Telomere shortening over 6 years is associated with increased subclinical carotid vascular damage and worse cardiovascular prognosis in the general population.

Author: Baragetti A1, Palmen J, Garlaschelli K, Grigore L, Pellegatta F, Tragni E, Catapano AL, Humphries SE, Norata GD, Talmud PJ.
Affiliation: 1Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Milan, Italy; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
Conference/Journal: J Intern Med.
Date published: 2014 Jul 5
Other: Special Notes: doi: 10.1111/joim.12282 , Word Count: 299



INTRODUCTION:
Leukocyte telomere length (LTL) is an important determinant of telomere function and cellular replicative capacity. The aim of the present study was to examine prospectively the associations between telomere shortening (TS) and both the progression of atherosclerosis and the incidence of cardiovascular events (CVEs).
MATERIALS AND METHODS:
LTL was measured by quantitative polymerase chain reaction to determine the ratio of telomere length to single copy gene (T/S) in 768 subjects (462 female and 306 male) enrolled in a large general population survey [the Progressione della Lesione Intimale Carotidea (PLIC study)]. Common carotid artery intima-media thickness was determined at baseline and after 6 years of follow-up, and the associations between TS and the progression of atherosclerosis and incidence of CVEs were evaluated.
RESULTS:
Mean LTL was 1.25 ± 0.92 T/S (median 1.14) at baseline and 0.70 ± 0.37 T/S (median 0.70) after 6 years of follow-up. Median 6-year LTL change was -0.46 T/S [interquartile range (IQR) -0.57 to 1.06], equating to -0.078 T/S [IQR(-0.092 to 0.176] per year. Of note, telomere lengthening occurred in 30.4% of subjects. After adjustment for classical cardiovascular disease risk factors (age, gender, smoking, physical activity, alcohol consumption, systolic blood pressure, glucose levels, lipid profile and therapies), TS was associated with incident subclinical carotid vascular damage [hazard ratio (HR) 5.19, 95% confidence interval (CI) 1.20-22.4, P = 0.028]. Finally, subjects in whom LTL shortened over time showed an increased risk of incident CVE, compared to those in whom LTL lengthened (HR 1.69, CI 1.02-2.78, P = 0.041).
CONCLUSION:
These data indicate that TS is associated with increased risk of subclinical carotid vascular damage and increased incidence of CVEs beyond classical cardiovascular disease risk factors in the general population, whereas LTL lengthening is protective. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
KEYWORDS:
IMT ; Ageing; cardiovascular disease; leukocytes telomere length; telomere shortening

PMID: 25040775