Excess risk of fatal coronary heart disease associated with diabetes in men and women: meta-analysis of 37 prospective cohort studies
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.38678.389583.7C (Published 12 January 2006) Cite this as: BMJ 2006;332:73
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Rachel Huxley and colleagues find that women with diabetes have a
higher risk of mortality from coronary heart disease (CHD) than men.1 An
obvious contributing factor is women are more likely to be given
progestogens and oestrogens which can stimulate angiogenesis and increase
the risk of vascular disease.2,3 Use of hormones causes metabolic upsets
and increases the risk of diabetes and also incresase the risk of fatal
CDH.
In the RCGP oral contraceptive study the risk of diabetes was
increased by 50% with 120 months of OC use. The relative risk of deaths
from heart disease was 7.3 for current users and 4.6 for former users by
1984 compared with controls.4 Therefore the effects of current and past
use of hormones should be specified in a study before hormone use can be
excluded as a reason for a higher CHD mortality in women with diabetes.
Long-lasting high mortality risk diseases can be caused by past
hormone use. For example, systemic lupus erythematosus (SLE) is nine times
more common in young women than in men.5 Persistent SLE carries a life-
times increased risk of thrombosis. Women with the anti-phospholipid
syndrome can also have a risk of accelerated atheromatous disease.
1 Huxley R, Barzi F, Woodward M. Excess risk of fatal coronary heart
disease associated with diabetes in men and women: meta-analysis of 37
prospective cohort studies. BMJ 2006; 332: 73-78
2 Grant ECG. Relation between headaches from oral contraceptives and
development of endometrial arterioles. BMJ 1968; 3: 402-5.
3 Grant ECG. The pill, hormone replacement therapy, vascular and
mood over-reactivity, and mineral imbalance. J Nutr Environ Med 1998; 8:
105-116.
4 Kay CR. The Royal College of General Practitioners’ Oral
Contraception Study:some recent observations. Clinics in Obstet &
Gynaecol 1984:11: 759-786.
5 Grant ECG. Systemic lupus erythematosus. Lancet 2001 358:586.
Competing interests:
None declared
Competing interests: No competing interests
The diagnosis of coronary artery disease (CAD) in women is usually
challenging. Diabetes in women can only add to delay and confound
diagnosis. Underdiagnosis and delays in diagnosis in women also have a
profound effect on the risks and mortality due to CAD.
Women usually present with atypical symptoms compared to men .WISE
(Women’s Ischemia Syndrome Evaluation) study investigators found that a
classification of "typical" angina missed 65% of the women who actually
had CAD. Investigations for CAD have lower diagnostic accuracy in women
compared to those in men. In a published meta-analysis that included 19
exercise ECG studies with 3721 women, sensitivity and specificity were 61%
and 70%,as compared with a mean sensitivity and specificity of 72% and 77%
for 1977 men(1). Angiography is the usual gold standard for diagnosis but
prior literature and the WISE Study demonstrate that women referred for
angiography have a lower likelihood of obstructive CAD than anticipated
from angiography in men.. The high prevalence of non-obstructive CAD and
single-vessel disease in women results in an observed decreased diagnostic
accuracy and higher false-positive rate for noninvasive testing in women
versus men (2). Stress echocardiography has a lower sensitivity and lower
predictive value compared to that in men (3). Myocardial perfusion imaging
also has been reported to have technical limitations in women, including
false-positive results due to breast attenuation and small left
ventricular chamber size (4).
Newer investigations like impaired vasomotor response to
acetylcholine, Multislice CT, Electron Beam Tomography and cardiac MRI
might improve diagnostic accuracy for CAD in women.
REFERENCES
1.Kwok Y, Kim C, Grady D, Segal M, Redberg R. Meta-analysis of exercise
testing to detect coronary artery disease in women. Am J Cardiol. 1999;
83: 660–666
2.Shaw LJ, Peterson ED, Johnson LL. Non-invasive stress testing. In
Charney P, ed. Coronary Artery Disease in Women: What All Physicians Need
to Know. Philadelphia, Pa: American College of Physicians; 1999: 327–350
3. Veronique L. Roger, MD; Patricia A et al1997 American Heart
Association, Inc. Sex and Test Verification Bias- Impact on the Diagnostic
Value of Exercise Echocardiography.Circulation. 1997;95:405-410
4. Mieres JH, Shaw LJ, Hendel RC, et al -Writing Group on Perfusion
Imaging in Women. American Society of Nuclear Cardiology consensus
statementJ Nucl Cardiol. 2003; 10: 95–101.
