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Comparison of Gender-Specific Mortality in Patients <70 YearsVersus >70 Years Old With Acute Myocardial Infarction

Masaharu Ishihara, MD, PhD*, Ichiro Inoue, MD, PhD, Takuji Kawagoe, MD, PhD,Yuji Shimatani, MD, Fumiharu Miura, MD, PhD, Yasuharu Nakama, MD, Kazuoki Dai, MD,

Takayuki Ootani, MD, Kuniomi Ooi, MD, Hiroki Ikenaga, MD, Takashi Miki, MD,Masayuki Nakamura, MD, Shinji Kishimoto, MD, and Youji Sumimoto, MD

The aim of the present study was to investigate the gender-specific mortality after acutemyocardial infarction in those aged <70 years versus >70 years. The present studyconsisted of 2,677 consecutive patients with acute myocardial infarction who had under-gone coronary angiography within 24 hours after the onset of symptoms. The patients weredivided into 2 groups: 1,810 patients <70 years old and 867 patients >70 years old. Womenwere older and had a greater incidence of hypertension and diabetes mellitus and a lowerincidence of current smoking and previous myocardial infarction in both groups. Thein-hospital mortality rate was significantly greater in women >70 years old age than in men>70 years old (16.2% vs 9.3%, respectively; p � 0.003) but was comparable between womenand men in patients <70 years old (5.7% vs 4.9%, respectively; p � 0.59). On multivariateanalysis, the association between female gender and in-hospital mortality in patients >70years old remained significant (odds ratio 1.78, 95% confidential interval 1.05 to 3.00), butthe gender difference was not observed in patients <70 years old (odds ratio 1.09, 95%confidence interval 0.53 to 2.24). In conclusion, female gender was associated with in-hospital mortality after acute myocardial infarction in patients >70 years old but not inpatients <70 years old. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;108:

772–775)

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Acute myocardial infarction (AMI) is a leading cause ofmortality in women and men in the developed countries.1 Itas been well demonstrated that the mortality after AMI isreater in women than in men.2–6 Age is another important

risk factor for both women and men7; however, femalepatients with AMI are an average of 10 years older thanmale patients. It has been reported that older age accountsfor a greater part of the excess deaths among female patientswith AMI.8–10 However, it remains unknown whether theender-specific mortality after AMI is different betweenlder and younger patients. In the present study, we as-essed the in-hospital mortality of women and men withMI aged �70 and �70 years.

ethods

The present study consisted of 2,677 consecutive patientsith AMI who had undergone coronary angiography within4 hours after the onset of symptoms at Hiroshima Cityospital, a tertiary referral institution of Hiroshima City.MI was diagnosed by chest pain consistent with ongoingyocardial ischemia persisting �30 minutes and concom-

tant electrocardiographic changes. The serum creatine ki-ase was measured every 3 hours for �24 hours, and theeak creatine kinase value was required to be more than

Department of Cardiology, Hiroshima City Hospital, Hiroshima, Japan.Manuscript received April 6, 2011; manuscript received and accepted April29, 2011.

*Corresponding author: Tel: (81) 82-221-2291; fax: (81) 82-223-1447.

ME-mail address: ishifami@fb3.so (M. Ishihara).

002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved.oi:10.1016/j.amjcard.2011.04.030

wice the normal upper limit. The patients were divided intogroups: 1,810 patients �70 years old and 867 patients70 years old. All patients provided written informed con-

ent, and the ethical committee of human research of Hiro-hima City Hospital approved the study.

Emergency coronary angiography was performed as pre-iously reported.11 Selective coronary angiography was

performed in multiple projections before the initiation ofreperfusion therapy. Immediately after diagnostic angiogra-phy, reperfusion therapy was performed. The allocation ofreperfusion therapy was the physician’s decision.

All coronary angiograms were reviewed by 2 angiogra-phers without knowledge of the clinical variables. The per-fusion status of the infarct-related artery was determined inaccordance with the Thrombolysis In Myocardial Infarction(TIMI) study classification.12 An initially occluded arterywas defined as TIMI 0 or TIMI 1 flow before the initiationof reperfusion therapy. Successful reperfusion was definedas TIMI 3 flow on the final shot of the angiogram. Multi-vessel coronary disease was defined as �75% stenosis in�1 vessels remote from the infarct artery. Collateral circu-lation was considered present if partial or complete filling ofthe infarct artery distal to the infarct lesion was present.

