Drugs Aging 2005; 22 (10): 859-876

ORIGINAL RESEARCH ARTICLE 1170-229X/05/0010-0859/$34.95/0

 2005 Adis Data Information BV. All rights reserved.

Prevention of Cardiovascular Events

in Elderly People
Wafik Farah Andrawes, Caroline Bussy and Joël Belmin
Service de Gériatrie, Hôpital Charles Foix et Université Paris 6, Ivry-sur-Seine, France

Abstract Background and objective: Cardiovascular disease has been identified as the
leading cause of morbidity and mortality in developed countries. Given the
increase in life expectancy and the development of cardiovascular preventive
measures, it has become increasingly important to detect and prevent cardiovascu-
lar diseases in the elderly. We reviewed the scientific literature concerning
cardiovascular prevention to assess the importance of cardiovascular preventive
measures in old (≥65 years of age) individuals.
Methods: We undertook a systematic search for references relating to prevention
of cardiovascular disease in the elderly, mainly ischaemic stroke, coronary artery
disease and heart failure, on the MEDLINE database 1962–2005. For cardiovas-
cular prevention by drugs or surgery, emphasis was placed on randomised
controlled trials, review articles and meta-analyses. For cardiovascular prevention
by lifestyle modification, major cohort studies were also considered.
Results: Stroke, coronary heart disease and heart failure were found to be the
main targets for cardiovascular prevention in published studies. Antihypertensive
treatment has proven its efficacy in primary prevention of fatal or nonfatal stroke
in hypertensive and high-risk patients >60 years of age, particularly through
treatment of systolic hypertension. Systolic blood pressure reduction is equally
important in the secondary prevention of stroke. Similarly, in nonvalvular atrial
fibrillation, an adjusted dose of warfarin with a target International Normalized
Ratio (INR) of between 2 to 3 prevents ischaemic stroke in elderly patients with an
acceptable haemorrhagic risk but is still under prescribed. Antiplatelet agents are
indicated in elderly patients with nonembolic strokes. Few large-scale studies
have investigated the effect of HMG-CoA reductase inhibitors (statins) on stroke
prevention in old individuals. To date, the largest trials suggest a beneficial effect
for stroke prevention with use of statins in high-risk elderly subjects ≤82 years of
age. Carotid endarterectomy is indicated in carotid artery stenosis >70% and
outcomes are even better in elderly than in younger patients. However, medical
treatment is still the first-line treatment in asymptomatic elderly patients with
<70% stenosis. In ischaemic heart disease, different trials in elderly individuals
have shown that use of statins, antithrombotic agents, β-adrenoceptor antagonists
and ACE inhibitors plays an important role either in primary or in secondary
cardiovascular prevention. Hormone replacement therapy has been used to treat
climacteric symptoms and postmenopausal osteoporosis and was thought to
confer a cardiovascular protection. However, controlled trials in elderly individu-
als changed this false belief when it was found that there was no benefit and even a
860 Andrawes et al.

harmful cardiovascular effect during the first year of treatment. Smoking cessa-
tion, regular physical activity and healthy diet are, as in younger individuals,
appropriate and effective measures for preventing cardiovascular events in the
elderly. Finally, antihypertensive treatment and influenza vaccination are useful
for heart failure prevention in elderly individuals.
Conclusions: Cardiovascular prevention should be more widely implemented in
the elderly, including individuals aged ≥75 years, and this might contribute to
improved healthy status and quality of life in this growing population.

Cardiovascular diseases are related essentially to bolisation (for example in cases of atrial fibrillation)
atherosclerosis, which starts to develop early in life or indirectly when the thrombus complicates athero-
and has a slowly progressive course.[1] Over many sclerotic changes of vessels. Thus, many targets can
years, a number of studies have shown that dys- be identified for preventing the complications of
lipidaemia is the major determinant of the pathogen- atherosclerosis in the elderly.
esis of atherosclerosis by promoting atherogenesis With cardiovascular disease having been identi-
and accelerating plaque development.[2,3] These fied as the leading cause of morbidity and mortality
findings suggest that prevention of atherosclerosis in developed countries over recent decades, preven-
should primarily be aimed at young or middle-aged tion of cardiovascular disease has emerged as a
individuals. major goal of public health. Historically, prevention
However, the problem of atherosclerosis is de- of cardiovascular disease commenced with antihy-
pendent not only on dyslipidaemia. In particular, pertensive therapy and detection and treatment of
several processes strongly associated with advanc- hypercholesterolaemia, focusing mainly on middle-
ing age promote the development of complications aged adults. As life expectancy increased and epide-
of atherosclerosis and help determine clinical miological studies progressed, it became more and
events. Many epidemiological studies have clearly more obvious that the burden of cardiovascular dis-
shown that other risk factors common in the elderly, ease in the elderly is considerable. However, little
such as hypertension, obesity, diabetes mellitus/glu- attention was paid to preventive medicine in elderly
cose intolerance and sedentary lifestyle, influence people until recent years, probably because of a false
atherosclerosis and its complications.[4-6] In particu- belief that prevention is too late to be effective in
lar, hypertension plays a major role by favouring elderly individuals. In fact, evidence from scientific
plaque rupture with resultant thrombosis and studies, namely randomised, controlled trials, shows
clinical complications. Inflammation, which is also not only that cardiovascular prevention is effective
a common condition in the elderly, plays a key role in the elderly, but that it also results in a greater
in the development of atherosclerosis[7] and immu- number of avoided events than in younger individu-
nocompetent cells are involved in many steps of the als (figure 1). Moreover, cardiovascular prevention
atherosclerotic process. The first visible lesions of in the elderly should take into consideration not only
atherosclerosis consist of macrophage-derived foam hypertension and dyslipidaemia but also other risk
cells that contain lipid droplets, and monocytes/ factors, such as atrial fibrillation, carotid artery ste-
macrophages may play a major role in the later nosis and smoking.
stages of atherosclerosis.[8-10] Thrombotic condi- We reviewed the scientific literature relating to
tions are also common in elderly patients and are prevention of cardiovascular diseases – primarily
directly involved in the onset of clinical complica- ischaemic stroke, coronary artery disease and heart
tions. In many cases, the pathogenesis of cardiovas- failure – in the elderly, with special emphasis on
cular diseases in elderly subjects is directly related randomised, controlled studies. We used a systemat-
to thrombosis as a complication of systemic em- ic search for references from the MEDLINE

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
Prevention of Cardiovascular Events in Elderly People 861

a 100 100 Control causes of death.[11] It is also a major cause of disabil-

100 Intervention
ity in at least 15 million patients annually.[12]
80 About 80% of strokes are a result of an ischaemic
Relative risk (%)

60 60
60 event, of which 50% of cases are related to ather-
othrombotic diseases of intra- or extracerebral arter-
40
ies, about 20% are related to embolism of cardiac
20 origin and 25% are a result of occlusion of one of the
0 small deep perforating cerebral arteries.[13] Hyper-
tension, heart disease and thoracic aorta and carotid
b
atherosclerosis are the main aetiologies of ischaemic
(events per 1000 patient-years)

60 stroke in the elderly.

