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

Background and aims: High levels of lipoprotein(a) could worsen the outcome of COVID-19 due to prothrombotic and proinflammatory properties of lipoprotein(a). We tested the hypotheses that during COVID-19 hospitalization i) increased thrombotic activity and inflammation are associated with lipoprotein(a) levels, and ii) lipoprotein(a) levels are associated with rate of hospital death and discharge. Methods: We studied 211 patients admitted to Copenhagen University Hospital in 2020 with COVID-19, that is, prior to any vaccination. Thrombotic activity was marked by elevated D-dimer while inflammation was marked by elevated interleukin-6, C-reactive protein, and procalcitonin. Patients were followed until death (N = 36) or discharge (N = 175). Results: A 2-fold higher D-dimer was associated with 14% (95%CI: 8.1–20%) higher lipoprotein(a). Conversely, 2-fold higher interleukin-6, C-reactive protein, and procalcitonin were associated with respectively 4.3% (0.62–7.8%), 5.7% (0.15–5.2%), and 8.7% (5.2–12%) lower lipoprotein(a). For hospital death, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 1.26 (95%CI:0.91–1.73). Corresponding hazard ratios per 2-fold higher biomarker were 0.93 (0.75–1.16) for D-dimer, 1.42 (1.17–1.73) for interleukin-6, 1.44 (0.95–2.17) for C-reactive protein, and 1.44 (1.20–1.73) for procalcitonin. For hospital discharge, the multivariable adjusted hazard ratio per 2-fold higher lipoprotein(a) was 0.91 (95%CI:0.79–1.06). Corresponding hazard ratios per 2-fold higher biomarker were 0.86 (0.75–0.98) for D-dimer, 0.84 (0.76–0.92) for interleukin-6, 0.80 (0.71–0.90) for C-reactive protein, and 0.76 (0.67–0.88) for procalcitonin. Conclusions: In COVID-19 patients, thrombotic activity marked by elevated D-dimer was associated with higher lipoprotein(a) while elevated inflammatory biomarkers of interleukin-6, C-reactive protein, and procalcitonin were associated with lower lipoprotein(a); however, elevated lipoprotein(a) was not associated with rate of hospital death or discharge.