Your Unstoppable Heart

Before you swallow what your doctor prescribes, we suggest you read this article

By Paul Scott

Two laboratory machines have played a role in perhaps the greatest medical misadventure of our time: the indictment of a villain -- LDL cholesterol -- with the ultimate crime of the heart, coronary artery disease.

One machine delivered the early, misleading evidence of cholesterol's guilt, and another may have just nabbed the actual killer. And because the killer's likeliest and earliest targets are men, we'd all better pay attention to the new case being made against it.

The first machine, an early prototype of a device called an analytical ultracentrifuge, was crucial to the 1949 discovery of high-density lipoprotein (HDL) and low-density lipoprotein (LDL). These common blood fats would become cemented in people's minds by their angel/devil personas, "good" and "bad" cholesterol. But now the halo-and-pitchfork images seem a little simplistic. And hardly useful.

These cholesterol characterizations were spun out of a wall-size contraption that rotated plasma at 40,000 revolutions per minute from the late 1940s until the machine's retirement in 2004. When you consider its role in the powerful beliefs we hold about heart disease, the sprawling, rattling beast should be mounted under flattering light in the Smithsonian.

For decades, a tidy narrative about the relationship between LDL cholesterol and heart disease has affected everything from the food we eat to the drugs we take to the test results we track and the worries we harbor. This over-simplified view of cholesterol -- that all LDL is the same and that all LDL is bad -- has enabled the adoption of an accompanying oversimplified dietary belief, that all saturated-fat consumption raises your risk of heart disease.

The LDL hypothesis has also encouraged many of us to swallow the most-prescribed class of drugs in recent history. Americans spent more than $14 billion on LDL-lowering medications in 2008. Whether that money came out of their own pockets -- straight up, or through ever-escalating co-pays -- or out of the hemorrhaging U.S. health-insurance system known as Medicare, it's a huge expenditure. Twenty-four million Americans take statins, and the latest health directives suggest that those numbers should be higher. And why stop at grown-ups? Some pediatricians want to start feeding Lipitor (and the like) to kids.

As John Abramson, M.D., writes in his book Overdosed America, "Largely as a result of these guidelines, cholesterol control has become the main focus of preventive health care in the United States."

So it's more than a little disconcerting that the other machine in this story, a complex pile of gadgetry quietly clicking away on a countertop in Berkeley, California, is only the most recent breakthrough that has called the entire LDL cholesterol premise into question.

On a balmy Sunday last August, Ronald M. Krauss, M.D., the director of the department of atherosclerosis research at Children's Hospital Oakland Research Institute, showed me into his workplace to demonstrate a novel new system for tabulating LDL. Using a particle-spitting process known as ion mobility analysis, Dr. Krauss and his colleagues have developed the first device capable of counting LDL and other lipoproteins down to their smallest subcomponents. (Several other ways of analyzing LDL subparticles exist, but they involve indirect methods.)

A New Jersey company, Quest Diagnostics, worked for 7 years with Dr. Krauss -- who is helping to set the new cholesterol recommendations from the NIH's National Cholesterol Education Program -- to develop a method of analyzing cholesterol. Borrowing the same processes used for testing air pollution and residue from explosives, the quarter-million-dollar prototype is very sophisticated technology. "It determines the size of the particle based on physics," says Dr. Krauss with nerdy admiration, "on the speed at which it flies through the air."

In other words, this machine won't be coming to your community clinic any time soon. But even if it's not ready for mass production, the information gleaned using technologies like ion mobility means that LDL cholesterol can no longer be identified as the single source of all heart trouble. Those pamphlets adorning your doctor's waiting room may portray LDL as a kind of lone gunman taking a bead on your heart, but they hide a basic fact of science: "Bad cholesterol" is at best a poor shorthand for four major types of independently behaving LDL, each with its own implications for heart disease. We ignore the distinctions at our peril.

Some of these forms of LDL are relatively safe and some are dangerous, and treating them all as one and the same -- the way we do every time we pay our clinic for a three-part lipid panel that simplistically says "LDL: 125" -- is telling us little about the LDL cholesterol that matters, all the while sending health costs through the roof. We may be medicating many people who have no clear need for medication, using drugs that don't target the right particles, and replacing foods that are benign with foods that are anything but.

So in the heart-disease world, we've been stalking the devil we know instead of the devils we don't know. But we need to get to know them if we hope to dodge the number one killer of men.