (70.6% vs 29.4% respectively). But more heterozygous ID among controlled than resistant patients (63.6% vs 36.4% respectively). The difference was statistically significant ( p  = 0.04). Analysis of clinical parameters indicated that physical activity contributes to resistant hypertension ( P  < 0.05). Based on our findings, the homozygous mutant for DD of ACE gene is associated with resistant hypertension in our population. Further studies with larger sample sizes are needed to confirm the results of this study. [ABSTRACT FROM AUTHOR]

Résumé La survenue d’une sténose de l’artère rénale au décours d’une dénervation est rare et survient dans les premiers mois. Nous rapportons la survenue d’une sténose de l’artère rénale à distance de la dénervation. Il s’agit d’un patient de 74 ans tabagique sevré depuis 1980, dyslipidémique traité avec coronaropathie revascularisée en 2011, artérite des membres inférieurs bien stabilisée depuis 2001, un athérome carotidien stable asymptomatique et une bonne fonction rénale qui présente une HTA connue depuis 1995 devenant résistante. Après contrôle des artères rénales par angioscanner, il bénéficie d’une dénervation en octobre 2012. Une baisse de la pression artérielle apparaît 3 mois plus tard confirmée en automesure et en mesure ambulatoire (MAPA) avec un angioscanner sans sténose significative des artères rénales en janvier 2014. Il reste normotendu sous traitement jusqu’en juillet 2015 mais une HTA mal équilibrée réapparaît fin 2015, devenant progressivement résistante et sévère en avril 2017, confirmée en automesure, sous pentathérapie antihypertensive associée à de l’atorvastatine et du clopidogrel avec découverte au scanner d’une sténose post-ostiale de l’artère rénale gauche avec diminution de la taille et du cortex du rein gauche par rapport à 2011. Angioplastie de l’artère rénale gauche avec stent en avril 2017. Baisse rapide de la pression artérielle mais nouvelle remontée de la pression artérielle fin 2017 et découverte d’une resténose justifiant une nouvelle angioplastie. Discussion de l’étiologie de cette sténose tardive après une dénervation rénale et de sa prise en charge. The onset of renal artery stenosis following a renal denervation is rare and occurs in the first few months after renal denervation. We report the onset of renal artery stenosis a long time after the renal denervation for resistant hypertension. This is a 74 year-old patient who stopped smoking in 1980 and who was treated for dyslipidemia with a revascularized coronary artery disease in 2011, a well-stabilized peripheral arterial disease since 2001, a stable asymptomatic carotid atheroma and a good kidney function. His hypertension known since 1995 became resistant. After the control of renal arteries by angio-CT scan, he had a renal denervation in October 2012. His blood pressure decreased 3 months later confirmed by self-blood pressure monitoring (SBPM) and ambulatory blood pressure monitoring (ABPM) with a CT scan with a non-significant renal artery stenosis in January 2014. He remained normotensive under treatment until July 2015 but his hypertension became uncontrolled at the end of 2015 then resistant and severe confirmed by SBPM in April 2017, despite a 5-drug antihypertensive treatment associated to atorvastatin and clopidogrel confirmed by SBPM in April 2017. A left post-ostial renal artery stenosis with decrease in size of left kidney and cortex as compared to 2011 was detected at CT and treated by angioplasty. It was associated with a rapid decrease in blood pressure but unfortunately a new increase related to a restenosis occurred at the end of 2017, which justified a new angioplasty. Discussion about the etiology and the management of this renal post-denervation late stenosis. [ABSTRACT FROM AUTHOR]

Résumé La prise en charge adaptée des patients présentant une hypertension artérielle résistante est un enjeu majeur afin de limiter l’impact macro et microvasculaires sur les organes cibles. Cependant, l’inobservance thérapeutique reste souvent une des principales étiologies de l’hypertension artérielle résistante. Au travers d’un cas clinique d’inobservance thérapeutique complexe, nous reviendrons sur la fréquence, les moyens de dépistage et la prise en charge spécifique de la non-compliance thérapeutique médicamenteuse. Enfin, nous préciserons l’apport des dosages médicamenteux et de l’expertise psychologique dans l’aide au dépistage des patients non observants présentant une hypertension artérielle présumée résistante. The management of patients with resistant hypertension remains a major challenge in daily clinical practice in order to limit macro and microvascular impact. However, lack of compliance often remains one of the main etiologies of resistant hypertension. Through a clinical case of complex therapeutic non-compliance, we will detail the frequency, the screening and the management of therapeutic non-compliance. Finally, we will specify the contribution of drug dosages and psychological expertise in screening non-observant patients with presumed resistant hypertension. [ABSTRACT FROM AUTHOR]

