Cardiovascular Epidemiologyand PreventionNathan D. Wong, PhD, FACC, FAHAProfessor and Director, Heart DiseasePrevention Program, Division ofCardiology, University of California, IrvinePresident, American Society of PreventiveCardiology
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)• CARDIOVASCULAR DISEASE or CVD includes CHD, cerebrovascular disease, peripheral vascular disease, and other cardiac conditions (congenital, arrhythmias, and congestive heart failure)
Definitions (cont.)• 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 stroke
Coronary Heart Disease Stroke 14 4 7 HF* 51 High Blood Pressure 7 17 Diseases of the Arteries OtherPercentage breakdown of deaths from cardiovascular diseases(United States: 2006) * - Not a true underlying cause.Source: NCHS.
16 13.8 14 12.2 Percent of Population 12 9.3 10 8 6 4.8 4 2.2 2 1.2 0.1 0.2 0 20-39 40-59 60-79 80+ Men WomenPrevalence of heart failure by age and sex(NHANES: 2005-2006). Source: NCHS and NHLBI.
700 Discharges in Thousands 600 500 400 300 200 100 0 79 80 85 90 95 00 06 Years Male FemaleHospital discharges for heart failure by sex.(United States: 1979-2006). Source: NHDS/NCHS and NHLBI.Note: Hospital discharges include people discharged alive, deadand status unknown.
Development of AtheroscleroticPlaques Fatty streak Normal Lipid-rich plaque Foam cells Fibrous cap Lipid core Thrombus Ross R. Nature. 1993;362:801-809.
PDAY: Percentage of Right Coronary Artery Intimal Surface Affected With Early Atherosclerosis 30 Raised lesions 30 Men Fatty streaks Women 20 20 10 10 0 0Intimal 15-19 20-24 25-29 30-34 15-19 20-24 25-29 30-34surface 30 White White 30 (%) 20 20 10 10 0 0 15-19 20-24 25-29 30-34 15-1920-2425-2930-34 Black Black Age (y)PDAY= Pathobiological Determinants of Atherosclerosis in Youth.Strong JP, et al. JAMA. 1999;281:727-735.
Most Myocardial Infarctions Are Causedby Low-Grade StenosesPooled 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.
Coronary Remodeling Progression Expansion Compensatory expansion overcome: maintains constant lumen lumen narrows Normal Minimal Moderate Severe vessel CAD CAD CAD(Adapted from Glagov et al.)Glagov et al, N Engl J Med, 1987. Med,
Atherosclerotic Plaque Rupture andThrombus Formation Growth of thrombus Intraluminal thrombus Blood Flow Intraplaque thrombus Lipid pool Adapted from Weissberg PL. Eur Heart J Supplements 1999:1:T13–18
Features of a RupturedAtherosclerotic Plaque • Eccentric, lipid-rich • Fragile fibrous cap • Prior luminal obstruction < 50% • Visible rupture and thrombusConstantinides P. Am J Cardiol. 1990;66:37G-40G.
Vulnerable Versus StableAtherosclerotic Plaques Vulnerable Plaque Lumen Lipid •Thin fibrous cap Fibrous Cap Core •Inflammatory cell infiltrates: proteolytic activity •Lipid-rich plaque Stable Plaque •Thick fibrous cap Lumen Lipid •Smooth muscle cells: Core more extracellular matrix Fibrous Cap •Lipid-poor plaqueLibby P. Circulation. 1995;91:2844-2850.
Correlation of CT angiography of thecoronary arteries with intravascularultrasound illustrates the ability of MDCTto demonstrate calcified and non-calcifiedcoronary plaques (Becker et al., Eur JRadiol 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)
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.
Other Recognized Risk Factors• Obesity: Body Mass Index (BMI) – Weight (kg)/height (m2) – Weight (lb)/height (in2) x 703• Obesity BMI >30 kg/m2 with overweight defined as 25-<30 kg/m 2• Abdominal 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/week
___________________________________________________________ _Lifetime Risk of Coronary Heart Diseasein 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
____________________________________________________________ First Coronary Events: Framingham Study ________________________________________________________ Percent as Specified Event Myocardial Angina Sudden Infarction Pectoris DeathAge Men Women Men Women Men Women35-64 43% 28% 41% 59% 9% 4%65-84 55% 44% 28% 41% 11% 7.4%____________________________________________________________ Framingham Study 44 year follow-up.
Estimated 10-Year CHD Risk in55-Year-Old Adults According to Levelsof Various Risk FactorsFramingham Heart Study A B C D Blood Pressure (mm Hg) 120/80 140/90 140/90 140/90 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 bloodSource: Circulation 1998;97:1837-1847.
