White-coat Resistant Hypertension Research Articles

Resistant Hypertension and Mortality: An Observational Cohort Study.

Resistant hypertension is characterized by elevated blood pressure (BP) despite using 3 antihypertensive agents. Ambulatory BP monitoring (ABPM) detects the presence of white-coat resistant hypertension (24-hour BP <130/80 mm Hg). The aim of the study was to evaluate risks of death in resistant hypertension compared with controlled hypertension, as well as in ABPM-confirmed (24-hour BP ≥130 or 80 mm Hg), versus white-coat resistant hypertension. We selected 8146 patients with controlled hypertension (office BP <140/90 mm Hg while being treated with ≤3 antihypertensive drugs) and 8577 with resistant hypertension (BP ≥140 or ≥90 mm Hg while being treated with ≥3 drugs). All-cause and cardiovascular mortalities (median follow-up, 9.7 years) were compared between groups, as well as between patients with white-coat (3289) and ABPM-confirmed (5288) resistant hypertension. Hazard ratios (HRs) from Cox models after adjustment for clinical confounders were used for comparisons. Compared with controlled hypertension, resistant hypertension was associated with an increased risk in all-cause (HR, 1.21 [95% CI, 1.12-1.30]) and cardiovascular mortalities (HR, 1.33 [95% CI, 1.17-1.51]) in confounder-adjusted models. Compared with white-coat, ABPM-confirmed resistant hypertension was associated with an increased risk of all-cause (HR, 1.45 [95% CI, 1.32-1.60]) and cardiovascular (HR, 1.68 [95% CI, 1.43-1.98]) mortalities. When ABPM-confirmed and white-coat resistant hypertension were separately compared with controlled hypertension, only the former was associated with an increased risk of death and cardiovascular death (HR, 1.36 [95% CI, 1.26-1.48] and 1.56 [95% CI, 1.36-1.79]), respectively. ABPM-confirmed resistant hypertension is associated with an increased risk of death and cardiovascular death with respect to both controlled hypertension and white-coat resistant hypertension.

PROGNOSIS OF RESISTANT HYPERTENSION, WHITE-COAT RESISTANT HYPERTENSION, AND REFRACTORY HYPERTENSION

Objective: To evaluate total and cardiovascular mortality in different forms of Resistant Hypertension (RH). Design and method: A total of 35129 treated patients were included from the Spanish ABPM Registry. Mean follow-up was 10 years. Total and cardiovascular mortality were compared in Cox models adjusted for clinical confounders. The following groups were compared: - Controlled Hypertension (CH; N = 8146; 23.2%): normal office BP treated with 3 or less antihypertensive drugs vs. RH (N = 9408; 26.8%): elevated office BP treated with 3 or more drugs or normal office BP treated with 4 or more drugs. - Controlled RH (CRH; N = 831; 8.8%): normal office BP treated with 4 or more drugs vs. Uncontrolled RH (UCRH; 8577; 91.2%): elevated office BP treated with 3 or more drugs. - Among patients with UCRH, the following groups were compared: True RH (TRH; 5288; 61.7%): elevated (&gt;130/80 mmHg) 24-h BP vs. White-coat RH (WCRH; 3289; 38.3%): normal 24-h BP. - Refractory hypertension (RefrH; 823; 8.7%): elevated office BP while treated with 5 or more drugs vs. Non-refractory RH (the remaining RH patients). Results: Compared to CH, RH was associated with an increased risk in total mortality (HR: 1.22; 95%CI: 1.13 - 1.31) and cardiovascular mortality (1.37; 1.21 - 1.55). Compared with CRH, UCRH was not associated with a significant increased risk in total or cardiovascular mortality. Compared to WCRH, TRH increased the risk of mortality (1.45; 1.32 - 1.60) and cardiovascular mortality (1.68 (1.43 - 1.98). Finally, RefrH also increased the risk of total mortality (1.16; 1.01 - 1.34) and cardiovascular mortality (1.30; 1.05 - 1.62) in comparison to non-refractory RH. Either total or cardiovascular mortality was not increased in WCRH, compared to CH. Conclusions: RH increased the risk of total and mortality with respect to CH. Among RH, office BP control does not modify such prognosis, while 24-h BP is a powerful determinant, with a clear increased risk in those with elevated 24-h BP (TRH), compared to those with normal 24-h BP (WCRH). The study confirms the clinical importance of RH, as well as the usefulness of ABPM in stratifying those patients, in order to improve therapeutical efforts to reduce the global risk.

