The most controversial of the guidelines call for twice as many American adults to consider taking cholesterol-lowering drugs.
Many Americans who do not have dangerously high cholesterol may soon be asked to consider taking statin drugs.
The guidelines, issued Tuesday by the American Heart Association and American College of Cardiology, are a big change. They offer doctors a new formula for estimating a patient's risk that includes many factors besides a high cholesterol level, the main focus now. The formula includes age, gender, race and factors such as whether someone smokes.
The guidelines for the first time take aim at strokes, not just heart attacks. Partly because of that, they set a lower threshold for using medicines to reduce risk.
The definition of high cholesterol isn't changing, but the treatment goal is. Instead of aiming for a specific number, using whatever drugs get a patient there, the advice stresses statins such as Lipitor and Zocor and identifies four groups of people they help the most.
Doctors say the new approach will limit how many people with low heart risks are put on statins simply because of a cholesterol number. Yet under the new advice, 33 million Americans - 44 percent of men and 22 percent of women - would meet the threshold to consider taking a statin. Under the current guidelines, statins are recommended for only about 15 percent of adults.
Some doctors worry that the recommendations will be difficult to understand. The original version of the article is 80 pages long.
The authors acknowledge that it will be controversial, but ultimately they hope it will save lives.
Heart disease is the leading cause of death worldwide. High cholesterol leads to hardened arteries that can cause a heart attack or stroke. Most cholesterol is made by the liver, so diet changes have a limited effect on it.
The patents on Lipitor, Zocor and other statins have expired, and they are widely available in generic versions for as little as a dime a day. One that is still under patent protection is AstraZeneca's Crestor, which had sales of $8.3 billion in 2012.
The Associated Press contributed to this report.