Age-Specific Gender Differences in In-Hospital Mortality by Type of Acute Myocardial Infarction

Age-Specific Gender Differences in In-Hospital Mortality by Type of Acute Myocardial Infarction Zefeng Zhang, MD, PhDa,*, Jing Fang, MDa, Cathleen Gillespie, MSca, Guijing Wang, PhDa, Yuling Hong, MD, PhDa, and Paula W. Yoon, ScDa Younger women hospitalized with an acute myocardial infarction (MI) have a poorer prognosis than men. Whether this is true for patients with acute ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI) is not extensively studied. Using the MarketScan 2004 to 2007 Commercial and Medicare supplemental admission databases, we assessed gender differences in in-hospital mortality according to age in 91,088 patients (35,899 with STEMI, 55,189 with NSTEMI) who were 18 to 89 years old and had acute MI as their primary diagnosis. Patients with STEMI had significantly higher in-hospital mortality than those with NSTEMI (4.35% vs 3.53%, p <0.0001). Compared to men women were older, had higher co-morbidity scores, and were less likely to undergo revascularization during hospitalization in the STEMI and NSTEMI populations. In patients with STEMI the unadjusted women-to-men odds ratio for in-hospital mortality was 2.29 (95% confidence interval 1.48 to 3.55) for the 18- to 49-year age group, 1.68 (1.28 to 2.21) for 50 to 59, 1.48 (1.17 to 1.88) for 60 to 69, 1.28 (1.06 to 1.57) for 70 to 79, and 1.01 (0.83 to 1.23) for 80 to 89. Corresponding unadjusted odds ratios were 1.51 (0.87 to 2.61), 1.46 (1.11 to 1.92), 1.29 (1.04 to 1.61), 0.83 (0.70 to 0.99) and 0.82 (0.70 to 0.94) for patients with NSTEMI. After adjustment for potential confounding factors, excess risk for in-hospital mortality in younger women versus their men counterparts (<60 years old) persisted in STEMI. In patients with NSTEMI the difference between younger women and younger men was not statistically significant; however, older women (>70 years old) had better survival than men. In conclusion, higher risk of in-hospital mortality in younger women compared to younger men is more evident in patients with STEMI. Published by Elsevier Inc. (Am J Cardiol 2012;109:1097–1103)

During the previous 2 decades studies have consistently shown that younger women hospitalized with an acute myocardial infarction (AMI) have a poorer prognosis than their men peers,1– 4 whereas older women (ⱖ70 or ⱖ75 years old) have similar or better outcomes compared to older men.1–7 Previous studies examining the gender difference on mortality after AMI have included acute ST-segment elevation MI (STEMI) and acute non-STEMI (NSTEMI), events that differ in pathophysiology, clinical presentation, initial management, and prognosis. Gender differences in in-hospital mortality appear to differ for these 2 types of AMI. Studies have shown that in STEMI in-hospital mortality is higher for women than for men,8 –10 but in NSTEMI women seem to have similar or even better outcomes than men.6,11–15 Researchers, however, have yet to determine whether there are age-specific gender-based differences in in-hospital mortality in STEMI and NSTEMI as have been found in the overall AMI population. Accordingly, we used the Thomson Reuters MarketScan 2004 to 2007 Commercial and Medicare supplemental inpatient admission databases (Thomson Reuters, Ann Arbor, Michigan) to examine

a

Division for Heart Disease and Stroke Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia. Manuscript received October 18, 2011; revised manuscript received and accepted December 2, 2011. *Corresponding author: Tel: 770-488-5904; fax: 770-488-8151. E-mail address: [email protected] (Z. Zhang). 0002-9149/12/$ – see front matter Published by Elsevier Inc. doi:10.1016/j.amjcard.2011.12.001

gender differences for in-hospital mortality across age groups by type of AMI after adjustment for sociodemographic and clinical characteristics. Methods The MarketScan 2004 to 2007 inpatient admission databases included information from approximately 40 privately insured employers including state governments. Databases included ⬎2.4 billion service records representing commercially insured employees, retirees, and dependents from ⬎100 geographically diverse health insurance plans in all 50 United States and the District of Columbia. These databases contain patient demographics, dates of service, length of hospital stay, primary and up to 14 secondary hospital discharge codes, primary and up to 14 secondary procedure codes, and other variables. The International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9CM) was used for hospital discharge codes. ICD-9-CM and Current Procedure Terminology-4 (CPT-4) codes were used for procedure codes. From 2004 through 2007, 91,609 patients (101,031 hospitalizations) 18 to 89 years old who had an AMI as their primary diagnosis were included in the inpatient admission databases. If a patient had ⬎1 hospitalization for AMI from 2004 through 2007, the first hospitalization was included in the analysis. We excluded 521 patients who had a hospital length of stay ⬎30 days. Thus, 91,088 patients (35,899 with www.ajconline.org

