Lipoprotein(a) and SARS‐CoV‐2 infections: Susceptibility to infections, ischemic heart disease and thromboembolic events

Abstract

Background Comorbidities including ischemic heart disease (IHD) worsen outcomes after SARS‐CoV‐2 infections. High lipoprotein(a) [Lp(a)] concentrations are a strong risk factor for IHD and possibly for thromboembolic events. We therefore evaluated whether SARS‐CoV‐2 infections modify the risk of high Lp(a) concentrations for IHD or thromboembolic events during the first 8.5 months follow‐up of the pandemic. Method Cohort study using data from the UK Biobank during the SARS‐CoV‐2 pandemic. Baseline Lp(a) was compared between SARS‐CoV‐2 positive patients and the population controls. UK Biobank received ethical approval from the North West Multi‐Centre Research Ethics Committee (REC reference: 11/NW/0382). All participants gave written informed consent before enrolment in the study, which was conducted in accordance with the principles of the Declaration of Helsinki. Results SARS‐CoV‐2 positive patients had Lp(a) concentrations similar to the population controls. The risk for IHD increased with higher Lp(a) concentrations in both, the population controls (n = 435,104) and SARS‐CoV‐2 positive patients (n = 6,937). The causality of the findings was supported by a genetic risk score for Lp(a). A SARS‐CoV‐2 infection modified the association with a steeper increase in risk for infected patients (interaction P‐value = 0.03). Although SARS‐CoV‐2 positive patients had a 5‐times higher frequency of thromboembolic events compared to the population controls (1.53% vs. 0.31%), the risk was not influenced by Lp(a). Conclusions SARS‐CoV‐2 infections enforce the association between high Lp(a) and IHD but the risk for thromboembolic events is not influenced by Lp(a). This article is protected by copyright. All rights reserved

Prognostic parameters of in‐hospital mortality in COVID‐19 patients—An Italian experience

“…In this context, following the hypothesis that PCSK9 may suppress the expression of interferon type I, 14,42 we measured this protein without finding any association with in-hospital mortality. Same conclusions were reached for lipoprotein(a), in line with findings reporting that high lipoprotein(a) concentrations do not increase the susceptibility either to SARS-CoV-2 infections or to thromboembolic events 43 .…”

Elevated Lp(a) and course of COVID-19: Is there a relationship?

“…In our study, the Lp(a)≥30mg/dl group had significantly higher d-dimer concentration, (median 1001 vs. 1256 μg/l) p = 0.0208, with no difference in other coagulation parameters including fibrinogen, INR, thrombin time, prothrombin time and APTT ( Table 3 ). Also, the incidence of pulmonary embolism was not significantly higher in the COVID-19 patients with elevated Lp(a), which is consistent with previous results obtained by Maio S Di et al [ 18 ]. The prothrombotic properties of Lp(a) have been well confirmed in in vitro studies; however, a previous meta-analysis suggests that the association between elevated Lp(a) and VTE remains questionable [ 19 , 20 ].…”

Lipoprotein(a) in COVID-19: Genetics and inflammation collide

“…First, Lp(a) is an acute phase reactant, and its concentration can be consistently boosted during sustained inflammatory states, like that characterizing severe forms of COVID-19 and other acute conditions. This is in keeping with the findings of Nurmohamed et al [ 6 ], who reported a gradual increase of this lipoprotein during hospital stay, directly correlated with IL-6 variations, as well as with those of Lippi et al, who found similar concentrations between patients with COVID-19 and other acute diseased states [ 7 ]. Then, in all three studies that we could identified based on our digital search, Lp(a) values both at baseline (e.g., presumably genetically determined) or during illness progression (i.e., boosted by COVID-19 related inflammation) were found to have an impact on clinical outcome of SARS-CoV-2 infection.…”

“…Then, in all three studies that we could identified based on our digital search, Lp(a) values both at baseline (e.g., presumably genetically determined) or during illness progression (i.e., boosted by COVID-19 related inflammation) were found to have an impact on clinical outcome of SARS-CoV-2 infection. The most important aspect here concerns the interplay of this lipoprotein with the risk of developing both venous and arterial thrombosis, in that a positive association was found in the studies of Nurmohamed et al [ 5 ] and Di Maio et al [ 6 ] ( Table 1 ).…”

“…In another article, Di Maio et al conducted a large-scale prospective study including over 500,000 subjects aged between 40 and 69 years recruited up to the year 2010, whose data were compared with those of a second cohort undergoing SARS-CoV-2 testing from March 2020 (55,199 subjects, 13,588 with at least one positive test for SARS-CoV-2) [ 6 ]. The incidence of ischemic heart disease in patients with Lp(a) values > 95th percentile (i.e., >220 nm/L) was 489/21755 in the control population and 37/343 in those with SARS-CoV-2 infection, respectively, thus reflecting an over 5-fold enhanced risk in the second cohort (odds ratio [OR], 5.26; 95%CI, 3.70–7.48; p < 0.001).…”