Transcript Cursus Ziekteleer: DIABETES

Individual differences in cardiovascular
reactivity to physical and mental challenge tasks
Center of Research
on Psychology
in Somatic diseases
Dr. Nina Kupper
Acknowledgment & disclosure
• Dr. Elizabeth Martens – 24 hour Holter recordings in MI patients (St Catharina
hospital Eindhoven and St Elisabeth hospital Tilburg)
• Dr. Robert Smith – data collection for stress experiment in undergraduate
student sample and chronic heart failure sample (TweeSteden hospital Tilburg,
Tilburg University)
• Funding:
– Dutch Heart Foundation (2003B038) awarded to Prof.dr. Johan Denollet
No conflicts of interest to disclose
This talk
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•
•
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Type D personality & risk of poor cardiovascular outcome
Potential biobehavioral mechanisms of effect
Why has stress reactivity additional value?
Stress reactivity in the lab
– Undergraduate students
– Chronic heart failure (HF)
• The effects of daily stress
– 24 hour Holters in post-MI patients
• Discussion: how to interpret these findings
What is Type D personality
– Negative affectivity (NA)
Tendency to experience negative emotions
(Watson & Pennebaker 1989)
– Social inhibition (SI)
Tendency to inhibit emotions and behaviors in social interaction
(Asendorpf, 1993)
≥10
≥10
NA
SI
Type D
personality
<10
<10
Other, non-Type D
Denollet. Psychosom Med 2005; 67:89-97
Assessment of Type D personality
Both subscales have good internal
validity (α=.88 for NA, α=.86 for SI)
A cut-off score of ≥10 on both NA &
SI classifies subjects as having a
Type D personality
Psychosomatic Medicine 67:89–97 (2005)
Prevalence of Type D personality
•
•
•
•
•
Ischemic heart disease: 25-36% (Al-Ruzzeh 2005; Denollet 2005)
Chronic heart failure: 24-45% (Schiffer 2005,2007)
ICD: 23-25% (Pedersen 2004,2007)
Peripheral arterial disease: 34-35% (Aquarius 2005,2007)
General population: 13-24% (Kupper 2007, Pedersen 2004,
Aquarius 2005)
Type D & cardiovascular risk
Fixed effects OR = 3.2 (95%CI=2.7-5.1)
Johan Denollet, et al. Circ Cardiovasc Qual Outcomes. 2010;3:546-557
The genetic underpinnings of Type D
personality
Type D personality and both subcomponents (NA & SI) are stable, heritable traits
(35-52%), with stable genetic influences and varying environmental influences
affecting Type D over time (9 year folllow-up)
Biobehavioral model
STRESS/DISTRESS
HPA axis
GENES
ANS function
(X)
Neurohormonal
pathways
ENVIRONMENTAL
HISTORY
Immune system
Heart rate
HRV
Cortisol
Obesity
Blood pressure
Oxidative stress
Inflammation
Cholesterol
Insulin resistance
Fibrinogen
C
V
D
R
I
S
K
Biobehavioral mechanisms
associated with Type D personality
• Cortisol (Molloy et al. 2008 Whitehead et al. 2007, Habra et al. 2003)
ACS pts: inconsistent findings awakening response, but higher total day output
undergraduates: higher cortisol reactivity with higher levels of NA & SI (univar)
• Oxidative stress (Kupper et al. 2009)
Oxidant/antioxidant ratio higher in Type D HF pts, with lower levels of Hsp70*
• Inflammation (Denollet, Kupper et al. 2009, Denollet 2008, Conraads et al. 2006)
HF pts: higher levels of soluble TNF-α receptors, IL-6, adverse IL-6/IL-10 ratio
• Cardiovascular reactivity (Howard et al. 2011 , Martin et al., 2010, Williams et al.
