Hypercholesterolemia Predicts Early Death from Coronary Heart Disease in Elderly Men but Not Women The Ranch0 Bernard0
Study
Elizabeth Barrett-Connor,
MD
In a 3-year follow-up study of 761 elderly men and 983 elderly women, total plasma cholesterol levelspredictedfatal coronary heart disease (CHD) m men but not women. Low-density lipoprotein level was no better a predictor of fatal CHD than total cholesterol in either sex. Women had higher levels of high-densitylipoprotein than men, which explains most of their usual higher total cholesterol levels. These data suggest that cholesterol screening of elderly women would have little value without a lipoprotein evaluation. Ann Epidemiol I992;2:77-83. KEY
WORDS:
Cholesterol,
screening, coronary heart disease, geriatrics.
INTRODUCTION There is a strong linear relation between total plasma cholesterol coronary artery disease in middle-aged men (1). Whether older men and women has received less attention. Task Force on Cholesterol
level and the risk of
there is a similar relation in
The American
Heart Association
Issues (2) recently noted the paucity of data to answer the
question, “Should age or gender change the approach to cholesterol management?” This may explain why the adult treatment panel report (3) did not address the screening or management
of hypercholesterolemia
in older adults in any detail. Because plasma
cholesterol levels increase with age, the application of National Cholesterol Education Program (NCEP) guidelines (4) could result in the treatment of a sizable proportion of older Americans. As noted by Denke and Grundy (S), this implies increased individual and total health care costs, and highlights the need for more information. Few studies have measured the short-term
implications
of lipid and lipoprotein
levels in the elderly of both sexes from the same cohort. In this article I report death rates that occurred within 3 years after measurement of lipid and lipoprotein levels in a population-based
study of men and women whose average age was 75 years.
METHODS Between 1984 and 1987, all surviving members of the previously characterized Ranch0 Bernard0 cohort (6), an upper-middle-class, white community in southern California, were invited to participate in a study of diabetes and its vascular complications in older adults. Eighty percent of survivors of the original cohort visited the clinic in the morning after a 12-hour fast for an oral glucose tolerance test and other evaluations. At the time of the visit, a medical history, including information on medication use San Diego, La Jolla, CA. Address reprint requests to: Elizabeth Barrett-Connor, MD, Department of Community and Family Medicine, M-0607, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0607. Received November 28. 1990; revised May 8, 1991.
From the Department of Community and Family Medicine, University of California,
0
1992ElsevierScience PublishingCo., Inc.
1047s2797/92/$03.50
78
TABLE
Barrett-Connor CHOLESTEROL
1
Ranch0
AND CORONARY
AEP Vol. 2, No. 1/Z .fanuary/March 1992: 77-83
HEART DISEASE IN ELDERLY
Bernard0 Study, 1984-1987,
cohort characteristics
(age 65-89)
Men Number Mean age (y) Mean systolic blood pressure
761 75.7 144.6
(mm Hg) Mean cholesterol (mmol/L) Mean triglycerides (mmol/L) Mean HDL (mmol/L) Mean LDL (mmol/L) % Smokers % Estrogen replacement % Known cardiovascular disease
Women 938 74.8 145.1
( 5.8) (20.4)
( ( 1.40 ( 3.38 ( 5.38 1.33
1.03) .95)
( 5.7) (21.0)
5.93 1.33 1.77 3.57 11.4 25.2 16.0
.4l) .93)
7.4 _ 23.0
( ( ( (
1.04) .77) .49) 1.01)
a Values in parenthesesare standarddevmions
and cigarette-smoking
habit, was determined by standardized interview. Blood pressure
was measured using a standard protocol in seated subjects. Lipid and lipoprotein
levels
were measured in a Centers for Disease Control (CDC) certified laboratory. Total cholesterol and triglyceride levels were measured by enzymatic techniques using an ABA-200
biochromatic
lipoprotein
(HDL)
analyzer (Abbott
cholesterol
Laboratories,
Irving,
was measured by precipitating
TX).
