1. The document discusses guidelines and strategies for the prevention, treatment, and control of hypertension. 2. It outlines 4 stages of intervention for hypertension: preventive, primary, secondary, and resistant hypertension. Treatment approaches differ depending on the stage. 3. The challenges of controlling hypertension include special patient populations, factors influencing drug choice, and issues related to resistant hypertension when blood pressure remains high despite treatment with 3 drug classes.

1. Prevention,
Treatment,
Control
of
hypertension Dr. B. K. Iyer

2. 10 tips to better knowledge
1. Introduction to hypertension effects
2. Assessment of hypertension control in India
3. Updated guidelines
4. Hypertension intervention stages
5. Challenges in hypertension control
6. Doctor expectations to improve control
7. Hypertension in special conditions
8. Microalbuminuria and cardiovascular events
9. Important Hypertension trials
10. Telmisartan range

3. Introduction to effects of
hypertension
1

4. Hypertension - Introduction
 Hypertension is the single largest risk factor for
cardiovascular disease mortality, accounting for 45%
of all CVD deaths
 Many surveys continue to show that BP remains↑
under diagnosed, undertreated & poorly controlled.
 Diastolic pressure is more commonly elevated in younger people.
 But, with ageing, systolic hypertension becomes a more
significant problem.
 Hypertension is often symptom less, so screening is
vital - before damage is done.

5. Effects of Systolic and Diastolic BP on CHD Mortality:
MRFIT*
Neaton JD, et al. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart
disease: overall findings and differences by age for 316,099 white men. Arch Intern Med. 1992;152:56-64
*
Data shown only for 316,099 white men 35 to 57 years
of age who were followed for a mean of 12 years.
CHD = coronary heart disease
MRFIT = Multiple Risk Factor Intervention Trial
<120<120
120-139120-139
140-159140-159
160+160+
CHD Death RateCHD Death Rate
Per 10,000Per 10,000
Person-YearsPerson-Years
100+100+
80-8980-89
70-7470-74
<70<70
75-7975-79
90-9990-99
SystolicSystolic
Blood PressureBlood Pressure
(mm Hg)(mm Hg)
DiastolicDiastolic
Blood PressureBlood Pressure
(mm Hg)(mm Hg)
48.348.3
37.437.4
34.734.7 43.843.8
38.138.1
80.680.6
31.031.0
25.525.5
24.624.6
25.325.3
25.225.2
24.924.9
23.823.8
16.916.9
13.913.9
12.812.8
12.612.6
11.811.8
20.620.6
10.310.3
11.811.8
8.88.8
8.58.5
9.29.2

6. <117
Systolic Blood Pressure (mm Hg)
Effects of Systolic Blood Pressure on ESRD : Multiple Risk
Factor Intervention Trial*
Klag MJ, et al. End-stage renal disease in African-American and white men.
16-year MRFIT findings. JAMA. 1997;277:1293-1298.
IncidenceofESRDper
100,000Person-Years
*
The original cohort of 332,544 men included 11,677 men in other ethnic groups
whose data are excluded from this comparison.
ESRD = end-stage renal disease
White Men (n = 300,645)
Black Men (n = 20,222)
117-123 124-130 131-140 >140
5.4
15.8
5.4
9.1
14.2
32.4
27.3 26.2
37.2
83.1

7. RelativeRiskof
StrokeDeath
<112
<71
Effects of Systolic and Diastolic BP on Stroke related
Death : MRFIT
1 2 3 4 5 6 7 8 9 10
Decile
112−
71−
118−
76−
121−
79−
125−
81−
129−
84−
132−
86−
137−
89−
142−
92−
≥151
≥98
(Lowest 10%) (Highest 10%)
SBP
DBP
Systolic Blood Pressure (SBP)
Diastolic Blood Pressure (DBP)
Stamler J, et al. Arch Intern Med. 1993;153:598-615;
He J, Whelton PK. Am Heart J. 1999;138(Pt 2):211-219.
MRFIT = Multiple Risk Factor Intervention Trial; *P < 0.01; †P < 0.001.
* * * *
*
†
†
†
†
†

