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Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC linical Professor of Medicine niversity of California at Irvine ssociate Medical Director CI Heart Disease Prevention Program rvine, California

Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

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Page 1: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Epidemiology of Hypertension

Stanley S. Franklin, MD, FACP, FACC

Clinical Professor of MedicineUniversity of California at IrvineAssociate Medical DirectorUCI Heart Disease Prevention ProgramIrvine, California

Page 2: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Agenda: epidemiology of hypertension

1 BP measurement

2 Defining hypertension

3 Why an important public health problem

4 Global risk assessment

5 Intervention trials and meta-analyses

6 Management strategies

7 Barriers to treatment

8 Prevention strategies

1 BP measurement

2 Defining hypertension

3 Why an important public health problem

4 Global risk assessment

5 Intervention trials and meta-analyses

6 Management strategies

7 Barriers to treatment

8 Prevention strategies

Page 3: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

1. How to measure blood pressure?

Page 4: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Nokolai Korotkoff, 1905

Ascultatory method of

blood pressure measurement

Page 5: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Noninvasive Blood Pressure Measurement

Noninvasive Blood Pressure Measurement

Methodologies

- Auscultatory (K sound) - Mercury

- Aneroid

- Oscillometric

Locations Situations

- Upper arm - Clinic

- Wrist - Home

- Finger - Ambulatory

Methodologies

- Auscultatory (K sound) - Mercury

- Aneroid

- Oscillometric

Locations Situations

- Upper arm - Clinic

- Wrist - Home

- Finger - Ambulatory

Page 6: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2. Defining Hypertension:

(a) By the numbers?≥95 DBP160/95140/90130/85 >120/80

“A number at which the benefits of intervention exceed those of

inaction”

Page 7: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #7

CV Mortality Risk Doubles withEach 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 pressureLewington S, et al. Lancet. 2002; 60:1903-1913. JNC 7. JAMA. 2003;289:2560-2572.

CVmortality

risk

SBP/DBP (mm Hg)

0

1

2

3

4

5

6

7

8

115/75 135/85 155/95 175/105

Page 8: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #8

JNC Reclassification of BP Based on Risk

Source for JNC VI: Arch Intern Med. 1997;157:2413-2446.Adapted with permission from Chobanian AV et al. Hypertension. 2003;42:1206-1252.

JNC VIJNC VISBP

(mm Hg)SBP

(mm Hg)DBP

(mm Hg)DBP

(mm Hg)SBP

(mm Hg)SBP

(mm Hg)DBP

(mm Hg)DBP

(mm Hg)

Optimal Normal80 <120<120 and 80and

Normal

Hi-normalPrehypertension

120-129

130-139120-139

80-84

or 85-89

and80-89or

Stage 1

Hypertension

Stage 1140-159 140-15990-99or 90-99or

Stage 2

Stage 3Stage 2

160-179

≥ 180≥ 160

100-109or

≥ 110or≥ 100or

CategoryCategory CategoryCategory

JNC 7JNC 7

Page 9: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

BP CategoryBP Category PrevalencePrevalence

NormalNormal 38%38%

PrehypertensionPrehypertension 31%31%

HypertensionHypertension 31%31%

Prevalence of Blood Pressure Prevalence of Blood Pressure Categories in US Adults ≥20 Years of Categories in US Adults ≥20 Years of

Age Age (NHANES 1999-2000)(NHANES 1999-2000)

Prevalence of Blood Pressure Prevalence of Blood Pressure Categories in US Adults ≥20 Years of Categories in US Adults ≥20 Years of

Age Age (NHANES 1999-2000)(NHANES 1999-2000)

Greenland, Croft, Mensah (CDC). Arch Intern Med. 2004;164:2113fGreenland, Croft, Mensah (CDC). Arch Intern Med. 2004;164:2113f

Page 10: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Prehypertension …Prehypertension …Prehypertension …Prehypertension …

• Is Is notnot a disease, a disease,

• Is Is notnot “hypertension”, “hypertension”,

• Is Is notnot an indication for drug treatment of HTN, an indication for drug treatment of HTN,

• Does Does notnot have a BP goal, have a BP goal,

• DoesDoes predict a higher risk for developing CV predict a higher risk for developing CV

events,events,

• DoesDoes predict a higher risk for developing HTN, predict a higher risk for developing HTN,

• Should be an incentive to improve lifestyle Should be an incentive to improve lifestyle

practices for prevention of HTN and CVD.practices for prevention of HTN and CVD.