2009, Habra et al. 2003)
undergraduates: blunted HR response, inconsistent findings for BP response,
higher CO during stress, lower HF (large SD), higher LF during stress (EA only)
* Also regulates TNF alpha expression in cardiac muscle
The added value of reactivity
Amplification Emergence
<
<
<
<
Because there is emergence of stress specific genes, it is worthwhile to add stress
measurements to your experimental protocol when looking for biobehavioral mechanisms
LABSTUDIES
Nina Kupper, Johan Denollet & Wijo Kop. Type D personality is associated with an attenuated
cardiovascular response to speech-induced stress. Submitted
Nina Kupper, Johan Denollet & Wijo Kop. The association between emotional distress and
cardiovascular stress reactivity in heart failure patients. Work in progress
Lab studies (1) Undergraduates
• 88 undergraduate students (19.3% males; avg age 20.5, 39% Type D)
• 5 were excluded because they constituted outliers (HR & HRV)
• Stress protocol
5 min BL
rest
6 min
MA task
computerized
indicate right/wrong
high expected performance
6 min
Speech task
5 min
recovery
1 min prep
5 min speaking
about their positive and negative
qualities within social situations
• HR & RMSSD were derived from ECG, checked and averaged over
periods
– 1000 Hz continuous sampling rate
– 2-electrode configuration
Results
• Repeated measures ANCOVA with task order as a covariate
Table 1. Baseline characteristics stratified by Type D personality
Total sample Type D
(n=33)
Male sex, % (n)
Age, mean (SD)
Having no partner, % (n)
Smoking, % (n)
Alcohol intake, mean # of glasses/week (SD)
Family history of cardiovascular risk factors, % (n)*
Family history of cardiovascular disease, % (n) †
* diabetes type 2, hypercholesterolemia, hypertension
† myocardial infarction, stroke
19 (16)
20.5 (4.0)
42 (35)
11 (9)
4.4 (5.9)
12 (10)
5 (4)
15 (5)
20.1 (2.6)
39 (13)
15 (5)
3.1 (4.8)
12 (4)
3 (1)
Non-Type D
(n=50)
22 (11)
20.8 (4.8)
44 (22)
8 (4)
5.3 (6.5)
12 (6)
6 (3)
p-value
.44
.44
.68
.31
.11
.99
.54
Heart rate reactivity & recovery
90.0
Type D
Non-Type D
87.5
• HR increased from BL to MA
(p<.0005) to Speech (p=.03)
Heart rate (bpm)
85.0
82.5
80.0
77.5
• Attenuated HR reactivity in Type D
participants in response to
speech(p=.002)
75.0
72.5
70.0
67.5
ve
ry
R
ec
o
ch
Sp
ee
et
ic
A
rit
hm
R
es
tin
g
B
L
65.0
Findings independent of family history of CVD
gender and age
• Faster HR recovery in non-Type Ds
compared to Type D participants,
(p=.006), although all reached BL
levels
HRV: RMSSD reactivity & recovery
70
Type D
• tendency for Type D individuals to have an
attenuated RMSSD response to the speech
task (p=.06)
Non-Type D
65
• Type D’s RMSSD recovered more slowly
(p=.012), although recovery levels were no
different from BL
55
50
45
• Sex differences for recovery phase (no
recovery in the males): significant Type D *
gender effect (p=.012)
40
Re
co
ve
ry
ec
h
Sp
e
ic
et
ith
m
Ar
gB
L
35
Re
st
in
RMSSD (ms)
60
• Familiy history significant covariate (lower
RMSSD and less react & recov in those
with increased risk)
Conclusion I
• Type D personality in young adults is associated with a blunted
HR response to a public speaking task (not to MA task).
• Both HR and RMSSD recovery were less steep in Type D
participants, in male Type D’s almost no recovery took place.
• In concordance with previous studies that found a blunted HR
response (Howard et al, 2011, Habra et al., 2003) and the study that
found lower parasympathetic activity during stress in
European Americans (Martin et al., 2010)
Lab studies (2) Heart failure patients
• 100 HF patients: avg. age 65 (±11.6), 74% male, 84% NYHA class II-III
• Type D classification missing for N=4. 18% Type D, No HR BP outliers
• Stress protocol
10 min BL
rest
3 min Prep
for speech
3 min
Speech task
10 min
recovery
• HR, BP were assessed using the OMRON M5-1 BP device, rate
pressure product (RPP) calculated
– Every 2 minutes during rest/recovery and every minute during preparation and speech
– El Assaad MA, et al. (2003). Evaluation of two devices for self-measurement of blood pressure according to the
international protocol: the Omron M5-I and the Omron 705IT. Blood Pressure Monitoring, 8(3), 127-133.