Review on in vivo and in vitro experimental model of anti-hypertensive agent

We aimed to evaluate the use of specific antihypertensive drugs and drug classes, as well as combinations in patients treated with 3 or more drugs classified as having or not resistant hypertension (RH), controlled or uncontrolled RH and true versus white-coat RH. From the Spanish ABPM Registry, we identified 21238 patients treated with 3 (14264) or more (6974) antihypertensive drugs of different classes. Among patients treated with 3 drugs we compared those with controlled (&lt;140/90 mmHg; No RH) or uncontrolled (RH) office BP. In patients treated with 4 or more drugs we compared controlled versus uncontrolled RH. Hypertension continues to be an important public health concern because of its associated morbidity, mortality and economic impact on the society. It is a significant risk factor for cardiovascular, cerebrovascular and renal complications. It has been estimated that by 2025, 1.56 billion individuals will have hypertension. The increasing prevalence of hypertension and the continually increasing expense of its treatment influence the prescribing patterns among physicians and compliance to the treatment by the patients. A careful selection of drug therapy along with close follow-up offers the best prospect to reduce the burden of morbidity and mortality in hypertension. This article provides an overview of drugs in the management of patients with hypertension.

Depression and anxiety in different hypertension phenotypes: a cross-sectional study

BackgroundHypertension is a major risk factor of cardiovascular mortality. Mood disorders represent a growing public health problem worldwide. A complex relationship is present between mood disorders and cardiovascular diseases. However, less data is available about the level of depression and anxiety in different hypertension phenotypes. The aim of our study was to evaluate psychometric parameters in healthy controls (Cont), in patients with white-coat hypertension (WhHT), with chronic, non-resistant hypertension (non-ResHT), and with chronic, treatment-resistant hypertension (ResHT).MethodsIn a cross-sectional study setup 363 patients were included with the following distribution: 82 Cont, 44 WhHT, 200 non-ResHT and 37 ResHT. The patients completed the Beck Depression Inventory (BDI) and the Hamilton Anxiety Scale (HAM-A).ResultsBDI points were higher in WhHT (7 (3–11)) and ResHT (6 (3–11.5)) compared with Cont (3 (1–6), p < 0.05). Similarly, HAM-A points were higher in WhHT (8 (5–15)) and ResHT (10.5 (5.25–18.75)) compared with Cont (4 (1–7), p < 0.05) and also compared with non-ResHT (5 (2–10), p < 0.05). ResHT was independently associated with HAM-A scale equal or above 3 points (Beta = 3.804, 95%CI 1.204–12.015). WhHT was independently associated with HAM-A scale equal or above 2 points (Beta = 7.701, 95%CI 1.165–18.973) and BDI scale equal or above 5 points (Beta = 2.888, 95%CI 1.170–7.126).ConclusionsOur results suggest psychopathological similarities between white-coat hypertension and resistant hypertension. As recently it was demonstrated that white-coat hypertension is not a benign condition, our findings can have relevance for future interventional purposes to improve the outcome of these patients.

Pseudo and resistant hypertension: A chaotic perspective.

