Marie Holmqvist

Bakgrund: Systemic sclerosis (SSc) is a complex autoimmune disease with high mortality

within five years of diagnosis, 20% of all patients have died, primarily from cardiovascular diseases or cardiopulmonary complications. Vascular abnormalities are hallmark features of SSc and play a crucial role in its pathogenesis, disease manifestations, and complications. Målsättning: This research program aims to explore two cardiovascular/cardiopulmonary complications related to the vasculopathy in SSc: heart failure (HF) and pulmonary hypertension (PH). In a collaboration between rheumatology and cardiology in Stockholm, Lund and Göteborg, and with deCODE Genetics on Iceland, we will also investigate potential biomarkers for these outcomes. The specific research questions include: *What is the prevalence, contributing factors, and outcomes of HFin patients with SSc? Focus will be on HF with preserved ejection fraction and HF without previous ischemic heart disease. *How do the contributing factors of HF with preserved ejection fraction influence the development of PH in SSc patients? *What are the risk factors and outcomes of PH in SSc patients? Focus will be on pulmonary arterial hypertension and its prognosis. *Are there SSc-specific biomarkers for HF or PH? Arbetsplan: The research will combine data from clinically well-characterized patients, recruited in clinical practice, where we have information from high-throughput genetics and proteomics, with data from high-quality registers to study clinically relevant outcomes. The work plan includes: *Detailed exploration of HF and PH in SSc patients. *Collaboration with deCODE Genetics to identify potential biomarkers. *Analysis of the prevalence, contributing factors, and outcomes of HF and PH. *Investigation of the interplay between HF with preserved ejection fraction and PH. Betydelse: This research program will enhance our understanding of the microvascular component in the development of cardiovascular/cardiopulmonary complications using SSc as a model of autoimmune-related microvascular dysfunction. The findings will be significant for other patient populations and will inform how we monitor patients over time. Additionally, the program will provide insights into the pathogenesis of different cardiovascular diseases, which is essential for implementing early screening and intervention strategies to optimize outcomes in the SSc population.

Purpose and aimPatients with systemic rheumatic disease (SRD) are severely affected: within five years of diagnosis, 25% have died. This results in a mortality that is three times as high as in a general population with the same age and sex distribution. One of the leading causes of death, and the most common disease affecting our patients is cancer. We know very little of why our patients develop cancer, and what their prognosis is. The aim of this study is to define the genetic and clinical characteristics of cancer, and quantify the consequences of cancer in patients with SRD.Following questions will be answered:What cancer types do patients with SRD develop in comparison with the general population?What is the genetic contribution to cancer development in SRD?Can we predict which patients with SRD will develop cancer?What is the risk of death and cancer relapse in patients with SRD and cancer?Project organization, time plan, scientific methodThis project is an international collaboration, that will span four years. Our study population consists of clinically well-defined patients that will be genotyped at deCODE Genetics, followed over time with respect to cancer, and studied using modern epidemiological methods including machine learning.SignificanceThis project will influence how we screen for cancer in our patients, help us identify cancer processes earlier, and improve how we take care of our patients after cancer. This will have a major impact on our patients lives.