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66 hypertension
1. Partners in Healthcare Education, LLC 2009 1
Hypertension:
A Focus on JNC VII
Wendy L. Wright, MS, RN, ARNP, FNP, FAANP
Adult/Family Nurse Practitioner
Owner – Wright & Associates Family Healthcare, PLLC
Partner – Partners in Healthcare Education, LLC
2. Partners in Healthcare Education, LLC 2009 2
Objectives
• Upon completion of this lecture, the
participant will be able to:
– Identify the various classifications of
prehypertension, Stage I and Stage 2
hypertension
– Discuss nonpharmacologic treatment options
for the patient with hypertension
– Discuss pharmacologic treatment options for
the patient with hypertension
3. Partners in Healthcare Education, LLC 2009 3
CVD Is the Most Common Health
Problem in the United States
More than 60 million Americans
(>20%) have some form of
cardiovascular disease
Adapted from American Heart Association. Heart Disease and Stroke Statistics – 2003 Update. Dallas, Tex; 2002.
4. CVD disease mortality trends for males and femalesCVD disease mortality trends for males and females (UnitedUnited
States: 1979-2004).States: 1979-2004).
SSource: NCHS and NHLBI.ource: NCHS and NHLBI.
400
450
500
550
79 80 85 90 95 00 04
DeathsinThousands
Years
Males Females
CVD disease mortality trends for males and females
4
Wright, 2009
5. Partners in Healthcare Education, LLC 2009 5
Evolution in Understanding Cardiovascular
Disease: Total Risk Perspective
Cardiovascular Disease Is an Interplay of Risk Factors
Age Gender
Smoking
Dyslipidemia Hypertension
Diabetes
Mellitus
Kannel WB. Am J Hypertens. 2000;13:3S-10S; Poulter N. Am J Hypertens. 1999;12:92S-95S.
6. Partners in Healthcare Education, LLC 2009 6
Hypertension and Dyslipidemia
Contribute to Atherogenesis
Endothelial
Dysfunction
CVD
Hypertension Dyslipidemia
Atherosclerosis
Smooth Muscle
Cell Contraction
Impaired Bioavailability
of Nitric Oxide
Impaired
Vasodilation
7. Partners in Healthcare Education, LLC 2009 7
Impact of Elevated SBP and Total
Cholesterol on CHD Mortality in MRFIT
Age-Adjusted CHD
Death Rates
Per 10,000 Person-Years
Cholesterol
Quintile (mg/dL)
SBP Quintile (mm Hg)
MRFIT = Multiple Risk Factor Intervention Trial.
Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64.
33.7
21
17.1
12.7 12.2
22.6
12.3
8.3 9.6
5.9
17.7
10.9
8.5
6.3
5.5
16.7
7.9 7.9
6
4.3
13.7
5 5.6
3.4 3.1
≥142
132-141
125-131
118-124 <118
<182
182-202
203-220
221-244
≥245
8. Partners in Healthcare Education, LLC 2009 8
Hypertension and Dyslipidemia:
A Significantly Undertreated Syndrome
Adapted from American Heart Association. Heart Disease and Stroke Statistics—2003 Update; CDC; NHANES III (1988-1994).
27 Million Affected by Both Hypertension and Dyslipidemia
9 million
diagnosed with both
3 million treated for both
300,000 at both
goals (~ 1%)
14.7 million
undiagnosed
9. 9
Impact of Hypertension
• 50 million individuals
in the United States
have hypertension1
• 277,000 deaths
annually in US due
to hypertension2
1
American Association of Clinical Endocrinologists Medical Guidelines For Clinical Practice for the Diagnosis and
Treatment of Hypertension. Endocrine Practice, Vol 12 No. 2 March/April 2006
2
National Center for Health Statistics. Health, United States, 2005, with Chartbook on the Health of Americans.
Hyattsville, Maryland: 2004. Available at: http://www.cdc.gov/nchs/hus.htm
10. Hypertension Remains One of the Most
Important Multipliers of CV Risk
BP >140/90 mm Hg is associated with:
• 277,000 deaths in 2003
BP, blood pressure; CHF, congestive heart failure; MI,
myocardial infarction.
Rosamond W et al. Circulation. 2007;115:1-103.
11. Partners in Healthcare Education, LLC 2009 11
It is currently estimated that…
• 90% of normotensive 55 year olds will
develop hypertension at some point in
his/her lifetime
12. Partners in Healthcare Education, LLC 2009 12
Hypertension: Controlled or Not?
Prevalence(%)
Hypertension
0
20
40
60
80
Controlled on medication
Uncontrolled on medication
Diagnosed
Adapted from NHANES III Morning Examination Subset: Hypertension (June 1998);
13. Partners in Healthcare Education, LLC 2009 13
Statistics of Interest
• 53% of patients with hypertension are
being treated with medications
• Of those treated, 29% have their blood
pressure < 140/90
Lookinland, S. and Beckstrand, R. Evidence-Based Treatment of Hypertension: JNC
7 Guidelines Provide an Updated Framework; Advance for Nurse Practitioners, Sept
2003.
14. 14
Hypertension and Management:
Old School
Hypertension = Systemic disease
Hemodynamics altered
Treat the blood pressure
Therapeutic options
Beta
Blockers
ACE ARB Diuretics CCB Others
Adapted from Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director
15. 15
Hypertension and Management: New School
Hypertension =
Disease of the blood vessels
Vascular biology altered
Treat the vasculature
Therapeutic options
Beta
Blockers
ACE ARB Diuretics CCB Others
Adapted from Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director
16. Physiology of the
Renin Angiotensin System
Ang, angiotensin.
Reid IA. Adv Physiol Edu. 1998;20:S236-S245.
↓ BLOOD PRESSURE
BLOOD VOLUME
Activation of
Baroreceptor
Reflexes
↑ Renal Sympathetic
Nerve Activity
Beta-adrenergic
Stimulation
↑ RENIN
SECRECTION
↓ Renal Artery
Pressure
Renal
Baroreceptor
↑ BLOOD PRESSURE
BLOOD VOLUME
Systemic
Vasoconstriction
↑ Plasma
Ang II
↑ Aldosterone
Secretion
↑ Plasma
Ang I
17. 17
RAAS and Adipose Tissue
• All components of the RAAS system are
expressed in adipose tissue, especially
the visceral adipose tissue1,2,3
• Visceral adipose tissue of patients with
insulin resistance and Type 2 diabetes is
dysfunctional and is a source of chronic
low-grade inflammation4
1 Sowers, James R. Insulin Resistance and Hypertension Physiol Heart Circ Physiol. 2004;286:
H1597-H1602
2 Ashish, A, El-Atat, R, et al. Hypertension and Obesity Recent Prog Horm Res. 2004;59:169-205.
3 Kershaw EE, Flier JS. Adipose Tissue as an Endocrine Organ Clin Endocrinol Metab. 2004;
98:2548-2556..
