1. Cardiovascular Epidemiology and Prevention Nathan D. Wong, PhD, FACC, FAHA Professor and Director, Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine President, American Society of Preventive Cardiology

2. Agenda April 26April 26 u CVD definitions, US and Global Statistics u Historical perspective and risk factor overview u Screening for subclinical atherosclerosis May 3May 3 u Dyslipidemia u Metabolic Syndrome/Diabetes u Behavioral Issues (Nutrition, Obesity, Physical Activity, Tobacco, Psychosocial Factors) May 10May 10 u Hypertension Chronic Kidney Disease u CVD Prevention Guidelines

4. Cardiovascular Epidemiology: Definitions, Concepts, Historical Perspectives and Statistics

5. A Total CVD B Cancer C Accidents D Chronic Lower Respiratory Diseases E Diabetes Mellitus F Alzheimer’s Disease CVD and other major causes of death for all males and females (United States: 2005). Source: NCHS.

6. Age-adjusted death rates for CHD, stroke, lung and breast cancer for white and black females (United States: 2005). Source: NCHS and NHLBI.

7. CVD deaths vs. cancer deaths by age. (United States: 2006). Source: NCHS.

8. Clinical Manifestations of Atherosclerosis Coronary heart diseaseCoronary heart disease – Stable angina, acute myocardial infarction, sudden death, unstable angina Cerebrovascular diseaseCerebrovascular disease – Stroke, TIAs Peripheral arterial diseasePeripheral arterial disease – Intermittent claudication, increased risk of death from heart attack and stroke American Heart Association, 2000.

9. Definitions CORONARY ARTERY DISEASE (CAD) or CORONARY HEART DISEASE (CHD) (often broadly referred to as ISCHEMIC HEART DISEASE (IHD): primarily myocardial infarction and sudden coronary death, broader definition may include angina pectoris, atherosclerosis, positive angiogram, and revascularization (perceutaneous coronary interventions, or PCI such as angioplasty and stents)CORONARY ARTERY DISEASE (CAD) or CORONARY HEART DISEASE (CHD) (often broadly referred to as ISCHEMIC HEART DISEASE (IHD): primarily myocardial infarction and sudden coronary death, broader definition may include angina pectoris, atherosclerosis, positive angiogram, and revascularization (perceutaneous coronary interventions, or PCI such as angioplasty and stents) CARDIOVASCULAR DISEASE or CVD includes CHD, cerebrovascular disease, peripheral vascular disease, and other cardiac conditions (congenital, arrhythmias, and congestive heart failure)CARDIOVASCULAR DISEASE or CVD includes CHD, cerebrovascular disease, peripheral vascular disease, and other cardiac conditions (congenital, arrhythmias, and congestive heart failure)

10. Definitions (cont.) SURROGATE MEASURES include: carotid intimal medial thickness (IMT), coronary calcium, angiographic stenosis, brachial ultrasound flow mediated dilatation (FMD)SURROGATE MEASURES include: carotid intimal medial thickness (IMT), coronary calcium, angiographic stenosis, brachial ultrasound flow mediated dilatation (FMD) Hard endpoints include myocardial infarction, CHD death, and strokeHard endpoints include myocardial infarction, CHD death, and stroke

11. Percentage breakdown of deaths from cardiovascular diseases (United States: 2006) * - Not a true underlying cause. Source: NCHS.

12. Deaths from diseases of the heart (United States: 1900–2006) Note: See Glossary for an explanation of “Diseases of the Heart.” Source: NCHS.

13. CVD disease mortality trends for males and females United States: 1979-2006). Source: NCHS and NHLBI. CVD disease mortality trends for males and females (United States: 1979-2006). Source: NCHS and NHLBI.

14. Hospital discharges for cardiovascular diseases. (United States: 1970-2006). Note: Hospital discharges include people discharged alive, dead and status unknown. Source: NCHS and NHLBI.

15. Trends in Cardiovascular Operations and Procedures (United States: 1979-2006). Source: NCHS and NHLBI. Note: In-hospital procedures only.

16. Estimated direct and indirect costs (in billions of dollars) of major cardiovascular diseases and stroke (United States: 2010). Source: NHLBI.

