Apparent Resistant Hypertension Research Articles

New Potential Treatments for Resistant Hypertension.

To provide an update and review approaches to the treatment of resistant hypertension (RH) with a focus on emerging potential therapies. Resistant hypertension is defined as a blood pressure that remains elevated above a patient's individualized target despite the concurrent use of 3 antihypertensive agents of different classes including a diuretic or use of 4 or more antihypertensive agents. Patients with RH have an increased risk of adverse cardiovascular and renal outcomes. Most RH is attributed to apparent RH and is not true RH. True RH is a diagnosis of exclusion after apparent RH has been excluded. Treatment of RH is challenging, and blood pressure goal is often difficult to achieve. Currently several new therapies have emerged with forthcoming data that provide promise for improved blood pressure control in those with resistant hypertension. Once RH has been diagnosed, patients should be on standardized therapy that includes agents from three different classes including a diuretic with addition in most cases of a mineralocorticoid as a fourth line agent. There are newer agents in development currently being studied in clinical trials including dual endothelin receptor antagonists and aldosterone synthase inhibitors that appear to be efficacious. Other approved medications including SGLT2 inhibitors and non-steroidal mineralocorticoids such as finerenone also need to be incorporated into treatment paradigms. Renal denervation with catheter based devices is another potential promising treatment option in this population.

Characterization of Individuals With Apparent Resistant Hypertension Using Contemporary Guidelines: Insights From CV-QUIC.

Apparent resistant hypertension (aRH) carries excess cardiovascular risk beyond nonresistant forms of hypertension; however, our understanding of this at-risk population, as defined by current US practice guidelines, is limited. Accordingly, we sought to evaluate the prevalence, clinical characteristics, and pharmacotherapeutic patterns of patients with aRH using contemporary blood pressure guidance. We classified patients at 3 large healthcare systems by hypertensive status using contemporary hypertension guidelines. We subsequently described the demographic and clinical characteristics of patients with aRH and compared these factors among hypertensive patients without aRH and between those with controlled and uncontrolled aRH. A total of 2 420 468 patients were analyzed, of whom 1 343 489 (55.6%) were hypertensive according to contemporary guidelines. Among hypertensive patients, 11 992 (8.5%) met criteria for aRH, with nearly all assessed comorbid conditions, particularly diabetes and heart failure, being more common in those with aRH. When compared with patients with uncontrolled aRH, those with controlled aRH were more frequently prescribed a beta-blocker, diuretic, and nitrate, with the largest standardized difference observed for a mineralocorticoid receptor antagonist (35.4% versus 10.4%, Cohen D 0.62). Consistent findings were noted in sensitivity analyses using the blood pressure threshold of 140/90 mm Hg. In an analysis of over 2.4 million individuals, a lower prevalence of aRH was observed than previously reported (12%-15%), but with a high burden of comorbidities. Identification of differences in pharmacotherapy between patients with controlled and uncontrolled aRH, particularly lower rates of mineralocorticoid receptor antagonist use, help define potential opportunities to improve care and lower cardiovascular risk.

Nonadherence Is Common in Patients With Apparent Resistant Hypertension: A Systematic Review and Meta-analysis.

The prevalence of medication nonadherence in the setting of resistant hypertension (RH) varies from 5% to 80% in the published literature. The aim of this systematic review was to establish the overall prevalence of nonadherence and evaluate the effect of the method of assessment on this estimate. MEDLINE, EMBASE, Cochrane, CINAHL, and Web of Science (database inception to November 2020) were searched for relevant articles. We included studies including adults with a diagnosis of RH, with some measure of adherence. Details about the method of adherence assessment were independently extracted by 2 reviewers. Pooled analysis was performed using the random effects model and heterogeneity was explored with metaregression and subgroup analyses. The main outcome measured was the pooled prevalence of nonadherence and the prevalence using direct and indirect methods of assessment. Forty-two studies comprising 71,353 patients were included. The pooled prevalence of nonadherence was 37% (95% confidence interval [CI] 27%-47%) and lower for indirect methods (20%, 95% CI 11%-35%), than for direct methods (46%, 95% CI 40%-52%). The study-level metaregression suggested younger age and recent publication year as potential factors contributing to the heterogeneity. Indirect methods (pill counts or questionnaires) are insufficient for diagnosis of nonadherence, and report less than half the rates as direct methods (direct observed therapy or urine assays). The overall prevalence of nonadherence in apparent treatment RH is extremely high and necessitates a thorough evaluation of nonadherence in this setting.

