Coronary Artery Disease in Women

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  • Despite advances in the detection and management of cardiovascular disease (CVD) in recent years, CVD risk remains under-recognized in many special populations, including women, African Americans, Hispanics, diabetics, and obese individuals According to the American Heart Association (AHA), mortality statistics (from the Centers for Disease Control and Prevention [CDC] and the National Center for Health Statistics [NCHS]) reveal a decline in cardiovascular disease (CVD)-related deaths in men over the past 2 decades. This decline may correlate with the start of the National Cholesterol Education Program (NCEP) initiative and promotion of earlier, more aggressive cholesterol management programs. Over this same time period, CVD-related mortality in women has not declined appreciably. According to the most recent AHA Heart Disease and Stroke Statistics, CVD-related mortality data for the year 2003 (preliminary) indicate 483,842 deaths in women compared with 426,772 deaths in men [Thom, pe87] . References Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA . 2001;285:2486-2497. Thom T, Haase N, Rosamond W, et al; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation . 2006;113:e85-151. http://www.americanheart.org/presenter.jhtml?identifier=3018163. Accessed July 2006
  • Female autopsy cases evaluated for the effect of traditional atherosclerosis risk factors on mechanisms of sudden cardiac death in women reveal distinct patterns of risk factors and plaque morphology, depending on menopausal status. In the study by Burke and colleagues, vulnerable plaque rupture with severe coronary stenosis was associated with elevated cholesterol and age >50 years, while plaque erosion with minimal vessel narrowing was more frequent in younger women <50 years of age who smoked. The intriguing implication in these findings is that while the etiology of the acute thrombotic event in sudden cardiac death may be the same in post-menopausal women and in men, this etiology is different in pre-menopausal women. Reference Burke AP, Farb A, Malcom GT, Liang Y, Smialek J, Virmani R. Effect of risk factors on the mechanism of acute thrombosis and sudden coronary death in women. Circulation . 1998;97:2110-2116.
  • Gender differences in CAD etiology and clinical presentation extend to mortality risk as well, highlighting the importance of early recognition, despite confounding or absent symptoms, and timely management of CAD in women. References Heart Attack Symptoms and Warning Signs. http://www.americanheart.org/presenter.jhtml?identifier=4595. Accessed June 15, 2006. Albert CM, Chae CU, Grodstein F, Rose LM, Rexrode KM, Ruskin JN, Stampfer MJ, Manson JE. Prospective study of sudden cardiac death among women in the United States. Circulation . 2003;107:2096-2101. Womena and Heart Disease Fact Sheet. http://www.womenheart.org/information/WH_fact_sheet_print.html. Accessed June 12, 2006.
  • Contemporary techniques of echo and nuclear SPECT imaging ( incorporating contrast with echo and attenuation correction and gated SPECT =high sensitivity and specificity for detecting physiologically significant disease.
  • Standard diagnostic tests, including angiography, reveal that for many women ischemic heart disease is not associated with luminal obstruction but rather with atypical plaque accumulation along the walls of the major coronary arteries, perhaps reflecting one of several forms of atherosclerotic disease – that, in women, are modulated by reproductive hormones. Approximately 50% of women referred for suspected ischemia do not have obstructive disease but are still at risk for future events and continued symptoms [Lerman pS61] . Therefore, among women referred for diagnosis of suspected ischemia, caution is warranted in the face of nonobstructive angiograms or results of noninvasive tests whose findings could be erroneously construed as falsely positive. References Bairey Merz CN, Shaw LJ, Reis SE, et al; WISE Investigators. Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;47(3 Suppl):S21-S29. Lerman A, Sopko G. Women and cardiovascular heart disease: clinical implications from the Women's Ischemia Syndrome Evaluation (WISE) Study. Are we smarter? J Am Coll Cardiol. 2006;47(3 Suppl):S59-S62.
  • Reference Lerman A, Sopko G. Women and cardiovascular heart disease: clinical implications from the Women's Ischemia Syndrome Evaluation (WISE) Study. Are we smarter? J Am Coll Cardiol. 2006;47(3 Suppl):S59-S62.
  • The gated portion of the SPECT study allows both the visual and quantitative assessment of left ventricular function. These measures include left ventricular ejection fraction and end-diastolic and end-systolic volumes. In addition, this modality achieves excellent visualization of both the endocardial and epicardial surfaces, allowing for the evaluation of left ventricular wall motion and wall thickening. In this scan, the top row represents 3 short axis images (apical, mid, and basal short-axis slices) and the bottom row represents the mid, horizontal, and vertical long-axis slices.

