ESH '07: New Consensus Hypertension Guidelines From the European Society of Hypertension/European Society of Cardiology (ESH/ESC)

ESC Congress, Vienna, 09 2007

Aim of guidelines
Educational, rather than prescriptive or coercive
Scientific/professional organizations Administration (e.g. Min of Health) Financing (e.g. CNAS)

Studies Evidence

Guidelines

Protocols

Reimbursement

Definition and Classification of Blood Pressure Levels (ESH) (2003 version)

Category Optimal Normal High normal Hypertension - Grade 1 (mild) - Grade 2 (moderate) - Grade 3 (severe) - Isolated systolic hypertension* 140-159 150-179 180 140 90-99 100-109 10 < 90 Systolic (mmHg) < 120 120-129 130-139 Diastolic (mmHg) < 80 80-84 85-89

When SBP and DBP fall into different categories, the highest category is used in assessing total cardiovascular risk. The authors have again omitted the "prehypertension" category, as defined in JNC 7, because they believe that it implies that:
a large part of the population is sick; this raises anxiety and leads to unnecessary physician visits.

*Isolated systolic hypertension graded (1, 2, or 3).

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

Category
Normal Prehypertension Hypertension stage 1 Hypertension stage 2

SBP mmHg
< 120 120-139 140-159 160

DBP mmHg
< 80 80-89 90-99 100

Blood Pressure Measurement

Methods
office blood pressure should be used as a reference ambulatory blood pressure monitoring (ABPM) may improve prediction of cardiovascular risk in both treated and untreated patients. ABPM is particularly recommended if office blood pressure measurements vary widely or are unexpectedly high in patients at otherwise low cardiovascular risk self-measurement of blood pressure at home is encouraged

Blood Pressure Thresholds for Definition of Hypertension According to Type of Measurement

The guidelines point out that blood pressure thresholds for the definition of hypertension differ according the type of measurement used
Type of Measurement Office or clinic SBP (mm Hg) 140 DBP (mm Hg) 90

24-hour
Day Night Home

125-130
130-135 120 130-135

90
85 70 85

DBP = diastolic blood pressure; SBP = systolic blood pressure

Can we correctly measure blood pressure ?

!! Physicians are often not capable of adequately measuring blood pressure themselves; The office blood pressure recordings are not sufficiently reliable and the timing of the start of the treatment is often not satisfactory. In a survey of 114 doctors, not a single physician completely followed the recommended blood pressure measuring techniques of the American Heart Association.

The most common mistakes

Due to sphygmomanometers In one study, 58% of aneroid sphygmomanometers have been shown to have errors >4mmHg, with ~33% of these having errors >7mmHg of 543 manual sphygmomanometers, only 14% were in perfect working order The average time since last service was 18 months Devices for home blood pressure measurement are produced worldwide at a rate of more than 10 million a year. Only a small percentage of those devices are sufficiently validated on a frequent basis

Due to doctor/nurse
the white coat hypertensive response during an office visit can be significant. too short of a resting period before measurement BP should be measured just before antihypertensive medication is taken to estimate the trough or nadir effect. use of an inappropriately sized cuff deflating the cuff too quickly failure to palpate maximal systolic pressure before auscultation Auscultation of Kortokoff sounds still underestimates intra-arterial systolic levels by 58 mmHg and overestimates diastolic levels by 37 mmHg. not measuring the BP in both arms. BP taken with a sphygmomanometer by an unfamiliar doctor may raise the SAP >20 mmHg within the first few minutes, an effect that attenuates within 510 min and that is less pronounced when a nurse measures the pressure a similar pattern can be seen with the DBP

 Based on these inaccuracies, up to 21% of patients are misdiagnosed with uncontrolled hypertension. We usually wait to treat patients until their blood pressure is high, but this may not be the optimal timing. Vascular wall damage mediated by BP possibly begins early.