Characteristics, management, and blood pressure control in patients with apparent resistant hypertension in the US

BackgroundPer treatment guidelines, resistant hypertension is defined as uncontrolled blood pressure (BP) while taking 3 concomitant antihypertensives (AHTs) or controlled BP while taking ≥4 AHTs. Characteristics, AHT therapy use, and BP control were analyzed in US patients with hypertension who were prescribed ≥3 classes of AHT medications. MethodsThis retrospective analysis of the Optum® Electronic Health Record Database evaluated patients ≥18 years of age with a diagnosis of hypertension classified based on the number of prescribed AHT medication classes (3, 4, or ≥5). For the primary analysis, uncontrolled hypertension was defined as systolic BP (SBP) ≥140 mmHg or diastolic BP (DBP) ≥90 mmHg. For secondary analyses, uncontrolled hypertension was defined as SBP ≥130 mmHg or DBP ≥80 mmHg. Results207,705 patients with hypertension and concurrent use of ≥3 AHT medication classes were included. Diuretics, beta blockers, ACE inhibitors and/or ARBs, and CCBs were the most prescribed classes; thiazides and thiazide-like agents were the most prescribed diuretics. Among patients who were prescribed 3, 4, or ≥5 AHT medication classes, approximately 70% achieved a BP goal of <140/90 mmHg; approximately 40% achieved BP <130/80 mmHg. After ≥1 year of follow-up, the number of concurrent AHT medication classes was unchanged from baseline in the majority of patients and the prevalence of uncontrolled hypertension (≥140/90 mmHg) was similar. ConclusionsThis study illustrates suboptimal BP control in many patients with apparent resistant hypertension despite the use of multidrug regimens and suggests a need for new drug classes and regimens that effectively manage resistant hypertension.

PS-C17-9: RELEVANT BLOOD PRESSURE REDUCTION WITH ORAL SEMAGLUTIDE IN PATIENTS WITH TYPE 2 DIABETES AND OBESITY, INDEPENDENT OF PREVIOUS ANTIHYPERTENSIVE TREATMENT

Objective: The antihypertensive effect of oral semaglutide is apparently modest in published trials but it has not been explored in uncontrolled hypertensive patients. We sought to assess whether oral semaglutide may elicit a clinically relevant reduction of systolic blood pressure (SBP) in patients with type 2 diabetes (T2D), obesity and uncontrolled hypertension, and whether the attained SBP reduction is diluted by the previous antihypertensive treatment. Design and Methods: Retrospective analysis of the SBP and antihypertensive medication data were performed in consecutive patients with T2D and obesity who started therapy with oral semaglutide. Data were obtained from a baseline visit in which oral semaglutide was initiated, and a second visit after 3–4 months. Patients who initiated or changed antihypertensive medication simultaneously with oral semaglutide were excluded. Consent for anonymous analysis and reporting of data were obtained from all included subjects. Results: 50 patients with T2D (by usual clinical criteria) and obesity (BMI &lt; 30 kg/m2) were included; their age was 56 ± 11 years. 32 (64%) were female, and their diabetes duration was 6.9 ± 2.9 years. 41 (82%) of them were diagnosed with hypertension (sitting office SBP &gt; 140 and/or taking antihypertensive drugs). Globally there was a significant but modest reduction in SBP (149.8 ± 11.7 to 146.7 ± 12.4 mmHg, p = 0.041, paired t-test), but this reduction was strongly correlated with the baseline SBP (Pearson's r 0.39, p &lt; 0.001). In the Figure (A) the reductions in SBP for patients with controlled SBP (&lt; 140 mmHg), stage 1 (SBP 140–159 mmHg), stage 2 (160–179 mmHg) and stage 3 hypertension (&gt; 180 mmHg) are shown (p = 0.0056 for differences among SBP categories, one-way ANOVA). The Figure (B) also shows the reductions in SBP for patients taking 0, 1, 2 or &gt; 3 different antihypertensive drugs, but there are no significant differences (p = 0.2312, one-way ANOVA). In the second visit the number of patients with SBP &lt; 140 mmHg had increased from 19 (38%) to 25 (50%). Conclusions: Treatment with oral semaglutide in patients with T2D, obesity and uncontrolled hypertension elicits a clinically significant decrease in SBP, enough to bring about acceptable SBP control in a relevant fraction. As expected, the reduction in SBP was strongly dependent on the baseline SBP. Interestingly, this reduction does not seem to be diluted by the use of multiple antihypertensive drugs, suggesting that oral semaglutide could be considered as an add-on in patients with apparent resistant hypertension.

Effectiveness of a remote care program in the management of patients with resistant hypertension or multiple medication intolerances