• Is Is notnot a disease, a disease,

• Is Is notnot “hypertension”, “hypertension”,

• Is Is notnot an indication for drug treatment of HTN, an indication for drug treatment of HTN,

• Does Does notnot have a BP goal, have a BP goal,

• DoesDoes predict a higher risk for developing CV predict a higher risk for developing CV

events,events,

• DoesDoes predict a higher risk for developing HTN, predict a higher risk for developing HTN,

• Should be an incentive to improve lifestyle Should be an incentive to improve lifestyle

practices for prevention of HTN and CVD.practices for prevention of HTN and CVD.

Page 11: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Defining Hypertension:

(b) By hemodynamic mechanism?

Increased peripheral vascular resistance

versus

Increased large artery stiffness

Page 12: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

The Arterial Pulse Wave

75

125

Pre

ssu

re (

mm

Hg

)

Systolic Systolic pressurepressure

Diastolic Diastolic pressurepressure

Mean Mean pressurepressure

Diastolic decay Diastolic decay curvecurve

Dicrotic notchDicrotic notch(aortic valve (aortic valve

closes)closes)

Time

Pulse Pulse pressurpressuree

= 1/3 SBP + 2/3 DBP

Page 13: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Hemodynamic Components of BP

MAP - STEADY COMPONENT (due to CO and SVR)

• PP – PULSATILE COMPONENT (due to LV ejection

and elastic artery stiffness)

• SBP – rises with increased resistance and stiffness

• DBP – rises with increased resistance and decreases

with increased stiffness

Elzinga G, Westerhof N. Circ Res 1973;32:178-186. Yano, et al. Basic Res Cardiol 1997;92:115-122.

Berne RM, Levy MN. Cardiovascular Physiology 1992:135-151.

Page 14: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Overview of Arterial Blood Pressure Hemodynamics

1. Steady component MAP = CO x PVR ↑Resistance small art. MAP = 1/3(SBP) + 2/3(DBP)

Predominantly diastolic “Essential HTN”--young

-- ↑VC or ↓VD responses -- ↑wall-to-lumen diameter -- Rarefaction (Art./Cap.)

2. Pulsatile component PP = SBP – DBP ↑Stiffness large arteries ↑CO and ↑SV Isolated systolic HTN Pathologic aging

-- Disarray of elastin protein-- Abn. extracellular matrix-- ↑Collagen/Calcium depos.

Page 15: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Defining Hypertension:

(c) By subtype?

IDH, SDH, ISH

Page 16: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

<40 40-49 50-59 60-69 70-79 80+Age (y)

17% 16% 16% 20% 20% 11%

Distribution of Hypertension Subtype in the Untreated Distribution of Hypertension Subtype in the Untreated Hypertensive Population by Age Hypertensive Population by Age (NHANES III)(NHANES III)

ISH (SBP 140 mm Hg and DBP <90 mm Hg) SDH (SBP 140 mm Hg and DBP 90 mm Hg)IDH (SBP <140 mm Hg and DBP 90 mm Hg)

0

20

40

60

80

100

Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension. 2001;37: 869-874.

Frequency of hypertension

subtypes in all untreated

hypertensives (%)

} Diastolic Hypertension

Page 17: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

An Analysis of NHANES III Blood Pressure DataSummary: Hypertensives fall into one of two categories:

1. A smaller (26%), younger (age 50 years), predominantly male (63%) with diastolic hypertension out of proportion to systolic hypertension (primarily IDH and SDH)

2. A larger (74%), older (age 50 years), predominantly female (58%) with systolic hypertension out of proportion to diastolic hypertension (primarily ISH).

Summary: Hypertensives fall into one of two categories:

1. A smaller (26%), younger (age 50 years), predominantly male (63%) with diastolic hypertension out of proportion to systolic hypertension (primarily IDH and SDH)

2. A larger (74%), older (age 50 years), predominantly female (58%) with systolic hypertension out of proportion to diastolic hypertension (primarily ISH).

