With Regards to Afflictions of the Heart, Are Men and Women Created Equal?

Transcription

1 With Regards to Afflictions of the Heart, Are Men and Women Created Equal? Jennifer S. Lawton, M.D. Associate Professor of Surgery Washington University School of Medicine AATS/STS Adult Cardiac Surgery Symposium AATS 90 th Annual Meeting, Toronto, Ontario, Canada May 2, 2010

2 Jennifer S. Lawton, M.D. No relationships to disclose

3 Outline Short answer is NO Sex differences in retrospective reports Knowledge deficits Focus primarily surgical diseases of the heart Operative mortality disparity evident Explanations likely multifactorial

4 Coronary Heart Disease is a Man s Disease 2600 BC Ebers papyrus If you find a man with cardiac discomfort, with pain in his arms, at the side of his heart, death is near 1768 William Heberden treatise on angina pectoris, I have seen nearly 100 people under this disorder, of which there have been 3 women 1960 s AHA Conference in Oregon entitled, How Can I Help My Husband Cope with Heart Disease Wenger N, Circulation 2004;109:

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6 Percent of Population Men Women Prevalence of CVD in adults age 20 and older by age and sex (NHANES ). Source: NCHS and NHLBI. These data include coronary heart disease, heart failure, stroke and hypertension.

7 Not Just a Disease of Older Women > 9000 women in the U.S. younger than 45 yrs. of age have a heart attack each year Incidence is 1 in 8 for women aged yrs.

8 Heart Disease in Women: The Equal Opportunity Killer Since 1984, the number of deaths due to cardiovascular disease for women has exceeded those for men The difference in deaths is now more than 67,000 per year N.Wenger, MD, AHA 2004, New Orleans

9 Deaths in Thousands Years Males Females

10 Deaths 500, , , , , , , , ,000 78,941 59,260 36,006 65,323 51,281 42,658 0 A B C D E A B D F C Males Females A CVD (I00-I99; Q20- Q28) B Cancer C Accidents D Chronic Lower Respiratory Diseases E Diabetes Mellitus F Alzheimer s Disease CVD and other major causes of death for all males and females (United States: 2006). Source: NCHS and NHLBI.

11 It Can t Happen to Me In 1997, only 30% of women surveyed perceived that cardiovascular disease was the leading health threat for women Increased to 55% in 2006; 54% in 2009 However, 30% of women underestimate their own personal risk of cardiovascular disease Survey women veterans 2002: 56% of women with 3 risk factors 41% of women with 4 risk factors

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13 Sex Differences Symptoms for Women Atypical chest pain more common in women: abdominal pain, shortness of breath, nausea or dizziness, unexplained fatigue Women have longer time from symptom onset to presentation do they tend to ignore symptoms?

14 Lack of Physician Knowledge Fewer than 1 in 5 physicians (PCP, OB/GYN, Cardiologists) knew that more women than men die each year of CVD Physicians are more likely to classify women in a lower-risk category for CVD than men despite similar calculated risk Mosca et al., Circulation 2005;111:499.

15 Sex / Gender Bias? Longer time between symptom onset and initial medical intervention and hospital admission Women are less likely to receive medications (ASA, β blockers, statins, ACE-I) Women are referred for testing less (stress test, cardiac catheterization, and surgery)

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17 Risk Factor Modification 1 in 4 women smoke 39-57% of women ( 18 yr) NO leisure-time physical activity Total cholesterol >200 mg/dl: 49% of white and 46% of black women LDL >130: 43% white and 42% of black women Women (20-74 yr): 47-69% overweight and 23-38% obese

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20 Surgical Treatment of Heart Disease

21 Surgical Treatment of Coronary Artery Disease 448,000 bypass operations per year (2006) in United States 30% are performed on women

22 Is Operative Mortality Higher in Women Following Isolated CABG?

23 Is the Difference Due to Comorbidities? Many studies confirm higher operative mortality (unadjusted) Studies with risk factor adjustment demonstrate contradictory findings

24 USA TODAY Feb. 19, 2002 Women Face Triple the Danger from Bypass Surgery Vaccarino et al., Circulation 2002;1005:1176.

