Could a simple blood test predict a person’s risk of dying from heart disease or cancer?
Reporting in an early online publication of the Journal of the American Medical Association and at the European Society of Cardiology Congress, Johan Arnlov and his colleagues say that a certain enzyme that is measured in the blood may be linked to both heart disease and cancer, and therefore could serve as an early predictor of who is mostly likely to die from these diseases.
In the study, which involved nearly 2,000 people enrolled in two separate long-term trials, Arnlov’s team measured the levels of cathepsin S, an enzyme involved in breaking up proteins. They then tracked these volunteers for up to 12.5 years, and found that those with the highest levels of cathepsin S were more likely to die than those with lower, or about half those levels.
What is unique about the study is that it’s the first to identify a marker associated with both heart disease and cancer, two of the leading killers of American adults. The effect remained strong even after the scientists adjusted for other factors that can contribute to heart- and cancer-related death, such as age, blood pressure, history of heart disease, diabetes and cholesterol levels.
Arnlov decided to focus on cathepsin S because previous studies have linked the enzyme to atheroslcerosis, or the buildup and hardening of the arteries that increase the risk of heart disease. In animal studies, mice without the gene for cathepsin S developed less heart disease, and, interestingly, less cancer, compared with those animals that had the gene. Early studies in people have also showed that obese individuals tend to have higher levels of cathepsin S, and that if they lose weight, their levels go down.
“Cathepsin S is involved in several processes in the body,” says Arnlov. “It is involved in the immune system, in regulating how [foreign material] is presented to the immune system, and it is highly expressed in [fat] tissue. It is involved in several crucial steps in the atherosclerotic process as well as in tumorgenesis.”
But, he says, it’s not clear exactly how cathepsin S might contribute to either heart disease or cancer. Nor is it obvious yet which tissues are producing the enzyme and whether there is a normal or healthy level. For example, the enzyme appears to be involved in inflammation, which can make plaques in the blood vessels unstable and trigger a heart attack, but it does not seem to be affected by levels of other inflammatory factors that have been linked to heart disease risk, such as C-reactive protein, or CRP.
“To be honest, we don’t know really what circulating levels of cathepsin S reflect,” says Arnlov. “We can’t be sure in what tissues it originates; we have no idea. So further studies need to elucidate what the circulating levels of cathepsin S really [mean].”
He says it’s too early to know whether cathepsin S can be useful in predicting who is at greatest risk of having heart disease, or whether levels of the enzyme in the blood can even become an early warning for cancer. But already pharmaceutical companies are targeting cathepsin S with compounds that block its activity. Those studies will likely provide answers to some critical questions about whether the enzyme really can be a biological crystal ball.