Abstract Background A remote hypertension (HTN) program, designed and implemented at Mass General Brigham (MGB), has demonstrated improved HTN control, reduced need for in-person visits, and increased access to care. The program excluded patients with resistant HTN or multiple intolerances/allergies to guideline-directed therapies, whose blood pressure (BP) is difficult to manage. Purpose To develop a more intensive but still remote program (“HTN-Plus”) for patients with resistant HTN or intolerances/allergies to multiple medications, and to assess its effectiveness for BP control. Methods From 10/2020 through 11/2021, we identified a subset of hypertensive patients from the total pool of those enrolled in our remote HTN management program, who required more personalized and intensive therapy than the overall remote management program provided. We developed ancillary management for these patients, who included: 1) patients with apparent resistant HTN (ARH), ie with uncontrolled BP despite maximum tolerated doses of at least three anti-HTN medications including a diuretic, and 2) patients with multiple medication intolerances or allergies that precluded appropriate triple therapy or limited dose-optimization. A nurse practitioner provided education and advice on BP measurement technique, lifestyle modifications, and adherence. Evaluation for primary aldosteronism (PA) was undertaken in those with ARH. Results We enrolled 3658 patients with uncontrolled HTN, of whom 117 qualified for the HTN-Plus program. The average BP on entry was 143/80 mmHg. 68% had apparent resistant HTN and 32% had multiple medication intolerances/allergies. Among all patients, 30% had incorrect BP-measurement technique upon interview, 10% who were tested for PA had a positive screening test, 56% had a history suggestive of an unmanaged secondary cause, and only 6% admitted imperfect adherence, but urine testing was not done. 74% of patients completed the program meaning they were reachable through the end and did not drop out. Across the program, 72 new medications were started, and 84 medication titrations were made. 50% of patients who enrolled in HTN-plus achieved BP &amp;lt;130/80 mmHg. 22% achieved BP control with education and coaching alone. For patients who completed the program, the average entry and final BPs were 139/78 mmHg and 126/70 mmHg respectively, with an average BP decrease of 13/8 mmHg. Conclusions In patients who remain hypertensive despite maximally tolerated guideline-directed medication utilization, our intensified but still entirely remote HTN management program helped patients reach their BP goal through education, coaching, and medication management. Nearly a quarter were able to achieve BP control with education and coaching alone. These results suggest that a significant value of remote care in patients with resistant HTN or medication intolerances/allergies lies in ongoing education and coaching, for which more cost-effective solutions may be considered. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Mass General Brigham as part of quality improvement initiative

Comparative Safety and Effectiveness of Aldosterone Antagonists Versus Beta-Blockers as Fourth Agents in Patients With Apparent Resistant Hypertension.

Limited evidence exists regarding long-term effectiveness and safety of aldosterone antagonists (AAs) versus beta blockers (BBs) as fourth-line antihypertensive agents in patients with resistant hypertension (RH). We evaluated the comparative effectiveness and safety of aldosterone AA versus BB. We conducted a real-world retrospective cohort study using IBM MarketScan commercial claims and Medicare Supplemental claims (2007-2019). Patients with RH entered the cohort (ie, index date) when they newly initiated either AA or BB. The effectiveness outcome was major adverse cardiovascular events. Safety outcomes were hyperkalemia, gynecomastia, and kidney function deterioration. Potential confounding was addressed by adjustment for baseline characteristics via stabilized inverse probability of treatment weighting (SIPTW) based on propensity scores. Cox proportional hazards regression with SIPTWs were used to estimate adjusted hazard ratio (aHR) and 95% CI comparing risk for outcomes between AA and BB groups. We identified 80 598 patients with RH (mean age: 61 years, 51% males), of which 6626 initiated AA and 73 972 initiated BB as the fourth antihypertensive agent. Among patients with RH, initiation of AA as a fourth-line antihypertensive agent did not significantly reduce major adverse cardiovascular event risk relative to BB initiation (aHR, 0.77 [95% CI, 0.50-1.19]) but did substantially increase the risk of hyperkalemia (aHR, 3.86 [95% CI, 2.78-5.34]), gynecomastia (aHR, 9.51 [95% CI, 5.69-15.89]), and kidney function deterioration (aHR, 1.63 [95% CI, 1.34-1.99]). Long-term clinical trials powered to assess major adverse cardiovascular events are necessary to understand the risk-benefit trade-off of AA as fourth-line therapy for RH.

Investigating the endothelin receptor antagonist aprocitentan in resistant hypertension: design and baseline characteristics of the PRECISION study

