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Aging and disease
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Longitudinal Association of Telomere Attrition with the Effects of Antihypertensive Treatment and Blood Pressure Lowering
Shuyuan Zhang1, Rongxia Li1, Yunyun Yang1, Yu Chen1, Shujun Yang1, Jian Li1, Cunjin Wu2, Tao Kong1, Tianlong Liu1, Jun Cai3, Li Fu4, Yanan Zhao1, Rutai Hui1, Weili Zhang1
1State Key Laboratory of Cardiovascular Disease, FuWai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
2 The Second Hospital of Tianjin Medical University, Tianjin, China
3 Hypertension Centre, FuWai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China
4Benxi Railway Hospital, Liaoning, China
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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.

Keywords leukocytes telomere length      telomere attrition      blood pressure lowering      antihypertensive therapy     
Just Accepted Date: 21 August 2019  
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Shuyuan Zhang
Rongxia Li
Yunyun Yang
Yu Chen
Shujun Yang
Jian Li
Cunjin Wu
Tao Kong
Tianlong Liu
Jun Cai
Li Fu
Yanan Zhao
Rutai Hui
Weili Zhang
Cite this article:   
Shuyuan Zhang,Rongxia Li,Yunyun Yang, et al. Longitudinal Association of Telomere Attrition with the Effects of Antihypertensive Treatment and Blood Pressure Lowering[J]. Aging and disease, 10.14336/AD.2019.0721
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http://www.aginganddisease.org/EN/10.14336/AD.2019.0721     OR     http://www.aginganddisease.org/EN/Y/V/I/0
Figure 1.  Inverse correlation between annual telomere attrition rate and baseline telomere length of leukocytes. The leukocyte telomere length of all participants was plotted as Lg-transformed T/S ratio. Annual telomere attrition rate was calculated by the equation: (follow-up telomere length- baseline telomere length)/follow-up years. The correlation coefficient β was -0.52 and R2 was 0.27 (P<0.001).
Annual telomere attrition rate
CharacteristicsTotal (n=1,108)Shorten group (n=386)Lengthen group (n=722)P value
Age, years61.7 ± 9.762.3 ± 9.661.4 ± 9.80.13
Men, No. (%)430 (38.8%)155 (40.2%)275 (38.1%)0.52
BMI, kg/m226.2 ± 3.126.3 ± 3.226.2 ± 3.10.85
Waist-to-hip ratio0.90 ± 0.050.90 ± 0.050.90 ± 0.050.09
Systolic BP, mm Hg160 ± 21159 ± 21160 ± 210.27
Diastolic BP, mm Hg89 ± 1289 ± 1189 ± 120.92
Fasting serum glucose, mmol/L6.2 ± 1.76.1 ± 1.56.3 ± 1.80.10
Lipids, mmol/L
Total cholesterol5.7 ± 1.15.6 ± 1.15.7 ± 1.10.41
Triglycerides1.6 (1.1-2.3)1.6 (1.1-2.2)1.6 (1.1-2.4)0.23
HDL-C1.3 ± 0.31.3 ± 0.31.3 ± 0.30.40
LDL-C3.6 ± 0.93.6 ± 0.93.6 ± 0.90.48
Smoking status, %
Never73.873.174.10.41
Former7.48.86.6
Current18.818.119.1
Alcohol intake, %
Never77.077.776.60.58
Former5.15.74.7
Current18.016.618.7
Medical history, %
Diabetes mellitus23.821.824.90.27
Stroke21.123.120.10.25
Coronary heart disease29.730.629.20.68
Antihypertensive drugs, No. (%)
Calcium channel blocker744 (67.1)251 (65.0)493 (68.3)0.28
Angiotensin receptor blocker590 (53.2)192 (49.7)398 (55.1)0.09
ACE inhibitor87 (7.9)35 (9.1)52 (7.2)0.29
Beta-blocker24 (2.2)11 (2.8)13 (1.8)0.28
Diuretics300 (27.1)104 (26.9)196 (27.1)0.99
Leukocytes telomere length, T/S ratio
At baseline1.4 (1.0-1.8)1.8 (1.4-2.3)1.2 (0.9-1.6)<0.001
At follow-up1.9 (1.3-2.5)1.1 (0.8-1.5)2.2 (1.7-3.0)<0.001
Telomere length, base pairs (Kb)*
At baseline6.6 (5.7-7.7)7.5 (6.5-8.9)6.3 (5.5-7.2)<0.001
At follow-up7.8 (6.3-9.4)6.0 (5.2-6.9)8.6 (7.4-10.4)<0.001
Table 1  Baseline characteristics of patients between the shorten and lengthen groups categorized by annual telomere attrition rate during 2014-2016.
