Plasma lipoprotein subclasses and risk of incident knee osteoarthritis: A population-based cohort study

Lipoprotein subclasses play diverse roles in health and disease. Although lipoproteins have been implicated in knee osteoarthritis (KOA), the relationship between lipoprotein subclasses and KOA remains unexplored.

We conducted a cohort study using UK Biobank data to examine the associations of 85 plasma lipoprotein subclasses, defined by combinations of density (high, low, intermediate, very-low), size (extremely-large, very-large, large, medium, small, very-small), and composition (triglyceride, free cholesterol, cholesteryl ester, phospholipid), with incident KOA in metabolome-wide analysis. Data were analyzed using Cox proportional hazards models, correcting for multiple tests (0.05/9). Targeted analyses were subsequently conducted to examine the association between key lipoprotein subclasses and the risk of knee replacement.

Among 115,237 participants followed for a median of 12.8 years, 38 lipoprotein subclasses were statistically significantly associated with incident KOA. Higher concentrations of very-large and large high-density lipoproteins (HDL), excluding triglyceride, were associated with a lower risk of incident KOA (hazard ratios [HRs] ranging from 0.87 to 0.94 per 1-standard deviation increase in log-transformed lipoprotein subclasses concentrations). Conversely, higher concentrations of small HDL, irrespective of composition, were associated with higher risks of incident KOA (HRs ranging from 1.04 to 1.09). After adjusting for body mass index as a continuous variable, differential effects among HDL subclasses remained evident, except for the association between large HDL and KOA. Similar associations were observed for targeted analysis in knee replacement.

We provided novel evidence of diverse associations between lipoprotein subclasses and incident KOA and knee replacement, indicating the distinct effects of HDL subclasses.