vascular calcification: bones, blood vessels, and outcomes ravi thadhani, md, mph associate...
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Vascular Calcification: Bones, Blood Vessels, and Outcomes
Ravi Thadhani, MD, MPH
Associate Professor of Medicine
Harvard Medical School
Massachusetts General Hospital
Disclosures: Grant Support from Abbott
Courtesy of Kevin Martin, MD
Calcified Plaque
Goodman WG et al, NEJM 2000
Schwarz et al, NDT
Plaque Morphology in ESRD
- Increased Media Thickness- Excess Calcification
Keelan et al, Circ 2000
London GM, JASN 2003
Okuno et al, AJKD 2007
DeLoach et al, NDT 2009
Aortic calcification and CVD events in Transplanted Patients
Haydar A et al, Kidney Int 2004
London GM, Kidney Int 2003
Klassen et al, JAMA 2002
Raggi P et al, Hypertension 2007
What has been linked with calcification?
• Ca• P• Ca X P• Fetuin• OPG• LDL• Matrix-Gla Protein• hsCRP• IL-6• TNF-
??
CAC and Minerals…
Frequent dialysis reduces need for P binders, but is this the mechanism of benefit?
Normally, mesenchymal stem cells differentiate to adipocytes, osteoblasts, chondrocytes, and vascular smooth muscle cells (VSMC)
Moe SM, JASN 2008
Kuro-o M et al, Nature 1997
Yumita et al, Tohuku J Exp Med 1996
Tsujikawa et al, Mol Endocrinol 2003
Tsujikawa H et al, Mol Endocrinol 2003
65%
70%
75%
80%
85%
90%
95%
100%
0 50 100 150 200 250 300 350Days
Surv
ival
Pro
babi
lity
(%
)
A/A A/C C/C
A
No. at risk
C/CC/AA/A
82327624
74725021
91530627
67923120
63221719
59420419
55120017
51719215
Log-Rank p=0.02165%
70%
75%
80%
85%
90%
95%
100%
0 50 100 150 200 250 300 350Days
Surv
ival
Pro
babi
lity
(%
)
A/A & A/C C/C
B
Log-Rank p=0.005
No. at risk
C/CA/A & A/C
823300
747271
679251
632236
594223
551217
517207
915333
65%
70%
75%
80%
85%
90%
95%
100%
0 50 100 150 200 250 300 350Days
Surv
ival
Pro
babi
lity
(%
)
A/A & A/C C/C
C
No. at risk
C/CA/A & CC
Log-Rank p=0.215
603231
562211
508194
473182
444170
411164
384154
643250
65%
70%
75%
80%
85%
90%
95%
100%
0 50 100 150 200 250 300 350Days
Surv
ival
Pro
babi
lity
(%
)
A/A & A/C C/C
D
No. at risk
C/CA/A & CC
Log-Rank p=0.007
22069
18560
17157
15954
15053
14053
13353
27283
+D Users - D Users
All Groups CEU, CHB, and JPT
+16%+21%
p=0.0045 p=0.0036
Friedman, Afkarian, et al, In Press
Rodriguez M et al, Kidney Int 2008
Cardus A et al, JBMR 2007
CAC and LVH tightly linked
Who Progresses?
What do the Statin Data tell us?
Fellström et al, NEJM 2009
55 yo F on HD for 8 years, dies of a CVA
IVST=1.4cm; EF 60%, Mod-Sev Concentric Hypertrophy
Circulation 2009
Some Ongoing Trials Examining Calcification in ESRD
• PRIMO I & II – Paricalcitol and LVH, MRI of Aorta Included• Cinacalcet + Low Dose Vitamin D (ADVANCE Trial)• P-Binders and CAC: Sevelamer, Phos-Lo, Fosrenol• Bisphosphonates and Calcification and BMD• Phosphate Control and Calcification
Conclusions
• Calcification and Outcomes linked?• Can Calcification be Modified?• What interventions accelerate/decelerate
calcification?• What Biomarkers do we follow?