{"sim_rules_version":"cardiorisk-tables-v1","engine_version":"cardiorisk-india-2026.07","cyp2c19_clopidogrel_activity":{"UM":{"activity_factor":1.3,"phenotype":"Ultra-rapid metabolizer","note":"Increased clopidogrel active metabolite - possible bleed-risk increment.","evidence_grade":"B","verification_required":true},"RM":{"activity_factor":1.15,"phenotype":"Rapid metabolizer","note":"Mild increase in active-metabolite exposure.","evidence_grade":"B","verification_required":true},"NM":{"activity_factor":1,"phenotype":"Normal metabolizer","note":"CPIC reference class - standard clopidogrel 75 mg maintenance appropriate.","evidence_grade":"A","verification_required":false},"IM":{"activity_factor":0.55,"phenotype":"Intermediate metabolizer","note":"Reduced active metabolite - HTPR risk. CPIC: consider prasugrel or ticagrelor.","evidence_grade":"A","verification_required":false},"PM":{"activity_factor":0.3,"phenotype":"Poor metabolizer","note":"Severely reduced active metabolite - avoid clopidogrel per CPIC 2022. Use prasugrel/ticagrelor.","evidence_grade":"A","verification_required":false}},"cyp2c19_diplotype_to_phenotype":{"*1/*1":"NM","*1/*17":"RM","*17/*17":"UM","*1/*2":"IM","*2/*17":"IM","*2/*2":"PM"},"slco1b1_statin_auc":{"simvastatin":{"tc_auc_multiplier":2.4,"tt_auc_multiplier":3.5,"myopathy_or_per_copy":2.6,"evidence_grade":"A","verification_required":false,"note":"CPIC 2022: dose <=20 mg simva in TC; avoid in TT."},"atorvastatin":{"tc_auc_multiplier":1.5,"tt_auc_multiplier":2.4,"myopathy_or_per_copy":1.5,"evidence_grade":"B","verification_required":true,"note":"Meta-analysis effect size approximate; verify against CPIC statin table row."},"rosuvastatin":{"tc_auc_multiplier":1.3,"tt_auc_multiplier":1.8,"myopathy_or_per_copy":1.4,"evidence_grade":"B","verification_required":true,"note":"Rosuvastatin partially non-OATP1B1 dependent - smaller effect."},"pravastatin":{"tc_auc_multiplier":1.2,"tt_auc_multiplier":1.6,"myopathy_or_per_copy":1.2,"evidence_grade":"B","verification_required":true,"note":"Least SLCO1B1-sensitive - preferred switch target for TT/TC on high statin dose."}},"statin_myopathy_baseline_pct_per_year":{"simvastatin_high_dose":0.9,"simvastatin_mod_dose":0.3,"atorvastatin_high_dose":0.5,"atorvastatin_mod_dose":0.2,"rosuvastatin_high_dose":0.4,"rosuvastatin_mod_dose":0.15,"pravastatin_any":0.1},"iwpc_intercept":5.6044,"iwpc_coefficients":{"age_by_decade":-0.2614,"height_cm":0.0087,"weight_kg":0.0128,"VKORC1_AG":-0.8677,"VKORC1_AA":-1.6974,"CYP2C9_star2_het":-0.5211,"CYP2C9_star2_hom":-0.9357,"CYP2C9_star3_het":-1.0616,"CYP2C9_star3_hom":-1.9206,"asian_race":-0.1092,"amiodarone_use":-0.5503,"enzyme_inducer_use":1.1816},"indian_cad_prs_seed":[{"variant":"rs10757278","gene":"CDKN2B-AS1 (9p21)","risk_allele":"G","af_india_approx":0.5,"or_per_risk_allele":1.25,"trait":"coronary artery disease","evidence_grade":"A","verification_required":true,"note":"9p21 - largest-effect common CAD SNP globally. Indian-specific effect size verification_required."},{"variant":"rs10455872","gene":"LPA","risk_allele":"G","af_india_approx":0.08,"or_per_risk_allele":1.7,"trait":"elevated Lp(a) -> premature CAD","evidence_grade":"A","verification_required":true,"note":"LPA intron 25 tag SNP for elevated Lp(a). India-specific frequency and effect verification_required."},{"variant":"rs688","gene":"LDLR","risk_allele":"T","af_india_approx":0.44,"or_per_risk_allele":1.1,"trait":"LDL-C elevation","evidence_grade":"B","verification_required":true,"note":"Modest effect on LDL-C; contributes marginally to composite score."},{"variant":"rs4149056","gene":"SLCO1B1","risk_allele":"C","af_india_approx":0.12,"or_per_risk_allele":1,"trait":"statin-response modifier (not CAD-causal)","evidence_grade":"A","verification_required":false,"note":"Included in cohort MC because it moderates the effect of the statin arm, not because it causes CAD."}],"interheart_south_asian_ors":{"current_smoker":2.6,"diabetes":3.8,"hypertension":2.6,"abdominal_obesity":2.2,"psychosocial_stress":2.7,"poor_diet":1.9,"physical_inactivity":1.4,"lp_a_elevated":2.5},"indian_annual_mi_baseline_per_100k":{"urban_male_40_49":360,"urban_male_50_59":680,"urban_female_40_49":140,"urban_female_50_59":300,"rural_male_40_49":210,"rural_male_50_59":400,"rural_female_40_49":90,"rural_female_50_59":190},"sinam_hla_association":{"hla_allele":"HLA-DRB1*11:01","reported_or_range":[4,8],"prevalence_estimate_per_100k_statin_users":[2,3],"evidence_grade":"B","verification_required":true,"note":"SINAM is rare (~2-3/100k statin users). HLA-DRB1*11:01 association well-published but Indian cohort data sparse. Direction-only output per PRD sec.3.3 immune-scenario guardrail."},"auditability_note":"This is the entire numeric substrate. All simulation math is arithmetic over these tables; same input -> same output every call."}