our study involved participants drawn from the whitehall ii epidemiological cohort ( 24 ) for psychophysiological testing between 2006 and 2008 . the criteria for entry into the study included no history or objective signs of clinical or subclinical cvd and no previous diagnosis or treatment for hypertension , inflammatory diseases , allergies , or kidney disease .
cvd was defined as prior mi , stable or unstable angina , revascularization procedure , heart failure , transient ischemic attack , stroke , or electrocardiographic abnormalities ( resting 12-lead electrocardiograms were  taken ) .
this information was confirmed by a telephone interview and  verified from clinical data collected from the previous 7 phases of the whitehall ii study .
volunteers were of white european origin , aged 53 to 76 years ; 56.5% were in full - time employment .
selection was stratified by grade of employment ( current or most recent ) to include higher and lower socioeconomic status participants . from the initially invited participants ( n = 1,169 ) ,
27.6% were not eligible ( mainly because of prescribed medications ) and 25.9% declined to take part .
participants were prohibited from using any antihistamine or anti - inflammatory medication for 7 days before testing and were rescheduled if they reported colds or other infections on the day of testing .
participants gave full informed consent to participate in the study , and ethical approval was obtained from the university college london hospitals committee on the ethics of human research .
we carried out psychophysiological stress testing in either the morning or afternoon in a light temperature - controlled laboratory .
this procedure was based on a protocol previously used in this laboratory ( 25 ) .
participants were instructed to refrain from drinking caffeinated beverages and smoking for at least 2 h before the study and  not to have performed vigorous physical activity or consumed alcohol the previous evening . after a 30-min rest period ,
baseline blood pressure ( using an automated ua-779 digital monitor [ a&d instruments ltd . , oxford , united kingdom ] ) and a saliva sample were taken .
two behavioral tasks , designed to induce mental stress , were then administered in random order .
the tasks were  a computerized version of the stroop task and mirror tracing , both of which have been used extensively in psychophysiological research ( 26 ) . the tasks each lasted for 5  min .
saliva samples were collected immediately before and after the  tasks for the assessment of salivary cortisol .
the samples were collected using salivettes ( sarsted , leicester , united kingdom ) , which were stored at  30c until analysis .
levels of cortisol were assessed using a time - resolved immunoassay with fluorescence detection at the university of dresden ( dresden , germany ) .
the intra - assay and interassay coefficients of variation ( cvs ) were less than 8% .
nonfasting blood samples were collected in edta tubes and centrifuged immediately at 2,500 rpm for 10 min at room temperature .
plasma was removed from the tube and aliquoted into 0.5-ml portions and stored at  80c until analysis .
we measured ctnt concentrations 75 min after the end of the mental stress test using a highly sensitive assay on an automated platform ( elecsys-2010 troponin t hs stat , roche diagnostics , haywards heath , united kingdom ) , with a lower detection limit of 3 ng / l and a reported 99th percentile value in apparently healthy individuals of 13.5 ng / l , at which the cv is 9% , confirmed by in - house studies ( 1719 ) .
we assayed baseline plasma interleukin ( il)-6 using a quantikine high - sensitivity 2-site enzyme - linked immunosorbent assay ( elisa ) from r&d systems ( oxford , united kingdom ) .
the sensitivity of the assay ranged from 0.016 to 0.110 pg / ml , with intra - assay and interassay cvs of 7.3% and 7.7% , respectively .
baseline c - reactive protein ( crp ) level was measured using a high - sensitivity elisa ( r&d systems ) .
cac was assessed with electron - beam computed tomography ( imatron c-150 , general electric , san francisco , california ) as previously described ( 27 ) . in brief ,
40 contiguous 3-mm slices were obtained during a single breath - hold starting at the carina and proceeding to the level of the diaphragm .
scan time was 100 ms / slice , synchronized to 40% of the r - r interval .
agatston and volumetric calcium scores were calculated to quantify the extent of cac by a single experienced investigator blinded to the psychophysiological and clinical data on an aquarius workstation ( terarecon inc .