Abstract The endothelin (ET) system plays an important role in hypertension, especially in volume and salt-dependent forms, which are common in patients with resistant hypertension (RHT). Therapies targeting the ET system may provide a new treatment option. A Phase 2 dose-finding study demonstrated an effect of the dual ET receptor antagonist aprocitentan monotherapy on blood pressure (BP) [1]. PRECISION is a randomized, parallel-group, Phase 3 study assessing the short-term effect of 2 doses of aprocitentan (12.5 mg and 25 mg) and its long-term sustained effect on BP. Following randomization, patients entered a 4-week, double-blind (DB), placebo-controlled part, followed by aprocitentan 25 mg for 32 weeks, and a 12-week, placebo-controlled, randomized withdrawal part (Figure 1). The primary endpoint is the change in systolic BP (SBP) from randomization to week 4 and the key secondary endpoint is the change in SBP from re-randomization to week 40. The study enrolled 1971 patients with RHT diagnosed according to the site's medical practice, from 193 centres worldwide. Entry criteria included sitting SBP [SiSBP] ≥140 mmHg, measured by unattended automated office BP (uAOBP, reducing the white coat effect), despite the use of ≥3 antihypertensive medications. During the screening period of 4 to 12 weeks, secondary causes of hypertension were excluded by the investigator and patients still having SiSBP ≥140 mmHg were switched from their individual antihypertensive drugs to a single-tablet, triple combination of valsartan 160 mg /amlodipine 5 or 10 mg /hydrochlorothiazide 25 mg o.d. (minimizing medical inertia and improving drug adherence) for at least 4 weeks before entering the placebo run-in (RI) period. The screening failure rate of 53% is indicative of the high incidence of apparent RHT within the hypertensive population. Patients continuing having SiSBP ≥140 mmHg on triple therapy (true RHT) then entered the 4-week, single-blind placebo RI period. Of these patients, 20% failed to be randomized, most frequently because of SiSBP &amp;lt;140 mmHg, possibly due to a placebo effect. As of 12 March 2021, 860 patients were in the placebo RI period and 664 patients were randomized, 30% from North America, 62% from Europe, and 8% from Asia/Australia. Mean age was 61.8 years (standard deviation [SD]=10.8). 40% of patients were women, 11% were Black, 5% Asian, and 83% White. Mean body mass index (BMI) was 33.6 kg/m2 (SD=6.4) and mean estimated glomerular filtration rate (eGFR) was 76.8 mL/min/1.73 m2 (including 21% chronic kidney disease [CKD] stage 3–4 patients). Medical history included diabetes (54%), myocardial infarction (30%), stroke (23%), congestive heart failure (19%), and sleep apnoea (15%). In addition to the standardized antihypertensive medication, 59% of patients used beta-blockers. Mean baseline SiSBP/SiDBP was 153/88 mmHg. Results of the trial will be available in 2022. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The PRECISION study is sponsored by Idorsia Pharmaceuticals Ltd.

Resistance to antihypertensive treatment and long-term risk: The Atherosclerosis Risk in Communities study.

More stringent blood pressure (BP) goals have led to greater prevalence of apparent resistant hypertension (ARH), yet the long‐term prognostic impact of ARH diagnosed according to these goals in the general population remains unknown. We assessed the prognostic impact of ARH according to contemporary BP goals in 9612 participants of the Atherosclerosis Risk in Communities (ARIC) study without previous cardiovascular disease. ARH, defined as BP above goal (traditional goal <140/90 mmHg, more stringent goal <130/80 mmHg) despite the use of ≥3 antihypertensive drug classes or any BP with ≥4 antihypertensive drug classes (one of which was required to be a diuretic) was compared with controlled hypertension (BP at goal with 1‐3 antihypertensive drug classes). Cox regression models were adjusted for age, sex, race, study center, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, and diabetes. Using the traditional BP goal, 133 participants (3.8% of the treated) had ARH. If the more stringent BP goal was instead applied, 785 participants (22.6% of the treated) were reclassified from controlled hypertension to uncontrolled hypertension (n = 725) or to ARH (n = 60). Over a median follow‐up time of 19 years, ARH was associated with increased risk for a composite end point (all‐cause mortality, hospitalization for myocardial infarction, stroke, or heart failure) regardless of whether traditional (adjusted HR 1.50, 95% CI: 1.23‐1.82) or more stringent (adjusted HR 1.43, 95% CI: 1.20‐1.70) blood pressure goals were applied. We conclude that in patients free from cardiovascular disease, ARH predicted long‐term risk regardless of whether traditional or more stringent BP criteria were applied.

Sacubitril-valsartan as a treatment for apparent resistant hypertension in patients with heart failure and preserved ejection fraction.

AimsPatients with heart failure and preserved ejection fraction (HFpEF) frequently have difficult-to-control hypertension. We examined the effect of neprilysin inhibition on ‘apparent resistant hypertension’ in patients with HFpEF in the PARAGON-HF trial, which compared the effect of sacubitril–valsartan with valsartan.Methods and resultsIn this post hoc analysis, patients were categorized according to systolic blood pressure at the end of the valsartan run-in (n = 4795). ‘Apparent resistant hypertension’ was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite treatment with valsartan, a calcium channel blocker, and a diuretic. ‘Apparent mineralocorticoid receptor antagonist (MRA)-resistant’ hypertension was defined as systolic blood pressure ≥140 mmHg (≥135 mmHg if diabetes) despite the above treatments and an MRA. The primary outcome in the PARAGON-HF trial was a composite of total hospitalizations for heart failure and death from cardiovascular causes. We examined clinical endpoints and the safety of sacubitril–valsartan according to the hypertension category. We also examined reductions in blood pressure from the end of valsartan run-in to Weeks 4 and 16 after randomization. Overall, 731 patients (15.2%) had apparent resistant hypertension and 135 (2.8%) had apparent MRA-resistant hypertension. The rate of the primary outcome was higher in patients with apparent resistant hypertension [17.3; 95% confidence interval (CI) 15.6–19.1 per 100 person-years] compared to those with a controlled systolic blood pressure (13.4; 12.7–14.3 per 100 person-years), with an adjusted rate ratio of 1.28 (95% CI 1.05–1.57). The reduction in systolic blood pressure at Weeks 4 and 16, respectively, was greater with sacubitril–valsartan vs. valsartan in patients with apparent resistant hypertension [−4.8 (−7.0 to −2.5) and 3.9 (−6.6 to −1.3) mmHg] and apparent MRA-resistant hypertension [−8.8 (−14.0 to −3.5) and −6.3 (−12.5 to −0.1) mmHg]. The proportion of patients with apparent resistant hypertension achieving a controlled systolic blood pressure by Week 16 was 47.9% in the sacubitril–valsartan group and 34.3% in the valsartan group [adjusted odds ratio (OR) 1.78, 95% CI 1.30–2.43]. In patients with apparent MRA-resistant hypertension, the respective proportions were 43.6% vs. 28.4% (adjusted OR 2.63, 95% CI 1.18–5.89).ConclusionSacubitril–valsartan may be useful in treating apparent resistant hypertension in patients with HFpEF, even in those who continue to have an elevated blood pressure despite treatment with at least four antihypertensive drug classes, including an MRA.Clinical trial registrationPARAGON-HF: ClinicalTrials.gov Identifier NCT01920711.

