Familial clustering of unexplained heart failure - A Danish nationwide cohort study

Charlotte Glinge*, Sara Rossetti, Louise Bruun Oestergaard, Niels Kjær Stampe, Mia Ravn Jacobsen, Lars Køber, Thomas Engstrøm, Christian Torp-Pedersen, Gunnar Gislason, Reza Jabbari, Jacob Tfelt-Hansen

*Corresponding author for this work


AIMS: To determine whether a family history of unexplained heart failure (HF) in first-degree relatives (children or sibling) increases the rate of unexplained HF.

METHODS AND RESULTS: Using Danish nationwide registry data (1978-2017), we identified patients (probands) diagnosed with first unexplained HF (HF without any known comorbidities) in Denmark, and their first-degree relatives. All first-degree relatives were followed from the HF date of the proband and until an event of unexplained HF, exclusion diagnosis, death, emigration, or study end, whichever occurred first. Using the general population as a reference, we calculated adjusted standardized incidence ratios (SIR) of unexplained HF in the three groups of relatives using Poisson regression models. We identified 55,110 first-degree relatives to individuals previously diagnosed with unexplained HF. Having a family history was associated with a significantly increased unexplained HF rate of 2.59 (95%CI 2.29-2.93). The estimate was higher among siblings (SIR 6.67 [95%CI 4.69-9.48]). Noteworthy, the rate of HF increased for all first-degree relatives when the proband was diagnosed with HF in a young age (≤50 years, SIR of 7.23 [95%CI 5.40-9.68]) and having >1 proband (SIR of 5.28 [95%CI 2.75-10.14]). The highest estimate of HF was observed if the proband was ≤40 years at diagnosis (13.17 [95%CI 8.90-19.49].

CONCLUSION: A family history of unexplained HF was associated with a two-fold increased rate of unexplained HF among first-degree relatives. The relative rate was increased when the proband was diagnosed at a young age. These data suggest that screening families of unexplained HF with onset below 50 years is indicated.

Original languageEnglish
Article number132028
JournalInternational Journal of Cardiology
Publication statusPublished - 2024


  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Child
  • Cluster Analysis
  • Cohort Studies
  • Denmark/epidemiology
  • Family
  • Female
  • Genetic Predisposition to Disease/epidemiology
  • Heart Failure/epidemiology
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Registries
  • Young Adult
  • Family history
  • Family aggregation
  • First-degree relative
  • Unexplained heart failure


Dive into the research topics of 'Familial clustering of unexplained heart failure - A Danish nationwide cohort study'. Together they form a unique fingerprint.

Cite this