Blood Biomarker Is Linked with Death

Older people who had higher than normal levels of a molecule that helps regulate inflammation in their blood were more likely to die within the next 12 years, according to a study of nearly 2,000 people in Sweden.

It’s not yet clear whether measuring this chemical, cathepsin S, could help doctors predict risk of death or disease in individuals. But the findings may renew interest in cathepsin S as a drug target. A number of drugs that inhibit the normal functioning of the molecule are already in development for autoimmune diseases, such as rheumatoid arthritis, and chronic pain.

The researchers studied two different groups of Swedes, each with an average age of about 70. Individuals were followed for eight to 12 years, during which nearly a quarter died. After controlling for other factors, such as age, weight, blood pressure, medications, and history of disease, cathepsin S levels were still linked to a greater risk of death.

In one of the two groups, those with the highest levels of the molecule had double the risk of dying during this time period than those with the lowest levels. In the second group, those with high levels of cathepsin S were more likely to die of two particular maladies: heart disease and cancer. The research was published today in the Journal of the American Medical Association.

“It predicts two of the most common causes of death, which is unusual,” says Johan Ärnlöv, a physician and scientist at Uppsala University, who led the study.

The findings follow research in animals suggesting that the molecule plays a role in both the generation of tumors and the buildup of arterial plaque, a sign of heart disease. In addition, a handful of small studies in humans found that those who were obese or had diabetes had higher levels of the molecule. “It has complex roles in the body,” says Ärnlöv. “It seems to be involved in a lot of diseases and with pain or chronic inflammation.”

That doesn’t necessarily mean that cathepsin S will help physicians predict the risk of cardiovascular disease or cancer better than existing tools can. The link to heart disease is modest, Thomas Wang, associate professor of medicine at Harvard Medical School, less than that for blood pressure or cholesterol levels. Researchers still need to determine whether the molecule is tied specifically to these diseases, or is simply a general sign of physiological aging or poor health, he says. Wang was not involved in the research.

“There are lots of things we can measure that are associated with future risk of death, but they are not useful for doctors to measure in the office,” because it remains unclear how these markers can help with treatment, says Wang. If researchers develop successful cathepsin inhibitor drugs, measuring these levels might predict who is most likely to respond.