Fare clic per modificare lo stile del sottotitolo dello schema

L’iperteso anziano: tra linee guida e buona pratica clinica

Giancarlo ANTONUCCISC Medicina InternaOspedale Galliera GENOVA

100

3020100

Perc

ent

40

Blacks

80

706050

90Whites

Mexican Americans

18-29 30-39 40-49 50-59 60-69 70-79 80 +

Burt V, et al. Hypertension, 1995

Age Group

Prevalence of High Blood Pressure by Age and Race/Ethnicity, Women, Age 18 and Older

2/3

Changes in systolic and diastolic blood pressure with age

Data from NHAES III, 1998–1991

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)

SBP

>14

0+

DBP <90

<40

40-49

50-59

60-69

70-79

80+

Age (y)

0

20

40

60

80

100

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

Frequency of hypertension

subtypes in all untreated

hypertensives (%)

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

Prospective Studies Collaboration, Lancet, 2002

Definition of Hypertension

Stroke Mortality by

Level of Usual Systolic BP

Meta-analysis of 61 prospective studies

Anziano =alto rischio assolutominore rischio relativo

* EWPHE SYST-EUR SYST-CHINA Blacher J. Arch Int Med 2000;160:1085

180/95 180/75

Rischio CV a 4 aa* 9,6% 13,6%

Sistole: aumento PAS Diastole: riduzione PAD

N Kaplan LANCET 2006;347:168

R R

mmHg

I 3 fattori della propagazione dell’onda pressoria

1) Progressione (PWV)

2) riflessione

3) Sommazione

100

80

mmHg

onda incidente + onda riflessa

=onda osservata

ME Safar. Curr Hypertens Rep (2010) 12:47

Rigidità grandi vasiDanno vascolare periferico

PA media

mmHgAP Augmentation pressure

R R

onda procidente

precoce ritorno dell’onda riflessa

Central haemodynamic indexes

carotid-femoral PWV

5-10 m/sec

Aortic PWV

2 systematic review and meta-analysis

► Aortic PWV is a strong predictor of future CV events and all cause mortality► Central haemodynamic indexes are independent predictors of future CV events

and all-cause mortality.

Vlachopoulos C et al. JACC 2010;55(13):1318Vlachopoulos C et al. European Heart Journal (2010) 31, 1865

L’ipertensione sistolica isolata è una ipertensione secondaria ?

Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials

Staessen et Al.Lancet 2000; 355: 865

mortalita totale –13%mortalita CV –18%ictus –30%eventi coronarici –23%

Associations of reduction in blood pressure with riskreduction for total major cardiovascular events

Blood Pressure Lowering Treatment Trialists’ Collaboration

BMJ 2008;336;1121

31 trials190.606

Does blood pressure reduction alone explain the preventive effect of the drugs?

MR Law et Al. BMJ 2009;338:b1665

Box 7. Antihypertensive treatment in the elderly

1. Since the publication of the last guidelines, evidence from large meta-analyses of published trials confirms that in the elderly antihypertensive treatment is highly beneficial. The proportional benefit in patients aged more than 65 years is no less than that in younger patients.

2. Data from meta-analyses do not support the claim that antihypertensive drug classes significantly differ in their ability to lower BP and to exert cardiovascular protection, both in younger and in elderly patients. The choice of the drugs to employ should thus not be guided by age. Thiazide diuretics, ACE inhibitors, calcium antagonists, angiotensin receptor antagonists, and b-blockers can be considered for initiation and maintenance of treatment also in the elderly.

3. 4.

Reappraisal of ESH guidelines. Journal of Hypertension 2009, Vol 27

Fino a quale età?

81 aa Vive solo Non fuma Non patologie rilevanti Creatinina 1,4 mg/dl; ECG, glicemia, colesterolo normali PA 180-190 / 74-80 da almeno sei mesi

3845 pt

80 aa

160 mmHg

Indapamide (SR) 1.5mg (± perindopril)

Target <150/80 mmHg

-15/6,1 mmHg

FU <2 anni

0 20.5

0.2

0.1

p<0,001

NNT (2 years):94 for stroke and 40 for mortality

N Engl J Med. 2008 May 1;358(18):1887

Treatment of hypertension in patients 80 years and older: The lower the better?

A meta-analysis of randomized controlled trials

Bejan-Angoulvant T et al, J Hypertens. 2010 Jul;28(7):1366

Secondary endpoints

Treatment of hypertension in patients 80 years and older: The lower the better?

A meta-analysis of randomized controlled trials

Bejan-Angoulvant T et al, J Hypertens. 2010 Jul;28(7):1366

Total mortality

Box 7. Antihypertensive treatment in the elderly

1. 2. 3.

1. At variance from previous guidelines, evidence is now available from an outcome trial (HYVET) that antihypertensive treatment has benefits also in patients aged 80 years or more. BP-lowering drugs should thus be continued or initiated when patients turn 80, starting with monotherapy and adding a second drug if needed. Because HYVET patients were generally in good conditions, the extent to which HYVET data can be extrapolated to more fragile octogenarians is uncertain. The decision to treat should thus be taken on an individual basis, and patients should always be carefully monitored during and beyond the treatment titration phase.

