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Y Does X Make A Difference

Y Does X Make A Difference. Myocardial Ischemia. The Three Paradoxes. 1. Women have a higher prevalence of angina compared to men, yet have an overall lower prevalence of atherosclerosis and obstructive coronary artery disease

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Y Does X Make A Difference

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  1. Y Does X Make A Difference Myocardial Ischemia

  2. The Three Paradoxes • 1. Women have a higher prevalence of angina compared to men, yet have an overall lower prevalence of atherosclerosis and obstructive coronary artery disease • 2. Symptomatic women undergoing coronary angiography have less extensive and severe CAD, despite being older with a greater risk factor burden, compared to men • 3. Despite relatively less CAD, women have a more adverse prognosis compared to men Bairey Merz, C. N. Women and Ischemic Heart Disease. JACC: Cardiovascular Imaging Vol 4, No 1, 2011.

  3. Presentation: 45 year-old woman in the Emergency Department • Exhaustion • Throat and jaw discomfort • Palpitations • Shortness of Breath Canto et al. Association of Age and Sex with Myocardial Symptom Presentation; Gender Differences in Symptoms of Myocardial Ischemia

  4. E.J. • 59 year old woman with history of dyslipidemia was playing poker in Las Vegas when she felt a “clinching” substernal discomfort for about 10 minutes. The discomfort radiated to her teeth. 2 days later while sleeping, she felt cold/clammy for 3 hours, which resolved with rest. She felt a loss of appetite and energy. • There was no resolution with Pepto-Bismol or acid reducer

  5. E.J.’s story • Family History: Brother with DM2, Father died suddenly of abdominal aortic aneurysm at 82, Mother has hypertension, diabetes, hyperlipidemia • PE: 5’7” 137#, waist circ. 34 • 98/56, pulse 62. Normal cardiopulmonary exam

  6. E.J.’s trip to the hospital • Total cholesterol 223; Triglycerides 243; HDL 34; LDL 124 • EKG with ST elevation • Troponin I: peak of 9.3 (normal <0.5) • Cath with LAD lesion of 20-30% stenosis • Echo normal • Cardiac CT normal • Thrombolysis was given

  7. Sex and Gender Differences in myocardial infarction

  8. Genderand MI Triggers • Women reported emotional stress prior to MI • Marital stress was reported to be more problematic in women • Work stress was more problematic for men • Men reported heavy physical activity prior to MI Sex and Gender Aspects in Clinical Medicine p. 18

  9. Ischemia symptoms in women: “atypical” • fatigue • right or left arm and shoulder pain • indigestion • epigastric pain • neck pain • syncope • nausea • abdominal pain • dyspnea • dizziness • palpitations • interscapular pain • weakness • vomiting • throat and jaw pain • asymptomatic

  10. Differences in Symptoms: Hypotheses of origin • Parasympathetic nerves innervate the posterior and inferior surfaces of the heart • Women and men are more likely to have right dominant coronary systems • Women have a predominance of parasympathetic influence on heart rate regulation • Theory: ischemia of those areas stimulates the vagus nerve • causes discomfort in locations also innervated by the vagus nerve Evans, J. Gender differences in autonomic cardiovascular regulation: spectral, hormonal, and hemodynamic indexes. J Applied Phys Dec. 1, 2001. Vol 91, No.6, 2611-2618.

  11. Atherosclerosis Risk Factors with Greater Detriment in Women • Smoking • Depression • Metabolic syndrome • Diabetes • Hypertension Yusuf, S. Effectt of potentially modifiable risk factors associated with myocardial infarctionin 52 countries. Lancet 2004; 364: 937-52.

  12. Relative Risk (95% CI) for mortality in subjects with hypertension, diabetes, or both adjusted for age, center, BMI, smoking and cholesterol.DECODE study

  13. Endothelial function and diabetes • Estrogen usually helps improve endothelial function • Diabetes negates the protective sex differences in endothelial function and nitric oxide effect Steinberg. Type II diabetes abrogates sex differences in endothelial function in premenopausal women. Circ 101. 2040-2046 (2000).

  14. Atherosclerosis Risk Factors Unique to Women • Climacteric symptoms- peri and early post menopausal symptoms are not associated with cardiovascular disease • Persistent or late-onset hot flashes are associated with heart disease • Hypertensive events during pregnancy • Hyperglycemic events during pregnancy • Acceleration of the prevalence of heart disease after menopause

  15. Other Risk Factors Under investigation • Systemic autoimmune disease greatly increases risk of cardiovascular disease • Higher prevalence of autoimmune disease in women Frostegard, J. Autoimmunity, oxidized LDL and cardiovascular disease. Autoimmunity Reviews Vol1, Issue 4, August 1, 2002. pp 233-237.

  16. Effects of menopausal transition on cardiac risk factors

  17. LDL Cholesterol Levels After Menopause Menopause Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31

  18. HDL Cholesterol Levels After Menopause Menopause Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31

  19. Estrogen’s effects on vessels • Estrogen effects • Improve response to nitric oxide • Allow for endothelial compliance • Increase coagulation factors • Estrogen withdrawal decreases vascular repair

  20. Endothelial Cell Layers in Healthy Postmenopausal and Premenopausal Women • Postmenopausal cells show evidence of endothelial cell death, denudation, and RBC, platelet, and protein attachment, as well as fractured basal membranes, and loss of intercellular junctions • Premenopausal cells show tight connections, a continuous layer of endothelial cells, and thick plasma membranes

  21. Differences in Coronary Vascular Plaque Pathology Female Male Localized endothelial plaque deposition Invades lumen diameter Present in medium-sized arteries • Continuous endothelial plaque deposition • Outward remodeling • Present in small distal arteries • More endothelial dysfunction Burke. Effect of risk factors on the mechanism of acute thrombosis and sudden death in women. circ. 1998;97: 2110-2116.