Systemic blood pressure (BP) may oscillate for homeostatic needs (equilibrium by constancy) or just as shifts in other intrinsic and extrinsic variables known as allostatic changes. This transitory pressure often rises alerts physicians to out‐of‐control hypertension or even hypertensive crisis. There is a very complex theory underlying these stochastic phenomena, which physicists and mathematicians translate into a single word: chaos. These changes happen according to a stochastic probabilistic pattern that presumes chaotic but somewhat predictable and nonlinear modeling of BP‐related dynamics as a mathematical approach. Based on the chaos theory, small changes at the initial BP (baseline overtime) values could disturb the homeostasis leading to extreme BP chaotic shifts. These almost insignificant oscillations may also affect other variables and systems, leading to the misdiagnosis of hypertension, “out‐of‐control” BP levels, and resistant hypertension (RHT). Thus, these unpredictable and transient increases in BP values may be improperly diagnosed as the white coat and masked or resistant hypertension. Indeed, the interference of the chaos in any phenotype of (true or false) hard to control BP is not considered in clinical settings. This review provides some basic concepts on chaos theory and BP regulation. Besides pseudoresistant hypertension (lack of adherence, circadian variations, and others (white‐coat, masked, early morning effects or hypertension), chaotic changes can be responsible for out‐of‐control hypertension.

Abstract 074: Use of Antihypertensive Drugs, Drug Classes, and Combinations in Resistant versus Non-resistant Hypertension, and in True versus White-coat Resistant Hypertension

We aimed to evaluate the use of specific antihypertensive drugs and drug classes, as well as combinations in patients treated with 3 or more drugs classified as having or not resistant hypertension (RH), controlled or uncontrolled RH and true versus white-coat RH. From the Spanish ABPM Registry, we identified 21238 patients treated with 3 (14264) or more (6974) antihypertensive drugs of different classes. Among patients treated with 3 drugs we compared those with controlled (&lt;140/90 mmHg; No RH) or uncontrolled (RH) office BP. In patients treated with 4 or more drugs we compared controlled versus uncontrolled RH. Moreover in uncontrolled RH patients, we compared those with white-coat (normal ABPM) versus true RH. We evaluated the use of different antihypertensive drug classes, specific antihypertensive drugs inside each class, and types of combinations. Results were adjusted for age, gender, and previous history of cardiovascular disease. With respect to RH treated with 3 drugs, those No RH used more frequently aldosterone antagonists (AA; Relative risk: 1.82; 1.40-2.37. They also used more frequently clorthalidone (CTL) among diuretics (RR: 1.54; 1.24-1.91), amlodipine (AML) among calcium channel blockers (CCB; RR: 1.12; 1.00-1.24) and bisoprolol (BIS) among beta blockers (RR: 1.18; 1.03-1.35). In patients treated with 4 or more drugs, controlled RH was also associated with the use of AA (RR: 1.41; 1.14-1.73) and AML (RR: 1.42; 1.25-1.62). No differences were observed in the type of combination used. When comparing patients with true versus white-coat RH, the latter group used more frequently diuretics (RR: 1.31; 1.16-1.47), CTL (RR: 1.79; 1.48-2.16) among diuretics, and AML (RR: 1.44; 1.32-1.57) among CCB. The triple combination of RAS blockers, CCB, and diuretics was also more frequently used in those with white-coat RH (RR: 1.09; 1.00-1.19). In conclusion, controlled office BP among patients treated with 3 or more drugs is associated with AA, CTL, and AML use. White-coat RH is associated with more diuretic use, especially CTL, AML, and the combination of RAS blockers, CCB, and diuretics. These results support the use of such triple combination, preferably including CTL and AML, and the addition of AA in order to reduce the prevalence of RH and true RH.

