Systemic telomere length and preclinical atherosclerosis: the Asklepios Study.

AIMS: Peripheral blood leucocyte (PBL) telomere length (TL) is a systemic ageing biomarker and has been proposed to be an independent predictor of cardiovascular disease (CVD). We aimed at providing an explanation for this association by the evaluation of the biomarker value of PBL-TL in preclinical atherosclerosis. METHODS AND RESULTS: Peripheral blood leucocyte telomere length was assessed by telomere restriction fragment analysis in 2509 volunteers free from established CVD, aged approximately 35-55 years old, from the Asklepios Study cohort. Intima-media thickness (IMT) and plaque presence were determined by ultrasonography in both left and right carotid and femoral arteries. Peripheral blood leucocyte telomere length was not a significant independent determinant of IMT (P > 0.3) or plaque presence (P > 0.05), in either artery or either sex. In women but not in men, PBL-TL was a weak determinant of combined (carotid or femoral) plaque presence, adjusted for other risk factors (women: P = 0.03, men: P > 0.4). However, even in women presenting plaques, PBL-TL was still longer than in men. CONCLUSION: Since systemic TL is not a substantial underlying determinant of preclinical atherosclerosis, the association between CVD and TL cannot be explained by the fact that subjects with shorter inherited TL are predisposed to atherosclerosis.

Telomere length and cardiovascular risk factors in a middle-aged population free of overt cardiovascular disease.

Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.

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.