Incidence,
aetiology and prognosis of coronary artery disease in women
Dr Diana R. Holdright
Department of Cardiology, The Middlesex Hospital (UCL Hospitals),
Mortimer St, London W1N 8AA, UK
Introduction
The earlier ignorance amongst the medical profession of the importance of coronary
artery disease in women has been virtually dispelled due to the ever-increasing
number of publications in this area. Although the message has yet to be fully
received and understood by the general public, all current and proposed studies
in coronary artery disease also address potential gender differences which
previously were generally not even considered in trial concept or design,
many studies being conducted exclusively in the typical middle-aged male
population. We are now able to paint a detailed picture of the woman at risk
of ischaemic heart disease.
Incidence
Generally speaking, a 50-year-old woman has a lifetime risk of developing coronary
artery disease of 31%. The Framingham data show that women are more likely
to present with angina (47%) than either myocardial infarction (32%), unstable
angina (7%) or cardiac death (14%).[1] Nearly one-half of
first presentations in men are due to myocardial infarction (46%), followed
by angina (32%), death (16%) and unstable angina (6%).
More than 236,000 women die each year in the US from myocardial infarction.
Approximately one-quarter of all deaths in women in industrialized nations
are due to coronary artery disease.[2] Before the age of 75,
the proportion of deaths from coronary artery disease is far less in women
than in men. Whereas the death toll from breast cancer is the same as that
from ischaemic heart disease in women aged less than 65, the overall mortality
for all ages is 23% from ischaemic heart disease and only 5% from breast cancer
(Table 1).
Table 1. Deaths in women in the UK (1992)
and the US (1990).[2]
Mortality rates rise rapidly with increasing age
for both men and women. The male excess, although particularly
pronounced at younger ages, lessens with increasing age to approximately
1.5:1 in the over-75s.
Worldwide there are marked geographical differences in coronary mortality rates
for men and women. There are remarkable differences between countries (Figure
1), with the highest rates in Eastern Europe and the lowest in Japan and China,
yet the ratio of men to women remains similar.
Figure 1. Ischaemic heart disease. Age-standardized
(to European Standard population) mortality rates for women
and men, 1991–1993.[2]
Changes in mortality rates over the last few decades
have been most impressive in the USA, which had the highest rate
in the 1950s but has shown the most dramatic decline in the last
two decades for both men and women. Increasing mortality rates
are seen for both sexes in many Eastern European countries.
The latest WHO MONICA publication[3] showed changes in coronary
event rates and survival among 37 populations in 21 countries over a 10-year
period, beginning in the early 1980s. Overall mortality rates fell by -2.7%
per year in men and by -2.1% per year in women. Coronary event rates fell more
(by -2.1% and -1.4% per year, respectively) than case fatalities (-0.6% and
-0.8% per year, respectively). Most rates fell and were similar for men and
women across populations (Figure 2).
Figure 2. Population rankings, by sex, of trends in
MONICA CHD mortality rate showing contribution of trends in
coronary-event rate and in case fatality.[3]
The male populations with the greatest increases
were predominantly Central and Eastern Europe and Asia, with
similar findings in women. Case fatality trends were more consistent
geographically in men than in women. The overall fall in mortality
was driven more by a change in event rates than by case fatalities.
This was seen for both sexes but there was less consistency in
women due to the smaller numbers.
Aetiology
Changes in coronary event rates in men and women are correlated within the
different countries, suggesting that whatever factors influence or determine
coronary risk, they affect men and women similarly. Most classical cardiovascular
risk factors operate similarly in men and women although the absolute risk
is typically lower in women.[4] The exception is diabetes
mellitus, which negates the female advantage: mortality rates are three to
seven times higher in diabetic vs non-diabetic women compared with a two- to
fourfold difference between diabetic and non-diabetic men. Oestrogen deficiency,
whether premature or natural, is an important and exclusive risk factor. Cigarette
smoking, which is increasing particularly in young women, quadruples the risk
of coronary artery disease.
Generally speaking, women tend to have a better risk factor profile at younger
ages in comparison with men until older age when the opposite is true. There
is compelling evidence from clinical trials of the benefit in women of lowering
serum cholesterol levels and reducing blood pressure. The relative risk reductions
are generally similar but the absolute risk reductions are less in women. A
15-year follow-up of over 15,000 adults (>50% women) from Scotland[5] showed
that women were more likely to have high cholesterol, to be obese and to come
from lower social classes than men, but they smoked less and had similar blood
pressures. Relative risks of coronary death were similar in men and women for
cholesterol but absolute risks were far lower in women: women in the top quintile
for cholesterol had lower mortality than men in the bottom quintile (Figure
3).
