Hypertension Update 2009 Adena Health System 2009 Cardiovascular Symposium October 2009.

Hypertension Update 2009

Adena Health System

2009 Cardiovascular Symposium

October 2009

Key ConceptsKey Concepts

• Hypertension is commonHypertension is common

• Hypertension increases cardiovascular riskHypertension increases cardiovascular risk

• Effective treatment confers benefitEffective treatment confers benefit

• Lessons from recent clinical trialsLessons from recent clinical trials

• Compelling indications for certain Compelling indications for certain antihypertensive agents and blood antihypertensive agents and blood pressure targetspressure targets

2

Epidemiology

• Over 65 million Americans age 20 and older have HTN

• Prevalence increases with age• Prevalence of hypertension varies by ethnic Prevalence of hypertension varies by ethnic

group several-fold higher in young African group several-fold higher in young African AmericansAmericans – >60% of Caucasians over 60>60% of Caucasians over 60– >70% of African American over 60>70% of African American over 60

• Primary Hypertension 95%Primary Hypertension 95%• Secondary Hypertension 5%Secondary Hypertension 5%

• Over 65 million Americans age 20 and older have HTN

• Prevalence increases with age• Prevalence of hypertension varies by ethnic Prevalence of hypertension varies by ethnic

group several-fold higher in young African group several-fold higher in young African AmericansAmericans – >60% of Caucasians over 60>60% of Caucasians over 60– >70% of African American over 60>70% of African American over 60

• Primary Hypertension 95%Primary Hypertension 95%• Secondary Hypertension 5%Secondary Hypertension 5%

Epidemiology

• Level of BP directly correlates with LVH/microalbuminuria

• LVH and hypertension:• Strong predictor of sudden death and MI

• Microalbuminuria and hypertension:(Persistent urinary albumin excretion of 30-300mg/24hrs)

• Increased risk of CVD

• Marker for endothelial dysfunction

Mortality Due to CHD per Quartile Mortality Due to CHD per Quartile of Usual SBPof Usual SBP

van den Hoogen et al. N Engl J Med 2000;342:1. 5

USA

Japan

Impact of Impact of High-Normal High-Normal

BP on the BP on the Risk of CV Risk of CV DiseaseDisease

Vasan RS et al. N Engl J Med

2001;345:1291.6

Relationship Between Hypertension and IHD Mortality

Lewington S, et al. Lancet 2002; 360:1903–13

Update Hypertension 2009Main Themes

• What level of BP should we achieve?

• What does the hypertension workup consist of ?

• How should we measure BP?

• Future directions……..personalized medicine and home monitoring !

Historical Trends in HTN

National Health and Nutrition Examination SurveyNational Health and Nutrition Examination Survey

AwarenessAwareness

TreatmentTreatment

ControlControl

1991-19941991-1994

68%68%

54%54%

27%27%

1976-19801976-1980

51%51%

31%31%

10%10%

1988-19911988-1991

73%73%

55%55%

29%29%

1994-20001994-2000

70%70%

59%59%

34%34%

SBP < 140 mmHg and DBP < 90 mmHgSBP < 140 mmHg and DBP < 90 mmHg

Trends in awareness, treatment, and control of high blood Trends in awareness, treatment, and control of high blood pressure in adults ages 18-74pressure in adults ages 18-74

Adapted from:Hajjar I, et al. JAMA. 2003;290:199-206.Ong KL et al Hypertension 2007: 49;69-75

2003-20042003-2004

75%

65%

33%

• Effective blood pressure control, regardless of which (or how Effective blood pressure control, regardless of which (or how many) agents are employed, is paramount to reduce CV many) agents are employed, is paramount to reduce CV endpointsendpoints

• Current control rates, even in idealized study populations, is Current control rates, even in idealized study populations, is sub-par. On a practical level, whatever potential benefits or sub-par. On a practical level, whatever potential benefits or drawbacks occur as a result of a specific property of one agent drawbacks occur as a result of a specific property of one agent vs. another at equivalent blood pressure levels is drowned out vs. another at equivalent blood pressure levels is drowned out by the adverse events of those that remain uncontrolledby the adverse events of those that remain uncontrolled

