Sex, Age, Cardiovascular Risk Factors, and
Coronary Heart Disease
A Prospective Follow-Up Study of 14 786 Middle-Aged Men and
Women in Finland
Pekka Jousilahti, MD; Erkki Vartiainen, MD; Jaakko Tuomilehto, MD; Pekka Puska, MD
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Background—Coronary heart disease (CHD) is markedly more common in men than in women. In both sexes, CHD risk
increases with age, but the increase is sharper in women. We analyzed the extent to which major cardiovascular risk
factors can explain the sex difference and the age-related increase in CHD risk.
Methods and Results—The study cohort consists of 14 786 Finnish men and women 25 to 64 years old at baseline. The
following cardiovascular risk factors were determined: smoking, serum total cholesterol, HDL cholesterol, blood
pressure, body mass index, and diabetes. Risk factor measurements were done in 1982 or 1987, and the cohorts were
followed up until the end of 1994. The Cox proportional hazards model was used to assess the relation between risk
factors and CHD risk. CHD incidence in men compared with women was '3 times higher and mortality was '5 times
higher. Most of the risk factors were more favorable in women, but the sex difference in risk factor levels diminished
with increasing age. Differences in risk factors between sexes, particularly in HDL cholesterol and smoking, explained
nearly half of the difference in CHD risk between men and women. Differences in serum total cholesterol level, blood
pressure, body mass index, and diabetes prevalence explained about one-third of the age-related increase in CHD risk
among men and 50% to 60% among women.
Conclusions—Differences in major cardiovascular risk factors explained a substantial part of the sex difference in CHD
risk. An increase in risk factor levels was associated with the age-related increase in CHD incidence and mortality in
both sexes but to a larger extent in women. (Circulation. 1999;99:1165-1172.)
Key Words: aging n epidemiology n coronary disease n sex n risk factors
T
women; (2) the extent to which differences in these risk
factors can explain the sex difference in CHD incidence and
mortality; and (3) how much the changes in the risk factor
levels by aging explain the difference in CHD risk between
age groups.
here is a marked difference in coronary heart disease
(CHD) risk between sexes.1– 8 Among middle-aged people, CHD is 2 to 5 times more common in men than in
women, and this sex ratio varies between populations.8 In
both sexes, the risk of CHD increases markedly with age.1,5,7
Lipid abnormalities, high blood pressure, and smoking are
major risk factors for CHD.9 –15 Obesity and diabetes also
contribute to CHD risk.16 –18 The role of major cardiovascular
risk factors in the development of CHD is well established
among men. Among women, the data are less extensive.
Reasons for the sex difference in CHD risk are not fully
understood. Even though in most populations, cardiovascular
risk factor patterns are more favorable among women than
among men,8 very limited data are available to assess the
extent to which cardiovascular risk factors can explain the
observed sex difference in CHD risk.
The aim of this study was to assess (1) whether the
association of smoking, total cholesterol, HDL cholesterol,
HDL cholesterol/total cholesterol ratio, blood pressure, diabetes, and obesity with CHD risk is similar in men and
Methods
Participants and Surveys
Baseline surveys were carried out in North Karelia and Kuopio
provinces in eastern Finland and in the Turku-Loimaa region in
southwestern Finland in 1982 and 1987.19 In both years, age- and
sex-stratified random samples were taken from the age group of 25
to 64 years according to the international World Health Organization
(WHO) MONICA (Monitoring of Trends and Determinants in
Cardiovascular Disease) project protocol.20 In this study, the 1982
and 1987 cohorts were combined. The samples included 9789 men
and 9538 women. The participation rate was 79% among men and
85% among women. The 168 subjects who participated in both
surveys were included only in the 1982 survey cohort. Excluded
were 261 subjects because of their previous history of myocardial
infarction and 611 because of incomplete data on $1 risk factors.
Received April 30, 1998; revision received November 2, 1998; accepted November 18, 1998.
From the National Public Health Institute, Department of Epidemiology and Health Promotion, Helsinki, Finland.
