ΠΡΟΛΗΨΗ ΣΗ ΣΕΥΑΝΙΑΙΑ ΝΟΟΤ

ΠΡΟΛΗΨΗ ΣΗ ΣΕΥΑΝΙΑΙΑ ΝΟΟΤ Ο ΡΟΛΟ ΣΩΝ ΛΙΠΙΔΙΩΝ ΘΩΜΑ ΠΑΠΑΔΟΠΟΤΛΟ MD, MBCIS,FSCAI,FACC ΕΠΕΜΒΑΣΙΚΟ ΚΑΡΔΙΟΛΟΓΟ ΙΑΣΡΙΚΟ ΔΙΑΒΑΛΚΑΝΙΚΟ ΚΕΝΣΡΟ ΕΠΙΣΗΜΟΝΙΚΟ ΤΝΕΡΓΑΣΗ ΒΚΚ ΙΠΠΟΚΡΑΣΕΙΟ ΓΠΝΘ 1 Ο ΚΑΡΔΙΟΛΟΓΙΚΟ ΤΝΕΔΡΙΟ ΔΤΣΙΚΗ ΜΑΚΕΔΟΝΙΑ, ΠΣΟΛΕΜΑΙΔΑ

Αζεξνζθιήξπλζε - ηεθαληαία Νόζνο Η Αζεξνζθιήξπλζε απνηειεί ηελ παζνινγναλαηνκηθή βιάβε πνπ αλαπηύζζεηαη ζην ηνίρσκα ησλ αξηεξηώλ εκαληηθό ξόιν ζηελ δεκηνπξγία θαη εμέιημε ηεο αζεξνζθιήξπλζεο δηαδξακαηίδεη ε ρνιεζηεξόιε Η ηεθαληαία λόζνο είλαη αθελόο ε εληόπηζε ηεο αζεξνζθιήξπλζεο ζηηο ηεθαληαίεο αξηεξίεο, θαη αθεηέξνπ νη θιηληθέο ηεο εθδειώζεηο

Development of Atherosclerotic Plaques Normal Fatty streak Lipid-rich plaque Foam cells Fibrous cap Thrombus Lipid core Ross R. Nature. 1993;362:801-809.

Activating Effect of LDL Infiltration on Inflammation in the Artery Hansson, G. K. N Engl J Med 2005;352:1685-1695

Lipoprotein Classes and Inflammation Chylomicrons, VLDL, and their catabolic remnants LDL HDL > 30 nm 20 22 nm Potentially proinflammatory Doi H, et al. Circulation. 2000;102:670-676; Colome C, et al. Atherosclerosis. 2000;49:295-302; Cockerill GW, et al. Arterioscler Thromb Vasc Biol. 1995;15:1987-1994. 9 15 nm Potentially antiinflammatory

Atherogenic Particles MEASUREMENTS: Apolipoprotein B Non-HDL-C VLDL VLDL R IDL LDL Small, dense LDL TG-rich lipoproteins

Atherogenic Lipoproteins Non-HDL-C = TC HDL-C Can be accurately measured in nonfasting state Apo B concentration represents total number of lipoprotein particles (LDL + IDL + VLDL) This may be called non-hdl cholesterol or atherogenic cholesterol Grundy SM. Circulation 1997;95:1-4.

Concept of cardiovascular risk factors Age, sex, hypertension, hyperlipidemia, smoking, diabetes, (family history), (obesity) Kannel et al, Ann Intern Med 1961

Major Risk Factors Cigarette smoking (passive smoking?) Elevated total or LDL-cholesterol Hypertension (BP 140/90 mmhg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dl) Family history of premature CHD CHD in male first degree relative <55 years CHD in female first degree relative <65 years Age (men 45 years; women 55 years) HDL cholesterol 60 mg/dl counts as a negative risk factor; its presence removes one risk factor from the total count.

