Heart Disease: the Epidemic of the 20th Century

• The twentieth century was the first century in which heart disease was the commonest cause of death in the US-

• And it may be the last century In which heart disease was the number one

cause of death in the US! How did it happen?

US HEART DISEASE DEATHS/100,0001900- 1950 115% INCREASE

What Caused the Marked Increase in Heart Disease Deaths from 1900 to the 1960s?

• Americans were living longer due to decreased death from infectious disease and:– Introduction of cigarettes–Changes in the US daily diet–Decreased physical activity

US HEART DISEASE DEATHS/100,0001960-2005 63% DECREASE

Heart Diseasethe Epidemic of the 20th Century

• From 1960 until 2005 US heart disease deaths decreased by 63%

• Cancer deaths decreased by 5%

The Marked Decrease in Heart Disease Deaths since 1965- How Did it Happen?

• Most heart disease deaths are due to coronary heart disease which was rare in 1900, became the commonest cause of death in the 50’s, peaked in the 60’s, and has continued to decline since the mid 60’s

The Marked Decline in CHD Deaths 1965-

How did it happen?• Research- clarified the pathophysiology of

CHD Which led to:• Prevention• Early, accurate diagnosis• Effective therapy

Prevention of CHDThe Identification of Risk Factors

• Risk factor: a personal characteristic (including test findings) that predicts an increased probability of a future disease or condition

• Eg: cigarette smoking predicts an increased probability of lung cancer in the future

Prevalence of Coronary Heart Disease by Age and Sex in the U.S. (1988-94)

0%

5%

10%

15%

20%

25-44 45-54 55-64 65-74 75+

Male

Female

Age, years

Per

cen

t of

Pop

ula

tion

Source: National Health and Nutrition Examination Survey

The Ideal Risk Factor

• 1. Associated with a common, serious disease

• 2. A frequent finding• 3. Easily determined• 4. Reversible or treatable• 5. If reversed or treated, the disease is

prevented

Prevention of CHDthe Identification of Risk Factors

• Framingham heart study 1948-• The Seven countries study 1958-70• The Interheart study 1999-2004

The Framingham Study1948-

• Prospective cohort study began in 1948• Citizens in Framingham, Mass were invited to have

a free PE, history,CXR, EKG and lab tests• Subjects were re-evaluated every two years. They

were not treated; This was not a clinical trial• Personal characteristics of those who developed

CHD or stroke during F/U were• compared to those who remained well

The Framingham Study 1948-Identification of CHD Risk Factors

• Advanced age• Male sex• Diabetes• Elevated cholesterol• Hypertension • Cigarette smoking• Physical inactivity

Seven Countries Study1958-1970

• The link between diet, serum cholesterol and coronary artery disease

Seven Countries Study1958-1970

Prospective cohort study of 11,575 healthy men in seven countries.

They found that the following varied considerably among the countries:

• Diet: esp the amount of sat. fat• Serum cholesterol levels • Death rates due to CHD

Seven Countries Study Findings

• As % of saturated fat in each country’s diet increased, the average cholesterol increased

• As the average serum cholesterol increased the death rate due to coronary heart disease increased

Seven Countries Study1958-1970

• Lowest cholesterol levels and lowest incidence of coronary artery disease in countries with a “Mediterranean diet”– Low in animal products and sat. fat–Principal fat = olive oil (mono sat)–Rich in legumes, fruit, fish

Risk Factors for CHDa World-wide View

• The Interheart study 1999-2004*

• A global study of CHD in 52 countries in Asia, Europe, Middle East, Africa, Australia, North and S America

• *Yusuf: Lancet,2004

The Interheart Study*

• Case- control study• 15,000 patients with first MI• Compared to 15,000 age, sex matched

healthy controls

• Yusuf: Lancet, 2004

The Interheart Study*

• Risk factor RR AMI• Increased lipids 3.3• Current smoker 2.9• Diabetes 2.4• Hypertension 1.9• Abdom. Obesity 1.6

Yusuf: Lancet,2004

The Interheart Study*

Current smoking, diabetes, hypertension and increased lipids accounted for 75% of the cases of myocardial infarction

RR with all 4 risk factors = 42 * Yusuf: lancet,2004

The Interheart Study*

Results consistent:• Men and women• Old and young• Different countries and continents• Different ethnic groups

Risk Factors for Coronary Heart Disease

• Reversible Irreversible• Increased LDL Advanced age• Decreased HDL Male sex• Cigarette Smoking Positive family Hx• Hypertension Diabetes• Estrogen, OCA Type A (?)• Physical Inactivity Stress (???)• Abdominal obesity

First Attempt at Primary Prevention ?

“Walking is man’s best medicine” Hippocrates 460BC-377BC

Cholesterol: LDL vs HDL

LDL Cholesterol – Increased LDL levels Lead to Increased

atherosclerotic plaqueHDL Cholesterol

Increased HDL levels are associated with a lower incidence of cardiovascular disease

LDL Cholesterol Treatment Guidelines

• National Cholesterol Education Program III Recommendations, 2003

• Patient Goal LDL Drug RX• CHD or Equiv <100 >130• 2+ Risk Factors <130 130-160• 0-1 Risk Factors <160 190

Dietary intervention to Lower Cholesterol MRFIT 1973-81

• Men and their wives attended weekly small group sessions. Dietary advice by nutritionists, supplemented by cardiologists, psychologists.

