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7
C
D
KRISTEN M. COOK
L O
1. Assess the significance of orthostatic hypotension and hypertension, appropriate goals for blood pressure, and
first-line treatment recommendations in the geriatric population.
2.
Evaluate a geriatric patient for appropriate lipid management.
3. Recognize potential barriers in diagnosis and treatment of peripheral arterial disease in geriatrics and the
considerations that must be taken when treating intermittent claudication.
4.
Describe the benefits versus risks of anticoagulation for stroke prevention in elderly patients with atrial fibrillation.
5.
Discuss the evidence base for using
beta
blockers, angiotensin-converting enzyme (ACE) inhibitors, diuretics,
and digoxin in geriatric heart failure patients as well as appropriate considerations when administering these
drugs to geriatric patients.
6.
Describe the significance of stroke in geriatric patients and recommend appropriate primary and secondary
stroke prevention.
7. Explain the appropriate and safe use of anticoagulants for prevention and management of venous thrombo-
embolism in elderly patients.
K T D
ANTITHROMBOTIC: Prevents or interferes with the formation of a thrombus (clot).
DIGOXIN TOXICITY: Occurs when concentrations of digoxin increase above desired therapeutic levels.
Arrhythmias are the most common manifestation and can be life threatening, especially in heart failure. Toxicity
usually occurs in concentrations of >2 ng/mL but can occur at any level. The elderly are predisposed to toxicity.
FIBRINOLYTIC: A pharmacological intervention that dissolves an existing clot.
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INTERMITTENT CLAUDICATION: A complication of peripheral arterial disease that presents as pain and fatigue
caused by ischemia of muscles, usually in the lower extremities and typically brought on by walking.
ISCHEMIC STROKE: A type of stroke caused by a blood clot from a cardiac or noncardiac source that cuts
blood flow off to a certain portion of the brain, causing tissue cell death.
LEFT VENTRICULAR FUNCTION: Measure of how well the left ventricle is contracting and expelling blood to
the aorta. Also known as systolic function and often measured by ejection fraction.
PULSE PRESSURE: The difference between the systolic and diastolic blood pressures.
THROMBOLYTIC: See Fibrinolytic.
I
C
ardiovascular diseases affect a large
number of individuals in the United States
each year. The prevalence and incidence of
major cardiovascular diseases increase with
advancing age. In many instances, there are
issues related to management of specific cardio-
vascular diseases, safety of medications used
to manage cardiovascular conditions, adher-
ence to therapy, and others that are particularly
pertinent in the elderly population. In this chapter,
the epidemiology, etiology, clinical presentation,
standard treatment, and treatment/safety issues
associated with major cardiovascular diseases
in elderly patients will be discussed. These
will include orthostatic hypotension, hyperten-
sion, dyslipidemia, acute coronary syndromes
and coronary artery disease, peripheral artery
disease, heart failure, atrial fibrillation, stroke, and
venous thromboembolism.
O H
Etiology, Epidemiology, and
Clinical Presentation in the
Geriatric Population
Orthostatic hypotension is defined as a reduction
in systolic blood pressure (SBP) of ≥ 20 mmHg or
a reduction in diastolic blood pressure (DBP) of
≥10 mmHg within 3 minutes of standing.
1
Some
evidence indicates that the prevalence of ortho-
static hypotension increases with age, although
the data are equivocal. The prevalence of ortho-
static hypotension in individuals >65 years of
age is approximately 20% and is as high as 30%
in individuals >75 years of age.
2
The prevalence
of orthostatic hypotension has been estimated to
be as high as 50% in the frail elderly residing in
nursing homes.
2
Rather than having lower baseline blood
pressures, elderly patients who develop ortho-
static hypotension often have developed age-
related increases in supine SBP.
2
In the National
Health and Nutrition Examination Survey II,
3
the relationship between postural changes on
blood pressure and age and SBP was evalu-
ated in 8,574 Caucasian, nondiabetic individuals
between the ages of 25 and 74 years. Logistic
regression analysis revealed that age was not
associated with postural changes in blood pres-
sure (relative odds 1.07, 95% confidence inter-
vals [CI] 0.89–1.19 for each 10-year increase in
age). However, increases in supine SBP were
associated with postural changes in blood pres-
sure (relative odds 1.59, 95% CI 1.49–1.70 for
each 10-mmHg increase in SBP). It has been
suggested that the association between age-
related increases in supine blood pressure and
increased risk of orthostatic hypotension may be
due to central autonomic degeneration, resulting
in baroreflex dysfunction in the presence of
residual sympathetic outflow.
