Deranged Resistant Blood Pressure- Challenges of Tailoring Medications!

Research Article | DOI: https://doi.org/10.31579/2693-4779/209

Deranged Resistant Blood Pressure- Challenges of Tailoring Medications!

  • Suresh Kishanrao *

Public Health Consultant, Bengaluru, India.

*Corresponding Author: Suresh Kishanrao, Public Health Consultant, Bengaluru, India.

Citation: Suresh Kishanrao, (2024), Deranged Resistant Blood Pressure- Challenges of Tailoring Medications!, Clinical Research and Clinical Trials, 10(3); DOI:10.31579/2693-4779/209

Copyright: © 2024, Suresh Kishanrao. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 28 May 2024 | Accepted: 20 June 2024 | Published: 02 August 2024

Keywords: antihypertensive agents; blood pressure; clinical protocols; hypertension; hypotension, treatment outcome

Abstract

Deranged blood pressure is a condition where an individual is hypertensive or Hypotensive. Hypertensive is a person over the age of 18 years with a systolic pressure reading of 140 mmHg or more or a diastolic reading of 90 mmHg or more as suggested by WHO. Similarly, a systolic BP lower than 90 mm Hg or a Diastolic BP of less than 60 mm Hg” is considered as Hypotension. European Society of Hypertension has tried to minimize the differences among multiple recommendations in 2023 and recommended ESH guidelines for management of arterial hypertension based on Hypertension disease staging and other risk factors like i) Hypertension mediated organ damage (HMOD), ii) cardiovascular disease, iii) diabetes and iv) chronic kidney disease.  HMOD refers to structural or functional changes in arteries or target organs that can be present in long-standing hypertension but found in never treated patients at the first consultation and diagnosis. Current management strategies are based on the association of Hypertension with the complications identified at the time of first diagnosis, contrary to age old belief of initiating mono-drug therapy initially and adding additional drugs if the response is poor.

Materials and Methods: 

This article aims to familiarise the Primary care providers and readers with the evaluation and management of resistant hypertension by discussing a recent patient’s case report of the struggle for last 6 months in author’s care, including consultations with a Nephrologist & a cardiologist, and lessons learnt of the most recent therapeutic approaches.

Treatment Outcome: It has taken more than 9 months from August 2023 till May 2024, to stabilize the patient’s (HTN, CVD &CKD) BP in recommended ranges.

Abbreviation

SBP=Systolic Blood Pressure, DBP= Diastolic Blood Pressure Hypertension= HTN = Hypertension, HOT= Hypotension, NFHS= National Family Health Survey, LFT= Liver function Test, KFT= Kidney Function Test. CKD- chronic kidney disease, ACEi= Angiotensin-converting enzyme (ACE) inhibitors, ARB= Angiotensin II Receptor Blockers (ARB), DHP= 1,4-dihydropyridine (DHP), CCB= calcium channel blocker, WHO= World Health Organization, ESH= European Society of Hypertension , ICMR= Indian Council of Medical Research.

Introduction

Hypertensives (or High Blood Pressure) is defined as persons 18 years of age and over with a systolic pressure reading of 140 mmHg or more or a diastolic reading of 90 mmHg or more, or those taking antihypertensive medications. Between 90-95% of cases are essential hypertension with no identifiable cause. The remaining cases of hypertension are secondary to a distinguishable process and would likely resolve if the underlying condition was treated. According to a 2023 report from the World Health Organization (WHO), hypertension is the most important preventable causes among the leading risk factors for death and disability worldwide. The number of people with hypertension doubled from 650 million to 1.3 billion from 1990 to 2019 globally. In their 2023 report WHO infers that high systolic BP (≥ 110-115 mm Hg) is the single most important risk factor for early death worldwide, causing more loss of life than even high blood glucose and tobacco use. However, of all adults with hypertension, only 54% receive a diagnosis, 42% receive treatment, and 21% have controlled hypertension despite growing numbers of safe, effective treatments.  In 2021, it contributed to 10.8 million cardiovascular deaths globally.

