Brief Article Open Access
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Cardiol. Feb 26, 2012; 4(2): 36-47
Published online Feb 26, 2012. doi: 10.4330/wjc.v4.i2.36
Gender gap in acute coronary heart disease: Myth or reality?
Mette Claassen, Kirsten C Sybrandy, Folkert W Asselbergs, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, 3508 GA Utrecht, The Netherlands
Yolande E Appelman, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Author contributions: Claassen M and Asselbergs FW performed the main research and writing; Sybrandy KC and Appelman YE provided essential comments and reviewed the manuscript.
Supported by A clinical fellowship from the Netherlands Organisation for Health Research and Development to Folkert W Asselbergs, No. 90700342
Correspondence to: Folkert W Asselbergs, MD, PhD, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Room E03.511, PO Box 85500, 3508 GA Utrecht, The Netherlands.
Telephone: +31-88-7553358 Fax: +31-88-7555423
Received: April 9, 2011
Revised: December 9, 2011
Accepted: December 16, 2011
Published online: February 26, 2012


AIM: To investigate potential gender differences in the prevalence of cardiovascular risk factors, cardiovascular disease (CVD) management, and prognosis in acute coronary syndrome (ACS).

METHODS: A systematic literature search was performed through Medline using pre-specified keywords. An additional search was performed, focusing specifically on randomized controlled clinical trials in relation to therapeutic intervention and prognosis. In total, 92 relevant articles were found.

RESULTS: Women with CVD tended to have more hypertension and diabetes at the time of presentation, whereas men were more likely to smoke. Coronary angiography and revascularization by percutaneous coronary intervention were performed more often in men. Women were at a greater risk of short-term mortality and complications after revascularization. Interestingly, women under 40 years presenting with ACS were at highest risk of cardiovascular death compared with men of the same age, irrespective of risk factors. This disadvantage disappeared in older age. The long-term mortality risk of ACS was similar in men and women, and even in favor of women.

CONCLUSION: Mortality rates are higher among young women with ACS, but this difference tends to disappear with age, and long-term prognosis is even better among older women.

Key Words: Cardiovascular disease, Gender, Myocardial infarction, Coronary artery bypass grafting, Percutaneous coronary intervention, Postoperative complications, Mortality, Prognosis, Estrogens


Cardiovascular disease (CVD) is an important cause of death among both men and women. In women, CVD develops 7 to 10 years later than in men, potentially because of a protective effect of estrogens. However, CVD is the main cause of death among women and its occurrence narrows women’s survival advantage over men[1]. In most parts of the world, the mortality rate has declined in the last 30 years, except for Eastern Europe and China[2]. In the United States in 2007, 391 886 men died because of CVD, compared with 421 918 women[3], while 10 years previously the mortality rate of CVD in men was significantly higher in several countries[4]. Some studies have suggested gender differences in presentation and treatment of CVD and acute coronary syndrome (ACS), but there are many uncertainties and discrepancies between these studies[4,5]. Besides differences in presentation, women also seem to have different abnormalities with regard to electrocardiography and scintigraphy, compared with men[4]. The aim of this review is to provide an overview of what is known nowadays with respect to possible gender differences in cardiovascular risk factors, therapy and prognosis of ACS.


A systematic literature search was performed through Medline using pre-specified keywords. The following keywords with synonyms were used for selecting relevant studies: CVD, coronary artery disease (CAD), ACS/event, ischemic heart disease, myocardial infarction (MI), gender, sex, women, men, differences, estrogens, hormone replacement therapy (HRT), coronary artery bypass surgery (CABG), percutaneous coronary intervention (PCI), revascularization, readmission, postoperative complications, outcome, and hospital mortality. Only studies that included both men and women were eligible for review. Of 2260 articles found, 199 articles appeared relevant after screening of the title and abstract. Furthermore, through a search of the references in the articles obtained by these keywords, 30 additional relevant articles were found.

A more focused exclusion of articles was then performed in relation to therapy and prognosis of ACS. Articles published before 2000 were excluded, because therapy, operative techniques and thereby prognosis have a high tendency to change over time. Selected articles included patients with ACS, unstable angina, acute MI, ST elevation MI (STEMI) and non-STEMI, and subsequently compared women with men. This provided 152 articles. After screening of the full text, a total of 92 articles were found to be relevant and valid.


