Biomarker-guided therapy in primary prevention

• Applicant: Privatdozent Dr. Johannes Neumann
• Subject Area: Cardiology, Angiology ; Epidemiology and Medical Biometry/Statistics
• Term: from 2019 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 435281291

Cardiovascular diseases have a high prevalence and are among the leading causes of death worldwide. In patients with known cardiovascular disease, preventive strategies, such as intake of acetylsalicylic acid or statins, are well established and resulted in substantially improved cardiovascular outcome. In addition, primary prevention is recommended in high-risk individuals without known cardiovascular disease. Therefore, identification of high-risk individuals is of major importance. For clinical routine, several risk prediction models are available, but the therapeutic consequences resulting from these models, are barely investigated. Treatment with acetylsalicylic acid in primary prevention has been intensively discussed in the past years. In 2018 the large Aspirin in Reducing Events in the Elderly (ASPREE) trial was presented and showed, that treatment with acetylsalicylic acid compared to placebo did not improve the primary endpoint of death, dementia, or persistent physical disability, but led to a higher rate of major hemorrhage than placebo. Therefore, it remains unclear which individuals benefit from therapy with acetylsalicylic acid. Cardiac specific biomarkers could potentially be used as markers of subclinical cardiovascular disease and therefore identify higher risk individuals. Biomarkers are detectable in peripheral blood and widely used in clinical routine. Cardiac troponin and BNP are established diagnostic biomarkers for acute myocardial injury and heart failure and might also visualize subclinical cardiovascular disease. Using newer, high-sensitivity assays, biomarker concentrations became detectable not only in diseases patients, but also in healthy individuals from the general population. This improvement opened the venue to use biomarkers for risk stratification also in the setting of primary prevention. The objective of the present proposal is to develop a biomarker-guided approach in a primary prevention setting. The proposed project aims to investigate cardiac biomarkers in primary prevention with acetylsalicylic acid and translate these findings to a potential clinical application. This would contribute to a more individualized preventive medicine, which could identify high-risk individuals at an early stage and thereby help to prevent incident cardiovascular diseases. For this purpose, a collaboration with the ASPREE study group at the Monash University in Melbourne is planned to 1) analyse cardiac biomarkers in the ASPREE study population and determination of their predictive value in primary prevention; 2) develop a biomarker-based prediction model to identify patients, who benefit from acetylsalicylic acid treatment in ASPREE; 3) translate these findings into a study protocol for a primary prevention trial based on biomarker measurements.

• DFG Programme: Research Fellowships
• International Connection: Australia
• Host: Professor John McNeil