Appendix 1: Clinical Inclusion Criteria of the THESIS Study

Appendix 1: Clinical Inclusion criteria of the THESIS study

Established (History) of Disease At Risk of Disease or Event  Coronary artery disease: history of stable or  Diabetic nephropathy with microalbuminuria > 30 μg./mL unstable angina with documented  Type 1 or 2 diabetes: initially diagnosed by fasting plasma multivessel coronary disease, history of glucose > 7 mmol/L on two or more occasions, and multivessel PCI, history of multivessel currently treated with insulin and/or other hypoglycemic CABG, history of MI) agents  Cerebrovascular disease: history of  Ankle-arm systolic blood pressure ratio [ankle-brachial ischemic stroke, history of transient index (ABI)] < 0.9 in either leg at rest ischemic attack)  Asymptomatic carotid stenosis > 70%, established by  Symptomatic Peripheral arterial disease: angiography or color-coded duplex ultrasound on the basis intermittent claudiation with history of of recognized criteria vascular intervention: amputation,  Presence of at least one carotid plaque (common carotid angioplasty, reconstructive vascular artery, carotid bulb, internal or external carotid arteries) surgery, atherectomy evidenced by ultrasonography: defined as a distinct area with an intima-media thickness (IMT) exceeding twice that of neighboring sites  Systolic blood pressure > 150mm Hg, despite appropriate therapy for at least 3 months  Primary hypercholesterolemia: with LDL cholesterol > 160 mg/dL, and / or HDL cholesterol < 35 mg / dL at diagnosis, whether or not treated

Appendix 2: Medications cost 22-THESIS study Medica tion Medication class Drug cost per month (€) class Calciu Antiplatelets PLAVIX 75mg 63.36 m NORVASC 5mg channel blocker s ISCOVER 75mg 39.80 TILDIEM 60mg SALOSPIR 100mg 0.60 ZANIDIP 10mg VASTAREL 20mg Anti-coagulants SINTROM 4mg 2.63 PLENDIL 5mg ADALAT 30mg CR Nonsteroidal anti- inflammatory XEFO 8mg 11.74 AMLOPEN 10mg MESULID 100mg 9.80 LACIPIL 4mg CELEBREX 100 mg 7.12 SYSCOR 10mg EGIGALM 100 mg 8.52 β- VOLTAREN Blocker 25mg 9.06 s LOPRESOR 100mg DILATREND 6.25mg Lipid-lowering agents ZOCOR 40mg 76.44 CARVEPEN 6.25mg VASTATIN 40 mg 62.48 SELECTOL 200mg VASSOR 40mg 48.05 LOBIVON 5mg SIMVASTATI N 40mg 62.46 KERLONE 20mg SIMVACOR 40mg 48.05 INDERAL 40mg PRAVOSTIN 40mg 62.49 NEOCARDON 100mg NORMOTHER IN 40mg 62.46 PACTENS 10mg MAXUDIN 40mg 59.89 LIPITOR 40mg 56.94 Nitrate LESCΟL 80mg 15.34 s TRINIPATCH TTS 10mg LEPUR 40mg 31.23 SUPRANITRIN 2,5mg INEGY 10/20 51.87 PANCORAN TTS 5mg EZETROL 10mg 51.48 NITRONG TTS 5mg EXTRASTATI NITROLINGUAL SPRA 0,40 N 40 mg 62.46 mg CRESTOR 20mg 48.30 NITRODYL TTS 5mg MONOSORDIL 60mg IMDUR 60mg EPINITRIL TTS 10mg Appendix 2 (cont): Medications cost22-THESIS study

Medication class Drug cost per month (€) Medication class Drug Other Diuretics LASIX 40 mg 10.80 antihypertensives SUPERACE (50+25 mg) FRUMIL (40+5 mg) 15.54 PENOPRIL 20mg FLUDEX 2.5mg 4.28 OLARTAN PLUS 20mg ALDACTONE 25 mg 5.73 LOGIMAX (5+47,5 mg) KARVEZIDE 12.5mg ZOFEPRIL ACE inhibitors 15mg 11.27 HYZAAR (50+12,5 mg) VEROXIL 20mg 10.06 ENIT (10+20 mg) VASCACE CO-RENITEC (20+12,5 2,5 mg 9.39 mg) TRIATEC 5mg 15.27 CO-DIOVAN 80mg TANATRIL CO-DALZAD 20mg 7.32 160mg+12.5mg PRINIVIL 5 mg 7.68 CIBADREX 20mg+25mg PRESSURIL 20mg 9.82 ATACAND PLUS ENALAPRIL 20mg 11.43 ALDOMET 250 mg DOSTUREL (50+25 mg) 9.68 COVERSYL Claudication 5mg 12.58 medications TARONTAL 400mg CAPOTEN 50mg 6.45 LOFTYL 600mg ACCUPRON 20mg 12.78 DAFLON 500