Reappraisal of ESH guidelines. Journal of Hypertension 2009, Vol 27

Fino a quali valori?

72 aa ex-fumatore Precedente SCA : rivascolarizzato

(PTCA+stent) 4 aa fa Iperteso in terapia con 3 farmaci da almeno 30 anni Creatinina 1,4 PA 145-150/70 da almeno tre mesi

When should antihypertensive drug treatment be initiated and to what levels should systolic blood pressure be > lowered?

A critical reappraisal.

Zanchetti A, J Hypertens. 2009 May;27(5):923

Elderly

Non raggiunte PAS medie

< 140 mmHg

Pochi soggetti con PAS < 160 mmHg

Box 7. Antihypertensive treatment in the elderly

1.

1.

1. In the elderly, outcome trials have only addressed patients with an entry SBP at least 160mmHg, and in no trial in which a benefit was shown achieved SBP averaged less than 140mmHg. Evidence from outcome trials addressing lower entry and achieving lower on-treatment values are thus needed, but common sense considerations suggest that also in the elderly drug treatment can be initiated when SBP is higher than 140mmHg, and that SBP can be brought to below 140mmHg, provided treatment is conducted with particular attention to adverse responses, potentially more frequent in the elderly.

2.

Reappraisal of ESH guidelines. Journal of Hypertension 2009, Vol 27

PA diastolica (mmHg)

Eventi cardiovascolari

60 90 120JCercando di prevenire un rischio si può generare malattia?

Aggressive lowering of blood pressure in hypertensive patients with coronary artery disease

Messerli FH, Ann Intern Med 2006; 144: 884–93.

INVEST trial

Insufficienza cardiaca

IVS

Disfunzione diastolica

Cardiopatia ipertensiva nell’anzianoPerdità del sincronismo cuore-grandi vasi

Fibrillazione atriale

Ischemia

AP

How stiffening of the aorta and elastic arteries leads to compromised coronary flow

MF O’Rourke Heart 2008 94: 690

Possible link between large artery stiffness and coronary flow velocity reserve. Saito M, et al. Heart 2008;94:e20

Blood Pressure and Outcomes in Very Old HypertensiveCoronary Artery Disease Patients: An INVEST Substudy

SJ. Denardo et al. The American Journal of Medicine (2010) 123, 719

Reappraisal of the European guidelines on hypertension management

The European Society of Hypertension Task Force document

The J‑curve phenomenon is unlikely to occur below 70-75, except perhaps in patients at high cardiovascular risk

J Hypertens. 2009

130-139 / 80-85

Ho un buon controllo nei diversi momenti della giornata?

73 aa Da circa 1 anno in terapia con enalapril 20 mg e bisoprololo 2,5

mg la mattina Durante il giorno lamenta “testa confusa” PA nello studio 154/80

Aggiunta idroclorotiazide 12,5 mg con peggioramento dei sintomi

Valori medi:24h 116/57 fc 607-22 109/57 fc 6422-7 131/56 fc 51

HCTZ 12,5 mgEnalapril 20Bisoprololo 2,5 mg

Prevalenza età-correlata dell’ipotensione ortostatica

1. Rose KM et al. Am J Hypertens 2000; 13:5712. Rutan GH et al. Hypertension 1992; 19:508

RIGIDITÀ ARTERIOSA↓ sensibilità barorecettoriale

↓ risposta SNS

POLIPATOLOGIA*POLITERAPIA

ARIC (1) CHS (2) 2% sintomatica16,2% asintomatica23% ISH

* M.Parkinson ≈ 50% Diabete 20-25%

Orthostatic hypotension, mortality, and CV disease

Atherosclerosis Risk in Communities (ARIC) study

Rotterdam study

Malmo Preventive Project

Honolulu Heart Program (HHP)

Five rural areas in Northern Finland

American Journal of Hypertension, advance online publication 2 September 2010

The value of ambulatory blood pressure in older adults. The Dublin outcome study

Age and Ageing 2008; 37: 201

Morning surge in blood pressure as a predictor of silent and clinical cerebrovascular disease in elderly hypertensives: a prospective study.

Kario et Al Circulation. 2003;107:1401

Postural Changes in Blood Pressure and Incidence of Ischemic Stroke Subtype: The ARIC Study

Hiroshi Yatsuya. Hypertension. 2011;57:167

12 817 follow-up of 18.7 years.

OHTOH OH

Somministrazione serale di antipertensivi

22 7

farmaco

Pro e Contro la somministrazione serale di antipertensivi

Può migliorare il controllo notturno e del picco mattutino

Assenza di forti evidenze sugli eventi CV

Possibile minor aderenza

Evidenza di riduzione della microalbuminaria

Politerapia/ uso farmaci LA

Gianfranco Parati and Grzegorz Bilo. Journal of Hypertension 2010, 28:1390

Effect of dosing time of AG II receptor blockade titrated by self measured blood pressure recordings on cardiorenal protection in hypertensives

The J-TOP study

Kario K et al. J Hypertens 2010; 28:1574.