• At equivalent levels of blood pressure control, newer agents At equivalent levels of blood pressure control, newer agents offer a more appealing biochemical profile… the long-term offer a more appealing biochemical profile… the long-term importance of which remains to be seenimportance of which remains to be seen

Lessons Learned from ALLHAT and ASCOT-BPLA on Lessons Learned from ALLHAT and ASCOT-BPLA on specific antihypertensive agentsspecific antihypertensive agents

10

Factors Contributing to Poor Blood Pressure Control

Took no action

Increased dose

Changed drug

Prescribed add-on therapy

18%

From: Taylor Nelson Healthcare, Epson, Surrey England - Cardiomonitor 1992

11

SBP=systolic BP, DBP=diastolic BP; HYTN=hypertension, ACEI=Angiotensin-converting enzyme inhibitor, ARB=angiotensin, CCB=calcium channel blocker

* Treatment determined by highest BP categorya Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mm Hgb Thiazide-type diuretics for most; may consider ACEI, ARB, -blocker, CCB or combinationc Other antihypertensive drugs (diuretics, ACEI, ARB,-blocker, CCB) as neededd Two-drug combination for most (usually thiazide-type diuretic and ACEI or ARB or b-blocker of CCB.

Initiation of combined therapy should be used cautiously in those at risk for orthostatic hypotension.e Other antihypertensive drugs (diuretics, ACEI, ARB, -blocker, CCB) as needed.

Blood Pressure (BP) Classification and Management*

Normal <120 and <80 encourage

Pre HYTN 120-139 or 80-89 Yes No Yesa

Stage 1 HYTN 140-159 or 90-99 Yes Yesb Yesc

Stage 2 HYTN >160 or >100 Yes Yesd Yese

Life- Initial Drug Therapy BP SBP, DBP, style Compelling Indications Classification mm Hg* mm Hg* Changes Without With

Life- Initial Drug Therapy BP SBP, DBP, style Compelling Indications Classification mm Hg* mm Hg* Changes Without With

JNC VII. JAMA 2003;289:2560.

What is the optimal target BP level…….normal kidney donors?

Rafey et al

NKF 2008

Goals of the Hypertensive Goals of the Hypertensive EvaluationEvaluation

• Does the patient have primary or Does the patient have primary or secondary (reversible) hypertension? secondary (reversible) hypertension?

• Is target organ damage present?Is target organ damage present?

• Are other cardiovascular (CV) risk Are other cardiovascular (CV) risk factors present?factors present?

14

JNC 7 Recommendations for Routine Work-up of Hypertensive Patients

Routine Tests• Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR,

and calcium• Lipid profile, after 9- to 12-hour fast, that includes high-density and

low-density lipoprotein cholesterol, and triglycerides

Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio

More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

JNC 7 Recommendations for Routine Work-up of Hypertensive Patients

Routine Tests• Electrocardiogram • Urinalysis • Blood glucose, and hematocrit • Serum potassium, creatinine, or the corresponding estimated GFR,

and calcium• Lipid profile, after 9- to 12-hour fast, that includes high-density and

low-density lipoprotein cholesterol, and triglycerides

Optional tests • Measurement of urinary albumin excretion or albumin/creatinine ratio

More extensive testing for identifiable causes is not generally indicated unless BP control is not achieved

Secondary Causes of Hypertension: Secondary Causes of Hypertension: Renovascular DiseaseRenovascular Disease

Clinical CluesAbrupt onsetAbrupt onset<30 or >55 years of age<30 or >55 years of ageRefractory to 3-drug regimenRefractory to 3-drug regimenEvidence of diffuse vascular Evidence of diffuse vascular

diseasediseaseARF with ACEIARF with ACEIAccelerated retinopathyAccelerated retinopathyEpigastric bruitEpigastric bruit