, san mateo , california ) . because calcified volume was highly correlated with agatston score ( spearman rho 0.99 ) , we present data for agatston score only .
participants reported current smoking levels , weekly alcohol intake ( units per week ) , employment grade ( as a marker of social position ) , and hours of moderate or vigorous physical activity per week .
we measured height and weight in light clothing for calculation of body mass index ( bmi ) .
total and high - density lipoprotein ( hdl ) cholesterol and triglycerides were measured within 72 h in serum stored at 4c using enzymatic colorimetric methods ( 28 ) .
low - density lipoprotein ( ldl ) cholesterol level was derived using the friedewald equation ( 29 ) .
glucose homeostasis was assessed from glycosylated hemoglobin ( hba1c ) concentration , assayed using boronate affinity chromatography , a combination of boronate affinity and liquid chromatography .
we quantified the cortisol response to stress by subtracting the values of salivary cortisol concentration measured immediately after the behavioral tasks from the baseline .
the resulting measure was normally distributed , and it was transformed for the main analyses into a binomial variable using a cut point at the value of 4 nmol / l , which corresponds to the mean value ( 0.54 nmol / l )  + 1 sd ( 3.47 nmol / l ) .
hs - ctnt was highly right skewed and was undetectable for 83.3% of the sample ( below the lower detection limit of 3
ng / l ) ; therefore , it was transformed into a binomial variable ( detectable vs. undetectable ) .
agatston score ( cac ) had a right - skewed distribution and was transformed for some analyses into a binomial variable by cutting at the value of zero ( 0 vs. > 0 ) or 100 ( < 100 vs.  100 ) .
francis heart study , which demonstrated maximum sensitivity and specificity for detecting cardiovascular events at a threshold calcium score  100 ( 30 ) .
we described the study sample according to the exposure  ( salivary cortisol response to stress tasks ) and the outcome ( plasma detectable hs - ctnt ) variables .
triglyceride and crp levels had right - skewed distributions and were described using medians and interquartile ranges .
afterward we used multiple logistic regression to model the association between cortisol stress response and odds of detectable hs - ctnt .
cortisol responses may differ according to baseline cortisol levels and time of testing ; therefore , these parameters were included as covariates .
we also adjusted for age , sex , employment grade , and smoking because they are related to cvd and may confound the association between cortisol reactivity and cvd .
additionally , we took into account clinical variables that are known to be linked to cvd such as systolic blood pressure , total cholesterol / hdl ratio , and hba1c .
finally , we examined whether the association between cortisol reactivity and hs - ctnt was independent of underlying coronary atherosclerosis using several approaches : we adjusted for cac score as a binomial variable using both cut points separately ( 0  and 100 ) , carried out a subanalysis of participants with no detectable coronary calcification , and carried out a subanalysis of participants with positive cac scores and in this case further adjusted for cac score as a log - linear variable .
we carried out sensitivity analyses on cortisol responses by testing several different methods of quantification . to test for dose - response associations
, we analyzed the cortisol response as a continuous variable ; we tested a different cutoff for binomial analysis , defining positive responses as  + 0.5 sd instead of 1 sd ; we calculated cortisol responses as the ratio between the post - stress and baseline values and tested the resulting variable as a linear variable and in binary analyses using both  + 1 sd and  + 0.5 sd as cut points .
additionally , we checked for an association between the baseline levels of salivary cortisol and hs - ctnt using multivariate and time - stratified ( am / pm ) logistic regression models . as for the multiple adjustments , we further included additional variables such as physical activity , bmi , alcohol consumption , and ldl cholesterol , which were not included in the principal analyses .
our study involved participants drawn from the whitehall ii epidemiological cohort ( 24 ) for psychophysiological testing between 2006 and 2008 . the criteria for entry into the study included no history or objective signs of clinical or subclinical cvd and no previous diagnosis or treatment for hypertension , inflammatory diseases , allergies , or kidney disease .
cvd was defined as prior mi , stable or unstable angina , revascularization procedure , heart failure , transient ischemic attack , stroke , or electrocardiographic abnormalities ( resting 12-lead electrocardiograms were  taken ) .
this information was confirmed by a telephone interview and  verified from clinical data collected from the previous 7 phases of the whitehall ii study .
volunteers were of white european origin , aged 53 to 76 years ; 56.5% were in full - time employment .
