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CARDIOPATIA ISCHEMICA NELLA DONNA: PERCORSI DIAGNOSTICI E TERAPEUTICI

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1 CARDIOPATIA ISCHEMICA NELLA DONNA: PERCORSI DIAGNOSTICI E TERAPEUTICI
ASSOCIAZIONE ITALIANA DONNE MEDICO REGIONE LIGURIA SOCIETA’ ITALIANA DI MEDICINA GENERALE SEZIONE LIGURIA 2° Congresso regionale congiunto Genova 23 ottobre 2010 CARDIOPATIA ISCHEMICA NELLA DONNA: PERCORSI DIAGNOSTICI E TERAPEUTICI Dr. Luigi Pizzorno Servizio di Cardiologia con UTIC PO Metropolitano Genovese / SO GE-Sestri

2 University of Alberta Edmonton Emergency Department
CMAJ • November 6, 2007 • 177(10) Differences in admission rates and outcomes between men and women presenting to emergency departments with coronary syndromes Background: Previous studies examining sex-related differences in the treatment of coronary artery disease have focused on patients in hospital. We sought to examine sexrelated differences at an earlier point in care — presentation to the emergency department. Methods: We collected data on ambulatory care and hospital admissions for patients (44% women) who presented to an emergency department in Alberta between July 1998 and March 2001 because of acute myocardial infarction, unstable angina, stable angina or chest pain. We used logistic regression and Cox regression analyses to determine sexspecific associations between the likelihood of dischargefrom the emergency department or coronary revascularization within 1 year and 1-year mortality after adjusting for age, comorbidities and socioeconomic factors. Results: Following the emergency department visit, 91.3% of patients with acute myocardial infarction, 87.4% of those with unstable angina, 40.7% of those with stable angina and 19.8% of those with chest pain were admitted to hospital. Women were more likely than men to be discharged from the emergency department: adjusted odds ratio (and 95% confidence interval [CI]) 2.25 (1.75–2.90) for acute myocardial infarction, 1.71 (1.45–2.01) for unstable angina, 1.33 (1.15–1.53) for stable angina and 1.46 (1.36–1.57) for chest pain. Women were less likely than men to undergo coronary revascularization within 1 year: adjusted odds ratio (and 95% CI) 0.65 (0.57–0.73) for myocardial infarction, 0.39 (0.35–0.44) for unstable angina, 0.35 (0.29–0.42) forstable angina and 0.32 (0.27–0.37) for chest pain. Female sex had no impact on 1-year mortality among patients with acute myocardial infarction; it was associated with a decreased 1-year mortality among patients with unstable angina, stable anginaand chest pain: adjusted hazard ratio (and 95% CI) 0.60 (0.46– 0.78), 0.60 (0.46–0.78) and 0.74 (0.63–0.87) respectively. Interpretation: Women presenting to the emergency department with coronary syndromes are less likely than men to be admitted to an acute care hospital and to receive coronary revascularization procedures. These differences do not translate into worse outcomes for women in terms of 1-year mortality. pz % donne luglio marzo 2001 Kaul P, 2007; 177: 1193