The prevalence of CVD increased with age and was higher among men. The prevalence of coronary heart disease (CHD) in the United States was 37.4% in men and 35.0% in women in 2008, with a mortality rate of 48.2% and 51.8% in men and women, respectively, in 2007. The prevalence of CHD in men and women of 20 years and older was 8.3% and 6.1%, respectively. When comparing different countries, France and Japan had the lowest prevalence of CHD for both men and women (Table 1)[3]. Although the incidence of CVD remained higher in men compared with women, figures of the last 30 years showed a declining incidence of CVD in men, while the incidence in women remained relatively stable. In North America CVD is the leading cause of hospital admission for both men and women. However, in women hospital stay tended to be longer and they experienced higher levels of pain, disability and discomfort, compared with men[2]. In the United States in 2007, one out of three deaths was caused by CVD and one out of six was due to CHD. However, the risk of heart disease in women often seemed to be underestimated, with CVD the major cause of death in women older than 75 years[3].

Table 1 Mortality rates of coronary heart disease per 100 000 population by gender[3].
CountryYear1Men 35-74 yrWomen 35-74 yr
United States2007153.360.4
The Netherlands200866.222.8
Russian Federation2006706.0237.1
New Zealand2005138.447.2
Risk factors

The INTERHEART study identified nine different global risk factors for an acute MI, namely smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins, and psychosocial factors. Altogether, they could predict the risk of an acute MI as 90% in men and 94% in women. Although most of these classic risk factors were of equal clinical significance in both men and women[6], women who presented with ACS more often had hypertension[7-61], diabetes[7-10,12,13,15-17,20,22-25,27,28,30-32,34-36,38,39,41-43,45-47,49-54,57-66], hypercholesterolemia[7,9,10,13,15-17,21,22,26,28-30,35,36,50], and a history of angina[7,50], heart failure[7,45,47,52,53,59,60,63,64], and cerebrovascular events (CVA)[7,39,47,50,52,63,64] than men. On the other hand, men tended to smoke more[7-10,13-17,19-22,25,26,28,30,31,33-44,46,47,49-51,53-56,62,66] and were more likely to have a history of MI[7-9,14,16,18,19,21-23,28-32,36,39,41,43,45,47,51,53-56,58,64] and prior CABG[7-10,12,13,15-17,23,28,30,31,34,39,43,44,54,55,62-64,67] as shown in Table 2. Although women smoked less, the relative risk (RR) for developing a MI was 1.57 (95% CI: 1.25-1.97) among smoking women in comparison to smoking men and this increased risk was pronounced in women at younger age (< 55 years)[68]. The prevalence of fatal CHD was substantially higher in patients with diabetes, in comparison to patients without diabetes (5.4% vs 1.6%). Among women, this effect of diabetes on mortality was even stronger, with a RR of 3.50 (95% CI: 2.70-4.53), compared with a RR of 2.06 (95% CI: 1.81-2.34) among men with diabetes vs no diabetes[69]. Women with ACS more often had a family history of CAD[23,33,70]. However, a family history of premature CAD was not a risk factor overall for in-hospital mortality[71]. The cardiovascular risk burden tended to be higher in women aged younger than 46 years, compared with men of the same age. Of all patients younger than 46 years presenting with ACS, 78.5% and 25.3% of women, respectively, had one or more than one risk factor for ACS, compared with 71.8% and 17.2%, respectively, among men (P = 0.008 and P < 0.001, respectively)[24]. Peirera et al[72] studied differences in hypertension between men and women as an important risk factor for CVD. Apart from the fact that women received treatment more often, they also had a greater awareness of the risk of hypertension for CVD. In both developing and developed countries, awareness, control and treatment of hypertension was significantly higher in women, compared with men. On the other hand, women were categorized at high-risk of CVD in risk assessment programs if a history of diabetes, stroke or chronic kidney disease was present[73], and all these conditions were generally more prevalent in women, compared with men, as noted above.

