Essential Hypertension <-> Peripheral Artery Disease

Comorbidity A_BEFORE_B CANDIDATE
Split out of `kb/disorders/Peripheral_Artery_Disease.yaml`'s `environmental:` block (dismech#8551): that entry listed `Hypertension` as an "exposure" acting on peripheral artery disease (PAD), but essential hypertension is a first-class `Disease` entry (`kb/disorders/Essential_Hypertension.yaml`), not something external to the organism the patient is exposed to. Modeling the relationship as a disease-disease comorbidity avoids a near-tautological "exposure" edge that ECTO/XCO can never bind a term for. Directionality is A_BEFORE_B: sustained elevated blood pressure contributes to atherosclerosis and is conventionally treated as an antecedent risk state for PAD. Evidence is carried over unchanged from the original `environmental:` entry rather than dropped.
A

Disease A

Essential Hypertension
Slug:Essential_Hypertension
B

Disease B

Peripheral Artery Disease
Slug:Peripheral_Artery_Disease
G

Causal Mechanism Graphs

Essential Hypertension

graph LR
    High_Sodium_Diet["High Sodium Diet"]
    Immune_and_Inflammatory_Activation["Immune and Inflammatory Activation"]
    Obesity["Obesity"]

    High_Sodium_Diet --> Immune_and_Inflammatory_Activation
    Obesity --> Immune_and_Inflammatory_Activation

    style High_Sodium_Diet fill:#dcfce7
    style Immune_and_Inflammatory_Activation fill:#dbeafe
    style Obesity fill:#dcfce7

Peripheral Artery Disease

graph LR
    Endothelial_Dysfunction_and_Subendothelial_LDL_Retention["Endothelial Dysfunction and Subendothelial LDL Retention"]
    Atherosclerosis["Atherosclerosis"]
    Monocyte_Recruitment_and_Macrophage_Foam_Cell_Formation["Monocyte Recruitment and Macrophage Foam Cell Formation"]
    Advanced_Atheroma_with_Necrotic_Core_and_Fibrous_Cap["Advanced Atheroma with Necrotic Core and Fibrous Cap"]
    Thrombosis["Thrombosis"]

    Endothelial_Dysfunction_and_Subendothelial_LDL_Retention --> Monocyte_Recruitment_and_Macrophage_Foam_Cell_Formation
    Monocyte_Recruitment_and_Macrophage_Foam_Cell_Formation --> Atherosclerosis
    Atherosclerosis --> Advanced_Atheroma_with_Necrotic_Core_and_Fibrous_Cap
    Advanced_Atheroma_with_Necrotic_Core_and_Fibrous_Cap --> Thrombosis

    style Endothelial_Dysfunction_and_Subendothelial_LDL_Retention fill:#dbeafe
    style Atherosclerosis fill:#dbeafe
    style Monocyte_Recruitment_and_Macrophage_Foam_Cell_Formation fill:#dbeafe
    style Advanced_Atheroma_with_Necrotic_Core_and_Fibrous_Cap fill:#dbeafe
    style Thrombosis fill:#dbeafe
S

Association Signals

Signal 1
LITERATURE LITERATURE_ASSOCIATION A_BEFORE_B
Population:CALIBER linked English electronic health records, 1.25 million patients aged 30 and over who were free of cardiovascular disease at baseline, followed for incident peripheral arterial disease among twelve cardiovascular endpoints.
Temporal: A before B: , B before A: , Same time:
HR: 1.23
CI: 1.2 - 1.27
p:
FDR:
Hazard ratio per 10 mm Hg of pulse pressure. Peripheral arterial disease is the strongest of the twelve endpoints on this measure, and the contrast is informative rather than incidental: the same analysis finds pulse pressure inversely associated with abdominal aortic aneurysm (0.91, 0.86-0.98), so this is not a generic blood-pressure effect.
PMID:24881994 (SUPPORT)
Source: HUMAN_CLINICAL
"Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27])."
States the hazard ratio recorded in the metric above, together with the inverse aneurysm comparison that establishes it as endpoint-specific.
H