Cardiovascular risk
Total Cardiovascular Risk particular emphasis on: a) Target organ damage b) Subclinical organ damage c) The metabolic syndrome is not regarded as a "pathogenetic entity" but rather as "a cluster of risk factors often associated with high blood pressure which markedly increases cardiovascular risk:
BP 130/85 mm Hg Low high-density lipoprotein cholesterol:
< 1.0 mmol/L (40 mg/dL) < 1.2 mmol/L (46 mg/dL)

High triglycerides: > 1,7 mmol/L (150 mg/dL) Altered fasting glucose: 5.6-6.9 mmol/L (102-125 mg/dL) Abdominal obesity: waist circumference:
> 102 cm > 88 cm

Factors influencing prognosis

Risk factors Systolic and diastolic BP level Subclinical organ damage LVH EKG: Sokolow>38, Cornell>2440mm/ms

Levels of pulse pressure (in the elderly)

Age: 55 ; >65 Smoking Dyslipidemia: TC>190 or LDLc>115 or HDLc<40 or TG>150 Fasting plasma glucose 102-125 Abnormal glucose tolerance

LVH Echo: LVMI125 ; 110

Carotid wall thickening (IMT>0.9mm) or plaque Carotid femoral pulse wave-velocity>12m/s Ankle-brachial index<0.9 Slight increase in plasma creatinine: 1.3-1.5 mg/dL ; 1.2-1.4 mg/dL Low eGFR <60mL/min/1.73m2 or Low creatinine clearance <60mL/min

Abdominal obesity >102cm ; >88cm

Family history of premature CV disease <55 ; <65

Microabuminuria: 30-300mg/24h; or albumine/creatinine ratio (mg/g): 22 , 31

Factors influencing prognosis

Established CV or renal disease

Cerebrovascular disease: ischemic stroke, cerebral haemorrhage, transient ischemic attack

Heart disease: myocardial infarction, angina, coronary revascularisation, heart failure Renal disease: diabetic nephropathy, renal impairment (sCr>1.5M, 1.4W), proteinuria Peripheral artery disease Advanced retinopathy: haemorrhages or exudates, papilloedema Diabetus mellitus Fasting plasma glucose 126mg/dL on repeated measurements or Postload plasma glucose >198mg/dL

Stratification of Cardiovascular Risk

Other Risk Factors Subclinical Organ Damage or Disease No other risk factors 1-2 risk factors ? 3 risk factors, metabolic syndrome, subclinical organ damage or diabetes Established CV or renal disease Blood Pressure Grade 1 Grade 2 hypertension hypertension Low Moderate added risk added risk Moderate Moderate added risk added risk High High added risk added risk

Normal Average risk Low added risk Moderate added risk

High normal Average risk Low added risk High added risk

Grade 3 hypertension High added risk Very high added risk Very high added risk

Very high added risk

Very high added risk

Very high added risk

Very high added risk

Very high added risk

High Vs 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 One or more of the following subclinical organ damage
EKG or echo LVH Ultrasound evidence of carotid artery wall thickening or plaque Increased arterial stiffness Slight increase in serum creatinine Reduced estimated glomerular filtration rate or creatinine clearance Microalbuminuria or proteinuria

Established cardiovascular or renal disease.

New European Guidelines on Treatment of Hypertension

WHY TO TREAT ?
Significant reduction in CV mortality/morbidity Benefit at older ages, including ISH Proportional CV risk reduction in men/women Benefit across various ethnic groups Major reduction in cause specific events Stroke (-30 to -40%) CHD (-20%) CHF (> -40%)

Benefits largely depends on BP lowering per se Conclusions based on multiple types of evidence Several drugs beneficial BP is related to CV events For similar BP reduction little/no events between different treatments

WHEN TO TREAT ?

General HT population

High risk patients (CAD/cerebrovascular disease/diabets/renal dysfunction) 130/85 mmHg < 130/80 mmHg

Threshold Target

140/90 mmHg < 140/90 mmHg

Concept of flexible threshold / target for therapy in relation to total CV risk

HOW TO TREAT ?
Lifestyle measures Instituted with adequate behavioural/expert support and periodical reinforcement!!
smoking cessation weight reduction and maintenance reduction of excessive alcohol intake physical exercise reduction of salt intake increases in fruit and vegetable intake decreases in saturated and total fat intake
unproven in preventing CV complications low compliance BP response highly variable

Drug Therapy Recommendations

Primary benefits of antihypertensive therapy are related to BP reduction. Five important drug classes
Diuretics calcium-channel blockers ACE-inhibitors beta-blockers (UK and USA: Anglo-Scandinavian Cardiac Outcomes TrialBlood Pressure Lowering Arm (ASCOT-BPLA / ESH advise against the use of beta-blockers in patients with metabolic syndrome or at high risk for diabetes) angiotensin-receptor blockers

Monotherapy or in combination No one is a choice of First-Line Therapy All suitable for initiation/maintenance of treatment If we have to make a choice, it should depend on comorbidities. Monotherapy allows to achieve BP target in only a limited number of hypertensive patients.

