2f:I[703058,["/_next/static/immutable/chunks/3bhq_5eh1d760.js","/_next/static/immutable/chunks/1855-ogyi8eh4.js","/_next/static/immutable/chunks/2pfsjpn6k6zlg.js","/_next/static/immutable/chunks/26c7v3_3uwnwu.js","/_next/static/immutable/chunks/25a3ozcrvi1ff.js","/_next/static/immutable/chunks/2r4wx50nvjh_4.js","/_next/static/immutable/chunks/23fsw06hsi5b1.js","/_next/static/immutable/chunks/06_yt270h41rg.js","/_next/static/immutable/chunks/3ezsiz-7shkna.js","/_next/static/immutable/chunks/20x2y96ldu5wx.js","/_next/static/immutable/chunks/2lxntcm3pd1_h.js","/_next/static/immutable/chunks/00dgco8irq3jw.js","/_next/static/immutable/chunks/00nwe-kq0rboc.js","/_next/static/immutable/chunks/2051ffx3xzio9.js"],"PaperListPageClient"] 30:T447,This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group (P < .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]).31:Taee,Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis. To investigate whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without known significant atherosclerosis. VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab conducted across 774 sites in 33 countries and enrolling 12 257 patients with no prior myocardial infarction or stroke, LDL-C level 90 mg/dL or greater, and qualifying atherosclerosis or high-risk diabetes. This prespecified subgroup analysis examined outcomes in patients without known significant atherosclerosis (none of the following: prior arterial revascularization, arterial stenosis ≥50%, or coronary artery calcium score ≥100 Agatston units), all of whom had diabetes. Enrollment started in June 2019 and the last patient visit was July 2025, with a median follow-up of 4.8 years. Patients were randomized in a 1:1 ratio to subcutaneous administration of either evolocumab (140 mg every 2 weeks) or matching placebo added to optimally tolerated statin therapy. The dual primary end points were composites of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Secondary end points included all-cause mortality. This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group (P < .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]). In high-risk patients without known significant atherosclerosis and with diabetes, evolocumab reduced the risk of a first major cardiovascular event. ClinicalTrials.gov Identifier: NCT03872401.32:T11e8, Importance Intensive lowering of low-density lipoprotein cholesterol (LDL-C) levels with PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for cardiovascular event reduction has largely been reserved for patients with significant atherosclerosis. Objective To investigate whether evolocumab could prevent a first major cardiovascular event (MACE) in patients without known significant atherosclerosis. Design, Setting, and Participants VESALIUS-CV was a randomized, double-blind, placebo-controlled trial of evolocumab conducted across 774 sites in 33 countries and enrolling 12 257 patients with no prior myocardial infarction or stroke, LDL-C level 90 mg/dL or greater, and qualifying atherosclerosis or high-risk diabetes. This prespecified subgroup analysis examined outcomes in patients without known significant atherosclerosis (none of the following: prior arterial revascularization, arterial stenosis ≥50%, or coronary artery calcium score ≥100 Agatston units), all of whom had diabetes. Enrollment started in June 2019 and the last patient visit was July 2025, with a median follow-up of 4.8 years. Intervention Patients were randomized in a 1:1 ratio to subcutaneous administration of either evolocumab (140 mg every 2 weeks) or matching placebo added to optimally tolerated statin therapy. Main Outcomes and Measures The dual primary end points were composites of coronary heart disease death, myocardial infarction, or ischemic stroke (3-P MACE) and 3-P MACE plus ischemia-driven arterial revascularization (4-P MACE). Secondary end points included all-cause mortality. Results This predefined subgroup included 3655 patients (1849 in the evolocumab group and 1806 in the placebo group) with a median age of 65 years (57% female). Among those in the lipid substudy, the median LDL-C level at 48 weeks was 52 mg/dL in the evolocumab group vs 111 mg/dL in the placebo group ( P &lt; .001). A 3-P MACE event occurred in 83 patients (5-year Kaplan-Meier estimate, 5.0%) in the evolocumab group compared with 117 patients (5-year Kaplan-Meier estimate, 7.1%) in the placebo group (hazard ratio [HR], 0.69 [95% CI, 0.52-0.91]; P = .009; between-group difference, 2.1% [95% CI, 0.4%-3.8%]). A 4-P MACE event occurred in 127 patients (5-year Kaplan-Meier estimate, 7.6%) in the evolocumab group compared with 178 patients (5-year Kaplan-Meier estimate, 10.5%) in the placebo group (HR, 0.69 [95% CI, 0.55-0.86]; P = .001; between-group difference, 2.9% [95% CI, 0.9%-4.9%]). There were 136 deaths (5-year Kaplan-Meier estimate, 7.8%) in the evolocumab group compared with 172 deaths (5-year Kaplan-Meier estimate, 10.1%) in the placebo group (HR, 0.76 [95% CI, 0.61-0.95]). Conclusions and Relevance In high-risk patients without known significant atherosclerosis and with diabetes, evolocumab reduced the risk of a first major cardiovascular event. Trial Registration ClinicalTrials.gov Identifier : NCT03872401 25:[[["$","script","0",{"type":"application/ld+json","dangerouslySetInnerHTML":{"__html":"{\"@context\":\"https://schema.org\",\"@type\":\"CollectionPage\",\"name\":\"Hyperlipidemia: condition Research & Clinical Takeaways\",\"description\":\"Explore peer-reviewed papers on Hyperlipidemia (condition). Clinician-written summaries and actionable practice insights. Updated daily.