Flatter Diurnal Cortisol Slope on Workdays is Associated with Pre-clinical Atherosclerosis

Transcription

1 Flatter Diurnal Cortisol Slope on Workdays is Associated with Pre-clinical Atherosclerosis Karissa G. Miller, B.A., Thomas W. Kamarck, Ph.D., Matthew F. Muldoon, M.D., Peter J. Gianaros, Ph.D., & Stephen B. Manuck, Ph.D. University of Pittsburgh

2 Outline Background Cortisol Cortisol & Cardiovascular Disease (CVD) risk Previous Literature Current Study Methods Participants Cortisol IMT Analyses Results Conclusions

3 Background Cortisol Hypothalamic-Pituitary-Adrenal (HPA) system

4 Background Cortisol & Cardiovascular Risk HPA Dysregulation? Psychosocial Factors Cardiovascular Disease (CVD)

5 Previous Literature CORTISOL INDEX STUDY SLOPE AUC CAR AM LEVELS AFTER- NOON LEVELS PM LEVELS 24 HOUR LEVELS PLAQUE Dekker et al., Matthews et al., CORONARY ARTERY CALCIFICATION Hajat et al., INTIMA-MEDIAL THICKNESS Eller et al., Eller et al., 2001 Eller et al., Peppa-Patrikiou et al., 1998 Soriano-Rodriguez et al., 2010 CORONARY ARTERY STENOSIS Alevizaki et al., Koertge et al., 2002 Reynolds et al.,

6 Previous Literature Slope AUC CAR Plaque Plaque Plaque Dekker et al., 2008 Dekker et al., Calcification Calcification Calcification Matthews et al., 2006 Hajat et al., Matthews et al., Hajat et al., 2012 Hajat et al., 2012 IMT IMT IMT Eller et al., 2005 Eller et al., 2001

7 Current Study Examine the association between 3 common measures of HPA activity (indexed on 4 days) and a measure of preclinical atherosclerosis, carotid artery intima-medial thickness (IMT). HPA ACTIVITY 1. Diurnal Slope 2. AUC 3. CAR Carotid Artery Intima Medial Thickness (IMT)

8 Method Participants 488 community volunteers from the Adult Health and Behavior study phase 2 (AHAB-2) project All participants: Worked 25 hours/week Completed 8 years of school Exclusions: History of cardiovascular disease Chronic kidney or liver disease Cancer treatment in previous 12 months Major neurological disorders Psychotic Illness Pregnancy Use of glucocorticoid, antiarrhythmic, psychotropic, or prescription weight loss medications

9 Method Participants N = 488 Mean (SD) or % Demographic Covariates Age (years) 42.8 (7.3) Sex: 52.1% female Race 80.7% white Risk Factor Covariates Systolic BP (11.2) Diastolic BP 72.3 (8.2 Waist (cm) 90.4 (14.1) HDL 55.8 (15.0) LDL (32.0) Triglycerides (68.2) Glucose 98.4 (11.3)

10 Method Cortisol Measurement 4 monitoring days: 3 work, 1 non-work 5 samples per day: Upon awakening +30 minutes +4 hours +9 hours Bedtime Indices: Slope: Regression-derived AUC: Trapezoidal formula CAR: Percentage increase Averaged across days

11 Method IMT Thickness of two innermost layers of the arterial wall (tunica intima and tunica media) Ultrasound of carotid artery. Averaged bilateral measurements of: Near and far walls of distal common carotid artery Far wall of the bulb First cm of internal carotid artery

12 Method Analyses Hierarchical linear regression analyses predicting mean IMT Step 1: Demographic Covariates Age Sex Race Step 2: Standard Risk Factor Composite Systolic, Diastolic Blood Pressure HDL (inverse) Glucose Triglycerides Waist circumference Step 3: HPA index (in separate analyses) Slope AUC CAR

13 Results HPA Index Correlations Pearson Correlations between Average HPA Indices AUC CAR Slope r =.20** r =.31** AUC -- r = -.20** **p.01 Slope, AUC Slope, CAR AUC, CAR

14 Results Average Slope & IMT SLOPE R 2 ΔR² β p Step 1. Demographic Covariates Step 2. Diurnal Slope

15 Results Average Slope & IMT SLOPE R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. Diurnal Slope Flatter decline in cortisol levels associated with more IMT.

16 Results Average AUC & IMT AUC R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. AUC No association between AUC & IMT

17 Results Average CAR & IMT CAR R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. CAR No association between CAR & IMT

18 Results Workday/Non-workday Correlations Mean correlation Workday:Workday Workday:Non-workday Awakening 30 Minute 4 Hour 9 Hour Bedtime Cortisol Sample

19 Results Workday Slope & IMT Workday Slope R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. Workday Slope Flatter decline in workday cortisol levels associated with more IMT.

20 Results Individual workday Slopes & IMT Workday 1 Slope R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. Workday 1 Slope Workday 2 Slope R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. Workday 2 Slope Workday 3 Slope R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. Workday 3 Slope

21 Results Non-workday Slope & IMT Non-workday Slope R 2 ΔR² β p Step 1. Demographic Covariates Step 2. CV Risk Factor Covariate Step 3. Non-workday Slope No association between nonworkday slope & IMT

22 Conclusion Summary Diurnal cortisol slope, but not AUC or CAR associated w/ IMT Flatter decline in cortisol more IMT Results persisted after adjustment for: Demographic covariates Cardiovascular risk factor covariates AUC, CAR. Workday average cortisol slope associated w/ IMT. Non-workday slope not associated w/ IMT. Consistent with: Matthews et al., 2006, Hajat et al., 2010.

23 Conclusion Conclusion/Future Directions Slope a more useful indicator than AUC/CAR for relationship between HPA function and CVD risk. Differential influence of workday versus nonworkday cortisol sampling. Psychosocial correlates Candidate mediators

24 P01 HL (Manuck) Thank you!