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Table 1 Comparison of baseline characteristics between men and women by type of acute myocardial infarction Variable

Age (years), mean ⫾ SD Charlson co-morbidity index Urban Region Northeast Central north South West Capitated insurance* Economic status Low Middle High Year 2004 2005 2006 2007

STEMI

NSTEMI

Overall (n ⫽ 35,899)

Women (n ⫽ 10,387)

Men (n ⫽ 25,512)

Overall (n ⫽ 55,189)

Women (n ⫽ 20,636)

Men (n ⫽ 34,553)

61.2 ⫾ 12.2 1.76 ⫾ 1.3 89.6%

65.5 ⫾ 13.3 1.93 ⫾ 1.4 89.6%

59.5 ⫾ 11.8† 1.69 ⫾ 1.2† 89.6%

66.1 ⫾ 13.1 2.13 ⫾ 1.5 89.1%

69.0 ⫾ 13.3 2.22 ⫾ 1.5 89.3%

64.4 ⫾ 13.0† 2.07 ⫾ 1.5† 89.0%

7.5% 33.2% 40.3% 19.0% 17.6%

7.5% 34.8% 37.6% 20.1% 19.2%

7.5% 32.6% 41.5% 18.5% 17.0%†

8.3% 37.1% 36.5% 18.1% 18.8%

8.1% 38.9% 33.9% 19.0% 19.2%

8.4% 36.0% 38.1% 17.5% 18.5%

34.3% 33.8% 31.9%

33.7% 34.5% 31.8%

34.6% 33.4% 32.0%

32.8% 33.3% 34.0%

32.5% 32.9% 34.7%

32.9% 33.5% 33.6%

21.2% 27.0% 21.5% 30.3%

21.7% 30.0% 21.3% 27.2%

21.0%† 25.8% 21.6% 31.6%

20.5% 27.7% 21.5% 30.2%

20.5% 29.0% 21.2% 29.3%

20.5%† 27.0% 21.6% 30.8%

* Capitated insurance includes health maintenance organization and point of service with capitation; noncapitated insurance includes basic/major medical, comprehensive, exclusive provider organization, point of service, preferred provider organization, and consumer-driven health plan. † p ⬍0.0001 for women versus men. Table 2 Gender and age distribution of acute myocardial infarction Age Group (years)

18–49 50–59 60–69 70–79 80–89

STEMI

NSTEMI

Overall (n ⫽ 35,899)

Women (n ⫽ 10,387)

Men (n ⫽ 25,512)

Overall (n ⫽ 55,189)

Women (n ⫽ 20,636)

Men (n ⫽ 34,553)

6,262 (17.4%) 11,380 (31.7%) 8,753 (24.4%) 5,710 (15.9%) 3,794 (10.6%)

1,333 (12.8%) 2,452 (23.6%) 2,271 (21.9%) 2,325 (22.4%) 2,006 (19.3%)

4,929 (19.3%) 8,928 (35.0%) 6,482 (25.4%) 3,385 (13.3%) 1,788 (7.0%)

6,082 (11.0%) 12,656 (22.9%) 12,867 (23.3%) 12,317 (22.3%) 11,267 (20.4%)

1,770 (8.6%) 3,700 (17.9%) 4,295 (20.8%) 5,128 (24.8%) 5,743 (27.8%)

4,312 (12.5%) 8,956 (25.9%) 8,572 (24.8%) 7,189 (20.8%) 5,524 (16.0%)