DiagnosisDuplex renal Duplex renal

arteriesarteriesCaptopril Captopril

renographyrenographyMRAMRAAngiogramAngiogramRenal vein reninRenal vein renin

TreatmentAngioplasty/stentAngioplasty/stentSurgerySurgeryMedical treatmentMedical treatment

17

Etiologies for Secondary Hypertension

Renal parenchymalRenal artery stenosisObstructionPCKD

Renal

Cushing’s syndromeAdrenogenital syndromePheochromocytomaAdrenal and adrenal-like AcromegalyLiddle’s syndrome, Gordon’s

syndrome

Endocrine

Other

Pre-eclampsiaAcute intermittent porphyriaThyroid (hyper, hypo)DrugsHypercalcemia

Coarctation of Aorta

Secondary Hypertension

Chronic Kidney Disease and hypertension:

• Present in more than 80% of patients

• Mechanism: Excessive salt retention and increased peripheral resistance– Exacerbates proteinuria– Accelerated progression of CKD

• ACEI and ARBs slow progression of CKD

Angioplasty and Stent for Renal Artery Lesions

ASTRAL

Cardiovascular Outcomes in Renal Atherosclerotic Lesions

CORAL

www.coralclinicaltrial.govwww.coralclinicaltrial.gov 23

New Features New Features and Key Messagesand Key Messages

JNC VIIJNC VII

• For persons over age 50, SBP is a more important than For persons over age 50, SBP is a more important than DBP as CVD risk factor.DBP as CVD risk factor.

• Persons who are normotensive at age 55 have a 90% Persons who are normotensive at age 55 have a 90% lifetime risk for developing HTN.lifetime risk for developing HTN.

• Starting at 115/75 mm Hg, CVD risk doubles with each Starting at 115/75 mm Hg, CVD risk doubles with each increment of 20/10 mm Hg throughout the BP range. increment of 20/10 mm Hg throughout the BP range.

• Those with SBP 120–139 mmHg or DBP 80–89 mm Hg Those with SBP 120–139 mmHg or DBP 80–89 mm Hg should be considered prehypertensive who require should be considered prehypertensive who require health-promoting lifestyle modifications to prevent CVD.health-promoting lifestyle modifications to prevent CVD.

24

JNC VIIJNC VII

New Features and New Features and Key Messages Key Messages (Continued)(Continued)

• Thiazide-type diuretics should be initial drug therapy for Thiazide-type diuretics should be initial drug therapy for most, either alone or combined with other drug classes. most, either alone or combined with other drug classes.

• Certain high-risk conditions are compelling indications for Certain high-risk conditions are compelling indications for other drug classes.other drug classes.

• Most patients will require two or more antihypertensive Most patients will require two or more antihypertensive drugs to achieve goal BP.drugs to achieve goal BP.

• If BP is >20/10 mmHg above goal, initiate therapy with two If BP is >20/10 mmHg above goal, initiate therapy with two agents, one usually should be a thiazide-type diuretic.agents, one usually should be a thiazide-type diuretic.

25

Combination Therapy Needed to Achieve Target SBP Goals

Updated from Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.

Number of BP meds

Trial/SBP Achieved

1 2 3 4

UKPDS (144 mm Hg)

RENAAL(141 mm Hg)

ALLHAT (135 mm Hg)

IDNT (138 mm Hg)

HOT (138 mm Hg)

INVEST (133 mm Hg)

ABCD (132 mm Hg)

MDRD (132 mm Hg)

AASK (128 mm Hg)

RAS Inhibitor use in Hypertensive Blacks

• ACEIs/ARBs should be considered first line in patients (including blacks) with nephropathy (esp. with proteinuria) and or heart failure

• Available data suggest that RAS inhibitors are less effective in lowering BP in black hypertensives in the absence of adequate

doses of a diuretic or CCB (and in preventing clinical outcomes)• ACEI also carry increased risk of angioedema , esp. in blacks• In the absence of HF or CKD, particularly in Black hypertensives,

beta blockers, ACEI,and ARBs(and presently renin inhibitors) should be prescribed only in combination with thiazide-type diuretics or calcium channel blockers

Blood pressure measurement…

• Recognize the diagnostic limitations of traditional office blood pressure measurement..