Annual telomereMode I*Model II
Change in BPattrition rateβSEP valueβSEP value
Total (n=1,108)
?SBPShorten (n=386)Ref.Ref.
Lengthen (n=722)-3.201.350.02-3.281.370.02
?DBPShorten (n=386)Ref.Ref.
Lengthen (n=722)-0.580.730.43-0.780.740.29
?PPShorten (n=386)Ref.Ref.
Lengthen (n=722)-2.741.100.01-2.531.110.02
Men (n=430)
?SBPShorten (n=155)Ref.Ref.
Lengthen (n=275)-2.192.140.31-2.682.160.15
?DBPShorten (n=155)Ref.Ref.
Lengthen (n=275)-0.781.200.52-1.051.190.38
?PPShorten (n=155)Ref.Ref.
Lengthen (n=275)-1.481.730.39-1.341.720.44
Women (n=678)
?SBPShorten (n=231)Ref.Ref.
Lengthen (n=447)-3.911.730.02-3.561.760.04
?DBPShorten (n=231)Ref.Ref.
Lengthen (n=447)-0.710.920.45-0.810.940.39
?PPShorten (n=231)Ref.Ref.
Lengthen (n=447)-3.421.420.02-3.251.440.03
≤60 years (n=506)
?SBPShorten (n=169)Ref.Ref.
Lengthen (n=337)-6.411.900.001-6.821.91<0.001
?DBPShorten (n=169)Ref.Ref.
Lengthen (n=337)-2.371.100.03-2.491.110.03
?PPShorten (n=169)Ref.Ref.
Lengthen (n=337)-3.971.460.007-4.231.470.004
>60 years (n=602)
?SBPShorten (n=217)Ref.Ref.
Lengthen (n=385)-1.532.080.46-1.422.130.51
?DBPShorten (n=217)Ref.Ref.
Lengthen (n=385)0.760.970.430.411.00.68
?PPShorten (n=217)Ref.Ref.
Lengthen (n=385)-1.461.580.35-1.741.770.33
Table 2  Association of annual telomere attrition rate with BP change during 2014-2016.
Fig 2.  Differences of blood pressure lowering between the lengthen and the shorten groups during 2014-2016. Abbreviations: SBP, systolic blood pressure; PP, pulse pressure. *P<0.05, **P<0.01. P values and adjusted mean were calculated by generalized linear model adjustment for covariates including age, gender (except in gender-stratified analysis), smoking status, alcohol intake, medical history, the stage of baseline blood pressures, baseline telomere length, and changes in BMI, waist-to-hip, fasting glucose, TC, triglycerides, HDL-C, and LDL-C from 2014 to 2016. Error bars indicate 95%CI.
Change in bloodAnnual telomereModel I*Model II
pressureattrition rateβSEP valueβSEP value
CCB therapy (n=744)
?SBPShorten (n=251)Ref.Ref.
Lengthen (n=493)-4.721.950.02-4.731.980.02
?DBPShorten (n=251)Ref.Ref.
Lengthen (n=493)-1.560.980.11-1.620.990.10
?PPShorten (n=251)Ref.Ref.
Lengthen (n=493)-3.591.510.02-3.531.530.02
ARB therapy (n=590)
?SBPShorten (n=192)Ref.Ref.
Lengthen (n=398)-5.082.130.02-4.752.160.03
?DBPShorten (n=192)Ref.Ref.
Lengthen (n=398)-1.191.080.27-1.311.090.23
?PPShorten (n=192)Ref.Ref.
Lengthen (n=398)-4.201.680.01-3.561.700.04
Diuretic therapy (n=300)
?SBPShorten (n=104)Ref.Ref.
Lengthen (n=196)-4.192.990.16-2.863.060.35
?DBPShorten (n=104)Ref.Ref.
Lengthen (n=196)-1.391.530.36-1.371.530.37
?PPShorten (n=104)Ref.Ref.
Lengthen (n=196)-2.102.610.42-0.842.650.75
Table 3  Association of telomere attrition with effects of antihypertensive treatment.
Fig 3.  Effects of antihypertensive drugs on blood pressure lowering in the lengthen and shorten groups during 2014-2016. Abbreviations: SBP, systolic blood pressure; PP, pulse pressure; CCB, calcium channel blocker; ARB, angiotensin receptor blocker. *P<0.05, **P<0.01. P value and adjusted mean were calculated by generalized linear model adjustment for covariates mentioned in the Figure 2. Error bars indicate 95%CI.
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