  22. Differences in Ischemia Testing for non-obstructive disease Less effective More effective Nuclear stress echo Cardiac Magnetic Resonance Imaging • Treadmill • Percutaneous Coronary Angiography • CT angiogram

  23. Angiography Differences • Of women with chest pain or an abnormal stress test, only 40% had flow-limiting stenosis on angiography • Women are more likely to have single vessel disease • Sex differences in vascular obstructions on angiography disappear with advancing age Prigione p23.

  24. The triad of microvascular dysfunction • Angina • Abnormal stress testing • No obstruction on angiography Samim, A. Treatment of Angina and Microvascular Coronary Dysfunction. Current Treatment Options in Cardiovascular Medicine. (2010) 12:355-364.

  25. Coronary Differences • Anatomical differences: Women have smaller coronary arteries • Women may experience endothelial dysfunction more commonly • Abnormal stress test New insights into ischemi heart disease in women. ccjm.org/content/74/8/585.full.pdf

  26. Impact of age on innervation in women • Cardiac innervation undergoes a sympathetic surge between the 5th and 6th decades of life in women Sakata. Physiological Changes in Human Cardiac Sympathtic Innervation and Activity Assessed by 123I-Metaiodobenzylguanidine (MIBG) Imaging. Circulation Journal Vol. 73. Feb. 2009.

  27. Sex Differences in Plaque Disturbance Women Men Plaque rupture • Superficial plaque erosion with thrombus formation Arbustini; Prigione p 23.

  28. Biomarkers in Acute Coronary Syndrome Women Men Troponin Creatinekinase • CRP • BNP Bairey Merz- Proceedings 2010; Wiviott. Differential expression of cardiac biomarkers by gender in patients with unstable angina/non-ST elevation myocardial infarction. Circ. 2004;109:580-586.

  29. Thrombolysis • Fibrinolyic therapy in (TIMI)-II • Higher rates of death and reinfarction in women at 6 weeks and one year • Fibrinolytic therapy in (ExTRACT-TIMI)-25 • Higher incidence of death after reperfusion in women

  30. Comparisons of revascularization procedures • Equally effective when performed in similar time frames • Percutaneous coronary intervention • Coronary Artery Bypass Grafting • Women tend to bleed more often with antiplatelet therapy • Women have greater mortality after CABG Prigione p 20.; Mortensen, OS. Gender differences in health-related quality of life following ST-elevation myocardial infarction: women and men do not benefit from primary percutaneous coronary intervention to the same degree. Eur J CardiovascPrev Rehab. 2007 Feb;14(1):37-43.

  31. Differences in Ischemia Mortality • Women without chest pain have higher in-hospital mortality • Especially under 65 years of age in the 30 days after hospitalization • Higher rates of in-hospital mortality, death, or myocardial (re)infarction • More frequent hospitalizations with nonobstructive disease Bridging the Gender Gap; Canto; Prigione p 20.

  32. Figure- Sex differences in acute myocardial infarction outcomes. Vaccarino. N Engl J Med 1999; 341:217-225.

  33. Sex-Specific Recommendations by ACC/AHA practice guidelines • Women with high-risk features, recommendations for invasive strategy are similar to men • Women with low-risk features, initial non-invasive strategy is recommended AHA practice guidelines

  34. Sex Differences in Risk Factor Impact After Infarction • Diabetic women are 3x more likely to die after a cardiac event than diabetic men • Women who smoke experience more complications in the 6 months following an MI • Repeat myocardial infarction • Heart-related hospitalization • Revascularization procedure Howe,M. Role of Cigarette Smoking and Gender in Acute Coronary Syndrome Events. Am J Cardiol 2011;108:1382-1386.

  35. Differences in evidence for secondary prevention therapy • Statin- equally effective • Aspirin- equally effective • Nitrates- equally effective • ACE inhibitors- equally effective • Beta blockers- equally effective • Aldosterone inhibitors- equally effective • GPIIb/IIIIa inhibitor- may be less effective in women Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. PURSUIT trial.

  36. Treatment for Microvascular Coronary Dysfunction • Statins, angiotensin-converting enzyme inhibitors, and aspirin • B-blockers, calcium channel blockers, nitrates Samim. Treatment of Angina and Microvascular Coronary Dysfunction.

  37. Emotional Impact of MI on the Sexes • Women are less likely to involve spouses in the recovery process • Women suffer from depression and anxiety after MI than men • Receiving health information from practitioners resulted in less depression • Sex after MI occurs less often in almost half of men and nearly 60% of women Prigione p 21. Stewart. Gender differences in health information needs and decisional preferences in patients recovering from an acute ischemic coronary event. Psychosom Med 2004 Jan-Feb;66(1):42-8. People ‘needlessly avoid sex after heart attacks’ PubMed Health Thu May 10 2012.

  38. Estrogen therapy after plaque is present conveys no benefit to the endothelium • Estrogen therapy for secondary prevention of coronary artery disease is discouraged HERS and ERA trials- Mosca in AHA Scientific Statement. circulation 2001.

  39. Lifestyle Impact on Women • Moderate alcohol consumption is more protective to women Yusuf. Lancet;

  40. CME Questions • Anginal symptoms are similar between younger men and women. F- younger women tend to have less chest pain and more atypical symptoms. • Catheterization is the best study to evaluate microvascular disease. F- Microvascular disease is best found with cardiac MRI or functional testing. • Atherosclerosis treatments are more effective in women. F- they appear to be equally effective. • The hormone changes with menopause decrease HDL and increase LDL.

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