WHAT MAKES ARTERIES BLOCK OFF?

 

The mythology of the narrow artery

You’ve heard the story numerous times.  It's part of our modern mythology:   

 

 A man (or woman) goes to a doctor with a seemingly minor complaint.  Before he knows it, he’s in the hospital having an angiogram.  It shows a ninety percent (or thereabouts) blockage of a coronary artery.  He ends up having emergency heart surgery. 

  “Thank God they found the blockage and fixed it before I had a heart attack,” he might say afterwards. “Now I’m walking three miles a day, and the doctor told me I have the heart of a twenty-year-old.” 

The teller usually dramatizes the story a little to emphasize the moral: danger lurks; be vigilant.  However, such reports are misleading.  Listeners tend to assume that the narrow artery was about to block off and that reopening it cured him, that good fortune--and, of course, quick thinking by his doctors--saved his bacon. 

 

The truth is the artery would probably have stayed open for years, and while the operation may have relieved some bothersome symptoms, it would have had, at best, a modest effect in preventing future heart problems.

 

The Seductive (and usually Wrongheaded) Logic of the Plumbing Analogy

 

Superficially, coronary artery disease seems easy enough to understand: arteries plug up and damage the heart--like blocked drainpipes, right?   When they plug up you call Roto-Rooter to ream them out. 

 

Don’t be deceived by the apparent straightforwardness of this disease.   Reasoning processes used to explain the behavior of more familiar kinds of tubes--like pipes--are misleading.  Coronary arteries don’t act as common sense might predict.  

 

If sludge or rust accumulated in a pipe in your house and you neglected to do anything about it, the buildup would just get worse and eventually plug things up completely.  If you called Rotor-Rooter to come clean out the pipe, it would probably stay open for years.  It’s natural to think that arteries would behave the same way, that a narrow artery left alone would just get worse but if the obstruction were removed the vessel would stay open for a long time. 

 

Plumbing-think is seductive, and in fact, doctors use it to communicate with their patients.  They take advantage of the apparent similarity of arteries to pipes to make what they do appear logical.  However, while such analogies might be convincing, they fail to reflect a murkier, more complex reality--a reality that will eventually reassert itself.   Arteries are not inert conduits, and the difference between arteries and pipes is the difference between effective and ineffective treatment of coronary artery disease. 

 

The culprit: atherosclerosis

 

To understand why arteries behave differently from drainpipes, you need to know about the process that causes artery blockage, the disease atherosclerosis.  Go back to the plumbing analogy for a moment, and think about what the inside of an old water pipe looks like.  It won’t be smooth and shiny like a new one.  Years of rust and accumulated salts will have corroded and narrowed it.  That’s what the arteries of a person with atherosclerosis look like, but it’s not rust or salts that infiltrates the walls of blood vessels.  The culprit here is cholesterol.  

 

Cholesterol is a normal part of everyone’s blood.  In fact, it’s an essential building block for cell membranes, hormones and other important things.  However, under certain conditions--no one understands the exact trigger--it starts to seep into the walls of arteries (Figure 1).  This is usually a harmless enough process that lightly coats a few arteries without causing problems.  However, sometimes it gets out of hand.  In vulnerable individuals, it can lead to artery narrowing or blockage and eventually damage vital organs.    

 

Tantalizingly, some people’s arteries escape atherosclerosis--their “pipes” remain clean and shiny throughout life.  But for most of us, if we live long enough some cholesterol will seep into the walls of our blood vessels. 

 

Because severely atherosclerotic arteries feel stiff to the touch, atherosclerosis is sometimes referred to as “hardening of the arteries.”  That term is misleading because it implies that hardness is a problem.  To the contrary, you will see that localized softening of the arterial wall is what causes the most havoc.

 

Atherosclerosis begins decades before heart attacks or strokes typically occur.  Pathologists have found streaks of cholesterol in the arteries of persons dying from car accidents in their teens and twenties.  Although it rarely gets bad enough in early adulthood to cause trouble, later in life the process tends to pick up speed.   For people who are prone to atherosclerosis, artery narrowing and blockage can lead to organ damage by the age of forty or fifty years.

 

How a misleading assumption led doctors astray

 

Comparing atherosclerosis to a buildup of rust or sludge in a pipe might be appropriate if the process resulted in a steady and gradual accumulation of inert sediment, which, in fact, was how doctors saw the disease for years.  However, the notion that artery narrowing crept up steadily never jived with the facts.  Practicing doctors knew that severely restricted arteries often stayed open for years and wide-open ones could suddenly and unpredictably block off. The disease just didn’t act like a gradual, accumulative process.  What were they missing?