50
50
Antihypertensive Treatment in Elderly
Absolute risk

40 **
30 Patients for Stroke Prevention
30
20
10 * Antihypertensive Drugs for Primary Prevention of
10 6
Stroke in Elderly Hypertensive Patients
0 A number of randomised studies have demon-
Middle-aged Old
strated the efficacy of antihypertensive treatment in
Fig. 1. Comparison of results expressed as relative risk reduction
(a) and absolute risk reduction (b) for an intervention producing a
the primary prevention of fatal or nonfatal stroke in
40% reduction in relative risk of cardiovascular events in middle- hypertensive patients >60 years of age.[14-16] Several
aged and old individuals. When results are expressed as number of meta-analyses of these trials have concluded that
events avoided, the efficacy of cardiovascular prevention in the
elderly is obvious. This pattern is often observed in intervention
antihypertensive treatment is effective in reducing
trials of cardiovascular prevention, as incidence rates of cardiovas- the risk of fatal and nonfatal stroke in elderly hyper-
cular events often increase with age. * indicates four events avoid- tensive patients. Table I shows the results of the
ed; ** indicates 20 events avoided.
major randomised trials of stroke prevention in eld-
erly hypertensives.
database (1962–2005) using the key words: ‘elder- Clearly, the importance of stroke-risk reduction
ly’, ‘cardiovascular diseases’, ‘prevention’, ‘stroke’, is related to the extent of blood pressure lowering. In
‘coronary heart disease’ and ‘heart failure’. For car- a meta-analysis of 13 trials conducted on 37 000
diovascular prevention by drugs or surgery, we fo- patients, it was found that for every 5mm Hg reduc-
cused our analysis on randomised controlled trials, tion in diastolic blood pressure there was 9.5%
review articles and meta-analyses. For cardiovascu- decrease in cardiovascular morbidity and mortality
lar prevention by lifestyle modification, we also outcomes.[30,31] Other investigators focused on sys-
considered major cohort studies. We also identified tolic hypertension in patients >60 years of age, some
and obtained references from selected review arti- of whom were up to 80 years of age in some studies.
cles and major textbooks. Our primary objective The results of these studies were analysed in a meta-
was to determine whether cardiovascular prevention analysis conducted by Staessen et al.[32] These inves-
is effective in elderly subjects. tigators found that, compared with diastolic hyper-
tension, systolic hypertension has a stronger correla-
Prevention of Ischaemic Stroke in tion with all-cause mortality (relative risk [RR]
Old Persons 1.14; 95% CI 1.07, 1.21; p = 0.0001) and stroke (RR
1.12; 95% CI 1.02, 1.21; p = 0.02) in untreated
Stroke is responsible for the death of about 5 patients. The net reductions with treatment in systol-
million individuals per year, which makes cer- ic and diastolic blood pressures expressed as per-
ebrovascular disease one of the most important centages of values at baseline were 5.96% (95% CI

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
862 Andrawes et al.

Table I. Stroke reduction in randomized, placebo-controlled trials of antihypertensive drugs

Trial Treatment Placebo Follow-up Mean age RR (95% CI)
n N n N (years) (years)
β-Adrenoceptor antagonists and/or diuretics vs placebo or no treatment
DUTCH TIA[17] 52 732 62 741 2.6 65 0.85 (0.6, 1.21)
Coope and Warrender[18] 20 419 39 465 4.4 69 0.57 (0.34, 0.96)
MRC OLDER[19] 101 2183 134 2213 5.8 70 0.76 (0.59, 0.98)
TEST[20] 3 372 69 348 2.6 70 1.00 (0.75, 1.35)
EWPHE[21] 32 416 48 424 4.7 72 0.68 (0.44, 1.04)
SHEP[22] 105 2365 162 2371 4.5 72 0.65 (0.51, 0.83)
STOP-Hypertension[23] 30 812 55 815 2.1 76 0.55 (0.35, 0.85)
HYVET[24] 6 386 18 394 1.1 84 0.31 (0.12, 0.79)

ACE inhibitors vs placebo or no treatment

PART-2[25] 7 308 4 309 4 61 1.76 (0.52, 5.94)
SCAT[26] 2 229 9 231 5 61 0.22 (0.05, 1.03)
PROGRESS[27] 307 3051 420 3054 4 64 0.73 (0.64, 0.84)
HOPE[28] 156 4654 226 4652 5 66 0.69 (0.57, 0.84)
HYVET[24] 12 397 18 394 1.1 84 0.63 (0.30, 1.31)

Calcium channel antagonist vs placebo

SYST-EUR II[29] 52 2398 77 2297 2 70 0.58 (0.41, 0.84)
DUTCH TIA = Dutch Transient Ischaemic Attack Trial Study Group; EWPHE = European Working Party on High Blood Pressure in the
Elderly Trial; HOPE = Heart Outcomes Prevention Evaluation; HYVET = Hypertension in the Very Elderly Trial Working Group; MRC
OLDER = Medical Research Council Working Party study in older adults; n = number of events; N = number of participants; PART-2 =
Prevention of Atherosclerosis with Ramipril-2; PROGRESS = Perindopril Protection Against Recurrent Stroke Study; RR = relative risk;
SCAT = Simvastatin/enalapril Coronary Atherosclerosis Trial; SHEP = Systolic Hypertension in the Elderly Program; STOP-Hypertension
= Swedish Trial in Old Patients with Hypertension; SYST-EUR = Systolic Hypertension in Europe II; TEST = TEnormin after Stroke and
Transient ischaemic attack.

