1. European and Global Awareness of Heart Disease in Women
Alaide Chieffo, MD
Interventional Cardiology Unit
San Raffaele Scientific Institute, Milan
Italy

2. I/we have no real or apparent conflicts of interest to report.
Alaide Chieffo, MD
I/we have no real or apparent conflicts of interest to report.

3. Cardiovascular Disease: The Leading Cause of Death in Women
Adapted from Anderson RN et al. Monthly Vital Statistics Report. Vol 45(suppl 2):June 12, 1997.

4. Symptoms Diagnosis Pathophysiology Treatment Prognosis
Lack of Awareness-
Women with ACS.. the Hidden Population
Gender gap in ACS
Symptoms
Diagnosis
Pathophysiology
Treatment
Prognosis

5. Different Symptoms
Sex Differences in Myocardial Infarction Presentation Without Chest Pain/Discomfort, Stratified by Age
P < .001 for all comparisons. In these multivariable models, candidate variables for inclusion in the model include demographics, baseline characteristics, cardiovascular risk factors, and medical history (Table 1). Separate adjusted models were performed within each age stratum to find the age-stratum–specific odds ratio (OR) for women vs men, and within each age stratum, the reference group was men.
Typical chest pain
Psychosocial/ somatic?
Canto, J. G. et al. JAMA 2012;307:

6. Hospital Mortality for MI by Chest Pain/Discomfort on Presentation, Age, and Sex NRMI, 1994-2006
Canto, J. G. et al. JAMA 2012;307:

7. Different Symptoms- Gender Bias or Missed Diagnosis - MI?
Myocardial Infarction (MI) without chest pain or discomfort and unrecognized MI by age and sex
Characteristic
All Patients
Age Group, Odds Ratio (Women vs Men)
Women %
Men %
National Registry of Myocardial Infarction 2
MI without chest pain or discomfort
(n=155565) 37
(n=229313) 28
30-59y
1.52
60-69
1.32
70-79y
1.15
80-89y
1.04
Framingham Heart Study
Unrecognized MI
(n=2818) 34
(n=2252) 27
45-54y
2.55
(M 18%; W 46%)
55-64y
1.73
(M 26%; W 45%)
65-74y
.081
(M 36%; W 29%)
75-84y
1.11
(M 36%; W 40%)

8. Gender Bias or Missed Diagnosis - ACS?
Women have higher proportion of ACS without chest pain
Source
Study Characteristic
Proportion w/out Chest Pain, %
Study Description
Pt Pop.
Study Years
Sample Size
Mean Age, Y
Age Adj.
Men
Women
Brieger et al. 2004
GRACE Registry
ACS
20881
65.8
Yes
7.3
10.6
Canto et al. 2000
National MI Registry MI
434,77
69.3
28.6
38.6
Canto et al. 2002
Alabama UA Registry UA
4167
72.3
50.2
53.0
Culic et al. 2002
CCUs Croatia
1996
58.8
12.4
20.3
Dorsch et al. 2001
United Kingdom
1995
2096
70.6
17.6
24.6
Goldberg et al. 1998
Worcester MI Study
1360
67.7
18.0
23.0
Milner et al. 2004
2073
70.2
30.9
45.8
Roger et al. 2000
Olmsted County, MN
2271
63.0
25.0
19.0
Stern et al. 2004
26 Hosp., CCU, Israel
2000
2113
64.9
18.7
29.7
Cumulative …
27.4
37.5
Could be women’s discussion at presentation. Men describe with nouns, women with verbs.
Canto et al Arch Intern Med.2007:167(22): 8

9. Symptoms Diagnosis Pathophysiology Treatment Prognosis
Lack of Awareness
Symptoms
Diagnosis
Pathophysiology
Treatment
Prognosis