3 performance donna insicura impacciata performance donna in carriera
Evaluating Chest Pain The Patient's Presentation Style Alters the Physician's Diagnostic Approach 1donna attrice 44 internisti divisi in 2 gruppi registra intervista non si sente l’ intervistatore ascoltano senza vedere performance donna insicura impacciata performance donna in carriera Stima iniziale probabilità CAD CAD 10 % CAD 20% Ricevono stessi dati strumentali e li valutano Rivalutano il caso e fanno la diagnosi CAD 13% CAD 50 % Programmano iter diagnostico ulteriore 53% 93 % Evaluating Chest Pain The Patient's Presentation Style Alters the Physician's Diagnostic Approach Brian G. Birdwell, MD; Jerome E. Herbers, MD; Kurt Kroenke, MD Arch Intern Med. 1993;153(17): Background Clinical prediction rules rely largely on objective data to estimate coronary artery disease (CAD) likelihood. However, characterization of chest pain, which is central to such prediction rules, depends in part on a physician's subjective judgments We performed a clinical trial to assess the influence of the patient's presentation style on the physician's approach to evaluating chest pain. Methods Forty-four internists were randomized to one of three treatment groups. Two groups viewed videotapes of the same actress performing the role of a patient in a scripted physician-patient interview in two distinct styles: one group saw a "histrionic" characterization, the other a "businesslike" portrayal. The interviewer was not seen or heard by the subjects; they saw only words on the screen. The third group read a verbatim transcript of the interview. After their initial CAD-likelihood estimates and impressions of probable cause for the patient's symptoms, which were based on history only, the participants in all three groups were given the same laboratory data and a second CAD-likelihood estimate was made. Finally, recommendations for further workup were elicited. Results Initial diagnostic impressions differed dramatically: a cardiac cause was suspected by 50% of physicians viewing the businesslike portrayal but by only 13% of those viewing the histrionic portrayal. Likewise, those viewing the histrionic and businesslike videos provided different CAD-likelihood estimates initially (10% vs 20%). However, after the patient's laboratory data were revealed, the difference in CAD-likelihood estimates was no longer significant. Despite their making a similar risk appraisal after receiving all of the data, internists viewing the histrionic portrayal were far less likely to pursue a cardiac workup (53% vs 93%). Conclusions Although physicians may evaluate patients who have the same history word for word and the same laboratory data and whom they regard as having nearly identical likelihoods of CAD, the physician's ultimate diagnostic approach can be profoundly affected by the patient's presentation style. (Arch Intern Med. 1993;153: ) Birdwell, BG, Arch Intern Med 1993; 153:1991

4 dolore anginoso tipico e atipico nella donna
retrosternale sensazione di bruciore pesantezza schiacciamento precipitato da sforzo o stress emotivo prontamente rilevato da riposo o nitroderivato localizzato all’ emitorace sn, addome, schiena, braccia in assenza di dolore retrosternale trafittivo o momentaneo ripetitivo o molto prolungato non relato a sforzo non rilevato da riposo o nitroderivato rilevato da antiacidi palpitazioni senza dolore di petto N Engl J Med Aug 2;301(5):230-5. Exercise stress testing. Correlations among history of angina, ST-segment response and prevalence of coronary-artery disease in the Coronary Artery Surgery Study (CASS). Weiner DA, Ryan TJ, McCabe CH, Kennedy JW, Schloss M, Tristani F, Chaitman BR, Fisher LD. Abstract To determine to what extent the diagnostic accuracy of stress testing is influenced by the prevalence of coronary-artery disease, we correlated the description of chest pain, the result of stress testing and the results of coronary arteriography in 1465 men and 580 women from a multicentered clinical trial. The pre-test risk (prevalence of coronary-artery disease) varied from 7 to 87 per cent, depending on sex and classification of chest pain. A positive stress test increased the pre-test risk by only 6 to 20 per cent, whereas a negative test decreased the risk by only 2 to 28 per cent. Aothough the percentage of false-positive results differed between men and women (12 +/- 1 per cent versus 53 +/- 3 per cent P less than 0.001), this difference was not seen in a subgroup matched for prevalence of coronary-artery disease. We conclude that the ability of stress testing to predict coronary-artery disease is limited in a heterogeneous population in which the prevalence of disease can be estimated through classification of chest pain and the sex of the patient. Angina definita Angina probabile Dolore non anginoso stenosi coronariche critiche Coronary Artery Surgery Study 62 % 32 % 4 % dolore tipico/maschio  82% stenosi critiche Weiner D NElM; 1979;301:230

5 DeVon HA, Heart Lung. 2002 Jul-Aug;31(4):235
Review 12 studi UA-STEMI-NSTEMI Sintomi M / F Dolore alla schiena Dolore al collo Dolore alla mandibola Nausea/vomito Dispnea Indigestione Palpitazioni Vertigine Astenia Anoressia Sincope Dolore al torace diaforesi STEMI “ Dato l’ attuale stato delle conoscenze, non possono essere tratte conclusioni definitive riguardanti differenze correlate al genere nei sintomi della SCA” DeVon HA, Heart Lung Jul-Aug;31(4):235

6 dolore toracico 94% nei maschi 92% nelle donne
Tra i Pz con infarto miocardico che alla presentazione non lamentavano dolore toracico risultava: Data not available for all patients; presenting symptoms were studied in the initial phases of GRACE and were discontinued in subsequent case report forms. Patients reporting more than one symptom were counted for all symptoms reported.