Reprint requests to Dr Pekka Jousilahti, National Public Health Institute, Department of Epidemiology and Health Promotion, Mannerheimintie 166,
FIN-00300 Helsinki, Finland. E-mail [email protected]
© 1999 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
1165
1166
Sex, Age, Risk Factors, and CHD
TABLE 1. CHD Incidence and Mortality per 100 000 Person-Years and Relative and Absolute Risk Differences Between Sexes
by Age Group
25– 49 Years
Incidence (No.
of events)
50 –59 Years
60 – 64 Years
25– 64 Years*
Men
(n54567)
Women
(n54697)
Men
(n51819)
Women
(n51974)
Men
(n5704)
Women
(n51025)
Men
(n57090)
Women
(n57696)
275 (134)
44 (22)
1391 (246)
391 (80)
2308 (140)
1036 (107)
786 (520)
256 (209)
Relative risk
6.25
3.56
2.23
3.07
Absolute risk
difference†
231
1000
1272
530
Mortality (No.
of deaths)
92 (45)
10 (5)
611 (113)
77 (16)
1124 (73)
393 (42)
339 (231)
76 (63)
Relative risk
9.20
7.94
2.86
4.46
Absolute risk
difference†
82
534
731
263
*Adjusted for age.
†Per 100 000 person-years.
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Thus, 7090 men and 7696 women were included in the present
analyses.
Risk Factor Assessment
A self-administered questionnaire was sent to the participants in
advance. Current smoking status was assessed by a set of standardized questions. At the study site, height, weight, and blood pressure
were measured according to the WHO MONICA project protocol.20
Body mass index (BMI, kg/m2) was used as a measure of relative
body weight. Total and HDL cholesterol were determined from fresh
serum samples by an enzymatic method (CHOD-PAP, Boehringer
Mannheim). On the questionnaire, the subjects were asked to report
the presence of diabetes. The data were complemented by information from the Social Insurance Institution’s register on persons
receiving free-of-charge medication for diabetes.
Prospective Follow-Up
Mortality data were obtained from the Central Statistical Office of
Finland. Data on nonfatal coronary events were received from the
national hospital discharge register. The International Classification
of Diseases, Injuries, and Causes of Death (ICD, 8th and 9th
revisions) codes 410 to 414 were classified as coronary deaths and
ICD codes 410 to 411 in the hospital discharge register as nonfatal
acute coronary events.
Two separate end points, an incident case of CHD and CHD death,
were analyzed. An incident CHD event was defined as either the first
acute nonfatal coronary event or CHD death without a preceding
nonfatal coronary event. The follow-up of each subject in our present
analyses continued through the end of 1994. During the follow-up,
156 095 person-years were accumulated. The numbers of incident
CHD events were 520 among men and 208 among women, and the
numbers of CHD deaths were 231 and 63, respectively.
Statistical Analyses
ANOVA was used to test the difference in risk factors between
sexes. Multivariate analyses were performed by use of a Cox
proportional hazards model.21 All models were adjusted for age,
study year, and area. To assess whether the association of risk factors
with CHD risk is different in men than in women, first-level
interactions between sex and risk factors were tested. To assess the
extent to which the sex difference in the risk of CHD may be
explained by differences in the risk factors, a model was built
including data for both sexes and using sex as an explanatory
variable. The model was then completed by addition of the other risk
factors. The proportion of the excess risk of CHD in men compared
with women that was explained by the differences in risk factors was
estimated by comparing the risk ratios of CHD associated with sex
before and after adjustment for the other risk factors [(RR02RR1)/
(RR021), where RR0 is age-, area-, and study year–adjusted risk ratio
and RR1 is age-, area-, study year–, and risk factor–adjusted risk
ratio]. A similar procedure was used to analyze the extent to which
the age-related changes in risk factors may explain the difference in
CHD risk between the age groups. The statistical analyses were
performed with the SAS statistical programs.22
Results
CHD incidence and mortality were 786 and 339 per 100 000
person-years among men and 256 and 76 per 100 000
person-years among women, respectively (Table 1). Relative
difference in CHD risk between sexes was largest among the
youngest subjects, 25 to 49 years old, and smallest among the
oldest subjects, 60 to 64 years old. The absolute difference in
CHD risk, however, was largest in the oldest age group.