STEMI, 55,189 with NSTEMI) who had AMI as a primary diagnosis were included in this analysis. STEMI was identified using ICD-9-CM codes 410.01, 410.11, 410.21, 410.31, 410.41, 410.51, 410.61, and 410.81 and NSTEMI was identified by 410.71. This method has been used to identify STEMI and NSTEMI in other studies.16,17 Using ICD-9-CM codes for the secondary diagnoses we identified co-morbidities of heart failure (402.01, 402.11, 402.91, 404.01, 404.03, 404.11, 404.13, 404.91, 404.93, and 428.xx), hypertension (401 to 405), diabetes (250), hyperlipidemia (272), kidney disease (403 to 404, 582 to 583, 585 to 587), and cancer (140 to 280) and complications of cardiac shock (785.51), stroke (430 to 438), ventricular tachycardia (427.1), ventricular fibrillation (427.41 or 427.42), atrial tachycardia (427.0), and atrial fibrillation (427.31 or 427.32). CPT-4 codes 92980 to 92982, 92984, and 92995 to 92996 and ICD-9-CM codes 00.66 and 36.01 to 36.09 were used to identify patients who underwent percutaneous coronary intervention, and CPT-4 codes 33510 to 33519, 33521 to 33523, and 33533 to 33536 and ICD-9-CM codes 36.10 to 36.19 were used to identify

patients who underwent coronary artery bypass grafting surgery. We used zip codes and the 2000 United States Census to classify economic status. Income for a zip code was characterized as low, middle, or high using tertiles of household income level derived from the census; patients living in that zip code were classified accordingly. Insurance status was categorized as capitated plan (health maintenance organization and point of service with capitation) or noncapitated plan (basic or major medical, comprehensive, exclusive provider organization, point of service without capitation, preferred provider organization, and consumerdriven health plan). Hospitals were classified as urban if they were included in a metropolitan statistical area and rural if they were not. The Charlson co-morbidity index, which measures the likelihood of death or serious disability in the subsequent year and was derived from up to 18 co-morbidities,18,19 was included in the multivariable regression analysis as a measurement of co-morbidity burden. This index has been used as an adjusting variable in AMI population.20

Table 3 Comparison of revascularization and in-hospital complications between men and women across age groups by type of acute myocardial infarction

ST-segment elevation myocardial infarction Patients Percutaneous coronary intervention Coronary artery bypass grafting Ventricular tachycardia Atrial tachycardia Ventricular fibrillation Atrial fibrillation Cardiogenic shock Non–ST-segment elevation myocardial infarction Patients Percutaneous coronary intervention Coronary artery bypass grafting Ventricular tachycardia Atrial tachycardia Ventricular fibrillation Atrial fibrillation Cardiogenic shock

Women

Men

Age Group (years), OR (95% CI)

Overall OR (age adjusted)

18–49

50–59

60–69

70–79

80–89

10,387 64.9% 7.1% 4.4% 0.7% 3.2% 8.1% 6.1%

25,512 75.0% 10.6% 7.1% 0.6% 4.4% 6.8% 4.6%

1,333/4,929 0.67 (0.58–0.78) 0.83 (0.65–1.07) 0.73 (0.56–0.95) 0.44 (0.13–1.47) 1.22 (0.92–1.60) 0.95 (0.65–1.40) 1.30 (0.95–1.78)

2,452/8,928 0.70 (0.63–0.77) 0.81 (0.69–0.96) 0.70 (0.58–0.85) 1.53 (0.94–2.49) 0.79 (0.63–0.99) 0.70 (0.55–0.89) 1.20 (0.97–1.49)

2,271/6,482 0.83 (0.75–0.93) 0.59 (0.50–0.69) 0.67 (0.53–0.83) 1.02 (0.56–1.89) 0.79 (0.61–1.03) 0.74 (0.61–0.90) 1.19 (0.96–1.46)

2,325/3,385 0.84 (0.75–0.93) 0.63 (0.53–0.74) 0.55 (0.43–0.70) 1.55 (0.78–3.06) 0.59 (0.43–0.81) 0.95 (0.81–1.12) 1.20 (0.97–1.48)

2,006/1,788 0.87 (0.76–0.98) 0.37 (0.27–0.51) 0.57 (0.40–0.81) 0.97 (0.43–2.21) 0.44 (0.29–0.67) 1.02 (0.86–1.22) 1.10 (0.86–1.41)

10,387/25,512 0.78 (0.74–0.83) 0.66 (0.60–0.73) 0.65 (0.58–0.72) 1.17 (0.87–1.59) 0.78 (0.68–0.91) 0.88 (0.79–0.97) 1.19 (1.07–1.33)