Background and aims Echocardiographic studies have shown improvements in cardiac indices associated with renal sympathetic denervation (RDN), however, the benefits on myocardial perfusion have never been assessed. This trial was designed to study the effects of RDN on myocardial perfusion using cardiac magnetic resonance (CMR) imaging. Methods A total of 14 patients with resistant hypertension were recruited for RDN and myocardial perfusion, alongside other CMR indices, was assessed at baseline and at 6 months. Results RDN showed significant reduction of mean office blood pressures from 181/100 ± 19/16 mmHg to 147/85 ± 19/17 mmHg, 6 months after the procedure ( p  < 0.0001). This was combined with significant improvement in regional aortic distensibility ( p  < 0.02) and associated with trends of improved myocardial perfusion reserve index (baseline = 2.2 ± 1; 6 months = 2.9 ± 1 units) ( p  = 0.08). Left ventricular end systolic volume index decreased from baseline to 6 months post procedure, 27 ± 13 ml/m 2 vs. 22 ± 10 ml/m 2 ( p  = 0.03), but there was no significant change in left ventricular end diastolic volume index ( p = 0.09). There was significant improvement in mean left ventricular ejection fraction from 68 ± 10% to 72 + 9%, 6 months post procedure ( p  = 0.04). T1 mapping failed to detect fibrosis in these patients at baseline and therefore no change was noted, however, extracellular volume percent improved from 46 ± 4% at baseline to 41 ± 8% at 6 months ( p  = 0.002). Conclusions This study demonstrates that renal sympathetic denervation increased myocardial perfusion by 32% as assessed by CMR, and, this was associated with improvements in cardiac volumes and function. Larger well controlled and randomized studies are required to assess the clinical significance of these findings. [ABSTRACT FROM AUTHOR]

Resistant hypertension (RH) can be diagnosed if blood pressure (BP) is not controlled with the combination of three antihypertensive drugs, including a diuretic, all at effective doses. Patients affected by this condition exhibit a marked increase in the risk of cardiovascular and renal morbid and fatal events. They also exhibit an increased activity of the sympathetic nervous system which is likely to importantly contribute at the renal and other vascular levels to the hypertensive state. Almost 10 years ago renal denervation (RDN) by radiofrequency thermal energy delivery to the walls of the renal arteries was proposed for the treatment of RH. Several uncontrolled studies initially reported that this procedure substantially reduced the elevated BP values but this conclusion has not been supported by a recent randomized control trial, which has almost marginalized this therapeutic approach. A revival, however, is under way because of recent positive findings and technical improvement that hold promise to make renal denervation more complete. The antihypertensive efficacy and overall validity of RDN will have to be tested against drug treatment of RH. Several studies indicate that an excess of aldosterone production contributes to RH and recent evidence documents indisputably that anti-aldosterone agents such as spironolactone can effectively control BP in many RH patients, although with some side effects that require close patients' monitoring. At present, it is advisable to treat RH with the addition of an anti-aldosterone agent. If BP control is not achieved or serious side effects become manifest RDN may then be considered. [ABSTRACT FROM AUTHOR]

Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Surgical treatment of unilateral PA usually resolves excessive aldosterone secretion. Obesity is an independent factor for postoperative persistent hypertension for patients with unilateral PA. Laparoscopic sleeve gastrectomy has become popular due to its efficacy in resolving obesity. A specific strategy might to be needed for patients with unilateral PA and obesity. Two males with PA and obesity (Body Mass Index: BMIs of 35.9 and 39.0, respectively) were referred for evaluation. Both patients had hypertension caused by PA and obesity. We performed laparoscopic sleeve gastrectomy (LSG) prior to adrenalectomy to avoid persistent postoperative hypertension and perioperative obesity related comorbidities. LSG could lead to decreasing of BMIs to 27.7 and 32.1. Comorbidities associated with obesity were also resolved in both patients. Laparoscopic adrenalectomy was then safely performed in these two patients with PA. Patients with PA developing resistant hypertension were estimated to be 20 % of those who underwent adrenalectomy. Decreased BMI can be an independent preoperative determinant for successful outcome after adrenalectomy regarding hypertension. We need to review with special care the preoperative BMI and the nature of hypertension before performing surgery on patients with unilateral PA. A successful strategy was used to treat two obese patients with unilateral PA who underwent laparoscopic adrenalectomy after LSG to minimize complications associated with obesity-related comorbidities. • A successful strategy for obese patients with unilateral aldosteronism. • Obesity can cause persistent hypertension after adrenalectomy. • Laparoscopic sleeve gastrectomy has shown efficacy in resolving obesity. • Initial sleeve gastrectomy followed by laparoscopic adrenalectomy was performed. [ABSTRACT FROM AUTHOR]

