H4HEstablishment of Molecular Fingerprinting Reference Norms for Healthy Aging and Disease Transition

BACKGROUND The H4H study monitors health changes for 10 years in participants who are healthy at the outset but are at risk to develop new-onset health conditions. It uses a prospective study design and encompasses over 100,000 person-years of follow-up, allowing close observation of disease trajectories in relation to risk factors and medication use. This provides a unique opportunity to collect data on current tendencies in non-communicable disease (NCD) presentation and management. Major NCDs (i.e., cardiovascular disease, cancer, type 2 diabetes and chronic respiratory disease) cause a significant loss in quality of life and are responsible for over 90 percent of Hungary's all-cause mortality. Therefore, there is growing demand for screening tools that might be used at minimal expense to reduce the overall burden of diseases. 'Early diagnosis' and recognition of high-risk states prior to the development of overt clinical diseases would allow better therapeutic outcomes and help preserve quality of life longer in the society. Blood tests are valuable screening tools for many conditions and may be used for population health monitoring. Better understanding of blood composition, along with establishing reference ranges for blood constituents, is essential for developing effective blood-based health monitoring strategies. High-information-content detection methods, including molecular fingerprinting, proteomics and metabolomics are expected to promote the discovery of novel disease biomarkers. By assessing a wide range of molecules, multiple disease-specific variables may be recognized. Apart from multimodal analysis of blood samples, aliquots of all samples are preserved in a dedicated biobank with a commitment to accommodate a comprehensive collection of biospecimens for decades and to facilitate long-term research arrangements with the intention to accelerate future discoveries. OBJECTIVES The study aims to address the following objectives: A) Establish reference ranges for infrared molecular fingerprinting and other high-information-content analysis methods (i.e., proteomics and metabolomics) in a non-symptomatic population using a cross-sectional approach. B) Define characteristics of healthy aging and establish personalized reference intervals for infrared molecular fingerprinting and other high-information-content analysis methods using a longitudinal approach. C) Identify novel biomarkers for non-communicable diseases, including coronary artery disease, lung cancer and diabetes, using infrared molecular fingerprinting and other high-information-content analysis on blood samples. D) Identify novel blood-based risk factors for non-communicable diseases and discover indicators of precursor diseases using infrared molecular fingerprinting and other high-information-content analysis methods. The findings of the current study will be instrumental in identifying disease specific deviations of human blood composition. This could lead to the discovery of 'novel biomarkers'. Overall, the study will determine whether the molecular composition of human plasma remains stable over time and will test whether deeper analysis of blood samples can form the basis of population health monitoring. STUDY DESIGN The project is conducted in a single-country, multicenter, prospective, longitudinal format. Sample collection is scheduled for ten years according to this protocol. PARTICIPANTS The study enrolls healthy subjects of > 40 years or > 50 years in low- or high-risk cohorts, respectively, who are followed up for ten years. Enrollment continues until 15,000 subjects are enrolled. PROCEDURES: Blood sample collection occurs in accordance with the clinical routine and plasma samples are processed for high-information-content analysis. Additional blood tubes are submitted to clinical laboratory testing. Health data collection utilizes self-report questionnaires and review of medical records. In the high-risk cohort, a comprehensive medical examination is performed after the first 4 blood samples are collected, including screening tests for lung cancer and coronary artery disease, i.e., a low-dose CT scan of the chest and coronary artery calcium score test (heart scan). These investigations are repeated after a follow-up period of 5 years. WITHDRAWAL OF CONSENT, DISCONTINUATION FROM THE STUDY Participation in this sample and data collection project is voluntary, and each participant has the right to withdraw their consent at any time without any consequence concerning possible future treatment or future blood donations.