Navin Suthahar: Novel aspects of heart failure biomarkers
Heart failure (HF) is a clinical syndrome resulting from structural or functional abnormality of the heart, along with disruption of cardiovascular homeostatic mechanisms. HF affects at least 25-30 million individuals globally, its prevalence continues to increase over time. The increasing prevalence of HF can partly be attributed to the increasing prevalence of cardiovascular risk factors, particularly type-2 diabetes and obesity. Adequately addressing cardiovascular risk factors once they develop, and specifically targeting shared pathophysiological mechanisms can help prevent HF development.
Circulating proteomic biomarkers provide insights into systemic and cardiovascular pathophysiologic mechanisms operating in HF. In this thesis, we used a biomarker-based approach to identify shared pathophysiological mechanisms operating in HF, type-2 diabetes and obesity. HF biomarkers are also useful in cardiovascular risk estimation, but plasma concentrations of several biomarkers are affected by obesity as well as by gender (sex). Therefore, we also examined the impact of obesity and sex on the predictive value of multiple HF biomarkers including cardiac natriuretic peptides and troponins.
Our most important results are:
1. Inflammation and fibrosis are major pathophysiological mechanisms operating in HF, type-2 diabetes and obesity, and may be amenable to therapy.
2. While using cardiac natriuretic peptides and troponins to predict HF in the community, the effects of obesity can largely be ignored.
3. Although baseline levels of cardiovascular biomarkers substantially differ among women and men, their predictive value for incident HF is comparable in both sexes.
4. Cardiac troponins are powerful predictors of HF, cardiovascular disease and mortality in both sexes. However, the threshold in which the cardiovascular risk becomes apparent is lower in women than in men.
Overall, this thesis examines several novel aspects of heart failure biomarkers, focussing on inflammation, obesity and sex-related differences.