Hypertension is widely encountered in family medicine. Despite its prevalence, some people have uncontrolled or difficult-to-control blood pressure. Resistant hypertension is defined as hypertension that is poorly responsive to treatment and requires the use of multiple medications to achieve acceptable blood pressure ranges. Primary Care Physicians use the word “Resistant hypertension “when the blood pressure remains above 140/90 mmHg despite optimal use of three antihypertensive medications of different classes, including a diuretic [1]. Resistant hypertension may be a consequence of secondary hypertension or have no identifiable cause, but it is important to recognise as it places patients at risk of end-organ damage. 
Burden of HT in India: The prevalence of hypertension as per the National Family Health Survey Series Five (NFHS-5) was 21% of females aged over 15 years had hypertension compared to 24% of males of the same age range, as estimated in NFHS-5 (2019-2021) [3] as compared to 18.1% in 2015-2016 (NFHS 4) [2]. Empirical calculations using these data show that the number of patients with hypertension in India is currently about 200–250 million. The overall prevalence of hypertension is significantly higher (300–320 million) in the recently reported ICMR-INDIAB study as compared to other nationwide studies {[2] Feb 2024}. In India, 28% of adults (18+) suffer from hypertension, numbering to 250 million, 90% of them don’t get treatment, as 70% of cases are undiagnosed, and about 12% among the treated are ineffective to keep their hypertension within normal range. a recent large-scale study found [4]. Undiscovered and untreated, hypertension significantly increases the risk of developing cardiovascular, brain, and kidney diseases. A considerable number of patients fail to reach target blood pressure ranges despite lifestyle advice and standard medical therapy. 

This article aims to familiarise the Primary care providers and readers with the evaluation and management of resistant hypertension by discussing a patient’s case report of the struggle for last 6 months in my care and seeking a Nephrologist and a cardiologist’s consultations and lessons learnt of the most recent therapeutic approach for hypertension management. 

Case Report

S Joshi, a 73-year-old male, sales executive was identified as hypertensive for the first time in January 2022. Due Rheumatoid arthritis of both knees his mobility was restricted since last 5 years, leading to hindering his freelance sales executive work. The wife also retired as private school teacher around 2020 and the family’s financial position was just enough to manage day to day life. She is also a known diabetic for last 20 years. The couple did not have any children which was another cause of psychological tension.

The local practitioner put him on Tab Cardace 2.5 mg {(an 'Angiotensin-Converting Enzyme (ACE) Inhibitors'} once a day in the morning when first diagnosed in January 2022. After 3 months observation the dose had to be increased 5mg per day and again 5 mg Twice day in June 2022. The BP was under control till December 2022, but he noticed a bit of swelling in lower limbs, for which he was give diuretic Tab Lasix (Furosemide a loop diuretic) to treat pedal oedema for about 10 days and then discontinued. For another 6 months he was maintaining the BP. In June 2023 He observed the oedema again and consulted me this time.

I first measured in sitting position, on both arms which were L= 180/110 mm Hg, R= 172/98 mm Hg. Repeated the measurements again after 10 minutes and got similar readings. Considering the arm with the higher systolic BP readings (180/110), I confirmed that the therapy given was not adequate. Ruled out any postural hypertension after measuring BP three times, at 1 min intervals, after 5 min of seated, supine and on standing, using an automated cuff sphygmomanometer. I had put him on   1) Embeta (Metoprolol Succinate with extended release) XR 25 mg once in the morning after breakfast (BF) (Which relaxes the blood vessels, slowing down the heart rate, and reduces the workload on the heart of pumping the blood effectively) 2) Lasix 20 mg in the morning after BF SOS (whenever oedema was noticed) and Tab. Anatensol 1 mg (used to treat depression). 

He was doing well but in September 2023 he his oedema over feet increased up to knees. This time I suggested a Nephrologist consultation to rule out chronic kidney disease (CKD). A battery of investigations confirmed CKD.

