Obesity <-> Heart Failure

name: com_Obesity__Heart_Failure
creation_date: "2026-08-27T00:00:00Z"
curation_status: CANDIDATE
notes: >-
  Split out of `kb/disorders/Heart_Failure.yaml`'s `environmental:` block
  (dismech#8296, dismech#8551). That entry listed `Obesity` as an exposure with
  the note "Risk factor for HFpEF", but obesity is a first-class `Disease` entry
  in its own right (`kb/disorders/Obesity.yaml`) rather than something external
  to the organism acting on it, and ECTO has no term that would bind it as an
  exposure. Modeling it here as a disease-disease comorbidity makes the
  relationship queryable and avoids an exposure edge that could never be
  grounded.

  The original note pointed specifically at heart failure with preserved
  ejection fraction. HFpEF is a `has_subtypes` entry on `Heart_Failure` rather
  than a separate disorder file, so `disease_b` is `Heart_Failure` and the
  subtype specificity is recorded here instead of being asserted by a term this
  KB does not carry. The evidence supports both readings: the Framingham cohort
  measured incident heart failure without ejection-fraction stratification,
  while the HFpEF-specific statement comes from a trial population selected for
  it.

  Directionality is A_BEFORE_B: obesity is the antecedent risk state. The
  reverse arm is real but different in kind -- heart failure causes cachexia
  rather than obesity -- and is not modeled here.

disease_a:
  slug: Obesity
  preferred_term: obesity disorder
  term:
    id: MONDO:0011122
    label: obesity disorder

disease_b:
  slug: Heart_Failure
  preferred_term: heart failure
  term:
    id: MONDO:0005252
    label: heart failure

directionality: A_BEFORE_B
effect_direction: RISK

hypotheses:
- description: >-
    Obesity raises heart failure risk through a combination of haemodynamic
    loading, adipose-driven inflammation and the metabolic comorbidities that
    accompany it, and does so across the body-mass index range rather than only
    at its extreme. The association is strongest for the preserved
    ejection-fraction phenotype.
  evidence:
  - reference: PMID:39555826
    reference_title: Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Obesity increases the risk of heart failure with preserved ejection fraction."
    explanation: >-
      States the subtype-specific relationship the original environmental entry
      asserted. This is the trial's framing of established risk rather than its
      own result -- SUMMIT measured tirzepatide, not whether obesity causes
      HFpEF -- so it is cited for the direction of the association only; the
      measured magnitude is carried by the Framingham signal below.

association_signals:
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    Framingham Heart Study community cohort, 5881 participants of mean age 55
    years, 54 percent women, followed a mean of 14 years, with heart failure
    incidence modeled against body-mass index by Cox proportional hazards and
    adjusted for established risk factors.
  directionality: A_BEFORE_B
  effect_direction: RISK
  statistics:
    metrics:
    - metric_type: HR
      metric_value: 2.12
      notes: >-
        Adjusted hazard ratio for incident heart failure in obese versus
        normal-body-mass-index women; 1.90 in men. A graded increase was seen
        across body-mass-index categories rather than only at the obese
        threshold, which is why the entry does not restrict the claim to extreme
        obesity.
    evidence:
    - reference: PMID:12151467
      reference_title: Obesity and the risk of heart failure.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "For women, the hazard ratio was 2.12 (95 percent confidence interval, 1.51 to 2.97); for men, the hazard ratio was 1.90 (95 percent confidence interval, 1.30 to 2.79)."
      explanation: >-
        Gives the adjusted hazard ratios behind this signal, measured
        prospectively in a community cohort followed forward from body-mass
        index to incident heart failure, which is what a directed A_BEFORE_B
        risk signal requires.
    - reference: PMID:12151467
      reference_title: Obesity and the risk of heart failure.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "As compared with subjects with a normal body-mass index, obese subjects had a doubling of the risk of heart failure."
      explanation: >-
        The study's own summary of the effect size, stated without the
        sex-stratified detail.