18. 18
RAAS and Endothelial Dysfunction
• Growing body of evidence
– Promotion of endothelial dysfunction
– Microalbuminuria1,2
• RAAS Inhibition (ACE, ARB and
Direct Renin Inhibitor)
– Decreased incidence of new onset Type
2 diabetes
– Improvement in CVD outcomes3
Higashi, Y, Sasaki S, Nakagawa K, et al. Endothelial Function and Oxidative Stress
In Renovascular Hypertension N Engl J Med 2002;346:1954-1962.
19. 19
Today –
The Hypertensive Patient Exhibits...
• More insulin resistance
• More hyperinsulinemia
• Dyslipidemia
• Microalbuminuria
• Obesity
...as compared to nonhypertensive
patients!
Reaven GM. Banting lecture 1988. Role of insulin resistance in human. Disease Diabetes.
1988.37;1595-1607.
21. Partners in Healthcare Education, LLC 2009 21
JNC VII:
Messages to Clinicians
JAMA. 2003:289:2560-2577.
22. Partners in Healthcare Education, LLC 2009 22
New Messages JNC VII
• The risk of CVD,
beginning at
115/75 mm Hg,
doubles with
each increment
of 20/10 mm Hg.
JAMA. 2003:289:2560-2577.
23. 23
CV Disease Risk Doubles with
Each 20/10 mm Hg BP Increment*
*Individuals aged 40-70 years, starting at BP 115/75 mm Hg.
CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure
CV
disease
risk
SBP/DBP (mm Hg)
0
1
2
3
4
5
6
7
8
115/75 135/85 155/95 175/105
1. Lewington S, Cardiovascular Issues in Ageing Pilots. et al. Lancet. 2002; 60:1903-1913
2. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, And Treatment of High Blood
Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1. Assessed 5-1-08
24. Partners in Healthcare Education, LLC 2009 24
Diagnosis
• 2 readings; separated apart
• Patient should not ingest caffeine or
smoke for 30 minutes before readings
• Patient should sit for 5 minutes with arm
at heart level before blood pressure is
checked
25. Partners in Healthcare Education, LLC 2009 25
JNC 7: New Blood Pressure
Classification
Blood Pressure Classification
SBP* DBP*
(mm Hg)
Normal
<120 and <80
Prehypertension
120-139 or 80-89
Stage 1 hypertension
140-159 or 90-99
Stage 2 hypertension
≥160 or ≥100
*Treatment determined by highest BP category (SBP or DBP).
Adapted from Chobanian AV et al. JAMA. 2003;289:2560-2572; NHBPEPCC. 2003. NIH Publication No. 03-5233.
26. Partners in Healthcare Education, LLC 2009 26
Prehypertension
• Individuals with a
systolic BP of 120-
139 mm HG or a
diastolic BP or 80-
89 mm HG should
be considered as
pre-hypertensive
and lifestyle
modification
initiated.JAMA. 2003:289:2560-2577.
27. Partners in Healthcare Education, LLC 2009 27
Most Cases of Hypertension
• Primary hypertension
– Also called essential
– Responsible for 90-95% of all hypertension
diagnoses
28. Partners in Healthcare Education, LLC 2009 28
Consider Secondary Causes of
HTN
• Sleep apnea
• Drug-induced or drug related
– Including OTC medications
• Chronic kidney disease
– Polycystic kidneys
• Renal artery stenosis
• Primary aldosteronism
• Renovascular disease
• Chronic steroid therapy and Cushing’s disease
• Pheochromocytoma
• Coarctation of the Aorta
• Thyroid or parathyroid disease
JAMA. 2003:289:2560-2577.
29. Partners in Healthcare Education, LLC 2009 29
What about White-Coat Hypertension?
• Patient involvement in the measurement of
his/her blood pressure is recommended,
particularly for those individuals whose blood
pressure is normal out of the office but
consistently elevated in the office
• The office blood pressure of elders is 5 mm Hg
higher than their ambulatory blood pressure
• Older the individual, the greater the discrepancy
between home and office blood pressures
• No longer considered a benign condition
JAMA. 2003:289:2560-2577.
30. 30
Initial Work-up
• History and review of systems
– Medications and risk factors
• Consider home blood pressure readings with
validated blood pressure cuff
• Laboratory workup: CBC, BUN, Creatinine,
Glucose, Lipids, GFR, urine - protein
• EKG and/or Echocardiogram, if indicated
• Urine for microalbuminuria
Pickering, TG, Hall JE, et al. AHA Scientific Statement: Recommendations for Blood Pressure
Measurement in Humans and Experimental Animals. Part 1: Blood Pressure Measurement in Humans
Hypertension. 2005;45:142-161.
32. Partners in Healthcare Education, LLC 2009 32
How Helpful is control of BP?
In stage 1 HTN, combined with additional
CVD risk factors, achieving a sustained
12 mmHg reduction in SBP over 10
years will prevent 1 death for every 11
patients treated.
JAMA. 2003:289:2560-2577.
33. 33
Benefits of Lowering Blood
Pressure
Average Percent Reduction
Stoke: 35% - 40%
MI: 20% - 25%
CHF: 50%
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
34. Partners in Healthcare Education, LLC 2009 34
Treatment Goals
• < 140/90 mm Hg for those with no
complications
• < 130/80 mm Hg for those with diabetes
or CRF (per ADA)
• < 130/80 mm Hg – all individuals per
NKF
35. Partners in Healthcare Education, LLC 2009 35
JNC 7: Algorithm for Treatment of
Hypertension
Prehypertension (SBP 120-139 mm Hg or DBP 80-89 mm Hg)
Not at Goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with
diabetes or chronic kidney disease)
Without Compelling Indications With Compelling Indications
Prehypertension
Stage 1 Hypertension
(SBP 140-159 or DBP 90-99 mm Hg)
Thiazide-type diuretics for most;
may consider ACEI, ARB, BB,
CCB, or combination.
