Women and men have similar outcomes after myocardial infarction
ACP J Club. 1995 Sept-Oct;123:49. doi:10.7326/ACPJC-1995-123-2-049
Vaccarino V, Krumholz HM, Berkman LF, Horwitz RI. Sex differences in mortality after myocardial infarction: is there evidence for an increased risk for women? Circulation. 1995 Mar 15;91:1861-71.
To study the relation between survival after myocardial infarction (MI) and sex.
English-language studies were identified through MEDLINE (1966 to June 1994) using the terms myocardial infarction, mortality, complications, and sex factors. Bibliographies of retrieved articles were also checked.
Studies were selected if they reported mortality rates by sex, sex-related relative risk for mortality, or significance tests for mortality differences between men and women. Studies were excluded if only prevalent cases of MI were included, numbers were very small, MI was not confirmed by enzymes or electrocardiogram, or adjustment was not made for age.
Data extracted were early mortality (in-hospital or during the first 4 to 6 weeks after MI); late mortality; and crude and age-adjusted mortality rates in men and women, crude and age-adjusted relative risk for death in men or women, or both.
Data were not pooled because of heterogeneity. 27 studies were included. 13 trials studied consecutive hospitalized patients, 9 were population-based, 4 were clinical trials, and 1 studied health insurance data. 19 339 women and 52 101 men were included. Across studies, women who had had an MI were older than men; had a higher prevalence of hypertension, diabetes, and congestive heart failure; and had more mechanical complications during hospitalization. Men had a higher rate of cigarette smoking, a higher incidence of previous MI, and more arrhythmic complications. Of 17 studies evaluating early mortality, most showed greater mortality in women, but age-adjustment in 11 studies reduced the sex difference to < 20%. Excess mortality in women was also reduced in 6 of the 8 studies that adjusted for risk factors other than age. Of 7 studies reporting mortality at > 1 year, 6 (5 significant, 1 trend) found that after adjusting for age and risk factors, women had a lower risk for mortality.
After adjustment for age and risk factors, women have slightly lower short-term survival compared with men after myocardial infarction. In the longer term, women have a survival advantage at all ages compared with men.
Source of funding: National Institutes of Health.
For article reprint: Dr H. Krumholz, Yale University School of Medicine, 333 Cedar Street, Box 208025, New Haven, CT 06520-8025, USA.
Why try to predict risk for death after MI? First, because an understanding of prognosis is almost always helpful to physicians, patients, and families. Second, some therapies may be preferentially directed to high-risk patients if concerns exist about side effects or costs (e.g., tissue plasminogen activator, the price of which is 10-fold higher than that of streptokinase). Third, risk prediction is valuable for researchers designing and interpreting clinical studies and for institutions seeking to benchmark clinical outcomes for quality improvement.
Any risk-prediction algorithm ideally should be accurate, widely applicable, and easy to use. Optimizing these features simultaneously is not easy. For example, an algorithm designed for wide application may either lose accuracy as it is applied to diverse subgroups of patients or require numerous variables that make it less user-friendly.
How does the algorithm devised by Lee and colleagues measure up? Their model shows outstanding predictive accuracy for a remarkable range of patients treated with thrombolytic drugs. Although the model was not tested in an independent population, rigorous methods were used for internal cross-validation. As to applicability, their analysis draws on patients enrolled in the GUSTO trial (1), with the inevitable selection bias that this entails. Short-term mortality in the GUSTO trial, for example, was about half that seen among patients hospitalized with MI outside of trials (2). The generalizability of the model must be established for patients presenting > 6 hours after symptom onset. The overall algorithm itself is too complex for bedside use. A simple scoring system or nomogram, however, is now being prepared by the same team (Lee KL. Personal communication).
Lee and colleagues found that female sex was only a weak predictor of 30-day mortality in women (P = 0.043) when other clinical factors were taken into account. Intriguingly, they also showed that taller, heavier persons fared better after MI. Because sex obviously correlates to some extent with body size, inclusion of body size variables may mask a biological disadvantage incurred by women.
The GUSTO findings support the conclusions of Vaccarino and colleagues, who systematically reviewed the literature on sex differences in prognosis after MI. They found insufficient similarities in study designs and data to allow a standard meta-analysis. Therefore, their review uses vote-counting; studies are weighted equally regardless of sample size or the magnitude of sex differences found. Vaccarino and colleagues do, however, convincingly show that the adverse short-term prognosis for women after MI occurs largely because women are older, on average, when they have an MI. Our recent analysis of population-wide data for Ontario provides corroborating evidence. In 1991, the crude (vs age- and sex-adjusted) in-hospital death rates for men and women with MI were 14.4% (15.8%) and 21.9% (17.5%), respectively. The 34% relative difference decreased to 10% with age adjustment (2).
Vaccarino and colleagues also highlight the favorable long-term prognosis for women. Beyond 1 year from the index MI, women have a lower age-adjusted mortality than men because their usual survival advantage over same-aged men re-emerges.
Taken together, these studies offer reassurance that little of the sex difference in mortality after MI is attributable to sex differences in MI treatment that have been reported in several countries. More research is needed to understand better whether (and why) women have even a small short-term mortality disadvantage after MI, and to determine whether sex differences in treatment have adverse effects on quality of life for women.
C. David Naylor, MD
University of TorontoToronto, Ontario, Canada