Refractory Hypertension Patients Research Articles

Effect of RDN on long-term blood pressure in refractory hypertensive patients with different cardiovascular risk stratification

Objective: To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality. Methods: This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone. Results: A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa),P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg,P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg,P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions: RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Efficacy and safety of 3D reconstruction and basket multi-electrode renal denervation (RDN) for refractory hypertensive patients with chronic kidney disease.

Renal Artery Sympathetic Denervation (RDN) can lower blood pressure. Different ablation catheters (single electrode, multi-electrode) have different scopes of ablation (renal artery main stem and branches). Few studies have compared the advantages and disadvantages of different ablation catheters and different procedures in terms of antihypertensive efficacy. To compare the efficacy and safety of 3D reconstruction radiofrequency ablation (3DRA) and basket multi-electrode radiofrequency ablation (BMRA) in Renal Artery Sympathetic Denervation. Fifty-three patients with Refractory hypertension (RHT) were divided into BMRA, (n=28) and 3DRA(n=25). BMRA group used a stereobasket multi-electrode ablation catheter with a controlled ablation temperature of 60°C and an ablation time of 120s per site. 3DRA group used a NavStar pressure-monitored perfusion monopolar ablation catheter with a controlled ablation temperature of 40°C, an ablation time of 40s per site, and an ablation energy of 12W. Baseline and RDN parameters and complications were compared in both groups. Home and 24h ambulatory blood pressure, type of anti-hypertensive medication taken, and serum creatinine were followed up at 1, 3, 6, 12, and 24 months after the RDN. There were no differences in baseline characteristics between the two groups. (23.14±2.00)months of follow-up in the BMRA group resulted in a total of (25.86±8.61) loci ablation. (19.28±7.40)months of follow-up in the 3DRA group resulted in a total of (21.04±6.47)loci ablation. Home SBP was significantly lower in both groups at 1 month after RDN treatment compared to baseline(H-SBP/mmHg: BMRA 149.9±10.59vs. baseline 168.36±12.76; 3DRA 152.6±14.91vs. 164.89±12.96, both p<.05). The proportion of people with 24h ambulatory SBP attainment was significantly higher in both groups and was maintained for 24 months. At each follow-up time point, there were no differences in home and 24-h flow SBP, DBP, or Scr between the two groups. There were two cases of severe renal artery complications from implanted vascular stents and one case of femoral artery pseudoaneurysm in the 3DRA group. At follow-up, 1 (1.9%) patient in the 3DRA group died of unexplained death and 1 (1.9%) patient developed heart failure, and 1 (1.9%) patient in the BMRA group died of unexplained death. Basket multi-electrode radiofrequency ablation and 3D reconstruction radiofrequency ablation of the renal artery applied to RDN have comparable efficacy in reducing systolic blood pressure.

0438 Obstructive sleep apnoea in patients with stroke verses those with refractory hypertension search for common pathogenic mechanism

Abstract Introduction Obstructive sleep apnea [OSA] is a risk factor for stroke and refractory hypertension [RH]. OSA causes disrupted sleep, intermittent hypoxia, and hypoxia-induced systemic inflammation and sympathetic activation are potential pathogenic mechanisms for the first ever stroke and refractory hypertension. The aim of the present study was to evaluate sleep quality among OSA among patients with first ever stroke, as compared to RH and to assess markers of sympathetic activation and systemic inflammation in patients with either stroke or RH. Methods All patients with stroke and RH were recruited from the Departments of Neurology and Cardiology, respectively at the All India Institute of Medical Sciences, New Delhi. All patients were interviewed for demographic details, clinical history and were scheduled for polysomnography. Fasting blood samples were collected during morning hours, to estimate biochemical markers [Norepinephrine, CRP, TNF-∞, VGEF and IL6] . CRP, TNF-alpha, and IL-6], measured by the chemiluminescence method. Nor-adrenaline and VEGF were measured using ELISA techniques. Results A total of 114 stroke patients and 56 refractory hypertension patients were included. The prevalence of OSA among stroke and RH patients was found to be 86.85 and 81% respectively. The mean number of wake after sleep onset periods (WASOs) [45±19.22 vs 29.8±11.14, p&amp;lt; 0.01]was significantly higher in patients with stroke. REM AHI [240.04±24.65 vs 33.20±22.35, p&amp;lt; 0.01] was significantly higher in patients with RH.CRP and VEGF values were higher than normal, in both groups. The median value of early morning serum nor-adrenaline was higher in the RH group[407 (66.6-1000) vs 515 (240-1250), p = 0.05]. Conclusion OSA is highly prevalent among the patients in both groups. Systemic inflammation is a common pathogenic mechanism linking OSA with RH and stroke, whereas early morning sympathetic activation appears significantly important in the pathogenesis of refractory hypertension. Support (if any) This study was funded by Indian council of Medical Research, New Delhi, India.

