1. EPIDEMIOLOGY OF CARDIOVASCULAR DISEASE (CVD) Public Health February 17, 2005 BETTINA PIKO, M.D., Ph.D.

2. „Cardiovascular disease has the same meaning for health care today as the epidemics of centuries had for medicine in earlier times: 50% of the population in developed countries die of cardiovascular disease” (Pál Kertai) Someone has a heart attack every two minutes (British Heart Foundation)

3. Public Health Significance - Leading cause of mortality in developed countries and a rising tendency in developing countries (disease of civilization)- Leading cause of mortality in developed countries and a rising tendency in developing countries (disease of civilization) - A major impact on life expectancy- A major impact on life expectancy - Significantly contributes to morbidity and death rates in the middle aged population: potential life years lost, common cause of premature death, labor force (economic costs), family life- Significantly contributes to morbidity and death rates in the middle aged population: potential life years lost, common cause of premature death, labor force (economic costs), family life - Morbidity: nearly 30% of all disability cases- Morbidity: nearly 30% of all disability cases - Contributes to deterioration of the quality of life- Contributes to deterioration of the quality of life

4. Types of Cardiovascular Disease - Coronary heart disease (CHD, ischemic heart disease, heart attack, myocardial infarction, angina pectoris)- Coronary heart disease (CHD, ischemic heart disease, heart attack, myocardial infarction, angina pectoris) - Cerebrovascular disease (stroke, TIA, transient ischemic attack)- Cerebrovascular disease (stroke, TIA, transient ischemic attack) - Hypertensive heart disease- Hypertensive heart disease - Peripheral vascular disease- Peripheral vascular disease - Heart failure- Heart failure - Rheumatic heart disease (streptococcal infection)- Rheumatic heart disease (streptococcal infection) - Congenital heart disease- Congenital heart disease - Cardiomyopathies- Cardiomyopathies

5. Tasks of Cardiovascular Epidemiology - Detection of the occurrence and distribution of CVD in populations, surveillance, monitoring, trends of changes- Detection of the occurrence and distribution of CVD in populations, surveillance, monitoring, trends of changes - Study of the natural history of CVD- Study of the natural history of CVD - Formulation and testing of etiological hypotheses (risk factors)- Formulation and testing of etiological hypotheses (risk factors) - Contribution to the development of cardiovascular prevention programs and the measurement of their effectiveness- Contribution to the development of cardiovascular prevention programs and the measurement of their effectiveness

6. Parts of Cardiovascular Epidemiology 1., Descriptive epidemiology:1., Descriptive epidemiology: = Describing distribution of cardiovascular disease by means of certain characteristics such as : PERSON (i.e., age, gender, ethnicity) TIME and PLACE= Describing distribution of cardiovascular disease by means of certain characteristics such as : PERSON (i.e., age, gender, ethnicity) TIME and PLACE 2., Analytic epidemiology2., Analytic epidemiology = Analyzing relationships between CVD and risk factors (which elevate the probability of a disease at population level), risk model and multicausal developments= Analyzing relationships between CVD and risk factors (which elevate the probability of a disease at population level), risk model and multicausal developments 3., Experimental epidemiology/Interventions3., Experimental epidemiology/Interventions = Strategies of cardiovascular prevention (primordial, primary, secondary, tertiary; individual and community levels)= Strategies of cardiovascular prevention (primordial, primary, secondary, tertiary; individual and community levels)

7. Descriptive Epidemiology I. Distribution Patterns in the World In the world: CVD deaths account for one third of all deaths (25-50% depending on the level of economic development) among which 50%: coronary deathsIn the world: CVD deaths account for one third of all deaths (25-50% depending on the level of economic development) among which 50%: coronary deaths CVD made up 16.7 million of global deaths in 2002, among which 7 million due to coronary heart disease, 6 million due to strokeCVD made up 16.7 million of global deaths in 2002, among which 7 million due to coronary heart disease, 6 million due to stroke Distribution of types of CVD in global deaths :Distribution of types of CVD in global deaths : Global cardiovascular deaths in 2002: 16.7 millionGlobal cardiovascular deaths in 2002: 16.7 million among which: coronary heart disease 7.2 million > stroke 6.0 million > 0.9 million hypertensive heart disease > 0.4 million inflammatory heart disease > 0.3 million rheumatic heart disease > 1.9 million other CVDamong which: coronary heart disease 7.2 million > stroke 6.0 million > 0.9 million hypertensive heart disease > 0.4 million inflammatory heart disease > 0.3 million rheumatic heart disease > 1.9 million other CVD

