(Vienna 10th January 2012) The results of a recent study at the University Department of Internal Medicine III at the MedUni Vienna could revolutionise the evaluation of HDL cholesterol: Thomas Weichhart and Marcus Säemann from the Department of Nephrology have discovered that the supposedly “good” HDL cholesterol can also be “bad” and can even aggravate inflammatory reactions.
Generally speaking, a distinction has been made so far between “good” HDL cholesterol and “bad” LDL cholesterol. LDL contributes to cardiovascular diseases such as myocardial infarction and stroke, while the “good” HDL protects against them. Now, however, experts at the MedUni Vienna have discovered that the anti-inflammatory effect of HDL was not detected in patients on renal dialysis. “In fact, the HDL amplified inflammatory reactions several times over and could explain the latent chronic inflammation that is associated with high cardiovascular risk,” says Säemann.
On closer investigation of HDL levels in dialysis patients, i.e. people with renal failure, it was learned that levels of a specific molecule, known as serum amyloid A (SAA), were significantly raised in these individuals. SAA is a highly likely cause for the defect in the HDL. Says Weichhart: “If you integrate SAA into healthy HDL, it ceases to function properly.”
Quality over quantity
This discovery could change the evaluation of HDL cholesterol. Until now, a high level of HDL was regarded as ideal. “Much more important than the quantity, however, is of course the quality of the HDL. Non-functioning HDL cholesterol is useless – even high HDL levels would cease to be healthy,” says Weichhart. Explaining another finding, Säemann adds: “Lowering the LDL level is therefore still even more important than raising the HDL level.”
It is currently not possible, however, to identify “bad” HDL quickly with a simple test. Weichhart and Säemann are currently working on the development of such a test. Together with the Medical University of Vienna, they have obtained a patent that will allow them to determine the changes in HDL using a simple laboratory test and therefore enable the risk of future cardiovascular disease to be estimated more accurately – allowing treatment to be commenced sooner.
In recent years, it has been found that certain conditions such as coronary heart disease (CHD), diabetes mellitus and rheumatoid arthritis have their own, characteristic HDL. Some of the proteins that have just been discovered in the HDL of patients with renal failure have also been found in the HDL of these conditions, causing HDL to lose its beneficial, anti-inflammatory and vessel-protecting properties. “With the new laboratory test, we have now been able to investigate whether modified HDL is associated with a poorer prognosis in patients with renal failure at an early stage of their condition, and whether this is also the case for patients with diabetes or after a heart attack, for example. This would mean that a simple test principle would enable us to commence therapy early on, thereby decisively changing the overall prognosis for the better," say the MedUni Vienna researchers.
Service: Journal of the American Society of Nephrology
“The proteomic signature of dysfunctional uremic HDL identifies SAA as proinflammatory component”. Thomas Weichhart, Chantal Kopecky, Markus Kubicek, Michael Haidinger, Dominik Döller, Karl Katholnig, Cacang Suarna, Philipp Eller, Markus Tölle, Christopher Gerner, Gerhard J Zlabinger, Markus van der Giet, Walter H. Hörl, Roland Stocker, Marcus D Säemann.