Pulse Wave Velocity is Inversely Related to

Vertebral Bone Density in Hemodialysis Patients

Paolo Raggi MD1

Antonio Bellasi, MD1,2

Emiliana Ferramosca, MD3

Geoffrey Block, MD4

Muntner Paul, PhD5

1Division of Cardiology and Department of Medicine and Radiology, Emory University School of Medicine, Atlanta, GA; 2Department of

Nephrology, Ospedale San Paolo and University of Milan, Milan, Italy;

3Department of Nephrology, Ospedale Malpighi and University of Bologna, Bologna, Italy; 4Denver Nephrology, PC, Denver, CO;

5Department of Epidemiology, Tulane University, New Orleans, LA

Hypertension 2007; 49:1278-1284

Muntner et al., JASN, 2002

CV Mortality and Chronic Kidney Disease (CKD):

0

5

10

15

20

25

30

35

40

>90 <89>70 <70

GFR (ml/min)C

V d

eath

s/1000

pers

ons/

yr

Mann et al., Ann Intern Med, 2001

02

46

810

1214

16

Tota

l Mor

talit

y

CV mor

talit

yMI

Heart

failu

re

(%)

CrCl >65ml/min CrCl <65ml/min

GFR 45-59ml/min/1.73m2

GFR 30-44ml/min/1.73m2

GFR 15-29ml/min/1.73m2

GFR <15ml/min/1.73m2

All cause of mortality

CV Events Hospitalization

Adju

sted risk

N=1.120.295

All-Cause and CV Mortality and Glomrular Filtration Rate (GFR):

Go et al. N. Engl J Med, 351:1296-305,2004

Relative Risk of Death by Serum Phosphorus in Haemodialysis

Patients

(n=40,538)

Serum phosphorus (mg/dL)3–4 4–5 5–6 6–7 7–8<3 8–9 >9

2.2

2.0

1.8

1.6

1.4

1.2

1.0

0.0

Rel

ativ

e ri

sk o

f d

eath

Ref.

2.4

RR 25% if P> 6 mg/dl!

Block GA et al. J Am Soc Nephrol 2004

Bone morphogenic protein type 2a

Osteopontin

MGP (matrix mineral-binding protein)

PTH-related peptide

PHOSPHORUS/CALCIUM

Cbfa-1

Osteocalcin

OsteoprotegerinBone Sialoprotein

Osteonectin ALP

Fetuin-A

Pyrophosphate

Vascular Calcification: a Link Between Bone Mineral

Abnormalities and Mortality?

Adapted from Cozzolino et al, J Am Soc Nephrol 2001.

Change in vertebral bone density

-8

-6

-4

-2

0

2

4

6

Sevelamer

Calcium salts

Trabecular Cortical

*

*

*P<0.05

%

cha

nge

(hou

nsfie

ld u

nits

)

5%

2%

-7%

-2%

-75

-25

25

75

125

175

CALCIUM (N=70)

SEVELAMER (N=62)

-46+88

151+56

Raggi et al.J Bone Min Res 2005

Aims of the study:

1) Assess the relationship of bone mineral density

(BMD) and a noninvasive measure of CV risk, such

as PWV, in CKD-5 patients.

2) Compare the reliability of dual energy x-ray

absorptiometry (DEXA) and quantitative computed

tomography (QCT)

Raggi et al. Hypertension 2007; 49:1278-1284

Study Design:

D.O.V.E. (Dialysis Outcome, Vascular Evaluation):

Multicenter, cross-sectional, one-arm, non invasive study

of cardiovascular disease in chronic dialysis patients

110 patients patients on maintenance dialysis (more than 3 months)from 2 centers (New Orleans, LA; Denver, CO)

Raggi et al. Hypertension 2007; 49:1278-1284

Aortic Pulse Wave Velocity (aPWV)

was assessed by applanation tonometry with the Sphygmocor Vx Software (AtCor Medical, Sydney, Au)

High compliance=Low PWV Low compliance=High PWV

Methods: arterial stiffness

Methods: BMD assessment

Bone Mineral Assessment (BMD)

(1) BMD was assessed by Quantitative Computed Tomography (QCT).

This is a highly reliable technique to measure BMD of the thoracic spine

(2) Lumbar spine BMD was also assessed by dual energy x-ray absorptiometry (DEXA)

Raggi et al. Hypertension 2007; 49:1278-

1284

Results: Age Standardized PWV by Tertile of BMD and T-scores

Assessed by QCT

10.610.4

8.7

8

9

10

11

12

<128 128 to 183 > 184

Bone mineral density, mg/cc

10.610.4

8.6

8

9

10

11

12

< -1.74 -1.74 to 0.47 > 0.48

Tertile of T-score

* p-trend=0.027 * p-trend=0.030

Pul

se w

ave

velo

city

, m

/se

c

Pul

se w

ave

velo

city

, m

/se

c

Raggi et al. Hypertension 2007; 49:1278-

1284

Age Standardized Prevalence and Adjusted Odds Ratios of PWV>9 m/sec Associated with Tertile of

BMD

73.0

59.2

37.6

0.0

20.0

40.0

60.0

80.0

P-trend<0.001

Age adjusted prevalence of PWV>9 m/sec by t-score tertiles

<-1.74 -1.74 - 0.47 >0.48

1

<-1.74

-1.74 - 0.470.39 (0.11, 1.38)

>0.48

0.21 (0.04, 1.04)

Ref.

*Adjusted for age, sex, dialysis vintage, current smoking, body mass index, and diabetes mellitus

Odds ratio (95% CI) p-trend=0.04*

Age Standardized Prevalence and Adjusted Odds Ratios of PWV>9 m/sec

Associated with Tertile of BMD

72.3

59.2

32.4

0

20

40

60

80

P-trend<0.001

Age adjusted prevalence of PWV>9 m/sec by BMD tertiles

<127

mg/cc

128 - 183

mg/cc

>184

mg/cc

Odds ratio (95% CI) p-trend=0.04*

1

<127 mg/cc

128 - 183 mg/cc0.38 (0.11, 1.36)

>184

0.22 (0.04, 1.12)

Ref.

*Adjusted for age, sex, dialysis vintage, current smoking, body mass index, and diabetes mellitus

Correlation Between T-scores Measured by QCT and DEXA in Presence and in Absence

of Aortic Calcification

T-score: DEXA and QCT correlation

0.6

0.37

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

No calcification Calcification Present

0.42

0.94

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

1.00

Abdominal Aorta X-ray Thoracic Aorta Computed Tomography

T-score: DEXA and QCT correlation

No calcification Calcification Present

Raggi et al. Hypertension 2007; 49:1278-

1284

Conclusions:

1. It appears to be an association between

BMD status and vascular stiffness

among hemodialysis patients.

2. DEXA is not a reliable measure of spine

BMD and QCT should be used instead