L’Ipertensione Arteriosa nel Paziente Diabetico: Nuovi Target Terapeutici Dr. Vittorio Emanuele...

L’Ipertensione Arteriosa

nel Paziente Diabetico:

Nuovi Target Terapeutici

Dr. Vittorio Emanuele

Scalea 16.5.09

Linee Guida

• JNC 7. 2003.

• WHO. 2003.

• BHS. 2004.

• ESH/ESC. 2007.

• Australian Heart F.2008.

U.S. Department of Health and Human

Services

National Institutes of Health

National Heart, Lung, and Blood Institute

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

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

National Heart, Lung, and Blood InstituteNational High Blood Pressure Education ProgramNational Heart, Lung, and Blood InstituteNational High Blood Pressure Education Program

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

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

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

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

New Features and Key Messages

Blood Pressure Classification

Normal <120 and <80

Prehypertension 120–139 or 80–89

Stage 1 Hypertension

140–159 or 90–99

Stage 2 Hypertension

>160 or >100

BP Classification

SBP mmHg

DBP mmHg

CVD Risk

HTN prevalence ~ 50 million people in the United States.

The BP relationship to risk of CVD is continuous, consistent, and independent of other risk factors.

Each increment of 20/10 mmHg doubles the risk of CVD across the entire BP range starting from 115/75 mmHg.

Prehypertension signals the need for increased education to reduce BP in order to prevent hypertension.

Benefits of Lowering BP

Average Percent Reduction

Stroke incidence 35–40%

Myocardial infarction 20–25%

Heart failure 50%

Benefits of Lowering BP

In stage 1 HTN and additional CVD risk factors, achieving a sustained 12 mmHg reduction in SBP over 10 years will

prevent 1 death for every 11 patients treated.

BP Control RatesTrends in awareness, treatment, and control of high

blood pressure in adults ages 18–74

National Health and Nutrition Examination Survey, Percent

II1976–80

II(Phase 1)1988–91

II(Phase 2)1991–94 1999–2000

Awareness 51 73 68 70

Treatment 31 55 54 59

Control 10 29 27 34

Sources: Unpublished data for 1999–2000 computed by M. Wolz, National Heart, Lung, and Blood Institute; JNC 6.

Patient Evaluation

Evaluation of patients with documented HTN has three objectives:

1. Assess lifestyle and identify other CV risk factors or concomitant disorders that affects prognosis and guides treatment. DIABETE?

2. Reveal identifiable causes of high BP.

3. Assess the presence or absence of target organ damage and CVD.

CVD Risk Factors Hypertension* Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia* Diabetes mellitus* Microalbuminuria or estimated GFR <60 ml/min 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.

Goals of Therapy

Reduce CVD and renal morbidity and mortality.

Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.

Achieve SBP goal especially in persons >50 years of age.

Algorithm for Treatment of Hypertension

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

Initial Drug Choices

Drug(s) for the compelling indications

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

as needed.

With Compelling Indications

Lifestyle Modifications

Stage 2 Hypertension (SBP >160 or DBP >100 mmHg)

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

mmHg) Thiazide-type diuretics for most.

May consider ACEI, ARB, BB, CCB,

or combination.

Without Compelling Indications

Not at Goal Blood Pressure

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

Consider consultation with hypertension specialist.

WHO 2003

http://www.who.int/en/

BHS Guidelines for the management of hypertension

BHS IV, 2004 and Update of the NICE Hypertension Guideline, 2006

Guidelines for management of hypertension: report of the fourth Working Party of the British Hypertension Society, 2004 BHS IVB Williams et al: J Hum Hyp (2004); 18: 139-185.

www.nice.org.uk/CG034NICEguideline

www.bhsoc.org

http://www.nice.org.uk/CG034NICEguideline

BHS classification of blood pressure levels

Category Systolic blood

pressure (mmHg)

Diastolic blood

pressure

(mmHg) Optimal blood pressure <120 <80

Normal blood pressure <130 <85

High-normal blood pressure 130-139 85-89

Grade 1 Hypertension (mild) 140-159 90-99

Grade 2 Hypertension (moderate) 160-179 100-109

Grade 3 Hypertension (severe) >180 >110

Isolated Systolic Hypertension (Grade 1) 140-159 <90

Isolated Systolic Hypertension (Grade 2) >160 <90

Target organ damageor

cardiovascular complicationsor

diabetesor

10 year CVD risk† 20%

>180/110 160 179100 109

140 15990 99

130 13985 89

<130/85

160/100 140 15990 99

<140/90

No target organ damageand

no cardiovascular complicationsand

no diabetesand

10 year CVD risk† <20%

* ** ***

Treat Treat Treat Observe, reassessCVD risk yearly

Reassessyearly

Reassessin 5 years

* Unless malignant phase of hypertensive emergency confirm over 1 2 weeks then treat** If cardiovascular complications, target organ damage or diabetes is present, confirm over 3 4 weeks then treat; if absent re-measure

weekly and treat if blood pressure persists at these levels over 4 12*** If cardiovascular complications, target organ damage, or diabetes is present, confirm over 12 weeks then treat: if absent re-measure

monthly and treat if these levels are maintained and if estimated 10 year CVD risk is 20%† Assessed with CVD risk chart