Table 2 Prevalence of cardiovascular risk factors and history of myocardial infarction and cardiac surgery stratified by gender.
AuthorDesignStudy populationPatientsAge (mean, yr)PHypertension (%)PDiabetes (%)PSmoking (%)PHistory of MI (%)PHistory of cardiac surgery (%)P
Reynolds et al[30] 2007RCTMI12 498409059.567.0< 0.00129.747.3< 0.00114.421.0< 0.00149.734.3< 0.00116.412.5< 0.001CABG3.72.2< 0.001
PCI7.54.5< 0.001
Moriel et al[28] 2005Pros cohortACS  82051178790.125874< 0.00133400.007135< 0.0013929< 0.001CABG147< 0.001
PCI2111< 0.001
Herlitz et al[18] 2009Retro cohortAMI  83558872.779.2< 0.000146560.012421NS2216NS4233< 0.0001CABG1070.06
Mehilli et al[54] 2002Pros cohortAMI  143550260.770.3< 0.00161.072.9< 0.00118.025.3< 0.00143.125.9< 0.00122.116.30.001CABG6.13.40.02
Mueller et al[55] 2002Pros cohortMI  103341764680.0160720.0119230.1533210.0137240.01CABG1760.01
Toumpoulis et al[34] 2006Pros cohortCABG  2598116263.266.2< 0.00165.979.4< 0.00128.845.5< 0.00116.112.90.01150.746.10.010CABG7.85.30.006
Dallongevillle et al[15] 2010Pros cohortACS  6698226862.265.8< 0.000180.387.9< 0.000133.638.40.00919.311.0< 0.000119.120.6< 0.0001CABG20.417.2< 0.0001
Anand et al[9] 2005TrialACS  7726483662.766.50.00015368.80.000120.924.60.000176.437.40.000136.923.90.0001CABG13.36.80.0001
Matsui et al[26] 2002Retro cohortAMI  34613662.970.444540.04725330.07860190.00118150.517CABG110.556
Tizón-Marcos et al[33] 2009RCTPCI  105029859.762.549590.00417200.1932360.2345410.19CABG6.36.41.00
Reina et al[51] 2007Pros cohortAMI  464115686471< 0.0141.061.1< 0.0125.541.2< 0.0153.615.7< 0.0116.613.0< 0.01Total7.212.0< 0.01
Thompson et al[53] 2006Pros cohortPCI  80735961.767.7< 0.00159.367.80.00623.830.10.0347.438.50.00525.222.40.33CABG8.37.20.53
Lee et al[78]Pros cohortSTEMI  2954108360.772.1< 0.00140.259.7< 0.00123.131.4< 0.00158.814.7< 0.0013.62.90.239CABG0.50.30.330
Jankowski et al[46] 2007Pros cohortCAD + PCI  73818757.560.6< 0.00172.687.8< 0.00114.521.3< 0.0513.66.4< 0.0163.266.0NSCABG1.50.5NS
Duvernoy et al[43] 2010Pros cohortPCI14848787761.966.9< 0.00171.082.5< 0.00129.238.5< 0.00127.321.7< 0.00136.032.6< 0.001CABG21.517.4< 0.001
PCI41.838.9< 0.001
Lansky et al[22] 2005RCTAMI + PTCA  152056257.066.0< 0.00129.059.3< 0.00114.025.7< 0.00145.337.40.00115.78.4< 0.001PCI12.77.1< 0.001
Lansky et al[67] 2009RCTPCI  68731461.865.9< 0.000172.781.50.002625.736.30.000724.021.20.371121.913.60.0022Total34.125.50.0066
De Luca et al[41] 2004Pros cohortSTEMI  11953535966< 0.0012439< 0.0018.715.8< 0.00152.142.70.00211.67.10.014CABG2.11.7NS
De Luca et al[42] 2010TrailSTEMI  12833795967< 0.00139.152.5< 0.00115.322.4< 0.0015636.9< 0.0019.27.70.35Total7.77.60.93
Bufe et al[62]Pros cohortSTEMI + PCI  3761245865< 0.0016654.80.05511.224.2< 0.00167.340.3< 0.00111.78.90.479CABG5.60.80.046
Carrabba et al[40] 2004Pros cohortSTEMI  62729367.776.30.00145.360.1< 0.00122.725.30.38534.114.3< 0.00117.214.70.331CABG2.61.00.129
Lawesson et al[24] 2010Retro cohortSTEMI aged < 46  174838440.840.40.1413.921.7< 0.00112.418.50.00258.
Berger et al[10] 2006Pros cohortPCI  2953133161.966.8< 0.0016678< 0.0012236< 0.0011510< 0.00136330.08CABG19140.001
Chiu et al[13]Pros cohortPCI12 738530162.366.5< 0.0015871< 0.0012434< 0.00121200.0143420.29CABG3021< 0.001
2004PCI64< 0.001
Koch et al[20]Pros cohortCABG  158846051.770.20.000122.536.30.000171.549.60.000114.310.70.044CABG14.47.00.0001
Setoguchi et al[31] 2008Pros cohortAMI  31713088082< 0.00171800.00133390.0315100.015237< 0.001CABG18130.03

