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Epidemiology of Hypertension. Stanley S. Franklin, MD, FACP, FACC Clinical Professor of Medicine University of California at Irvine Associate Medical Director UCI Heart Disease Prevention Program Irvine, California. Agenda: epidemiology of hypertension. BP measurement

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epidemiology of hypertension
Epidemiology of Hypertension

Stanley S. Franklin, MD, FACP, FACC

Clinical Professor of Medicine

University of California at Irvine

Associate Medical Director

UCI Heart Disease Prevention Program

Irvine, California

agenda epidemiology of hypertension
Agenda: epidemiology of hypertension
  • BP measurement
  • Defining hypertension
  • Why an important public health problem
  • Global risk assessment
  • Intervention trials and meta-analyses
  • Management strategies
  • Barriers to treatment
  • Prevention strategies
slide3

1. How to measure

blood pressure?

slide4

Ascultatory method of

blood pressure measurement

Nokolai Korotkoff, 1905

noninvasive blood pressure measurement

Noninvasive Blood Pressure Measurement

Methodologies

Auscultatory (K sound)

- Mercury

- Aneroid

- Oscillometric

Locations Situations

- Upper arm - Clinic

- Wrist - Home

- Finger - Ambulatory

slide6

2. Defining Hypertension:

(a) By the numbers?

≥95 DBP

160/95

140/90

130/85

>120/80

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

slide7

CV Mortality Risk Doubles withEach 20/10 mm Hg BP Increment*

8

7

6

5

CVmortalityrisk

4

3

2

1

0

115/75

135/85

155/95

175/105

SBP/DBP (mm Hg)

*Individuals aged 40-70 years, starting at BP 115/75 mm Hg.

CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure

Lewington S, et al. Lancet. 2002; 60:1903-1913.

JNC 7. JAMA. 2003;289:2560-2572.

jnc reclassification of bp based on risk

and

<120

80

Optimal

and

Normal

<120

80

and

120-129

80-84

Normal

or

Prehypertension

120-139

80-89

or

130-139

85-89

Hi-normal

Hypertension

or

140-159

90-99

or

Stage 1

Stage 1

140-159

90-99

or

Stage 2

160-179

100-109

or

≥160

≥100

Stage 2

Stage 3

≥180

or

≥110

JNC Reclassification of BP Based on Risk

JNC VI

JNC 7

DBP

(mm Hg)

SBP

(mm Hg)

DBP

(mm Hg)

SBP

(mm Hg)

Category

Category

Source for JNC VI: Arch Intern Med. 1997;157:2413-2446.

Adapted with permission from Chobanian AV et al. Hypertension. 2003;42:1206-1252.

slide9

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

(NHANES 1999-2000)

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

prehypertension
Prehypertension …
  • Is not a disease,
  • Is not “hypertension”,
  • Is not an indication for drug treatment of HTN,
  • Does not have a BP goal,
  • Does predict a higher risk for developing CV events,
  • Does predict a higher risk for developing HTN,
  • Should be an incentive to improve lifestyle practices for prevention of HTN and CVD.
slide11

Defining Hypertension:

(b) By hemodynamic mechanism?

Increased peripheral vascular resistance

versus

Increased large artery stiffness

the arterial pulse wave

Systolic pressure

Dicrotic notch

(aortic valve closes)

125

Mean pressure

Pressure (mm Hg)

Diastolic decay curve

Diastolic pressure

75

Time

The Arterial Pulse Wave

Pulse pressure

=1/3 SBP + 2/3 DBP

hemodynamic components of bp
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.

overview of arterial blood pressure hemodynamics
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.

Overview of Arterial Blood Pressure Hemodynamics
slide15

Defining Hypertension:

(c) By subtype?

IDH, SDH, ISH

slide16

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

ISH (SBP ³140 mm Hg and DBP <90 mm Hg)

SDH (SBP ³140 mm Hg and DBP ³90 mm Hg)

IDH (SBP <140 mm Hg and DBP ³90 mm Hg)

100

80

60

40

20

0

}

Diastolic Hypertension

17%

16%

16%

20%

20%

11%

Frequency of hypertension

subtypes in all untreated hypertensives

(%)

<40

40-49

50-59

60-69

70-79

80+

Age (y)

Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age.