1,4
KEY POINT:
Orthostatic hypotension that
develops in association with advancing age
is directly correlated with age-related
incr
eases in supine SBP.
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Orthostatic hypotension may be classified
as acute or chronic. Acute orthostatic hypo-
tension develops over a short period of time.
Causes of acute orthostatic hypotension include
dehydration, diarrhea, extreme heat, myocar-
dial ischemia, adrenal insufficiency, vomiting,
or, more rarely, sepsis. Importantly, acute ortho-
static hypotension may be caused by medica-
tions, including antihypertensive agents. Anti-
hypertensives that are more likely to cause
orthostatic hypotension are those that are short
acting, vasodilators, or volume depleting. These
include centrally acting alpha receptor agonists,
peripheral alpha receptor antagonists, nitrates,
and other vasodilators such as hydralazine or
minoxidil, and loop diuretics. Other medica-
tions that can cause this include antipsychotic
drugs, dopamine agonists, levodopa, marijuana,
narcotics, sedatives, sildenafil, and tricyclic anti-
depressants.
2
Chronic orthostatic hypotension develops
gradually over a more prolonged period of time.
It may develop as a result of pathophysiological
changes, including diminished baroreceptor
sensitivity, diastolic dysfunction, or development
of hypertension. In addition, chronic orthostatic
hypotension may arise due to dysfunction of the
autonomic nervous system, from causes such
as brain stem lesions, Lewy Body dementia,
multiple cerebral infarctions, myelopathies,
Parkinson disease, or multiple system atrophy.
2
Other etiologies of orthostatic hypotension may
include increased venous insufficiency, alco-
holism, amyloidosis, diabetes mellitus, and
pernicious anemia.
2
Orthostatic hypotension
may be more likely in patients with a low body
mass index.
5
Most patients with orthostatic hypotension
experience symptoms associated with postural
change, including dizziness, lightheadedness,
weakness, pre-syncope, syncope, blurred
vision, nausea, dyspnea, neck pain, angina, and
transient ischemic attacks.
1,2
Elderly patients
are particularly susceptible to symptoms such
as slurred speech, falls, confusion, and cogni-
tive impairment. In some patients, symptoms
may be worsened by prolonged standing, exer-
tion, increased ambient temperature, or eating.
Orthostatic hypotension is a common cause of
hospitalization. In 2004, there were nearly 81,000
hospitalizations related to orthostatic hypoten-
sion.
Treatment Recommendations in the
Geriatric Population
Because orthostatic hypotension most commonly
occurs in elderly patients, the treatment recom-
mendations for all adults are written with the
elderly in mind. If the orthostatic hypotension is
believed to be drug-induced, therapy with the
causative agent should be discontinued. Patients
should be advised to rise slowly from a sitting or
supine to a standing position, particularly indi-
viduals that have undergone long periods of
inactivity or bedrest. Patients should be coun-
seled to avoid coughing, straining, or prolonged
standing, especially in hot weather, as these
activities reduce venous return to the heart.
2
Crossing the legs while standing and contracting
muscles for 30 seconds may increase venous
return. Raising the head of the bed by 20–
30 degrees may minimize hypertension and over-
night volume loss. Use of waist-high compres-
sion stockings and abdomen-binders may be
helpful, as may increasing sodium and water
intake
.
2
Hypertension is a risk factor for ortho-
static hypotension, and maintaining adequate
control of elevated blood pressures may help
prevent orthostatic hypotension from occurring
or worsening.
Nonpharmacological management and
hypertension control are the preferred methods
to help prevent and alleviate symptoms of ortho-
static hypotension. Medications for orthostatic
hypotension should only be used in select cases
when other methods for symptoms have been
exhausted. Drugs that are most often used for
the management of orthostatic hypotension
are fludrocortisone and midodrine. Fludrocorti-
sone is a synthetic mineralocorticoid agent that
promotes fluid and sodium retention.