 Figure
3. Adjusted mortality from coronary heart disease (CHD)
in deaths per 1000 patient-years by quintile of plasma cholesterol.[5]
The relative risks in women were similar, but
the absolute and attributable risks were also lower than in men
for smoking and diastolic blood pressure (Table 2).
 Table
2. Relative and attributable risk of coronary death in
men and women.[5]
A recent comparison of 27 different potential risk factors for coronary artery
disease in men and women indicated that the classical risk factors scored
more strongly in both sexes for predicting cardiovascular risk than new ones.[6] Total
cholesterol, HDL cholesterol, triglycerides, systolic blood pressure and
previous angina all ranked within the top six risk factors for coronary artery
disease in men and women. Diabetes ranked 7th in women and 21st in men.
The oestrogen status of a woman is a unique and highly important factor with
regard to coronary risk. Premature menopause, natural or surgical, is associated
with a marked increase in risk. How much the increased cardiovascular risk
with natural menopause is due to oestrogen deficiency and how much is due to
the other effects of age is uncertain, since the two are inextricably linked.
There is only a small attributable risk associated with oral contraception,
since the group of women using it are relatively young with low rates of coronary
artery disease.
Old trials of hormone replacement therapy (HRT) suggested a significant protective
effect[7] but it is impossible to dissect out the ‘healthy
cohort’ effect, since women likely to use HRT are generally speaking at lower
cardiovascular risk in any case.[8] The HERS study,[9] which
is the only reported study of secondary prevention using HRT, showed no overall
effect on the occurrence of non-fatal myocardial infarction or coronary heart
disease death but there was a time trend towards benefit in years 4 and 5.
There was a significant, but hardly surprising, increased risk of thromboembolic
disease and gallbladder disease. Consequently, HRT is no longer recommended
for secondary prevention of coronary artery disease. However, the trial can
be criticized on several counts, which is beyond the scope of this article,
and some would argue that the HERS study has simply created more confusion
on this issue than it has answered any fundamental questions.
Prognosis
The Framingham database provides insight into the prognosis of women given
a diagnosis of coronary artery disease, broken down according to the mode of
presentation (angina, myocardial infarction, etc).[1] In subjects
with angina, which was the most common presentation in women, men experienced
a higher myocardial infarction rate than did women during follow-up. The male:female
hazard risk for subsequent myocardial infarction was 2.2, for coronary death
it was 2.1 and for total mortality it was 1.6. After a recognized myocardial
infarction, women had a worse prognosis, although the sex difference diminished,
but did not disappear, after adjustment for age and other risk factors (Table
3).
Table 3. Sex differences in risk for outcome
events according to initial coronary heart disease (CHD) presentation:
10-year follow-up in men vs women.[1]
 The better outcome for women with angina has been
found in numerous studies and undoubtedly relates to the difficulty
in establishing whether chest pain in a woman is cardiac in origin.[10] Angiographic
studies have shown that women with ‘angina’ are far more likely
to have angiographically normal coronary arteries compared with
men. Hence, a significant proportion of women are erroneously
given a label of coronary artery disease. It is hardly surprising,
therefore, that women with ‘angina’ have a better prognosis than
men.
Outcome after myocardial infarction was extensively investigated in the GUSTO
IIb study,[11] which enrolled more than 12,000 patients (>25%
women) with acute coronary syndromes. Women were older and sicker at presentation
(with higher rates of diabetes, hypertension and prior heart failure). Women
also had more complications in hospital and a higher 30-day mortality (6 vs
4% in men). To a great extent the worse outcome in women could be accounted
for by baseline variables. Women with unstable angina had a better outcome,
undoubtedly related in part to less severe coronary artery disease; indeed,
30.5% of women were subsequently shown to have no significant disease at angiography,
compared with 13.9% of men.