Background and aims Catheter-based renal denervation for the treatment of drug-resistant hypertension has been intensively investigated in recent years. To date, only limited data have been published using multi-electrode radiofrequency ablation systems that can deliver lesions with a pre-determined pattern. This study was designed to evaluate the safety and performance of the second generation EnligHTN™ Renal Denervation System. Methods This first-in-human, prospective, multi-center, non-randomized study included 39 patients (62% male, mean age 63 years, and mean baseline office blood pressure 174/93 mmHg) with drug-resistant hypertension. The primary safety and performance objectives were to characterize, from baseline to 6 months post procedure, the rate of serious procedural and device related adverse events, as adjudicated by an independent Clinical Events Committee, and the reduction of office systolic blood pressure. Results Renal artery denervation, using the second generation EnligHTN multi-electrode system significantly reduced office blood pressure from baseline to 1, 3, 6, 12, 18 and 24 months by 19/7, 26/9, 25/7, 23/7, 25/8 and 27/9 mmHg, respectively ( p ≤ 0.0005). No serious device or procedure related adverse events affecting the renal arteries or renal function occurred through 24 months of follow-up. Conclusions Renal sympathetic denervation using the second generation EnligHTN Renal Denervation System resulted in safe, rapid, and significant mean office blood pressure reduction that was sustained through 24 months. Future studies will need to address the utility of this system against an appropriate sham based comparator. [ABSTRACT FROM AUTHOR]

Background and aim Baroreceptor activation therapy (BAT) leads to a decrease in blood pressure (BP) in patients affected by resistant hypertension (RH) by reducing sympathetic outflow. This study aimed at evaluating the effects of BAT on RH patients’ retinal arteriolar microvasculature, a territory devoid of adrenergic innervation. Patients and methods Five patients defined as affected by RH after excluding secondary causes of hypertension and based on number of antihypertensive treatments, underwent the implantation of Barostim™ neo ™. Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) were assessed by office and 24-hours ambulatory BP monitoring (ABPM). Adaptive Optics Camera RTX1 ® (ImagineEye, Orsay, France) was used to measure wall thickness (WT), internal diameter (ID), wall cross-sectional area (WCSA) and wall-to-lumen ratio (WLR). A cohort of 21 not-controlled hypertensive patients matched for age, gender and follow-up time, undergoing standard-antihypertensive therapy changes, was selected as a control group. SBP and DBP were assessed by office and home BP monitoring (HBPM). Evaluations were performed at baseline and after 6 months mean follow-up. Results Office SBP decreased by 9.7 ± 12.3% and 29.7 ± 12.4% in standard-therapy and BAT group respectively, while office DBP decreased by 7.6 ± 17.4% and 14.8 ± 15.7%. Concerning ABPM/HBPM, a mean reduction of both SBP and DBP of 7.9 ± 11% was observed for the standard-therapy while a reduction of 15.8 ± 10.5% and 15.8% ± 5.3% was observed for SBP and DBP respectively in BAT group. While in the standard-therapy group a significant reduction in WLR (–5.9%) due to both ID increase (+2.3%) and WT reduction (–5.7%) was observed, without changes in WCSA (–0.3%), RH patients had a significant reduction in WCSA (–12.1%), due to a trend in both WT and ID reduction (–6.5% and –1.7% respectively), without significant changes in WLR (–2%). Conclusion While a reverse eutrophic remodeling was observed in patients undergoing a standard-antihypertensive treatment, hypotrophic changes were found in RH patients undergoing BAT. Despite the lack of adrenergic receptors on retinal vessels, chronic baroreflex stimulation may exert an effect on retinal microvasculature in RH patients by more systemic than local mechanisms. [ABSTRACT FROM AUTHOR]

Correlation between blood pressure (BP) and target organ damage, vascular risk, and long-term patient prognosis is stronger for measurements derived from around-the-clock ambulatory BP monitoring (ABPM) than in-clinic daytime ones. Numerous studies consistently substantiate the asleep BP mean is both an independent and much better predictor of cardiovascular disease (CVD) risk than either the awake or 24 h means. Elevated sleep-time BP, i.e., sleep-time hypertension, which can only be diagnosed by around-the-clock ABPM, is much more common than suspected, not only in patients with sleep disorders, but, among others, in those who are elderly or have type 2 diabetes, chronic kidney disease, or resistant hypertension. Hence, medical guidelines increasingly recommend ABPM to make the accurate differential diagnosis of hypertension versus normotension and recognize the marked clinical importance of adequate management of sleep-time BP. The ingestion time, according to circadian rhythms, of hypertension medications of six different classes and their combinations significantly impacts their beneficial, particularly on sleep-time BP control, and/or adverse effects. The MAPEC (monitorización ambulatoria para predicción de eventos cardiovasculares (i.e., ambulatory blood pressure monitoring for prediction of cardiovascular events)) study was the first prospective randomized treatment-time investigation designed to test the worthiness of bedtime chronotherapy with ≥1 conventional hypertension medications to specifically target attenuation of asleep BP. This 5.6 y median follow-up outcomes trial found the bedtime chronotherapy strategy most advantageous, resulting in the differential reduction of total CVD events by 61% and decrease of major CVD events - CVD death, myocardial infarction, and ischemic and hemorrhagic stroke - by 67%. The MAPEC study plus other earlier conducted less refined trials document the asleep BP mean is the most significant prognostic marker of CVD morbidity and mortality. It further substantiates attenuation of the asleep BP mean by a bedtime hypertension treatment strategy entailing the entire daily dose of ≥1 hypertension medications significantly reduces CVD risk, both in the general hypertension population and in more vulnerable patients, i.e., those diagnosed with chronic kidney disease, diabetes, and resistant hypertension. [ABSTRACT FROM AUTHOR]