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

an analysis of nhanes iii blood pressure data
An Analysis of NHANES III Blood Pressure Data

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 IDHand 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

slide18

3. Why is hypertension considered a major

Public health problem in the United States?

Firstly, hypertension is very

common In the adult population

slide19
Increased Prevalence of Hypertension in the United States from 1988-1994 (NHANES III) to 1999-2000 NHANES

30% increase, p<.001

Population With Hypertension (millions)

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

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

trends in prevalence of hypertension in the us population by race ethnicity 1988 2000
Trends in Prevalence of Hypertension in the US Population, by Race/Ethnicity,1988-2000

*

*

**

**

**

*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.

slide21

Hypertension Paradox: Changes in the Prevalence and Control of

Hypertension in the United States (1988-2004)

Rate of control:

27% to 35%

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

colors of salt
White

Black

Red

Yellow

Green

Brown

Clear

Table salt

Soy sauce

Catsup

Mustard

Pickles

Soups & gravies

Saline

Colors of Salt
the connection between salt obesity hypertension and cvd mortality
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.
slide24

3. Why is hypertension considered a major

Public health problem in the United States?

Secondly, hypertension is

associated with considerable

cardiovascular risk.

global mortality 2000 impact of hypertension and other health risk factors

High mortality, developing region

Lower mortality, developing region

Developed region

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

High blood pressure

Tobacco

High cholesterol

Underweight

Unsafe sex

High BMI

Physical inactivity

Alcohol

Indoor smoke from solid fuels

Iron deficiency

0

1000

2000

3000

4000

5000

6000

7000

8000

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

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

slide26

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.

complications of hypertension

TIA, stroke

LVH, CHD, HF

Renal failure

Retinopathy

Peripheral vascular disease

Complications of Hypertension:

Hypertension is a risk factor

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.

slide28

:

“Diabesity”

association of systolic bp and cv death in type 2 diabetes

250

225

200

175

150

125

100

75

50

25

0

Association of Systolic BP andCV Death in Type 2 Diabetes

Without diabetes

With diabetes

CV mortality rate/10,000 person-y

<120

120–139

140–159

160–179

180–199

200

Systolic BP (mm Hg)

Stamler et al. Diabetes Care. 1993;16:434.

progression of diabetes

Genetic susceptibility

  • Environmental factors
    • Nutrition
    • Obesity
    • Inactivity
Progression of Diabetes

Diagnosis of

diabetes

Appearance of complications

Disability

  • Insulin resistance
  •  HDL-C
  •  Triglycerides
  • Atherosclerosis
  • Hypertension

Death

IGT

Ongoing hyperglycemia

Blindness

ESRD/Dialysis/Transplantation

CHD

Stroke

Amputation

Hyperglycemia

Retinopathy

Nephropathy

Neuropathy

Brown. Diabetes Obes Metab. 2000;2:S11.

proteinuria is an independent risk factor for mortality in type 2 diabetes
Proteinuria Is an Independent Risk Factor for Mortality in Type 2 Diabetes

1.0

Normoalbuminuria

(n=191)

0.9

Microalbuminuria

(n=86)

0.8

Survival

(all-cause mortality)

0.7

Macroalbuminuria

(n=51)

0.6

0.5

0

1

2

3

4

5

6

Years

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

P<0.05, micro- vs macroalbuminuria.

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

diabetes the most common cause of esrd

Diabetes

Hypertension

50.1%

27%

Diabetes:The Most Common Cause of ESRD

Primary Diagnosis for Patients Who Start Dialysis

Glomerulonephritis

Other

No. of patients

10%

13%

700

Projection

95% CI

600

500

400

No. of dialysis patients (thousands)

520,240

300

281,355

200

243,524

100

r2=99.8%

0

1984

1988

1992

1996

2004

2000

2008

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

esrd in the usa
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)
life expectancy for selected u s populations
Life Expectancy for Selected U.S. Populations

Expected remaining years

USRDS 1993 Annual Data Report

slide36

3. Why is hypertension considered a major

Public health problem in the United States?

