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4) Risk Factors

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  • 1. Risk Factors
  • 2. Definition of Hypercholesterolemia
  • 3. Total cholesterol by age and sex Average distribution of plasma total cholesterol (means and selected percentiles) Plasma total cholesterol (mg/dL) Age (years) Age (years) 320 280 240 200 160 120 0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70 White males White females 90th Mean 50th 10th 90th Mean 50th 10th
  • 4. Risk Factors: Serum Cholesterol (carried by LDL particles) How do we know who is at risk? ALSO Implicated: Family History Smoking  why? Hypertension  why? Death rate per 1000 men Percentile mmol/l 18 16 14 12 10 8 6 4 2 0 5 15 25 35 45 55 65 75 85 95 4.1 4.8 5.3 5.8 6.5 7.8 Top 15% cholesterol = 43/1000 N = 100/1000 50% Serum Cholesterol in N = 360,000 men over 6 years
  • 5. CHD Risk Factors Plasma Cholesterol (mmol/l) %
  • 6. Note – those countries with  risk also have  serum cholesterol  dietary fat & cholesterol intake Finland USA New Zeeland Australia UK Ireland Canada Norway Belgium-Lux. Yugoslavia Denmark Netherlands West Germany Austria Sweden Italy Switzerland Portugal Spain France Greece Japan Isochemic Heart disease Other possible coronary deaths 0 100 200 300 400 500 600 Mortality rates per 100,000 Mortality rates due to coronary heart disease
  • 7. 2 1 0.5 100 200 300 Relative Risk of Death From CHD by blood cholesterol (mg/dl) 6 prospective studies 100 200 300 100 200 300 2 1 0.5 Finland 347 CHD MRFIT (US) 3,243 CHD Whitehall (UK) 455 CHD Framingham (US) 216 CHD Israel 615 CHD Hawaii 242 CHD
  • 8. Ideal, Feasible And Existing Total Serum Cholesterol Levels in Adults Ideal Mean 4.3 mMl 2.7 4.0 5.4 6.7 8.1 Feasible Mean 5.1 mM Present Mean 5.7 mM Total Serum Cholesterol mmol/L
  • 9. CANADIAN HEART HEALTH SURVEY PREVALENCE OF TOTAL CHOLESTEROL LEVELS % 52% 57% 55% 30% 27% 29% 18% 16% 17%
  • 10. Classification Based on Total Blood Cholesterol mg/dl (mmol/L=mM) 220+ (5.7) 180-220 (4.6-5.7) <180 (4.6) 18-30 240+ (6.2) 200-240 (5.2-6.2) <200 (5.2) 30+ High Risk Moderate Risk Desirable Men & Women Age
  • 11. What is the risk of coronary heart disease in the next 6 years in these individuals? [ 1%, 5%, 10%, 15%, 25%, 35%, 60%, 90% ]
    • « WORST » SYSTOLIC
    • BLOOD
    • AGE SEX TOTAL HDL PRESSURE DIABETES SMOKING
    • 55 M 7.2 0.8 150 NO YES
    • 55 F 7.2 0.8 150 NO YES
    • 55 M 7.2 0.8 150 NO NO
    • 55 M 5.2 1.1 150 NO YES
    • 55 M 5.2 1.1 120 NO NO
    • 55 M 10.0 0.8 170 YES YES
    • 25 M 10.0 0.8 170 YES YES
    • 55 F 10.0 0.8 170 YES YES
    • 25 M 7.2 0.8 150 NO YES
  • 12. What is the risk of coronary heart disease in the next 6 years in these individuals? [ 1%, 5%, 10%, 15%, 25%, 35%, 60%, 90% ]
    • « LEAST LIKELY » SYSTOLIC
    • BLOOD
    • AGE SEX TOTAL HDL PRESSURE DIABETES SMOKING
    • 55 M 7.2 0.8 150 NO YES
    • 55 F 7.2 0.8 150 NO YES
    • 55 M 7.2 0.8 150 NO NO
    • 55 M 5.2 1.1 150 NO YES
    • 55 M 5.2 1.1 120 NO NO
    • 55 M 10.0 0.8 170 YES YES
    • 25 M 10.0 0.8 170 YES YES
    • 55 F 10.0 0.8 170 YES YES
