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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
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Review Article
Hypertension (HTN) has reached a staggering gure all over
the world, and one in three adults in India is hypertensive.[1]
Resistant hypertension (RH) is dened as uncontrolled ofce
blood pressure (BP) >130/80 mmHg despite three different
groups of antihypertensive medications in optimum dose,
including one of the long-acting diuretics.[2] Studies show that
the prevalence of RH is 10% of total hypertensive patients.[3]
What are the caveatS of dIaGnoSIS of reSIStant
There are multiple caveats of diagnosis of RH.
1. SPRINT trial showed that benet of intensive lowering
of BP, especially in aged hypertensives with higher
cardiovascular risk,[4] has been the driving force behind
the American heart Association/ American College of
Cardiology (AHA/ACC) 2017 HTN guideline to set a
lower target (<130/80 mmHg) to achieve.[5] Accordingly,
the BP cutoff for diagnoses of RH has been changed from
<140/90 mmHg to <130/80 mmHg in 2017 guideline
2. Uncontrolled office BP has been used to define RH
according to the 2018 European Society of Cardiology
(ESC) guideline for HTN.[6] However, ambulatory BP
monitoring (ABPM) has revolutionized the essence of BP
lowering and stressed over 24-h control of BP including
at nighttime. ABPM has identied four subsets of RH
[Figure 1]. AHA/ACC and european society of cardiology
(ESC) suggest that ABPM is mandatory before diagnosing
RH to rule out white coat hypertension (WCH), which can
be as high as 20% of the RH group, and also to follow-up
the WCH patients.[6] Recently, there is growing evidence
Pseudo‑Resistant, Resistant, and Refractory Hypertension:
The Good, the Bad, and the Ugly
Dibbendhu Khanra, Bhanu Duggal
Department of Cardiology, All India Institution of Medical Sciences, Rishikesh, Uttarakhand, India
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 dened when ve 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 denitely 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.
Keywords: Ambulatory blood pressure monitoring, refractory hypertension, resistant hypertension
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Address for correspondence: Dr. Dibbendhu Khanra,
Department of Cardiology, All India Institute of Medical Sciences,
Rishikesh, Uttarakhand, India.
How to cite this article: Khanra D, Duggal B. Pseudo-resistant, resistant,
and refractory hypertension: The good, the bad, and the ugly. J Pract
Cardiovasc Sci 2019;5:76-80.
This is an open access journal, and arcles are distributed under the terms of the Creave
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Date of Submission : 02-May-2019
Date of Revision : 17-May-2019
Date of Acceptance : 28-May-2019
Date of Web Publication : 19-Aug-2019
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Khanra and Duggal: Resistant hypertension
Journal of the Practice of Cardiovascular Sciences ¦ Volume 5 ¦ Issue 2 ¦ May-August 2019 77
to support the use of home BP monitoring (HBPM)[7] for
6 times a day including nighttime BP and early morning
BP, which has been shown to have good correlation with
ABPM [Figure 2]
3. National Institute for Health and Care Excellence (NICE)
stressed upon using combination of angiotensin-converting
enzyme inhibitor/angiotensin receptor blockers, calcium
channel blockers, and diuretic (A + C + D) including a
long-acting thiazide. However, prescriptions of long-acting
thiazides such as chlorthalidone or spironolactone
have been found to be persistently low across the
spectrum of RH.[8] A recent study has reiterated the role
of chlorthalidone to reduce BP throughout the clock,
whereas hydrochlorothiazide (HCTZ) has turned resistant
hypertensive patients into masked HTN due to their
short-acting property.[8] PATHWAY 3 has shown that a
combination of amiloride with HCTZ was neutral for
glucose and K+ and reduced BP more than each single
diuretic.[9] Hence, in regard to a treatment RH, choosing
the correct diuretic is of supreme importance.
Secondary hyPertenSIon IS not aS Same aS
reSIStant hyPertenSIon
All hypertensive patients at the time of diagnosis must have a
thorough clinical history (for obstructive sleep apnea [OSA]
and history suggestive of pheochromocytoma), clinical
examinations (including peripheral pulses and abdominal mass),
and echocardiography (to rule out coarctation of the aorta)
and markers for connective tissue diseases (e.g., anti-nuclear
antibody). Figure 3 one of the most underrated causes of HTN is
OSA, and sleep study may clinch the diagnosis for the suspected
ones. Drugs such as nonsteroidal anti‑inammatory drugs and
oral contraceptive pills and other hormonal therapies including
steroids are also looked for while dealing with patients of RH.
