Abstract
There is growing evidence of, and biological plausibility for, elevated levels of high-density lipoprotein cholesterol (HDL-C) being related to lower rates of respiratory disease. We tested whether pre-pandemic HDL-C within the normal range is associated with subsequent COVID-19 hospitalisations and death. We analysed data on participants from UK Biobank, a prospective cohort study, baseline data for which were collected between 2006 and 2010. Follow-up for COVID-19 was via hospitalisation records (1845 events in 317,306 individuals) and a national mortality registry (458 deaths in 317,833 individuals). After controlling for a series of confounding factors which included health behaviours, inflammatory markers, and socio-economic status, higher levels of HDL-C were related to a lower risk of later hospitalisation. The effect was linear (p-value for trend 0.001), whereby a 0.2 mmol/L increase in HDL-C was associated with a 7% lower risk (odds ratio; 95% confidence interval: 0.93; 0.90, 0.96). Corresponding relationships for mortality were markedly weaker, such that statistical significance at conventional levels were not apparent for both the linear trend (p-value 0.25) and the odds ratio per 0.2 mmol/L increase (0.98; 0.91, 1.05). While our finding for HDL-C and hospitalisations for COVID-19 raise the possibility that favourable modification of this cholesterol fraction via lifestyle changes or drug intervention may impact upon the risk of the disease, it warrants testing in other studies.
Highlights
High-density lipoprotein cholesterol (HDL-C) has traditionally been linked with coronary heart disease and stroke (Gordon et al, 1989)
Using UK Biobank, a prospective cohort study, we have recently shown that an unfavourable pre-pandemic vascular risk factor profile – low HDL-C included – is associated with a higher risk of hos pitalization for COVID-19 (Batty and Hamer, 2020)
There was evidence of a stepwise relationship (p-value linear trend < 0.001) such that lower disease risk was apparent in people with higher level of this cholesterol fraction. Summarising this trend, a 0.2 mmol/L increase in HDL-C was associated with a 12% lower risk of subsequent hospitalisation (0.88; 0.86, 0.91)
Summary
High-density lipoprotein cholesterol (HDL-C) has traditionally been linked with coronary heart disease and stroke (Gordon et al, 1989). Plausible mechanisms include the HDL-C–mediated sequestration of pathogen-associated lipids, and regulation of immune cells proliferation, maturation, and function which results in neutralization or clearance of pro-inflammatory endo toxins (Catapano et al, 2014). This evidence base raises the possibility of a link between HDL-C and COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2. Using UK Biobank, a prospective cohort study, we have recently shown that an unfavourable pre-pandemic vascular risk factor profile – low HDL-C included – is associated with a higher risk of hos pitalization for COVID-19 (Batty and Hamer, 2020). As the present pandemic has unfolded, this cohort has accumulated sufficient deaths from this disease to facilitate analyses with the aim of corroborating any associations with hospitalisations
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