High-density-
the other lipoproteins
with heparin and manganese chloride according to the standard Lipid Research Clinic (LRC)
protocol
(7). Low-density-lipoprotein
(LDL)
cholesterol
was estimated using
the Friedwald formula (8). Vital status was determined
to 1990 in 100% of subjects and death certificates
were obtained for all decedents and coded for underlying cause of death by a certified nosologist using the ninth revision of the International Classification of Diseases (ICD9): coronary
heart disease (CHD)
deaths were those coded 410-414.
This
article
describes 3-year mortality rates in those aged 65 to 89; only three persons less than 65 years old died from CHD. The sex-specific distribution of lipid and lipoprotein quintiles in Ranch0 was compared with the quintiles of distribution
from all LRCs combined
Bernard0 (9). Rates
and relative risks of death from CHD were calculated
by these lipid and lipoprotein
quintiles,
Sex-specific
and by NCEP cutpoints for total cholesterol.
relative risks were
also estimated after adjusting for age and other heart disease risk factors using a Cox proportional hazards model (10). All P values were based on two-tailed tests of significance.
RESULTS
There were 761 male and 938 female participants 65 to 89 years old in the 1984 to 1987 visit who had complete lipid data. As shown in Table 1, members of this older population had relatively good profiles for heart disease risk factors, with few current cigarette smokers, an average systolic blood pressure of 145 mm Hg, and average total cholesterol levels well below 6.21 mmol/L. Compared to men, women had higher mean levels of total, LDL, and HDL cholesterol and similar average triglyceride values (see Table 1). As shown graphically in Figure 1, the distribution of all lipids and lipoproteins was shifted to the right in women, with HDL showing the most striking difference between the genders.
AEP Vol. 2, No. 112 January/March 1992:77-83
CHOLESTEROL
AND CORONARY
Barrett-Connor HEART DISEASE IN ELDERLY
Cholesterolmmol/L
Triglycerides mmol/L
LDLrmlOl/L
FIGURE
79
HDLmmol/L
1 Distribution of lipids and lipoproteins by sex in the Ranch0 Bernard0 cohort, 1984 to 1987.
65 to 89,
aged
Table 2 shows the gender-specific CHD death rates over the next 3 years. As expected, men had approximately twice the CHD death rate as women. Even in this healthy older cohort,
23% of men and 16% of women had known CHD,
based on a
history of heart attack, angina pectoris, or coronary artery surgery. Over half the CHD deaths in men and 30% of the CHD deaths in women occurred in those with known cardiovascular Compared
disease. to data from men and women aged 20 to 69 in ten North American
LRCs, Ranch0 Bernard0 men had lower and women had higher total cholesterol
levels.
This difference largely reflected the higher HDL levels in the Ranch0 Bernard0 women, since the LDL distribution did not differ systematically whole. Figure 2 shows CHD mortality by collaborative and lipoprotein
TABLE
2
for all Ranch0
Bernard0
CHD deaths in Ranch0
Bernard0 n
Men All Without CVD Women All Without CVD CVD = Cardiovasculardisease.
participants.
elderly,
from that of the LRCs as a LRC quintile of each lipid Higher levels of total or LDL
1984-1987 n Deaths
to 1990 90 Deaths
761 584
36 15
4.7 2.6
983 816
29 14
2.0 1.7
80
AEP Vol. 2, No. II2 January/March 1992:77-83
Barrett-Connor
CHOLESTEROL AND CORONARY HEART DISEASE IN ELDERLY
4.0 3.5
3
$
2.5 3.0
g
2.0
i$
s!
1.5
Y
I
ii 1.0 0.5
2
1
A 0
0.0 1
2
3
4
QuinttIe Cholesterol
!i -
Quint&
4.0
Triglycerides
10
3.5
6
3.0 3 E? 2.5 g 2
2.0 1.5
a”
1.0
6 P a ,Y
4
ii
2
0.5
Relative risk of CHD by quintile of lipids and lipoproteins Ranch0 Bemardo, aged 65 to 89, 1984 to 1987.
FIGURE 2
cholesterol
showed
a strong
relation
in men and women in
to CHD risk in men but not in women.
