hypertension

Partners in Healthcare Education, LLC 2009

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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



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Objectives
Upon completion of this lecture, the participant will be able to:Identify the various classifications of prehypertension, Stage I and Stage 2 hypertensionDiscuss nonpharmacologic treatment options for the patient with hypertensionDiscuss pharmacologic treatment options for the patient with hypertension


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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.



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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 mans 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.


CVD disease mortality trends for males and females (United States: 1979-2004).
Source: NCHS and NHLBI.

CVD disease mortality trends for males and females

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Wright, 2009

Wright, 2009

Wright, 2009

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Chart17979808085859090959500000404MalesFemalesYearsDeaths in Thousands496.676466.361506.154487.194487.453495.286444.763475.482452.452503.139440.175505.661410.628459.096Sheet1CVDCVDCardiovascular Disease Mortality Trends for Males and FemalesCVD *CVD*CVDCVDMalesFemalesUnited States: 1979-2004MalesFemalesMalesFemales7950046979497466794974668051049080506487805064878150048449748185487495824954844924819044547583498494495491954525038449149348749100440506854914988548749504411459864814984784958747549947249688476504473501894564864534839044847890445475914474794444779244447944147793457500454498944524984494969545550595452503964535064515049745050344850198446504Actual MortalityAdjusted Mortality*44350299446513adjusted by 9-10 comparability ratio. (0.9981)445.024511.92944651300440506440.175505.661439.339504.7000044050601432499432.245498.863431.424497.915432499Source: Final mortality data, NCHS.433.827493.69002433.003492.752434494Numbers are in thousands.427.891483.37203427.078482.454428483CVD including congenital CV disease.410.365461.15204409.585460.27604411459* - Since comparability ratio is so close to 1.00it is not necessary to adjust. As per TT 9/26/06.Sheet1MalesFemalesYearsDeaths in ThousandsSheet2Sheet3


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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.



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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 individualseven those with mild levels of 2 risk factorsat profound risk for CVD.
Fuster V, Gotto AM Jr. Risk reduction. Circulation. 2000;102:IV94IV102.

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.



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Hypertension and Dyslipidemia Contribute to Atherogenesis

Endothelial

Dysfunction

CVD

Hypertension

Dyslipidemia

Atherosclerosis

Smooth Muscle

Cell Contraction

Impaired Bioavailability

of Nitric Oxide

Impaired

Vasodilation



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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 AT1 receptor, which increases the deleterious effects of this vasoactive peptide.By downregulating AT1 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, Lscher 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.



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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


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Hypertension and Dyslipidemia:
A Significantly Undertreated Syndrome

Adapted from American Heart Association. Heart Disease and Stroke Statistics2003 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



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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.


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Impact of Hypertension
50 million individuals in the United States have hypertension1277,000 deaths annually in US due to hypertension2
1American 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

2National 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

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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.

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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 statistics2007 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.
Chart10.690.740.770.91First MIsCurrent CHFFirst StrokesEventual CHFSheet1First MIs69%Current CHF74%First Strokes77%Eventual CHF91%


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It is currently estimated that
90% of normotensive 55 year olds will develop hypertension at some point in his/her lifetime


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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);



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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


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Statistics of Interest
53% of patients with hypertension are being treated with medicationsOf 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.


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Hypertension and Management:
Old School

Hemodynamics altered

Treat the blood pressure

Therapeutic options

Adapted from Vascular Biology Working Group, University of Florida

College of Medicine, Carl Pepine, MD, Director

Hypertension = Systemic disease

Beta

Blockers

ACE

ARB

Diuretics

CCB

Others

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Hypertension and Management: New School

Hypertension =

Disease of the blood vessels

Vascular biology altered

Treat the vasculature

Therapeutic options

Adapted from Vascular Biology Working Group, University of Florida

College of Medicine, Carl Pepine, MD, Director

Beta

Blockers

ACE

ARB

Diuretics

CCB

Others

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

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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 secretion1

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 pressure1
Reid IA. The renin-angiotensin system: physiology, pathophysiology, and pharmacology. Adv Physiol Edu. 1998;20:S236-S245.

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RAAS and Adipose Tissue
All components of the RAAS system are expressed in adipose tissue, especially the visceral adipose tissue1,2,3Visceral 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..