In the evaluation of CVD, coronary angiography (CAG) was less often performed in women than in men[9,11,18,30,44,49,60]. Age might be an important confounding factor in this regard, because women present with an ACS 10 years later than men, and CAGs were less likely to be performed in the elderly[28]. Age was found to be a predictor for undergoing PCI, with an odds ratio (OR) of 0.98 (95% CI: 0.97-0.98) for each additional year[51,60,74]. Nevertheless, even after adjustment for age[18] and other cardiovascular risk factors[9,11], women with ACS were still less likely to have CAG or PCI[45,47,49] (OR, 0.70; 95% CI: 0.64-0.76)[75]. In men and women younger than 46 years, no differences were seen in the number of performed angiograms[24]. In ACS patients who underwent CAG, an equal number of men and women received a PCI afterwards[18,30,60,66]. In STEMI patients, results were inconsistent. Some studies found no significant differences in the number of CAGs and PCIs performed after adjustment for age[40,44,50,51], while Radovanovic et al found that women with both STEMI and non-STEMI underwent primary PCI less often (30.9% and 22.0%, respectively) compared with men (40.3% and 30.9%, respectively). This difference persisted after adjustment for cardiovascular risk factors (OR, 0.70) and after adjustment for age alone (OR, 0.71; 95% CI: 0.63-0.80)[58,74].

The mortality rate for ACS was highest among female patients who did not undergo a CAG; 12.9% vs 4.7% in those who underwent a CAG, compared with 5.6% and 2.9%, respectively, in men[30]. A higher mortality rate among women compared with men was also reported in patients who suffered a STEMI. A possible explanation may be the higher rate of comorbidity in women and a greater delay between onset of complaints and arrival at the emergency department compared with men. At 6 mo follow-up, no significant differences in mortality were present[28].

Several studies compared the coronary anatomy of men and women presenting with ACS. In general, women tended to have a smaller diameter of coronary arteries, in proportion with the lower body surface area, and this was associated with a higher mortality rate[13,16,20,22,34,36,43,53,75,76]. Women more often had one-vessel disease[8,19,23,24,34,43,52,62,67] and less often three-vessel disease[8,9,19,23-25,34,43,55,66,67] as shown in Table 3. Multiple vessel disease was associated with a higher mortality rate[77]. In addition, women with ACS had less extensive obstructive CAD, whereas men not only had more lesions, but also lesions of greater length and complexity[23]. Nevertheless, among patients who underwent PCI no differences were seen between men and women in the number of stents placed; 69% vs 66%[19] and 77% vs 77%[10]. Furthermore, no differences were found in length or diameter of the stents placed, nor in success rate of the performed PCI[25,41,43,46,48,53,56,57,59,78]. It remains uncertain whether women would benefit as much as men from early invasive strategy in the case of an ACS, because the power of the different studies was limited[14,21].