20,636 33.0% 7.4% 2.1% 1.1% 0.7% 11.5% 1.4%

34,553 44.9% 13.2% 4.2% 0.8% 1.3% 10.5% 1.6%

1,770/4,312 0.55 (0.50–0.62) 0.63 (0.52–0.77) 0.92 (0.68–1.26) 1.09 (0.57–2.11) 0.76 (0.44–1.32) 0.68 (0.45–1.03) 1.26 (0.70–2.26)

3,700/8,956 0.61 (0.56–0.66) 0.55 (0.49–0.62) 0.51 (0.40–0.66) 1.56 (1.04–2.36) 0.59 (0.40–0.86) 0.84 (0.70–1.00) 0.88 (0.62–1.24)

4,295/8,572 0.72 (0.67–0.78) 0.60 (0.53–0.67) 0.50 (0.40–0.62) 1.14 (0.79–1.66) 0.59 (0.40–0.86) 0.75 (0.66–0.86) 0.90 (0.66–1.21)

5,128/7,189 0.82 (0.76–0.89) 0.62 (0.55–0.70) 0.46 (0.37–0.57) 1.38 (0.96–1.98) 0.54 (0.37–0.80) 0.93 (0.85–1.03) 0.85 (0.65–1.12)

5,743/5,524 0.82 (0.75–0.90) 0.51 (0.42–0.61) 0.37 (0.29–0.48) 1.24 (0.86–1.79) 0.44 (0.26–0.73) 0.98 (0.89–1.07) 0.75 (0.56–1.01)

20,636/34,553 0.71 (0.68–0.74) 0.54 (0.51–0.58) 0.50 (0.44–0.56) 1.29 (1.07–1.56) 0.57 (0.47–0.69) 0.90 (0.84–0.96) 0.86 (0.74–1.00)

Coronary Artery Disease/AMI Mortality by Age and Gender

Variable

CI ⫽ confidence interval; OR ⫽ odds ratio.

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Results Of the 91,088 patients, 60,065 (65.9%) were men and 31,023 (34.1%) were women. There were 28.9% women in the STEMI group and 37.4% women in the NSTEMI group (p ⬍0.0001). As can be calculated from Table 1, STEMI accounted for a smaller percentage of AMI in women than in men (33.5% vs 42.5%, p ⬍0.0001). Mean age was older in patients with NSTEMI than in those with STEMI (66.1 vs 61.2 years, p ⬍0.0001). Women were older than men at admission in the STEMI group (mean age 65.5 ⫾ 13.3 vs 59.5 ⫾ 11.8 years, p ⬍0.0001) and NSTEMI group (69.0 ⫾ 13.3 vs 64.4 ⫾ 13.0 years, p ⬍0.0001). Sixty-four percent of women with STEMI but only 46% of their men counterparts were ⱖ60 years old; the corresponding percentages by gender (for ⱖ60 years of age) in the NSTEMI group were 73% versus 62% (p ⬍0.0001 for the 2 comparisons; Table 2). Women were more likely than men to have heart failure but less likely to have hyperlipidemia (Supplemental Tables 1 and 2) and they had significantly higher co-morbidity scores in the 2 populations (Table 1). Younger women were more likely than younger men to have diabetes, obesity, heart failure, cancer, stroke, and other co-morbidities but less likely to have hyperlipidemia (Supplemental Tables 1 and 2). Differences by gender for co-morbidities generally decreased with increasing age, with women 80 to 89 years old less likely than men to have cancer and kidney disease. Women were less likely to undergo revascularization (percutaneous coronary intervention or coronary artery bypass grafting surgery) than men during hospitalization in the 2 populations (p ⬍0.0001 for all comparisons). The younger

20

In-hospital Mortality (%)

Categorical data were reported as frequency and percentage and compared by chi-square test. Continuous variables were expressed as mean ⫾ SD and compared using unpaired t test. Breslow-Day test was used to assess whether there was an interaction between age group (in years, 18 to 49, 50 to 59, 60 to 69, 70 to 79, and 80 to 89) and gender for all characteristics and in-hospital mortality. All comparisons were presented in terms of odds ratios in women compared to that in men in addition to 95% confidence intervals. We used a series of multivariate regression models to determine the gender difference in in-hospital mortality according to age in the 2 populations. The significance of interaction between gender and age groups was assessed using the Wald test and type III analysis. The first model, which included gender as a sole variable, was used to calculate the unadjusted odds ratio for women (vs men) for in-hospital mortality and its 95% confidence interval. The second model added age, and the interaction term between gender and age was added in the third model. The fourth model adjusted for other demographic factors (insurance status, region, economic status, and urban/rural), disease severity (Charlson co-morbidity index), and 3 dummy variables for year of discharge (2005, 2006, and 2007, with 2004 used as the reference category). All tests of statistical significance were 2-tailed and a p value ⬍0.05 was considered statistically significant. All statistical analyses were performed using SAS 9.1.3 (SAS Institute, Cary, North Carolina).