\",\"url\":\"https://www.reachrx.ai/hub/tag/condition/Hyperlipidemia\",\"breadcrumb\":{\"@type\":\"BreadcrumbList\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https://www.reachrx.ai\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"Research Hub\",\"item\":\"https://www.reachrx.ai/hub\"},{\"@type\":\"ListItem\",\"position\":3,\"name\":\"Conditions\",\"item\":\"https://www.reachrx.ai/hub/tag/condition\"},{\"@type\":\"ListItem\",\"position\":4,\"name\":\"Hyperlipidemia\",\"item\":\"https://www.reachrx.ai/hub/tag/condition/Hyperlipidemia\"}]}}"}}]],["$","$L2f",null,{"title":"Hyperlipidemia: Research & Clinical Takeaways","description":"Discover peer-reviewed research on Hyperlipidemia with concise clinician summaries and next-step guidance.","papers":[{"doi":"10.1161/circulationaha.126.082436","pmid":"42670293","title":"Effects of Evolocumab on Mortality Outcomes in Patients Without Previous Myocardial Infarction or Stroke: A Prespecified Analysis of the VESALIUS-CV Randomized Clinical Trial","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2026-08-31T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.126.082436","source_score":55,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-03T06:20:00.423Z","updated_at":"2026-09-03T06:20:00.423Z","tags":[{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"condition","value":"Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"sample_size","value":"n=12257","value_numeric":12257},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"warning","value":"Median age of 66 years places most participants in the older_adult category, though the full age range is not reported; age_group tag reflects this.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"warning","value":"The brand name 'Repatha' was inferred from the generic 'evolocumab'; the paper itself does not explicitly state the brand name.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.082436","tag_type":"warning","value":"The non-CV mortality reduction did not reach conventional statistical significance (HR 0.85, 95% CI 0.71–1.01); the overall all-cause mortality result is driven substantially by CV death and undetermined-cause death reductions.","value_numeric":null}],"summaries":{"what_studied":"This prespecified analysis of the VESALIUS-CV double-blind RCT evaluated the effect of evolocumab vs. placebo on all-cause and cause-specific mortality in 12,257 high-risk patients (median age 66; 43% women) without prior MI or stroke, over a median follow-up of 4.6 years.","key_result":"All-cause mortality was 20% lower with evolocumab (HR 0.80, 95% CI 0.70–0.91; P=0.0005): 7.9% vs. 9.7% at 5 years. CV death HR was 0.79 (95% CI 0.64–0.98); non-CV death HR was 0.85 (95% CI 0.71–1.01). Multistate modeling suggested ~78% of the non-CV mortality benefit was mediated through prevention of antecedent nonfatal CV events (MI, ischemic stroke, or revascularization).","limitations":"- Non-CV death reduction did not reach statistical significance (HR 0.85; CI crossed 1.0).\n- Causal mediation via multistate modeling is observational in nature and cannot definitively establish mechanistic pathways.\n- Median follow-up of 4.6 years may underestimate long-term survival benefit.","practice_takeaway":"Evolocumab reduced all-cause mortality by 20% in high-risk patients without prior MI or stroke, including those with high-risk diabetes and LDL-C ≥90 mg/dL — a population often undertreated with PCSK9 inhibitors. Clinicians should consider evolocumab for survival benefit, not just event prevention, in this primary-prevention-adjacent group."}},{"doi":"10.1016/j.exer.2026.111198","pmid":"42628827","title":"Lycium barbarum polysaccharides ameliorates high-fat diet induced lipid accumulation and aging through triggering lipophagy","journal_title":"Experimental Eye Research","journal_issn":"0014-4835","published_at":"2026-08-21T00:00:00.000Z","url":"https://doi.org/10.1016/j.exer.2026.111198","source_score":3,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-02T06:22:21.211Z","updated_at":"2026-09-02T06:22:21.211Z","tags":[{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"condition","value":"Diet-Induced Obesity","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"condition","value":"Meibomian Gland Dysfunction","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"generic","value":"Lycium barbarum polysaccharides","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"modality","value":"Polysaccharide Supplement","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"study_design","value":"Preclinical Study (In Vivo and In Vitro)","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"warning","value":"No human clinical data are reported; all findings are from mouse models and cell culture. Clinical applicability is speculative at this stage.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"warning","value":"Sample sizes for the mouse HFD model are not reported in the abstract, so a numeric sample size tag could not be assigned.","value_numeric":null},{"paper_doi":"10.1016/j.exer.2026.111198","tag_type":"warning","value":"The DOI year (2026) matches the stated publication date, but the journal issue details were not available for further verification.","value_numeric":null}],"summaries":{"what_studied":"This study examined whether Lycium barbarum polysaccharides (LBP) protect against high-fat diet (HFD)-induced meibomian gland dysfunction (MGD) in mice and in oleic acid (OA)-treated human meibomian gland epithelial cells (HMGECs), focusing on lipid accumulation, autophagy, and cellular aging via the AMPK pathway.","key_result":"LBP improved OA-induced lipid accumulation and cellular aging in HMGECs by restoring the p-AMPK/AMPK ratio and enhancing autophagy flux (lipophagy); blocking autophagy with chloroquine largely reversed these protective effects, confirming the AMPK-lipophagy mechanism.","limitations":"The study relies on an in vitro cell model and a mouse HFD model without clinical validation in human MGD patients; the specific LBP dose-response and long-term safety in vivo are not established; no direct clinical lipid or MGD outcome measures (e.g., meibum quality scores) are reported.","practice_takeaway":"LBP is not yet ready for clinical use in MGD, but these preclinical findings suggest it may be a candidate functional food additive targeting lipid-driven meibomian gland disease. Clinicians should watch for future translational studies before considering LBP in hyperlipidemia-associated MGD management."