selection was stratified by grade of employment ( current or most recent ) to include higher and lower socioeconomic status participants . from the initially invited participants ( n = 1,169 ) ,
27.6% were not eligible ( mainly because of prescribed medications ) and 25.9% declined to take part .
participants were prohibited from using any antihistamine or anti - inflammatory medication for 7 days before testing and were rescheduled if they reported colds or other infections on the day of testing .
participants gave full informed consent to participate in the study , and ethical approval was obtained from the university college london hospitals committee on the ethics of human research .
we carried out psychophysiological stress testing in either the morning or afternoon in a light temperature - controlled laboratory .
this procedure was based on a protocol previously used in this laboratory ( 25 ) .
participants were instructed to refrain from drinking caffeinated beverages and smoking for at least 2 h before the study and  not to have performed vigorous physical activity or consumed alcohol the previous evening . after a 30-min rest period ,
baseline blood pressure ( using an automated ua-779 digital monitor [ a&d instruments ltd . , oxford , united kingdom ] ) and a saliva sample were taken .
two behavioral tasks , designed to induce mental stress , were then administered in random order .
the tasks were  a computerized version of the stroop task and mirror tracing , both of which have been used extensively in psychophysiological research ( 26 ) . the tasks each lasted for 5  min .
saliva samples were collected immediately before and after the  tasks for the assessment of salivary cortisol .
the samples were collected using salivettes ( sarsted , leicester , united kingdom ) , which were stored at  30c until analysis .
levels of cortisol were assessed using a time - resolved immunoassay with fluorescence detection at the university of dresden ( dresden , germany ) .
the intra - assay and interassay coefficients of variation ( cvs ) were less than 8% .
nonfasting blood samples were collected in edta tubes and centrifuged immediately at 2,500 rpm for 10 min at room temperature .
plasma was removed from the tube and aliquoted into 0.5-ml portions and stored at  80c until analysis .
we measured ctnt concentrations 75 min after the end of the mental stress test using a highly sensitive assay on an automated platform ( elecsys-2010 troponin t hs stat , roche diagnostics , haywards heath , united kingdom ) , with a lower detection limit of 3 ng / l and a reported 99th percentile value in apparently healthy individuals of 13.5 ng / l , at which the cv is 9% , confirmed by in - house studies ( 1719 ) .
we assayed baseline plasma interleukin ( il)-6 using a quantikine high - sensitivity 2-site enzyme - linked immunosorbent assay ( elisa ) from r&d systems ( oxford , united kingdom ) .
the sensitivity of the assay ranged from 0.016 to 0.110 pg / ml , with intra - assay and interassay cvs of 7.3% and 7.7% , respectively .
baseline c - reactive protein ( crp ) level was measured using a high - sensitivity elisa ( r&d systems ) .
cac was assessed with electron - beam computed tomography ( imatron c-150 , general electric , san francisco , california ) as previously described ( 27 ) . in brief , 40 contiguous 3-mm slices were obtained during a single breath - hold starting at the carina and proceeding to the level of the diaphragm .
scan time was 100 ms / slice , synchronized to 40% of the r - r interval .
agatston and volumetric calcium scores were calculated to quantify the extent of cac by a single experienced investigator blinded to the psychophysiological and clinical data on an aquarius workstation ( terarecon inc .
, san mateo , california ) . because calcified volume was highly correlated with agatston score ( spearman rho 0.99 ) , we present data for agatston score only .
participants reported current smoking levels , weekly alcohol intake ( units per week ) , employment grade ( as a marker of social position ) , and hours of moderate or vigorous physical activity per week .
we measured height and weight in light clothing for calculation of body mass index ( bmi ) .
total and high - density lipoprotein ( hdl ) cholesterol and triglycerides were measured within 72 h in serum stored at 4c using enzymatic colorimetric methods ( 28 ) . low - density lipoprotein ( ldl )
glucose homeostasis was assessed from glycosylated hemoglobin ( hba1c ) concentration , assayed using boronate affinity chromatography , a combination of boronate affinity and liquid chromatography .
we carried out psychophysiological stress testing in either the morning or afternoon in a light temperature - controlled laboratory .
this procedure was based on a protocol previously used in this laboratory ( 25 ) .