Franklin et al. Hypertension 2001;37: 869-874

Page 18: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #18

3. Why is hypertension considered a major Public health problem in the United States?

Firstly, hypertension is very common In the adult population

Page 19: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

50

65

0

20

40

60

80

100

1988-1994 1999-2000

National Health and Nutrition Survey (NHANES)

Increased Prevalence of Hypertension in the Increased Prevalence of Hypertension in the United States from 1988-1994 (NHANES III) to United States from 1988-1994 (NHANES III) to

1999-2000 NHANES1999-2000 NHANES

Increased Prevalence of Hypertension in the Increased Prevalence of Hypertension in the United States from 1988-1994 (NHANES III) to United States from 1988-1994 (NHANES III) to

1999-2000 NHANES1999-2000 NHANES

Fields, et al. Hypertension. 2004;44:398f

Po

pu

lati

on

Wit

h

Hyp

erte

nsi

on

(m

illi

on

s)

30% increase, p<.00130% increase, p<.001

Nearly 1 in 3 Adults (31%) in the US Has Hypertension

Page 20: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #20

Trends in Prevalence of Hypertension in the US Population, by Race/Ethnicity,1988-2000

0

5

10

15

20

25

30

35

Pre

vale

nce

(%)

Non-Hispanic White Non-Hispanic Black Mexican American

1988-1991

1991-1994

1999-2000

*p<0.01, **p<0.001,compared to Non-Hispanic Whites within given time period; no significant trends across time periods within gender; analyses are age-adjusted to 2000 US population. Data from Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA 2003; 290: 199-206.

** ****

* *

Page 21: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Chobanian A. N Engl J Med 2009;361:878-887

Hypertension Paradox: Changes in the Prevalence and Control of Hypertension in the United States (1988-2004)

Rate of control:27% to 35%Rate of control:27% to 35%

Page 22: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Colors of Salt

• White• Black• Red• Yellow• Green• Brown• Clear

• Table salt• Soy sauce• Catsup• Mustard• Pickles• Soups & gravies• Saline

Page 23: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

The connection between salt, obesity, hypertension and CVD mortality• During the past 25 years salt intake has

increased by 1/3 to 150-170 mmol/day (3.5 to 4.0 g sodium/day).

• This has contributed to the growing obesity epidemic and increased prevalence of hypertension by causing increased intake of high-calorie soft drinks containing corn sugar

• Recent studies suggests that a decrease of 50 mmol/day below the current level (a reduction of 1/3) would decrease BP by 4.0/2.5 mm Hg in hypertensives and reduce CVD mortality in the US by more than 100,000/yr.

• During the past 25 years salt intake has increased by 1/3 to 150-170 mmol/day (3.5 to 4.0 g sodium/day).

• This has contributed to the growing obesity epidemic and increased prevalence of hypertension by causing increased intake of high-calorie soft drinks containing corn sugar

• Recent studies suggests that a decrease of 50 mmol/day below the current level (a reduction of 1/3) would decrease BP by 4.0/2.5 mm Hg in hypertensives and reduce CVD mortality in the US by more than 100,000/yr.

Page 24: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Secondly, hypertension is

associated with considerable

cardiovascular risk.

3. Why is hypertension considered a major Public health problem in the United States?

Page 25: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #25

Global Mortality 2000: Impact of Hypertension and Other Health Risk Factors

Ezzati et al. Ezzati et al. Lancet.Lancet. 2002;360:1347-1360. 2002;360:1347-1360.Attributable Mortality Attributable Mortality

(In thousands; total 55,861,000)(In thousands; total 55,861,000)

High mortality, developing regionHigh mortality, developing region

Lower mortality, developing regionLower mortality, developing region

Developed regionDeveloped region

00 8000800070007000600060005000500040004000300030002000200010001000

High blood pressureHigh blood pressure

TobaccoTobacco

High cholesterolHigh cholesterol

Unsafe sexUnsafe sex

High BMIHigh BMI

Physical inactivityPhysical inactivity

AlcoholAlcohol

Indoor smoke from solid fuelsIndoor smoke from solid fuels

Iron deficiencyIron deficiency

UnderweightUnderweight

Page 26: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Is it a true risk factor or a risk marker?

A true risk factor is suspected of being causative of the disease process.

A risk marker is associated with the disease process without being in the

causal pathway.

Page 27: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

TIA = transient ischemic attack; LVH = left ventricular hypertrophy; CHD = coronary heart disease; HF = heart failure.Cushman WC. J Clin Hypertens. 2003;5(Suppl):14-22.

Retinopathy Renal failurePeripheral vascular

disease

Complications of Hypertension:

LVH, CHD, HF

TIA, stroke

Hypertension Hypertension is a risk factoris a risk factor

Page 28: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #28

:“Diabesity”

Page 29: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Association of Systolic BP andCV Death in Type 2 Diabetes

0

25

50

75

100

125

150

175

200

225

250

<120 120–139 140–159 160–179 180–199 200

Without diabetes

With diabetes

CV

mort

alit

y r

ate

/10,0

00 p

ers

on-y

Systolic BP (mm Hg)Stamler et al. Diabetes Care. 1993;16:434.