…..bedtime dosing of an ARB may be superior to awakening dosing for reducing microalbuminuria.

Morning HT group (n°=170)

Ogni giorno è uguale ad un altro?

74 aa Ipertesa da almeno 15 aa in terapia con atenololo 50 mg Precedente TIA 5 anni prima (ASA basse dosi) valori pressori molto variabili da visita a visita

Consistency of BP control between visitsINVEST trial

23 000 hypertensive patients with a history of CAD% of visits withBP < 140/90 mmHg

Mancia G, Hypertension. 2007;50:299

► Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. Rothwell PM et all. Lancet 2010;375:895-905

► Effects of beta blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke. Rothwell PM, et al; ASCOT-BPLA and MRC Trial Investigators. Lancet Neurol 2010;9:469-80

► Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke: a systematic review and meta-analysisRothwell PM et al. Lancet 2010;375:906-15

► Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension. Rothwell PM. Lancet 2010;375:938-48

Dr Peter M Rothwell Neurologist

(John Radcliffe Hospital, Oxford, UK)

Limitations of the usual blood-pressure Epidemiological evidence

Peter M Rothwell. Lancet 2010; 375: 938

Analisi post-hoc di RCTs: valore predittivo indipendente della variabilità pressoria “da visita a visita” (soggetti con pregresso TIA o ictus)

*On the basis of measurements at seven consecutive follow-up clinic visits.

Rothwell PM, Lancet 2010; 375: 895

Relative strength of association of mean versus SD SBP* with baseline SBP in the UK TIA trial

Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension

UK-TIA trial (pt 1324)

HR 3,27

Visit-to-visit variability * in systolic blood pressure (SBP) was a strong predictor ofsubsequent stroke

HR 6.22

*7 consecutive follow-up clinic

visits.

Rothwell PM et all. Lancet 2010;375:895

The opposite effects of calcium-channel blockers and β blockers on variability

ASCOT-BPLA and MRC Trial Investigators. Lancet Neurol 2010; 9: 469

in ASCOT-BPLA

19.257 pt x4

Effects of β blockers and calcium-channel blockers on within-individual variability in blood pressure and risk of stroke

ASCOT-BPLA and MRC Trial Investigators. Lancet Neurol 2010; 9: 469

Visit-to-visit CV (SD/mean) SBP

CV=coefficient of variation

STROKEComparisons of different active treatments

RR (95% CI)

Favours first listed

Favours second listed

0.5

1.0

2.0

Relative Risk

BP difference(mm Hg)

1.09 (1.00,1.18)

ACE vs. D/BB

0.93 (0.86,1.01)

CA vs. D/BB

1.12 (1.01,1.25)

ACE vs. CA

2/0

1/0

1/1

Lancet 2003;362:1527-35

DOI:10.1503/cmaj.060110

N. Khan. CMAJ2006;174(12):1737-42

Re-examining the efficacy of -blockers for the treatment of hypertension: a meta-analysis in olders

+ 17% stroke

Effects of antihypertensive-drug class on interindividual variation in blood pressure and risk of stroke:

a systematic review and meta-analysis

Rothwell PM. Lancet 2010;375:938-48

398 trials

Maggior efficacia di CaA e D nel ridurre il rischio di eventi CBV e la variabilità pressoria “da visita a visita”

All large randomised trials of calcium-channel blocking drugs versus β blockers or ACE inhibitors in which the mean and SD SBP during follow-up were reported by treatment group

The Relationship Between Visit-to-Visit Variability in Systolic Blood Pressure and All-Cause Mortality in the General Population:

Findings From NHANES III, 1988 to 1994

Paul Muntner et al. Hypertension 2011;57;160

G.Mancia. Hypertension. 2011;57:141

“Espansione” del concetto di variabilità pressoria e nuova rilevanza

1. A breve termine Effetto camice bianco

2. A medio termine DS diurna (MPA) Dipping (MPA)/OH Surge (MPA)/OHT PA mattutina e serale (domiciliare)

3. A lungo termine Da visita a visita (visit-to-visit) Domiciliare

Instabilità pressoria

Lesioni della sostanza bianca

Cervello: vittima o colpevole?

74 aa Ipertesa da almeno 15 aa in terapia con atenololo 50 mg Fumatrice di poche sigarette die Sedentaria, ansiosa Precedente TIA 5 anni prima (ASA basse dosi) I valori pressori sono molto variabili da visita a visita e risulta difficile

il controllo

sostituzione dell’atenololo con Nifedipina GITS bassa-media dose

Conclusioni Dobbiamo prevenire un rischio cercando di non

generare malattia In assenza di chiara EBM consideriamo sempre il

singolo paziente Misuriamo meglio Importanza della qualità della vita