participants were instructed to refrain from drinking caffeinated beverages and smoking for at least 2 h before the study and  not to have performed vigorous physical activity or consumed alcohol the previous evening . after a 30-min rest period ,
baseline blood pressure ( using an automated ua-779 digital monitor [ a&d instruments ltd . , oxford , united kingdom ] ) and a saliva sample were taken .
two behavioral tasks , designed to induce mental stress , were then administered in random order .
the tasks were  a computerized version of the stroop task and mirror tracing , both of which have been used extensively in psychophysiological research ( 26 ) . the tasks each lasted for 5  min .
saliva samples were collected immediately before and after the  tasks for the assessment of salivary cortisol .
the samples were collected using salivettes ( sarsted , leicester , united kingdom ) , which were stored at  30c until analysis .
levels of cortisol were assessed using a time - resolved immunoassay with fluorescence detection at the university of dresden ( dresden , germany ) .
the intra - assay and interassay coefficients of variation ( cvs ) were less than 8% .
nonfasting blood samples were collected in edta tubes and centrifuged immediately at 2,500 rpm for 10 min at room temperature .
plasma was removed from the tube and aliquoted into 0.5-ml portions and stored at  80c until analysis .
we measured ctnt concentrations 75 min after the end of the mental stress test using a highly sensitive assay on an automated platform ( elecsys-2010 troponin t hs stat , roche diagnostics , haywards heath , united kingdom ) , with a lower detection limit of 3 ng / l and a reported 99th percentile value in apparently healthy individuals of 13.5 ng / l , at which the cv is 9% , confirmed by in - house studies ( 1719 ) .
we assayed baseline plasma interleukin ( il)-6 using a quantikine high - sensitivity 2-site enzyme - linked immunosorbent assay ( elisa ) from r&d systems ( oxford , united kingdom ) .
the sensitivity of the assay ranged from 0.016 to 0.110 pg / ml , with intra - assay and interassay cvs of 7.3% and 7.7% , respectively .
baseline c - reactive protein ( crp ) level was measured using a high - sensitivity elisa ( r&d systems ) .
cac was assessed with electron - beam computed tomography ( imatron c-150 , general electric , san francisco , california ) as previously described ( 27 ) . in brief , 40 contiguous 3-mm slices were obtained during a single breath - hold starting at the carina and proceeding to the level of the diaphragm .
scan time was 100 ms / slice , synchronized to 40% of the r - r interval .
agatston and volumetric calcium scores were calculated to quantify the extent of cac by a single experienced investigator blinded to the psychophysiological and clinical data on an aquarius workstation ( terarecon inc .
, san mateo , california ) . because calcified volume was highly correlated with agatston score ( spearman rho 0.99 ) , we present data for agatston score only .
participants reported current smoking levels , weekly alcohol intake ( units per week ) , employment grade ( as a marker of social position ) , and hours of moderate or vigorous physical activity per week .
we measured height and weight in light clothing for calculation of body mass index ( bmi ) .
total and high - density lipoprotein ( hdl ) cholesterol and triglycerides were measured within 72 h in serum stored at 4c using enzymatic colorimetric methods ( 28 ) . low - density lipoprotein ( ldl )
glucose homeostasis was assessed from glycosylated hemoglobin ( hba1c ) concentration , assayed using boronate affinity chromatography , a combination of boronate affinity and liquid chromatography .
we quantified the cortisol response to stress by subtracting the values of salivary cortisol concentration measured immediately after the behavioral tasks from the baseline .
the resulting measure was normally distributed , and it was transformed for the main analyses into a binomial variable using a cut point at the value of 4 nmol / l , which corresponds to the mean value ( 0.54 nmol / l )  + 1 sd ( 3.47 nmol / l ) .
hs - ctnt was highly right skewed and was undetectable for 83.3% of the sample ( below the lower detection limit of 3
ng / l ) ; therefore , it was transformed into a binomial variable ( detectable vs. undetectable ) .
agatston score ( cac ) had a right - skewed distribution and was transformed for some analyses into a binomial variable by cutting at the value of zero ( 0 vs. > 0 ) or 100 ( < 100 vs.  100 ) .
francis heart study , which demonstrated maximum sensitivity and specificity for detecting cardiovascular events at a threshold calcium score  100 ( 30 ) .
