Prevention & lipidsDiagnostic or prognostic study
Genetic variants lowering lipoprotein(a) and downregulating interleukin-6 signalling are additively associated with a decreased risk of cardiovascular disease
- Mendelian randomization study
- observational validation analyses
Authors' conclusion
Lower Lp(a) levels were associated with a reduced risk of CVD, independent of IL-6 signalling activity. Combined exposure to genetic variants lowering Lp(a) and downregulating IL-6 signalling was associated with an additive reduction in cardiovascular risk.
Study context
- Population
- UK Biobank participants of European ancestry (mean age 57 years; 54% women)
- Participants
- 408,687 participants
- Comparison
- Genetically predicted lower Lp(a) and lower IL-6 signalling, separate and combined
- Outcome
- CHD, ischaemic stroke, heart failure (HF), atrial fibrillation (AF), peripheral artery disease (PAD) and aortic aneurysm
Performance
As reported in the abstract
CVD outcomes:
- Mendelian randomization
- OR per 50 mg/dL lower Lp(a)
- Per 0.5 log[mg/L] lower log CRP
OR
Genetically predicted lower Lp(a)CHD; per 50 mg/dL reduction in Lp(a)
0.68(95% CI 0.65–0.71)
Genetically predicted lower Lp(a)IS
0.89(CI 0.80–0.98)
Genetically predicted lower Lp(a)PAD
0.68(CI 0.62–0.76)
Genetically predicted lower Lp(a)HF
0.82(CI 0.77–0.88)
Genetically predicted lower Lp(a)AA
0.71(CI 0.61–0.82)
Genetically lower IL-6 signallingCHD; per 0.5 log[mg/L] reduction in log CRP
0.67(95% CI 0.55–0.82)
Genetically lower IL-6 signallingAF
0.72(CI 0.55–0.94)
Genetically lower IL-6 signallingAA
0.43(CI 0.23–0.83)
Each row per its own increment, as printed
- lower Lp(a) · coronary heart disease (CHD), combined-exposure analysis
- 0.67 (CI 0.63–0.71)
- lower IL-6 signalling · CHD, combined-exposure analysis
- 0.61 (CI 0.46–0.80)
- combined · CHD; P for interaction = 0.144
- 0.25 (CI 0.21–0.30)
- Lp(a)–cardiovascular disease (CVD) association consistent across IL-6 signalling activity
- P for difference > 0.05
Further findings
CHD, observational analyses
| Comparison | HR | |
|---|---|---|
| Lp(a) < 50 mg/dL | 0.82 (95% CI 0.72–0.93) | |
| IL-6 < median | 0.79 (CI 0.65–0.96) | |
| Combined | 0.65 (CI 0.56–0.74) | |
| 0.512Hazard ratio (log scale) |
- CHD, observational analyses: P for interaction = 0.102
CHD, combined genetic exposure
- P for interaction = 0.144
Original publication
Genetic variants lowering lipoprotein(a) and downregulating interleukin-6 signalling are additively associated with a decreased risk of cardiovascular disease. Eur J Prev Cardiol. Published 20 February 2026. doi:10.1093/eurjpc/zwag090
Summarised from the published abstract; every number is checked against it