The worse outcome in women following myocardial infarction probably has several
explanations. As well as having greater comorbidity at presentation, studies
have shown that women are treated less aggressively than men and are less likely
to be admitted to a coronary care unit, to receive thrombolysis and to proceed
to coronary angiography and revascularization.[12] Women
are also older at presentation, raising the possibility of ageism, particularly
where coronary care units have upper age limits, denying older patients the
benefit of careful monitoring and thrombolysis, which is not usually administered
outside the coronary care unit.[13]
Many earlier studies showed that women with suspected or presumed coronary
artery disease were less likely to undergo invasive testing with a view to
revascularization.[14] One of several possible explanations
was that women were generally thought to fare less well after PTCA and bypass
surgery, with a greater incidence of periprocedural complications and a poorer
symptomatic result during follow-up. More recent reports, incorporating contemporary
practice and recent technological and pharmaceutical advances show that this
is no longer likely to be true, particularly when baseline differences in clinical
status are taken into account.[15]
Conclusions
Compared with men, coronary artery disease is less common in women but it remains
the major cause of mortality in developed societies. Coronary risk factors
are similar, although attributable risks are generally lower in women than
in men. The role of HRT remains uncertain. The prognosis of women with coronary
artery disease differs according to the mode of presentation and is partly
explained by the accuracy of diagnosis and differing risk factor profiles,
particularly age, at presentation.
REFERENCES
-
Comment in:
Prognosis after the onset of coronary heart disease.
An investigation of differences in outcome between the sexes according
to initial coronary disease presentation.
Murabito JM, Evans JC, Larson MG, Levy D.
Framingham Heart Study, MA 01701.
BACKGROUND. Differences exist between men and women in prognosis after the
onset of coronary heart disease (CHD). METHODS AND RESULTS. All Framingham
Heart Study subjects with the onset of clinically apparent coronary disease
from 1951 through 1986 were studied to compare prognosis in men and women
according to CHD presentation. Coronary disease presentations included angina,
coronary insufficiency (unstable angina), recognized myocardial infarction,
unrecognized myocardial infarction, and coronary death. Less than 1% of subjects
were lost to follow-up for overall mortality. Cox modeling was used to examine
the sex differences in outcome for each coronary presentation. New nonfatal
coronary disease developed in 750 men (mean age, 63 years) and 583 women
(mean age, 67 years). After onset of angina, men were at greater risk than
women for myocardial infarction (hazards ratio [HR], 2.20; 95% confidence
interval [CI], 1.45 to 3.34) and coronary death (HR, 2.11; 95% CI, 1.32 to
3.36) after adjustment for age and coronary disease risk factors. After a
recognized myocardial infarction, there was a trend toward greater risk for
overall mortality in women than men after adjustment for age and risk factors
(HR, 0.75; 95% CI, 0.53 to 1.08). In contrast, after an unrecognized myocardial
infarction, men were at increased risk for death compared with women (HR,
2.01; 95% CI, 1.28 to 3.15). CONCLUSIONS. Women fare at least as poorly as
men after recognized myocardial infarction, whereas women have a more favorable
outlook than men after the onset of angina or unrecognized myocardial infarction.
The favorable outcome in women after angina and unrecognized myocardial infarction
is due, in part, to greater misclassification of these coronary events in
women than in men.
PMID: 8252666 [PubMed - indexed for MEDLINE]
2. World Health Statistics Annuals
1982–1994. Geneva: World Health Organization, 1982–1994.
-
Comment in:
Contribution of trends in survival and coronary-event
rates to changes in coronary heart disease mortality: 10-year results from
37 WHO MONICA project populations. Monitoring trends and determinants in
cardiovascular disease.
Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, Tolonen H,
Ruokokoski E, Amouyel P.
Cardiovascular Epidemiology Unit (MONICA Quality Control Centre for Event
Registration), University of Dundee, Ninewells Hospital and Medical School,
UK. h.tunstallpedoe@dundee.ac.uk
BACKGROUND: The WHO MONICA (monitoring trends and determinants in cardiovascular
disease) Project monitored, from the early 1980s, trends over 10 years in
coronary heart disease (CHD) across 37 populations in 21 countries. We aimed
to validate trends in mortality, partitioning responsibility between changing
coronary-event rates and changing survival. METHODS: Registers identified
non-fatal definite myocardial infarction and definite, possible, or unclassifiable
coronary deaths in men and women aged 35-64 years, followed up for 28 days
in or out of hospital. We calculated rates from population denominators to
estimate trends in age-standardised rates and case fatality (percentage of
28-day fatalities=[100-survival percentage]). FINDINGS: During 371 population-years,
166,000 events were registered. Official CHD mortality rates, based on death
certification, fell (annual changes: men -4.0% [range -10.8 to 3.2]; women
-4.0% [-12.7 to 3.0]). By MONICA criteria, CHD mortality rates were higher,
but fell less (-2.7% [-8.0 to 4.2] and -2.1% [-8.5 to 4.1]). Changes in non-fatal
rates were smaller (-2.1%, [-6.9 to 2.8] and -0.8% [-9.8 to 6.8]). MONICA
coronary-event rates (fatal and non-fatal combined) fell more (-2.1% [-6.5
to 2.8] and -1.4% [-6.7 to 2.8]) than case fatality (-0.6% [-4.2 to 3.1]
and -0.8% [-4.8 to 2.9]). Contribution to changing CHD mortality varied,
but in populations in which mortality decreased, coronary-event rates contributed
two thirds and case fatality one third. INTERPRETATION: Over the decade studied,
the 37 populations in the WHO MONICA Project showed substantial contributions
from changes in survival, but the major determinant of decline in CHD mortality
is whatever drives changing coronary-event rates.