HDL was
inversely associated with CHD only in women, and only those in the lowest quintile of HDL distribution (5 1 .Ol mmol/L or 39 mg/dL) were at increased risk. Fatal CHD was also associated with higher triglyceride both sexes in the fourth quintile. These associations were examined each lipid or lipoprotein
levels, with the highest risk occurring
in a Cox proportional
value was entered
separately,
in
hazards model in which
adjusting
for age, current
cigarette smoking, systolic blood pressure, and estrogen use (in women). As shown in Table 3. for each .26-mmol/L increment in total cholesterol in men there was a small
TABLE 3 Bernard0
Relative hazards” for death from CHD in men and women aged 65-89, 1984-1987 to 1990 Men
Ranch0
Women
Cholesterol
l.llb
1.00
LDL HDL
1.120
1.02
1.09
1.24
Tnglycerides
1.03‘
1.03
” Relative halard, adjusted (GM model) fw age, sy~ol~c blood pressure, current smoking stxus. and estrogen replacement therapy (in women), by .26-mmol/L mcrement m cholestcml, LDL, and triglyceride, OT .26-mmoliL decrement in HDL. h I’ = ,005.
LP < .05.
81
Barrett-Connor CHOLESTEROL AND CORONARY HEART DISEASE IN ELDERLY
AEP Vol. 2, No. J/2 January/March 1992:77-83
TABLE 4 Relative risk for fatal CHD after age 65 by National Cholesterol Program cholesterol levels: Ranch0 Bernardo, 1984-1987 to 1990 Cholesterol
Education
Men
(mmol/L)
5 5.15 5.17-6.18 2 6.21
Women
1.0 2.21 2.71
but highly significant
increased risk of death from CHD.
1.0 .64 .82
In men, LDL values were
similarly predictive,
and triglycerides were also weakly associated with risk, but HDL
was not. In contrast,
in women none of the lipid variables was significantly associated
with CHD risk, and the adjusted hazard ratio for each .26-mmol/L cholesterol
was 1.00. The strongest association
for a. 26-mmol/L decrement significance,
increment
in total
(in either sex) was the 1.24 risk ratio
in HDL in women; this association did not reach statistical
however.
Table 4 shows the value of NCEP guidelines for total cholesterol in predicting short-term risk of fatal CHD in these older men and women. A total plasma cholesterol level of 5. I7 mmol/L or greater was associated with a significant and stepwise increased risk of fatal CHD
in men. No such association
seemed to do slightly (but not significantly)
was observed
in the women,
who
better at higher levels of total cholesterol.
DISCUSSION With
the aging of the US population,
there has been increased interest in the risk
factors for and possible prevention of CHD in the elderly. Surprisingly few prospective studies of CHD risk factors have included both lipids and lipoproteins measured in old men and women from a community In this cohort,
unselected
for health status.
whose average age was 75 years, the NCEP
guidelines predicted
risk of fatal CHD in a stepwise fashion within a very short follow-up period in men, but not in women.
In men, the relative risk associated with a total cholesterol
level
of 6.2 1 mmol/L or greater was increased nearly threefold, and for those in the highest quintile (~6.47 mmol/L or 250 mg/dL) it was nearly fourfold. These risk increments are similar to those found in the Multiple Risk Factor Intervention
Trial (MRFIT)
in
a 6-year follow-up of a large sample of younger men (1). Most of the epidemiologic
studies have found a cholesterol-heart
tion in women, but did not include elderly women with cholesterol
disease associameasured after age
65 (11). Very few elderly women in the Ranch0 Bernard0 cohort died, and of the 20 who died from CHD, one-third were women who had a history of CHD. Although there was insufficient power to be certain that total cholesterol was unrelated to risk, the lack of any pattern by quintile suggests that total cholesterol is not a good measure for potential intervention in old women. This may reflect the fact that in a population with a relatively high HDL level, much of the total cholesterol is HDL. These results resemble the findings in the Donolov-Tel Aviv study (12) where only women with low HDL levels showed an increased risk with higher total cholesterol. As Kuller (13) noted, screening for total plasma cholesterol in older women will entail a greater cost than screening in men, since there are more women with high total cholesterol (and high HDL) who have less disease. In this cohort, LDL cholesterol was no better than total cholesterol as a predictor
82
AEP Vol. 2, No. l/2 JanuaryiMarch1992:77-83
Barrett-Connor
CHOLESTEROL AND CORONARY HEART DISEASE IN ELDERLY
of subsequent CHD in men or women. In Framingham
(14), LDL was a better predictor
of CHD than was total cholesterol in both men and women aged 50 to 75; after age 75, however, the relationship was not stepwise and resembled results in the older Ranch0
Bernard0 cohort.