    • 25 M 7.2 0.8 150 NO YES
  • 13. What is the risk of coronary heart disease in the next 6 years in these individuals? [ 1%, 5%, 10%, 15%, 25%, 35%, 60%, 90% ]
    • SYSTOLIC
    • BLOOD
    • AGE SEX TOTAL HDL PRESSURE DIABETES SMOKING
    • 55 M 7.2 0.8 150 NO YES
    • 55 F 7.2 0.8 150 NO YES
    • 55 M 7.2 0.8 150 NO NO
    • 55 M 5.2 1.1 150 NO YES
    • 55 M 5.2 1.1 120 NO NO
    • 55 M 10.0 0.8 170 YES YES
    • 25 M 10.0 0.8 170 YES YES
    • 55 F 10.0 0.8 170 YES YES
    • 25 M 7.2 0.8 150 NO YES
    26% 35%
  • 14. What is the risk of coronary heart disease in the next 6 years in these individuals? [ 1%, 5%, 10%, 15%, 25%, 35%, 60%, 90% ]
    • SYSTOLIC
    • BLOOD
    • AGE SEX TOTAL HDL PRESSURE DIABETES SMOKING
    • 55 M 7.2 0.8 150 NO YES
    • 55 F 7.2 0.8 150 NO YES
    • 55 M 7.2 0.8 150 NO NO
    • 55 M 5.2 1.1 150 NO YES
    • 55 M 5.2 1.1 120 NO NO
    • 55 M 10.0 0.8 170 YES YES
    • 25 M 10.0 0.8 170 YES YES
    • 55 F 10.0 0.8 170 YES YES
    • 25 M 7.2 0.8 150 NO YES
    10% 15% 10% 5% 10%
  • 15. LDLC = TC – HDL – (TG/2) < 3.5 nM < 5.2 mM > 1.5 – 2.0 < 2.0 mM ppt Chylo LDL VLDL VLDL VLDL LDL HDL 95% Fasting NO Apo B Chylos no apoB very little Particles apoB in VLDL 80-120 mg/dL Calculation of LDL Cholesterol
  • 16. Calculation of LDL Cholesterol LDL C = TC – HDL C – (TG/2) 3.0 = 6.0 – 1.0 – (4.0/2) calculated (not direct) apoB = < 120 (direct)
  • 17. LDL cholesterol and apoB distribution in CAD patients
  • 18. Threshold Effect of LDL Cholesterol Frequency 50 LDL Cholesterol 56.5% of CAD had LDL C > 50th percentile, therefore no threshold for LDL C. N CAD
  • 19. Threshold for LDL Particle Number 88% of CAD had LDL apoB > 50th percentile NA population. Frequency 50 LDL apoB N CAD
  • 20. Lipoprotein Screening
    • Canadian Consensus Conference on
    • Cholesterol
    • « As resources permit »
    • A priority for those with risk factors and established CHD
    • U.S. National Cholesterol Education Program
    • At least every five years for all adults aged 20 and over
    • More often as follow-up for those with elevated serum
    • cholesterol
    • Canadian Cardiovascular Society
    • Within 24 hours of myocardial infraction,
    • repeated 6-12 weeks after hospital discharge
  • 21. CCCC recommendations: Screening priorities
    • Screening for priority groups
    • Priority screening for individuals with:
      • Coronary heart disease
      • Family history of hyperlipidemia or CHD at an
      • early age
      • Hypertension
      • Diabetes
      • Renal failure
      • Abdominal obesity
    • Screening for all Canadians
    • As part of a periodic health examination
  • 22. Interpretation of Lipid Values Men and Women Age 18-29 DRUGS? DIETARY MODIFICATION TG >200 HDL <35 LDL >115 39% 19% 180 (4.6) 220 (5.7) Other risk factors mg/dl (mM/L) Other risk factors
  • 23. Coronary Heart Disease Main Risk Factors Non-Modifiable Modifiable Family History of CHD Dyslipidemia Male Sex Hypertension Age Diabetes Smoking Obesity
  • 24. Normal Endothelial Function  EDRF  PC  EDRF  PC  EDRF  PC  EDRF  EDRF  EDRF