Stage 2 Hypertension
(SBP ≥160 or DBP ≥100 mm Hg)
2-drug combinations for most
(usually thiazide-type diuretics and
ACEI, or ARB, or BB, or CCB).
Drug(s) for compelling indications
Other antihypertensive drugs
(diuretic, ACEI, ARB, BB, CCB)
as needed.
Adapted from NHBPEPCC. 2003. NIH Publication No. 03-5233.
LIFESTYLE MODIFICATIONS
If not at goal BP, optimize dosages or add additional drugs until
goal BP is achieved. Consider consultation with hypertension specialist.
INITIAL DRUG CHOICES
37. Partners in Healthcare Education, LLC 2009 37
New Messages JNC VII
• The most effective
therapy prescribed
by the most careful
clinician will control
hypertension….only
if the patient is
motivated.
JAMA, May 21, 2003 Vol 289;No 19.
38. Partners in Healthcare Education, LLC 2009 38
Lifestyle Modifications to Manage Hypertension
Modification Recommendation Systolic Diastolic Chgs
Weight Reduction BMI 18.5-24.9 5-20mm/10 kg wt loss
Adopt DASH eating Diet rich in fruits 8-14 mm Hg
vegetables and low
fat with reduced
saturated and total fat
Dietary Sodium 2.4g Na 2-8 mm Hg
Physical Inactivity Brisk exercise 30” day 4-9 mm Hg
most days of week
Moderation of
Alcohol intake 2 drinks day max 2-4 mm Hg
24 oz beer; 10 oz wine
2 oz 100 proof whiskey
JAMA. 2003:289:2560-2577.
39. Partners in Healthcare Education, LLC 2009 39
Lifestyle Modifications
• Dietary sodium reduction
– Most helpful in African Americans and
patients with diabetes
– Recommend limiting sodium to < 2000
mg/day for these individuals
• Average individual ingests 4000 mg / day
– ACE inhibitors and diuretics work best with
a relatively low sodium diet
40. Partners in Healthcare Education, LLC 2009 40
How Successful Is It?
• Combination of the DASH diet and a
dietary sodium reduction to 1600
mg/day is as effective as 1 medication
41. Partners in Healthcare Education, LLC 2009 41
Alcohol Intake
• Limit alcohol intake to < 30 mL or 1 ounce of
ethanol/day
– Translation: 2 ounces of whiskey
– 10 ounces of wine
– 24 ounces of beer
• Excessive amounts increases treatment
resistance
• Also increases risk of a CVA** Women: ½ this amount
42. Partners in Healthcare Education, LLC 2009 42
Electrolytes
• Diets high in potassium, calcium and
magnesium are associated with a lower
blood pressure
• JNC VII recommends an adequate
dietary intake of these but does not
recommend supplementing from an
outside source to lower blood pressure
43. Partners in Healthcare Education, LLC 2009 43
Additional Recommendations
• Omega-3 fatty acids may lower blood
pressure
• Caffeine may increase it but tolerance
often develops
– Most studies do not support a relationship
between hypertension and caffeine
• Smoking: discontinuation is important
• Exercise: 30 minutes daily
recommended
45. Partners in Healthcare Education, LLC 2009 45
New Messages JNC VII
• Thiazide
diuretics should
be used in drug
treatment for
patients with
uncomplicated
hypertension.
JAMA. 2003:289:2560-2577.
46. Partners in Healthcare Education, LLC 2009 46
Thiazide Diuretics
• Dosing:
– Start @ 12.5 mg of HCTZ
– Increase to 25 mg at 6 weeks
• Benefits
– 55% reduction in CHF
– 37% reduction in CVA
– 27% reduction in cardiac events
• If not adequately controlled, add
additional agents
47. 47
Diuretic Precautions
• Electrolyte imbalances
• Syncope/presyncope when combined
with ACE/ARB
• Hemoconcentration
• Decrease in urate excretion
• Worsening of insulin resistance at
higher doses
• Fatigue
Product inserts accessed 04-20-2008
48. 48
Angiotensin Converting
Enzyme (ACE) Inhibitors
•Increased nitrous oxide at vessel for
vasodilatation
•Improved glucose disposal
•Reduction in LV geometry changes
•Reduction in inflammation
•Stabilization of fibrous cap of lipid lesion
•Decreased proteinuria
•Improves endothelial function
•Reduced mortality in patients with CHF
•Decreases post-MI mortality
Sato Atsuhisa, Pleiotropic effects of angiotensin-converting enzyme inhibitors; differentiation
Among ace inhibitors may lead to further organ protection. Abstr 21st
Sci Meet Int Soc Hypertens
2006. 423(2006)
49. 49
ACE Inhibitor Trials
1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 2000 2001
CONSENSUS I
ValHeFT II
SOLVD treatment
SAVE
AIRE
TRACE
SMILE
CATS
CONSENSUS II
GISSI-3
ISIS-4
PEACE
HOPE
Latini, et al. Curr Perspect. 1995;92:3132-7
CCS-1
CHF
Anterior
AMI
AMI
CAD
LVD
Post-AMI
50. 50
ACE Inhibitors Precautions
• Hyperkalemia
• Increase in creatinine
• May improve insulin
sensitivity
• Decrease in serum
Na+ may result in
syncope and dizziness
when used with
diuretics
Product inserts accessed 04-20-2009
• Angioedema
• Cough
51. 51
Effects on Hypoglycemia
• Several studies have shown the ability
of ACE inhibition to improve glycemic
control – even decrease the risk of
hypoglycemia in patients using
sulfonylureas.
