Risks of Incident Cardiovascular Disease Associated With Concomitant Elevations in Lipoprotein(a) and Low‐Density Lipoprotein Cholesterol—The Framingham Heart Study
Bibliographic record
Abstract
Background Elevated lipoprotein(a) is a well‐established risk factor for atherosclerotic vascular disease but is not measured in routine clinical care. Screening of high lipoprotein(a) in individuals with moderate elevations of low‐density lipoprotein cholesterol (LDL‐C) may identify individuals at high risk of cardiovascular disease. Methods and Results We examined 2606 Framingham Offspring participants (median age, 54 years; 45% men) prospectively with a median follow‐up of 15 years (n=392 incident cardiovascular events). Individuals with higher (≥100 nmol/L) versus lower lipoprotein(a) were divided into groups based on LDL‐C <135 mg/dL versus ≥135 mg/dL. In Cox models, after adjustment for known risk factors, high lipoprotein(a) (≥100 nmol/L) and LDL‐C ≥135 mg/dL were each significant predictors of cardiovascular disease (LDL‐C ≥135 mg/dL: hazard ratio [HR], 1.34; 95% CI, 1.09–1.64; P =0.006; high lipoprotein (a): HR, 1.31; 95% CI, 1.03–1.66; P =0.026). Across the groups of high/low lipoprotein (a) and LDL‐C ≥135 mg/dL or <135 mg/dL, the absolute cardiovascular disease risks at 15 years were 22.6% (high lipoprotein(a)/LDL‐C ≥135 mg/dL, n=248), 17.3% (low lipoprotein(a)/LDL‐C ≥135 mg/dL, n=758), 12.7% (high lipoprotein(a)/LDL‐C <135 mg/dL, n=275) and 11.5% (low lipoprotein(a)/LDL‐C <135 mg/dL, n=1328, reference group). Among individuals with LDL‐C ≥135 mg/dL, those with high lipoprotein(a) had a 43% higher risk (HR, 1.43; 95% CI, 1.05–1.97; P =0.02). Presence of high lipoprotein(a) with moderate LDL‐C levels (135–159 mg/dL) yielded absolute risks equivalent to those with LDL‐C ≥160 mg/dL (23.5%, 95% CI, 17.4%–31.3%; and 20.7%, 95% CI, 16.8%–25.3%, respectively). Conclusions Concomitant elevation of LDL‐C ≥135 mg/dL and lipoprotein(a) ≥100 nmol/L is associated with a high absolute risk of incident cardiovascular disease. lipoprotein(a) measurement in individuals with moderate elevations in LDL‐C, who do not otherwise meet criteria for statins, may identify individuals at high cardiovascular risk.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".