Diagnosis Of Resistant Hypertension Research Articles

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.

PS-R04-7: UNSOLVED CASE OF RESISTANT HYPERTENSION: A CHALLENGING ISSUE IN A DEVELOPING COUNTRY

Introduction: It is difficult to find a definite etiology of resistant hypertension (RH) in developing countries due to limited resources. We present a case report and discuss RH's diagnosis and treatment approaches, which we suspected owing to Obstructive Sleep Apnea (OSA) after extensive assessment, including nuclear imaging and renal arteriography. Case presentation: A 58-year-old female was referred to Hasan Sadikin General Hospital for RH assessment. Having conducted ambulatory blood pressure monitoring and echocardiography, which suggested hypertensive heart disease, we confirmed the diagnosis of RH in this patient. The patient has a 4-year history of hypertension, accompanied by throbbing headaches and snores. She underwent percutaneous coronary intervention two years ago due to angina. During the physical examination, she was fully alert with a blood pressure of 170/90 mmHg and a heart rate of 62 times/minute, mild exophthalmos, and cardiomegaly. Her renal (including proteinuria), and thyroid function were within normal limits. Echocardiography revealed concentric left ventricular (LV) hypertrophy with normal LV systolic function. An abdominal Computed Tomography indicated pheochromocytoma or adrenal tumor. Metanephrines examination was not feasible due to cost issues. Using metaiodobenzylguanidine scan (Tc-99 and I-131), nuclear imaging failed to establish diagnosis of pheochromocytoma. Renal artery ultrasonography increased the suspicion of renal artery stenosis; however, renal arteriography showed mild renal artery stenosis. We referred the patient to a neurologist for OSA screening, from STOP-Bang questionnaire result indicated that the patient was likely to have OSA. Unfortunately, the diagnosis was inconclusive due to unavailability of polysomnography facility. The unavailability of minoxidil, renal denervation and continuous positive airway pressure (CPAP) hinders the optimal treatment in this patient. The blood pressure target remains unachievable despite Amlodipine 1x10 mg, candesartan 2x16 mg, bisoprolol 1x10 mg, tamsulosin 1x400 mg, spironolactone 1x50 mg, dan isosorbide mononitrate 2x2.5 mg consumption. The unavailability of chromatography-mass spectrometry for evaluation of medication adherence was also a significant limitation. Conclusion: This case showed that the blood pressure remains uncontrolled despite six different medications, which may be due to the untreated etiology of secondary hypertension. Furthermore, although extensive examinations have been performed, a definite diagnosis could not be made due to cost/facility issues for other diagnostic approach. To further complicate matters, the evaluation of medication adherence and optimal treatment were not available. Therefore, RH remains a challenging issue in developing countries.

May the brief physical activity assessment tool accurately measure physical activity in patients with resistant hypertension?

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): FEDER Funds through the Operational Competitiveness Factors Program—COMPETE National Funds through the Portuguese Foundation for Science and Technology (FCT) “PTDC/DTP-DES/1725/2014”. SL is a PhD fellow supported by the FCT (Grant Ref: SFRH/BD/129454/2017). Introduction Resistant hypertension is a major health problem due to the increased risk of cardiovascular events and mortality. Physical activity and exercise reduces blood pressure in resistant hypertension and is associated with lower cardiovascular risk and mortality. It is presently recommended that physical activity assessment should be a priority in all visits to health settings Purpose This study aims to determine if the Brief Physical Activity Assessment Tool (BPAAT), a 2-question tool to assess physical activity, is a valid instrument to detect inactive patients with resistant hypertension. Methods Sixty patients with a diagnosis of resistant hypertension were recruited. Outcome measures included clinical data, blood pressure and daily physical activity. Physical activity was objectively measured over a 7-day period with an accelerometer and subjectively assessed (self-assessment) by the BPAAT. The association between the BPAAT and accelerometry, according to the BPAAT scoring categories, was assessed bythe percentage of agreement, Cohen’s Kappa and sensitivity and specificity. Results Patients (33 were male) had a mean age of 59.4 ± 9.1years, were on average overweight (BMI 29.5 ± 4.5 kg/m2) and on an average of 4.5 ± 0.7 antihypertensive medications. Forty-two patients (70%) were classified as insufficiently active by the BPAAT compared to the 38 (63.3%) insufficiently active patients identified by the accelerometry data. Regarding the questionnaire’s specificity and sensitivity, the BPAAT correctly identified 32 [84.2 (73.1 – 95.3) %] of the 38 ‘insufficiently active’ patients and 12 [54.5 (34.3 – 74.7) %] of the 22 ‘sufficiently active’ patients identified by accelerometry. The agreement between BPAAT and accelerometry to identify sufficiently/insufficiently active patients, according to the BPAAT’s cut-off values was fair to moderate (Kappa = 0.403 (0.162 – 0.674), with a percentage of agreement of 73.3%. Conclusion The BPAAT, a 2-question tool to assess physical activity, seems to be a valid and fast solution to identify insufficiently active adults with resistant hypertension during routine clinical visits.