Yamashita et al.[10] have developed PFK score which consists of
U pH >7, female sex, K <3.5, primary hyperaldosteronism can be
suspected if PFK scores are positive. Prescribing spironolactone ahs
been found to be useful in controlling hypertension in this subset.
It has been found that plasma renin is low across the
spectrum of RH, and PATHWAY 2 study demonstrated that
spironolactone was the most effective BP -lowering agent
throughout the distribution of baseline plasma renin, but it
was particularly effective in patients with lower rennin.[11]
However, changing antihypertensive medications according
to plasma rennin to plasma aldosterone ratio was intuitively
appealing but practically not feasible in most instances owing
to poor availability, standardization, and hyporeninemic
hypoaldosteronism in diabetes mellitus.
hoW to aPProach manaGement reSIStant
Studies have shown that 50% of the total RH patients are
actually having pseudo-RH and the rest 50% have true RH
(TRH), and it can be due to white coat effect, inaccurate BP
measurement, undertreatment, or medical nonadherence.[12]
Hence, whenever ofce BP is >140/90 with A + C + D regimen,
ABPM should be advised to rule out WCH and diuretics
should be changed to long-acting chlorthalidone. Accuracy
of BP measurement, adherence to prescribed medications, and
adequacy of prescribed dosages are to be ensured (Triple-A).
According to the NICE guideline, in RH patients, after A + C
+ D regimen, the fourth drug to be decided as per the serum
potassium (k) level. If k <4.5, a spironolactone has to be added,
whereas if k >4.5, either double the dose of thiazide or adding
a loop diuretic has been advised.[13]
can We IdentIfy the true reSIStant hyPertenSIon
and maSKed reSIStant hyPertenSIon at the
In a large community-based study of 8295 patients with RH
classied on the basis of ABPM, de la Sierra et al.[14] found that
Figure 2: Normal and abnormal pattern of ambulatory blood pressure
Figure 1: Spectrum of resistant hypertension as per ambulatory blood
pressure monitoring. RH: Resistant hypertension.
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Khanra and Duggal: Resistant hypertension
Journal of the Practice of Cardiovascular Sciences ¦ Volume 5 ¦ Issue 2 ¦ May-August 2019
true resistant hypertension patients who had longer duration
of uncontrolled hypertension and needed four or more drugs
to control BP, had a worse cardiovascular outcome. The group
included larger proportions of smokers, diabetics, target organ
damage (including left ventricular hypertrophy, impaired
renal function, and microalbuminuria), and documented
cardiovascular disease. Moreover, true resistant hypertensives
exhibited in a greater proportion of a riser pattern in ABPM.
In J-HOME study[15] proling of 3400 Japanese patients with
RH by HBPM, it has been found that compared to controlled
HTN, factors associated with isolated uncontrolled home HTN
included obesity, relatively higher ofce systolic BP (SBP),
habitual drinking, and the use of two or more prescribed
antihypertensive drugs. Compared to uncontrolled HTN,
factors associated with isolated uncontrolled ofce HTN
included female gender, lower body mass index, and relatively
lower ofce SBP. The presence of hypercholesterolemia was
found to have a signicant and independent association with
isolated ofce RH. Higher ofce SBP, past history of ischemic
heart disease, and lower prescription rate of potassium-sparing
diuretics were found to have a signicant and independent
association with isolated home RH. Patients with sustained RH
had a signicantly lower prescription rate of potassium‑sparing
diuretics than those with controlled HTN.
What IS “refractory hyPertenSIon:” IS It a
novel PhenotyPe?
One subset of TRH patients are not amenable to achievement of
target BP despite using ve different classes of antihypertensive
drugs, including a long-acting thiazide lke diuretic and
spironolactone. Acelajado et al. have coined them to have
'refractory hypertension (RfH).[16] They have found that 10% of
the truly RH patients are RfH and they have a dismal outcome
in terms of stroke and heart failure in comparison to TRH.