1,2
The initial
recommended dose of fludrocortisone is 0.1 mg
orally daily. The dose may be titrated upward
in weekly increments of 0.1 mg daily if neces-
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sary, until the maximum dose of 0.3 mg daily
is attained, or pedal edema occurs.
1
Adverse
effects of fludrocortisone include supine hyper-
tension, ankle edema, headache, hypokalemia,
and, rarely, heart failure in susceptible patients.
1,2
Elderly patients may be more susceptible to
some of the adverse effects associated with
fludrocortisone, particularly fluid overload and
hypokalemia. Many elderly patients receiving
this drug may require potassium supplementa-
tion, especially those taking higher doses.
In patients who continue to exhibit symp-
toms despite therapy with fludrocortisone, or in
those patients in whom fludrocortisone is poorly
tolerated, midodrine is a reasonable alterna-
tive. Midodrine is a peripheral selective
alpha
-
receptor agonist.
1
The initial recommended
midodrine dose is 2.5 mg orally three times daily
during daytime hours; if necessary, the dose
may be titrated upward in weekly increments of
2.5 mg per dose, until the maximum recom-
mended dose of 10 mg three times daily is
reached.
1,2
Adverse effects of midodrine include
supine hypertension, pruritus, paresthesias,
piloerection, bradycardia, and urinary reten-
tion.
1,2
Midodrine should not be administered to
patients with a history of coronary artery disease,
heart failure, urinary retention, acute kidney
disease, or thyrotoxicosis. In addition, the risk of
midodrine-associated bradycardia is increased
when the drug is used concomitantly with other
heart rate-lowering drugs, such as
beta blockers
,
diltiazem, verapamil, amiodarone, or digoxin.
Increasing caffeine intake up to doses of 200 mg
may be an effective intervention as well.
Barriers to Treatment in the
Geriatric Population
There are few barriers to treatment in the geriatric
population, once a diagnosis of orthostatic hypo-
tension has been made. However, appropriate
recognition and diagnosis can be difficult. Blood
pressure measurements are routinely performed
with patients in the sitting position, limiting the
ability to diagnose orthostatic hypotension. Clini-
cians should be aware of the potential for ortho-
static hypotension in older patients and should
be alert to detect symptoms. The Joint National
Committee on Prevention, Detection, Evaluation,
and Treatment of High Blood Pressure (JNC) VII
recommends that supine and standing blood
pressure be measured periodically in all hyperten-
sive patients >50 years of age.
6
The new JNC VIII
guidelines do not make a specific recommenda-
tion in measuring orthostatic blood pressure.
7
The
ACCF/AHA 2011 Expert Consensus on Hyperten-
sion in the Elderly recommend a sitting blood pres-
sure and blood pressure taken within 1–3 minutes
of standing in those ≥65 years of age.
8
H
Etiology, Epidemiology, and
Clinical Presentation in the
Geriatric Population
Cardiovascular disease (CVD) is the leading
cause of mortality among individuals over the
age of 65 years. Hypertension is one of the most
prevalent and important risk factors contrib-
uting to CVD among adults. The prevalence of
hypertension increases with advancing age, with
elevated SBP of particular importance. Strati-
fying populations of elderly patients based on
age reveals that 8% of the population over the
age of 60 years has elevated SBP, while 25%
of the population over the age of 80 years has
elevated SBP.
9
Women 65 years and older have
a higher prevalence of hypertension than men of
the same age.
8
Despite this increase in preva-
lence with age, it may not be accurate to assume
that hypertension correlates with the increasing
incidence of CVD events and mortality in all age
subsets of elderly patients. A divergence in clin-
ical outcomes has been observed among indi-
viduals with hypertension who are over 65 years
of age as compared with those over 85 years.
In patients between the ages of 65 and 84
years, survival rates are lowest in those individ-
uals with SBP >180 mmHg. However, in patients
over the age of 85 years, differences in survival
rates in those with SBP <130 mmHg compared
to those with SBP >180 mmHg are less clear.