Smoking was more common, total cholesterol and blood
pressure were higher, HDL cholesterol was lower, and BMI
was higher among men in both the 25- to 64- and 25- to
49-year age groups (Table 2). In the age group 50 to 59 years,
systolic blood pressure of women nearly reached that of men,
and serum total cholesterol and BMI were already higher in
women. In the age group 60 to 64 years as well, systolic blood
pressure was higher in women. The HDL/total cholesterol
ratio was higher among women, but this difference diminished with increasing age. Diabetes prevalence was fairly
similar and increased similarly with age in both sexes.
The above-mentioned risk factors, except BMI, predicted
the risk of CHD in both sexes (Table 3). In univariate
analyses, BMI and CHD risk had a statistically significant
association (risk ratio, 1.04 [P50.002] for incidence and 1.04
[P50.024] for mortality in men and 1.04 [P50.002] for
incidence and 1.08 [P50.002] for mortality in women), but
the association disappeared when the other risk factors were
included in the analyses. BMI and diabetes had a stronger
association with coronary mortality in women than in men.
Otherwise, the association of risk factors with CHD incidence
and mortality was similar in both sexes.
The risk ratio of CHD associated with sex (men versus
women) was 3.38 for incidence and 5.00 for mortality (Table
4). The risk ratios decreased to 2.31 and 3.20 after smoking,
Jousilahti et al
TABLE 2.
March 9, 1999
1167
Levels of Cardiovascular Risk Factors by Age Group and Sex
25– 49 Years
Cardiovascular
Risk Factor
Smoking, %
Men
(n54567),
Mean
Women
(n54697),
Mean
44.7
24.2
50 –59 Years
P*
Men
(n51819),
Mean
Women
(n51974),
Mean
,0.001
35.5
11.4
60 – 64 Years
P*
Men
(n5704),
Mean
Women
(n51025),
Mean
,0.001
34.2
7.5
25– 64 Years
P*
Men
(n57090),
Mean
Women
(n57696),
Mean
P*
,0.001
41.0
19.0
,0.001
Cholesterol,
mmol/L
5.94
5.51
,0.001
6.42
6.66
,0.001
6.42
7.00
,0.001
6.13
5.99
,0.001
HDL
cholesterol,
mmol/L
1.27
1.52
,0.001
1.24
1.52
,0.001
1.20
1.45
,0.001
1.26
1.51
,0.001
HDL/cholesterol
ratio
0.22
0.28
,0.001
0.20
0.24
,0.001
0.19
0.21
,0.001
0.21
0.26
,0.001
140.8
132.3
,0.001
150.6
149.2
BMI, kg/m2
25.9
24.6
,0.001
27.4
Diabetes, %
1.7
1.4
0.241
6.7
Systolic blood
pressure, mm Hg
0.039
154.6
157.8
0.002
145.0
139.7
,0.001
27.8
0.002
27.3
29.0
,0.001
26.5
25.9
,0.001
5.0
0.023
8.1
9.5
0.312
3.7
3.3
0.174
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*Difference between men and women, adjusted for age.
HDL/total cholesterol ratio, systolic blood pressure, BMI, and
diabetes were introduced into the model. Thus, '45% of the
excess CHD risk of men was associated with the sex
differences in cardiovascular risk factors. This proportion was
highest, '60% for both CHD incidence and mortality, in the
age group 25 to 49 years. The corresponding proportions
were 47% and 46% in the age group 50 to 59 years and 35%
and 39% in the age group 60 to 64 years. In all age groups,
the sex difference in the HDL/total cholesterol ratio explained
most of the risk factor–associated excess CHD risk. Smoking
was the second most important determinant of the sex
difference in CHD risk.
Age-related change in risk factors explained about onethird in men and over half in women of the higher CHD risk
in the age group 50 to 64 years compared with the age group
25 to 49 years (Table 5). A decrease in the HDL/total
cholesterol ratio and increase in systolic blood pressure
contributed most to the risk factor–associated increase of
CHD risk by aging. Also, the increase in BMI and diabetes
prevalence was associated with the increase of CHD incidence and mortality by aging.
Discussion
The role of major cardiovascular risk factors in the development of CHD was fairly similar in both sexes. Among young
subjects, the overall risk factor level was more favorable in
women. With age, however, this advantage of women diminished markedly.