Dudenbostel et al. dened RfH as failure to achieve BP control
with treatment prescribed by HTN experts at a minimum of
three follow-up visits during at least 6 months of care, receiving
ve or more different antihypertensive medications, including
chlorthalidone and spironolactone. This stricter denition led
the researchers to have a prevalence of RfH as 4% in their
prospective study comprising 700 patients of TRH.[17]
Birmingham Hypertension Clinic at the University of Alabama
at has proposed a classication of HTN according to number
of drugs [Figure 4].[17] Dudenbostel et al. compared the prole
of RfH to TRH patients and found that RfH patients are younger
with low renin and high sympathetic activity [Figure 5].[17]
Figure 6 summarizes the approach to RH.
What can be the laSt reSort for refractory
hyPertenSIon PatIentS?
For the subset of RfH patients, transcatheter renal artery
denervation (RDN) has been studied. However, the surge
of initial enthusiasm was refuted in SIMPLICITY 3
study, where RDN was not found to be superior to a sham
procedure and medical therapy in reducing office and
ambulatory BP at 6 months. However, RDN has been found
to have greater benet in RfH patients with high mean BP
(>199 mmHg), age <65 years, and estimated glomerular
ltration rate >60 ml/min/m2.[18] However, recent studies such
HTN-ON MED and OFF MED showed the promising result of
Figure 4: Classification of hypertension according to number of drugs.
Figure 3: Causes of secondary hypertension.
Figure 5: Comparison of true resistant hypertension and refractory
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Khanra and Duggal: Resistant hypertension
Journal of the Practice of Cardiovascular Sciences ¦ Volume 5 ¦ Issue 2 ¦ May-August 2019 79
RDN, and the practice is rejuvenated with availability newer
SPYRAL catheter by Medtronic.[19,20]
Baroreceptor activation technique has been also studied in RfH
patients. Initial phase III Rheos Pivotal Trial on continuous
carotid baroreceptor pacing with RHEOS device for RH with
the rst‑generation baroreceptor pacemaker yielded equivocal
data on efcacy and adverse effects due to facial nerve injury
during surgical implantation.[21]
Creation of a central iliac arteriovenous anastomosis (cAV)
using a novel nitinol coupler device (ROX device) results in
an immediate, signicant reduction of BP. In ROX CONTROL
HTN study, extended follow-up of patients with uncontrolled
HTN treated with an iliac cAV anastomosis has demonstrated
durable ofce and ABP reduction with no newly identied
safety reports. The magnitude of ofce BP reduction that
was observed at 6-month follow-up was greater than that
reported after the use of renal denervation in TRH and also the
use of spironolactone as a fourth-line antihypertensive drug
strategy for TRH. However, after coupler therapy, one-third of
patients developed ipsilateral venous stenosis; all were treated
successfully with venous stenting.[22]
IndIan ScenarIo
In a study by Bharatia et al.,[23] 19.5% of hypertensive
patients were resistant to A + C + D combination. Eighty
percent of them were aged in the range of 46–65 years and
67.2% of patients were male. A higher proportion of patients
were residents of Andhra Pradesh (21.4% patients) and
Maharashtra (19.3% patients) in the aforesaid study. In a study
reported from Varanasi, the prevalence of HTN was found to
be staggering 32.9%. Out of the total hypertensive patients,
only 38.4% were aware of their HTN status; of those, 70.4%
were seeking treatment and 66% had their BP above target.[24]
In a study by Roy et al., it has been found that the prevalence
of HTN increased from 23.0% to 42.2% and 11.2% to 28.9%
in urban and rural National Capital Region, respectively,
over a span of two decades, irrespective of high education,
alcohol use, obesity, and high fasting blood glucose being
at a higher risk for HTN . Moreover, surprisingly, the study
showed that, overall, there was no improvement in awareness,
treatment, and control rates of HTN in the population.[25] In
a meta-analysis by Anchala et al., about 33% of urban and
25% of rural Indians were found to be hypertensive. Of these,
25% of rural and 42% of urban Indians were aware of their
hypertensive status. Only 25% of rural and 38% of urban
Indians were being treated for HTN. Only one-tenth of rural
and one‑fth of urban Indian hypertensive population had
their BP under control.[1] However, data on RH in India are
limited, and Narang and Srikant have elucidated the nuances
in the application of 2017 HTN guidelines for Indian patients
in their article.[26]
The actual prevalence of RH may be lower than what is
perceived in the literature when triple-A (accuracy of BP
measurement, adherence of medications, and adequacy
of anti-HTN medications) are ensured. It is important to
emphasize that the sea of RH starts when the shore of secondary
HTN is over and the island of RfH is still uncharted. RfH is
emerging as a novel phenotype, and growing evidence suggest
that these patients have sympathetic hyperactivity. However,
the role of beta-blockers and interventions such as RDN and
baroreceptor activation techniques is yet to be studied.
