THE EPICOR STUDY Vittorio Krogh Unità di Epidemiologia Nutrizionale Fondazione IRCCS, Istituto Nazionale Tumori, Milano on behalf of all Italian colleagues AIRTUM, Sabaudia 2010 1

Esperienze CVD in EPIC EPIC-HEART (Mortalità) Alcuni centri EPIC Europei hanno pubblicato importanti lavori su CVD EPIC-HEART (Incidenza) EPICOR 2

1 -- EPICOR -- 2 CHRONOGRAM: EPIC-ITALY COLLABORATION MoH Compagnia 1990-1993 1993-1996 <2004 <2007 2008 2009+ Compagnia San Paolo Compagnia San Paolo MoH European Union, AIRC Project START recruitment Data analysis CVD 1° follow-up 2° follow-up Biochemical analyses 1° follow-up CVD DNA Extraction and Storage & Genetic Analyses (Epigenetics, SNPs, GWAS) 3° follow-up 2° follow-up CVD 1 -- EPICOR -- 2 3° follow-up CVD 3

Esperienza EPICOR Specifici finanziamenti per l’implementazione componente CVD in EPIC Sviluppo di procedure ad hoc di attivo follow-up per la validazione della diagnosi Creazione di un Consorzio di banche biologiche 4

EPIC R 5

Centri EPICOR Milano, Fondazione IRCCS, Istituto Nazionale Tumori V. Krogh, F. Berrino, S. Sieri, V. Pala, S. Grioni, C. Agnoli, A. Evangelista Torino, Università di Torino/Imperial College London P. Vineis, C. Sacerdote Firenze, ISPO (Screening e Prevenzione Oncologica) D. Palli, G. Masala, B. Bendinelli Napoli, Università Federico II Napoli S. Panico, A. Mattiello, P. Chiodini Ragusa, Registro Tumori Ragusa R. Tumino, G. Frasca 6

Ricercatori Associati and Lab Centres EPICOR Giuseppe Matullo Dept. Genetics, Biology and Biochemistry, Turin University, Turin, Italy & ISI Foundation and HuGeF, Turin, Italy Licia Iacoviello Laboratory of Genetic and Environmental Epidemiology – Catholic University – Campobasso, Italy 7

Distribuzione per genere nei centri EPIC italiani 47.749 recrutati (1993-98) Age 30-74 8

EPICOR: Procedure di follow-up Documentazione medica EPIC vital statistics database Linkage agli archivi Anagrafe comunale Schede dimissione ospedaliera Registri di mortalità Stato in vita Data di morte Data di morte Certificato di morte Documentazione medica Validazione e data della diagnosi STATO IN VITA CAUSE DI MORTE CASI INCIDENTI (CASI PREVALENTI)

Searching for cases… Incidenza Diagnosi alla dimissione (in qualsiasi posizione) 410-414 (cardiopatia ischemica) 430-438 (cerebrovasculopatie) procedure per PTCA, CABG, CEA Mortalità ICD-IX – Coronarica 410-414, 798, 799 (morte improvvisa), oppure 250 (diabete), 401-404 (associate a ipertensione), 428 (insufficienza cardiaca), 440 (arteriosclerosi) nella posizione principale in associazione con 410-414 in altre Mortalità ICD-IX – Cerebrovascolare 430-438, 342 (emiplegia) 798, 799 (morte improvvisa), oppure 250 (diabetes), 401-404 (associata a ipertensione), 427 (aritmie cardiache), 440 (arteriosclerosi) nella posizione principale in associazione con 430-436 in altre

Gli eventi cardiovascolari maggiori Cardiaci Infarto miocardico Sindrome coronarica acuta Rivascolarizzazione coronarica Cerebrali Ictus ischemico Ictus emorragico Rivascolarizzazione carotidea

Major cardiovascular events identified in EPICOR 1 (7,5 yrs.) CORONARY CEREBROVASCULAR Men Women 331 182 96 150

