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Lipoprotein(a) and Cardiovascular Risk Prediction Among Women
Nancy R Cook1, Samia Mora1, Paul M Ridker1
1Center for Cardiovascular Disease Prevention, Divisions of Preventive Medicine and Cardiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Insights
Lipoprotein(a) [Lp(a)] increases cardiovascular disease (CVD) risk in women with high total cholesterol, but its predictive value is minimal. These findings impact clinical practice and Lp(a)-lowering drug trials for women.
Area of Science:
- Cardiovascular Medicine
- Clinical Chemistry
- Epidemiology
Background:
- Lipoprotein(a) [Lp(a)] is recognized as a risk factor for incident cardiovascular disease (CVD).
- The precise role and clinical utility of Lp(a) in CVD prediction, particularly in women, remain subjects of ongoing research and debate.
- Understanding Lp(a)'s contribution to CVD risk is crucial for refining risk assessment and therapeutic strategies.
Purpose of the Study:
- To investigate the association between Lp(a) levels and incident CVD specifically in women.
- To evaluate the clinical utility of Lp(a) in improving CVD risk prediction models for women.
- To compare the association of Lp(a) with CVD risk in women versus men.
Main Methods:
- Lp(a) levels were measured using a turbidimetric assay across three large cohorts of women (WHS, WHI, JUPITER) and one cohort of men (JUPITER).
- A derivation sample from the Women's Health Study (WHS) established the form of the association between Lp(a) and CVD.
- Risk reclassification models, comparing traditional CV risk factors with and without Lp(a), were used to assess clinical utility.
Main Results:
- A curvilinear association was observed between Lp(a) and CVD risk in women, with elevated risk noted only when Lp(a) exceeded 50 mg/dl and total cholesterol (TC) was above 220 mg/dl.
- In the WHS, Lp(a) showed a statistically significant but small improvement in the C-statistic (0.790 to 0.797), with no significant enhancement in risk reclassification measures.
- These findings were consistent across women in the WHI and JUPITER trials, while a strong association was found between Lp(a) and CVD in men with low TC levels.
Conclusions:
- In women, Lp(a) is associated with CVD risk primarily in the presence of high total cholesterol, and its contribution to prediction models offers minimal improvement.
- The findings suggest that the clinical utility of Lp(a) for CVD risk prediction in women is limited.
- These results have important implications for the clinical application of Lp(a) testing and the development of Lp(a)-lowering therapies in women.
Background:
Although lipoprotein(a) [Lp(a)] is associated with incident cardiovascular disease (CVD), its contribution to prediction remains controversial.
Objectives:
This study examined the association and clinical utility of Lp(a) with incident CVD in women.
Methods:
A turbidimetric assay assessed Lp(a) in 3 cohorts of women (the WHS [Women's Health Study] [N = 24,558], a case-cohort sample from the WHI [Women's Health Initiative] Observational Study [n = 1,815 cases, subcohort n = 1,989], and the JUPITER [Justification for Use of Statins in Prevention] trial [n = 2,569]) and in men from JUPITER (n = 5,161). A WHS derivation sample (n = 16,400) determined the form of association with incident CVD. This was tested in WHS validation data (n = 8,158) and the other study samples. Models including traditional CV risk factors but with and without Lp(a) were compared using risk reclassification.
Results:
In the WHS, there was a curvilinear association, with increased CVD risk among those with Lp(a) >50 mg/dl, but only among women with total cholesterol (TC) >220 mg/dl. In the WHS test sample, there was a small but significant change in the C-statistic (0.790 to 0.797; p = 0.035) but no improvement in measures of reclassification. This pattern was replicated among women in the WHI and JUPITER trial. In contrast, there was a strong association of Lp(a) with CVD among men with low TC levels in JUPITER.
Conclusions:
In 3 cohorts of women, Lp(a) was associated with CVD only among those with high TC, and improvement in prediction was minimal. These data have implications for Lp(a) in clinical practice among women and for trials of Lp(a)-lowering agents.
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