Heart rate reactivity & recovery
75
74
Type D
• HR changed significantly from
BL to stress (p<.008) back to
recovery (p<.005)
non-Type D
73
Heart rate (bpm)
72
71
70
69
68
67
66
65
64
63
resting BL
preparation
speech
recovery
• Attenuated HR reactivity in
Type D participants in response
to stress (prep & speech
together; p=.03
• All returned to BL levels (p=.12)
HR in detail
Type D
More within-period
variability in Type Ds
re 1
co
v
re 2
co
v
re 3
co
v4
ov
re
c
pr
ep
pr 1
ep
pr 2
e
sp p 3
ee
c
sp h 1
ee
c
sp h 2
ee
ch
3
75
74
73
72
71
70
69
68
67
66
65
64
63
re
st
1
re
st
2
re
st
3
re
st
4
Heart rate (bpm)
non-Type D
More worry
or
rumination?
Significant response in
both Type D’s and nonType D’s from rest4 to
prep1, from prep3 to
speech1 and from speech3
to recov1
Larger SEM in Type D’s
Blood pressure reactivity and recovery
155
non-Type D
Type D
150
• Significant response of BP to stress,
significant recovery to BL levels (all
p<.0005)
SBP (mmHg)
145
140
135
130
125
120
115
115
resting BL preparation
speech
recovery
110
105
• No differences in response between
Type D and non-Type D patients
100
DBP (mmHg)
95
• Larger variability in Type D BP
90
85
80
75
70
65
60
resting BL
preparation
speech
recovery
Rate pressure product
rate pressure product (HR*SBP)
11000
non-Type D
Type D
• Significant response to stress (all
p<.0005)
10500
10000
9500
• No differences in responses
between Type D and non-Type D
patients
9000
8500
8000
7500
resting BL preparation
speech
recovery
Conclusion II
• In HF patients the HR response was also attenuated.
However, in HF patients this was due to a higher BL, as
well as a smaller response from that baseline
• No differences in BP or RPP response associated with
Type D personality
• There seems to be more within-period variability in
the HR of Type Ds.
AMBULATORY STUDY
Nina Kupper, Liesje Martens, Johan Denollet. Type D personality and 24-hour heart rate
variability. In preparation.
The added value of 24-hour
recordings
• Chronic, every day stress may have a different impact on cardiovascular
physiology than acute stress in the lab
• 24-hour recordings in real life settings
• Semi-experiment:
compare daytime arousal with nighttime rest
The effects of daily stress: post-MI
study
• 82 post-MI patients: avg. age 56 (±9.8), 82% male,
• Type D classification missing for N=1. 21% Type D
24 hour Holter ECG
Daytime:
9.30h-12.30h
3 hour averages
Nighttime
1.30h-3.30h
3 hour averages
• HP, time domain HRV (SDNN, SDANN, RMSSD, pNN50), frequency
domain HRV (VLF, LF, HF) (1 pt with >8,000 PVCs during 24-hr rec excluded)
• PCV, couplet, bigeminy were counted, only NN intervals were used for analysis
Results Total 24-hour period
35
Type D
non-Type D
*
25
20
15
10
5
0
LF
Type D
1300
1250
1200
1150
1100
1050
1000
950
900
850
800
750
700
HF
• Type D post-MI patients had a smaller
LF/HF ratio (p=.04) with relatively
lower LF and equal HF activity
LF/HF
non-Type D
160
140
120
100
80
60
40
20
0
IBI
SDNN SDANN ASDNN RMSSD pNN50
HRV
IBI (ms)
VLF
LF/HF ratio
power (ms2)
30
2.50
2.25
2.00
1.75
1.50
1.25
1.00
0.75
0.50
0.25
0.00
• No significant differences in time
domain measures
Response to daytime arousal
3-hr averages daytime vs. nighttime
RM ANOVA daytime . nighttime
Covariates: age, betablocker use
Healthy middle-aged persons: expect a small rise in both LF & HF
Daytime
Night
Daytime
Armstrong et al. Diurnal variation in HRV Chronobiol Int. 2011 May;28(4):344-51.