CHD incidence among men was '3-fold and mortality
'5-fold greater than in women. The sex differences in the
measured cardiovascular risk factors explained nearly half of
the observed sex difference in CHD incidence and mortality.
The difference in the HDL/total cholesterol ratio was the
major determinant of the sex difference in CHD risk. In
TABLE 3. Risk Ratio* of CHD Incidence and Mortality Associated With Smoking, Cholesterol, HDL
Cholesterol, HDL/Cholesterol Ratio, Systolic Blood Pressure, BMI, and Diabetes Among Men and Women 25
to 64 Years Old
CHD Incidence, Risk Ratio (95% CI)
CHD Mortality, Risk Ratio (95% CI)
Men
Women
Men
Women
Smoking (smokers vs nonsmokers)
1.77 (1.49–2.11)
2.14 (1.46–3.14)
2.19 (1.68–2.84)
3.03 (1.53–6.00)
Cholesterol (per mmol/L)
1.34 (1.26–1.43)
1.21 (1.10–1.33)
1.36 (1.24–1.49)
1.21 (1.03–1.43)
HDL cholesterol (per 0.1 mmol/L)
0.92 (0.89–0.94)
0.91 (0.87–0.95)
0.91 (0.87–0.95)
0.90 (0.84–0.98)
HDL/cholesterol ratio
0.45 (0.38–0.54)
0.50 (0.39–0.64)
0.42 (0.33–0.55)
0.49 (0.31–0.78)
1.11 (1.07–1.16)
1.11 (1.04–1.18)
1.11 (1.04–1.19)
1.11 (1.00–1.23)
Body mass index (per kg/m )
0.99 (0.97–1.01)
1.01 (0.98–1.04)
0.99 (0.96–1.02)
1.04 (0.99–1.09)
Diabetes (diabetics vs nondiabetics)
2.00 (1.51–2.61)
2.29 (1.57–3.35)
2.37 (1.63–3.44)
4.26 (2.42–7.60)
7090
7696
7090
7696
520
209
231
63
Systolic blood pressure (per 10 mm Hg)
2
No. of subjects
No. of events/deaths
Interactions between risk factors and sex: Coronary disease incidence: smoking3sex P50.773, cholesterol3sex P50.180, HDL
cholesterol3sex P50.385, HDL/cholesterol ratio3sex P50.984, systolic blood pressure3sex P50.650, BMI3sex P50.079,
diabetes3sex P50.301. Coronary disease mortality: smoking3sex P50.998, cholesterol3sex P50.597, HDL cholesterol3sex
P50.181, HDL/cholesterol ratio3sex P50.484, systolic blood pressure3sex P50.271, BMI3sex P50.014, diabetes3sex P50.009.
*Adjusted for age, study year, and other risk factors.
1168
Sex, Age, Risk Factors, and CHD
TABLE 4. Risk Ratio of CHD Incidence and Mortality Associated With Sex* and the Proportion (%) of Excess Risk in Men Associated
With the Difference of Risk Factors Included in Each Model†
25– 49 Years
50 –59 Years
CHD Incidence
Explanatory Variables
Included in the Model
CHD Mortality
Relative Risk
Effect Ratio*
CHD Mortality
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Risk
Ratio*
95% CI
Age, study year, area, and
sex
6.45
4.11–10.13
zzz
9.47
3.76–23.86
zzz
3.60
2.80–4.63
zzz
Age, study year, area, sex,
and smoking
5.27
3.33–8.34
22
7.03
2.75–17.97
29
3.04
2.34–3.95
Age, study year, area, sex,
and HDL/cholesterol ratio
3.64
2.26–5.85
52
5.55
2.12–14.49
46
2.85
Age, study year, area, sex,
and systolic blood
pressure
6.10
3.88–9.58
6
9.06
3.59–22.83
5
Age, study year, area, sex,
and BMI
6.10
3.89–9.58
6
9.17
3.63–23.14
Age, study year, area, sex,
and diabetes
6.46
4.12–10.15
0
9.40
Age, study year, area, sex,
smoking, HDL/cholesterol
ratio, systolic blood
pressure, BMI and
diabetes
3.18
1.97–5.14
60
4.38
No. of subjects
Relative Risk
Effect Ratio*
CHD Incidence
95% CI
Relative
Effect
8.06
4.78–13.61
zzz
22
6.38
3.74–10.90
24
2.20–3.69
28
6.04
3.55–10.29
29
3.55
2.76–4.57
2
7.89
4.67–13.32
2
4
3.65
2.84–4.71
22
8.38
4.95–14.18
25
3.73–23.67
1
3.53
2.75–4.55
3
7.82
4.63–13.21
3
1.66–11.53
60
2.37
1.81–3.10
47
4.83
2.80–8.32
46
95% CI
95% CI
Relative Risk
Effect Ratio*
9264
9264
3793
3793
156
50
326
129
*Men vs women.
