Telomere length in cardiovascular disease: new challenges in measuring this marker of cardiovascular aging

Atherosclerosis is an age-related systemic disease characterized by systemic oxidative stress and low grade chronic inflammation. Various types of leukocytes play an important role within this process. Telomeres, the ends of chromosomes, shorten during each and every cell division and have therefore been regarded as a cellular clock. Telomere dysfunction has been implicated in aging and senescence, and shorter leukocyte telomere length (LTL) has been demonstrated to predict cardiovascular disease and mortality. However, although LTL can predict cardiovascular events in population studies, a number of factors have prevented its broad use as a surrogate end point, such as serum levels of LDL cholesterol. In this article we will provide an overview of telomere biology and telomere dynamics of different leukocyte populations, and we will also discuss pitfalls in the methodology of LTL quantification, in context with landmark studies, which measured LTL in cardiovascular disease. Finally, we will attempt to critically assess and explain the shortcomings of LTL as a biomarker and identify further research avenues that require further investigation before telomere length can be implemented as an individual biomarker for cardiovascular aging. From this it becomes evident that LTL can be susceptible to methodological errors affecting longitudinal reproducibility. LTL is generally confounded at least by genetic factors, population variation and leukocyte composition.