Publication Types:
PMID: 10334252 [PubMed - indexed for MEDLINE]
-
Risk factors for cardiovascular disease
in women.
Holdright DR.
Department of Cardiology, The Middlesex Hospital, London, UK.
Publication Types:
PMID: 9819013 [PubMed - indexed for MEDLINE]
-
Comment in:
Relation between coronary risk and coronary mortality
in women of the Renfrew and Paisley survey: comparison with men.
Isles CG, Hole DJ, Hawthorne VM, Lever AF.
Dumfries and Galloway Royal Infirmary, UK.
Most epidemiological and intervention studies in patients with coronary artery
disease have focused on men, the assumption being that such data can be extrapolated
to women. However, there is little evidence to support this belief. We have
completed a fifteen-year follow-up of 15,399 adults, including 8262 women,
who lived in Renfrew and Paisley and were aged 45-64 years when screened
between 1972 and 1976. We identified 490 deaths from coronary heart disease
(CHD) in women and 878 in men. Women were more likely to have high cholesterol,
to be obese, and to come from lower social classes than men, but they smoked
less and had similar blood pressures. The relative risk--top to bottom quintile
(95% Cl)--of cholesterol for coronary death after adjustment for all other
risk markers was slightly greater in women (1.77 [1.45,2.16]) than in men
(1.56 [1.32, 1.85]), but absolute and attributable risk were lower. Thus,
women in the top quintile for cholesterol had lower coronary mortality (6.1
deaths per thousand patient years) than men in the bottom quintile (6.8 deaths
per thousand patient years). Moreover, it was estimated that there would
have been only 103 (21%) fewer CHD deaths in women, yet 211 (24%) fewer in
men, if mortality had been the same for women and men in the lowest quintiles
of cholesterol. Trends showing similar relative risks in these women, but
lower absolute and attributable risks than in men, were present for smoking,
diastolic blood pressure, and social class. There was no relation between
obesity and coronary death after adjustment for other risks. Our results
suggest that some other factors protect women against CHD. The potential
for women to reduce their risk of CHD by changes in lifestyle may be less
than for men.
PMID: 1347584 [PubMed - indexed for MEDLINE]
-
Erratum in:
- BMJ 1998 Jun 20;316(7148):1881
Comparison of the prediction by 27 different factors
of coronary heart disease and death in men and women of the Scottish Heart
Health Study: cohort study.
Tunstall-Pedoe H, Woodward M, Tavendale R, A'Brook R,
McCluskey MK.
Cardiovascular Epidemiology Unit, Ninewells Hospital, and Medical School,
Dundee. h.tunstallpedoe@dundee.ac.uk
OBJECTIVE: To compare prediction by 27 different factors in men and women
of coronary heart disease events, coronary deaths, and deaths from all causes.
DESIGN: Cohort study. SETTING: Scottish population study. SUBJECTS: In 1984-7
random sampling of residents aged 40-59 produced 11,629 men and women who
generated survey clinic questionnaires, examination findings, and blood and
urine specimens. MAIN OUTCOME MEASURES: Subsequent death, coronary artery
surgery, and myocardial infarction. Risks were calculated for each category
of factor or fifth of continuous variables. 27 factors were ranked by descending
age adjusted hazard ratio of the top to bottom class in each factor, by sex
and end point. RESULTS: Follow up averaged 7.6 years, during which the 5754
men had 404 coronary events, 159 coronary deaths, and 383 deaths and the
5875 women 177, 47, and 208 respectively. The rankings for factors for the
three end points were mainly similar in men and women, although hazard ratios
were often higher in women. Classical risk factors ranked better for predicting
coronary risk than newer ones. Yet strong prediction of coronary risk was
no guarantee of significant prediction of all cause mortality. Findings included
an anomalous coronary protective role for type A behaviour in women; raised
plasma fibrinogen as a strong predictor of all end points; and an unexpectedly
powerful protective relation of dietary potassium to all cause mortality.
