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Link found between HDL cholesterol and infectious disease risk

Most people recognise that there is a relationship between cholesterol levels and risk of heart disease. But new research from Copenhagen University Hospital and the University of Copenhagen shows that a certain kind of cholesterol might affect our health differently – that is, through a role in the immune system.

In brief, the concentration of HDL cholesterol – which is often called the 'good' cholesterol – seems to matter with respect to getting infectious diseases, such as gastroenteritis or pneumonia.

"Surprisingly, we found that individuals with both low and high HDL cholesterol had high risk of hospitalisation with an infectious disease. Perhaps more importantly, these same groups of individuals had high risk of dying from infectious disease," explains professor and chief physician at University of Copenhagen and Copenhagen University Hospital, Børge Nordestgaard.

The results were based on data from 100,000 individuals from the Copenhagen General Population Study who were followed for more than 6 years using national Danish health registries.

"Numerous studies in animals and cells indicate that HDL is of importance for the function of the immune system and thereby the susceptibility to infectious disease, but this study is the first to examine if HDL is associated with the risk of infectious disease among individuals from the general population," explains one of the authors PhD-student and physician Christian Medom Madsen from University of Copenhagen and Copenhagen University Hospital.

The authors cannot, based on this study, conclude that very low or very high HDL is the direct cause of the increased risk of infectious disease, but conversely they cannot rule out a direct causal relationship either, as data from the genetic part of the study indicates that this might be the case.

"Our findings indicate that, in the future, research into the role and function of HDL should not narrowly focus on cardiovascular disease, but rather focus on the role of HDL in other disease areas, such as infectious disease," says Nordestgaard.

The 21% of the population with the lowest concentrations of HDL cholesterol and the 8% of the population with the highest concentrations of HDL cholesterol had high risk of infectious disease.

Individuals with very low HDL cholesterol had a 75% higher risk of infectious disease as compared to the reference group and the risk was 43% higher in those with very high HDL cholesterol.

Abstract
Aims: Preclinical evidence has indicated that HDL may play an important role in the immune system; however, very little is known about the role of HDL in the immune system in humans. We tested the hypothesis that low and high concentrations of HDL cholesterol are associated with risk of infectious disease in the general population.
Methods and results: We included 97 166 individuals from the Copenhagen General Population Study and 9387 from the Copenhagen City Heart Study with measurements of HDL cholesterol at baseline. The primary endpoint was any infectious disease requiring hospital admission, ascertained in the Danish health registries from baseline in 2003–13 or 1991–94 through 2014; 9% and 31% of individuals in the two studies experienced one or more infectious disease events. Using restricted cubic splines, there was a U-shaped association between concentrations of HDL cholesterol and risk of any infection. Following multifactorial adjustment, individuals with HDL cholesterol below 0.8 mmol/L (31 mg/dL) and above 2.6 mmol/L (100 mg/dL) had hazard ratios for any infection of 1.75 (95% confidence interval 1.31–2.34) and 1.43 (1.16–1.76), compared to those with HDL cholesterol of 2.2–2.3 mmol/L (85–95 mg/dL). In the Copenhagen City Heart Study, corresponding hazard ratios for any infection were 2.00 (1.16–3.43) and 1.13 (0.80–1.60).
Conclusion: Low and high HDL cholesterol concentrations found in 21% and 8% of individuals were associated with higher risk of infectious disease in the general population. These findings do not necessarily indicate causality.

Authors
Christian M Madsen, Anette Varbo, Anne Tybjærg-Hansen, Ruth Frikke-Schmidt, Børge G Nordestgaard

[link url="http://healthsciences.ku.dk/news/2018/04/higher-risk-of-infectious-disease-with-both-high-and-low-cholesterol/"]University of Copenhagen material[/link]
[link url="https://academic.oup.com/eurheartj/article-abstract/39/14/1181/4710060?redirectedFrom=fulltext"]European Heart Journal abstract[/link]

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