we described the study sample according to the exposure  ( salivary cortisol response to stress tasks ) and the outcome ( plasma detectable hs - ctnt ) variables .
triglyceride and crp levels had right - skewed distributions and were described using medians and interquartile ranges .
afterward we used multiple logistic regression to model the association between cortisol stress response and odds of detectable hs - ctnt .
cortisol responses may differ according to baseline cortisol levels and time of testing ; therefore , these parameters were included as covariates .
we also adjusted for age , sex , employment grade , and smoking because they are related to cvd and may confound the association between cortisol reactivity and cvd .
additionally , we took into account clinical variables that are known to be linked to cvd such as systolic blood pressure , total cholesterol / hdl ratio , and hba1c .
moreover , we adjusted for crp and il-6 levels to account for vascular inflammation . finally , we examined whether the association between cortisol reactivity and hs - ctnt was independent of underlying coronary atherosclerosis using several approaches : we adjusted for cac score as a binomial variable using both cut points separately ( 0  and 100 ) , carried out a subanalysis of participants with no detectable coronary calcification , and carried out a subanalysis of participants with positive cac scores and in this case further adjusted for cac score as a log - linear variable .
we carried out sensitivity analyses on cortisol responses by testing several different methods of quantification . to test for dose - response associations
, we analyzed the cortisol response as a continuous variable ; we tested a different cutoff for binomial analysis , defining positive responses as  + 0.5 sd instead of 1 sd ; we calculated cortisol responses as the ratio between the post - stress and baseline values and tested the resulting variable as a linear variable and in binary analyses using both  + 1 sd and  + 0.5 sd as cut points .
additionally , we checked for an association between the baseline levels of salivary cortisol and hs - ctnt using multivariate and time - stratified ( am / pm ) logistic regression models . as for the multiple adjustments , we further included additional variables such as physical activity , bmi , alcohol consumption , and ldl cholesterol , which were not included in the principal analyses .
a total of 543 participants participated in the study , but 34 ( 6.3% ) had missing information for hs - ctnt and one had an hs - ctnt value > 35
the final analytic sample comprised 508 participants ( mean age of 62.9  5.7  years and 55.1% men ) .
the sample is described according to cortisol stress response in table  1 and according to hs - ctnt categories in table  2 .
older and male participants were more likely to have detectable hs - ctnt and higher salivary cortisol responses to stress tasks .
hs - ctnt , cortisol response , and cac appeared to be associated with each other : participants with detectable levels of hs - ctnt were more likely to have higher cortisol responses and cac ( table  2 ) , and participants having high cortisol responses were more likely to have cac  100 ( table  1 ) .
participants with cortisol responses  < 4 nmol / l were more likely to be smokers , and those with detectable levels of hs - ctnt had higher il-6 plasma concentrations ( tables  1 and 2 ) .
baseline cortisol was not associated with hs - ctnt either in bivariate or multivariate models .
we found a robust association between cortisol response and detectable hs - ctnt ( odds ratio [ or ] : 3.83 ; 95% confidence interval [ ci ] : 1.86 to 7.90 ; p  < 0.001 ) .
after adjustment for demographic variables and cardiovascular risk factors , the association between cortisol response and detectable hs - ctnt did not differ from that in the unadjusted analysis .
after further adjustments for crp and il-6 , the association remained ( or : 3.98 ; 95% ci : 1.60 to 9.92 ; p  = 0.003 ) . the adjustment for cac score as a binary variable did not change the effect estimates . in sensitivity analyses ,
the results remained unchanged after further adjustment for physical activity , bmi , alcohol consumption , and ldl cholesterol ( data not shown ) .
we also performed sensitivity analyses using different approaches to quantify the cortisol stress response , although the same pattern of results emerged .
for example , after treating the stress response as a linear proportional change in cortisol , the fully adjusted or for hs - ctnt was 1.38
( 95% ci : 1.10 to 1.73 ; p  =  0.005 ) for each unit increase in change .
when we restricted the analysis to participants without detectable coronary calcification , the evidence of association remained despite the 40% drop in sample size ( n  = 222 ; or : 4.77 ; 95% ci : 1.22 to 18.72 ; p  = 0.025 ) . when the analysis was restricted to participants with coronary calcification and adjusted for agatston cac score as a log - linear variable , the association between cortisol stress responses and ctnt concentration remained ( n  = 286 ; or : 7.39 ; 95% ci : 2.22 to 24.64 ; p  = 0.001 ) ( table  3 ) .