Abstract Number ‐ 146: Re‐stenting Following Recurrence after Venous Sinus Stenosis Stenting for Idiopathic Intracranial Hypertension

Introduction Venous sinus stenosis (VSS) stenting in medically refractory Idiopathic Intracranial Hypertension (IIH) patients has emerged as an effective treatment with low rates of failure and recurrence. However, the best treatment strategy following recurrence of symptoms in previously stented patients with initial response is unclear and frequently leads to shunt placement. We investigated the role of re‐stenting in patients with recurrence after prior successful stenting. Methods This is a retrospective review of a prospectively maintained IIH registry. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012–2022. Patients were divided into those who underwent a single stenting procedure (Group S) and those who underwent placement of an additional stent due to recurrence of clinical symptoms and angiographic stenosis (Group R). All re‐stenting was performed in adjacent or remote regions of stenosis. Bivariate analyses were utilized to compare clinical outcomes. Results 86 patients were included with a median age of 33 [IQR 26‐39] and 94% were females. Group S (79/86) and Group R (7/86) had similar baseline characteristics. There was similar improvement in post‐stenting opening pressure (22.4±6.7 vs. 25.2±4.6 cm H2O, p = 0.35, Group S vs. Group R), change in opening pressure (11.6±10.4 vs. 5.3±12.2 cm H2O, p = 0.20, Group S vs. Group R) and resolution of tinnitus (91.8 vs. 80%, p = 0.28, Group S vs. Group R). Headache improvement was higher in Group S at 6 weeks, but similar at 6 months (92.8 vs. 60%, p = 0.02 and 88.2 vs. 80%, p = 0.59, Group S vs. Group R). Group S also had higher improvement in visual disturbances at 6 months (93.8 vs. 60%, p = 0.01, Group S vs. Group R), but similar improvement in papilledema (92.2 vs 100%, p = 0.68, Group S vs. Group R). None of the re‐stented patients required VPS rescue. Conclusions VSS re‐stenting in IIH patients with recurrence after initial stenting is feasible with similar efficacy in reducing intracranial pressure and symptoms.

Prevalence and associated factors of obstructive sleep apnea in refractory hypertension.

Refractory hypertension (RfHT) and obstructive sleep apnea (OSA) share common pathophysiological mechanisms and probably are intrinsically associated, but their prevalence, clinical profile, and polysomnography (PSG) pattern remain misunderstood. To describe OSA prevalence and PSG pattern of patients with RfHT in a large cohort of resistant hypertension (RHT). This is a cross-sectional study involving 418 RHT patients (30.9% male; mean age of 62.5 ± 9.9 years) who were submitted to full-night PSG. RfHT was defined as uncontrolled ambulatory blood pressure monitoring using five or more antihypertensive drugs, including spironolactone. Bivariate analysis compared RHT and RfHT and multivariate analysis was performed to assess the independent correlates of OSA. A total of 90 patients (21.5%) were diagnosed with RfHT (26.7% male; mean age of 58.5 ± 8.3 years). In comparison with resistant ones, RfHT patients were younger, with higher smoking and previous cardiovascular diseases prevalence, especially stroke. There was no difference regarding anthropometric measures. OSA prevalence (80.0 vs. 82.9%) and moderate/severe OSA (51.1 vs. 57.0%) were similar in both groups as well as apnea-hypopnea index. In its turn, refractory hypertensive patients presented better sleep efficiency (78 vs. 71%), with higher total sleep time (315 vs. 281 min) and lower sleep latency (11 vs. 17 min). There was no difference regarding rapid eye movement sleep, oxygen saturation, microarousals index, and periodic limb movement. In this large RHT cohort, resistant and refractory hypertensive patients have similar OSA prevalence, although refractory ones, which by definition use spironolactone, are younger and apparently have a better sleep pattern.

