Association of Lipoprotein(a) With Atherosclerotic Plaque Progression

Literature - Kaiser Y, Daghem M, Tzolos E et al. - J Am Coll Cardiol. 2022 Jan 25;79(3):223-233. doi: 10.1016/j.jacc.2021.10.044.

Introduction and methods

Background

Lp(a) is associated with an increased risk of ASCVD, even in patients on intensive lipid-lowering therapy [1]. However, the underlying mechanisms of the relationship between elevated Lp(a) and residual CV risk remain unclear.

Aim of the study

This study investigated whether elevated Lp(a) is associated with adverse plaque progression in patients with ASCVD on guideline-directed preventive therapies.

Methods

191 patients aged ≥40 years and proven multivessel CAD (≥ 2 major epicardial vessels with >50% luminal stenosis or previous PCI or CABG) were included in this study. Patients with coronary revascularization within the previous 3 months or ACS within the previous 12 months were excluded.

Patients underwent coronary computed tomography angiography (CCTA) at baseline and at 12 months. The same imaging protocol and the same scanner were used for repeat CCTA. Coronary atherosclerotic plaque volumes were measured for total plaque, calcific plaque, noncalcific plaque, fibro-fatty plaque, and low-attenuation plaque (a marker of necrotic core). Plaque progression was defined as the difference in plaque volumes between the two scans.

The effect of high Lp(a) (≥70 mg/dL) vs. low Lp(a) (<70 mg/dL) on change in plaque volume from baseline to follow-up CCTA was analyzed. In addition, the percentage change in plaque volume, standardized for each 50 mg/dL increase in Lp(a) was assessed in univariable and multivariable linear regression analyses.

Main results

Baseline characteristics

• 94.7% of all patients were on statin therapy and 100% received anti-platelet therapy.
• 43 patients had high Lp(a) (≥70 mg/dL) and 148 patients had low Lp(a) concentrations (<70 mg/dL).
• There were no differences in LDL-c, BMI, smoking status, diabetes mellitus and serum creatinine concentrations between patients with high vs. low Lp(a).
• Patients with high Lp(a) had higher HDL-c and lower SBP compared to those with low Lp(a).
• The ASSIGN score (a Scottish CV risk score comprised of age, sex, smoking status, BP, total cholesterol, HDL-c, diabetes, rheumatoid arthritis and deprivation index) was higher in patients with low Lp(a) compared to those with high Lp(a).
• There were no differences at baseline in total, calcific, noncalcific, fibro-fatty and low-attenuation plaque volumes between patients with high and low Lp(a).

Plaque progression in those with Lp(a) ≥70 mg/dL vs. Lp(a) <70 mg/dL

• Patients with high Lp(a) (≥70 mg/dL) had a larger increase in low-attenuation plaque volumes compared to patients with low Lp(a) (<70 mg/dL) (26.2 ± 242.8 mm³ vs. -0.7 ± 50.1 mm³, P=0.020).
• Patients with high Lp(a) also showed a larger increase in fibro-fatty plaque volumes compared to patients with low Lp(a) (55.0 ± 242.8 mm³ vs. -25.0 ± 157.4 mm³, P=0.020).
• No differences were observed for change in total plaque volume, calcific plaque volume and noncalcific plaque volume between those with high and low Lp(a).

Percentage change in plaque volume for each 50 mg/dL increase in Lp(a)

• Lp(a) was associated with progression of low-attenuation plaque volume in univariable and multivariable (adjusted for BMI, ASSIGN score and segment involvement score) regression analyses (β= 11.6% for each 50 mg/dL increase in Lp(a), 95% CI 2.0-21.2%, P= 0.018; and β = 10.5% for each 50 mg/dL increase, 95% CI 0.7-20.3%, P=0.037, respectively).
• Lp(a) was also associated with progression of fibro-fatty plaque in univariable regression (β = 7.0% for each 50 mg/dL increase, 95% CI 0.9-13.2%, P=0.025), but this association was no longer significant in the multivariable regression analysis (P=0.053).
• No association was found between Lp(a) and progression of total, calcific and noncalcific plaque volumes.

Conclusion

References

Find this article online at J Am Coll Cardiol.