{"publication_id":"467ebee6-15d2-4907-bf9c-0b97ec47f608","traces":[{"claim_id":"claim_1","claim":"Evidence-honesty note: 38/65 retained sources are coded as null or no extracted directional signal; this corpus is non-supportive for clinical efficacy claims and hypothesis-generating only. Source-bundle reconciliation note: Directional coding is conservative claim-level coding from extracted claim records, not a statement that the source texts contain no directional findings; source-level positive, negative, or unclear findings should be interpreted through the coded outcome class, directness, and claim-count fields. The retained evidence has no direct interventional hard-endpoint evidence; indirect, review-level, adjacent, or mechanistic sources are used only to bound interpretation. The conclusion therefore does not support broad causal, clinical, or policy claims.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_2","claim":"This paper synthesizes evidence on statin use effects across 65 accepted source papers and 3513 high-confidence extracted claims.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_3","claim":"The evidence profile contains no sources classified primarily as direct interventional hard-endpoint evidence, 37 adjacent clinical sources, and 2 mechanistic or model-system sources, with 592 cross-study disagreements across the evidence base.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_4","claim":"Positive study-level signals are summarized in the longevity, mortality and survival, cardiometabolic outcome classes, null signals in the contextual adjacent evidence, mortality and survival, safety and comorbidity outcome classes, and negative signals in the cardiometabolic outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_5","claim":"The conclusion is that statin use effects remains a bounded geroscience case: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_6","claim":"The global burden of age-related disease continues to mount as populations grow older, creating an urgent search for interventions that might compress morbidity and extend healthspan rather than merely treating individual conditions in isolation. Statins — 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors — occupy a unique position in this landscape because they are among the most widely prescribed medications worldwide, with an estimated hundreds of millions of patient-years of accumulated exposure, and their primary cardiovascular indications already encompass a large share of the older-adult population. Yet the question of whether Statin Use Effects extend beyond low-density lipoprotein lowering to influence fundamental aging biology has gained considerable momentum over the past decade, fueled by observational signals linking statin use to reduced mortality in diverse clinical contexts ranging from sepsis to cancer. Whether these associations represent genuine geroprotective activity, residual confounding by indication, or selective survivorship bias remains deeply uncertain, and the stakes are high: if even a fraction of the observed benefit reflects true anti-aging mechanisms, the public-health implications for a low-cost, globally accessible drug class would be substantial. At the same time, concerns about Statin Use Effects on muscle function, gait speed, and sarcopenia risk in older adults raise the possibility that any longevity gain could be offset by accelerated physical decline — a tradeoff that is especially consequential for frail or mobility-limited individuals. The present moment therefore demands a structured, cross-domain evidence synthesis that can weigh competing signals rather than relying on any single outcome class to define the overall risk–benefit profile of Statin Use Effects.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_7","claim":"Several unresolved questions complicate efforts to draw definitive conclusions about Statin Use Effects as a geroprotective strategy, and these uncertainties span mechanistic plausibility, clinical translation, and population specificity. The dose-response and duration-response relationships for both benefits and harms remain poorly characterized: some evidence suggests that higher statin doses may carry greater osteoarthritis risk (Zhang 2022), while cancer-related benefits in colorectal cancer may be duration-dependent (Sun 2023), but these findings require replication in prospective designs. Additionally, the question of whether Statin Use Effects differ meaningfully between primary and secondary prevention contexts, or between younger and older subpopulations, has been raised but not resolved, as most meta-analytic estimates pool across these strata. Concomitant medication use represents another underexplored confounder; one study found that the association between statin use and gait speed reserve was modified by the presence of other cardiovascular medications (Spiegeleer 2025). Finally, the potential for statin use to increase the risk of daptomycin-related rhabdomyolysis (Chuma 2022) or to influence the incidence of specific conditions such as microscopic colitis (Rancz 2025) underscores that the safety profile of long-term statin use in aging populations may be more complex than the cardiovascular-focused risk–benefit calculus that currently dominates clinical guidelines.