Percent Lifetime Risk of CHD Increases with Serum Cholesterol 60 50 40 30 20 34 44 57 Cholesterol <200 mg 200-239 mg >240 mg 29 33 10 19 0 Men Women Framingham Study: Subjects age 40 years DM Lloyd-Jones et al Arch Intern Med 2003; 1966-1972

6-Year CVD Death Rate Per 1000 Correlation Between Serum Cholesterol and CVD Mortality 30 25 Multiple Risk Factor Intervention Trial (MRFIT) N=325,346 Untreated Patients 55-57 years 20 50-54 years 15 10 5 45-49 years 40-44 years 35-39 years 0 Q 1 (<182) Q 2 (182-202) Q = serum cholesterol quintile. Kannel WB et al. Am Heart J. 1986;112:825-836. Q 3 (203-220) Q 4 (221-244) Serum Cholesterol Quintile (mg/dl) Q 5 (>244)

Effects of Increasing TC Levels on the Risk for CHD in the Presence of Other Risk Factors 40 35 30 25 20 15 10 5 0 185 210 235 260 285 310 335 Schaefer EJ, adapted from the Framingham Heart Study Low HDL Smoking Hyperglycemia Hypertension No Other Risk Factors Serum Cholesterol (mg/dl)

Framingham Point Scores Age Points 20-34 -7 35-39 -3 40-44 0 45-49 3 50-54 6 55-59 8 60-64 10 65-69 12 70-74 14 75-79 16 HDL (mg/dl) Points >60-1 50-59 0 40-49 4 <40 2 Systolic BP (mmhg) If Untreated If Treated <120 0 0 120-129 1 3 130-139 2 4 140-159 3 5 >160 4 6 Points Total Cholesterol Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 1 200-239 8 6 4 2 1 240-279 11 8 5 3 2 >280 13 10 7 4 2 Points Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 Nonsmoker 0 0 0 0 0 Smoker 9 7 4 2 1 Point Total 10-Year Risk % <9 <1 9 1 10 1 11 1 12 1 13 2 14 2 15 3 16 4 17 5 18 6 19 8 20 11 21 14 22 17 23 22 24 27 >25 >30 NCEP ATP III. National Heart, Lung and Blood Institute Web site. http://www.nhlbi.nih.gov/guidelines/cholesterol/risk_tbl.html

CHD risk ratio CHD Risk According to HDL-C Levels Framingham Study 4.0 4.0 3.0 2.0 2.0 1.0 1.0 0 25 45 65 HDL-C (mg/dl) Kannel WB. Am J Cardiol 1983;52:9B 12B

Incidence of ischaemic heart disease, age adjusted with 95% confidence intervals, according to fifths of distribution of serum cholesterol concentration in 10 cohort studies. Law M R et al. BMJ 1994;308:367-372 1994 by British Medical Journal Publishing Group

Incidence of ischaemic heart disease according to mean serum cholesterol concentration of different communities in three international studies. Law M R et al. BMJ 1994;308:367-372 1994 by British Medical Journal Publishing Group

Cholesterol and CHD: Seven Countries Study CHD mortality rates (%) 30 25 20 15 10 5 Northern Europe United States Southern Europe, Inland Southern Europe, Mediterranean Siberia Japan 0 100 125 150 175 200 225 250 275 300 325 350 (2.60) (3.25)(3.90)(4.50) (5.15) (5.80)(6.45) (7.10) (7.75) (8.40)(9.05) TC mg/dl (mmol/l) Verschuren WMM et al. JAMA. 1995;274:131-136.

Pyramid of Risk (Werner et al. Canadian Journal of Cardiology 1998; 14(Suppl) B:3B-10B)

Πξσηνγελήο θαη δεπηεξνγελήο πξόιεςε ηεο ηεθαληαίαο Νόζνπ Η πξσηνγελήο πξόιεςε αθνξά ηελ πξόιεςε πξηλ από ηελ εκθάληζε ηεο λόζνπ ζε άηνκα ρσξίο ζπκπηώκαηα. Αξρηθή πξόιεςε αθνξά ηελ πξόιεςε παξαγόλησλ θηλδύλνπ πνπ αηηηνινγηθά ζρεηίδνληαη κε ηε λόζν θαη κε απηό ηνλ ηξόπν ηελ ειάηησζε ηεο πηζαλόηεηαο εκθάληζεο ηεο λόζνπ. Δεπηεξνγελήο πξόιεςε αλαθέξεηαη ζηελ πξόιεςε ηνπ ζαλαηεθόξνπ επεηζνδίνπ ε ηεο ππνηξνπήο ηεο λόζνπ ζε άηνκα πνπ είλαη ήδε ζπκπησκαηηθά.

Risk Factor Concepts in Primary Prevention Nonmodifiable risk factors include age, sexc, race, and family history of CVD, which can identify high-risk populations Behavioral risk factors include sedentary lifestyle, unhealthful diet, heavy alcohol or cigarette consumption. Physiological risk factors include hypertension, obesity, lipid problems, and diabetes, which may be a consequence of behavioral risk factors.