Transcript

  • 1. Credit: Slides Based on Presentation from Dr. Jennifer Mieres New York University School of Medicine
  • 2. Img Source: http://www.flickr.com/photos/yourdon/2683324564/
    • 65 y/o female
      • Presents to local ER
      • Sudden onset of SSCP, 8/10, pressure like, radiating to the jaw
      • Intense nausea / vomiting x2.
      • Soon became SOB and lightheaded.
      • BP  80/45.
  • 3.
    • PMHx: HTN, DM, Hyperlipidemia
    • PSHx: None
    • SoHx: No Tobacco
    • Social drinker
    • No Hx of drug use
    • Retired, married lives with husband
    • FHx: No Hx of CAD, MI, SCD.
    • Meds: Lipitor 10mg Daily
    • Atenolol 25mg Daily
    • Metformin 500mg Twice Daily
  • 4.
    • T: 98.9 HR: 110 BP: 78/43 RR: 32 93% 2L
    • HEENT: Atraumatic, PERRL, mmm
    • Neck: Supple, No JVD, No bruit
    • Chest: Bibasilar crackles
    • CVS: Tachy, S1, S2- no gallops or rub, II/VI holosystolic murmur LSB
    • Abd: Soft, Tender in epigastric area, ND, NO BS
    • Ext: No edema
    Image: Lisa F Young, Flickr
  • 5.  
  • 6. 137 109 18 3.9 22 1.0 244 8.6 2.1 1.0 11.7 14.8 34.3 390 CPK: 152 MB: 13.6 Trop: 1.9 AST:29 TP: 6.1 ALT: 24 Alb: 3.0 Bili: 1.1/0.4
  • 7.
    • Started on 5mcg dopamine
    • Became more hypotensive, developed pink frothy sputum.
    • Intubated, STEMI alert called.
    • Given 300mg plavix via NG tube,
    • half dose lytics
    • Transferred to HUH
  • 8.
    • SOME FACTS
    • DIAGNOSTICS
    • TREATMENT
    • ACTION
  • 9. Leading Causes of Death for All Males and Females US 2004 A Total CVD (Preliminary) B Cancer C Accidents D Chronic Lower Respiratory Diseases E Diabetes Mellitus F Alzheimer’s Disease Source: CDC/NCHS/AHA Deaths in thousands
  • 10. *2004 statistics are preliminary ; NCEP, National Cholesterol Education Program http://www.americanheart.org/presenter.jhtml?identifier=3018163. Accessed July 31, 2006 Thom T, et al. Circulation . 2007;113:e85-151 Year 400 420 440 460 480 500 520 1980 1985 1990 1995 2000 2004 Deaths in thousands Males Females NCEP I NCEP II NCEP III
  • 11.
    • Leading cause death US women
        • ~½ million CVD annually
        • ~220,000 Coronary heart disease in 2004
    • CHD symptoms appear ~10 years later in women
        • CHD/MI can occur premenopausal
    Wenger N, Prog Cardiovasc Disease, 2003;46:199-229 AHA. Heart Disease and Stroke Statistics – 2006 Update, Dallas: AHA 2006
  • 12.
    • More co-morbidities in women with CHD
      • Hypertension
      • Diabetes
      • Heart failure
    • CHD substantial cause of disability in women. Since 1984 women > men CV mortality
    Wenger N, Prog Cardiovasc Disease, 2003;46:199-229 AHA. Heart Disease and Stroke Statistics – 2006 Update, Dallas: AHA 2006
  • 13. Courtesy :Dr Sharonne Hayes Mayo Clinic Smoking Diabetes HTN Obesity Sedentary lifestyle Hyperlipidemia Family Hx/genetics “ Conventional” Risk Factors Psychosocial factors Depression Environmental stress Oxidative stress Homocysteine Inflammation CRP, Collagen vascular Dz
    • Thrombotic factors
      • Fibrinogen,
      • TpA, PAI-1
    Infection Vitamin deficiency Iron load “ Nonconventional” Risk Markers
  • 14.
    • 65% of diabetics die from heart disease or stroke
    • 4.2 million American women have diabetes
      • Diabetes increases CAD risk 3-fold to 7-fold in women vs 2-fold to 3-fold in men
      • Diabetes doubles the risk of a second heart attack in women but not in men
    • Far more powerful coronary risk factor for women than men, negating much of the protective effects of the female sex.
    Manson JE et al, Prevention of Myocardial Infarction , 1996:241-273. American Heart Association. Centers for Disease Control and Prevention.