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161
One study evaluated the relationship between
blood pressure and survival in patients over the
age of 85 years, found that the risk of death was
actually highest among individuals with SBP
<140/90 mmHg, who would have been defined
as “at goal” per JNC VII guideline
s.
6,10
The relationship between DBP and risk
may also change with age. Physiologically,
DBP decreases with normal aging due to the
decreased ability of vessels to expand during
systole and contract during diastole. A negative
relationship has been demonstrated between
lower DBP and total mortality.
9
In a population
of 7,557 patients over the age of 60 (average
age of 70 years), lower DBP was associated
with increased mortality rates across all strata of
SBP.
11
This suggests that a high pulse pressure
may be a predictive factor of CVD events in this
population.
Elderly patients may also have more varia-
tion in their blood pressure readings than younger
patients. This is referred to as labile hypertension
and may be due to loss of elasticity of arterial
walls, changing the manner in which barore-
ceptors respond.
12
Labile hypertension has not
been proven to be an independent risk factor for
cardiovascular disease.
11
However, in patients
with labile hypertension, these blood pressure
variations emphasize the need for several blood
pressure measurements to be taken, including
home readings, prior to treatment decisions.
Decreased renal function and ability to excrete
salt loads occur with age.
8
These changes can
create salt sensitivity and make diet history a very
important part of a patient history in the elderly,
as well as a salt reduction as a treatment target.
Based on these data, the association
between hypertension and CVD outcomes
among individuals over the age of 60 is well
established. However, it appears that the asso-
ciation between treating hypertension and CVD
outcomes is not as clear among the strata of
elderly patients who are of extremely advanced
age, in whom high pulse pressures may actu-
ally be associated with increased mortality.
Therefore, the optimal blood pressure goal
across all strata of older individuals remains
somewhat unclear.
Standard Adult Treatment
Recommendations
The standard of care for the treatment of hyper-
tension in the adult population has been well
established by the JNC VII guidelines.
6
The
new JNC VIII guidelines, released in late 2013,
changed blood pressure goals for many situa-
tions and were met with some controversy and
criticism.
7
The American College of Cardiology
and American Heart Association will likely be
releasing a new guideline on blood pressure
management some time in 2015 for clinicians
because they did not endorse JNC VIII. One of
the major changes in the new JNC VIII is that the
SBP goal for those 60 years and older was set at
150 mmHg.
7
The previous goal was 140 mmHg
in JNC VII. Some of the authors of the new JNC
VIII have disagreed with their own guidelines on
this recommendation, after the guidelines were
published. The SBP goal remains <140 mmHg for
those younger than 60 years in and the diastolic
goal remains 90 mmHg.
7
The <140/90 mmHg
target was also extended to diabetes and chronic
kidney disease (CKD) patients.
7
JNC VIII recom-
mends starting pharmacological treatment with
a thiazide diuretic, ACE inhibitor, angiotensin
receptor blocker (ARB), or calcium channel
blocker. In the African American population, a
thiazide diuretic or calcium channel blocker are
preferred as initial therapy, unless patients have
CKD or diabetes, due to the reduced efficacy of
other agents in this population. All other medi-
cations are to be used later in treatment, unless
they have a compelling indication.
Goal blood pressure can be achieved with
monotherapy or combination drug therapy,
although the guidelines recommend that medica-
tion therapy should be initiated at low doses and
titrated slowly to avoid orthostatic hypotension,
to which elderly patients are more susceptible.
The acceptance and implementation of JNC VIII
into clinical practice is still undetermined. Some
clinicians are still referring to JNC VII and await
the ACC/AHA guidelines in the near future.
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Treatment Recommendations in the
Geriatric Population
While current guidelines are well supported
with randomized clinical trials, it is reasonable
to examine whether these recommendations
apply to all subgroups in the elderly population.
To determine this and to select specific medi-
cations that are the best choices for treatment,
one must consider the literature on which the
JNC VII and JNC VIII recommendations for older
patients are based.
6,7
Specifically, the clinical
trials that included at least some elderly patients
who also met criteria for inclusion in the JNC VIII
guidelines include the Systolic Hypertension in
the Elderly Program (SHEP), the Swedish Trial
in Old Patients with Hypertension (STOP), the
Systolic Hypertension in Europe (Syst-Eur), and
the Medical Research Council (MRC) trial.
