1. Hypertension and Its Management
Dr. Suman Chowdhury
CMCH
Examinee of FCPS

2. Hypertension:
Hypertension is a condition in which arterial BP is chronically elevated.

3. And, What is the upper limit?

4. > 140/90 mmHg

5. For Diabetic Patients: > 130/80mmHg

6. Is it a Sign or Disease? It is more than a sign
It will not be an exaggeration if we consider it as a disease!

7. Classification

8. Classification of Hypertension
Category
BHS
JNC 7
SBP (mmHg)
DBP (mmHg)
Optimal
Normal
< 120
< 80
Pre hypertension
< 130
< 85
High Normal
85-89
Hypertension
Grade 1 (Mild)
Stage 1
90-99
Grade 2 (Moderate)
Stage 2
Grade 3 (Severe)
≥ 180
≥ 110
Isolated Systolic Hypertension
Grade 1
< 90
Grade 2
≥ 160
BHS = British Hypertension Society
JNC 7= Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

9. The Primary/Essential Hypertension is said to be due to these following mechanisms:

10. Sympathetic nervous system hyperactivity
This is most apparent in younger persons with hypertension, who may exhibit tachycardia and an elevated cardiac output. However, correlations between plasma catecholamines and blood pressure are poor. Insensitivity of the baro-reflexes may play a role in the genesis of adrenergic hyperactivity.
Abnormal cardiovascular or renal development
The normal cardiovascular system develops so that elasticity of the great arteries is matched to the resistance in the periphery to optimize large vessel pressure waves. In this way, myocardial oxygen consumption is minimized and coronary flow maximized. Elevated blood pressure later in life could arise from abnormal development of aortic elasticity or reduced development of the microvascular network. This has been postulated as the sequence of events in low birth weight infants who have an increased risk of hypertension developing in adulthood. Another hypothesis proposes that the association between low birth weight and hypertension arises from reduced nephron number.

11. Renin–angiotensin system activity
Renin, a proteolytic enzyme, is secreted by cells surrounding glomerular afferent arterioles in response to a number of stimuli, including reduced renal perfusion pressure, diminished intravascular volume, circulating catecholamines, increased sympathetic nervous system activity, increased arteriolar stretch, and hypokalemia. Renin acts on angiotensinogen to cleave off the ten-amino-acid peptide angiotensin I. This peptide is then acted upon by angiotensin-converting enzyme (ACE) to create the eight-amino-acid peptide angiotensin II, a potent vasoconstrictor and stimulant of aldosterone release from the adrenal glands. Despite the role of renin in the regulation of blood pressure, it probably does not play a central role in the pathogenesis of most primary (essential) hypertension; only 10% of patients have high renin activity, whereas 60% have normal levels, and 30% have low levels. Black persons with hypertension and older patients tend to have lower plasma renin activity, which may be associated with expanded intravascular volume.

12. Intracellular sodium and calcium
Defect in natriuresis
Normal individuals increase their renal sodium excretion in response to elevations in arterial pressure. In hypertensive patients, this pressure-natriuresis relationship is reset so that maintenance of sodium homeostasis requires increased extracellular fluid volume and higher arterial pressure.
Intracellular sodium and calcium
Intracellular Na+ is elevated in primary (essential) hypertension. An increase in intracellular Na+ may lead to increased intracellular Ca2+ concentration as a result of facilitated exchange and might explain the increase in vascular smooth muscle tone that is characteristic of established hypertension.

13. Though secondary causes are only 5%, the list is not too short!!!!

14. Identifiable causes of Hypertension
Sleep apnea
Drug-induced or drug-related
Chronic kidney disease
Primary aldosteronism
Renovascular disease
Long-term corticosteroid therapy and Cushing syndrome
Pheochromocytoma
Coarctation of the aorta
Thyroid or parathyroid disease