}},{"doi":"10.1097/aog.0000000000006381","pmid":"42492078","title":"Influence of Cardiometabolic Status on Cardiovascular Effects of Oral Menopausal Hormone Therapy","journal_title":"Obstetrics & Gynecology","journal_issn":"0029-7844","published_at":"2026-07-24T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13403345/","source_score":7,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-08-04T18:18:01.895Z","updated_at":"2026-08-04T18:18:01.895Z","tags":[{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"brand","value":"Premarin","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"category","value":"Obstetrics & Gynecology","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"condition","value":"Coronary Heart Disease","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"condition","value":"Menopause","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"condition","value":"Metabolic Syndrome","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"generic","value":"conjugated equine estrogens","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"generic","value":"medroxyprogesterone acetate","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"modality","value":"Estrogen","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"modality","value":"Hormone Therapy","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"modality","value":"Progestogen","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"sample_size","value":"n=27347","value_numeric":27347},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"sex","value":"female","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"study_design","value":"Randomized Controlled Trial (Secondary Analysis)","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"warning","value":"Results apply specifically to oral CEE-based regimens and may not generalize to non-oral or non-CEE hormone therapies.","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"warning","value":"The Premarin brand tag is inferred from the description of conjugated equine estrogens 0.625 mg/d, the standard WHI formulation; the paper does not explicitly name the brand.","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"warning","value":"This is a secondary subgroup analysis of WHI trials; findings, especially for CEE-alone, should be interpreted with caution due to reduced statistical power in subgroups.","value_numeric":null},{"paper_doi":"10.1097/aog.0000000000006381","tag_type":"warning","value":"Total sample size of 27,347 combines both trial arms (CEE-alone: 10,739; CEE+MPA: 16,608); subgroup analyses involve considerably smaller numbers.","value_numeric":null}],"summaries":{"what_studied":"Secondary analysis of two WHI double-blind, placebo-controlled RCTs evaluating how baseline cardiometabolic status (lipid profile, blood pressure, blood glucose, metabolic syndrome) modifies CHD risk from oral CEE alone (n=10,739, post-hysterectomy) or CEE+MPA (n=16,608, intact uterus) in postmenopausal women aged 50–79 years.","key_result":"In the CEE+MPA trial, untreated LDL <130 mg/dL conferred no significant CHD increase (HR 0.59; 95% CI 0.31–1.10), but LDL ≥190 mg/dL more than doubled risk (HR 2.77; 95% CI 1.42–5.40; P-trend=.002); higher LDL/HDL ratio also raised risk (ratio <2.5: HR 0.73 vs ratio ≥4: HR 1.76; P-trend=.008). Women with prior treated hyperlipidemia showed no elevated CHD risk on either regimen. Blood pressure, glucose, triglycerides, and metabolic syndrome did not modify CHD risk.","limitations":"- Secondary/subgroup analysis with potential for multiple comparisons and residual confounding.\n- LDL/HDL findings for CEE-alone trended similarly but did not reach statistical significance.\n- Applies only to oral CEE-based regimens; results may not generalize to transdermal or other progestogen formulations.","practice_takeaway":"Before starting oral CEE or CEE+MPA, check a fasting lipid panel — women with untreated LDL ≥190 mg/dL face substantially higher CHD risk and may warrant alternative routes or lipid treatment first. Women with already-treated hyperlipidemia or favorable lipid profiles do not appear to carry excess CHD risk from these oral regimens."}},{"doi":"10.1001/jamacardio.2026.2510","pmid":"42485013","title":"Digitally Enabled Quality Improvement Intervention and LDL-C Control in Atherosclerotic Cardiovascular Disease","journal_title":"JAMA Cardiology","journal_issn":"2380-6583","published_at":"2026-07-22T00:00:00.000Z","url":"https://pubmed.ncbi.nlm.nih.gov/42485013/","source_score":39,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-09-13T06:21:42.083Z","updated_at":"2026-09-13T06:21:42.083Z","tags":[{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"modality","value":"Digital Health / Quality Improvement Intervention","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"modality","value":"Lipid-Lowering Therapy","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"sample_size","value":"n=1465","value_numeric":1465},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"study_design","value":"Cluster Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"warning","value":"Multiple study investigators and Novartis employees are listed as co-authors, and the trial received Novartis funding; this potential conflict of interest should be considered when interpreting findings.