8. Effects of Systolic BP reduction
Stambler .Hypertension.
1991; 117-120.
After
Intervention
Before
Intervention
Reductions
in SBP
% Reduction in Mortality
Stroke CHD Total
2 -6 -4 -3
3 -8 -5 -4
5 -14 -9 -7
Reduction
in BP

9. Hypertension - the need for control
 Approximately 1 in 3 have hypertension.
 Only 46% of adults with hypertension have adequately
controlled blood pressure.
 The risk associated with increasing blood pressure is
continuous with
 Each 2 mmHg in systolic BP =↑
• 7% increased risk of mortality from ischemic heart disease, &
• 10% increased risk of mortality from stroke.
 A 10mmHg lower systolic blood pressure (SBP) – or
5mmHg lower diastolic blood pressure (DBP) – is
associated with an approximately 20–25% lower risk of
CVD & an approximately 40% lower risk of stroke.

10. Hypertension Control - comprehensive approach
 The Million Hearts™ initiative has set a goal of 65%
control by 2017 overall.
 Focused clinical interventions with Lifestyle advice &
complication-based strategies
 Stages of Intervention in hypertension
1. Preventive – Before risk factors develop
2. Primary – Treatment of risk factors
3. Secondary – After a CVD event occurs

11. Assessment of hypertension
control in India
2

12. Patient pattern
• Prescription patterns of antihypertensive drugs and
adherence to JNC 7 guidelines in a tertiary care hospital in
north India
• Out Patient Department of Punjab Institute of Medical
Sciences Hospital, Jalandhar.
International Journal of Medical and Clinical Research, BAJAJ J.K et al
ISSN:0976-5530 & E-ISSN:0976-5549, Volume 3, Issue 2, 2012, pp.-118-120.

13. Prescription pattern

14. Updated guidelines in
hypertension
3

15. JNC VIII thresholds for diagnosis & treatment

16. Intervention stages in
hypertension
4

17. Hypertension Control – stages of intervention
 Stages of Intervention in hypertension
 Preventive – Before risk factors develop
 Primary – Treatment of hypertension + risk factors
 Secondary – Treatment of hypertension after a CVD event
occurs

18. DASH Trials
 Dietary Approaches to Stop Hypertension (DASH) Trial
 Compared the effects of 3 diets –
• typical American diet,
• fruits and vegetable diet, and
• Diet rich in fruits and vegetables and low fat dairy, and reduced in
saturated fat, total fat, and cholesterol
 All diets provided ~ 3,000 mg sodium per day
 Combination diet (DASH) produced the largest blood
pressure reduction after 8 weeks – average of 5.5 / 3.0↓
mm Hg
• Participants with hypertension experienced an average BP of 11.4 /↓
5.5 mm Hg

19. Sodium and Hypertension
9 in 10
people eat
too much
sodium
44% of the
sodium we
eat comes
from 10
types of
foods
Reducing
sodium by
1,200
mg/day can
save lives
Every 39
seconds an
adult dies of
heart attack,
stroke, or other
cardiovascular
disease
Nearly 1 in 2
people with
hypertension
doesn't have it
under control
Image adapted from CDC Vital Signs Fact
Sheet, Where’s the Sodium
Image adapted from CDC Vital Signs Fact Sheet,
High Blood Pressure and Cholesterol

20. Effect of sodium intake on BP
 Sodium intake is 1 of several dietary factors that BP↑
 Sodium is the principal cation of the extracellular fluid
 Sodium functions as the osmotic determinant in regulating
extracellular fluid volume and plasma volume
 Sodium is stored in the blood and in the fluid surrounding the cells;
 Absorbed Na+ remains in the extracellular
compartments & maintains BP in the normal range
 Sodium affects BP by changing blood volume
 ↑ sodium intake = blood volume = blood pressure↑ ↑
 Sodium = blood volume = blood pressure↓ ↓ ↓

21. Effect of sodium intake on BP
 In most individuals blood pressure is reduced within days
to weeks of reducing sodium intake
 Average blood pressure was reduced by 22.7/9.1 mm
Hg in patients with resistant hypertension when switched
from a high to low sodium diet
 Patients may be able to lower the required dose of blood
pressure medicines through ↓ sodium intake
 Patients with normotension or prehypertension may ↓ or
prolong their risk for developing hypertension through ↓
sodium.

