Prof. Vitantonio Di Bello. DIPARTIMENTO CARDIO TORACICO e VASCOLARE UNIVERSITA DI PISA

Il rilievo di lesioni aterosclerotiche in distretti periferici autorizza le indagini per la ricerca di ischemia miocardica? Prof. Vitantonio Di Bello DIPARTIMENTO CARDIO TORACICO e VASCOLARE UNIVERSITA DI PISA

Atherosclerosis: A Systemic Disease

E. Braunwald definisce l Aterosclerosi come un processo morboso a carattere progressivo che inizia generalmente nell infanzia e si esprime clinicamente durante la media e terza età Libby P. Changing concepts of atherogenesis. J Intern Med. 2000 Mar;247(3):349-58. Review

Cardiac, Thoracic and Vascular Department - University of Pisa

La superficie delle cellule endoteliali in un uomo adulto è composta: - da 1 a 6 x 10 13 cellule - 1,5 Kg di peso - copre un superficie di circa 600 m 2

L ENDOTELIO NELLA PATOLOGIA CARDIOVASCOLARE ENDOTHELIAL CELLS (ARE) (ARE) MORE THAN A SHEAT OF NUCLEATED CELLOPHANE LORD FLOREY, 1966 RUOLO CENTRALE NELLA REGOLAZIONE DELL OMEOSTASI CARDIOCIRCOLATORIA 1998 TONO VASCOLARE ADESIONE E AGGREGAZIONE PIASTRINICA COAGULAZIONE LOCALE CRESCITA VASCOLARE Cardiac, Thoracic and Vascular Department - University of Pisa

NORMAL ENDOTHELIAL FUNCTION AND MAJOR ENDOTHELIAL MEDIATORS VASOMOTOR TONE Vasodilation Nitric Oxide Prostacyclin EDHF* Vasoconstriction Endothelin-1 Thromboxane A2 ACE INTIMAL GROWTH REGULATION * EDHF: endothelium-derived hyperpolarizing factor Growth regulation Nitric Oxide Glycosaminoglycans Transforming growth Factor-beta Inhibitors of platelets and leukocyte adhesion Growth promotion Endothelin-1 D.L. Sherman, J. Loscalzo CARDIOLOGIA 1997

NORMAL ENDOTHELIAL FUNCTION AND MAJOR ENDOTHELIAL MEDIATORS HEMOSTASIS/ ANTITHROMBOTIC ACTIVITY Anticoagulation Glycosaminoglycans Thrombomodulin Fibrinolysis t-pa u-pa Platelet inhibition Nitric Oxide Prostacyclin Ecto-ADPase Thrombosis PAI-1 Platelet activation Thromboxane A2 t-pa: tissue-type plasminogen activator; u-pa: urokinase-type plasminogen activator; PAI-1: plasminogen activator inhibitor type 1. D.L. Sherman, J. Loscalzo CARDIOLOGIA 1997

L ipotesi della Response to injury, poggia su la perdita da parte dell endotelio di queste importanti funzioni e costituisce l evento preliminare del processo aterosclerotico. Numerose sono le fonti di danno endoteliale: FATTORI ATEROGENETICI SISTEMICI Alterazione del metabolismo lipidico (aumento dell LDL soprattutto delle LDL ossidate, lipoproteina (a), mmldl, betavldl, etc) Alterazione del metabolismo glucidico (diabete mellito) Iperomocisteinemia Danno meccanico (ipertensione arteriosa, alterazioni dello shear stress Alterazioni immunologiche, tossine, batteri, virus. Citochine infiammatorie ed altri stimoli capaci di attivare le cellule endoteliali D.A. Vorp - Journal of Vascular Research Nov 2007

FATTORI ATEROGENETICI LOCALI Sono legati a modificazioni dello shear stress determinate da variazioni del flusso ematico (ad esempio un rallentamento) che portano ad una diminuzione della produzione di NO da parte delle cellule endoteliali con conseguente aumento dell espressione delle molecole di adesione sulla superficie endoteliale. D.A. Vorp - Journal of Vascular Research Nov 2007

DISFUNZIONE ENDOTELIALE E UN ALTERAZIONE DELL EQUILIBRIO TRA I VARI FATTORI CHE REGOLANO LE FUNZIONI DELL ENDOTELIO. QUESTO SQUILIBRIO SI SVILUPPA PER UNA RIDUZIONE DELLA SINTESI E/O DEL RILASCIO DEI FATTORI PROTETTIVI (ES.: NO, PGI2) O PER L AUMENTO DELLA SINTESI E/O DEL RILASCIO DEI FATTORI CHE INDUCONO I PROCESSI DI VASOCOSTRIZIONE, DI CRESCITA VASCOLARE E DELLA COAGULAZIONE. Cardiac, Thoracic and Vascular Department - University of Pisa