THE DEVELOPMENT OF RESISTANT HYPERTENSION INDEPENDENT OF THE PRECEDING PERIOD OF THE BLOOD PRESSURE CONTROL IS ASSOCIATED WITH THE INCREASED RISK OF CARDIOVASCULAR EVENTS AND DEATH

Objective: Resistant hypertension (RH) is associated with the increased risk of cardiovascular events (CVEs); that excess risk is often attributed to the legacy of the previous period of uncontrolled blood pressures (BPs). We used the database of the ASCOT trial to evaluate the risk of CVEs (non-fatal myocardial infarction, fatal coronary heart disease, and fatal/non-fatal stroke) and death, after controlling for the cumulative mean of BPs for a preceding period of 2-years (using area-under-curve [AUC]). Design and method: 18,926 hypertensive patients were initially followed up for the development of RH or not for a period of 2-years. During that period, we calculated the AUC of the cumulative mean BPs (AUCcmBPs) until the RH diagnosis or the end of the 2-year period if no-RH. These patients were then followed up from this new baseline for the risk of CVEs or death. We estimated incidence rates and developed a multivariable Cox regression model after adjusting for a-priori confounders (age, sex, socio-economic status, BMI, total cholesterol, HDL-cholesterol, systolic-BP at baseline, randomized treatment allocation, diabetes, other vascular diseases) and the AUCcmBPs. Interaction tests were done for those who were taking antihypertensive medications prior to the randomization or not. Results: About one-third (n = 5,660) developed RH by the end of 2-years. During the further median follow-up of 3.9 years, there were 1113 CVEs and 745 deaths. The incidence rate of CVE and death was higher in those with RH vs those without (34.8 and 18.9 per 1,000 person-years vs 24.0 and 15.4, respectively). In the multivariable model after controlling for the AUCcmBPs, those with RH, as compared to those without, had a significantly higher risk of CVE and death (HR: 1.15 [95% CI 1.03–1.27], p-value = 0.010, and 1.16 [1.02–1.33], p-value = 0.028, respectively). This excess in the risk didn’t differ significantly between those who were on prior antihypertensive therapy or not (interaction test p-value = 0.430 and p-value = 0.310, respectively). Conclusions: After accounting for prior BPs, the presence of RH is associated with the increased risk of CVEs and death; which could be because of the additional risk due to associated genotypical or phenotypical factors.

Is There Any Role for Device Therapies in Resistant Hypertension? Commentary.

In this issue of Kidney360 , two titans of hypertension, Drs. Ray Townsend and Aldo Peixoto, debate whether there is any role for device therapies in resistant hypertension. As the debate’s moderator, I will provide background information to set the stage for this epic showdown and offer a nonpartisan opinion on the topic. First, what is meant by “resistant hypertension?” According to the most recent ACC/AHA High Blood Pressure Clinical Guidelines, the diagnosis of resistant hypertension is made when a patient takes three antihypertensive medications, including at least one diuretic, but does not achieve control or when BP control is achieved but requires four or more medications (1). Using the BP target of <130/80 mm Hg, the prevalence of resistant hypertension among United States adults taking antihypertensive medication is estimated at 20% or 10.3 million persons (2). Second, with so many different types of antihypertensive medications that can effectively and reliably lower BP, why turn to device therapy for hypertension management given the inherent risks that come with these invasive procedures? Many patients cannot or will not take antihypertensive medications as prescribed due to unacceptable side effects or other factors. Moreover, even patients with perfect medication adherence to multiple antihypertensive medications will sometimes still have poorly controlled BP (3). Thus, …