13-16
Collectively, these trials enrolled patients with an
average age of 74 years. Study populations were
large, ranging from 1,627 to 4,736 subjects. All
of the trials lasted at least 2 years and showed a
reduction in the risk of endpoints such as stroke
or cardiovascular death.
The Hypertension in the Very Elderly Trial
(HYVET) was also included in the analysis for the
new JNC VIII guidelines. HYVET enrolled 3,845
subjects over the age of 80 years, with an average
follow-up period of 21 months.
17
The baseline SBP
was 173/90 mmHg in the treatment and control
groups, and the treatment blood pressure goal
was <150/80 mmHg. The treatment intervention
was a diuretic or placebo, with the possible addi-
tion of an ACE inhibitor in the treatment group.
The results showed a significant decrease in rate
of fatal/nonfatal stroke (30%), incidence of death
from stroke (39%), rate of death from any cause
(21%), and incidence of heart failure (64%)
associated with antihypertensive therapy.
17
The
benefits began to appear in the treatment group
at 1 year. Limitations of the trial included the fact
that, based on demographic characteristics of
patients enrolled, the elderly population enrolled
in this study was likely healthier than the typical
elderly population. Therefore, the results may
not be applicable to the frail elderly population.
Exact causes of death were difficult to validate
in some cases; evidence was required to clas-
sify as a death from stroke. Rapid, unexpected
deaths were classified as cardiac causes. None-
theless, the incidence of death from all causes
was significantly reduced in the antihypertensive
treatment group. This study also demonstrated
that thiazide diuretics, with or without the addi-
tion of an ACE inhibitor, have been associated
with the favorable outcomes among patients of
advanced age.
Based on evidence from these trials, blood
pressure goals established for the adult popula-
tion are likely appropriate for patients over the
age of 65 and remain valid endpoints throughout
the seventh decade of life. The criticism that
the goal for those 60–80 years should have
remained <140/90 mmHg is still being debated,
and in 2015, with the release of the ACC/AHA
guidelines, this may be clarified further. With
the inclusion of the HYVET trial into JNC VIII,
the blood pressure goal of <150/90 mmHg in
the new guidelines is also probably a valid goal
for those 80 years and older as well. This blood
pressure goal is also supported by other inter-
national guidelines for those over 80 years. The
Canadian Hypertension Education Program and
the European Society of Hypertension/European
Society of Cardiology 2013 guidelines both
recommend a blood pressure goal of <150/90
mmHg for those 80 years and older.
18,19
Given
these controversies, decisions about antihy-
pertensive medication and target blood pres-
sure should be guided by the presence of other
cardiovascular risk factors and non-cardiovas-
cular co-morbidities and individualized for each
older adult.
Blood pressure assessment in the elderly
has some special consideration that clinicians
should keep in mind. Sclerotic arteries are
more difficult to compress with the blood pres-
sure cuff. This can result in falsely elevated
blood pressure readings.
8
Auscultatory gap and
white-coat hypertension is also more common
in the elderly.
8
Standing blood pressures should
always be measured due to risk of orthostasis.
The ACCORD BP trial was taken into account
in the 2011 ACC/AHA consensus document on
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163
hypertension in the elderly. This trial showed
no additional benefit with a systolic BP of 120
mmHg versus 140 mmHg in high-risk patients
over 55 years with diabetes.
20
In fact, there
were increased adverse effects from the antihy-
pertensives in this group. The 2011 ACC/AHA
consensus document on hypertension in the
elderly recommended a SBP of 140–145 mmHg
for those 80 years and older. They also recom-
mend SBPs under 130 mmHg and diastolic
under 65 mmHg be avoided in those over 80
years.
8
When looking at all of the recent evidence
and guidelines released over the past few years,
it seems reasonable to target a blood pressure
of <150/90 mmHg in those 80 years and over.
In those younger than 80 years the new JNC
VIII document would suggest the same goal;
however, many still believe the <140/90 mmHg is
the better target. Both JNC VII and VIII included
a fair number of patients who were between 65
and 80 years. Blood pressure targets and treat-
ment should always have risks and benefits
assessed rather than using a “one goal/treat-
ment fits all” approach.