The rationale for the renal denervation treatment of severe, drug-resistant essential hypertension remains valid, but the field is now at a procedural watershed. With the commonly flawed procedures of the past, most notably in the Symplicity HTN-3 trial, which typically directed ablating energy into the proximal renal arteries, coupled with the absence of testing for achieved denervation, who could guess which of the past negative renal denervation trials, if any, are valid? But renal denervation procedures will now be different in two important ways. First, energy will be directed into the distal renal arteries and renal artery branches, where the renal nerves lie closest to the artery lumen. The need for this change is emphatic and unequivocal. Second, the number of energy point applications will be increased to 12–16 bilaterally. This is required because local perivascular anatomy distorts energy flow, making it unpredictable, so that multiple overlapping energy doses are needed. Applying these principles in experimental animals achieves near-total renal sympathetic nerve ablation, and lowers blood pressure. The “smart” renal denervation trials of the future will include a sham procedure and 24-h ambulatory blood pressure endpoints, but more important than these, which in comparison is clinical trialist “tinkering”, will be the procedural revolution in ablative energy delivery. [ABSTRACT FROM AUTHOR]

Objective The efficacy of add-on use of spironolactone in patients with resistant hypertension has been investigated in several small studies. We performed this meta-analysis evaluating the efficacy of add-on use of spironolactone in these patients. Methods We searched Pubmed, Web of Science, and Cochrane Central for all published studies evaluating add-on use of spironolactone in patients with resistant hypertension. Only randomized controlled trials determining antihypertensive effects of spironolactone were considered. Results The antihypertensive effects were assessed in 869 patients included in 4 trials with a mean follow-up of 12 ± 3 weeks. The reduction of systolic blood pressure (SBP) and diastolic BP (DBP) in patients treated with spironolactone was greater than placebo (weighted mean differences (WMD) for SBP − 16.67 mm Hg (95% confidence interval (CI), − 27.54, − 5.80), p < 0.01; WMD for DBP − 6.11 mm Hg (95% CI, − 9.34, − 2.88), p < 0.001), respectively. The rates of serious adverse effects or patient withdrawals from the trials tended to be higher in patients treated with spironolactone than placebo (WMD for odds ratio 2.11 (95% CI, 0.98, 4.53), p = 0.05). Conclusions This meta-analysis provides the evidence that add-on use of spironolactone in patients with resistant hypertension is effective in lowering SBP and DBP, suggesting an add-on use of spironolactone as fourth line therapy in patients with resistant hypertension. [ABSTRACT FROM AUTHOR]

Objective In clinical practice, patient characteristics predicting resistant hypertension (RH) include higher blood pressure levels, left ventricular hypertrophy, older age, obesity, chronic kidney disease and diabetes. On the contrary little is known about the role of serum uric acid (SUA) as a risk factor for RH in subjects from general population. Material and methods 580 elderly subjects aged ≥65 years were enrolled in the Risk Of Vascular complications Impact of Genetics in Old people (ROVIGO) study. RH was defined as the failure to maintain blood pressure values below 140 mmHg (systolic) and 90 mmHg (diastolic) despite therapeutic interventions that include appropriate lifestyle measures plus adherence to treatment with full doses of at least three antihypertensive drugs, including a diuretic. RH was confirmed using 24-h ambulatory blood pressure measurement. Hyperuricemic was defined as the subjects having SUA ≥6.8 mg/dl or taking uricosuric drugs. Gender-specific odds ratio (OR) for RH was calculated by logistic regression analysis. Results The prevalence of RH was 5.7% in the cohort and was higher in women (8.3%) than in men (3.0%, p < 0.05). Independent of chronic kidney disease (OR 3.89, 95% confidence interval 1.49–10.1), hyperuricemia predicted resistant hypertension in women (odds ratio 3.11, 95% confidence intervals 1.06–9.1, p = 0.03) but not in men. Conclusions In elderly women from the general population, an SUA value of ≥6.8 mg/dl triples the risk of RH. SUA assessment should be recommended to better define the pattern of risk associated with RH. [ABSTRACT FROM AUTHOR]