Table 3 Extent of coronary artery disease stratified by gender.
Author study/dateDesignStudy populationPatientsAge (mean, yr)P1 vessel disease (%)P3 vessel disease (%)P
Lansky et al[22] 2005RCTAMI + PTCA  152056257.066.0< 0.00151.151.6NS15.715.3NS
Lansky et al[67] 2009RCTPCI  68731461.865.9< 0.000161.374.2< 0.000111.54.5  0.0002
Tizón-Marcos et al[33] 2009RCTPCI  105029859.762.55865  0.0669.87.4  0.066
Hirakawa et al[19] 2007Pros cohortAMI  204856662.9271.08< 0.0160.156.0< 0.0534.8140.11< 0.05
Mueller et al[55] 2002Pros cohortMI  10334176468 0.012426  0.454229  0.01
Duvernoy et al[43] 2010Pros cohortPCI14 848787761.966.9< 0.00149.455.0< 0.00122.818.0< 0.001
Liu et al[25] 2008Pros cohortSTEMI + PCI  14311668.168.7 0.6114.710.3  0.2948.261.2  0.03
Jibran et al[81] 2010Retro cohortACS + PCI  33113760.766.1< 0.0000141.148.9 0.322.712.4 0.3
De Luca et al[41] 2004Pros cohortSTEMI  11953535966< 0.00147.943.8NS20.722.3NS
Bufe et al[62] 2010Pros cohortSTEMI + PCI  3761245865< 0.00148.154.0  0.03124.221.8  0.667
Lawesson et al[24] 2010Retro cohortSTEMI aged < 46  174838440.840.4 0.1459.372.9< 0.00133.619.2< 0.001
Berger et al[10] 2006Pros cohortPCI  2953133161.966.8< 0.0014850  0.1951817NS
Toumpoulis et al[34] 2006Pros cohortCABG  2598116263.266.2< 0.0014.67.3  0.00173.769.3  0.005
Tillmanns et al[32] 2005Pros cohortSTEMI  5131786066< 0.00014344NS571561NS
Vakili et al[57] 2001Retro cohortPTCA first MI  7273175965< 0.0055659NS1512NS

The proportion of men and women undergoing CABG was equal[10,11,26,28,30-32,37,79] as shown in Table 4. In women undergoing CABG, the internal mammary artery was used less often than in men. The usage of this artery was associated with a decrease in mortality after CABG[16]. Furthermore, women underwent surgery more commonly on an urgent basis than men[12,16,20,34,36,63,75].

Table 4 Percentage of performed revascularizations stratified by gender.
Author study/dateDesignStudy populationPatientsAge (mean, yr)PCABG (%)PPCI (%)P
Reynolds et al[30] 2007RCTMI12 498  409059.567.0< 0.0013.43.10.4527.423.6< 0.01
Matsui et al[26] 2002Retro cohortAMI  346  13662.970.40.01470.1799584 0.001
Moriel et al[28] 2005Pros cohortACS  820  51178790.12760.473228  0.06
Herlitz et al[18] 2009Retro cohortAMI  835  58872.779.2< 0.000192< 0.0001157NS
Setoguchi et al[31] 2008Pros cohortAMI  317  13088082< 0.001330.731012  0.40
Tillmanns et al[32] 2005Pros cohortSTEMI  513  1786066< 0.000132NS95.193.8
Toumpoulis et al[34] 2006Pros cohortCABG  2598  116263.266.2< 0.0011001001.63.1  0.002
Berger et al[10] 2006Pros cohortPCI  2953  133161.966.8< 0.0010.10.00.179100100
Alfredsson et al[11] 2007Pros cohortUnstable/NSTEMI34020197616973< 0.001751814
Lagerqvist et al[21] 2001RCTAMI  1708  7496468< 0.00130243428
SoS[37] 2004RCTMultivessel disease  782  20660.664.7< 0.00150.152.449.947.6
Singh et al[79] 2008Retro cohortPCI  7616  336564.769.40.80.8100100
Liu et al[25] 2008Pros cohortSTEMI + PCI  143  11668.168.70.6185.384.3NS

Many discrepancies existed between the different studies investigating the prognosis of men and women with an ACS. Some studies showed that women had more complications during hospital admission compared with men[7,9,13,18,22,30,36,53,61,64,78,80], while others showed no differences[23,25,28,33-35,38,40,44,46,48,54,56-58,62,81] (Table 5). Particularly at younger ages, women tended to have a greater risk for cardiac events compared with men at the same age[64,82]. This difference disappeared in patients older than 65 years[82,83].