PP.25.27] REFRACTORY HYPERTENSION

Objective: The term refractory hypertension has been recently proposed for a small group of patients with uncontrolled hypertension despite the simultaneous use of >=5 different drug classes. To assess the prevalence of true refractory hypertension and their associated factors in comparison with resistant hypertension. Design and method: The present analysis was conducted from the Spanish Ambulatory Blood pressure monitoring (ABPM) Registry database containing 70997 treated patients who had enough information regarding office BP measurements, ABPM of good quality and complete clinical information. Blood pressure was measured at the office with a validate oscillometric device after 5-minute rest in a sitting position, and office BP estimated as the mean of 2 readings. 24h-ABPM was performed using the Spacelabs 90207 automated non-invasive oscillometric device, programmed to register BP at 20 minutes interval for the 24-hour period. Results: A total of 11.972 (16.9%) patients fulfilled the standard criteria of resistant hypertension (Office BP >= 140 and/or 90 mm Hg) despite the use of >=3 antihypertensive drugs, and 955 (1.35%) were considered as having refractory hypertension (elevated office BP despite the simultaneous use of >=5 antihypertensive agents). The prevalence of white coat (24-hour BP < 130/80 mm Hg) refractory hypertension was lower than white-coat resistant hypertension (26.7% vs 37.1%, p < 0,0001. Compared with resistant hypertension, patients with refractory hypertension had a significantly higher prevalence of diabetes mellitus (48.1% vs 33.5%; p < 0.001), and obesity (59.6% vs 51.4%; p < 0.001), and a longer duration of hypertension (13.9 vs 10.9 years; p < 0.0001). The prevalence of microalbuminuria (38.5% vs 24.5%; p < 0.0001), ECG-left ventricular hypertrophy(27.6% vs 14.9%; p < 0.0001), and previous history of a cardiovascular event (20.5% vs 14.9%;p < 0.0001) were also significantly higher in refractory, compared to resistant hypertension. Conclusions: The prevalence of refractory hypertension is low. Compared with resistant hypertension, patients with refractory hypertension have more frequently target organ damage, a higher prevalence of diabetes and a longer duration of hypertension.

Blood Pressure Monitoring in Cardiovascular Disease

While the practice of taking blood pressure readings at the physician’s office continues to be valid, home blood pressure monitoring is being increasingly used to enhance diagnostic accuracy and ensure a more personalized follow-up of patients. In the case of white coat hypertension and resistant arterial hypertension, ambulatory blood pressure monitoring is indispensable. Recent studies attach great importance to nocturnal blood pressure patterns, with a reduction in these becoming a treatment goal, a strategy known as chronotherapy. Home blood pressure monitoring is useful for both diagnosis and follow-up of arterial hypertension. Its use, particularly if combined with other patient-support interventions, serves to improve blood pressure control. Telemonitoring is associated with a decrease in blood pressure values and an increase in patient satisfaction. All studies highlight the importance of patients being supported by a multidisciplinary health care team, since blood pressure telemonitoring with a support team is more effective than simple data telemonitoring. Further studies are called for, especially on the illiterate population, with difficulties posed by technological accessibility and transcriptions into different languages. More cost-effectiveness studies and long-term results are needed to ascertain the true benefit of blood pressure telemonitoring.

Prognostic Importance of Ambulatory Blood Pressure Monitoring in Resistant Hypertension: Is It All that Matters?

This article reviews the current knowledge on the prognostic importance of ambulatory blood pressure (BP) monitoring parameters in patients with apparent treatment-resistant hypertension. Although mean 24-h ambulatory BPs have been consistently established as better cardiovascular risk predictors than clinic (office) BPs in several clinical settings, and ambulatory BP monitoring is generally indicated in patients with resistant hypertension; there were only five previous longitudinal prospective studies that specifically evaluated the prognostic importance of ambulatory BP monitoring parameters in resistant hypertensive patients. These studies are carefully reviewed here. In conjunction, they demonstrated that office BP levels have little, if any, prognostic value in resistant hypertensive patients. Otherwise, several ambulatory BP monitoring parameters are strong cardiovascular risk predictors, particularly nighttime sleep BPs and the non-dipping pattern. Most relevant, the ambulatory BP monitoring diagnosis of true resistant hypertension (i.e., patients with uncontrolled ambulatory BPs, either daytime or nighttime) doubled the risk of future occurrence of major cardiovascular events in contrast to patients with white-coat resistant hypertension (i.e., with controlled ambulatory BPs despite uncontrolled office BPs). This review reinforces the pivotal role of serial ambulatory BP monitoring examinations in the clinical management of patients with resistant hypertension.

A randomized controlled study of CPAP effect on plasma aldosterone concentration in patients with resistant hypertension and obstructive sleep apnea.