25 Higher Mortality in Younger Women Women <50 yrs. of age were 3 times more likely to die than men (3.4% vs. 1.1%) Women yrs. 2.6% vs. 1.1% Women yrs. 3.6% vs. 2.6% Women yrs. 7.2% vs. 4.4% Women >80 yrs. 9.0% vs. 8.3%

26 Gender Profiling in CABG Profiles dissimilar between women and men Significant predictors of female gender Shorter height Higher weight More HTN Insulin treated diabetes Heart failure Higher TG, LDL Lower Hct, bilirubin, Cr Koch et al., J Thorac Cardiovasc Surg 2003;126:2044.

27 Propensity Matched Comparisons Only 26% of women (945) and 8% of the men could be matched (minimal overlap of scores between women and men) Koch et al., J Thorac Cardiovasc Surg 2003;126:2044. Only 280 (26%) could be matched with men Parolari et al., Ann Thorac Surg 2008;85:885. No increased mortality in women in matched pairs

28 Is the Difference due to Operative Technique? Anatomy? Surgeon Bias? Choice of conduit Use of CPB Completeness of revascularization Small BMI, body size Small coronary arteries

29 Choice of Conduit Under utilization of arterial grafts in women Women are less likely to receive LIMA, RIMA, radial Female gender associated with nonuse of LIMA Mickleborough et al., J Thorac Cardiovasc Surg 2003;126:950. Aldea et al., Ann Thorac Surg 1999;67:1097. Parolari et al., Ann Thorac Surg 2008;85:885. Lawton et al., Ann Thorac Surg 2005;80:559.

30 Radial Artery Use in Women Barnes Jewish Hospital (301 women and 786 men) received at least one radial artery graft Significantly more men (44%) received a radial artery graft vs. women (35%, p<0.001) Lawton et al., Ann Thorac Surg 2005;80:559.

31 Results The radial artery was used less frequently in women Radial artery was smaller in size (proximal and distal) and had less flow (free and transonic) in women The use of a radial artery graft did not influence operative mortality in women The use of a radial artery graft was associated with better 5 yr. survival in women

32 Survival (%) Kaplan-Meier Survival in 588 Matched Women % (n=274) 86.1% (n=253) 88.9% (n=232) 81.7% (n=113) 79.9% (n=201) 74.1% (n=124) RA Graft (n=294) No RA Graft (n=294) p= Time from Surgery (years)

33 Use of CPB Retrospective comparison in 6,368 CABG operations Operative mortality 2.3% off pump vs. 4.1% on pump in women Petro et al., Heart Surg Forum 2000;1:41.

34 Off Pump CABG in Women Barnes Jewish Hospital 2,699 isolated CABG operations Operative Mortality Off pump Women 0.07% Men 0.04%

35 Off Pump CABG in Women Multivariate regression and propensity matching Women who undergo off pump CABG have mortality similar to that of men Brown et al., Ann Thorac Surg 2002;74:2113 Mack et al., Circulation 2004;110:II1 Puskas et al., Ann Thorac Surg 2008;86:1139 Puskas et al., Circulation 2007;116:I192

36 Completeness of Revascularization Fewer grafts Fewer distals No difference in completeness of revascularization More likely to influence mid or late term mortality Emmert et al., Int Cardiovasc Thorac Surg 2009 Epub (Zurich, Switzerland) Parolari et al., Ann Thorac Surg 2008;85:885 Ibrahim et al., J Thorac Cardiovasc Surg 2003;126:959 Aldea et al., Ann Thorac Surg 1999;67:1097 Mickleborough et al., J Thorac Cardiovasc Surg, 2003;126:950

37 ESTROGEN

38 Smaller Coronary Arteries? Technically more challenging? Then why do women fare better with off pump CABG which is the ultimate technical challenge (small vessels a contraindication) Disparity in operative mortality lessens with age (Vaccarino et al., Circulation 2002;1005:1176 ) Time to construct distal anastomosis similar between women and men (Aldea et al., Ann Thorac Surg 2002;1005:1176)

39 Innate Differences? Sex Differences Prior to the Development of CVD? Noninvasive testing in women has reduced specificity and sensitivity MRI normal volunteers to evaluate myocardial contractile function

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41 Potential Explanations? Multiple comorbidities Incorrect patient perception of risk Physician lack of knowledge Delayed diagnosis Treatment conservatism Referral bias Unstable / acute presentation Established diagnostic tests less sensitive and specific in women Intraoperative factors Lack of involvement of women in clinical trials

42 STS Guidelines for CABG in Women At least one IMA is used in every CABG procedure Periop blood glucose levels are maintained in the range of mg/dl Ensure adequate intraoperative hematocrit Indications for OPCAB are the same for women as for men Anesthetic management tailored to body size Hypothyroid women are maintained in a euthyroid state during surgery HRT is not used for postmenopausal women Edwards et al., Ann Thorac Surg 2005;79:2189.