HTA essentielle résistante : place de la spironolactone

Resistant hypertension is defined as uncontrolled blood pressure (BP) despite three antihypertensive agents including a diuretic (thiazide diuretic if renal function is normal or loop diuretic in case of chronic kidney disease with eGFR<30mL/min), a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, at optimal doses. Resistance must be confirmed by out-of-office measurements (ambulatory blood pressure monitoring or home blood pressure monitoring) and patients should be asked about treatment compliance and excessive salt or alcohol intake. If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for secondary causes of hypertension as they are frequent in this context. If essential resistant hypertension is confirmed, the mineralocorticoid receptor antagonist, spironolactone, should be added (25 to 50mg daily). In the event of a contraindication to spironolactone, or if adverse effects occur, a beta-blocker, an alpha-blocker, or a centrally acting antihypertensive drug should be prescribed.

Factors associated with the changes from a resistant to a refractory phenotype in hypertensive patients: a Pragmatic Longitudinal Study.

Refractory hypertension (RfH) is defined as a lack of blood pressure control despite the administration of at least 5 anti-hypertensive drugs. The factors associated with its natural history are unknown. This study aimed to evaluate both the incidence of RfH in an cohort of patients with resistant hypertension (RH) and the factors involved in that progression. This was an observational prospective multicenter study (24 centers) with 172 patients with confirmed RH (24-h ABPM) who underwent a further 24 h ABPM study at the end of the follow-up. Prospective information was obtained from all patients in their corresponding Hypertension Units via a standard clinical protocol, and they all underwent a sleep study. Thirty patients were diagnosed with RfH (17.4%) after a mean follow-up of 57 months, despite the prescription of a greater number of long-acting thiazide-like diuretics and mineralocorticoid receptor antagonists. The factors associated with progression to RfH were: a longer period since the diagnosis of RH (OR: 1.06, 95% CI: 1.01-1.1, p = 0.007); the HbA1c concentration (OR: 1.42, 95% CI: 1.42-1.8; p = 0.005); the initial heart rate (OR: 1.05, 95% CI: 1.01-1.09, p = 0.004); and poor adherence to continuous positive airway pressure (CPAP) in cases of obstructive sleep apnea (OR: 3.36, 95% CI: 1.47-7.7, p = 0.004). In conclusion, a considerable percentage of patients evolved from the RH to the RfH phenotype despite changes in their treatment. Some easily measurable variables, such as heart rate, the time since the diagnosis, the HbA1c level, and the presence of untreated obstructive sleep apnea (or poor adherence to CPAP) have been demonstrated to be prognostic factors in the progression to RfH.

The value of ABPM and subclinical target organ damage parameters in diagnosis of resistant hypertension

IntroductionWe aimed to assess the effectiveness of ambulatory blood pressure monitoring (ABPM) and subclinical target organ damage parameters for diagnosis of resistant hypertension (RH). MethodsWe assessed demographic and anthropometric variables, the incidence of cardiovascular events and subclinical target organ damage (n=112). We also studied the relationship between these variables and the ABPM results. ResultsOf the 112 patients referred from primary care with a diagnosis of RH, 69 (61.6%) were confirmed by ABPM. We found statistically significant differences (p<0.001) between patients with RH and pseudo-resistant hypertension in the appearance of subclinical target organ damage. A percentage of 84 of the patients had microalbuminuria: 66.25±30.7mg/dl); 44.9% had stage 3 chronic kidney disease: the average glomerular filtration was 59ml/min/1.73m2; and 56.5% had left ventricular hypertrophy on echocardiography. Fundoscopy revealed that 64% of the patients had hypertensive retinopathy. Three variables were associated with an increased HR risk: microalbuminuria, hypertensive retinopathy and left ventricular hypertrophy (OR 5.7, 6.2 and 11.2, respectively). ConclusionsThis study shows that the systematic testing for target organ damage, particularly in terms of albuminuria, is a simple and inexpensive tool, with a high predictive value for RH (85%), which could be useful for prioritizing patients who need ABPM.