Thamer M, Ray NF, Taylor T. Association between antihypertensive drug use and
hypoglycemia: A case-control study of diabetic users of insulin or sylfonylureas. Clin
Therapeutics 1999; 21:1387
53. 53
** ** ** **** ** ** **
* = p<0.001 versus placebo* = p<0.001 versus placebo
Plasma ACEPlasma ACE
(mmol/ml/min)(mmol/ml/min)
Plasma ANG IIPlasma ANG II
(pg/ml)(pg/ml)
**
Placebo 4h 24h 1 2 3 4 5 6Placebo 4h 24h 1 2 3 4 5 6
HospitalHospital MonthsMonths
Modified fromModified from Journ Cardiovasc PharmJourn Cardiovasc Pharm 1982; 966-721982; 966-72
Long Term Effect of Enalapril (20mg)
on Plasma ACE and Angiotensin II
Vascular Biology Working Group, University of Florida
College of Medicine, Carl Pepine, MD, Director
54. 54
If you block the receptor
site, you don’t have to worry
about the angiotension levels…
AT1
56. 56
Angiotension Receptor
Blockers (ARB’s)
• Utilized since April 1995
• Blocks uptake at receptor site
• Angiotension II produced in locations
other than in the lungs
• BP decreased by reducing vascular
tone and enhancing NA+ and water
clearance
57. 57
Metabolic Effects of ARB’s
• Angiotensin II
Receptor Blockers
• Metabolically neutral
• No impact on lipids
• No impact on insulin
• No impact on K+
• Lowers uric acid
levels
• Minimal side effect
profile
Product Inserts accessed 04-20-2009
58. 58
ARB Trials
1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
ValHeFTELITE I
ELITE II
IDNT
RENAAL
IRMA II
OPTIMAAL
LIFE
VALIANT
VALUE
CHARM
MARVAL
ON TARGET
CHF
CV
MI
Renal/CV
Renal
IPreserve
59. ACE vs ARB
ONTARGET Trial
Goal: 1. Assess the effects of ACE VS ARB in
terms of efficacy
2. Assess if the combination ACE & ARB
was superior
Results: Telmisartan was found to be “noninferior” to
ramipril in patients with vascular disease or high
risk diabetes
Combination of these two agents was
associated with more adverse events without an
increase in benefit.
59
Yusuf, S, Teo KK, Pogue, J et al for the ONTARGET investigators. Telmisartan, ramipril, or both in patients
At high risk for vascular events N Engl J Med 2008;358:1547-1559.
60. 60
Beta
Blockers
•Reduction in blood pressure
•Decreased contractility
•Decreased heart rate
•Decreased myocardial oxygen
demand
•Reduction in LVH
•Reduced arrhythmias
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
61. 61
Beta Adrenergic Receptors
• 3 receptors are found in human
cardiac myocytes that are coupled to a
positive inotropic response and cell
growth.
– Beta1
– Beta2
– Alpha1
Hunt, et al. ACC/AHA 2005 Chronic Heart Failure Guideline Update. JACC.2005; 46:1116-43.
62. Beta Blocker Trials
SHEP Systolic Hypertension
in the Elderly Program
Step Approach
Chlorthalidone/Atenolol
Reduced incidence
of major CV events
and CVA;
chlorthalidone
decreased CHF
STOP
HTN 2
Swedish Trial in Old
Persons with
Hypertension
Beta Blocker Vs CCB VS
ACE on CV Morbidity
ACE /BB similar
efficacy in preventing
CV mortality.
CAPPP Captopril Prevention
Project
Beta Blocker + Diuretic
vs Captopril
Captopril not better
than conventional
HTN Rx in prevention
of CV morbidity and
mortality; Diabetic
patients on captopril
did better than BB
+Diuretics in
decreasing morbidity
62
64. 64
Calcium Channel Blockers
• Effectively treat systolic hypertension
• May be superior to other
antihypertensives for stroke prevention
• Effective in patients with:
– Comorbid conditions (Raynauds, migraine)1
• Particularly effective in
– Elderly and African American’s2
1. Materson BJ, Reda DJ, eta l. Single drug therapy for hypertension in men. A comparison of six
Antihypertensive agents with placebo. N Engl J Med. 1993;328:914-921.
2. Tuomilehto J, Rastenyte D, et al. Effects of calcium channel blockade in older patients with
Diabetes and hypertension. N Engl J med. 1999;340:677-684.
65. The Calcium Blockers
Dihydropyridines
– Studies of DPH’s effects on
proteinuria have produced
conflicting results
– NKF recommends that in
patients who have diabetes
and kidney disease, DPH’s
should only be used in
combination with and ACE
or ARB
Nondihydropyridines
– Regression of proteinuria
– Combination of Verapamil +
ACE, reduction in proteinuria
can be greater than
achievable with verapamil
alone.
– NKF now recommends
adding a NDH to treat
hypertension with an ACE
inhibitor or an ARB to slow
the progression of kidney
disease.
65
Thornley-Brown D, et al for the African American
Study of Kidney Disease and
Hypertension Study Group. Differing effects of
antihypertensive drugs on the incidence
Of Diabetes mellitus among patients with
hypertensive kidney disease. Arch Intern Med.
2006;166(7):797-805.
National Kidney Foundation. K/DOQI clinical
practice guidelines on hypertension
and antihypertensive agents in chronic kidney
disease. Am J Kidney Dis. 2004;
43(suppl 1):S1-S290.
67. 67
Alpha Blockers
• Block postsynaptic Alpha1 Receptors
• Results in vasodilatation
• Relatively inexpensive
• Fair tolerability; May cause postural effects
• Additive agent for older men to decrease BPH
symptomatology
• Add-on agent only
• Should never be used as monotherapy due to
increased risk of stroke and CHF
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
69. 69
Centrally Acting Agents
• Stimulates central alpha2 receptors which
results in:
– Inhibiting efferent sympathetic activity
• Additive agents
• Should be used 3rd
or 4th
line
– Examples: Clonidine (catapress, catapress
TTS); methyldopa
• Caution: sedation, orthostatic hypotension
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
71. 71
Direct Vasodilators
• Direct smooth muscle vasodilatation,
primarily arteriolar
• Two agents
– Apresoline (Hydralazine)
– Minoxidil
**Precautions include: tachycardia, significant
peripheral edema and hair growth
**Agents to reduce heart rate may be needed
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
74. 74
Aldosterone as a
Therapeutic Target
• Aldosterone promotes:
– Retention of sodium
– Loss of magnesium and potassium
– Sympathetic activation
– Parasympathetic inhibition
– Baroreceptor dysfunction
– Impaired arterial compliance
Mac Fadyen RJ, et al Aldosterone blockade reduces vascular collagen
turnover, improves heart rate variability and reduces early morning rise in
heart rate in heart failure patients. Cardiovasc Res 1997;35:30-34.
75. 75
• May be recommended in the following
individuals:
– Post MI
– NYHA Class III or IV
– Ejection fraction of < 35%
– Serum creatinine of < 2.5 mg/dl
– K+ < 5.0 mmol/L
Mardi Gomberg-Maitland, Baran DA, Fuster, V. Treatment of Congestive Heart Failure
Guidelines for the Primary Care Physician and Heart Failure Specialist. Arch Intern
Med 2001;161:324-352et al. ACC/AHA 2005 Chronic Heart Failure Guideline Update.
JACC.2005; 46:1116-43.