THRESHOLDS FOR INTERVENTIONInitial blood pressure (mmHg)

Suggested target blood pressures during antihypertensive treatment. Systolic and diastolic blood pressures should both be attained, e.g. <140/85 mmHg means less than 140 mmHg for systolic blood pressure and less than 85 mmHg

for diastolic blood pressure

Clinic BP (mmHg)

No diabetes Diabetes

Optimal treated BP pressure <140/85 <130/80

Audit Standard <150/90 <140/80

Audit standard reflects the minimum recommended levels of blood pressure control.

Despite best practice, the Audit Standard will not be achievable in all treated hypertensives.

For ambulatory (mean daytime) or home blood pressure monitoring - reducing these targets by ~10/5 is recommended.

2007 Guidelines for the Management of Arterial Hypertension

Journal of Hypertension 2007;25:1105-1187

European Society of Hypertension European Society of Cardiology

<90and≥140Isolated Systolic Hypertension

≥110and/or≥180Grade 3 Hypertension

100-109and/or 160-179Grade 2 Hypertension

90-99and/or 140-159Grade 1 Hypertension

85-89and/or 130-139High Normal

80-84and/or120-129Normal

<80and<120Optimal

DiastolicSystolicCategory

Definitions and Classification of Blood Pressure Levels (mmHg)

Stratification of CV risk in four categoriesBlood pressure (mmHg)

Other risk factors, OD or disease

Normal

SBP 120-129 or DBP 80-84

High normal

SBP 130-139 or DBP 85-89

Grade 1 HT

SBP 140-159 or DBP 90-99

Grade 2 HT

SBP 160-179 or DBP 100-109

Grade 3 HT SBP ≥180 or DBP ≥110

No other risk factors

Average

risk

Average

risk

Low

added riskModerate added risk

High added risk

1-2 risk factorsLow

added risk

Low

added riskModerate added risk

Moderate added risk

Very high added risk

3 or more risk factors, MS, OD or diabetes

Moderate added risk

High added risk

High added risk

High added risk


Established CV or renal disease






SBP: systolic blood pressure; DBP: diastolic blood pressure; CV: cardiovascular; HT: hypertension. Low, moderate, high, very high risa refer to 10year risk of a CV fatal or non-fatal event. The term “added” indicates that in all categories risk is greater than average. OD: subclinical organ damage; MS: metabolic syndrome.

Factors influencing PrognosisRisk Factors Subclinical Organ DamageSystolic and diastolic BP levels Electrocardiographic LVH

(Sokolow-Lyon >38 mm; Cornell >2440 mm*ms) or

Levels of pulse pressure (in the elderly) Echocardiographic LVH (LVMI M≥ 125g/m², W ≥110 g/m²)

Age (M>55 years; W>65 years) Carotid wall thickening (IMT >0.9 mm) or plaque

Smoking Carotid-femoral pulse wave velocity >12 m/sec

Dyslipidaemia•TC>5.0 mmol/l (190 mg/dL) or•LDL-C >3.0 mmol/l (115 mg/dL) or•HDL-C:M <1.0 mmol/l (40 mg/dL), W <1.2 mmol/l (46 mg/dL) or•TG >1.7 mmol/l (150 mg/dL)

Slight increase in plasma creatinine: M: 115-133 μmol/l (1.3-1.5 mg/dL);W: 107-124 μmol/l (1.2-1.4 mg/dL)

Fasting plasma glucose 5.6-6.9 mmol/L(102-125 mg/dL)

Low estimated glomerular filtration rate (<60 ml/min/1.73 m ²) or creatinine clearance (<60 ml/min)

Abnormal glucose tolerance test Ankle/Brachial BP index <0.9

Abdominal obesity (Waist circumference >102cm (M), 88cm (W))

Microalbuminuria 30-300 mg/24h or albumin-creatinine ratio: ≥22 (M), or ≥31 (W) mg/g creatinine

Family history of premature CV disease (M at age <55 years, W at age <65 years)

Factors influencing Prognosis

Diabetes Mellitus Established CV or renal disease

Fasting plasma ≥7.0 mmol/l

(126 mg/dL) on repeated measurement, or

Cerebrovascular disease: ischaemic stroke; cerebral haemorrhage; transient ischaemic attack

