--- title: "Evidence: NMR LDL/HDL particle number" description: "Plozasiran significantly reduces harmful triglyceride-rich lipoproteins and shifts LDL to larger, potentially less atherogenic particles, without…" url: "https://magellanlongevity.com/study/s150.md" canonical: "https://magellanlongevity.com/study/s150.html" html: "https://magellanlongevity.com/study/s150.html" type: "study" study_key: "s150" journal: "J Am Coll Cardiol" year: 2025 pmid: "40099777" doi: "10.1016/j.jacc.2025.03.496" citations: 1 updated: 2026-09-02 author: "Gabriel Radu, DO" author_credentials: "Physiatrist (PM&R). NY medical license 275110. NPI 1376861765." publisher: "Magellan Longevity" content_format: "markdown" --- # Evidence: NMR LDL/HDL particle number [Home](https://magellanlongevity.com/) › [Research map](https://magellanlongevity.com/longevity-research-map.html) › Evidence: NMR LDL/HDL particle number **HTML version:** https://magellanlongevity.com/study/s150.html · **In the Magellan app:** https://magellanlongevity.com/#/study/s150 ## Citation | Field | Value | | --- | --- | | Journal | J Am Coll Cardiol | | Year | 2025 | | PMID | [40099777](https://pubmed.ncbi.nlm.nih.gov/40099777/) | | DOI | [10.1016/j.jacc.2025.03.496](https://doi.org/10.1016/j.jacc.2025.03.496) | | Study key | s150 | ## Takeaway Plozasiran significantly reduces harmful triglyceride-rich lipoproteins and shifts LDL to larger, potentially less atherogenic particles, without increasing overall LDL particle count. ## The question What is the impact of plozasiran, an investigational siRNA targeting hepatic apoC-III, on lipoprotein particle concentration and subclass distribution in patients with severe hypertriglyceridemia and mixed hyperlipidemia? ## Hypothesis Reductions in the number of triglyceride-rich lipoprotein particles (TRL-P) and a shift to possibly less atherogenic large low-density lipoprotein particles (LDL-P) are expected. ## Methods This study analyzed data from 403 patients across two phase 2 studies, SHASTA-2 (severe hypertriglyceridemia) and MUIR (mixed hyperlipidemia). Patients received two subcutaneous doses of plozasiran (10, 25, or 50 mg) or placebo at baseline and week 12. Lipoprotein profiling was performed using nuclear magnetic resonance (NMR). ## Results In SHASTA-2, plozasiran led to dose-dependent reductions in TRL-P, with total TRL-P decreasing by -46%. Total LDL-P remained unchanged, but large LDL-P increased by +53% and medium LDL-P by +56%, while small LDL-P trended lower (-13%). Total HDL-P increased by +8%, primarily due to a +36% increase in large HDL-P. In MUIR, total TRL-P was reduced by -48% (pooled plozasiran). Total LDL-P was unchanged, but large and medium LDL-P increased by +88% and +46% respectively, and small LDL-P decreased by -28%. Total HDL-P increased by +12%, driven by an +83% increase in large HDL-P. ## Conclusion Plozasiran reduced apoC-III and induced potentially favorable quantitative and qualitative changes in lipoproteins, including a ~50% reduction in TRL-P, a shift in LDL to larger particles, and a modest increase in HDL-P concentration, without increasing total LDL-P or apoB. ## Limitations The abstract does not explicitly state limitations of the study. It suggests that the potential of plozasiran to lower cardiovascular risk needs to be evaluated in a prospective outcomes trial. ## Verbatim from the abstract > shifted LDL particle size distribution from small dense toward larger sizes ## Plozasiran's Impact on Lipoprotein Particle Changes | Measure | Percentage Change (%) | | --- | --- | | SHASTA-2 Total TRL-P Reduction | -46 | | SHASTA-2 Large LDL-P Increase | 53 | | SHASTA-2 Medium LDL-P Increase | 56 | | SHASTA-2 Small LDL-P Decrease | -13 | | SHASTA-2 Total HDL-P Increase | 8 | | SHASTA-2 Large HDL-P Increase | 36 | | MUIR Total TRL-P Reduction | -48 | | MUIR Large LDL-P Increase | 88 | | MUIR Medium LDL-P Increase | 46 | | MUIR Small LDL-P Decrease | -28 | | MUIR Total HDL-P Increase | 12 | | MUIR Large HDL-P Increase | 83 | *Percentage change in various lipoprotein particle concentrations and subclasses in SHASTA-2 and MUIR studies after plozasiran administration, relative to placebo or pooled plozasiran.