Categorical data are reported as the proportions andcontinuous data as the mean � SD. Statistical analysis wasperformed using the chi-square test for categorical vari-ables. The t test was used for continuous variables. Logisticegression analysis was used to obtain the odds ratio (OR)nd 95% confidence interval (CI) for in-hospital mortality.

ultivariate analysis was performed, adjusting for age

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773Coronary Artery Disease/Gender and Age in AMI

(model 1) or for age, hypertension, diabetes mellitus, cur-rent smoking, Killip class, interval to angiography, infarctlocation, initial occlusion of the infarct artery, collateral circu-lation, multivessel disease, use of primary percutaneous coro-nary angioplasty (PCI) and final reperfusion (model 2). Weused the JMP statistical package, version 5.1 J (SAS Institute,Cary, North Carolina), for statistical analysis. A significancelevel of p � 0.05 was used and 2-tailed tests were applied.

esults

Of the 2,677 patients, 559 were women (20.9%) and,118 were men (79.1%). The women were significantlylder than the men (69.2 � 10.8 vs 61.5 � 11.4 years,espectively; p �0.001). The proportion of women was

Table 1Baseline characteristics of patients �70 years old

Variable

Age (y)HypertensionDiabetes mellitusCurrent smokerPrevious myocardial infarctionKillip class 2–4Interval to admission (hr)Anterior wall locationInitial Thrombolysis In Myocardial Infarction 0-1CollateralsMultivessel coronary diseaseReperfusion therapy

Primary coronary angioplastyUse of stentsThrombolysisCoronary bypass surgery

Final Thrombolysis In Myocardial Infarction 3 (n � 837)*

* Patients undergoing bypass surgery were excluded.

Table 2Baseline characteristics of patients �70 years old

Variable

Age (y)HypertensionDiabetes mellitusCurrent smokerPrevious myocardial infarctionKillip class 2–4Interval to admission (hr)Anterior wall locationInitial Thrombolysis In Myocardial Infarction 0-1CollateralsMultivessel coronary disease

eperfusion therapyPrimary coronary angioplastyUse of stentsThrombolysisCoronary bypass surgeryinal Thrombolysis In Myocardial Infarction 3 (n � 1,731)*

* Patients undergoing bypass surgery were excluded.

ignificantly larger in the �70-year-old group than in the

70-year-old group (34.1% vs 14.5%, respectively; p0.001). The baseline clinical and angiographic character-

stics of the women and men aged �70 years are listed inable 1. These variables for the patients aged �70 years are

isted in Table 2.Of the 2,677 patients, 192 (7.2%) died before hospital

discharge. The in-hospital mortality rate was significantlygreater in the women than in the men (11.3% vs 6.1%,respectively; p �0.001) and in those aged �70 years thanged �70 years (11.7% vs 5.0%, respectively; p �0.001).

Of the patients �70 years old, in-hospital mortality wassignificantly greater in women than in men (16.2% vs 9.3%,respectively; p � 0.003; Figure 1). However, no significantgender difference in mortality was found among patients

Women(n � 290)

Men(n � 571)

p Value

7.1 � 5.5 75.4 � 4.6 �0.001176 (60%) 288 (45%) �0.001

88 (30%) 135 (24%) 0.0534 (12%) 242 (42%) �0.00128 (10%) 89 (16%) 0.0154 (18%) 81 (14%) 0.12

5.9 � 5.5 5.3 � 4.9 0.12143 (48%) 253 (44%) 0.26217 (73%) 412 (72%) 0.72

64 (22%) 144 (25%) 0.24120 (41%) 242 (42%) 0.60

233 (79%) 447 (78%) 0.88150 (51%) 291 (51%) 0.94

40 (14%) 72 (13%) 0.717 (2%) 27 (5%) 0.08

214 (74%) 421 (77%) 0.28

Women(n � 263)

Men(n � 1,547)

p Value

60.4 � 8.2 56.4 � 8.5 �0.001136 (51%) 612 (40%) �0.00180 (30%) 370 (24%) 0.0392 (35%) 984 (64%) �0.00110 (4%) 187 (12%) �0.00133 (13%) 181 (12%) 0.67

5.1 � 4.9 5.0 � 4.9 0.81135 (51%) 815 (53%) 0.88202 (77%) 1,194 (77%) 0.8973 (28%) 467 (30%) 0.4296 (37%) 537 (35%) 0.57

186 (71%) 1,152 (75%) 0.21103 (39%) 671 (43%) 0.2050 (19%) 255 (17%) 0.327 (3%) 72 (5%) 0.12

195 (76%) 1,188 (81%) 0.11

7

�70 years old (5.7% vs 4.9%, p � 0.59).

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774 The American Journal of Cardiology (www.ajconline.org)

Female gender was associated with in-hospital mortalityin patients �70 years old but not those aged �70 years(Table 3). Multivariate analysis (model 2) found that age,Killip class, infarct location, multivessel disease, and finalreperfusion were independently associated with in-hospitalmortality in patients �70 years old. All these variables andprevious myocardial infarction were significant in patients�70 years old. On multivariate analysis, the association offemale gender and in-hospital mortality remained signifi-cant in patients �70 years old. However, gender was not apredictor of in-hospital mortality in patients �70 years old.