Baroreflex activation therapy (BAT) is a device-based therapy for patients with treatment-resistant hypertension. In a randomized, controlled trial, the first-generation system significantly reduced blood pressure (BP) versus sham. Although an open-label validation study of the second-generation system demonstrated similar BP reductions, controlled data are not presently available. Therefore, this investigation compares results of first- and second-generation BAT systems. Two cohorts of first-generation BAT system patients were generated with propensity matching to compare against the validation group of 30 second-generation subjects. The first cohort was drawn from the first-generation randomized trial sham group and the second cohort from the active therapy group. Safety and efficacy were compared for the second-generation group relative to the first generation. At 6 months, second-generation BAT outperformed first-generation sham systolic BP reduction by 20 ± 28 mm Hg (mean ± standard deviation, P = .008), while BP reduction in first- and second-generation active groups was similar. At 12 months, efficacy was comparable between all three groups after the sham group had received 6 months of therapy; 47% of second-generation patients achieved goal systolic BP of 140 mm Hg or less after 12 months, comparable to 50% of patients at goal in the first-generation group ( P > .999). Implant procedure time, system/procedural safety, and pulse generator longevity improved with the second-generation system. Propensity-matched cohort analysis of the first- and second-generation BAT systems suggests similar therapeutic benefit and superior BP reduction of the second-generation system relative to sham control. Implantation procedure duration and perioperative safety were improved with the second-generation device. These findings should be validated in a prospective randomized trial. [ABSTRACT FROM AUTHOR]

Background and Objective: Elevated systolic blood pressure (SBP) is potently associated with risk of recurrent strokes. In resource-limited settings, there is a dearth of data on the rates and determinants of uncontrolled SBP among stroke survivors at high risk of recurrent events. The objective of this study is to assess the rates and determinants of uncontrolled SBP over the first year post stroke.Methods: This is a retrospective observational study involving stroke survivors who enrolled into an outpatient neurology clinic in Kumasi, Ghana, between January 2012 and June 2014. Baseline demographic features, clinical characteristics, antihypertensive medications prescribed at each clinic visit, treatment modifications, and clinic blood pressure measurements were recorded. Predictors of uncontrolled SBP during follow-up were assessed using a multivariable logistic regression model.Results: A total of 602 stroke survivors enrolled for follow-up within the study period of which 89.8% had hypertension. Up to 35% of subjects had an SBP above 140 mmHg during follow-up clinic visits. Among those with uncontrolled SBP, 17% had antihypertensive treatment modifications during follow-up. Predictors of uncontrolled SBP were SBP at enrollment into clinic, with an adjusted odds ratio (OR [95% confidence interval {CI}]) of 1.31 (1.17-1.47)/10 mmHg increase, and average number of antihypertensive medications prescribed, with an adjusted OR (95% CI) of 1.30 (1.06-1.60) for an increase in the number of antihypertensives prescribed.Conclusion: A third of stroke survivors had SBP not on target during follow-up possibly due to a combination of therapeutic inertia, apparent treatment resistance, and poor adherence to therapy. Longer-term prospective interventional studies on hypertension control among stroke survivors are warranted in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Résumé Nous présentons ici le cas d'un infarctus de type 2 survenu immédiatement après une dénervation rénale chez un patient souffrant d'hypertension artérielle résistante. L'hypotension secondaire au geste a engendré une nécrose myocardique inférieure révélant une sténose pré occlusive de l'artère coronaire droite. Abstract We report the case of a type-2 myocardial infarction immediately after renal denervation. The patient was followed for coronary artery disease. Low blood pressures were responsible for inferior acute myocardial infarction that revealed a sub occlusive stenosis of the right coronary artery. [ABSTRACT FROM AUTHOR]

Several disturbed blood pressure (BP) patterns, including disparities between office and out-of-office BP measurements (such as white-coat and masked hypertension), disturbed circadian BP variability (such as abnormal dipping patterns and nocturnal hypertension) and treatment-resistant hypertension, are common in individuals with type 1 diabetes. Consequently, office or home BP measurements alone may not reflect real BP variation and may lead to inadequate diagnosis and treatment of hypertension. The early detection of these disturbed BP patterns is especially crucial in individuals with type 1 diabetes, as these patterns may indicate future development of adverse cardiovascular and renal outcomes. In this review we will describe these disturbed BP patterns and discuss recent findings on their prevalence and outcomes. We will also address critical areas for future research to determine the true prevalence and prognosis of disturbed BP patterns, and to optimize and improve the knowledge and management of high-risk individuals with type 1 diabetes and disturbed BP patterns. [ABSTRACT FROM AUTHOR]

