Heart failure & cardiomyopathiesCohort study
Transthyretin Tetramer Destabilization and Increased Mortality in the General Population
- Prospective cohort study
- genetic analyses
- observational subsample analyses
Authors' conclusion
Transthyretin tetramer destabilization was associated with all-cause and cardiovascular mortality in the Danish general population.
Study context
- Population
- Individuals aged 20 to 80 years from the Danish general population (Copenhagen City Heart Study (CCHS) and Copenhagen General Population Study (CGPS))
- Participants
- 102,204 individuals
- Exposure
- TTR genotypes by tetramer stability vs p.T139M stabilizing variant
- Outcome
- All-cause and CV mortality
- Follow-up
- Median 10 years
Main finding
As reported in the abstract
Each group vs p.T139MHazard ratio (95% CI)
Noncarriersall-cause mortality
1.37(1.06–1.77)
Amyloidogenic variant heterozygotesall-cause mortality
1.65(0.95–2.88)
NoncarriersCV mortality
1.63(0.92–2.89)
Amyloidogenic variant heterozygotesCV mortality
2.23(0.78–6.34)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Mortality by plasma transthyretin <20 vs 20 to 40 mg/dL in noncarriers (observational) — <20 mg/dL vs 20 to 40 mg/dL · all-cause mortality | 1.12 (1.02–1.23) | |
| Mortality by plasma transthyretin <20 vs 20 to 40 mg/dL in noncarriers (observational) — <20 mg/dL vs 20 to 40 mg/dL · CV mortality | 1.16 (0.97–1.39) | |
| 0.512Hazard ratio (log scale) |
| Outcome | difference |
|---|---|
| Plasma transthyretin by TTR genotype — Noncarriers vs p.T139M | −18% |
| Plasma transthyretin by TTR genotype — Amyloidogenic variant heterozygotes vs p.T139M | −29% |
- Plasma transthyretin by TTR genotype: P for trend < .001
- Mortality by plasma transthyretin <20 vs 20 to 40 mg/dL in noncarriers (observational): n = 19 619
Original publication
Transthyretin Tetramer Destabilization and Increased Mortality in the General Population. JAMA Cardiol. Published 1 February 2025. doi:10.1001/jamacardio.2024.4102
Summarised from the published abstract; every number is checked against it