21 September 2023: Nephrologist Consultation: BP = 175/95, Heart Rate= 95/min, 

Tests done                 Value                      

(Parenthesis indicate Reference Value) 

  1. Serum Electrolytes:  a) Sodium=144.4 mmol/L (135-145) b) Potassium = 3.97(3.5-5.5) c) Chloride = 104.4 (94-110)
  2.  Hb1Ac= 5.0 (<5 eAG)=96.8>
  3. Serum Creatinine = 2.06 (0.7-1.3)
  4. Serum Lipid Profile a) Total Cholesterol= 175 mf /L (<200>) b) Triglyceride = 131 (<150 xss=removed xss=removed xss=removed>39.0 (40-60), f) non-HDL Chol= 136 (<130 xss=removed>
  5. Routine Urine Examination = Nothing abnormal
  6. KFT: a) Blood Urea= 20 mg/Dl (7-18), b) Serum Creatinine = 2.06 c) Serum Uric Acid= 7.79 (3.5-7.2), d) Hb.3 G/Dl (14-17)
  7. LFT= a) Albumin/Globulin Ratio= 1.59 (0.8-1.2), All other Biomarkers were normal.
  8. Abdomen & Pelvis Scanning: Renal Cyst (Rt) and Benign Enlargement of Prostate

The Nephrologist’s Diagnoses: 

“Hypertension, Renal Dysfunction, Renal Cyst and Vit D Deficiency”

Prescription:

  1. Tab DytoR10 mg-1-tab Daily morning, 2. Tab. Telma Beta 40/60mg 1 tab morning 3. Urimax CAPSUE 0.4 mg1 in the night 4. Volini Gel for local application, three times a day on knees. 5. D Rise 60,000 Units once a week 6, Tab Ultracet Semi SOS for knee pain.
  2. Other advises: Salt Restriction, Fluid Restriction to 1 Liter/day Avoid analgesics.
  3. Cardiac Assessment as soon as possible

Cardiologists Consultation:

29/08/2023:  BP 187/87 & second reading after half an hour= 174/83, Pedal Oedema++, 

ECG= Normal, 

ECHO-Two-Dimensional Study: a) Valves: i) Mitral valve: PMAC+, ii) Aortic Valve= Calcified, iii) Tricuspid & iv) Pulmonary Valves- normal.  b) Chambers: i) Left Atrium= Dilated, ii) Left Ventricle= Shows LVH, iii &iv) Right Atrium & Right Ventricle= Normal. c) Septae: IAS & IVS- Normal d) Great Arteries:  Aorta, Pulmonary Artery & IVC- all normal. e) Wall motion abnormalities: Absent. Pericardium -normal, & Vegetation /Thrombus= Absent

Doppler Study: a) Mitral Valve: Grade I LVDD, Mild MR, Aortic Valve- Normal, Tricuspid Calve- Mild TR, Jet Gradient: 30mm Hg, PASP: 38mm Hg. Pulmonary valve- Normal.

Final Impression: Concentric LV Hypertrophy, Dilated LA, NO RWMA of LV at REST, Normal LV Systolic Function, Grade I LV Diastolic Dysfunction and MILD MR, MILD PAH

Ultrasound of Abdomen & Pelvis:

  1. Liver- Normal, 2. Gall Bladder- Moderately distended, No calculi, other markers -Normal 3. Pancreas - Normal, 4. Spleen- Normal, 5. Kidneys- Normal in size & Texture, Rt kidney showed 2-3 cortical cysts, largest 1.9 cm. Left Kidney showed-3-4 cortical cysts largest -4.4cm, 6. Bladder- distended and normal, Pre-void volume=120 cc, post-void volume- 5 cc.7. Prostate- Enlarged measures 61 cc.

Prescriptions:

1.Tab Dytor 10 mg Once in the morning and second in the afternoon.

2. Tab Silodal D 8mg one in the night

3. Tab Telma Beta 50 mg Once in the morning

4. Met XL 50 mg one in the night (to compensate lack of walking /exercise)

5. Tab Met XL 50mg once in the night 0.2 mg one in the morning

Advised follow-up after 2 weeks.