CONCLUSIONS: These initial unifactorial rankings and comparisons must be
interpreted with caution until potential interaction, confounding, and problems
of measurement and causation are further explored.
PMID: 9314758 [PubMed - indexed for MEDLINE]
-
Estrogen replacement therapy and coronary
heart disease: a quantitative assessment of the epidemiologic
evidence.
Stampfer MJ, Colditz GA.
Channing Laboratory, Boston, MA 02115.
Considerable epidemiological evidence has accumulated regarding the effect
of postmenopausal estrogens on coronary heart disease risk. Five hospital-based
case-control studies yielded inconsistent but generally null results; however,
these are difficult to interpret due to the problems in selecting appropriate
controls. Six population-based case-control studies found decreased relative
risks among estrogen users, though only 1 was statistically significant.
Three cross-sectional studies of women with or without stenosis on coronary
angiography each showed markedly less atherosclerosis among estrogen users.
Of 16 prospective studies, 15 found decreased relative risks, in most instances,
statistically significant. The Framingham study alone observed an elevated
risk, which was not statistically significant when angina was omitted. A
reanalysis of the data showed a nonsignificant protective effect among younger
women and a nonsignificant increase in risk among older women. Overall, the
bulk of the evidence strongly supports a protective effect of estrogens that
is unlikely to be explained by confounding factors. This benefit is consistent
with the effect of estrogens on lipoprotein subfractions (decreasing low-density
lipoprotein levels and elevating high-density lipoprotein levels). A quantitative
overview of all studies taken together yielded a relative risk of 0.56 (95%
confidence interval 0.50-0.61), and taking only the internally controlled
prospective and angiographic studies, the relative risk was 0.50 (95% confidence
interval 0.43-0.56).
Publication Types:
PMID: 1826173 [PubMed - indexed for MEDLINE]
-
Comment in:
Cardioprotective effect of hormone replacement therapy
in postmenopausal women: is the evidence biased?
Posthuma WF, Westendorp RG, Vandenbroucke JP.
Department of Clinical Epidemiology, Leiden University Hospital, Netherlands.
OBJECTIVE--To quantify the effect of selection of relatively healthy women
in studies reporting reduced relative risk for cardiovascular disease in
postmenopausal women taking hormone replacement therapy. DESIGN--Review of
the follow up studies reported in three recent meta-analyses to determine
the effect of oestrogen therapy on both total cancer and cardiovascular disease.
The same standard statistical methods as in the original analyses were used.
MAIN OUTCOME MEASURES--Relative risks of total cancer and cardiovascular
disease. RESULTS--In most of the follow up studies the relative risk for
total cancer was below 1. The studies that showed the largest reduction in
cardiovascular disease also showed the largest reduction in cancer, indicating
a healthy cohort effect. Although heterogeneity within the studies prevented
pooling, the best estimate for the protective effect on total cancer was
a relative risk of 0.83 among women taking oestrogen (95% confidence interval
0.71 to 0.96), while in the same studies the relative risk for cardiovascular
disease was 0.57 (0.50 to 0.64). CONCLUSIONS--Unintended selection of relatively
healthy women for oestrogen therapy may have influenced the reported beneficial
effect of oestrogen therapy on cardiovascular disease. It is unclear how
much of the cardioprotection is due to this selection. Universal preventive
hormonal replacement therapy for postmenopausal women is unwarranted at present.
Publication Types:
PMID: 8205018 [PubMed - indexed for MEDLINE]
-
Comment in:
Randomized trial of estrogen plus progestin for secondary
prevention of coronary heart disease in postmenopausal women. Heart and
Estrogen/progestin Replacement Study (HERS) Research Group.
Hulley S, Grady D, Bush T, Furberg C, Herrington D,
Riggs B, Vittinghoff E.
University of California, San Francisco 94143, USA.
CONTEXT: Observational studies have found lower rates of coronary heart disease
(CHD) in postmenopausal women who take estrogen than in women who do not,
but this potential benefit has not been confirmed in clinical trials. OBJECTIVE:
To determine if estrogen plus progestin therapy alters the risk for CHD events
in postmenopausal women with established coronary disease. DESIGN: Randomized,
blinded, placebo-controlled secondary prevention trial. SETTING: Outpatient
and community settings at 20 US clinical centers. PARTICIPANTS: A total of
2763 women with coronary disease, younger than 80 years, and postmenopausal
with an intact uterus. Mean age was 66.7 years. INTERVENTION: Either 0.625
mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate
in 1 tablet daily (n = 1380) or a placebo of identical appearance (n = 1383).
