High HDL cholesterol may increase glaucoma risk in older adults

'Good' (HDL) cholesterol, usually considered to be beneficial for health, may be linked to a heightened risk of the serious eye condition, glaucoma-at least among the over 55s- suggest the results of a large observational study, published online in the British Journal of Ophthalmology.

Paradoxically, 'bad' (LDL) cholesterol, usually regarded as harmful to health, may be associated with a lower risk of glaucoma, a condition that damages the optic nerve, potentially leading to irreversible sight loss or total blindness.

The findings challenge received wisdom about what may help and hinder eye health, and suggest that a rethink may be needed of how patients with high blood fats and who are at risk of glaucoma, are treated, say the researchers.

Glaucoma is projected to affect around 112 million people by 2040. Risk factors include age, ethnicity, the build-up of pressure within the eye (IOP), and family history, explain the researchers.

Abnormally high levels of circulating fats (lipids) in the bloodstream have been linked to eye conditions, such as macular degeneration and diabetic retinopathy. Recently published research has also implied a link with glaucoma, but the findings have been inconsistent, and it's not clear which type of lipid might be most influential, they add.

To strengthen the evidence base, the researchers drew on 400,229 participants aged 40 to 69 in the UK Biobank Study. They had all filled in a questionnaire, been interviewed, and had undergone a standard panel of blood tests, including those to measure blood fats.

Their health was tracked for an average of 14 years, during which time 6868 (nearly 2%) of them developed glaucoma. 

Compared with participants who didn't develop glaucoma, those who did, tended to be older, and of non-White ethnicity. They had higher HDL, but lower LDL, cholesterol and a higher waist-to-hip ratio (indicative of central obesity). 

They were also more likely to be ex-smokers, and to be taking statins, and they had a higher prevalence of diabetes, high blood pressure, and cardiovascular disease.

But analysis of the blood test results showed that higher levels of 'good' HDL cholesterol were associated with a heightened risk of glaucoma while higher levels of 'bad' LDL cholesterol, total cholesterol, and triglycerides were associated with a lower risk. 

Those with the highest level of HDL cholesterol in their bloodstream were 10% more likely to develop glaucoma than those with the lowest level, with every (standard deviation) increase associated with a 5% higher risk. 

Similarly, participants with the highest levels of LDL cholesterol and triglycerides were 8% and 14%, respectively, less likely to develop glaucoma than those with the lowest levels. 

And each (standard deviation) increase in LDL cholesterol, total cholesterol, and triglycerides lowered the risks by 4%, 3%, and 4%, respectively. 

But these observed associations only persisted among those older than 55, with no significant association seen in those aged 40–55; the findings were also influenced by sex and type of glaucoma.

The researchers drew up a polygenic risk score-a number that provides a personalised measure of genetic susceptibility to diseases by combining genetic risk information from across the genome.

This showed that each additional genetic risk was associated with 5% higher odds of developing glaucoma. But there were no significant individual associations between LDL cholesterol, total cholesterol, or triglycerides and glaucoma. 

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers acknowledge various limitations to their findings, including that blood samples weren't taken after fasting and only at a single time point. 

The findings might also not be applicable to other ethnic groups, as UK Biobank participants are predominantly of European ancestry.

But they suggest: "These findings challenge existing paradigms about 'good' and 'bad' cholesterol in relation to eye health. This could prompt a re-evaluation of lipid management strategies in patients at risk for glaucoma."

And they conclude: "HDL cholesterol has been regarded as the 'good cholesterol' for seven decades. However, this study demonstrates that high levels of [it] are not consistently associated with a favourable prognostic outcome. Further studies are needed to investigate the mechanisms behind these associations."