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"warning","value":"No specific lipid-lowering drug was tested; the modality tag reflects the QI/digital intervention and general lipid-lowering therapy class rather than a single agent.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2510","tag_type":"warning","value":"The intervention is a composite 'bundle'; the relative contribution of individual components (e.g., decision support vs. audit/feedback) cannot be separated from this trial design.","value_numeric":null}],"summaries":{"what_studied":"A pragmatic 2-arm cluster randomized trial (28 outpatient clinics in Brazil, n=1,465 adults with established ASCVD) evaluated a digitally enabled, multifaceted quality improvement (QI) strategy—including previsit screening, electronic clinical decision support, audit/feedback, and clinician/patient engagement tools—versus routine care over 6 months.","key_result":"Mean LDL-C at 6 months was 76.3 mg/dL (intervention) vs. 85.6 mg/dL (control); adjusted mean difference −6.62 mg/dL (95% CI, −11.11 to −2.13; P=.004). More intervention patients hit LDL-C <50 mg/dL (23.5% vs. 13.4%; OR 1.86) or achieved ≥50% LDL-C reduction (18.6% vs. 13.4%; OR 1.76). No significant difference in major cardiovascular events was observed.","limitations":"- Short 6-month follow-up limits assessment of hard cardiovascular outcomes.\n- Single-country setting (Brazil) may limit generalizability to other health systems.\n- Most patients still did not reach the LDL-C <50 mg/dL target, indicating only partial effectiveness; residual confounding from cluster-level differences is possible.","practice_takeaway":"A digitally enabled QI bundle (decision support, audit/feedback, patient engagement) can modestly lower LDL-C and nearly double the rate of target attainment in ASCVD patients, but most patients will still not reach guideline targets—additional strategies are needed to close the gap."}},{"doi":"10.1001/jamacardio.2026.2314","pmid":"42455545","title":"Development and Validation of a Simplified Martin-Hopkins LDL-C Equation Using Machine Learning","journal_title":"JAMA Cardiology","journal_issn":"2380-6583","published_at":"2026-07-15T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13373734/","source_score":52,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-19T13:39:49.482Z","updated_at":"2026-07-19T13:39:49.482Z","tags":[{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"age_group","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"condition","value":"Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"modality","value":"LDL-C Estimation Equation","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"modality","value":"Machine Learning","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"sample_size","value":"n=4939528","value_numeric":4939528},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"study_design","value":"Cross-Sectional Study","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"warning","value":"Full text of the paper was not accessible (publisher page only); summary is based solely on the abstract and results section provided.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"warning","value":"The MARS equation is described as a 'single equation' simplification, but its machine learning nature may still require computational implementation — manual bedside use is not confirmed in the abstract.","value_numeric":null},{"paper_doi":"10.1001/jamacardio.2026.2314","tag_type":"warning","value":"The study is cross-sectional, so the 'level of evidence' rating reflects diagnostic/accuracy study hierarchy rather than an interventional hierarchy.","value_numeric":null}],"summaries":{"what_studied":"This cross-sectional study developed and validated a simplified machine learning-based LDL-C estimation equation (LDL-C-MH-MARS, using multivariate adaptive regression splines) as an alternative to the Martin-Hopkins equation, comparing it against the Friedewald, Sampson-NIH, Modified Sampson, and Martin-Hopkins equations in ~4.9 million adult and pediatric patients from the Very Large Database of Lipids (2015–2019), with external validation in Mayo Clinic and FOURIER trial datasets.","key_result":"LDL-C-MH-MARS achieved the lowest RMSE (4.7 mg/dL vs. 4.9 for Martin-Hopkins, 5.8 for Sampson-NIH, and 7.2 for Friedewald) and correctly classified 89.7% of patients by guideline category (vs. 89.6% for Martin-Hopkins and 83.1% for Friedewald); at low LDL-C (<70 mg/dL) with elevated triglycerides (200–399 mg/dL), underestimation occurred in only 16% with MARS vs. 60% with Friedewald.","limitations":"- Cross-sectional convenience sample may not fully represent all clinical populations.\n- LDL-C reference standard was ultracentrifugation, which itself has known variability.\n- The MARS equation may be harder to implement manually than simpler formulas, despite being a single equation.","practice_takeaway":"The new LDL-C-MH-MARS equation matches the accuracy of the Martin-Hopkins method while using a single equation, making it easier to embed in lab or EHR systems—especially useful for patients with elevated triglycerides or low LDL-C where Friedewald significantly underestimates. Clinicians managing high-risk patients on intensive lipid-lowering therapy (e.g., PCSK9 inhibitors) should prefer MARS or Martin-Hopkins over Friedewald for LDL-C estimation."