Thirdly, there is considerable

reduction in cardiovascular risk

with effective lowering of blood

pressure with therapy.

slide37

Long-Term Antihypertensive Therapy Significantly Reduces CV Events

Stroke

Heart failure

Myocardial

infarction

0

–10

–20

Average

reduction

in events (%)

20%-25%

–30

–40

35%-40%

–50

>50%

–60

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

slide38

3. Why is hypertension considered a major

Public health problem in the United States?

Fourthly, there is insufficient

awareness, treatment and

control of hypertension.

hypertension awareness treatment and control us 1976 to 2000

Healthy People 2000/2010 Control

Target = 50%

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

73%

70%

68%

Awareness

59%

55%

54%

51%

34%

31%

% Adults

29%

27%

Treated

10%

Control

NHANES II 1976-1980

NHANES III (Phase 2) 1991-1994

NHANES 1999-2000

NHANES III (Phase 1) 1988-1991

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

slide41

Risk Factor Clustering With Hypertension

30

Men

25

27%

Women

26%

25%

24%

20

22%

RiskFactors(%)

20%

19%

17%

15

10

12%

8%

5

0

0

1

2

3

≥4

Number of Risk Factors

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

Kannel WB. Am J Hypertens. 2000.

bp is a risk marker for the metabolic syndrome

Men: >102 cm (>40 in)

  • Women: >88 cm (>35 in)

Abdominal obesity (waist circumference)

  • ≥150 mg/dL

Triglycerides

  • Men: <40 mg/dL
  • Women: <50 mg/dL

HDL-C

  • ≥130/≥85 mmHg (risk marker)

Blood pressure

  • ≥100 mg/dL

Fasting glucose

BP is a risk marker for “The Metabolic Syndrome”

NCEP-ATP III Definition: ≥3 of the Following*

*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.

other cvd risk factors jnc 7
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. JAMA. 2003;289:2560-2572

slide44

Framingham Heart Study (1983)

CV Risk Profile

703

700

600

500

459

400

8 Year Probability Per 1,000

326

300

210

200

100

46

Systolic BP:Cholesterol:Glucose Intol.:Cigaretes:

ECG-LVH:

  • >>> 185
  • 185
  • 0
  • 0
  • 0
  • >>> 185
  • 335
  • 0
  • 0
  • 0
  • >>> 185
  • 335
  • +
  • 0
  • 0
  • >>> 185
  • 335
  • +
  • +
  • 0
  • >>> 185
  • 335
  • +
  • +
  • +

Kannel, 1983

atp iii framingham point scores estimate of 10 year risk for men
ATP-III: Framingham Point ScoresEstimate of 10-Year Risk for Men

1

3

5

Age Age Age Age Age 20-39 40-49 50-59 60-69 70-79

Age, y Points

Systolic BP If If mm Hg Untreated Treated

20-34 -9

35-39 -4

40-44 0

45-49 3

50-54 6

55-59 8

60-64 10

65-69 11

70-74 12

75-79 13

<120 0 0 120-129 0 1 130-139 1 2 140-159 1 2160 2 3

Nonsmoker 0 0 0 0 0Smoker 8 5 3 1 1

6

Point Total 10-Year Risk, %

<0 <1 0 1 1 1 2 1 3 1 4 1 5 2 6 2 7 3 8 4 9 5 10 6 11 8 12 10 13 12 14 1615 20 16 2517 30

4

HDL mg/dL Points

60 -1 50-59 0 40-49 1 <40 2

2

Total Age Age Age Age Age Cholesterol 20-39 40-49 50-59 60-69 70-79

<160 0 0 0 0 0 160-199 4 3 2 1 0 200-239 7 5 1 3 0 240-279 9 6 4 2 1280 11 8 5 3 1

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

slide48

Trials & meta-analyses:

What we do not know (...and maybe will never know)

  • 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.
slide49
“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.

clinical trials in hypertension

HOTUKPDS

HDFP

Syst-EurSyst-China

SCOPE

CONVINCEALLHAT ANBP2LIFE

VALUEASCOTACCOMPLISH

VA Cooperative Studies

EWPHE

HAPPHYMAPHY

MRC-1ANHBP-1

SHEP

MRC-2

STOP-1

INSIGHT

NORDIL

CAPPPSTOP-2

TOMHSVA MONORx

Clinical Trials in Hypertension

Should we treat ISH in older persons?

