The numbers are frightening. Each year 1.5 million Americans have heart attacks, 500.000 of them fatal. The statistics or even scarier for anyone with a family history of heart disease, because if one family member develops heart disease before age 55, other blood relatives like children, brothers, sisters will face a fivefold to tenfold risk of becoming cardiac casualties t
hemselves. In fact, just 3% to 8% of American families account for 40% to 60% of premature coronary deaths.
In the most extreme conditions a single gene can virtually guarantee a person’s destiny. One in a million Americans inherit 2 copies of a flawed gene that causes familial hyper cholesterolemia, for example. This disorder hampers the ability of cells to take cholesterol from the blood, allowing cholesterol levels to soar as high as 1000 mg. Frequently people with severe familial hyper cholesterolemia develop artery blockages by the age of two. Without radical treatment, such as a liver transplant, they usually die in their teens.
By contrast, Helen Boley, a 63 year old Kansas woman, inherited two copies of the rare “Methuselah” gene, which prompts her body to make HDL at three times the normal rate. Boley’s HDL measures about 200 mg (60 mg is average for a woman her age). Several of Boley’s ancestors lived past 100 years, seven of her great grandparents were alive when she was born. Helen Boley could not die of heart disease if she tried.
Of course, genetics doesn’t deal most people as good a hand as Boley’s or as bad as the one held by people with familial hyper cholesterolemia. But there’s usually no way to tell exactly what kind of genetic odds you face when it comes to heart disease.
Instead, doctors trying to predict their patients risk have turned to markers in the blood that can contribute to heart disease. The first push, in the late 1980’s was to get everyone tested for total blood cholesterol, a measurement that primarily reflects of the levels of low density lipoprotein also known as LDL (“bad” cholesterol). There’s good reason to get that number since LDL is the real culprit in clogged arteries but is difficult to measure by itself. Generally, the higher the level of total cholesterol, the greater the heart-disease risk. Someone with a total cholesterol reading of 240, for example is at twice the risk of someone with a reading of 210. But it has become clear in the past few years that these medical horoscopes can be misleading. As many as one in 5 people with scores considered desirable (under 200) eventually have heart attacks. Others with riskier levels are spared. In June 1993 heart experts with the US National Cholesterol Education Program announced a major missing puzzle piece. Everyone over the age of 19, the experts said, should also be tested for HDL, the “good” cholesterol the same stuff that is present in a souped-up form in the Limone villagers.
HDL, it seems is one reason why premenopausal women are comparatively free of heart disease. Their HDL runs about 10 mg higher on average than in men of the same age. (Estrogen therapy, which boosts HDL levels by about 10%, also cuts the risk of heart disease in postmenopausal women by half.) In study after study, HDL levels above 60 mg seem to protect against heart disease.
“Cholesterol is a was”, says John Oram, a cell biologist at the University of Washington in Seattle. “It adds strength to cell membranes, but if cells accumulate too much cholesterol it jams up their membranes. If we did not have some way to take it out, we’d turn into candles”. So if cholesterol is the was gumming up the works, HDL is the dump truck that carts it from the cell to the liver for disposal. The more HDL, the more efficiently the trash is hauled. Researchers have been particularly interested in how the portatori’s mutated version works, because it apparently binds and releases cholesterol quickly, perhaps as much as ten times faster than normal, like a tiny fleet of dump trucks tearing through the blood stream in hyperdrive.
It’s been suspected that HDL helps in another way as well, by making blood platelets less sticky. That leaves platelets less likely to form clots that can get stuck in narrowed arteries, choking off the blood supply and causing a heart attack. Investigation of the portatori appears to confirm this second role for HDL. In the test tube Apo A-1 Milano has shown remarkable anti-clotting properties.
A Swedish drug firm is exploring ways to turn the hyperactive Apo A-1 Milano into a heart medicine. Kabi Pharmaceutics is doing animal tests on an inject-able drug derived from the protein to see if it can keep arteries from reclogging after they’ve been cleared by balloon angioplasty. Eventually the work may lead to drugs that can scour out blocked arteries without the need for surgery at all.
Experts agree that measuring both total cholesterol and HDL offers the best chance of evaluating someone’s heart disease risk. Other blood markers may join the list in the future, since some people at high risk will still be missed by these tests. One leading candidate is something called small dense LDL. This type of cholesterol is the best signal of syndrome X, a disorder that increases the risk of high blood pressure, heart disease and diabetes. Syndrome X may affect as many as one in 4 Americans.
For now, though scientists trying to learn how to predict cardiovascular disease gather important information from groups like the Limone folk. Of course, it won’t do much good to identify people heading for heart attacks if they can’t do anything about it. Which raises two crucial questions, Can a healthful lifestyle override dangerous genes ? And can a lifetime of bad habits produce heart disease in someone with no particular predisposition to it ?