 

Atherosclerotic buildup is worse in parts of blood vessels that are subject to distortion and hydraulic stress such as bends or branches.  When it concentrates in one area and is large enough to cause a discernible bump on the inside of the artery wall, it’s called a “plaque”. 

 

If a plaque protrudes into an artery channel, it can interfere with blood during times of peak demand.  In the heart, this causes a characteristic chest-discomfort during exertion, called angina.   Because narrowings cause angina and are easily visible on X-rays, plaques that cause such choke points they have dominated the attention of doctors for years (Figure 2).  Doctors paid little attention to plaques that did not cause narrowing.  

Several decades ago, doctors made an unfortunate assumption about narrow arteries that set back progress in heart disease for years.  They presumed, without proof, that the plaques that caused the narrowings they saw on X-rays were the ones that caused heart attacks.  They thought that, like old rusty pipes, such constrictions just got worse until they blocked off completely.  The risk of a plaque was simply a matter of how much it narrowed the artery.  Tight narrowings were thought to be dangerous because only a small amount of further growth seemed to be necessary to cause complete stoppage.  Minor narrowings were less significant because it seemed that years would have to pass for them to progress to complete blockage.

 

The notion that the danger of atherosclerotic build-up is simply a matter of how much it narrows arteries was the basis for a massive mobilization of medical resources devoted to finding such restrictions and surgically reopening them.  The appeal of that approach was that it was relatively easy to diagnose coronary artery narrowings--they interfered with blood flow during exertion, caused chest pains and produced characteristic findings on treadmill tests.  With the means to find them and the tools in hand to fix them, the dominant mentality became “search and destroy.” 

 

In fact, artery-opening procedures seemed like a blessing for patients whose activities were limited by exertional chest pains.  It was gratifying for doctors to see patients who had been disabled by chest pains get back to doing the things they wanted.  However, after fifteen or twenty years of experience with artery-opening operations, they realized that the campaign to hunt down and reopen narrow arteries was less of a winning strategy than they had hoped.  Doctors had higher expectations for artery-opening operations than relieving exertional chest pains.  As inconvenient as such symptoms can be, they rarely kill anybody.  What doctors really wanted was a way to prevent heart attacks, but these kept occurring despite their best efforts reopen narrow arteries. 

 

Its now apparent why: they were looking in the wrong place for what caused heart attacks. 

 

A Daring Experiment Sheds Light on the Issue

 

In the nineteen seventies, some astonishing revelations about heart disease revealed to doctors where their thinking had gone wrong.  But as with many scientific advancements, it took some mavericks to break away from the herd. 

 

Doctors had assumed that heart attack patients were too fragile to undergo any procedure that might irritate their heart.  It would have been considered reckless to inject x-ray dye into the coronary arteries in the middle of an attack.  Nevertheless, a forward-thinking team of doctors, in Spokane , Washington , decided to do just that.  They X-rayed the coronary arteries of a group of patients within a few hours of a heart attack.   They saw something they had never seen before.  In every case, there was a blood clot stuck in the middle of an artery blocking blood flow.

 

Clearly, previous thinking had been wrong.  Narrowings don’t cause blockages; blood clots are the problem.  Clots usually originate from plaques, but the narrowings created by those plaques are usually quite mild.  Sometimes there’s no discernible narrowing at all before a heart attack.

 

Why hadn't doctors noticed this before?   Although they had done X-rays on heart attack patients before, they had always waited a few days for the condition to stabilize.  That was too late to see the clots.  In fact, when the Spokane team repeated their X-rays a few days later, the clots they had seen earlier had disappeared. 

 A few years later, another group of researchers tracked down the X-rays of patients who happened to have pictures of their arteries taken before having a heart attack.  They confirmed the Spokane teams conclusions.  Most of the arteries that blocked off and caused heart attacks were not severely narrowed beforehand.  The average reduction in cross-sectional diameter before the heart attacks was in the range of a 40 to 60 percent, not enough to interfere with blood flow even during exertion.  Sometimes the offending plaque was undetectable with X-rays.

 Let me clarify something.  Although mild narrowings trigger most heart attacks, severe choke points are, in fact, somewhat more prone to blockage.  Tight narrowing is not necessarily a good sign.  The main reason mild narrowings are more often the culprits is simply that they’re more numerous.  In a typical diseased artery there are, perhaps, ten or twenty mild narrowings for every severe one.  By virtue of their numbers alone, they are more likely to cause blockage. 

 Also, doctors can’t accurately gauge the size of a plaque by how much it narrows an artery.  Sometimes large plaques cause only mild restrictions and smaller ones produce severe narrowings. 

 There’s one more reason mild narrowings are dangerous.  When choke points interfere with blood flow, it stimulates nearby arteries to sprout new blood vessels.  These grow into the deficient area and provide alternate routes of blood supply.  But if the artery is wide open to begin with there’s no stimulus for such vessels to grow, so clots that strike open arteries tend to cause more damage than those that block narrowed ones.