15. Hypertensive Crisis

16. Hypertensive Emergency
Hypertensive Crisis
Hypertensive Urgency
Hypertensive Emergency
May be defined as acute and rapidly developing end organ damage with significant hypertension. Here blood Pressure is usually > 220 mm of Hg.
Hypertensive emergencies require substantial reduction of blood pressure within 1 hour to avoid the risk of serious morbidity or death
There is target organ damage.
Hypertensive emergencies are treated in an ICU
BP is progressively (although not abruptly) reduced using a short-acting, titratable IV drug.
Choice of drug and speed and degree of reduction vary somewhat with the target organ involved, but generally a 20 to 25% reduction in MAP over an hour or so is appropriate, with further titration based on symptoms. Then if stable, to 160/100–110 mmHg within the next 2–6 hours.
These include patients with asymptomatic severe hypertension, very high blood pressure diastolic > 120 to 130 mm Hg
There is no target organ damage
BP at these levels often worries the physician; however, acute complications are unlikely, so immediate BP reduction is not required.
Patients should be started on a 2-drug oral combination, and close evaluation (with evaluation of treatment efficacy) should be continued on an outpatient basis.

17. Target Organ damage Cardiac Renal Retinal Organs CNS
Acute MI, acute left ventricular
failure with pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm
Hypertensive nephropathy
Hypertensive Retinopathy Grade 4
Disorders
Hypertensive Encephalopathy
Signs and Symptoms
Transient disturbances of speech or vision, paraesthesiae, fits, disorientation, and loss of consciousness, Papilloedema is common A CT scan of the brain often shows haemorrhage in and around the basal
ganglia.
Chest pain, Dyspnoes, sudden severe pain in back with shock
Hematuria,proteinuria,and progressive kidney
'Cotton wool' exudates are associated with retinal ischaemia or infarction, central retinal vein thrombosis

18. And also, In Pregnancy Disorders Preeclampsia Eclampsia
Proteinuria, Edema
Preeclampsia +
Convulsion
Signs and Symptoms

19. Attention!!!
Interesting to note that, in case of Hypertensive encephalopathy, we have to very cautious to exclude stroke of any kind. For which, even an early MRI (T2 weighted) should be done if we are not confident enough after history, and physical (neurological) examination!!
Because, the target and the management plan will be totally changed in case of stroke.

20. Regarding anti Hypertensive in stroke
In Haemorrhagic stroke*
In ischaemic stroke
Intracerebral
SAH
If thrombolytic therapy is to be used
Who are not candidates for thrombolytic therapy
Target is SBP> 180mmHg and DBP > 130mmHg
Target is MAP > 130mmHg
Target is SBP> 185mm Hg and DBP > 110mm Hg
Target is SBP> 220mmHg and DBP> 130mmHg

21. Suggested Recommended Guidelines for Treating Elevated Blood Pressure in Spontaneous ICH
If SBP is 200 mm Hg or MAP is 150 mm Hg, then consider aggressive reduction of blood pressure with continuous intravenous infusion, with frequent blood pressure monitoring every 5 minutes
If SBP is 180 mm Hg or MAP is 130 mm Hg and there is evidence of or suspicion of elevated ICP, then consider monitoring ICP and reducing blood pressure using intermittent or continuous intravenous medications to keep cerebral perfusion pressure 60 to 80 mm Hg

22. Accelerated Hypertension Malignant Hypertension
1. Complication with high blood pressure, target organ damage
Malignant hypertension is by historical definition characterized by encephalopathy or nephropathy with accompanying papilledema
Complication of high blood pressure characterized by very elevated high blood pressure
2. There is no fibrinoid necrosis of arterioles and small arteries
2. There is fibrinoid necrosis of arterioles and small arteries.
3. Target organ(eyes, heart, lungs, kidney)
damage is present
4. Fundoscopy shows flame shaped
hemorrhages, or soft exudates, but no
papilledema.
4. Fundoscopy shows papilledema
5. There is no microangiopathic hemolytic
anemia.
5. There is microangiopathic hemolytic anemia
6. There is no such demarcation
6. Systolic and diastolic blood pressures are usually greater than 240 and 120, respectively.

