On the other hand, diabetics are now automatically in the high-risk camp, considered to be as likely to have a heart attack, stroke, or other cardiac event within 10 years as someone who's already had one—about a 1-in-5 chance. "Diabetes causes multiple risks to the arteries, like high levels of inflammation and more blood clots," says cardiologist Melissa Walton-Shirley, who moderates a forum at theheart.org, a cardiologists' website, and is codirector of the cardiovascular lab at TJ Samson Community Hospital in Glasgow, Ky. Plus, elevated blood sugar levels make proteins and fats "stickier" and more likely to accumulate as plaque on the arteries.
In diabetics, like heart patients, explains Jacobson, "we can prevent one heart attack for every 30 high-risk people that we treat for five years." According to the guidelines, anyone with established heart disease or diabetes should follow a low-fat diet and exercise program and take medication to lower LDL levels above 100 mg/dL; doctors are also given the option of aiming for a more aggressive goal of 70.
To determine if the rest of the world is at high risk, moderately high risk, moderate risk, or low risk of developing heart disease, doctors are supposed to take into account five key factors: age, smoking history, blood pressure, HDL levels (lower than 40 mg/dL is a bad sign), and a family history of early heart disease (before age 55 for a male relative or age 65 in a female relative). Using a mathematical modeling tool such as the Framingham risk assessment calculator, they assign patients points for each factor and can calculate a 10-year likelihood of having a heart event. Those who have two or more of the five risk factors and 10-year odds of at least 1 in 5 are considered "high risk" and should aim to get below that LDL threshold of 100 mg/dL. High-risk folks who have low HDL, too, might benefit from adding a moderate dose of prescription niacin or a fibrate drug, such as TriCor or Gemcor, that raises HDL by altering fat metabolism.
Those who are at "moderately high risk" should aim for an LDL level of less than 130 mg/dL. This group includes anyone who has a somewhat lower Framingham score and two or more risk factors. If this is you, consider drugs if you can't get your cholesterol to a healthy level with lifestyle changes. If your likelihood of a heart attack is less than 1 in 10 over the next 10 years, the guidelines say medication isn't necessary unless LDL tops 160 mg/dL.
In people with just one risk factor or none at all, elevated cholesterol often shouldn't be treated with medication. The likelihood that the drugs will prevent a cardiac event is extremely slim, so any side effects are apt to be for naught. If LDL levels soar above 160 mg/dL, it's time for lifestyle changes; medication becomes more pressing if LDL levels hit 190 mg/dL.
The female factor. Whether women with high LDL and no heart disease derive any benefit from statins is questionable. Those who take the drugs are as likely to die of heart disease as those who do not, according to a 2004 review of 13 studies of women published in the Journal of the American Medical Association. The researchers did find that statins may reduce the likelihood of heart attacks, strokes, and heart surgery—but 140 women would need to be treated to prevent just one of these events. "We don't have a good idea of how the drug is metabolized in women compared to men," says Goldberg. "Do females need higher or lower doses?" Goldberg limits statins primarily to high-risk women. "If she has just one risk factor and her LDL is approaching where the guidelines say to medicate," she says, "I give her time to work things out with diet and exercise."
Like Larry Cohen, some people can't push low enough using statins alone; others simply can't tolerate the drugs. In Vytorin, they could get a lower dose statin plus the cholesterol-absorbing action of Zetia in the intestine. If, as it now appears, the combination's LDL-lowering benefit may not translate into a lower risk of heart disease, what does that mean for patients? Research suggests that statins offer bonus effects: They also raise HDL levels, reduce inflammation, and stabilize plaque so it's less likely to rupture. Zetia may not—and despite its LDL-lowering benefit, studies hint that it might also have some detrimental effect on the arteries, according to Allen Taylor, chief of cardiology at Walter Reed Army Medical Center in Washington. "These actions aren't intended and certainly weren't understood when the drug was approved [in 2002]," he says.