Both the Framingham
analyses, based on the most recent
lipid measurements before the event, and the present study reflect the short-term to 4 years) predictive value of lipids and lipoproteins.
(2
What do these results mean for the practicing physician? Studies in middle-aged men have clearly shown that improving (15,
16). Theoretically,
the lipid profile reduces the risk of CHD
the same result would occur in the elderly unless (a) their
atherosclerosis is too far advanced to be impacted, or (b) diet or medication work differently or have more untoward effects in the elderly. Only clinical trials can completely address this issue. The American
Heart Association
Task Force (2) recom-
mended a less aggressive approach to dietary restriction and drug therapy in the elderly, and stressed that NCEP and American Heart Association guidelines leave room for clinical judgment, not compromise
particularly in the elderly. For the present, a prudent diet that does overall
nutrition
can be recommended
and may prevent
chronic diseases ( 17). At what age should the elderly no longer be screened for cholesterol? and Kwiterovich
(18) recommended
healthy active persons. Screening
screening
and treatment
age group already subject to malnutrition one favors screening for cholesterol based on chronologic
through
several Kafonek
75 years of age in otherwise
do entail some potential
and polypharmacy.
risks in an
On the other hand, if
in younger individuals, failure to screen the elderly
age alone may be viewed as ageist, assigning a limited value (or
limited potential for change)
to persons over some arbitrarily defined (and constantly
redefined) age limit (5). Just as the label “elderly” seems more or less appropriate for different individuals, the decision to test for or treat cholesterol
in older adults should
be based on the apparent years of quality life remaining. Although the relative risk or risk ratio associated with hyperlipidemia decreases with age, the absolute risk is much higher because older persons of either sex are so much more likely to have a CHD benefited by reduction
in cholesterol
event.
The number
the present
study is limited only to CHD
intervention
in older ages, clinical manifestations
Prevention
of old persons potentially
is therefore great (19). death.
It should be noted that
Even if life is not extended
by
of CHD may nevertheless be delayed.
of new onset or progression of CHD theoretically
could improve the quality
of life if not the life span.
REFERENCES 1. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356 222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT), JAMA. 1986;256:2823-8. 2. Task Force on Cholesterol Issues, American Heart Association. AHA medical/ scientific statement. Special report. The cholesterol facts. A summary of the evidence relating dietary fats, serum cholesterol, and coronary heart disease. A joint statement by the American Heart Association and the National Heart, Lung, and Blood Institute, Circulation. 1990;81:1721-33. 3. evaluation Med.
Report
of the National
and treatment
1988; 148:36-69.
Cholesterol
Education
of high blood cholesterol
Program expert panel on detection,
in adults. The expert panel,
Arch
Intern
AEP Vol. 2, No. 112
4.
Lenfant
Program,
C.
A new challenge
Circulation.
5.
Denke
treatment 6.
MA,
Criqui
Grundy
SM.
Ann Intern
The
Hypercholesterolemia
Med.
M, Barrett-Connor
in
for America:
National
Cholesterol
Education
1986;73:855-6.
dilemma,
respondents
83
Barrett-Connor AND CORONARY HEART DISEASE IN ELDERLY
CHOLESTEROL
January/March 1992:77-83
a
population
in elderly persons:
Resolving
the
1990;112:780-92. E, Austin
M. Differences
cardiovascular
based
between
disease
respondents
study,
Am
J
andnon-
Epidemiol.
1978;108:367-72. 7.
Lipid Research
Lipoprotein Health,
Analysis.
Education, 8.
Program. Manual of Laboratory DC: US Government
and Welfare
Friedwald
WJ,
density lipoprotein Chem.
Clinics
Washington,
Publication
No. (NIH)
Levy RI, Fredrickson
cholesterol
DS.
in plasma without
Operations.
Printing Office; 75-628,
Estimation
vol. 1. Lipid and
1974. Department
of
2nd ed. of the concentration
use of the preparative
of low-
ultracentrifuge,
Clin
1972;18:459-502. 9.
Benfante
R, Reed D. Is elevated
heart disease in the elderly?, 10.
