Telomeres are shorter in myocardial infarction patients compared to healthy subjects: correlation with environmental risk factors

Cécilia G Maubaret, Klelia D Salpea, Anjly Jain, Jackie A Cooper, Anders Hamsten, Julie Sanders, Hugh Montgomery, Andrew Neil, Devaki Nair, Steve E Humphries, HIFMECH consortium, Simon Broome Research Group, Cécilia G Maubaret, Klelia D Salpea, Anjly Jain, Jackie A Cooper, Anders Hamsten, Julie Sanders, Hugh Montgomery, Andrew Neil, Devaki Nair, Steve E Humphries, HIFMECH consortium, Simon Broome Research Group

Abstract

Shorter telomeres have been reported in premature myocardial infarction (MI) patients. Our work aimed at confirming the association of shorter telomere with MI in two case-control studies and in familial hypercholesterolemia (FH) patients with coronary heart disease (CHD). The HIFMECH study compared 598 white male patients (<60 years) who survived a first MI and 653 age-matched controls from North and South Europe. Additionally, from the UK, 413 coronary artery bypass graft (CABG) patients and two groups of 367 and 94 FH patients, of whom 145 and 17 respectively had premature CHD, were recruited. Leukocyte telomere length (LTL) was measured using a real-time polymerase chain reaction-based method. In HIFMECH, LTL was significantly shorter in subjects from the North (7.99 kb, SD 4.51) compared to the South (8.27 kb, SD 4.14; p = 0.02) and in cases (7.85 kb, SD 4.01) compared to controls (8.04 kb, SD 4.46; p = 0.04). In the CABG study, LTL was significantly shorter (6.89 kb, SD 4.14) compared to the HIFMECH UK controls (7.53, SD 5.29; p = 0.007). In both samples of FH patients, LTL was shorter in those with CHD (overall 8.68 kb, SD 4.65) compared to the non-CHD subjects (9.23 kb, SD 4.83; p = 0.012). Apart from a consistent negative correlation with age, LTL was not associated across studies with any measured CHD risk factors. The present data confirms that subjects with CHD have shorter telomeres than controls and extends this to those with monogenic and polygenic forms of CHD.

Figures

Fig. 1
Fig. 1
Decrease of telomere length with age. Telomere length is plotted as loge T/S ratio. r values were −0.18 (p = 0.0003), −0.07 (p = 0.03) and −0.16 (p < 0.0002), −0.35 (p = 0.0002) for CABG, HIFMECH, FH-SB and FH-RH, respectively
Fig. 2
Fig. 2
Comparison of leukocyte telomere length (kilobytes) between North and South in HIFMECH study. Geometric mean of age, exercise and status adjusted telomere length (in kilobytes) and confidence interval
Fig. 3
Fig. 3
Comparison of telomere length between cases and controls. Geometric mean of telomere length (in kilobytes) and confidence interval. In HIFMECH, telomere lengths are adjusted by age, region and exercise, in CABG adjusted to 65 years old and in FH age and gender adjusted
Fig. 4
Fig. 4
Correlation between telomere length and duration of statin use in FH patients. Telomere length is plotted as loge T/S ratio. r values were −0.16 (p = 0.03, N = 175) and −0.18 (p = 0.05, N = 127) for CHD and no CHD, respectively

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