An evidence-based approach to Hypertension

Agenda

• Hypertension: The global epidemic

• Classification and Management

• Which is more important SBP or DBP?

• Diuretics in the Guidelines

• Support of recent trials for diuretics

• Conclusion

Hypertension: The global epidemic

Hypertension: Leading cause of death

Attributable Mortality (In millions)Attributable Mortality (In millions)

High mortality, developing regionHigh mortality, developing region

Lower mortality, developing regionLower mortality, developing region

Developed regionDeveloped region

00 8877665544332211

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

Ezzati et al. WHO 2000 Report. Lancet. 2002;360:1347-1360.

%

Reuters Business Insight – Healthcare – 2004 (USA, JAP, FRA, GER, ITALY, SPAIN, UK)

Hypertension prevalence world-wide

Hypertension prevalence world-wide

Billions

+ 60%

2000 2025

Hypertension prevalence world-wide

WHO Report 2004; 2. Wolf-Maier K et al. Hypertension 2004.

Italy38%Spain

47%

England42%

Germany55%Canada

27%

U.S.A.28%

Sweden38%

Finland21%

Italy9-23%

Spain5-16%

France27%

England6-10%

Scotland18%

Germany8-23%Canada

16-17%

U.S.A.29-31%

Sweden6%

BP<140/9035-64 years

WHO Report 2004; 2. Wolf-Maier K et al. Hypertension 2004.

Hypertension control world-wide

Hypertension Awareness, Treatment and Control:US 1976 - 2000

JNC-VII. Hypertension. 2003;42:1206–1252

Blood Pressure and risk of CV events

Lawes CM et al. J Hypertens. 2006;24:423-430

2/3 of strokes and 1/2 of cases of ischemic

heart disease

are attributable to suboptimal blood pressure

control

Blood Pressure and risk of Stroke Mortality

MRFIT trial. Arch Intern Med 1992; 152:56-64

0

2

4

6

8

10

<85 85-89 90-99 100+ <130 130-139 140-159 160+

Blood pressure (mm Hg)

Ris

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f s

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pe

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10

,00

0 p

ers

on

-ye

ars Diastolic Systolic

Blood Pressure and risk of CAD Mortality

0

5

10

15

20

25

30

35

40

75-79 80-89 90-99 100+ <120 120-139 140-159 160+

Blood pressure (mm Hg)

Ris

k o

f C

AD

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10

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0 p

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Diastolic Systolic

MRFIT trial. Arch Intern Med 1992; 152:56-64

Classification and Management

BP Classification

JNC-VII. Hypertension. 2003;42:1206–1252

BP Classification

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

BP threshold with different types of measurement

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

Risk Stratification

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

When to initiate antihypertensive treatment?

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

Factors influencing prognosis

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

Risk Factors:Systolic and diastolic BP levels

Levels of pulse pressure (in the elderly)Age > 55 for men, > 65 for women

SmokingDyslipidemia

Abnormal glucose tolerance testAbdominal obesity Physical inactivity

Family history of premature CVD

Subclinical organ damage:LVH

Carotid wall thickening or plaqueCarotid-femoral PWV >12m/s

Slight increase in plasma creatinineLow GFR or creatinine clearance (<60ml/mn)

Microalbuminuria

Established CV or renal disease:Cerebrovascular disease

Heart diseaseRenal disease

Peripheral artery diseaseAdvanced retinipathy

Diabetes mellitus:Fasting plasma glucose >7mmol/L

Postload plasma glucose >11mmol/L

SBP or DBP?

SBP increases with age

Franklin SS et al. Circulation. 1997;96:308-315.

Are people with elevated SBP always elderly?

NHANNES III

>50 years

79.7%

45.1%

40-50 years

SBP is most predictive of cardiovascular events

MRFIT trial. Arch Intern Med 1992; 152:56-64

SBP is most predictive of stroke

Borghi c et al. J Hypertens. 2002;20:1737-1742.

SBP control, difficult to achieve

J Hypertens 2002;20:1461-1464.

Hypertension control in European countries

Erdine S. J Hypertens. 2000;18:1348-1349.

Guidelines Recommendation

• Greater emphasis must clearly be placed on managing systolic hypertension.

• Otherwise, the toll of uncontrolled SBP will cause increased rates of:

– Cardiovascular diseases.

– Renal diseases.

JNC 7 report, Hypertension. 2003; 42: 1206-1252.