7        caratteristiche
“Female Angina” Assessment for the Identification of Obstructive Coronary Disease Women’s Ischemia Syndrome Evaluation percentuali non stenosi stenosi critiche critiche (n= 337) (n= 98) p caratteristiche Bairey Merz CN, 2001;7:959

8 Dolore toracico atipico cod. ICD-9 786.50 786.51 786.59
donne età 50– FU medio 8 anni senza precedente diagnosi di CAD dimesse da DEA con diagnosi NSCP Women’s Ischemia Syndrome Evaluation Women's Health Initiative Observational Study FU medio 8 anni 11% evento CV nel FU ODDs 2,20 per angina 1,75 per CHF 1,62 PCI/BAC 1,50 IMA NF Journal of Women's HealthElderly Women Diagnosed with Nonspecific Chest Pain May Be at Increased Cardiovascular RiskTo cite this article: Jennifer G. Robinson, Robert Wallace, Marian Limacher, Alicia Sato, Barbara Cochrane, Sylvia Wassertheil-Smoller, Judith K. Ockene, Patricia L. Blanchette, Marcia G. Ko. Journal of Women's Health. December 2006, 15(10): doi: /jwh Published in Volume: 15 Issue 10: January 2, 2007 Full Text: • PDF for printing (75.4 KB) • PDF w/ links (115.6 KB) Jennifer G. Robinson, M.D Background: omen are more likely than men to have nonspecific chest pain (NSCP) symptoms. The long-term outcomes in women discharged with a diagnosis of NSCP are unknown. Methods: The Women's Health Initiative Observational Study enrolled postmenopausal women aged 50–79 years. After excluding those with prior cardiovascular disease (CVD), 83,622 women were studied. NSCP cases were defined as having an initial primary hospital discharge diagnosis of NSCP (ICD-9 codes , , ) without a prior diagnosis of coronary heart disease (CHD). Risks of subsequent CHD events were estimated from Cox proportional hazard ratio (HR) models stratified by clinic and adjusted for baseline age, cardiovascular risk factors, and hormone use. Results: Over an average of 8 years of follow-up, 11% (230 of 2,092) of women with NSCP experienced a cardiovascular event compared with 9.5% (7,724 of 81,530) who did not. Compared with women without a hospitalization for NSCP during follow-up, those with NSCP had a greater than 2-fold higher risk of a subsequent hospitalization for clinically diagnosed angina (HR 2.18, 95% CI ) and at least a 1.5-fold higher risk of nonfatal myocardial infarction (MI) (HR 1.59, ), revascularization (HR 1.67, ), and congestive heart failure (HR 1.75, ). Women with NSCP who subsequently experienced a CHD event were more likely to be over age 65 or to have cardiovascular risk factors. Conclusions: Older women discharged with a diagnosis of NSCP may be at increased risk of CHD morbidity. Further research is needed to replicate these findings in other populations. le donne > 65 con NSCP sono  rischio di eventi CV nel FU NSCP = nonspecific chest pain Robinson JG, 2006; 15: 1151

9 INTERHEART Study rischio di IMA in maschi e femmine
52 paesi casi/ controlli 9 fattori individuano il 90% delle persone che hanno sviluppato eventi: fumo ipertensione diabete obesità addominale stress psicosociale ApoB/ApoA1 presents odds ratios and PARs for risk of in men and women. Similar odds ratios were recorded in women and men for the association of with smoking, raised lipids, abdominal , composite of psychosocial variables, and and consumption. However, the increased risk associated with hypertension and , and the protective effect of exercise and alcohol, seemed to be greater in women then in men (figure 4). Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Population Health Research Institute, Hamilton General Hospital, 237 Barton Street East, Hamilton, Ontario, Canada L8L 2X2. BACKGROUND: Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. METHODS: We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent cases and controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. FINDINGS: Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p< for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. INTERPRETATION: Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction. frutta / verdura attività fisica alcool Yusuf S, Lancet 2004; 364:937

10 Rischio CV a 10 anni in adulti di età 50 – 54 anni in relazione ai principali FR
Framingham Heart Study A B C D Età HDL Col, mg/dL Colesterolo T, mg/dL PA Sist, mm/Hg, non tratt Fumo No No No Si Diabete No No No Si D’Agostino et al., Circulation. 2008;117:743

