Transcript Cardiovascular Aging

Cardiovascular Aging
Dorothy D. Sherwood, M.D.
Health Core Physician Group
Presbyterian Hospital of Dallas
Division of Geriatrics
July 26th, 2006
Epidemiology
• Currently, 12 % of the population is
>65 years of age – 35 million
people.
• In 2030, 20% of the population will
be >65 years of age – 71 million
people – one in five.
• Half of the people > 65 years of age
have after tax incomes at the
poverty level.
Epidemiology
• Cardiovascular disease is the leading
cause of death in the population >65
years.
• One half to two thirds of the
population > 65 years have
hypertension.
• The leading discharge diagnosis for>
65 years is congestive heart failure.
Epidemiology
• Compelling data indicates that
aggressive treatment of
hypertension, heart failure, coronary
artery disease, and hyperlipidemia in
those between the ages of 65 and 74
reduces morbidity and mortality.
• Few trials have enrolled those over
75 or those with co-morbid
conditions.
Pathophysiology
• Hallmarks of cardiovascular aging
include
– Increase in systolic blood pressure
– Increase in pulse pressure and pulse
wave velocity (PWV)
– Increase in left ventricular mass
– Increase in CAD
– Increase in Atrial fibrillation
Pathophysiology
• Aging is associated with a:
– Decrease in early left ventricular diastolic
filling.
– Decrease in maximal heart rate
– Decrease in maximal cardiac output
– Decrease in maximal aerobic capacity
– Decreased exercise induced augmentation of
LVEF and heart rate
– Decreased vasodilatation in response to beta
adrenergic stimulation or endothelial mediated
vasodilatation.
Pathophysiology
• Cellular, enzymatic, and molecular alterations in
the arterial vessel:
– Smooth muscle cells (SMC) migrate to the intima,
causing intimal thickening.
– Metalloproteinases, angiotensin II, transforming growth
factor beta, intracellular cell adhesion molecules, result
in increased production of collagen, collagen cross
linking, fibronectin, calcification, in the media with
decrease in elastin in the media – leading to stiff vessel.
– Reduced endothelial function due to apoptosis and
senescence results in decreased NO
– Decreased vasodilatory response to beta adrenergic
agonists and alpha adrenergic antagonist
Pathophysiology
• This results in arterial dilation with
increased arterial stiffness and
decreased NO induced vasodilatation.
Pathophysiology
• Cellular, enzymatic, and molecular
alterations in the Heart:
– Similar to those in the arterial wall – with
similar enzymatic changes resulting in
increased collagen cross linking, increased
fibronectin, decrease in elastin
– In the atria, decrease in sinus node cells, and
alterations in the extracellular matrix results in
sinus node dysfunction leading to atrial
fibrillation; similar changes occur in the AV
node.
Pathophysiology
• Reduced, but hypertrophied
myocytes result in alteration in
calcium channels, leading to
– Prolongation of contraction and
relaxation of the myocardium with
aging.
Pathophysiology
• Changes in the intravascular
environment with age:
– Increase in prothrombotic factors s such
as V, VIII, IX, plasminogen, resulting in
impaired fibrinolyisis
– Increased pro-thrombotic cytokines –
especially interleukin 6
– All of these potentiate the development
of atherosclerosis
Pathophysiology
• Autonomic nervous system
– Decreased number of alpha and beta
adrenergic cells and decreased function
of the cells with aging.
– Decreased dopaminergic responsiveness
with aging
– Decreased vascular response to
cholinergics, but increased central
nervous system response
Pathophysiology
• The combined effect of the changes
in the autonomic nervous system
results in a decreased baroreceptor
response in the elderly and
decreased ability to respond to
stress.
Pathophysiology
• We can impact some of the age
related changes:
– Exercise increases endothelial function
– Exercise decreases arterial wall stiffness
– ACEI, ARB, Aldosterone inhibitors, Beta
blockers may influence remodeling of
the vessels and the myocardium.