5.36, 6.28) and 4.91% (95% CI 4.44, 5.38), respec- lower the diastolic pressure at any given level of
tively. Whatever the antihypertensive used, active systolic pressure the higher the death rate (p = 0.05).
treatment of systolic hypertension was associated Thus, these investigators highlighted the importance
with reductions in total mortality of 17% (95% CI 5, of pulse pressure and its relationship to total mortali-
28; p = 0.008), cardiovascular mortality by 25% ty.
(95% CI 8, 39; p = 0.005), all cardiovascular com- The role of antihypertensive agents in stroke-risk
plications by 32% (95% CI 13, 41; p < 0.001) and reduction has also been examined[33] in a recent
stroke by 37% (95% CI 24, 48; p < 0.001). With review article. Although there was no strong evi-
respect to absolute benefits, the number of patients- dence that stroke-risk reduction was importantly
to-treat for 5 years to prevent one stroke was 32 in related to the type of antihypertensive drug used,
patients ≥70 years of age versus 99 patients in those this meta-analysis found a marginally greater risk
60–69 years of age. In young hypertensive patients reduction with diuretics and/or β-adrenoceptor an-
(mean age 52 years), the corresponding number of tagonists than with ACE inhibitors (RR 0.91; 95%
persons that needed to be treated for 5 years to CI 0.83, 0.99), and with calcium channel antagonists
prevent one stroke was about 177.[19,32] compared with ACE inhibitors (RR 0.89; 95% CI
Finally, the role of pulse pressure as a risk factor 0.80, 0.99).
for total mortality was indirectly evaluated in this Since most randomised controlled trials have
meta-analysis.[32] The investigators concluded that been conducted in elderly subjects <80 years of age,
although systolic blood pressure was positively cor- there has remained a concern about the efficacy of
related with higher total mortality (p = 0.0001), the antihypertensive drugs in very old hypertensive pa-

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
Prevention of Cardiovascular Events in Elderly People 863

tients. A meta-analysis of the effect of reduction of ACE inhibitor perindopril for secondary prevention
blood pressure in hypertensive patients ≥80 years of of stroke among 6105 hypertensive and nonhyper-
age was conducted by Gueyffier et al.[34] In five tensive patients.[27] A new stroke occurred in 307
trials that included 1670 patients of that age, 57 patients in the active treatment group compared with
patients developed stroke in the treated group com- 420 patients in the placebo group (RR 28%; 95% CI
pared with 77 in the control group (RR 0.66; 95% CI 17, 38), confirming the importance of blood pres-
0.48, 0.92; p = 0.014), suggesting that there is no sure reduction in the secondary prevention of stroke.
age threshold above which hypertension should not Interestingly, stroke-risk reduction was similar in
be treated. Furthermore, preliminary results from hypertensive and normotensive patients.
the ongoing Hypertension in the Very Elderly Trial
Working Group study[24] showed a positive effect of Anticoagulants for Stroke Prevention in
antihypertensive treatment on fatal and nonfatal Elderly Patients with Atrial Fibrillation
stroke prevention in hypertensive patients >80 years
of age (hazard ratio [HR] 0.47; 95% CI 0.24, 0.91) Atrial fibrillation is the most prevalent arrhyth-
with no significant changes in total mortality. These mia seen by physicians.[36] It is well established that
results confirm the conclusions of the meta-analysis nonvalvular atrial fibrillation is associated with a
by Gueyffier et al.[34] 5-fold increased risk in stroke compared with sinus
rhythm.[37] Lip and Lowe[38] stated that the annual
Antihypertensive Drugs for Primary Prevention of relative risk of stroke is 8–12% in patients who have
Stroke in Other High-Risk Elderly Subjects
atrial fibrillation associated with structural heart dis-
One part of the HOPE (Heart Outcomes Preven- ease, earlier embolic events and thyrotoxicosis, and
tion Evaluation) trial[35] investigated the effect of an in those ≥75 years of age with a history of diabetes
antihypertensive drug, namely the ACE inhibitor or hypertension. These investigators also found that
ramipril 10 mg/day, on stroke incidence in 9297 patients ≥75 years of age with lone atrial fibrillation
patients ≥55 years of age with vascular disease or (atrial fibrillation in the absence of clear aetiology
diabetes plus an additional risk factor, with a mean and/or complications) have an annual risk of stroke
follow-up of 4.5 years. The patients were 66 years of of 4–8%.[38]
age on average and about half of them were hyper- Preventive treatment of stroke among patients
tensive. Stroke occurred in 156/4645 patients with atrial fibrillation is based on anticoagulation.
(3.4%) in the ramipril group and in 226/4652 pa- Adjusted-dose warfarin has been shown to be effec-
tients (4.9%) in the control group (RR 0.68; 95% CI tive in reducing risks of stroke and thromboembolic
0.56, 0.84). Interestingly, stroke-risk reduction was disease in people with nonrheumatic atrial fibrilla-
not dependent on blood pressure level. Moreover, tion.[39] Meta-analysis according to the intention-to-
cognitive alteration was also significantly reduced treat principle showed that adjusted-dose oral an-
in the ramipril group. It should be noted that in this ticoagulation is highly efficacious for the prevention
study, about half of the patients were ≥65 years of of all strokes with a risk reduction of 61% (95% CI
age and the risk reduction for the composite cardio- 47, 71) versus placebo.[40] This reduction was simi-
vascular outcome related to ramipril was not only lar for both primary and secondary prevention. An-
lower in the elderly subjects, but tended to be greater other meta-analysis of four studies of primary pre-
than in subjects ≤65 years of age.[28] vention in patients >75 years found a comparable
Antihypertensive Drugs for Secondary Prevention benefit to that demonstrated in younger age
of Stroke in Patients with Previous Stroke or groups.[41] The target of anticoagulation therapy in-
Transient Ischaemic Attack volves obtaining a balance between avoiding is-
The PROGRESS (Perindopril Protection Against chaemic stroke and avoiding haemorrhagic compli-
Recurrent Stroke Study) collaborative group investi- cations. It is important to provide the lowest ade-
gated the effect of blood pressure-lowering with the quate intensity of anticoagulation to minimise the

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
864 Andrawes et al.