}},{"doi":"10.1007/s11695-026-08837-5","pmid":"42432395","title":"Beyond Initial Resolution: Predictors of Recurrence of Obesity-related Medical Conditions after Metabolic and Bariatric Surgery","journal_title":"Obesity Surgery","journal_issn":"0960-8923","published_at":"2026-07-10T00:00:00.000Z","url":"https://doi.org/10.1007/s11695-026-08837-5","source_score":4,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-21T13:34:30.027Z","updated_at":"2026-07-21T13:34:30.027Z","tags":[{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"category","value":"Surgery","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"condition","value":"Obesity","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"condition","value":"Obstructive Sleep Apnea","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"condition","value":"Type 2 Diabetes Mellitus","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"generic","value":"duodenal switch","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"generic","value":"Roux-en-Y gastric bypass","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"generic","value":"sleeve gastrectomy","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"modality","value":"Bariatric Surgery","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"sample_size","value":"n=1323","value_numeric":1323},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"warning","value":"OSA recurrence rate (5.4%) may be underestimated; the paper does not specify whether repeat objective sleep studies were used for confirmation.","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"warning","value":"The finding that 'White race was protective against HTN recurrence' is an observational association and may reflect unmeasured socioeconomic or access-to-care confounders rather than a biological effect.","value_numeric":null},{"paper_doi":"10.1007/s11695-026-08837-5","tag_type":"warning","value":"The study is single-institution and retrospective; selection bias toward patients with ≥36 months follow-up and ≥20% total weight loss may limit generalizability to broader bariatric populations.","value_numeric":null}],"summaries":{"what_studied":"This retrospective cohort study examined predictors of recurrence of obesity-related medical conditions (T2D, HTN, HLD, OSA) in 1,323 adults who had initial remission after primary sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), or duodenal switch (DS) between 2008 and 2022, with ≥36 months of follow-up.","key_result":"Recurrence rates were 16.2% for T2D, 21.3% for HTN, 19.0% for HLD, and 5.4% for OSA. Severe recurrent weight gain (>50%) independently predicted only HLD recurrence. RYGB and DS carried lower T2D and HLD recurrence risk vs. SG. T2D recurrence was driven by pre-op insulin use and higher HbA1c; HTN recurrence by greater antihypertensive burden and older age. White race was protective against HTN recurrence.","limitations":"- Retrospective single-institution design limits generalizability.\n- OSA recurrence may be underestimated due to reliance on symptom-based or clinical criteria rather than repeat polysomnography.\n- Dataset is not publicly available; full multivariate model details require journal access.","practice_takeaway":"Baseline disease severity (insulin dependence, HbA1c, antihypertensive burden) is a stronger predictor of ORMC recurrence than weight regain alone — so screen and manage underlying disease intensity closely before and after bariatric surgery. RYGB or DS may offer more durable metabolic protection than SG for T2D and HLD, which should factor into procedure selection."}},{"doi":"10.1167/tvst.15.5.29","pmid":"42212887","title":"Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration","journal_title":"Translational Vision Science & Technology","journal_issn":"2164-2591","published_at":"2026-05-29T00:00:00.000Z","url":"https://doi.org/10.1167/tvst.15.5.29","source_score":3,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-03T13:44:39.163Z","updated_at":"2026-06-03T13:44:39.163Z","tags":[{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"brand","value":"Leqvio","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"brand","value":"Praluent","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"category","value":"Ophthalmology","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"condition","value":"Age-Related Macular Degeneration","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"generic","value":"alirocumab","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"generic","value":"inclisiran","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"impact_flag","value":"limited_evidence","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"level_of_evidence","value":"3","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"modality","value":"Statin","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"sample_size","value":"n=56660","value_numeric":56660},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"study_design","value":"Retrospective Cohort Study","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"AMD subtype (wet vs. dry/geographic atrophy) could not be distinguished due to ICD-10-code-only outcome ascertainment; results apply to AMD overall.","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"Brand tags (Praluent, Repatha, Leqvio) are inferred from the generic drug names listed; the paper does not explicitly name brand products.","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"Follow-up duration differed between groups (mean ~1037 