Risk Factors for Coronary Artery Disease The Symphony of Life Yehuda Adler, M.D, MHA. Medical Diretor Shfela Region, Leumit Health Fund, Cardiac Rehabilitation,

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Presentation transcript:

Risk Factors for Coronary Artery Disease The Symphony of Life Yehuda Adler, M.D, MHA. Medical Diretor Shfela Region, Leumit Health Fund, Cardiac Rehabilitation, Chaim Sheba Medical Center and Sackler Medical School, Tel Aviv University, Israel

Your Chances of Dying From: Aids: 1/1,000,000 Murder: 1/10,000 Car accident: 1/5,000 Heart disease: 1/2* Aids: 1/1,000,000 Murder: 1/10,000 Car accident: 1/5,000 Heart disease: 1/2* * So look at the person next to you!

Endothelial cells Contractile VSMCs Normal artery wall

Lipid Lipid accumulates in the intimal space and is associated with abnormal endothelial cell function Early atherosclerosis

Lipid Activated endothelial cells express adhesion molecules and recruit inflammatory cells, predominantly monocytes Early atherosclerosis

Lipid Early atherosclerosis Monocytes migrate into the intima, differentiate into macrophages and ingest lipid to form foam cells

Lipid core Adventitia Thrombus Thrombus forms and extends into the lumen and the plaque Unstable coronary artery disease

Nonmodifiable Factors – –Age – –Gender – –Family History Nonmodifiable Factors – –Age – –Gender – –Family History Modifiable Factors – –Cigarette smoking – –Obesity – –Hypertension – –Physical inactivity – –Diabetes – –Elevated LDL-C – –Low HDL Modifiable Factors – –Cigarette smoking – –Obesity – –Hypertension – –Physical inactivity – –Diabetes – –Elevated LDL-C – –Low HDL Established Cardiovascular Risk Factors

Lipoproteins Total Cholesterol Total Cholesterol LDL- Cholesterol LDL- Cholesterol TG TG Total Cholesterol Total Cholesterol LDL- Cholesterol LDL- Cholesterol TG TG HDL- Cholesterol HDL- Cholesterol

. MRFIT. Lancet. 1986;2:933. Epidemiologic Data – MRFIT Relationship between Serum Cholesterol and CHD Death Serum Cholesterol mg/dl Age-Adjusted CHD Death Rate/1000 Men/6 Years

Age-adjusted CHD death rate per 1,000 person-years in men with CHD Pekkanen, et al, N Engl. J Med.. 322(24)

Risk Factor Status LDL-C Goal No CHD and < 2 CHD Risk Factors <160 mg/dL No CHD and 2 or more CHD Risk Factors <130 mg/dL Established CHD* <100 mg/dL Risk Factor Status LDL-C Goal No CHD and < 2 CHD Risk Factors <160 mg/dL No CHD and 2 or more CHD Risk Factors <130 mg/dL Established CHD* <100 mg/dL NCEP ATP III Guidelines For LDL Cholesterol NCEP ATP III Guidelines For LDL Cholesterol JAMA 2001;285: Or 10-year risk for hard CAD>20%, PVD, abdominal aortic aneurysm, symptomatic carotid stenosis, diabetes *

Primary Prevention Evidence with Statins

WOSCOPS Study Design Males aged years with total-C  252 mg/dl and no prior MI Diet therapy x 4 weeks LDL-C  155 mg/dl on visits 2 and 3 and  174  232 mg/dl on 1 of these visits 5 years Placebo (n = 3293) Pravastatin 40 mg QD (n = 3302) Shepherd et al. N Engl J Med. 1995;333: Prevention of Coronary Heart Disease with Pravastatin in Men with Hypercholesterolemia

Early Benefit with Pravastatin in WOSCOPS Myocardial Infarction* Shepherd et al. N Engl J Med. 1995;333: Percent with Event Years 456 Pravastatin (n = 3302) Placebo (n = 3293) 31% risk reduction P < *Primary endpoint: Nonfatal MI and CHD death

Benefit with Pravastatin in WOSCOPS Total Mortality Shepherd et al. N Engl J Med. 1995;333: Percent with Event Years % risk reduction P = Pravastatin (n = 3302) Placebo (n = 3293)

Benefit with Pravastatin in WOSCOPS PTCA/CABG Shepherd et al. N Engl J Med. 1995;333: Percent with Event 12 Years % risk reduction P = Placebo (n = 3293) Pravastatin (n = 3302)

Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) Gotto AM, AHA Orlando, 1997MS

Study Design 6605 Males & females aged years with no clinical evidence of atherosclerotic CVD Diet + Placebo run-in Total C between 180 & 264 mg/dl; LDL between 130 & 190 mg/dl HDL < 50 mg/dl; Total-C/HDL ratio < 5 5 years Placebo Lovastatin mg QD (titrate to LDL < 110 mg/dl) AFCAPSTexCAPS Gotto A. AHA 1997.

