New Risk for Sudden Death in Dialysis Patients

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New Risk for Sudden Death in Dialysis Patients

By Todd Neale, Senior Staff Writer, MedPage Today
Published: July 29, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner   
Action Points 
Explain that a low concentration of homoarginine in the blood appears to be a risk factor for sudden cardiac death and heart failure death among diabetic patients who require hemodialysis.


Point out that this was a post-hoc analysis, and that the cause of the association is unknown, but may be related to decreased levels of nitric oxide in patients with low homoarginine levels.
A low concentration of homoarginine in the blood appears to be a risk factor for sudden cardiac death and heart failure death among diabetic patients who require hemodialysis, researchers found.

Patients with the lowest homoarginine levels were about twice as likely to die suddenly during a four-year study period as those with the highest (HR 2.1, 95% CI 1.2 to 3.9), according to Christiane Drechsler, MD, PhD, of the University of Würzburg in Germany, and colleagues.

Those with the lowest levels also had about a three-fold greater risk of dying from heart failure (HR 3.3, 95% CI 1.1 to 10.1), the researchers reported in the August issue of the European Journal of Heart Failure.

"Longitudinal assessment of homoarginine may be useful for risk monitoring of dialysis patients," they wrote. "Beyond this, homoarginine may become a promising novel target for therapeutic interventions in populations with high incidences of heart failure and sudden cardiac death."

Sudden cardiac death is a major cause of death for patients on maintenance dialysis. Although some risk factors for sudden cardiac death in these patients have been identified -- including poor glycemic control and vitamin D deficiency -- they do not fully explain the excess mortality.

Previous studies have suggested that homoarginine -- a cationic amino acid -- may increase the availability of nitric oxide, and that a deficiency in the amino acid may increase the risk of endothelial and myocardial dysfunction.

"We reasoned that endothelial dysfunction may play a crucial role in the arrhythmogenesis of patients with kidney failure and tested the hypothesis that low blood concentrations of homoarginine increase the risk of sudden cardiac death in dialysis patients," Drechsler and colleagues wrote.

They performed a post hoc analysis of 1,244 patients from the German 4D Study, which evaluated atorvastatin versus placebo in patients with type 2 diabetes who were undergoing maintenance hemodialysis. The primary endpoint was a composite of cardiac death, stroke, and MI.

The researchers measured homoarginine concentrations in baseline blood samples obtained before the start of hemodialysis or drug treatment. The mean concentration was 1.2 µmol/L.

Low homoarginine concentrations were strongly associated with signs of impaired cardiac function, including congestive heart failure, left ventricular hypertrophy, and higher levels of brain natriuretic peptide.

During a median follow-up of about four years, 617 patients died -- 160 of sudden cardiac death and 41 of congestive heart failure -- and 469 patients had one of the cardiovascular events from the composite endpoint of the 4D Study.

For every unit decrease in homoarginine concentration, the risk of sudden cardiac death increased three-fold (HR 3.1, 95% CI 2.0 to 4.9). The magnitude of the risk was reduced -- but not entirely -- after accounting for various confounders (HR 2.2, 95% CI 1.4 to 3.5).

When the patients were divided into quintiles based on baseline homoarginine concentration, those with the lowest concentration (≤0.81 µmol/L) had an increased risk of both sudden cardiac death and heart failure death compared with those with the highest concentration (>1.48 µmol/L).

There was also an increased risk of combined cardiovascular events in the lowest quintile, although sudden cardiac death and heart failure death accounted for that relationship.

Stroke and MI were not significantly associated with homoarginine levels in the fully adjusted model.

"Potential effects of homoarginine on MI may not have been seen because of competing risks in diabetic dialysis patients," the authors wrote, noting that the findings of the study might not be generalizable to other patient populations.

Additional limitations included the possibility of residual confounding and the inability to draw conclusions about causality from a post hoc analysis.

But, Drechsler and colleagues wrote, the fact "that single-nucleotide polymorphisms (SNPs) or activity of the key enzyme for homoarginine synthesis have been previously related to renal and myocardial diseases supports a causal association between homoarginine metabolism and adverse health outcomes."

Drechsler reported support from a research fellowship from the Deutsche Forschungsgemeinschaft and the Medical Faculty of the University of Würzburg.

The authors reported that they had no conflicts of interest.



Primary source: European Journal of Heart Failure
Source reference:
Drechsler C, et al "Homoarginine, heart failure, and sudden cardiac death in hemodialysis patients" Eur J Heart Fail 2011; 13: 852-859.
 
http://www.medpagetoday.com/Cardiology/Arrhythmias/27794