 

A means of prevention

 

When researchers discovered that clots rather than narrowed arteries were what caused heart attacks, they had found the key to preventing them.  If they could stop the clots, they could avert heart attacks--narrowing or not.  Indeed, simply taking aspirin, a drug that inhibits blood clotting, is an effective way to reduce the risk of heart attacks as well as strokes.  How effective?   Put it this way; it works better than heart surgery. 

 

The discovery that heart attacks are caused by blood clots rather than progressive choking-off of arteries rejuvenated interest in drugs to dissolve clots after they have formed.  Cardiologists resurrected an old “clot buster” discovered in the nineteen fifties called steptokinase and began giving it to patients with heart attacks.  When the patients got the drug within three or four hours of an attack, they improved dramatically.  As you might expect, when doctors took x-rays after they had dissolved the clot, the narrowing that caused the blockage was often quite mild.  Usually, they didn't interfere with blood flow at all.

 

Taking medication to inhibit blood clotting is a useful strategy, but there’s a problem: you need your blood to clot.  Potent anti-clotting medication raises the risk of dangerous bleeding, and the kind you can safely take, like aspirin, isn’t strong enough to prevent heart attacks altogether.  The forces that trigger clots are often strong enough to overwhelm the preventive effects of such drugs.  However, there is a better way to prevent heart attacks: stop what provokes clots in the first place.  

 

What causes the clot?

 

When researchers finally realized that clots rather than progressive narrowing of arteries were what caused heart attacks, they were puzzled. Why would a clot suddenly crop up in an otherwise serviceable artery?   They knew cholesterol buildup was somehow responsible, but how it triggered clots was a mystery. 

So they began looking more closely inside the walls of arteries that had blocked off.  They discovered that cholesterol buildup is not a gentle process; the body fights it.  Indeed, collateral damage from this battle--not cholesterol buildup per se--is what causes the trouble.   It’s also what makes coronary disease so unpredictable, so dangerous, and, ironically, so treatable. 

 

Here’s how the battle takes place.  When enough cholesterol seeps into the artery wall to cause a lump or “plaque”, scavenger cells, called macrophages, move in from the bloodstream to remove the offending substance just as they would foreign invaders like viruses or bacteria.  Usually, when these cells encounter an adversary, they secrete destructive enzymes designed to dissolve holes in enemy armor.  The problem is, while those enzymes are good at killing germs, they don’t do much to cholesterol.  The scavenger cells keep secreting the enzymes, but the cholesterol remains unfazed.  The result of this standoff is--and this is critical in causing heart attacks--those enzymes start eroding holes in the plaque. 

 

Those cavities don’t heal normally.  They fill with cholesterol, which hinders scar tissue formation.  Cholesterol has the consistency of toothpaste or soft cheese.  (The resemblance to cheese was striking enough to lead nineteenth century pathologists to suspect that atherosclerosis had something to do with cholesterol, which they knew was an ingredient of cheese.)  It has little structural strength so ultimately it weakens the plaque. 

 

If plaque erosion and cholesterol deposition gets intense enough, smaller pools of cholesterol coalesce into larger ones and finally into a single large core which further weakens the plaque.  Although only about one in ten plaques have this boil-like structure, those are the ones that cause trouble.  Arteries have to be tough to withstand the steady pounding they get, but those cholesterol pockets create an unstable situation.  Sometimes they burst open into the artery channel, which ruptures the plaque and tears the inner lining of the artery.  

 

The critical role of overzealous clotting

 

Plaque rupture would be harmless enough if it weren’t for the body’s attempt to fix the damage.  When a cholesterol pocket bursts open and tears the inner lining of the artery, coagulation mechanisms in the blood respond as they would to any wound.  Clot-forming cells, called platelets, spring into action.  They cling to the damaged area, clump together and within a few minutes form a patch to cover the tear.

 

It would be fine if the platelet patch were shaped in such a way as to conform to the contour of the vessel wall--like a patch on a pair of trousers, but nature isn’t quite up to that task.  The clot is a formless blob, and that causes trouble.  Owing to its cumbersome shape and excessive bulk, it not only covers the tear but sometimes also plugs the artery entirely.   That’s how arteries go from being wide open to completely blocked in a matter of minutes. 

 

Notice that artery narrowing plays no role in the sequence of events that leads to plaque rupture and blockage.  Most plaques that go on to cause heart attacks don’t encroach upon the artery channel enough to interfere with blood flow. That’s why bypassing or prying open narrow spots does little to prevent heart attacks.