23. Management

24. A person with Increased BP Yes No
Look for Hypertensive Crisis
Yes No
Urgency
Emergency
Establish HTN*
Call for ICU/HDU
Life style Modification
Start Oral drugs
If not available, manage in Ward
If not controlled
Drug Rx §
e.g. Captopril
Add other drugs later if necessary
IV drugs with titratable doses
Look for compelling indications
IV GTN, Hydralazine, Labeteolol
Select drugs after excluding compelling Contraindications
When the blood pressure has been brought under control, combinations of oral antihypertensive agents can be added as parenteral drugs are tapered off
over a period of 2–3 days. Most subsequent regimens should include a diuretic.
Look for co-morbid conditions
Consider special conditions

25. * Persistent Raised BP:
Measured at past two visits and
Systolic BP or DBP or Both are > 140/90mmHg
§ Threshold for offering Drug treatment:
BP > 160/100mmHg, or
Isolated Systolic HTN (Systolic BP> 160 mmHg), or
BP > 140/90mmHg, and
10 yr CVD risk at list 20 % or
Existing CVD or
Target organ damage

26. Management of Hypertensive urgency

27. Previously treated hypertension Previously Untreated hypertension
General strategies:
All patients should be provided a quiet room to rest; this can lead to a fall in BP of 10 to 20 mmHg or more. The approach varies depending on whether the patient has already been treated for hypertension or is untreated.
Previously treated hypertension
Previously Untreated hypertension
Increase the dose of existing antihypertensive medications, or add another agent.
Reinstitution of medications in non-adherent patients.
Addition of a diuretic, and reinforcement of dietary sodium restriction, in patients who have worsening hypertension due to high sodium intake.
In the previously untreated patient, several options are available. The approach should take into consideration:
The individual patient's risk with persistence of severe hypertension
The likely duration of severe hypertension,
Of cerebrovascular or myocardial ischemia with rapid reduction in blood pressure
Relatively rapid initial blood pressure reduction (over several hours). We use Oral captopril

28. Following administration of drugs, the patient is observed for a few hours, to ascertain a reduction in blood pressure of 20 to 30 mmHg. Thereafter, a longer acting agent is prescribed and the patient is sent home to follow up within a few days. The drop in blood pressure may take relatively longer with captopril, and may be too large among patients with hemodynamically significant unilateral renal artery stenosis.
Blood pressure reduction over one to two days. There are no data supporting the use of a particular agent in this setting although we generally do not begin therapy with extended release preparations or with a diuretic alone. Depending on the patient, a calcium channel blocker (but not sublingual nifedipine), beta blocker or angiotensin converting enzyme (ACE) inhibitor or receptor blocker can be started, like ramipril 10 mg once daily.

29. The choice of agent should take into consideration the type of antihypertensive agent that is most appropriate in the long term (eg, calcium channel blockers and thiazide-like diuretics are preferred over ACE inhibitors and beta blockers as monotherapy in blacks), and underlying conditions that may be favorably or adversely affected by the antihypertensive agent .
Some experts initiate therapy with two agents or a combination agent, one of which is a thiazide diuretic. The rationale is that most patients with blood pressure ≥20/10 mmHg above goal will require two or more antihypertensive agents in order to achieve the goal blood pressure .
It is unlikely that a diuretic in combination with a modest dose of another agent will cause a dangerous reduction in the blood pressure; however, initiation of two agents simultaneously must be done with close blood pressure follow-up, since the full effects of both agents may not occur for a few days, and adverse consequences may ensue if the blood pressure is lowered too quickly. This is particularly true among patients with cerebrovascular disease in whom more cautious blood pressure reduction is warranted.

30. Monitoring and follow-up

31. The patient with severe asymptomatic hypertension is usually managed in the emergency room, since exclusion of acute end-organ damage requires laboratory testing, and the patient may require administration of medications and several hours of observation. However, the patient can often be safely managed in the physician's office if the evaluation and management can be carried out.
The management of a patient who does not have established HTN, follow-up is difficult. Rarely, such patients may require admission.
In addition, patients at high risk for cardiovascular events (e.g, long-standing diabetes, known coronary artery disease or prior stroke), should probably be admitted.

32. Ideally, the patient should be observed for a few hours to ascertain that the blood pressure is stable or improving, and that indeed they are asymptomatic. If so, the patient can be sent home with close follow-up over the subsequent days directed towards evaluation for symptoms related to hypertension or hypotension, and adjustment of medications to achieve the initial blood pressure goal of ≤160/100 mmHg.
In reliable patients who can monitor their blood pressure at home, close phone follow-up may substitute for direct physician visits. If the patient does not have a physician, follow-up may need to be in the emergency room or other acute care setting.
Over the subsequent weeks and months, the dose and selection of medications should be adjusted as needed to achieve the desired blood pressure goals. These issues are discussed elsewhere.