Follow-up averaged 4.1 years; 82% of those assigned to hormone treatment
were taking it at the end of 1 year, and 75% at the end of 3 years. MAIN
OUTCOME MEASURES: The primary outcome was the occurrence of nonfatal myocardial
infarction (MI) or CHD death. Secondary cardiovascular outcomes included
coronary revascularization, unstable angina, congestive heart failure, resuscitated
cardiac arrest, stroke or transient ischemic attack, and peripheral arterial
disease. All-cause mortality was also considered. RESULTS: Overall, there
were no significant differences between groups in the primary outcome or
in any of the secondary cardiovascular outcomes: 172 women in the hormone
group and 176 women in the placebo group had MI or CHD death (relative hazard
[RH], 0.99; 95% confidence interval [CI], 0.80-1.22). The lack of an overall
effect occurred despite a net 11% lower low-density lipoprotein cholesterol
level and 10% higher high-density lipoprotein cholesterol level in the hormone
group compared with the placebo group (each P<.001). Within the overall
null effect, there was a statistically significant time trend, with more
CHD events in the hormone group than in the placebo group in year 1 and fewer
in years 4 and 5. More women in the hormone group than in the placebo group
experienced venous thromboembolic events (34 vs 12; RH, 2.89; 95% CI, 1.50-5.58)
and gallbladder disease (84 vs 62; RH, 1.38; 95% CI, 1.00-1.92). There were
no significant differences in several other end points for which power was
limited, including fracture, cancer, and total mortality (131 vs 123 deaths;
RH, 1.08; 95% CI, 0.84-1.38). CONCLUSIONS: During an average follow-up of
4.1 years, treatment with oral conjugated equine estrogen plus medroxyprogesterone
acetate did not reduce the overall rate of CHD events in postmenopausal women
with established coronary disease. The treatment did increase the rate of
thromboembolic events and gallbladder disease. Based on the finding of no
overall cardiovascular benefit and a pattern of early increase in risk of
CHD events, we do not recommend starting this treatment for the purpose of
secondary prevention of CHD. However, given the favorable pattern of CHD
events after several years of therapy, it could be appropriate for women
already receiving this treatment to continue.
Publication Types:
- Clinical Trial
- Multicenter Study
- Randomized Controlled Trial
PMID: 9718051 [PubMed - indexed for MEDLINE]
10. Collins P. Metabolic imaging — diagnosis of CAD in women
vs men.
-
Comment in:
Sex, clinical presentation, and outcome in patients
with acute coronary syndromes. Global Use of Strategies to Open Occluded
Coronary Arteries in Acute Coronary Syndromes IIb Investigators.
Hochman JS, Tamis JE, Thompson TD, Weaver WD, White
HD, Van de Werf F, Aylward P, Topol EJ, Califf RM.
St. Luke's-Roosevelt Hospital Center and Columbia University, New York, NY
10025, USA.
BACKGROUND: Studies have reported that women with acute myocardial infarction
have in-hospital and long-term outcomes that are worse than those of men.
METHODS: To assess sex-based differences in presentation and outcome, we
examined data from the Global Use of Strategies to Open Occluded Coronary
Arteries in Acute Coronary Syndromes IIb study, which enrolled 12,142 patients
(3662 women and 8480 men) with acute coronary syndromes, including infarction
with ST-segment elevation, infarction with no ST-segment elevation, and unstable
angina. RESULTS: Overall, the women were older than the men, and had significantly
higher rates of diabetes, hypertension, and prior congestive heart failure.
They had significantly lower rates of prior myocardial infarction and were
less likely ever to have smoked. A smaller percentage of women than men had
infarction with ST elevation (27.2 percent vs. 37.0 percent, P<0.001),
and of the patients who presented with no ST elevation (those with myocardial
infarction or unstable angina), fewer women than men had myocardial infarction
(36.6 percent vs. 47.6 percent, P<0.001). Women had more complications
than men during hospitalization and a higher mortality rate at 30 days (6.0
percent vs. 4.0 percent, P<0.001) but had similar rates of reinfarction
at 30 days after presentation. However, there was a significant interaction
between sex and the type of coronary syndrome at presentation (P=0.001).
