During the study period, the MHS registry abstracted data on 3019 subjects treated for AMI. From this sample, 368 (12%) subjects developed an AMI while hospitalized for a non-cardiac cause and were excluded. An additional 31 (1%) subjects failed to meet validation criteria for AMI, leaving 2,620 subjects – 1242 women and 1378 men – in our study sample.
Baseline characteristics of subjects are shown in . The mean age of the study sample was 70.8 ± 15 years and 47% of the sample was female. Women averaged 5.4 ± 14.8 years older than men. While hypertension and CHF were more prevalent in women, men were more likely to report hyperlipidemia and smoking. Women reported a lower prevalence of CAD than men. There were no differences in reported race, diabetes, or family history of CAD.
Demographic, Risk Factor, and Medical Characteristics of Men and Women with Acute Myocardial Infarction
There were several differences in clinical presentation between men and women (). Although the most common symptom was chest pain in both genders, it occurred less frequently in women (68.0% vs. 75.6%, p<0.01). Women were more likely to report atypical symptoms of AMI such as nausea, weakness, and back pain at the time of presentation. Among patients who did not present with chest pain, women reported dyspnea (56.5%), weakness (43.0%), and nausea (23.0%) in a similar proportion to men; women were more likely to report back pain (8.4% vs. 4.0%, p=0.02), whereas men were more likely to report abdominal pain (4.8% vs. 9.4%, p=0.02). Hemodynamic instability, as indicated by bradycardia or hypotension, occurred in a similar proportion of men and women. Renal insufficiency, defined by a serum Cr ≥2.5 mg/dl, was less common in women than men (7.2% vs. 10.7%, p<0.01). The proportion of cases with elevated cardiac biomarkers (troponin or CK-MB) and elevated ST-segments was similar between genders.
Initial Presentation of Those with Acute Myocardial Infarction by Gender
Prescription of standard medical therapies during hospitalization was similar for women and men. Overall, aspirin was provided to 94% of patients; women were as likely to receive aspirin as men [OR=0.90 (0.63-1.27)]. Beta-blockers were provided to 83% of patients; women were similar to men [OR=0.95 (0.75-1.21)]. ACE-I and ARBs were least likely to be prescribed (63%), but again indistinguishable between genders [OR=0.92 (0.77-1.09)]. There was no difference in the prescription of any of these medications by gender at the time of discharge.
Diagnostic Angiography and Severity of Coronary Artery Disease
Eleven of the 21 MHS hospitals had both diagnostic and interventional capacity at the time of the survey. A total of 2158 patients (1019 women and 1139 men) were admitted to these hospitals. There was no difference by gender in patients admitted to hospitals with angiography/PCI services (p=0.68). Women were 46% [OR=0.54 (0.45-0.64)] less likely to undergo diagnostic coronary angiography than men (). After accounting for confounding variables (Model 1), women were still 27% [(OR=0.73 (0.57-0.94)] less likely to undergo angiography. Attempts to identify potential sources of gender bias focused on the severity of CAD (). Women more often had non-obstructive CAD (17% vs. 5.4%, p<0.01) and were less likely to have either three-vessel disease (15% vs. 20%, p=0.02) or a significant LMCA stenosis (6.8% vs. 11%, p<0.01).
Use of Diagnostic Coronary Angiography and Severity of Coronary Artery Disease Among Those Treated for AMI at Hospitals with Cardiac Catheterization Laboratories
Coronary revascularization was assessed among patients identified with significant CAD. Whereas angiography was less commonly performed in women, there was no difference in the rates of revascularization after angiography [OR=0.96 (0.72-1.28)] (). However, the selection of revascularization technique did vary by gender. In the unadjusted analysis, women were more likely to be referred for percutaneous revascularization [OR=1.29 (1.01-1.65)] and were less likely to be treated surgically [OR=0.63 (0.44-0.89)]. After adjusting for demographic and clinical characteristics as well as presenting features (Model 1), the estimates were similar [OR=1.41 (1.07-1.86) for PCI, and OR=0.57 (0.39-0.84) for CABG]. When coronary anatomic characteristics were incorporated into the model (Model 2), the association between gender and modality of coronary revascularization was attenuated and no longer statistically significant. However, there was a strong trend favoring PCI [OR=1.27 (0.95-1.69)] and disfavoring CABG [OR=0.69 (0.45-1.05)] in women.