Postload plasma glucose >11.0 mmol/l (198 mg/dL)

Heart disease: myocardial infarction; angina; coronary revascularization; heart failure

Renal disease: diabetic nephropathy; renal impairment (serum creatinine M >133, W >124 mmol/l); proteinuria (>300 mg/24 h)

Peripheral artery disease

Advanced retinopathy: haemorrhages or exudates, papilloedema

High/ Very High Risk Subjects

• BP ≥180 mmHg systolic and/or ≥110 mmHg diastolic

• Systolic BP >160 mmHg with low diastolic BP (<70 mmHg)

• Diabetes mellitus

• Metabolic syndrome

• ≥3 cardiovascular risk factors

SBP DBP

Office or Clinic

140 90

24-hour 125-130 80

Day 130-135 85

Night 120 70

Home 130-135 85

Blood Pressure Thresholds (mmHg) for Definition of Hypertension

with Different Types of Measurement

Initiation of antihypertensive treatment

Other risk factors, OD or disease

Normal

SBP 120-129 or DBP 80-84

High normal

SBP 130-139 or DBP 85-89

Grade 1 HT

SBP 140-159 or DBP 90-99

Grade 2 HT

SBP 160-179 or DBP 100-109

Grade 3 HT SBP ≥180 or DBP ≥110

No other risk factors

No BP intervention

No BP intervention

Lifestyle changes for several months then drug treatment if BP uncontrolled

Lifestyle changes for several weeks then drug treatment if BP uncontrolled

Lifestyle changes + immediate drug treatment

1-2 risk factors Lifestyle changesLifestyle changes




3 or more risk factors, MS, OD or diabetes

Lifestyle changes

Lifestyle changes and consider drug treatment Lifestyle changes

+ drug treatmentLifestyle changes + drug treatment

Lifestyle changes + immediate drug treatmentDiabetes Lifestyle changes

Lifestyle changes + drug treatment

Established CV or renal disease






Goals of Treatment• In hypertensive patients, the primary goal of

treatment is to achieve maximum reduction in the long-term total risk of cardiovascular disease

• This requires treatment of the raised BP per se as well as of all associated reversible risk factors

• BP should be reduces to at least below 140/90 mmHg (systolic/diastolic) and to lower values, if tolerated, in all hypertensive patients

Goals of Treatment• Target BP should be at least <130/80 mmHg in

diabetics and in high or very high risk patients, such as those with associated clinical conditions (stroke, myocardial infarction, renal dysfunction, proteinuria)

• Despite use of combination treatment, reducing SBP to <140 mmHg may be difficult and more so if the target is a reduction to <130 mmHg. Additional difficulties should be expected in elderly and diabetic patients and, in general, in patients with CV damage

• In order to more easily achieve goal BP, antihypertensive treatment should be initiated before significant cardiovascular damage develops

Monotherapy versus combination strategies

Choose between

If goal BP not achieved

If goal BP not achieved

Previous agent at full dose

Switch to different agent at low dose

Previous combination at full dose

Add a third drug at low dose

Two-to three-drug combination at full dose

Full dose monotherapy

Two-three drug combination at full doses

Mild BP elevationLow/moderate CV riskConventional BP target

Marked BP elevationHigh/very CV high riskLower BP target

Single agent at low dose Two-drug combination at low dose

Thiazide diuretics

ACE inhibitors

β-blockers Angiotensin receptor

antagonists

Calcium antagonists

α- blockers

The preferred combinations in the general hypertensive population are represented as thick lines. The frames indicate classes of agents proven to be beneficial in controlled intervention trials

Possible combinations between some classes of antihypertensive drugs

Antihypertensive Treatment in Diabetics

• Where applicable, intense non-pharmacological measures should be encouraged in all diabetic patients, with particular attention to weight loss and reduction of salt intake in type 2 diabetes

• Goal BP should be <130/80 mmHg and antihypertensive drug treatment may be started already when BP is in the high normal range

• To lower BP, all effective and well tolerated drugs can be used. A combination of two or more drugs is frequently needed

• Available evidence indicates that lowering BP also exerts a protective effect on appearance and progression of renal damage. Some additional protection can be obtained by the use of a blocker of the renin angiotensin system (either an angiotensin receptor antagonist or an ACE inhibitor)

Antihypertensive Treatment in Diabetics

• A blocker of the renin-angiotensin system should be a regular component of combination treatment and the one preferred when monotherapy is sufficient

• Microalbuminuria should prompt the use of antihypertensive drug treatment also when initial BP is in the high normal range. Blockers of the renin-angiotensin system have a pronounced antiproteinuric effect and their use should be preferred