Page 30: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Progression of Diabetes

DeathIGTIGT

•Genetic susceptibility

•Environmental factors– Nutrition– Obesity

– Inactivity

– Insulin resistance– HDL-C

– Triglycerides– Atherosclerosis– Hypertension

Hyperglycemia RetinopathyNephropathyNeuropathy

BlindnessESRD/Dialysis/Transplantation

CHDStroke

AmputationBrown. Diabetes Obes Metab.

2000;2:S11.

Ongoing Ongoing hyperglycemiahyperglycemia

Diagnosis ofDiagnosis ofdiabetesdiabetes

Appearance of Appearance of complicationscomplications

DisabilityDisability

Page 31: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Stages of Chronic Kidney Disease

Stage Description GFR

mL/min/1.73 m2

1 Kidney damage with normal or increased GFR

≥ 90

2 Kidney damage with mild decreased GFR

60-89

3 Moderate decreased GFR 30-59

4 Severe decreased GFR 15-29

5 Kidney failure < 15 (or dialysis)

Page 32: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Proteinuria Is an Independent Risk Factor for Mortality in Type 2 Diabetes

1.0

0.9

0.8

0.7

0.6

0.50 1 2 3 4 5 6

Years

Surv

ival

(all-

cause

mort

alit

y)

Normoalbuminuria(n=191)

Microalbuminuria(n=86)

Macroalbuminuria(n=51)

P<0.01, normo- vs micro- and macroalbuminuria.P<0.05, micro- vs macroalbuminuria.

Gall et al. Diabetes. 1995;44:1303.

Page 33: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Diabetes:The Most Common Cause of ESRD

United States Renal Data System. Annual data report. 2000.

Primary Diagnosis for Patients Who Start Dialysis

Diabetes50.1%

Hypertension27%

Glomerulonephritis

13%

Other

10% No. of patientsProjection95% CI

1984 1988 1992 1996 2000 2004 20080

100

200

300

400

500

600

700

r2=99.8%243,524

281,355520,240

No

. o

f d

ialy

sis

pat

ien

ts

(th

ou

san

ds)

Page 34: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

ESRD in the USA

↓ Mortality from MI & stroke over past 30 years

↑ Life expectancy contributed to ↑ ESRD

Currently in USA > 300,000 patients on dialysis

The cost exceeds $ 50,000 per patient per year

Twenty one billion $ projected cost in 2002

First year mortality ~ 20%

~ 50% of deaths are cardiac (USRDS)

Page 35: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Life Expectancy for Selected U.S. Populations

0

5

10

15

20

25

30

35

Age 49 Age 59

U.S.Prostate cancerColon cancerESRDLung cancer

USRDS 1993 Annual Data Report

USRDS 1993 Annual Data Report

Expe

cted

rem

aini

ng y

ears

Page 36: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Thirdly, there is considerablereduction in cardiovascular riskwith effective lowering of blood

pressure with therapy.

3. Why is hypertension considered a major Public health problem in the United States?

Page 37: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

35%-40%

20%-25%

>50%

Average reduction in events

(%)

–60

–50

–40

–30

–20

–10

0Stroke

Myocardialinfarction Heart failure

Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet. 2000;355:1955-1964.

Long-Term Antihypertensive Therapy Significantly Reduces CV Events

Page 38: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Fourthly, there is insufficientawareness, treatment andcontrol of hypertension.

3. Why is hypertension considered a major Public health problem in the United States?

Page 39: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

0

10

20

30

40

50

60

70

80

Hypertension Awareness, Treatment, and Control: US 1976 to 2000*

NHANES III NHANES III (Phase 2) (Phase 2) 1991-19941991-1994

NHANES III NHANES III (Phase 1) (Phase 1) 1988-19911988-1991

51%51%

73%73% 68%68%

31%31%

55%55% 54%54%

10%10%

29%29% 27%27%

% A

du

lts

% A

du

lts

NHANES II NHANES II 1976-19801976-1980

NHANES NHANES 1999-20001999-2000

70%70%

59%59%

34%34%

Healthy People Healthy People

2000/2010 2000/2010

Control Control

Target = 50%Target = 50%

ControlControl

AwarenessAwareness

TreatedTreated

Chobanian et al. Chobanian et al. JAMAJAMA. 2003;289:2560-2572.. 2003;289:2560-2572.

Page 40: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

4. Global Risk Assessment

Page 41: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Risk Factor Clustering With HypertensionRisk Factor Clustering With Hypertension

Risk factor clustering with hypertension, ages 18–74 years. Framingham offspring.