8. Descriptive Epidemiology II. AGE Question: What is the relative amount of CVD in death rates in different age groups?Question: What is the relative amount of CVD in death rates in different age groups? - Early lesions of blood vessel, atherosclerotic plaques: around 20 years - adult lifestyle patterns usually start in childhood and youth (smoking, dietary habits, sporting behavior, etc.)- Early lesions of blood vessel, atherosclerotic plaques: around 20 years - adult lifestyle patterns usually start in childhood and youth (smoking, dietary habits, sporting behavior, etc.) - Increase in CVD morbidity and mortality: in age-group of 30-44 years- Increase in CVD morbidity and mortality: in age-group of 30-44 years - Premature death (<64 years of age, or 25-64 years): in the elderly population more difficult to interpret death rate due to multiple ill health causes- Premature death (<64 years of age, or 25-64 years): in the elderly population more difficult to interpret death rate due to multiple ill health causes

9. 4,6% 11,4% 22,5% 61,5% 32,7% 26,9% 26,0% 14,0% 55,8% 24,6% 14,9% 4,7% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1-24 yrs25-64 yrs>65 yrs PROPORTION OF MORTALITY IN DIFFERENT AGE-GROUPS (MEN) external others cancer CVD

10. 7,3% 17,7% 35,0% 40,0% 31,3% 36,5% 24,0% 8,2% 64,7% 12,2% 18,3% 4,8% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 1-24 yrs25-64 yrs >65 yrs PROPORTION OF MORTALITY IN DIFFERENT AGE-GROUPS (WOMEN) external others cancer CVD

11. Descriptive Epidemiology III. SEX Question: What is the relative amount of CVD in death rates in women and men?Question: What is the relative amount of CVD in death rates in women and men? - Widespread idea: CVD is often thought to be a disease of middle-aged men.- Widespread idea: CVD is often thought to be a disease of middle-aged men. - Cardiovascular mortality (fatal cases) are more common among men. However, CVD affect nearly as many women as men, albeit at an older age- Cardiovascular mortality (fatal cases) are more common among men. However, CVD affect nearly as many women as men, albeit at an older age - Women: special case (WHO, 2004)- Women: special case (WHO, 2004) a., Higher risk in women than men (smoking, high triglyceride levels)a., Higher risk in women than men (smoking, high triglyceride levels) b., Higher prevalence of certain risk factors in women (diabetes mellitus, depression)b., Higher prevalence of certain risk factors in women (diabetes mellitus, depression) c., Gender-specific risk factors (risks for women only) (oral contraceptives, hormone replacement therapy, polycystic ovary syndrome)c., Gender-specific risk factors (risks for women only) (oral contraceptives, hormone replacement therapy, polycystic ovary syndrome)

12. SDR, coronary heart disease in selected European countries by gender, 0-64 yrs, per 1000000

13. Descriptive Epidemiology IV. ETHNICITY Question: What is the relative amount of CVD in death rates in different ethnic groups?Question: What is the relative amount of CVD in death rates in different ethnic groups? - In the US: increased cardiovascular disease deaths in African-American and South-Asian populations in comparison with Whites- In the US: increased cardiovascular disease deaths in African-American and South-Asian populations in comparison with Whites - Increased stroke risk in African-American, some Hispanic American, Chinese, and Japanese populations- Increased stroke risk in African-American, some Hispanic American, Chinese, and Japanese populations - Migration: Ni-Hon-San Study: Japanese living in Japan had the lowest rates of CHD and cholesterol levels, those living in Hawaii had intermediate rates for both, those living in San Francisco had the highest rates for both- Migration: Ni-Hon-San Study: Japanese living in Japan had the lowest rates of CHD and cholesterol levels, those living in Hawaii had intermediate rates for both, those living in San Francisco had the highest rates for both