Adherence to antihypertensive medications among adult hypertensive patients attending chronic follow-up units of Dessie Referral Hospital, Northeastern Ethiopia: A cross-sectional study.

Hypertension is the leading cause of increased morbidity and mortality rates worldwide. Despite adherence to therapies is the important determinant of treatment success to reduce apparent resistant hypertension, maintaining good adherence to antihypertensive medications remained the most serious challenge. Thus, this study aimed to assess adherence to antihypertensive medications among adult hypertensive patients in Dessie Referral Hospital.A cross-sectional study design was conducted among hypertensive patients during May and June 2020. The study participants were selected using a systematic random sampling technique. The collected data were entered into EpiData version 4.4 and exported to SPSS version 25.0 software for data cleaning and analysis. Data were analyzed using bivariable and multivariable logistic regression at a 95% confidence interval (CI). A variable that has a P-value < .05 was declared as statistically significant. Hosmer–Lemeshow test was used to test goodness-of-fit and multicollinearity was tested.The overall good adherence to antihypertensive medications was 51.9%; 95% CI: (46.8–58.3%) and poor adherence was 48.1%. Factors associated with good adherence were: sex—female adjusted odd ratio (AOR) = 1.31; 95% CI (1.06–2.52), occupational status-employed AOR = 2.24; 95% CI (1.33–3.72), good knowledge of the disease AOR = 2.20; 95% CI (1.34–3.72) and good self-efficacy AOR = 1.38; 95% CI (1.20–2.13).This study revealed that almost half of the hypertensive patients in Dessie Referral Hospital had good antihypertensive medication adherence. Sex, occupational status, knowledge, and self-efficacy were factors associated with good adherence. Therefore, health education should be given to patients on the importance of complying with medication and patients should be monitored by health extension workers.

Assessment of a strategy combining ambulatory blood pressure, adherence monitoring and a standardised triple therapy in resistant hypertension

Purpose Poor adherence to drug therapy and inadequate drug regimens are two frequent factors responsible for the poor blood pressure (BP) control observed in patients with apparent resistant hypertension. We evaluated the efficacy of an antihypertensive management strategy combining a standardised therapy with three long acting drugs and electronic monitoring of drug adherence in patients with apparent resistant hypertension. Materials and Methods In this multicentric observational study, adult patients with residual hypertension on 24 h ambulatory BP monitoring (ABMP) despite the use of three or more antihypertensive drugs could be included. Olmesartan/amlodipine (40/10 mg, single pill fixed-dose combination) and chlorthalidone (25 mg) were prescribed for 3 months in two separated electronic pills boxes (EPB). The primary outcome was 24 h ambulatory systolic BP (SBP) control at 3 months, defined as mean SBP <130 mmHg. Results We enrolled 48 patients (36.0% women) of whom 35 had complete EPB data. After 3 months, 52.1% of patients had 24 h SBP <130 mmHg. 24 h SBP decreased by respectively −9.1 ± 15.5 mmHg, −22.8 ± 30.6 mmHg and −27.7 ± 16.6 mmHg from the tertile with the lowest adherence to the tertile with the highest adherence to the single pill combination (p = 0.024). A similar trend was observed with tertiles of adherence to chlorthalidone. Adherence superior to 90% was associated with 24 h systolic and diastolic blood pressure control in multiple logistic regression analysis (odds ratio = 14.1 (95% confidence interval 1.1–173.3, p = 0.039). Conclusions A simplified standardised antihypertensive therapy combined with electronic monitoring of adherence normalises SBP in about half of patients with apparent resistant hypertension. Such combined management strategy enables identifying patients who need complementary investigations and those who rather need a long-term support of their adherence.

Prognostic value of masked uncontrolled apparent resistant hypertension detected through home blood pressure monitoring.