Kannel WB. Am J Hypertens. 2000.

0 1 2 3

5

0

10

15

20

25

30MenWomen

17%19%

26% 27% 25% 24%22%

20%

8%12%

≥4

RiskFactors

(%)

Number of Risk Factors

Page 42: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

BP is a risk marker for “The Metabolic Syndrome”

*Diagnosis is established when ≥3 of these risk factors are present.

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.

NCEP-ATP III Definition: ≥3 of the Following*NCEP-ATP III Definition: ≥3 of the Following*• Men: >102 cm (>40 in)

• Women: >88 cm (>35 in)

Fasting glucose

• ≥130/≥85 mmHg (risk marker)

Blood pressure

HDL-C

• ≥150 mg/dLTriglycerides

Abdominal obesity (waist circumference)

• Men: <40 mg/dL

• Women: <50 mg/dL

• ≥100 mg/dL

Page 43: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Other CVD Risk Factors: JNC 7

Physical inactivity Cigarette smoking Age (older than 55 for men, 65 for women) Family history of premature CVD

(men under age 55 or women under age 65)

*Components of the metabolic syndrome in blue Chobanian et al. Chobanian et al. JAMAJAMA. 2003;289:2560-. 2003;289:2560-25722572

Page 44: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

700

600

500

400

300

200

100

8 Y

ea

r P

rob

ab

ility

Pe

r 1

,00

0

Systolic BP:Cholesterol:Glucose Intol.:Cigaretes:ECG-LVH:

105 >>> 185185

000

105 >>> 185335

000

105 >>> 185335+00

105 >>> 185335++0

105 >>> 185335+++

Kannel, 1983

Framingham Heart Study (1983)Framingham Heart Study (1983) CV Risk ProfileCV Risk Profile

703

459

326

210

46

Page 45: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Expert Panel on Detection, Evaluation, and Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Treatment of High Blood Cholesterol in Adults. JAMAJAMA. 2001;285:2486-2497.. 2001;285:2486-2497.

Age, yAge, y PointsPoints

20-3420-34 -9-935-3935-39 -4-440-4440-44 0045-4945-49 3350-5450-54 6655-5955-59 8860-6460-64 101065-6965-69 111170-7470-74 121275-7975-79 1313

11

22

55

TotalTotal AgeAge AgeAge AgeAge AgeAge AgeAgeCholesterolCholesterol 20-3920-39 40-4940-49 50-5950-59 60-6960-69 70-7970-79

<160<160 00 00 00 00 00160-199160-199 44 33 22 11 00200-239200-239 77 55 11 33 00240-279240-279 99 66 44 22 11

280280 1111 88 55 33 11

AgeAge AgeAge AgeAge AgeAge AgeAge20-3920-39 40-4940-49 50-5950-59 60-6960-69 70-7970-79

HDL mg/dLHDL mg/dL PointsPoints

6060 -1-150-5950-59 0040-4940-49 11

<40<40 22

Systolic BPSystolic BP IfIf IfIfmm Hgmm Hg UntreatedUntreated TreatedTreated

<120<120 00 00120-129120-129 00 11130-139130-139 11 22140-159140-159 11 22160160 22 33

Point TotalPoint Total 10-Year Risk, %10-Year Risk, %

<0<0 <1<100 1111 1122 1133 1144 1155 2266 2277 3388 4499 55

1010 661111 881212 10101313 12121414 16161515 20201616 2525

1717 3030

66

ATP-III: Framingham Point ScoresEstimate of 10-Year Risk for Men

NonsmokerNonsmoker 00 00 00 00 00SmokerSmoker 88 55 33 11 11

44

33

Page 46: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #46

Page 47: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

5. Intervention Trials

Page 48: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Trial duration is <10 years; treatment benefits should be considered in the very long term (decades).

Drop-in effect (subjects under placebo are given active drug) and drop-out effect (drop-outs in the active treatment group.

Subjects included in the trials are generally healthier than those treated in the clinical practice (selection of low-risk subjects).

Secondary end-points & subgroup analyses difficult to interperet.

Trials & meta-analyses:What we do not know (...and maybe will never

know)

Page 49: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #49

•“Hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it.”

•“Hypertension may be an important compensatory mechanism which should not be tampered with, even were it certain that we could control it.”Paul Dudley White, 1931 Textbook of Cardiology.