risk of bleeding, particularly in elderly patients. Finally, as far as possible, it is also important to
Maximum protection against ischaemic stroke in explain these points to the patient and to ask for the
atrial fibrillation is probably achieved with an Inter- patient’s preference.
national Normalized Ratio (INR) of 2–3.[42,43] An
Despite the higher risk of stroke in patients >75
INR of 1.6–2.5 appears to be associated with incom-
years of age with atrial fibrillation and a favourable
plete efficacy compared with higher intensity an-
benefit-risk ratio, warfarin is still underused. In the
ticoagulation.
study conducted by Brass et al.,[48] it was found that
Aspirin (acetylsalicylic acid) offers only modest among 304 patients with atrial fibrillation and with-
protection against stroke in patients with atrial fibril- out contraindication for anticoagulation, only 117
lation. The effect is less consistent than that (38%) were receiving warfarin. Among elderly peo-
achieved with oral anticoagulants.[40] ple with atrial fibrillation, warfarin underuse was
Older age had been identified as a risk factor for more pronounced in the oldest old. White et al.[49]
haemorrhagic complications of anticoagulant ther- observed that among patients with no contraindica-
apy in previous studies.[44,45] To clarify this relation- tions, warfarin was given to 2/13 (15%) of patients
ship, Palareti et al.[46] conducted a study comparing >90 years of age, 15/62 (24%) of those 80–89 years
subjects >75 years of age with younger patients of age and 46/97 (47%) of those 69–79 years of age.
(mean age 61 years) taking oral anticoagulants. In a more recent study conducted among benefi-
These investigators found that the oldest group had a ciaries of a large healthcare system in northern Cali-
nonsignificant increase in incidence of major fornia, the rate of prescription of warfarin for
haemorrhage (2.1% vs 1.1% patient-years; p = nonvalvular atrial fibrillation patients with no con-
0.19). Conversely, the increase in fatal complica- traindication to anticoagulation ranged between
tions was statistically significant in the older age 57.0% and 61.1% among patients aged 55–64 years,
group (1.1% vs 0.2% patient-years in younger indi- 65–74 years and 75–84 years, and was 35.6% in
viduals; RR 6.4; p = 0.047). A study by Fihn et al.[47] those >85 years of age.[50] Vasishta et al.[51] also
reported a 4-fold increase in fatal haemorrhage found that prescription of anticoagulants to elderly
among patients >80 years of age compared with patients by physicians is still underused in daily
those <50 years of age (3.38 vs 0.75 per 100 patient- practice. In a questionnaire exploring physicians’
years). Thus, age >75 or 80 years should be consid- opinions and attitudes about prescription of antico-
ered a risk factor for warfarin-induced fatal haemor- agulants, 46 of 68 respondents (68%) considered
rhage, but probably not a risk factor for nonfatal that warfarin-related bleeds were more likely in
bleeding. Because of the major impact of stroke on patients ≥75 years of age, but 38 (56%) still thought
disability and quality of life in the elderly, the bene- that the benefits of warfarin outweighed the risks.
fit/risk ratio for warfarin seems to favour treatment Among the 68 clinicians who responded, 84% pre-
of very old individuals when advanced age is the scribed warfarin in the presence of high-risk factors
only risk factor for bleeding. As with younger pa- for stroke, 70% for patients with moderate risk
tients, other risk factors for warfarin-induced bleed- factors and only 45% for patients with lone atrial
ing, such as severe renal and/or hepatic failure, fibrillation. Nearly all respondents (94%) agreed
alcoholism, recent haemorrhage, use of aspirin or that the risk of bleeding was lowest with an INR of
NSAIDs, uncontrolled hypertension, poor compli- 2–3. The factors influencing prescription of antico-
ance with treatment and recreational activities ex- agulants consisted mainly of the risk of falls and
posing the head to trauma, should be identified. previous stroke and, to a lesser extent, dementia,
Thus, the risk of warfarin-induced bleeding should limited life expectancy, age >80 years and drug
be assessed taking into account all risk factors and interactions. However, the risk of severe haemor-
not just age. Moreover, the risk should be evaluated rhagic complication in older persons with a history
against that of stroke and consequent disability. of fall has probably been exaggerated. Man-Son-

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
Prevention of Cardiovascular Events in Elderly People 865

Hing et al.[52] found that in persons taking warfarin, Role of Lipid-Lowering Drugs in Stroke
fall-related subdural haematomas were infrequent Prevention in Elderly
and the benefits of warfarin in the prevention of
stroke in elderly patients with nonvalvular atrial Direct evidence relating to the relationship be-
fibrillation greatly exceeded the risk of subdural tween hypercholesterolaemia and stroke remains
haematoma. unclear.
The Asia Pacific Cohort Studies Collaboration
Recently, a new line of treatment, the oral direct showed that a high total cholesterol level was asso-
thrombin inhibitor ximelagatran, was found to be ciated with a significantly increased risk of fatal and
effective in preventing thromboembolism in patients nonfatal ischaemic stroke of the order of 25% (95%
with atrial fibrillation. To compare its efficacy with CI 13, 40) compared with subjects with normal
warfarin, a randomised, double-blind, multicentre cholesterol level.[54] However, risk of thromboem-
trial was conducted among 3922 patients (mean age bolic stroke was not significantly related to hyperc-
71.6 years) with nonvalvular atrial fibrillation and holesterolaemia after adjustment for other risk fac-
additional stroke risk factors.[53] Adjusted-dose war- tors in men in the Honolulu Heart Program and the
farin (target INR 2–3) or fixed-dose oral ximelaga- Framingham study.[55]
tran 36mg twice daily were administered to patients. The Scandinavian Simvastatin Survival Study
The primary endpoint was all strokes (ischaemic or Group study of patients with a mean age of 58.1
haemorrhagic) and systemic embolic events. The years and coronary heart disease showed a signifi-
primary event rate with ximelagatran was 1.6% per cant reduction in the incidence of stroke in patients
year compared with 1.2% per year with warfarin receiving simvastatin (RR reduction 30%;
(absolute difference, 0.45% per year; 95% CI –0.13, p = 0.024).[56] In the Cholesterol and Recurrent
1.03 per year; p < 0.001 for the predefined noninfer- Events study,[57] stroke risk was reduced by 32% in
iority hypothesis). When all-cause mortality was pravastatin-treated subjects (p = 0.03), whereas in
included in addition to stroke and systemic embolic the West of Scotland Coronary Prevention Study,[58]
events, the rate difference was 0.10% per year (95% the reduction in stroke risk was nonsignificant
CI –0.97, 1.2 per year; p = 0.86). There was no (11%; p = 0.57).[58] However, the number of old
difference between treatment groups in rates of ma- subjects (>70 years of age) in these trials was small.
jor bleeding, but total bleeding (major and minor) Only two large-scale, randomised trials have in-
vestigated the effects of HMG CoA reductase inhib-
was lower with ximelagatran (37% vs 47% per year;
itors (statins) in large samples of elderly subjects.
95% CI for the difference, –14, –6.0 per year;
The PROSPER (Prospective Study of Pravastatin in
p < 0.001). Serum ALT levels rose to greater than
the Elderly at Risk)[59] trial conducted on 5804 sub-
three times the upper limit of normal in 6.0% of
jects 70–80 years of age with a history of risk factors
patients treated with ximelagatran, usually within 6 for cardiovascular disease found that pravastatin did
months, and typically declined whether or not treat- not reduce the incidence of stroke compared with
ment continued; however, one case of documented placebo (RR 1.03; 95% CI 0.81, 1.31). However,
fatal liver disease and one other suggestive case there was a trend towards a reduction in transient
occurred. Since treatment by oral thrombin inhibi- ischaemic attack (TIA) risk (RR 0.75; 95% CI 0.55,
tors has similar efficacy to anti-vitamin K drugs and 1.00; p < 0.051). In the Heart Protection Study,
is easier to manage (because of use of fixed doses which included 20 536 individuals 40–80 years of
and simpler biological surveillance), these drugs are age (of whom 5806 subjects were ≥70 years of age)
of great interest for old patients with atrial fibrilla- with coronary heart disease, occlusive arterial dis-
tion,[53] and their use in this age group should be ease and/or diabetes, treatment with simvastatin was
evaluated in appropriate trials that include elderly associated with a significant reduction in the rate of
patients. fatal and nonfatal stroke (RR 0.75; 95% CI 0.66,