The high prevalence of obstructive sleep apnea in patients with resistant hypertension could be mediated by an activation of the renin-angiotensin-aldosterone system. This study assessed the impact of continuous positive airway pressure (CPAP) treatment on plasma aldosterone concentration (PAC). One hundred and twenty-four patients with resistant hypertension were assessed, and those who fulfilled inclusion criteria (n = 116) underwent full night polysomnography, 24-h ambulatory blood pressure monitoring, and PAC measurement. Patients with an apnea-hypopnea index above 15 (n = 102) were randomized to CPAP (n = 50) or to conventional treatment (n = 52) for 3 months. Seventy-eight patients completed the follow-up (36 CPAP, 42 conventional treatment); 58 had true resistant hypertension (74.3%), whereas 20 had white-coat resistant hypertension (25.6%). Most patients were men (70.7%), age 58.3 ± 9.4 years, and the mean apnea-hypopnea index was 50.1 ± 21.6. In patients with true resistant hypertension, CPAP achieved a significant decrease in most 24-h BP measurements and a nonsignificant decrease in PAC (25 ± 8.7 vs. 22.7 ± 9 ng/dl; P < 0.182). In patients with white-coat resistant hypertension, CPAP achieved a significant decrease in PAC (26.1 ± 11.2 vs. 18.9 ± 10.1 ng/dl; P < 0.041) and in night-time DBP. After adjustment, a weak but significant association was found between cumulative time spent with SaO2 below 90% (CT90%) and baseline PAC (P < 0.047, R 0.019), and between changes in PAC and changes in office DBP (P < 0.020, R 0.083) CONCLUSIONS:: Night-time hypoxemia and changes in DBP showed an association with baseline and changes in PAC, respectively. CPAP achieved a significant reduction in PAC only in patients with white-coat resistant hypertension, although the CPAP effect on BP was highest in patients with true resistant hypertension.

Heart rate and heart rate variability in resistant versus controlled hypertension and in true versus white-coat resistance

Sympathetic nervous system has an important role in resistant hypertension. Heart rate (HR) is a marker of sympathetic activity, but its association with resistant hypertension has not been assessed. We aimed to evaluate differences in HR values and variability between resistant and controlled patients and between true and white-coat resistant hypertensives (RHs). We compared office and ambulatory HR, nocturnal dip and s.d. in 14,627 RHs versus 11,951 controlled patients (on ⩽ 3 drugs) and in 8730 true (24 h blood pressure (BP) ⩾ 130 and/or 80 mm Hg) versus 4825 white-coat (24-h BP < 130/80 mm Hg) RHs. After adjusting for age, gender, body mass index, diabetes status and beta blocker use, HR values and variability were significantly elevated in resistant versus controlled patients and in true versus white-coat RHs. In logistic regression models, after adjustment for confounders, office HR (odds ratio for each increase in tertile: 1.337; 95% confidence interval: 1.287-1.388; P < 0.001), nocturnal dip (0.958; 0.918-0.999; P = 0.035) and night time s.d. (1.115; 1.057-1.177; P = 0.013) were all significantly associated with the presence of resistant hypertension. Moreover, night time HR (1.160; 1.065-1.265; P < 0.001), nocturnal dip (0.876; 0.830-0.925; P < 0.001) and 24-h s.d. (1.148; 1.092-1.207; P < 0.001) were all significantly associated with true resistant hypertension. In conclusion, both increased HR and variability are associated with resistant hypertension and with true resistance. These suggest the involvement of the sympathetic nervous system in the development of resistance to antihypertensive treatment.

Abstract 64: Heart Rate Values and Variability in Controlled versus Resistant Hypertensive Patients and in True versus False Resistant Hypertensives