The JNC VIII recommendation for first-line
choice of pharmacologic therapy applies to the
entire adult population, including the elderly
population. It was noted in JNC VIII that in
those older than 75 years with CKD, there was
no evidence that using an ACE inhibitor or ARB
improved kidney outcomes.
7
These agents can
still be used in those older than 75 years, but a
thiazide diuretic or calcium channel blocker are
also reasonable first-line choices in this popula-
tion. Considerations for the use of some of the
common antihypertensive classes in the geri-
atric population are listed in Table 7-1.
Barriers to Treatment of the
Geriatric Population
Patients older than 75 years are not as likely
to receive counseling on lifestyle recommen-
dations compared to younger adults.
8
Given
the potential for salt-sensitive hypertension
discussed above, lifestyle recommendations
should be implemented in all patient age
groups. Salt restriction can be an important
part of treatment for those 65 years and over
who are consuming large quantities of salt in
their diet and who have no history of hypona-
tremia. The Trial of Nonpharmacologic Inter-
ventions in the Elderly (TONE) studied sodium
reduction and weight loss as interventions for
hypertension in those 60–80 years old. Salt
intake was limited to less than 1800 mg/day
and participants lost an average of 3.9 kg in a
little over 2 years. Both of these interventions
led to significant blood pressure reductions,
with some patients being able to discontinue
antihypertensives.
21
A decreased ability to
taste salty foods may occur with aging, as well
as a lack of transportation to obtain fresh fruits
and vegetables on a regular basis. Lifestyle
recommendations are important in elderly
patients because they may help to avoid
medications in some cases.
Adverse outcomes can be associated with
failure to initiate an appropriate dose and titrate
on an appropriate schedule. Therapeutic goals,
frailty, patient prognosis, and age-related
decline in kidney function must be considered
when initiating and titrating therapy; although
once a maintenance dose has been achieved,
the reduction of antihypertensive medication
based on age or creatinine clearance (CrCl) is
inappropriate without an assessment of whether
the patient has been tolerating the regimen and
has achieved the desired therapeutic goal.
Instead, increasing the frequency of monitoring
may be prudent. For example, elderly patients
with reduced CrCl are particularly vulnerable
to hyperkalemia asso
ciated
with ACE inhibi-
tors, requiring increased frequency of serum
chemistry monitoring. Due to age-related
changes in pharmacokinetics and pharmaco-
dynamics, some classes of antihypertensive
medication, including
beta blockers, centrally
acting
alpha
-
agonists, peripheral
alpha
-
antag-
onists, nitrates, and other vasodilators present
special concerns for older patients
,
as noted in
Chapter 3.
22
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Table 7-1. Characteristics of Common Classes of Antihypertensives Used in the Elderly
8
Antihypertensive
Class
Compelling
Indications Adverse Effects
Route of Elimination/Dosing
Adjustments
Alpha-1 adrenergic
blockers
Benign prostatic hyper-
trophy
Orthostatic hypotension Hepatic: start at lowest dose and
titrate
ACE inhibitors and
angiotensin II
receptor blockers
Heart failure, post-MI,
CKD, diabetes
Hyperkalemia, cough,
angioedema, renal
impairment
ACE inhibitors:
•
Renal: start at lowest dose
and titrate
» fosinopril is both hepatic
and renal
Angiotensin II receptor blockers:
•
Hepatic: no dose
adjustment
» candesartan and
eprosartan are both
hepatic and renal
Beta adrenergic
blockers
Heart failure, post-MI,
atrial fibrillation rate
control, essential
tremor, migraine
Bradycardia, fatigue,
bronchospasm
Renal: initiate at lowest dose
and titrate:
•
nadolol, atenolol, carvedilol,
nebivolol
Hepatic: initiate at lowest dose
and titrate:
• propranolol,
metoprolol, labetalol,
nebivolol
Calcium channel
blockers
Atrial fibrilla
tion rate
control
(nondihydropyridine)
Nondihydropyridine:
exacerbation of GERD,
gingival hyperplasia,
constipation (vera-
pamil), heart block,
bradycardia
Dihydropyridine:
peripheral edema
Hepatic: start at lowest dose and
titrate
Loop diuretics Heart failure Hyponatremia,
hypokalemia
Renal: no dose adjustment
•
furosemide, bumetanide
Hepatic: no dose adjustment
• bumetanide, torsemide
Thiazide diuretics Osteoporosis Gout, hyponatremia,
hypokalemia
Renal: no dose adjustment
needed
ACE, angiotensin-converting enzymes; CKD, chronic kidney disease; GERD, gastroesophageal reflux disease;
MI, myocardial infarction.