AFCAPS/TexCAPS: Lipid Change from Baseline to Year 1 % TCTCLDL-CLDL-CTGTG HDL-CHDL-C Gotto AM, AHA Orlando, 1997 MS

AFCAPS/TexCAPS : Primary Endpoint First Acute Major Coronary Event/Mortality YearsYears Percent with Event % risk reductionreduction p < Lovastatin (n = 3304) Placebo (n = 3301) Gotto AM, AHA Orlando, 1997 MS

Biggest-ever statin study will change practice worldwide... Dr. Rory Collins The Heart Protection Study (HPS) Lancet 2002;360:7-22

The Heart Protection Study (HPS) 20,000 volunteers, ages 40 to 80 yrs, T. Chol > 135 mg/dl, who were at high risk of CAD Simva 40 mg QD vs placebo for 5.5 years with/without antioxidant vitamins E (600 mg), C (250 mg) and  carotene (20 mg) Baseline LDL: <116 (33%), (25%), >135 (42%) Lancet 2002;360:7-22

HPS - All Cause Mortality % P<0.001

HPS - Tolerability StatinPlacebo n=10269 n=10267 ALT>3xULN 0.8% 0.9% CPK>10xULN 0.09% 0.05% Lancet 2002;360:7-22

Secondary Prevention Evidence with Statins

Early secondary prevention trials only focussed on long-term event reductions in stable patients Proportion alive Risk reduction, 30% Log-rank p= Simvastatin Placebo 4S4S 0 0 Fatal CHD/nonfatal MI (%) Risk reduction, 24% p<0.001 Pravastatin Placebo LIPID Fatal CHD/nonfatal MI (%) Risk reduction, 24% p=0.003 Pravastatin Placebo CARE Years 4S 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.

LIPID: Cardiovascular Event Reduction with Pravastatin % P< % 22% P=0.001 RelativeRiskReduction (%) * RelativeRiskReduction N Engl J Med. 1998;339:1349–1357. CHD Death TotalMortalityTotalMortality StrokeStroke * 24% of the placebo group were receiving lipid lowering therapy at the end of the trial.

Effect of Lowering Total Cholesterol Concentration on CHD Events The influence of LDL reduction on CHD events in primary and secondary prevention trials with simvastatin, pravastatin and lovastatin Primary prevention trials Secondary prevention trials Percent with CHD Event LDL cholesterol (mg/dl) CARE-Rx 4S-Rx LIPID-PL 4S-PL CARE-PL LIPID-Rx AFCAPS-Rx WOSCOPS-Rx WOSCOPS-PL AFCAPS-PL

CURVES Mean Percent Change in LDL-C at Starting Doses *P<0.002 vs atorvastatin. 10 mg Dose % Change -38% -24%* -28%* -29%* -17%* 20 mg AtorvastatinLovastatinPravastatinSimvastatinFluvastatin

Statins LDL-C reduction Reduction in chylomicron and VLDL remnants, IDL, LDL-C Restore endothelial function Maintain SMC function Anti-inflammatory effects Decreased thrombosis Lumen Lipid core Macrophages Smooth muscle cells Potential mechanisms of benefit of statins

Serum Cholesterol and FMD   FMD (%)     Serum Cholesterol Level (mg/dl)    Simvastatin 10 mg/d Simvastatin 10 mg/d Pravastatin 20 mg/d Pravastatin 40 mg/d CAD Patients Vogel RA. Am J Med 1999;107:479-87

Cholesterol Lowering With Statin Drugs: Risk of Stroke, and Total Mortality 29%22%28% Stroke Total Mortality CVD Deaths % Herbert PR, et al. JAMA 1997;278:

HMG CoA Reductase Inhibitors (Statins) Demonstrated Therapeutic Benefits Reduce major coronary events Reduce major coronary events Reduce CHD mortality Reduce CHD mortality Reduce coronary procedures (PTCA/CABG) Reduce coronary procedures (PTCA/CABG) Reduce stroke Reduce stroke Reduce total mortality Reduce total mortality Demonstrated Therapeutic Benefits Reduce major coronary events Reduce major coronary events Reduce CHD mortality Reduce CHD mortality Reduce coronary procedures (PTCA/CABG) Reduce coronary procedures (PTCA/CABG) Reduce stroke Reduce stroke Reduce total mortality Reduce total mortality JAMA 2001;285:

Lessons from WOSCOPS Number of yrs Treated to Prevent One Event Number Treated to Prevent One Event Isolated Hypertension - MRC Isolated Hypercholesterolemia Total WOSCOPS Cohort Hypertension Family History Smoking or HDL < 42 mg/dL Pre-existing vascular disease Minor ECG Abnormality WOSCOPS

מה היא רמת סוכר תקינה בדם ? קטגוריהתקין רמת סוכר מוגברת סוכרתבצום mg/dl פחות מ mg/dl mg/dl מעל 125 גם לנבדקים עם רמת סוכר מוגברת שאינה מגיעה לטווח של סוכרת סיכון מוגבר לחלות בטרשת עורקים. חלק ניכר מהם לוקים גם בסוכרת של ממש תוך מספר שנים.