†(RR02RR1)/(RR021); RR05age-, study year–, and area-adjusted risk ratio; RR15age-, study year–, area-, and risk factor–adjusted risk ratio.
TABLE 5. CHD Incidence and Mortality in Age Groups 50 –59 Years and 60 – 64 Years Compared With the Age Group 25– 49 Years*
and the Proportion of CHD Risk Increase Associated With Age-Related Risk Factor Changes†
Men 50 –59 Years
CHD Incidence
Explanatory Variables
Included in the Model
Risk
Ratio*
Study year, area, and
age group
Study year, area, age
group, and smoking
Study year, area, age
group, and
HDL/cholesterol ratio
Study year, area, age
group, and systolic
blood pressure
Study year, area, age
group, and BMI
Study year, area, age
group, and diabetes
Study year, area, age
group, smoking,
HDL/cholesterol ratio,
systolic blood
pressure, BMI,
diabetes
No. of subjects
No. of CHD
events/deaths
Men 60 – 64 Years
CHD Mortality
95% CI
Relative
Effect
95% CI
Relative
Effect
5.18
4.20–6.39
zzz
6.79
4.81 –9.59
zzz
5.51
4.46–6.80
28
7.32 5.22 –10.45
4.44
3.59–5.49
18
4.43
3.57–5.50
4.84
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
9.08
7.16–11.53
zzz
12.93
8.91–18.77
zzz
210
9.75
7.68–12.39
27
14.21
19.78–20.66
211
5.67 4.20 –8.02
19
7.45
5.86–9.49
20
10.24
7.83–14.94
23
18
5.73 4.02 –8.16
18
7.04
5.78–9.47
25
10.29
6.99–15.14
22
3.91–5.99
8
6.33 4.47 –8.98
8
8.59
6.76–10.92
6
12.16
8.35–17.70
6
4.82
13.90–5.96
9
6.16 4.35 –8.74
11
8.33
6.55–10.60
9
11.55
7.90–16.80
4.02
3.22–5.00
28
5.14 3.52 –7.36
28
6.43
4.99–8.78
33
8.81
5.94–13.07
1819
113
Risk
Ratio*
CHD Mortality
95% CI
1819
246
Risk
Ratio*
CHD Incidence
704
146
*Reference group.
†(RR02RR1)/(RR021); RR05study year– and area-adjusted risk ratio; RR15study year–, area-, and risk factor–adjusted risk ratio.
704
73
35
Jousilahti et al
TABLE 4.
March 9, 1999
1169
Continued
60 – 64 Years
CHD Incidence
25– 64 Years
CHD Mortality
CHD Incidence
CHD Mortality
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Risk
Ratio*
95% CI
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
2.39
1.86–3.08
zzz
3.13
2.14–4.59
zzz
3.38
2.87–3.97
zzz
5.00
3.78–6.62
zzz
2.05
1.56–2.70
25
2.49
1.65–3.76
30
2.84
2.40–3.36
23
3.91
2.92–5.23
27
2.13
1.65–2.76
19
2.69
1.82–3.96
21
2.65
2.25–3.13
31
3.84
2.89–5.12
29
2.47
1.95–3.19
26
3.25
2.21–4.77
26
3.40
2.89–3.99
21
5.06
3.82–6.69
22
2.55
1.96–3.31
212
3.50
2.36–5.18
27
3.51
2.98–4.13
25
5.32
4.01–7.06
28
2.43
1.88–3.13
23
3.22
2.20–4.73
24
3.38
2.88–3.98
0
5.01
3.79–6.63
0
1.90
1.43–2.52
35
2.30
1.50–3.53
39
2.31
1.94–2.75
45
3.20
2.37–4.33
45
1729
1729
14 786
247
115
729
TABLE 5.