Night
VLF power (ms 2/Hz)
36
non Type D
Type D
34
• Trend interaction time*Type D (p=.08)
32
30
*
28
26
• Significant between subjects effects of age (p=.02)
24
• Significant Type D* BB use between subjects effect (p=.03)
22
20
22
VLF day
VLF night
• LF power increased significantly (p=.04)
20
LF power (ms 2/Hz)
• VLF power remains equal over time as expected (p=.45)
18
• Interaction time*Type D (p=.05)
16
14
• Significant between-subjects of age (p=.02)
12
10
8
HF power (ms 2/Hz)
18
LF day
LF night
16
• Significant increase in HF power during nighttime (p=.02)
• Significant time*age (p=.03) and time*BB use (p=.047) effects
14
12
*
10
8
HF day
HF night
• Significant between subjects effects of age (p=.02) and a trend
effect for Type D personality (p=.09)
• Trend for Type D*BB use between-subjects effect (p=.08)
Conclusions III
• No differences between Type Ds and non-Type Ds in mean 24h HR and HRV measures, except LF/HF ratio (depressed LF)
• Significant difference between Type Ds and non-Type Ds in the
effect of betablockers on VLF HRV
• Significant difference in change from day to night between
Type Ds and non-Type Ds in LF (larger difference, lower
daytime LF)
Taken together
• Type D personality is associated with:
Healthy undergrads
Previous lit
Lab study
Blunted HR
reactivity
Blunted HR
reactivity
Lower HF and Delayed RMSSD
higher LF during
recovery (T)
stress
Mixed BP
findings
Higher CO
during stress
-
HF patients
Post-MI
patients
Blunted HR
reactivity
depressed LF
activity and
LF/HF ratio
Larger VLF & LF
day-night
difference
No differences
in BP response
How to interpret these findings
• Depressed LF power and LF/HF ratio has been
associated with...
– Mortality (Janszky et al. J Intern Med. 2004 Jan;255(1):13-21.; May & Arildsen, Acta
Diabetol. 2011 Mar;48(1):55-9.)
– Increased inflammation [IL-6] (Janszky et al. J Intern Med. 2004
Nov;256(5):421-8.)[CRP] Haarala et al. Eur J Clin Invest. 2011 Feb 17.
Candidate
mediating
mechanism
How to interpret these findings
• Blunted HR reactivity went together with somewhat blunting of
the parasympathetic RMSSD response.
– Suggests that in Type Ds there is not enough sympathetic activation as
well as not enough parasympathetic withdrawal
• Blunted HR response was not accompanied by a difference in
blood pressure response
– Indicates that the observed effect is cardiac, not vascular
– E.g. might point towards desensitisation of β-adrenergic receptors
General discussion & limitations
• Considerable debate on use of dichotomous Type D classification
(Ferguson et al., 2009)
– Alternative (which isn’t exactly the same) is using the interaction term
NA*SI as an indication of Type D
– Reanalysis of all results only revealed small differences
• Response to lab stress seems specific for a social stressor
– Ambiguous/neutral stimuli seem to be more stressful for Type Ds (Grynberg et
al 2011)
• Limitations: sample sizes, no info on subjective emotional response
Nina Kupper
Center of Research on Psychology in Somatic diseases
 [email protected]
 +31 13 466 2956
• Reanalysis of all results only revealed small
differences
– Lab undergraduates: less recovery, but no gender
effect
– HF patients: similar findings
– post-MI patients: Type D results disappeared, BB and
age effects smaller (more variables, less power)