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_8","claim":"The present synthesis aims to address these cross-domain tensions by applying a structured evidence-weighting framework that explicitly separates clinical-effect estimates from mechanistic rationale, and that maps the concordance or discordance of Statin Use Effects across multiple aging-relevant outcome classes simultaneously. Rather than treating longevity, cardiometabolic health, muscle function, cancer prognosis, and safety as independent literatures, this approach examines whether signals in one domain are reinforced or contradicted by findings in another — for example, whether the positive mortality associations observed in sepsis and cancer cohorts are compatible with the negative muscle-function signals reported in community-dwelling older adults. The synthesis draws on approximately 65 curated reference papers spanning observational cohorts, systematic reviews, and meta-analyses, and identifies hundreds of cross-study disagreements across outcome classes that collectively define the current evidence boundary for Statin Use Effects as an anti-aging intervention. By foregrounding these tensions rather than averaging across them, the framework is designed to help clinicians and researchers distinguish between contexts in which statin use appears to confer broad-spectrum benefit and those in which the evidence remains ambiguous or points toward net harm. The central argument is not that statins are or are not geroprotectors, but rather that the case for geroprotection is currently incomplete: mechanistic plausibility coexists with mixed human evidence, and the boundary conditions — encompassing population, duration, dose, statin type, and competing risk — remain to be systematically established. This structured approach is intended to inform both clinical decision-making for older adults already taking statins and the design of future trials that could definitively test the geroprotective hypothesis.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_9","claim":"Preclinical and disease-model evidence suggests that statins modulate pathways relevant to aging biology, though effect directions vary by context. In colorectal cancer models, statin exposure has been associated with improved prognosis, including reduced all-cause mortality (HR: 0.80; 95% CI: 0.74-0.87) and cancer-specific mortality (HR: 0.74; 95% CI: 0.67-0.82), though heterogeneity across studies was substantial (I² = 90% and I² = 88%, respectively) (Vahed 2026). Prostate cancer analyses report a similar survival signal in men receiving androgen-deprivation therapy, with a pooled 27% reduction in overall mortality risk (Jayalath 2022). Thus, Statin Use Effects appear to operate along a mechanistic duality: anti-neoplastic and anti-inflammatory pathways may be enhanced, while skeletal muscle function may be compromised.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_10","claim":"Methodological questions critically shape interpretation of the Statin Use Effects literature and illuminate the mechanism-to-clinic gap. Endpoint selection is a major source of heterogeneity: mortality-survival outcomes range from 30-day in-hospital death to long-term cancer-specific survival, each with distinct confounding structures. Muscle-function endpoints such as grip strength, gait speed, and appendicular lean mass may be sensitive to pharmacogenomic variability, though Statin Use Effects on decline persisted irrespective of pharmacogenomic score in at least one large analysis (Gentreau 2025). The overall synthesis suggests that while Statin Use Effects are biologically plausible across multiple aging-related domains, the evidence remains fragmented by heterogeneous methods, variable follow-up durations, and the absence of large-scale randomized trials testing geriatric-specific endpoints—leaving the anti-aging hypothesis as currently constituted incomplete.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_11","claim":"The biological rationale is treated as context rather than as clinical proof. Population fit, comparator alignment, clinical directness, follow-up length, ascertainment method, baseline risk, adherence, exposure dose, and external validity are kept separate during interpretation. The interpretation","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_12","claim":"The following fields were extracted from each included source: study design, population / cohort, intervention or exposure, comparator, outcome class, effect direction, effect size, confidence interval or credible interval, p-value, sample size, follow-up duration, risk-of-bias rating. Under the calibration rule, source verification in the public bundle is limited to reference-level metadata; exact statistics and effect directions are drawn from these structured extraction artifacts (the synthesis manifest, risk-of-bias appraisal, and claim registry) rather than from re-parsed full text.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_13","claim":"Per-source risk-of-bias was rated using design-appropriate Cochrane RoB-2 (RCTs), ROBINS-I (non-randomised studies), and AMSTAR-2 (systematic reviews / meta-analyses). Ratings recorded in `risk_of_bias.json`.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_14","claim":"Evidence-tension synthesis: claims grouped by outcome class (cardiometabolic, contextual adjacent evidence, deficiency prevalence, longevity, mortality and survival, muscle function, safety and comorbidity); within-class agreement, disagreement, and directness gaps surfaced explicitly. Quantitative pooling applied only where ≥3 sources reported a comparable endpoint with extractable effect estimates.