Aldosterone Antagonists
76. 76
Precautions
• Must monitor electrolytes
• Must obtain baseline renal function
• Should discontinue the K+
supplement
• Should limit to use in severe heart
failure and post MI patients
Clavell, Alfredo L. Common Mistakes made in the Treatment of Congestive Heart Failure. Success with
Failure: New Strategies for Evaluation and Treatment of CHF.
Whistler BC, Canada 8-2000.
78. 78
Direct Renin Inhibitor
Renin is the enzyme at the
beginning of the RAAS, one
of the key regulating centers
for blood pressure. Blocking
this enzyme can decrease the
downstream impact of the
RAAS system.
Suppression of the RAAS
has been shown to treat
hypertension and reduce
target organ damage.
79. Direct Renin Inhibition
Inhibits the Entire Renin System1-4
Class
ACEI
ARB
Direct Renin Inhibitor (DRI)
PRA Ang I Ang II
Increased peptide levels have not been shown to overcome the blood pressure–lowering effect of these agents.
ACEI, angiotensin-converting enzyme inhibitor; Ang, angiotensin; ARB, angiotensin receptor blocker;
PRA, plasma renin activity.
1.Johnston CI. Blood Press Suppl. 2000;1:9(suppl 1):9-13.
2.Widdop RE et al. Hypertension. 2002;40:516-520.
3.Fabiani ME et al. Angiotensin II Receptor Antagonists. 2001:263-278.
4.Lin C et al. Am Heart J. 1996;131:1024-1034.
80. Aliskiren
Dosage:
–150 mg or 300 mg once daily
Indications:
–Adults with hypertension
–May be administered with any
other antihypertensive
Product Insert, 2007
81. Partners in Healthcare Education, LLC 2009 81
New Messages JNC VII
• Certain high risk conditions
are compelling indications
for the initial use of other
antihypertensive drug
classes.
– Angiotensin-converting
enzyme inhibitors
– Angiotensin-receptor
blockers
– Beta blockers
– Calcium channel blockers
JAMA. 2003:289:2560-2577.
82. Partners in Healthcare Education, LLC 2009 82
JNC 7: Compelling Indications for Individual
Antihypertensive Drug Classes
Compelling
Indication*
Recommended Drugs
DIURETIC BB ACEI ARB CCB
Aldo
ANT
Heart failure • • • • •
Post-MI • • •
High coronary disease
risk
• • • •
Diabetes • • • • •
Chronic kidney disease • •
Recurrent stroke
prevention
• •
*Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines; the compelling indication is managed parallel with the BP.
ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; Aldo ANT = aldosterone antagonist; BB = beta-blocker; CCB = calcium channel blocker.
Adapted from NHBPEPCC. 2003. NIH Publication No. 03-5233.
85. 85
JNC 7 (2003)
Combination Therapy
•Most hypertensive patients will require
two or more antihypertensive
medications to achieve goal BP
(<140/90 mm Hg or <130/80 mm Hg in
patients with diabetes/renal disease)
•Initiating therapy with combination
therapy should be considered when BP
is >20/10 mm Hg above goal.
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
86. 86
•“When BP is more than 20/10 mm Hg
above goal, consideration should be given
to initiating therapy with two drugs, either
as separate prescriptions or in fixed-dose
combinations.”
•“Failure to titrate or combine medications,
despite knowing the patient is not at goal
BP, represents clinical inertia and must be
overcome.”
JNC 7 (2003)
Combination Therapy
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation,
And Treatment of High Blood Pressure. http://jama.ama-assn.org/cgi/content/full/289.19.2560v1.
Assessed 5-1-08
87. 87
AASK MAP
<92
Target BP (mm
Hg)
Multiple Antihypertensive AgentsMultiple Antihypertensive Agents
Are Needed to Achieve Target BPAre Needed to Achieve Target BP
No. of antihypertensive agents
1
UKPDS DBP
<85
ABCD DBP
<75
MDRD MAP
<92
HOT DBP
<80
Trial 2 3 4
DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood
pressure.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
Lewis EJ et al. N Engl J Med. 2001;345:851-860.
IDNT SBP <135/DBP
<85
89. Partners in Healthcare Education, LLC 2009 89
Target Organ Damage
• Heart
– LVH, Angina, CHF, MI
• Brain
– Stroke or TIA
– Dementia
• Chronic Kidney Disease
• Peripheral Vascular Disease
• Retinopathy
JAMA. 2003:289:2560-2577.
90. Partners in Healthcare Education, LLC 2009 90
Pick the agent wisely
• Benefits are not the same in
antihypertensive therapy at
the same commensurate
blood pressure control.
American Heart Association Scientific Sessions 2003; November 9-12, 2003,
Orlando, Florida, USA.
91. Partners in Healthcare Education, LLC 2009 91
Additional Considerations for
the Patient with Hypertension
92. Partners in Healthcare Education, LLC 2009 92
New Messages JNC VII
• In presenting the
NEW JNC VII, the
committee
recognizes that the
responsible
practitioner’s
judgment remains
paramount.
JAMA. 2003:289:2560-2577.
93. Partners in Healthcare Education, LLC 2009 93
Summary
• Hypertension is highly prevalent and is a
significant risk factor for CHD
• Current guidelines recognize the importance of
assessing multiple cardiovascular risk factors in
patients with hypertension
• Health-promoting lifestyle modifications are an
important part of prevention and treatment of
hypertension
• Antihypertensive therapy reduces CHD risk
• ≥2 antihypertensive agents are usually required
to achieve BP goals in patients with hypertension
94. Partners in Healthcare Education, LLC 2009 94
Thank You!
I Would Be Happy To Entertain Any
Questions
95. Partners in Healthcare Education, LLC 2009 95
Wendy L. Wright, ARNP
Adult/Family Nurse Practitioner
www.4healtheducation.com
WendyARNP@aol.com
Hinweis der Redaktion
Partners in Healthcare Education, LLC 2009
Partners in Healthcare Education, LLC 2009 More than 60 million persons in the United States have some form of cardiovascular disease (CVD), such as congestive heart failure, stroke, hypertension, or hardening of the arteries or other disease of the circulatory system. Although CVD may have traditionally been considered “a man’s disease,” National Health and Nutrition Examination Survey (NHANES) III data (1988-1994) showed a nearly equal prevalence between males and females, with actually ~ 32 million females and ~ 30 million males affected. According to the NHANES III data, occurrence of CVD is highest among blacks. Of the total population of women with CVD, ~ 40% are black, ~ 24% are white, and ~ 27% are Mexican Americans. Of males with CVD, ~ 41% are black, ~ 30% are white, and ~29% are Mexican Americans. American Heart Association. Heart Disease and Stroke Statistics – 2003 Update. Dallas, Tex: American Heart Association; 2002.