  • 15. Increasing Public Awareness of Heart Disease in Women: NHLBI, AHA and Womenheart The National Coalition for Women with Heart Disease. www.womenheart.org
  • 16.
    • Gaps in knowledge of heart disease in women:
      • Underestimation of risks by healthcare professionals
      • Disparities in women’s knowledge of heart disease
  • 17. CAD, coronary artery disease Burke AP, et al. Circulation . 1998;97:2110-2116. Age Plaque morphology Coronary artery stenosis Associated risk factor < 50 years plaque erosion minimal cigarette smoking > 50 years vulnerable plaque rupture severe hypercholesterolemia
  • 18.
    • Typical in both sexes
    • Pain, pressure, squeezing, or stabbing pain in the chest
    • Pain radiating to neck, shoulder, back, arm, or jaw
    • Pounding heart, change in rhythm
    • Difficulty breathing
    • Heartburn, nausea, vomiting, abdominal pain
    • Cold sweats or clammy skin
    • Dizziness
    Source: AHA &: WISE data JACC 2006
  • 19.
    • Typical in both sexes
    • Pain, pressure, squeezing, or stabbing pain in the chest
    • Pain radiating to neck, shoulder, back, arm, or jaw
    • Pounding heart, change in rhythm
    • Difficulty breathing
    • Heartburn, nausea, vomiting, abdominal pain
    • Cold sweats or clammy skin
    • Dizziness
    • Can be Seen more commonly in women
    • Milder symptoms (without chest pain)
    • Sudden onset of weakness, shortness of breath, fatigue, body aches, or overall feeling of illness (without chest pain)
    • Unusual feeling or mild discomfort in the back, chest, arm, neck, or jaw (without chest pain)
    Source: AHA &: WISE data JACC 2006
  • 20. Milner et al: Am J Cardiol, 1999 % Dyspnea Nausea Indigestion Dizziness Fatigue Sweating Arm/ Vomiting Fainting Shoulder/pain Women Men
  • 21.
    • Fewer women than men presented with ST elevation MI
      • 27.2% in women vs 37% in men
      • GUSTO IIb 12,142 (30% women)
    • Women less likely to have angiography 53% vs 59%, however
    • Women in all subgroups were less likely to have severe stenoses
    Hochman et al NEJM341:4:276,1999
  • 22.
    • Gender differences in mortality
      • 57% of women who die suddenly from CAD had no prior typical warning symptoms
      • 38% of women vs 25% of men will die within 1 year post-MI
    • Early recognition of symptoms, accurate diagnosis and proper treatment of CAD are of great importance.
    Albert CM et al. Circulation 2003;107:2096-101; Women and Heart Disease Fact Sheet. http://www.womenheart.org/information/WH_fact_sheet_print.html . Accessed June 12, 2006 Heart Attack Symptoms and Warning Signs. http://www.americanheart.org/presenter. jhtml?identifier=4595 . Accessed June 15, 2006
  • 23. ASNC Patient Management Strategy for CT Imaging & SPECT In Asymptomatic, Int-High Framingham Risk Low FRS Int-High FRS SPECT CCS > 400 or 90th %ile CCS <100 or <75 th %ile CCS > 100<400 or > 75 th <90 th %ile Cath - ? CTA Primary Prevention EBT-CT Mod-Severe Abnml Low Risk Mildly Abnml Primary Prevention Consider Re-Testing 3-5 Yrs Secondary Prevention Consider Re-Testing 2-3 Yrs Medical Rx Consider Re-Testing 1-2 Yrs Highlighted box indicates patients treated to secondary prevention goals Source: Shaw LJ, Berman DS, Bax JJ, Brown KA, Cohen MC, Hendel RC, Mahmarian JJ, Williams KA, Ziffer JA. The complementary roles of nuclear cardiology and cardiac CT in the current healthcare environment. J Nuc Cardiol 2005;12:131-142.
  • 24. Source: Kwok AJC 1999, klocke et al JACC,, Shaw Eur Heart J 2005 Mar;26(5):447-56.
  • 25. Improved CAD Detection & Prognostication through Visualization of Wall Motion, Perfusion, & Function SPECT Imaging: Visualize Wall Motion, Perfusion, & Function Echo Imaging: Visualize Wall Motion & Function
  • 26.
    • Exertional Symptoms - Low Predictive Value
    • Shorter Exercise Duration - Affects diagnostic accuracy
    • High Rate of “False Positives” Reported
    • Exercise Electrocardiogram Testing: Beyond the ST Segment:
      • ST/HR index,
      • QRS duration and amplitude,
      • QT and T wave changes .