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_15","claim":"Source retrieval, claim extraction, evidence routing, and prose drafting were assisted by large language models under a deterministic audit-trail protocol. Every manuscript claim is traceable to a source record in the supplementary `manifest.json`. Final eligibility and interpretation decisions are author-verified.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_16","claim":"| Evidence domain | Corpus slice | Strongest signal | Directness | Main limitation |","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_17","claim":"| Contextual Adjacent Evidence | n=32; claims=1343 | no extracted directional signal in 24/32 sources | 15 indirect; 1 mechanistic; 16 review | limited corpus depth in this outcome class |","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_18","claim":"Outcome-class note:** Contextual Adjacent Evidence denotes background, boundary-condition, or adjacent-outcome sources. It is not pooled with direct outcome evidence; these sources bound scope, safety, methods, and translation rather than serving as equal-weight support for the main efficacy claim.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_19","claim":"Mechanistically, the functional decline observed by Spiegeleer 2025 in older adults aligns with proposed statin-associated myopathy pathways, where mitochondrial dysfunction and reduced CoQ10 bioavailability may impair muscle energetics, affecting gait performance. The protective signal in the acute ICH setting from Chen 2026 is consistent with pleiotropic effects of statins, including anti-inflammatory and endothelial stabilization properties that may mitigate secondary injury cascades in the cerebrovascular milieu. The null findings in the oncologic cohort of Maurer 2025 suggest that any potential statin effects on cancer cell proliferation via HMG-CoA reductase inhibition may not translate to clinically meaningful survival benefits in early-stage HER2-positive breast cancer.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_20","claim":"This discordance underscores the context-dependency of statin effects, where benefits observed in acute, severe cerebrovascular injury may not extend to functional outcomes in community-dwelling older adults. The observational design of all four studies precludes causal inference, and the effect directions (positive, negative, null, unclear) highlight the heterogeneous impact of statins across different patient populations, disease stages, and clinical endpoints.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_21","claim":"The corpus comprises predominantly observational cohort studies and systematic reviews examining statin effects across diverse clinical contexts, including cancer prognosis, cardiovascular calcification, neuropsychiatric outcomes, and metabolic disease. Study designs included population-based cohort studies in dialysis patients (Lee 2023), target trial emulations in community-dwelling older adults (Debele 2026), and multicenter retrospective observational studies (Takechi 2025). The outcome class encompasses cancer-specific survival endpoints, cardiovascular imaging biomarkers, neurological disease risk, and treatment-related toxicities.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_22","claim":"Mechanistically, the anti-cancer effects of statins have been attributed to inhibition of the mevalonate pathway, which suppresses Rho GTPase signaling and may reduce tumor cell proliferation and metastatic potential. Preclinical data from Yin 2022 suggest associations with reduced biochemical recurrence after curative prostate cancer treatment (P < 0.01 in certain subgroup analyses), supporting a biological plausibility for statin-mediated anti-neoplastic effects. Prior statin use was associated with lower in-hospital arrhythmia incidence in acute coronary syndrome (Wibawa 2023, P < 0.00001). Dong 2025 found that pre-stroke statin use influenced intracranial atherosclerotic plaque characteristics with P < 0.001 for plaque burden differences.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_23","claim":"Concomitant CPK elevations were observed, and the between-group difference at baseline reached statistical significance (P < 0.001), supporting the hypothesis that higher-intensity statin therapy may carry a greater burden of subclinical skeletal muscle stress. These findings are consistent with the known pharmacological mechanism whereby HMG-CoA reductase inhibition depletes intracellular mevalonate pathway intermediates critical for mitochondrial function in myocytes. The effect direction was classified as null for the broader deficiency prevalence outcome class, suggesting that while CPK changes are detectable, they may not cross clinical diagnostic thresholds for frank myopathy in most patients.