  • 25. B B B B B B In One Door… And Out the Other
  • 26. Tg Tg Tg Tg Tg Tg Tg Tg Tg Tg Tg Tg Tg Tg CE CE CE CE CE B CE CE CE CE Tg B VLDL LDL
  • 27. B B B B B The Pathogenic Power Of Particle Number B B B B B B B B B B B
  • 28. B B B B B B B B B B B B Oxidation of LDL Particles within the vessel wall B B
  • 29. Hypertension -> Subintimal Thickening
  • 30. 400 350 300 250 200 150 100 50 0 0 2 4 6 8 10 mol Fibrinogen X 10 12 /cm 2 Perfusion Time (MIN) n=17 n=20 n=22 * * * High Shear, Non-Parallel Sreamlines Low Shear, Parallel Sreamlines Effect of Shear Rate and Flow Condition on Fibrinogen Deposition
  • 31. HyperapoB -> Hyperthrombogenicity ↑ PAI-1 ↑ Fibrinogen ↑ Factor VII ↑ Factor VII c + ← ↑ FFA ← ↑ CE B Tg CE Tg B CE Tg B CE Tg B CE Tg B CE Tg B CE Tg B
  • 32. B B B B B B B Thicker ith Thlower
  • 33. CAD Mortality in NIDDM 60 50 40 30 20 10 0 Mortality Rate per 1000 0-3 4-7 8-11 13-15 18-19 20-23 0-3 4-7 8-11 13-15 18-19 20-23 Duration of Follow-up (years) Men Women Diabetes Diabetes No Diabetes No Diabetes
  • 34. Can Glucose Glycate Glycosaminoglycans which then Grab apoB? B B B B B B B B
  • 35. Relative odds of developing IHD over a 5-yr follow-up period in a sample of 91 IHD cases and 91 matched controls The Quebec Cardiovascular Study Relative Odds >50th <50th Total HDL-C Fasting Insulin (pmol/l) 1.0 3.8 4.4 8.7 6.3 14.1 RO adjusted for medication, systolic BP, family history of IHD
  • 36. Why is smoking atherogenic? Tg B CE Tg B CE Tg B CE
  • 37. A Dysfunctional Artery ↓ EDRF ↑ TF ↓ t-PA ↑PAI-1 ↓ EDRF ↓PC ↑TF Tg B CE Tg B CE Tg B CE
  • 38. Risk Factor – Obesity!
    • Although excess obesity is a risk factor, so is moderate
    • obesity especially abdominal android obesity:
          • “ beer belly” -Men
          •  diabetes  hypertension
  • 39.  BMI  age  men CORONARY MORBIDITY AND MORTALITY ASSOCIATED WITH RELATIVE WEIGHT Metropolitan relative weight Age-adjusted annual rate per 1,000 35 - 30 - 25 - 20 - 15 - 10 - 5 - 54-104 105-114 115-124 125-134 135-272 Men aged 65-94 years (p<0.01) Women aged 65-94 years (p<0.05) Men aged 35-64 years (p<0.001) Women aged 35-64 years (p<0.001)
  • 40. Alcohol Obesity Diet Saturated Fat Salt Genetic Susceptibility Kidney Damage Diabetes High Blood Pressure OC’s (female) Smoking Psycho-Social Factors Family History of CVD Dietary Cholesterol Physical Activity Blood Lipids Age Sex (male) Lower S/E CVD IHD Stroke
  • 41.
    • RISK FACTORS FOR CORONARY ARTERY DISEASE        
    • Modifiable
    • Smoking (> 10 cigarettes / day)
    • Obesity, especially Android Obesity
    • Hypercholesterolemia and/or Low HDL cholesterol (< 1 mM) *:
    • A high HDL cholesterol (>1.6 mM) is a negative risk factor
    • (i.e. protective)
    • Hypertension (> 140/90 or treated)
    • Diabetes Mellitus
            • *** MODIFIABLE BY DIET
    • Non Modifiable
    • Age (>45 in men, >55 in women)
    • Family history of premature coronary artery disease:
    • Myocardial infarct or sudden death in a 1st degree
    • parent < 55 years of age.
    • Gender (males are at increased risk

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