Wright, 2009
Partners in Healthcare Education, LLC 2009 The traditional view of CVD is based on the Framingham Heart Study model of a stepwise increase in CVD risk with multiple independent risk factors. Recently, this model has evolved into a more dynamic one as new epidemiologic and clinical evidence has been published. The current model shows clustering of risk factors, such as hypertension, dyslipidemia, and diabetes along with smoking, gender, and increasing age, emphasizing the synergistic interaction of these risk factors. This dynamic, interactive effect of risk factors places individuals—even those with mild levels of 2 risk factors—at profound risk for CVD. Fuster V, Gotto AM Jr. Risk reduction. Circulation. 2000;102:IV94–IV102. Kannel WB. Framingham study insights into hypertensive risk of cardiovascular disease. Hypertens Res. 1995;18:181-196. Kannel WB. Risk stratification in hypertension: new insights from the Framingham study. Am J Hypertens . 2000;13:3S-10S. Poulter N. Coronary heart disease is a multifactorial disease. Am J Hypertens. 1999;12:92S-95S.
Partners in Healthcare Education, LLC 2009 Hypertension and hypercholesterolemia impair vascular endothelial function by reducing the bioavailability of nitric oxide, an important contributor to vascular smooth muscle relaxation and consequential vasodilation. Nitric oxide depletion also accelerates other atherogenic mechanisms. The endothelium is damaged by the release of reactive molecular groups (eg, oxidants) and elevation of angiotensin II via upregulation of the AT 1 receptor, which increases the deleterious effects of this vasoactive peptide. By downregulating AT 1 receptor expression and activation, statins reduce BP as well as LDL-C. Although hypertension and hypercholesterolemia exert their major effect at the level of the resistance vessels (small arteries), these disorders also reduce the ability of large vessels to distend, a deleterious effect that is reversible with lowering of BP and LDL-C. Some studies have shown a BP-reducing effect of statins in patients with untreated hypertension as well as in those treated with angiotensin-converting enzyme inhibitors (ACEIs) or calcium channel blockers (CCBs) and suggest that statins may act synergistically with antihypertensive agents. John S, Schmieder RE. Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia. Curr Hypertens Rep. 2003;5:199-207. Sander GE, Giles TD. Hypertension and lipids: lipid factors in the hypertension syndrome. Curr Hypertens Rep. 2002;4:458-463. Spieker LE, Noll G, Ruschitzka FT, Maier W, Lüscher TF. Working under pressure: the vascular endothelium in arterial hypertension. J Hum Hypertens . 2000;14:617-630. Giannattasio C, Mancia G. Arterial distensibility in humans: modulating mechanisms, alterations in diseases and effects of treatment. J Hypertens. 2002;20:1889-1899. Borghi C, Dormi A, Veronesi M, Immordino V, Ambrosioni E. Use of lipid-lowering drugs and blood pressure control in patients with arterial hypertension. J Clin Hypertens . 2002;4:277-285.
Partners in Healthcare Education, LLC 2009 Neaton et al analyzed data from 316,099 white men aged 35 to 57 years screened for the Multiple Risk Factor Intervention Trial (MRFIT) to assess the combined influence of BP, serum cholesterol level, and smoking on age-adjusted CHD mortality per 10,000 person-years. One of the more interesting findings was the combined effect of SBP ≥142 mm Hg and total serum cholesterol level 245 mg/dL, which was associated with a death rate of 33.7. This represented a greater than 2-fold increase in risk compared with persons in the same SBP quintile (≥142 mm Hg) and a cholesterol level of 182 mg/dL. It represented nearly a tripling of the risk in persons with SBP of 118 to 124 mm Hg and a cholesterol level 245 mg/dL. For both smokers and nonsmokers, in each SBP quintile, CHD death rates increased with increasing serum cholesterol; similarly, in each serum cholesterol quintile, the rates increased with increasing SBP (shown in green). The graph also shows that 2 moderately elevated risk factors can present a higher risk for a fatal CHD event than 1 severely elevated risk factor (shown in blue). These findings of the association of BP and cholesterol as predictors of CHD strongly support intensified efforts to prevent the development of these risk factors in all age groups. Neaton JD, Wentworth D, for the Multiple Risk Factor Intervention Trial Research Group. 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.
Partners in Healthcare Education, LLC 2009 An estimated 27 million American adults have hypertension and dyslipidemia concurrently. Both conditions are important independent risk factors for CVD, and their effects are additive. Yet the presence of both simultaneously has been diagnosed in only 9 million individuals, or one third of the population at risk. About 6 million persons with the hypertension/dyslipidemia syndrome are being treated for only 1 of the 2 conditions, which means that only 3 million persons are being treated for both. A mere 300,000 of these at-risk individuals are reaching the goals for both BP and lipids. This generalized undertreatment clearly calls for testing for both conditions in the context of overall risk and initiating more aggressive therapy to bring both BP and lipids in line with national guidelines. American Heart Association. Heart Disease and Stroke Statistics – 2003 Update. Dallas, Tex: American Heart Association; 2002. Working Group Report on Management of Patients with Hypertension and High Blood Cholesterol. Bethesda, Md: National Heart, Lung, and Blood Institute; 1990. NIH Pub. No. 90-2361. Working Group Report on Management of Patients with Hypertension and High Blood Cholesterol. National Education Programs Working Group Report on the Management of Patients with Hypertension and High Blood Cholesterol. Ann Intern Med. 1991;114:224-237. Meigs JB, D'Agostino RB Sr, Wilson PWF, Cupples LA, Nathan DM, Singer DE. Risk variable clustering in the insulin resistance syndrome: the Framingham Offspring Study. Diabetes. 1997;46:1594-1600.