    Source: Shaw et al JACC 2006; Kligfield and Lauer .Circ. Vol 114. Nov 06 Image: http://farm2.static.flickr.com/1247/3171917389_c96c5970de.jpg?v=0
  • 27. Follow-up (Years) 3.0 2.5 2.0 1.5 1.0 .5 0.0 Cumulative Survival 1.00 .95 .90 .85 .80 Nondiabetics Diabetics p<0.00001 Source: Giri S, et al. Circulation. 2002;105:32-40. Re-Test @ ~1-1.5 years
  • 28. 39 y/o AAF Multiple Risk Factors Chest Pain Stress Perfusion
  • 29.  
  • 30. Arterial Wall Atherosclerosis Symptomatic Luminal Obstruction Courtesy LJ Shaw, PhD; Cedars-Sinai Medical Center
  • 31.
    • Approximately 50% of women referred for evaluation of ischemia do not have obstructive coronary disease
    • Intermediate risk – future cardiac events and persistent symptoms
  • 32.
    • Impact for practitioners
      • Can no longer ignore non-obstructive coronary angiograms in women
      • Can no longer assume a positive troponin or an abnormal stress perfusion test is falsely positive just because a woman’s angiogram shows no obstruction
    Lerman A, Sopko G. J Am Coll Cardiol. 2006;47(3 Suppl):S59-S62.
  • 33. Noninvasive Coronary anatomy: evaluation of coronary stenosis ( calcified and non-calcified plaque and the vessel wall) CTA LM/LAD CATH LM/LAD
  • 34.
    • Similar benefit in men and women for
      • Statins
      • Antiplatelet therapy
      • Beta Blockers
      • Nitroglycerin
      • Thrombolytics
      • ACE- inhibitors
    Img Source: Flickr, 2588342742_8634700f43.jpg
  • 35.
    • NOT for prevention of heart Disease
    • Postmenopausal Hormone Therapy is FDA approved for:
    • Treatment of postmenopausal symptoms
    • Prevention of osteoporosis
    • Black Box warning (3/03)
    • Use lowest dose for shortest duration
  • 36.
    • Intermediate- risk Women ( 10-20% risk)
      • Class I Recommendations
        • Smoking Cessation
        • Physical Activity
        • Heart Healthy Diet
        • Weight Maintenance / Reduction
        • Blood Pressure Control
        • Lipid Control
      • Class IIa Recommendations
        • Aspirin Therapy ( women >65 YO)
  • 37.
    • Lower- risk Women ( <10% risk)
      • Class I Recommendations
        • Smoking Cessation
        • Physical Activity
        • Heart Healthy Diet
        • Weight Maintenance / Reduction
        • Treat Individual CVD Risk Factors as Indicated
  • 38.
    • Recent improved outcomes for women following PCI
    • Women are older , more DM,HTN,CHF,USA,and single vessel disease
    • One year mortality higher in women 6.5% than men 4.3% post PCI
  • 39.
    • In-hospital mortality for women is higher
      • 50 < y/o and have 3.4% operative mortality vs. 1.1% in men.
    • Differences have persisted for > 20 yrs
    • Less like to get LIMA grafts
    • Women have increased Angina symptoms post CABG
    • Women have better long term survival
    Vaccarino V et al. Circ 2002
  • 40.  
  • 41.
    • RHC: RA: 3 PAP: 28/7/15 CO: 4.2
    • RV: 28/4 PCW: 8 CI: 2.3
    • PA Sat: 64%
    • LHC: AO: 70/43
    • LM: NL LAD:Mid/distal bridge, LI’s
    • LCX: Non-dominant, LI’s
    • RCA: Dominant, LI’s
  • 42.
    • LV gram: Apical ballooning
    • 3+ MR
    • Dopamine D/Ced, norepinephrine started at 200mcg.
    • LV 192/15 pull back 160/91
  • 43.
    • NL LV size, Proximal septum is thickened
    • Late peaking LVOT gradient measuring 80mm
    • Basal ventricle is hyperdynamic
    • Apex and distal ventricle are akinetic with ballooning appearance
  • 44.  
  • 45.
    • H/H stable
    • Decreased O2 requirement on the vent
    • Cardiac enzymes
    • CPK 146  187  179  195
    • MB 13.0  14.2  11.2  10.4
    • Trop 1.9  3.07  2.44  2.00
  • 46.  
  • 47.  
  • 48.