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165
L M
Etiology, Epidemiology, and
Clinical Presentation in the
Geriatric Population
Approximately 25% of adults have elevated
plasma low-density lipoprotein (LDL) concentra-
tions.
21
Roughly 63% of patients with elevated
plasma LDL concentrations are aware of the
condition, and about 41% of those with elevated
LDL are taking lipid-lowering medications.
23
Serum concentrations of total cholesterol and
LDL increase throughout life, and hyperlipidemia
is a common condition in elderly patients.
Published data indicate that the risk associ-
ated with elevated plasma cholesterol concen-
trations observed in younger patients persists in
the elderly. In a multicenter, longitudinal study of
4,066 men and women 65 years of age or older
(average age 79.2 years at initiation of study),
there was a significant correlation between
increasing plasma cholesterol concentrations
and the increased adjusted relative risk of death
due to coronary heart disease over a 4-year
period.
24
In addition, in a prospective cohort study
of patients 80 years and older, higher plasma
high-density lipoprotein (HDL) concentrations
were shown to be associated with survival during
a 2-year period.
25
Men who survived during this
period had mean plasma HDL concentration
of 43.4 ± 10.3 mg/dL, compared with 36.7 ±
7.6 mg/dL in those who died (p = 0.001). Simi-
larly, women who survived had higher plasma
LDL concentrations than those who did not
(49.3 ± 14.9 mg/dL versus 42.2 ± 11.5 mg/dL,
p = 0.001).
A meta-analysis of 61 prospective observa-
tional studies that enrolled almost 900,000 adults
was performed to determine the relevance of
blood pressure and total cholesterol on vascular
mortality.
26
The investigators reported that a
prolonged reduction in total cholesterol concen-
tration of 1 mmol/L (38.6 mg/dL) from mean usual
concentrations was associated with the following
age-related reductions in the hazard ratio (HR)
for death due to ischemic heart diseases: age
40–49 years, HR 0.44 (95% CI 0.42–0.48); age
50–59 years, HR 0.58 (0.56–0.61); age 60–69
years, HR 0.72 (0.69–0.74); age 70–79 years,
HR 0.82 (0.80–0.85); 80–89 years, HR 0.85
(0.82–0.89). Therefore, while the magnitude of
reduction in HR for death due to ischemic heart
disease diminished in patients between the ages
of 70–79 years and 80–89 years, the reduction
in hazard remained statistically significant in
both groups. In addition, there was a strong and
significant inverse relationship between plasma
HDL concentration and hazard of death due to
ischemic heart disease in every age group. Para-
doxically, the HR for ischemic stroke associated
with a 1-mmol/L (38.6-mg/dL) lowering of plasma
cholesterol concentration compared to usual
values was reduced only in patients between
the ages of 40–59 years, and it was increased
in patients between the ages of 80–89 years
(HR 1.06, 95% CI 1.00–1.13). The investigators
were unable to explain the absence of an inde-
pendent positive association of cholesterol with
stroke mortality at older ages.
Standard Adult Treatment
Recommendations
Treatment recommendations for hyperlipidemias
are based on the 2013 ACC/AHA Guide on
the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults,
which came out in late 2013.
27
These new
guidelines represent a very different approach
to prescribing drug therapy for hyperlipidemia.
Four statin benefit groups were identified to help
clinicians decide which of their patients would
benefit from statins. All statins were also divided
into low-, moderate-, and high-intensity doses.
Goals for LDL and other lipid parameters were
not used in the new guidelines, which focus on
an appropriate intensity for certain risk groups.