Table 5 Percentage of peri-procedural complications during index admission stratified by gender.
Author study/dateDesignStudy populationPatientsAge (mean, yr)PComplications < admission (%)P
Lansky et al[22] 2005RCTAMI + PTCA  152056257.066.0< 0.001MACE3.26.4  0.002
Bleeding2.05.2  0.0003
Lansky et al[67] 2009RCTPCI  68731461.865.9< 0.0001MACE11.33.2  0.0766
Vascular10.61.0  0.6844
MI11.02.9  0.0526
Tizón-Marcos et al[33] 2009RCTPCI  105029859.762.5< 0.0001MACE13.93.4  0.86
Bleeding11.12.4  0.16
MI13.53.0  0.86
Thompson et al[53] 2006Pros cohortPCI  80735961.767.7< 0.0001MACE2.73.9  0.29
Vascular4.212.0< 0.0001
Jibran et al[81] 2010Retro cohortACS + PCI  33113760.766.1< 0.0001MACE13.92.9  0.8
Access site11.56.2  0.02
MI11.50.7  1.0
Duvernoy et al[43] 2010Pros cohortPCI14 848787761.966.9< 0.001MACE4.485.19< 0.001
Vascular1.023.34< 0.001
MI1.601.66  0.70
Bufe et al[62] 2010Pros cohortSTEMI + PCI  3761245865< 0.001Shock10.111.3  0.838
Renal failure1.31.6  0.835
Reynolds et al[30] 2007RTCMI12 498409059.567.0< 0.001CVA10.20.6< 0.01
Heart failure4.06.7< 0.001
Re-MI2.73.5  0.004
Matsui et al[26] 2002Retro cohortAMI  34613662.970.4Heart failure1626  0.013
Re-MI56  0.568
Moriel et al[28] 2005Pros cohortACS  8205117879  0.12CVA21  0.79
Heart failure2121  0.86
Re-MI1514  0.61
Uva et al[35] 2009RCTCABG  148548164.769.0  0.001MACE3.96.6NS
CVA0.71.2  0.2
MI0.71.3  0.08
Herlitz et al[18] 2009Retro cohortAMI  83558872.779.2< 0.0001Re-MI42  0.02
Toumpoulis et al[34] 2006Pros cohortCABG  2598116263.266.2< 0.001CVA2.84.2NS
Bleeding1.81.5  0.592
MI0.60.7  0.657
Liu et al[25] 2008Pros cohortSTEMI + PCI  14311668.168.7  0.61MACE4.26.0  0.50
Berger et al[10] 2006Pros cohortPCI  2953133161.966.8< 0.001MACE2.93.0  0.922
CVA0.10.2  0.905
Access site0.00.3  0.018
Chiu et al[13] 2004Pros cohortPCI12 738530162.366.5< 0.001Transfusion412< 0.001
Haematoma56  0.568
Setoguchi et al[31] 2008Pros cohortAMI  31713088082< 0.001CVA34  0.57
Singh et al[79] 2008Retro cohortPCI  7616336564.769.4 0.48CVA0.50.9  0.29
MI1.11.4  0.44
Tillmanns et al[32] 2005Pros cohortSTEMI  5131786066< 0.0001Re-MI32NS

Many discrepancies existed in the short-term mortality rate of patients with ACS. Some studies revealed a higher short-term mortality risk among women[7,12,17,22,24,27,28,35,36,57,64,78], while others did not[9-11,16,18,26,32-34,46,48,54,59,65,81] (Table 6). As discussed above, older age at presentation was an important confounding factor in this regard[29,39,54,58,75,77,84].