STEMI 15

10

5

0 18-49

50-59

54/4929 33/1333 2.29 1.48-3.55

171/8928 78/2452 1.68 1.28-2.21

60-69

70-79

80-89

233/3385 202/2325 1.28 1.06-1.57

219/1788 248/2006 1.01 0.83-1.23

Age (years) Men Women Odds ratio 95% CI

213/6482 109/2271 1.48 1.17-1.88

A 20 In-hospital Mortality (%)

1100

NSTEMI

15 10 5 0 18-49

50-59

60-69

70-79

80-89

Age (years) Women 21/1770 Odds ratio 1.51 95% CI 0.87-2.61

85/3700 1.46 1.11-1.92

135/4295 207/5128 1.29 0.83 1.04-1.61 0.70-0.99

355/5743 0.82 0.70-0.94

B Figure 1. Rates and unadjusted odds ratios of in-hospital mortality in women (white bars) and men (black bars) by age and acute (A) STsegment elevation myocardial infarction and (B) non–ST-segment elevation myocardial infarction.

the age of the patients, the greater the gender difference for percutaneous coronary intervention. In contrast, the older the age of the patients, the greater the gender difference for coronary artery bypass grafting surgery (Table 3). During hospitalization women were less likely to have ventricular tachycardia and ventricular fibrillation but more likely to have atrial tachycardia and atrial fibrillation. Inhospital cardiogenic shock was higher in women than in men with STEMI but no difference by gender was found in NSTEMI. Gender difference for in-hospital ventricular

Coronary Artery Disease/AMI Mortality by Age and Gender

STEMI

18-49 years

50-59 years

60-69 years

70-79 years

80-89 years

adjusted unadjusted

0.1

0.2

0.5

1.0

2.0

5.0

10.0

Odds Ratio (Women versus Men)

A NSTEMI

18-49 years

50-59 years

60-69 years

1101

patients with NSTEMI. Mortality difference by gender decreased with age, with women having a similar risk of death at ⱖ80 years of age in patients with STEMI (1.01, 0.83 to 1.23) and marginally better outcomes at ⱖ70 years of age in patients with NSTEMI (70 to 79 years old, 0.83, 0.70 to 0.99; 80 to 89 years old, 0.82, 0.70 to 0.94; Figure 1). The interaction between gender and age was significant for the 2 populations (p ⬍0.001). After adjustment for potential risk factors, excess risk for in-hospital mortality for women ⬍50 years old persisted, with a 98% (1.98, 1.26 to 3.12) greater odds of death. Excess risk of in-hospital mortality in women decreased with age, with no statistical difference between women and men at ⱖ60 years of age (50 to 59 years old, 1.54, 1.16 to 2.06; 60 to 69 years old, 1.24, 0.96 to 1.60; 70 to 79 years old, 1.17, 0.95 to 1.45; 80 to 89 years old, 0.95, 0.77 to 1.18; Figure 2). In patients with NSTEMI a noticeable decrease in gender differences in patients ⬍60 years old was observed after adjusting for sociodemographic and clinical factors. After adjustment the odd ratios for in-hospital mortality for women versus men were 1.23 (95% confidence interval 0.69 to 2.17), 1.28 (0.96 to 1.70), and 1.22 (0.96 to 1.54) for age groups 18 to 49, 50 to 59, and 60 to 69, respectively, but the differences were not significant. Older women (ⱖ70 years old), however, had better outcomes than men (70 to 79 years old, 0.81, 0.67 to 0.98; 80 to 89 years old, 0.85, 0.73 to 0.99; Figure 2). The interaction between age and gender was significant in the adjusted models for patients with STEMI and those with NSTEMI.