מה הוא סיפור משפחתי למחלת לב כלילית ? הכוונה היא למחלת לב כלילית מוקדמת ! קרובת משפחה מדרגה ראשונה שלקתה במחלה מתחת לגיל 65 קרוב משפחה מדרגה ראשונה שלקה במחלה מתחת לגיל 55

6.2003

LEMOYNE V. de MILO BOTICELLI LEMOYNE V. de MILO BOTICELLI

Or...

The Prevalence of Obesity Sweden Obese (%) Denmark Iceland UK W. Ger E. Ger Belgium France Spain Italy Whites Blacks Whites Aborig. Women Men USAAustraliaEurope

Obesity is usually measured as body mass index (BMI) Weight (kg) Height (m 2 ) World Health Organization, 1998 Classification BMI (kg/m 2 ) Risk of co-morbidities Normal range 18.5  24.9Average Overweight  25 Pre-obese 25  29.9Increased Obese class I 30.0  34.9Moderate Obese class II 35.0  39.9Severe Obese class III  40.0  Very severe BMI =

Waist circumference is a surrogate marker of visceral fat 1 Lean C et al. Lancet 1998 Women >88 cm = increased risk 1 Men >102 cm = increased risk 1

< Cardiovascular disease Cancer All other causes Relative risk of death BMI  35.0 High BMI Increases Risk of Mortality in Men Calle EE et al. N Engl J Med 1999; 341:

Abdominal fat – an endocrine tumor IL CA PO DI TUTTI I I CAPI Resistin RELM-  Resistin RELM-  PAI-1 FFA IL-6 TNF-  Leptin Angiotensin Adiponectin↓ Visfatin↑ Adiponectin↓ Visfatin↑ Inflammation & Hypercuagulability Inflammation & Hypercuagulability Hypertension Insulin resistance Dyslipidemia excess edipocyte behaviour

Obesity and the risk of heart failure Kenchaia et al. NEJM 2002;347: Overweight >=25 Obese >=30 עודף משקל הסיכון לאי ספיקת לב מכפיל את עצמו כבר לאחר 10 שנים בקרב נשים ולאחר 15 שנים בקרב גברים

BMI and Age-related BMI and Age-related Mortality BMI (kg/m 2 ) Relative risk Adapted Waaler et al. Acta Med Scand 1984 Females Males 50–54 55–59 60–64 Age

Consequences of Obesity

Exercise

Stefanick et al. Effects of diet and exercise in men and postmenopausal women with low levels of HDL Cholesterol and high levels of LDL Cholesterol. New England Journal of Medicine 1998;339: פעילות גופנית ושיפור פרופיל הכולסטרול דיאטה הצליחה להוריד את רמת הכולסטרול (LDL-C) באופן משמעותי רק בקרב אלו שביצעו פעילות גופנית באופן קבוע כ-400 גברים ונשים בגיל הבלות HDL-C LDL-C פעילות גופנית וגורמי סיכון

לאחר 6 שנים: 60% פחות סוכרת בקבוצת המתעמלים! P < פעילות גופנית ומניעת סוכרת Tuomilehto et al. Prevention of Type 2 Diabetes Mellitus by Changes in Lifestyle among Subjects with Impaired Glucose Tolerance. New England Journal of Medicine 2001;344: מעל 500 נבדקים בני בעלי עודף משקל ונטייה לעליה מוגזמת ברמת הסוכר לאחר ארוחה פעילות גופנית וגורמי סיכון

Diabetes Program Research Group. Reduction in the incidence of Type-2 Diabates With Lifestyle Intervention. NEJM 2002;346: Diabetes Prevention Program Research Group. Reduction in the incidence of Type-2 Diabates With Lifestyle Intervention. NEJM 2002;346: פעילות גופנית ומניעת סוכרת פעילות גופנית וגורמי סיכון פעילות גופנית יעילה יותר מתרופה כנגד סוכרת !

