Endothelial dysfunction in patients with elevated lipoprotein(a) levels

Background: Endothelial dysfunction is considered an initial step in the development of atherosclerosis. Epidemiological studies have identified lipoprotein (a) (Lp(a)) as a potential predictor for cardiovascular events. Retinal vessel analysis (RVA) represents a novel approach for detecting and quantifying endothelial dysfunction. RVA includes dynamic measurements of retinal vascular dilation as well as static assessments of retinal vessels. The impact of elevated Lp(a) levels on retinal microvasculature remains unclear.

Objective: The aim of this study is to examine the relationship between Lp(a) levels and retinal microvascular function, using both dynamic and static RVA techniques. The following analysis includes preliminary study data.

Methods: This cross-sectional, preliminary observational study prospectively enrolled 50 patients with at least one cardiovascular risk factor (mean age 57.6 ± 11.6 years; 39% female). Based on Lp(a) levels, participants were classified into high Lp(a) and low Lp(a) groups using the rule-out value (<30 mg/dl) recommended by the European Atherosclerosis Society. The primary outcome was flicker-induced dilation of retinal arterioles (FIDart), with secondary exploratory outcomes including flicker-induced dilation of venules (FIDven), arteriovenous ratio, flow-mediated dilation. Multivariate regression analysis was performed to adjust for potential confounding factors.

Results: The low Lp(a) group included 34 patients (mean age 57.5±13.0; 41% female), whereas 16 patients belonged to the high Lp(a) group (mean age 57.7±7.9; 35% female). FIDart was significantly lower in patients with high Lp(a) levels compared to those with low Lp(a) levels (mean FIDart: high Lp(a) 1.2 ± 1.3% vs low Lp(a) 2.4 ± 1.5%, P = 0.006). Additionally, FIDart and Lipoprotein(a) showed a negative Spearman-correlation (r= -0.34, p=0.02), suggesting impaired microvascular function with higher Lp(a) levels. This association remained significant after adjusting for potential confounders (age, sex, hypertension, dyslipidemia, smoking status, renal function) using multiple linear regression analysis (Lp(a) β-coefficient -0.41; p = 0.01). No significant differences were observed between the groups for FIDven, flow-mediated dilation or arteriovenous ratio. 

Conclusion: Elevated Lp(a) levels are associated with significant retinal microvascular dysfunction, as indicated by a reduction in flicker-induced dilation of retinal arterioles. Dynamic RVA could serve as a promising tool for studying retinal microvascular dysfunction in populations at increased cardiovascular risk.