El valor de la MAPA y de los parámetros de lesión subclínica de órgano diana en el diagnóstico de hipertensión refractaria

IntroductionWe aimed to assess the effectiveness of ambulatory blood pressure monitoring (ABPM) and subclinical target organ damage parameters for diagnosis of resistant hypertension (RH). MethodsWe assessed demographic and anthropometric variables, the incidence of cardiovascular events and subclinical target organ damage (n=112). We also studied the relationship between these variables and the ABPM results. ResultsOf the 112 patients referred from primary care with a diagnosis of RH, 69 (61.6%) were confirmed by ABPM. We found statistically significant differences (P<.001) between patients with RH and pseudo-resistant hypertension in the appearance of subclinical target organ damage. A percentage of 84 of the patients had microalbuminuria: 66.25±30.7mg/dl); 44.9% had stage 3 chronic kidney disease: the average glomerular filtration was 59ml/min/1.73m2; and 56.5% had left ventricular hypertrophy on echocardiography. Fundoscopy revealed that 64% of the patients had hypertensive retinopathy. Three variables were associated with an increased HR risk: microalbuminuria, hypertensive retinopathy and left ventricular hypertrophy (OR 5.7, 6.2 and 11.2, respectively). ConclusionsThis study shows that the systematic testing for target organ damage, particularly in terms of albuminuria, is a simple and inexpensive tool, with a high predictive value for RH (85%), which could be useful for prioritising patients who need ABPM.

Resistant hypertension: an overview.

Despite the availability of anti-hypertensive medications with proven efficacy and good tolerability, many hypertensive patients have blood pressure (BP) levels not at the goals set by international societies. Some of these patients are either non-adherent to the prescribed drugs or not optimally treated. However, a proportion has resistant hypertension (RH) defined as office BP above goal despite the use of ≥3 antihypertensive medications at maximally tolerated doses (one ideally being a diuretic). Diagnosis of RH based upon office measurements, however, needs confirmation through 24-h BP monitoring to exclude "white coat" RH since cardiovascular events and mortality rates follow mean ambulatory BPs. Standardized combination therapy based upon angiotensin converting enzyme inhibitors or angiotensin receptor blockers, amlodipine or other dihydropiridine calcium channel blockers and thiazide or thiazide-like diuretics has been advocated to treat RH with spironolactone as preferred fourth add-on drug. Interventional procedures such as renal denervation have been devised to treat RH and tested with insofar not positive results in series of patients not responding to medical treatment. It is unclear whether RH constitutes a specific phenotype of EH or should rather be considered a more serious form of uncontrolled hypertension. Whatever the case, its presence associates with an increased cardio- and cerebrovascular risk and deserves, therefore, particular care.

Diagnosis of Resistant Hypertension

Hypertension is a major risk factor of cardiovascular death in Bangladesh and worldwide. Resistant hypertension as well as uncontrolled hypertension with 3 or more antihypertensive agents is increasingly common in clinical practice. Clinicians should exclude pseudoresistant hypertension, which results from nonadherence to medications or from elevated blood pressure related to the white coat syndrome. Resistant hypertension may be associated with secondary causes of hypertension including obstructive sleep apnea or primary aldosteronism.Northern International Medical College Journal Vol.8(1) July 2016: 196-198

Three Different Imaging Modalities of a Patient with the Aortic Coarctation

The patient was a 19 year-old woman with the diagnosis of resistant hypertension, although she was under treatment of three classes of anti-hypertensive drugs (beta blocker, angiotensin receptor blocker, diuretic) for more than one year. In physical examination there was only a significant difference between the systolic blood pressure of upper and lower extremities (200 vs. 120 mmHg), without any other remarkable finding. Three different imaging modalities (echocardiography (Figure 1), CT angiography (Figure 2), conventional aortography (Figure 3) confirmed the aortic coarctation at 30 mm after left subclavian artery origin, with the 3.5-4 mm diameter of the narrowest segment. She underwent implantation of a self-expanding aortic stent and therefore the systolic pressure gradient decreased from 90 to 15 mmHg. After three months, her blood pressure was stable on 110/80 mmHg, while she received only metoprolol 25 mg twice daily and follow-up echocardiography showed 15-20 mmHg pressure gradient through the stent.