70-79 years

Discussion 80-89 years

adjusted unadjusted

0.1

0.2

0.5

1.0

2.0

5.0

10.0

Odds Ratio (Women versus Men)

B Figure 2. Adjusted and unadjusted women-to-men odds ratios for inhospital mortality by age and acute (A) ST-segment elevation myocardial infarction and (B) non–ST-segment elevation myocardial infarction.

tachycardia and ventricular fibrillation increased with advancing age in the 2 populations. Women in 18 to 49 years old had a trend of a higher risk of cardiogenic shock than their men counterparts in the 2 populations (Table 3). In-hospital mortality rate for the overall AMI population was 3.85%, with 4.35% for STEMI and 3.53% for NSTEMI (odds ratio 1.24, 95% confidence interval 1.16 to 1.33, p ⬍0.0001). Women had a higher unadjusted in-hospital mortality rate than men in the STEMI group (6.45% vs 3.45%, 1.91, 1.72 to 2.11) and NSTEMI group (3.89% vs 3.31%, 1.18, 1.08 to 1.30). When mortality rate was examined by age group, gender-based differences varied according to age (Figure 1). Women ⬍50 years old had higher odds of in-hospital mortality than men of similar age in the 2 populations, with the odds ⬎2 times as high for women in patients with STEMI (odds ratio 2.29, 95% confidence interval 1.48 to 3.55) and 51% higher (1.51, 0.87 to 2.61) in

Our analysis using contemporary data on the privately insured population indicates that when the in-hospital mortality rate was examined in patients with STEMI and with NSTEMI separately, the diseases were found to have different patterns by gender. In patients with STEMI women ⬍60 years old had higher odds of in-hospital mortality than men of the same age. In contrast, in patients with NSTEMI and ⬍70 years old the difference in risk of in-hospital death was not statistically significant between women and men, whereas women ⱖ70 years old had better outcomes than their men counterparts. Our analysis expands on previous findings that women who develop an AMI are less likely to have this event be a STEMI than are their men counterparts.9,13,21 Also consistent with previous reports was that women with AMI were less aggressively treated, partly owing to older age, less extensive atherosclerosis, and unsystematic symptoms. Our analysis demonstrated that women with AMI, whether STEMI or NSTEMI, tended to be older and had more co-morbidities, which further confirms findings from previous reports.1,2,4 – 6 In our study the in-hospital mortality rate for women and men was lower than in previous reports from other investigators. For example, a study using the AMI in Switzerland Plus Registry (in Switzerland) found that unadjusted inhospital mortality was 7.5% in the overall AMI population; in-hospital mortality was 13% for women and 7.2% for men in patients with STEMI and 7.5% versus 4.9% in those with

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NSTEMI.4 In a United States study that used data from the National Registry of Myocardial Infarction, in-hospital mortality from 2003 through 2006 was 6.3% overall for patients with AMI, 8.0% for patients with STEMI, and 5.2% for patients with NSTEMI.22 The lower rate of in-hospital mortality found in our analysis may be due to the characteristics of patients in MarketScan such as younger age, the fact that most are privately insured, the first record of AMI hospitalization for a patient from 2004 through 2007, and the larger percentage of percutaneous coronary intervention procedures. Although numerous studies have focused on the gender difference in mortality after AMI, its age-specific gender difference by AMI type has been studied less extensively. Champney et al23 used the 2000 to 2006 national Registry of Myocardial Infarction data and found that gender-related differences in in-hospital mortality rate were age dependent in patients with STEMI and with NSTEMI. Adjusted excess risks for women ⬍50 years old were 17% for patients with STEMI and 15% for those with NSTEMI, but older women had a better survival rate than older men in the NSTEMI population. We found women with STEMI and ⬍50 years old had a 98% higher risk of in-hospital death than men of the same age. Several factors have been shown to be associated with excess risk of in-hospital mortality in younger women (vs younger men). First, after AMI younger women were found to wait longer before going to the hospital1 and to be less likely to receive timely reperfusion,9,24 reperfusion therapy, and other established treatment.1,9 Second, younger women are generally spared from coronary heart disease in part because of the protection of estrogen, and thus younger women who develop AMI may have particularly aggressive disease or more risk factors. Third, plaque erosions are more common in younger women, whereas men and older women are more prone to plaque ruptures.25 Fourth, younger women may be more likely to present with atypical symptoms of AMI, causing delayed recognition and diagnosis.1 Regardless of these points, however, it is hard to explain why there is excess risk for in-hospital mortality for younger women compared to younger men in patients with STEMI but not in those with NSTEMI. Some issues must be taken into account when interpreting our results. First, patients included in the analysis were mostly privately insured and thus do not represent the whole United States population, limiting the generalizability of our results. Second, inability to confirm ICD-9-CM diagnostic coding is a limitation for any study using a claims database; the possibility of coding error must be acknowledged. Third, information on prehospital AMI death was not available. Data from some registries have indicated that the higher in-hospital mortality in younger women is counterbalanced by a higher mortality before hospitalization in men.26 –28 This hypothesis was, however, not supported by other studies.29 Moreover, studies have suggested that younger and older patients with AMI benefit from thrombolysis30 and from treatment with aspirin, ␤ blockers, and angiotensin-converting-enzyme inhibitors. These are treatments that women are less likely to receive during hospitalization.9 Unfortunately, information on these treatments was not collected in the MarketScan data, and its impact on