Competing interests:
None declared
Competing interests: No competing interests
This is a very interesting article.However, I refer to past studies
in the UK, where it was shown that Asian women in the United Kingdom, have
a 50% higer risk of mortality
from coronary heart disease, as compared to their Caucasian
counterparts.So probably the ethnicity factor, is very important, in the
prognosis of heart disease.Asian women were found to have a higher
abdominal girth and a higher body mass index, along with a lifestyle which
did not allow
a lot of opportunity for exercise, including fatty diets.
I wonder if this group would like to review their data in the light of
ethnicity, and diabetes, and the relative risk from coronary heart disease
among Caucasian and Asian populations of women.
regards,
Dr Mona Verma
Competing interests:
None declared
Competing interests: No competing interests
An important reason not mentioned for type 2 diabetes increasing the
risk of dying from coronary heart disease (c.h.d.)by up to 50% more in
women than men is shown in the comparison of the risk factor differences
between men and women with and without diabetes (1). The difference in the
body mass index (b.m.i.)for women with and without diabetes is a mean of
1.98 kg/m2 compared with 0.69kg/m2 for men - about three times as much.
B.M.I. is one measure of obesity which was thus much greater in female
diabetics.
Obesity is
thought to be a causal factor of both type 2 diabetes and c.h.d.and it
follows that a greater degree of obesity in females will lead to more
fatal heart attacks in women than in men.
Reference.
Rachel Huxley,
Federica Barzi, Mark Woodward. Excess risk of fatal coronary heart disease
associated with diabetes in men amd women: meta-analysis of 37 prospective
cohort studies. BMJ.2006 332:73 (14 January).
Competing interests:
None declared
Competing interests: No competing interests
We read with great interest the article by Huxley et al(1)
entitled "Excess risk of fatal coronary heart disease
associated with diabetes in men and women: meta-analysis of
37 prospective cohort studies". The relative risk for
fatal coronary heart disease associated with diabetes is
50% higher in women than it is in men. The crude absolute
risk for fatal coronary heart disease was reported to be
7.7% in women with diabetes versus 4.5% in men with
diabetes. It is important to remember, however, that the
adjusted absolute risk imposed by diabetes is higher in
men.(2) The age-adjusted death rate in men with diabetes
is approximately three times higher than that in women with
diabetes.(3) Therefore, we would like to know not the
crude but the adjusted absolute risk for fatal coronary
heart disease in men versus women in the meta-analysis by
Huxley et al.
1. Huxley R, Barzi F, Woodward M. Excess risk of fatal
coronary heart disease associated with diabetes in men and
women: meta-analysis of 37 prospective cohort studies. BMJ
2006;332:73-6.
2. Lee WL, Cheung AM, Cape D, Zinman B. Impact of diabetes
on coronary artery disease in women and men: a meta-
analysis of prospective studies. Diabetes Care
2000;23:962-8.
3. Kleinman JC, Donahue RP, Harris MI, Finucane FF, Madans
JH, Brock DB. Mortality among diabetics in a national
sample. Am J Epidemiol 1988;128:389-401.
Competing interests:
None declared
Competing interests: No competing interests
World Wide Risks?!
With great interest I read the article by Huxley et al (2006). I was
happily surprised that their results correspond with my Dutch research
results . Huxley et al found that multiple adjusting (for more than age)
substantially reduces the differences in risk of fatal coronary heart
disease between sexes.
I also found an reduced odds ratio of coronary heart disease when multiple
adjusting for gender, age, social economic status and population density.
Huxley et al found a pooled ratio of the relative risks (women;men) of
1,46 (1,14 to 1,88).
I found, in diabetes two, an multiple adjusted odds ratio of 1,36 (1,27 to
1,46) for ‘causal comorbidity’ defined as hypertension ánd coronary heart
disease.
The odds ratio reduces when excluding cornonary heart disease from causal
comorbidity. So both studies support the theory that coronary heart
disease is a substantially contributing factor of risk.
However this similarity, differences in the study designs must be
mentioned. My study design was not as prospective as Huxley’s. In my study
‘risk of comorbidity in cara, diabetes and hypertension in the
Netherlands’, I selected cases on out-patient prescription drugs data from
1999-2003 from health care insurance data. These Pharmacy-based Groups were
computed to analyse epidemiological and economic factors . Walckiers and
Sartor also estimated the prevalence rate of chronic diseases through drug
consumption at national level in nine countries. This approach provides an
inexpensive and practical marker of disease frequency.
Odds ratios were multiple adjusted for different risk factors as Huxley
et al did. But Huxley et al took different levels of other cardio
vascular risk factors into account. I couldn’t, because of lack of data.
Although these discussion points it is encouraging for health cara
insurances in Europe that their results correspond to results of
prospective cohort studies. Therefore there is a path for future research
using the results from prospective studies in retrospective studies and
vice versa.
Competing interests:
None declared
Competing interests: No competing interests