JAMA.
serum cholesterol
Cox DR, Oakes D. Analysis of Survival
Probability. 11.
London:
Chapman
and Hall;
12.
Brunner
1988;34:B60-B70.
D, Weisbort
J, Meshulamn,
lipoprotein
Twenty-year
follow-up
Am J Cardiol. 13.
cholesterol
of the Donolov-Tel
lipoproteins,
N et al. Relation
percentage
in Statistics
and Applied
11.
E. Cholesterol,
Clin Chem.
high-density
Data. Monographs
1984:91-l
Bush TL, Fried LP, Barrett-Connor
disease in women,
level a risk factor for coronary
1990;263:393-6.
of serum total cholesterol
to the incidence
Aviv Prospective
and coronary heart
of definite
Coronary
coronary
Artery
and
events:
Disease Study,
1987;59:1271-6.
Kuller LH. Are risk factors for CHD
the same at different
ages, J Clin Epidemiol.
1989;42:91-3. 14. elderly,
Castelli
WP,
Am J Cardiol.
15.
Wilson
The Lipid Research
Prevention
Trial
WF,
Levy D, Anderson
K. Cardiovascular
risk factors
in the
1989;63:12H-19H.
results.
I.
Clinics
Program. The Lipid Research
Reduction
in
incidence
Clinics
of coronary
heart
Coronary
Primary
disease,
JAMA.
1984;251:351-64. 16.
Frick MH, Eli 0,
gemfibrozil 17.
in middle-aged National
Implications
Haapa K, et al. Helsinki men with dyslipidemia,
Research
for Reducing
Council,
Chronic
Heart Study: Primary prevention N Engl J Med.
Committee
Disease Risk.
on Diet Washington,
trial with
1987;317:1237-45.
and Health. DC: National
Diet
and Health.
Academy
Press;
1989. 18. Ann Intern 19.
Kafonek Med. Malenka
patient-specific
SD,
Kwiterovich
PO. Treatment
of hypercholesterolemia
in the elderly,
1990; 112:723-5. DJ, Baron JA. Cholesterol
attributable
risk, Arch Intern
and coronary Med.
heart disease. The importance
1988;148:2247-52.
of
Study
Elizabeth Barrett-Connor,
MD
In a 3-year follow-up study of 761 elderly men and 983 elderly women, total plasma cholesterol levelspredictedfatal coronary heart disease (CHD) m men but not women. Low-density lipoprotein level was no better a predictor of fatal CHD than total cholesterol in either sex. Women had higher levels of high-densitylipoprotein than men, which explains most of their usual higher total cholesterol levels. These data suggest that cholesterol screening of elderly women would have little value without a lipoprotein evaluation. Ann Epidemiol I992;2:77-83. KEY
WORDS:
Cholesterol,
screening, coronary heart disease, geriatrics.
INTRODUCTION There is a strong linear relation between total plasma cholesterol coronary artery disease in middle-aged men (1). Whether older men and women has received less attention. Task Force on Cholesterol
level and the risk of
there is a similar relation in
The American
Heart Association
Issues (2) recently noted the paucity of data to answer the
question, “Should age or gender change the approach to cholesterol management?” This may explain why the adult treatment panel report (3) did not address the screening or management
of hypercholesterolemia
in older adults in any detail. Because plasma
cholesterol levels increase with age, the application of National Cholesterol Education Program (NCEP) guidelines (4) could result in the treatment of a sizable proportion of older Americans. As noted by Denke and Grundy (S), this implies increased individual and total health care costs, and highlights the need for more information. Few studies have measured the short-term
implications
of lipid and lipoprotein
levels in the elderly of both sexes from the same cohort. In this article I report death rates that occurred within 3 years after measurement of lipid and lipoprotein levels in a population-based
study of men and women whose average age was 75 years.
METHODS Between 1984 and 1987, all surviving members of the previously characterized Ranch0 Bernard0 cohort (6), an upper-middle-class, white community in southern California, were invited to participate in a study of diabetes and its vascular complications in older adults. Eighty percent of survivors of the original cohort visited the clinic in the morning after a 12-hour fast for an oral glucose tolerance test and other evaluations. At the time of the visit, a medical history, including information on medication use San Diego, La Jolla, CA. Address reprint requests to: Elizabeth Barrett-Connor, MD, Department of Community and Family Medicine, M-0607, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0607. Received November 28. 1990; revised May 8, 1991.