PP.34.04] EFFECT OF EPLERENONE ON APNOEA-HYPOPNOEA INDEX IN PATIENTS WITH RESISTANT HYPERTENSION AND OBSTRUCTIVE SLEEP APNEA

Objective: To determine if the addition of eplerenone to the hypotensive treatment reduces the severity of obstructive sleep apnea (OSA) in patients with resistant hypertension and OSA Design and method: 38 consecutive patients with OSA (25 men and 13 women) aged 57.76+/-6.16 were referred to Department of Hypertension with diagnosis of resistant hypertension. Resistant hypertension was defined as uncontrolled hypertension despite the use of at least three hypotensive drugs including diuretics. Exclusion criteria were: secondary hypertension, myocardial infarction, stroke within six months before the study, chronic heart failure NYHA III and IV, chronic kidney failure (GFR<30 ml/min), alcohol or drugs abuse, active cancer. All subjects underwent following examinations: BP measurement with OMRON 705IT sphygmomanometer – mean value from 3 measurements after 15 min. of rest was used; 24-hour ambulatory BP monitoring using 2430TM A&D device; assessment of aortic pulse wave and arterial wall stiffness parameters of the large conduit arteries measured using applanation tonometry method with SphygmoCorPVx system by a single observer. In all patients polysomnography was performed using a all-night polysomnographic monitoring system EMBLA S4000, Remlogic with Somnologica studio 3.3.2 software. Apnea was defined as a cessation of airflow lasting for more than 10 sec. After primary evaluation eplerenone 50 mg once daily was added to existing antihypertensive treatment regimen in all subjects. After 3 months all procedures were repeated. Results: Eplerenone therapy reduced SBP24 h from 144,6+/−9,4 to 135,7+/−4,9 p < 0,05, DBP24 h from 87,8+/−7,9 to 84,1+/−4,9,p < 0,05, MAP24 h from 106,7+/−6,8 to 101,5+/−4,1 p < 0,05, PWV from 15,3+/−1,3 to 12,8+/−2,2 p < 0,05, AoAlx (%) from 31,6+/−4,2 to 27,1+/−4,6 p < 0,05, AlxHR75 (%) from 28,4+/−4,2 to 22+/−5,4 p < 0,05, AHI (/h) from 44,5+/−19,9 to 29,5+/−12,9 p < 0,05. There was a significant positive correlation between AHI and SBP24 h 0,487 p = 0,014, AHI and MAP 24 h 0,477p = 0,016 AHI and PWV 0,659 p = 0,003, AHI and AoAlx 0,436 p = 0,029, AHI and AlxHR75 0,530 p = 0,006. Conclusions: Treatment with eplerenone reduces severity of obstructive sleep apnoea in patients with resistant hypertension.

Resistant Hypertension and Chronic Kidney Disease: a Dangerous Liaison

Treatment-resistant hypertension is an increasingly recognised problem and is markedly over-represented in patients with chronic kidney disease (CKD). Recent evidence has clarified the heightened risk for both adverse renal and cardiovascular outcomes associated with resistant hypertension, even when blood pressure control is attained. The diagnosis of resistant hypertension in CKD is reliant on accurate blood pressure measurement, and out of office measurements are important due to the high prevalence of masked hypertension in these patients. Treatment strategies include careful dietary measures to restrict sodium intake, and a focus on improving adherence to antihypertensive medications. Medication choices should focus on a sensible foundation and then diuretic titration to combat the salt and volume retention inherent in CKD. In this review, we discuss the epidemiology, pathogenesis and consequences of resistant hypertension in CKD, and then review the optimal diagnostic and management strategies.

Prevalence and determinants of resistant hypertension in a sample of patients followed in Italian hypertension centers: results from the MINISAL-SIIA study program.