Population vs. High-Risk Approach Risk factors, such as cholesterol or blood pressure, have a wide bell-shaped distribution, often with a tail of high values. The high-risk approach involves identification and intensive treatment of those at the high end of the tail, often at greatest risk of CVD, reducing levels to normal. Κσδσλνεηδήο Καηαλνκή But most cases of CVD do not occur among the highest levels of a given risk factor, and in fact, occur among those in the average risk group. Significant reduction in the population burden of CVD can occur only from a population approach shifting the entire population distribution to lower levels.

Total Cholesterol Distribution: CHD vs Non-CHD Population Framingham Heart Study 26-Year Follow-up 35% of CHD occurs in people with TC<200 mg/dl No CHD CHD 150 200 Total Cholesterol (mg/dl) Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9. 1996 Reprinted with permission from Elsevier Science. 250 300

Expected Shifts in Cholesterol Distribution from High-Risk, Population, and Combined Approaches

Communitywide CVD Prevention Programs Stanford 3-Community Study (1972-75) showed mass media vs. no intervention in high-risk residents to result in 23% reduction in CHD risk score North Karelia (1972-) showed public education campaign to reduce smoking, fat consumption, blood pressure, and cholesterol Stanford 5-City Project (1980-86) showed reductions in smoking, cholesterol, BP, and CHD risk Minnesota Heart Health Program (1980-88) showed some increases in physical activity and in women reductions in smoking

Effect of Lifestyle Changes on Angiographic CAD Study N Patient type Therapy Duration (yr) % (Control-Treatment) ProgressionRegression Lifestyle 28 CAD Diet,exercise, meditation 1 35-40 STARS 90 CAD, hightc Diet (including fiber) 3.2 35-38 Heidelberg 113 CAD Diet + exercise 1 25-15 Superko HR,Krauss RM.Circulation. 1994;90:1056-1069.

Wine Consumption and CHD 1000 Finland CHD = -4.99W + 652.4 r = -0.580 800 U.S. Ireland U.K. Australia New Zealand Mortality rate 600 400 Norway Canada Denmark Sweden Netherlands W. Germany Belgium Austria 200 Japan Switzerland Italy France 0 20 40 60 80 100 Wine, liter/capita-year

IN CLINICAL TRIALS WE TRUST

Early Primary-Prevention Trials: Overview %+ 0-5 -10-15 -20-25 -30-35 -40-45 -50-9 -9 TC * CHD events * -8.5-11 -14-20 -19-23 -34-47 Oslo: Diet/smoking cessation N=1,232, P=0.02 WHO: Clofibrate N=15,745, P<0.05 Upjohn: Colestipol N=2,278, P 0.02 LRC-CPPT: Cholestyramine N=3,806, P<0.05 HHS: Gemfibrozil N=4,081, P<0.02 N=number enrolled. * Net difference between treatment and control groups (P values are for events).

Early Secondary-Prevention Trials: Overview 0-5 -10-15 -20-25 -30-35 -40-45 -50 %+ -6-10 TC * CHD events * -9-13 -13-23 -29-35 CDP: Clofibrate (n=1,103) N=8,341, P=ns CDP: Niacin (n=1,119) N=8,341, P=ns Stockholm: Clofibrate + niacin N=555, P=ns POSCH: Partial ileal bypass N=838, P<0.001 N=number enrolled; ns=not significant. * Net difference between treatment and control groups (P values are for events).

STATIN MEGA TRIALS: PRE-ATP III Primary Prevention Secondary Prevention 1994-4S (Scandinavian Simvastatin) 1995 - WOSCOP (West of Scotland) 1996 - CARE 1998 - LIPID Trial 1998 - AFCAPS / TexCAPS

WOSCOPS: Effects of Lipid Lowering on Coronary Events in Primary Prevention Trial in Men 10 5 0-5 TC LDL-C 5 HDL-C Nonfatal MI/CHD death CHD death All-cause mortality %+ -10-15 -20-25 -30-20 -26-22 -35 * P<0.0005. P=0.042. P=0.051. -31* -33 Shepherd J et al. N Engl J Med. 1995;333:1301-1307.

