Although an invasive strategy has predominately been studied in men with non–ST-segment elevation acute coronary syndromes (NSTE-ACSs), its role in low-risk women is unclear. We sought to examine gender differences in a real-world registry of patients with NSTE-ACS who underwent percutaneous coronary intervention (PCI). Patients with NSTE-ACS undergoing PCI at the Cleveland Clinic, Cleveland, Ohio from 2003 through 2007 (n = 1,874) were included. In-hospital and long-term mortalities were assessed. Cox proportional hazards models were constructed to study the influence of gender on mortality. Interactions with age and biomarker status were examined. Women were older and had a higher incidence of co-morbid conditions compared to men. They had a smaller reference vessel diameter compared to men. Despite these characteristics there was no overall difference in in-hospital (1.4% vs 1.6%) or long-term (14.6% vs 15.8%) mortality between men and women. However, there was evidence of a significant effect modification by age (p = 0.012) and troponin status (p = 0.0073) for long-term mortality such that women <60 years of age, especially those who were troponin negative, had more than a twofold increase in long-term mortality compared to men (p = 0.007). In conclusion, although overall mortality rates are similar between men and women undergoing PCI for NSTE-ACS, women <60 years old with negative biomarkers have a higher mortality than their men peers.
Based on data from randomized controlled trials, current practice guidelines recommend an early invasive approach in most patients presenting with non–ST-segment elevation acute coronary syndromes (NSTE-ACSs). However, these data also suggest that patient gender may influence outcomes and response to such an invasive approach. A meta-analysis of 8 trials comparing an invasive strategy to conservative management in patients presenting with NSTE-ACS noted a significant decrease in the primary end point of death, myocardial infarction (MI), or recurrent ACS hospitalization in men but not women up to 12 months of follow-up. The response for women was heterogeneous, with biomarker-positive women demonstrating significant benefit with an invasive strategy, whereas biomarker-negative women demonstrated a trend toward harm. Data from multiple studies also suggested that younger women who present with ACSs represent a distinct group in risk factors and pathophysiology and have significantly higher mortality compared to men. Despite these differences data on long-term outcomes based on gender in patients presenting with NSTE-ACS and undergoing percutaneous coronary intervention (PCI) are limited. Accordingly, we sought to study differences in outcomes for men and women presenting with NSTE-ACS in a “real-world” registry and undergoing PCI during index hospitalization.
Methods
Successive patients presenting to the Cleveland Clinic, Cleveland, Ohio from March 1, 2003 through June 30, 2007 who underwent an index PCI procedure (n = 11,161) were included. This information was obtained from the prospective PCI patient registry. Baseline characteristics, history, risk factors, medications, and laboratory, angiographic, and procedural data were prospectively obtained and recorded by experienced research coordinators. Individual socioeconomic level data were not available; therefore, each patient’s home address was geocoded and matched to the United States 2000 Census data. Census block-level data, a geographic unit containing approximately 1,000 residents, was used to calculate a composite socioeconomic status score for each patient as described previously. The institutional review board waived requirements for informed consent for the institutional PCI registry.
Patients presenting with NSTE-ACS were identified based on prospectively recorded diagnosis in the PCI registry. Patients with STEMI or PCI for other reasons were excluded. For our study a diagnosis of unstable angina required presentation with chest pain, admission to the hospital before the PCI, and a negative troponin T value, whereas non-STEMI required a similar presentation with a positive troponin T value. These requirements including troponin status of all patients were confirmed by chart review. The same sensitivity troponin assay was used throughout the study period. The primary end point was all-cause mortality, which was assessed by querying the Social Security Death Index. In-hospital mortality was assessed by chart review.
Aspirin 325 mg orally was administered before angiography and daily during the index hospitalization. Dosing and timing of clopidogrel were left to the discretion of the operators, but as a policy at our hospital all patients undergoing PCI receive 300 to 600 mg ≥2 hours before PCI. Clopidogrel 75 mg/day was recommended for 1 year in all patients after PCI and aspirin 81 to 325 mg/day indefinitely. Unfractionated intravenous heparin was used as the upfront preprocedure anticoagulant of choice. Choice of intraprocedural anticoagulant and stent was at the discretion of the assigned interventionalist.
Wilcoxon rank-sum tests and analysis of variance were used for continuous variables and chi-square tests for categorical variables. Mean ± SD and percentage were reported for continuous and categorical variables, respectively. Kaplan–Meier curves compared long-term mortality between men and women presenting with NSTE-ACS. Cox proportional hazards regression model was used to evaluate the relation between risk factors and long-term mortality using stepwise regression. Patient gender was forced into the final model to assess for significance. Initially, hazard ratios and their confidence intervals were estimated in a univariate model. Relevant variables (patient demographic characteristics, medical history, medications at time of PCI, and angiographic and procedural characteristics) were then entered into a multivariate analysis. Interaction terms between gender and age (as a continuous variable and categorized as <60, 60 to 75, and >75 years) and between gender and biomarker status, which were defined a priori, were examined for statistical significance.