The guidelines recommend a 2-drug combination as initial treatment in:

patients presenting with grade 2 or 3 hypertension or with high or very high total cardiovascular risk

The following 2-drug combinations are recommended because they "have been found to be effective and well tolerated":
Thiazide-type diuretic and ACE inhibitor; Thiazide-type diuretic and ARB; CCB and ACE inhibitor; CCB and ARB; CCB and thiazide-type diuretic Beta-blocker and CCB.

Initiation of Antihypertensive Treatment

Other Risk Factors, Subclinical Organ Damage or Disease No other risk factors Blood Pressure Normal No blood pressure intervention High normal No blood pressure intervention Grade 1 HPT Lifestyle changes for several months, then drug treatment if blood pressure uncontrolled Lifestyle changes for several weeks, then drug treatment if blood pressure uncontrolled Lifestyle changes +drug treatment Grade 2 HPT Lifestyle changes for several weeks, then drug treatment if blood pressure uncontrolled Lifestyle changes for several weeks, then drug treatment if blood pressure uncontrolled Lifestyle changes+drug treatment Grade 3 HPT Lifestyle changes + immediate drug treatment

1-2 risk factors

Lifestyle changes

Lifestyle changes

Lifestyle changes +i immediate drug treatment

3 risk factors, metabolic syndrome, subclinical organ damage Diabetes

Lifestyle changes

Lifestyle changes and consider drug treatment

Lifestyle changes+im immediate drug treatment

Lifestyle changes

Lifestyle changes + drug treatment Lifestyle changes +immediate drug treatment Lifestyle changes +immediate drug treatment Lifestyle changes +immediate drug treatment Lifestyle changes +immediate drug treatment

Established cardiovascular or renal disease

Lifestyle changes +immediate drug treatment

Special Patient Subsets

Antihypertensive Treatment: Preferred Drugs as Per New European Guidelines

Subclinical organ damage LVH

Treatment ACE inhibitors, calcium antagonists, angiotensin receptor blockers Calcium antagonists, ACE inhibitors ACE inhibitors, angiotensin receptor blockers

Asymptomatic atherosclerosis Microalbuminuria

Renal dysfunction

ACE inhibitors, angiotensin receptor blockers

LVH = left ventricular hypertrophy; ESRD = renal failure; PAD = peripheral arterial disease; ISH = isolated systolic hypertension

Special Patient Subsets

Antihypertensive Treatment: Preferred Drugs as Per New European Guidelines Clinical event Previous stroke Previous MI Angina pectoris Heart failure Atrial fibrillation - Recurrent Permanent Treatment Any BP-lowering agent Beta blockers, ACE inhibitors, angiotensin receptor blockers Beta blockers, calcium antagonists Diuretics, beta blocker, ACE inhibitors, angiotensin receptor blockers, antialdosterone agents Angiotensin receptor blockers, ACE inhibitors Beta blockers, nonhydropyridine calcium antagonists ACE inhibitors, angiotensin receptor blockers, loop diuretics Calcium antagonists

ESRD/proteinuria PAD

LVH = left ventricular hypertrophy; ESRD = renal failure; PAD = peripheral arterial disease; ISH = isolated systolic hypertension

Special Patient Subsets

Antihypertensive Treatment: Preferred Drugs as Per New European Guidelines

Condition ISH (elderly) Metabolic syndrome Diabetes mellitus Pregnancy Blacks

Treatment Diuretics, calcium antagonists ACE inhibitors, angiotensin receptor blockers, calcium antagonists ACE inhibitors, angiotensin receptor blockers Calcium antagonists, methyldopa, beta blockers Diuretics, calcium antagonists

LVH = left ventricular hypertrophy; ESRD = renal failure; PAD = peripheral arterial disease; ISH = isolated systolic hypertension

Conditions favouring use of some antihypertensive drug classes

ACE Inhibitors
Heart failure; LV dysfunction; Post MI; Diabetic nephropathy; LV hypertrophy; Carotid atherosclerosis; Proteinuria/microalbuminuria; Atrial fibrillation;

Metabolic syndrome.