WOSCOPS: Relation of Baseline LDL-C to Event Rate 5-year event rate (per 100) 14 12 10 8 6 4 2 0 Placebo Pravastatin 170 182 190 200 220 Baseline LDL-C (mg/dl) WOSCOPS Group. Circulation. 1998;97:1440-1445.

Scandinavian Simvastatin Survival Study (4S) Secondary prevention 4444 patients Cholesterol: 272 ± 23 mg/dl Simvastatin 20 mg/d 40 mg/d in 37% LDL-C reduced 38% Survival and events Proportion Alive 30% decreased death rate 34% decreased CHD events Subsequent secondary prevention trials 1.00 Simvastatin 0.95 0.90 Placebo 0.85 0.80 Log rank: p=0.0003 0.00 0 1 2 3 4 5 6 Years Since Randomization Reprinted from The Lancet, Vol. 344, Scandinavian Simvastatin Survival Study Group, 1383-1389, copyright 1994, with permission from Elsevier.

Endpoint Trials with the Statins Trial Drug CHD Risk Reduction Primary Prevention AFCAPS/TexCAPS Lovastatin 40%* WOSCOPS Pravastatin 31%* Secondary Prevention 4S Simvastatin 34%* CARE Pravastatin 24%* LIPID Pravastatin 24%* Ischemia MIRACL Atorvastatin 26%** AVERT Atorvastatin 36%** *Nonfatal MI or CHD death; **ischemic events Downs JR et al. JAMA 1998;279:1615-1622. Shepherd J et al. N Engl J Med 1999;333:1301-1307. Scandinavian Simvastatin Study Group. Lancet 1994;344:1383-1389. Sacks FM et al. N Engl J Med 1996;335:1001-1009. LIPID Study Group. N Engl J Med 1998;339:1349-1357. Schwartz GG et al. JAMA 2001;285:1711-1718. Pitt B et al. N Engl J Med 1999;341:70-76.

NEWER STATIN TRIALS: POST-ATP III Primary Prevention Secondary Prevention 2002 - Heart Protection Study (simva 40) 2002 - PROSPER (prava 40) 2003 - ALLHAT (prava 40) 2003 - ASCOT (atorva 10) 2004 - PROVE IT (prava 40 vs atorva 80) 2004 - CARDS (atorva 10 in DM) 2005 - TNT (atorva 10 vs atorva 80)

Figure 1. The percent of subjects in the control group (blue) and percent of subjects in the treatment groups (red) are designated by the height of the bars for a representative group of lipid-lowering clinical trials. Superko H R, and King S Circulation 2008;117:560-568 Copyright American Heart Association

LDL Goal and Cutpoints in Patients with CHD and CHD Risk Equivalents (10-Year Risk >20%) 2001 LDL Goal <100 mg/dl LDL Level at Which to Initiate Diet 100 mg/dl LDL Level at Which to Consider Drug Therapy 130 mg/dl (100 129 mg/dl: drug optional)

Death of Major Cardiovascular Event (%) PROVE IT TIMI 22 Randomized, doubleblind N=4162; ACS <10 d Atorvastatin 80 mg/d, pravastatin 40 mg/d Design: equivalence Primary endpoint: composite CV events LDL-C Baseline: 106 mg/dl Study: 95 mg/dl vs 62 mg/dl 3.9% adjusted risk reduction of outcomes Is Very Low LDL-C the Answer? Cannon CP et al. N Engl J Med 2004;350:1495-1504. Copyright 2004 Massachusetts Medical Society. All rights reserved. 30 25 20 15 10 5 40 mg of pravastatin P = 0.005 0 0 3 6 9 12 15 18 21 24 27 30 No. at Risk Months of Follow-up Prav 2063 1688 1536 1423 810 138 Atorv 2099 1736 1591 1485 842 133 ALT >3 : atorvastatin 3.3%, pravastatin 1.1% (P < 0.001) Myalgias similar, ~3% 80 mg of atorvastatin

The Lower, the Better 3.7 1 Relative Risk for CHD (Log Scale) 2.9 2.2 1.7 1.3 1.0 0 40 70 100 130 160 190 LDL-C (mg/dl) Grundy SM et al. Circulation 2004;110:227 239.