The aim of this study was to detect the prevalence of resistant hypertension (RH), allowing for adherence to appropriate lifestyle measures according to European Society of Hypertension-European Society of Cardiology (ESH-ESC) 2013 guidelines, in a sample of 1284 hypertensive subjects participating at the MINISAL-SIIA study. Hypertensive patients were recruited in 47 Italian centres, recognised by the Italian Society of Hypertension. Anthropometric indexes, blood pressure and 24-h urinary sodium (Na24h) and potassium (K24h) excretion were measured. Data on antihypertensive therapy were available for 1177 (92%) subjects. The population was divided into three groups (North, Central and South), according to their geographical location. Accounting only at the treatment criteria, the prevalence of RH was 8.2% (96/1177). RH prevalence in the southern, central and northern regions was respectively: 1, 3.8 and 3.3% (P<0.001). Participants with RH were older and showed a higher body mass index (BMI) and waist circumference compared with other subjects (P<0.005). RH risk was statistically significant (P<0.01) increased of 1.52-fold (95% confidence interval (CI):1.20-1.92) for one unit increase in s.d. score of age (11 years), and 1.50-fold (95% CI:1.22-1.83) for one unit increase in s.d. score of BMI (4.5 kg m-2). Including in RH diagnosis also the adherence to appropriate lifestyle measures, such as dietary salt restriction (Na24h <100 mmol) and normal BMI (18-25 kg m-2), RH prevalence felt respectively to 2.2% (26/1177) and 0.8% (9/1177). In conclusion in this national sample of Italian hypertensive population, among participants following both drug treatment and lifestyle modifications advises, the 'true' RH prevalence appears to be particularly low.

Management of resistant hypertension: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology.

To improve the management of resistant hypertension, the French Society of Hypertension, an affiliate of the French Society of Cardiology, has published a set of eleven recommendations. The primary objective is to provide the most up-to-date information based on the strongest scientific rationale and that is easily applicable to daily clinical practice. Resistant hypertension is defined as uncontrolled blood pressure on office measurements and confirmed by out-of-office measurements despite a therapeutic strategy comprising appropriate lifestyle and dietary measures and the concurrent use of three antihypertensive agents including a thiazide diuretic, a renin-angiotensin system blocker (ARB or ACEI) and a calcium channel blocker, for at least 4 weeks, at optimal doses. Treatment compliance must be closely monitored, as must factors that are likely to affect treatment resistance (excessive dietary salt intake, alcohol, depression, drug interactions and vasopressor drugs). If the diagnosis of resistant hypertension is confirmed, the patient should be referred to a hypertension specialist to screen for potential target organ damage and secondary causes of hypertension. The recommended treatment regimen is a combination therapy comprising four treatment classes, including spironolactone (12.5-25 mg per day). In the event of a contraindication or a non-response to spironolactone, or if adverse effects occur, a β-blocker, an α-blocker, or a centrally acting antihypertensive drug should be prescribed. Because renal denervation is still undergoing assessment for the treatment of hypertension, this technique should only be prescribed by a specialist hypertension clinic.

HIPERTENSIUNEA ARTERIALĂ REZISTENTĂ ŞI SINDROMUL DE APNEE ÎN SOMN

Arterial hypertension is an important risk factor for cardiovascular morbidity and mortality, with increasing incidence and prevalence. Diagnosis of resistant hypertension may be established when the values of blood pressure are ≥ 140/90 mmHg, despite lifestyle changes and treatment with three antihypertensive drugs from different therapeutic classes, one being a diuretic. One common comorbidity in patients with resistant hypertension is obstructive sleep apnea. Obesity, defined as a body mass index ≥ 30 kg/m2, is a common risk factor linking the obstructive sleep apnea syndrome (OSAS) with resistant hypertension. The diagnosis of OSAS in patients with resistant hypertension is made by polysomnography. For the confirmation of diagnosis of resistant hypertension it is necessary the ambulatory blood pressure monitoring, which allows the exclusion of false cases of resistant hypertension, white coat or masked hypertension. Treatment of OSAS with CPAP (continuos positive airway pressure) offers improvement of blood pressure values and better control of resistant hypertension, reducing the cardiovascular risk.

CO-35: ALPHA-1 Antitrypsin deficiency : a novel cause of isolated systolic resistant hypertension?