Follow-up 21/09/2023

Pedal oedema ++, BP= 175/95, HR=95/Minute,       

Serum Electrolytes:  a) Sodium=144.4 mmol/L (135-145) b) Potassium = 3.97(3.5-5.5) c) Chloride = 104.4 (94-110)

Continued the drug regiment for another fortnight and follow up. 

Follo-up 19 December 2023:

Disappointing, BP= 225/113, after half an hour 221/109, 

No Pedal oedema. 

Repeat Laboratory Report of 18/12/23 showed: Serum Creatinine= 2.06 mg/Dl, 

Serum Lipid Profile a) Total Cholesterol= 175 mf /L (<200 xss=removed xss=removed xss=removed xss=removed xss=removed xss=removed>

That made the cardiologist to suspect if the patient is taking medicine prescribed, both of us queried him. In view of no response to the drugs, terming it as ‘Resistant Hypertension’ he added Tab Minipress XL 5 mg one tablet in the morning and another in the night. Follow-up advised after 2 weeks.

The expenses on consultation fees (Laboratory investigations of INR 2000 every 2-4 weeks added to the financial problem, despite the cost next follow-up was compiled by end January 2024.

Follow-up on 30 January 2024:  Despite changing the drugs in the last 2 monthly visits the BP recorded read 209/101 and the cardiologist and me suspected if the drugs are being consumed, However, after due verification learnt that tab. Minipress was not bought due to high cost. A revised prescription included:  1) Tab Dytor once in the morning, 2) Tab Telpres- MT 50 mg (Blocks an enzyme responsible for constricting blood vessels) Once in the morning 3) Tab Starpress XL 50 mg (A betablocker) 4) Tab Moxcent 0.2mg (another Blood vessels relaxant) one tablet twice (M/E) a day, 5) Tab Amlodac 5mg twice a day (M/E) 6) Tab Przaopress XL 5 mg Twice a day (M/E) (addresses BP and Mild BEP) 7) Silodal D (for BEP) one tab. In the night. Thus, 6 drugs combination was prescribed to address the resistant hypertension. I as family physician was bit surprised but assured the Cardiologist to monitor the compliance. Though the cost of treatment went beyond INR 100/day. 

Thankfully, the progress was noted in the next 2 months, SBP &DBP coming in the range of 140-150 and 76-90 respectively by 13 March 2024, soon got stabilized by 16 March 2024, but the Diastolic BP came down to 64-70 and signs of postural hypotension were noticed. 

Then I started reducing the number of drugs from first week of April 2024. First, I stopped the costliest drug of Prazopress (costing INR 30 daily) By 1 April 24 the BP was stabilized but much lower levels SBP=130-150 and DBP=70-74. By the end April BP remained at acceptable levels of SBP-124-140 and DBP-75-76. In mid-May the SBP= 130-134 and DBP= 57-62. I stopped another drug from 23 May 2024 Tab Telpress and for the last 3 days SBP is around 140 and DBP around 80 mm Hg. I plan to play with drugs choice, keeping in mind the cost and come down to most essentials 3 drugs regiment as recommended globally.

Discussion

Blood pressure may be defined as the pressure exerted by the blood on the arteries and veins. It is measured by a sphygmomanometer and varies throughout the day, depending on: Body position, Breathing, Food & drink, Medications, Physical condition, Stress, Time of day.

Blood pressure is usually lowest at night and rises sharply on waking. Anxiety, Tensions for varied reasons elevate Blood pressure. Advanced age (50+), Dehydration, Pregnancy, low blood volume, lower BP. Health conditions like Pregnancy, Heart and heart valve conditions, endocrine disorders, Dehydration, Blood loss, Septicaemia), anaphylaxis, lack of nutrients in the diet and use of medications with poor monitoring cause low blood pressure.