LDL Goal and Cutpoints in Patients with CHD and CHD Risk Equivalents (10-Year Risk >20%) 2004 LDL Goal <100 mg/dl Optional : <70 LDL Level at Which to Initiate Diet 100 mg/dl LDL Level at Which to Consider Drug Therapy 100 mg/dl (<100mg/dL: drug optional)

Lipid levels in patients hospitalized with coronary artery disease An analysis of 136,905 hospitalizations in Get With The Guidelines Conclusions: In a large cohort of patients hospitalized with CAD, almost half have admission LDL levels <100 mg/dl. More than half the patients have admission HDL levels <40 mg/dl, whereas <10% have HDL 60 mg/dl. These findings may provide further support for recent guideline revisions with even lower LDL goals and for developing effective treatments to raisehdl. (Am Heart J 2009;157:111-7.e2.)

14-y incidence rates (%) for CHD Low HDL-C Levels Increase CHD Risk Even When ( Framingham ) Total-C Is Normal 14 12 10 8 6 4 2 0 < 40 40 49 50 59 60 HDL-C (mg/dl) 260 230 259 200 229 < 200 Risk of CHD by HDL-C and Total-C levels; aged 48 83 y Castelli WP et al. JAMA 1986;256:2835 2838

Low HDL-C is an Independent Predictor of CHD Risk Even When LDL-C is Low 3,0 2,0 1,0 0,0 100 160 220 85 65 45 25 HDL-C (mg/dl) LDL-C (mg/dl) Gordon T et al. Am J Med 1977;62:707-714.

Incidence per 1,000 (in 6 years) CHD Risk According to HDL-C Levels Prospective Cardiovascular Münster Study 120 100 110 186 events in 4,407 men (aged 40 65 y) 80 60 40 20 30 21 0 < 35 35 55 > 55 HDL-C (mg/dl) Assmann G, ed. Lipid Metabolism Disorders and Coronary Heart Disease. Munich: MMV Medizin Verlag, 1993

% change in risk per 1 mg/dl increment in HDL-C CHD Incidence Related to HDL-C Levels in Various Trials 0 CHD incidence Men Women -2-4 -6-8 -10 FHS CPPT LRCF MRFIT FHS LRCF

Incidence per 1,000 (in 6 years) Hypertriglyceridemia Increases CHD Risk in Patients with Low HDL-C Levels Prospective Cardiovascular Munster Study 250 200 150 TG < 200 mg/dl TG 200 mg/dl * 245 100 116 50 0 24 31 5.0 > 5.0 LDL-C/HDL-C ratio * Bar represents 5% of subjects in which 25% of CHD events occurred.

Management of Low HDL-C Therapeutic lifestyle changes Smoking cessation Regular aerobic exercise Weight loss Alcohol use?

% CHD Death/Nonfatal MI 30 25 20 15 10 5 0 Trials of Fibrates: Effects on Cardiac Events 34% Rx Placebo 2.7 4.1*** 2.7 66% 8.0 PRIMARY PREVENTION 9% 15.0 13.6 42% 13.0 * Post hoc analysis of subgroup with TG >200 mg/dl and HDL-C <42 mg/dl. ** Post hoc analysis of subgroup with TG 200 mg/dl and HDL-C <35 mg/dl. *** Difference between placebo and Rx for primary endpoint was statistically significant (p < 0.05). Frick MH et al. N Engl J Med 1987;317:1237-1245. Manninen V et al. Circulation 1992;85:37-45. BIP Study Group. Circulation 2000;102:21-27. Rubins HB et al. N Engl J Med 1999;341:410-418. 22.3 17.3 SECONDARY PREVENTION 22% 21.7*** HHS HHS BIP BIP VA-HIT (Post Hoc)* (Post Hoc)** Deaths 2.2 2.1 10.4 9.9 15.7 17.4