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RAAS and Endothelial Dysfunction
Growing body of evidencePromotion of endothelial dysfunctionMicroalbuminuria1,2RAAS Inhibition (ACE, ARB and Direct Renin Inhibitor)Decreased incidence of new onset Type 2 diabetesImprovement 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.

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Today
The Hypertensive Patient Exhibits...
More insulin resistanceMore hyperinsulinemiaDyslipidemiaMicroalbuminuriaObesity
...as compared to nonhypertensive patients!

Reaven GM. Banting lecture 1988. Role of insulin resistance in human. Disease Diabetes.

1988.37;1595-1607.

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Cardiovascular Disease

Hypertension

Diabetes

Blocking the RAAS has been shown to be beneficial in

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JNC VII:
Messages to Clinicians

JAMA. 2003:289:2560-2577.



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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.


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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

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.



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Diagnosis
2 readings; separated apartPatient should not ingest caffeine or smoke for 30 minutes before readingsPatient should sit for 5 minutes with arm at heart level before blood pressure is checked


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JNC 7: New Blood Pressure Classification

*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.
Blood Pressure ClassificationSBP*DBP*(mm Hg)Normal


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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.



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Most Cases of Hypertension
Primary hypertensionAlso called essentialResponsible for 90-95% of all hypertension diagnoses


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Consider Secondary Causes of HTN
Sleep apneaDrug-induced or drug relatedIncluding OTC medicationsChronic kidney diseasePolycystic kidneysRenal artery stenosisPrimary aldosteronismRenovascular diseaseChronic steroid therapy and Cushings diseasePheochromocytomaCoarctation of the AortaThyroid or parathyroid disease
JAMA. 2003:289:2560-2577.



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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 officeThe office blood pressure of elders is 5 mm Hg higher than their ambulatory blood pressureOlder the individual, the greater the discrepancy between home and office blood pressuresNo longer considered a benign condition
JAMA. 2003:289:2560-2577.


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Initial Work-up
History and review of systemsMedications and risk factorsConsider home blood pressure readings with validated blood pressure cuffLaboratory workup: CBC, BUN, Creatinine, Glucose, Lipids, GFR, urine - proteinEKG 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.


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Treatment of Hypertension



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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.


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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

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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


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JNC 7: Algorithm for Treatment of Hypertension

Prehypertension (SBP 120-139 mm Hg or DBP 80-89 mm Hg)

Not at Goal BP (


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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.



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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 Sodium2.4g Na 2-8 mm Hg

Physical InactivityBrisk exercise 30 day 4-9 mm Hg

most days of week

Moderation of

Alcohol intake2 drinks day max 2-4 mm Hg

24 oz beer; 10 oz wine

2 oz 100 proof whiskey

JAMA. 2003:289:2560-2577.



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Lifestyle Modifications
Dietary sodium reductionMost helpful in African Americans and patients with diabetesRecommend limiting sodium to < 2000 mg/day for these individualsAverage individual ingests 4000 mg / dayACE inhibitors and diuretics work best with a relatively low sodium diet


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How Successful Is It?
Combination of the DASH diet and a dietary sodium reduction to 1600 mg/day is as effective as 1 medication


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Alcohol Intake
Limit alcohol intake to < 30 mL or 1 ounce of ethanol/dayTranslation: 2 ounces of whiskey10 ounces of wine24 ounces of beerExcessive amounts increases treatment resistanceAlso increases risk of a CVA
** Women: this amount



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Electrolytes
Diets high in potassium, calcium and magnesium are associated with a lower blood pressureJNC VII recommends an adequate dietary intake of these but does not recommend supplementing from an outside source to lower blood pressure


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Additional Recommendations
Omega-3 fatty acids may lower blood pressureCaffeine may increase it but tolerance often developsMost studies do not support a relationship between hypertension and caffeineSmoking: discontinuation is importantExercise: 30 minutes daily recommended


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Pharmacologic Treatments



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Thiazide diuretics should be used in drug treatment for patients with uncomplicated hypertension.
JAMA. 2003:289:2560-2577.