14. Descriptive Epidemiology V. TIME and PLACE Question: What is the relative amount of CVD in different geographical places? What are the time trends? International and regional characteristics of distributionQuestion: What is the relative amount of CVD in different geographical places? What are the time trends? International and regional characteristics of distribution SDR: Standardized Death RateSDR: Standardized Death Rate Direct mode of standardization, using the age distribution of a hypothetical European standard populationDirect mode of standardization, using the age distribution of a hypothetical European standard population Premature death rates for comparison purposes (<64 years of age)Premature death rates for comparison purposes (<64 years of age)

15. Descriptive Epidemiology VI. World Trends Developed countries: decreasing tendencies (e.g, USA: 30% between 1988-98, Sweden: 42%)Developed countries: decreasing tendencies (e.g, USA: 30% between 1988-98, Sweden: 42%) - improvement of lifestyle factors, for example, a decrease of smoking and a higher level of health consciousness in many developed countries- improvement of lifestyle factors, for example, a decrease of smoking and a higher level of health consciousness in many developed countries - better diagnostic and therapeutic procedures (e.g., bypass surgeries, hypertension screening, pharmacological treatment of hypertension and hypercholesterinaemia, access to health care)- better diagnostic and therapeutic procedures (e.g., bypass surgeries, hypertension screening, pharmacological treatment of hypertension and hypercholesterinaemia, access to health care) Developing countries: increasing tendenciesDeveloping countries: increasing tendencies - increasing longevity, urbanization, and western type lifestyle- increasing longevity, urbanization, and western type lifestyle

16. Descriptive Epidemiology VII. International Comparisons Aims:Aims: a., Where are the rates higher or lower?a., Where are the rates higher or lower? b., Interpretation of time trendsb., Interpretation of time trends c., Inequalities in cardiovascular deathc., Inequalities in cardiovascular death

17. Cardiovascular deaths in Europe (SDR, 2000)

18. SDR, diseases of circulatory system in Western Europe, 0-64 yrs, per 1000000 EU-15 average United Kingdom Switzerland Spain Netherlands Italy Greece France Finland Denmark Austria

19. SDR, diseases of circulatory system in Eastern Europe, 0-64 yrs, per 1000000 EU-15 average (MSs prior 1.5.2004) Slovakia Russian Federation Romania Hungary Croatia

20. SDR, diseases of circulatory system in Hungary, 0-64 yrs, per 1000000 Finland Hungary EU-15average

21. Analytic Epidemiology I. Role of Risk Factors Over 300 risk factors have been associated with coronary heart disease, hypertension and strokeOver 300 risk factors have been associated with coronary heart disease, hypertension and stroke Approx. 75% of CVD can be attributed to conventional risk factorsApprox. 75% of CVD can be attributed to conventional risk factors Risk factors of great public health significance:Risk factors of great public health significance: - high prevalence in many populations- high prevalence in many populations - great independent impact on CVD risk- great independent impact on CVD risk - their control and treatment result in reduced CVD risk- their control and treatment result in reduced CVD risk Developing countries: double burden of risks (problems of undernutrition and infections + CVD risks)Developing countries: double burden of risks (problems of undernutrition and infections + CVD risks)

22. Analytic Epidemiology II. Classification of Risk Factors Major modifiable risk factors -High blood pressure -Abnormal blood lipids -Tobacco use -Physical inactivity -Obesity -Unhealthy diet -Diabetes mellitus Other modifiable risk factors -Low socioeconomic status -Mental ill health (depression) -Psychosocial stress -Heavy alcohol use -Use of certain medication -Lipoprotein(a) Non-modifiable risk factors -Age -Heredity or family history -Gender -Ethnicity or race ”Novel” risk factors -Excess homocysteine in blood -Inflammatory markers (C- reactive protein) -Abnormal blood coagulation (elevated blood levels of fibrinogen)

23. Analytic Epidemiology III. Hypertension - Systolic blood pressure >140 Hgmm and/or a diastolic blood pressure > 90 Hgmm- Systolic blood pressure >140 Hgmm and/or a diastolic blood pressure > 90 Hgmm - Free of clinical symptoms for many years (screening)- Free of clinical symptoms for many years (screening) - In most countries, up to 30 percent of adults suffering, increasing with age in civilized countries- In most countries, up to 30 percent of adults suffering, increasing with age in civilized countries - Positive family history- Positive family history - Dietary habits (a high intake of salt, processed food, low levels of water hardness, high thyramine content of food, alcohol use)- Dietary habits (a high intake of salt, processed food, low levels of water hardness, high thyramine content of food, alcohol use) - Modern lifestyle (increased sympathetic activity, psychosocial stress, leading position in job)- Modern lifestyle (increased sympathetic activity, psychosocial stress, leading position in job)

