Neural correlates of stress and leucocyte telomere length in patients with coronary artery disease

Abstract

Background: Accelerated biological aging, as indicated by telomere shortening, is associated with CAD pathogenesis. In a cross-sectional study, we investigated neural correlates of acute psychological stress and short telomeres in patients with CAD.

Methods: Individuals with CAD (N = 168) underwent a validated mental stress protocol including public speaking and mental arithmetic. Imaging of the brain with [O-15] water and high-resolution positron emission tomography (HR-PET) was performed during mental stress and control conditions. Blood flow during stressful tasks (average of speech and arithmetic) and control tasks were assessed. Telomere length in peripheral leucocytes was measured by quantitative polymerase chain reaction and expressed as Telomere/Single Copy Gene (T/S) ratio. Voxel-wise regression models were constructed to assess the association between brain areas and activity during rest and mental stress after adjustments for demographic factors and clinical characteristics.

Results: The mean (SD) age of the sample was 62 (8) years, and 69% were men. Increased activation with mental stress in the lingual gyrus, cerebellum and superior and inferior frontal gyri were associated with reduced telomere length; 1.6 higher voxel activation of these areas was associated with 0.1 T/S-units reduction in telomere length (P < 0.005). Additionally, during neutral counting and speaking tasks, brain activity in the precentral, middle and superior frontal and middle temporal gyri was inversely associated with telomere length. Results remained consistent after adjustment for demographic and clinical risk factors.

Conclusion: Increased stress-induced activity in brain areas mediating the stress response was associated with shortened telomere length in CAD patients.

Keywords: Aging; Cardiovascular disease; Stress.

Figure 1.. Sagittal brain slices showing areas with significant (p < .001) negative relationships between leucocyte telomere length and brain activity during control tasks.

Leucocyte telomere length as measured with (T/S) and brain activity as measured with [¹⁵O] H₂O positron emission tomography. Values underneath brains present Talairach x axis values (negative, left; positive, right hemisphere).

Figure 2.. Sagittal brain slices showing areas with significant (p < .001) negative and positive relationships between leucocyte telomere length and brain activity during stress.

Leucocyte telomere length as measured with (T/S) and brain activity as measured with [¹⁵O] H₂O positron emission tomography. Values underneath brains present Talairach x axis values (negative, left; positive, right hemisphere

Figure 3.. Negative correlations between brain activations (net difference in blood flow in mL⁻1·min⁻ 1·100g⁻¹) and leukocyte telomere length (in T/S).

Brain activations were computed from mean activity within significant (p < .001) clusters as identified with voxel-wise regression.

Figure 4.. Correlations between regional brain activation and the relative change in C-Reactive Protein (change in CRP/baseline CRP levels).

dashed lines indicate 95% confidence interval. Abbreviations: CRP= C-reactive protein. * net difference ml⁻¹* min ⁻¹*100mg⁻¹

Figure 5.. A model of acute psychological stress leading to biological aging.

Mental stress-induced activation of brain areas is directly associated with shorter telomere length. Greater sympathetic activation, higher catecholamine and pro-inflammatory cytokines release to stress may help explain the relationship between inferior brain activation and shorter telomere.