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Thiazide Diuretics
Dosing:Start @ 12.5 mg of HCTZIncrease to 25 mg at 6 weeksBenefits55% reduction in CHF37% reduction in CVA27% reduction in cardiac eventsIf not adequately controlled, add additional agents

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Diuretic Precautions
Electrolyte imbalancesSyncope/presyncope when combined with ACE/ARBHemoconcentrationDecrease in urate excretionWorsening of insulin resistance at higher dosesFatigue
Product inserts accessed 04-20-2008

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Angiotensin Converting
Enzyme (ACE) Inhibitors
Increased nitrous oxide at vessel for vasodilatationImproved glucose disposalReduction in LV geometry changesReduction in inflammationStabilization of fibrous cap of lipid lesionDecreased proteinuria Improves endothelial functionReduced mortality in patients with CHFDecreases 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)

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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

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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.


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ACE Inhibitors Precautions
HyperkalemiaIncrease in creatinineMay improve insulin sensitivityDecrease in serum Na+ may result in syncope and dizziness when used with diuretics
Product inserts accessed 04-20-2009
AngioedemaCough
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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

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But

ACE Inhibitors
Are Highly Effective..

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*

*

*

*

*

*

*

*

* = p

*

If you block the receptor

site, you dont have to worry

about the angiotension levels

AT1

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Angiotensin
Receptor
Blockers

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Angiotension Receptor Blockers (ARBs)
Utilized since April 1995Blocks uptake at receptor site Angiotension II produced in locations other than in the lungsBP decreased by reducing vascular tone and enhancing NA+ and water clearance
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Metabolic Effects of ARBs
Angiotensin II Receptor BlockersMetabolically neutralNo impact on lipidsNo impact on insulinNo impact on K+Lowers uric acid levelsMinimal side effect profile
Product Inserts accessed 04-20-2009

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ARB Trials

1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006

ValHeFT

ELITE I

ELITE II

IDNT

RENAAL

IRMA II

OPTIMAAL

LIFE

VALIANT

VALUE

CHARM

MARVAL

ON TARGET

IPreserve

CHF

CV

MI

Renal/CV

Renal

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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.


ACE vs ARB
ONTARGET Trial

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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.
Goal:Assess the effects of ACE VS ARB in terms of efficacy2. Assess if the combination ACE & ARB was superiorResults: Telmisartan was found to be noninferior to ramipril in patients with vascular disease or high risk diabetesCombination of these two agents was associated with more adverse events without an increase in benefit.

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Beta Blockers
Reduction in blood pressureDecreased contractilityDecreased heart rateDecreased myocardial oxygen
demand
Reduction in LVHReduced arrhythmias


Assessed 5-1-08

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Beta Adrenergic Receptors
3 receptors are found in human cardiac myocytes that are coupled to a positive inotropic response and cell growth.Beta1Beta2Alpha1
Hunt, et al. ACC/AHA 2005 Chronic Heart Failure Guideline Update. JACC.2005; 46:1116-43.

Beta Blocker Trials

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SHEPSystolic Hypertension in the Elderly ProgramStep Approach Chlorthalidone/AtenololReduced incidence of major CV events and CVA; chlorthalidone decreased CHFSTOP HTN 2Swedish Trial in Old Persons with HypertensionBeta Blocker Vs CCB VS ACE on CV MorbidityACE /BB similar efficacy in preventing CV mortality.CAPPPCaptopril Prevention ProjectBeta Blocker + Diuretic vs CaptoprilCaptopril 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

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Calcium Channel
Blockers

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Calcium Channel Blockers
Effectively treat systolic hypertensionMay be superior to other antihypertensives for stroke preventionEffective in patients with:Comorbid conditions (Raynauds, migraine)1Particularly effective in Elderly and African Americans2
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.

The Calcium Blockers

Dihydropyridines
Studies of DPHs effects on proteinuria have produced conflicting resultsNKF recommends that in patients who have diabetes and kidney disease, DPHs 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.
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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.

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Alpha Blockers

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Alpha Blockers
Block postsynaptic Alpha1 ReceptorsResults in vasodilatationRelatively inexpensiveFair tolerability; May cause postural effectsAdditive agent for older men to decrease BPH symptomatologyAdd-on agent onlyShould never be used as monotherapy due to increased risk of stroke and CHF


Assessed 5-1-08

*


*

Centrally Acting Blockers

*

Centrally Acting Agents
Stimulates central alpha2 receptors which results in:Inhibiting efferent sympathetic activityAdditive agentsShould be used 3rd or 4th lineExamples: Clonidine (catapress, catapress TTS); methyldopaCaution: sedation, orthostatic hypotension