Pharmacodynamic effects of
aging
• Suffice it to say, that elderly are
highly sensitive to:
– The therapeutic effects of a drug: i.e. a
direct vasodilator such a prazocin; the
rate effects of beta blockers
– The toxic effects of the drug: i.e.
digoxin toxicity occurs at a much lower
dose in the elderly
– The drug-drug interactions: ACEI and
NSAID for example –
Pharmacodynamic effects of
aging
• Elderly patients can not take a joke!
– Look up every drug before you give it
– If renally cleared – adjust the dose –
i.e. beta blockers are renally cleared.
– Know the drug-drug interactions
– Know the complications
– Start low – go slow, and re-address
need for drug at every visit.
Hypertension
• Measure BP in both arms, supine, sitting,
and standing.
– Elderly patients are very susceptible to
orthostatic hypotension.
• The risk of hypertension is greater in the
elderly, at least up to age 80, than in the
younger population, and the reduction in
CAD and heart failure is greater in the
elderly with treatment than in the young.
Hypertension
• Limited data from placebo controlled
trials reveals a decrease in strokes
and heart failure in patients over the
age of 80 with treated hypertension,
but no difference in mortality.
Trial
N
Age (yr)
Type
Stroke
CAD
H
F
All CVD
HDFP
2374
60–69
D
44
15
N
R
16
Australian
582
60–69
D
33
18
N
R
31
EWPHE
840
>60
D (+S)
36
20
2
2
29
Coope
884
60–79
D (+S)
42
-3
3
2
24
STOP-HTN
1627
70–84
D (+S)
47
13
5
1
40
MRC
4396
65–74
D (+S)
25
19
N
R
17
SHEP
4736
≥60
S
33
27
5
5
32
Multiple trials demonstrating benefit of treatment of
hypertension in the elderly
Hypertension
• Thiazides are as effective as any
other drug for first line treatment.
– Risk of hyponatremia
– Risk of incontinence
– Risk of hypokalemia
– Never go above 25 mg, start at 6.25 mg
Hypertension
• To evaluate the best second line
therapy for each patient, take into
account their co-morbid conditions,
and the drug-drug interactions that
will occur. Use
www.geriatricsatyourfingertips.com.
• Or JNC 7 to determine the best
choice
Hypertension
• Postural Hypotension – a fall of 20
mm Hg with standing is associated
with a marked increase in falls.
– Increases the risk associated with antidepressants, anti-psychotics, and antiparkinsonian medications
– Increases the risk associated with postprandiol hypotension
• Greatest fall in BP is 1 hour after eating,
returning to normal 3 to 4 hours after eating
CAD
• Autopsy studies show that > 50% of
the men over the age of 60 have
significant CAD with increase in the
incidence of multi-vessel disease and
left main disease
• The life time risk for developing CAD
is estimated to be 1 in 3 for men and
1 in 4 for women
CAD
• By the age of 80, 20 to 30% of men
and women have symptomatic CAD.
• History is atypical: epigastric
discomfort; shoulder pain; back
pain; SOB; nausea or no symptoms
at all
• Symptoms not necessarily related to
exertion.
CAD
• Testing:
– Exercise stress testing has about an 80%
sensitivity and 75% specificity
– The addition of an echocardiogram or nuclear
study improves the validity of the test
– In men and women who can not exercise,
dobutamine or adenosine can be used.
– Due to high levels of calcification in the
arteries, CT may not be useful in the elderly.
CAD
• Treatment: the same as the younger
population, unless there is less than
a 2 year life expectancy.
– Heart Protection Study showed benefit
in patients with disease treated with
statins
– There is no data regarding statins and
primary prevention in patients over the
age of 75
CAD
• Age is a risk factor for myopathy
with statin therapy. Therefore, the
lowest effective dose should be used
in this population.
• Beta blockers, ACEI, and long-acting
nitrates should be used.