days for PCSK9i vs. ~1317 days for statins), which may affect cumulative incidence comparisons despite Cox modeling.","value_numeric":null},{"paper_doi":"10.1167/tvst.15.5.29","tag_type":"warning","value":"Propensity score matching balanced measured covariates, but PCSK9 inhibitor users likely had more severe dyslipidemia or statin intolerance at baseline—confounding by indication may persist.","value_numeric":null}],"summaries":{"what_studied":"This retrospective propensity score–matched cohort study (TriNetX database, 2015–2024, up to 5 years follow-up) compared incident AMD risk in adults ≥50 years with hyperlipidemia who used PCSK9 inhibitors (alirocumab, evolocumab, or inclisiran) versus statin monotherapy, with no prior retinal disease at baseline.","key_result":"Among 56,660 matched participants (28,330 per group), PCSK9 inhibitor use was associated with a significantly lower AMD risk vs. statins (HR 0.82; 95% CI 0.73–0.90). The benefit was consistent in sensitivity analyses (US-only network: HR 0.85; intention-to-treat: HR 0.87) and in subgroups including both age groups (50–75 yrs: HR 0.83; ≥75 yrs: HR 0.84), males (HR 0.82), non-diabetic individuals (HR 0.79), non-obese individuals (HR 0.70), and those with <2 years of hyperlipidemia (HR 0.81). No significant benefit was seen in those with ≥2 years of hyperlipidemia (HR 0.92; 95% CI 0.83–1.02).","limitations":"- AMD diagnosis relied solely on ICD-10-CM codes (no fundus imaging, visual acuity, or drusen data), with ~80–85% accuracy vs. image-derived ground truth.\n- Confounding by indication is likely: PCSK9 inhibitors are typically reserved for more severe dyslipidemia or statin-intolerant patients, which may not be fully captured even after propensity matching.\n- Residual confounding from unmeasured factors (diet, genetics, supplement use) cannot be excluded, and the observational design precludes causal inference.","practice_takeaway":"In adults ≥50 years on lipid-lowering therapy, PCSK9 inhibitor use was linked to an 18% relative reduction in AMD risk vs. statins—a finding that may inform treatment discussions, especially in patients already requiring PCSK9 inhibition for cardiovascular reasons. Causal confirmation requires prospective trials with standardized ophthalmic endpoints."}},{"doi":"10.1161/circulationaha.126.080616","pmid":"42153665","title":"Evolocumab in Patients With Prior Percutaneous Coronary Intervention and No Prior Myocardial Infarction: Results From the VESALIUS-CV Trial","journal_title":"Circulation","journal_issn":"0009-7322","published_at":"2026-05-19T00:00:00.000Z","url":"https://doi.org/10.1161/circulationaha.126.080616","source_score":41,"is_retracted":false,"is_open_access":false,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-07-07T13:26:26.620Z","updated_at":"2026-07-07T13:26:26.620Z","tags":[{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"brand","value":"Repatha","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"condition","value":"Coronary Artery Disease","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"generic","value":"evolocumab","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"impact_flag","value":"practice_changing","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"level_of_evidence","value":"2","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"modality","value":"PCSK9 Inhibitor","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"sample_size","value":"n=3627","value_numeric":3627},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"warning","value":"Cardiovascular death and all-cause death reductions are described as 'nominally' significant, suggesting these were not primary endpoints and may not be adjusted for multiple comparisons.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"warning","value":"Median age of 66 years with 30.7% women; generalizability to younger or predominantly female PCI populations is uncertain.","value_numeric":null},{"paper_doi":"10.1161/circulationaha.126.080616","tag_type":"warning","value":"This is a prespecified subgroup analysis (n=3,627) from the larger VESALIUS-CV trial (n=12,257); results should be interpreted with caution as the subgroup was not independently powered.","value_numeric":null}],"summaries":{"what_studied":"This prespecified subgroup analysis of the VESALIUS-CV RCT evaluated evolocumab vs. placebo in 3,627 patients with prior PCI but no prior MI or stroke, with LDL-C ≥90 mg/dL, over a median follow-up of 4.6 years.","key_result":"Evolocumab reduced 3-point MACE by 30% (7.0% vs. 9.5%; HR 0.70, 95% CI 0.56–0.89), MI by 50% (3.0% vs. 6.1%; HR 0.50), and urgent revascularization by 39% (HR 0.61); nominally lower all-cause death (8.2% vs. 10.2%; HR 0.76) was also observed. Benefit appeared as early as 6 months.","limitations":"- Subgroup analysis, so not powered independently for these endpoints.\n- LDL-C data at 48 weeks came from a lipid substudy, not the full cohort.\n- Death and cardiovascular death findings are described as 'nominally' significant, suggesting no formal multiplicity correction was applied.","practice_takeaway":"Consider adding evolocumab to stable post-PCI patients without prior MI who remain at LDL-C ≥90 mg/dL, as intensive LDL-C lowering cut MI risk in half and reduced major cardiovascular events meaningfully. Benefit appeared within 6 months, supporting early initiation."