Sympathetic nervous system seems to play an important role in resistant hypertension (RH) as both renal denervation and baroreflex stimulation reduce BP in such patients. Heart rate (HR) is an indirect, but probably the only clinical marker of sympathetic activity which can be measured in every hypertensive. We aimed to evaluate differences in clinical and ambulatory HR, as well as in HR variability between RH and those controlled on therapy. Moreover, we examined differences among RH patients, depending on ABPM normalcy. We included 14627 RH (uncontrolled with 3 drugs or treated with ≥ 4 drugs) versus 11951 controlled patients (on ≤ 3 drugs). Moreover, among 13555 patients uncontrolled with ≥ 3 drugs, we compared those with elevated 24h BP (≥ 130 and/or 80 mmHg; 8730 true-RH) versus those with normal 24-h BP (&lt;130/80 mmHg; 4825 white-coat RH). Variables analyzed were office, 24-h, daytime and nighttime HR, and HR variability (nocturnal HR dip, SD and coefficient of variation of HR). After adjusting for age, gender and the use of beta blockers, HR values and variability were slightly, but significantly elevated in RH vs controlled patients and in true vs false RH (Table shows adjusted means±sem). In logistic regression models a blunted HR dip and elevated HR-SD increased the risk of having RH, whereas elevated nocturnal HR, HR-SD and a blunted HR dip were associated with true RH. In conclusion, RH present increased HR variability, whereas night HR and increased variability are both associated with true RH. The increase in HR and HR variability may suggest the involvement of the sympathetic nervous system in the development of resistance to antihypertensive treatment.

Resistant hypertension: patient characteristics, risk factors, co-morbidities and outcomes

Among the vast population of hypertensive subjects, between 10 and 15% do not achieve an adequate blood pressure (BP) control despite the use of at least three antihypertensive agents. This group, designated as having resistant hypertension (RH), represents one of the most important clinical challenges in hypertension evaluation and management. Resistant hypertensives are characterized by several clinical particularities, such as a longer history of hypertension, obesity and other accompanying factors, such as diabetes, left ventricular hypertrophy, albuminuria and renal dysfunction. In addition to other diagnostic and therapeutic maneuvers, such as excluding secondary hypertension, ensuring treatment adherence and optimizing therapeutic schemes, ambulatory BP monitoring (ABPM) is crucial in the clinical evaluation of patients with RH. ABPM distinguish between those with out-of-office BP elevation (true resistant hypertensives) and those having white-coat RH (WCRH; normalcy of 24-h BPs), the prevalence of the latter estimated in about one-third of the population with RH. True resistant hypertensives also exhibit more frequently other co-morbidities, more severe target organ damage and a worse cardiovascular prognosis, in comparison to those with WCRH. Some device-based therapies have recently been developed for treatment of RH. This requires a better characterization of a potential candidate population. A better knowledge of the clinical features of resistant hypertensive subjects, the confirmation of elevated BP values out of the doctor's office, and improvements in the search for secondary causes would help to select those candidates for newer therapies, once the pharmacological possibilities have been exhausted.

Resistant hypertension: a practical clinical approach

Resistant hypertension (RH) is defined as an uncontrolled office blood pressure (BP) despite the use of at least three antihypertensive drugs. With an increasing prevalence, RH implies in a very high cardiovascular risk and needs a careful clinical approach, aiming to control BP and to reduce its morbidity and mortality. The initial diagnostic approach involves drug adherence checking and the evaluation of antihypertensive scheme, emphasizing the use of diuretics and adequate combination and dosages of the two other drugs, which preferentially reduces cardiovascular risk and promotes prevention/regression of target organ damages. Because of an exaggerated white-coat effect, ambulatory BP monitoring (ABPM) at baseline is mandatory to classify patients into true RH (uncontrolled ambulatory BPs) and white-coat RH (controlled ambulatory BPs), and define initial therapeutic approach. Ideally, the objective is ambulatory BP control, so the treatment follow-up shall be based on ABPM measurements. The treatment involves lifestyle changes and use of adequate combinations of antihypertensive agents from different classes. In this way, patients with true RH need to intensify antihypertensive treatment by adding aldosterone antagonists as the fourth drug and also changing antihypertensive treatment to bedtime. Otherwise, in patients with controlled ambulatory BP, the therapeutic scheme should be maintained and ABPM or home BP monitoring repeated serially. Despite pharmacological interventions, ambulatory BP control in RH patients remains challenging and new interventional procedures have been recently proposed, as renal denervation and baroreflex activation therapy. Currently, these procedures shall be reserved to true RH patients in whom other alternatives have failed.