17. Prevalence of stroke by age and sex (NHANES: 2005-2006). Source: NCHS and NHLBI.

18. Annual age-adjusted incidence of first-ever stroke, by race. Inpatient plus out-of-hospital ascertainment. (GCNKSS: 1993-94 and 1999). Source: Stroke 2006;37;2473-2478.

19. Prevalence of heart failure by age and sex (NHANES: 2005-2006). Prevalence of heart failure by age and sex (NHANES: 2005-2006). Source: NCHS and NHLBI.

20. Note: Hospital discharges include people discharged alive, dead and status unknown. Hospital discharges for heart failure by sex. (United States: 1979-2006). Source: NHDS/NCHS and NHLBI.

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

22. PDAY: Percentage of Right Coronary Artery Intimal Surface Affected With Early Atherosclerosis PDAY= PDAY= Pathobiological Determinants of Atherosclerosis in Youth. Strong JP, et al. JAMA. 1999;281:727-735. Fatty streaks Raised lesions White 15-1920-2425-2930-34 0 10 20 30 Women 0 10 20 30 15-1920-2425-2930-34 Black Age (y) 0 10 20 30 White 15-1920-2425-2930-34 Men Black 15-1920-2425-2930-34 0 10 20 30 Intimal surface (%)

23. Most Myocardial Infarctions Are Caused by Low-Grade Stenoses Pooled data from 4 studies: Ambrose et al, 1988; Little et al, 1988; Nobuyoshi et al, 1991; and Giroud et al, 1992. (Adapted from Falk et al.) Falk E et al, Circulation, 1995.

24. (Adapted from Glagov et al.) Coronary Remodeling NormalvesselMinimalCAD Progression Compensatory expansion maintains constant lumen Expansion overcome: lumen narrows SevereCADModerateCAD Glagov et al, N Engl J Med, 1987.

25. Intraluminal thrombus Growth of thrombus Intraplaque thrombusLipid pool Blood Flow Atherosclerotic Plaque Rupture and Thrombus Formation Adapted from Weissberg PL. Eur Heart J Supplements 1999:1:T13–18

26. Eccentric, lipid-rich Fragile fibrous cap Prior luminal obstruction < 50% Visible rupture and thrombus Constantinides P. Am J Cardiol. 1990;66:37G-40G. Features of a Ruptured Atherosclerotic Plaque

27. Libby P. Circulation. 1995;91:2844-2850. Vulnerable Plaque Thin fibrous cap Inflammatory cell infiltrates: proteolytic activity Lipid-rich plaque Lumen Lipid Core Fibrous Cap Thick fibrous cap Smooth muscle cells: more extracellular matrix Lipid-poor plaque Stable Plaque Lumen Lipid Core Fibrous Cap Vulnerable Versus Stable Atherosclerotic Plaques

28. Correlation of CT angiography of the coronary arteries with intravascular ultrasound illustrates the ability of MDCT to demonstrate calcified and non-calcified coronary plaques (Becker et al., Eur J Radiol 2000) Non-calcified, soft, lipid-rich plaque in left anterior descending artery (arrow) (Somatom Sensation 4, 120 ml Imeron 400). The plaque was confirmed by intravascular ultrasound (Kopp et al., Radiology 2004)

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

31. Major Risk Factors Cigarette smoking (passive smoking?)Cigarette smoking (passive smoking?) Elevated total or LDL-cholesterolElevated total or LDL-cholesterol Hypertension (BP  140/90 mmHg or on antihypertensive medication)Hypertension (BP  140/90 mmHg or on antihypertensive medication) Low HDL cholesterol (<40 mg/dL) †Low HDL cholesterol (<40 mg/dL) † Family history of premature CHDFamily 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)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.