Resistant hypertension carries a poor prognosis and current guidelines recommend the exclusion of the white-coat phenomenon for proper diagnosis. However, guidelines do not focus on patients treated with at least three drugs whose blood pressure (BP) is controlled at the office but elevated out of it. We aimed at determining whether this masked uncontrolled apparent resistant hypertension (MUCRH) detected through home blood pressure monitoring (HBPM) has prognostic value for fatal and nonfatal events in these hypertensive patients. Hypertensive patients treated with at least three drugs who performed a baseline HBPM between 2008 and 2015 were followed to register the occurrence of total mortality, cardiovascular mortality, and fatal and nonfatal cardiac and cerebrovascular events. MUCRH was defined as office blood pressure less than 140/90 mmHg and home BP at least 135 and/or 85 mmHg. Multivariable Cox proportional hazard models were adjusted to determine the independent prognostic value of MUCRH for the events of interest. We included 470 patients, 35.5% male, mean age 71.9 years, and treated with 3.3 antihypertensive drugs on average. Among study population, 15.5% had MUCRH (33.3% when considering only patients with adequate BP control at the office). Median follow-up was 6.7 years. In multivariable models, MUCRH was an independent predictor for cardiovascular mortality and cerebrovascular events: hazard ratio 4.9 (95% CI 1.2-19.9, P = 0.03) and 5.1 (95% CI 1.5-16.9, P = 0.01), respectively. MUCRH is not rare and is independently associated with cardiovascular morbidity and mortality. The systematic monitoring of intensively treated individuals through HBPM would be useful for the detection of patients at increased risk of events.

Apparent treatment-resistant hypertension among ambulatory hypertensive patients: a cross-sectional study from 13 general hospitals.

Background/AimsTo examine the prevalence and clinical characteristics of apparent treatment-resistant hypertension among ambulatory hypertensive patients.MethodsWe enrolled adult ambulatory hypertensive patients at 13 well-qualified general hospitals in Korea from January to June 2012. Apparent resistant hypertension was defined as an elevated blood pressure > 140/90 mmHg with the use of three antihypertensive agents, including diuretics, or ≥ 4 antihypertensives, regardless of the blood pressure. Controlled hypertension was defined as a blood pressure within the target using three antihypertensives, including diuretics.ResultsAmong 16,915 hypertensive patients, 1,172 (6.9%) had controlled hypertension, and 1,514 (8.9%) had apparent treatment-resistant hypertension. Patients with apparent treatment-resistant hypertension had an earlier onset of hypertension (56.8 years vs. 58.8 years, p = 0.007) and higher body mass index (26.3 kg/m2 vs. 24.9 kg/m2, p < 0.001) than those with controlled hypertension. Drug compliance did not differ between groups. In the multivariable analysis, earlier onset of hypertension (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97 to 0.99; p < 0.001) and the presence of comorbidities (OR, 2.06; 95% CI, 1.27 to 3.35; p < 0.001), such as diabetes mellitus, ischemic heart disease, heart failure, and chronic kidney disease, were independent predictors. Among the patients with apparent treatment-resistant hypertension, only 5.2% were receiving ≥ 2 antihypertensives at maximally tolerated doses.ConclusionsApparent treatment-resistant hypertension prevalence is 8.9% among ambulatory hypertensive patients in Korea. An earlier onset of hypertension and the presence of comorbidities are independent predictors. Optimization of medical treatment may reduce the rate of apparent treatment-resistant hypertension.

Drug Profile and Therapeutic Adherence of African-Brazilians with Apparent Resistant Hypertension

Background Resistant hypertension (RH) is manifested by the presence of blood pressure values resistant to antihypertensive therapy. RH is highly prevalent among black individuals, increasing cardiovascular risk in this population and requiring effective control of this comorbidity. Objectives To investigate the medication profile and therapeutic adherence in black people with apparent RH. Methods This is a cross-sectional study, with a convenience sample of individuals with apparent RH. Data were obtained from medical records. Therapeutic adherence was assessed using the [...]

Cardiovascular Benefits of Angiotensin-Converting Enzyme Inhibition Plus Calcium Channel Blockade in Patients Achieving Tight Blood Pressure Control and With Resistant Hypertension.