22. DASH Sodium Trials
 Dietary Approaches to Stop Hypertension (DASH
Sodium Trial)
 DASH diet and 3 levels of sodium intake –
1. 1,150 mg,
2. 2,300 mg, and
3. 3,450 mg
 DASH diet at the low level of sodium SBP by 7.1 mg Hg↓
• Participants with HTN experienced a BP of 11.5 mm Hg↓
 Actual average daily sodium intake is >3,300 mg/day
 ↓ sodium intake to 2,300 mg/day could ↓ cases of hypertension by
11 million & Gain 312,000 Quality Adjusted Life Years (QALYs)
 ↓ sodium intake to 1,500 mg/day may ↓ cases of hypertension by
16 million & Gain 459,000 Quality Adjusted Life Years (QALYs)

23. Sources of sodium
Mattes RD, et al. Relative
contributions of dietary
sodium sources. J AM Coll
Nutr 1991;10:383–393.

24. Challenges in hypertension
control
5

25. Factors affecting choice of antihypertensive
drug
1. The cardiovascular risk profile of the patient
2. Coexisting disorders / risk factors
3. Target organ damage
4. Interactions with other drugs used for concomitant
conditions
5. Tolerability of the drug
6. Cost of the therapy

26. Special Populations
 Minorities
 Genetically predisposed patients with increased rate of
conversion from pre-hypertension to hypertension
 Over age 80
 Significant benefits from treatment
 May be more sensitive to medication side effects or
drug interactions due to an increased number of
medications taken
Selassie A, et al. Progression is accelerated from prehypertension to hypertension in blacks. Hypertension. 2011;
58:579-587.

27. BP Treatment in the very elderly, i.e. aged over
80yrs
 New evidence suggests that BP lowering reduces the
risk of stroke, heart failure and death in people aged
over 80yrs;
 Offer people aged >80yrs same treatment as people
aged >55yrs, taking account of co-morbidities;
 Initiate therapy in people aged > 80yrs at stage 2
hypertension;
 Treat to <150/90mm Hg.

28. Step 1 Treatment Recommendations
 To people aged < 55 years, step 1 antihypertensive
treatment is started with an ACE inhibitor or a low cost
ARB. If an ACE inhibitor is used and not tolerated, offer
an ARB. [new 2011]
 Do not combine an ACE inhibitor with an ARB to treat
hypertension. [new 2011]
 To people aged > 55 years, step 1 antihypertensive
treatment is started with a CCB.
 If a CCB is not suitable, for example due to oedema or intolerance,
or if there is evidence of heart failure, or a high risk of heart failure,
offer a thiazide-like diuretic . [new 2011]

29. Why is a CCB preferred to Diuretic?
 CCB (usually amlodipine) = the most cost-effective
treatment option for treating BP unless the patient↑
had CCF or high risk of developing it – i.e. older patient
≥75yrs;
 CCB is metabolically neutral – easy to use;
 CCB is best at reducing BP variability
 BP variability is an independent predictor of clinical outcomes -
especially stroke;

30. Why is a BB not preferred as 1st choice?
 These days, Beta-blockers are not a preferred initial
therapy for hypertension but beta-blockers may be
considered in younger people, particularly:
 Those with an intolerance or contraindication to ACE inhibitors
and ARBs, or
 Women of child-bearing potential or
 People with evidence of increased sympathetic drive. [2006]
 If therapy is initiated with a beta-blocker and a second
drug is required, add a CCB rather than a thiazide-like
diuretic to reduce the person’s risk of developing
diabetes. [2006]