According to a 2023 report from the World Health Organization (WHO), hypertension is among the leading risk factors for death and disability worldwide. Resistant hypertension is defined as hypertension that is poorly responsive to treatment and requires the use of multiple medications to achieve acceptable blood pressure ranges. In developing countries like India BP is a vital measurement by Primary care doctors, Nursing staff in major institutions and Trained field workers in community research like NFHS and Screening programs. Accounting that, four big ways-BP measurement can go wrong i) Equipment and the facility, ii) Staff, iii) Preparation of patients and iv) Procedure of measurement, Primary Care Physicians use the word “Resistant hypertension “when the blood pressure remains above 140/90 mmHg despite optimal use of three antihypertensive medications of different classes, including a diuretic. A systolic BP lower than 90 mm Hg or a Diastolic BP of less than 60 mm Hg” is considered as Hypotension. Five types of Hypotension are: 

1) Orthostatic hypotension /Postural hypotension (OHT/PHT): is a sudden drop in blood pressure when standing from a sitting position or after lying down, which is defined as a sustained decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes of standing compared with blood pressure from the sitting or supine position or by head-up tilt-table testing. 

2. Delayed orthostatic hypotension (DOSHT): When sustained blood pressure (BP) drop is after three minutes of upright posture is called DOSHT. Dehydration, long-term bed rest, pregnancy, diabetes & some medications, cause this type of low blood pressure in older adults.

3. Postprandial hypotension (PHT). Blood pressure dropping after 1 to 2 hours after eating. Mostly affects older adults, especially those with high blood pressure or autonomic nervous system diseases -Parkinson's disease. Eating small, low-carbohydrate meals, drinking more water, and avoiding alcohol might help reduce symptoms.

4. Neurally mediated hypotension (NMHT): A BP dropping after standing for long periods, affects mostly young adults & children, due to miscommunication between the heart & brain.

5.Multiple system atrophy with orthostatic hypotension: called Shy-Drager syndrome                       A rare disorder affects the nervous system that controls involuntary functions such as blood pressure, heart rate, breathing and digestion. It's associated with having very high blood pressure while lying down. 

Hormonal problems such as Hypothyroidism, diabetes, hypoglycaemia, some over-the-counter medications and prescription medicines for high blood pressure, depression, or Parkinson's disease and Heart failure may cause Hypotension.

Consequences of Deranged Blood Pressure:

High blood pressure eve if is resistant, damages the vessels when left untreated, it raises the risk of heart attack and stroke and develop heart failure and Aneurism. One can experience chest pain and severe headaches, it often causes kidney damage leading to chronic kidney disease (CKD), Likely to develop vision problems, by damaging blood vessels in the retina, called hypertensive retinopathy. It could lead to developing sexual dysfunction. Of late Hypertension is strongly associated with CVD and death while asleep.

Low BP / Hypotension on the other hand leads to Blurry vision, Confusion, Dizziness, Fainting, Light headedness, Nausea or vomiting, Sleepiness and Weakness. Orthostatic Hypotension is associated with increased odds of falls, increased co-morbidities, number of medicines used, and orthostatic intolerance.  Elderly with diabetes, hypertension and cognitive impairment are at a higher odd of having OHT. 

Practical implications: 

In busy clinical practice, it may appear impossible to do both seated and supine, as well as standing BP. However, if blood pressure is only measured while people are seated upright, cardiovascular disease risk may be missed, as hypertension in supine position on backs is key sign. For patients who had hypertension while supine but not while seated, risks are like those of peers who have hypertension while both seated and supine. These findings suggest people with known risk factors for heart disease and stroke may benefit from having their blood pressure checked while lying flat on their backs. Efforts to manage blood pressure during daily life may help lower blood pressure while sleeping [6]. 

Blood Pressure Management:

Globally, 2023 Standards update the definition of hypertension for people having more than a systolic blood pressure of 130 mm Hg or diastolic BP of 80 mm Hg. Maintaining BP below 130/80 mm Hg is the recommended strategy for people with hypertension [6].  The practitioners must also keep in mind avoiding hypotension. 