Ethics clearance
Ethical clearance taken.
Financial support and sponsorship
Conflicts of interest
There are no conicts of interest.
1. Anchala R, Kannuri NK, Pant H, Khan H, Franco OH, Di Angelantonio E,
et al. Hypertension in India: A systematic review and meta-analysis
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2. Guideline for the Prevention, Detection, Evaluation, and Management
of High Blood Pressure in Adults; 2017.
3. Abdalla M. Ambulatory blood pressure monitoring: A complementary
strategy for hypertension diagnosis and management in low-income and
middle-income countries. Cardiol Clin 2017;35:117-24.
4. Berlowitz DR, Foy CG, Kazis LE, Bolin LP, Conroy MB, Fitzpatrick P,
et al. Effect of intensive blood-pressure treatment on patient-reported
outcomes. N Engl J Med 2017;377:733-44.
5. Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM,
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7. George J, MacDonald T. Home blood pressure monitoring. Eur Cardiol
Figure 6: Approach to resistant hypertension.
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8. Pareek AK, Messerli FH, Chandurkar NB, Dharmadhikari SK,
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13. National Institute of Health and Care Excellence: Hypertension in
adults: diagnosis and management (CG127). 2016.
14. de la Sierra A, Segura J, Banegas JR, Gorostidi M, de la Cruz JJ,
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hypertension classied on the basis of ambulatory blood pressure
monitoring. Hypertension 2011;57:898-902.
15. Obara T, Ohkubo T, Asayama K, Metoki H, Inoue R, Kikuya M, et al.
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control: The J-HOME study. J Hum Hypertens 2008;22:197-204.
16. Acelajado MC, Pisoni R, Dudenbostel T, Dell’Italia LJ, Cartmill F,
Zhang B, et al. Refractory hypertension: Denition, prevalence, and
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17. Dudenbostel T, Siddiqui M, Gharpure N, Calhoun DA. Refractory
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19. Kandzari DE, Böhm M, Mahfoud F, Townsend RR, Weber MA,
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Lancet 2018;391:2346-55.
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22. Lobo MD, Ott C, Sobotka PA, Saxena M, Stanton A, Cockcroft JR, et al.
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23. Bharatia R, Chitale M, Saxena GN, Kumar RG, Chikkalingaiah,
Trailokya A, et al. Management practices in Indian patients with
uncontrolled hypertension. J Assoc Physicians India 2016;64:14-21.
24. Singh S, Shankar R, Singh GP. Prevalence and associated risk factors of
hypertension: A cross-sectional study in urban Varanasi. Int J Hypertens
25. Roy A, Praveen PA, Amarchand R, Ramakrishnan L, Gupta R, Kondal D,
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... Hence, the preparation of the patient, environmental conditions, size of the cuff and the techniques of blood pressure measurement can have a substantial influence on the blood pressure result. Studies have revealed that about 50% of the total resistant hypertensive patients are actually having pseudo-resistance hypertension and not resistant hypertension 11 Although, the prevalence of resistant hypertension is unknown but cross-sectional studies and hypertension outcome studies suggest that resistant hypertension is common 12,13 . In an analysis carried out by the National Health and Nutrition Examination Survey (NHANES), only 53% of the participants being treated for hypertension had their blood pressure controlled to less than 140/90 mmHg 14 . ...
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Background: Resistant hypertension is a common medical challenge facing clinicians and specialists. Although, the prevalence is currently unknown but various clinical trials have suggested that this problem is not rare. Resistant hypertension is blood pressure that remains above goal despite the use of at least three antihypertensive agents including a diuretic. It is a subtype of hypertension that increases the risk of cardiovascular, cerebrovascular and kidney disease. However, it is important to distinguish between pseudo-resistant hypertension and apparent hypertension from true resistant hypertension as they are often misdiagnosed. Objectives: This review focuses on resistant hypertension, its pathophysiology and established therapy. Methodology: Relevant articles used for this review covered a period of 2008-2022 using search engines and databases including PubMed, Scopus, Web of Science, and Google Scholar. Main observation: Evaluation of patients with true resistant hypertension includes appropriate blood pressure measurement, screening for causes of secondary hypertension and screening for interfering medications. Management of resistant hypertension that has proved successful includes non-pharmacological approach like lifestyle modification and optimization of pharmacological agents, often including the use of mineralocorticoid receptor antagonist. Conclusion: Considering the future management of resistant hypertension, a bunch of new device-based therapies are under effective development. Of these, renal denervation and carotid baroreflex activation are two potential devices for the significant reduction of blood pressure. However, further study is necessary before these devices can be approved for the routine treatment of resistant hypertension. Keywords: Aldosterone; Cardiovascular disease; Resistant Hypertension; Therapy.