Examination of the periaqueductal gray as a site for controlling arterial pressure in the conscious spontaneously hypertensive rat.

Our understanding of central nervous system regulation of the set-point of arterial pressure remains incomplete, especially in conditions of hypertension. The ventrolateral periaqueductal gray (vlPAG) is of particular interest given that its acute activation induces hypotension and sympatho-inhibition in anaesthetised, normotensive animals, and recent preliminary studies have shown that vlPAG stimulation can reduce blood pressure in refractory hypertensive patients. To assist our mechanistic understanding, we investigated whether electrical stimulation of the vlPAG had depressor actions in a model of neurogenic hypertension, the spontaneously hypertensive (SH) rat. We found that electrical stimulation of the lateral and vlPAG (2-6V, 20-40Hz, 0.18-0.2ms pulse width) decreased arterial pressure (-19±4mmHg, n=8) and heart rate (median-18bpm) in anaesthetised SH rats. In contrast, in conscious freely-moving SH rats fitted with blood pressure telemetry, stimulation of this same region produced failed to evoked a hypotensive response (n=13; either no change, n=9; or an increase in arterial pressure of 23±4mmHg, n=4). The hypotensive action of the vlPAG observed in anaesthetised animals has been attributed to inhibition of pre-sympathetic neurones originating in the rostral ventrolateral medulla. We therefore used an un-anaesthetised, decerebrate SH rat preparation to investigate whether activation of vlPAG neurons produced sympatho-inhibition that might be below the threshold at which a peripheral vascular response could be observed. Only sympatho-excitatory responses to electrical and excitatory amino acid microinjections were observed, and these were evoked from both the dorsal and ventral PAG; no responses were evoked from the vlPAG. We conclude that the vlPAG is not a reliable antihypertensive locus in the awake SH rat. We discuss the potential importance of the state-dependency of the hypotensive response that can be evoked from the vlPAG, which has important implications for translating to humans.

IMPACT OF LONG-TERM USE OF CPAP TREATMENT ON BLOOD PRESSURE AMONG REFRACTORY HYPERTENSIVE PATIENTS WITH OBSTRUCTIVE SLEEP APNEA

Objective: To assess blood pressure response to long-term continuous positive airway pressure (CPAP) treatment among patients with refractory hypertension (RfHTN) with moderate and severe obstructive sleep apnea (OSA). Design and method: An observational prospective study was performed in 26 patients (35.7% male, average age 59.3 ± 7.9 years) with diagnostic of RfHTN and moderate and severe OSA who were divided in 2 groups to use CPAP (CPAP group, n = 13) or not (control group, n = 15). All of them were submitted to clinical follow-up and their anti-hypertensive medication was adjusted according to the assistant physician. 24-hour ABPM was performed both at the beginning and at the end of the study. Primary outcomes were changes in office and ambulatory blood pressure (BP) and BP control. The comparison between groups of BP changes were calculated by a general linear model with group allocation as a fixed factor and adjusted by its respective BP basal values in addition to gender and age. Results: The median follow-up time was 68 months (IQR: 49–81 months). CPAP and control groups were similar in their baseline demographic, anthropometric, laboratory characteristics, and office and ambulatory BP. They had mean systolic and diastolic 24-hour BP of 142 (15) and 83 (14), respectively. At the end of follow-up, refractory patients using CPAP had a reduction of 8.5 and 5.0 mmHg of office systolic and diastolic BP with an intergroup difference (CPAP and control) of 13.5 (-15.2 – 42.3) mmHg and 10.1 (-7.5 – 5.4) mmHg, respectively. The most important difference between groups was noticed at nighttime with an intergroup difference of 10.0 (-8.6 – 28.7) mmHg of systolic BP and 6.7 (-3.9 – 17.3) mmHg of nighttime diastolic BP. Out of 28 initial refractory patients, 12 are not refractory anymore, being 3 (20%) in control group and 9 (69.2%) in CPAP group with a significant difference between the groups (p = 0.02) Conclusions: Long-term use of CPAP among refractory hypertensive patients with moderate/severe OSA seems to be effective to reduce and control blood pressure measured both in the office BP and 24-hour ABPM, especially lowering nighttime blood pressure.

