graph LR
Dysregulated_Hepatic_Lipogenesis_and_VLDL_Overproduction["Dysregulated Hepatic Lipogenesis and VLDL Overproduction"]
Increased_LDL_Cholesterol["Increased LDL Cholesterol"]
Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance["Impaired Hepatic ApoB-Containing Lipoprotein Clearance"]
Oxidized_LDL_Infiltration_of_Arterial_Intima["Oxidized LDL Infiltration of Arterial Intima"]
Atherosclerotic_Plaque_Development["Atherosclerotic Plaque Development"]
LPL["LPL"]
Elevated_Triglycerides["Elevated Triglycerides"]
APOA5["APOA5"]
High_Saturated_Fat_Diet["High Saturated Fat Diet"]
Coronary_Artery_Disease["Coronary Artery Disease"]
APOB["APOB"]
Macrophage_Recruitment_to_Arterial_Intima["Macrophage Recruitment to Arterial Intima"]
Macrophage_Derived_Foam_Cell_Formation["Macrophage-Derived Foam Cell Formation"]
Obesity["Obesity"]
LDLR["LDLR"]
PCSK9_Mediated_LDL_Receptor_Degradation["PCSK9-Mediated LDL Receptor Degradation"]
Sedentary_Lifestyle["Sedentary Lifestyle"]
Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation["Impaired Lipoprotein Lipase Activity and ApoC-III Dysregulation"]
Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance --> Increased_LDL_Cholesterol
Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance --> Oxidized_LDL_Infiltration_of_Arterial_Intima
PCSK9_Mediated_LDL_Receptor_Degradation --> Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance
Dysregulated_Hepatic_Lipogenesis_and_VLDL_Overproduction --> Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation
Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation --> Elevated_Triglycerides
Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation --> Oxidized_LDL_Infiltration_of_Arterial_Intima
Oxidized_LDL_Infiltration_of_Arterial_Intima --> Macrophage_Recruitment_to_Arterial_Intima
Macrophage_Recruitment_to_Arterial_Intima --> Macrophage_Derived_Foam_Cell_Formation
Macrophage_Derived_Foam_Cell_Formation --> Atherosclerotic_Plaque_Development
Atherosclerotic_Plaque_Development --> Coronary_Artery_Disease
High_Saturated_Fat_Diet --> Increased_LDL_Cholesterol
Sedentary_Lifestyle --> Dysregulated_Hepatic_Lipogenesis_and_VLDL_Overproduction
Obesity --> Dysregulated_Hepatic_Lipogenesis_and_VLDL_Overproduction
LDLR --> Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance
APOB --> Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance
LPL --> Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation
APOA5 --> Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation
style Dysregulated_Hepatic_Lipogenesis_and_VLDL_Overproduction fill:#dbeafe
style Increased_LDL_Cholesterol fill:#fef3c7
style Impaired_Hepatic_ApoB_Containing_Lipoprotein_Clearance fill:#dbeafe
style Oxidized_LDL_Infiltration_of_Arterial_Intima fill:#dbeafe
style Atherosclerotic_Plaque_Development fill:#dbeafe
style LPL fill:#f3e8ff
style Elevated_Triglycerides fill:#fef3c7
style APOA5 fill:#f3e8ff
style High_Saturated_Fat_Diet fill:#dcfce7
style Coronary_Artery_Disease fill:#fef3c7
style APOB fill:#f3e8ff
style Macrophage_Recruitment_to_Arterial_Intima fill:#dbeafe
style Macrophage_Derived_Foam_Cell_Formation fill:#dbeafe
style Obesity fill:#dcfce7
style LDLR fill:#f3e8ff
style PCSK9_Mediated_LDL_Receptor_Degradation fill:#dbeafe
style Sedentary_Lifestyle fill:#dcfce7
style Impaired_Lipoprotein_Lipase_Activity_and_ApoC_III_Dysregulation fill:#dbeafe
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
name: com_Hyperlipidemia__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 `Dyslipidemia` as an "exposure"
acting on peripheral artery disease (PAD), but dyslipidemia is modeled in
this KB as the first-class `Disease` entry `Hyperlipidemia`
(`kb/disorders/Hyperlipidemia.yaml`, MONDO:0021187), 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: LDL
elevation is a causal antecedent risk state for PAD (Mendelian randomization
and trial evidence). Evidence is carried over unchanged from the original
`environmental:` entry rather than dropped.
disease_a:
slug: Hyperlipidemia
preferred_term: hyperlipidemia
term:
id: MONDO:0021187
label: hyperlipidemia
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: >-
Elevated LDL cholesterol drives atherosclerotic plaque formation in
peripheral arteries (see the `atherogenesis` module), and Mendelian
randomization and trial evidence support a causal, not merely
associative, role for LDL-cholesterol elevation in the development of
peripheral artery disease.
evidence:
- reference: PMID:33221847
reference_title: "LDL-Cholesterol versus Glucose in Microvascular and Macrovascular Disease"
supports: SUPPORT
evidence_source: HUMAN_CLINICAL
snippet: "LDL-cholesterol has a causal effect on risk of peripheral arterial disease"
explanation: >-
Review synthesizing Mendelian randomization and trial evidence,
supporting the LDL fraction specifically and stating the relationship
causally rather than as an association. Carried over unchanged from the
original `Peripheral_Artery_Disease.yaml` `environmental:` entry.