}},{"doi":"10.1161/jaha.125.048903","pmid":"42047192","title":"Ketogenic Diets and Low‐Density Lipoprotein Cholesterol in Adults With Normal Weight: An Emerging Clinical Challenge","journal_title":"Journal of the American Heart Association","journal_issn":"2047-9980","published_at":"2026-04-28T00:00:00.000Z","url":"https://doi.org/10.1161/jaha.125.048903","source_score":23,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-06-05T13:26:50.153Z","updated_at":"2026-06-05T13:26:50.153Z","tags":[{"paper_doi":"10.1161/jaha.125.048903","tag_type":"age_group","value":"adult","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"category","value":"Cardiac & Cardiovascular Systems","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"condition","value":"Atherosclerotic Cardiovascular Disease","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"impact_flag","value":"safety_signal","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"level_of_evidence","value":"5","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"modality","value":"Dietary Intervention","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"study_design","value":"Narrative Review","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"warning","value":"No sample size is reported; this is a review article synthesizing existing trial data rather than an original study.","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"warning","value":"Study design tagged as 'Narrative Review' — it is not a systematic review or meta-analysis, so synthesis may be subject to selection bias.","value_numeric":null},{"paper_doi":"10.1161/jaha.125.048903","tag_type":"warning","value":"The LDL-C ranges cited (18–70 mg/dL) are drawn from multiple short-term trials with varying designs; individual study results may differ.","value_numeric":null}],"summaries":{"what_studied":"This narrative review evaluates the evidence on ketogenic diet (KD)-induced LDL-C elevations in normal-BMI adults, explores mechanisms, and discusses ASCVD risk assessment and clinical management strategies.","key_result":"Short-term trials in normal-BMI adults on KDs report mean LDL-C increases of **18–70 mg/dL**. Moderate carbohydrate reintroduction (50–100 g/day) can substantially reverse these elevations; pharmacologic therapy can reduce them further. Long-term ASCVD outcomes in this population have not been directly studied.","limitations":"- No long-term ASCVD outcome data exist specifically in lean KD-following individuals.\n- Available coronary imaging data are limited and do not establish cardiovascular safety.\n- Evidence on reversibility and pharmacologic management is largely from case reports.","practice_takeaway":"Monitor lipids regularly in normal-weight patients following a KD, especially those with extreme LDL-C elevations, as they may appear low-risk by conventional metrics yet harbor meaningful ASCVD risk. If LDL-C rises significantly, counsel on moderate carbohydrate reintroduction (50–100 g/day) or consider pharmacologic therapy."}},{"doi":"10.1001/jama.2026.3277","pmid":"41903215","title":"Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes","journal_title":"JAMA","journal_issn":"0098-7484","published_at":"2026-03-29T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13033171/","source_score":427,"is_retracted":false,"is_open_access":true,"raw_metadata":{"ooir":{"day":"2026-05-01","doi":"10.1001/jama.2026.3277","days":"14","issn":"0098-7484","rank":"9","field":"Clinical Medicine","score":"427","category":"Medicine, General & Internal","categories":["Medicine, General & Internal"],"_categories":["Medicine, General & Internal"]},"pubmed":{"doi":"10.1001/jama.2026.3277","title":"Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes: Results From the VESALIUS-CV Trial.","journal":"JAMA","methods":"","results":"$30","abstract":"$31","keywords":[],"pubmed_id":"41903215","conclusions":"","publication_date":"2026-03-29T00:00:00"},"crossref":{"DOI":"10.1001/jama.2026.3277","URL":"https://doi.org/10.1001/jama.2026.3277","ISSN":["0098-7484"],"link":[{"URL":"https://jamanetwork.com/journals/jama/articlepdf/2847162/jama_marston_2026_oi_260016_1776721410.63448.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"page":"1400","type":"journal-article","issue":"16","score":1,"title":["Evolocumab to Reduce First Major Cardiovascular Events in Patients Without Known Significant Atherosclerosis and With Diabetes"],"author":[{"given":"Nicholas A.","family":"Marston","sequence":"first","affiliation":[{"name":"TIMI Study Group, Heart and Vascular Institute, Brigham and Women’s Hospital, Boston, Massachusetts"}]},{"given":"Erin 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inaccessible; safety and tolerability data (e.g., adverse events) could not be extracted and are not reflected in the summary.","value_numeric":null},{"paper_doi":"10.1001/jama.2026.3277","tag_type":"warning","value":"The median age of 65 years and 57% female composition may not represent all diabetic patient populations seen in primary prevention settings.","value_numeric":null},{"paper_doi":"10.1001/jama.2026.3277","tag_type":"warning","value":"The 'practice_changing' flag is applied cautiously — this subgroup analysis supports a shift in PCSK9 inhibitor use to primary prevention in diabetic patients, but guideline updates will be needed to confirm broad adoption.","value_numeric":null},{"paper_doi":"10.1001/jama.2026.3277","tag_type":"warning","value":"This is a prespecified subgroup analysis, not the primary trial result — findings should be interpreted with appropriate caution regarding statistical power and multiple comparisons.","value_numeric":null}],"summaries":{"what_studied":"This prespecified subgroup analysis of the VESALIUS-CV RCT evaluated whether evolocumab (140 mg subcutaneously every 2 weeks) vs placebo, added to optimally tolerated statin therapy, could prevent a first major cardiovascular event (MACE) in 3,655 patients with diabetes but **no** known significant atherosclerosis (no prior MI or stroke, no revascularization, no arterial stenosis ≥50%, no CAC ≥100), followed for a median of 4.8 years.","key_result":"Evolocumab reduced 3-P MACE (CHD death, MI, ischemic stroke) by 31% vs placebo (5.0% vs 7.1%; HR 0.69 [95% CI 0.52–0.91]; absolute difference 2.1%). It also cut 4-P MACE by 31% (7.6% vs 10.5%; HR 0.69 [95% CI 0.55–0.86]; absolute difference 2.9%) and showed a mortality signal (7.8% vs 10.1%; HR 0.76 [95% CI 0.61–0.95]). Median LDL-C at 48 weeks was 52 mg/dL (evolocumab) vs 111 mg/dL (placebo).","limitations":"- This is a **prespecified subgroup** of the main VESALIUS-CV trial, so statistical power was designed for the overall cohort, not this subgroup alone.