Abstract 193: Remnant-Like Particle Cholesterol, Low-Density Lipoprotein Triglyceride and Incident Cardiovascular Disease in the Atherosclerosis Risk in Communities Study: Can Genetic Variants Provide New Insights on Triglycerides and Atherogenic Lipoproteins?
Bibliographic record
Abstract
Recent genetic studies have focused on the atherogenicity of remnant-like particle cholesterol (RLPC) with paucity of data on TGs in LDL (LDL-TG). We examined the association of RLPC and LDL-TG with incident CVD and the genetic variants associated with their levels in the biracial ARIC study. Fasting plasma RLPC and LDL-TG were measured by automated homogeneous assays (Denka Seiken, Tokyo) in 9334 men and women without prevalent CVD at baseline. Incident CHD and stroke over 16-y follow-up were obtained from medical records. Associations between LDL-TG and RLPC and the genomic variants (Illumina HumanExome Beadchip) were assessed using single variant analysis for common variants and gene-based burden tests for rare variants. Variants with minor allele frequency >1% were analyzed individually. RLPC and LDL-TG were correlated with elevated TG (r=0.85 and 0.64, p<0.0001). In minimally adjusted analyses, both were associated with CVD risk, but after adjusting for traditional CVD risk factors including lipids, only LDL-TG was positively associated with incident CHD (HR 1.28 [95% CI 1.10-1.50]) and stroke (HR 1.47 [95% CI 1.13-1.92]; p<0.01). Single variant tests showed a common APOE variant (rs7412) had the strongest association with LDL-TG and RLPC in both races (p<5x10 -8 ). Since rs7412 defines apoE isoforms, we assessed APOE haplotypes and found E2/2 was associated with reduced LDL-TG and increased RLPC (Fig). Although elevated TGs are associated with increased RLPC and LDL-TG, only LDL-TG remained significant for CVD risk in multivariable-adjusted models. ApoE2 locus variants were associated with RLPC and LDL-TG, but individuals with apoE2/E2 had decreased LDL-TG and increased RLPC. These findings, and prior studies showing that apoE2 is associated with lower CVD risk, suggest that the increased risk of CVD with high TGs may be related more to LDL-TG than RLPC. Further research is needed to understand whether LDL-TG plays a causal role in CVD and is a target for therapy.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".