Leukocyte telomere length is associated with measures of subclinical atherosclerosis

被引:48
作者
Panayiotou, A. G. [1 ,2 ,5 ]
Nicolaides, A. N. [2 ,3 ]
Griffin, M. [4 ]
Tyllis, T. [5 ]
Georgiou, N. [5 ]
Bond, D. [4 ]
Martin, R. M. [6 ]
Hoppensteadt, D. [7 ,8 ]
Fareed, J. [7 ,8 ]
Humphries, S. E. [1 ]
机构
[1] UCL, Dept Med, Div Cardiovasc Genet, London, England
[2] Univ Cyprus, Dept Biol Sci, Nicosia, Cyprus
[3] Univ London Imperial Coll Sci Technol & Med, Dept Vasc Surg, London, England
[4] Vasc Screening & Diagnost Ctr, London, England
[5] VSDC, CY-2368 Nicosia, Cyprus
[6] Univ Bristol, Dept Social Med, Bristol, Avon, England
[7] Loyola Univ, Dept Pathol, Chicago, IL 60611 USA
[8] Loyola Univ, Dept Pharmacol, Chicago, IL 60611 USA
关键词
Aging; Atherosclerosis; Telomeres; IMT; Plaque area; CORONARY-ARTERY-DISEASE; INTIMA-MEDIA THICKNESS; CAROTID PLAQUE AREA; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; HEART-DISEASE; RISK; MEN;
D O I
10.1016/j.atherosclerosis.2010.01.037
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims: Our aim was to test the association of mean leukocyte telomere length (LTL) with ultrasonic measures of subclinical atherosclerosis such as intima-media thickness in the common carotid (IMTcc) and sum of plaque areas (SPA) and with serological markers. Methods and results: Carotid and femoral bifurcations were scanned in 762 general population volunteers (46% men) over 40. Four features were considered: (a) IMTcc, (b) sum plaque areas of carotid plaques (SPAcar), (c) sum plaque area of common femoral plaques (SPAfem) and (d) sum plaque area (SPA - sum of the plaque areas of the largest plaques present in each of both carotid and femoral bifurcations). Mean LTL was determined with a quantitative real-time PCR-based method. IMTcc was strongly associated with mean LTL both before and after correction for traditional risk factors (B = -0.002; 95% CI = -0.004 to -0.00; p = 0.014). In sex-specific analysis, the association was stronger in men (p for sex interaction < 0.001). SPAfem was associated with LTL in women before and after correction (B = -0.195; 95% CI = -0.38 to -0.01; p = 0.037) (p for sex interaction < 0.001). LTL was also associated with age and sex-adjusted levels of hsCRP (p = 0.012), sCD40L (p = 0.042), homocysteine (p = 0.006), creatinine (p = 0.02), ApoA1 (p = 0.01), Lp(a) (p = 0.04) and HOMA-IR (p = 0.008). Conclusions: Our results support the telomere hypothesis and highlight potential differences in the biological mechanisms leading to intima-media thickening and/or plaque formation between vascular beds. They may provide insights into a novel treatment of antisenescence to prevent atherosclerosis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:176 / 181
页数:6
相关论文
共 30 条
[1]   CD40L stabilizes arterial thrombi by a β3 integrin-dependent mechanism [J].
André, P ;
Prasad, KSS ;
Denis, CV ;
He, M ;
Papalia, JM ;
Hynes, RO ;
Phillips, DR ;
Wagner, DD .
NATURE MEDICINE, 2002, 8 (03) :247-252
[2]   Menopause modifies the association of leukocyte telomere length with insulin resistance and inflammation [J].
Aviv, A ;
Valdes, A ;
Gardner, JP ;
Swaminathan, R ;
Kimura, M ;
Spector, TD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2006, 91 (02) :635-640
[3]   Short telomeres are associated with increased carotid atherosclerosis in hypertensive subjects [J].
Benetos, A ;
Gardner, JP ;
Zureik, M ;
Labat, C ;
Lu, XB ;
Adamopoulos, C ;
Temmar, M ;
Bean, KE ;
Thomas, F ;
Aviv, A .
HYPERTENSION, 2004, 43 (02) :182-185
[4]   Soluble CD40 ligand levels indicate lipid accumulation in carotid atheroma -: An in vivo study with high-resolution MRI [J].
Blake, GJ ;
Ostfeld, RJ ;
Yucel, EK ;
Varo, N ;
Schönbeck, U ;
Blake, MA ;
Gerhard, M ;
Ridker, PM ;
Libby, P ;
Lee, RT .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (01) :E11-E14
[5]   A negative carotid plaque area test is superior to other noninvasive atherosclerosis studies for reducing the likelihood of having underlying significant coronary artery disease [J].
Brook, RD ;
Bard, RL ;
Patel, S ;
Rubenfire, M ;
Clarke, NS ;
Kazerooni, EA ;
Wakefield, TW ;
Henke, PK ;
Eagle, KA .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (03) :656-662
[6]   Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study [J].
Brouilette, Scott W. ;
Moore, Jasbir S. ;
D McMahon, Alex ;
Thompson, John R. ;
Ford, Ian ;
Shepherd, James ;
Packard, Chris J. ;
Samani, Nilesh J. .
LANCET, 2007, 369 (9556) :107-114
[7]   Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study [J].
Demissie, S. ;
Levy, D. ;
Benjamin, E. J. ;
Cupples, L. A. ;
Gardner, J. P. ;
Herbert, A. ;
Kimura, M. ;
Larson, M. G. ;
Meigs, J. B. ;
Keaney, J. F. ;
Aviv, A. .
AGING CELL, 2006, 5 (04) :325-330
[8]   Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women - The British Regional Heart Study [J].
Ebrahim, S ;
Papacosta, O ;
Whincup, P ;
Wannamethee, G ;
Walker, M ;
Nicolaides, AN ;
Dhanjil, S ;
Griffin, M ;
Belcaro, G ;
Rumley, A ;
Lowe, GDO .
STROKE, 1999, 30 (04) :841-850
[9]  
Fitzpatrick AL, 2007, AM J EPIDEMIOL, V165, P14, DOI [10.1093/aje/kw346, 10.1093/aje/kwj346]
[10]   Carotid and femoral arterial wall changes and the prevalence of clinical cardiovascular disease [J].
Griffin, Maura ;
Nicolaides, Andrew ;
Tyllis, Theodosis ;
Georgiou, Niki ;
Martin, Richard M. ;
Bond, Dawn ;
Panayiotou, Andrie ;
Tziakouri, Chrysa ;
Dore, Caroline J. ;
Fessas, Charris .
VASCULAR MEDICINE, 2009, 14 (03) :227-232