Page 50: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #50Messerli, F. H. Messerli, F. H. N Engl J MedN Engl J Med 1995 1995

Page 51: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Hypertension Intervention Trials: 1959-1970

Trial Severity of Hypertension

CV events/yr. In CTRL Group

CV events/yr: CTRL vs Ther. Group

Harrington, et al (1959)

Malignant Hypertension

90% Mortality 90% vs 50% (Mortality / Yr)

VA Coop. Study (1967)

Severe (DBP 115 mmHg) 187/121

29% 10:1 (1.5 Yr.)

VA Coop. Study (1970)

Moderate (DBP 105-114 mmHg) 165/105

5.5% 3.5:1 (4.5 Yr.)

Page 52: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

TOMHSTOMHSVA MONORxVA MONORx

CONVINCECONVINCEALLHAT ALLHAT ANBP2ANBP2

LIFELIFE

HAPPHYHAPPHYMAPHYMAPHY

INSIGHTINSIGHTNORDILNORDIL

CAPPPCAPPPSTOP-2STOP-2

VALUEVALUEASCOTASCOT

ACCOMPLISHACCOMPLISH

Clinical Trials in Hypertension

HR Black, 2003.HR Black, 2003.

1960s1960s 1970s1970s 1980s1980s 1990-19951990-1995 1996-19991996-1999 20002000 2001-20032001-2003 2004-20082004-2008

Should we treat Should we treat diastolic HBP?diastolic HBP?

What is the What is the best way to best way to treat HBP?treat HBP?

Should we treat Should we treat DBP in older DBP in older

persons?persons?

What is theWhat is the goal of goal of

treatment?treatment?

Should we Should we treat ISH in treat ISH in

older older persons?persons?

Can we Can we prevent prevent

hypertension?hypertension?

VA VA Cooperative Cooperative

StudiesStudiesMRC-1MRC-1

ANHBP-1ANHBP-1

EWPHEEWPHE

MRC-2MRC-2

STOP-1STOP-1

SCOPESCOPEHDFPHDFP HOTHOT

UKPDSUKPDS

Syst-EurSyst-EurSyst-ChinaSyst-China

SHEPSHEP TROPHYTROPHY

Page 53: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

SHEP Trial:Design

• N: 4736; 43% male

• Age: >60

• BP: SBP 160-219 and DBP <90

• Design: Placebo control, double blind

• Active Rx: Chlorthalidone (atenolol as step 2)

• SBP difference: 12 mm Hg

• Duration: 4.5 years

JAMA 1991;265:3255

Page 54: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #54

SHEP Trial:Cardiovascular Disease Endpoints

JAMA 1991;265:3255

Page 55: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

HR 95% CI P value

All stroke - 34% 0.46 - 0.95 0.025

Total mortality - 28% 0.59 - 0.88 0.001

Fatal stroke - 45% 0.33 - 0.93 0.021

Cardiovascular mortality - 27% 0.55-0.97 0.029

Heart failure - 72% 0.17-0.48 <0.001

Cardiovascular events - 37% 0.51-0.71 <0.001

HYVETResults All Outcomes

Per Protocol

Beckett N. N Engl J Med. 2008;358: epub. March 31, 2008.

Page 56: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

6. Management of Hypertension

Page 57: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Seventh Report of the Joint National Committee onPrevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) EXPRESS

Seventh Report of the Joint National Committee onPrevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) EXPRESS

National Heart, Lung, andBlood Institute

National High Blood PressureEducation Program

Page 58: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

JNC 7: Appropriate BP Targets• For both CVD and kidney disease, systolic BP is far

more important than diastolic BP

• Systolic BP should be <140 mm Hg in all patients, and ideally between 120-130 mm Hg in patients with complications (diabetes, heart failure, kidney disease)

• Only a small fraction of hypertensives are achieving appropriate BP control

• Multiple antihypertensive agents are needed for most patients

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

• For both CVD and kidney disease, systolic BP is far more important than diastolic BP

• Systolic BP should be <140 mm Hg in all patients, and ideally between 120-130 mm Hg in patients with complications (diabetes, heart failure, kidney disease)

• Only a small fraction of hypertensives are achieving appropriate BP control

• Multiple antihypertensive agents are needed for most patients

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

Page 59: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

JNC 7: Considerations for olderpersons with hypertension

This population has the lowest rates of BP control and the greatest absolute benefit with effective therapy.

Lower initial drug doses may be indicated to avoid symptoms; standard doses and multiple drugs will be needed to reach BP targets.

More than two-thirds of people over 65 have HTN, i.e. ISH (Isolated systolic hypertension).