14 786
94
Continued
Women 54 –59 Years
CHD Incidence
Women 60 – 64 Years
CHD Mortality
CHD Incidence
CHD Mortality
Risk
Ratio*
95% CI
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
Risk
Ratio*
95% CI
Relative
Effect
9.01
5.62–14.44
zzz
7.84
2.87–21.40
zzz
24.12
15.24–38.17
zzz
40.38
15.38–102.01
zzz
9.88
6.14–15.91
211
8.78
3.26–24.71
217
27.47
17.19–43.89
215
49.29
19.10–127.17
223
6.18
3.82–10.00
35
4.90
1.77–13.58
43
13.90
8.60–22.47
44
20.30
7.76 –53.13
51
7.06
4.35–11.47
24
5.61
2.01–15.65
33
16.84
10.35–27.38
32
24.82
9.39 –65.59
40
7.69
4.76–12.44
17
5.92
2.14–16.38
28
19.59
12.19–31.48
20
28.11
10.87 –72.69
31
8.42
5.25–13.51
7
6.67
2.43–18.26
17
20.83
13.10–33.14
14
28.64
11.16 –73.50
30
5.53
3.36–9.08
44
4.10
1.44–11.6
55
11.40
6.83–19.05
55
15.04
5.40 –41.91
64
1974
80
1974
16
1025
107
1025
42
1170
Sex, Age, Risk Factors, and CHD
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addition, differences in smoking rate contributed markedly to
the excess CHD risk of men. The role of smoking in the sex
difference in CHD risk may be even larger than estimated in
our analyses, because smoking may also decrease HDL
cholesterol level.23
In both sexes, the risk of CHD increased markedly with
age. In most populations, serum total cholesterol increases as
age increases. In men, this increase usually levels off around
the age of 45 to 50 years, whereas in women, the increase
continues sharply until the age of 60 to 65 years.24 Like serum
cholesterol, blood pressure also tends to increase with age,
and more prominently in women than in men.25 The increase
in blood pressure and its different relations to age in men and
women are probably explained in part by obesity.25,26
In the 1970s, on the basis of Framingham data, Johnson27
analyzed the role of cardiovascular risk factors on sex
difference in CHD risk. His conclusions were that differences
in smoking, serum total cholesterol, blood pressure, and the
occurrence of left ventricular hypertrophy and glucose intolerance did not explain the observed sex difference in CHD
risk. The shortcoming of the study, however, was that HDL
cholesterol was not included in the analyses.
In the early 1990s, Larsson and colleagues28 analyzed
whether sex differences in smoking rate, serum total cholesterol, blood pressure, BMI, and waist-to-hip ratio could
explain the sex difference in CHD incidence among 54-yearold Swedish men and women. Their conclusion was that
differences in waist-to-hip ratio explained practically all of
the sex difference in CHD risk and that the other risk factors
included in the analyses altered the results only marginally.
This study did not include HDL cholesterol in the analyses,
either. Another problem was that waist-to-hip ratio largely
depends on anatomic structure, which differs markedly between sexes. Therefore, it is questionable whether the same
reference values can be applied in both men and women.
The WHO MONICA Project and ARIC Study researchers
recently analyzed the contribution of sex differences in
cardiovascular risk factors to sex differences in CHD mortality between 46 communities.8 In this study, communities
were used as the unit of the analyses. Sex differences in CHD
mortality between communities were correlated with sex
differences in the following risk factors: smoking, obesity,
high blood pressure, high total cholesterol, and low HDL
cholesterol. Approximately 40% of the variation in the sex
ratios of CHD mortality could be explained by differences in
the sex ratios of the 5 risk factors examined.
In our study, the major cardiovascular risk factors explained nearly half of the sex difference in CHD risk. An
interesting question is which factors explain the other half.