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
866 Andrawes et al.

0.85; p < 0.0001).[60] Interestingly, in this trial the Medical treatment in the form of platelet antiag-
risk reduction in vascular disease was similar in gregation agents and risk factor modification are
subjects ≥70 years of age compared with younger most appropriate for symptomatic patients with
subjects. <50% stenosis.[64] The Asymptomatic Carotid Ath-
Overall, even if their conclusions are not in com- erosclerosis Study Group trial showed that combin-
plete agreement, the results of these studies suggest ing surgical and medical therapy may be beneficial
that statins might provide a beneficial effect in terms in asymptomatic patients with 60% stenosis but the
of stroke prevention in high-risk elderly subjects. It trial investigators concluded that medical treatment
should be noted that if only a few subjects were ≥80 remains the main treatment even when stenosis
years of age at entry in these trials, many more were reaches 70%.[65]
≥80 years of age at the end of follow-up.
Finally, adverse events were reported in similar Antiplatelet Agents for Stroke Prevention in
frequencies in patients receiving and not receiving the Elderly
statins with no clear evidence of increasing rate of
cancers in the statin-treated group.[59,60] Antiplatelet agents have been shown to be capa-
ble of reducing risk of stroke in patients with prior
Management of Carotid Stenosis noncardioembolic TIA and stroke compared with
placebo.[66,67] Aspirin, dipyridamole, ticlopidine and
Clinical studies have shown that ischaemic stroke clopidogrel all reduce the risk of stroke when used
is influenced by large vessel atherosclerosis, partic- for secondary prevention.[68-70] Furthermore, the An-
ularly internal carotid artery stenosis, and increases tiplatelet Trialists’ Collaboration meta-analysis re-
with the degree of stenosis.[61,62] Among sympto- viewed 287 randomised placebo-controlled trials
matic patients with 70–99% carotid stenosis >75 that included subjects at high risk for cardiovascular
years of age, the risk of ipsilateral ischaemic stroke events and concluded that antiplatelet agents re-
was higher than in younger patients following medi- duced the risk of stroke by 25%, whether or not
cal treatment. Similarly, the risk of stroke was patients had prior stroke or TIA.[71] Unfortunately,
greater among older patients with a 50–69% stenosis the effects of antiplatelet agents were not reported
under medical treatment than in the younger age by age group. In the 1994 meta-analysis by the
group. Antiplatelet Trialists’ Collaboration, the reduction
Surgical treatment consisting of carotid endarter- in risk of cardiovascular events with antiplatelet
ectomy has yielded better results in patients ≥75 agents was similar in high-risk subjects ≥65 years of
years of age with 50–99% internal carotid artery age to that seen in younger high-risk subjects.[72] In
stenosis than in younger patients.[63] Among surgi- subjects with hypertension and no prior cardiovas-
cally-treated patients in the North American Symp- cular disease, aspirin was not found to be more
tomatic Carotid Endarterectomy Trial, the absolute effective than placebo for the primary prevention of
risk reduction for ipsilateral ischaemic stroke in stroke.[73,74]
patients with 70–99% stenosis was 28.9% (95% CI In a randomised, double-blind trial conducted in
12.9, 44.9) in those ≥75 years of age, 15.1% (95% middle-aged (mean age 63 years) patients with prior
CI 7.2, 23) in those 65–74 years of age and 9.7% history of stroke or TIA, no difference in stroke was
(95% CI 1.5, 17.9) in those <65 years of age. Among seen in patients receiving aspirin (325 mg/day) com-
patients with 50–69% stenosis, the absolute risk pared with those taking warfarin (target INR
reduction was significant only in those ≥75 years of 1.4–2.8). However, minor bleeding was significant-
age. The absolute risk reduction was 17.3% (95% CI ly more frequent in the warfarin group than in the
6.6, 28) versus 5.3% (95% CI 0.1, 10.7) in those aspirin group (RR 1.51; 95% CI 1.22, 1.87).[75]
65–74 years of age and –1.2% (95% CI 7.1 4.7) in Similar conclusions were reported in a recent Coch-
those <65 years of age. rane review[76] that evaluated studies comparing me-