Summary: Hypertension is associated with increased cardiovascular morbidity and mortality, leading to an estimated direct and indirect cost of $63.5 billion in 2006. Cardiovascular morbidity and mortality are high among patients with hypertension, which is evident in as many as 69% of patients suffering a first heart attack and 74% of those with congestive heart failure (CHF). In fact, according to a 2006 report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee, approximately 91% of patients with CHF had hypertension before the development of heart failure. 1 This same report indicates that among the 2.4 million deaths that occurred in the United States in 2003, 2 approximately 277,000 were attributable to high blood pressure. The estimated direct and indirect costs of hypertension in 2007 total $66.4 billion. 1 References Rosamond W, Flegal K, Friday G, et al. Heart disease and stroke statistics—2007 update. Circulation . 2007;115:1-103. Centers for Disease Control and Prevention. Number of deaths, death rates, and age-adjusted death rates, by race and sex: United States, 1940, 1950, 1960, 1970, and 1980-2003. Available at: http://www.cdc.gov/nchs/fastats/pdf/mortality/nvsr54_13_t01.pdf. Accessed January 29, 2007.
Partners in Healthcare Education, LLC 2009 Although hypertension is the most common primary diagnosis in the United States, the current control rate for hypertension (~ 30%) is still below the goal of 50% set by the national prevention initiative, Healthy People 2010. Nevertheless, patients with hypertension are more likely to be treated and controlled with medication than are those with dyslipidemia. Based on ATP III guidelines and NHANES III data, approximately 40% of adults aged 20 years require fasting lipoprotein analysis whereas <60% of persons with high cholesterol have been diagnosed with dyslipidemia. Patients’ noncompliance is a likely reason for inadequate lipid-lowering treatment. Their noncompliance with lipid-lowering therapies may be due to the length of therapy or complexity of therapy if multiple medications are required. Patients may also be reluctant to adhere to pharmacologic therapy if the condition appears to be asymptomatic. Additionally, inadequate lipid-lowering treatment may be due to poor compliance by healthcare providers. This may include a tendency to see more urgency in treating hypertension than other CVD risk factors, poor adherence to treatment guidelines, and reluctance to appropriately modify pharmacologic regimens to achieve therapy goals. The NCEP ATP III and JNC 7 guidelines encourage physicians, nurse practitioners, nurses, physician assistants, dietitians, and pharmacists to work as a team in educating, treating, and following up patients. Braunstein JB, Cheng A, Cohn G, Aggarwal M, Nass CM, Blumenthal RS. Lipid disorders: justification of methods and goals of treatment. Chest. 2001;120:979-988. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572. National Cholesterol Education Program. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel [ATP] III). Final Report. Bethesda, Md: National Heart, Lung, and Blood Institute; 2002. NIH Publication No. 02-5215. Sempos CT, Cleeman JI, Carroll MD, et al. Prevalence of high blood cholesterol among US adults: an update based on guidelines from the second report of the National Cholesterol Education Program Adult Treatment Panel. JAMA. 1993;269:3009-3014.
SLIDE SUMMARY: PHYSIOLOGICALLY, THE RENIN ANGIOTENSIN SYSTEM HELPS TO REGULATE BLOOD PRESSURE AND BLOOD VOLUME BY RESPONDING TO EXTRACELLULAR FLUID VOLUME AND BLOOD PRESSURE REDUCTIONS The diagram shows the cascade of events characteristic of the physiologic operation of the renin angiotensin system Reductions in blood volume and arterial pressure, perhaps caused by dehydration or blood loss, result in decreased firing of low- and high-pressure baroreceptors. This causes an increase in renal sympathetic nerve activity, which, together with decreases in renal artery pressure, glomerular filtration rate, and macula densa salt load, stimulates renin secretion 1 Renin secretion initiates processes resulting in increased plasma concentrations of angiotensin II, which causes vasoconstriction, renal sodium reabsorption, and thirst (stimulating fluid intake). These processes lead to restoration of blood volume and blood pressure 1 Reid IA. The renin-angiotensin system: physiology, pathophysiology, and pharmacology. Adv Physiol Edu . 1998;20:S236-S245.
Slide Summary According to a meta-analysis of over 60 prospective studies, the risk of cardiovascular disease doubles with each rise of 20 mm Hg in systolic blood pressure (BP) and 10 mm Hg in diastolic BP. Background In a meta-analysis of 61 prospective, observational studies conducted by Lewington et al involving one million adults with no previous vascular disease at baseline, the researchers found that between the ages of 40-69 years, each incremental rise of 20 mm Hg systolic BP and 10 mm Hg diastolic BP was associated with a twofold increase in death rates from ischemic heart disease and other vascular disease. The researchers also noted that when attempting to predict vascular mortality risk from a single BP measurement, the average of systolic and diastolic BP was “slightly more informative” than either alone, and that pulse pressure was “much less informative.” The seventh report Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) notes this study result as yet more information linking hypertension to high risk for cardiovascular events. Lewington S, Clarke R, Qizilbash H, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet . 2003;361:1903-1913. JNC 7. JAMA. 2003;289:2560-2572.
Partners in Healthcare Education, LLC 2009 The most important departure from JNC 6 in JNC 7 is a new category designated prehypertension (SBP of 120-139 mm Hg or DBP of 80-89 mm Hg) . The addition of this category emphasizes the importance of preventing BP from reaching hypertensive levels (>140/90 mm Hg). Patients with prehypertension are considered to have twice the risk of progressing to clinical hypertension than those with lower values. In addition, stages 2 and 3 hypertension of JNC 6 have been combined based on the recognition that BP ≥160/100 mm Hg should be treated aggressively, generally with 2 drugs upon diagnosis rather than a stepwise approach. JNC 7 emphasizes elevated SBP as a more accurate predictor of cardiovascular risk than elevated DBP in persons older than 50 years. Beginning at a BP of 115/75 mm Hg, CVD risk doubles with each increment of 20/10 mm Hg; individuals who are normotensive at age 55 years have a 90% lifetime risk for developing hypertension. The JNC 7 report is available online at http://www.nhlbi.gov/guidelines/hypertension/express.pdf. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-2572. National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . Bethesda, Md: National Heart, Lung, and Blood Institute; 2003. NIH Publication No. 03-5233.
Partners in Healthcare Education, LLC 2009 Health-promoting lifestyle modification(s) should be applied in persons with prehypertension as primary prevention. These nonpharmacologic treatments, such as diet and exercise, should also be encouraged in patients with all stages of hypertension, as they may enhance the efficacy of antihypertensive agents and minimize risk factors associated with hypertension. While lifestyle modifications are helpful, pharmacologic therapy is usually needed to treat high BP. Most patients with hypertension require 2 antihypertensive agents to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease). A thiazide-type diuretic is recommended as initial therapy for uncomplicated hypertension, either alone or in combination with an antihypertensive agent from another class (ACEI, angiotensin receptor blocker [ARB], β- blocker, or CCB). A drug from a different class should be added if the first drug is insufficient for achieving goal BP. Patients whose BP is >20/10 mm Hg above goal should receive pharmacologic therapy, either singly or in a fixed-dose combination. National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . Bethesda, Md: National Heart, Lung, and Blood Institute; 2003. NIH Publication No. 03-5233.