32. Other Recognized Risk Factors Obesity: Body Mass Index (BMI)Obesity: Body Mass Index (BMI) –Weight (kg)/height (m 2 ) –Weight (lb)/height (in 2 ) x 703 Obesity BMI >30 kg/m 2 with overweight defined as 25- 30 kg/m 2 with overweight defined as 25-<30 kg/m 2 Abdominal obesity involves waist circumference >40 in. in men, >35 in. in womenAbdominal obesity involves waist circumference >40 in. in men, >35 in. in women Physical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/weekPhysical inactivity: most experts recommend at least 30 minutes moderate activity at least 4-5 days/week

33. Lifetime Risk of Coronary Heart Disease in the Framingham Study Men Women At age 40 years:48.6%31.7% At age 70 years:34.9%24.2% Lloyd-Jones et al. Lancet 1999; 353:89-92 ____________________________________________________________ ______________________________________________________________ _________________________________________________________________

34. First Coronary Events: Framingham Study Percent as Specified Event MyocardialAngina Sudden InfarctionPectoris Death AgeMen Women Men Women Men Women 35-64 43%28% 41% 59% 9% 4% 65-8455%44% 28% 41% 11% 7.4% Framingham Study 44 year follow-up. ____________________________________________________________ ________________________________________________________ ____________________________________________________________

35. Estimated 10-Year CHD Risk in 55-Year-Old Adults According to Levels of Various Risk Factors Framingham Heart Study A B C D A B C D Blood Pressure (mm Hg)120/80140/90140/90140/90 Total Cholesterol (mg/dL) 200 240 240 240 HDL Cholesterol (mg/dL) 50 50 40 40 Diabetes No No Yes Yes Cigarettes No No No Yes mm Hg = millimeters of mercury mg/dL = milligrams per deciliter of blood Source:Circulation 1998;97:1837-1847.

36. Estimated 10-Year Stroke Risk in 55- Year-Old Adults According to Levels of Various Risk Factors Framingham Heart Study ABCDEF Systolic BP*95-105130-148130-148130-148130-148130-148 DiabetesNoNoYesYesYesYes CigarettesNoNoNoYesYesYes Prior Atrial Fib.NoNoNoNoYes Yes Prior CVDNoNoNoNoNoYes Source: Stroke 1991;22:312-318. *BP in millimeters of mercury (mmHg)

37. Offspring CVD Risk by Parental CVD Status: Framingham Study Risk Ratio 2.5 2 1.5 1 0.5 0 MenWomen 1.0 1.7 2.2 1.0 1.7 Adjusted for: age, total/HDL Chol. ratio, SBP, smoking, diabetes, BMI Parental CVD <55 men, <65 Women

38. Multivariable Risk Risk imposed by a strong family history of heart attacks varies widely depending on the burden of modifiable risk factors

39. 9 Doubts about cholesterol as late as 1989

40. Lifetime Risk of CHD Increases with Serum Cholesterol Framingham Study: Subjects age 40 years DM Lloyd-Jones et al Arch Intern Med 2003; 1966-1972 34 44 57 19 29 33 Cholesterol ___________________________________________________________________________ _______________________________________________________________________________

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

42. Trends in mean total serum cholesterol among adults age 20 and older, by race/ethnicity, sex and survey (NHANES : 1988-94, 1999-02 and 2003-04). Source: NCHS and NHLBI. NH – non-Hispanic.

43. Age-adjusted prevalence of Adults age 20 and older with LDL cholesterol of 130 mg/dL or higher, by race/ethnicity and sex (NHANES: 2003-2004). Source: NCHS and NHLBI. NH – non-Hispanic.

44. Age-adjusted prevalence of Adults age 20 and older with HDL cholesterol <40 mg/dL, by race/ethnicity and sex (NHANES: 2003-2004). Source: NCHS and NHLBI. NH – non-Hispanic.

46. CK Friedberg on Hypertension: Diseases of the Heart 1996 “ There is a lack of correlation in most cases between the severity and duration of hypertension and development of cardiac complications.” ___________________________________________________________ ________________________________________________________ _______________________________________________________________

49. Relation of Non-Hypertensive Blood Pressure to Cardiovascular Disease Vasan R, et al. N Engl J Med 2001; 345:1291-1297 10-year Age- Adjusted Cumulative Incidence Hazard Ratio* SBPWomenMen <120/80 1.0 1.0 120-129 1.5 1.3 130-139 2.5 1.6 H.R. adjusted for age, BMI, Cholesterol, Diabetes and smoking *P<.001 Framingham Study: Subjects Ages 35-90 yrs. 1.9 2.8 4.4 5.8 7.6 10.1

50. Prevalence of high blood pressure in Adults by age and sex (NHANES: 2005-2006). Source: NCHS and NHLBI.

51. Extent of awareness, treatment and control of high blood pressure by race/ethnicity (NHANES : 2005-2006). Source: NCHS and NHLBI.