in-hospital mortality in women and men could not be determined. However, studies have shown that excess risk of in-hospital death in younger women persists even after adjustment for the difference in in-hospital treatment between women and men.1,2,4 Furthermore, key drivers of AMI outcomes including hemodynamic status, cardiac arrest, and renal function as continuous variable are not available. This will possibly affect our estimates. In addition, studies have shown that younger women are less likely to be given an initial diagnosis of AMI.1 The higher risk in younger women in our analysis may be overestimated because of the underdiagnosis of AMI in younger women. Also, we were unable to determine whether heart failure and other co-morbidities were a pre-existing co-morbidity or a complication of AMI. Race is an important predictor of in-hospital mortality after AMI. It was, however, not collected in MarketScan databases, which, to some extent, may affect the risk estimate for women versus men in our analysis. Supplementary Data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.amjcard. 2011.12.001. 1. Vaccarino V, Parsons L, Every NR, Barron HV, Krumholz HM. Sex-based differences in early mortality after myocardial infarction. National Registry of Myocardial Infarction 2 participants. N Engl J Med 1999;341:217–225. 2. Mahon NG, McKenna CJ, Codd MB, O’Rorke C, McCann HA, Sugrue DD. Gender differences in the management and outcome of acute myocardial infarction in unselected patients in the thrombolytic era. Am J Cardiol 2000;85:921–926. 3. Vaccarino V, Krumholz HM, Yarzebski J, Gore JM, Goldberg RJ. Sex differences in 2-year mortality after hospital discharge for myocardial infarction. Ann Intern Med 2001;134:173–181. 4. Radovanovic D, Erne P, Urban P, Bertel O, Rickli H, Gaspoz JM; AMIS Plus Investigators. Gender differences in management and outcomes in patients with acute coronary syndromes: results on 20,290 patients from the AMIS Plus Registry. Heart 2007;93:1369 –1375. 5. Vaccarino V, Krumholz HM, Mendes de Leon CF, Holford TR, Seeman TE, Horwitz RI, Berkman LF. Sex differences in survival after myocardial infarction in older adults: a community-based approach. J Am Geriatr Soc 1996;44:1174 –1182. 6. Alfredsson J, Stenestrand U, Wallentin L, Swahn E. Gender differences in management and outcome in non-ST-elevation acute coronary syndrome. Heart 2007;93:1357–1362. 7. Norhammar A, Stenestrand U, Lindbäck J, Wallentin L; Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA). Women younger than 65 years with diabetes mellitus are a high-risk group after myocardial infarction: a report from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admission (RIKS-HIA). Heart 2008; 94:1565–1570. 8. Weaver WD, White HD, Wilcox RG, Aylward PE, Morris D, Guerci A, Ohman EM, Barbash GI, Betriu A, Sadowski Z, Topol EJ, Califf RM. Comparisons of characteristics and outcomes among women and men with acute myocardial infarction treated with thrombolytic therapy. GUSTO-I investigators. JAMA 1996;275:777–782. 9. Jneid H, Fonarow GC, Cannon CP, Hernandez AF, Palacios IF, Maree AO, Wells Q, Bozkurt B, Labresh KA, Liang L, Hong Y, Newby LK, Fletcher G, Peterson E, Wexler L; Get With the Guidelines Steering Committee and Investigators. Sex differences in medical care and early death after acute myocardial infarction. Circulation 2008;118: 2803–2810. 10. Reynolds HR, Farkouh ME, Lincoff AM, Hsu A, Swahn E, Sadowski ZP, White JA, Topol EJ, Hochman JS; GUSTO V Investigators. Impact of female sex on death and bleeding after fibrinolytic treatment

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