Angiotensin II– receptor antagonists PRITOR 80mg 24.64 Insulin PROTAPHANE OLMETEC 18.51 MIXTARD 30mg 10mg OLARTAN 10mg 18.51 HUMULIN M3 MICARDIS 80mg 24.64 ACTRAPID LOSADRAC 50mg 15.80 KARVEA 75 mg 33.94 Biguanides GLUCOPHAGE 850mg DIOVAN 80mg 25.02 COZAAR 50mg 18.34 Sulfonylureas SOLOSA 4mg ATACAND 8mg 18.45 NOVONORM 1mg APROVEL 300mg 26.65 Thiazolidinediones AVANDIA 8mg ZOFEPRIL Other PLUS (30+12,5 antihypertensives mg) 11.27 ACTOS 15mg VASTAREL 20mg 9.11 VASCACE PLUS 9.40 Other antidiabetics STARLIX 60mg TRIATEC PLUS 5+25 mg 15.30 TIADEN (50+5mg) 4.12 TEVETEN PLUS 600+12,5 mg 23.86 TENORETIC 50mg 5.78 Appendix 3: Hospitalization, outpatient visits, vascular interventions and laboratory and imaging diagnostic test costs – THESIS study Laboratory and imaging diagnostic tests Cost per item (€) Hospitalization (without management of implications) Computed tomography scans 70 In clinic of public hospital Magnetic resonance imaging (MRI) 250 In clinic of private hospital Ultrasound 30 In Intensive Care Unit of public hospital Thallium scintigraphy 250 In Intensive Care Unit of private hospital Triplex 30 Rehabilitation center Echocardiography 30 Digital subtraction angiography (DSA) 250 Management of complications during hospitalization Magnetic resonance angiography (MRA) 250 Stroke Blood and biochemistry tests 50 Myocardial infarction Vascular interventions Cost per item (€) Heart failure Angiography 250 Arrythmia Percutaneous transluminal coronary angioplasty 5000 Other cardiovascular events (PTCA)/stenting Coronary artery bypass graft (CABG) surgery 7000 Death Other vascular surgery 3500-6500 Bleeding Pacemaker implantation Thrombosis temporary implantation 2500 permanent implantation 5000 Outpatient visits to Cost per visit (€) Respiratory infections Hospital outpatient department 20 UTI Hospital accident and emergency department 20 General practitioner 40 Other healthcare professionals (i.e. physiotherapists) 40 Appendix 4

List of investigators and centres

Steering Committee: Prof. N. Maniadakis, Prof. J. Kyriopoulos, Prof. E. Bastounis, Prof. D.

Kokkinos, Prof. D. Vasilopoulos.

Main Investigators by participating center

1. University General Hospital of Heraklion in Crete (South): Prof. P. Vardas

2. University General Hospital of Patras in Peloponnesus (South West): Prof. I. Tsolakis

3. General Hospital of Thessalonica “Papageorgiou” (North): Dr. G. Roudolf

4. University General Hospital of Thessalonica “AHEPA” (North): Dr. S. Gavriilides

5. General Hospital of Athens “Euangelismos” (Centre): Dr. A. Manolis

6. General Hospital of Athens “Attikon” (Centre): Dr. S. Vasdekis

7. General Hospital of Athens “Alexandra” (Centre): Dr. K. Vemmos

8. Cardiosurgery Center “Onasseio” (Centre): Prof. D. Kokkinos

9. General Hospital of Athens “Agia Olga-Konstantopouleio” (Centre): Dr. E. Varsamis

10. General Hospital of Athens “Georgios Gennimatas” (Centre): Dr. K. Karageorgiou

11. General Hospital of Athens “Erythros Stauros” (Centre): Dr. V. Andrikopoulos