Rationale, design, methods and baseline characteristics of the Asklepios Study.

The Asklepios Study is a longitudinal population study focusing on the interplay between ageing, cardiovascular haemodynamics and inflammation in (preclinical) cardiovascular disease. The 2524 participants (1301 women) are a representative cohort of 35-55-year-old individuals, free from overt cardiovascular disease at study initiation, randomly sampled from the twinned Belgian communities of Erpe-Mere and Nieuwerkerken. Baseline examinations (all single-observer, single-device, single-site, single 2-year consecutive timeframe) include: questionnaires, conventional risk factors and biochemistry. Additional phenotypes under study include: (a) vascular structure and function: carotid and femoral atherosclerosis (intima-media thickness, plaque), arterial distension and pressure curves (brachial, carotid, femoral; wall-tracking and applanation tonometry); (b) cardiac structure and function. A novel aspect of the study is 'integrated' non-invasive biomechanical assessment of cardiac, arterial and ventriculovascular function through a combination of modeling, fundamental hydraulical measurements and system identification techniques. Integrated phenotypes result from combining at least two sets of curves (flow/pressure/distension). The value of this 'integrated' haemodynamic phenotype in the detection, prediction and prevention of clinical cardiovascular pathology (atherosclerosis progression, atherothrombosis, development of heart failure) will be tested. A second novel aspect is the systematic determination of peripheral blood leukocyte telomere length as a marker for biological ageing. During follow-up, baseline examinations will be repeated and the incidence of cardiovascular events will be monitored. Sex-specific baseline risk factor and biochemical data are provided in the current analyses. The primary aim is to build a combined dataset that will act as a tool to answer a cluster of questions about ageing, haemodynamics and the emergence of cardiovascular disease, especially the incidence of atherothrombotic events and the development of adverse haemodynamic profiles (arterial stiffening, heart failure). The study will reassess current risk factors and provide a long-term base for the detection of novel (epi)genetic and non-genetic risk factors and for more performant risk stratification modalities. Within these broader goals, a constant will be to strive towards more fundamental mechanistic-haemodynamic insights into cardiovascular disease processes.