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A longitudinal analysis of haemoglobin levels and major cardiovascular events
Lisa Le Gall1, Natalia Alencar de Pinho2, Jérôme Harambat1,3
1Univ. Bordeaux, INSERM, BPH, U1219, CIC 1401, F-33000 Bordeaux, France.
Insights
Women with chronic kidney disease (CKD) face a higher risk of major adverse cardiovascular events (MACE+) when experiencing anaemia compared to men. This sex-specific difference in anaemia risk underscores the need for tailored treatment strategies in CKD patients.
Area of Science:
- Nephrology
- Cardiology
- Internal Medicine
Background:
- Standard anaemia management in chronic kidney disease (CKD) lacks age- and sex-specific risk stratification.
- Investigating sex-based differences in haemoglobin-associated cardiovascular risk is crucial for non-dialysis CKD patients.
Purpose of the Study:
- To assess sex- and age-specific associations between haemoglobin levels and major adverse cardiovascular events (MACE+) in non-dialysis CKD patients.
- To determine if the risk of MACE+ differs between men and women with CKD across different age groups.
Main Methods:
- Utilized 5-year longitudinal data from the CKD-REIN cohort, including patients with CKD stages 2-5 not on erythropoiesis stimulating agents (ESA).
- Defined MACE+ as cardiovascular death, myocardial infarction, stroke, or acute heart failure hospitalization.
- Employed cause-specific Cox models within sex and age subgroups (≤70 vs. >70 years) to estimate hazard ratios (HR) for haemoglobin levels, adjusting for glomerular filtration rate and transferrin saturation.
Main Results:
- The association between haemoglobin and MACE+ risk showed a linear pattern in men and a J-shape in women.
- A haemoglobin of 10.5 g/dL, compared to 11.5 g/dL, increased MACE+ hazard by 60% in younger women and 70% in older women.
- The corresponding increase in MACE+ hazard was 30% in younger men and 20% in older men, indicating a stronger association in women.
Conclusions:
- A significantly stronger association exists between anaemia and increased MACE+ hazard in women compared to men with CKD not receiving ESA therapy.
- These findings highlight critical sex differences in cardiovascular risk related to anaemia in CKD.
- The identified sex-specific risks should guide the design of future clinical trials for anaemia management in CKD patients.
Background And Hypothesis:
The standard approach to anaemia in non-dialysis chronic kidney disease (CKD) does not account for potential age- or sex-specific related risks. We assessed differences in the association between haemoglobin and major cardiovascular events (MACE+) in men and women with CKD, by age groups.
Methods:
Using 5-year longitudinal data from the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort, we studied patients with CKD stage 2-5 not treated with erythropoiesis-stimulating agents (ESA). The main outcome was MACE+, defined as cardiovascular death, myocardial infarction, stroke or hospitalization for acute heart failure. Competing events were initiation of kidney replacement therapy and non-cardiovascular death. In each of the four predefined subgroups by sex and age (≤70 versus >70 years at baseline), we estimated hazard ratios (HR) of current values of haemoglobin using a cause-specific Cox model adjusted for current values of glomerular filtration rate and transferrin saturation. All current values of biomarkers were first estimated in a multivariate-shared random effect joint model.
Results:
Analyses considered 29 042 haemoglobin measurements from 2791 patients, and 364 MACE+. The association between current haemoglobin and log hazard of MACE+ was linear in men and J-shaped in women. For a haemoglobin of 10.5 g/dL, as compared with 11.5 g/dL, the hazard of MACE+ at any time was increased by 60% in younger women [HR = 1.6, 95% confidence interval (CI) 1.1-2.4], 70% in older women (HR = 1.7, 95% CI 1.3-2.4), 30% in younger men (HR = 1.3 95% CI 1.1-1.5) and 20% in older men (HR = 1.2 95% CI 1.1-1.4). Results were similar in the sensitivity analysis not censoring at the first ESA treatment.
Conclusion:
Our longitudinal analysis in patients with CKD not on ESA therapy highlights a stronger association between anaemia and increased hazard of MACE+ in women than in men. This sex difference should inform the design of trials addressing anaemia correction in CKD.
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