Serum Biomarkers in the MORGAM Populations

The role of risk factors, such as raised blood cholesterol and blood pressure to heart disease, to determining future heart disease and stroke has been known for more than thirty years. More recently the level of a protein (C reactive protein)in the blood has been shown to improve prediction but better prediction is needed to identify patients at increased risk, on whom preventive efforts can be concentrated. To do this it is necessary to follow up large groups of people to see if many novel new proteins (biomarkers) can improve our ability to identify persons at higher risk of developing heart disease or stroke. We need to study human populations as the reevance of studing these new factors in animals is dubious. MORGAM is a large European studt which has included 120,000 men and women in 9 countries. A sample of serum is available for all these persons and we will use the latest tecchnology to measure a battery of 19 Biomarkers, some of which are highly novel. The results obtained in the United Kingdom samples will be verified in other European poulations, in men and women separately. In this fashion we plan to derive a scoring system to quantify the cahace of developing a heart attack in the future so that steps can be taken to avert them. The Team is based at the Queen s University of Belfast and in Helsinki, Finland, and in Mainz, Germany.

Background: Cardiovascular disease is the leading cause of morbidity and mortality in the industrialised world. Biomarkers can substantially improve the early identification of high-risk patients for future cardiovascular events.
Aim of the Study: The primary aim is to produce a British/European risk score that allows improved risk prediction beyond that obtained from current scoring systems. The objective of the present proposal is to identify a single biomarker or a group of biomarkers which, in the primary prevention setting, are highly predictive of future cardiovascular disease.
Methods:
MORGAM (MOnica, Risk, Genetics, Archiving, and Monography, www.ktl.fi/morgam/) is a multinational study (53 cohorts in 9 countries) of the epidemiology and genetics of cardiovascular disease morbidity and mortality. These harmonized data are completely available at the MORGAM data centre. MORGAM is sufficiently large to permit the development of a biomarker instrument in the UK cohorts like Belfast (PRIME), Scotland (SHHS), Wales (Caerphilly), and London (UKWHS) which will then be compared to European populations with an overall sample size of 120,000 subjects. A panel of 21 easily detectable biomarkers covering distinct pathophysiological pathways has been selected. For the inflammatory pathways hs-CRP, PLA2 (PAF-AH), IL-18, sTNFR-1, hs-IL-10, and sICAM-1. To assess oxidative stress, MPO and PON will be determined. Hemodynamics and vascular remodelling are represented by (Nt-pro)BNP, (pro)ANP and TIMP-1, MMPs, and metabolic pathways include TSH, adiponectin, APO A-I and B 100. In additiion, renal function parameter will be assessed including cystatin C and neutrophil gelatinase associated lipocalin. The risk estimates will be derived primarily using time-to-event models. The predictive performance of the biomarkers will be evaluated in the UK training data-set and assessed in the overall European cohort.
Overall, the study concept provides unique opportunity to identify single biomarkers or a discrete panel of biomarkers of clinical relevance for early cardiovascular risk prediction in primary prevention.