52. Treatment (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007) *P<0.05, **P<0.01 when compared to No-Disease group Treatment is in persons with HTN **

53. Control (all treated) (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007) **P<0.05**P<0.01 when compared to No-Disease Group Control is in persons with HTN defined as BP < 140/90 If DM and CKD is based on BP<130/80 control is **35.3% and **23.2%, respectively. If MetS is based on BP<130/85 control is **46.7% * **

54. CK Friedberg on Hypertension Diseases of the Heart 1966 “Hypertension imposes a load on the heart which for many years may be compensated by left ventricular hypertrophy” _______________________________________________________________

55. CVD Risk Imposed by ECG-LVH Framingham Study 36-yr. Follow-up Age-adjusted Risk Excess Risk Rate per 1000 Ratio per 1000 Rate per 1000 Ratio per 1000 Age Men Women Men Women Men Women 35-64 164 135 4.7*** 7.4*** 129 117 65-94 234 235 2.8*** 4.1*** 51 178 Biennial Rate per 1000. CVD=CHD, stroke, peripheral vascular disease, heart failure ***P<0.001 _______________________________________________________________ _____________________________________________________________

56. Smoking Statement Issued in 1956 by American Heart Association “It is the belief of the committee that much greater knowledge is needed before any conclusions can be drawn concerning relationships between smoking and death rates from coronary heart disease. The acquisition of such knowledge may well require the use of techniques and research methods that have not hitherto been applied to this problem.” Circulation 1960; vol. 23 ___________________________________________________________ ____________________________________________________________ ___________________________________________________________

57. CHD Risk by Cigarette Smoking. Filter Vs. Non-filter. Framingham Study. Men <55 Yrs. 14-yr. Rate/1000 119 206 210 59 112 210

58. Prevalence of current smoking for Adults age 18 and older by race/ethnicity and sex (NHIS:2007). Source: MMWR. 2008;57:1221-26. NH – non-Hispanic.

59. Prevalence of students in grades 9-12 reporting current cigarette smoking by race/ethnicity and sex. (YRBS:2007). Source: MMWR. 2008;57:SS04. NH – non-Hispanic.

60. Diseases of The Heart Charles K Friedberg MD, WB Saunders Co. Philadelphia, 1949 “The proper control of diabetes is obviously desirable even though there is uncertainty as to whether coronary atherosclerosis is more frequent or severe in the uncontrolled diabetic” ________________________________________________________________ ______________________________________________________________

61. Risk of Cardiovascular Events in Diabetics Framingham Study Age-adjusted Age-adjusted Biennial Rate Age-adjusted Biennial Rate Age-adjusted Per 1000 Risk Ratio Per 1000 Risk Ratio Cardiovascular Event Men Women Men Women Coronary Disease 39 21 1.5** 2.2*** Stroke15 6 2.9*** 2.6*** Peripheral Artery Dis. 18 18 3.4*** 6.4*** Cardiac Failure 23 21 4.4*** 7.8*** All CVD Events 76 65 2.2*** 3.7*** Subjects 35-64 36-year Follow-up **P<.001,***P<.0001 _________________________________________________________________

62. Prevalence of physician-diagnosed diabetes in Adults age 20 and older by race/ethnicity and sex (NHANES: 2005-2006). Source: NCHS and NHLBI. NH – non-Hispanic.

63. Prevalence of Physician Diagnosed Type 2 diabetes in Adults age 20+ by Race/Ethnicity, and Years of Education. (NHANES: 2005-2006). Source: NCHS and NHLBI. NH – non-Hispanic.

64. Trends in diabetes prevalence in adults age 20+ by Sex (NHANES: 1988-94 and 2005-2006). Source: NCHS and NHLBI. NH – non-Hispanic.

65. Mortality rates in U.S. adults, age 30-75, with metabolic syndrome (MetS), with and without diabetes mellitus (DM) and pre-existing CVD (NHANES II: 1976-80 Follow-up Study). ** Source: Malik et al., Circulation. 2004;110:1245-50. ** Average of 13 years of follow-up. Note: Age and gender adjusted. ** Average of 13 years of follow-up. Note: Age and gender adjusted.