After stratification according to coronary syndrome and adjustment for base-line
variables, there was a nonsignificant trend toward an increased risk of death
or reinfarction among women as compared with men only in the group with infarction
and ST elevation (odds ratio, 1.27; 95 percent confidence interval, 0.98
to 1.63; P=0.07). Among patients with unstable angina, female sex was associated
with an independent protective effect (odds ratio for infarction or death,
0.65; 95 percent confidence interval, 0.49 to 0.87; P=0.003). CONCLUSIONS:
Women and men with acute coronary syndromes had different clinical profiles,
presentation, and outcomes. These differences could not be entirely accounted
for by differences in base-line characteristics and may reflect pathophysiologic
and anatomical differences between men and women.
PMID: 10413734 [PubMed - indexed for MEDLINE]
-
Comment in:
- BMJ. 1994 Sep 3;309(6954):555-6
Acute myocardial infarction in women: survival analysis
in first six months.
Wilkinson P, Laji K, Ranjadayalan K, Parsons L, Timmis
AD.
Department of Environmental Epidemiology, London School of Hygiene and Tropical
Medicine.
OBJECTIVE--To examine the influence that being female has on the outcome
of acute myocardial infarction. DESIGN--Observational follow up study. SETTING--London
district general hospital. PATIENTS--216 women and 607 men with acute myocardial
infarction admitted to a coronary care unit from 1 January 1988 to 31 December
1992. MAIN OUTCOME MEASURES--All cause mortality and recurrent ischaemic
events in the first six months. RESULTS--Event free survival (95% confidence
interval) at six months was 63.3% (56.3% to 69.4%) in women and 76.1% (72.4%
to 79.4%) in men, P < 0.001. The difference was confined to the first
30 days but thereafter the hazard plots for women and men converged, with
reduction of the hazard ratio from 2.36 (1.70 to 3.27) to 0.81 (0.44 to 1.48).
Women were older, but their excess risk persisted after adjustment for age,
other baseline variables, and indices of severity of infarction (hazard ratio
1.53 (1.09 to 2.15), P = 0.015). Women tended to be treated with thrombolysis
less commonly than men but the difference was small. Substantially fewer
women than men, however, were discharged taking beta blockers (23.3% v 41.4%,
P < 0.001), and although additional adjustment for discharge treatment
did not further reduce the point estimate of the hazard ratio (1.84 (0.89-3.83)),
the 95% confidence interval was wide and statistical significance was lost.
CONCLUSIONS--Women with acute myocardial infarction have a worse prognosis
than men but the excess risk is confined to the first 30 days and is only
partly explained by age and other baseline variables. The tendency for women
to receive less vigorous treatment than men must be remedied before gender
can be considered to be an independent determinant of risk.
PMID: 7916229 [PubMed - indexed for MEDLINE]
-
Women and myocardial infarction: agism
rather than sexism?
Adams JN, Jamieson M, Rawles JM, Trent RJ, Jennings
KP.
Cardiac Department, Aberdeen Royal Infirmary, Foresterhill.
OBJECTIVE--To determine whether women with myocardial infarction are treated
differently from men of the same age and to assess the effect of changes
in the coronary care unit admission policy. DESIGN--Clinical audit. SETTING--The
coronary care unit and general medical wards of a teaching hospital. In 1990
the age limit for admission to coronary care was 65 years. This age limit
was removed in 1991. PATIENTS--539 female and 977 male patients admitted
with myocardial infarction between 1990 and 1992. MAIN OUTCOMES--Admission
to the coronary care unit, administration of thrombolysis, and in-hospital
mortality. RESULTS--409 men and 254 women were admitted with myocardial infarction
in 1990 and 568 men and 285 women in 1992. Removal of the age limit for admission
to the coronary care unit resulted in an increase in the numbers of both
sexes admitted with myocardial infarction. In both years, however, proportionately
more men with infarction were admitted to coronary care: 226 men (55%) and
96 women (38%) (P < 0.01) (95% CI 7 to 28) in 1990 and 459 men (81%) and
200 women (70%) (P < 0.01) (%CI 2 to 19) in 1992. Some 246 men (60%) and
133 women (52%) with infarction (P < 0.01) received thrombolytic treatment
in 1990 compared with 319 men (56%) and 130 women (46%) (P < 0.01) in
1992. The mean age of women sustaining a myocardial infarction was significantly
greater in both years studied. In 1992 a total of 78 men (7%) and 34 women
(4%) (P < 0.05) admitted with chest pain underwent cardiac catheterisation
before discharge from hospital. CONCLUSIONS--Differences in admission rates
to the coronary care unit and the rate of thrombolysis between the sexes
can be explained by the older age of women sustaining infarction. The application
of age limits for admission to coronary care or administration of thrombolysis
places elderly patients at a disadvantage. As women sustain myocardial infarctions
at an older age they are placed at a greater disadvantage.
