Vascular endothelial growth factors and risk of cardio-renal events: Results from the CREDENCE trial
Authors' conclusion
People with T2D and DKD with elevated levels of PlGF, sFLT-1, and PlGF/sFLT-1 ratio were at a higher risk for cardiorenal events. Canagliflozin did not meaningfully decrease concentrations of PlGF, sFLT-1, and VEGF-A.
Study context
- Population
- Individuals with T2DM and diabetic kidney disease randomised to canagliflozin or placebo
- Participants
- 2,602 individuals
- Comparison
- Baseline and 1-year vascular endothelial growth factor (VEGF) family biomarker levels and cardio-renal risk
- Primary endpoint
- Composite of:
- End-stage kidney disease
- Doubling of serum creatinine
- Renal/CV death
Methodological detailsbiomarker analysis
- Biomarker analysis
Primary result
As reported in the abstract
Primary composite outcome per 1-unit increase in baseline log biomarker (multivariable)
Hazard ratio (95% CI)P value
Log PlGF (per 1 unit)
1.76(1.23–2.54)
P = 0.002Log sFLT-1 (per 1 unit)
3.34(1.71–6.52)
P < 0.001Log PlGF/sFLT-1 ratio (per 1 unit)
4.83(0.86–27.01)
P = 0.07Log VEGF-A (per 1 unit)did not increase risk
0.96(0.81–1.07)
Per 1 unit, as printed
Further findings
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| Primary composite outcome per 1-unit increase in 1-year concentration of biomarker1-year log PlGF (per 1 unit) | 2.45 (1.70–3.54) | ||
| Primary composite outcome per 1-unit increase in 1-year concentration of biomarker1-year log sFLT-1 (per 1 unit) | 4.19 (2.18–8.03) | ||
| Primary composite outcome per 1-unit increase in 1-year concentration of biomarker1-year log PlGF/sFLT-1 (per 1 unit) | 21.08 (3.79–117.4) | ||
| Primary composite outcome per 1-unit increase in 1-year concentration of biomarkerIncrease in 1-year log VEGF-A · not associated with primary composite outcome | 1.08 (0.93–1.24) | P = 0.30 | |
| 0.050.21520Hazard ratio (log scale) |
Biomarker concentrations with canagliflozin · years 1 and 3
- Canagliflozin did not meaningfully change placental growth factor (PlGF), sFLT-1 and VEGF-A concentrations
Prevalent CVD at baseline by PlGF level
- Higher PlGF levels associated with more prevalent CVD vs lower values
Original publication
Vascular endothelial growth factors and risk of cardio-renal events: Results from the CREDENCE trial. Am Heart J. Published 22 February 2024. doi:10.
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