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
Prevention of Cardiovascular Events in Elderly People 867

dium-intensity anticoagulation with warfarin (target with 473 events in 2913 persons who received pla-
INR 2.1–3.6) and antiplatelet agents for secondary cebo (RR 0.85; 95% CI 0.74, 0.97; p = 0.014). The
prevention of stroke. In these trials, the effects by combined endpoint of coronary heart disease death
age group were not detailed, but because haemor- and nonfatal myocardial infarction risk was also
rhagic complications of warfarin therapy are known reduced (RR 0.81; 95% CI 0.69, 0.94; p = 0.006).
to increase with age, aspirin appears to be more Similarly, in the Heart Protection Study, which
appropriate than warfarin for secondary prevention included 20 536 individuals 40–80 years of age,
of nonembolic stroke in the elderly. simvastatin was found to produce a highly signifi-
Moreover, as indicated in the previous section, cant proportional reduction in the incidence of first
antiplatelet agents were found to be effective in nonfatal myocardial infarction or coronary death in
preventing stroke in asymptomatic patients with treated patients (27% reduction; 95% CI 21, 33;
carotid stenosis <70% and might represent the main p < 0.0001). As mentioned previously, the risk re-
treatment for elderly patients with carotid stenosis duction in vascular disease in this trial was similar in
>70% who are either ineligible for or refuse surgery. subjects ≥70 years of age compared with younger
patients.[60]
Prevention of Coronary Heart Disease in Statins appear to act by exerting a plaque-
Elderly Patients stabilising effect, not only by lowering LDL choles-
terol but also by reducing the level of isoprenoids,
Because of increased life expectancy, coronary
molecules that play an important role in the metabo-
heart disease is an increasing cause of morbidity and
lism of proteins responsible for cell growth.[79,80]
mortality in elderly individuals. Trials in elderly
Statins also have an anti-inflammatory effect and
individuals have shown that treatment of hyperten-
reduce platelet reactivity,[81,82] roles that are addi-
sion and use of antithrombotic agents, β-adre-
tional to their antiatherosclerotic effect.
noceptor antagonists, ACE inhibitors and statins
plays important roles in the primary and secondary
Antithrombotic Therapy for Prevention of
prevention of ischaemic heart disease.
Ischaemic Heart Disease in the Elderly
Treatment of Dyslipidaemia
Platelet activation and thrombin generation are
The causal role of elevated serum cholesterol in the key mechanisms in the pathogenesis of acute
the pathogenesis of atherosclerosis and its clinical coronary syndromes, and antithrombotic therapy is
complications is well established. Moreover, reduc- therefore a cornerstone in their prevention.[83]
ing serum cholesterol with statins has been shown to Inhibition of platelet aggregation by aspirin has
significantly reduce mortality and morbidity from been found to be effective for preventing myocardial
cardiovascular disease in randomised, controlled infarction and cardiovascular death, especially in
primary and secondary prevention trials.[56,77,78] Tri- postinfarction patients and in those with coronary
als conducted on elderly subjects have focused only heart disease.[71] Moreover, aspirin has also been
on secondary prevention. The PROSPER study that found to be effective in the secondary prevention of
included 5804 vascular patients between 70 and 82 vascular events in subjects with vascular disease
years of age showed that statin therapy significantly and/or hypertension.[72,73]
reduced risk of death by coronary heart disease.[59] In the Antiplatelet Trialists Collaboration meta-
In this study, pravastatin lowered low-density lipo- analysis,[72] there was a 27% reduction in cardiovas-
protein (LDL) cholesterol by 34% and also reduced cular complications (myocardial infarction, stroke
the incidence of the primary endpoint (composite of and vascular deaths) in aspirin-treated versus non-
coronary death, nonfatal myocardial infarction and treated patients and the secondary prevention risk
fatal or nonfatal stroke) to 408 events in 2891 treated reduction was similar in middle- as well as old-aged
persons between 70 and 82 years of age compared individuals.

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
868 Andrawes et al.

Similarly, long-term oral anticoagulation with coronary artery disease, stroke, peripheral vascular
warfarin alone or in association with aspirin was disease, diabetes, hypercholesterolaemia, cigarette
found to reduce cardiovascular events in postinfarc- smoking, hypertension or documented microalbu-
tion patients <75 years of age compared with treat- minuria. This trial showed that ramipril significantly
ment with aspirin alone (203 events/1216 [16.7%] reduced the incidence of myocardial infarction (RR
warfarin-treated patients versus 181 events/1208 0.8; 95% CI 0.7, 0.9; p < 0.001) compared with
[14.2%] aspirin- and warfarin-treated patients and placebo in these high-risk patients. Interestingly,
241 events/1206 [20%] aspirin-treated patients). subgroup analysis revealed a similar or even greater
However, use of warfarin is very restricted because risk reduction in subjects >65 years of age compared
of numerous food-drug interactions and the high risk with younger patients included in this study. More-
of bleeding when combined with aspirin.[84] over, ACE inhibitors have been proven to be effec-
Ximelagatran has been shown to be effective in tive in postinfarction patients for reducing the risk of
preventing death, nonfatal myocardial infarction and cardiovascular death and events, including re-infarc-
severe recurrent ischaemia in post-infarction pa- tion.[28] Similarly, use of enalapril reduced mortality
tients with a mean age of 69 years.[85] To our knowl- and morbidity among 4228 patients with a mean age
edge, age subgroup analyses of this study have not of 59.1 years, asymptomatic left ventricular dys-
been published. function and a history of ischaemic heart disease,
hypertension, diabetes and cigarette smoking in-
Role of β-Adrenoceptor Antagonists and cluded in the Studies of Left Ventricular Dysfunc-
ACE Inhibitors for Prevention of Coronary tion trials.[91] There was a marked reduction in the
Heart Disease in the Elderly risk of myocardial infarction (RR 23%; 95% CI 11,
34; p < 0.001) and unstable angina (RR 20%; 95%
The risk of death in elderly subjects surviving CI 9, 29; p < 0.001). Cardiac deaths also decreased
myocardial infarction is considerably diminished by (p < 0.03). Other ACE inhibitors have shown simi-
administration of β-adrenoceptor antagonists. In pa- lar effects.[92]
tients 65–75 years of age included in a randomised, Shilpak et al.[87] have confirmed the beneficial
multicentre study with a mean follow-up of 17 effect of β-adrenoceptor antagonists and ACE inhib-
months after infarction,[86] there were 52 deaths itors on survival in elderly post-infarction patients.
among the 348 patients administered timolol versus These investigators found a lower adjusted 1-year
83 in the 384 patients who received placebo mortality for patients treated with ACE inhibitors
(p < 0.05). Moreover, there were 38 reinfarctions in (HR 0.80; 95% CI 0.73, 0.87) or β-adrenoceptor
the treated group versus 69 in the nontreated group antagonists (HR 0.76; 95% CI 0.64, 0.90) than for
(p < 0.01). Age subgroup analysis in this study patients who received no medication. The combina-
showed that the effect of β-adrenoceptor antagonists tion of these two drugs offered a greater benefit over
was similar in patients <65 years of age and those the use of either medication alone (HR 0.68; 95% CI
≥65 years of age. Other randomised studies also 0.59, 0.80).
concluded that there are favourable effects with use
of β-adrenoceptor antagonists in elderly subjects Hormonal Therapy in Elderly Women and
surviving myocardial infarction.[87,88] Despite these Prevention of Coronary Heart Disease
results, several studies have reported underutilisa-
tion of this therapeutic class as secondary prevention Hormone replacement therapy has been used es-
in this group of patients.[89,90] sentially to treat climacteric symptoms, such as vas-
Similarly, ACE inhibitors have been found to omotor symptoms and vulvovaginal atrophy, and to
prevent coronary events in high-risk individuals. prevent osteoporosis related to menopause.
The HOPE study[28] was conducted in 9297 subjects Numerous observational studies have found a
with a mean age of 66 ± 7 years and a history of lower incidence rate of coronary heart disease