CHD Risk: Non-HDL vs. HDL Cholesterol

Intervention strategies as a function of total CV risk and LDL-C level TotalCVrisk (SCORE) % LDL-Clevels <70mg/dL <18mmDi/L 70to<100mg/dL 1.8to<2.5mmol/L 100to<195mg/dL 2.5to<4jOmmol/L 155to<190mg/dL 4.0to<4.9mmol/L >190mg/dL >4.9mmol/L <1 N0 lipid intervention No lipid intervention Lifestyle intervention Lifestyle intervention Lifestyle intervention, Consider drug if uncontrolled Class/Level l/c l/c l/c l/c lla/a >1 to <5 Lifestyle intervention Lifestyle intervention Lifestyle intervention, Consider drug if uncontrolled Lifestyle intervention, Consider drug if uncontrolied Lifestyle intervention, Consider drug if uncontrolled Class/Level l/c l/c IIa/A lla/a I/A >5to<10,or High risk Lifestyleintervention considerdrug* Lifestyle intervention Consider drug* Lifestyle intervention And immediate drug intervention Lifestyle intervention And immediate drug intervention Lifestyle intervention And immediate drug intervention Class/Level IIa/A IIa/A lla/a I/A I/A 10 or very High risk Lifestyle intervention Consider drug* Lifestyle intervention And immediate drug intervention Lifestyle intervention And immediate drug intervention Lifestyle intervention And immediate drug intervention Lifestyle intervention And immediate drug intervention Class/Level IIa/A IIa/A I/A I/A I/A www.escardio.ong/guidelines European Heart Journal 2011;32 (14):17G9-181S Atherosclerosis 2011 Jul;217{1):346 SOCIETY OF CAnotouxt*

Risk of CHD CV Risk: HDL-C and LDL-C Interaction Data From Framingham Study 3.0 For any level of LDL- C, HDL-C is inversely related to CHD risk Rule of 1 s 2.0 1.0 0.0 25 45 65 100 160 220 85 LDL-C (mg/dl) For every 1% shift in HDL-C or LDL-C, event rates are ~1% lower Gordon T et al. Am J Med 1977;62:707-714.

A RISK-BASED APPROACH Risk reduction $$ Harm The magnitude of benefit from any given intervention is a function of: 1) The relative risk reduction conferred by the intervention, and 2) The native risk of the patient

Α ΕΤΥΑΡΙΣΩ ΓΙΑ ΣΗΝ ΠΡΟΟΥΗ Α

ΒΟΗΘΗΤΙΚΕΣ ΔΙΑΦΑΝΕΙΕΣ

Recommendations for treatment targets for LDL-C Recommendations Class Level In patients at VERY HIGH CV risk {established CVD, type 2 diabetes *, type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level > 10%) the LDL-C goal is < 1.8 mmol/l {less than ~ 70 mg/dl) and/or > 50% LDL-C reduction when target level cannot be reached. IC In patients at HIGH CV risk {type 2 diabetes **, markedly elevated single risk factors, a SCORE level > 5 to < 10%) an LDL-C goal < 2.5 mmol/l {less than ~ 100 mg/dl) should be considered. lla In subjects at MODERATE risk {SCORE level > 1 to< 5%) an LDL-C goal < 3.0 mmol/l {less than -115 mg/dl) should be considered. lla over the age of 40 with one or more other CVD risk factor{s) or target organ dannage Except those at very high risk www.escardio.ong/guidelines European Heart Journal 2011;32 (14):17G9-181S Atherosclerosis 2011Jul;217{1):346 SOCIETY OF CAnotouxt*

Framingham Study 3,0 Risk of CHD after 4 Years* 2,0 1,0 NOW 25 0,0 100 160 220 85 65 45 HDL-C (mg/dl) LDL-C (mg/dl) *Risk of coronary heart disease (CHD) over 4 years of follow-up for men ages 50 to 70 Reprinted from Castelli WP. Can J Cardiol. 1988;4(Suppl A): 5A 10A, with permission from Pulsus Group Inc.

COLLABORATIVE ATORVASTATIN DIABETES STUDY (CARDS) RCT of 2838 patients, 40-70, with DM2 + HTN, cigs, or diabetic complication LDL 117 mg/dl Atorvastatin 10 vs placebo Followed for 4 years Research question: is statin better than placebo for primary prevention in patients with diabetes? Colhoun, Lancet, 2004

FENOFIBRATE INTERVENTION AND EVENT LOWERING IN DIABETES (FIELD) STUDY RCT of 9795 patients, 50-75, with DM2 Fenofibrate 200 vs placebo Followed for 5 years Outcome: coronary events Lancet, 2005

FENOFIBRATE INTERVENTION AND EVENT LOWERING IN DIABETES (FIELD) STUDY Coronary events: 5.9% on placebo vs. 5.2% on fenofibrate 11% reduction, not statistically significant HR 0.89 (95% CI 0.75-1.05) p=0.16 Lancet, 2005