24. Analytic Epidemiology IV. Rheumatic Fever and Rheumatic Heart Disease Development: Rheumatic fever usually follows an untreated beta-haemolytic streptococcal throat infection in childrenDevelopment: Rheumatic fever usually follows an untreated beta-haemolytic streptococcal throat infection in children As a consequence, the heart valves are permanently damaged which may progress to heart failureAs a consequence, the heart valves are permanently damaged which may progress to heart failure Today mostly affects children in developing countries, linked to poverty, inadequacy of health care accessToday mostly affects children in developing countries, linked to poverty, inadequacy of health care access Occurrence: 12 million people currently affected by rheumatic fever and RHD, two-thirds are children (5-15 years), for example: approx. 1 000 000 in Sub-Saharan Africa, 700 000 in South-Central Asia, 176 000 in China, 150 000 in North Africa, 40 000 in Eastern Europe (!)Occurrence: 12 million people currently affected by rheumatic fever and RHD, two-thirds are children (5-15 years), for example: approx. 1 000 000 in Sub-Saharan Africa, 700 000 in South-Central Asia, 176 000 in China, 150 000 in North Africa, 40 000 in Eastern Europe (!)

25. Analytic Epidemiology V. Abnormal Blood Lipids - Se cholesterol: structure and functioning of blood vessels, atherosclerotic plaques- Se cholesterol: structure and functioning of blood vessels, atherosclerotic plaques - Altering functions of cholesterol fractions (LDL: risk, HDL: protection)- Altering functions of cholesterol fractions (LDL: risk, HDL: protection) - Estrogen: tends to raise HDL-cholesterol and lower LDL-cholesterol, protection for women in reproductive age- Estrogen: tends to raise HDL-cholesterol and lower LDL-cholesterol, protection for women in reproductive age - Partially genetic determination of metabolism, partially dependent of nutrition (egg, meats, dairy products)- Partially genetic determination of metabolism, partially dependent of nutrition (egg, meats, dairy products)

26. Current Recommended Lipid Levels European guidelines US guidelines Total cholesterol<5.0 mmol/l<240 mg/dl (6.2 mmol/l) LDL-cholesterol<3.0 mmol/l<160 mg/dl (3.8 mmol/l) HDL-cholesterol>=1.0 mmol/l (men) >=1.2 mmol/l (women) >=40 mg/dl (1 mmol/l) Triglycerides (fasting)<1.7 mmol/l<200 mg/dl (2.3 mmol/l)

27. Analytic Epidemiology VI. Tobacco Use - The link between smoking and CVD (mainly CHD) was identified in 1940- The link between smoking and CVD (mainly CHD) was identified in 1940 - Greatest risk: initiation < 16 years- Greatest risk: initiation < 16 years - Passive smoking: additional risk- Passive smoking: additional risk - Women smokers: are at higher risk of CHD and CVD than male smokers- Women smokers: are at higher risk of CHD and CVD than male smokers - Several mechanisms: damages the endothelium lining, increases atherosclerotic plaques, raises LDL and lowers HDL, promotes artery spasms, raises oxigen demand of the heart muscle- Several mechanisms: damages the endothelium lining, increases atherosclerotic plaques, raises LDL and lowers HDL, promotes artery spasms, raises oxigen demand of the heart muscle - Nicotine accelerates the heart rate (RR), and raises blood pressure- Nicotine accelerates the heart rate (RR), and raises blood pressure

28. Analytic Epidemiology VII. Physical Inactivity - Regular physical activity: protective factor- Regular physical activity: protective factor - Intensity and duration (150 minutes/week intermediate or 60 minutes/week heavy)- Intensity and duration (150 minutes/week intermediate or 60 minutes/week heavy) - Modernization, urbanization, mechanized transport: sedentary lifestyle (60% of global population)- Modernization, urbanization, mechanized transport: sedentary lifestyle (60% of global population) - Raises CVD risk and also the development of other risk factors (glucose metabolism, diabetes mellitus, blood coagulation, obesity, high blood pressure, worsening lipid profile)- Raises CVD risk and also the development of other risk factors (glucose metabolism, diabetes mellitus, blood coagulation, obesity, high blood pressure, worsening lipid profile) - Physical activity: helps reduce stress, anxiety and depression- Physical activity: helps reduce stress, anxiety and depression