Hypotheses

Sustained elevated blood pressure promotes endothelial injury and atherogenesis in peripheral arteries (see the `atherogenesis` module), making hypertension a contributing antecedent risk state for peripheral artery disease.
PMID:24881994 (SUPPORT, indirect)
Source: HUMAN_CLINICAL
"raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease"
CALIBER cohort of 1.25 million initially cardiovascular-disease-free patients; pulse pressure showed its strongest association of any of the twelve endpoints assessed with peripheral arterial disease. Graded INDIRECT because it evidences the association rather than the atherogenic mechanism this hypothesis names; for that step, see the `atherogenesis` module. Carried over from the original `Peripheral_Artery_Disease.yaml` `environmental:` entry, whose retired PARTIAL grade this replaces.
Y

Raw YAML

Show YAML 
name: com_Essential_Hypertension__Peripheral_Artery_Disease
creation_date: "2026-08-19T00:00:00Z"
curation_status: CANDIDATE
notes: >-
  Split out of `kb/disorders/Peripheral_Artery_Disease.yaml`'s `environmental:`
  block (dismech#8551): that entry listed `Hypertension` as an "exposure"
  acting on peripheral artery disease (PAD), but essential hypertension is a
  first-class `Disease` entry (`kb/disorders/Essential_Hypertension.yaml`), not
  something external to the organism the patient is exposed to. Modeling the
  relationship as a disease-disease comorbidity avoids a near-tautological
  "exposure" edge that ECTO/XCO can never bind a term for. Directionality is
  A_BEFORE_B: sustained elevated blood pressure contributes to atherosclerosis
  and is conventionally treated as an antecedent risk state for PAD. Evidence
  is carried over unchanged from the original `environmental:` entry rather
  than dropped.

disease_a:
  slug: Essential_Hypertension
  preferred_term: essential hypertension
  term:
    id: MONDO:0001134
    label: essential hypertension

disease_b:
  slug: Peripheral_Artery_Disease
  preferred_term: peripheral arterial disease
  term:
    id: MONDO:0005386
    label: peripheral arterial disease

directionality: A_BEFORE_B
effect_direction: RISK

hypotheses:
- description: >-
    Sustained elevated blood pressure promotes endothelial injury and
    atherogenesis in peripheral arteries (see the `atherogenesis` module),
    making hypertension a contributing antecedent risk state for peripheral
    artery disease.
  evidence:
  - reference: PMID:24881994
    reference_title: "Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people"
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: HUMAN_CLINICAL
    snippet: "raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease"
    explanation: >-
      CALIBER cohort of 1.25 million initially cardiovascular-disease-free
      patients; pulse pressure showed its strongest association of any of the
      twelve endpoints assessed with peripheral arterial disease. Graded
      INDIRECT because it evidences the association rather than the atherogenic
      mechanism this hypothesis names; for that step, see the `atherogenesis`
      module. Carried over from the original `Peripheral_Artery_Disease.yaml`
      `environmental:` entry, whose retired PARTIAL grade this replaces.

association_signals:
- source: LITERATURE
  method: LITERATURE_ASSOCIATION
  population: >-
    CALIBER linked English electronic health records, 1.25 million patients
    aged 30 and over who were free of cardiovascular disease at baseline,
    followed for incident peripheral arterial disease among twelve
    cardiovascular endpoints.
  directionality: A_BEFORE_B
  effect_direction: RISK
  statistics:
    metrics:
    - metric_type: HR
      metric_value: 1.23
      metric_ci_lower: 1.20
      metric_ci_upper: 1.27
      notes: >-
        Hazard ratio per 10 mm Hg of pulse pressure. Peripheral arterial disease
        is the strongest of the twelve endpoints on this measure, and the
        contrast is informative rather than incidental: the same analysis finds
        pulse pressure inversely associated with abdominal aortic aneurysm
        (0.91, 0.86-0.98), so this is not a generic blood-pressure effect.
    evidence:
    - reference: PMID:24881994
      reference_title: "Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people"
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27])."
      explanation: >-
        States the hazard ratio recorded in the metric above, together with the
        inverse aneurysm comparison that establishes it as endpoint-specific.
Source:GitHub