Lp(a) Predicts Non-Achievement of LDL-C Targets in Coronary Artery Disease

José Javier Gómez-Barrado, MD

Credit: Colegio Oficial De Medicos de Caceres

Elevated levels of lipoprotein(a) influence low-density lipoprotein cholesterol (LDL-C) levels and may negatively impact the achievement of LDL-C targets among patients with coronary artery disease (CAD), according to new research.¹

The cross-sectional study, performed in a cardiology department in Spain, indicated the proportion of patients achieving target LDL-C was lower in those with Lp(a) >50 mg/dL than those with Lp(a) ≤50 mg/dL.

“The prevalence of high levels of Lp(a) (>50 mg/dL) is higher in individuals with CAD than described in the general population,” wrote the investigative team, led by José Javier Gómez-Barrado, MD, department of cardiology, Hospital San Pedro de Alcantara. “High concentrations of Lp(a) are associated with higher levels of LDL-C and in these patients, there is a difficulty in achieving optimal LDL-C levels as established in clinical practice guidelines.”

Lp(a) is a molecule, like LDL-C, with proatherogenic, proinflammatory, and prothrombotic properties.² Multiple studies have reported its effect on the physiopathological process of atherosclerosis and other vascular conditions. It is known that Lp(a) concentrations influence serum LDL-C levels, but its influence on the achievement of LDL-C targets has not been well-researched.

Recent analyses found elevated lp(a) levels were independently associated with a long-term risk of major adverse cardiovascular events (MACE), regardless of baseline atherosclerotic cardiovascular disease, among more than 16,000 patients.³ The risk was most evident in those without baseline ASCVD.

For the current analysis, Gómez-Barrado and colleagues sought to assess the prevalence of elevated Lp(a) in individuals with coronary artery disease and assess its influence on LDL-C target achievement.¹ The team performed a cross-sectional analysis in a Spanish tertiary hospital's cardiology department, involving 870 consecutive patients with stable CAD, from September 2016 to March 2020.

Participants in the study were divided into 2 groups based on the threshold proposed by the European Atherosclerosis Society (EAS) for Lp(a) 20. Patients were separated into groups with levels of Lp(a) >50 mg/dL and Lp(a) ≤50 mg/dL. Logistic regression analysis was conducted to evaluate the association of Lp(a) >50 mg/dL with the achievement of LDL-C targets.

Overall, 376 (43.2%) patients had Lp(a) levels >30 mg/dL, and 268 (30.8%) patients had >50 mg/dL, with a median Lp(a) level of 22.10 mg/dL. Individuals with Lp(a) >50 mg/dL exhibited higher baseline (142.30 ± 47.54 vs. 130.47 ±40.75 mg/dL; P = .0001) and current (72.91 ± 26.44 vs. 64.72 ± 25.30 mg/dL; P = .0001) levels.

This finding was notable despite these patients being treated with more high potency statins (77.2 vs. 70.9%; P = .058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; P = .001).

Gómez-Barrado found the proportion of patients achieving target LDL-C was lower in those with Lp(a) >50 mg/dL. Independent predictions of elevated Lp(a) levels >50 mg/dL included the use of high-potency statins (odds ratio [OR], 1.5; 95% CI, 1.08 - 2.14), combination lipid-lowering therapy with ezetimibe (OR, 2.0; 95% CI, 1.45 - 2.73), and failure to achieve LDL-C ≤55 mg/dL (OR, 2.3; 95% CI, 1.63 - 3.23).

Based on these data, Gómez-Barrado indicated new drugs that act directly on Lp(a) are needed for patients at very high cardiovascular risk.

“In the context of very high and extremely high cardiovascular risk and elevated Lp(a) levels, the use of other targeted drugs is necessary,” they wrote.

References

1. _{Gómez-Barrado JJ, Gómez-Turégano P, Beltrán Moreno M, Fernández-Chamorro AI, Roque Rodríguez B, Kounka Z. Lipoprotein (a) is a predictor of non-achievement of LDL-C goals in patients with chronic heart disease. Lipoproteína (a) es un factor predictor de no consecución de objetivos de C-LDL en pacientes con cardiopatía isquémica crónica. Clin Investig Arterioscler. Published online February 23, 2024. doi:10.1016/j.arteri.2024.01.002}
2. _{Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res. 2016;57(11):1953-1975. doi:10.1194/jlr.R071233}
3. _{Campbell, P. (2024) Elevated lp(a) levels linked to cardiovascular event risk, regardless of ASCVD history, HCP Live. Available at: https://www.hcplive.com/view/elevated-lpa-levels-linked-to-cardiovascular-event-risk-regardless-of-ascvd-history (Accessed: 21 March 2024).}