11 Paesi a maggior prevalenza CAD Paesi a minor prevalenza CAD
rischio stimato a 10 anni di morte CV in Europa per popolazioni ad alto o a basso rischio. Paesi a maggior prevalenza CAD Paesi a minor prevalenza CAD DIABETE: per ogni combinazione di FR il rischio di eventi CV è doppio nei ♂ e quadruplo nelle ♀ Conroy M.R., Eur Heart J 2003; 24: 987

12 Classificazione del Rischio CV nella Donna
Evidence-Based Guidelines for Cardiovascular Disease Prevention in Women Update Classificazione del Rischio CV nella Donna A RISCHIO 1 fattore di rischio maggiore: fumo sedentarietà obesità, specie centrale familiarità per CVD < 55 anni per Parente maschio < 65 anni per Parente femmina ipertensione dislipidemia sindrome metabolica evidenza di malattia vascolare subclinica (calcio coronarico / IMT ) ALTO RISCHIO CAD nota Malattia cerebrovascolare Vasculopatia periferica Aneurisma aorta addominale Nefropatia cronica avanzata Diabete Rischio a 10 anni > 20 % Mosca L. Circulation 2007;115:1481 Rischio ottimale = non Fattori di Rischio/ stile di vita corretto/ Rischio globale < 10%

13 AHA Scientific Statement
Un alto “calcium score” (Agatston > 100) si associa con un rischio di eventi annuo = 2% ( = alto rischio) La misura del calcio coronarico può migliorare la previsione del rischio nelle Pz “ a rischio intermedio ” ( 1-2% annuo) Un altro score di calcio non correla con la presenza di stenosi critiche > 4000 donne / FU 5 anni RR Morte tutte le cause CAC < 100 = CAC = 3, CAC = 6, CAC >1000 = 12,3 Raggi, Womens Healt 2004; 13: 273 Detrano, NEJM. 2008;

14 PdS - specificità e sensibilità
uomini donne sensibilità specificità Kvok Y, Am J Cardiol 1999, 83:660

15 accuratezza diagnostica PdS nella donna / estrogeni
effetto digoxin-like EE  alterazioni ST = falsi positivi angina/ischemia possono variare con il ciclo mestruale; fase luteinica/mestruale =  estradiolo  maggior prevalenza ischemia  soglia ischemica pre- menopausa post- menopausa Prevalenza CAD =  accuratezza predittiva del test Estrogeni esogeni modificano vasoreattività periferica  aumento del tempo di esercizio  ischemia ecg ( non perfusionale) nelle donne CAD Shaw LJ, JACC 2006; 47:4S

16 accuratezza diagnostica PdS nella donna capacità funzionale
Se non si raggiunge una adeguata frequenza cardiaca e un adeguato numero di METs la capacità del test di individuare l’ ischemia è diminuita. Inutile fare il test da sforzo se la donna è incapace di svolgere una attività che richieda almeno 5 METs per essere compiuta Shaw LJ, JACC 2006; 47:4S MET Metabolic Equivalent of Task esprime il costo energetico di quella attività in rapporto al riposo ( VO2 3,5 ml/Kg/min) 1 MET 18 MET

