👤 Thomas Sejersen

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Lipid biomarkers, including direct low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (ApoB), and apolipoprotein A1 (ApoA1), are essential tools for cardiovascular risk assessment. Monitoring patient-derived median values over time may provide insights into population health and analytical performance. This study provides a descriptive analysis of population-level lipid results spanning nearly two decades. While trends in patient medians may support quality assurance, these data do not constitute a validated approach to risk prediction or definitive analytical monitoring due to the absence of outcome and treatment information. We retrospectively analyzed routine clinical laboratory data from Uppsala University Hospital, Sweden, covering January 2006-December 2024. A total of 890,948 LDL-C, 867,446 HDL-C, 64,787 ApoB, and 65,500 ApoA1 results were included. Measurements were performed on Abbott Architect systems until 2021, after which assays were transferred to Roche Cobas Pro platforms. Statistical analyses included trend evaluation, variability assessment, and seasonal pattern analysis. Women had modestly higher LDL-C and HDL-C levels compared to men, while ApoB values were similar between sexes. ApoA1 was notably higher in women. Over the 19-year period, median LDL-C declined from 3.18 to 2.62 mmol/L, consistent with improved lipid management. HDL-C remained stable (1.36-1.45 mmol/L), while ApoB and ApoA1 concentrations showed minimal change. Variability was highest for LDL-C (median CV 6.4%) and lowest for ApoA1 (median CV 2.6%). Seasonal variation was negligible across all analytes. Testing volumes increased substantially for LDL-C and HDL-C, whereas ApoB and ApoA1 requests peaked around 2010 and later declined. Long-term monitoring of median patient values demonstrates declining LDL-C, stable HDL-C, and consistent ApoB/ApoA1 ratios with minimal seasonal effects. These findings highlight the potential utility of patient medians as supplementary quality indicators and for population-level lipid surveillance. Show less

Myosin-binding protein C (MyBPC) in the muscle sarcomere interacts with several contractile and structural proteins. Mutations in the cardiac isoform (MyBPC-3) in humans, or animal knockout, are associated with cardiomyopathy. Function of the fast skeletal isoform (MyBPC-2) in living muscles is less understood. This question was addressed using zebrafish models, combining gene expression data with functional analysis of contractility and small-angle x-ray diffraction measurements of filament structure. Fast skeletal MyBPC-2B, the major isoform, was knocked down by >50% using morpholino antisense nucleotides. These morphants exhibited a skeletal myopathy with elevated apoptosis and up-regulation of factors associated with muscle protein degradation. Morphant muscles had shorter sarcomeres with a broader length distribution, shorter actin filaments, and a wider interfilament spacing compared with controls, suggesting that fast skeletal MyBPC has a role in sarcomere assembly. Active force was reduced more than expected from the decrease in muscle size, suggesting that MyBPC-2 is required for optimal force generation at the cross-bridge level. The maximal shortening velocity was significantly increased in the MyBPC-2 morphants, but when related to the sarcomere length, the difference was smaller, reflecting that the decrease in MyBPC-2B content and the resulting myopathy were accompanied by only a minor influence on filament shortening kinetics. In the controls, equatorial patterns from small-angle x-ray scattering revealed that comparatively few cross-bridges are attached (as evaluated by the intensity ratio of the 11 and 10 equatorial reflections) during active contraction. X-ray scattering data from relaxed and contracting morphants were not significantly different from those in controls. However, the increase in the 11:10 intensity ratio in rigor was lower compared with that in controls, possibly reflecting effects of MyBPC on the cross-bridge interactions. In conclusion, lack of MyBPC-2 results in a severe skeletal myopathy with structural changes and muscle weakness. Show less