Everything You Know about Cholesterol Is Probably Wrong

Most of us know that too much cholesterol promotes heart disease. And many know that cholesterol comes in good and bad forms. “Bad” (low-density lipoprotein, or LDL) cholesterol clogs the arteries that pump blood to the heart and feed the brain, raising the risk of heart attack and stroke. “Good” (high-density lipoprotein, or HDL) cholesterol removes excess cholesterol and fat from the bloodstream, keeping arteries healthy.

But a little knowledge can be a dangerous thing: this good versus bad scenario offers a simplistic view of cholesterol’s role in heart disease.

Doctors assess cardiac health with routine blood tests that estimate LDL and HDL cholesterol levels along with total cholesterol and triglycerides. But cholesterol is just one component of the lipoprotein particles (spherical balls made of proteins and other lipids) that transport the water-phobic molecules through the blood. Most blood tests reflect how much cholesterol the particles carry but don’t provide any information about the particles themselves.

“But it all starts with the particle,” says Ronald Krauss, senior scientist and director of Atherosclerosis Research at Children’s Hospital Oakland Research Institute. “The LDL particles go into the artery wall and carry the cholesterol with them. So we see the cholesterol in the plaque but it’s the particle concentration and the number of particles that really determine the process.”

Smaller LDL particles carry less cholesterol than larger LDL particles, yet it’s the smaller particles that are most strongly associated with heart disease risk.

That’s because smaller particles are more likely to glom on to artery walls and do so more often because they circulate in the blood longer. Once they get stuck, they undergo chemical changes that make them more toxic to arteries.

So if you have mostly small LDL particles, your cholesterol levels could be normal, but you may still be at risk for heart disease, Krauss says. “It turns the cholesterol story upside down.”

New methods for evaluating risk

That’s why more researchers are turning to methods that can measure the size and density of lipoprotein particles to better understand how heart disease develops. In a new study, published in the Journal of Lipid Research last month, researchers at the University of Pittsburgh used a method (called nuclear magnetic resonance spectroscopy) designed to measure the characteristics of lipoprotein particles as a first step to understanding how menopause may facilitate cardiovascular disease in women.

Risk of heart disease increases with age as decades of inactivity and unhealthy eating habits promote plaque formation inside artery walls, ultimately blocking blood flow and causing a heart attack. Estrogen has a beneficial effect on arteries, which helps explain why women have a lower risk of heart disease than men—until they stop menstruating.

Why that edge disappears around menopause isn’t entirely clear. Lower estrogen levels may alter cholesterol abundance or metabolism, as suggested by studies linking menopause to higher levels of total cholesterol, LDL cholesterol and triglycerides. In the new study, the researchers found an association between lower levels of estrogen and “low quality” cholesterol carriers, including the smaller LDL particles associated with increased risk.

The study was small—it examined just 120 women of the 3,302 women enrolled in an ongoing study of menopausal change (the Study of Women’s Health Across the Nation). But it lends support to the notion that as women approach midlife, their falling estrogen levels may help drive a shift from high-quality lipoproteins, which can clear excess cholesterol from the bloodstream, to lower-quality molecules that can’t.

That doesn’t mean boosting estrogen is a good idea. The U.S. Preventive Services Task Force recommends against using hormone replacement therapy to reduce cardiac risk. Instead, women over 45 should get their cholesterol levels checked every five years. Routine blood tests will spot signs of trouble in most people, Krauss says, though more physicians are using the specialized tests for both women and men with diabetes, obesity or a family history of early heart disease to better assess their health status.

Reducing risk

Every year about 600,000 people will die of heart disease, the leading cause of death in the United States since 1921, when it surpassed pneumonia and flu.

These numbers are particularly troubling because heart disease is largely preventable. And though people can reduce their risk—primarily by exercising, losing weight and not smoking—many don’t. Cleveland Clinic researchers reported in February that a third of adults wouldn’t change their exercise or eating habits and just half of respondents said they’d stop smoking, despite a two- to fourfold increased risk.

Though logic suggests that raising good cholesterol through drugs or supplements could help those not inclined to change bad habits, the evidence suggests otherwise. There’s no doubt that HDL has protective features, Krauss says, but there’s no guarantee that raising HDL levels will reduce your risk of heart disease. The evidence that small LDL particles promote heart disease, however, is “rock solid.”

The best way to thwart those LDL particles, Krauss says, is not by avoiding saturated fats, as we’ve long assumed. Saturated fats don’t affect the LDL particles, but sugar and carbohydrates do. “Taking away eggs and milk has virtually no effect on the bad guys,” says Krauss. “But you can make a really big improvement if you cut the sugar out.”