All statistical analyses were performed using SAS 9.1 (SAS Institute, Cary, North Carolina). All p values were 2-tailed with statistical significance set at 0.05. All confidence intervals were calculated at the 95% level.
Results
In total 1,874 patients (1,177 men and 697 women) with NSTE-ACS were included, of which 805 (43%) presented with non-STEMI and 1,069 (57%) with unstable angina. Women were equally likely as men to be positive for troponin (42% vs 44%, p = 0.32). Baseline characteristics of the study population are listed in Table 1 . Women with NSTE-ACS were more likely to be older and have more co-morbid conditions including diabetes mellitus, chronic obstructive pulmonary disease, obesity (body mass index >30 kg/m 2 ), and anemia (hematocrit <35%). In contrast, they were less likely than men to have left ventricular ejection fraction ≤40%, family history of premature coronary artery disease, current smoking, previous MI, renal insufficiency (serum creatinine >1.5 mg/dl), and previous coronary artery bypass graft surgery. Women were less likely than men to be on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers at baseline; no differences in other baseline or intraprocedural medications were noted. Angiographically, women with NSTE-ACS were more likely to have a significant lesion in the left anterior descending coronary artery, whereas men were more likely to have a significant lesion in the left circumflex coronary artery. Men were also more likely to undergo a vein graft intervention. Reference vessel diameter was smaller in women compared to men.
| Characteristic | Men | Women | p Value |
|---|---|---|---|
| (n = 1,177) | (n = 697) | ||
| Age (years) | 64.6 ± 11.7 | 68.0 ± 12.6 | <0.0001 |
| Diabetes mellitus | 443 (37.6%) | 301 (43.2%) | 0.012 |
| New York Heart Association class 3/4 | 537 (45.6%) | 326 (46.8%) | 0.63 |
| Chronic obstructive lung disease | 195 (16.6%) | 155 (22.2%) | 0.002 |
| Peripheral arterial disease | 200 (17.0%) | 135 (19.4%) | 0.19 |
| Body mass index (kg/m 2 ) | 29.5 ± 5.8 | 30.2 ± 7.4 | 0.039 |
| Socioeconomic status score | −0.59 ± 4.4 | −1.1 ± 4.5 | 0.011 |
| Depression | 16 (1.4%) | 12 (1.7%) | 0.53 |
| Left ventricular ejection fraction (%) | 48.5 ± 12.1 | 50.4 ± 11.4 | 0.0007 |
| Family history of coronary artery disease | 362 (30.8%) | 166 (23.8%) | 0.0012 |
| Current smoker | 256 (21.8%) | 114 (16.4%) | 0.0046 |
| Cerebrovascular disease | 152 (12.9%) | 103 (14.8%) | 0.26 |
| Hematocrit (%) | 39.8 ± 5.2 | 36.8 ± 4.8 | <0.0001 |
| Serum creatinine (mg/dl) | 1.35 ± 1.3 | 1.1 ± 0.95 | <0.0001 |
| Cancer | 55 (4.7%) | 21 (3.0%) | 0.078 |
| Previous myocardial infarction | 724 (61.6%) | 389 (55.8%) | 0.015 |
| Previous coronary artery bypass surgery | 418 (35.5%) | 198 (28.4%) | 0.0015 |
| Baseline heart rate (beats/min) | 70.3 ± 13.0 | 73.3 ± 14.3 | <0.0001 |
| Troponin positive | 43.9% | 41.5% | 0.32 |
| Medications | |||
| Aspirin | 1,121 (95.2%) | 657 (94.3%) | 0.35 |
| Clopidogrel | 1,172 (99.6%) | 691 (99.1%) | 0.35 |
| β Blocker | 507 (43.1%) | 305 (43.8%) | 0.77 |
| Angiotensin-converting enzyme inhibitor/angiotensin receptor blocker | 552 (46.9%) | 288 (41.3%) | 0.019 |
| Statin | 859 (73.0%) | 497 (71.3%) | 0.43 |
| Unfractionated heparin | 699 (59.4%) | 384 (55.1%) | 0.07 |
| Glycoprotein IIb/IIIa inhibitor | 588 (50.0%) | 333 (47.8%) | 0.36 |
| Angiographic and procedural characteristics | |||
| Procedural success | 1,127 (95.8%) | 669 (96.0%) | 0.81 |
| Proximal left anterior descending artery lesion | 178 (15.1%) | 117 (16.8%) | 0.34 |
| Left anterior descending artery lesion | 522 (44.4%) | 356 (51.1%) | 0.0048 |
