SUPPLEMENTARY DATA
Do treatment induced changes in arterial stiffness affect left ventricular structure? – A meta-analysis
Koen M. VAN DER WAAIJ a,b,*, Maarten H.G. HEUSINKVELD a,*, Tammo DELHAAS a, Abraham A.
KROON b, Koen D. REESINK a
Corresponding Author:
M.H.G. Heusinkveld, MSc Biomedical Engineering
CARIM School for Cardiovascular Diseases/CardioVascular Centre Maastricht University Medical Centre
Telephone: +31 43 3881659
E-mail: [email protected] P.O. box 616, 6200 MD, Maastricht, the Netherlands
a Department of Biomedical Engineering, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands
b Department of Internal Medicine, CARIM School for Cardiovascular Diseases, Maastricht University Medical Centre, Maastricht, the Netherlands
** These authors contributed equally to this work
SUPPLEMENTARY FILES
Figure S1: Top: Scatter plots displaying the relation between changes in left ventricular mass index
(∆LVMI), and changes in carotid-femoral, brachial-ankle, and aortic pulse wave velocity (∆cfPWV,
∆baPWV, ∆aoPWV, respectively). Bottom: Relation between changes in ∆cfPWV, ∆baPWV, ∆aoPWV and changes in systolic blood pressure (∆SBP).
Table S1: Assessment of risk of bias within the included RCT-studies
1.
Adequate sequence generatio n
2.
Alloc ation conc ealm ent used
3.
Blinding of participa nts and personnel
4.
Blinding of outcome assessme nt
5.
Concur rent therapi es are similar?
6.
Follow- up patients adequat e
If no:
selective loss to follow- up excluded
7. Patients analysed in group randomisat ion
8. Patients treated equally in all
treatment groups
9. Free of selective outcome reporting
10.
Undesira ble influence sponsors excluded
Ra tin g
Au et al.
(20)
+ - - ? + + + + + + 5
Beaussier et al. (21)
+ - - + + + + + + + 6
Vizzardi et al. (22)
+ - - - + + + + + + 4
Mancusi et al. (23)
+ - + ? + + + + ? ? 5
Ripley et al.
(24)
+ - - + - - ? + + + + 2
Jekell et al.
(25) + - + ? + + + + + + 7
Takami et
al. (26) + + - + + + + + + + 8
Rekhraj et al. (27)
+ - + + + + + + + ? 8
Tomiyama et al. (28)
+ - - ? + + + + + + 5
Edwards et al. (29)
+ - + + + + + + + + 8
Malfatto et al. (30)
+ - - ? + + + + + + 5
Anan et al.
(31)
+ - ? ? + + + + + + 6
de Luca et al. (32)
+ - + + + - + + + + ? 5
Topouchian + - + + + + + + + + 8
et al. (33)
Note: ‘+’ = in agreement with, ‘-‘ = in disagreement with and ‘?’ = unclear
Table S2: Assessment of risk of bias within the prospective observational cohort studies
Selection Comparability Exposure Ratin g 1.
Representativene ss exposed cohort
2.
Selectio n non- exposed cohort
3.
Ascertainme nt exposure
4. Outcome of interest not present at start study
1.
Comparability cohorts on basis design analysis
1.
Assessmen t of outcome
2. Follow- up long enough for outcomes to occur
3.
Adequac y of follow- up cohorts Kwon et al.
(34)
a c a a a,b a a a 8
Watanabe et al. (35)
a a a a a,b a a a 9
Collin et al.
(36)
a a a a a,b a a b 8
Mizuguchi et al. (37)
a a a a a,b a a a 9
Ruvolo et al.
(38)
a a a a d b a 5
Hashimoto et al. (39)
a a a a a,b a a a 9
Hashimoto et al. (40)
a a a a a,b a a a 9
Ikonomidis et al. (41)
a a a a a,b d a a 8
Tomiyama et al. (42)
b c a a a,b d a b 6
Note: Selection 1) a=truly representative-, b=somewhat representative compared to community 2) a=drawn from same community as exposed cohort, c=no description, 3) a=secure record, 4) a=yes. Comparability 1) a= study controls for most important factor, b=study controls for
additional factor, Outcome 1) a= independent blind assessment, d=no description, 2) a= yes, b= no, 3) a= complete follow-up, b= small number lost-to-follow-up
Table S3: Significant Quantitative changes in blood pressure, and cardiac and vascular properties/markers.
Study design
Treatment BP changes (mmHg) Cardiac changes Vascular changes
Au et al.