The 2017 hypertension guidelines lowered systolic blood pressure (BP) goals to <130 mm Hg and redefined resistant hypertension. We investigated if these changes alter the cardiovascular benefits demonstrated by combining a calcium channel blocker (CCB), rather than hydrochlorothiazide (HCTZ), with an angiotensin-converting enzyme inhibitor (ACEI). In this post hoc analysis of the Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension trial (n = 11,506), we compared the primary composite outcome (cardiovascular death, myocardial infarction, stroke, hospitalization for angina, resuscitation after sudden cardiac death, and coronary revascularization) between the 2 combination-treatment limbs in patients achieving a systolic BP ≤130 mm Hg and those with "apparent resistant hypertension" (prescribed ≥4 antihypertensive medications). Among study patients, 5,221 (45.4%) achieved a systolic BP ≤130 mm Hg. There were fewer primary endpoints in the amlodipine/benazepril (9.2%) vs. the HCTZ/benazepril (10.9%) limb (adjusted hazard ratio [HR] 0.83, 95% confidence interval [CI], 0.70-0.99). There were also fewer primary endpoints in the amlodipine/benazepril (12.8%) vs. the HCTZ/benazepril (15.2%) limb (n = 4,451, 38.7%) among patients with apparent resistant hypertension (HR 0.81, 95% CI, 0.70-0.95). Combination therapy adding a CCB, rather than HCTZ, to an ACEI was more effective in preventing composite cardiovascular events even in hypertensive patients achieving aggressive systolic BP targets as well as in those with apparent resistant hypertension. Our findings add support that most patients, including those following contemporary clinical guidelines, will benefit from this combination. Trial Number NCT00170950.

Abstract 14482: Apparent Resistant Hypertension is a Marker of Risk: The Atherosclerosis Risk in Communities (ARIC) Study

Introduction: Apparent resistant hypertension (ARH) is a common marker of risk in patients with established cardiovascular disease. We ascertained the prevalence and prognostic significance of ARH in patients without prior cardiovascular disease. Methods: This prospective observational cohort study included 9669 community-based participants without a history of heart failure, myocardial infarction, or stroke, who completed the Atherosclerosis Risk in Communities (ARIC) study visit 4 between 1996-1998. The definition of ARH was blood pressure (BP) above goal (traditional goal &lt;140/90mmHg, more stringent goal &lt;130/80mmHg) despite use of ≥3 antihypertensive drug classes, or any BP with ≥4 antihypertensive drug classes. Participants with controlled hypertension (CH), defined as BP at goal with use of 1-3 antihypertensive drug classes, constituted the reference group. The outcome was a composite endpoint of heart failure, myocardial infarction, stroke, or death. Cox regression models were adjusted for age, sex, race, BMI, heart rate, smoking, eGFR, LDL, HDL, triglycerides, glucose, and diabetes. Results: Applying the traditional BP goal, 154/9669 participants (1.6%) had ARH, and there were 2311 participants with CH (23.9%). Using the more stringent BP goal, 218/9669 participants (2.3%) had ARH, and 1523 participants (15.8 %) had CH. The median follow-up time was 19 years. Apparent resistant hypertension was associated with an increased risk for the composite endpoint (adjusted hazard ratio 1.58 [95% CI 1.32-1.90] with the traditional BP goal, and adjusted hazard ratio 1.51 [95% CI 1.28-1.79] with the more stringent BP goal). Conclusions: Apparent resistant hypertension had a low prevalence but was independently associated with adverse outcome during long term follow-up, compared to controlled hypertension and even compared to uncontrolled hypertension. This was observed for both traditional and more stringent BP goals.

Anatomically optimized distal renal denervation — sustained blood pressure lowering efficacy during 3 years after the intervention

Aim. To test the hypothesis that anatomical optimisation of radiofrequency renal denervation (RDN) by redistribution of treatment to segmental branches of the renal artery causes a durable increase in the efficacy of the intervention.Methods. A double-blind randomised control study in parallel groups with a 3-year follow-up was performed in patients with apparent resistant hypertension (office systolic BP ≥160 or diastolic BP ≥100 mmHg despite stable treatment with ≥3 drugs, including a diuretic). Exclusion criteria were secondary hypertension, mean 24-h systolic BP &lt;135 mmHg, eGFR &lt;30 mL/min/m2 and severe comorbidity increasing procedural risks (investigator’s assessment). Eligible patients were randomised 1:1 into distal RDN or RDN in the main trunk of the renal artery. Treatment assignment was done in the operation room immediately before the procedure. For the duration of the study, the assigned treatment was unknown to patients, physicians and other outcome assessors. Long-term efficacy of the procedure was measured by changes in BP (office and ambulatory), whereas safety was assessed by changes in the 24-h protein excretion, serum creatinine and eGFR 3 years post-procedure.Results. Of the 55 randomised patients, 39 (71%) completed a 3-year assessment (21 after distal RDN and 18 after RDN in the main trunk of the renal artery). Compared to baseline, the mean 24-h BP remained significantly lowered in the distal RDN group by −16.9 (95% CI −27.3;−6.5)/−8.5 (95% CI −14.2;−2.9) mmHg, p = 0.002/0.004 (systolic/diastolic, respectively). The lowering of the mean 24-h BP was almost twofold less and non-significant in the group of RDN in the main trunk of the renal artery: −8.7 (95% CI −19.6;2.2)/−5.8 (95% CI −11.8;0.1).Conclusion. Anatomical optimisation of endovascular renal denervation produces a powerful and sustained increase in the efficacy of the intervention. Received 19 May 2020. Revised 10 July 2020. Accepted 7 September 2020. Funding: The study did not have sponsorship. Conflict of interest: Authors declare no conflict of interest. Clin.Trials.gov Identifier: NCT02667912. Author contributionsConception and design: S.E. PekarskiyData collection and analysis: S.E. Pekarskiy, A.E. Baev, A.Yu. Falkovskaya, E.S. Sitkova, I.V. Zyubanova, V.A. Lichikaki, V.F. MordovinStatistical analysis: S.E. PekarskiyDrafting the article: S.E. Pekarskiy, A.E. BaevCritical revision of the article: S.V. PopovFinal approval of the version to be published: S.E. Pekarskiy, A.E. Baev, A.Yu. Falkovskaya, E.S. Sitkova, I.V. Zyubanova, V.A. Lichikaki, V.F. Mordovin, S.V. Popov