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
Prevention of Cardiovascular Events in Elderly People 869

among women using hormonal therapy compared trolled trials show that antihypertensive strategies
with nonusers. One of the largest cohort studies, the that include diuretics, β-adrenoceptor antagonists or
Nurses’ Health study, found that hormone replace- ACE inhibitors as first-line strategies significantly
ment therapy reduced cardiovascular events.[93] reduce the incidence of heart failure.[18,22,27,99] In the
Among 48 470 menopausal women between 30 and small number of studies that have compared differ-
63 years of age followed for 10 years, major corona- ent antihypertensive strategies in the prevention of
ry events were significantly lower in hormone re- heart failure, diuretics were more effective than α-
placement therapy users (RR 0.56; 95% CI 0.40, adrenoceptor antagonists, calcium channel antago-
0.80; p < 0.0001) than in nonusers. However, after nists and even ACE inhibitors.[98,100]
taking into account women’s socioeconomic status Heart failure is a preventable disease also in
in multivariate analysis, it was concluded that the normotensive elderly subjects. Interestingly, the
benefits of hormone replacement therapy on corona- HOPE trial[101] showed that the ACE inhibitor
ry heart disease were not significant. In fact, ramipril is capable of reducing the incidence of heart
randomised studies conducted in women with coro- failure in patients at high risk for cardiovascular
nary heart disease (HERS [Heart and Estrogen/Pro- events (figure 2), and this effect was found to be
gestin Replacement Therapy] I and II) and in independent of hypertension or left ventricular dys-
healthy women not only demonstrated the lack of function.
benefits of hormone replacement therapy on corona- Influenza vaccination also seems to be an effec-
ry heart disease but also found an unexpected in- tive way of preventing hospitalisation for heart fail-
crease in the incidence of ischaemic events, espe- ure and other cardiac reasons in the elderly. This
cially during the first year of treatment.[94,95] Howev- was supported by the cohort study of Nichol et
er, it should be noted that in these trials, hormonal al.,[102] who investigated the association between
therapy consisted of conjugated estrogen and influenza vaccination during the 1998–1999 and
methylprogesterone acetate. Thus, the conclusions 1999–2000 seasons and the risk of hospitalisation
of these studies cannot be extrapolated to use of for heart disease in elderly subjects. They found that
other types of hormone replacement therapy, partic- there was a significant reduction in hospitalisation
ularly transdermal estrogen and microdose proges- for congestive heart failure during both influenza
terone, which have rather different cardiovascular seasons (odds ratio [OR] 0.81 and 0.73, respective-
and metabolic effects than those of hormone re- ly; p < 0.001). It should be noted that this effect was
placement therapy regimens used in these tri- also demonstrated in subjects with no major medical
als.[96,97] Nevertheless, hormone replacement ther- conditions at baseline.
apy is currently no longer considered appropriate for
cardiovascular prevention in elderly women. Lifestyle Modification for the Prevention
of Cardiovascular Disease in the Elderly
Prevention of Heart Failure in the Elderly
Smoking, physical activity and diet are the main
lifestyle habits related to cardiovascular health in
Several studies support the concept that heart
elderly.
failure is a preventable disease in the elderly. Meta-
analysis of trials of hypertensive elderly subjects Benefits of Smoking Cessation in the Elderly
found a significant risk reduction with active treat-
ment compared with placebo (RR 0.60; 95% CI Several studies ascertained the noxious effects of
0.49, 0.74).[98] A meta-analysis analysing outcomes smoking in the elderly. For example, LaCroix et
of hypertensive patients ≥80 years of age in con- al.[103] prospectively examined the relationship be-
trolled trials confirmed that antihypertensive treat- tween cigarette-smoking habits and mortality from
ment significantly diminished the risk of heart fail- all causes, cardiovascular causes, and cancer among
ure (RR 0.58; 95% CI 0.37, 0.83).[34] Placebo-con- 7178 persons ≥65 years of age without a history of

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
870 Andrawes et al.

a Placebo
100
Ramipril
Contrary to false beliefs, smoking-cessation
counselling can be effective in elderly subjects. Dale
−21.8 −22.5
80 et al.[106] reported a 24.8% 6-month abstinence rate
Relative risk (%)

after counselling 313 patients 65–82 years of age

60
with nicotine dependence. Similarly, in a study of
40
1070 non-institutionalised male and female smokers
65–74 years of age, Orleans et al.[107] implemented a
20 programme of smoking cessation with transdermal
nicotine patch and reported a 29% 6-month absti-
0 nence rate. These encouraging results seem better
b than the abstinence rates reported in middle-aged
160
individuals (up to approximately 18.5%).[108] How-
(events per 1000 patient-years)