43 STOP the #1 Killer of Women H High index of suspicion for CVD E Enable access to care A Awareness / Education R Risk factor modification T Treat aggressively

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45 Impact of Coronary Artery Disease Cardiovascular disease is the #1 cause of death for adult women in the U.S. and in most developed areas of the world Exceeds the number of deaths of the next 5 causes of death in women COMBINED

46 Impact of Coronary Artery Disease In America and most developed countries this is 44.6% of all female deaths = Approximately 1 death every minute First among all disease categories in hospital discharges for women

47 Comparison to Breast Cancer Women are 3X more likely to die of cardiovascular disease versus breast cancer One in 2.4 women will die of cardiovascular dz. versus 1 in 29 who will die of breast cancer >500,000 deaths annually versus 43,800 deaths due to breast cancer

48 Congenital Heart Disease Female sex a risk factor for operative mortality (in hospital) among children (<21 yrs) undergoing cardiac surgery (UCLA) Mortality males 4.98% Mortality females 5.54% Females with adult congenital heart disease demonstrate no increase in mortality vs. men (mean age 35 yrs) (Dutch nationwide registry)

49 Valvular Disease in Women All age groups Particularly important in women of childbearing age More than 60% of heart valve replacement procedures are performed in women Higher hospital mortality in women vs. men when combined valve + CABG (Ibrahim et al, 2003)

50 Valvular Disease In Women Smaller aortic root Women with AI have later onset of left ventricular enlargement and poorer late survival (Klodas et al.) Bicuspid aortic valve less common 30 day and late mortality after AVR for AS higher in women (esp. if CABG)

51 Valvular Disease In Women Mitral valve prolapse in 6% of women (60% asymptomatic) Women comprise more than 70% of mitral stenosis cases Women aged years 2.5 times higher mortality of mitral valve operation vs. men (Song et al.)

52 Surgery for Heart Failure in Women 34.1% of heart donors are female 22.4% of heart transplant recipients Female heart transplant recipients higher mortality vs. male recipients Higher risk of cardiac rejection and need for increased immunosuppression

53 Sex Differences Women are an average of 10 yrs. older More women have multiple risk factors More likely to have silent heart attack Higher % of women present with sudden death Women are more likely to die within one year following a heart attack

54 Sex Differences Women seek medical care more often with urgent or emergent presentation Women have more severe angina class Diabetes more powerful risk factor in women (essentially negates estrogen protective influence in younger women) Greater disabling symptoms despite less extensive coronary disease (small vessel disease)

55 To Fight the #1 Killer of Women: More research specifically on women is needed Educate women about the symptoms and the disease Urge women to modify risk factors that contribute to the disease

56 Acute Heart Attack Mortality by Age and Sex Death During Hospitalization (%) Men Women < Age Source: Adapted from Vaccarino 1999

57 Delayed Referrals and Impaired Access Systematically lower utilization of treatments and diagnostic procedures in women compared to men Women less likely to Undergo exercise ECG Be referred for catheterization Receive antiplatelet and statin therapy Be revascularized

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59 Heart Failure Women surpass men in incidence of heart failure around age 74 yrs. Slower progression of heart failure Better age-matched cardiac contractility when presenting with heart failure Better preservation of myocardial mass with aging

60 Discharges in Thousands Years Male Female Hospital discharges for heart failure by sex. (United States: ). Source: NHDS/NCHS and NHLBI. Note: Hospital discharges include people discharged alive, dead and status unknown.

61 Operative Mortality Hartz et al., (STS database) 97,153 women Higher operative mortality (4.52% vs. 2.61% overall) in the low and medium risk categories BJC ,699 isolated CABG operations (30% women) Women 1.33% Men 2.15%

62 Utilization of Radial Artery Conduit in Women Demographic data, radial artery graft utilization, and outcome retrospectively evaluated in 2633 patients who underwent isolated CABG between 1997 and 2002 Follow-up by phone, mail, and mortality data

63 Patient Population Isolated CABG between 1/97 and 12/02 in 2633 patients (862, 1771 ) 1087 (301, 786 ) patients had at least one radial artery graft utilized