PROGNOSTIC OF PATIENTS WITH REFRACTORY HYPERTENSION IN A COHORT OF RESISTANT HYPERTENSIVES

Objective: To determine prognostic value of true refractory hypertension diagnosis in a large cohort of resistant hypertensives Design and method: Prospective cohort study enrolled 835 patients of a large historical cohort of RHTN. After at least 6 months of follow-up, 147 (17.6%) patients remained refractory to treatment in ABPM despite the use of 5 or more drugs, including a thiazide-like diuretic and spironolactone. All of them were submitted to a standard protocol including laboratory tests, ABPM, echocardiography, and pulse wave velocity (PWV). Primary outcomes were total mortality, cardiovascular mortality, and fatal and non-fatal cardiovascular events. Secondary outcomes were major cardiovascular events separately (coronary artery disease, cerebrovascular disease, chronic kidney disease with substitutive therapy, peripheral arterial disease). Person-time rates for interest outcomes were calculated to find correlations of Kaplan-Meier survival curves using Cox regression multivariate models, after adjustments for several risk factors. Follow-up remained until December 2021 Results: The median follow-up was 162 months [IQR 115–196]. When compared to resistant hypertensives, patients with RfHTN were younger and more obese. Regarding subclinical lesions, refractories presented less aortic stiffness (13 vs 21%, p = 0.02) and stage 3 chronic kidney diseases (26 vs 34%, p = 0.03) with albuminuria and LVMI similar to those of resistant hypertension despite uncontrolled ambulatory blood pressure. There were 232 all causes deaths (21.1 vs 29.2%), of which 122 from CV causes (12.9% vs 15%), and 253 total CV events (44.1% vs 49%). The diagnosis of RfHTN was associated with a significantly lower risk of all-cause mortality when adjusted by sex and age. It also presented a tendency to be a protective factor of cardiovascular death, chronic kidney disease with substitutive therapy and peripheral arterial disease, although without statistical significance. Risk ratio ranged from 0.62 to 0,94 for every analysis/adjustment, except incidence of stroke (IC95%:1.22(0.70–2.17) after every adjustment in RfHTN. Conclusions: Despite uncontrolled ABPM, refractory hypertensive patients presented lower overall and cardiovascular morbimortality at long-term when compared to non-refractory ones, except stroke, which seems to be at least partially influenced by spironolactone use.

Efficacy of angiotensin receptor neprilysin inhibitor in Asian patients with refractory hypertension

Sacubitril/valsartan, simultaneously inhibits neprilysin and angiotensin II receptor, showed an effect in reducing blood pressure (BP). The authors aimed to study whether it can be used as an antihypertensive agent in patients with refractory hypertension who have already been treated. A total of 66 Chinese patients with refractory hypertension were enrolled. Patients received sacubitril/valsartan 200 instead of angiotensin II receptor blocker or angiotensin converting enzyme inhibitor while other agents continued. If BP was uncontrolled after 4 weeks, sacubitril/valsartan was increased to 400 mg. The BP reduction was evaluated by office BP and ambulatory BP monitoring after 8‐week treatment. The baseline office BP and mean arterial pressure (MAP) were 150.0/95.0 mmHg and 113.3 mmHg. BP and MAP reduced to 130.6/83.2 mmHg and 99.0 mmHg at week 8. Office BP and MAP reductions were 19.4/11.8 mmHg and 14.3 mmHg at endpoint (all p < .001). The 24‐h, daytime and nighttime ambulatory BP were 146.2/89.1, 148.1/90.3, and 137.5/83.7 mmHg, respectively at baseline, and BP reduced to 129.6/79.8, 130.6/81.1, and 121.7/75.8 mmHg, respectively at week 8. The 24‐h, daytime and nighttime ambulatory BP reductions were 16.6/9.3, 17.5/9.2, and 15.8/7.9 mmHg, respectively at endpoint (all p < .001). Sacubitril/valsartan significantly reduced office and ambulatory BP in refractory hypertension patients. Our study provided new evidence for sacubitril/valsartan in refractory hypertension.