Assessed 5-1-08

*


*

Direct
Vasodilators

*

Direct Vasodilators
Direct smooth muscle vasodilatation, primarily arteriolarTwo agentsApresoline (Hydralazine)Minoxidil
**Precautions include: tachycardia, significant peripheral edema and hair growth

**Agents to reduce heart rate may be needed



Assessed 5-1-08

*


*

Aldosterone Agonists

*
Spironolactone (Aldactone) HCTZ / spironolactone (Aldactazide)Eplerenone (Inspra)
Aldosterone
Antagonists

*

Aldosterone as a
Therapeutic Target
Aldosterone promotes:Retention of sodiumLoss of magnesium and potassiumSympathetic activationParasympathetic inhibitionBaroreceptor dysfunctionImpaired 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.

*
May be recommended in the following individuals:Post MINYHA Class III or IVEjection fraction of < 35%Serum creatinine of < 2.5 mg/dlK+ < 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

*

Precautions
Must monitor electrolytes Must obtain baseline renal functionShould discontinue the K+ supplementShould 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.

*

New Classes/Agents

*

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.

Direct Renin Inhibition
Inhibits the Entire Renin System1-4

Class

PRA

Ang I

Ang II

Increased peptide levels have not been shown to overcome the blood pressurelowering effect of these agents.

ACEI, angiotensin-converting enzyme inhibitor; Ang, angiotensin; ARB, angiotensin receptor blocker;

PRA, plasma renin activity.
Johnston CI. Blood Press Suppl. 2000;1:9(suppl 1):9-13.Widdop RE et al. Hypertension. 2002;40:516-520.Fabiani ME et al. Angiotensin II Receptor Antagonists. 2001:263-278. Lin C et al. Am Heart J. 1996;131:1024-1034.
ACEI

ARB

Direct Renin Inhibitor (DRI)

*

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 AT1 receptor stimulation. Such a process may overcome the effects of ACE inhibition1

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 AT1-mediated negative feedback on renin release2,3

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 resistance7

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. AT2 receptor-mediated relaxation is preserved after long-term AT1 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.

Aliskiren

Dosage:
150 mg or 300 mg once daily
Indications:
Adults with hypertensionMay be administered with any other antihypertensive
Product Insert, 2007


*

Certain high risk conditions are compelling indications for the initial use of other antihypertensive drug classes.Angiotensin-converting enzyme inhibitorsAngiotensin-receptor blockersBeta blockersCalcium channel blockers
JAMA. 2003:289:2560-2577.



*

JNC 7: Compelling Indications for Individual Antihypertensive Drug Classes

*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.
Compelling Indication*Recommended Drugs DIURETICBBACEIARBCCBAldo ANTHeart failure Post-MI High coronary disease riskDiabetesChronic kidney diseaseRecurrent stroke prevention


*
Patients with prehypertension or hypertension who have compelling indications (specific high-risk conditions) require therapy with specific antihypertensive agents (ACEIs, ARBs, -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.


*

Combination
Therapy

*

When you put your hand in the cabinet

*


*

JNC 7 (2003)

Combination Therapy
Most hypertensive patients will require two or more antihypertensive medications to achieve goal BP (

*
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



Assessed 5-1-08

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.


*

AASKMAP


*

35.unknown


*

Target Organ Damage
HeartLVH, Angina, CHF, MIBrainStroke or TIADementiaChronic Kidney DiseasePeripheral Vascular DiseaseRetinopathy
JAMA. 2003:289:2560-2577.



*

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.



*

Additional Considerations for the Patient with Hypertension



*

In presenting the NEW JNC VII, the committee recognizes that the responsible practitioners judgment remains paramount.
JAMA. 2003:289:2560-2577.



*

Summary
Hypertension is highly prevalent and is a significant risk factor for CHDCurrent 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 hypertensionAntihypertensive therapy reduces CHD risk 2 antihypertensive agents are usually required to achieve BP goals in patients with hypertension


*



*

Thank You!

I Would Be Happy To Entertain Any Questions



*



*

Wendy L. Wright, ARNP
Adult/Family Nurse Practitioner
www.4healtheducation.com
[email protected]



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40045050055079808590950004Deaths in ThousandsYears

Males Females

hypertension

Documents

healthcare education

heart disease

cvd disease mortality

pllcpartner partners

occurrence of cvd

american heart association

females united states

final mortality data