Despite the JUPITER trial that found benefits for assessing patients with a high-sensitivity C-reactive protein (hs-CRP) test, researchers from London found screening for hs-CRP does little or nothing to improve heart disease risk assessment, according to a late-breaking clinical trial presented Nov. 17 at this year’s American Heart Association (AHA) Scientific sessions in Chicago.
The ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) study was used to evaluate the relationship between administering CRP prior to, and on-treatment with statins and their association with cardiovascular (CV) events.
Peter S. Sever, MD, of the Imperial College in London, and colleagues evaluated 4,853 patients with cholesterol levels less than or equal to 6.5 mmol/L who were randomized to receive either a 10 mg dose of atorvastatin (Lipitor, Pfizer) or placebo.
Trial participants had an average age of 65 and the majority were male.
ASCOT aimed to better evaluate whether both baseline and on-treatment levels of biomarkers were important predictors of CV outcomes.
“The first series of analysis we did were with CRP because of the great interest that’s been raised about its use and whether or not it is an independent predictor of outcomes,” Sever told Cardiovascular Business News. “We also looked to find the extent at which CRP is lowered in patients treated with statins because it is an important predictor of outcomes.”
The researchers found that while CRP at baseline is a good predictor of cardiovascular events, which modestly predicted events independently with a hazard ratio of about 1.2. However, adjusting for various variables such as age, sex, comorbidities, among others, “could influence that," said Sever.
"The real question is does it really add anything when you include CRP to the risk prediction offered by the Framingham risk score, for example,” Sever said.
Results showed that at six-month follow-up, patients administered atorvastatin saw LDL cholesterol levels that were reduced by 40.3 percent and median CRP levels reduced by 27.4 percent.
During the 5.5 year follow-up, a total of 485 CV events occurred. The researchers then utilized statistical modeling to evaluate the association between CV events and patients’ cholesterol and CRP levels.
“Most of what we saw actually showed that there was no added value to measuring CRP despite the fact that in the initial analysis it is a risk predictor,” said Sever. “Once you put it into the equation with other factors such as age, blood pressure, smoking, diabetes, cholesterol and so on it really doesn’t matter much and, in fact, it adds an incredibly small amount.”
For those taking atorvastatin, LDL levels below the median while on the treatment were associated with a reduction in CV events compared to those taking placebo and who had LDL cholesterol levels that were above the median; however, this was unchanged after the researchers adjusted for baseline risk factors such as smoking, diabetes, etc.
“When CRP is used, you don’t reclassify any patients or maybe a couple of percent get reclassified when you put CRP into the equation,” he said.
In addition, Sever said that when the researchers evaluated the level of CRP within the trial, they found that it did not predict outcomes as well as other data, such as that within the JUPITER trial, which found that taking rosuvastatin (Crestor, AstraZeneca) reduced CV events by 37 percent in patients with normal cholesterol levels and no other risk factors besides elevated CRP levels.
“We found that once you lowered LDL cholesterol levels with statins, adding in a lowered CRP produced no additional benefit of cardiovascular risk prediction.
“Our results were diametrically opposed to the data that had been produced from the JUPITER trial,” Sever said. “When you look at the totality of the evidence, it seems to me that in for the usual sorts of patients that we see in the office or surgery every day with blood pressure, diabetes and coronary disease, measuring CRP adds nothing to the management scheme.
“The big debate is whether CRP is a useful tool that physicians