The phenomenal difference between men and women is
determined by the X and Y chromosomes. During the fetal
period, male and female phenotypes are developed through
the action of sex hormones. Among women, estrogen is the
predominant sex hormone. The decrease in estrogen production after menopause changes the female lipid metabolism
toward a more atherogenic form by decreasing the HDL
cholesterol level and by increasing LDL and total cholesterol,
triglyceride, and lipoprotein(a) levels.29,30 In addition to the
lipid effect, estrogen may have cardioprotective effects
through glucose metabolism and the hemostatic system, and it
may also have a direct effect on endothelial cell function.31,32
The role of the major risk factors for the sex difference in
CHD risk may also be larger than estimated from our models.
Because we measured the risk factors only once, we have
probably underestimated the association between the risk
factors and CHD risk because of regression dilution bias.33
Atherosclerosis is also a cumulative process, starting at a
fairly young age.34 Even though sex differences in serum
cholesterol levels and blood pressure disappeared with age, it
is possible that the cumulative effects of these risk factors on
arteriosclerosis remain larger in men than in women, because
of the longer exposure time in men. In addition to the risk
factors included in our analyses, other factors, such as family
history of CHD, physical activity, nutrition, and alcohol
intake, may explain part of the sex difference in CHD risk.
The prevalence of positive family history of CHD and its
association with CHD risk does not differ markedly between
sexes.35 Even though physical activity, nutrition, and alcohol
intake differ somewhat between sexes, their role in the sex
difference in CHD risk is probably small.
The major clinical and public health challenges are how to
reduce the risk of CHD among middle-aged men closer to
that in women and how to prevent the marked increase in
CHD risk with aging, particularly in women. The HDL/total
cholesterol ratio was the major determinant of the sex
difference in CHD risk, and the increase in risk factor levels,
particularly in serum cholesterol and blood pressure, explained a substantial part of the age-related increase in CHD
incidence and mortality. Both HDL and total cholesterol
levels can be modified by dietary and lifestyle changes.36,37
The increase in serum cholesterol and blood pressure with
age is not an inevitable physical phenomenon. It does not
occur in some nonwesternized populations, and in western
populations, it can be prevented.24,38 Reduction in smoking
would also reduce CHD incidence and mortality markedly,
particularly in men.
In addition to lifestyle changes, cardiovascular risk can be
controlled by pharmacological means, such as antihypertensive and cholesterol-lowering drug treatments.39 – 42 Two factors, however, need to be noted when drugs are used in the
primary prevention of CHD. First, the initiation of drug
treatment should be based on the assessment of the expected
absolute reduction in disease risk. Even though the relative
risk of CHD associated with risk factors is similar or even
higher in women than in men, the risk factors operate at
different levels. Second, because the number of people who
have only moderately increased CHD risk is large, most of
the coronary events occur among them.37,43 Therefore, the
public health impact of even small but population-wide risk
factor reduction is usually larger than more marked risk
reduction among the high-risk individuals alone.
Even though the major cardiovascular risk factors were the
same in both sexes, there are also preventive strategies that
are unique to women. Several studies have shown that in
postmenopausal women, hormone replacement therapy reduces the risk of CHD markedly.44 – 47 In clinical trials, the
CHD risk of women in the treatment group has decreased by
40% to 50% compared with the control group. Part of this
Jousilahti et al
reduction in risk has been attributed to changes in the levels
of lipoproteins, but other mechanisms are also involved. Even
though the evidence supporting the cardioprotective effect of
hormone replacement therapy is quite strong, the overall
health effects of hormone replacement therapy in women is
still a controversial issue.7
In conclusion, differences in major cardiovascular risk
factors, particularly in HDL cholesterol level and smoking
rate, explained a substantial part of the sex difference in CHD
risk. Increases in serum total cholesterol, blood pressure,
relative weight, and diabetes prevalence were associated with
the age-related increase of CHD incidence and mortality in
both sexes but to a larger extent in women. In both sexes,
CHD can be effectively prevented by reducing the levels of
these risk factors.
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Sex, Age, Cardiovascular Risk Factors, and Coronary Heart Disease: A Prospective
Follow-Up Study of 14 786 Middle-Aged Men and Women in Finland
Pekka Jousilahti, Erkki Vartiainen, Jaakko Tuomilehto and Pekka Puska
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Circulation. 1999;99:1165-1172
doi: 10.1161/01.CIR.99.9.1165
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