2017 (20)
RCT Arm 1: HR-RET, Arm 2: LR-RET
Arm 1: SBP -2 mmHg, DBP: -2 mmHg (both ns) Arm 2: SBP -1 mmHg (ns) DBP: -6 mmHg (p<0.05)
Arm 1: HR: -5 bpm (p<0.05), Arm 2: HR: -3 bpm (p<0.05)
Arm 1: cfPWV HR group: -0.7 m/s (p<0.05),
Arm 2: cfPWV: -0.4 m/s (p<0.05) Beaussier
et al. 2015 (21)
RCT Arm 1: spironolactone, furosemide, amiloride;
Arm 2: ramipril, bisoprolol
Arm 1: SBP: -19.9 mmHg (p<0.001), Arm 2: SBP:
-9.2 mmHg (p<0.001)
Arm 1: LVMI: -17.2 g/m2 (p<0.001),
Arm 2: LVMI +4.5 g/m2 (p<0.001)
Arm 1: cfPWV: -1.0 m/s (p<0.001) Arm 2: cfPWV: -0.6 m/s (p<0.001)
Vizzardi et al. 2015 (22)
RCT spironolactone - - ASI: -2.4 mmHg-1 (p=0.03), DC: +0.9
mmHg-1 (p=0.01), AoS: +2.0 % (p=0.01), *calculated aoPWV -0.8 m/s Mancusi et
al. 2014 (23)
RCT losartan/atenolol SBP -29 mmHg (p<0.05), DBP -9 mmHg (p<0.05)
#calculated LVMI: -9.4 g/m2 (p<0.05)
PP/Svi: -0.33 mmHg/ml · m2.04 (p<0.05)
Ripley et al. 2014 (24)
RCT Arm 1:
valsartan/moxonidine, Arm 2:
bendroflumethiazide/a mlodipine
Arm 1: SBP: -34 mmHg (p<0.001), DBP -15 mmHg (p<0.001);
Arm 2: SBP: -38 mmHg (p<0.001), DBP: -18 mmHg (p<0.001)
Arm 1: LVM: -24 g (p<0.001), LVMI: -12 g/m2 (p<0.001), Arm 2: LVM: -20 g (p<0.001), LVMI: -10 g/m2 (p<0.001)
Arm 1: DC +1.4 mmHg-1 (p<0.001), CC: +3.2 10-3 ml/mmHg (p<0.001), PP: -19 mmHg (p<0.001), *calculated aoPWV -1.2 m/s,
Arm 2: DC: +1.3 mmHg-1 (p<0.01), CC: +2.3 10-3 ml/mmHg (p<0.01), PP:
-20 mmHg (p<0.001), *calculated aoPWV -0.8 m/s
Jekell et al.
2013 (25)
RCT irbesartan/atenolol - - PP: -11 mmHg (p<0.001), SV/PP: -0.3
ml/mmHg (p<0.001) Takami et
al. 2013 (26)
RCT Arm 1:
olmesartan/azelnidipin e; Arm 2
olmesartan/amlodipine
Arm 1: SBP: -17.1 mmHg (p<0.001), DBP: -2.9 mmHg (p<0.001),
Arm 2: SBP: -19.4 mmHg (p<0.001), DBP: -3.7 mmHg (p<0.001)
Arm 1: LVMI: -7.5 g/m2 (p<0.001), E/e': -1.7 (p=0.002), E/A: +0.1 (p=0.03),
Arm 2: LVMI: -2.8 g/m2 (p<0.001), E/e': -0.7 (p=0.002), E/A: +0.1 (p=0.03)
Arm 1: baPWV: -3.2 m/s (p<0.001);
Arm 2: baPWV: -1.0 m/s (p<0.001)
Rekhraj et al. 2012 (27)
RCT allopurinol SBP: -5 mmHg (ns), DBP:
-4.2 mmHg (ns)
HR (p<0.001) improved, LVM:
-5.2±5.8g (p=0.007), LVMI:
-2.2±2.8 g/m2 (p=0.023),
cfPWV: -0.14 m/s (ns)
LVESV: -2.81±7.8 ml (p=0.047) Tomiyama
et al. 2011 (28)
RCT Arm 1: candesartan;
Arm 2: amlodipine Arm 1: SBP: -28 mmHg (p<0.01), DBP: -15 mmHg (p<0.01),
Arm 2: -SBP -29 mmHg (p<0.01), DBP: -14 mmHg (p<0.01)
Arm 1: LVMI: -7 g/m2 (p=0.03), E/A: 0.08 (p<0.03),
Arm 2: LVMI: -6 g/m2 (p=0.03), E/A: 0.01 (p<0.03)
Arm 1: baPVW: -2.0 m/s (p<0.01), Arm 2: baPWV: -1.41 m/s (p<0.01)
Edwards et al. 2009 (29)
RCT spironolactone SBP: -11 mmHg (p<0.05), DBP -6 mmHg (ns)
LVMI: -6.9 g/m2 (p<0.05), LVM -14 g (p<0.01)
cfPWV: -0.8 m/s (p<0.01), DC: 0.8∙10-3 mmHg-1 (p<0.01)
Malfatto et al. 2009 (30)
RCT physical training PAPS: -4 mmHg (p<0.05) LVMI: -3.0 g/m2 (p<0.05), LV elastance: -0.084 mmHg/ml (p<0.01)
-
Anan et al.
