vulnerable plaque overview
TRANSCRIPT
#1 killer of human
beings in the 21st century?
Fatal Heart Attack!
What causes heart attack?
Vulnerable Plaque
The short answer is:
What is vulnerable plaque?
Dangerous forms of atherosclerotic plaques
that can rupture or induce thrombosis and
lead to critical disruption of blood flow.
The short answer is:
Everybody has atherosclerosis, the question is who has vulnerable plaque
Sudden Cardiac DeathAcute MI
What Do We Know About Vulnerable Plaque?
Morteza Naghavi, MD
Center for Vulnerable Plaque ResearchUniversity of Texas at Houston
Texas Heart InstituteOctober 2001
Mohammad Madjid, MD Silvio Litovsky, MD Alireza Zarrabi, MDMaziar Azadpour, MD Parsa Mirhaji, MD Cornelius Nwora, MD
Ward Casscells, MD James Willerson, MD
Salute to Pioneers
Carl von Rokitansky (1804-1878)
Rokitansky gave early detailed descriptions of arterial disease. He
is alleged to have performed 30,000
autopsies.
Rokitansky in 1841 championed the Thrombogenic Theory. He proposed that the deposits observed in the inner layer of the arterial wall
derived primarily from fibrin and other blood elements rather than being the result of a purulent process. Subsequently, the atheroma resulted from the
degeneration of the fibrin and other blood proteins as a result of a preexisting crasis of the blood, and finally these deposits were modified toward a pulpy
mass containing cholesterol crystals and fatty globules. This theory came under attack by Virchow
First studies on inflammation of vessels, particularly phlebitis, Started at a time when Cruveilhier2had just stated: La phlebite domine toute la pathologie.3 First a great number of preparatory studies on fibrin, leukocytes, meta-morphosis of blood, published separately. …
Rudolf Virchow 1821-1902
The Father of Cellular Pathology
Virchow appreciates prior works.
Virchow presented his inflammatory theory. He utilized the name of "endarteritis deformans." By this he meant that the atheroma was a product of an inflammatory process within the intima with the fibrous thickening evolved as a consequence of a reactive fibrosis induced by proliferating connective tissue cells within the intima.
Olcott 1931 “plaque rupture”
Leary 1934 “rupture of atheromatous abscess”
Wartman 1938 “rupture-induced occlusion”
Horn 1940 “plaque fissure”
Helpern 1957 “plaque erosion”
Crawford 1961 “plaque thrombosis”
Gore 1963 “plaque ulceration”
Friedman 1964 “macrophage accumulation”
Byers 1964 “thrombogenic gruel”
Chapman 1966 “plaque rupture”
Plaque Fissure in Human Coronary Thrombosis (Abstract) Fed. Proc. 1964, 23, 443 Paris Constantinidis
“The destruction of the hyalinized wall separating lumen from the atheroma was almost always observed to be preceded by or associated with its invasion by lipid containing macrophages.”
Friedman and van den Bovenkamp 1965
Unheralded Pioneers
N Engl J Med 1999
“Atherosclerosis; an inflammatory disease”
Ross R.
Russell Ross
Atherosclerosis; arterial “Response to Injury”
N Engl J Med 1976 Aug 12;295(7):369-77 The pathogenesis of atherosclerosis (first of two parts).Ross R, Glomset JA.
James T. Willerson 1981N Engl J Med 1981 Mar 19;304(12):685-91
Plaque Thrombosis
Erling Falk Michael Davies
Autopsy Series
Thin Fibrous Cap + Large Lipid Core + Dense Macrophage
A culprit ruptured plaque
1981-1990
Seymour GlagovCompensatory enlargement of human atherosclerotic coronary arteries N Engl J Med 1987 May
28;316(22):1371-5
<50% stenosis
Luminal area is not endangered until more than 40% of IEL is destructed and occupied by plaque
Coronary artery disease is a disease of arterial wall disease not lumen.
Angiographic progression of coronary artery disease and the development of myocardial infarction.Ambrose JA, Tannenbaum MA, Alexopoulos D, Hjemdahl-Monsen CE, Leavy J, Weiss M, Borrico S, Gorlin R, Fuster V.
Department of Medicine, New York Cardiac Center, Mount Sinai Medical Center, New York 10029.
Simultaneously, Little et al, Haft et al reported that majority of culprit lesions are found on previously non-critical stenosis plaques.
Conclusion: “Myocardial infarction frequently develops from non-severe lesions.”
J Am Coll Cardiol 1988 Jul;12(1):56-62
Ambrose, Fuster, and colleagues
Angiographically Invisible Plaques
Falk E., Shak P.K., Fuster V. Circulation 1995
Non-stenotic (<75%) plaques cause about 80% of deadly MI
Macrophage- driven MMPs soften plaque cap and prompt it to rupture
P.K. Shah
Peter LibbyAtherosclerosis and its thrombotic complication is governed by immune
cells.
Goran Hansson…
Allard van der Wal
Muller JE, Abela GS, Nesto RW, Tofler GH.
Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier.
J Am Coll Cardiol. 1994 Mar 1;23(3):809-13
James E. Muller 1994
Muller coined the term of “Vulnerable” Plaque
Muller likened Vulnerable Plaques to American nuclear missiles stored underground in Nevada desert where they could be vulnerable to Russians’ long-range missile attack!
•Eroded Plaque
Rupture-prone plaques are not the only type of vulnerable plaque
•Calcium Nodulevan der Wal - Netherlands
Renu Virmani -USA
Thiene - Italy
Kolodgie F., Burk A.P., Farb A., and Virmani R.
“Who is Who” on
www.VP.org
The field of vulnerable plaque is best owed to many known and unknown
scientists who have worked hard to shed light on our way to prevent and
eradicate heart attacks in the future. To see a more complete list please visit:
Natural History ofVulnerable Plaques
Illustrated:
~65%
Percent of stenosis
Frequency of plaques
“Risk” per each plaque
Culprit Risk per each type of Vulnerable Plaque
(Log)
Culprit lesions found in autopsy series of acute MI
Different Types of Plaque Vulnerable to Thrombosis
All
Male
Female
~10% <5% ~20%
50%
Angiography
~70% <5% ~20%
~55% ~20%
<5%
<5% ~20%
Rupture Prone Eroded Calcified NoduleHemorrhage
Positive Remodeling
Fissured /Healed
Natural History of Vulnerable Atherosclerotic Plaques
Ruptured Plaques (~70%)1. Stenotic (~20%)2. Non-stenotic (~50%)
Non-ruptured Plaques (~ 30%)1.Erosion (~20%)2.Calcified Nodule (~5%)3.Others / Unknown (~5%)
Plaque Pathology Responsible for Coronary Thrombotic Death
In summary:
Culprit Plaque; a retrospective terminology
Vulnerable Plaque; a prospective terminology
Vulnerable Plaque = Future Culprit Plaque
Clarification of Terminologies
Rupture-Prone Plaque
Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001
Macrophage
Necrotic Lipid Core
Thin Fibrous Cap
Eroded Plaque
Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001
Fissured / Healed Plaque
Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001
Plaque with a Subluminal Calcified Nodule
Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001
Intra-Plaque Hemorrhage with Intact Cap
Vulnerable Plaque Naghavi et al, Cur Ath Rep 2001
Critically Stenotic but Asymptomatic Plaque
Naghavi et al, Cur Ath Rep 2001Vulnerable Plaque