Hakim et al. Effects of walking on mortality among nonsmoking retired men. New England Journal of Medicine 1998;338: פעילות גופנית והורדת תמותה בקרב גברים כ-700 גברים בגילאים שנים ללא מחלת לב ידועה הליכה מעל 3 ק ” מ ביום לעומת הליכה של פחות 1.5 ק ” מ הקטינה את הסיכון למוות ב-% 50 במשך 12 שנים 43% 22% 63% פחות אוטם שריר הלב או שבץ מוחי 56% פחות מחלות סרטן ! פעילות גופנית וגורמי סיכון

פעילות גופנית ומניעת מחלת לב בנשים מידת הפעילות הגופנית הסיכון היחסי 32% 31% 42% Manson et al. Prospective study of walking as compared with vigorous exercise in the prevention of coronary artery disease in women. New England Journal of Medicine 1999;341: הליכה נמרצת במשך 3-4 שעות בשבוע הורידה את הסיכון לחלות ממחלת לב כלילית ב 35%, לא פחות מהתעמלות נמרצת אחרת. 72,488 אחיות בגילאים שנים ללא מחלת לב ידועה פעילות גופנית וגורמי סיכון

Manson et al. Prospective study of walking as compared with vigorous exercise in the prevention of coronary artery disease in women. New England Journal of Medicine 1999;341: פעילות גופנית ומניעת מחלת לב בקרב נשים די בהליכה בינונית בקצב ממוצע כדי להוריד את הסיכון לחלות ממחלת לב באופן משמעותי < 3.2 km/h km/h> 4.8 km/h פעילות גופנית וגורמי סיכון

Leitzmann et al. Recreational physical activity and the risk of cholecystectomy in women. New England Journal of Medicine 1999;341: פעילות גופנית ומניעת מחלות בקרב נשים נשים הפעילות מבחינה גופנית עוברות פחות ניתוחי כיס מרה פעילות גופנית וגורמי סיכון

Murray CJL and Lopez DA. "Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study." Lancet 1997;349: הנזק שנגרם לבריאות ע ” י העדר פעילות גופנית, דומה בחשיבותו לזה הנגרם ע ” י גורמי סיכון עיקריים כגון יתר לחץ דם ורמה גבוהה של כולסטרול בדם פעילות גופנית וגורמי סיכון

פעילות גופנית - מורידה את הסיכון לחלות במחלות לב, שבץ מוחי, סרטן ומחלות דרכי משפרת את המצב המטבולי - מורידה את הסיכון לחלות בסוכרת ומאפשרת הורדה יעילה של כולסטרול באמצעות מביאה להפחתה מורידה מתח ומשפרת את המצב הנפשי-חברתי משפרת את הכושר הגופני מורידה את הסיכון לחלות במחלות לב, שבץ מוחי, סרטן ומחלות דרכי משפרת את המצב המטבולי - מורידה את הסיכון לחלות בסוכרת ומאפשרת הורדה יעילה של כולסטרול באמצעות מביאה להפחתה מורידה מתח ומשפרת את המצב הנפשי-חברתי משפרת את הכושר הגופני והגמישות פעילות גופנית וגורמי סיכון

STRESS

Smoking and Heart Disease

Hypertension

מהו לחץ דם תקין ? קטגוריהרצויתקין תקין גבוה יתר לחץ דם דרגה 1 דרגה 2 דרגה 3 ל”ד דיאסטולי > 110 ל”ד סיסטולי > 180 יעד הטיפול ביתר לחץ דם הוא להגיע לערכים של פחות מ-140/90 ממ”כ, במקרה של סוכרת אף לפחות מ-130/80 ממ”כ.

Hypertension and Dyslipidaemia Are Major Risk Factors for CHD Kannel W. In: Hypertension: Pathophysiology and Treatment. New York: McGraw-Hill, Inc.; 1977: ; Castelli WP. Am J Med. 1984;76:4-12. CHD incidence/1000 Probability of CVD/1000 Age Framingham study SBP (mm Hg) in men TC (mg/dL) in men

Additive Effect of Cholesterol and Systolic BP on Risk of CHD Death Neaton JD, Wentworth D. Arch Intern Med. 1992;152: < Cholesterol quintile (mg/dL) SBP quintile (mm Hg) < Deaths /10,000 patient-years N=316,099

36% reduction Primary End Point: Nonfatal MI and Fatal CHD HR=0.64 ( ) Atorvastatin 10 mgNumber of events100 PlaceboNumber of events 154 P= Sever PS, et al. Lancet. 2003;361:

Healthy Nutrition

Vitamins and food supplements

“ ועוד כלל אמרו בבריאות הגוף כל זמן שאדם מתעמל ויגע אין חולי בא עליו וכוחו מתחזק, וכל מי שיושב לבטח ואינו מתעמל, אפילו אכל מאכלות טובים ושמר על עצמו על פי הרפואה, כל ימיו יהיו מכאובים וכוחו תשש ” הרמב ” ם ספר מדע פרק ד ’, הלכות י ” ד -ט ” י פעילות גופנית וגורמי סיכון