67. Skepticism About Importance of Obesity Keys A, Aravanis C, Blackburn H, et al. Ann Intern Med 1972; 77:15-27. Concluded that all the excess risk of coronary heart disease in the obese derives from its atherogenic accompaniments, illogically leaving the impression that obesity is therefore unimportant. Mann GV. N Engl J Med 1974; 291:226-232. “The contribution of obesity to CHD is either small or non-existent. It cannot be expected that treating obesity is either logical or a promising approach to the management of CHD”. Barrett-Connor EL. Ann Intern Med 1985; 103:1010-1019 NIH consensus panel is equivocal about the role of obesity as a cause of CHD.

68. Relation of Weight Change to Changes in Atherogenic Traits: The Framingham Study Frantz Ashley, Jr. and William B Kannel J Chronic Dis 1974 “Weight gain is accompanied by atherogenic alterations in blood lipids, blood pressure, uric acid and carbohydrate tolerance.” “It seems reasonable to expect that correction of overweight will improve the coronary risk problem.” “Avoidance of overweight would seem a desirable goal in the general population if the appalling annual toll from disease is to be substantially reduced.”

69. 3 2.4 1.8 1.2 0.6 0 (1971) (1989) Q1Q2Q3Q4Q5Overall ThinObese Risk Factor Sum and Obesity (1971-74) and (1989-93) Risk Factor Sum Risk variables include bottom quintile for HDL-C and top quintiles for cholesterol, SBP, triglycerides and glucose Wilson PWF, & Kannel WB Nutr Clin Care 1999; 1:44-50 Framingham Study Risk factors accumulate with weight gain

70. Note: Obesity is defined as a BMI of 30.0 or higher. Age-adjusted prevalence of obesity in Adults ages 20-74 by sex and survey. (NHES, 1960-62; NHANES, 1971-74, 1976-80, 1988- 94 and 2001-2004). Source: Health, United States, 2007. NCHS.

71. Prevalence of overweight among students in grades 9-12 by race/ethnicity and sex (YRBS: 2007). Source: MMWR. 2008 57: No. SS-4. BMI 95th percentile or higher by age and sex of the CDC 2000 growth chart. NH – non-Hispanic.

73. Prevalence of regular leisure-time physical activity among adults age 18 and older by race/ethnicity, and sex. (BRFSS: 2001 and 2005). Source: MMWR, 2007;56:No. 46. NH – non-Hispanic.

74. Prevalence of students in grades 9-12 who did not meet currently recommended moderate-to-vigorous physical activity during the past 7 days by race/ethnicity, and sex. (YRBS: 2007). Source: MSSE 2008;40:181-8. NH – non-Hispanic.

75. Risk Assessment Count major risk factors For patients with multiple (2+) risk factorsFor patients with multiple (2+) risk factors –Perform 10-year risk assessment For patients with 0–1 risk factorFor patients with 0–1 risk factor –10 year risk assessment not required –Most patients have 10-year risk <10%

76. ATP III Assessment of CHD Risk For persons without known CHD, other forms of atherosclerotic disease, or diabetes: Count the number of risk factors:Count the number of risk factors: –Cigarette smoking –Hypertension (BP  140/90 mmHg or on antihypertensive medication) –Low HDL cholesterol (<40 mg/dL) † –Family history of premature CHD u CHD in male first degree relative <55 years u CHD in female first degree relative <65 years –Age (men  45 years; women  55 years) Use Framingham scoring for persons with  2 risk factors* (or with metabolic syndrome) to determine the absolute 10-year CHD risk. (downloadable risk algorithms at www.nhlbi.nih.gov)Use Framingham scoring for persons with  2 risk factors* (or with metabolic syndrome) to determine the absolute 10-year CHD risk. (downloadable risk algorithms at www.nhlbi.nih.gov) 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

77. Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Assessing CHD Risk in Men Step 1: Age YearsPoints 20-34-9 35-39-4 40-440 45-493 50-546 55-598 60-6410 65-6911 70-7412 75-7913 Step 2: Total Cholesterol TC Points atPoints atPoints atPoints atPoints at (mg/dL) Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 <16000000 160-19943210 200-23975310 240-27996421  280118531 HDL-C (mg/dL) Points  60-1 50-590 40-491 <402 Step 3: HDL-Cholesterol Systolic BPPointsPoints (mm Hg)if Untreatedif Treated <12000 120-12901 130-13912 140-15912  16023 Step 4: Systolic Blood Pressure Step 5: Smoking Status Points atPoints atPoints atPoints atPoints at Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 Nonsmoker00000 Smoker85311 Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total Step 6: Adding Up the Points Point Total10-Year RiskPoint Total10-Year Risk <0<1%118% 01%1210% 11%1312% 21%1416% 31%1520% 41%1625% 52%  17  30% 62% 73% 84% 95% 106% Step 7: CHD Risk ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

78. Point Total10-Year RiskPoint Total10-Year Risk <9<1%2011% 91%2114% 101%2217% 111%2322% 121%2427% 132%  25  30% 142% 153% 164% 175% 186% 198% Assessing CHD Risk in Women Note: Risk estimates were derived from the experience of the Framingham Heart Study, a predominantly Caucasian population in Massachusetts, USA. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Step 1: Age YearsPoints 20-34-7 35-39-3 40-440 45-493 50-546 55-598 60-6410 65-6912 70-7414 75-7916 TC Points atPoints atPoints atPoints atPoints at (mg/dL) Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 <16000000 160-19943211 200-23986421 240-279118532  2801310742 HDL-C (mg/dL) Points  60-1 50-590 40-491 <402 Step 3: HDL-Cholesterol Systolic BPPointsPoints (mm Hg)if Untreatedif Treated <12000 120-12913 130-13924 140-15935  16046 Step 4: Systolic Blood Pressure Step 5: Smoking Status Points atPoints atPoints atPoints atPoints at Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 Nonsmoker00000 Smoker97421 Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total Step 6: Adding Up the Points Step 7: CHD Risk Step 2: Total Cholesterol ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

79. Men YearsPoints 20-34-9 35-39-4 40-440 45-493 50-546 55-598 60-6410 65-6911 70-7412 75-7913 Step 1: Age Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Women YearsPoints 20-34-7 35-39-3 40-440 45-493 50-546 55-598 60-6410 65-6912 70-7414 75-7916 ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

80. Step 2: Total Cholesterol Note: TC and HDL-C 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. Men TC Points atPoints atPoints atPoints atPoints at (mg/dL) Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 <16000000 160-19943210 200-23975310 240-27996421  280118531 Women TC Points atPoints atPoints atPoints atPoints at (mg/dL) Age 20-39Age 40-49Age 50-59Age 60-69Age 70- 79 <16000000 160-19943211 200-23986421 240-279118532  2801310742 ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

81. Step 3: HDL-Cholesterol 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. Men HDL-C (mg/dL) Points  60-1 50-590 40-491 <402 Women HDL-C (mg/dL) Points  60-1 50-590 40-491 <402 ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

82. Step 4: Systolic Blood Pressure Men Systolic BPPointsPoints (mm Hg)if Untreatedif Treated <12000 120-12901 130-13912 140-15912  16023 Note: The average of several BP measurements is needed for an accurate measurement of baseline BP. If an individual is on antihypertensive treatment, extra points are added. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Women Systolic BPPointsPoints (mm Hg)if Untreatedif Treated <12000 120-12913 130-13924 140-15935  16046 ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

83. Step 5: Smoking Status Note: Any cigarette smoking in the past month. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Men Points atPoints atPoints atPoints atPoints at Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 Nonsmoker00000 Smoker85311 Women Points atPoints atPoints atPoints atPoints at Age 20-39Age 40-49Age 50-59Age 60-69Age 70-79 Nonsmoker00000 Smoker97421 ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

84. Step 6: Adding Up the Points (Sum From Steps 1–5) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Age Total cholesterol HDL-cholesterol Systolic blood pressure Smoking status Point total ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

85. Step 7: CHD Risk for Men Note: Determine the 10-year absolute risk for hard CHD (MI and coronary death) from point total. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Point Total10-Year RiskPoint Total10-Year Risk <0<1%118% 01%1210% 11%1312% 21%1416% 31%1520% 41%1625% 52%  17  30% 62% 73% 84% 95% 106% ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

