Protein Thought to Cause Heart Disease Doesn’t, Study Finds

C-reactive protein, or CRP, a marker of inflammation in the body, is unquestionably associated with heart disease and only a short time ago was thought to be more important than cholesterol in heart disease. Multiple studies found that the higher a persons CRP, the greater the likelihood of heart disease. A widely publicized study released last year suggested that even people with low cholesterol could protect themselves from heart attacks if they took a statin, a cholesterol-lowering drug that also lowers CRP levels.

But in a paper to be published Wednesday in The Journal of the American Medical Association, researchers analyzing genetic data from more than 100,000 people conclude that their study “argues against” the notion that the protein causes heart disease. Dr. David Altshuler, a professor of at Harvard Medical School, said the distinction was important. If CRP caused heart disease, lowering it would protect people. But if it was merely associated with the disease, lowering CRP would have no more effect on health than stopping a fire alarm would have on putting out a fire.

The new study, by Dr. Paul Elliott of Imperial College in London and 35 co-authors, made use of a recently developed technique that can get answers quickly about causality. Without it, the only method was what is seen as the gold standard in medicine — large controlled clinical trials in which people are randomly assigned to take a drug, or not, and followed for years. The new method, Mendelian randomization, “is changing the way we think about causality,” Dr. Lauer said. It is a type of study that recently became feasible as researchers found genetic variants associated with proteins like CRP and developed tools to analyze data from what was, in this case, more than 100,000 people.

Different people produce different amounts of CRP, and the amount a person produces is determined by inherited changes in the CRP gene. So in a population, there are people who just happen to produce more CRP throughout their lives and others who just happen to produce less. If CRP causes heart disease, those who make more CRP would have more heart disease. That, however, is not what the study found.

“There was no association” between CRP genes and heart disease rates, Dr. Elliott said. People with genes that increased CRP production throughout life had no more heart disease than those with genes resulting in less CRP. The association between CRP and heart disease must be reflecting something else. For example, if CRP levels go up when heart disease begins, because there is inflammation in the arteries, CRP levels would be higher in people with incipient heart disease. But CRP itself would be playing no role in heart disease risk — it was just marker of inflammation in the arteries.

It is still not clear whether doctors should routinely add CRP tests to their arsenal. The test is not now recommended but a constituency of cardiologists argued that it should be.” Guideline writers are now chomping on this,” said Dr. Steven Nissen, of the Cleveland Clinic. “New guidelines are coming out this year, and the commission is probably struggling about what to say.”

While the quest for a blood test for CVD goes on, here in Central Ohio we have the most accurate non-invasive test for the earliest detection of CVD, the EBT heartscan. Our data and recommendations help you guide your patients care accurately with evidence-based recommendations.

J.A. Rumberger, M.D. FACC

Medical Director, PrevaHealth