From the Department of Community and Family Medicine, University of California,
0
1992ElsevierScience PublishingCo., Inc.
1047s2797/92/$03.50
78
TABLE
Barrett-Connor CHOLESTEROL
1
Ranch0
AND CORONARY
AEP Vol. 2, No. 1/Z .fanuary/March 1992: 77-83
HEART DISEASE IN ELDERLY
Bernard0 Study, 1984-1987,
cohort characteristics
(age 65-89)
Men Number Mean age (y) Mean systolic blood pressure
761 75.7 144.6
(mm Hg) Mean cholesterol (mmol/L) Mean triglycerides (mmol/L) Mean HDL (mmol/L) Mean LDL (mmol/L) % Smokers % Estrogen replacement % Known cardiovascular disease
Women 938 74.8 145.1
( 5.8) (20.4)
( ( 1.40 ( 3.38 ( 5.38 1.33
1.03) .95)
( 5.7) (21.0)
5.93 1.33 1.77 3.57 11.4 25.2 16.0
.4l) .93)
7.4 _ 23.0
( ( ( (
1.04) .77) .49) 1.01)
a Values in parenthesesare standarddevmions
and cigarette-smoking
habit, was determined by standardized interview. Blood pressure
was measured using a standard protocol in seated subjects. Lipid and lipoprotein
levels
were measured in a Centers for Disease Control (CDC) certified laboratory. Total cholesterol and triglyceride levels were measured by enzymatic techniques using an ABA-200
biochromatic
lipoprotein
(HDL)
analyzer (Abbott
cholesterol
Laboratories,
Irving,
was measured by precipitating
TX).
High-density-
the other lipoproteins
with heparin and manganese chloride according to the standard Lipid Research Clinic (LRC)
protocol
(7). Low-density-lipoprotein
(LDL)
cholesterol
was estimated using
the Friedwald formula (8). Vital status was determined
to 1990 in 100% of subjects and death certificates
were obtained for all decedents and coded for underlying cause of death by a certified nosologist using the ninth revision of the International Classification of Diseases (ICD9): coronary
heart disease (CHD)
deaths were those coded 410-414.
This
article
describes 3-year mortality rates in those aged 65 to 89; only three persons less than 65 years old died from CHD. The sex-specific distribution of lipid and lipoprotein quintiles in Ranch0 was compared with the quintiles of distribution
from all LRCs combined
Bernard0 (9). Rates
and relative risks of death from CHD were calculated
by these lipid and lipoprotein
quintiles,
Sex-specific
and by NCEP cutpoints for total cholesterol.
relative risks were
also estimated after adjusting for age and other heart disease risk factors using a Cox proportional hazards model (10). All P values were based on two-tailed tests of significance.
RESULTS
There were 761 male and 938 female participants 65 to 89 years old in the 1984 to 1987 visit who had complete lipid data. As shown in Table 1, members of this older population had relatively good profiles for heart disease risk factors, with few current cigarette smokers, an average systolic blood pressure of 145 mm Hg, and average total cholesterol levels well below 6.21 mmol/L. Compared to men, women had higher mean levels of total, LDL, and HDL cholesterol and similar average triglyceride values (see Table 1). As shown graphically in Figure 1, the distribution of all lipids and lipoproteins was shifted to the right in women, with HDL showing the most striking difference between the genders.
AEP Vol. 2, No. 112 January/March 1992:77-83
CHOLESTEROL
AND CORONARY
Barrett-Connor HEART DISEASE IN ELDERLY
Cholesterolmmol/L
Triglycerides mmol/L
LDLrmlOl/L
FIGURE
79
HDLmmol/L
1 Distribution of lipids and lipoproteins by sex in the Ranch0 Bernard0 cohort, 1984 to 1987.
65 to 89,
aged
Table 2 shows the gender-specific CHD death rates over the next 3 years. As expected, men had approximately twice the CHD death rate as women. Even in this healthy older cohort,
23% of men and 16% of women had known CHD,
based on a
history of heart attack, angina pectoris, or coronary artery surgery. Over half the CHD deaths in men and 30% of the CHD deaths in women occurred in those with known cardiovascular Compared
disease. to data from men and women aged 20 to 69 in ten North American
LRCs, Ranch0 Bernard0 men had lower and women had higher total cholesterol
levels.
