br Methods br Results A total of patients males

Methods
Results A total of 102 patients (69 males and 33 females, 70.1±9.2years) were registered in the study. Baseline clinical characteristics are presented in Table 1. Telomere G-tail length was negatively correlated with aging and positively correlated with total telomere length (ρ −0.287, P=0.004 and ρ 0.406, P<0.001, Fig. 1). Neither telomere G-tail length nor total telomere length was associated with laboratory findings, including altered mecamylamine manufacturer levels, lipid levels, renal dysfunction or inflammation (Supplemental Table 1). Patients in this study had a shorter mean telomere G-tail length than control subjects (13653.0±2787.4RLU/μg DNA vs. 22504.9±3249.1RLU/μg DNA, P<0.001), but did not significantly differ by total telomere length (Supplemental Table 2). Further, the groups significantly differed by distribution of the association between age and telomere G-tail length (Fig. 1A), and also significantly differed in the distribution of associations with total telomere length and telomere G-tail length (Fig. 1B).
Discussion Several epidemiologic studies have demonstrated that shorter leukocyte telomere length is associated with atherosclerosis and cardiovascular risk factors (Brouilette et al., 2003; Demissie et al., 2006). Thus, the assessment of telomere length has been considered useful for the prediction of progressive atherosclerosis or cardiovascular events (De Meyer et al., 2011; Butt et al., 2010; Khan et al., 2012). Individuals with shorter telomeres may have an increased risk of early vascular cell aging and senescence, which causes progressive atherosclerosis. On the other hand, inflammation, oxidative stress, and insulin resistance, which are associated with cardiovascular disease, result in accelerated telomere attrition and shorter telomeres. Given that these indicators are also associated with endothelial dysfunction, we and others speculated that shorter telomeres might also be associated with endothelial dysfunction. Minamino et al. reported that endothelial senescence downstream of telomere function inhibition is related to endothelial dysfunction (increased intercellular adhesion molecule [ICAM]-1 expression and decreased endothelial nitric oxide synthase [eNOs] activity) in vitro (Minamino et al., 2002). Nakashima et al. assessed the cardiovascular damage (CVD) score (hypertension, dyslipidemia, diabetes, coronary artery disease, stroke and peripheral artery disease), endothelial function using FMD, and leukocyte telomere length by measuring mean telomere restriction fragment (TRF) length using the Southern blot technique in patients with cardiovascular risk factors (Nakashima et al., 2004). Although they found that CVD score was associated with FMD and leukocyte telomere length, it was unclear whether leukocyte telomere length was associated with FMD values. In our study, total telomere length using telomere HPA methods was not associated with endothelial function. Aged and hypertensive changes of the brain (ARWMCs) appear as hyperintense foci on T2-weighted MRI (Pantoni and Garcia, 1997). Patients with severe ARWMCs exhibit an elevated long-term risk of stroke recurrence and unfavorable stroke outcomes (Palumbo et al., 2007; Neumann-Haefelin et al., 2006). The pathogenesis of ARWMCs is thought to be associated with endothelial dysfunction. In addition, shorter leukocyte telomere length measured using quantitative real-time polymerase chain reaction (PCR) was associated with the severity of ARWMCs in non-demented community-based subjects after adjustment for age, sex and some confounders (Wikgren et al., 2014). In our study, the total telomere length of leukocytes, as measured using telomere HPA methods, was slightly associated with the severity of ARWMCs in univariate analysis. However, the association between total telomere length and the severity of ARWMCs was not significant on multivariate analysis. The inconsistencies between our present and these previous results might have been due to differences in baseline characteristics, or in methods used to measure telomere length and evaluate the severity of ARWMCs.