There have been many outcome trials performed with ACE inhibitors showing positive cardiovascular and renal outcomes suggesting that agents that affect the RAAS system are beneficial in reducing mortality and morbidity.
Similarly the ARBs, the newest class of antihypertensive agents, have shown they are also beneficial in improving renal and cardiovascular outcomes. Lending further credence to the fact that interruption of the RAAS system is beneficial in patients with hypertension.
Summary: Diuretics, ACEIs, and ARBs activate the RS; renin inhibition does not Although angiotensin-converting enzyme (ACE) inhibition reduces levels of angiotensin (Ang) II (by preventing the formation of Ang II from Ang I), angiotensin-converting enzyme inhibitor (ACEI) therapy is associated with a reactive rise in plasma renin activity and plasma Ang I levels, perhaps due to the negation of the short feedback loop wherein Ang II inhibits renin secretion by AT 1 receptor stimulation. Such a process may overcome the effects of ACE inhibition 1 Far from blocking the formation of circulating Ang II, angiotensin receptor blocker (ARB) therapy is associated with elevated plasma Ang II concentrations, driven by a rise in plasma renin activity linked to inhibition of AT 1 -mediated negative feedback on renin release 2,3 Direct renin inhibitors block the formation of Ang I, and thus Ang II becomes unavailable to maintain its vasopressor and volume-regulatory effects on the circulation Thus, renin inhibitors decrease PRA in addition to systemic blood pressure and systemic vascular resistance 7 References Johnston CI. Angiotensin II type 1 receptor blockade: a novel therapeutic concept. Blood Pressure. 2000;9(suppl 1):9-13. Widdop RE, Matrougui K, Levy BI, Henrion D. AT 2 receptor-mediated relaxation is preserved after long-term AT 1 receptor blockade. Hypertension. 2002;40:516-520. Fabiani ME, Johnston CI. AT1 receptor antagonists as antihypertensive agents. In: Epstein M, Brunner HR, eds. Angiotensin II Receptor Antagonists . Philadelphia, Pa: Hanley & Belfus, Inc; 2001:263-278. Lin C, Frishman WH. Renin inhibition: a novel therapy for cardiovascular disease. Am Heart J . 1996;131:1024-1034.
Partners in Healthcare Education, LLC 2009 Patients with prehypertension or hypertension who have compelling indications (specific high-risk conditions) require therapy with specific antihypertensive agents (ACEIs, ARBs, β -blockers, CCBs). Compelling indications include heart failure, post-MI, high CHD risk, diabetes, chronic kidney disease, and prevention of recurrent stroke. The selections of agents for patients with these high-risk conditions are based on favorable outcome data from clinical trials. Also in these patients, however, a combination of agents may be required to lower BP. Other management considerations include medications already being taken by the patient, tolerability, and desired BP targets. National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure . Bethesda, Md: National Heart, Lung, and Blood Institute; 2003. NIH Publication No. 03-5233.
Slide Summary The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) acknowledges the evidence from recent clinical trials (eg the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]) that most patients with hypertension will require two or more drugs to reach target blood pressure (BP) levels. Further, JNC 7 recommends that combination therapy be considered as initial therapy where BP is greater than 20/10 mm Hg above goal. Background JNC 7 notes the increased cardiovascular risk due to hypertension, and in its recommendations has set out guidelines aimed at effective and timely ways of achieving goal BP in hypertensive patients. The JNC authors recommend that initial combination therapy be considered as optimal therapy in patients who are greater than 20/10 mm Hg from goal BP. JNC 7. JAMA. 2003;289:2560-2572. ALLHAT Investigators. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor, or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA . 2002;288:2981-2997.
Slide Summary The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends that combination therapy be considered as initial therapy where BP is greater than 20/10 mm Hg above goal. The JNC 7 authors note that a failure to tailor antihypertensive therapy to assist patients to meet BP goals, either by titration or the addition of medications, is a problem among some clinicians that requires urgent attention. Background The JNC 7 authors recommend that clinicians consider factors that affect patient adherence to therapeutic regimens – eg, cultural differences, beliefs, and previous experience with the health care system – when determining hypertensive therapy. The JNC 7 report also notes that physicians may need assistance in monitoring that their hypertensive patients are reaching goal BP. This assistance may come from electronic or paper decision support systems, flow charts, feedback reminders, and the involvement of other members of the health care team including nurses and pharmacists. JNC 7. JAMA. 2003;289:2560-2572.
Slide Summary In 6 large double-blind, placebo-controlled studies, more than one agent was required to achieve desired target blood pressure (BP) goals. Background This slide shows evidence from 6 large placebo-controlled trials [1-6] demonstrating that when target BP values were set for subjects, 2 or more agents were required to achieve these goals [7]. In the Hypertension Optimal Treatment (HOT) study, for example, 68% of subjects required more than one agent [4]. 41% of subjects were taking felodipine plus an ACE inhibitor, and 28% were taking felodipine plus a beta blocker. In the United Kingdom Prospective Diabetes Study (UKPDS) [1], 29% of subjects required 3 or more agents to achieve a BP of <150/85 mm Hg at 9 years after randomization. 1. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ . 1998;317:703-713. 2. Estacio RO, Schrier RW. Antihypertensive therapy in type 2 diabetes: implications of the Appropriate Blood pressure Control in Diabetes (ABCD) trial. Am J Cardiol . 1998;82(9B):9R-14R. 3. Lazarus JM, Bourgoignie JJ, Buckalew VM, et al, for the Modification of Diet in Renal Disease Study Group. Achievement and safety of a low blood pressure goal in chronic renal disease. Hypertension. 1997;29:641-650. 4. Hansson L, Zanchetti A, Carruthers SG, et al, for the HOT Study Group. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet . 1998;351:1755-1762. 5. Kusek JW, Lee JY, Smith DE, et al. Effect of blood pressure control and antihypertensive drug regimen on quality of life: the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study. Control Clin Trials . 1996;16(suppl 4):40S-46S. 6. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851-860. 7. Bakris GL, Williams M, Dworkin L, et al, for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000;36:646-661.