86. Presentation Examination:Examination: –Height: 6 ft 2 in –Weight: 220 lb (BMI 28 kg/m 2 ) –Waist circumference: 41 in –BP: 150/88 mm Hg –P: 64 bpm –RR: 12 breaths/min Cardiopulmonary exam: normalCardiopulmonary exam: normal Laboratory results:Laboratory results: –TC: 220 mg/dL –HDL-C: 36 mg/dL –LDL-C: 140 mg/dL –TG: 220 mg/dL –FBS: 120 mg/dL

87. What is WJC’s 10-year absolute risk of fatal/nonfatal MI? A 12% absolute risk is derived from points assigned in Framingham Risk Scoring to:A 12% absolute risk is derived from points assigned in Framingham Risk Scoring to: –Age: 6 –TC: 3 –HDL-C: 2 –SBP: 2 –Total: 13 points In 1992 he exercised 14 minutes in a Bruce protocol exercise stress test to 91% of his maximum predicted heart rate without any abnormal ECG changes. He started on a statin in 2001. But in Sept 2004, he needed urgent coronary bypass surgery.

88. Step 7: CHD Risk for Women Note: Determine the 10-year absolute risk for hard CHD (MI and coronary death) from point total. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. Point Total10-Year RiskPoint Total10-Year Risk <9<1%2011% 91%2114% 101%2217% 111%2322% 121%2427% 132%  25  30% 142% 153% 164% 175% 186% 198% ATP III Framingham Risk Scoring © 2001, Professional Postgraduate Services ® www.lipidhealth.org

89. CHD Risk Equivalents Risk for major coronary events equal to that in established CHDRisk for major coronary events equal to that in established CHD 10-year risk for hard CHD >20%10-year risk for hard CHD >20% Hard CHD = myocardial infarction + coronary death

90. Diabetes as a CHD Risk Equivalent 10-year risk for CHD  20%10-year risk for CHD  20% High mortality with established CHDHigh mortality with established CHD –High mortality with acute MI –High mortality post acute MI

91. CHD Risk Equivalents Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease)Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) DiabetesDiabetes Multiple risk factors that confer a 10- year risk for CHD >20%Multiple risk factors that confer a 10- year risk for CHD >20%

92. Framingham 10-year Total CVD Risk Algorithm (D’Agostino et al 2008)

93. International Comparisons in CVD Morbidity and Mortality CVD accounts for 25-45% of deaths among different countriesCVD accounts for 25-45% of deaths among different countries CVD death rates (per 100,000) range from 1310 in Russia to 201 in Japan (6.5 fold difference) in men and from 581 in Russia to 84 in France (7-fold difference)CVD death rates (per 100,000) range from 1310 in Russia to 201 in Japan (6.5 fold difference) in men and from 581 in Russia to 84 in France (7-fold difference) USA ranks 16th for both men (413) and women (201)USA ranks 16th for both men (413) and women (201)

94. Secular Trends in CHD and Stroke Mortality From 1985-1992, greatest annual decline (6-7%) in CHD seen in Israel among men and France among women, USA intermediate (4%), increases in Poland and Romania.From 1985-1992, greatest annual decline (6-7%) in CHD seen in Israel among men and France among women, USA intermediate (4%), increases in Poland and Romania. Stroke death rates declined most in Australia, Italy, and France (8-9%), USA about 3%.Stroke death rates declined most in Australia, Italy, and France (8-9%), USA about 3%.

95. Age-Adjusted Death Rates for Coronary Heart Disease by Country and Sex, Ages 35-74, 1999 Age-Adjusted to European Standard Data for 1999 unless noted Source: NHLBI 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases

96. Age-Adjusted Death Rates for Stroke by Country and Sex, Ages 35-74, 1999 Age-Adjusted to European Standard Data for 1999 unless noted Source: NHLBI 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases

97. Change in Age-Adjusted Death Rates for Coronary Heart Disease by Country and Sex, Ages 35-74, 1990-1999 Age-Adjusted to European Standard Latest data year note in parentheses Source: NHLBI 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases Men Women

98. Change in Age-Adjusted Death Rates for Stroke by Country and Sex, Ages 35-74, 1990-1999 Age-Adjusted to European Standard Latest data year note in parentheses Source: NHLBI 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases Men Women