Prevalence and clinical profile of refractory hypertension in a large cohort of patients with resistant hypertension.

Refractory hypertension (RfHT) is an extreme phenotype of resistant hypertension (RHT) and is considered uncontrolled blood pressure (BP) despite the use of five or more antihypertensives. The objective of this study was to characterize the prevalence and clinical profile of RfHT patients in a historical cohort of patients with RHT at two different times: before and after the introduction of spironolactone. First, this cross-sectional study evaluated 1048 RHT patients (72.3% females, mean [SD] age: 61.2 [11.3] years) referred to a hypertension clinic (prespironolactone period). All patients were submitted to a standard protocol including clinical and complementary exams. Second, the analysis evaluated patients after the introduction of spironolactone (postspironolactone period). Statistical analysis included bivariate comparisons between patients with RHT and patients with RfHT and logistic regressions to assess the independent correlations of RfHT. A total of 146 patients (13.9%) remained refractory despite the use of at least five antihypertensives (prespironolactone period). After the introduction of spironolactone, the prevalence increased to 17.6%. For any criterion, RfHT patients were younger and more obese. In the initial period, current smoking and left ventricular hypertrophy were independently correlated with RfHT. Furthermore, after spironolactone use, RfHT patients had lower aortic stiffness and peripheral artery disease (PAD), pointing to a lower cardiovascular risk despite the lack of BP control. Younger age and lower prevalence of PAD correlated independently with RfHT. In conclusion, there was a high prevalence of RfHT, especially in younger and obese patients, and spironolactone use seemed to reduce cardiovascular risk despite the lack of BP control.

Clinical Characteristics of Resistant vs. Refractory Hypertension in a Population of Hypertensive Afrodescendants.

ResumoFundamentos Afrodescendentes têm sido associados a uma maior gravidade da hipertensão arterial e maior incidência de complicações cardiovasculares. Características na apresentação da hipertensão resistente (HR) ou hipertensão refratária (HRf), especificamente nessa etnia, não têm sido devidamente estudadas.Objetivos O estudo compara características clínicas e epidemiológicas e prevalência de eventos cardiovasculares em afrodescendentes com diagnóstico de HR ou de HRf. Métodos: Estudo transversal realizado em ambulatório de referência para pacientes com Hipertensão Grave. O nível de significância foi de 5%.Resultados Avaliados 146 pacientes consecutivos, dos quais 68,7% eram do sexo feminino. A média de idade foi de 61,8 anos, sendo 88,4% afrodescendentes (pardos ou negros). 51% apresentavam HRf. Houve alta prevalência de fatores de risco cardiovascular: 34,2% tinham diabetes, 69,4% dislipidemia, 36,1% obesidade e 38,3% história de tabagismo. Função renal reduzida foi observada em 34,2%. Eventos cardiovasculares prévios ocorreram em 21,8% para infarto do miocárdio e em 19,9% para acidente vascular cerebral. O escore de risco de Framingham foi moderado/alto em 61%. Os pacientes com HRf eram mais jovens (média de idade de 59,38±11,69 anos versus 64,10±12,23 anos, p=0,02), tinham mais dislipidemia (83,8 versus 66,7%, p=0,021) e acidente vascular cerebral (30,4 versus 12,3%, p=0,011) quando comparados aos com HR. O uso de combinação de ACEi/BRA+CCB+Diurético, clortalidona e espironolactona também foi mais frequente em indivíduos com HRf.Conclusão Afrodescendentes com HR apresentaram alto risco cardiovascular, alta prevalência de HRf, maior frequência de dislipidemia e de acidente vascular cerebral, compatível com alta incidência de lesão a órgãos-alvo. (Arq Bras Cardiol. 2020; 115(1):31-39)

Resistant/Refractory Hypertension and Sleep Apnoea: Current Knowledge and Future Challenges.