Ληπώδεηο γξακκώζεηο Απνηεινύλ ηελ πξώηε βιάβε ζην ηνίρσκα ηνπ αγγείνπ Απνηεινύληαη από πινύζηα ζε ιίπνο θύηηαξα ζην ηνίρσκα ηνπ αγγείνπ Σα θύηηαξα απηά θπξίσο είλαη: Μαθξνθάγα καδί κε ιίγα Σ-θύηηαξα

Αζεξσκαηηθή βιάβε Οη ιηπώδεηο γξακκώζεηο είηε εμαθαλίδνληαη, είηε εμειίζζνληαη ζε αζεξσκαηηθή πιάθα Απηή απνηειείηαη από αθξώδε θύηηαξα καδί κε ιηπώδε ζηαγνλίδηα θαιπκκέλα από κία θάςα από ιεία κπτθά θύηηαξα θαη θνιιαγόλν νπζία

Coronary Artery Disease (CAD) Relative Risk CAD Risk as a Function of LDL-C and HDL-C in Men (Ages 50 to 70 Years Old): Framingham Heart Study 3 2 1 0 220 160 100 mg/dl 5.69 4.14 2.58 mmol/l LDL Cholesterol (LDL-C) 25 0.65 45 1.16 65 1.68 85 2.2 Reprinted from Castelli WP. Can J Cardiol. 1988;4: 5A 10A, with permission from Pulsus Group Inc.

Dietary Patterns and MI Risk in 52 Countries: INTERHEART

ATP III Framingham Risk Scoring Step 2: Total Cholesterol Men TC Points at Points at Points at Points at Points at (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 0 200-239 7 5 3 1 0 240-279 9 6 4 2 1 280 11 8 5 3 1 Women TC Points at Points at Points at Points atpoints at (mg/dl) Age 20-39 Age 40-49 Age 50-59 Age 60-69 Age 70-79 <160 0 0 0 0 0 160-199 4 3 2 1 1 200-239 8 6 4 2 1 240-279 11 8 5 3 2 280 13 10 7 Note: TC and HDL-C values should be the average of at least two fasting lipoprotein measurements. 4 2 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. 2001, Professional Postgraduate Services www.lipidhealth.org

ATP III Framingham Risk Scoring Step 3: HDL-Cholesterol HDL-C (mg/dl) Men Points 60-1 50-59 0 40-49 1 <40 2 HDL-C (mg/dl) Women Points 60-1 50-59 0 40-49 1 <40 2 Note: HDL-C and TC values should be the average of at least two fasting lipoprotein measurements. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. 2001, Professional Postgraduate Services www.lipidhealth.org

Αθηρωματική πλάκα Είςοδοσ LDL ςτο τοίχωμα. Οξείδωςη ςε oxldl Ανεξζλεγκτη απορρόφηςη oxldl από τα μονοκφτταρα> αφρϊδη κφτταρα Παραγωγή κυτοκινών, χημειοκινών, πρωτεαςών από τα μακροφάγα με ςυμμετοχή και Τ-κυττάρων. Περαιτζρω δυςλειτουργία ενδοθηλίου, οξείδωςη LDL, ζλξη νζων μονοκυττάρων. Σχηματιςμόσ νεκρωτικοφ πυρήνα από τα κατεςτραμμζνα αφρώδη κφτταρα και κάψας από τα λεία μυϊκά κφτταρα

TREATING TO NEW TARGETS (TNT) LDL Event % Death % LFTs % Atorv 10 101 10.9 2.5 0.2 Atorv 80 77 8.7 2.0 1.2 p value <0.001 0.09 LaRosa, NEJM 2005

Recommendations for treatment targets for LDL-C Recommendations Class Level In patients at VERY HIGH CV risk {established CVD, type 2 diabetes *, type 1 diabetes with target organ damage, moderate to severe CKD or a SCORE level > 10%) the LDL-C goal is < 1.8 mmol/l {less than ~ 70 mg/dl) and/or > 50% LDL-C reduction when target level cannot be reached. IC In patients at HIGH CV risk {type 2 diabetes **, markedly elevated single risk factors, a SCORE level > 5 to < 10%) an LDL-C goal < 2.5 mmol/l {less than ~ 100 mg/dl) should be considered. lla In subjects at MODERATE risk {SCORE level > 1 to< 5%) an LDL-C goal < 3.0 mmol/l {less than -115 mg/dl) should be considered. lla European Heart Journal 2011;32 (14):17G9-181S Atherosclerosis 2011Jul;217{1):346 www.escardio.ong/guidelines SOCIETY OF CAnotouxt*