The 2023 WHO guideline recommend for the pharmacological treatment of hypertension in adults with a confirmed diagnosis of hypertension and systolic blood pressure of ≥ 140 mmHg or diastolic blood pressure of ≥ 90 mmHg. Latest, from the 2023 ESH guidelines maintain the same BP grade classifications and recommends a threshold of >140/90 mm Hg (grade 1) for the diagnosis of hypertension, whereas the ACC/AHA guideline recommends a lower threshold of >130/80 mm Hg (stage 1 [7].

Promotion of lifestyle interventions to prevent, treat, and delay onset of hypertension feature prominently in all guidelines. All the guidelines recommend treatment initiation at higher BP thresholds of SBP ≥140 mm Hg and/or DBP ≥90 mm Hg regardless of calculated cardiovascular (CV) risk or established CVD. For older adults (>80 years of age), the ESH guidelines explicitly recommend drug therapy when SBP is >160 mm Hg. Treatment initiation with antihypertensive agents for patients who have established CVD and BP ≥130/80 mm Hg, and patients who have an estimated 10-year risk of atherosclerotic CVD of >10% should also be started on treatment. 


 General BP lowering strategy in patients with hypertension:

  1. Management of Only Hypertension at Diagnosis: Contrary to what the author and his cohorts had learnt in 1960’s of starting first with monotherapy, today Monotherapy is recommended only in selected patients with low-risk hypertension and BP <150>
  2. Management of Hypertension with CAD at Diagnosis:  For clinical management of patients in their forties having uncontrolled Hypertension with CAD: 1) Add a Beta Blocker 2) Add A CCB if BP remains uncontrolled, combined in an SPC is possible (RAC blocker /CCB/ Diuretic and Beta Blocker.
StepsHT with CVD 
1ACEi (ARB if not tolerated) + B blockers- Increase to full dose If tolerated 
 
2

With Angina-Add

DHP-CCB

Without Angina add DHP-CB to Diuretic T/TL 
    
3Add further drugs, targeting heart rate<80> 
  

ACEi= Angiotensin-converting enzyme (ACE) inhibitors, ARB= Angiotensin II Receptor Blockers (ARB), DHP= 1,4-dihydropyridine (DHP), CCB= calcium channel blocker

  1. Management of Hypertension with CKD at Diagnosis:

Hypertension being the most risk factor for end stage kidney disease, BP should be monitored and managed with immediate lifestyle management and drug treatment if BP is 140/90 or more, with a primary goal of keeping it under 140/90, if tolerated try to reach 130/80.

Basic approach for OSH/ PHT includes: 

Orthostatic /Postural hypotension is common among elderly and diabetic patients. While treating a patient if a practitioner comes across such situations needs to follow:

  1. Advising to wear waist-high compression stockings to improve blood flow. 
  2. Getting plenty of fluids to minimize dehydration, increasing salt in the diet, avoiding alcohol, and eating small meals. 
  3. Exercising. Moving and stretching in certain ways.
  4. Getting up slowly trying to stand from sleeping position or even sitting on a chair.
  5. Fludrocortisone (0.1 mg) can increase the blood pressure and reduce the effects of postural hypotension, give this medicine under close monitoring of the BP. It is a synthetic mineralocorticoid to replace endogenous aldosterone and acts on the kidneys to increase both sodium reabsorption and potassium excretion.
  6. Monitoring BP regularly & adjusting the dosage or even changing the drug is advised. 

Neurogenic orthostatic hypotension (nOH):

For nOH Droxidopa (Northera®), orally active synthetic precursor of norepinephrine, is available since 2014.

