Residual Risk of Atherosclerotic Cardiovascular Events in Relation to Reductions in Very‐Low‐Density Lipoproteins
Bibliographic record
Abstract
Background It is uncertain whether pharmacological reductions in very‐low‐density lipoproteins (VLDLs), and their component triglyceride and cholesterol could reduce residual risk of atherosclerotic cardiovascular disease (ASCVD) events among individuals in whom low‐density lipoprotein cholesterol (LDL‐C) has been adequately lowered. We examined whether individuals with greater on‐statin reductions in VLDL‐related measures—beyond reductions in LDL‐C—were at further reduced risk of ASCVD. Methods and Results In 9423 participants in the JUPITER (Justification for the Use of Statins in Prevention) trial (NCT00239681), at baseline and on statin we measured standard lipids, 400‐MHz proton nuclear magnetic resonance spectroscopy‐measured VLDL particle subclasses (small, medium, and large VLDL lipoprotein particle concentration), and total VLDL cholesterol mass. Compared with individuals allocated to placebo, we examined risk of incident ASCVD (N=211) among statin‐allocated participants who achieved minimal ( r ≤0.29) with change in LDL‐C. On‐statin median LDL‐C was 54 mg/dL and triglyceride was 101 mg/dL. Dose‐response reductions in ASCVD risk were observed for greater reductions in LDL‐C, VLDL cholesterol mass, and small VLDL lipoprotein particle concentration; the latter 2 remained significant after incremental adjustment for change in LDL‐C ( P ≤0.006). Conversely, there was no further risk reduction with greater reductions in triglycerides or large/medium VLDL lipoprotein particle concentration. Conclusions Pharmacological reduction in small, cholesterol‐enriched, triglyceride‐depleted VLDL was associated with reduction in ASCVD risk. Chemically measured triglycerides may not sufficiently capture risk related to VLDL pathways. These findings also support broader profiling of lipid and lipoprotein changes in response to statins as prognostic markers of individual benefit, supporting more precision‐medicine, individualized approaches to cardiovascular risk reduction. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00239681.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".