Y Does X Make A Difference - PowerPoint PPT Presentation

Y Does X Make A Difference. Myocardial Ischemia. The Three Paradoxes. 1. Women have a higher prevalence

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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
  • 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.

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

  • 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
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
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
Sex and Gender Differences in myocardial infarctionGenderand 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

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
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.

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.

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

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).

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
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.

Effects of menopausal transition on cardiac risk factorsLDL Cholesterol Levels After Menopause


Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31

HDL Cholesterol Levels After Menopause


Jensen J, et al. Influence of menopause on serum lipids and lipoproteins. Maturitas 1990; 12:321-31

Estrogen’s effects on vessels
  • Estrogen effects
    • Improve response to nitric oxide
    • Allow for endothelial compliance
    • Increase coagulation factors
  • Estrogen withdrawal decreases vascular repair
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
Differences in Coronary Vascular Plaque Pathology



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.

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
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.

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.

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

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.

Sex Differences in Plaque Disturbance



Plaque rupture

  • Superficial plaque erosion with thrombus formation

Arbustini; Prigione p 23.

Biomarkers in Acute Coronary Syndrome





  • 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.

  • 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
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.

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.

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

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

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.

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.

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.

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.

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.

Lifestyle Impact on Women
  • Moderate alcohol consumption is more protective to women

Yusuf. Lancet;

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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