la relazione tra cuore e cervello nell’anziano ipertesole relazioni (spesso pericolose…) tra...

Giovambattista Desideri Divisione di Geriatria

Università degli Studi Dell’Aquila

La relazione tra cuore e

cervello nell’anziano iperteso

Redfors B et al. Vascular Health and Risk Management 2013:9 149–154

Stress-induced cardiomyopathy

(Takotsubo): broken heart and mind?

Cardio-regulatory sympathetic pathways

Mazzeo AT et a. British Journal of Anaesthesia 112 (5): 803–15 (2014)

Brain–heart crosstalk: the many faces of stress-related

cardiomyopathy syndromes

Mazzeo AT et a. British Journal of Anaesthesia 112 (5): 803–15 (2014)

563,704 adult patients with stroke presenting to the ED in the US

Strata of systolic blood pressure according to

stroke and stroke subtype

Qureshi AJ et al. Am J Emerg Med. 2007; 25(1): 32–38

Changes in Systolic and Diastolic Blood

Pressure after stroke: CHHIPS study.

Potter JF et al. Lancet Neurol 2009; 8: 48–56

Risk of Myocardial Infarction or Vascular Death After First

Ischemic Stroke stratified by age and history of CAD:

The Northern Manhattan Study,

Dhamoon MS et al. Stroke. 2007;38:1752-1758

Gan et al. BMC Psychiatry (2014) 14:371

Depression and the risk of coronary heart disease:

a meta-analysis of prospective cohort studie

Atrial fibrillation is a leading cause of embolic stroke

Kannel WB et al. Am J Cardiol 1998

0

5

10

15

20

25

50-59 60-69 70-79 80-89

AF, even in the absence of cardiac valvular disease, is associated

with a 4- to 5-fold increased risk of ischemic stroke

Percentage of strokes

attributable to AF

Increased risk of cognitive and functional decline

in patients with atrial fibrillation: results of the

ONTARGET and TRANSCEND studies

Marzona I et al. CMAJ 2012. DOI:10.1503

Mortalità e morbilità nel mondo e fattori di rischio cardiovascolare

Diabete

ipercolesterolemia

Fumo

Obesità

Ipertensione

*Chart is not to scale; illustrates overlapping of risk factors

La mortalità per ictus e cardiopatia ischemica aumenta con l’aumentare dei valori pressori

Mo

rta

lità

per ictu

s

(ris

ch

io a

ssolu

to e

95

% C

I)

Pressione sistolica usuale (mm Hg)

50-59 anni

60-69 anni

70-79 anni

80-89 anni

Fasce di età:

256

128

64

32

16

8

4

2

1

0

120 140 160 180

Mo

rta

lità

per c

ard

iop

ati

a isch

em

ica

(ris

ch

io a

sso

luto

e 9

5%

CI)

Pressione sistolica usuale (mm Hg)

256

128

64

32

16

8

4

2

1

0

120 140 160 180

50-59 anni

60-69 anni

70-79 anni

80-89 anni

Fasce di età:

40-49 anni

Modificato da: Prospective Studies Collaboration. Lancet 2002;360:1903-1913

SENESCENCE = DEMENTIA

Staessen JA, et al. Hypertension 2007

Staessen JA, et al. Hypertension 2007 Gorelick PH, et al. Stroke 2011, 42:2672-2713

The innatural aging of the brain

CVRFs

silent brain

infarcts

vascular dementia

b amyloid

Alzheimer’s disease

amyloid precursor protein

neural

damage

Atherosclerosis and Neurodegeneration. Unexpected Conspirators in Alzheimer’s Dementia

Iadecola C. Arterioscler Thromb Vasc Biol 2003

brain hypoperfusion

Endothelial

dysfunction/activation

Vascular dysfunction

Secretase activity

Anatomical and perfusion images from a patient with HT and DM and an age-matched healthy control

Novak, V. & Hajjar, I. Nat. Rev. Cardiol. 7, 686–698 (2010);

Value of low dose combination treatment with blood

pressure lowering drugs: analysis of 354 randomised trials

Law MR et al. 2003;326:1427

Reduction of the incidence of stroke and IHD

events (%) when durg are used separately and

in combination at half standard dose

Efficacy: blood pressure lowering effects

(mmHg) of drugs when used at half standard

dose separately and in combination

Benefits and Harms of Intensive BP Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis

Weiss J et al. Ann Intern Med. 2017;166:419-429.

Benefits and Harms of Intensive BP Treatment in Adults Aged 60 Years or Older: A Systematic Review and Meta-analysis

Weiss J et al. Ann Intern Med. 2017;166:419-429.

Antihypertensive treatment strategies in the elderly

2013 ESH-ESC Guidelines, J Hypertens 2013

Recommendations Class Level

In elderly hypertensives with SBP ≥160 mmHg there is solid evidence to recommend reducing SBP to

between 150 and 140 mmHg.

I A

In fit elderly patients <80 years old antihypertensive

treatment may be considered at SBP values ≥140

mmHg with a target SBP <140 mmHg if treatment is well tolerated.

IIb C

In individuals older than 80 years with an initial SBP ≥160

mmHg it is recommended to reduce SBP to between

150 and 140 mmHg, provided they are in good physical and mental conditions.

