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Lipoprotein (a) and coronary artery calcification: prospective study assessing interactions with other risk factors
Kwok Leung Ong1, Robyn L McClelland2, Matthew A Allison3
1Lipid Research Group, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
Insights
Elevated lipoprotein (a) [Lp(a)] increases coronary artery calcification (CAC) volume, particularly in individuals with high inflammation and coagulation markers. This suggests Lp(a) may predict CAC progression.
Area of Science:
- Cardiovascular Medicine
- Atherosclerosis Research
- Biomarker Discovery
Background:
- Lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are recognized cardiovascular risk factors.
- A correlation exists between elevated Lp(a) and CAC.
- The influence of other cardiovascular risk factors on this relationship is under investigation.
Purpose of the Study:
- To investigate the interaction between baseline lipoprotein (a) [Lp(a)] and 24 cardiovascular risk factors.
- To determine the effect of these interactions on the change in coronary artery calcification (CAC) volume and density over time.
Main Methods:
- Analysis of 5975 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
- Assessment of interactions between baseline Lp(a) levels and 24 variables (dyslipidemia, diabetes, hypertension, inflammation, coagulation).
- Longitudinal evaluation of changes in CAC volume and density over a 9.5-year period.
Main Results:
- Elevated Lp(a) correlated with a greater absolute increase in CAC volume, but not relative change.
- No association was observed between Lp(a) and changes in CAC density.
- The Lp(a)-CAC volume association was significantly amplified by higher levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1, and fibrinogen.
Conclusions:
- Elevated Lp(a) is linked to increased coronary artery calcification volume progression.
- This association is particularly pronounced in individuals with elevated markers of inflammation and coagulation.
- Lipoprotein (a) shows potential as a predictive biomarker for CAC volume progression.
Background:
Elevated plasma lipoprotein (a) [Lp(a)] and coronary artery calcification (CAC) are established cardiovascular risk factors that correlate with each other. We hypothesized that other cardiovascular risk factors could affect their relationship.
Methods:
We tested for interactions of 24 study variables related to dyslipidemia, diabetes, insulin resistance, hypertension, inflammation and coagulation with baseline Lp(a) on change in CAC volume and density over 9.5 years in 5975 Multi-Ethnic Study of Atherosclerosis (MESA) participants, free of apparent cardiovascular disease at baseline.
Results:
Elevated Lp(a) was associated with larger absolute increase in CAC volume (3.21 and 4.45 mm3/year higher for Lp(a) ≥30 versus <30 mg/dL, and Lp(a) ≥50 versus <50 mg/dL, respectively), but not relative change in CAC volume. No association was found with change in CAC density when assessing continuous ln-transformed Lp(a). The association between elevated Lp(a) (≥30 mg/dL) and absolute change in CAC volume was greater in participants with higher circulating levels of interleukin-2 soluble receptor α, soluble tumor necrosis factor alpha receptor 1 and fibrinogen (15.33, 11.81 and 7.02 mm3/year in quartile 4, compared to -3.44, -0.59 and 1.91 mm3/year in quartile 1, respectively). No significant interaction was found for other study variables. Similar interactions were seen when assessing Lp(a) levels ≥50 mg/dL.
Conclusions:
Elevated Lp(a) was associated with an absolute increase in CAC volume, especially in participants with higher levels of selected markers of inflammation and coagulation. These results suggest Lp(a) as a potential biomarker for CAC volume progression.
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