ATTIVAZIONE ENDOTELIALE NUOVE PROPRIETA FUNZIONALI ED ANTIGENICHE ACQUISITE DALL ENDOTELIO CHE INFLUENZANO PRINCIPALMENTE LE INTERAZIONI DELLE CELLULE ENDOTELIALI CON I LEUCOCITI CIRCOLANTI Cardiac, Thoracic and Vascular Department - University of Pisa

Cardiac, Thoracic and Vascular Department - University of Pisa

PAD

PERIPHERAL ARTERIAL DISEASE DETECTION, AWARENESS, AND TREATMENT IN PRIMARY CARE A.T. Hirsch, M. H. Criqui, W.R. Hiatt et al. Context Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice Patients A total of 6979 patients aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes were evaluated by history and by measurement of the ankle-brachial index (ABI) PAD was considered present if the ABI was 0.90 or less, if it was documented in the medical record, or if there was a history of limb revascularization. Hirsch AT, Criqui MH, Hiatt WR et al. - JAMA. 2001 Sep 19;286(11):1317-24.

PERIPHERAL ARTERIAL DISEASE DETECTION, AWARENESS, AND TREATMENT IN PRIMARY CARE A total of 6979 patients Results PAD was detected in 1865 patients (29%) 825 of these (44%) had PAD only, without evidence of CAD. Overall 13% had PAD only, 16% had PAD and CAD, 24% had CAD only, 47% had neither PAD nor CAD (the reference group). Hirsch AT, Criqui MH, Hiatt WR et al. - JAMA. 2001 Sep 19;286(11):1317-24.

The epidemiology of peripheral arterial disease: importance of identifying the population at risk. Patients With Peripheral Arterial Disease In the San Diego Artery Study, 29% of the men and 21.2% of the women with PAD also presented cardiovascular or cerebrovascular involvement, and this involvement was three times more frequent than that observed in the absence of PAD. Lahoz C, Mostaza JM. - Rev Esp Cardiol. 2007 Feb;60(2):184-95

Mortality over a period of 10 years in patients with peripheral arterial disease. Individuals with PAD have a risk 565 patients 4 fold higher of coronary events 2-3 fold higher of stroke than those without PAD Thus, the relative risk of mortality 10 years after the diagnosis of PAD was 3.1 % for total mortality 5.9 % for cerebrovascular mortality 6.6 % for coronary artery disease mortality in comparison with that of subjects in whom PAD was not present at the initiation of follow-up. Criqui MH et al. Vasc Med. 1997;2:221-6.

Occult vascular lesions in patients with atherothrombotic events: the AIRVAG cohort. 269 patients younger than 70 yrs. In the AIRVAG study, 21% of the subjects with PAD had asymptomatic involvement of some other vascular territory, diagnosed by carotid, cardiac or abdominal aortic ultrasound. Lujan S. et al. Eur J Vasc Endovasc Surg. 2005

CAD in PAD The prevalence of CAD in PAD patients ranged from 14% to 90%, which clearly reflects differences in sensitivity of the detection technique for CAD. CAD was present in 19% to 47% of PAD patients in studies using clinical history plus ECG; in 62% to 63% using stress tests (modified stress ECG or dipyridamole-stress thallium); and in 90% of subjects when angiography was used. Golomb BA et al. Circulation 2006;114;688-699 Cardiac, Thoracic and Vascular Department - University of Pisa

Golomb BA et al. Circulation 2006;114;688-699 Cardiac, Thoracic and Vascular Department - University of Pisa

Cardiac, Thoracic and Vascular Department - University of Pisa

Cardiac, Thoracic and Vascular Department - University of Pisa

STROKE

Patients With Acute Stroke The prevalence of extracerebral vascular involvement in cases of cerebral infarction has been evaluated in a number of studies. Predisposing factors for cerebral infarction: the Oxfordshire community stroke In the Oxfordshire Community Stroke Project, the subjects who were admitted to the hospital with an Acute Stroke 244 patients 38% 25% had a previous history of Ischemic Heart Disease (IHD) had PAD Sandercock PA, Warlow CP, Jones LN, Starkey IR. project. BMJ. 1989;298:75-80.

Patients With Acute Stroke In a study involving patients, with Acute Stroke, in Rochester, Minnesota 21% had been diagnosed in the past with angina 15% had had an AMI Asociación entre accidente cerebrovascular y enfermedad arterial periférica: estudio de casos y controles en Asturias, España. In a study involving sex- and age-matched patients and controls carried out in Spain. 458 patients and 470 controls Prevalence of IHD was 14.5% among patient versus 7.1% among controls, Prevalence of of symptomatic PAD was 7.9% among patient Versus 2.7% among controls, Caicoya M. et al. - Rev Clin Esp. 1995;195:830-5.