PMID: 7888271 [PubMed - indexed for MEDLINE.
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Comment in:
Differences in the use of procedures between women and
men hospitalized for coronary heart disease.
Ayanian JZ, Epstein AM.
Department of Medicine, Brigham and Women's Hospital, Boston, MA.
BACKGROUND AND METHODS. Previous studies at individual hospitals have reported
differences in the use of major diagnostic and therapeutic procedures for
women and men with coronary heart disease. To assess whether these differences
can be generalized, we performed retrospective analyses of coronary angiography
and revascularization (coronary-artery bypass surgery or percutaneous transluminal
coronary angioplasty) in women and men hospitalized for coronary heart disease
in 1987, using abstract data on 49,623 discharges in Massachusetts and 33,159
discharges in Maryland. We used multiple logistic regression to estimate
the adjusted odds of the use of a procedure, controlling for principal diagnosis,
age, secondary diagnosis of congestive heart failure or diabetes mellitus,
race, and insurance status. RESULTS. The adjusted odds of undergoing angiography
were 28 percent and 15 percent higher for men than for women in Massachusetts
and Maryland, respectively (95 percent confidence intervals for the odds
ratios, 1.22 to 1.35 and 1.08 to 1.22). The respective adjusted odds of undergoing
revascularization were 45 percent and 27 percent higher for men than for
women (95 percent confidence intervals, 1.35 to 1.55 and 1.16 to 1.40). Because
these differences could be related to differing thresholds for hospital admission,
we performed a second analysis limited to patients with diagnosed acute myocardial
infarction (11,865 discharges in Massachusetts and 6894 discharges in Maryland),
a group in which all patients would be expected to receive hospital care.
The male-to-female odds ratios in both states remained similar in magnitude
and were statistically significant for angiography and revascularization.
CONCLUSIONS. These findings demonstrate that women who are hospitalized for
coronary heart disease undergo fewer major diagnostic and therapeutic procedures
than men. These differences may represent appropriate levels of care for
men and women, but it is also possible that they reflect underuse in women
or overuse in men. Further study should assess the cause of these differences
and their effect on patients' outcomes.
PMID: 2057022 [PubMed - indexed for MEDLINE]
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Comment in:
Better outcome for women compared with men undergoing
coronary revascularization: a report from the bypass angioplasty revascularization
investigation (BARI)
Jacobs AK, Kelsey SF, Brooks MM, Faxon DP, Chaitman
BR, Bittner V, Mock MB, Weiner BH, Dean L, Winston C, Drew
L, Sopko G.
Evans Memorial Department of Clinical Research and the Section of Cardiology,
Department of Medicine, Boston Medical Center, Boston, MA, USA. alice.jacobs@bmc.org
BACKGROUND: Numerous studies have shown that women undergoing coronary revascularization
procedures do so at a higher risk for an adverse outcome compared with men.
However, the impact of advances in technology and improvements in techniques
on in-hospital and long-term outcome after revascularization in women is
unclear. METHODS AND RESULTS: We evaluated 1829 patients with symptomatic
multivessel coronary disease randomized to CABG or PTCA in the Bypass Angioplasty
Revascularization Investigation (BARI), of whom 27% were women. As expected,
women were older (64.0 versus 60.5 years), with more congestive heart failure
(14% versus 7%), hypertension (68% versus 42%), treated diabetes mellitus
(31% versus 15%), and unstable angina (67% versus 61%) than men but had similar
preservation of left ventricular function and extent of multivessel disease.
Women assigned to surgery received the same number of total grafts but fewer
internal mammary artery grafts (72% versus 85%, P<0. 01), and those assigned
to angioplasty had more intended lesions (76% versus 71%, P<0.01) successfully
dilated than men. At an average of 5.4 years' follow-up, crude mortality
rates were similar in women (12.8%) and men (12.0%). The Cox regression model
adjusting for baseline differences revealed that women had a significantly
lower risk of death (relative risk, 0.60; 95% CI, 0.43 to 0.84; P=0. 003)
but not a significantly lower risk of death plus myocardial infarction (relative
risk, 0.84; 95% CI, 0.66 to 1.07; P=0.16) than men. CONCLUSIONS: Although
the unadjusted mortality rate suggests that women and men undergoing CABG
and PTCA have a similar 5-year mortality, women have higher risk profiles;
consequently, contrary to previous reports, female sex is an independent
predictor of improved 5-year survival after we control for multiple risk
factors.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 9751675 [PubMed - indexed for MEDLINE]
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