33. Drugs for the Hypertensive Crisis

34. I.V. Drugs for Hypertensive Emergency:
Dosage
Sodium Nitropruside
Initially 0.3 µg/kg/min, then 0.25–10 μg/kg/min
IV infusion (maximum dose for 10 min only)
Labetelol
20-80 mg IV bolus over 2 min, followed q 10 min by 40 mg, then up to 3 doses of 80 mg; or 0.5–2 mg/min IV infusion
Nicardipine
Initial 5mg/hr , Max. 15 mg/hr
Nitroglycerine
Initial 5 μg/min , then titrate 5 μg/min at 3-5 mins interval
Range is: 5–100 μg/min IV infusion
Hydralazine
10-50mg at 30 mins interval , (10–40 mg IV, 10–20 mg IM)
Esmolol
250–500 μg/kg/min for 1 min, then 50–100 μg/kg/min for 4 min; may repeat sequence
Enalapril
mg over 5mins. Every 6-8 hrs, max. 5mg/hr

35. Preferred I.V drugs in Selected conditions:
Situations
Drugs
Hypertensive encephalopathy
Nitropruside, Nicardipine, Labetelol
Acute LVF
Nitroglycerine, Enalapril, Loop diuretics
MI, Unstable angina
Nitroglycerine, Nicardipine, Labetelol, Esmolol
Eclampsia
Labetelol, Hydralazine
Aortic dissection
Nitropruside, Esmolol, Labetelol

36. Management: Non pharmacologic therapy:
Lifestyle modification may have an impact on morbidity and mortality. A diet rich in fruits, vegetables, and low-fat dairy foods and low in saturated and total fats (DASH diet) has been shown to lower blood pressure.

37. Lifestyle modifications to manage hypertension
Recommendation
Approximate Systolic BP Reduction, Range
Weight reduction
Maintain Norma l Body weight (BMI )
5-20mmHg, 10 kg weight loss
Adopt DASH eating plan
Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated fat and total fat
8–14 mm Hg
Dietary Sodium restriction
Reduce dietary sodium intake to no more than 100 mEq/d (2.4 g sodium or 6 g sodium chloride)
2–8 mm Hg
Physical activity
Engage in regular aerobic physical activity such as brisk walking (at least 30 minutes per day, most days of the week)
4–9 mm Hg
Moderation of alcohol
consumption
Limit consumption to no more than two drinks per day (1 oz or 30 mL ethanol [eg, 24 oz beer, 10 oz wine, or 3 oz 80-proof whiskey]) in most men and no more than one drink per day in women and lighter-weight persons
2–4 mm Hg

38. Pharmacological approach:
Depends mainly on:
Compelling indications
Contraindications
Presence of co-morbid conditions
Some special situations

39. Compelling Indications:
CVD risk+ IHD+ (Previous H/O CVD= ACEi, ARB
Cardiac:
Post MI=ACEi, Aldosterone antagonists
LVF = ARB, Aldosterone antagonists
DM Type 1= ACEi
DM Type = ARB
Older patients+ Isolated Systolic HTN= Thiazide or Thiazide like diuretics
CKD= ARB, ACEi

40. Old Concept
New Concept

41. That means, Beta blocker is less favored as an Antihypertensive drug!!

42. Contraindications: Pregnancy: No ACEi, ARB Asthma+ COPD= No β Blocker
Young male patient = No β Blocker (Relative)
Significant Renal artery stenosis = ARB, ACEi
Hyperkalaemia = ARB, ACEi

43. Investigations: For all patients:
Urinalysis for blood, protein and glucose
Blood urea, electrolytes and creatinine
N.B. Hypokalaemic alkalosis may indicate primary hyperaldosteronism but is usually due to diuretic therapy
Blood glucose
Serum total and HDL cholesterol
12-lead ECG (left ventricular hypertrophy, coronary artery disease)