– Avoid Beta blockers in SA or AV nodal
disease
– Avoid Calcium Channel Blockers
CAD
• Revascularization:
– BARI study – 109 patients ages 65 to 83.
– CABG vs. PTCA
– CABG associated with increased early mortality
and morbidity, but less angina and less repeat
procedures
– Stroke was more common after CABG and
heart failure after PTCA
– 5 year survival was 86% for CABG and 81 %
for PTCA
– In hospital mortality for CABG in patients over
75 is 6 to 8% and stroke is 3 to 6%
CAD
• TIME trial compared re-vasularization
to optimal medical therapy. At 6
months, revascularization was
favored, but a 1 year there was no
difference in outcomes
• Data is limited in the use of drug
eluting stents and off pump bypass.
CAD
• Treatment of acute MI in the elderly
with thrombolysis or primary
angioplasty is associated with better
outcomes, but also, with increased
risk of complications including
hemorrhage and stroke.
– Thin, black, female, prior cva, Bp >160
associated with increased risk of ICH
CAD
• Post MI treatment
– Beta Blockers, ACEI, ASA, Statins all
have been shown to be of benefit in the
elderly.
• Start with lower doses and titrate carefully
CHF
• Five year mortality is 50% for
patients with systolic impairment and
25% for patients with diastolic HF
• There is a 4 fold increase in mortality
in patients with diastolic dysfunction
compared to those without HF.
• Age is associated with HF with
preserved systolic function
CHF
• Exercise intolerance is the mark of
heart failure
• Nocturnal cough, PND, DOE are
common signs of heart failure, but
may not be recognized
– Less than 50% of patients with
moderate diastolic HF by doppler had
the diagnosis of Hf
CHF
• Physical exam in the elderly is not
easy – they all have edema; their
neck veins are always distended or
appear to be; S3 and rales are only
present when decompensated.
• One must rely on ECHO and BNP to
diagnose heart failure at times.
CHF
• Treatment
– Not good data in the elderly – most CHF
studies are with patients with systolic
dysfunction. Women and the frail
elderly are not included at all.
CHF
• Treatment of Systolic Failure
– Control BP
– Diurese
– Control heart rate if in A fib.
– ACEI or ARB gently
– Beta blocker gently
– Exercise
CHF
• Diastolic Dysfunction
– Diuretics
– ACEI or ARB gently
– Beta blockers gently
– Exercise
Arrhythmia
• Up to 90 % of the sinus node cells
are lost by the age of 75!
• Resting heart rate is not effected by
age, but maximal heart rate and
beat to beat variability are both
reduced.
• SN response to beta adrenergic and
parasympathetic stimulation is
reduced.
Arrhythmia
• EKG shows prolonged PR and LAD
• Arrhythmias requiring treatment
– Bradycardia due to SA or AV nodal
dysfunction
– A Fib – 8 to 10% of 80 year olds have A
fib.
• 50% of patients with A fib are > 75 years
old
Arrhythmia
• A fib
– Focus should be on anticoagulation for
stroke prevention and rate control.
Rarely is rhythm control needed or
possible.
• Warfarin – INR 2 to 2.5
– Don’t forget – associated with osteoporosis
• ASA 325 mg in very elderly or very
debilitated.
Summary
• CV aging is associated with
– Decreased arterial compliance
– Decreased cardiac compliance
– Decreased maximal heart rate and EF with
exercise/stress
– Decreased adrenergic sensitivity
– Increased systolic hypertension
– Increased LV mass
– Increased CAD
– Increased arrhythmias
Summary
• Treatment
• Encourage Exercise and:
–
–
–
–
Monitor orthostatic BP.
Start low, go slow.
Avoid vasodilators if possible.
May have increased sensitivity to bradycardia
from beta blockers, calcium channel blockers.
– Watch for drug/drug interactions.
– Monitor frequently, be careful.