• 24hr ambulatory BP measurement: diagnostic utility and clinical correlations…

• Understand the physiology of the arterial waveform, central BP measurement, vascular stiffness indices and pulsology in clinical practice

Center for Blood Pressure Disorders

Clinical Program: Goals

• Accurate BP Measurement

• Comprehensive Vascular Evaluation

180 –

170 –

160 –

150 –

140 –

130 –

120 –

110 –

100 –

90 –

80 –

0 –

152

140

132 134

8780 75 77

FamilyPhysician

ResearchTechnician

BpTRU Ambulatory BP

Blo

od

Pre

ssu

re (

mm

Hg

)

Myers M, et al, Journal of Hypertension 2009 27(2) 280-286 n=309

Reduction of WCE in Clinical Practice

BpTRU

• White coat effect

• Work in progress

BpTRU

Comprehensive Evaluation of Hypertension

SphigmocorRetinal ExamABI

Nurse/MA

Limited EchoUrine protein

Peripheral BP

Lab Review

•Dyslipidemia

•Fasting plasma glucose

H & P

Physician Evaluation

Central BP /PWV

PVD TOD TOD TOD

Comprehensive Management Plan Based on Risk Estimates

24 Hour Ambulatory Blood Pressure Monitoring

HBPM: New Recommendations May 2008

Indications for 24 Hour ABPM

Clinical situations in which ABPM may be helpful:

• Rule out white-coat HTN • Apparent drug resistance (office resistance)• To better define resistant HTN• Hypotensive symptoms with antihypertensives• Episodic hypertension• Autonomic dysfunction

Dipping Pattern and Decline in GFR

Davidson et al Arch Intern Med. 2006;166:846-852

•322 consecutive patients

•137 dippers

•185 nondippers

•Follow-up 3.2 yrs

•Dippers mean change in GFR 1.3%

•Nondippers mean change in GFR 15.9% (P<0.001)

Prevalence of Nocturnal Hypertension in AASK Study

24 Hour Ambulatory Blood Pressure Monitoring

• Central Aortic Pressure

• Pulse Wave Velocity (PWV)

• Augmentation Index (AIx)

Measures of Arterial Stiffness

7.6 m/sec605 mm690 mm85 mm80 msec135 msec55 msec

Aortic PWV (distance/time)

distance

Notch-femoral

Notch-carotid

timeQRS-femoral

QRS-carotid

85 mm

690 mm

EKG-QRS

CAROTID

55 msec 135 msec

FEMORAL

EKG-QRS

How PWV is measured...

Velocity = Distance/Time

APWV measurement (cont.)

Systole

Aortic Stiffening and Early Wave Reflection

Diastole

Systole

Young compliant arteries : Normal PW velocity (8 m/sec)

Elderly stiff arteries with ISH : Increased PW velocity (12 m/sec)

(1) Ventricular-Vascular coupling

(2) coronary blood flow

(1) Ventricular-vascular mismatch(2) The reflected wave increases or “augments” central SBP during late systole:

SphygmoCor

• Arterial stiffness measures– CBP (central BP)– AIX (Augmentation Index)– PVW(Pulse wave velocity)

• ? Evidence to change management?

• Does depend on accurate peripheral blood pressure measurement eg: BPtru / manual BP

• How to incorporate it with out interfering with the work flow?

TOP: Brachial (solid symbols) and derived central aortic (open

symbols) systolic blood pressure with time (mean, 95% CI) for patients randomized to receive atenolol ± thiazide- or

amlodipine ± perindopril-based therapy.