Modalities of Revascularization Among Those With Significant Coronary Artery Disease
As part of the investigation, we repeated the analysis in the subgroup of patients who presented with ST elevation (STEMI). We identified 916 STEMI patients; 456 (50%) were women. 753 of the STEMI patients were treated at facilities capable of performing diagnostic angiography and PCI; 380 (50%) were women. Thrombolytics were administered to 101 (11%) of STEMI patients; women were less likely to receive thrombolytics than men [8.3% vs. 13.7%, OR=0.57 (0.37-0.87), p=0.01]. Coronary angiography was performed on 527 (70%) of these patients; women were less likely to be referred for coronary angiography [64% vs. 76%, OR=0.56 (0.41-0.76), p=0.0003]. After adjustment for confounders (Model 1), the difference was no longer statistically significant [OR=0.93 (0.58-1.50)]. 490 (93%) patients had significant disease in at least one coronary artery and 421 patients underwent either PCI or CABG; there was no difference by gender (88% vs. 85%, p=NS). Women were more likely to be treated with PCI [80% vs. 71%, OR=1.6 (1.07-2.49), p=0.02] and less likely to undergo CABG [8% vs. 15%, OR=0.48 (0.27-0.88), p=0.01]. After risk adjustment (Model 1), women tended to be more likely to undergo PCI [OR=1.57 (0.97-2.53)] and were significantly less likely to undergo CABG [OR=0.41 (0.21-0.81)]. After accounting for the severity of CAD (Model 2), women remained less likely to undergo CABG, although this estimate was no longer statistically significant [OR=0.49 (0.23-1.04)].
A post-hoc analysis was performed to ascertain whether other variables could explain our initial findings (). Although women more likely to be identified as DNR/DNI, the odds ratios did not vary by catheterization use (p-value for heterogeneity=0.70). We also found no gender difference in post-discharge plans for cardiac catheterization (p-value for heterogeneity = 0.56). Among patients undergoing coronary angiography, men were less likely than women [OR=0.54 (0.35-0.84)] to have undergone stress testing. However, among those treated conservatively, there was no difference in the use of stress testing by gender [OR=1.17 (0.74-1.84), p-value for heterogeneity=0.02].
Resuscitation Status, Stress Testing, and Planned Angiography Among Subjects Treated at Hospitals with Catheterization Laboratories by Angiography Status and Gender
A search of the medical record was performed to identify less common comorbidities that could explain the gender bias in the use of diagnostic cardiac catheterization for AMI. Included among these conditions were atrial fibrillation, acquired immune deficiency syndrome, alcohol use, chronic obstructive pulmonary disease, connective tissue disorders, mental status changes, hepatic disease, leukemia, lymphoma, tumors, renal disease, peptic ulcer disease, acute bleeding, bleeding diathesis, and surgery/biopsy/trauma within two weeks. Women were still less likely to have angiography after these variables were considered in the model [OR=0.70 (0.54-0.91)].
Our final analysis assessed the possibility of an interaction between gender and renal function. We dichotomized the study population using a CrCl cutoff of ≥60 ml/min. Among MI patients with CrCl ≥60 ml/min (n=1141) treated at hospitals with catheterization labs, women remained less likely to undergo coronary angiography after adjusting for the variables in Model 1 [OR=0.58 (0.39-0.88)], p=0.0094. Among the cohort with CrCl <60 ml/min (n=1017), gender was no longer a significant predictor of angiography [OR=0.99 (0.71-1.37)], p=0.94. In summary, women with preserved renal function remain less likely to have angiography than men.