Guidelines Recommendation

J Hypertens 2003;21:1983-1992

Goals of treatment

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

To achieve maximum reduction in the long-term risk of cardiovascular disease

• BP should be reduced to at least < 140/90 mmHg, and to lower values if tolerated, in all hypertensive patients

or• Target BP should be at least < 130/80 mmHg in

diabetics and in high risk patients (Stroke, MI, Renal dysfunction…)

J Hypertens 2003;21:1983-1992

Goals of treatment

• Despite use of combination treatment, reducing SBP to <140 mmHg may be difficult

• Additional difficulties should be expected in elderly and diabetic patients, and in patients with CV damage

• SBP control is particularly rare…this explains why high BP remains a leading cause of death and cardiovascular morbidity worldwide

2007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

J Hypertens 2003;21:1983-19922007 ESC/ESH Guidelines for the management of Arterial Hypertension. J Hypertens. 2007;25:1105-1187.

Benefits of treating SBP

“Whenever SBP is reduced by 10 mmHg, both

stroke and coronary events are markedly reduced”.

Diuretics in the Guidelines

JNC VII algorithm for HT treatment

JNC-VII. Hypertension. 2003;42:1206–1252

JNC VII algorithm for HT treatment

« Thiazide-type diuretics should be in drug treatment for most patients, either alone or in

combination »

« Thiazide-type diuretics are unsurpassed in lowering blood pressure, reducing clinical

events, and tolerability»

JNC-VII. Hypertension. 2003;42:1206–1252

Thiazide-type Diuretics first-line

2006 NICE / BHS algorithm for HT treatment

• After reviewing all the reliable literature, including the most recent one (ASCOT-BPLA), the guideline committee decided to reject the BBs to the 4th line treatment (unless other indications such as CAD, arrythmias, … are present), and to keep the gold standard position of the diuretics as a cornerstone 1st line treatment for hypertension

NICE / BHS

• CCBs are not recommended for use in elderly hypertensive patients because of side effects.

JNC 7 report, Hypertension. 2003; 42: 1206-1252.

Diuretics versus CCBs

Diuretic antihypertensives:Support of recent trials

SHEPThe Systolic Hypertension in the Elderly Program

• Double blind, randomized, placebo controlled study.

• Thiazide diuretic (chlorthalidone) Vs Placebo• 4,736 elderly HT Patients with ISH.

– 583 of them with T2 diabetics.

• Average follow up for 4.5 Ys.• Main outcome is fatal and nonfatal Stroke.

Curb Dj, et al. JAMA.1996;276(23):1886-1892

SHEP morbidity and mortality for non diabetics

Curb Dj, et al. JAMA.1996;276(23):1886-1892

SHEP morbidity and mortality for diabetics

Curb Dj, et al. JAMA.1996;276(23):1886-1892

• Prospective, randomised trial in 6614 patients aged 70-84 years with hypertension

• ACEI ,Ca blockers versus diuretics and ß-blockers

• “ Prescribers who had decided that thiazide diuretics should be first-line treatment for elderly hypertensive people will be further encouraged by the results of STOP 2”

Kendall,co mentary, Lancet,1999

STOP 2Swedish Trial in Old Patients,2

• Diuretic based treatment reduced:- CHD

- MI

- Stroke

To the same degree as therapy based on ACE I, and CCB.

ALLHAT(Thiazide-type diuretic vs ACEi and CCB-33,357 hypertensives patients)

2. ALLHAT JAMA 2002;288:2981-29971. Appel LJ. JAMA. 2002;288:3039-3042.

ALLHAT(Thiazide-type diuretic vs ACEi and CCB-33,357 hypertensives patients)

ALLHAT JAMA 2002;288:2981-2997

ALLHAT(Thiazide-type diuretic vs ACEi and CCB-33,357 hypertensives patients)

2. ALLHAT JAMA 2002;288:2981-29971. Appel LJ. JAMA. 2002;288:3039-3042.

High-dose diuretic and low-dose diuretic, both reduced the

incidence of stroke (-51%, -34%).

Psaty BM et al. JAMA. 1997;277:739-745.

Diuretics clearly reduce strokes

Low-dose diuretic reduced the incidence of CHD (-28%).

Psaty BM et al. JAMA. 1997;277:739-745.

Diuretics clearly reduce CHD

High-dose and low-dose diuretic therapy both significantly reduced cardiovascular mortality(-22% ,-

24%).

Psaty BM et al. JAMA. 1997;277:739-745.

Diuretics clearly reduce CV death

Diuretics versus β-blockers

Trials in

elderly: Diuretics

or -Blockers

Diuretics

-Blockers

-Blockers are reported to compare poorly with diuretics in reducing CV

events and strokes

Diuretics versus β-blockers

Conclusion

Diuretics: The cornerstone of hypertension treatment

They enhance the antihypertensive efficacy of all other antihypertensive drugs

1.Chobanian AV, Bakris GL, Black HR, et al. (JNC-7). Hypertension. 2003;42:1206-1252.2. WHO, ISH writing group statement on management of hypertension. J Hypertens. 2003;21:1983-1992

1. The ALLHAT study JAMA. 2002; 288: 2981-2997 2. JNC - VII Report, JAMA , 2003;289:2560-2572

Conclusion

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