Hypertension is one of the most frequent cardiovascular risk factors. The population of hypertensive patients includes some phenotypes whose blood pressure levels are particularly difficult to control, thus putting them at greater cardiovascular risk. This is especially true of so-called resistant hypertension (RH) and refractory hypertension (RfH). Recent findings suggest that the former may be due to an alteration in the renin–angiotensin–aldosterone axis, while the latter seems to be more closely related to sympathetic hyper-activation. Both these pathophysiological mechanisms are also activated in patients with obstructive sleep apnoea (OSA). It is not surprising, therefore, that the prevalence of OSA in RH and RfH patients is very high (as reflected in several studies) and that treatment with continuous positive airway pressure (CPAP) manages to reduce blood pressure levels in a clinically significant way in both these groups of hypertensive patients. It is therefore necessary to incorporate into the multidimensional treatment of patients with RH and RfH (changes in lifestyle, control of obesity and drug treatment) a study of the possible existence of OSA, as this is a potentially treatable disease. There are many questions that remain to be answered, especially regarding the ideal combination of treatment in patients with RH/RfH and OSA (drugs, renal denervation, CPAP treatment) and patients’ varying response to CPAP treatment.

The Potential Role of Obstructive Sleep Apnoea in Refractory Hypertension.

This review seeks to present an overview of the recently found association between refractory hypertension (RfH) and obstructive sleep apnoea (OSA). RfH was recently defined as an extreme phenotype of resistant hypertension characterized by the lack of blood pressure control despite using ≥ 5 antihypertensive drugs at optimal doses. Current data support that the pathophysiological pathway of both types of hypertension is different. The main mechanism involved in resistant hypertension is fluid retention whereas in the case of RfH is the sympathetic over-activity. OSA is now recognized as a cause of hypertension (especially in the case of difficult-to-treat hypertension). It seems that the biological mechanism linking OSA and arterial hypertension is the sympathetic over-activity related to the respiratory events (apnoeas and hypopnoeas) during the night. So, it is not surprising that, although the literature is scarce, some studies have found a very high prevalence of OSA and an excess of sympathetic activity in patients with RfH. Finally, a very recent study demonstrated that continuous positive airway pressure (CPAP) treatment, which controls sympathetic activation in OSA patients, achieves very significant reductions in blood pressure levels in RfH patients, even greater than in those with resistant (non-refractory) hypertension. The prevalence of OSA in patients with RfH is very high. CPAP treatment achieves a clinically significant reduction in blood pressure levels in those patients with RfH (especially in night readings). Patients with RfH must be sent to a sleep unit for a study.

Effect of continuous positive airway pressure in patients with true refractory hypertension and sleep apnea: a post-hoc intention-to-treat analysis of the HIPARCO randomized clinical trial.