Page 60: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

JNC 7: Considerations for special populations with hypertension

• Treatment generally similar for all demographic groups

• Socioeconomic factors and lifestyle important barriers to BP control

• Prevalence, severity of hypertension increased in blacks

• Treatment generally similar for all demographic groups

• Socioeconomic factors and lifestyle important barriers to BP control

• Prevalence, severity of hypertension increased in blacks

JNC 7. JAMA. 2003;289:2560-2672.

Page 61: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Intervention

Exercise

Weight reduction

Alcohol intake reduction

Sodium intake reduction

DASH diet

Intervention

Exercise

Weight reduction

Alcohol intake reduction

Sodium intake reduction

DASH diet

Lifestyle Interventions for Prevention or Treatment of Hypertension

Blood Pressure Effect

5-10 mm Hg (>30 min >3x/wk)

1-2 mm Hg/Kg

1 mm Hg/drink/d

1-3 mm Hg/40 mmol/d

3-10 mm Hg

Blood Pressure Effect

5-10 mm Hg (>30 min >3x/wk)

1-2 mm Hg/Kg

1 mm Hg/drink/d

1-3 mm Hg/40 mmol/d

3-10 mm Hg Adapted from Cushman et al. Endocrine Practice 1997;3:106 & Sacks, et al. NEJM 2001;334:3

Page 62: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #62

Page 63: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Lifestyle Treatment Measures

Nonpharmacologic treatments are used for:

Lowering blood pressure

Reducing need for antihypertensive agents

Minimizing associated risk factors

Primary prevention of hypertension

Page 64: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

19721972 19731973 19761976 19801980 19841984 19881988 19931993 19971997 20032003

Development of Hypertension Guidelines: the JNCs and Drug Therapy

NHBPEPNHBPEPSTARTSSTARTS

EarliestEarliestGuidelinesGuidelines

28 drugs28 drugsDBP DBP 105105DiureticsDiuretics

JNC IJNC I

43 drugs43 drugs

diuretics,diuretics,-blockers-blockers

AddedAdded

JNC IIIJNC III

JNC IIJNC II

34 drugs34 drugsDiureticsDiuretics

JNC IVJNC IV

50 drugs50 drugsACEI, CAsACEI, CAs

addedadded

JNC VIJNC VI

84 drugs84 drugs7 options7 options

Low-doseLow-dose

JNCs I-7.JNCs I-7.

68 drugs68 drugsDiuretics/Diuretics/-blockers-blockers

JNC VJNC V JNC 7JNC 7

> 125 drugs> 125 drugsDiureticsDiuretics

Page 65: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #65

0.5 1.0 2.0

BP-Lowering Treatment TrialistsComparisons of Different Active Treatments

Relative Risk RR (95% CI)RR (95% CI)BP DifferenceBP Difference

(mm Hg)(mm Hg)

FavorsFavorsFirst ListedFirst Listed

FavorsFavorsSecond ListedSecond Listed

Major CV eventsMajor CV events

CV mortalityCV mortality

Total mortalityTotal mortality

1.02 (0.98, 1.07)1.02 (0.98, 1.07)2/02/0 ACEI vs D/BBACEI vs D/BB

1.03 (0.95, 1.11)1.03 (0.95, 1.11)2/02/0 ACEI vs D/BBACEI vs D/BB

1.00 (0.95, 1.05)1.00 (0.95, 1.05)2/02/0 ACEI vs D/BBACEI vs D/BB

1.04 (0.99, 1.08)1.04 (0.99, 1.08)1/01/0 CA vs D/BBCA vs D/BB

1.05 (0.97, 1.13)1.05 (0.97, 1.13)1/01/0 CA vs D/BBCA vs D/BB

0.99 (0.95, 1.04)0.99 (0.95, 1.04)1/01/0 CA vs D/BBCA vs D/BB

0.97 (0.95, 1.03)0.97 (0.95, 1.03)1/11/1 ACEI vs CAACEI vs CA

1.03 (0.94, 1.13)1.03 (0.94, 1.13)1/11/1 ACEI vs CAACEI vs CA

1.04 (0.98, 1.10)1.04 (0.98, 1.10)1/11/1 ACEI vs CAACEI vs CA

Blood Pressure Lowering Treatment Trialists’ Collaboration. Blood Pressure Lowering Treatment Trialists’ Collaboration. LancetLancet. 2003;362:1527-1535.. 2003;362:1527-1535.