Background Alpha-1 Antitrypsin (AAT), a serine protease of the SERPIN superfamily inhibits various tissue proteases such as neutrophil elastase and proteinase 3. Mutations in the corresponding gene, SERPINA1, are at the origin of AAT deficiency (AATD). The most frequent manifestations of AATD are panacinar emphysema and chronic liver disease. AATD has been occasionally associated with aneurysms and dissection of large vessels. Compared to matched controls, AATD patients homozygous for the common Z variant have larger ascending aortas with abnormal elastic properties (Vizzardi et al. Heart 2012 ; 98: 1354–58). However, so far, increased arterial stiffness and isolated systolic hypertension have not been documented in AATD patients. We describe the case of a young patient with isolated systolic refractory hypertension associated with a mild, atypical form of AATD, and discuss the potential link between both entities. Methods A 43-year-old non-smoker man was referred at the hypertension consultation for severe, early-onset resistant hypertension with very high pulse pressure, despite intake of eight antihypertensive drugs. He reported a history of eosinophilic esophagitis and left popliteal stent for lower limb arteriopathy. Results In a context of moderate increase in ALAT ( Genetic testing confirmed the presence of the frequent Z variant of SERPINA1 at the heterozygous state, in the absence of AAT-related liver or pulmonary disease. Sitting office blood pressure was 160/50mmHg. Body mass index was 31.3kg/m 2 . Clinical examination was otherwise unremarkable. Mean day – and night-time ambulatory blood pressre were 142/58 and 115/43mmHg, respectively. Blood and urine analysis, urinary metanephrines and abdominal CT-angiography were normal. Echocardiography showed mild concentric left ventricular hypertrophy (LVMI : 134g/m 2 ). Carotid-femoral pulse wave velocity (SphygmoCor ® ) was markedly increased (14.2 m/s; age-adjusted reference values : 4.6–9.8 m/s). By contrast, detailed assessment of retinal and sublingual capillaries showed no evidence of microvascular dysfunction. Conclusions This case report suggests that increased arterial stiffness and isolated systolic hypertension are an integral part of the spectrum of AATD-related vascular abnormalities. Conversely, AATD may be considered in the differential diagnosis of resistant hypertension, especially in the presence of increased pulse pressure in a young patient. Future perspectives include indepth blood pressure and vascular characterization of a cohort of patients with both heterozygous and homozygous AATD.

Around-the-clock ambulatory blood pressure monitoring is required to properly diagnose resistant hypertension and assess associated vascular risk.

Diagnosis of resistant hypertension (RH) is currently based upon awake-time office blood pressure (BP). An increasing number of studies have documented abnormally elevated sleep-time BP in most RH patients, indicating that diagnosis of true RH cannot be determined solely by comparison of office BP with either patient awake-time BP self-measurements or awake-BP mean from ambulatory monitoring (ABPM), as is customary in the published literature. Moreover, the ABPM-determined sleep-time BP mean is an independent and stronger predictor of cardiovascular and cerebrovascular disease (CVD) risk than either daytime office/ABPM-derived awake or 24-hour means. Results of the recently completed MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares) prospective outcomes study, which included a large cohort of RH patients, established that time of treatment relative to circadian rhythms constituted a critically important yet often neglected variable with respect to BP control. The study found that bedtime versus morning ingestion of the full dose of ≥1 BP-lowering medications resulted in both better therapeutic normalization of sleep-time BP and reduced CVD morbidity and mortality, including in RH patients. Accordingly, ABPM is highly recommended to properly diagnose and manage true RH, with a bedtime hypertension medication regimen as the therapeutic scheme of choice.

Baroreflex activation therapy in hypertension

The sympathetic nervous system is an effective homeostatic mechanism for modulating hemodynamics in times of stress and illness. Unfortunately, in some patients, this mechanism escapes physiologic control and through various mechanisms leads to resistant hypertension. Antihypertensive drug therapy is successful only to a point, leaving a significant percentage of patients nationwide with blood pressure measurements above guidelines despite being treated with at least three agents at maximally tolerated doses, consistent with a diagnosis of resistant hypertension. Novel methods of modifying the activity of the sympathetic nervous system have been studied in animals, and this review discusses the data in support of one of the techniques at the forefront of non-pharmacologic blood pressure therapy.