Lipoprotein(a), venous thromboembolism and COVID-19: A pilot study

Abstract

Background and aims Thrombosis is a major driver of adverse outcome and mortality in patients with Coronavirus disease 2019 (COVID-19). Hypercoagulability may be related to the cytokine storm associated with COVID-19, which is mainly driven by interleukin (IL)-6. Plasma lipoprotein(a) [Lp(a)] levels increase following IL-6 upregulation and Lp(a) has anti-fibrinolytic properties. This study investigated whether Lp(a) elevation may contribute to the pro-thrombotic state hallmarking COVID-19 patients. Methods Lp(a), IL-6 and C-reactive protein (CRP) levels were measured in 219 hospitalized patients with COVID-19 and analyzed with linear mixed effects model. The baseline biomarkers and increases during admission were related to venous thromboembolism (VTE) incidence and clinical outcomes in a Kaplan-Meier and logistic regression analysis. Results Lp(a) levels increased significantly by a mean of 16.9 mg/dl in patients with COVID-19 during the first 21 days after admission. Serial Lp(a) measurements were available in 146 patients. In the top tertile of Lp(a) increase, 56.2% of COVID-19 patients experienced a VTE event compared to 18.4% in the lowest tertile (RR 3.06, 95% CI 1.61–5.81; p < 0.001). This association remained significant after adjusting for age, sex, IL-6 and CRP increase and number of measurements. Increases in IL-6 and CRP were not associated with VTE. Increase in Lp(a) was strongly correlated with increase in IL-6 (r = 0.44, 95% CI 0.30–0.56, p < 0.001). Conclusions Increases in Lp(a) levels during the acute phase of COVID-19 were strongly associated with VTE incidence. The acute increase in anti-fibrinolytic Lp(a) may tilt the balance to VTE in patients hospitalized for COVID-19.

Lipoprotein(a) during COVID-19 hospitalization: Thrombosis, inflammation, and mortality

“…In line with our findings, a recent study including 219 hospitalized COVID-19 patients in the Netherlands [ 32 ], did not find lipoprotein(a) levels or inflammatory markers at admission to be associated with risk of venous thromboembolism; however, increases in lipoprotein(a) – but not changes in inflammatory markers – during hospitalization were associated with higher risk of venous thromboembolism. Additionally, baseline interleukin-6 was associated with risk of being admitted to an intensive care unit, which is in line with our finding that inflammatory markers were associated with risk of death.…”

Understanding the ins and outs of lipoprotein (a) metabolism

“…To date, several factors that control LPA transcription have been identified; the responsible cis elements in and nearby LPA as well as the associated transcription factors have been pinpointed. Transcriptional effects likely underlie the rise in Lp(a) levels in women after menopause [15,16], the reduction in Lp(a) levels in cases of biliary obstruction [17] and the increase in Lp(a) levels induced by inflammatory cytokines [18], such as in the acute phase after atherothrombotic events and in COVID-19 [19,20 ▪ ].…”

Long-Term Cardiovascular and Cerebrovascular Challenges Posed by COVID-19 in Patients With Familial Hypercholesterolemia

“…Accordingly, we can estimate that among the currently reported over 500 million total cases of COVID-19 worldwide, more than one million are likely FH patients. FH patients have a markedly elevated serum low-density lipoprotein cholesterol (LDL-C) already in utero which is often accompanied by an elevated level of serum lipoprotein(a) [Lp(a)], and if left untreated, a lifelong dysfunction of the arterial endothelium ensues in these patients ( Sorensen et al, 1994 ; Vuorio et al, 2020 ; Nurmohamed et al, 2022 ). In FH patients with COVID-19, the pre-existing endothelial dysfunction is likely to increase the risk of macrovascular and microvascular thrombosis caused by a direct viral attack of the endothelial cells (endothelitis) and by the cytokine storm typically seen during severe COVID-19 illness ( Vuorio et al, 2021b ).…”