I B

Antihypertensive treatment strategies in the elderly

2013 ESH-ESC Guidelines, J

Hypertens 2013

Recommendations Class Level

In frail elderly patients, it is recommended to leave

decisions on antihypertensive therapy to the treating

physician, and based on monitoring of the clinical

effects of treatment.

I C

The dark side

of………aging

Recommendations for Treatment of Hypertension in

Older Persons - AHA Guidelines

Whelton PK, et al. Hypertension 2017

Recommendations COR LOE

Treatment of hypertension with a SBP treatment goal of less

than 130 mm Hg is recommended for non institutionalized

ambulatory communitydwelling adults (≥65 years of age)

with an average SBP of 130 mm Hg or higher

I A

For older adults (≥65 years of age) with hypertension and a

high burden of comorbidity and limited life expectancy,

clinical judgment, patient preference, and a team-based

approach to assess risk/benefit is reasonable for decisions

regarding intensity of BP lowering and choice of

antihypertensive drugs.

IIa C-EO

MI and stroke: adjusted hazard ratio for achieved

SBP and DBP (reference level, 140/82 mm Hg)

Verdecchia P et al. Hypertension. 2015;65:108-114.

Vidal-Petiot et al. Lancet august 2016

CV event rates and mortality according to achieved SBP and DBP in

patients with stable CAD: an international cohort study - CLARIFY

Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials

Bohm M et al. Lancet 2017

CV death, MI, Stroke,

hospitalization for HF

Does hypertension still

represent a risk factor

for stroke?

SBP differences between randomized

groups (mm Hg)

STROKE

0.25

0.50

0.75

1.00

1.25

1.50

-10 -8 -6 -4 -2 0 2 4

Rel

ati

ve

Ris

k

A B C D E F G

A = CA vs placebo;

B = ACE –I vs placebo;

C = intensive Tx vs less intensive;

D = ARB vs placebo;

E = ACE-I vs CA;

F = CA vs diuretic or β-blocker; G = ACE-I vs diuretic and β-blocker.

Blood Pressure Lowering Treatment Trialists’ Collaboration. Lancet 2003 2SPRINT NEJM 2015

1Williamson JD et al. JAMA. May 19, 2016.

-16 -14 -12

SPRINT

“elderly”2

SPRINT1

Effects of Low Blood Pressure in Cognitively Impaired Elderly

Patients Treated With Antihypertensive Drugs

Mossello E et al. JAMA Intern Med. 2015;175(4):578-585.

Normal cerebral autoregulation curve with its lower and upper

limits of MAP, and a narrowed range with a steeper curve.

Bo

od

flo

w

0 50 100 150 200 Mean blood pressure (mmHg)

Normal

Bo

od

flo

w

0 50 100 150 200 Mean blood pressure (mmHg)

Normal

Narrowed: hypertension,

hypotension, diabetes, vascular

disease, stroke, smoking

Normal cerebral autoregulation curve with its lower and upper

limits of MAP, and a narrowed range with a steeper curve.

Treatment of individual VRF including hypertension, diabetes, and hypercholesterolemia is associated with the reduced risk

of AD conversion.

Li J, et al. Neurology 2011;76:1485–1491

Vinyoles E et al. Curr Med Res Opin 2008;24:3331-3339

Toward defining the preclinical stages of Alzheimer’s disease

Modified from Mura T, et al. European Journal of Neurology 2010, 17: 252–259

CV RISK FACTORS

Circ Res 2015

Journal of Hypertension 2014, 32:1478–1487

Total mortality 0.71 0.56–0.90 0.95 0.69–1.31

CV mortality 0.69 0.50–0.97 0.94 0.61–1.47

All strokes 0.69 0.44–1.07 0.73 0.39–1.36

Heart failure 0.42 0.23–0.76 0.28 0.12–0.65

All CV events 0.65 0.50–0.86 0.69 0.48–0.99

HR CI HR CI

Subgroup starting

treatment vs. no treatment

(placebo): n: 1359

Subgroup continuing

treatment vs. no treatment

(placebo): n: 2486

J Hypertens 2014, 32:1400–1401

Le relazioni (spesso pericolose…) tra cuore e cervello

nell’anziano iperteso: i segreti di un buon rapporto di coppia

Controllare l’ipertensione fa bene

al cuore e al cervello

“The lower the better” può andare bene per

l’anziano “fit” ma non per l’anziano “frail”

“The earlier the better” aiuta

cuore e cervello rimanere “fit”

Cumulative incidence of first time acute myocardial infarction and stroke in people with and without chronic obstructive pulmonary

disease (COPD) during the follow-up period.

Feary et al, Thorax 2010;65:956

The computerised primary care records of 1 .204 .100 members of the general population aged >35 years: COPD and are at high risk of acute arteriovascular events

Myocardial infarction First time stroke

Singh B et al. JAMA Neurol. 2014 May 1; 71(5): 581–588

COPD, a potentially modifiable factor, is associated

with an increased risk of Mild Cognitive Impairment

Demenza BPCO

Diabete

Artrosi

Depressione

IRC

HF CHD

PAD

HBP

Obesità Acido Urico

Le relazioni (spesso pericolose…) tra cuore e cervello

nell’anziano iperteso: i segreti di un buon rapporto di coppia