Subclinical Atherosclerosis Not Predicted by Average Leucocyte Telomere Length or Short Telomere Load

Researchers studied associations between telomeres and atherosclerosis burden in femoral and carotid arteries in 3 regression models.

Average leucocyte telomere length (LTL) and short telomere load were not significant independent determinants of subclinical atherosclerosis, according to results from a cross-sectional exploratory analysis of the PESA (Progression of Early Subclinical Atherosclerosis) study.

Researchers found highly prevalent subclinical atherosclerosis in nearly one-half of the 4066 individuals who participated in the original PESA study, all of whom did not have established cardiovascular disease (CVD).

Noting a lack of studies investigating possible associations between telomere length and subclinical atherosclerosis, they set out to determine whether shortened LTL may be a prognostic biomarker in patients at high risk for CVD.

“Attrition of telomeric DNA is assumed to be a biomarker of aging and health status,” they wrote. “Telomeres are capping DNA-nucleoprotein complexes that protect the ends of all eukaryotic chromosomes from degradation, unwanted recombination, or fusion.”

Peripheral blood samples from 1459 individuals were included in the present study. Subclinical atherosclerosis was determined by vascular ultrasound as the presence of plaques in the infrarenal aorta, carotid arteries, or iliofemoral arteries (plaque presence and total plaque burden) or by computed tomography determination of coronary artery calcium scores (CACS).

CACS ≥1 and plaques in all territories were more prevalent in men (P<.001), and men had a much higher total plaque burden among individuals with observed plaques (P<.001). Age in both men and women was inversely associated LTL, as researchers expected (men: Pearson’s r = –0.108; women: Pearson’s r = –0.138; P=.001) and directly associated with abundance of short telomeres (%LTL<3 kb; men: Pearson’s r = 0.071; P=.039; women: Pearson’s r = 0.084; P=.038).

Women had significantly longer LTL vs men (women: 10.19 kb ± 1.69 kb vs men: 9.96 kb ± 1.84 kb; P=.019). An additional inverse association was discovered between LTL and %LTL<3 kb in both men and women (men: Pearson’s r = –0.762; P<.001; women: Pearson’s r = –0.751; P<.001).

Researchers studied associations between telomeres and atherosclerosis burden in femoral and carotid arteries in 3 regression models: unadjusted, adjusted for age (and sex in nonstratified models) and adjusted for 8 additional CVD risk factors. LTL reached statistical significance as a determinant of femoral plaque and total plaque burden in men, in the unadjusted model.

However, after adjustment for age and sex or additional CVD risk factors, this association did not persist. None of the regression models showed significant associations for men, women, or the total sample for %LTL<3 kb.

“Our analysis shows that neither high %LTL<3 kb nor short mean TL [telomere length] in circulating leukocytes is an independent determinant of subclinical atherosclerosis after adjusting for age or other well-known CV risk factors,” researchers wrote.

“Future longitudinal studies are warranted to determine whether variation in telomere length over time is a predictor of subclinical atherosclerosis progression or the occurrence of CV ischemic events.”


Fernandez-Alvira JM, Fuster V, Dorado B, et al. Short telomere load, telomere length, and subclinical atherosclerosis. The PESA study. J Am Coll Cardiol. 2016;67(21):2467-2476. doi: 10.1016/j.jacc.2016/03.530.