Continuous positive airway pressure (CPAP) can significantly reduce blood pressure (BP) levels in patients with resistant hypertension and sleep apnea (OSA); however, the effect on patients with refractory hypertension (RfH) is not known. This study seeks to evaluate the effect of CPAP treatment on BP levels in patients with OSA and RfH, compared with those with OSA and resistant hypertension. Post-hoc analysis of the HIPARCO randomized clinical trial on the effect of CPAP treatment on BP levels in patients with resistant hypertension. Those patients with uncontrolled 24-h ambulatory BP monitoring readings (>130 and/or >80 mmHg) in SBP or DBP were considered to have resistant hypertension (if they were taking three or four antihypertensive drugs) or RfH (if they were taking at least five drugs). OSA patients were randomized to receive CPAP or usual care for 3 months. They underwent a second 24-h ambulatory BP monitoring study to establish the effect of CPAP treatment on BP levels in both groups. A total of 98 patients were randomized to CPAP (19 RfH/79 resistant hypertension) and 96 to usual care (21 RfH/75 resistant hypertension). BP readings dropped more marked in patients with RfH than resistant hypertension, in both 24-h SBP (-9 vs. -1.6 mmHg, P = 0.021) and 24-h DBP (-7.3 vs. -2.3 mmHg, P = 0.074), especially at night (-11.3 vs. -3.8, P = 0.121 and -8.8 vs. -2.2, P = 0.054) respectively. Adjusted difference between groups was statistically significant in 24-h SBP levels (-7.4 mmHg, P = 0.021). CPAP lowers BP levels in both resistant hypertension and RfH patients although the degree of this reduction is higher in those with RfH especially during the night.

Pseudo-resistant, resistant, and refractory hypertension: The good, the bad, and the ugly

Resistant Hypertension (RH) not uncommon in daily clinical practice but is often loosely coined. Accuracy of BP measurement, Adherence to prescribed medications and Adequacy of prescribed dosages are to be ensured before diagnosing RH. Ambulatory blood pressure monitoring and home blood pressure monitoring are becoming standard of care in evaluation of RH patients. Management of RH in recent years has been evolved and spiranolactone has become the fourth drug when combination of Renin-Angiotensin system blockers, calcium channel blockers and long acting thiazide like diuretics fail. Scores like PFK comprising of Urinary pH>7, Female Sex, K<3.5 mg/dl has been handy in decision making to start spiranolactone. However, Refractory Hypertension (RfH) has been defined when five anti-hypertensive drugs including spiranolactone fail and has been emerging to be a novel phenotype. RH patients are known to be volume dependent whereas RfH patients are known to have sympathetic overdrive. Management strategy of RfH is challenging and beta-blockers or alpha-blockers may be of role in these subset. Renal artery denervation is being resurrected with newer evidence and definitely an option for RfH patients. Novel therapies like Barroreceptor Activation Techniques and Central iliac arteriovenous anastomosis are being evaluated in resistant and refractory hypertension patients.

Abstract P209: Antihypertensive Medication Non-Adherence is Common in Patients With Suspected Refractory Hypertension

Introduction: Refractory hypertension is a phenotype of antihypertensive treatment failure defined as uncontrolled BP (&gt; 135/85 mmHg) despite the use of five or more different antihypertensive agents, including long-acting thiazide like diuretic (chlorthalidone) and mineralocorticoid receptor antagonist (Spironolactone or Eplerenone). Recently white coat effect has been shown to be uncommon in patients with refractory hypertension. However, the degree of medication non-adherence, an important cause of apparent refractory hypertension, is unknown. Methods: In this prospective evaluation, 37 refractory hypertensive patients were recruited from the University of Alabama at Birmingham Hypertension Clinic after having uncontrolled BP at three or more clinic visits. All patients were evaluated by automated office BP (AOBP) with the BpTRU device, ambulatory BP monitoring (ABPM), and 24-hr urine collection to detect antihypertensive medication adherence by high-performance liquid chromatography-tandem mass spectrometry. Out of 34 patients who underwent ABPM monitoring, 30 (88%) patients were refractory hypertensive by AOBP and by ABPM. Of these, 27 patients had 24-hr urine collection for detection of prescribed antihypertensive medications or their metabolites. Results: Out of 27 patients, 11 (40.7%) patients had complete adherence with five or more antihypertensive medications, indicating true refractory hypertension. Ten (37.0%) patients were partially adherent, and 6 (22.2%) patients had total non-adherence to their antihypertensive medications. Conclusion: Of patients identified as having apparent refractory hypertension, 40% were adherent with at least 5 of their prescribed antihypertensive agents, confirming true refractory hypertension. The remaining 60% were partially or fully non-adherent. These results indicate that non-adherence is common in patients suspected of having refractory hypertension.