Page 66: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Not at Goal Blood Pressure (<140/90 mm Hg) (<130/80 mm Hg for those with diabetes or chronic kidney disease)

Not at Goal Blood Pressure (<140/90 mm Hg) (<130/80 mm Hg for those with diabetes or chronic kidney disease)

Initial Drug ChoicesInitial Drug Choices

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed

Drug(s) for the compelling indications

Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB)

as needed

With Compelling Indications

With Compelling Indications

Lifestyle ModificationsLifestyle Modifications

Not at Goal Blood Pressure

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved

Consider consultation with hypertension specialist

Optimize dosages or add additional drugs until goal blood pressure is achieved

Consider consultation with hypertension specialist

Stage 2 Hypertension (SBP >160 or DBP >100 mm Hg)

2-drug combination for most (usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

Stage 2 Hypertension (SBP >160 or DBP >100 mm Hg)

2-drug combination for most (usually thiazide-type diuretic and

ACEI, or ARB, or BB, or CCB)

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 1 Hypertension(SBP 140-159 or DBP 90-99 mm

Hg) Thiazide-type diuretics for most

May consider ACEI, ARB, BB, CCB,

or combination

Without Compelling Indications

Without Compelling Indications

JNC 7 Algorithm for Treatment of Hypertension

Chobanian et al. Chobanian et al. JAMAJAMA. 2003;289:2560-2572.. 2003;289:2560-2572.

Page 67: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Number of Medications to Achieve Goal BP in 5 Trials of DM &/or Renal Disease

3.8

3.3

3.6

2.8

2.7

0 1 2 3 4

AASK (<92 mm Hg MAP)

HOT (<80 mm Hg DBP)

MDRD (<92 mm Hg MAP)

ABCD (< 75 mm Hg DBP)

UKPDS (<150/85 mm Hg)

Number of BP Meds

Bakris. Bakris. J Clin HypertensJ Clin Hypertens 1999;1:141-7 1999;1:141-7

Page 68: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

7. Barriers to Treatment

Page 69: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Barriers to Controlling Hypertension

HealthcareSystem

Patients Providers

Page 70: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

2098 Franklin #70

The Initial Confrontation of the HTN Problem

• Upon making a diagnosis of HTN, tell patient the BP reading and what it should be (provide a written copy).

• Prepare patient for the probable necessity for polypharmacy to control BP with a minimum of side effects

• Advise Home BP measurement (135/85 mmHg is considered to be hypertensive).

• Upon making a diagnosis of HTN, tell patient the BP reading and what it should be (provide a written copy).

• Prepare patient for the probable necessity for polypharmacy to control BP with a minimum of side effects

• Advise Home BP measurement (135/85 mmHg is considered to be hypertensive).

Table 28. JNC 7 Report. Hypertension. 2003;42(6):1240.

Page 71: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Self-Measurement of BP

Provides information useful for:

1. assessing response to antihypertensive Rx

2. improving adherence with therapy

3. evaluating white-coat HTN

Home BP is more strongly related to target organ damage and has better prognostic accuracy than office BP.

Page 72: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

8. Prevention Strategy:

General Population StrategyVersus

Targeted Intensive Strategy

Page 73: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

Strategies for Prevention of High Blood Pressure

General Population Strategy

Attempt to shift (downwards) the distribution of BP in entire population

Targeted Intensive Strategy

More intensive efforts to reduce BP in individuals/groups at highest risk of hypertension

High normal BP

Family history of hypertension

High risk groups

Environmental exposures that increase probability of hypertension

High weight High salt intake Alcohol consumption Physical inactivity

17% reduction in prevalence of hypertension

14% reduction in average annual incidence of stroke

6% reduction in average annual incidence of CHD

Estimated Effect of 2 mm Hg Reduction inAverage Diastolic BP in General Population

Cook N R et al., Arch Intern Med 1996

35-64 year old White Residents of United States

FollowingIntervention

BeforeIntervention

Whelton, PK, He J, Appel LA et al., JAMA 2002;288:1882-1888

Page 74: Epidemiology of Hypertension Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director

• Epidemiology Summary:

– Increasing prevalence; world wide problem

– Blood pressure as a moving target

– ↑ PVR in the young, ↑ stiffness in the elderly

– Predominantly isolated systolic hypertension

– Consider special populations at increased risk

– Hypertension as a part of absolute global CV risk

– Population vs. high risk approaches for prevention

• Epidemiology Summary:

– Increasing prevalence; world wide problem

– Blood pressure as a moving target

– ↑ PVR in the young, ↑ stiffness in the elderly

– Predominantly isolated systolic hypertension

– Consider special populations at increased risk

– Hypertension as a part of absolute global CV risk

– Population vs. high risk approaches for prevention