our results suggest that in healthy participants with no history of cvd , a heightened cortisol response to mental stress is associated with detectable concentrations of circulating ctnt when measured using a high - sensitivity assay .
these findings add to previous data from our laboratory that demonstrate an association between cortisol reactivity and cac ( 12,13 ) .
however , importantly , although this study confirms the findings from other work that stress responsivity is associated with increased cac ( 12 ) , the association between cortisol stress responses and circulating ctnt was independent of cac , a reliable indicator of subclinical coronary atherosclerosis .
therefore , cortisol may be involved in structural and functional adaptations to the heart as well as in the atherosclerotic process .
the prevalence of detectable hs - ctnt in our british sample was 16.7% , which is similar to levels reported ( 15.7% ) in a nationally representative cvd - free population sample in the united states ( 20 ) . to our knowledge , this is the first study to examine the association between mental stress and ctnt in humans .
our data are consistent with research on stress - induced takotsubo cardiomyopathy , in which emotional stress increases troponin and cortisol levels in the absence of coronary artery disease ( 31,32 )
( 33 ) , who showed that mental stress in laboratory animals increases troponin levels . although stress responses seem to be positively correlated with troponin , evidence for a direct or indirect glucocorticoid modulation of troponin is still scarce .
the troponin gene contains a transcription factor binding site ( 34,35 ) , previously shown to bind the activated glucocorticoid receptor ( 36 ) . despite the presence of this binding site
, the effect of glucocorticoids on troponin levels does not seem to be via direct modulation of gene expression ( 3741 ) .
cortisol has a strong diurnal pattern that can cause difficulties in the interpretation of the data ; we dealt with this issue by considering stress response as the difference between the post - test and pre - test measurements and by adjusting for cortisol baseline level and day and time of testing at the data analysis stage .
we also performed sensitivity analyses using different approaches to quantify the cortisol stress response , although the same pattern of results emerged .
it is possible that the cortisol response to stress contributes to the increased levels of troponin t observed here by several indirect mechanisms .
first , oxidative stress could play a role in cortisol - induced troponin release ( 42,43 ) . supporting this hypothesis ,
the temporal change in serum troponin levels matches the increase in the concentration of myocardial malondialdehyde , a marker of free radical lipid peroxidation ( 44 ) .
second , stress - induced cortisol levels could increase troponin levels by modulating ion channels .
for example , dexamethasone , a synthetic glucocorticoid , significantly increases the l - type ca currents in neonatal rat cardiomyocytes ( 45 ) and accelerates myocyte spontaneous contractions ( 46 )
. finally , cortisol responses to stress could induce troponin levels by potentiation of adrenergic signaling .
corticosteroid - potentiated adrenergic signaling increases mineralocorticoid and glucocorticoid receptor expression and function in cardiomyocytes ( 47 ) .
detectable hs - ctnt is associated with noncardiac conditions such as severe renal disease ( 48,49 ) , and theoretically , our results could be due to confounding if patients with renal disease are more likely to test positive on mental stress tests
. however , it is unlikely that this mechanism underlies our results because the study participants were free from any chronic conditions at the time of testing , as explained in the methods section .
the effect of stress - related cortisol release on cardiomyocytes may be mediated by atherosclerosis and consequent ischemia , although the adjustments for cac , which is  a recognized index of atherosclerosis , did not attenuate the findings .
cac and hs - ctnt do not appear to lie on the same causal pathway because their effect was not diminished by mutual adjustment , despite being correlated with each other .
noncalcified coronary plaques are not detectable using cardiac computed tomography , and that may partly explain why cac did not attenuate the association between cortisol and hs - ctnt . however , there is a direct relationship between the number of calcified plaques present and total plaque burden , and cac correlates highly with the severity of coronary artery disease ; therefore , the absence of calcification implies that there is probably little significant coronary artery disease ( 50 ) . on the other hand , it has been argued that raised troponin t levels may be due to occult or undetected plaque rupture ( 51 ) , and it is known that plaque rupture is a relatively common event that is usually not followed by an acute cardiac event ( 52 ) .