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The new US blood pressure guideline lowers the definition of high blood pressure to 130/80 mm Hg.The new guideline adopts a key component of the 2013 cholesterol guideline and incorporates overall cardiovascular risk. The AAFP has decided to not endorse the recent hypertension guideline because it gave undue importance to the SPRINT trial and cardiovascular risk which was not validated and would lead to overtreatment. The guidelines are discussed in this article.
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Hypertension is a major public health problem and important area of research due to its high prevalence and being major risk factor for cardiovascular diseases and other complications. Objectives . (1) To assess the prevalence of hypertension and its associated factors and (2) to estimate awareness, treatment, and adequacy of control of hypertension among study subjects. Methods and Materials . A community based cross-sectional study with multistage sampling design was conducted among urban population of Varanasi. A modified WHO STEPS interview schedule on 640 study subjects aged 25–64 years was used. Results . The prevalence of hypertension was 32.9% (male: 40.9%, female: 26.0%). Mean systolic and diastolic BP were 124.25 ± 15.05 mmHg and 83.45 ± 9.49 mmHg, respectively. Higher odds of being hypertensive were found in male subjects, eldest age group, married subjects, subjects of upper socioeconomic status, illiterate subjects, and retired subjects. Tobacco and alcohol consumption, overweight, obesity, and abdominal obesity were also associated with hypertension. Out of the total hypertensive 211 subjects, only 81 (38.4%) were aware about their hypertension status; out of those, 57 (70.4%) were seeking treatment and 20 (35.08%) had their blood pressure adequately controlled. Conclusion . Around one-third of the subjects were hypertensive and half of the study subjects were prehypertensive in this area. The awareness, treatment, and control of high blood pressure were also very low.
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Creation of a central iliac arteriovenous anastomosis using a novel nitinol coupler device results in an immediate, significant reduction of blood pressure (BP). We present efficacy and safety findings at 12 months post-coupler insertion. This open-label, multicenter, prospective, randomized trial enrolled patients with a baseline office systolic BP ≥140 mm Hg and average daytime ambulatory BP ≥135/85 mm Hg. Subjects were randomly allocated to coupler implantation and continuing previous pharmacotherapy or to maintain previous treatment alone. At 12 months, 39 patients who had coupler therapy were included in the intention-to-treat analysis. Office-based systolic BP reduced by 25.1±23.3 mm Hg (baseline, 174±18 mm Hg; P<0.0001) post-coupler placement, and office diastolic BP reduced by 20.8±13.3 mm Hg (baseline, 100±13 mm Hg; P<0.0001). Mean 24-hour ambulatory BP reduced by 12.6±17.4/15.3±9.7 mm Hg (P<0.0001 for both). In a prespecified subset of patients who failed to respond adequately to prior renal denervation, coupler therapy led to highly significant reduction in office systolic/diastolic BP (30.7/24.1 mm Hg) and significant reduction in 24-hour ambulatory systolic/diastolic BP (12.4/14.4 mm Hg) at 12 months (n=9). After coupler therapy, 14 patients (33%) developed ipsilateral venous stenosis; all were treated successfully with venous stenting. These findings confirm the importance of arterial mechanics in the pathophysiology of hypertension and support the clinical use of a central iliac arteriovenous anastomosis. Clinical trial registration: URL: Unique identifier: NCT01642498.