64 Propensity Matching The selection bias to use a radial artery graft or not was evaluated in 862 women Logistic regression analysis utilized to identify baseline differences in the two groups (women with a radial graft and women without) Using regression coefficients, a propensity score calculated Matched 294 women in each group for comparison

65 Radial Artery Size and Flow Women (N=62) Men (N=145) p Value Age (yrs.) Mean proximal RA diameter (mm) Mean distal RA diameter (mm) < <0.01 Mean free flow (ml/min) Mean transonic flow (ml/min) <0.001

66 Women Who Received a Radial Artery Graft Longer cross clamp time Higher rate of LIMA graft utilization Shorter length of mechanical ventilation Shorter ICU stay No difference in operative mortality Improved long term survival

67 Conclusions Factors associated with the use of a radial artery graft in women: Younger age Nonurgent/Emergent operative status No current hemodialysis requirement Previous CABG Higher LV ejection fraction

68 Study Limitations Not possible to comment on patency due to too few caths post op Flow may be influenced by many factors: vessel size, target vessel run-off, systemic blood pressure, and the presence of vasoactive medications Retrospective

69 NIH-NHLBI sponsored WISE study (Women s Ischemia Syndrome Evaluation) 256 women with symptoms or chest pain phase I Phase II add 680 women, Phase III follow-up Microvascular dysfunction 20% of women with no angio signif lesions had altered myocardial metabolism on stress test with P-MR spectroscopy suggesting the presence of ischemia Persistence of symptoms associated with signif occurrence of coronary events, increased hospitalization, poor quality of life, and ongoing healthcare costs Syndrome X

70 New and Recurrent MI or Fatal CHD Ages Men Women Annual number of U.S. Adults having diagnosed heart attack by age and sex (ARIC: and CHS: ). Source: NHLBI. Includes MI and fatal CHD but not silent MI s.

71 Percent of Population Men Women Prevalence of CHD by age and sex (NHANES : ). Source: NCHS and NHLBI.

72 500,000 Deaths 400, , , ,000 Alzheimer CLRD Cancer All Other CVD Stroke Heart Disease 0 All Ages < CVD and other major causes of death: females (United States: 2006). Source: NCHS and NHLBI.

73 Per 100,000 Population Coronary Heart Disease Stroke Lung Cancer Breast Cancer White Females Black Females Age-adjusted death rates for CHD, stroke, lung and breast for white and black females (United States: 2006). Source: NCHS.

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76 Radial Artery Patency N=17 (7, 10 ) Women Men p Value RA occlusion post-op cath 2 (3.9%) 3 (2.7%) 0.649

77 Intraoperative and Postoperative Variables Cross Clamp Time (min) No Radial Artery Graft (N=294) Radial Artery Graft (N=294) p Value <0.001 CPB time (min) LIMA used 248 (84.4%) 280 (95.2%) <0.001 Operative Mortality 15 (5.1%) 12 (4.1%) Mechanical Ventilation (hrs) 14 (IQR 8-20) 11 (IQR 7-17) ICU stay (days) 2 (IQR 1-3) 1 (IQR 1-2) Hospital stay (days) 6 (IQR 5-8) 6 (IQR 5-7) F/U (years)

78 Radial Artery Size and Flow Indexed to BMI Women (N=62) Men (N=145) p Value BMI (kg/m 2 ) Mean proximal RA diameter (mm) / BMI Mean distal RA diameter (mm) / BMI Mean free flow (ml/min) / BMI Mean transonic flow (ml/min) / BMI < < <0.001

79 Use of a Radial Artery in Women Non-significant Variables Race Smoking status Diabetes Hypercholesterolemia Chronic renal insufficiency HTN COPD PVD History of MI Unstable angina NYHA classification # of diseased vessels Cardiogenic shock Significant Variables Younger age Non-urgent/emergent status No current hemodialysis Previous CABG Higher LV ejection fraction

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81 Hormonal / Molecular Response to Injury? Estrogen protection? Improved myocardial functional recovery, decreased proinflammatory cytokine production, and reduced apoptotic signaling after I/R Endogenous estrogen mediates a higher threshold for endotoxin-induced myocardial protection in female rats Wang et al., Circulation 2008;118:S38.

82 Exogenous Administration of Estrogen HERS Trial: No reduction in heart disease events Increased rate of events in first year HERS II = Follow-up: Unblinded No difference in cardiovascular disease outcome WHI: HRT not recommended for heart disease prevention (should not be initiated or continued) in postmenopausal women Class III AHA guideline (not beneficial and potentially harmful)