Can we prevent hypertension?

What is the

goal of treatment?

Should we treat DBP in older persons?

What is the best way to treat HBP?

Should we treat diastolic HBP?

1960s 1970s 1980s 1990-1995 1996-1999 2000 2001-2003 2004-2008

TROPHY

HR Black, 2003.

shep trial design
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

hyvet results all outcomes
HYVETResults All Outcomes

Per Protocol

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

slide56

6. Management of

Hypertension

slide57

National Heart, Lung, andBlood Institute

National High Blood PressureEducation Program

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

jnc 7 appropriate bp targets
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.
jnc 7 considerations for older persons with hypertension
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).

jnc 7 considerations for special populations with hypertension
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

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

lifestyle interventions for prevention or treatment of hypertension
Intervention

Exercise

Weight reduction

Alcohol intake reduction

Sodium intake reduction

DASH diet

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 

Lifestyle Interventions for Prevention or Treatment of Hypertension

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

lifestyle treatment measures
Lifestyle Treatment Measures
  • Nonpharmacologic treatments are used for:

Lowering blood pressure

  • Reducing need for antihypertensive agents
  • Minimizing associated risk factors

 Primary prevention of hypertension

development of hypertension guidelines the jncs and drug therapy
Development of Hypertension Guidelines: the JNCs and Drug Therapy

JNC I

JNC III

JNC V

JNC 7

EarliestGuidelines

JNC II

JNC IV

JNC VI

1972 1973 1976 1980 1984 1988 1993 19972003

34 drugs

Diuretics

50 drugs

ACEI, CAs

added

84 drugs

7 options

NHBPEP

STARTS

43 drugs

diuretics,b-blockersAdded

28 drugsDBP 105Diuretics

68 drugs

Diuretics/

b-blockers

> 125 drugs

Diuretics

Low-dose

JNCs I-7.

bp lowering treatment trialists comparisons of different active treatments

ACEI vs D/BB

2/0

1.02 (0.98, 1.07)

CA vs D/BB

1/0

1.04 (0.99, 1.08)

ACEI vs CA

1/1

0.97 (0.95, 1.03)

ACEI vs D/BB

1.03 (0.95, 1.11)

2/0

CA vs D/BB

1.05 (0.97, 1.13)

1/0

ACEI vs CA

1.03 (0.94, 1.13)

1/1

ACEI vs D/BB

1.00 (0.95, 1.05)

2/0

CA vs D/BB

0.99 (0.95, 1.04)

1/0

ACEI vs CA

1/1

1.04 (0.98, 1.10)

BP-Lowering Treatment TrialistsComparisons of Different Active Treatments

BP Difference(mm Hg)

RR (95% CI)

Relative Risk

Major CV events

CV mortality

Total mortality

FavorsFirst Listed

FavorsSecond Listed

0.5

1.0

2.0

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

jnc 7 algorithm for treatment of hypertension

Without Compelling Indications

With Compelling Indications

Drug(s) for the compelling indications

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

Stage 1 Hypertension(SBP 140-159 or DBP 90-99 mm Hg) Thiazide-type diuretics for most May consider ACEI, ARB, BB, CCB, or combination

Stage 2 Hypertension(SBP >160 or DBP >100 mm Hg) 2-drug combination for most (usually thiazide-type diuretic and ACEI, or ARB, or BB, or CCB)

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achievedConsider consultation with hypertension specialist

JNC 7 Algorithm for Treatment of Hypertension

Lifestyle Modifications

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

Initial Drug Choices

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

number of medications to achieve goal bp in 5 trials of dm or renal disease
Number of Medications to Achieve Goal BP in 5 Trials of DM &/or Renal Disease

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

barriers to controlling hypertension
Barriers to Controlling Hypertension

Patients

Providers

HealthcareSystem

the initial confrontation of the htn problem
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).

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

self measurement of bp
Self-Measurement of BP
  • Provides information useful for:
    • assessing response to antihypertensive Rx
    • improving adherence with therapy
    • evaluating white-coat HTN
  • Home BP is more strongly related to target organ damage and has better prognostic accuracy than office BP.
slide72

8. Prevention Strategy:

General Population Strategy

Versus

Targeted Intensive Strategy

slide74
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