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Lipoprotein(a) and coronary heart disease risk
S M Marcovina1, R A Hegele, M L Koschinsky
1Department of Medicine, University of Washington, 2121 North 35th Street, Seattle, WA 98103-9103, USA.
Insights
Plasma lipoprotein(a) [Lp(a)] may not be an independent risk factor for coronary heart disease (CHD), but elevated levels can increase risks associated with traditional factors. Routine Lp(a) testing is not recommended currently.
Area of Science:
- Cardiovascular Medicine
- Lipidology
- Atherosclerosis Research
Background:
- Retrospective studies suggest a link between plasma lipoprotein(a) [Lp(a)] concentrations and coronary heart disease (CHD).
- However, large prospective studies have not consistently confirmed Lp(a) as an independent CHD risk factor.
- Existing evidence indicates Lp(a) may potentiate risks from traditional cardiovascular risk factors.
Purpose of the Study:
- To evaluate the role of plasma lipoprotein(a) [Lp(a)] in coronary heart disease (CHD) risk.
- To assess the clinical utility of routine Lp(a) measurement.
- To define specific patient groups who might benefit from Lp(a) testing.
Main Methods:
- Review and synthesis of findings from retrospective case-control and population-based prospective studies.
- Analysis of structural similarities between Lp(a), plasminogen, and low-density lipoprotein (LDL).
- Consideration of challenges in clinical determination and application of Lp(a) concentrations.
Main Results:
- Conflicting evidence regarding Lp(a) as an independent CHD risk factor between study types.
- Demonstrated association of elevated Lp(a) with increased risk in the presence of other traditional risk factors.
- Structural similarities suggest potential prothrombotic or atherogenic roles for Lp(a).
Conclusions:
- Routine measurement of plasma Lp(a) is not currently recommended due to clinical determination and application challenges.
- Lp(a) testing may be valuable for high-risk or borderline-risk patients with uncertainty regarding aggressive treatment of modifiable risk factors like elevated LDL cholesterol.
Abstract:
Although retrospective case-control studies continue to indicate that plasma lipoprotein(a) concentrations are associated with coronary heart disease (CHD), several large population-based prospective studies have failed to confirm that Lp(a) is an independent risk factor. However, evidence exists from several studies to suggest that elevated plasma Lp(a) increases the CHD risk associated with more traditional risk factors. Although identification of the functional role of Lp(a) in atherogenesis has been thwarted by the physical, chemical, and genetic complexity of Lp(a), the structural similarity of Lp(a) to both the fibrinolytic proenzyme plasminogen and low-density lipoprotein (LDL) has suggested a prothrombotic or atherogenic role (or both) for this lipoprotein. Because the clinical determination and application of plasma Lp(a) concentration poses several challenges, we cannot recommend its routine measurement at this time. Rather, plasma Lp(a) determinations should be limited to either patients at high risk for the development of CHD or patients at borderline risk for the development of CHD in whom uncertainty may exist about how aggressively to treat modifiable risk factors such as elevated LDL cholesterol.