\n- All patients in this subgroup had diabetes, limiting generalizability to non-diabetic patients without significant atherosclerosis.\n- Full-text safety and tolerability data were not accessible from the available abstract.","practice_takeaway":"Consider evolocumab as a primary prevention option in patients with diabetes and elevated LDL-C (≥90 mg/dL) who lack known significant atherosclerosis — a population previously excluded from routine PCSK9 inhibitor use. A 2.1% absolute reduction in 3-P MACE over ~5 years translates to roughly 1 event prevented per 48 patients treated."}},{"doi":"10.1001/jamaneurol.2026.0359","pmid":"41870419","title":"Effects of Exercise and Intensive Vascular Risk Reduction on Cognitive Function in Older Adults","journal_title":"JAMA Neurology","journal_issn":"2168-6149","published_at":"2026-03-23T00:00:00.000Z","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13010195/","source_score":122,"is_retracted":false,"is_open_access":true,"raw_metadata":{"pubmed":true,"crossref":true,"unpaywall":true},"created_at":"2026-05-18T13:25:22.619Z","updated_at":"2026-05-18T13:25:22.619Z","tags":[{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"age_group","value":"older_adult","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"brand","value":"Lipitor","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"category","value":"Clinical Neurology","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"condition","value":"Cognitive Decline","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"condition","value":"Hyperlipidemia","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"condition","value":"Hypertension","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"generic","value":"atorvastatin","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"impact_flag","value":"confirms_prior","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"level_of_evidence","value":"1","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"modality","value":"Aerobic Exercise Training","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"modality","value":"Intensive Vascular Risk Reduction","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"modality","value":"Statin","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"sample_size","value":"n=513","value_numeric":513},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"sex","value":"mixed","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"study_design","value":"Randomized Controlled Trial","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"warning","value":"Atorvastatin dose and achieved BP/LDL targets are not specified in the available text, limiting assessment of intervention intensity.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"warning","value":"The full text was not accessible (browser check gate); summary is based solely on the abstract and results excerpt.","value_numeric":null},{"paper_doi":"10.1001/jamaneurol.2026.0359","tag_type":"warning","value":"The trial enrolled participants with subjective cognitive decline and/or family history of dementia but not confirmed MCI — findings may not apply to higher-risk groups.","value_numeric":null}],"summaries":{"what_studied":"This 2×2 factorial RCT (24 months, 4 US sites) tested aerobic exercise training, intensive vascular risk reduction (IRVR: systolic BP target <130 mmHg + atorvastatin), their combination, or usual care in 513 older adults (aged 60–85) without dementia but with hypertension, family history of dementia, and/or subjective cognitive decline.","key_result":"Neither exercise nor IRVR improved global cognition significantly vs. control at 24 months: PACC score difference was +0.1 units for exercise (95% CI, −0.1 to 0.2; P=.37) and −0.1 units for IRVR (95% CI, −0.3 to 0.03; P=.12). Secondary NIH Toolbox fluid composite scores showed similar null results.","limitations":"- Trial duration (24 months) may be too short to detect cognitive benefits of these interventions.\n- Single-blind design; participants could not be blinded to exercise assignment.\n- Study enrolled a relatively healthy, high-functioning older adult cohort, which may limit generalizability to higher-risk populations.","practice_takeaway":"Exercise and intensive BP/lipid lowering did not produce measurable cognitive gains over 2 years in at-risk older adults without dementia. Clinicians should not yet rely on these interventions primarily for short-term cognitive benefit, though cardiovascular benefits remain well-established."}}],"initialOffset":11,"fetchConfig":{"kind":"tags","tags":[{"tag_type":"condition","value":"Hyperlipidemia"}]},"breadcrumbItems":[{"name":"Home","href":"/"},{"name":"Research Hub","href":"/hub"},{"name":"Conditions","href":"/hub/tag/condition"},{"name":"Hyperlipidemia"}],"hrefConfig":{"basePath":"/hub/papers","webViewQueryParams":{"hub_ctx":"tag","hub_tag_type":"condition","hub_tag_value":"Hyperlipidemia"}}}]]

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