* ## Where this study is used on Magellan This paper is one of the citations behind the evidence grade on the pages below. Grades are assigned from the published research and are independent of affiliate commissions. | Compound or device | Evidence grade | Graded pages | | --- | --- | --- | | NMR Lipoprotein Particle Test | — | — | ## Reference 1. **Evidence: NMR LDL/HDL particle number** J Am Coll Cardiol 2025 · [PMID 40099777](https://pubmed.ncbi.nlm.nih.gov/40099777/) · [DOI 10.1016/j.jacc.2025.03.496](https://doi.org/10.1016/j.jacc.2025.03.496) > shifted LDL particle size distribution from small dense toward larger sizes ## Structured data ```json {"@context":"https://schema.org","@graph":[{"@type":"MedicalWebPage","@id":"https://magellanlongevity.com/study/s150.html#page","url":"https://magellanlongevity.com/study/s150.html","name":"Evidence: NMR LDL/HDL particle number","description":"Plozasiran significantly reduces harmful triglyceride-rich lipoproteins and shifts LDL to larger, potentially less atherogenic particles, without…","inLanguage":"en","isPartOf":{"@type":"WebSite","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"author":{"@type":"Person","name":"Gabriel Radu, DO","jobTitle":"Physiatrist (PM&R)","identifier":[{"@type":"PropertyValue","name":"NPI","value":"1376861765"},{"@type":"PropertyValue","name":"NY medical license","value":"275110"}]},"publisher":{"@type":"Organization","name":"Magellan Longevity","url":"https://magellanlongevity.com/"},"encoding":{"@type":"MediaObject","encodingFormat":"text/markdown","contentUrl":"https://magellanlongevity.com/study/s150.md"},"dateModified":"2026-09-02"},{"@type":"BreadcrumbList","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https://magellanlongevity.com/"},{"@type":"ListItem","position":2,"name":"Research map","item":"https://magellanlongevity.com/longevity-research-map.html"},{"@type":"ListItem","position":3,"name":"Evidence: NMR LDL/HDL particle number","item":"https://magellanlongevity.com/study/s150.html"}]},{"@type":"ScholarlyArticle","@id":"https://magellanlongevity.com/study/s150.html#study","name":"Evidence: NMR LDL/HDL particle number","headline":"Evidence: NMR LDL/HDL particle number","datePublished":"2025","isPartOf":{"@type":"Periodical","name":"J Am Coll Cardiol"},"identifier":"PMID:40099777","url":"https://pubmed.ncbi.nlm.nih.gov/40099777/","sameAs":"https://doi.org/10.1016/j.jacc.2025.03.496","abstract":"Plozasiran significantly reduces harmful triglyceride-rich lipoproteins and shifts LDL to larger, potentially less atherogenic particles, without increasing overall LDL particle count."}]} ``` ## Related on Magellan Longevity - [ApoB-containing lipoproteins: count, type, size, and risk of coronary artery disease](https://magellanlongevity.com/study/d40289348.md) - [The benefits of measuring the size and number of lipoprotein particles for…](https://magellanlongevity.com/study/d36522243.md) - [Longevity research map](https://magellanlongevity.com/longevity-research-map.html) - [Evidence-based longevity supplements](https://magellanlongevity.com/longevity-supplements.md) ## Scope and disclosures Educational information, not medical advice. Nothing here is intended to diagnose, treat, cure, or prevent any disease. Talk to your physician before starting any supplement or device, especially if you are pregnant, nursing, or taking medication. Editorial firewall: evidence grades are assigned from the published research and are independent of any affiliate commission. As an Amazon Associate, Magellan Longevity earns from qualifying purchases. Reviewed for accuracy by a board-certified physician (DO).