This difference largely reflected the higher HDL levels in the Ranch0 Bernard0 women, since the LDL distribution did not differ systematically whole. Figure 2 shows CHD mortality by collaborative and lipoprotein
TABLE
2
for all Ranch0
Bernard0
CHD deaths in Ranch0
Bernard0 n
Men All Without CVD Women All Without CVD CVD = Cardiovasculardisease.
participants.
elderly,
from that of the LRCs as a LRC quintile of each lipid Higher levels of total or LDL
1984-1987 n Deaths
to 1990 90 Deaths
761 584
36 15
4.7 2.6
983 816
29 14
2.0 1.7
80
AEP Vol. 2, No. II2 January/March 1992:77-83
Barrett-Connor
CHOLESTEROL AND CORONARY HEART DISEASE IN ELDERLY
4.0 3.5
3
$
2.5 3.0
g
2.0
i$
s!
1.5
Y
I
ii 1.0 0.5
2
1
A 0
0.0 1
2
3
4
QuinttIe Cholesterol
!i -
Quint&
4.0
Triglycerides
10
3.5
6
3.0 3 E? 2.5 g 2
2.0 1.5
a”
1.0
6 P a ,Y
4
ii
2
0.5
Relative risk of CHD by quintile of lipids and lipoproteins Ranch0 Bemardo, aged 65 to 89, 1984 to 1987.
FIGURE 2
cholesterol
showed
a strong
relation
in men and women in
to CHD risk in men but not in women.
HDL was
inversely associated with CHD only in women, and only those in the lowest quintile of HDL distribution (5 1 .Ol mmol/L or 39 mg/dL) were at increased risk. Fatal CHD was also associated with higher triglyceride both sexes in the fourth quintile. These associations were examined each lipid or lipoprotein
levels, with the highest risk occurring
in a Cox proportional
value was entered
separately,
in
hazards model in which
adjusting
for age, current
cigarette smoking, systolic blood pressure, and estrogen use (in women). As shown in Table 3. for each .26-mmol/L increment in total cholesterol in men there was a small
TABLE 3 Bernard0
Relative hazards” for death from CHD in men and women aged 65-89, 1984-1987 to 1990 Men
Ranch0
Women
Cholesterol
l.llb
1.00
LDL HDL
1.120
1.02
1.09
1.24
Tnglycerides
1.03‘
1.03
” Relative halard, adjusted (GM model) fw age, sy~ol~c blood pressure, current smoking stxus. and estrogen replacement therapy (in women), by .26-mmol/L mcrement m cholestcml, LDL, and triglyceride, OT .26-mmoliL decrement in HDL. h I’ = ,005.
LP < .05.
81
Barrett-Connor CHOLESTEROL AND CORONARY HEART DISEASE IN ELDERLY
AEP Vol. 2, No. J/2 January/March 1992:77-83
TABLE 4 Relative risk for fatal CHD after age 65 by National Cholesterol Program cholesterol levels: Ranch0 Bernardo, 1984-1987 to 1990 Cholesterol
Education
Men
(mmol/L)
5 5.15 5.17-6.18 2 6.21
Women
1.0 2.21 2.71
but highly significant
increased risk of death from CHD.
1.0 .64 .82
In men, LDL values were
similarly predictive,
and triglycerides were also weakly associated with risk, but HDL
was not. In contrast,
in women none of the lipid variables was significantly associated
with CHD risk, and the adjusted hazard ratio for each .26-mmol/L cholesterol
was 1.00. The strongest association
for a. 26-mmol/L decrement significance,
increment
in total
(in either sex) was the 1.24 risk ratio
in HDL in women; this association did not reach statistical
however.
Table 4 shows the value of NCEP guidelines for total cholesterol in predicting short-term risk of fatal CHD in these older men and women. A total plasma cholesterol level of 5. I7 mmol/L or greater was associated with a significant and stepwise increased risk of fatal CHD
in men. No such association
seemed to do slightly (but not significantly)
was observed
in the women,
who
better at higher levels of total cholesterol.