    • Stress-induced Cardiomyopathy / Apical Ballooning Syndrome / Broken Heart Syndrome:
      • Increasingly reported
      • Characterized by transient systolic dysfunction of the apical and/or mid segments of the left ventricle
      • Mimics myocardial infarction (MI)
      • BUT in the absence of significant coronary artery disease
  • 49.
    • “ Typical&quot; stress-induced cardiomyopathy:
      • Contractile function of the mid and apical segments of LV are depressed
      • Compensatory hyperkinesis of the basal walls
      • Ballooning of the apex with systole.
      • In a minority of cases (40 percent in one report), the ventricular hypokinesis is restricted to the midventricle (&quot;atypical&quot;) with relative sparing of the apex
  • 50. http://www.flickr.com/photos/yourdon/2683324564/
  • 51.
    • Women present with milder and more atypical symptoms
    • Imaging is critical for early diagnosis
    • Aggressive approach to management
  • 52.
    • WISE Study:
      • Can no longer ignore non-obstructive coronary angiograms in women
      • Can no longer assume a positive troponin or an abnormal stress perfusion test is falsely positive just because a woman’s angiogram shows no obstruction
  • 53. http://www.flickr.com/photos/yourdon/2683324564/
  • 54. http://www.flickr.com/photos/yourdon/2683324564/
  • 55.
    • Gender Differences in Pathophysiology of CAD and Clinical Recognition of CAD in Women
    • Risk factors for CAD in Women and Prevention
    • Gender Differences in the Diagnostic Evaluation of Coronary Heart Disease
  • 56. Percentage of Men with one vessel, two vessel, three vessel left main or no CAD on coronary angiography Reference: JACC 2003;41:158-68 N indicates Normal or <50% stenosis; one-vessel, two-vessel, three-vessel disease; LM: Left main disease
  • 57. Percentage of Women with one vessel, two vessel, three vessel left main or no CAD on coronary angiography Reference: JACC 2003;41:158-68 N indicates Normal or <50% stenosis; one-vessel, two-vessel, three-vessel disease; LM: Left main disease
  • 58.
    • Epidemiological data – CAD uncommon in premenopausal women
    • Observational data
      • 30-50 studies, overwhelmingly positive
    • Physiologic benefits – cholesterol lowering, etc.
  • 59.
    • Randomized control trial(PEPI): intermediate outcome was positive
    • Studies: Clinical or angiographic endpoints all negative – HERS, ERA, WHI
      • No benefit of Hormone Therapy in primary or secondary prevention
  • 60.
    • CVD kills 2X American Women than from all cancers combined.
    • ~ 500,000 women die from CVD vs. ~ 41,500 by breast cancer.
    • CVD declining but rate of decline for Women < Men;
      • African-American < Caucasian Women
    • Women develop CHD ~10 yr later than Men
    • Men have a greater risk of MI & at earlier ages
    • Ave 1 st MI 65.8 yr Men vs. 70.4 yr Women
    • Strokes more common in Women than Men & associated with atrial fibrillation
  • 61.
    • Type II Diabetic Women
      • 3-4X more likely to develop CHD
      • 2X risk of a 2 nd heart attack
      • have lower E2 & loose “estrogen’s protective effect”
      • experience reproductive problems
      • 2-4X more likely to be African American, Hispanic, American Indian, or Asian Pacific Islander than Caucasian
    • Diabetes associated with
        • low total testosterone in Men
        • high levels of bioavailable testosterone in Women
    • Lower estrogen levels may account for the same rate of kidney and CV disease-related conditions.
  • 62.
    • Cardiac arrest ~ 3x > in Men than Women, but lower
        • recovery and
        • survival rates in Women
    Pathophysiology: Cardiovascular II
    • Cardiac arrhythmias, drug-induced torsades de pointes, and long QT syndrome more prevalent in Women
    • At younger ages, prevalence of CHF > Men; after 75 reverses
    • Women with CHF more likely to have co-morbid diabetes and hypertension than Men.
  • 63. 1. Chest discomfort or uncomfortable pressure, fullness, squeezing or pain in the center of the chest that lasts longer than a few minutes, or comes and goes. 2. Spreading pain to one or both arms, back, jaw, or stomach. 3. Cold sweats and nausea .
  • 64.
    • Women often don’t experience the “hallmarks” (only 30%), instead:
        • shortness of breath,
        • nausea,
        • vomiting
        • sleeplessness
        • back pain or jaw pain, and
        • a feeling of generalized weakness, fatigue in weeks prior to Acute MI!
    Consequently treatment delayed, inappropriate, or wrong leading to preventable deaths.