W hen scientists decry the sharp decline in the number of autopsies, they talk about what
       medical science may lose by not having the chance, after a patient’s death, to explore the body in a way that wouldn’t have been possible when the patient was alive. One of medicine’s earliest diagnostic tools, autopsies have helped solve myriad medical mysteries—including the link between Alzheimer’s disease and heart disease, and the discovery of the West Nile Virus—and in the 1980s, evidence uncovered during postmortems began solidifying the case for a risk factor that may have a profound role in the development of heart attacks, strokes and a laundry list of other plagues.

During the first half of the twentieth century, the prevailing view of heart disease considered arteries to be simple pipes, and cholesterol the gunk accumulating in those pipes until blood could no longer reach the heart or brain. But research in lab animals during the 1970s began to suggest that there was much more to it than grungy hardware. In 1973, University of Washington researcher Russell Ross proposed that arteries react to cholesterol and other environmental influences. This set the stage for a new view of atherosclerosis, and, in 1979, pathologist Ross Gerrity, then at the Cleveland Clinic Foundation, found some of the first evidence that atherosclerosis emerges in part because our own immune system attacks our arteries. When he examined the arteries of pigs that ate a high-cholesterol diet, he found inflammatory cells called monocytes packing the regions that developed atherosclerotic plaques. In two landmark 1981 papers, he made the case that these inflammatory cells are in fact the most important factors for plaque development: They not only absorb the low-density lipoprotein (LDL, or “bad” cholesterol) that trespasses into the blood vessel wall, but they also become foam cells, which researchers knew to form the core of a plaque.

And when pathologists autopsied patients who had suffered from atherosclerosis, it seemed the disease in humans followed a similar trajectory. Autopsied blood vessels revealed clots, like scabs on cuts, as well as monocytes and macrophages, which are cells that monocytes mature into once they’re in the artery wall.

Soon, Peter Libby, chief of cardiovascular medicine at Brigham and Women’s Hospital in Boston, along with many other scientists across the country, was researching the details of this phenomenon in lab animals. The emerging consensus was that it’s not just cholesterol that causes problems in the bloodstream; it’s also the chronic low-level inflammation that responds to the cholesterol—and to elevated blood sugar, smoking and a diet high in saturated fat, among other “injuries.”

This long-term inflammatory response was very different from acute short-term inflammation, which is a vital part of the so-called innate immune system, the body’s first-line defense against bacteria and viruses. When you slice your finger on a jagged can, vessels dilate to allow more blood into the area. The finger becomes red and hot (from the extra blood), and white blood cells ooze into the wound to combat bacteria. The process accelerates until the site is clear, then stops. Inflammatory cells and proteins go back to their normal patrol in the bloodstream, and the finger heals.

Long-term inflammation, on the other hand, is never-ending, and it may be happening inside two of every three Americans, according to the Centers for Disease Control and Prevention and the American Heart Association. Always on, it attacks things that aren’t foreign—abnormally high cholesterol levels, for instance—and damages not only the blood vessels but also the brain, the liver, other organs and even fat. There’s a growing consensus that modern lifestyles—fatty, processed foods; a dearth of physical exercise; smoking—are sparking this immune response that’s contributing to heart disease and other conditions, including type 2 diabetes, Alzheimer’s disease and inflammatory bowel disease. It’s as if today’s environment were invading us, with our body doing all it can to fend off the onslaught. But we keep shooting ourselves in the foot.

When there’s a lot of cholesterol in the bloodstream, it builds up in the artery walls, where destructive free radicals (highly reactive molecules with unpaired electrons) modify it into an odd shape. Sensing the cholesterol as a foreign object, endothelial cells in the walls deploy a molecule called VCAM-1 (vascular cell adhesion molecule-1), a protein that attracts inflammatory cells such as monocytes so they can repair the “injury.” Monocytes then burrow into the artery lining, beginning an inflammatory reaction that attacks the modified cholesterol. But because the assault by cholesterol and other insults (such as carbon monoxide in smokers) is constant, so is the inflammatory reaction. The monocytes mature into macrophages that live inside the tissue, multiply and release inflammatory-signaling proteins called cytokines; those recruit more cells that may in turn produce their own signaling cytokines. The resulting level of inflammation is common in Americans, with one study that showed a sixth of U.S. teenagers already displaying signs of atherosclerosis in the heart.

Often, such accumulations of cholesterol and the accompanying inflammation don’t form a clump large enough to block an artery. Instead, increasing inflammation weakens the top of the plaque by breaking down existing collagen and preventing new collagen fibers from forming. Then, if this tenuous cap ruptures, blood may come into contact with the plaque’s lipid core. When the inside of the blood vessel is exposed, a clot will rapidly form to heal the injury, and that can block the flow of blood and cause a heart attack or stroke.