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_24","claim":"Mechanistically, statin-associated CPK elevation is hypothesized to stem from impaired CoQ10 biosynthesis and reduced mitochondrial electron transport chain efficiency, both downstream consequences of mevalonate pathway blockade. The Ha 2024 findings in adults with preserved thyroid function are particularly relevant because thyroid dysfunction independently elevates CPK, meaning this cohort isolates the statin-specific signal more cleanly than mixed-population studies. This mechanistic substrate connects the deficiency prevalence outcome class to broader concerns about statin tolerability, as even subclinical CPK elevations may predict treatment discontinuation in clinical practice. Integrating the Ha 2024 observational data with the broader corpus suggests that routine CPK monitoring in high-intensity statin users warrants prospective evaluation in dedicated clinical RCTs.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_25","claim":"By contrast, the evidence base for statin-related muscle effects remains heterogeneous across the curated corpus, and the Ha 2024 null effect-direction classification for deficiency prevalence underscores a key tension: detectable biochemical CPK changes may not translate into clinically meaningful myopathy in population-level analyses. The Statin Use Effects anti-aging case as currently constituted is incomplete, and the CPK data from Ha 2024 illustrate this gap — mechanistic plausibility for statin-induced muscle stress coexists with observational null findings at the clinical outcome level. Future research linking serial CPK trajectories to patient-reported muscle symptoms in statin-treated cohorts would help clarify whether the observed P < 0.001 baseline differences carry downstream clinical relevance.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_26","claim":"Mechanistically, the longevity signal is consistent with pleiotropic anti-inflammatory and endothelial-protective effects of statins that extend beyond lipid lowering. In clinical RCTs, the seepsis mortality benefit aligns with preclinical data demonstrating reduced inflammatory cytokine cascading (Philippou 2025). The cardiovascular primary prevention meta-analysis by Huang 2022 synthesized observational studies from PubMed, EMBASE, Cochrane Library, and Web of Science, showing consistent risk reduction across multiple endpoints with P < 0.01 for cardiovascular events. Yang 2022b documented that statin use reduced ischemic stroke risk in diabetic primary prevention populations (RR = 0.83) alongside all-cause mortality reduction (P < 0.0001). Braun 2023 found that statin use before lower-limb arterial angioplasty improved primary patency and reduced mortality, with effects reaching P < 0.00001 for certain endpoints. Breast cancer analyses (Jia 2023) showed associations between statin use and reduced recurrence and mortality using random-effects models calculating pooled hazard ratios, with multiple endpoints reaching P = 0.001 to P < 0.001.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_27","claim":"Quantitative findings across these cohorts were heterogeneous. Per-study endpoint details and individual p-values are catalogued in the evidence synthesis.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_28","claim":"Mechanistically, the observed survival associations may relate to pleiotropic effects of statins beyond lipid lowering, including anti-inflammatory and immunomodulatory properties that could influence cancer progression and cardiovascular event rates. Systematic review data from Scott 2025 supported a protective association between statin use and breast cancer-specific mortality and recurrence, though the analysis acknowledged concerns about immortal time bias. Preclinical and mechanistic human studies suggest statins may modulate tumor biology through Rho GTPase inhibition and reduced mevalonate pathway flux, yet the translation of these effects into consistent clinical mortality benefit remains uncertain.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_29","claim":"Within the corpus, a clear tension exists between studies reporting positive mortality associations and those reporting null findings. These disagreements likely reflect differences in population characteristics, statin timing and duration, underlying disease states, and potential confounding by indication, underscoring that the mortality-survival signal is context-dependent rather than universal across clinical settings.","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]},{"claim_id":"claim_30","claim":"Quantitative findings across these cohorts were mixed. These discrepancies are summarized in the evidence synthesis (Per-Study Endpoint Evidence).","candidate_sources":[{"study":"Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity","doi":"10.1016/j.ajpc.2024.100647","url":"https://doi.org/10.1016/j.ajpc.2024.100647"},{"study":"The impact of statin use on colorectal cancer prognosis: a systematic review and meta-analysis","doi":"10.1186/s12876-025-04398-6","url":"https://doi.org/10.1186/s12876-025-04398-6"},{"study":"The association between statins and gait speed reserve in older adults: effects of concomitant medication","doi":"10.1007/s11357-025-01682-x","url":"https://doi.org/10.1007/s11357-025-01682-x"},{"study":"Statin use in older people primary prevention on cardiovascular disease: an updated systematic review and meta-analysis","doi":"10.31083/j.rcm2304114","url":"https://doi.org/10.31083/j.rcm2304114"},{"study":"Statin Use and Coronary Artery Calcification: a Systematic Review and Meta-analysis of Observational Studies and Randomized Controlled Trials","doi":"10.1007/s11883-023-01151-w","url":"https://doi.org/10.1007/s11883-023-01151-w"}]}]}