99. Migrant Studies Ni-Hon-San Study showed Japanese living in Japan to have the lowest cholesterol levels and lowest rates of CHD, those living in Hawaii to have intermediate rates for both, and those living in San Francisco to have the highest cholesterol levels and CHD incidenceNi-Hon-San Study showed Japanese living in Japan to have the lowest cholesterol levels and lowest rates of CHD, those living in Hawaii to have intermediate rates for both, and those living in San Francisco to have the highest cholesterol levels and CHD incidence

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

101. Approaches to Primary and Secondary Prevention of CVD Primary prevention involves prevention of onset of disease in persons without symptoms.Primary prevention involves prevention of onset of disease in persons without symptoms. Primordial prevention involves the prevention of risk factors causative o the disease, thereby reducing the likelihood of development of the disease.Primordial prevention involves the prevention of risk factors causative o the disease, thereby reducing the likelihood of development of the disease. Secondary prevention refers to the prevention of death or recurrence of disease in those who are already symptomaticSecondary prevention refers to the prevention of death or recurrence of disease in those who are already symptomatic

102. Risk Factor Concepts in Primary Prevention Nonmodifiable risk factors include age, sexc, race, and family history of CVD, which can identify high-risk populationsNonmodifiable 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.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.Physiological risk factors include hypertension, obesity, lipid problems, and diabetes, which may be a consequence of behavioral risk factors.

103. 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.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”.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”. 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.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.Significant reduction in the population burden of CVD can occur only from a “population approach” shifting the entire population distribution to lower levels.

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

105. Population and Community- Wide CVD Risk Reduction Approaches Populations with high rates of CVD are those with Western lifestyles of high-fat diets, physical inactivity, and tobacco use.Populations with high rates of CVD are those with Western lifestyles of high-fat diets, physical inactivity, and tobacco use. Targets of a population-wide approach must be these behaviors causative of the physiologic risk factors or directly causative of CVD.Targets of a population-wide approach must be these behaviors causative of the physiologic risk factors or directly causative of CVD. Requires public health services such as surveillance (e.g.,BFRSS), education (AHA, NCEP), organizational partnerships (Singapore Declaration), and legislation/policy (Anti-Tobacco policies)Requires public health services such as surveillance (e.g.,BFRSS), education (AHA, NCEP), organizational partnerships (Singapore Declaration), and legislation/policy (Anti-Tobacco policies) Activities in a variety of community settings: schools, worksites, churches, healthcare facilities, entire communitiesActivities in a variety of community settings: schools, worksites, churches, healthcare facilities, entire communities

106. A conceptual framework for public health practice in CVD prevention. (From Pearson et al., J Public Health. 2001; 29:69 –78)

107. 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 scoreStanford 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 cholesterolNorth 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 riskStanford 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 smokingMinnesota Heart Health Program (1980-88) showed some increases in physical activity and in women reductions in smoking

108. Materials Developed for US Community Intervention Trials Mass media, brochures and direct mailMass media, brochures and direct mail Events and contestsEvents and contests ScreeningsScreenings Group and direct educationGroup and direct education School programs and worksite interventionsSchool programs and worksite interventions Physician and medical setting programsPhysician and medical setting programs Grocery store and restaurant projectsGrocery store and restaurant projects Church interventionsChurch interventions PoliciesPolicies

109. Individual and High-Risk Approaches Primary Prevention Guidelines (1995) and Secondary Prevention Guidelines (Revised 2001) released by the American Heart Association provide advice regarding risk factor assessment, lifestyle modification, and pharmacologic interventions for specific risk factorsPrimary Prevention Guidelines (1995) and Secondary Prevention Guidelines (Revised 2001) released by the American Heart Association provide advice regarding risk factor assessment, lifestyle modification, and pharmacologic interventions for specific risk factors Barriers exist in the community and healthcare setting that prevent efficient risk reductionBarriers exist in the community and healthcare setting that prevent efficient risk reduction Surveys of CVD prevention-related services show disappointing results regarding cholesterol- lowering therapy, smoking cessation, and other measures of risk reductionSurveys of CVD prevention-related services show disappointing results regarding cholesterol- lowering therapy, smoking cessation, and other measures of risk reduction