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Atherothrombosis Pathophysiology
What Is Atherothrombosis?
The formation of a thrombus on an existing atherosclerotic plaque
Atherothrombosis is a new term recognizing that atherosclerosis (plaque development) and acute thrombosis are integrally related to the presentation of vascular events
A generalized progressive disease of large- and mid-size arteries that affects multiple vascular beds, including cerebral, coronary, and peripheral arteries
The underlying disease leading to myocardial infarction (MI), peripheral arterial disease (PAD), ischemia and many forms of stroke
MI, myocardial infarction; PAD, peripheral artery disease. Fuster V, et al. Vasc Med. 1998;3:231-239.
Rauch U, et al. Ann Intern Med. 2001;134:122-238.
Atherothrombosis* is the Leading Cause of Death Worldwide1
* Atherothrombosis defined as ischemic heart disease and cerebrovascular disease.
1 The World Health Report 2001. Geneva. WHO. 2001.
22.3
19.3
12.6
9.7
9
6.3
0
5
10
15
20
25
30
Atherothrombosis*
Infectious Disease
Cancer
Injuries
Pulmonary Disease
AIDS
Causes of Mortality (%)
Atherothrombosis Significantly Shortens Life
Analysis of data from the Framingham Heart Study.
Peeters A, et al. Eur Heart J. 2002;23:458-466.
Atherothrombosis reduces life expectancy by around 8-12 years in patients aged over 60 years1
Average Remaining Life Expectancy at Age 60 (Men)
0
4
8
12
16
20
Healthy
Years
History of AMI
-9.2 years
History of
Cardiovascular Disease
-7.4 years
History of Stroke
-12 years
3.2 Million Hospital Admissions
Coronary
Atherosclerosis
Acute Myocardial Infarction
1,153,000
Admissions
829,000 Admissions
Hospitalizations in the US Due to Vascular Disease
Cerebrovascular Disease
961,000 Admissions
Vascular Disease
Other Ischemic Heart Disease
280,000 Admissions
Popovic JR, Hall MJ. Advance Data. 2001;319:1-20.
Preventable Deaths
Approximately 57,000 deaths could be avoided each year in the US if patients were given appropriate care.
National Committee for Quality Assurance. Washington, DC 2003.
Cervical-cancer screening
Prenatal care
?-blocker treatment
Breast-cancer screening
Smoking cessation
Cholesterol management
Diabetes care
High-blood pressure control
* Based on data from the ARIC study of the National Heart, Lung, and Blood Institute, 1987-1994. Includes Americans hospitalized with definite or probable MI or fatal CHD, not including silent MIs. ACS, acute coronary syndrome; MI, myocardial infarction; ARIC, Atherosclerotic Risk in Communities, CHD, coronary heart disease. American Heart Association. Heart Disease and Stroke Statistics—2003 Update.
Epidemiology of ACS in the United States
Single largest cause of death
515,204 US deaths in 2000
1 in every 5 US deaths
Incidence
1,100,000 Americans will have a new or recurrent coronary attack each year and about 45% will die*
550,000 new cases of angina per year
Prevalence
12,900,000 with a history of MI, angina, or both
Epidemiology of Stroke in the United States
Prevalence
4.7 million cases
Incidence
700,000 new or recurrent strokes each year
Morbidity/mortality
Third leading cause of death
1 of every 14 deaths (?168,000 deaths)
Stroke: a leading cause of long-term disability
American Heart Association. Heart Disease and Stroke Statistics—2003 Update.
Peripheral Arterial Disease
PAD affects 12% of the adult population1,2
20% of the population aged >70
Associated with 6-fold increase in CV mortality3
Underrecognized and undertreated4
Measurement simple, inexpensive, and noninvasive
Appropriate for risk assessment and screening
Patients at high risk need aggressive risk-factor modification and antiplatelet drugs4
PAD, peripheral artery disease; CV, cardiovascular.
1 Nicolaides AN. Symposium. Nov. 1997. 2 Hiatt WR, et al. Circulation. 1995; 91:1472-1479.
3 Criqui MH, et al. N Engl J Med. 1992; 326:381-386. 4 Hirsch AT, et al. JAMA. 2001;286:1317-1324.
Diabetes: Impact in United States
12 million people with diabetes1
Diabetes is the 5th leading cause of death1
Half of diabetic patients will experience kidney failure1
Diabetes is the leading cause of new adult cases of blindness2
Direct and indirect diabetes costs were estimated at $132 billion1 in 2002
1 American Diabetes Association. Diabetes Care. 2003;26:917-932.
2 Juvenile Diabetes Research Foundation International. Diabetes Figures, http://www.jdrf.org.
Cerebral
Ischemic stroke
Transient ischemic attack
Cardiac
Myocardial infarction
Angina pectoris (stable, unstable)
Peripheral Arterial Disease
Critical limb ischemia, claudication
Clinical Manifestations of Atherothrombosis
Overlap of Vascular Disease in Patients With Atherothrombosis
PAD, peripheral artery disease.
Adapted from TransAtlantic Inter-Society Consensus Group. J Vasc Surg. 2000;31:S16.
Coronary Disease
PAD
12%
33%
15%
5%
14%
13%
8%
Cerebral Disease
Coronary Disease
PAD
19%
30%
25%
4%
12%
7%
3%
Cerebral Disease
CAPRIE
Aronow & Ahn
Common Underlying Atherothrombotic Disease Process
MI, myocardial infarction; PAD, peripheral arterial disease; CV, cardiovascular.
Ness J, et al. J Am Geriatr Soc. 1999;47:1255-1256.
Schafer AI. Am J Med. 1996;101:199-209.
Atherothrombotic Events (MI, Stroke, or CV Death)
Plaque Rupture
Platelet Adhesion, Activation, and Aggregation
Thrombus Formation
MI
Atherothrombotic Stroke
PAD
Unstable Angina
Risk of a Second Atherothrombotic Event
* Death documented within 1 hour of an event attributed to CHD.
Note:This chart is based on epidemiologic data and is not intended to provide a direct basis for comparison of risks between event categories.
MI, myocardial infarction; TIA, transient aschemic attack, PAD, peripheral artery disease.
Adult Treatment Panel II. Circulation. 1994;89:1333-1363.
Kannel, WB. J Cardiovasc Risk. 1994;1:333-339.
Wilterdink, JI, et al. Arch Neurol. 1992;49:857-863. Crique, MH, et al. N Engl J Med. 1992;326:381-386.
Unstable angina MI
Ischemic stroke/TIA
Critical leg ischemia
Intermitent claudication
CV death
ACS
Atherosclerosis
Stable angina/ Intermittent claudication
Atherothrombosis: A Generalized and Progressive Process
Thrombosis
Adapted from Libby P. Circulation. 2001;104:365-372.
Atherothrombosis: Thrombus Superimposed on Atherosclerotic Plaque
Adapted from Falk E, et al. Circulation. 1995;92:657-671.
Characteristics of Unstable and Stable Plaque
Thin fibrous cap
Inflammatory cells
Few SMCs
Eroded endothelium
Activated macrophages
Thick fibrous cap
Lack of inflammatory cells
Foam cells
Intact endothelium
More SMCs
Libby P. Circulation. 1995;91:2844-2850.
Unstable
Stable
Plaque Rupture
Andrew Farb, MD by permission.
Risk Factors for Plaque Rupture
Impaired Fibrinolysis
Fibrinogen
Diabetes Mellitus
Cholesterol
Smoking
Cap Fatigue
Atheromatous Core (size/consistency)
Cap Inflammation
Systemic Factors
Local Factors
Homocysteine