Copeptin Pegged as Mortality Predictor in High-Risk Systolic HF

August 29, 2012

August 29, 2012 (Munich, Germany) — Levels of the peptide copeptin could possibly be used to risk-stratify and track the progress of a particularly high-risk group of heart-failure patients, those with prior hospitalization for acute decompensation, suggests an observational study of >900 patients [1]. The peptide with biomarker potential in HF is a fragment of a molecular precursor to vasopressin, which is produced in the brain and helps modulate renal function, among other things.

"We found that copeptin is a promising surrogate marker of chronic and acute stress and that it was elevated in heart-failure patients," Dr Stefan Störk (Julius-Maximilians University of Würzburg, Germany) told heartwire . Levels of copeptin tracked with a range of clinical features and laboratory markers that predict future outcomes, he said, and independently predicted mortality in higher-risk patients with heart failure.

"They are a fairly sick group of patients, but a certain proportion of them can be safely [stabilized after decompensation] and they do fairly well," Störk said. "But some of them [do] not, and it would be very interesting to define as early as possible those who would actually need an aggressive therapeutic strategy, because sometimes we wait too long."

Störk presented the observational study, based on a cohort from the Germany-based Interdisciplinary Network Heart Failure Study, here at the European Society of Cardiology (ESC) 2012 Congress. The findings are consistent with earlier research that suggested copeptin levels can contribute independently to the diagnosis of heart failure and seem to be prognostic in heart failure of most any degree of severity.

Correlation of CV Risk Markers to Copeptin Levels, by Copeptin Concentration Quartiles (Quartile 1 <10.10 Pmol/L; Quartile 4= >40.60 Pmol/L)

Parameter Quartile 1 Quartile 2 Quartile 3 Quartile 4
NYHA class 3–4 (%) 28 41 49 61
GFR <60 mL/min (%) 12 28 48 78
Diabetes (%) 25 34 37 43
Anemia (%) 20 25 32 48
NT-proBNP (pg/mL) 1401 2166 4187 7864
hs-CRP (mg/L) 7.2 7.8 10.2 15.8

p<0.01 for all interquartile trends

GFR=glomerular filtration rate

hs-CRP=high-sensitivity C-reactive protein

The cohort's 926 patients were predominantly male, with average age 68, had LVEF <40% (mean, 30%), and were enrolled before discharge from hospitalization for acute decompensation; 70% had ischemic heart disease, and 44% were in NYHA class 3–4.

Their median copeptin level was 20.4 pmol/L; 30% of patients had levels in the normal range, <12 pmol/L.

Mortality at Baseline and 18 Months by Copeptin Concentration Quartiles

Parameter Quartile 1 Quartile 2 Quartile 3 Quartile 4
18-mo all-cause mortality (%) 10 12 19 39
HR (95% CI) assayed before discharge 1.0 1.3 (0.7–2.2) 2.1 (1.3–3.5) 4.7 (2.9–7.5)
HR (95% CI) assayed at 6 mo 1.0 0.8 (0.2–2.9) 5.5 (1.5–9.9) 9.8 (4.0–24.2)

Störk observed that the patients were on types and dosages of medications one would expect for their condition; they included ACE inhibitors in 80%, beta blockers in 85%, and diuretics in 95%. And the sicker they were, the more medications they received. But copeptin was just as prognostic in an analysis that controlled for medication types and degree of usage.

Copeptin's potential as a biomarker in some ways resembles how natriuretic-peptide levels are used in heart failure and other conditions, but Störk notes that levels of N-terminal pro-brain-type natriuretic peptide (NT-proBNP), for example, aren't entirely reliable as a predictor--sometimes they're in the normal range while the patient remains at high risk by other standards, and vice versa.

"It might well be good to combine information from different biomarkers to give a complementary image from a different compartment of the body system," he said. NT-proBNP comes from heart tissue, while copeptin is secreted from the hypothalamus gland and the anterior and posterior pituitary glands.

There are other differences. When high NT-proBNP levels fall, generally the patient is also improving clinically. But, "if baseline levels [of copeptin] are very high, regardless of subsequent lowering, those patients actually have a very dire prognosis," he said. Still, there is "still a long way to go" before copeptin may be considered for inclusion in a multimarker panel and possibly made part of clinical practice.

Copeptin measurements were performed by ThermoFisher Scientific, which "was not involved in the analysis or interpretation of the data." Störk had no disclosures.

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