Fat tissue produces hormones and chemical messengers that can damage blood vessels, increase the risk of blood clots and cause insulin resistance that makes people prone to diabetes -- all without elevating blood pressure or cholesterol.

Northwestern University researchers tracked 17,643 patients for three decades and found that being overweight in mid-life substantially increased the risk of dying of heart disease later in life -- even in people who began the study with healthy blood pressure and cholesterol levels.

High blood pressure and cholesterol are strong risk factors for heart disease. Both are common in people who are too fat, and often are thought to explain why overweight people are more prone to heart disease.

But there is a growing body of science suggesting that excess weight alone is an independent risk factor for heart attacks, strokes and diabetes.

Pay More Attention to Your Weight

The new study fits with that evolving school of thought and contrasts with a controversial government study published last year that suggested excess weight might not be as deadly as previously thought.

"The take-home message would be pay more attention to your weight even if you don't have an unhealthy risk factor profile yet," said lead author Lijing Yan, a researcher at Northwestern and Peking University.

The study appears in Wednesday's Journal of the American Medical Association.

Participants were Chicago-area men and women in their mid-40s on average who had no heart disease or diabetes when the study began. They were followed for an average of 32 years. The researchers tracked deaths from cardiovascular disease and diabetes, and hospitalizations for those conditions, starting at age 65.

Heart-Disease Risk

A total of 1,594 heart disease deaths occurred, 31 of them in people who started the study with normal blood pressure and cholesterol.

Among participants with normal blood pressure and cholesterol at the start, those who were obese -- or grossly overweight -- were 43 percent more likely than normal-weight participants to die of heart disease later on. They were also four times as likely to be hospitalized for heart disease.

Participants who were modestly overweight but had normal blood pressure and cholesterol still ran a higher risk than the normal-weight people.

A total of 1,187 participants -- 494 of them overweight or obese -- had normal blood pressure (120 over 80 or lower) and cholesterol levels (under 200) at the outset. Standard body-mass index categories were used to define weight -- BMIs of 25 to 29 were considered overweight and 30 and above was obese.

Obesity Is a Disease

Yan said it is possible that some overweight participants developed high blood pressure and cholesterol problems during the study, which could have contributed to their deaths. But she said researchers increasingly believe that being too fat causes other cardiovascular problems, too.

Fat tissue "is not like an inert storage depot -- it's a very dynamic organ that is actually producing hormones and chemical messengers," said Dr. JoAnn Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital. These substances can damage blood vessels, increase the risk of blood clots and cause insulin resistance that makes people prone to diabetes -- all without elevating blood pressure or cholesterol, said Manson, who was not involved in the Northwestern study.

Still, there is a common misconception that excess weight is nothing to worry about until high blood pressure and poor cholesterol develop, and those can then be treated with medications,Manson said. "Patients say that all the time, and many doctors actually will say that to patients" too, she said.

The study "will help define obesity as a disease" in itself, said Dr. Samuel Klein, an obesity expert at Washington University in St. Louis.

Dr. David Katz, an obesity researcher and director of Yale University's Prevention Research Center, said the findings help prove obesity is a real public health crisis. "People who say obesity has been hyped are wrong," Katz said.