this process may have operated in our patients with minimal cac score levels and detectable hs - ctnt .
a single measure of plasma hs - ctnt concentration can not be regarded as a robust test if it is not stable in time ( i.e. , if it shows remarkable intraindividual short - term variation ) .
however , the results from the aric ( atherosclerosis risk in  communities ) study showed that hs - ctnt intraindividual variability over 6 weeks is almost null , with a correlation coefficient of 0.94 ( 53 ) .
thus , although our study collected hs - ctnt after a brief and moderately stressful behavioral challenge , it is improbable that troponin t was released in response to this task . to the contrary
, we hypothesized that high cortisol responders are individuals who are hyperreactive to mental stress in everyday life .
if these responses are elicited on a regular basis over extended periods of time , they might lead to chronic elevations in hs - ctnt concentrations .
this was a cross - sectional study , and therefore , we can not determine the causal sequence . heightened cortisol stress responsivity may contribute to early signs of cvd , or people at an early stage of cardiac disease may be more prone to disturbed stress responses .
in fact , cardiac troponins are the  most sensitive and specific biochemical markers of myocardial damage ( 54 ) , but their elevation can be due to a variety of reasons such as pericarditis , myocarditis , pulmonary embolism , and others ( 55 ) . however , it is unlikely that the undetected presence of those conditions can explain our findings because no participants reported any symptoms or signs of cardiac disease ; had any previous diagnosis of or treatment for hypertension , inflammatory disease , or allergies ; and did not show any electrocardiographic indications of congenital heart disease on tests carried out over more than 20 years in the whitehall ii study .
moreover , we found a strong association in people with and without coronary calcification , which is consistent with another study showing that hs - ctnt is predictive of cvd in healthy people and of secondary events in patients with cvd ( 56 ) .
it is interesting to note that detectable levels of hs - ctnt were associated with salivary cortisol response to stress test but not with its baseline levels ( pre - test ) , corroborating its relationship with stress - induced neuroendocrine dysregulation .
heightened cortisol responses to mental stress were associated with detectable levels of ctnt using high - sensitivity assays in the plasma of healthy people .
heightened stress - induced cortisol release may increase the risk of chd through several pathways , including atherosclerotic processes , or other indirect effects on the cardiomyocytes .
further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage .
 objectivesthe objective of this study was to examine the association between cortisol response to mental stress and high - sensitivity cardiac troponin t ( hs - ctnt ) in healthy older individuals without history of cardiovascular disease ( cvd).backgroundmental stress is a recognized risk factor for cvd , although the mechanisms remain unclear . 
 cortisol , a key stress hormone , is associated with coronary atherosclerosis and may accentuate structural and functional cardiac disease.methodsthis cross - sectional study involved 508 disease - free men and women aged 53 to 76 years drawn from the whitehall ii epidemiological cohort . 
 we evaluated salivary cortisol response to standardized mental stress tests ( exposure ) and hs - ctnt plasma concentration using a high - sensitivity assay ( outcome ) . 
 we measured coronary calcification using electron - beam dual - source computed tomography and agatston scores.resultsafter adjustment for demographic and clinical variables associated with cvd as well as for inflammatory factors , we  found a robust association between cortisol response and detectable hs - ctnt ( odds ratio [ or ] : 3.98 ; 95% confidence interval [ ci ] : 1.60 to 9.92 ; p  = 0.003 ) . 
 the association remained when we restricted the analysis to participants without coronary calcification ( n  = 222 ; or : 4.77 ; 95% ci : 1.22 to 18.72 ; p  = 0.025 ) or when we further adjusted for coronary calcification in participants with positive agatston scores ( n  = 286 ; or : 7.39 ; 95% ci : 2.22 to 26.24 ; p  = 0.001).conclusionswe found that heightened cortisol response to mental stress was associated with detectable plasma levels of ctnt using high - sensitivity assays in healthy participants , independently of coronary atherosclerosis . 
 further research is needed to understand the role of psychosocial stress in the pathophysiology of cardiac cell damage . 
Methods
Study design
Data collection
Psychophysiological Testing
Cardiac Troponin T
Covariates
Data analysis
Results
Discussion
Conclusions