Blood Clotting and Your Heart

Q. I've heard blood clotting is more common in people who are obese or who have diabetes. Is this true -- and is there anything I can do to prevent it?

A: Since the late 1940s, experts have recognized that a substance found in the blood, called "tissue plasminogen activator" or t-PA, is responsible for breaking up clots. Because of technical limitations, however, t-PA was hard to measure or study in patients.

By 1983, techniques improved, and it soon became clear that there was another substance in the blood -- a plasminogen inactivator (PAI-1) -- that balanced the effects of the activator (t-PA). Studies showed that both substances are present in the blood of healthy people in small amounts. They function together like yin and yang, to keep the blood clotting system in balance and prevent both clotting and excessive bleeding.

Since then, doctors have discovered large amounts of PAI-1 (pronounced "pie-one") in patients who have blood clots in their veins, as well as those who have severe coronary heart disease, obesity and diabetes. These high levels of PAI-1 upset the blood's natural balance, and can lead to dangerous blood clots.

Preventing Heart Attacks with t-PA

In 1986, doctors at Johns Hopkins Bayview Medical Center used genetically engineered t-PA for the first time to treat a patient who was having a fresh heart attack. About 30 minutes after giving her genetically engineered t-PA through an intravenous line, her chest pain suddenly stopped, and a repeat coronary angiogram showed that the clot had dissolved -- restoring blood flow to the heart, and thereby stopping the heart attack.

It's now recognized that the blood levels of PAI-1 (the blood clot maker), which blocks the effect of t-PA (the blood clot breaker), are at their highest in the body during the morning hours. The high levels of PAI-1 in the early morning hours may be one of the reasons why most heart attacks occur in the morning. It could also help explain why t-PA is less effective when given to patients in the morning.

People with diabetes have higher levels of PAI-1 than those without diabetes. But, unfortunately, they also are more resistant to t-PA when they are having a heart attack. As a result, many doctors believe that those with diabetes fare better if their blocked coronary artery is opened with balloon angioplasty.

Although PAI-1 is not yet measured routinely in clinical practice, research studies show that PAI-1 levels may be very high in people with insulin resistance, type 2 diabetes, and obesity. These levels also tend to be higher in stressed, aged individuals. Therefore, high PAI-1 can be an early indicator of insulin resistance and type 2 diabetes. Some recent studies suggest that PAI-1 may have less of an impact on the development of coronary artery disease in those with type 1 diabetes.

The Exercise Factor

Here's the good news: a recent study in the Journal of Physiology, by Hittel, Kraus, and Hoffman, showed that vigorous aerobic exercise training in previously inactive middle-aged subjects who were overweight or obese and had high fasting insulin levels "dramatically" reduced the level of PAI-1 in skeletal muscle, and increased the level of t-PA.

The net result was a marked reduction in the tendency to develop blood clots. Two weeks after they stopped exercising vigorously, however, the balance of PAI-1 and t-PA -- and therefore the tendency to form blood clots -- returned to the levels they had been at before exercise training.

So how can you keep your PAI-1 and t-PA levels in healthy balance? All recent studies come to the same familiar conclusion: Stop smoking, eat a proper diet, exercise regularly, lose excess weight, reduce stress, and get your blood sugars under control.

When you make all of these basic self-management goals part of your daily routine, you'll be able to say: "Managing my diabetes is as easy as apple PAI."

Sheldon H. Gottlieb, MD, FACC, is a cardiologist at Johns Hopkins Bayview Medical Center, Divison of Cardiology, in Baltimore, MD. He also directs the Diabetes-Heart Failure Program at Johns Hopkins HealthCare, LLC.