PRIMI RISULTATI DEL PROGETTO EPICOR - 1

Arch Intern Med. 2010 Apr 12;170(7):640-7. Dietary glycemic load and index and risk of coronary heart disease in a large italian cohort: the EPICOR study. Sabina Sieri 1, PhD, Vittorio Krogh1, MD, Franco Berrino2, MD, Alberto Evangelista1, BSc, Claudia Agnoli1, PhD, Furio Brighenti3, PhD, Nicoletta Pellegrini3, PhD, Domenico Palli4, MD, Giovanna Masala4, MD , Carlotta Sacerdote5, MD, Fabrizio Veglia5,6, MD, Rosario Tumino7, MD, Graziella Frasca, PhD 8, Sara Grioni1, BSc, Valeria Pala1, PhD, Amalia Mattiello9, MD, Paolo Chiodini10, PhD, Salvatore Panico9, MD 1Nutritional Epidemiology Unit, National Cancer Institute, Milan, Italy. 2Etiological and Preventive Epidemiology Unit, National Cancer Institute, Italy. 3Department of Public Health, University of Parma, Italy. 4Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy. 5ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. 6Centro Cardiologico Monzino IRCCS, Milan, Italy. 7Cancer Registry and Histopathology Unit Department of Oncology "Civile - M.P.Arezzo" Hospital, Ragusa, Italy. 8Cancer Registry Department of Oncology "Civile - M.P. Arezzo" Hospital, Ragusa, Italy. 9Department of Clinical and Experimental Medicine, University of Naples Federico II , Naples, Italy 10 Department of Public Health and Preventive Medicine, University of Naples Federico II , Naples, Italy. Arch Intern Med. 2010 Apr 12;170(7):640-7. 14

INDICE GLICEMICO L’indice glicemico (GI) degli alimenti è un indice basato sul loro effetto immediato sui livelli di glucosio nel sangue.

Il GI è un test in vivo (su soggetti umani) che si basa sul calcolo dell’area sottesa alla curva di risposta glicemica quando un alimento test ed un alimento standard vengono consumati in quantità isoglucidiche (tali cioè da contenere la stessa porzione di carboidrati - di solito 50g). Indice Glicemico = (Area Alimento / Area Glucosio) * 100

CARICO GLICEMICO Il carico glicemico (GI) degli alimenti è basato sul loro effetto generale sui livelli di glucosio (e di insulina) nel sangue. Viene calcolato moltiplicando il contenuto in carboidrati di un alimento per il suo IG. Carico Glicemico = (Indice Glicemico * Carboidrati) / 100

Relative risk (with 95% confidence intervals) of coronary heart disease in women by increasing quartiles of carbohydrate, carbohydrate high and low GI, and glycemic load

Relative risk (with 95% confidence intervals) of coronary heart disease in men by increasing quartiles of carbohydrate, carbohydrate high and low GI, and glycemic load

Healthy Eating Index (2005) Basato sulle raccomandazioni contenute nelle Dietary Guidelines for Americans 2005 12 componenti con score da 0 a 5, 10 o 20 Score complessivo da 0 a 100 Guenther PM, 2008, J Am Diet Assoc 4 Healthy Eating Index 2005 5 Solid Fat, Alcohol, and Added Sugar

DASH (Dietary Approaches to Stop Hypertension) diet Dieta mirata alla riduzione della pressione e del colesterolo LDL Inclusa nelle Dietary Guidelines for Americans 2005 come esempio di dieta salutare Basato su 8 componenti con score da 1 a 5 Lo score di ogni componente è calcolato dividendo la variabile in quintili: frutta, verdura, legumi e frutta secca, latticini a basso contenuto di grasso, cereali integrali: lo score rispecchia il ranking dei soggetti 1 per il quintile più basso – 5 per il pù alto bevande zuccherate, carne rossa e lavorata, sodio: lo score è invertito 1 per il quintile più alto – 5 per il pù basso Score complessivo da 0 a 40 Fung TT, 2008, Arch Intern Med