31. Step 2 Treatment Recommendations
 If step 2 antihypertensive treatment is required, offer a
CCB in combination with either an ACE Inhibitor or an
ARB.
 If a CCB is not suitable, for example because of oedema or
intolerance, or if there is evidence of heart failure or a high risk of
heart failure, offer a thiazide-like diuretic [new 2011]
 Why?
 At step 2, the combination of A + CCB is seen as superior to A + D
in clinical outcomes↓ .

32. Step 3 Treatment Recommendations
 Before considering step 3 treatment, review
medication to ensure step 2 treatment is at optimal or
best tolerated doses. [new 2011]
 If treatment with three drugs is required, the
combination of ACE inhibitor or an ARB + CCB +
thiazide-like diuretic should be used. [2006]

33. Step 4 - RESISTANT HYPERTENSION
 When Hypertension is not controlled using a
combination of 3 antihypertensive drug classes &
remains higher than 140/90 mmHg with the optimal or
best tolerated doses of an ACE inhibitor or ARB + CCB +
diuretic, it is known as resistant hypertension
 Study from Colorado Kaiser Permanente, found that 1.9% of
patients (1 in every 50 patients) with incident hypertension who
were on treatment; developed resistant hypertension within a
median of 1.5 years from initial treatment
• They found 16% of patients on 3 or more drugs continued to have
resistant hypertension

34. Step 4 - RESISTANT HYPERTENSION
 Reasons include -
 Non-compliance / adherence with medication
 Fluid imbalance – renal failure
 Hormonal imbalance - hyperkalaemia.
 Therapy consists of adding a fourth antihypertensive
drug [new 2011]
 If blood potassium levels
1. < than 4.5 mmol/l, consider further diuretic addition with low-
dose spironolactone (25 mg once daily) OR amiloride.
2. > than 4.5 mmol/l, consider therapy addition with a higher-dose
thiazide-like diuretic treatment.[new 2011]
 Caution is required in patients with ↓ renal function
who are at higher risk of developing hyperkalaemia.

35. Step 4 - Treatment Recommendations
 When using further diuretic therapy for resistant
hypertension at step 4, monitor monthly & repeat
thereafter as needed
 blood Na+ & K+ and
 renal function.
 If further diuretic therapy for resistant hypertension at
step 4 is not tolerated, contraindicated or ineffective;
 Consider an alpha- or beta-blocker. [new 2011]
 If blood pressure remains uncontrolled with the optimal
or maximum tolerated doses of 4 drugs,
 Seek expert advice if it has not yet been obtained.[new 2011]

36. Summary - Antihypertensive Drug Treatment
Aged <55yrsAged <55yrs Aged ≥55yrsAged ≥55yrs
Step 1 AA C*C*
A + C*A + C*
A + C* + DA + C* + D
A + C* + D + Further DiureticA + C* + D + Further Diuretic++
Consider specialist AdviceConsider specialist Advice
Step 2
Step 3
Step 4
Resistant
Hypertension
A = ACEi or ARB
C = CCB
D = Thiazide-like diuretic
C* = CCB preferred but
D is an alternative in
people intolerant of C or
at high risk of heart
failure
Further Diuretic:
Consider low dose
spironolactine or higher
dose thiazide

37. Doctor expectations in
hypertension control
6

38. Proven improvement support
 To improve compliance!
 Combipills
 Weekly / monthly packs /
combipacks
 Range to tailor make fit
decisions
 Strengths to tailor make fit
decisions
 Easy to recall brand names
 Enhanced product appeal
 To improve care!
 Alerts
 Follow up Reminders
 Templates for management
 Built-in access to reporting
 Report monitoring
 Measures to enhance
implementation of quality
improvement initiatives