| Left circumflex artery lesion | 517 (43.9%) | 264 (37.9%) | 0.01 |
| Right coronary artery lesion | 432 (36.7%) | 274 (39.3%) | 0.26 |
| American College of Cardiology lesion type | |||
| A | 50 (4.3%) | 22 (3.2%) | 0.23 |
| B1 | 145 (12.3%) | 88 (12.6%) | 0.85 |
| B2 | 513 (43.6%) | 329 (47.2%) | 0.13 |
| C | 469 (39.9%) | 258 (37.1%) | 0.22 |
| Number of diseased vessels | |||
| 1 | 744 (63.2%) | 441 (63.3%) | 0.98 |
| 2 | 296 (25.2%) | 180 (25.8%) | 0.75 |
| 3 | 137 (11.6%) | 76 (10.9%) | 0.63 |
| Lesion length (mm) | 15.4 ± 7.1 | 15.3 ± 7.3 | 0.77 |
| Reference vessel diameter (mm) | 3.07 ± 0.55 | 2.95 ± 0.47 | <0.0001 |
| Stent length (mm) | 26.7 ± 13.1 | 26.3 ± 13.0 | 0.47 |
| Multivessel coronary intervention | 293 (24.9%) | 186 (26.7%) | 0.39 |
| Use of drug-eluting stent | 851 (72.3%) | 521 (74.8%) | 0.25 |
| Saphenous vein graft intervention | 133 (11.3%) | 54 (7.8%) | 0.013 |
| Chronic total occlusion intervention | 60 (5.1%) | 34 (4.9%) | 0.83 |
| In-stent restenosis | 41 (3.5%) | 18 (2.6%) | 0.28 |
Overall in-hospital mortality was 1.5% (1.4% vs 1.6% for men vs women, respectively, p = 0.82). Troponin-positive patients had a significantly higher in-hospital mortality compared to troponin-negative patients (2.6% vs 0.7%, p = 0.0006).
Mean duration of follow-up in our cohort was 2.1 ± 1.3 years. In total 182 deaths were recorded. There was no difference in all-cause mortality between men and women (14.6% vs 15.8%, p = 0.49). Kaplan–Meier curves are presented in Figure 1 . Significant predictors of all-cause mortality on Cox proportional hazards regression analysis are listed in Table 2 . Gender was not significantly associated with mortality in the final adjusted model (p = 0.79). However, interaction terms between gender and age (p = 0.012 with age as continuous variable, p = 0.044 with age as categorical) and between gender and troponin status (p = 0.0073) were statistically significant. On stratified analysis younger women (<60 years old) had more than a twofold increase in long-term mortality compared to men (15.0% vs 7.4%, p = 0.003). When further stratified by troponin status, this was true for troponin-negative (12.9% vs 5.1%, p = 0.007), and trended to be so in troponin-positive (18.9% vs 10.5%, p = 0.08) women <60 years of age. Further, older men (>75 years old) had a significantly higher long-term mortality compared to women (27.9% vs 19.0%, p = 0.023), which was predominantly true for troponin-positive patients (34.5% vs 15.5%, p = 0.0013; Figure 2 ).
| Variable | HR (95% CI) | p Value |
|---|---|---|
| Age, per 10-year increment | 1.18 (1.05–1.32) | 0.005 |
| Chronic obstructive lung disease | 2.18 (1.69–2.83) | <0.0001 |
| Peripheral arterial disease | 1.48 (1.14–1.94) | 0.004 |
| Cerebrovascular disease | 1.34 (1.00–1.80) | 0.048 |
| Obesity (body mass index >30 kg/m 2 ) | 0.66 (0.51–0.86) | 0.002 |
| Diabetes mellitus | 1.39 (1.08–1.80) | 0.013 |
| Previous myocardial infarction | 1.44 (1.10–1.89) | 0.009 |
| Previous coronary artery bypass surgery | 1.34 (1.03–1.73) | 0.027 |
| Cancer | 2.23 (1.39–3.59) | 0.001 |
| Anemia (hematocrit <35%) | 1.53 (1.18–1.98) | 0.001 |
| Renal insufficiency (creatinine >1.5 mg/dl) | 2.15 (1.63–2.83) | <0.0001 |
| Heart rate >100 beats/min | 1.99 (1.25–3.17) | 0.004 |
| Proximal left anterior descending artery lesion | 1.38 (1.02–1.88) | 0.038 |
| Right coronary artery lesion | 0.69 (0.53–0.91) | 0.007 |
| Single-vessel disease | 0.74 (0.58–0.95) | 0.016 |
| American College of Cardiology lesion type C | 1.41 (1.10–1.81) | 0.007 |
| Use of drug-eluting stent | 0.70 (0.53–0.93) | 0.015 |
| Male gender | 0.97 (0.75–1.25) | 0.79 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