Profile of ambulatory blood pressure in resistant hypertension

Resistant hypertension (HT) is a condition that confers a high cardiovascular risk to the patient due to both persistent blood pressure elevation and the high prevalence of comorbidities and organ damage. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and follow-up of the hypertensive patient, and it is even more important in the evaluation of those with resistant HT. Data from the Spanish ABPM Registry have allowed the comparison between large groups of resistant hypertensive patients seen in daily life and those controlled on antihypertensive treatment, as well as in resistant hypertensive patients who are classified based on ambulatory blood pressure values. In comparison with controlled patients, the cohort of resistant hypertensives has a worse circadian profile with a high proportion of nondipping, but also stark differences between office and ambulatory blood pressures. This enhanced white-coat effect was responsible for more than one-third of resistant hypertensive patients having normal 24-h blood pressures. Clinical data, including comorbidities, organ damage and circadian patterns, suggest a lower cardiovascular risk among white-coat resistant hypertensives. This finding was in agreement with longitudinal studies in smaller cohorts, suggesting fewer cardiovascular events and less mortality. In summary, it seems reasonable to routinely use ABPM in the initial evaluation of all resistant hypertensive patients. In a significant number of these patients, ABPM will also be an essential tool in follow-up, especially regarding the possible effects of all therapeutic maneuvers that are devoted to bringing blood pressure into target ranges.

New Developments in the Diagnosis and Management of Resistant Hypertension

Arterial hypertension is a well-known disease with a worldwide high prevalence and impaired prognosis with respect to normotensive subjects, due to increased cardiovascular mortality and morbidity. Blood pressure levels over range can be successfully controlled with adequate treatment, but more than 10% of hypertensive people have their blood pressure uncontrolled despite a therapeutic regimen of 3 or more antihypertensive drugs. These patients, named to have resistant hypertension, have a worse cardiovascular prognosis than controlled hypertensive subjects. Twenty-four hour-ambulatory blood pressure monitoring (ABPM) reveals that at least one third of these patients have indeed white-coat resistant hypertension, a rather more benign entity. In view of this evidence, performance of 24 h-ABPM is mandatory and to document the occurrence of subclinical target organ damage in this population before the development of cardiovascular disease is needed. This would help the physician to more rigorously implement adequate measures to control hypertension. On the other hand, the definition itself of the disease implies that conventional pharmacological treatment is not effective enough for these patients to reach normal blood pressure values. To treat resistant hypertensives, recent reports pay attention to the need to recover traditional treatments--either non-pharmacologic such as strict sodium diet restriction or pharmacologic such as the use of aldosterone receptor blockers--or to implement those treatments that are novelties, such as renal sympathetic nervous system ablation or carotid barorreceptors stimulation. This review focuses on outlining the current evidence about the diagnostic confirmation of resistant hypertension, the need to characterize these patients through 24 h-ABPM, to identify the presence of subclinical target organ damage, and to deal with not only classical but also novel treatment approaches for blood pressure control.

Appropriate Time Interval to Repeat Ambulatory Blood Pressure Monitoring in Patients With White-Coat Resistant Hypertension

Resistant hypertension is defined as uncontrolled office blood pressure, despite the use of ≥3 antihypertensive drugs. Ambulatory blood pressure monitoring (ABPM) is mandatory to diagnose 2 different groups, those with true and white-coat resistant hypertension. Patients are found to change categories between controlled/uncontrolled ambulatory pressures without changing their office blood pressures. In this way, ABPM should be periodically repeated. The aim of this study was to evaluate the most appropriate time interval to repeat ABPM to assure sustained blood pressure control in patients with white-coat resistant hypertension. This prospective study enrolled 198 patients (69% women; mean age: 68.9±9.9 years) diagnosed as white-coat resistant hypertension on ABPM. Patients were submitted to a second confirmatory examination 3 months later and repeated twice at 6-month intervals. Statistical analyses included Bland-Altman repeatability coefficients and multivariate logistic regression. Mean office blood pressure was 163±20/84±17 mm Hg, and mean 24-hour blood pressure was 118±8/66±7 mm Hg. White-coat resistant hypertension diagnosis presented a moderate reproducibility and was confirmed in 144 patients after 3 months. In the third and fourth ABPMs, 74% and 79% of patients sustained the diagnosis. In multivariate regression, a daytime systolic blood pressure ≤115 mm Hg in the confirmatory ABPM triplicated the chance of white-coat resistant hypertension status persistence after 1 year. In conclusion, a confirmatory ABPM is necessary after 3 months of the first white-coat-resistant hypertension diagnosis, and the procedure should be repeated at 6-month intervals, except in patients with daytime systolic blood pressure ≤115 mm Hg, in whom it may be repeated annually.