Estimated 10-Year Stroke Risk in 55- Year-Old Adults According to Levels of Various Risk FactorsEstimated 10-Year Rate (%) Framingham Heart Study 30 27 25 22.4 19.1 20 14.8 15 10 8.4 5.4 6.3 5 4 3.5 2.6 2 1.1 0 A B C D E F Men Women A B C D E F Systolic BP* 95-105 130-148 130-148 130-148 130-148 130-148 Diabetes No No Yes Yes Yes Yes Cigarettes No No No Yes Yes Yes Prior Atrial Fib. No No No No Yes Yes Prior CVD No No No No No Yes Source: Stroke 1991;22:312-318. *BP in millimeters of mercury (mmHg)
Offspring CVD Risk by Parental CVD Status: Framingham Study Parental CVD <55Risk Ratio men, <65 Women 2.5 2.5 NONE MATERNAL 2 2 PATERNAL 2.2 1.5 1.7 1.7 1.7 1 1 1.0 1.0 0.5 0.5 0 0 Men MEN Women WOMEN Adjusted for: age, total/HDL Chol. ratio, SBP, smoking, diabetes, BMI
Risk imposed by a strong familyhistory of heart attacks varies widelydepending on the burden ofmodifiable risk factors Multivariable Risk
________________________________________________________ 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.”______________________________________________________________ _
Relation of Non-Hypertensive BloodPressure to Cardiovascular DiseaseVasan R, et al. N Engl J Med 2001; 345:1291-1297 10-year Age- Adjusted Cumulative Incidence12% Hazard Ratio* <120/80 mm Hg 120-129/80-84 mm Hg SBP Women Men10% 130-139/85-89 mm Hg 10.1 <120/80 1.0 1.0 8% 120-129 1.5 1.3 7.6 130-139 2.5 1.6 6% 5.8 H.R. adjusted for age, BMI, 4% Cholesterol, Diabetes and 4.4 smoking *P<.001 2.8 2% 1.9 0% Women Men Framingham Study: Subjects Ages 35-90 yrs.
90 82.3 78.8 79.0 Percent of Population With 80 69.1 70.1 74.7 67.6 70 Hypertension 60 52.1 46.5 50 45.4 46.1 40 35.2 30 20 10 0 Awareness Treatment Controlled Total Population NH Whites NH Blacks Mexican AmericansExtent of awareness, treatment and control of high bloodpressure by race/ethnicity (NHANES : 2005-2006).Source: NCHS and NHLBI.
______________________________________________________________ _ 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”
______________________________________________________________ CVD Risk Imposed by ECG-LVH _ Framingham Study 36-yr. Follow-up_______________________________________________________________ Age-adjusted Risk Excess Risk 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
___________________________________________________________ _ 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.” _
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” ______________________________________________________________
Risk of Cardiovascular Events in Diabetics Framingham Study________________________________________________________________ _ Age-adjusted Biennial Rate Age-adjusted Per 1000 Risk RatioCardiovascular Event Men Women Men WomenCoronary Disease 39 21 1.5** 2.2***Stroke 15 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 _
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.
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 inblood lipids, blood pressure, uric acid and carbohydratetolerance.”“It seems reasonable to expect that correction of overweightwill improve the coronary risk problem.”“Avoidance of overweight would seem a desirable goal in thegeneral population if the appalling annual toll from diseaseis to be substantially reduced.”
Risk Factor Sum and Obesity Framingham Study 3 (1971-74) and (1989-93) 2.4 (1971) (1989)Risk Factor Sum Risk factors accumulate with weight gain 1.8 1.2 0.6 0 Q1 Q2 Q3 Q4 Q5 Overall Thin Obese 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
Risk AssessmentCount major risk factors• For patients with multiple (2+) risk factors – Perform 10-year risk assessment• For patients with 0–1 risk factor – 10 year risk assessment not required – Most patients have 10-year risk <10%
What is WJC’s 10-year absoluteriskof fatal/nonfatal MI?• 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 exercisestress test to 91% of his maximum predicted heart rate withoutany abnormal ECG changes. He started on a statin in 2001. But in Sept 2004, he needed urgent coronary bypass surgery.
CHD Risk Equivalents• Risk for major coronary events equal to that in established CHD• 10-year risk for hard CHD >20%Hard CHD = myocardial infarction + coronarydeath
Diabetes as a CHD RiskEquivalent• 10-year risk for CHD ≅ 20%• High mortality with established CHD – High mortality with acute MI – High mortality post acute MI
CHD Risk Equivalents• Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease)• Diabetes• Multiple risk factors that confer a 10- year risk for CHD >20%
Framingham 10-year Total CVDRisk Algorithm (D’Agostino et al2008)
International Comparisons inCVD Morbidity and Mortality• CVD 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)• USA ranks 16th for both men (413) and women (201)
Secular Trends in CHD andStroke 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.• Stroke death rates declined most in Australia, Italy, and France (8-9%), USA about 3%.
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 notedSource: NHLBI 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases
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
Change in Age-Adjusted Death Rates for Coronary Heart Disease by Country and Sex, Ages 35-74, 1990-1999 Men Women •Age-Adjusted to European Standard •Latest data year note in parentheses
Change in Age-Adjusted Death Rates for Stroke by Country and Sex, Ages 35-74, 1990-1999 Men Women •Age-Adjusted to European Standard •Latest data year note in parentheses Source: NHLBI 2002 Chart Book on Cardiovascular, Lung, and Blood Diseases
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 incidence
Pyramid of Risk (Werner et al. Canadian Journal of Cardiology 1998; 14(Suppl) B:3B-10B)
Approaches to Primary and Secondary Prevention of CVD• 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.• Secondary prevention refers to the prevention of death or recurrence of disease in those who are already symptomatic
Risk Factor Concepts inPrimary 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”.• 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.
Expected Shifts in Cholesterol Distributionfrom High-Risk, Population, andCombined Approaches
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.• 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)• Activities in a variety of community settings: schools, worksites, churches, healthcare facilities, entire communities
A conceptual framework for publichealth practice in CVD prevention.(From Pearson et al., J Public Health. 2001; 29:69 –78)
Communitywide CVDPrevention 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
Materials Developed for USCommunity InterventionTrials• Mass media, brochures and direct mail• Events and contests• Screenings• Group and direct education• School programs and worksite interventions• Physician and medical setting programs• Grocery store and restaurant projects• Church interventions• Policies
Individual and High-RiskApproaches• 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 factors• Barriers 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 reduction