Table 6 Mortality rates in male and female patients with coronary artery disease at admission, at thirty days and after one-year of follow-up.
Author study/dateDesignStudy populationPatientsAge (mean, yr)PMortality < admission (%)P Mortality < 30 d (%)PMortality < 1 year (%)P
Lansky et al[22] 2005RCTAMI + PTCA  1520  56257.066.0< 0.0011.03.40.00031.14.6< 0.0013.07.6< 0.001
Singh et al[79] 2008Retro cohortPCI  7616  336564.769.4  0.481.82.50.3823 0.25440.490
Alfredsson et al[11] 2007Pros cohortUnstable/NSTEMI34 02019 7616973< 0.00157791619
Setoguchi et al[31] 2008Pros cohortAMI  317  13088082< 0.00114.513.99.88.621.518.2
Matsui et al[26] 2002RCTMI  346  13662.970.4440.851410  0.013
Uva et al[35] 2009RCTCABG  1485  48164.769.0  0.0010.820.011.22.3 0.09
Toumpoulis et al[34] 2006Pros cohortCABG  2598  116263.266.2< 0.0012.72.90.6393.73.9  0.747
Moriel et al[28] 2005Pros cohortACS  820  5117879  0.127120.0071912110.480
Herlitz et al[18] 2009Retro cohortAMI  835  58872.779.2< 0.00011214NS18220.040
Lawesson et al[24] 2010Retro cohortSTEMI aged < 46  1748  38440.840.4
Berger et al[10] 2006Pros cohortPCI  2953  133161.966.8< 0.0010.50.50.9188.921020.197
Liu et al[25] 2008Pros cohortSTEMI + PCI  143  11668.168.7  0.612.85.203.4
Anand et al[9] 2005TrialACS  7726  483662.766.5  0.00014.94.4  0.23511.19.70.040
Tizón-Marcos et al[33] 2009RCTPCI  1050  29859.762.5< 0.00010.20
Tillmanns et al[32] 2005Pros cohortSTEMI  513  1786066< 0.000166.2NS912.50.600
Lansky et al[67] 2009RCTPCI  687  31461.865.9< 0.0001001.00.30.447
Koch et al[20] 2003Pros cohortCABG  1588  4602.53.4
Lagerqvist et al[21] 2001RCTAMI  1708  7496468< 0.0015.77.2NS
Chiu et al[13] 2004Pros cohortPCI12 738  530162.366.5< 0.00157< 0.001

An important finding was that women with ACS had an increased mortality risk at younger ages compared with men of the same age[39,45,52,64]. Figure 1 illustrates the gender differences in mortality after a MI among different age categories. As shown in this Figure, the difference in mortality risk was reduced in older age[12,26,27,64,83,85].

Figure 1
Figure 1 Gender differences in mortality after a myocardial infarction among different age categories. An odds ratio higher than one indicates an increased mortality after a myocardial infarction in women in comparison to men.

Independent predictors of mortality were old age[20,29,39-41,49,50,54,59,75,77,84], with an OR of 1.06 (95% CI: 1.05-1.07) for each additional year[40,74], diabetes[20,24,29,49,54,62,74,77,84], heart failure[20,29,39], CAD[29], duration of ischemia, multiple vessel disease, history of MI, hypertension[41,77], CVA[77], anemia[20], cardiogenic shock, peripheral vascular disease[39], and ST-elevation[74]. Whether female gender can be considered as an independent risk factor remains unclear. Some studies claimed it could[24,27,51,55,57,75,77], but others showed no significant association after adjustment for risk factors[16,22,29,34,38-40,42-46,49,50,53,54,58,59,61,62,66,80,82,84]. After adjustment for several risk factors, female gender persisted as a risk factor for in-hospital mortality in ACS only for patients aged 51-60 years (OR, 1.78; 95% CI: 1.04-3.04)[74]. After adjustment for age and cardiovascular risk factors, the long-term mortality rate was equal for both men and women[13,20,22-24,29,31,32,40,41,44-46,48,49,58-60,62,65,79] or even in favor of women[10,31,34,42,54,55,63,77,84], as shown in Table 6 and Figure 2.

Figure 2
Figure 2 Gender differences in mortality risk in patients with coronary artery disease. An odds/hazard ratio higher than one indicates an increased mortality in women in comparison to men. OR: Odds ratio; HR: Hazard ratio.

In the past 20-25 years the mortality rate at 30 d after PCI or CABG has declined equally in both men and women[76,79]. Data were inconsistent on the differences between men and women in the number of readmissions[86-88] and the number of second PCIs[10,18,21,23-26,28,33,35]. Interestingly, differences were found in the restenosis rates after PCI. In the first 6 mo after coronary stenting, restenosis was found in 28.9% of the women, compared with 33.9% of men (P = 0.01)[60,89]. After adjustment of gender, age and multiple risk factors, women showed a 23% risk reduction in angiographic restenosis compared with men (OR, 0.77; 95% CI: 0.63-0.93). Diabetes and small vessel size were identified as the most important predictors of restenosis. However, despite the higher prevalence of diabetes in women and smaller vessel size, women tended to have a lower incidence of restenosis[89]. Whether this can be explained by the protective mechanism of estrogens in women is still unknown. Estrogens were shown to have an antiinflammatory effect on the vessel wall and induce vasodilatation in coronary arteries[1]. However HRT in post-menopausal women did not lower the risk of mortality from CVD after adjustment for other risk factors[90-92]. HRT is therefore not recommended as primary or secondary prevention of CVD in women[73].