44. Cont…… For Selected Patients:
Chest X-ray: to detect cardiomegaly, heart failure, coarctation of the aorta
Ambulatory BP recording: to assess borderline or 'white coat' hypertension
Echocardiogram: to detect or quantify left ventricular hypertrophy
Renal ultrasound: to detect possible renal disease
Renal angiography: to detect or confirm presence of renal artery stenosis
Urinary catecholamines: to detect possible phaeochromocytoma
Urinary cortisol and dexamethasone suppression test: to detect possible Cushing's syndrome
Plasma renin activity and aldosterone: to detect possible primary aldosteronism

45. RESISTANT HYPERTENSION
Resistant hypertension is defined in JNC 7 as the failure to reach blood pressure control in patients who are adherent to full doses of an appropriate three drug regimen (including a diuretic). In this situation, the clinician should first exclude identifiable causes of hypertension, and then carefully explore reasons why the patient might not be at goal blood pressure.
The clinician should pay particular attention to the type of diuretic being used in relation to the patient's kidney function. Aldosterone may play an important role in resistant hypertension and aldosterone receptor blockers can be very useful. If goal blood pressure cannot be achieved following completion of these steps, consultation with a hypertension specialist should be considered.

46. Causes of resistant hypertension
Improper blood pressure measurement
Volume overload and pseudotolerance
Excess sodium intake
Volume retention from kidney disease
Inadequate diuretic therapy
Drug-induced or other causes:
Nonadherence
Inadequate doses
Inappropriate combinations
Nonsteroidal anti-inflammatory drugs; cyclooxygenase-2 inhibitors
Cocaine, amphetamines, other illicit drugs
Sympathomimetics (decongestants, anorectics)

47. Associated conditions
Oral contraceptives
Adrenal steroids
Cyclosporine and tacrolimus
Erythropoietin
Licorice (including some chewing tobacco)
Selected over-the-counter dietary supplements and medicines (eg, ephedra, ma huang, bitter orange)
Associated conditions
Obesity
Excess alcohol intake

48. Follow-Up of Patients Receiving Hypertension Therapy
Once antihypertensive drug therapy is initiated, most patients should return for follow up and adjustment of medications at monthly intervals or until the BP goal is reached and laboratory testing limited to tests appropriate for the patient and the medications used.
More frequent visits will be necessary for patients with stage 2 hypertension or with complicating co morbid conditions. Serum potassium and creatinine should be monitored at least one to two times per year. Yearly monitoring of blood lipids is recommended, and an electrocardiogram should be repeated at 2- to 4-year intervals depending on whether initial abnormalities are present, the presence of coronary risk factors, and age.

49. Optimal target blood pressures during antihypertensive treatment:
No diabetes
Diabetes
Clinic measurements
< 140/85 mmHg
< 130/80 mmHg
Mean day-time ambulatory or home measurement
< 130/75 mmHg

50. After BP is at goal and stable, follow up visits can usually be at 3- to 6-month intervals. Co morbidities such as HF, associated diseases such as diabetes, and the need for laboratory tests influence the frequency of visits. Other cardiovascular risk factors should be monitored and treated to their respective goals, and tobacco avoidance must be promoted vigorously.
Low-dose aspirin therapy should be considered only when BP is controlled because of the increased risk of hemorrhagic stroke when the hypertension is not controlled. Pharmacy care programs have been shown to improve compliance with medications. Patients who have had excellent blood pressure control for several years, especially if they have lost weight and initiated favorable lifestyle modifications, should be considered for "step-down" of therapy to determine whether lower doses or discontinuation of medications are feasible.

51. Interesting to note:
Target BP is similar to that for younger patients.
Antihypertensives are tolerated in elder patients as well as in younger patients.
Not only the SBP, but DBP is also equally important regarding treatment
Sometimes, antihypertensives are used not only to reach the target BP, but also for some other beneficial effects.
We should be cautious about the combination antihypertensive drugs, as they causes Electrolytes Imbalance, Bradycardia, Exacerbation of Br. Asthma etc.

52. Cont……..
It is helpful if we consider the contraindications rather than the indications
Effectiveness of some antihypertensive drugs may only be seen after a long period, so we should not hurry