Prediction of Long‐Term Survival in Chronic Heart Failure by Multiple Biomarker Assessment: A 15‐Year Prospective Follow‐Up Study

Abstract

Background: In chronic heart failure (CHF), several plasma biomarkers identify subjects at risk of death over the midterm. However, their long-term predictive value in the context of other candidate predictors has never been assessed. This information may prove valuable in the management of a chronic disease with a long natural history, as CHF is today. Hypothesis: We aimed to assess the very-long-term prognostic power of a set of biomarkers to identify CHF patients at highest risk for all-cause mortality. Methods: A group of 106 consecutive outpatients with CHF (85 male and 21 female, median age 56 y) was followed for 15 years. Echocardiographic tracings and blood samples were collected at study entry to evaluate cardiac function, plasma atrial natriuretic peptide (ANP), aldosterone, and erythropoietin, and plasma renin activity. The relationships between biomarkers, clinical and echocardiographic variables, and mortality were assessed. Results: After 15 years, 86 of the 106 patients (81%) had died. Multivariate analysis showed that ANP was the best independent predictor of survival over several clinical, echocardiographic, and humoral variables (hazard ratio: 5.62, 95% confidence interval: 3.37-9.39, P < 0.001 for plasma levels < median value of 71 pg/mL). Plasma renin activity and erythropoietin provided prognostic information in univariate analysis, but lost their predictive power when adjusted for covariates. Conclusions: The present study represents the longest available follow-up of patients with CHF evaluating the prognostic power of multiple biomarkers. It shows that a simple assessment of plasma ANP levels is the strongest long-term predictor of death in all stages of heart failure.

Vasoregulatory peptides pro-endothelin-1 and pro-adrenomedullin are associated with metabolic syndrome in the population-based KORA F4 study

“…This excludes the possibility of undiagnosed glucose intolerance in subjects classified as NGT. Several studies have described a correlation between high VVP levels and cardiovascular complications and mortality (9,13,14,36,37). The limitation of our study is that we have only cross-sectional data.…”

Prognostic value of novel biomarkers compared with detailed biochemical evaluation in patients with heart failure

“…36 RDW is regarded by some authors as a more powerful scores presented a positive association with a predefined outcome, [16][17][18] but still their clinical value remains a matter of debate. 2, 19,20 In studies evaluating the risk reclassification with regard to biomarker use in patients with HF, the advantage of redefining the risk was established.…”

“…12, 16,25 In a critical review, the authors raised concerns with regard to inconsistency in developing prognostic models, with some of the studies using stepwise analysis with data at hand, while others adopting literature-based information.…”

Plasma Renin and Cardiovascular Risk: What Is the Evidence for an Association?

“…A 15-year prospective follow-up study in 105 chronic HF patients did not support PRA as a robust indicator of all-cause mortality. In the univariate analysis, PRA provided prognostic information; however, this predictive power was lost on adjustment for covariates [20]. Atrial natriuretic peptide, however, was a strong, long-term predictor of all-cause mortality in HF.…”

“…A number of studies have assessed the association between plasma renin and subsequent CV events in a variety of populations, including community-based groups [10,11,12], hypertensives [13,14] and patients at high risk for CVD [15,16,17] or with preexisting heart failure (HF) [18,19,20]. The causality of any statistical association is difficult to unravel because plasma renin can be elevated prior to initiation of therapy, but can also increase in response to antihypertensive treatment, including diuretics, angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) [1,21,22,23,24].…”