Refractory Hypertension Is not Attributable to Intravascular Fluid Retention as Determined by Intracardiac Volumes.

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P=0.003) and had a greater proportion of women (75.0% versus 43%; P=0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m2; P<0.001), posterior wall thickness (10.1±3.1 versus 7.7±1.5 mm; P=0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P<0.001). There was no difference in B-type natriuretic peptide levels and left atrial or ventricular volumes. Diastolic dysfunction was noted in RfHTN. Our findings demonstrate greater left ventricular hypertrophy without chamber enlargement in RfHTN, suggesting that antihypertensive treatment failure is not attributable to intravascular volume retention.

PR276: Lack of association between generalized severe chronic periodontitis and metabolic syndrome in a population of refractory hypertension patients

PR276: Lack of association between generalized severe chronic periodontitis and metabolic syndrome in a population of refractory hypertension patients

Influence of 3 calcium channel blockers on gingival overgrowth in a population of severe refractory hypertensive patients.

The aim of the current study was to assess the association between 3 different calcium channel blockers (CCBs) (nifedipine, amlodipine and felodipine) and gingival overgrowth in patients with a diagnosis of severe refractory hypertension. One hundred and sixty-two patients with severe refractory hypertension, taking CCBs, were selected. Gingival overgrowth was graded and periodontal measurements were recorded (probing pocket depth, clinical attachment level, plaque index and bleeding on probing). Unconditional multivariable binary logistic regression analyses were performed to assess the association between CCB intake and gingival overgrowth after adjusting for potential confounders. Of the 162 patients, 26 (16.0%) were current smokers and 101 (62.3%) were females. The mean age (SD) was 54.1 (8.5) years and the median age (range) 52.5 (39-78) years. Gingival overgrowth was observed in 55 patients (34.0%). Nifedipine was the most common medication (35.2%; 57 of 162). The results of multiple binary logistic regression showed statistically significant associations between CCB intake (exposure) and gingival overgrowth (outcome) after adjusting for the variables treatment time with antihypertensive and plaque index. Patients with gingival overgrowth were 2.5 (odds ratio=2.46; 95% confidence interval: 1.04-5.82) and 4.0 (odds ratio=3.90; 95% confidence interval: 1.47-10.35) times more likely to be taking nifedipine and amlodipine, respectively, than patients without gingival overgrowth. On the other hand, this significant association was not observed for felodipine. Nifedipine and amlodipine, but not felodipine, were associated with gingival overgrowth in patients with severe refractory hypertension.

Prevalence and risk factors for atherosclerotic renal artery stenosis in elderly patients with refractory hypertension

Objective To investigate the prevalence and risk factors for atherosclerotic renal artery stenosis (ARAS) in elderly patients with refractory hypertension. Methods Two hundred and eight elderly patients with a mean age of (68.3±4.9 )years (53.8% in men) diagnosed with refractory hypertension were recruited in this retrospective study from January 2010 to January 2017 in Beijing hospital. Fifty of the 208 patients with ultrasonography-suspected renal artery stenosis received renal arteriography and 39 were confirmed as renal artery stenosis. Renal artery stenosis was defined when stenosis located in at least one of renal arteries and only if the stenosis equal or over 50%. The prevalence of ARAS was calculated. Besides, univariate and final multivariate Logistic regression analyses were conducted to detect independent risk factors for development of ARAS. Results Thirty-nine of 208 patients (18.8%) were confirmatively diagnosed as ARAS. Although univariate Logistic regression showed that diabetes, coronary heart disease, renal insufficiency, and peripheral artery disease (P=0.034, 0.040, 0.022, and 0.030) might be risk factors for ARAS, a multivariate regression analysis demonstrated that only the peripheral artery disease (OR=3.218, P<0.01) and renal insufficiency (OR=3.827, P<0.01) were independent risk factors for ARAS. Conclusions Renal angiography should routinely be performed in refractory hypertension patients with renal insufficiency or peripheral artery disease to identify ARAS in time. Key words: Hypertension; Atherosclerosis; Risk factors; Renal artery stenosis