140 ever, to date, no large-scale study has assessed the

120 effects of a smoking cessation programme on car-
−31
Absolute risk

100 diovascular mortality in the elderly. In our view,

80 −19 smoking cessation should be widely recommended
60 to elderly smokers, even to those with nicotine de-
40 pendence.
20
0 Beneficial Cardiovascular Effects of Physical
<65 years ≥65 years Activity in the Elderly
Fig. 2. (a) Relative and (b) absolute risk of heart failure in patients
<65 years of age or ≥65 years of age in the Heart Outcomes Several large-scale epidemiological studies have
Prevention Evaluation trial.[101] Although the relative risk reductions
were very similar in subjects <65 years of age compared with older
reported that elderly individuals partaking in regular
subjects, the number of cardiovascular events avoided was much physical activity have better cardiovascular out-
greater in the latter group. comes than age-matched sedentary individu-
als.[109-112] Studies have also examined outcomes in
myocardial infarction, stroke or cancer. These in- elderly subjects who have changed their physical
vestigators found that current smokers had higher activity habits. Wannamethee et al.[113] measured the
rates of cardiovascular mortality than those who had effects of physical activity on all-cause mortality
never smoked (figure 3) [adjusted for age and com- and major cardiovascular events during 4-year fol-
munity, RR 2.0 (95% CI 1.4, 2.9) for men and RR low-up in 4311 men without a history of coronary
1.6 (95% CI 1.1, 2.3) for women].[103] A study artery disease and a mean age of 63 years. In the
conducted in 2030 Chinese subjects ≥70 years of inactive/occasionally active, light, moderate and
age[104] with a mean follow-up of 36 months found moderately vigorous/vigorous activity groups, the
an elevated risk of all-cause mortality among current mortality rates per 1000 person-years were 18.5,
smokers, both in males (RR 1.4; 95% CI 0.9, 1.9) 11.4, 7.3 and 9.1, respectively (adjusted RR 1.00;
and females (RR 1.6; 95% CI 1.0, 2.5). Similar 0.61 [95% CI 0.48, 0.86]; 0.50 [95% CI 0.31, 0.79];
conclusions were obtained in a prospective French 0.65 [95% CI 0.45, 0.94]). Men who were sedentary
cohort study among 2786 subjects ≥65 years of and who began at least light activity during follow-
age.[105] The risk of mortality was similar in never up had significantly lower all-cause mortality than
smokers and former smokers who had stopped 20 those who remained sedentary. Physical activity was
years previously (figure 3), confirming what has associated with lower cardiovascular (RR 0.66 [95%
already been found by other investigators.[103] This CI 0.35, 1.23]) and noncardiovascular mortality (RR
point emphasises the importance of smoking cessa- 0.48 [95% CI 0.27, 0.85]) than inactivity. In another
tion, regardless of age. study, the 811 sedentary women with a mean age of

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
Prevention of Cardiovascular Events in Elderly People 871

75.9 years who became active had a significantly sumers.[121] Also, the Mediterranean diet which
lower mortality rate from cardiovascular causes than combines several of these dietary patterns has been
the 2198 women who remained sedentary (HR 0.64; found to be associated with lower cardiovascular
95% CI 0.42, 0.97).[114] Similarly, Schnohr et al.[115] mortality in the elderly (HR 0.71; 95% CI 0.58,
found that among 7023 healthy subjects 20–79 years 0.88).[122] Interestingly, the effect of this healthy diet
of age in Denmark, those who increased their lei- pattern on cardiovascular outcomes seems indepen-
sure-time physical activity from low to moderate dent of other healthy lifestyle factors such as physi-
had a significantly lower risk of death than those cal activity, nonsmoking habits and moderate alco-
reporting low physical activity at both examinations hol consumption and a dose-effect type relationship
(RR 0.64; 95% CI 0.49, 0.83 in men; RR 0.75; 95% was found between the number of healthy lifestyle
CI 0.57, 0.97 in women). Exercise programmes per- patterns and cardiovascular risk reduction (figure 4).
formed in elderly subjects have been shown to be Moderate alcohol consumption has been found to
associated with improvements in functional capaci- be protective against coronary atherosclerosis in
ty, percent body fat, body mass index and serum middle-aged women.[123] In the Healthy Ageing: a
lipids, and these changes are comparable to those Longitudinal Study in Europe project, moderate al-
seen in younger subjects.[116-118] Even if intervention cohol consumption in elderly subjects was associat-
trials showing a clear-cut reduction in cardiovascu- ed with a lower incidence of all-cause and coronary
lar events are lacking, moderate and regular physical heart disease mortality compared with noncon-
activity should be widely recommended to elderly sumers.[122]
sedentary individuals. A salt-restricted diet has consistently been found
to diminish blood pressure in the elderly. However,
Effects of Diet on Cardiovascular Health in the blood pressure lowering effect is small and no
the Elderly impact of salt restriction on the incidence rate of
cardiovascular disease has been demonstrated.[124]
Diet has also been recognised as a significant Even if intervention trials investigating the ef-
environmental factor related to cardiovascular fects of dietary modification in the elderly are lack-
health. Observational studies have shown that in ing, we think that sufficient data are available to
elderly subjects, consumption of vegetables, fruits, recommend the Mediterranean-type diet, rich in
cereals[119] and unfried fish[120] are associated with vegetable and fruits, to elderly individuals in order
better cardiovascular outcomes than in noncon- to prevent cardiovascular events. In addition, mod-
erate alcohol consumption should not be forbidden
Global mortality rate (per 1000 patient-years)

140 Nonsmokers
in elderly people without specific alcohol-related
Former smokers
120 Current smokers
problems.

100
Perspectives
80
Cardiovascular prevention is not only important
60 in middle-aged patients but must be implemented in
the continually expanding population of elderly sub-
40
jects who are at a more advanced stage of athero-
20 sclerosis. An increasing number of investigators are
including elderly patients in studies and demonstrat-
0
65–69 70–74 ≥75 ing the benefits of different preventive strategies,
Age group (years) until now limited to middle-aged individuals, in this
Fig. 3. Mortality rates among 7678 individuals ≥65 years of age by particular group. The beneficial effects of cardiovas-
smoking status[103] cular prevention are strikingly apparent when the

 2005 Adis Data Information BV. All rights reserved. Drugs Aging 2005; 22 (10)
872 Andrawes et al.

Healthful lifestyle factor score

4
and ACE inhibitors[129] are underused in elderly
3 patients, especially by those with a history of myo-
2 cardial infarction despite the important need for
1.0 0 to 1 cardiovascular prevention in this setting.
In conclusion, we believe that cardiovascular
0.8 prevention should be more widely implemented in
the elderly, including subjects ≥75 years of age, and
Survival probability

0.6 that this might contribute to improved health status

and quality of life in this growing segment of the
0.4 population.

0.2 Acknowledgements
No sources of funding were used to assist in the prepara-
0.0 tion of this study. The authors have no conflicts of interest
0 1 2 3 4 5 6 7 8 9 10 that are directly relevant to the content of this study.
Time (years)
No. at risk factor score
4 437 433 426 415 406 392 376 360 337 267 192
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