Indice Mediterraneo Greco Basato sull’indice mediterraneo sviluppato da Trichopoulou et al. Comprende 9 componenti con score 1 o 0 Verdura, legumi, frutta fresca e secca, latticini, cereali, pesce e rapporto monoinsaturi/saturi: score=1 per intake superiore alla mediana Carne rossa e lavorata: score=1 per intake inferiore alla mediana Mediane sesso-specifiche Alcool: score=1 per intake di 5-25 (donne) o 10-50 (uomini) g/d Score complessivo da 0 a 9 Trichopoulou A, 2003, N Engl J Med

Indice Mediterraneo Italiano Sviluppato adattando l’Indice Mediterraneo Greco alle abitudini alimentari italiane Comprende 11 componenti con score 1 o 0. Pasta, verdure mediterranee (pomodori crudi, verdure a foglia, verdure a frutto, cipolla e aglio), legumi, frutta, pesce, olio d’oliva: score=1 se appartenenti al 3° terzile di intake Bevande gasate, burro, carne rossa e patate: score=1 se appartenenti al 1° terzile di intake Alcool: score=1 per intake ≤1 porzione/giorno Score complessivo da 0 a 11

A priori - defined dietary patterns and risk of stroke in the EPICOR study Claudia Agnoli1, Vittorio Krogh1, Franco Berrino2, Sara Grioni1, Sabina Sieri1, Domenico Palli3, Giovanna Masala3, Carlotta Sacerdote4, Paolo Vineis5, Rosario Tumino6, Graziella Frasca6, Valeria Pala1, Paolo Chiodini7, Amalia Mattiello8, Salvatore Panico8 1Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2 Etiological and Preventive Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 3Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy. 4ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. 5Imperial College London, UK, and University of Torino, Italy. 6Cancer Registry Department of Oncology "Civile - M.P. Arezzo" Hospital, Ragusa, Italy. 7Department of Medicine and Public Health, Second University of Naples, Naples, Italy. 8Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy. 24

Hazard ratios (HR) for developing all types of stroke (cases=178) in relation to adherence to the Healthy Eating Index (HEI 2005), the Dietary Approaches to Stop Hypertension (DASH) diet, the Greek Mediterranean Index and the Italian Mediterranean Index.

Hazard ratios (HR) for developing ischemic stroke (cases=100) in relation to adherence to the Healthy Eating Index (HEI 2005), the Dietary Approaches to Stop Hypertension (DASH) diet, the Greek Mediterranean Index and the Italian Mediterranean Index.

Hazard ratios (HR) for developing hemorrhagic stroke (cases=47) in relation to adherence to the Healthy Eating Index (HEI 2005), the Dietary Approaches to Stop Hypertension (DASH) diet, the Greek Mediterranean Index and the Italian Mediterranean Index.

A priori - defined dietary patterns and the risk of acute myocardial infarction in Italy. Results of the EPICOR study. Sara Grioni1, Vittorio Krogh1, Franco Berrino2, Claudia Agnoli1, Sabina Sieri1, Benedetta Bendinelli 3, Giovanna Masala3, Carlotta Sacerdote4, Paolo Vineis5, Rosario Tumino6, Graziella Frasca6, Valeria Pala1, Paolo Chiodini7, Amalia Mattiello8, Salvatore Panico8 1 Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 2 Etiological and Preventive Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 3 Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy. 4 ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. 5 Imperial College London, UK, and University of Torino, Italy. 6 Cancer Registry Department of Oncology "Civile - M.P. Arezzo" Hospital, Ragusa, Italy. 7 Department of Medicine and Public Health, Second University of Naples, Naples, Italy. 8 Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy. 28

HR for developing CHD (cases=396) in relation to Healthy Eating Index (HEI 2005), Dietary Approaches to Stop Hypertension (DASH) diet, Greek Mediterranean Index and new Italian Mediterranean Index. 29

HR for developing CHD (cases=126) in relation to Healthy Eating Index (HEI 2005), Dietary Approaches to Stop Hypertension (DASH) diet, Greek Mediterranean Index and new Italian Mediterranean Index. Women

HR for developing CHD (cases=266) in relation to Healthy Eating Index (HEI 2005), Dietary Approaches to Stop Hypertension (DASH) diet, Greek Mediterranean Index and new Italian Mediterranean Index. Men