2005 (31)
RCT Arm 1: valsartan Arm 2: perindopril Arm 3:
valsartan/perindopril
Arm 1: SBP: -23 mmHg DBP: -12 mmHg Arm 2: SBP: -23 mmHg DBP: -12 mmHg
Arm 3: SBP: -24 mmHg, DBP: -13 mmHg (all p<0.0001)
Arm 1: IVST: -1.4 mm, PWT:
-1.4 mm (all p<0.0001), LVMI:
-27 g/m2(p<0.01), E/A: +0.12 (p<0.05)
Arm 2: IVST: -1.3 mm, PWT:
-1.4 mm m2 (all p<0.0001), LVMI: -24 g/m2 (p<0.01), E/A:
+0.10 (p<0.05)
Arm 3: IVST: -2 mm, PWT:
-2.0 mm, LVMI: -35 g/m2 (all p<0.0001), E/A: +0.15 (p<0.01)
Arm 1: baPWV: -2.4 m/s (p<0.0001) Arm 2: baPWV: -2.1 m/s (p<0.0001) Arm 3: baPWV: -3.7 m/s (p<0.0001)
de Luca et al. 2004 (32)
RCT Arm 1: perindopril, indapamide; Arm 2:
atenolol
Arm 1: SBP: -21.2±14.9 mmHg (p<0.001), DBP:
-12.1±8.9 mmHg (p<0.001); Arm 2: SBP:
-15.3±18.2 mmHg
(p<0.001), DBP: -11.3±9.9 mmHg (p<0.001)
Arm 1: LVM: -13.6 g (p<0.001) LVMI: -6.6±15.5 g/m2
(p<0.001). Arm 2: LVM: -4.3 g (ns), LVMI: -2.1 g/m2 (ns)
Arm 1: PP: -9.1±11.5 mmHg (p<0.001), Arm 2: PP: -4.0±14.6 mmHg (p<0.001)
Topouchia n et al.
1999 (33)
RCT Arm 1: verapamil, Arm 2: trandolapril, Arm 3:
trandolapril/verapamil
Arm 1: SBP: -19 mmHg (p<0.01), DBP: -11 mmHg (p<0.01),
Arm 2: SBP: -19 mmHg (p<0.01),
DBP: -10 mmHg (p<0.01)
Arm 1: septal thickness: -0.4 mm (p<0.01), PWT: -0.5 mm (p<0.01), LVIDd: +3.4 mm (p<0.02), #calculated LVMI:
-6.8 g/m2
Arm 2: septal thickness: -0.5
Arm 1: cfPWV: -2.0 m/s (p<0.01) Arm 2: cfPWV: -2.0 m/s (p<0.01) Arm 3: cfPWV: -2.0 m/s (p<0.01)
Arm 3: SBP: -26 mmHg (p<0.01), DBP: -16 mmHg (p<0.01), MBP: -19 mmHg (p<0.01)
mm (p<0.01), PWT: -0.4 mm (p<0.01), LVIDd: +0.6 mm (p<0.02), #calculated LVMI:
-7.1 g/m2
Arm 3: septal thickness: -0.5 mm (p<0.01), PWT: -0.3 mm (p<0.01), LVIDd: +0.6 mm (p<0.02), #calculated LVMI:
-5.7 g/m2 Kwon et
al. 2015 (34)
cohort study
follow-up after AHT SBP: -32.2 mmHg (p<0.001), DBP: -16.7 mmHg (p<0.001)
LVMI: -11.0 g/m2 (p<0.05), night-time HR (p=0.008), mitral E/A (p=0.003), mean-annulus (p=0.003), mean annulus e'/a' (p=0.020), mitral peak E (p=0.042)
-
Watanabe et al. 2013 (35)
cohort study
follow-up after telmisartan
SBP: -12 mmHg (p<0.001), DBP: -9 mmHg (p<0.001)
LVMI: -13 g/m2 (p=0.006) baPWV: -1.1 m/s (p=0.002)
Collin et al. 2011 (36)
cohort study
agalsidase-beta suppletion, follow-up
MBP: -3 mmHg/yrs (ns) LVMI -7.8±2.3 g/m2/yr (p<0.005), #calculated LVMI -35.1 g/m2
aoPWV: -0.56±0.13 m/s/yr (p<0.0002), cIMT: +18±6 µm/y (p<0.005), CWS:
-1.7±0.6 kPa/yrs (p<0.01), *calculated aoPWV -2.2 m/s
Mizuguchi et al. 2010 (37)
cohort study
follow-up after telmisartan
- LVMI -17 g/m2 (p<0.001),
decreased end-diastolic LV PWT (p<0.0001), peak A velocity (p<0.01), E/A
(p<0.001) and E-DT (p=0.0273) -
Ruvolo et al. 2010 (38)
cohort study
hydrochlorothiazide, valsartan, follow-up
SBP: -25 mmHg (p<0.001), DBP: -13 mmHg (p<0.001)
LVMI: -24 g/m2 (p<0.005), RWT: -0.05 cm (p<0.05), E/A:
+0.2 (p<0.05), LVRT: -17 ms (p<0.05), LA-diam: -3 mm (p<0.05)
PP/SV: -0.18 mmHg/ml (p<0.005),