The final reperfusion (TIMI 3 flow) was a strong inde-pendent predictor of decreased in-hospital mortality inwomen (OR 0.16, 95% CI 0.07 to 0.37) and men (OR 0.14,95% CI 0.06 to 0.32) �70 years old, women (OR 0.14, 95%CI 0.03 to 0.67) and men (OR 0.15, 95% CI 0.08 to 0.28)�70 years old. However, even when only patients �70years old with final reperfusion were analyzed, female gen-der was still associated with in-hospital mortality (8.8% vs4.0%, p � 0.02).

Discussion

A considerable number of studies have demonstrated thatmortality after AMI is greater in women than in men. Thefemale patients with AMI were older, had more co-morbid-ities, and less often received reperfusion therapy. Althoughit remains controversial whether female gender is an inde-pendent predictor of mortality after AMI after adjustmentfor age and co-morbid factors,13,14 most studies are inagreement that women’s older age is largely contributory to

Figure 1. In-hospital mortality of women and men. (A) In patients �70 yearifferences in mortality were not observed.

able 3nadjusted and adjusted odds ratios for women and in-hospital mortality

Variable Age 70 yr

OR 95% CI

nadjusted 1.89 1.24–2.88Adjusted (model 1) 1.77 1.16–2.71Adjusted (model 2) 1.78 1.05–3.00

Model 1 adjusted for age.Model 2 adjusted for age, hypertension, diabetes mellitus, current smokin

artery, collateral circulation, multivessel disease, use of primary percutane

the adverse outcomes of women with AMI. The third In- s

ternational Study of Infarct Survival (ISIS-3) reported thatmore than 2/3 of the excess mortality among women waseliminated by the adjustment for age.8 Although some pre-vious studies have reported that younger women havepoorer outcomes than younger men,15 the results of thepresent study found no gender-specific difference in mor-tality after AMI among patients �70 years old. In contrast,in patients �70 years old, women had an approximately1.9-fold greater risk of in-hospital mortality after AMI.

Consistent with previous studies, we found that womenhad more co-morbidities than men, including hypertensionand diabetes. In contrast, men were more likely to be smok-ers and to have a history of previous myocardial infarction.Although these findings were comparable between patients�70 years old and those �70 years old, the effect of genderon mortality was different. In patients �70 years old, theconventional risk factors, including age, Killip class, infarctlocation, multivessel disease, and final reperfusion status,were associated with in-hospital mortality, but gender wasnot. In patients �70 years old, however, female gender wasa predictor of mortality after AMI, as were other conven-tional risk factors. Compared to men �70 years old, women�70 years old had greater mortality, even after adjustmentfor age and co-morbid risk factors.

Gender differences in the clinical manifestation of acutecoronary syndrome have been demonstrated in several stud-ies.16 Women generally present with atypical symptoms.

revious studies have reported that women with AMI wereess likely to receive reperfusion therapy, or if received, itould be delayed.17,18 At catheterization, women have

omen had greater mortality than men. (B) In patients �70 years old, gender

Age �70 yr

Value OR 95% CI p Value

.003 1.17 0.66–2.08 0.59

.009 1.01 0.57–1.79 0.98

.03 1.09 0.53–2.24 0.82

p class, interval to angiography, infarct location, initial occlusion of infarctronary angioplasty, and final reperfusion.

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775Coronary Artery Disease/Gender and Age in AMI

use for PCI, with a lower use of stents.19 The risk of adversevents during PCI is greater in women than in men. In theresent study, we registered only patients who had under-one emergent coronary angiography. Female gender wasot associated with a delayed interval to angiography. Mostf the patients underwent primary PCI, and the use of stentsas comparable between both genders. Final reperfusionas achieved in �75% of the patients, with no genderifferences. Final reperfusion was associated with an ap-roximately 85% decrease in mortality in both women anden and in patients both �70 years old and �70 years old.lthough final reperfusion effectively reduced mortality

ven in women �70 years old, in-hospital mortality wasignificantly greater in women �70 years old than in men,ven with timely reperfusion.

This was a retrospective and observational study. How-ver, all consecutive patients with AMI who underwentoronary angiography were prospectively included in a sin-le-center registry. The prevalence of women was relativelymaller in our study than in previous studies from tertiaryeferral institutions, suggesting a possible selection bias forhe present study because we included only patients under-oing coronary angiography. Gender differences in theanifestation of acute coronary syndromes, includingT-segment elevation myocardial infarction (STEMI),on-STEMI, and unstable angina, have been reported.owever, our study included those with STEMI andon-STEMI and did not include those with unstable an-ina. The small sample size was another limitation of ourtudy. Analyses from large-scale nationwide registriesre warranted to assess the gender–age interaction in theortality of patients with AMI.

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