Purpose Resistant hypertension (RH) is a major and growing public health problem. While noncompliance to antihypertensive medication is a major concern in RH patients, it is estimated that even with adequate multi-drug regimens, approximately 10% of patients diagnosed with hypertension fulfill the criteria of true RH. Patients with sustained blood pressure (BP) elevation display high risk for development of target organ damage and associated cardiovascular morbidity and mortality. While optimized pharmacologic therapy, including the use of mineralocorticoid receptor antagonists to guideline-based antihypertensive drug therapy, is effective for improving BP control in this patient cohort, a sizable proportion of RH patients’ BP remains uncontrolled, and alternative therapeutic strategies are warranted. Methods In the past few years, device-based approaches have been studied extensively. Among these, robust clinical experience in patients with RH exists for renal denervation, baroreflex activation therapy, central arteriovenous anastomosis, and, to a lesser extent, deep brain stimulation. Carotid body modulation is the most recent approach under clinical investigation. The common aim of these approaches is direct targeting of relevant pathophysiologic mechanisms involved in BP control, most commonly activation of the sympathetic nervous system. Findings This review article briefly summarizes relevant clinical and experimental evidence and highlights the potential utility, as well as limitations, of each approach. Implications Several device-based approaches show promise in the treatment of RH and have been associated with improved BP control, while generally finding an acceptable side effect profile. Ongoing research is addressing relevant issues relating to patient selection and technical and procedural aspects, and will help to define the future role of device-based approaches for RH in the next few years. [ABSTRACT FROM AUTHOR]

Background: The treatment of resistant hypertension (RH) is challenging. Several observational studies have suggested that the addition of spironolactone to triple-drug therapy might have a promising anti-hypertensive effect on RH. To provide more definite evidence for the benefit of spironolactone, we performed a meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy and safety of spironolactone in RH patients.Methods: Articles were searched from PubMed, EMBASE and Cochrane Library. Randomised controlled trials investigating the effect of additional spironolactone on office blood pressure (BP), ambulatory BP or adverse events in RH patients were included for analysis. Then quality assessment, subgroup, sensitivity, and publication bias analyses were performed.Results: Five RCTs involving a total of 553 patients were eligible for inclusion. Compared with control therapies, additional spironolactone treatment in RH patients significantly decreased 24-h ambulatory systolic BP (ASBP, weight mean difference [WMD]= -10.50, 95% confidence interval [CI] = -12.30 to -8.71, P<0.001), 24-h ambulatory diastolic BP (ADBP, WMD = -4.09, 95% CI = -5.28 to -2.91, P<0.001), daytime ASBP (WMD = -10.20, 95% CI = -12.41 to -7.99, P<0.001), daytime ADBP (WMD = -4.14, 95% CI = -5.50 to -2.78, P<0.001), night-time ASBP (WMD = -10.02, 95% CI = -12.63 to -7.41), night-time ADBP (WMD=-3.21, 95% CI=-4.84 to -1.58, P<0.001), office systolic BP (WMD=-16.99, 95% CI=-25.04 to -8.95, P<0.001) and office diastolic BP (WMD=-6.18, 95% CI=-9.30 to -3.05, P<0.001). However, serum potassium might be slightly elevated by additional spironolactone (WMD=0.181, 95% CI=0.042 to 0.319, P=0.011).Conclusion: Spironolactone combined with triple-drug therapy may be an effective and relatively safe strategy for the management of RH patients. [ABSTRACT FROM AUTHOR]

Introduction Increased central sympathetic activity has a central role in the pathophysiology of cardiac arrhythmias. Despite the recently published negative results regarding the impact of renal sympathetic denervation (RDN) on resistant hypertension treatment, the beneficial effects of this intervention on cardiac arrhythmias seems to be promising. The aim of this systematic review is to analyze the existing data regarding the impact of RDN on atrial and ventricular arrhythmias. Methods We systematically searched MEDLINE/PubMed database until January 2016 by using the algorithm “renal denervation AND (arrhythmias OR atrial OR ventricular)” without limitations. Additionally, the reference lists of the included studies and the relevant review studies were also manually searched. Results Of the 467 studies yielded from the initial search, 34 were finally included in the systematic review (15 human studies, 18 animal studies and 1 study with both experimental and clinical data). The critical analysis of data from both human and animal studies indicates that RDN can modulate atrial and ventricular electrophysiological properties and exerts favorable effects in the development and recurrence of atrial and ventricular arrhythmias. Conclusion In this systematic review we showed that RDN reduces the burden of atrial and ventricular arrhythmias in various experimental and clinical settings. Appropriately designed randomized sham controlled trials are needed in order to elucidate the exact impact of RDN on arrhythmia management. [ABSTRACT FROM AUTHOR]