• Treatment strategies should consider an intervention against all cardiovascular risk factors, including a statin

• Because of the greater change of postural hypotension, BP should also be measured in the erect measure

The Metabolic Syndrome• The metabolic syndrome is characterized by the variable

combination of visceral obesity and alterations in glucose metabolism, lipid metabolism and BP. It has a high prevalence in the middle age and elderly population

• Subjects with the metabolic syndrome also have a higher prevalence of microalbuminuria, left ventricular hypertrophy and arterial stiffness than those without the metabolic syndrome. Their cardiovascular risk is high and the chance of developing diabetes markedly increased

• In patients with a metabolic syndrome diagnostic procedures should include a more in-depth assessment of subclinical organ damage. Measuring ambulatory and home BP is also desirable

Treatment of Associated Risk Factors

Lipid Lowering Agents

• All hypertensive patients with established cardiovascular disease or with type 2 diabetes should be considered for statin therapy aiming at serum total and LDL cholesterol levels of, respectively, <4.5 mmol/L (175 mg/dL) and <2.5 mmol/L (100 mg/dL) and lower, if possible

• Hypertensive patients without overt cardiovascular disease but with high cardiovascular risk ( ≥20% risk of events in 10 years) should also be considered for statin treatment even if their baseline total and LDL serum cholesterol levels are not elevated


Antiplatelet Therapy

• Antiplatelet therapy, in particular low-dose aspirin, should be prescribed to hypertensive patients with previous cardiovascular events, provided that there is no excessive risk of bleeding

• Low-dose aspirin should also be considered in hypertensive patients without a history of cardiovascular disease if older that 50 years, with a moderate increase in serum creatinine or with a high cardiovascular risk. In all these conditions, the benefit-to-risk ratio of this intervention (reduction in myocardial infraction greater than the risk of bleeding) has been proven favourable

• To minimize the risk of haemorrhagic stroke, antiplatelet treatment should be started after achievement of BP control


Glycaemic Control

• Effective glycaemic control is of great importance in patients with hypertension and diabetes

• In these patients dietary and drug treatment of diabetes should aim at lowering plasma fasting glucose to values ≤6 mmol/L (108 mg/dL) and at glycated haemoglobin of <6.5%

CONCLUSIONE

Il Diabete espone ad elevato rischio CHD

…

CVD Risk Factors Hypertension* Cigarette smoking Obesity* (BMI >30 kg/m2) Physical inactivity Dyslipidemia* Diabetes mellitus* Microalbuminuria or estimated GFR <60 ml/min 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.

http://www.who.int/en/

High/ Very High Risk Subjects

• BP ≥180 mmHg systolic and/or ≥110 mmHg diastolic

• Systolic BP >160 mmHg with low diastolic BP (<70 mmHg)

• Diabetes mellitus

• Metabolic syndrome

• ≥3 cardiovascular risk factors

Goals of Therapy

Reduce CVD and renal morbidity and mortality.

Treat to BP <140/90 mmHg or BP <130/80 mmHg in patients with diabetes or chronic kidney disease.

Achieve SBP goal especially in persons >50 years of age.

Suggested target blood pressures during antihypertensive treatment. Systolic and diastolic blood pressures should both be attained, e.g. <140/85 mmHg means less than 140 mmHg for systolic blood pressure and less than 85 mmHg

for diastolic blood pressure

Clinic BP (mmHg)

No diabetes Diabetes

Optimal treated BP pressure <140/85 <130/80

Audit Standard <150/90 <140/80

Audit standard reflects the minimum recommended levels of blood pressure control.

Despite best practice, the Audit Standard will not be achievable in all treated hypertensives.

For ambulatory (mean daytime) or home blood pressure monitoring - reducing these targets by ~10/5 is recommended.

Goals of Treatment• Target BP should be at least <130/80 mmHg in

diabetics and in high or very high risk patients, such as those with associated clinical conditions (stroke, myocardial infarction, renal dysfunction, proteinuria)

• Despite use of combination treatment, reducing SBP to <140 mmHg may be difficult and more so if the target is a reduction to <130 mmHg. Additional difficulties should be expected in elderly and diabetic patients and, in general, in patients with CV damage

• In order to more easily achieve goal BP, antihypertensive treatment should be initiated before significant cardiovascular damage develops

CONCLUSIONE

PZ Diabetico = PA <130/80mmHg

PRAIA A MAREVista da Ospedale4 Agosto 2006Ore 06:30 am

GRAZIE

L’Ipertensione Arteriosa nel Paziente Diabetico: Nuovi Target Terapeutici Dr. Vittorio Emanuele...

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