{
  "slug": "ldl-ascvd",
  "completed": true,
  "provider_mode": "Consensus MCP keyword search and fetch; independent reconciliation against the frozen review ledger and its documented PubMed primary-record checks",
  "cutoff": "2026-09-29 (frozen review cutoff)",
  "queries": [
    "LDL cholesterol causally causes atherosclerotic cardiovascular disease Mendelian randomization statin randomized trials PCSK9 genetic natural experiment",
    "primary randomized trials 4S Scandinavian Simvastatin Survival Study 1994 PCSK9 genetic variants lower LDL coronary heart disease Cohen 2006 IMPROVE-IT FOURIER primary studies"
  ],
  "raw_paths": [
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  "source_counts_preserved": {
    "evidence_inventory_rows": 33,
    "claims": 28
  },
  "primary_comparisons": [
    {
      "pmid": "12066187",
      "doi": "10.1038/nature00804",
      "review_source": "Skålén et al. 2002",
      "source_type": "primary animal mechanism experiment",
      "access_depth": "PubMed abstract and metadata as documented in review",
      "result_comparison": "ApoB proteoglycan-binding change altered murine atherosclerosis; supports mechanism but not human outcomes or unique LDL particle-number causality.",
      "already_present": true
    },
    {
      "pmid": "16554528",
      "doi": "10.1056/NEJMoa054013",
      "review_source": "Cohen et al. 2006",
      "source_type": "human genetic natural experiment",
      "access_depth": "PubMed abstract and metadata as documented in review",
      "result_comparison": "PCSK9 loss-of-function and LDL-C reduction associated with lower CHD risk; LDL-C and particle traits co-vary, leaving particle-versus-cargo unresolved.",
      "already_present": true
    },
    {
      "pmid": "7968073",
      "doi": null,
      "review_source": "4S",
      "source_type": "primary randomized secondary-prevention trial",
      "access_depth": "PubMed abstract and metadata as documented in review; DOI absent from original ledger",
      "result_comparison": "Simvastatin reduced coronary events and mortality in established CHD; supports LDL lowering, not LDL-P versus LDL-C specificity.",
      "already_present": true
    },
    {
      "pmid": "28304224",
      "doi": "10.1056/NEJMoa1615664",
      "review_source": "FOURIER",
      "source_type": "primary randomized outcome trial",
      "access_depth": "PubMed abstract and final metadata as documented in review",
      "result_comparison": "Evolocumab lowered LDL-C and cardiovascular events, while LDL-C, apoB, and LDL-P co-move; does not isolate particle count from cholesterol cargo.",
      "already_present": true
    }
  ],
  "score_before": {
    "hsef_level": "Ζ",
    "hsef_descriptor": "Multiple independent causal lines converge",
    "confidence": "Moderate",
    "confidence_rationale": "The binding subclaim (SC4) has dense but directionally inconsistent evidence from independent groups and heterogeneous assays (NMR LDL-P, immunoassay apoB, calculated non-HDL-C and remnant-C). Confidence in LDL-class causality (SC2, SC3, SC5) remains High and is reported separately.",
    "rests_on_non_peer_reviewed_work": false,
    "rationale": "Cumulative LDL-class apoB exposure is a primary causal driver of ASCVD (SC1, SC3, SC5 at Η; SC2 at Θ). The submitted wording adds that particle concentration (number) is the operative quantity; that is well supported against LDL-C but contested against total cholesterol cargo, and per-particle risk varies by particle class [20,35,36]. The preregistered weakest-link rule therefore returns Ζ; scope-matched aggregation would return Η."
  },
  "score_after": {
    "hsef_level": "Ζ",
    "hsef_descriptor": "Multiple independent causal lines converge",
    "confidence": "Moderate",
    "confidence_rationale": "The binding subclaim (SC4) has dense but directionally inconsistent evidence from independent groups and heterogeneous assays (NMR LDL-P, immunoassay apoB, calculated non-HDL-C and remnant-C). Confidence in LDL-class causality (SC2, SC3, SC5) remains High and is reported separately.",
    "rests_on_non_peer_reviewed_work": false,
    "rationale": "Cumulative LDL-class apoB exposure is a primary causal driver of ASCVD (SC1, SC3, SC5 at Η; SC2 at Θ). The submitted wording adds that particle concentration (number) is the operative quantity; that is well supported against LDL-C but contested against total cholesterol cargo, and per-particle risk varies by particle class [20,35,36]. The preregistered weakest-link rule therefore returns Ζ; scope-matched aggregation would return Η."
  },
  "grade_changed": false,
  "conclusion": "Consensus discovery does not resolve the frozen review's load-bearing LDL particle-number versus cholesterol-cargo discordance. Established LDL-class causality remains distinct from the stronger concentration-specific wording; no grade or inventory change.",
  "addendum_path": "deliverables\\consensus_consistency_audit_2026-10-09\\checks\\ldl-ascvd\\consensus-addendum.md",
  "independent_blinded_audit": false,
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  "primary_comparison_count": 4,
  "status": "completed_retrospective_original_source_reconciliation",
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  "manifest_source": "deliverables\\consensus_consistency_audit_2026-10-09\\checks\\ldl-ascvd\\final-structured-consensus-validation.json",
  "literature_cutoff_preserved": true
}