10. Different Symptoms/delayed diagnosis
Chest pain, diaphoresis more common in men 1
Back pain, jaw pain, nausea, neck pain shortness of breath more common in women 1
Women delay seeking treatments for cardiac related events 2
Chest pain per se is not adequate predictor of significant coronary disease in women 3
Chest pain
Diaphoresis
Back pain
Jaw pain
Nausea
Neck pain
Shortness of breath
We need to teach diagnosis differently since women don’t tend to have classic symptoms. Diastolic stiffening caused by shortness of breath – first sign of heart disease
0.5 1
1.5 2
Goldberg AHJ 1998:136:189
Damon M.Seils, Joelle Y Friedmann, Kevin Schulmann JAMWA.2001;56:
Shaw et al J Am Coll Cardiol 2006;47:4S–20S)
More common in women
More common in men
Goldberg, AHJ 1998; 135:189 10

11. Symptoms Diagnosis Pathophysiology Treatment Prognosis
Gender Gap in ACS
Symptoms
Diagnosis
Pathophysiology
Treatment
Prognosis

12. Pathophysiology Loss of sex hormones At presentation 10 yrs older
More risk factors (HT, dyslipidemia, diabetics)
Blood vessels
smaller (macro and micro)
stiffer
more inflamed
more diffuse
microvascular dysfunction
endothelial and smooth muscle cell disfunction
more plaque erosion (instead of plaque rupture)
collateral flow
positive remodelling
Pepine et al; JACC 2006;47 Suppl:S1-3
Shaw et al; JACC 2009;54:

13. Gender Gap in CAD Significance after Coronary Angio for ACS
ACC/NCDR database
P<0.0001
N =
23,382
8,708
1,596
3,725
412,918
% Female
50.2
39.1
37.6
39.4 38
Circ 2008;117:1792

14. Symptoms Diagnosis Pathophysiology Treatment Prognosis
Gender Gap in ACS
Symptoms
Diagnosis
Pathophysiology
Treatment
Prognosis

15. “Get with the Guidelines” registry database
Underutilization of evidence-based treatments for women
Delayed reperfusion among women (STEMI)
Measure/Treatment
Men (n=47 556), % (n)
Women (n=30 698), % (n) P
Early medical therapy
Aspirin within <24 h
-Blockers within <24 h
93.3 (40 332)
87.2 (34 653)
91.0 (24 686)
84.7 (21 124)
<0.0001
Invasive procedures
Cardiac catheterization
PCI
CABG
Revascularization
56.2 (26 733)
52.3 (22 253)
9.2 (3893)
60.2 (25 614)
45.6 (14 012)
36.1 (10 070)
5.4 (1501)
40.9 (11 409)
Timeliness of reperfusion
DTN time, median (25th-75th), min
DTB time, median (25th-75th), min
39.0 ( )
95.0 ( )
47.0 ( )
103.0 ( )
Evidence based therapies for women are under-used and delayed.
Hani Jneid et al Circulation 2008;118; ;

16. Disparities in Use of Same-Day PCI for Patients With STEMI
n = 58,308 (females n= 21,433)
Pathak et al Am J Cardiol 2008;102:802– 808

17. Symptoms Diagnosis Pathophysiology Treatment Prognosis
Gender Gap in ACS
Symptoms
Diagnosis
Pathophysiology
Treatment
Prognosis

18. Gender Gap in Outcomes Following AMI
Male (n = 21,323)
Female (n = 14,552)
Unadjusted OR
Death
4.3%
5.6%
1.27
Death or myocardial infarction
7.1%
8.6%
1.17
Postadmission myocardial infarction
3.5%
4.0%
1.12
Cardiogenic shock
2.7%
3.1%
1.10
Congestive heart failure
8.8%
12.1%
1.35
Stroke
0.8%
1.1%
1.37
Red blood cell transfusion
13.2%
17.2%
Women have higher rates of Death, MI, Cardiogenic shock, CHF and Bleeding complications 1
When you hospitalize a women with MI, women are more likely to die or have serious complications. One opportunity to improve is bleeding complications. Gender gap is decreasing, but highest in younger women
Blomkalns et al J Am Coll Cardiol 2005;45: 832–7