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Resistant hypertension (RHTN) is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is defined as blood pressure (BP) >140/90 mmHg treated with >3antihypertensive medications, including a diuretic, if tolerated. Refractory hypertension is a novel phenotype of severe antihypertensive treatment failure. The proposed definition for refractory hypertension, i.e. BP >140/90 mmHg despite the use of >5 medications, including a diuretic and a mineralocorticoid receptor antagonist (MRA) has been applied inconsistently. In comparison to RHTN, refractory hypertension seems to be less prevalent than RHTN. This review focuses on current knowledge about this novel phenotype compared with RHTN including definition, prevalence, mechanisms, characteristics and comorbidities, including cardiovascular risk. In patients with RHTN excess fluid retention is thought to be a common mechanism for the development of RHTN. Recently, evidence has emerged suggesting that refractory hypertension may be more of neurogenic etiology due to increased sympathetic activity as opposed to excess fluid retention. Treatment recommendations for RHTN are generally based on use and intensification of diuretic therapy, especially with the combination of a long-acting thiazide-like diuretic and an MRA. Based on findings from available studies, such an approach does not seem to be a successful strategy to control BP in patients with refractory hypertension and effective sympathetic inhibition in such patients, either with medications and/or device based approaches may be needed.
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Background and objectives Despite being one of the leading risk factors of cardiovascular mortality, there are limited data on changes in hypertension burden and management from India. This study evaluates trend in the prevalence, awareness, treatment and control of hypertension in the urban and rural areas of India’s National Capital Region (NCR). Design and setting Two representative cross-sectional surveys were conducted in urban and rural areas (survey 1 (1991–1994); survey 2 (2010–2012)) of NCR using similar methodologies. Participants A total of 3048 (mean age: 46.8±9.0 years; 52.3% women) and 2052 (mean age: 46.5±8.4 years; 54.2% women) subjects of urban areas and 2487 (mean age: 46.6±8.8 years; 57.0% women) and 1917 (mean age: 46.5±8.5 years; 51.3% women) subjects of rural areas were included in survey 1 and survey 2, respectively. Primary and secondary outcome measures Hypertension was defined as per Joint National Committee VII guidelines. Structured questionnaire was used to measure the awareness and treatment status of hypertension. A mean systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg was defined as control of hypertension among the participants with hypertension. Results The age and sex standardised prevalence of hypertension increased from 23.0% to 42.2% (p<0.001) and 11.2% to 28.9% (p<0.001) in urban and rural NCR, respectively. In both surveys, those with high education, alcohol use, obesity and high fasting blood glucose were at a higher risk for hypertension. However, the change in hypertension prevalence between the surveys was independent of these risk factors (adjusted OR (95% CI): urban (2.3 (2.0 to 2.7)) rural (3.1 (2.4 to 4.0))). Overall, there was no improvement in awareness, treatment and control rates of hypertension in the population. Conclusion There was marked increase in prevalence of hypertension over two decades with no improvement in management.
Background: Previous catheter-based renal denervation studies have reported variable efficacy results. We aimed to evaluate safety and blood pressure response after renal denervation or sham control in patients with uncontrolled hypertension on antihypertensive medications with drug adherence testing. Methods: In this international, randomised, single-blind, sham-control, proof-of-concept trial, patients with uncontrolled hypertension (aged 20-80 years) were enrolled at 25 centres in the USA, Germany, Japan, UK, Australia, Austria, and Greece. Eligible patients had an office systolic blood pressure of between 150 mm Hg and 180 mm Hg and a diastolic blood pressure of 90 mm Hg or higher; a 24 h ambulatory systolic blood pressure of between 140 mm Hg and 170 mm Hg at second screening; and were on one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned to undergo renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were masked to randomisation assignments. The primary efficacy endpoint was blood pressure change from baseline (measured at screening visit two), based on ambulatory blood pressure measurements assessed at 6 months, as compared between treatment groups. Drug surveillance was used to assess medication adherence. The primary analysis was done in the intention-to-treat population. Safety events were assessed through 6 months as per major adverse events. This trial is registered with, number NCT02439775, and follow-up is ongoing. Findings: Between July 22, 2015, and June 14, 2017, 467 patients were screened and enrolled. This analysis presents results for the first 80 patients randomly assigned to renal denervation (n=38) and sham control (n=42). Office and 24 h ambulatory blood pressure decreased significantly from baseline to 6 months in the renal denervation group (mean baseline-adjusted treatment differences in 24 h systolic blood pressure -7·0 mm Hg, 95% CI -12·0 to -2·1; p=0·0059, 24 h diastolic blood pressure -4·3 mm Hg, -7·8 to -0·8; p=0.0174, office systolic blood pressure -6·6 mm Hg, -12·4 to -0·9; p=0·0250, and office diastolic blood pressure -4·2 mm Hg, -7·7 to -0·7; p=0·0190). The change in blood pressure was significantly greater at 6 months in the renal denervation group than the sham-control group for office systolic blood pressure (difference -6·8 mm Hg, 95% CI -12·5 to -1·1; p=0·0205), 24 h systolic blood pressure (difference -7·4 mm Hg, -12·5 to -2·3; p=0·0051), office diastolic blood pressure (difference -3·5 mm Hg, -7·0 to -0·0; p=0·0478), and 24 h diastolic blood pressure (difference -4·1 mm Hg, -7·8 to -0·4; p=0·0292). Evaluation of hourly changes in 24 h systolic blood pressure and diastolic blood pressure showed blood pressure reduction throughout 24 h for the renal denervation group. 3 month blood pressure reductions were not significantly different between groups. Medication adherence was about 60% and varied for individual patients throughout the study. No major adverse events were recorded in either group. Interpretation: Renal denervation in the main renal arteries and branches significantly reduced blood pressure compared with sham control with no major safety events. Incomplete medication adherence was common. Funding: Medtronic.
