“Vulnerable Coronary Plaque” is the topic of today’s discussion, and what we have observed in a meta-analysis of 17 different invasive intravascular ultrasound (IVUS) studies is that every 1% reduction in percent atheroma volume (PAV), which is a measure of plaque burden, is associated with a 20% reduction in cardiovascular events. I call this “The Power of 1,” since when you initially hear this number, it sounds pretty trivial. But a 20% reduced risk of heart attack is much more meaningful.  So saddle up….I’m taking you all down Memory Lane and onto the Oregon Trail for the rest of this discussion (and if you don’t feel like having fun, just skip to the chart at the end)!

An early Core Memory for children of the late 80s was playing the Oregon Trail Computer game.  You would insert the floppy disk, wait several hours for the computer to boot up, remove the floppy disk after encountering the Blue Screen of Death, blow on the floppy disk, re-insert the disk, and then by the following school day you were ready to play!  Even before all of the valuable life lessons gleaned on the trek from Independence, Missouri to the Willamette Valley we were learning PATIENCE and DELAYED GRATIFICATION. 

And then we were faced with tough life questions such as the following:

• Should I pack more beef jerky or buy a spare wagon wheel?
• Should I see if I can shoot the agile and elusive squirrels when hunting, or simply wait for the buffalo?
• Should I ford the river or caulk the wagon and float it? 
• What is dysentery and why did Jeffrey just die from it?

We were building problem-solving skills, building vocabulary, and unwittingly learning about RESILIENCE.  And, quite remarkably, I would sometimes be afflicted with cholera, typhoid fever, a broken leg, and a bad haircut but still survive the journey to the Pacific Coast.  But then on other journeys I would only have a mild bout of the flu before the ominous message “Josh has died” would flash across the screen and ruin my day.

And our bodies are really good at NOT DYING; we are masters of Damage Control.  And one way that we observe this is something called “Glagovian Remodeling.”  When a lipoprotein mailman goes rogue into the arterial wall and kicks off the maladaptive immune response that results in plaque formation, the vessel remodels OUTWARD rather than INWARD.  Inward remodeling would compromise blood flow, so until a threshold of 40% stenosis is reached, the vessel adapts to preserve the diameter of the vessel. 

But, as we know, 2/3 of myocardial infarctions occur in a vessel without any significant degree of stenosis due to a vulnerable plaque rupture.  This is because atherosclerosis is a “disease of the donut.”  Plaque is like mold on a donut; mold is gross, but it takes a lot of mold to encroach into the donut hole.  However, that mold can ruin your life at any time if you mistakenly take a bite out of the nasty donut. 

So although our bodies are very resilient, identifying any moldy plaque is of paramount importance when discussing prevention of coronary events.  Because even a “mild case” of atherosclerosis on paper can lead to a premature end of your proverbial Oregon Trail pilgrimage.  Below is a table that shows some of the high-risk plaque features that can be identified with non-invasive imaging and their associations with clinical events.

Feature	Description	Risk in Clinical Trials
Low-attenuation plaque (LAP)	<30 HU Appears darker since it absorbs less x-rays due to lipid content	5x risk of MACE when >4% in SCOTHEART
High total plaque burden (TPV)	Commonly used threshold is 238.5 mm3	5x risk of MACE from PROMISE 7x risk of MI from SCOTHEART
Fat-attenuation Index (FAI)	Threshold is <-70.1	4.7x risk of MACE from ORFAN
Non-calcified plaque	“Soft plaque” including fibrofatty and necrotic core	Strongest predictor of MACE in ICONIC
Obstructive Disease	>50% stenosis	Even in 1 vessel obstructive disease, 2.2x risk of MACE from CONFIRM
Multivessel Disease	Risk increases with number of vessels involved	From CONFIRM: 2 vessels: 2.9x 3 vessels: 3.5x 4 vessels: 4.7x