Family history of premature atherosclerotic cardiovascular disease and lipoprotein(a) levels: a multicohort analysis
Bibliographic record
Abstract
Lipoprotein(a) [Lp(a)] is a risk factor for premature atherosclerotic cardiovascular disease (ASCVD), thrombosis, and aortic stenosis.1 Inherited LPA gene variants explain approximately 75–95% of the variability in plasma Lp(a),1 and genetic risk scores for LPA and measured plasma Lp(a) have very similar magnitude associations with incident ASCVD (∼25–30% risk per 55 mg/dL increase).2 Whether reported family history of premature ASCVD may assist with case finding and prioritizing those who may most benefit from Lp(a) testing is not well defined. In 2024, a United States National Lipid Association Scientific Statement recommended universal screening for Lp(a),3 joining prior European,4 Canadian,5 and Australian6 guidelines that recommend Lp(a) testing at least once in an individual’s lifetime. While clinical consensus may be shifting towards universal screening, prioritizing Lp(a) testing earlier in life in those at the highest risk may be helpful in the setting of limited healthcare system resources and office visit time. The presence of a family history of premature ASCVD independently associates with up to a two-fold higher risk of ASCVD events.7 However, this risk varies depending on the first degree relative affected, which may have implications for Lp(a) testing in routine ASCVD risk stratification. For example, a family history of premature coronary heart disease (CHD) in a sibling compared to parent more strongly associates with the presence and burden of coronary artery calcium (CAC).8 Given that Lp(a) is a risk factor for CAC9 and is more strongly associated with CHD compared to stroke, assessing the strength of association across various family history components with plasma Lp(a) levels may provide further precision for recommendations regarding Lp(a) testing in the general population. Here, we aimed to evaluate the association between family history of premature ASCVD (CHD, stroke) and plasma Lp(a) levels in the Multi-Ethnic Study of Atherosclerosis (MESA) and Atherosclerosis Risk in Communities (ARIC) Study.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".