Women with CVD tended to have more cardiovascular risk factors such as diabetes, hypertension, and hypercholesterolemia when presenting with ACS. More importantly, women with an ACS at a young age had a higher mortality rate during index hospitalization and during 30 d of follow-up compared with men[24]. A possible explanation could be that pre-menopausal women enjoyed some protection against ACS from estrogens and those women who developed ACS despite this hormonal protection were more likely to have a higher cardiovascular risk factor burden leading to a more severe clinical presentation and worse outcome. None of the discussed studies adjusted for the use of hormone therapy among women. This might lead to information bias, because hormone therapy could influence the outcome of women with ACS. In the elderly, the long-term mortality rate was equal for both men and women, and even slightly in favor of women[13,20,22-24,29,31,32,79]. This small advantage in survival might possibly be due to the greater awareness and control of hypertension in women, compared with men, as hypertension is an important risk factor for CVD[72].

Study results were inconsistent, but it seems that an angiogram was less often performed in women than in men. This phenomenon could partly be explained by the higher average age of women as fewer diagnostic CAG were performed in both male and female patients of older age. However, where a CAG was performed, women and men received the same therapy for similar vessel disease[9,11,18,24,28,30]. No differences between genders were found in the number of performed CABGs.

The current review has several limitations. Most included studies were retrospective in nature and performed a post hoc analysis by stratifying by gender. Included studies were hard to compare due to different patient characteristics; some studies included patients with STEMI, while others also included non-STEMI or patients with unstable angina. Another important limitation is the large difference in mean age between the included men and women across the different studies. Consequently, a comparison between the two genders was very difficult and no firm conclusion can be drawn. In addition, women are still underrepresented in most studies (inclusion rate < 30%). Due to the relatively low incidence of outcomes (e.g. complications, death), greater statistical power is needed to reach statistical significance. Therefore, large prospective observational cohort studies are needed in the future to provide sufficient power to answer the question whether female gender is an independent risk factor for cardiovascular morbidity and mortality.

CVD is the main cause of death among women. The prevalence of CVD is higher among men, but this gap narrows after the menopause. Women present approximately 10 years later with ACS than men, and at the time of presentation have a higher cardiovascular risk factor burden. Women are less often assigned to receive a CAG and subsequently less PCIs are performed. In addition, women have more complications and a higher short-term mortality after revascularization. Finally, mortality rates are higher among young women with ACS, but this difference tends to disappear with age, and long-term prognosis is even better among older women during long-term follow-up.


Cardiovascular disease (CVD) is the main cause of death among women and its occurrence narrows women’s survival advantage over men. Many studies investigated gender differences in CVD, but results were inconsistent due to several limitations. Women were generally underrepresented in mainly retrospective studies and a true comparison between genders was difficult due to large differences in age at presentation between the included men and women.

Research frontiers

It is important to clarify possible differences between men and women in a large prospective cohort study, with equal numbers of male and female patients. Furthermore, as age is an important confounding factor, men and women of similar age should be compared. A systematic literature search was performed to assess the current state of knowledge on possible gender differences in CVD.

Innovations and breakthroughs

In the short-term, women with CVD seem to have a worse outcome compared with men. In particular, young women have an increased mortality risk, but this disadvantage disappears at older age. Moreover, long-term mortality is slightly better in elderly women compared with men.

Peer review

This is an interesting meta-analysis on putative gender differences in cardiovascular care.


Peer reviewers: Paul Erne, MD, Professor, Head, Department of Cardiology, Luzerner Kantonsspital, CH-6000 Luzern 16, Switzerland; Pietro A Modesti, MD, PhD, Professor of Internal Medicine, Department Critical Care Medicine, University of Florence, Viale Morgagni 85, 50124 Florence, Italy

S- Editor Cheng JX L- Editor Cant MR E- Editor Zheng XM

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