39. What happens if Hypertension isn’t controlled?
 if Hypertension is not controlled, complications will
develop like -
1. Left ventricular hypertrophy (LVH)
2. Heart failure
3. Chronic kidney failure
4. Stroke (cerebral hemorrhage)
5. Vascular dementia
6. Retinopathy

40. Hypertension in special
conditions
7

41. Hypertension in special conditions
 HTN in Young - Causes
 HTN in elderly - Difference
 HTN and Pregnancy - Cautions
 HTN and Diabetes - Proteinurea
 HTN and Renal Failure – Drug dosing
 Hypertensive Emergencies - Urgency, Emergency

42. Choosing right antihypertensive drug

43. Choosing right antihypertensive drug

44. Choosing right antihypertensive drug

45. Choosing right antihypertensive drug

46. Antihypertensive drugs in special conditions

47. Side effects of antihypertensive drugs

48. Side effects of antihypertensive drugs

49. Microalbuminuria and
cardiovascular events
8

50. Microalbuminuria
• Microalbuminuria – what is it?
• The term microalbuminuria refers to a level
of urinary albumin excretion, commonly
defined as being between 30 and 299 mg
albumin per day and below the sensitivity
threshold of conventional dipsticks.
• It is usually detected by measuring the
albumin-creatinine ratio, either in a spot
urine sample or in a timed urine collection.

51. Microalbuminuria
• Microalbuminuria – why is it important?
• Microalbuminuria is considered the earliest
detectable stage of diabetic nephropathy
– This finding should alert the clinician to signs
of vascular disease at other sites in the body
in addition to the kidney.
– This stage is potentially reversible with
prompt but correct intervention.

52. Microalbuminuria
• Microalbuminuria is an indicator of ↓ renal
function and an accepted risk marker for
cardiovascular events and mortality
• Coexistence of type 2 diabetes and arterial
hypertension significantly risk of cardio-↑
renal disease & development of CV events,
to potentially mortality.↑
• This has led to the recommendation of use
of albuminuria as a therapeutic target.

53. Microalbuminuria
• Most antihypertensive
treatment trials [but not
all] —have shown that
in patients with type 2
diabetes, a reduction in
microalbuminuria was
consistently associated
with evidence of renal
protection.
Annual risk of cardiovascular (CV)
death in patients with
type 2 diabetes mellitus and different
degrees of nephropathy in
the UKPDS (United Kingdom
Prospective Diabetes Study).

54. Microalbuminuria
• Microalbuminuria – why is antihypertensive
choice important?
• Antihypertensive drugs or combinations
differ in their ability to prevent major renal
and cardiovascular events, even if they
produce similar reductions in BP.
• Adding further antihypertensives may not
improve renal & mortality outcomes even if
it produces further ↓ in BP.

55. Microalbuminuria

56. Microalbuminuria
• Renin-angiotensin-aldosterone system
(RAAS) Overactivity is known to cause
deterioration of renal function in patients
with diabetic nephropathy.
• Increases in microalbuminuria are ↓ by BP
reduction using inhibitors of the RAAS.
• ACEIs are medication of choice in reducing
microalbuminuria in diabetic hypertensives.

57. Microalbuminuria
• Studies with telmisartan clearly show that
blocking of RAAS in patient with type II
diabetes mellitus
1. Reduces the risk of progression of
microalbuminuria to overt proteinuria and
2. may even revert back to normoalbuminuria.

