Press Release Universitätsmedizin Halle
High uric acid levels increase the risk of cardiovascular disease: However, a recent study by a multidisciplinary consortium at the University Medical Centre Halle found that uric acid levels even within the normal range are linked to vascular stiffness and can therefore be a risk factor for cardiovascular disease. The analysis was based on data and samples from over 70,000 people in the German National Cohort (NAKO) and showed that this correlation is more pronounced in women. The results, published in the journal “BMC Medicine”, question the existing limits for “normal” uric acid levels and emphasise the importance for women’s healthcare.
*
In mammals, uric acid is normally converted into a water-soluble substance that can be easily excreted. In humans, however, the enzyme responsible has been lost in the course of evolution. “Most people think of uric acid as gout and a fat toe. But this view is very one-sided, because in evolutionary terms it once offered a physiological advantage in times of salt scarcity. Due to our modern lifestyle, high uric acid levels are now considered a risk factor for vascular disease, which in turn can be associated with high blood pressure and organ damage,” explains Prof Michael Gekle, last author of the study and Director of the Julius Bernstein Institute of Physiology at the University Medical Centre Halle.
Until now, it was unclear exactly how the risk of vascular disease is linked to uric acid. This question was investigated by a study consortium of scientists from physiology, nephrology, biometry, biobanking and the Digital Research Methods working group at the University Medical Centre Halle and the local NAKO Study Centre. The researchers analysed the uric acid concentration in the blood serum of 70,649 participants in the NAKO Health Study aged between 19 and 74 years in relation to their vascular stiffness. The so-called pulse wave velocity was measured, i.e. the speed at which a pressure wave travels through the vascular system. The higher this value is, the stiffer the vessels are.
Rethink limit values?
Nine out of ten of the people analysed had uric acid levels within the normal range. However: “Even in the physiological concentration range, which is considered harmless, uric acid was positively linked to vascular stiffness and therefore to the risk of cardiovascular disease. This correlation was more pronounced in women than in men,” says Gekle.
According to the authors, the current uric acid limits should therefore be reconsidered. These are currently 140-360 µmol/l for women and 180-420 µmol/l for men. “When the limits were set, the link with vascular stiffness as a risk factor was not yet known. It is possible that the concentration ranges to be aimed for must be much narrower than previously assumed,” says Prof Oliver Thews, lead author of the study and specialist in physiology at the University Medical Centre Halle. According to an estimate by the study team, an increase in uric acid concentration of 100 µmol/l corresponds to vascular ageing of around seven years in women and four years in men.
Preventive therapy within the normal range conceivable
There are other gender differences: women generally have a lower pulse wave velocity. In addition, it has been shown in the past that uric acid therapy works better in women with high levels than in men. “The body excretes uric acid via the kidneys differently depending on gender. This may be why the increase in uric acid has a stronger effect in women. It is also possible that the observations can be explained by different molecular signalling pathways between the sexes,” continues Thews.
The findings suggest that preventive therapy with uric acid-lowering medication could be useful even at “normal” levels. In particular, women with other cardiovascular risk factors, such as obesity or metabolic diseases, could benefit in terms of their health.
In the study, in which a large data set was analysed, a machine learning method (random forest) was also used to identify and weight previously unknown risk factors for vascular stiffness. Uric acid came out ahead of aspects such as smoking, long-term blood sugar and alcohol consumption.
The study reveals a clear link between uric acid and vascular stiffness – but proof of a cause-and-effect relationship is still pending: “We now have a mechanistic explanation for why uric acid is considered a cardiovascular risk factor. However, further investigations are needed to clarify the causal relationship, for example experimental studies with primary vascular cell cultures of both sexes or interventional studies in humans,” reports Gekle. The research team is already working on a follow-up study with around 7,000 participants from the NAKO Study Centre in Halle. For this, data was collected at various points in time and additional parameters were included.