BOTTOM: Systolic blood pressure difference (brachial minus central aortic; mean,

95% CI) with time. For calculation of AUC, see the Data Supplement. Numbers

below abscissa represent the number of patients seen at each time point. Time represents the

duration from randomization into ASCOT to patient follow-up

visit at which tonometry measurement was made in the

CAFE study. PP indicates pulse pressure.

CAFE Investigators, for ASCOT Investigators. Circulation 2006;113:1213.

CAFÉ Study Results

AIx in CKD vs. non CKD

• AIx was significantly higher in the non-CKD patients compared to the CKD patients (median AIx 27 % [18, 32] vs. 21 % [14, 29], P = 0.002).

• AIx was similar in the CKD and non-CKD groups after adjusting for age, gender, height, SBP and eGFR

-10

0

10

20

30

40

50

60

AIx

(%

)

0 1

CKD vs. non-CKDNon-CKD CKD

Linear Regression of AIx by SBP

80 100 120 140 160 180 200 220

-10

010

20

30

40

50

60

P_SP

Augm

enta

tion In

dex

FemaleMale

SBP

Aug

men

tatio

n In

dex

(%)

R = 0.24, P <0.0001

Linear Regression of AIx by PPP

20 40 60 80 100 120

-10

01

02

03

04

05

06

0

P_PP

Au

gm

en

tatio

n In

de

x

FemaleMale

Future Developments in Hypertension

Personal medicine

Home BP monitoring

cell membrane

Corin Variants in African-Americans with Hypertension and Heart Disease

enzyme

T555I Q568P

enzyme

Dries et al. Circulation 2005;112:2403 Wang et al. Circ Res 2008;103:502

Home Blood Pressure Monitoring

Graph from the daily readings

Hypertension Clinic Review

Internet Based Hypertension Clinic Program:Achieve individual blood pressure goals

Wireless/USB

Phone/email:

•Titrate medication dose

•Add medications

Secure Data Transfer

CONTROLLED BLOOD PRESSURE

The EverOnTM System

• Not another monitor, a Patient Supervision System

– Continuously observes patient’s: cardiac, respiratory, and motion status

– Alerts nurses when attention is needed

– Empowers more effective physician decisions including earlier discharge

– Improves documentation

“There is a clear, present and immediate need for an innovative, high tech system that can automatically, and without imposing upon patient comfort, track movement and vital signs and warn of possible life threatening situations.” Mark Meyers, President of California Hospital Medical Center

Blood Pressure Monitoring – Preliminary Data

PTT ECG [ms] PTT EverOn[ms]

MAP [mmHg]

SBP [mmHg]

DBP [mmHg]

Baseline (rest)

282.3±17.6 - 81±4.7 123.9±4.4 62.1±6.4

Maximal Effort

264.6±15.3Δ=-17.7±4.4 Δ=-11.9±0.6

95.2±6.5 Δ=+14.2

138.8±9.2 Δ=+14.9

68±4.4Δ=+5.9

Recovery 280.4±15.5Δ=-1.9±5.8 Δ=-0.7±6.8

80.5±6Δ=-0.5

125.8±9.9Δ=+1.9

55.2±5.6Δ=-6.9

240 250 260 270 28080

85

90

95

100

105

110

PTT (ms)

BP (m

mH

g)

Mean Blood PressureVs. PTT from ECG

BaselineMax EffortRecovery

190 200 210 220 23080

85

90

95

100

105

110

PTT (ms)

BP (m

mH

g)

Mean Blood PressureVs. PTT from EverOn

BaselineMax EffortRecovery

240 250 260 270 280190

195

200

205

210

215

220

PTT ECG (ms)

PTT

Ever

On

(ms)

PTT from ECGVs. PTT from EverOn

BaselineMax EffortRecovery

Take Home Points …Hypertension Update 2009

• Hypertension is sub optimally controlled in the US

• Target BP may be lower than traditionally thought

• Resistant hypertension should trigger a workup for secondary causes

• Methods for BP measurement are evolving • Home monitoring is the future for BP

management