Background The previously published results of the Systolic Blood Pressure Intervention Trial showed that among participants with hypertension and an increased cardiovascular risk, but without diabetes, the rates of cardiovascular events were lower among those who were assigned to a target systolic blood pressure of less than 120 mm Hg (intensive treatment) than among those who were assigned to a target of less than 140 mm Hg (standard treatment). Whether such intensive treatment affected patient-reported outcomes was uncertain; those results from the trial are reported here. Methods We randomly assigned 9361 participants with hypertension to a systolic blood-pressure target of less than 120 mm Hg or a target of less than 140 mm Hg. Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), patient-reported satisfaction with their blood-pressure care and blood-pressure medications, and adherence to blood-pressure medications. We compared the scores in the intensive-treatment group with those in the standard-treatment group among all participants and among participants stratified according to physical and cognitive function. Results Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3 to 15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. No significant differences between the treatment groups were noted when participants were stratified according to baseline measures of physical or cognitive function. Satisfaction with blood-pressure care was high in both treatment groups, and we found no significant difference in adherence to blood-pressure medications. Conclusions Patient-reported outcomes among participants who received intensive treatment, which targeted a systolic blood pressure of less than 120 mm Hg, were similar to those among participants who received standard treatment, including among participants with decreased physical or cognitive function. (Funded by the National Institutes of Health; SPRINT number, NCT01206062.)
Objective: To develop and validate a scoring system for selection of patients who should proceed to endocrinologic examinations of primary aldosteronism in newly diagnosed hypertensive patients. Methods: A multivariate logistic regression analysis for primary aldosteronism was undertaken by use of seven possible primary aldosteronism markers, age less than 40 years, female sex, moderate-to-severe hypertension, hypokalemia, serum Na minus Cl at least 40 mmol/l, serum uric acid 237.92 μmol/l or less (4.0 mg/dl), and urine pH (U-pH) at least 7.0, in consecutive outpatients newly diagnosed with hypertension. The diagnostic criteria of primary aldosteronism were plasma aldosterone concentration-to-plasma renin activity ratio [ARR, (ng/dl)/(ng/ml per h)] at least 20 and at least one positive result in four types of challenge tests. Results: Of 130 patients, 24 were diagnosed with primary aldosteronism. The area under the receiver operating characteristic curve (AUC) for a logistic model incorporating all possible primary aldosteronism markers was 0.73 [95% confidence interval (CI): 0.61-0.85]. Removing high U-pH, female sex, and hypokalemia from the full model decreased the AUC by 0.059, 0.035, and 0.011, respectively. We devised pH of urine, female sex, low serum K (PFK) score, in which one point each was assigned to high U-pH, female sex, and hypokalemia. The prevalences of primary aldosteronism in patients with 0, 1, 2, and 3 points were 11, 14, 42, and 60%, respectively. In external validation datasets (n = 106), AUC of PFK score was significantly higher than that of hypokalemia alone (0.73, 95% CI: 0.63-0.83 vs. 0.53, 95% CI: 0.44-0.63, P < 0.01). Conclusion: PFK score may be a better parameter than hypokalemia alone for identifying patients with a high probability of having primary aldosteronism.