*calculated aoPWV: -1.9 m/s (using SV/PP and aortic diastolic diameter)
Hashimoto et al. 2008 (39)
cohort study
follow-up after AHT SBP: -31mmHg (p<0.001), DBP: -18mmHg (p<0.001)
LVM: -13 g (p<0.01), LVMI: -8 g/m2 (p<0.01)
PP: -13 mmHg (p<0.001), cfPWV: -0.7 m/s (p<0.01)
Hashimoto et al. 2007
cohort study
follow-up after AHT SBP: -30 mmHg (p<0.001), DBP: -17 mmHg (p<0.001)
LVMI: -6.5 g/m2 (p=0.001) PP: -14 mmHg (p<0.001), pulse amplification: +5.1 (p=0.02)
(40) Ikonomidi s et al.
2007 (41)
cohort
study follow-up after
bariatric surgery SBP: -16 mmHg (p<0.01),
DBP: -6.1 mmHg (ns) LVM: -63 g (p<0.01), IVRT:
-9±6 ms (p<0.01), PWT: -3.0 mm (p=0.04), IVST: 1.8 mm (p<0.01), E/A ratio: +0.13 (ns),
# calculated LVMI: -22.2 g/m2 (p<0.01)
PP: -9.2 mmHg (p<0.01), DC: 2.4∙10-3 mmHg-1 (p<0.01), AoS: -4.92%
(p<0.01), *calculated aoPWV: -2.4 m/s (p<0.01) (using aortic distensibility)
Tomiyama et al. 2000 (42)
cohort study
follow-up after AHT SBP: -2mmHg (p<0.05), DBP: -2 mmHg (p<0.05)
LVMI: -11 g/m2 (p<0.01), A/E:
-0.2 (p<0.05) 3
cIMT: 0.12 mm (p<0.05)
1Calculated as posterior wall thickness/ internal wall thickness at end diastole; 2Aortic root distensibility, initially reported in units of cm2 ∙ dyn-1;
3Ratio between peak late ventricular filling velocity and peak early ventricular filling velocity -: Not measured or not significantly different between groups
ns: not significantly different between groups
*: PWV calculated using either the DC value or the CC value as well as cross-sectional lumen area, respectively
#: LVMI calculated from the LVM/height2.7 value
Note: Significant reductions in blood pressure after antihypertensive treatment, hormones and surgery. Abbreviations: 24-BP = 24 hour blood pressure, ACE = angiotensin converting enzyme inhibitor, aoPWV: aortic pulse wave velocity, AHT = antihypertensive treatment, ARB =
angiotensin receptor blockers, ASI = aortic stiffness index, baPWV: brachial ankle pulse wave velocity, BP = Blood pressure, CBP = central blood pressure, CC = arterial/aortic compliance, CCB = calcium channel blockers, cfPWV: carotid femoral pulse wave velocity, cIMT = carotid intima- media thickness, cSBP = carotid systolic blood pressure, CWS: carotid wall stiffness, DBP = diastolic blood pressure, DC = arterial/aortic distensibility, E-DT = e-wave deceleration time, FMD = flow-mediated dilatation, HR: heart rate, IMT: intima media thickness, IVST:
interventricular septal thickness, LV = left ventricle / left ventricular, LVEF = left ventricular ejection fraction, LVID = left ventricular internal dimension, LVM = left ventricular mass, LVMI = left ventricular mass index, LVRT = left ventricular relative thickness, MBP = mean blood pressure, PAPS: estimated systolic pulmonary pressure, PP = pulse pressure, PWT = posterior wall thickness of LV, RET= resistance exercise training, SBP = systolic blood pressure, SV: stroke volume, SVi: stroke volume index.
