Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study
Authors' conclusion
This study provides genetic evidence supporting the anti-inflammatory effects of SGLT-2 inhibitors and their beneficial impact in reducing the risk of HF. CXCL10 emerged as a potential mediator, offering a novel intervention pathway for HF treatment.
Study context
- Population
- Individuals of European ancestry; Heart failure (HF) Genome-wide association study (GWAS) meta-analysis of 26 cohorts (47,309 HF cases, 930,014 controls); 92 inflammatory biomarkers from datasets of 14,824 and 575,531 individuals47,309 HF cases · 930,014 controls
- Comparison
- Genetically predicted SGLT-2 inhibition and HF risk, mediation by inflammatory biomarkers
- Outcome
- HF, OR per 1 unit change of HbA1c
Methodological detailstwo-step, multivariable Mendelian Randomization (MR)
- Two-step
- Multivariable MR
Main finding
As reported in the abstract
HF
Genetically predicted SGLT-2 inhibition and reduced risk of HF, OR (95% CI), P
0.42
0.30–0.59P < 0.0001
Further findings
Inflammatory biomarkers associated with both SGLT-2 inhibition and HF
- Of 92 biomarkers, associated with both (CXCL10 and leukemia inhibitory factor)
- 2
CXCL10 as primary inflammatory cytokine related to HF (multivariable MR)
- MIP
- 0.861
- MACE
- 0.224
- FDR-adjusted P
- 0.0844
Mediation of SGLT-2 inhibition effect on HF by CXCL10
- Proportion of total effect mediated (95% CI), P
- 17.85% (3.03%-32.68%), P = 0.0183
Original publication
Sodium-glucose cotransporter 2 inhibitors, inflammation, and heart failure: a two-sample Mendelian randomization study. Cardiovasc Diabetol. Published 2 April 2024. doi:10.
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