Atherosclerosis As a Systemic Disease Life expectancy of patients with vascular disease according to the number of vascular territories involved and their location. AMI indicates acute myocardial infarction; PAD, peripheral arterial disease. Mostaza - Rev Esp Cardiol. 2007

Cardiac, Thoracic and Vascular Department - University of Pisa

Cardiac, Thoracic and Vascular Department - University of Pisa

ARAS

Di notevole interesse è la Malattia Aterosclerotica Renovascolare in quanto è noto che la stenosi aterosclerotica dell arteria renale è molto frequentemente associata ad aterosclerosi in altri distretti. La prevalenza di stenosi aterosclerotica dell arteria renale (ARAS) nella popolazione generale rimane ancora poco definita. The prevalence and associated risk factors of renal artery stenosis in patients undergoing cardiac catheterization. In uno studio del 2000 Hyun Yong Song ha rilevato, su di un totale di 427 pazienti, età media 59 anni, sottoposti ad esame coronarografico, una prevalenza di stenosi dell arteria renale (>50%) del 5,6%. Song HY et al. - Yonsei Med J. 2000 Apr

Indications for Renal Arteriography at the Time of Coronary Arteriography There is a marked increase in the prevalence of ARAS in patients with known or suspected coronary artery disease In the largest series of screening renal arteriography, 1302 unselected, consecutive patients had both coronary arteriography and abdominal aortography. 29% of patients were found to have some evidence of ARAS, and 15% had lesions 50% diameter stenosis. In a selected population of 297 hypertensive patients referred for coronary arteriography who also had concurrent abdominal aortography during the same procedure, 34% had evidence of renal artery stenosis, and 19% had ARAS lesions 50% diameter stenosis. Bilateral ARAS was noted in 19% to 29% of patients with 50% ARAS Christopher J. - Circulation 2006;114;1892-1895;

Prevalenza dell ARAS in pazienti con coronaropatia PREVALENZA STENOSI DELL ARTERIA RENALE % 14 12 10 8 6 4 2 0 Correlazione tra la prevalenza della stenosi dell arteria renale ed il numero delle coronarie con stenosi significativa 7 11 4/56 9/81 22/160 1 2 3 N di vasi coronarici con stenosi significativa (>75%) Uzu T, Am J of Kidney Diseases, 1997 14 297 pts IMA 18 16 14 12 10 8 6 4 2 0 0 Moderata (75-90%) 3 2 1 0 Severa (>90%) 0 1 2 3 Grado di stenosi Correlazione tra la prevalenza della stenosi dell arteria renale e la severità della coronaropatia in pazienti con malattia dei tre vasi 7 0/5 2/28 8/60 12/67 13 N di vasi coronarici colpiti 18

Frequency of coronary artery disease in patients with renal artery stenosis without clinical manifestations of coronary insufficiency. 23 pazienti con ARAS emodinamicamente significativa ( 50%) contemporanea presenza di CAD diagnosticata mediante coronarografia nel 74% (17 pazienti), 7 dei quali erano affetti da malattia dei 3 vasi coronarici. Cardoso de Carvalho F, et al. - Am J Hypertens. 2006 Nov

Prevalenza dell ARAS in pazienti con arteriopatia obliterante degli arti inferiori Stenosi arteria renale % 70 60 50 40 30 20 10 0 P=0.00015 65 51 21 9/42 29/56 19/29 1 o 2 vasi 3 o 4 vasi 5 o più vasi * * Malattia vascolare periferica Missouris Am J of Medicine, 1994

Prevalenza di Stenosi Carotidee in pazienti con ARAS Missouris CG, Nephrol Dial Transplant 1998 38 pts con stenosi dell arteria renale sottoposti a PTA Stenosi carotidee % 60 50 40 30 20 10 45 33 53 4/12 5/11 8/15 * 0 1 2 3 Grado di stenosi dell arteria renale St.unil. St.bil. 1 Occl.-1 St. Cerebrovascular events (n (%)) 2 (20%) 3(30%) 5(50%) Peripheral Vascular Disease (n(%)) 6(31.5%) 4 (21.1% ) 9 (47.4%) Coronary Artery Disease (n(%)) 4(28.6%) 2(14.3%) 8(57.1%) Current or ex-smoker (n(%)) 11(36.7%) 6(20%) 13(43.3%)

CONCLUSIONI 1. I risultati di questi studi enfatizzano ancora una volta la natura polidistrettuale della malattia aterosclerotica. 2. La malattia vascolare di natura aterosclerotica a carico del circolo periferico può essere complicata dalla presenza di malattia aterosclerotica in altri distretti, in particolare a livello del circolo coronarico. 3. Una severa malattia renovascolare può essere considerata predittiva di severa malattia aterosclerotica polidistrettuale, in particolare di CAD. 4. Pazienti con malattia vascolare aterosclerotica diagnosticata in un distretto dovrebbero pertanto essere sottoposti ad un aggressivo screening morfologico-funzionale degli altri distretti vascolari, in particolare di quello coronarico. Cardiac, Thoracic and Vascular Department - University of Pisa