Lp(a) with CRP Levels Predict Death, MI Risk in Korean Cohort With Documented CAD

March 27, 2015

GLASGOW, SCOTLAND — For patients in a Korean study with coronary artery disease undergoing coronary angiography, measuring high-sensitivity C-reactive protein (hs-CRP) and lipoprotein(a) (Lp[a]) helped stratify patients into different categories of risk, with investigators reporting that those with higher levels of both biomarkers were at a significantly increased risk of major adverse cardiovascular events (MACE)[1].

For those with normal levels of CRP and Lp(a), the overall MACE rate was less than 1%, a very low rate despite the high-risk patient population, according to lead investigator Sung Woo Kwon (Inha University Hospital, Incheon, South Korea).

For patients with elevations in both the biomarkers, the risk of MACE was significantly increased compared with those with normal levels, even after adjustment for baseline patient characteristics, said Kwon.

The results of the study, which included just over 5200 patients, were presented this week here at EAS 2015: the European Atherosclerosis Society 2015 Congress. In the analysis, patients were stratified into four groups: those with normal Lp(a) and normal CRP levels; elevated Lp(a) and normal CRP levels; normal Lp(a) and elevated CRP levels; and elevated Lp(a) and elevated CRP levels. The cutoff for elevated Lp(a) and CRP levels were values greater than 20.7 mg/dL and 2.0 mg/L, respectively.

Overall, the MACE rate, defined as cardiac death and nonfatal MI, was 2.3%. For those with normal levels of both biomarkers, the rate was 0.8%. For those with elevated Lp(a) and normal CRP, the MACE rate was 2.2%, while for patients with normal Lp(a) but higher CRP levels, the rate was 3.5%. And finally, for those with elevations in both biomarkers, the MACE rate was 5.3%.

The researchers did observe differences in the characteristics among patients in the different groups. Patients with elevations in Lp(a) and CRP were more likely to be older, have more diabetes, have higher cholesterol levels, and be more likely to have more diffuse disease. They were also significantly more likely to undergo coronary revascularization, including PCI and CABG.

In a multivariate-adjusted risk model, there remained a significantly increased risk of MACE among patients with elevations in either Lp(a) or CRP alone. For those with elevated CRP and normal Lp(a), the risk of MACE was increased more than fourfold compared with those with normal levels. For those with normal CRP but elevated Lp(a), the risk of MACE was more than doubled. Among those with elevations in both Lp(a) and CRP, the risk of MACE was increased 5.5 fold.

As for the two biomarkers, Kwon suspects that patients with elevated Lp(a) levels but normal CRP might have an increased burden of atherogenicity. CRP, he noted, is a marker of inflammation. During the discussion, Kwon pointed out that the European Society of Cardiology (ESC) uses a much higher Lp(a) cutoff value of 50 mg/dL to identify at-risk patients, but the present study included only East Asian patients, a group that is known to have lower Lp(a) values than those of European or African descent.

"The cutoff value of 50 mg/dL is too high for East Asian populations," said Kwon.

Dr John Chapman (Hôpital de la Pitié, Paris, France), who was not involved in the study, believes Lp(a) "seems to have fallen off the totem pole" in terms of use. Previous studies have shown that the cardiovascular risk profile of individuals is significantly heightened at values above approximately the 80th percentile, but while it is mentioned in clinical guidelines and is included in the Reynold's risk score, it is not frequently used in clinical practice.

Commenting on the issue, Dr Naveed Sattar (University of Glasgow, Scotland), who was also not involved in the trial, noted that Lp(a) is the risk factor that appeared to improve the reclassification of cardiovascular risk the most in an analysis from the Emerging Risk Factors Collaboration. However, the improvement was only modest, he said. Similar findings from the group were observed in 2009, a study reported by heartwire from Medscape.

"I think with the way that most clinicians look at Lp(a), you're right—it does need a little more thought," said Sattar. "We currently measure it in clinical practice where we have an individual who has a cardiovascular event for which we can't find any other obvious risk factor. A lot of us will do that. 'Let's measure Lp(a) just in case.' And occasionally we will find that it's very high. So should we be measuring Lp(a) more often? How much better will it improve risk classification? I think we need better individual participant data to try to look at this."

The authors report no relevant financial relationships.


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