Cardiovascular disease

Cardiometabolic diseases are the largest single contributor to global mortality in women and men. Our group aims to better understand and characterise cardio-metabolic diseases including myocardial infarction, stroke and diabetes mellitus, among others.

An important pillar of our research in atherosclerosis is the Prospective Studies of Atherosclerosis Consortium (Proof-ATHERO), a collaboration coordinated by our institute, which involves studies focussing on atherosclerosis and cardiovascular disease. Proof-ATHERO holds individual-level data of over 70 studies with more than 100,000 participants and serves as an essential data resource for large-scale analyses.

Based on Proof-ATHERO data, we have shown that progression of intima-media thickness, measured by using carotid ultrasound, can be used as a so-called surrogate marker for cardiovascular events in clinical trials (Circulation 2020). We have also characterised the relationship between two frequently used atherosclerosis markers, as we have shown that carotid intima-media thickness is related to a higher risk for first-ever carotid plaque (JAHA 2023). Further projects within this consortium compare the predictive value of intima-media thickness measurements at different sites of the carotid artery and will quantify improvements in cardiovascular risk prediction when assessing carotid intima-media thickness repeatedly over time.

Another important part of our research is the characterisation of sex differences in atherosclerosis and cardiovascular disease. Previous research at our institute has investigated the contribution of traditional cardiovascular risk factors to sex differences in cardiovascular mortality (Atherosclerosis 2015).

Within the Proof-ATHERO collaboration, we analyse a range of female-specific risk factors for cardiovascular disease, including factors related to pregnancy and menopause to try to understand the relation of these factors to atherosclerosis and its sequelae. In a literature-based meta-analysis, we have also shown that mothers who breastfed have a reduced risk of future cardiovascular disease (JAHA 2022).

As part of the European Society of Cardiology Cardiovascular Risk working group, we have contributed to the development of the updated risk prediction algorithms to be used for primary prevention of cardiovascular disease in the general European population (Eur Heart J 2021) and patients with diabetes (Eur Heart J 2023).

Using data from the population-based Vorarlberg health examination database (VHM&PP), we have been investigating the role of metabolic risk factors such as obesity, blood pressure, blood lipids, blood sugar, gamma-glutamyl transferase and uric acid in cardiovascular disease since 2003. The latest publications in a long tradition focused on risk factors for end stage kidney disease (ESKD). This endpoint for our cohort was added by matching the participant data with the Austrian Dialysis and Transplant Registry. In a first study, we investigated whether the triglyceride-glucose (TyG) index as a measure of insulin resistance is associated with the risk of developing ESKD. We found that the TyG index seemed to be strongly associated with ESKD risk and mediated almost half of the total association between BMI and ESKD in Austrian adults (JAMA Netw Open 2021).

We worked on statistical methods that allow multiple mediators in complex situations and they are applying these methods to a study, with the aim of better understanding of the underlying mechanism of the effect of obesity on the risk of end-stage chronic kidney disease. This study found that TyG index, mean arterial pressure and uric acid, but not total cholesterol, mediated the association of BMI with ESKD in middle-aged adults. Our findings highlight that, in addition to weight reduction, the control of metabolic risk factors are essential in mitigating the adverse effects of BMI on kidney function. For this work, Josef Fritz was awarded with the “Förderpreis der Österreichischen Gesellschaft für Nephrologie 2022” (J Am Soc Nephrol 2022).