29. Analytic Epidemiology VIII. Obesity, Diabetes Mellitus, Unhealthy Diet - Body Mass Index: > 25: overweight, > 30: obesity- Body Mass Index: > 25: overweight, > 30: obesity - A modern ”epidemic”: More than 60% of adults in the US are overweight or obese, in China: 70 million overweight people- A modern ”epidemic”: More than 60% of adults in the US are overweight or obese, in China: 70 million overweight people - Elevates the risk of both CVD and diabetes mellitus- Elevates the risk of both CVD and diabetes mellitus - Diabetes mellitus: damages both peripheral and coronary blood vessels- Diabetes mellitus: damages both peripheral and coronary blood vessels -Unhealthy diet: low fruit and vegetable, fiber content, and high saturated fat intake, refined sugar-Unhealthy diet: low fruit and vegetable, fiber content, and high saturated fat intake, refined sugar

30. Analytic Epidemiology IX. Psychological and social factors - Psychological factors (Type A behavior, hostility)- Psychological factors (Type A behavior, hostility) - Depression and CVD: bidirectional link- Depression and CVD: bidirectional link a., depression may increase the risk of CVD and worsen recovery processa., depression may increase the risk of CVD and worsen recovery process b., CVD may induce depressionb., CVD may induce depression - Low socioeconomic status (SES):- Low socioeconomic status (SES): a., in developed countries: less educated and lower SES groups (accumulation of risk factors)a., in developed countries: less educated and lower SES groups (accumulation of risk factors) b., in developing countries: more educated and higher SES groups (western lifestyle)b., in developing countries: more educated and higher SES groups (western lifestyle)

31. Cardiovascular Prevention I. Primordial: Social, legal and other (often nonmedical) activities which may lead to a lowering of risk factors (e.g., socioeconomic development, smoke-free restaurants)Primordial: Social, legal and other (often nonmedical) activities which may lead to a lowering of risk factors (e.g., socioeconomic development, smoke-free restaurants) Primary: Controlling risk factors contributing to CVD (health education programs, anti-smoking campaign, sports programs, nutrition counselling, regular check of blood pressure and certain blood parameters, e.g., cholesterol, blood lipids, glucose)Primary: Controlling risk factors contributing to CVD (health education programs, anti-smoking campaign, sports programs, nutrition counselling, regular check of blood pressure and certain blood parameters, e.g., cholesterol, blood lipids, glucose) Secondary: Screening and treatment of symptomatic patients, set up personal risk profileSecondary: Screening and treatment of symptomatic patients, set up personal risk profile Tertiary: Cardiovascular rehabilitation, prevention of recurrence of CVD (new heart attack: 5-7 times higher risk among CVD patients)Tertiary: Cardiovascular rehabilitation, prevention of recurrence of CVD (new heart attack: 5-7 times higher risk among CVD patients)

32. Cardiovascular Prevention II. The individual approach (detecting those at greatest risk): lifestyle guidelines (e.g., smoking cessation)The individual approach (detecting those at greatest risk): lifestyle guidelines (e.g., smoking cessation) The population-wide approach: (the whole population, western lifestyle )The population-wide approach: (the whole population, western lifestyle ) Example for community-wide CV prevention programs:Example for community-wide CV prevention programs: - Framingham Heart Study (1948-) Framingham Risk Scoring- Framingham Heart Study (1948-) Framingham Risk Scoring - North-Karelia Project (1972-) Finland- North-Karelia Project (1972-) Finland - Stanford Projects (1972-75, 1980-86) USA- Stanford Projects (1972-75, 1980-86) USA - Minnesota Cardiovascular Health Program (1980-88) USA- Minnesota Cardiovascular Health Program (1980-88) USA - Multiple Risk factor Intervention Trial (1972-79) USA- Multiple Risk factor Intervention Trial (1972-79) USA