 

A fortuitous discovery provides a cure

 

About the time researchers were sorting all this out, other scientists were studying the effects of a new cholesterol-lowering medication called lovastatin.   Coming from the mindset that artery narrowness was the adversary, they were anxious to see if lovastatin could reopen arteries and designed a research trial to test that theory.  At the conclusion of the study, they were disappointed to find that, although the drug did a good job of lowering cholesterol, it had only a modest effect on narrowing.  Two years of treatment reduced average blockage by only about three percent. 

 

Then they discovered something amazing.  The patients who took lovastatin had far fewer heart attacks than the ones who didn’t.  The idea that lowering blood cholesterol levels could prevent heart attacks but have such little effect on coronary narrowings was too extraordinary to be believed.  Artery blockage was thought to be the result of a gradual process, one that took place over decades.  No one expected that lowering blood cholesterol would have life-saving benefits so soon after treatment and so late in the course of the disease.

 

Although that finding was hard to explain in terms of the thinking at the time, it makes perfectly good sense now.  Lovastatin stopped cholesterol from seeping into plaques and inciting the scavenger cells.  They stopped secreting their erosive enzymes, which allowed plaques to heal and prevented them from rupturing.

 

Another look at the patient with the narrow artery 

 

Remember the patient with the narrow artery who thought that discovering and reopening it was his salvation?  People who have had such experiences often believe--and, in fact, usually can’t be disabused of the notion--that a) the artery would inevitably have blocked off completely and b) opening it up markedly reduced the odds of having a heart attack.

 

Certainly, it’s unnerving to find out you have a narrow artery in your heart.  You imagine something closing off, like a faucet, with one twist of the handle left before it shuts off.  You wonder, ‘What’s to keep the narrowing from closing off altogether?’  Indeed, if artery narrowing were a steadily progressive process, it would lead to complete blockage. The only way to prevent it would be to bypass or reopen the narrowing, which would guarantee years of security against heart attacks.  But that’s not how it works.  The behavior of coronary narrowings bears little resemblance to the mechanical analogies that patients--and even some doctors--often conjure up in their minds.  

 

If you want a plumbing analogy, here’s a better one.  Have you ever tried to stop water from flowing through a garden hose by kinking it?  It’s easy to restrict the channel a little but tough to block flow completely.  You usually have to use both hands and bear down hard.   The point is, a narrowing is one thing, a complete blockage is something else.  Narrow arteries resist blockage.  Most narrowings never progress to complete occlusion.  When a narrow artery is diagnosed in the course of a routine visit to the doctor, it’s impossible to tell that it’s going to block off no matter how tight it is.

 

Back to the man with the narrow artery…  It would have been important for him and his doctor to avoid overreacting.  A rush to reopen narrowings exposes patients to the risks of surgical procedures and diverts attention from what is most important--that is, correcting the high blood cholesterol and overly vigorous clotting mechanisms that cause artery damage and blockage.

 

It would also have been important for the doctor to discourage the patient from truly believing he was “as good as new” after the surgery.  Indeed, after going through a major operation, some patients think they ought to be able to throw away their pills.  Unfortunately, atherosclerosis is rarely a matter of one or two narrow spots in an otherwise healthy vascular system.  Even if all narrowings have been successfully reopened or bypassed, a diseased artery can block off anytime.  Unless something is done about the underlying process of cholesterol infiltration, plaque rupture and clot formation, the chances of having a heart attack are changed little by artery-opening operations. 

 

Arteries can do mind-blowing things.  They can remodel themselves to accommodate atherosclerotic build-up.  They can birth new blood vessels that detour around blockages.  The blood that flows through them can deposit cholesterol then carry it away.  And they can go from being wide open to completely occluded in a matter of minutes. The difference between arteries and inert tubes is the difference between the old way of looking at coronary artery disease and the new.  Leading cardiologists describe this new awareness as a “sea change” or “new paradigm” in thinking about coronary artery disease. 

 

But old, familiar ideas seem to die hard.  Doctors and patients alike often forget how complex and dynamic arteries are and revert to the plumbing mentality.  This is a harmful misconception.  Such simplistic thinking can lead to unnecessary treatment and missed opportunities for prevention. 

 

Cholesterol’s central role

 

Cholesterol seeps into arteries, incites scavenger cells and provokes them to secrete their erosive enzymes.  Then it collects in the holes the enzymes make and hinders repair.  Cholesterol forms pockets under the artery lining, which rupture, activate clotting mechanisms and cause heart attacks. 

 

Reducing blood levels of cholesterol does more than halt gradual buildup.   Almost immediately, it pacifies scavenger cells, stabilizes plaques and within days reduces the risk of heart attack.  The fact is it’s all about cholesterol.  If you have any reason to believe that cholesterol is infiltrating your arteries, your first priority should be to get your blood cholesterol level down.