DISCUSSION With
the aging of the US population,
there has been increased interest in the risk
factors for and possible prevention of CHD in the elderly. Surprisingly few prospective studies of CHD risk factors have included both lipids and lipoproteins measured in old men and women from a community In this cohort,
unselected
for health status.
whose average age was 75 years, the NCEP
guidelines predicted
risk of fatal CHD in a stepwise fashion within a very short follow-up period in men, but not in women.
In men, the relative risk associated with a total cholesterol
level
of 6.2 1 mmol/L or greater was increased nearly threefold, and for those in the highest quintile (~6.47 mmol/L or 250 mg/dL) it was nearly fourfold. These risk increments are similar to those found in the Multiple Risk Factor Intervention
Trial (MRFIT)
in
a 6-year follow-up of a large sample of younger men (1). Most of the epidemiologic
studies have found a cholesterol-heart
tion in women, but did not include elderly women with cholesterol
disease associameasured after age
65 (11). Very few elderly women in the Ranch0 Bernard0 cohort died, and of the 20 who died from CHD, one-third were women who had a history of CHD. Although there was insufficient power to be certain that total cholesterol was unrelated to risk, the lack of any pattern by quintile suggests that total cholesterol is not a good measure for potential intervention in old women. This may reflect the fact that in a population with a relatively high HDL level, much of the total cholesterol is HDL. These results resemble the findings in the Donolov-Tel Aviv study (12) where only women with low HDL levels showed an increased risk with higher total cholesterol. As Kuller (13) noted, screening for total plasma cholesterol in older women will entail a greater cost than screening in men, since there are more women with high total cholesterol (and high HDL) who have less disease. In this cohort, LDL cholesterol was no better than total cholesterol as a predictor
82
AEP Vol. 2, No. l/2 JanuaryiMarch1992:77-83
Barrett-Connor
CHOLESTEROL AND CORONARY HEART DISEASE IN ELDERLY
of subsequent CHD in men or women. In Framingham
(14), LDL was a better predictor
of CHD than was total cholesterol in both men and women aged 50 to 75; after age 75, however, the relationship was not stepwise and resembled results in the older Ranch0
Bernard0 cohort.
Both the Framingham
analyses, based on the most recent
lipid measurements before the event, and the present study reflect the short-term to 4 years) predictive value of lipids and lipoproteins.
(2
What do these results mean for the practicing physician? Studies in middle-aged men have clearly shown that improving (15,
16). Theoretically,
the lipid profile reduces the risk of CHD
the same result would occur in the elderly unless (a) their
atherosclerosis is too far advanced to be impacted, or (b) diet or medication work differently or have more untoward effects in the elderly. Only clinical trials can completely address this issue. The American
Heart Association
Task Force (2) recom-
mended a less aggressive approach to dietary restriction and drug therapy in the elderly, and stressed that NCEP and American Heart Association guidelines leave room for clinical judgment, not compromise
particularly in the elderly. For the present, a prudent diet that does overall
nutrition
can be recommended
and may prevent
chronic diseases ( 17). At what age should the elderly no longer be screened for cholesterol? and Kwiterovich
(18) recommended
healthy active persons. Screening
screening
and treatment
age group already subject to malnutrition one favors screening for cholesterol based on chronologic
through
several Kafonek
75 years of age in otherwise
do entail some potential
and polypharmacy.
risks in an
On the other hand, if
in younger individuals, failure to screen the elderly
age alone may be viewed as ageist, assigning a limited value (or
limited potential for change)
to persons over some arbitrarily defined (and constantly
redefined) age limit (5). Just as the label “elderly” seems more or less appropriate for different individuals, the decision to test for or treat cholesterol
in older adults should
be based on the apparent years of quality life remaining. Although the relative risk or risk ratio associated with hyperlipidemia decreases with age, the absolute risk is much higher because older persons of either sex are so much more likely to have a CHD benefited by reduction
in cholesterol
event.
The number
the present
study is limited only to CHD
intervention
in older ages, clinical manifestations
Prevention
of old persons potentially
is therefore great (19). death.
It should be noted that
Even if life is not extended
by
of CHD may nevertheless be delayed.
of new onset or progression of CHD theoretically
could improve the quality
of life if not the life span.
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