Prognostic value of human serum alpha-klotho concentrations in patients with heart failure with reduced ejection

Ajay Mahenthiran1, Silvio Augusto Nunes2, Chia-Feng Liu2

  • 1Case Western Reserve University, Cleveland, OH, United States.

Clinical Biochemistry
|January 21, 2026
PubMed

Insights

Higher serum alpha-klotho levels are linked to better survival and lower NT-proBNP in heart failure (HF) patients. This suggests alpha-klotho is a promising biomarker for HF risk stratification.

Area of Science:

  • Cardiology
  • Biomarker Discovery
  • Gerontology

Background:

  • Heart Failure (HF) presents a significant global health challenge with high mortality rates.
  • Identifying novel biomarkers is crucial for managing HF progression.
  • Serum α-klotho's role in HF outcomes requires further investigation.

Purpose of the Study:

  • To evaluate the association between serum α-klotho concentrations and long-term all-cause mortality in stable heart failure (HF) patients.
  • To explore α-klotho as a potential biomarker for risk stratification in HF.

Main Methods:

  • Serum α-klotho levels were measured in 230 adults (135 HF patients, 95 controls).
  • Classification and regression tree analysis stratified patients by α-klotho levels.
  • Kaplan-Meier survival analysis assessed 5-year all-cause mortality.
  • Kruskal-Wallis test compared log-NT-proBNP levels across groups.

Main Results:

  • Higher serum α-klotho concentrations correlated with significantly lower all-cause mortality.
  • Patients with higher α-klotho showed lower log-NT-proBNP levels.
  • Kaplan-Meier analysis revealed a significant survival benefit associated with higher α-klotho levels (log-rank p < 0.01).

Conclusions:

  • Elevated serum α-klotho is associated with reduced mortality and lower NT-proBNP in HF patients.
  • α-klotho may serve as a valuable cardioprotective biomarker for risk stratification in heart failure.
  • These findings highlight α-klotho's potential in improving HF management strategies.
Abstract

Related Concept Videos

Heart Failure II: Pathophysiology01:29

Heart Failure II: Pathophysiology

Systolic Heart Failure and Compensatory MechanismsSystolic heart failure (also termed HFrEF, Heart Failure with Reduced Ejection Fraction) is the most prevalent type of heart filure. It results in a decreased volume of blood being pumped from the ventricle. The aortic arch and carotid sinuses have baroreceptors that detect reduced blood pressure, triggering the sympathetic nervous system (SNS) to release epinephrine and norepinephrine. Initially, this response aims to boost heart rate and...
790
Pathophysiology of Heart Failure01:17

Pathophysiology of Heart Failure

Heart failure (HF) is a progressive syndrome involving ventricles that leads to inadequate cardiac output. It can be classified based on location and output or ejection fraction. Ejection fraction (EF) is an essential measurement in the diagnosis and surveillance of HF. Reduced EF corresponds to systolic heart failure (HFrEF). However, HF with preserved ejection fraction (HFpEF) is becoming increasingly prevalent. Also known as diastolic HF, this form of HF is related to aging. The...
3.0K
Heart Failure I: Introduction01:27

Heart Failure I: Introduction

Heart failure refers to a clinical syndrome caused by structural or functional cardiac disorders that prevent the heart from pumping an adequate amount of blood to meet the body's metabolic needs. This condition often arises from myocardial infarction or ischemia, leading to decreased cardiac output, reduced tissue perfusion, impaired gas exchange, fluid volume imbalance, and decreased functional ability.Heart failure can result from disruptions in the mechanisms that regulate cardiac output...
729
Heart Failure VI: Adjunct Therapies01:22

Heart Failure VI: Adjunct Therapies

Additional therapies for treating patients with heart failure (HF) may include procedural interventions, supplemental oxygen, the management of sleep disorders, and nutritional therapy.Procedural InterventionsImplantable Cardioverter-Defibrillator: For patients at risk of life-threatening arrhythmias due to severe left ventricular dysfunction, an Implantable Cardioverter-Defibrillator (ICD) can detect and terminate these arrhythmias, preventing sudden cardiac death and improving survival rates.
278
Heart Failure Drugs: Diuretics01:22

Heart Failure Drugs: Diuretics

Heart failure and kidney perfusion are interconnected in a complex way. Reduced renal perfusion and venous congestion are two significant factors that contribute to renal dysfunction in heart failure. The kidneys, primarily responsible for fluid balance in the body, are adversely affected due to compromised cardiac output and increased venous pressure. In response to reduced renal perfusion, the kidneys activate neurohumoral mechanisms to restore balance. However, these mechanisms can be...
825
Heart Failure V: Medical Management01:30

Heart Failure V: Medical Management

Medical Management of Acute Decompensated Heart Failure (ADHF)The primary goals of therapy for patients hospitalized with acute decompensated heart failure (ADHF) include:Relieving symptomsOptimizing volume statusSupporting oxygenation and ventilationMaintaining cardiac output (CO) and end-organ perfusionIdentifying and addressing the cause of ADHFPreventing complicationsProviding patient education on factors precipitating HF exacerbationPlanning for dischargeOngoing monitoring and assessment...
227