17 Duke Activity Status Index (DASI)
attività METS 1 Mangi, ti vesti, ti lavi, vai in bagno da sola ? 2.75 2 Cammini per la casa e in giardino? 1.75 3 Cammini attorno ad un isolato ? 4 Sali un piano di scale? Cammini in salita? 5.50 5 Puoi far una breve corsa ? 8.00 6 Fai lavori domestici leggeri ( spolverare o lavare i piatti)? 2.70 7 Fai lavori domenstici moderati (usare aspirapolvere, spazzare, portare la spesa)? 3.50 8 Fai lavori domestici pesanti come lavare il pavimento o spostare mobili? 9 Fai lavori pesanti ( usare decespugliatore, rastrellare, spingere un tosaerba)? 4.50 10 Fai sport con impegno fisico moderato ( ballo, bocce, passeggiate, bici)? 6.00 11 Hai rapporti sessuali ? 5.25 12 Fai sport con impegno fisico moderato( nuoto, sci, football, basket)? 7.50 Am J Cardiol Sep 15;64(10):651-4. A brief self-administered questionnaire to determine functional capacity (the Duke Activity Status Index). Hlatky MA, Boineau RE, Higginbotham MB, Lee KL, Mark DB, Califf RM, Cobb FR, Pryor DB. Department of Medicine, Duke University Medical Center, Durham, North Carolina Abstract To develop a brief, self-administered questionnaire that accurately measures functional capacity and assesses aspects of quality of life, 50 subjects undergoing exercise testing with measurement of peak oxygen uptake were studied. All subjects were questioned about their ability to perform a variety of common activities by an interviewer blinded to exercise test findings. A 12-item scale (the Duke Activity Status Index) was then developed that correlated well with peak oxygen uptake (Spearman correlation coefficient 0.80). To test this new index, an independent group of 50 subjects completed a self-administered questionnaire to determine functional capacity and underwent exercise testing with measurement of peak oxygen uptake. The Duke Activity Status Index correlated significantly (p less than ) with peak oxygen uptake (Spearman correlation coefficient 0.58) in this independent sample. The Duke Activity Status Index is a valid measure of functional capacity that can be obtained by self-administered questionnaire. Hlatky MA, Am J Cardiol 1980; 64: 644

18 capacità funzionale e prognosi
1 MET  8 % rischio MACE Wessel TR JAMA. 2004; 292:1179 914 donne 10 anni FU 5 anni EP: M/IMA OBJECTIVES Our objective was to determine the prognostic value of estimated metabolic equivalents (METs) based on self-reported functional capacity by the Duke Activity Status Index (DASI) in symptomatic women. BACKGROUND Functional capacity is an important component affecting the predictive value of exercise testing, yet current guidelines offer limited assistance regarding identification of functional impairment and choice of pharmacologic stress testing. METHODS A total of 914 women underwent clinically indicated coronary angiography and completed the 12-item DASI questionnaire; a subgroup of 251 women also underwent exercise testing. Cox proportional hazards modeling was used to estimate five-year death or myocardial infarction by DASI scores. In a secondary analysis, additional events included unstable angina, heart failure, or stroke at five years. RESULTS Average DASI-estimated functional capacity was 5.7  4.2 METs and, for exercising women, 6.0  2.6 METs. In the 914 women, event-free survival ranged from 83% to 95% in subgroups with 4.7 to 9.9 METs (p ); 67% of the events occurred in women scoring 4.7 METs (p ). Event rates were similar by exercise and DASI MET values. In women with DASI-estimated METs 4.7 (n 75), ischemia occurred less (39% vs. 64%, p ), and exercise testing results were more often indeterminate (85% predicted maximum heart rate 37% vs. 6%, p ) as compared to women achieving 4.7 METs. CONCLUSIONS Among women with suspected myocardial ischemia, functional impairment estimated by the DASI correlates with indeterminate exercise test results and is associated with an adverse prognosis. Use of the DASI before exercise testing can risk stratify symptomatic women and may improve the identification of higher-risk, functionally impaired subjects that would benefit from pharmacologic stress imaging and targeted risk management. (J Am Coll Cardiol 2006;47:36S– 43S) © 2006 by the American College of Cardiology Foundation Shaw LH, JACCl 2006;47:36S

19 Aumenta la contrattilità VS Ipercinesia Ischemia
Normale Aumenta la contrattilità VS Ipercinesia Ischemia Nuove alterazioni cinesi segmentaria Ridotta FE Aumento vol TS VS Cicatrice da IMA Alterazioni fisse della cinesi  Parete sottile iperecorifrangente  Discinesia tredmill ciclo/letto- ergometro stress farmacologico

20 Eco stress Donna sensibilità 81-89% specificità 86%
tredmill–ciclo/letto- ergomentro / stress farmacologico Donna sensibilità 81-89% specificità 86% Dobutamina sensibilità 78–91% specificità % Picano E CV Ultrasound 2008, 6:30 “ the magnitude of risk associated with stress echocardiographic abnormalities is independent of sex”. ASE GL Ecostress 2007 Dipiridamolo sensibilità % specificità % Mortalità a 5 anni ♀ DSE negativo 1/ DSE positivo 3/100 ECO stress/ECG stress Shaw LJ, Eur Heart J 2005; 26:447 Marwick TH, J Am Coll Cardiol 1995; 26: 335


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