19. Gender Gap in Outcomes Following AMI
Study N
Unadjusted Mortality Rate
% Women
Women vs. Men (%)
P-Value
Watanabe20
82783 35
1.1
0.5
<0.0001
Alfonso19
981 16
6.0
2.0
0.01
WHC15
7372 28
1.39
0.66
<0.002
Malenka24
12232 NA
1.64
0.7
<0.001
Bell34
3557 27
4.2
2.7
0.005
NHLBI22
2136 26
2.6
0.3
NCN*21
150918 33
1.8
1.0 --
Mehilli**23,42
4264 24
3.1
1.9
0.02
Welty33
5989
1.2
0.1
Malenka16
33666
NHLBI13
2524
2.2
1.3
NCN32
109708
Arnold31
5000 25
0.001
NACI30
2855 34
1.4 NS
Weintraub29
10785
Unadjusted Mortality rates higher in women across various studies of outcomes of MI

20. Death during hospitalization (%)
"The younger the age of the patients, the higher the risk of death among women relative to men"
Women
Death during hospitalization (%)
Men
<50
50-54
55-59
60-64
65-69
70-74
75-79
80-84
85-89
3.0
2.5
2.0
1.5
1.0
0.5
0.0 20 30 40 50 60 70 80 90
>90
Age (years)
Adjusted Odds Ratio for Death in Women versus Men with AMI
Women
Men
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Vaccarino V et al, NEJM 1999;341:

21. The proportion of younger women with STEMI has increased over a 15 year period
Four 1 month French nationwide registries conducted 5 years apart including a total of 6707 STEMI patients. Endpoints changes over time in 30 day mortality.
Increase is consistent with increased prevalence of smoking.
Proportion of women < 50 years hospitalised for STEMI has increased considerably from 3.7% to 11.1%.
Puymirat et al. JAMA. 2012; 1-8. doi: /2012.jama.11348

22. However, 30 day mortality is improving with the introduction of PPCI
Puymirat et al. JAMA. 2012;():1-8. doi: /2012.jama.11348

23. In Hospital Mortality in STEMI In-hospital mortality by sex and age In
Champney et al. Heart 2009 Jun;95(11):895-9 23

24. In-hospital Mortality by Sex and Age
Champney et al. Heart 2009 Jun;95(11):895-9 24

25. Women generally older with more frequent co-morbidities
Gender Impact on Prognosis in ACS patients treated with Contemporary DES
Women generally older with more frequent co-morbidities
Fath-Ordoubadi et al. Am J Cardiol 2012;110:636-42

26. Despite worse baseline characteristics, no differences in outcomes between gender in ACS treatment with contemporary DES
Results consistent to one year
Fath-Ordoubadi et al. Am J Cardiol 2012;110:636-42

27. Outcomes consistent to 2 years
Fath-Ordoubadi et al. Am J Cardiol 2012;110:636-42

28. Conclusions Women worse prognosis in ACS is due to age and comorbidity
Update on ACS/AMI: Have we made any progress?
ACC 2011/WIN Symp. N.O.
Conclusions
Women worse prognosis in ACS is due to
age and comorbidity
different presentation symptoms
different pathophysiology
insufficient awareness women –delayed symptoms to FMC- and health care providers-delayed treatment
in general lack of treatment according to guidelines
Cindy L. Grines, M.D. 28

29. Future Perspectives Improve Awareness among professionals and patients
Update on ACS/AMI: Have we made any progress?
ACC 2011/WIN Symp. N.O.
Future Perspectives
Improve Awareness among professionals and patients
Treatment timing and strategy
Identify where are the “barriers”-SAVE Her Life Initiative in Europe
Stimulate research including female specific risk factors
Cindy L. Grines, M.D. 29

30. For more information and to join WIN for FREE visit www. SCAI-WIN
For more information and to join WIN for FREE visit OR Contact WIN Director Rebecca Ortega at