Adding Copeptin Test Could Improve HF Diagnosis

Copeptin could add incremental prognostic information to NT-proBNP

May 26, 2011

May 24, 2011 (Linköping, Sweden) - New research suggests that a blood test for elevated levels of a new biomarker, copeptin, could one day be used in the primary-care setting in addition to N-terminal pro-brain-type natriuretic peptide (NT-proBNP) as a screening tool to help determine who does and does not have heart failure, thereby avoiding unnecessary expensive echocardiograms in a proportion of patients [1].

Dr Urban Alehagen (University of Linköping, Sweden) and colleagues report the first long-term study, with 13 years of data, on outcomes with regard to NT-proBNP, an established marker of heart failure produced by cardiac muscle, and copeptin, a newer marker, in older patients with symptoms of heart failure. Both NT-proBNP and copeptin provided independent prognostic information, with elevated levels of both markers being associated with an increased risk of mortality, they report in the May 25, 2011 issue of the Journal of the American Medical Association.

Alehagen told heartwire that it's very difficult in certain patients--particularly the elderly with many comorbidities--to interpret symptoms and successfully diagnose heart failure. Although there is "great experience with NT-proBNP," he notes that it has "a high negative predictive value," so it's often necessary to send people on for echocardiograms to confirm a diagnosis of HF.

"I am advocating not that doctors drop NT-proBNP testing but that copeptin could be added in for a multimarker strategy," he asserts. He acknowledges that "more studies" are needed on copeptin but speculates, "If we could add a copeptin test and show that this marker is not elevated in certain patients, then they would not need to go for echos." In Sweden, at least, an echo costs about 10 times the simple blood test for copeptin, he notes, at around €200 to €250 compared with €20.

Mortality twice as high in those with highest levels of copeptin

Alehagen and colleagues explain that copeptin is a surrogate marker of the hormone vasopressin, produced by the brain. Levels of vasopressin are increased in heart failure, but it is not a useful marker because it degrades too quickly. In their study, they set out to evaluate the association between plasma levels of copeptin combined with concentrations of NT-proBNP and mortality in a cohort of elderly patients with symptoms of heart failure.

In the study, 470 patients from the primary-healthcare population in Sweden were enrolled between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up, through December 2009.

After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes.

Increased concentration of copeptin was associated with increased risk for all-cause mortality, with those in the highest quartile having around twice the risk of death as those in the lowest (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio 2.04 [p<0.001]).

For cardiovascular mortality, the hazard ratio was 1.94 for those in the highest quartile vs the lowest of copeptin (46.6% vs 26.5%; p=0.007).

"Even after a 13-year follow-up period, copeptin concentrations possessed prognostic information concerning mortality risk," Alehagen et al observe.

Prognostic information from the two markers "greater when combined"

NT-proBNP and copeptin levels were then examined at the same time, and in a multivariate model, which was also associated with higher death rates (copeptin fourth quartile: HR 1.63; p=0.01; NT-proBNP fourth quartile: HR 3.17; p<0.001).

There was a significant association for copeptin in the presence of NT-proBNP (log likelihood test, p=0.048), illustrating that copeptin has significant independent prognostic effect in this setting, Alehagen told heartwire . And the prognostic information obtained by the biomarkers was greater when they were combined, he says.

By way of example, 63.7% of the group with low plasma concentrations of both markers survived compared with only 16.5% of those with high plasma concentrations of both.

"Both NT-proBNP and copeptin provided independent prognostic information during a follow-up period of 13 years. To our knowledge, this has not been demonstrated in a corresponding population with such a lengthy follow-up period," they comment. "Combining a biomarker produced locally in the myocardium with a marker produced centrally in the body may be useful in patients with symptoms of heart failure."

They add that the results also suggest that vasopressin "may be a potential target for therapeutic intervention" in heart failure.

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