The four groups that were identified to benefit
from statins include (1) those with arterioscle-
rotic cardiovascular disease, (2) those with LDL
≥190 mg/dL, (3) those between the ages of
40–75 years with diabetes, and (4) those with a
≥7.5% estimated 10-year risk between the ages
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| Fundamentals of Geriatric Pharmacotherapy
of 40–75 years old. A new Pooled Cohort Equa-
tion was developed to calculate this 10-year risk,
which is different than the previous Framingham
equation used.
27
In general, use of lipid-lowering
medications other than statins was discouraged
in the new guidelines due to the lack of benefit
on cardiovascular outcomes in recent studies
with these agents.
27
Standard treatment still includes therapeutic
lifestyle changes to reduce the dietary intake of
saturated fats, weight reduction, and increasing
physical activity.
27
These lifestyle recommenda-
tions should be implemented in everyone but are
no longer recommended to reduce LDL before
drug therapy is initiated. If drug therapy is indi-
cated, it should be initiated concurrently.
Treatment Recommendations in the
Geriatric Population
Relatively few studies have been conducted to
determine the benefits associated with manage-
ment of hyperlipidemias in the elderly, especially
those over age 80. The new guidelines focused
exclusively on randomized controlled clinical
trials. There were few people in these trials older
than 75 years. Data from secondary prevention
trials showed support for continuation of statins
in patients age 75 and older as well as benefits
in initiating statins in this age group. Interestingly,
the new guidelines recommend moderate-inten-
sity statin therapy in those over age 75 instead of
the high intensity recommended for secondary
prevention in all others. This was supported by
the small amount of data available in this age
group, showing that titration to high intensity did
not provide better outcomes. Patients age 75
or older, with or without diabetes, should have
risks and benefits weighed to determine whether
statin therapy should be initiated. The guide-
lines focus on the discussion of these risks and
benefits between the clinician and patient. The
Pooled Cohort Equations can estimate 10-year
risk in patients aged 76–79 that can be used as
a factor in this decision. Age is a strong predictor
of 10-year risk in the new equation, with a large
number of elderly patients meeting the criteria
for statin use in primary prevention based on
this calculation. This again places emphasis on
the need for older adults to have a risk versus
benefit discussion with their care provider. Other
factors to weigh in primary prevention in those
older than 75 include drug-drug interactions,
risk of adverse effects, antherosclerotic cardio-
vascular disease (ASCVD) reduction benefits,
current disease states, life expectancy, and
patient preference.
27
One of the few trials to specifically evaluate
treatment of dyslipidemia in the elderly is the
pravastatin in elderly individuals at risk of vascular
disease (PROSPER) trial.
28
It randomized 5,804
patients between the ages of 70–82 with a history
of or risk factors for vascular disease to receive
therapy with pravastatin 40 mg daily or placebo.
The mean serum LDL concentration in random-
ized patients was 147 ± 31 mg/dL. In patients
randomized to receive pravastatin, serum LDL
concentrations were relatively reduced (34%),
and the incidence of primary endpoint events
(composite endpoint of death from coronary
heart disease, nonfatal myocardial infarction
[MI], and fatal or nonfatal stroke) was reduced by
15% in pravastatin-treated patients. Pravastatin
therapy was not associated with a significantly
greater deterioration of cognitive function than
placebo, and there was no significant difference
between the groups in the incidence of myalgias.
Overall, the results of the PROSPER trial support
that elderly patients appear to benefit from
lipid-lowering therapy, both those with vascular
disease or those merely at risk.
The Justification for the Use of Statins in
Prevention: an Intervention Trial Evaluating
Rosuvastatin (JUPITER) study looked at primary
prevention with rosuvastatin. The original trial
looked at patients with an LDL <130 mg/dL.
29
A
subgroup analysis of 5,695 patients 70 years and
older was done to evaluate primary prevention in
the elderly. There was a significant reduction in
occurrence of first cardiovascular event in the
rosuvastatin group in those 70 years and older.
Absolute reduction was greater in this elderly
group as well.
30
One must take into account that
the JUPITER trial was not designed initially to
evaluate primary prevention in those 70 years
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