• Used food models, sample menus• Results at 6 years: special care 7.2%

reduction, usual care 5.2%

LDL Cholesterol Lowering Drugs-Statins

• Decrease production of cholesterol by the liver, and increase removal of LDL

• Serious side effects:– Liver damage: rare–Muscle damage: very rare

Hypertension Treatment Guidelines*

• Normal BP <120/80• Pre-Hypertension 120-139/80-89• Hypertension >140/90

• *Joint National Committee on Prevention, Detection. And Treatment of High Blood Pressure (JNC VII, 2003)

Prevalence of Hypertension (SBP>140 or DBP >90) by Age*

• AGE PREVALENCE• 20-34 10%• 35-44 20%• 45-54 36%• 55-64 55%• 65-74 67%• 75+ 70%

*American Heart Association statistics, 2009

Hypertension in US Adults (>18)1988 -2008*

Year % HBP** % Controlled***

1988-94 24% 27%

1999-00 29% 31%

2003-04 29% 33%

2007-08 29% 50%

* Egan: JAMA May 30, 2010

** HBP = systolic> 140 and diastolic >90

***Controlled = systolic,140 and diastolic < 90

Importance of Smoking Cessation

• Patients who survive a myocardial infarction and who are clinically stable but continue to smoke have a 6-fold increased risk of dying during the next 5 years.

What Caused the Decrease in CHD Deaths in the Late 1960s?

Prevention

– Smoking: Surgeon General’s report–Diet: recognition of cholesterol as a risk

factor–Hypertension: introduction of effective

drugs

Healthy life style1988 vs 2006*

US adults ages 40 to 74 1988 2006•Obese 28% 36%•Smokers 27% 26%•Regular Exercise 53% 43%•Healthy Diet 42% 26%

• * King: Am J Med, 2009

The Interheart Study*

• Negative risk factors RR AMI**• Daily fruits/vegs .7• Physical activity .9• Alcohol .9

* Yusuf: lancet,2004• ** Adjusted relative risk

LDL Cholesterol

• Approximately 50% of Adult Americans Have High LDL Cholesterol Levels – Over 100 Million People

• High LDL cholesterol is almost always associated with cardiovascular disease

American Heart Association: Heart Disease and Stroke Statistics, 2006

Aspirin to Prevent Heart Attack and Stroke

• Who Should Take Aspirin?

• In the Absence of Contraindications:– Patients With Known Cardiovascular

Disease – Adults with Diabetes– Those with Cardiovascular Risk Factors–Men age 50+–Women post Menopause

Low HDL Cholesterol*

• Levels Below 40 in Men and Below 50 in Women are Associated with Increased Risk of Death From Cardiovascular Disease.

• Increasing HDL Levels Decreases the Risk of Cardiovasacular Disease

• Average HDL in Us Adults = 51 *Ashen and Blumenthal NEJM, 2005

UA Post MI PTCA CABG Primary

0

10

-10

-20

-30

-40

-50

-60

%R

isk

Death

MI

12 Trials 186,800 patient-years follow-up

NEJM 1995;333:1301 Lancet 1994;344:1383 Circulation 1995;91:2528

Statins in Cardiovascular DiseaseStatins in Cardiovascular Disease

The Multiple Risk Factor Trial1971-1981*

• Linear relationship between serum cholesterol at baseline and risk of CHD death during 6 year followup

• Cholesterol RR CHD death

• <181 1.0– 182-202 4.7-5.2– 203-220 5.3-5.7– 221-244 5.7-6.3– >245 >6.3 * Stamler: JAMA, 2008

86 studies86 studies670,000 patient-years670,000 patient-years Fuster V, et al. Fuster V, et al. CirculationCirculation. 1993;87:659-675.. 1993;87:659-675.

Aspirin in Cardiovascular DiseaseR

isk

(%)

MIMI Post MIPost MI Unstable Unstable CADCAD PrimaryPrimary angina angina

Death

MI

0

10

−10

−20

−30

−40

−50

−60

Increasing HDL Levels With Life Style Changes*

• Regular exercise• Smoking cessation• Weight control• Moderate alcohol consumption• Decreased dietary fat

*Ashen and Blumenthal NEJM , 2005

Aspirin to Prevent Heart Attack and Stroke

• In 1950, Lawrence Craven reported that one aspirin a day prevents heart attack in men with CHD risk factors

• In 1956, he reported that aspirin also prevents strokes

• No one believed him until the 1970s when randomized clinical trials proved him right

• Now 50 million Americans take aspirin for prevention of heart attack and stroke

Aspirin to Prevent Heart Attack and Stroke

• Major side effect of aspirin is bleeding• In randomized clinical trials the incidence of

major bleeding is the same for 81 mg/day and 162 mg/day:

• 1 to 2 cases per 1000 years of treatment• Dalen: Am J Med, 2007

Aspirin to Prevent Heart Attack and Stroke

• Doses less than 162 mg/d may be ineffective in preventing mi and stroke

• My recommendation: 162 mg/day*

• *Dalen: Am J Med, 2007

Coronary Heart Disease (CHD), 2006*

• Prevalence 18 million

• Deaths/year 425,000

• 70% of CHD Deaths occur outside of hospitals

*American Heart Association statistics, 2009