Abstract
Leukocytes telomere length has been associated with hypertension, but, whether longitudinal telomeres change could serve as a useful predictive tool in hypertension remains uncertain. This study aimed to examine the longitudinal trajectory of leukocytes telomere length in a population-based prospective study of 1,108 individuals with hypertension. Leukocytes telomere length were measured at baseline and again after a median 2.2 (range 1.5-2.4) years of follow-up. Age as an independent predictor was inversely associated with baseline telomeres and follow-up telomeres. Annual telomere attrition rate was calculated as (follow-up telomeres-baseline telomeres)/follow-up years, and participants were categorized into the shorten and the lengthen groups. Results showed that telomere lengthening was significantly correlated with decreased systolic blood pressure (SBP) (β=-3.28; P=0.02) and pulse pressure (PP) (β=-2.53; P=0.02), and the differences were respectively -3.3 mmHg (95%CI, -6.2 to -0.3; P=0.03) in ∆SBP and -2.4 mmHg (95%CI, -4.9 to -0.1; P=0.04) in ∆PP between two groups after adjustment for vascular risk factors and baseline blood pressures. When stratified by age and gender, the correlations were observed in women and patients ≤60 years. Furthermore, among patients using calcium channel blocker (CCB) and angiotensin receptor blocker (ARB), those with telomeres lengthening showed a significantly lower level of ∆SBP and ∆PP. There was no correlation between telomere attrition and incidence of cardiovascular events. Our data indicated that increased telomere length of leukocytes was associated with decreased SBP and PP, particularly for patients who received CCB and ARB, supporting that telomere attrition may provide new sight in clinical intervention for hypertension.
Highlights
Telomeres are tandem repeat nucleotides sequence (TTAGGG)n at the end of linear chromosomes which form a protective cap and maintain the chromosomal stability [1]
All studied participants were divided into two groups depending on annual rate of telomere attrition, one is the shorten group (n=386) who had a decrease of telomere length, and the other is the lengthen group (n=722) who had an increase of telomere length (Supplemental Figure S4)
With the use of generalized linear regression analysis adjusting for covariates including age, gender, smoking and alcohol status, medical history, the stage of baseline blood pressures, baseline telomere length, and changes in body mass index (BMI), waist-to-hip, fasting serum glucose, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) during 2014-2016, the results showed that ∆systolic blood pressure (SBP) was -10.2 mm Hg (95%CI, -12.8 to 7.6) for the lengthen group and -6.9 mm Hg (95%CI, -10.1 to -2.9) for the shorten group (P=0.03) (Fig. 2A); the ∆pulse pressure (PP) was -7.9 mm Hg (95%CI, -10.0 to -5.8) for the lengthen and -5.5 mm Hg (95%CI, -8.1 to -2.9) for the shorten group (P=0.04) (Fig. 2B)
Summary
Telomeres are tandem repeat nucleotides sequence (TTAGGG)n at the end of linear chromosomes which form a protective cap and maintain the chromosomal stability [1]. Telomere Attrition Rate and Hypertension length shortening in circulating leukocytes is correlated with higher risk of atherosclerosis as well as cardiovascular diseases [5,6,7,8], and leukocytes telomere dynamics contribute to the age-related process of vascular damage and cardiovascular mortality [9,10,11]. The Framingham heart study has demonstrated that association between hypertension and leukocyte telomere length is attributable to insulin resistance [18]. There is lack of data whether change of telomere length in patients with hypertension is related to the heterogeneity of blood pressure response to antihypertensive therapy. In this study, we aimed to investigate longitudinal change of leukocytes telomere length in a prospective population-based study of 1,108 individuals with hypertension who received antihypertensive therapy, and further assess the relationship between BP lowering and telomere attrition rate, which may provide new sight on telomere biology in hypertension and antihypertensive intervention
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