Background Defining an adequate endpoint for renal denervation trials represents a major challenge. A high inter-individual and intra-individual variability of blood pressure levels as well as a partial or total non-adherence on antihypertensive drugs hamper treatment evaluations after renal denervation. Blood pressure measurements at a single point in time as used as primary endpoint in most clinical trials on renal denervation, might not be sufficient to discriminate between patients who do or do not respond to renal denervation. Methods We compared the traditional responder classification (defined as systolic 24-hour blood pressure reduction of − 5 mm Hg six months after renal denervation) with a novel definition of an ideal respondership (based on a 24 h blood pressure reduction at no point in time, one, or all follow-up timepoints). Results We were able to re-classify almost a quarter of patients. Blood pressure variability was substantial in patients traditionally defined as responders. On the other hand, our novel classification of an ideal respondership seems to be clinically superior in discriminating sustained from pseudo-response to renal denervation. Conclusion Based on our observations, we recommend that the traditional response classification should be reconsidered and possibly strengthened by using a composite endpoint of 24 h-BP reductions at different follow-up-visits. [ABSTRACT FROM AUTHOR]

Résumé Objectif Estimer la prévalence de l’HTA résistante (HTAr) chez des patients hypertendus traités, non contrôlés, adressés dans un centre de soins tertiaires. Patients et méthodes Étude prospective observationnelle ayant inclus des patients hypertendus de plus de 18 ans, traités depuis au moins 12 mois et adressés pour HTA non contrôlée à l’unité d’hypertension du centre hospitalo-universitaire de Tizi-ouzou entre janvier 2013 et avril 2015. L’HTAr était définie par une pression artérielle (PA) de consultation ≥ 140/90 mmHg malgré une trithérapie incluant un bloqueur du système rénine-angiotensine-aldostérone, un anticalcique et un diurétique, à doses optimales pendant au moins 4 semaines. Résultats Sur les 2637 patients dépistés, d’âge moyen de 61,1 ± 11,2 ans, dont 64,2 % d’hommes, 843 (35,6 %) recevaient un traitement non optimal, 364 (15,4 %) étaient des mauvais observants du traitement et 202 (8,5 %) présentaient un effet blouse blanche. Deux cent quatre-vingt et un (11,9 %) patients avaient une consommation excessive de sel et 36 (1,5 %) consommaient des substances ou médicaments pouvant favoriser la résistance. Une cause secondaire d’HTA a été identifiée chez 468 (19,8 %) patients. Finalement, seuls 173 patients présentaient une HTAr vraie nécessitant une quadrithérapie ou plus, soit une prévalence de 7,3 % (IC 95 % : 6,3–8,3). Conclusion Moins d’un patient sur dix adressé dans notre centre pour HTA non contrôlée présente une HTAr vraie, et plus d’un patient sur deux présentent une pseudo-résistance. La majorité des patients avec une HTA en apparence résistante peuvent atteindre l’objectif tensionnel s’ils sont correctement explorés et traités. Objectives Estimate the prevalence of resistant hypertension (rHTN) in uncontrolled hypertensive treated patients referred to a tertiary care center specialized for hypertension management. Methods The study was prospective observational. Between January 2013 and April 2015, we recruited hypertensive treated patients, 18 years age or older, under antihypertensive drugs since at least 12 months, and referred to the hypertension unit of Tizi-ouzou university hospital for uncontrolled hypertension. rHTn was defined as an office blood pressure ≥ 140 mmHg despite a triple therapy including renin angiotensin system blockers, calcium antagonists and diuretics at optimal doses, since at least 4 weeks. Results We screened 2367 patients with a mean age of 61.1 ± 11.2 years and 64.2% of men. Eight hundred forty-three (35.6%) patients had suboptimal treatment, 364 (15.4%) a poor adherence to treatment and 202 (8.5%) a white-coat effect. An excessive salt intake and a drug-related hypertension were identified in 281 (11.9%) and 36 (1.5%) patients, respectively. A secondary cause of hypertension was diagnosed in 468 (19.8%) subjects. Finally, only 173 patients showed a true rHTN requiring four drugs or more and its prevalence was 7.3% (CI 95%: 6.3–8.3). Conclusion Less than one patient from ten referred in our center for uncontrolled hypertension had a true rHTN, and more than fifty percent of patients had pseudo-resistance. Most of patients with seemingly rHTN can reach blood pressure target provided they undergo thorough work up and care by a specialized team. [ABSTRACT FROM AUTHOR]