Different measures of body mass and risk of coronary events a large Mediterranean cohort of men and women: findings from the EPICOR Study. Paolo Chiodini1, Amalia Mattiello2, Vittorio Krogh3, Claudia Agnoli3, Sabina Sieri3, Franco Berrino4, Maria Santucci de Magistris2, Carlotta Sacerdote5, Paolo Vineis6, Domenico Palli7, Giovanna Masala7, Rosario Tumino8, Graziella Frasca8, Salvatore Panico2. 1Department of Medicine and Public Health, Second University of Naples, Naples, Italy. 2Department of Clinical and Experimental Medicine, University of Naples Federico II, Naples, Italy. 3Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 4 Etiological and Preventive Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy 5ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin, Turin, Italy. 6Imperial College London, UK, and University of Torino, Italy. 7Molecular and Nutritional Epidemiology Unit, ISPO-Cancer Research and Prevention Institute, Florence, Italy. 8Cancer Registry Department of Oncology "Civile - M.P. Arezzo" Hospital, Ragusa, Italy. 32

WHR and risk of CHD - EPICOR 33

Total antioxidant capacity of the diet and risk of stroke: findings from the EPICOR prospective cohort study. Daniele Del Rio1, Claudia Agnoli2, Nicoletta Pellegrini1*, Vittorio Krogh2, Furio Brighenti1, Teresa Mazzeo1, Giovanna Masala3, Benedetta Bendinelli3, Franco Berrino2, Sabina Sieri2, Rosario Tumino4, Patrizia Concetta Rollo4, Valentina Gallo5,6, Carlotta Sacerdote6, Amalia Mattiello7, Paolo Chiodini8, Salvatore Panico7 1Department of Public Health, University of Parma, 43100 Italy. 2Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, 20133 Italy. 3Molecular and Nutritional Epidemiology Unit ISPO -Cancer Prevention and Research Institute, Florence, Italy. 4Cancer Registry, Azienda Ospedaliera "Civile - M.P.Arezzo", Ragusa, Italy. 5Imperial College London, Department of Epidemiology and Public Health, UK. 6ISI Foundation, Turin, Italy. 7Dipartimento di Medicina Clinica e Sperimentale, Università “Federico II”, Napoli, Italy. 8Dipartimento di Medicina Pubblica, Clinica e Preventiva, Seconda Università, Napoli, Italy

Dietary antioxidant capacity, single antioxidants and hazard ratio (HR)* for developing cerebrovascular disease

Fruit, vegetables, olive oil and risk of coronary heart disease (CHD) in Italian women: the EPICOR study Benedetta Bendinelli1, Giovanna Masala1, Melania Assedi1, Simonetta Salvini1, Calonico C1, Carlotta Sacerdote2, Sabina Sieri3, Graziella Frasca4, Amalia Mattiello5, Paolo Chiodini6, Rosario Tumino4, Paolo Vineis7, Vittorio Krogh3, Domenico Palli1 , Salvatore Panico5 1 Molecular and Nutritional Epidemiology Unit Cancer Prevention and Research Institute (ISPO), Florence, Italy 2 ISI Foundation and Department of Genetics, Biology and Biochemistry, University of Turin , Turin, Italy 3 Nutritional Epidemiology Unit, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy 4 Cancer Registry and Histopathology Unit, “ Civile –M.P. Arezzo” , Ragusa, Italy 5 Department of Clinical and Experimental Medicine University Federico II, Naples, Italy 6 Department of Medicine and Public Health, Second University of Naples, Naples, Italy. 7 Imperial College London, UK, and University of Turin, Italy. 36

A reduction in CHD risk among women in the highest quartile of intake of leafy vegetables (HR=0.59; 95%CI 0.36-0.97) was shown. After further adjustment for red meat consumption the risk reduction in CHD for increasing consumption of leafy vegetables was more evident (p-value for trend=0.03). Suggestion of a protective effect of olive oil was found (p-value for trend=0.06). 37