Conditions favouring use of some antihypertensive drug classes

ARB
Heart failure Post MI Diabetic nephropahy Proteinuria/microalbuminuria LV hypertrophy Atrial fibrillation Metabolic syndrome ACEI induce cough

Conditions favouring use of some antihypertensive drug classes

Thiazide Diuretics
ISH (elderly) Heart failure HT in blacks

Anti-aldosterone Diuretics
Heart failure Post MI

Loop Diuretics
End stage renal disease Heart failure

Conditions favouring use of some antihypertensive drug classes

Beta blockers
Angina pectoris Post MI Heart failure Tachyarrythmias Glaucoma Pregnancy

Conditions favouring use of some antihypertensive drug classes

CA (dihydropyridines)
ISH (elderly) Angina pectoris LV hypertrophy Carotid/coronary atherosclerosis Pregnancy HT in blacks

CA (verapamil/diltiazem)
Angina pectoris Carotid atherosclerosis Supraventriular tachycardia

The gap between recommandation and real BP control

Proportion of patients treated/non treated for HTA in Europe (WolfMaler et al. Hypertension 2004; 43:10-17)

100 80 60 40 20 0 England Sweden Germany treated untreated Spain Italy 25 26 26 27 32 75 74 74 73 68

Approximately 70% of patients in Europe do not reach BP goal < 140/90 mmHg (Wolf-Maler et al. Hypertension 2004; 43:10-17)
100 80 60 60 40 20 0 England Sweden Germany Spain Italy 40 21 30 19 28 79 70 81 72

BP goal achieved

BP goal not achieved

Reasons for inadequate control of BP

Ineffective drugs Resistant HTA (ASCOT + Spironolactone 25-50 mg/day, irrespective of plasma aldosterone ); Guideline confusion; Drug costs; Drug side - effects; Poor compliance; Physician inertia;

How to overcome obstacles for inadequate BP control

1. 2. 3. 4. 5. Use non drug methods; Use higher drug doses (if tolerated) Use the right drugs/combination; Use more drugs + fewer tablets; Future prospects? Education Cheaper, more effective drugs More trial data

NEW METHODS
Aliskiren renin inhibitor Vaccination against hypertension (CYT006-AngQb Switzerland, ATR12181, China) Vaccine against angiotensin II, obtained by coupling the octapeptide with a virus like particle; It produces anti-angiotensin II antibodies NF-kB inhibition (?) prevent vascular damages in hypertension Erythropoietin prevent vascular (cerebral) damage via NO formation. ACE inhibitors + NO donor group (NCX899 Merck)

Critical Comments of ESH Guidelines

1. Suzanne Oparil, President of the American Society of Hypertension
the scholarship of the guidelines for primary care physicians it might be better to focus on blood pressure, the most easily modifiable cardiovascular risk factor, rather than including all risk factors and the metabolic syndrome in the United States, guidelines cannot omit grading of recommendations according to level of scientific evidence, as in the European guidelines.

2.

Lars H. Lindholm, (Sweden), President of the International Society of Hypertension

inclusion of beta blockers as first-line treatment

Newer Beta-blockers
Negative evidence for beta-blockers from the AngloScandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA), Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) and Medical Research Council (MRC) trials, and from a 2005 meta-analysis. Carvedilol and nebivolol are the 2 leading newer antihypertensive agents in the United States. Carvedilol, a nonselective beta-blocker and an alpha1-blocker with no intrinsic sympathomimetic activity, was approved in the United States for the treatment of heart failure in 1995, but has only recently been actively marketed for hypertension. Nebivolol has high specificity for the beta1 receptor and may have a nitric oxide-mediated vasodilatory effect.