{"id":"4d18fbef-69ec-5e82-81bb-e76614213de6","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-4py-risk","predicate":"associated_with","statement":"Higher serum 4PY was associated with three-year major adverse cardiovascular events in both validation cohorts.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"9c9726e4-f1dd-58aa-a4cd-87672f131e5b","mechanism_event_label":"A second terminal metabolite also tracked risk in the studied cardiac patients.","subject":{"id":"257094c9-2e70-5e55-9831-7d04d73dcb85","slug":"n1-methyl-4-pyridone-3-carboxamide","display_name":"N1-methyl-4-pyridone-3-carboxamide (4PY)","entity_type_key":"small_molecule"},"object":{"id":"8f08bd23-f5e8-5787-b7b5-d6e1e26ed99c","slug":"major-cardiovascular-event-incidence","display_name":"Major cardiovascular event incidence","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9c9726e4-f1dd-58aa-a4cd-87672f131e5b","stable_key":"a9dd23c6-978a-5755-8bd8-f29bd1fe0cda:nia-clin-4py-risk-event","event_type":"observed_intervention","label":"A second terminal metabolite also tracked risk in the studied cardiac patients.","description":"Higher serum 4PY was associated with three-year major adverse cardiovascular events in both validation cohorts.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"257094c9-2e70-5e55-9831-7d04d73dcb85","slug":"n1-methyl-4-pyridone-3-carboxamide","display_name":"N1-methyl-4-pyridone-3-carboxamide (4PY)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8f08bd23-f5e8-5787-b7b5-d6e1e26ed99c","slug":"major-cardiovascular-event-incidence","display_name":"Major cardiovascular event incidence","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"cross_nutrient","value_text":"Niacin precursor form and the measured endpoint are separate graph entities.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/niacin-clinical-sources/ferrell2024.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\", \"start_char\": 0, \"end_char\": 2066, \"text_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Prospective stable cardiac patient cohorts with three-year event follow-up","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Niacin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"niacin","display_name":"Niacin (vitamin B3)","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A second terminal metabolite also tracked risk in the studied cardiac patients.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. (2024). https://pubmed.ncbi.nlm.nih.gov/38374343/ DOI: 10.1038/s41591-023-02793-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Serum metabolites and clinical cardiovascular outcomes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"e503e52b-d6bd-5914-a221-555b43ffd5c6","evidence_kind":"source_excerpt","locator":"Lines 1571-1583","start_line":1571,"end_line":1583,"excerpt":"### nia-clin-4py-risk\nHigher serum 4PY was associated with three-year major adverse cardiovascular events in both validation cohorts.\nCondition category: biomarker_context\nnutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A second terminal metabolite also tracked risk in the studied cardiac patients.\norganism: Homo sapiens\ntissue_or_cell_type: Serum metabolites and clinical cardiovascular outcomes\nexperimental_model: Prospective stable cardiac patient cohorts with three-year event follow-up\nlimitations: Human metabolite associations are not randomized effects of niacin intake. Renal handling and other determinants of levels matter. Mouse exposure results do not prove dietary niacin or supplements caused human events.\nexposure: Discovery cohort 1,162; US validation 2,331 and European validation 832; three-year cardiovascular follow-up; physiological-level mouse metabolite exposure\ncross_nutrient: Niacin precursor form and the measured endpoint are separate graph entities.\nevidence_span: {\"source_cache\": \"artifacts/niacin-clinical-sources/ferrell2024.abstract.txt\", \"locator\": \"Indexed primary abstract\", \"file_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\", \"start_char\": 0, \"end_char\": 2066, \"text_sha256\": \"09530c87779c7a8db8507c847dcb29ae3b7e439967c9271dec5f7cbda6c33d19\"}\n[nia-clin-ferrell2024] A terminal metabolite of niacin promotes vascular inflammation and contributes to cardiovascular disease risk. 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