Abnormalities of vascular function in resistant hypertension

We aimed to evaluate markers of vascular dysfunction in patients with resistant hypertension (RH). A group of 144 patients (61 years, 42% women) with essential RH were divided in two groups based on ambulatory blood pressure monitoring (ABPM). True RH (72%) was considered when 24-h blood pressure (BP) was ≥ 130 and/or 80 mmHg. Otherwise, patients were classified as white coat RH (28%). Hyperemia-induced forearm vasodilation (HIFV), serum inflammatory biomarkers (hs-CRP, s-ICAM-1, s-VCAM-1, e-selectin, p-selectin and MCP-1) and large (C1) and small arterial (C2) compliance (HDI/Pulse Wave CR 2000) were determined in all individuals. In comparison with patients with white coat RH, and after adjustment for age, office systolic BP and diabetes status, those with true RH had a more impaired HIFV (201 ± 159 vs 436 ± 157%; p < 0.001), increased e-selectin (53.1 ± 29.8 vs 40.7 ± 23.5 ng/ml; p = 0.035), and MCP-1 (445 ± 120 vs 386 ± 126 ng/ml; p = 0.027). No significant differences were observed in arterial compliance. Maximal HIFV inversely correlated with urinary albumin excretion (Rho: − 0.278; p = 0.004) and with some inflammatory biomarkers (MCP-1: − 0.441; p < 0.001, e-selectin: − 0.468; p < 0.001 and p-selectin: − 0.329; p = 0.001). We conclude that true RH, diagnosed by ABPM, is associated with a more severe degree of vascular dysfunction, as measured by HIFV and serum biomarkers, whereas other types of vascular alterations, such as compliance, are not directly linked with the level of BP.

Response to Bedtime Hypertension Treatment Increases Ambulatory Blood Pressure Control and Reduces Cardiovascular Risk in Resistant Hypertension

We have read with interest the letter from Ayala et al1 concerning our article on resistant hypertension (RH).2 The first comment concerns a possible overestimation of white-coat RH by using 24-hour blood pressure (BP) as the criteria for definition of true and white-coat RH. Ayala et al1 stated that patients on ≥4 medications were true RH, and they should not be considered as having white-coat RH, even if 24-hour BP was normal. As contained in the American Heart Association definition, RH is a condition where patients remain above BP target despite the use of ≥3 medications.3 The inclusion in the definition of patients on ≥4 medications with normal clinic BP understands that these patients have been uptitrated to 4 medications because of …

Subtypes of Resistant Hypertension Based on Out-of-Office Blood Pressure Measurement

To the Editor: We read with considerable interest the article by de la Sierra et al1 clarifying the prevalence and clinical features of resistant hypertension based on office and ambulatory blood pressure (BP) monitoring in a large cohort of treated hypertensive patients in Spain. The prevalence of white-coat resistant hypertension (24-hour ambulatory BP <130/80 mm Hg for systolic/diastolic) and true resistant hypertension (24-hour ambulatory BP ≥130 and/or 80 mm Hg) was 37.5% and 62.5% among patients with uncontrolled office BP (≥140 and/or 90 mm Hg) and taking ≥3 antihypertensive drugs. They also demonstrated a difference in characteristics between white-coat and true resistant hypertension. These findings indicate that physicians …