58. Important Hypertension trials
9

59. Important Hypertension Trials
• SHEP (Systolic Hypertension in the Elderly Program)
– In persons aged 60 years and over with isolated systolic hypertension, antihypertensive stepped-care drug
treatment with low-dose chlorthalidone as step 1 medication reduced the incidence of total stroke by 36%
• ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial)
– The mean systolic blood pressure was 4mm Hg higher in blacks and 2 mm Hg higher in non-blacks in the lisinopril
group than in the chlorthalidone group. Blood pressure control was 8-13% better in the chlorthalidone group than
in the lisinopril group for blacks. Although in the trial overall the chlorthalidone group was better controlled than
the lisinopril group, this difference between the two groups among blacks is quite striking.
• MRFIT (Multiple Risk Factor Intervention Trial)
– Changed protocol in clinics using primarily HCTZ to chlorthalidone due in part to an a higher trend in mortality in
clinics using predominantly hydrochlorothiazide. Changing to chlorthalidone was associated with a trend toward
better outcomes.
• TROPHY (Trial of Preventing Hypertension)
– Found that it is possible to prevent or delay the onset of clinical hypertension in people with blood pressure that
falls within the "prehypertension" category

60. Important Hypertension Trials
• TOHP (Trials of Hypertension Prevention)
– Sodium reduction, previously shown to lower blood pressure, may also
reduce long term risk of cardiovascular events.
• TONE (Trial of Nonpharmacologic Interventions in the
Elderly)
– Reduced sodium intake and weight loss constitute a feasible, effective,
and safe nonpharmacologic therapy of hypertension in older persons.
• HYVET (Hypertension in the Very Elderly Trial)
– According to Timothy Gardner, M.D., President of the American Heart
Association: ‘The results of HYVET demonstrate that effective
antihypertensive treatment with indapamide (Natrilix SR) in persons
aged 80 years old or older, is beneficial in reducing the risk of
cardiovascular events, and thus extends the patient group in whom
prevention must be pursued.’

61. Fixed dose combinations

62. Take home message
The brand The application
Telmisartan Step 1 case, Intolerance to ACE
inhibitors
Telmisartan-H Step 2 case with slight pedal oedema
Telmisartan-AM Step 2, Type 2 diabetic nephropathy,
Diabetic microalbuminuria
Telmisartan-MT Hypertension in patients who have
IHD or Myocardial Infarction or heart
failure.
Telmisartan-AMH Step 3 case
Metoprolol H ?????

63. Metoprolol
The dependable beta blockerThe dependable beta blocker

64. Metoprolol
• Metoprolol is a competitive, beta-1 selective
(cardioselective) adrenergic antagonist, which is
most similar to atenolol but more lipid soluble &
– Has good lipid solubility,
– Has membrane stabilizing activity (MSA), and
– Lacks intrinsic sympathomimetic activity (ISA)
Without ISA actvity With ISA actvity

65. Metoprolol
• Less lipid soluble than propranolol with relatively
short elimination half-life compared to other
cardioselective beta-blockers.
• In low doses, selectively blocks beta1-receptors in
the heart and vascular smooth muscle.
► But, selectivity for the beta1-receptor is lost at higher
doses.
• Consequences:
– ↓ in both resting /exercise heart rate & cardiac output,
– ↓ in both systolic and diastolic BP.
– ↓ of renin release from the kidneys.
– ↓ reflex orthostatic hypotension.

66. Metoprolol
• Metoprolol affects blood pressure via multiple
mechanisms.
1. Reduction in the heart rate and cardiac output at
rest and upon exercise,
2. Reduction of systolic blood pressure upon
exercise.

67. Metoprolol
• Absorption: Rapid and complete
• First pass metabolism: approx. 50%
• Plasma protein binding: 12%
• Half life: Ranges from 3-7 hours
• Metabolized in Liver & excreted via kidney
► IndicationsIndications
 Hypertension, Angina pectoris, Heart failure
► ContraindicationsContraindications
 Hypersensitivity & Severe bradycardia

68. Metoprolol
• Warnings and Precautions
– Use cautiously in bronchospastic disease
patients.
– Use cautiously in diabetic patients
– Use cautiously in patients with impaired
hepatic function.

69. Metoprolol H
• Combination of metropolol succinate [ short
acting is metoprolol tartarate]
The combo The application
Telmisartan-Mt Great value in HF cases with
hypertension with no fluid overload
Metoprolol-H Great value in HF cases with
hypertension and fluid overload