Hypertension treatment coverage is low in India:

A stepwise simple treatment protocol is lacking and is one of the strategies to improve hypertension treatment in primary care. A study of 281,209 patients initiated on amlodipine 5 mg, 159,292 continued on protocol drugs and came for a follow-up visit during the first quarter of 2022. Of 159,292 individuals who came for the follow-up 70% had controlled BP. respectively, at the first step with amlodipine 5 mg.  In the second step with amlodipine 10 mg, the cumulative BP control increased to 75%. A similar 5% (76%–81%) increase was seen in the second step after adding telmisartan 40 mg. Overall, the mean systolic blood pressure (SBP) decreased by 15- 16 from 148 mmHg at the baseline. [5] 
 

 

India Hypertension Control Initiative (IHCI) Protocol

 

The reported outcome of the project based on the drug combination was:

Drugs prescribe in last visitFollow up Jan-Mach 2022% BP Control in recent Jan-March 22 visit% Cumulative BP Control
Amlodipine 5 mg14621981.674
Amlodipine 10 mg26177575
Amlo 5 +Telma 4084927281
Amlo 5 +Telma 807046482
Amlo 10 +Telma 408046577
Amlo 10 +Telma 803476080
Amlo 10 +Telma 40+Chlo 6.25556982
Amlo 10 +Telma 40+Chlo 12.5445079
Amlo 10 +Telma 40+Chlo 25.0104077

Newer drugs:
Aprocitentan is the first endothelin receptor antagonist indicated for treatment of resistant hypertension. It is used in combination with other antihypertensive drugs in adults whose disease is not adequately controlled on other drugs. A dual endothelin receptor antagonist, it inhibits the binding of ET-1 to ETA and ETB receptors. Tab Teveten 600 mg (Erosartan) once daily achieves maximal BP reduction in 2-3 weeks of treatment. Teveten plus (Eprosartan 600 mg + Hydrochlorothiazide 12.5 mg. Research indicate that Aprocitentan is superior to placebo in lowering BP at week 4 (12.5-mg dose, P = .0042; 25-mg dose, P = .0046), with a sustained effect at week 40 (P < .0001). Subgroup analyses in PRECISION showed that the BP-lowering effect of aprocitentan appeared to be consistent irrespective of age, baseline urine albumin-to-creatinine ratio, baseline estimated glomerular filtration rate, body mass index, race, sex, and medical history of diabetes. Researchers also did not observe differences between methods of BP measurement [6]. 

Ambrisentan, Bosentan, and macitentan are also endothelin receptor antagonists. These agents are indicated for pulmonary arterial hypertension and not for high BP.

A study aimed to analyse the relationship between patients' knowledge and adherence with antihypertensive medication. The researchers found that patient knowledge and understanding of hypertension was associated with improved adherence. A systematic review aimed to investigate the effect of different strategies for medication adherence in patients with hypertension and dyslipidaemia. The researchers found that health education was the most widely used intervention and significantly improved adherence compared with usual care. Other research found that various medication organization strategies were common, but none were associated with improved antihypertensive medication adherence.

Conclusion

Hypertension is defined as a systolic pressure reading of 140 mmHg or more or a diastolic reading of 90 mmHg or more, or those taking antihypertensive medications among persons 18 years of age and over. Between 90-95% of cases are essential hypertension with no identifiable cause. The remaining cases are secondary to a distinguishable process and would resolve if the underlying condition was treated.

Resistant hypertension is defined as hypertension that is poorly responsive to treatment and requires the use of multiple medications to achieve acceptable blood pressure ranges. Primary Care Physicians use the word “Resistant hypertension “when the blood pressure remains above 140/90 mmHg despite optimal use of three antihypertensive medications of different classes, including a diuretic. Globally about 5% of HTN cases are estimated to belong to this category.

The strategies and newer medicines are being tried but no single gold standard is approved as of now. Each approach needs to be given about 3 months’ time to prove efficiency.

Current management strategies include based on the association of Hypertension with the complications identified at the time of first diagnosis, contrary to age old belief of initiating mono-drug therapy initially and adding additional drugs if the response is poor. 

References

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Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

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Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

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Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

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Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

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Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

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Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

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Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

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Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

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Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

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Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

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Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

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Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

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S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

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Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

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George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

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Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

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Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

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Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

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Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

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Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

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Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

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Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

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Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

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Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

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Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

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Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

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Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

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Luiz Sellmann