When Heart Disease Happens

What causes the blockages that set off these events? In a word, atherosclerosis. The term is a combination of two Greek words: athere, meaning pudding, and sclerosis, meaning hardening. The root words describe what happens in atherosclerosis: the artery walls become filled with soft, mushy deposits that eventually harden to make the artery stiff and narrow.

Put simply, the arteries get clogged in the same way the pipe in your bathroom sink might when too much debris sticks to its walls, blocking the flow of water. Though the pipe analogy might make artery clogging seem straightforward, it’s a fairly complicated process. There are four steps that occur in what is known as the coronary cascade to a heart attack.

Step 1

The first step in the road to heart disease appears to require an elevated level of blood cholesterol, carried in one of the lipoprotein particles, particularly LDL. When there’s excess LDL in the bloodstream, some of it moves out of the blood and into the artery wall. The higher the LDL level, the more LDL finds its way into the artery wall.

Every artery wall has three layers. The inner layer, or intima, has a delicate, single layer of cells (called endothelial cells) between it and the bloodstream, which acts like a kind of Teflon coating for the artery, making it possible for the blood to flow smoothly through the vessel.

These cells also send out signals to recruit inflammatory cells and help those cells stick in the right locations so they can penetrate into the tissues when they are needed to help clear away debris or infectious agents. High cholesterol, high blood pressure, smoking, and diabetes, among other things, can disrupt the function of endothelial cells.

This disruption can take on many forms—it may increase or decrease levels of the constricting and relaxing hormones as well as the signals that recruit inflammatory cells. The regulation of blood flow and blood pressure can be disrupted. The endothelial cells can also loosen their attachment to the intimal layer and to each other, resulting in gaps in the lining.

No matter what a person’s cholesterol level is, the endothelial cells ship some LDL from the blood into the intimal layer. However, the higher the LDL concentration in the blood, the more the endothelial cells ship LDL into the artery wall. The LDL may also take advantage of some of the breaches in the lining layer and directly penetrate to the interior of the artery wall.

Step 2

These events generate an inflammatory response. The endothelial cells at key locations in the arteries release chemical messengers called chemokines, which in turn call immune cells known as macrophages to the scene. Macrophages ingest the LDL and become engorged with cholesterol, forming a foam cell (so named because the cholesterol makes the cells look foamy).

Though the macrophages are trying to clear away the LDL and clean up any debris left in the artery wall, they end up making things worse because they continue to call for reinforcements in the war against the LDL, and the extra cells cause more clogging of the arteries.

We think this occurs because macrophages are designed to fight off infectious microbes, that is, to kill their prey, control the infection, and then quietly disappear. When the prey is instead a lipid particle that is continually produced by the body, it is like an infection that never ends.

More LDL keeps being deposited, and more macrophages keep getting called to clean up the mess. These steps result in a chronic and sustained inflammation in the artery wall. Ultimately, the accumulation of cholesterol in the macrophage kills it, and all the cholesterol in the cell gets released into the artery wall, along with many other inflammatory substances contained in macrophages, further inflaming the process.

Step 3

In an attempt to wall off this inflammation, the body signals the smooth muscle cells to proliferate and to make more fibrous material to contain the process. Eventually, a cap forms over the inflammation. This is the birth of a plaque that can narrow the artery.

Plaques vary in size, and there is evidence that some early stages of plaque formation are reversible, whereas later stages are permanent. Most of us probably form and resolve small plaques throughout much of our lives. Studies in teenagers who have died from traumatic events, such as car accidents, have shown early-stage plaques in the arteries of even these very young men and women.

Step 4

Though the reduced blood flow caused by the plaque and inflammation taxes the heart, it doesn’t usually cause a heart attack. Heart attacks occur when the plaque ruptures. Plaque deposits teem with inflammatory cells (particularly macrophages and other inflammatory cells called T-lymphocytes) as well as cholesterol.

The more inflammatory cells and cholesterol—and the thinner the cap that covers them—the more unstable the plaque. This sets the stage for disaster. T-cells slow the production of the fibrous materials that strengthen the cap (such as collagen), and macrophages produce enzymes that degrade collagen. This two-pronged attack degrades the cap until it breaks.

Large plaques, of course, narrow the arteries more than small plaques (think of a truck blocking a tunnel as opposed to a car), but that doesn’t necessarily mean they are more dangerous. In fact, research suggests the reverse. About two-thirds of all heart attacks result from the rupture of smaller plaques—those that narrow coronary arteries only by 40 percent to 60 percent.

Though large plaques narrow the arteries by 70 percent to 80 percent, they tend to be covered by thicker caps with fewer inflammatory cells underneath. This suggests a successful walling off of the inflammatory process. Smaller plaques tend to have thinner caps that are usually associated with the presence of more inflammatory cells.

These two factors make the smaller caps more susceptible to rupture. Once the cap breaks, blood seeps into the inner layer of the artery wall rather than flowing smoothly over the endothelial cell lining. This contact triggers the release of clotting factors, just as a cut to your finger would.

Small clotting particles called platelets are activated at such wound sites and play a key role in the clotting and wound-healing process. The problem is that in the case of an atherosclerotic plaque rupture, the wound is inside the artery wall.

Having a big scab covering a skin wound may be unsightly, but it isn’t life threatening. In the coronary arteries, however, the clot further blocks the blood flow. Going back to the tunnel metaphor, the clot serves as an additional car that stalls in the one lane of traffic that had been moving around the accident.

This clot is known as a thrombus. Deprived of blood and oxygen, the portion of the heart muscle that depends on this artery begins to die. This process is known medically as a myocardial infarction or MI (em-eye). In everyday language, it’s a heart attack.