Refractory hypertension in a young person is an uncommon clinical problem, but one that may be referred to hypertension specialists. Factitious hypertension is fortunately quite rare but should be considered when evaluating patients who are refractory to numerous classes of antihypertensive therapies and have failed to achieve control despite input from multiple providers. A 19-year-old woman was referred to us after failing to achieve blood pressure control by a primary physician and two subspecialists in nephrology and hypertension; she also had numerous emergency department visits for symptomatic and severe hypertension. Exhaustive diagnostic testing for secondary causes and witnessed medication dosing in an outpatient setting was unrevealing. Subsequent inpatient admission demonstrated normalization of BPs with small doses of intravenous antihypertensive agents. During the hospitalization, she was observed “pocketing” her oral medications in the buccal folds and then discarding them in a trash container. Confrontation by psychiatrists and the hypertension specialists led to the admission that she had learned to start and stop beta-blockers and clonidine to induce severe, rebound hypertension. Factitious and induced hypertension is a rare cause of resistant or refractory hypertension. Nevertheless, hypertension specialists should suspect the diagnosis when there is a history of visits to multiple institutions and physicians, negative secondary workup, absence of overt target organ damage, history of psychiatric illness, and employment in the medical field. [ABSTRACT FROM AUTHOR]

The prevalence of pseudoresistant hypertension (HTN) due to inaccurate BP measurement remains unknown. Triage BP measurements and measurements obtained at the same clinic visit by trained physicians were compared in consecutive adult patients referred for uncontrolled resistant HTN (RHTN). Triage BP measurements were taken by the clinic staff during normal intake procedures. BP measurements were obtained by trained physicians using the BpTRU (VSM Med Tech Ltd. Coquitlam, Canada) device. The prevalence of uncontrolled RHTN and differences in BP measurements were compared. Of 130 patients with uncontrolled RHTN, 33.1% (n = 43) were falsely identified as having uncontrolled RHTN based on triage BP measurements. The median (inter-quartile range) of differences in systolic BP between pseudoresistant and true resistant groups were 23 (17–33) mm Hg and 13 (6–21) mm Hg, respectively ( P = .0001). The median (inter-quartile range) of differences in diastolic BP between the two groups were 12 (7–18) mm Hg and 8 (4–11) mm Hg, respectively ( P = .001). Triage BP technique overestimated the prevalence of uncontrolled RHTN in approximately 33% of the patients emphasizing the importance of obtaining accurate BP measurements. [ABSTRACT FROM AUTHOR]

Background Resistant hypertension (RH) is defined as uncontrolled blood pressure (BP) despite ≥ 3 antihypertensive agents. It is estimated to account for 12–28% of all hypertensive patients. Despite a higher risk of cardiovascular events, hypertension therapy in these patients is often insufficient. In a previous study we successfully tested an evidence-based, physician manager-centered hypertension management. Methods For this cluster randomized trial (CRT), a random sample of 102 German primary care practices will be randomized into two study arms (1:1). Physician managers and practice assistants of the intervention arm will participate in three-session medical education on hypertension management to implement 1) standardized diagnostic and therapeutic procedures for RH patients, 2) structured recall of patients with uncontrolled BP, and 3) teaching and supervision of RH patients on BP self-measurements. Practice tools are provided to facilitate implementation, e.g., how to distinguish true from pseudo RH and guideline-based medication selection. Physicians will specify guideline-algorithms for their practice to manage RH. A secured web-based peer-group exchange with hypertension specialists is offered to both professional groups. Physicians of both study arms will consecutively recruit patients with RH. BP will be measured by ambulatory BP monitoring at baseline and after 12 months. The primary endpoint is defined as treatment success with either normalized BP (24 h < 130/80 mm Hg) and/or a reduction by ≥ 20 mm Hg systolic and/or ≥ 10 mm Hg diastolic. Secondary analyses will focus on changes in physicians' knowledge and practice routines. Discussion This CRT will determine the effectiveness of a physician manager-centered intervention on treatment success in high-risk patients. [ABSTRACT FROM AUTHOR]

Background Renal denervation (RDN) has been shown to reduce blood pressure (BP), muscle sympathetic nerve activity (MSNA) and target organ damage in patients with resistant hypertension (RH) and bilateral single renal arteries. The safety and efficacy of RDN in patients with multiple renal arteries remains unclear. Methods We measured office and 24-hour BP at baseline, 3 and 6 months following RDN in 91 patients with RH, including 65 patients with single renal arteries bilaterally (group 1), 16 patients with dual renal arteries on either one or both sides (group 2) and 10 patients with other anatomical constellations or structural abnormalities (group 3). Thirty nine out of 91 patients completed MSNA at baseline and follow-up. Results RDN significantly reduced office and daytime SBP in group 1 at both 3 and 6 months follow-up (P < 0.001) but not in groups 2 and 3. Similarly, a significant reduction in resting baseline MSNA was only observed in group 1 (P < 0.05). There was no deterioration in kidney function in any group. Conclusion While RDN can be performed safely irrespective of the underlying renal anatomy, the presence of single renal arteries with or without structural abnormalities is associated with a more pronounced BP and MSNA lowering effect than the presence of dual renal arteries in patients with RH. However, when patients with dual renal arteries received renal nerve ablation in all arteries there was trend towards a greater BP reduction. Insufficient renal sympathetic nerve ablation may account for these differences. [ABSTRACT FROM AUTHOR]