Apparent resistant hypertension and the risk of recurrent cardiovascular events and mortality after a first manifestation of vascular disease

Abstract Background Previous studies have shown that patients with resistant hypertension carry a higher risk of developing cardiovascular disease than patients with non-resistant hypertension. However, little is known about the prognosis of apparent resistant hypertension in patients with symptomatic vascular disease. Purpose The aim of this study was to examine the relation between different stages of hypertension and the risk of recurrent cardiovascular events and mortality in a cohort of hypertensive patients with symptomatic vascular disease. Methods Hypertensive patients (n=7280) with symptomatic vascular disease (cerebrovascular disease, coronary heart disease, peripheral artery disease or abdominal aortic aneurysm) were included from the ongoing SMART cohort between 1996 and 2018. Patients were classified into three groups according to baseline office blood pressure (BP): controlled (BP &amp;lt;140/90 mmHg and a hypertension diagnosis or on 1 to 3 antihypertensive drugs), uncontrolled (BP ≥140/90 mmHg on ≤2 drugs) and apparent resistant (BP ≥140/90 mmHg despite treatment with three or more antihypertensive drugs including a diuretic or treatment with four or more antihypertensive medications irrespective of BP status). Cox proportional hazard models were used to quantify the relation between the different stages of hypertension and the risk of recurrent major adverse cardiovascular events (MACE including stroke, myocardial infarction and vascular death) and death from any cause. Models were adjusted for age, sex, current smoking, body mass index, renal function and diabetes. In addition, survival according to the different stages of hypertension was plotted, taking competing risk of non-vascular mortality into account by using the Fine and Gray method. Results In total 3123 patients (43%) had controlled hypertension, 3354 patients (46%) had uncontrolled hypertension and 803 (11%) had apparent resistant hypertension. A total of 1498 MACE and 1762 deaths occurred in 64,469 person-years (median follow-up of 8.6 years, IQR 4.6–12.7 years). Compared to patients with controlled hypertension patients with apparent resistant hypertension were at increased risk of recurrent MACE (HR 1.32; 95% CI 1.11–1.58) and death from any cause (HR 1.46; 95% CI 1.25–1.72). At the age of 60 years, patients with apparent resistant hypertension after a first cardiovascular event on average had a recurrent cardiovascular event 10 years earlier than patients with controlled or uncontrolled hypertension (Figure 1). Conclusions Irrespective of age at first cardiovascular event, apparent resistant hypertension is related to a higher risk of recurrent vascular events and death from any cause. These findings support the need for greater efforts toward improving blood pressure control and treatment of other cardiovascular risk factors among patients with apparent resistant hypertension. Figure 1 Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): UMC Utrecht

Frequency & factors associated with apparent resistant hypertension among Ghanaians in a multicenter study.

Apparent resistant hypertension (ARH) is rife among people living with hypertension and is associated with significant morbidity and mortality. There is however paucity of data from sub-Saharan Africa on the burden of ARH. We sought to report on the frequency and factors associated with ARH among a cohort of Ghanaians with hypertension. A cross-sectional study involving 2912 participants with hypertension enrolled at five health facilities in Ghana. ARH was defined as either office BP≥140/90 mm Hg on 3 or more antihypertensive medications or on 4 or more antihypertensive medications regardless of BP. Factors associated with ARH were evaluated in a multivariate logistic regression model. We found 550 out of 2,912 (18.9%) of study participants had ARH. Out of these 550 subjects, 511 (92.9%) were on 3 or more antihypertensive medications with BP≥140/90mm Hg and 39 (7.1%) were on 4 or more antihypertensive medications with BP≥140/90mm Hg. The prevalence of ARH was 15.5% among elderly aged 75+years (n=341), 20.7% among 65-74years (n=588), and 18.9% among those≤64years (n=1983). The adjusted odds ratio (95% CI) of factors independently associated with ARH was duration of hypertension, 1.05 (1.03-1.06) for each year rise; eGFR<60mL/min, 1.73 (1.33-2.25); and diabetes mellitus, 0.59 (0.46-0.76). Attaining secondary level education and residence in a peri-urban setting were significantly associated with ARH though not in a dose-dependent manner. ARH is rife among Ghanaians and may negatively impact on cardiovascular outcomes in the long term.