TOPLINE:

Among patients with chronic kidney disease (CKD) not treated with erythropoiesis-stimulating agents (ESAs), lower haemoglobin levels were linked to a higher risk for major adverse cardiovascular events (MACE+) in women than in men. The association was linear in men but showed a J-shaped pattern in women and was particularly strong in older women.

METHODOLOGY:

• Researchers in France conducted a study to examine the longitudinal association between haemoglobin levels and MACE+ in patients with CKD not treated with ESAs and stratified the analyses on the basis of sex and age.
• They analysed 5-year longitudinal data from 2791 patients with CKD stages 2-5 (median age, 68 years) who were not receiving ESAs at baseline and divided them into younger women (≤ 70 years; n = 566), older women (> 70 years; n = 357), younger men (≤ 70 years; n = 1026), and older men (> 70 years; n = 842).
• Baseline data, extracted from medical records and patient interviews, included demographics, anthropometrics, lifestyle factors, clinical comorbidities, kidney‑specific variables, and laboratory markers; all available longitudinal data on the estimated glomerular filtration rate and transferrin saturation were collected alongside haemoglobin levels.
• The analysis included 29,042 haemoglobin measurements, with the main outcome being MACE+, defined as cardiovascular death, acute myocardial infarction, stroke, or hospitalisation for acute heart failure.

TAKEAWAY:

• During follow-up, 364 (13%) patients had at least one MACE+.
• Compared with a haemoglobin level of 11.5 g/dL, a level of 10.5 g/dL was associated with a 60% increased risk for MACE+ in younger women (adjusted hazard ratio [aHR], 1.6; 95% CI, 1.1-2.4) and a 70% increased risk in older women (aHR, 1.7; 95% CI, 1.3-2.4).
• The same comparison was associated with a 30% increased risk for MACE+ in younger men (aHR, 1.3; 95% CI, 1.1-1.5) and a 20% increased risk in older men (aHR, 1.2; 95% CI, 1.1-1.4).
• The relationship between haemoglobin levels and MACE+ was linear in men but showed a J-shaped pattern in women.

IN PRACTICE:

"Compared to a reference value of 11.5 g/dL, the hazard of MACE+ increased gradually with the decrease of haemoglobin. This association was strongest in women, especially in those of older age. Of note, for a reference value at 11.5 g/dL, there was no significant increase in the hazard of MACE+ in patients with spontaneously high haemoglobin levels, and possibly even a protective effect in men," the authors wrote.

SOURCE:

This study was led by Lisa Le Gall, Institut Bergonié, Bordeaux, France. It was published online on November 08, 2025, in Nephrology Dialysis Transplantation.

LIMITATIONS:

This study was restricted to patients not on ESA therapy, which may not have fully reflected real-world clinical practice. The study cohort was limited to France, restricting the generalisability to other populations. In addition, atherosclerotic and non-atherosclerotic events could not be analysed separately due to a limited number of events.

DISCLOSURES:

The study cohort was funded by the Agence Nationale de la Recherche through the 2010 "Cohortes-Investissements d'Avenir" programme, the 2010 national Programme Hospitalier de Recherche Clinique, and various pharmaceutical companies. Some authors reported receiving grants, payment for lectures, consulting and speaker fees, or research support and having other ties with several pharmaceutical companies, including the funding agency.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.