Christie M Ballantyne MD

1
High-Sensitivity CRP - How Will Recent Statin
Trials Impact CV Risk Assessment?
Christie M Ballantyne MD Professor of
Atherosclerosis and Lipoprotein Research,
Director, Center for Cardiovascular Disease
Prevention, Baylor College of Medicine and
Methodist DeBakey Heart Center, Houston, TX
Paul M Ridker MD Eugene Braunwald Professor of
Medicine, Harvard Medical School Director,
Center for Cardiovascular Disease Prevention,
Brigham Women's Hospital, Boston, MA
M John Chapman PhD DSc Director, Dyslipidemia and
Atherosclerosis Research Unit National Institute
of Health and Medical Research Hôpital de la
Pitié, Université Pierre et Marie Curie, Paris,
France
2
C-Reactive Protein
High-sensitivity (hs) CRP Measured in mg/L CRP
Measured in mg/dL
3
JUPITER Justification for the Use of Statins in
Prevention An Intervention Trial Evaluating
Rosuvastatin

Ridker PM, et al. N Engl J Med.
20083592195-2207.
4
JUPITER MI, Stroke, CV Death
HR 0.53, 95CI 0.40-0.69 P lt 0.00001
0.05
Placebo (N 157)
0.04
- 47
0.03
Cumulative incidence
0.02
Rosuvastatin (n 83)
0.01
0.00
0
1
2
3
4
Follow-up (years)
Reproduced with permission from Ridker PM, et
al. N Engl J Med. 20083592195-2207.
5
Inflammation, Statin Therapy, and hs-CRP Initial
Observations
P Trend 0.005
-21.6 (P 0.007)
3
0.25
0.24
Placebo
0.23
2
0.22
Median hs-CRP (mg/dL)
Relative risk
0.21
1
0.20
Pravastatin
0.19
0.18
0
Pravastatin
Placebo
Pravastatin
Placebo
Baseline
5 Years
Inflammation absent
Inflammation present
Reproduced with permission from Ridker PM, et
al. Circulation. 199898839844.
Adapted from Ridker PM, et al. Circulation.
1999100230-235.
6
AFCAPS/TexCAPS Air Force/Texas Coronary
Atherosclerosis Prevention Study
Ridker PM, et al. N Engl J Med.
20013441959-1965.
7
Clinical Importance of Achieving LDL-C lt70 mg/dL
and hs-CRP lt2 mg/L Following Initiation of Statin
Therapy
LDLgt70, hs-CRPgt2
LDLlt70, hs-CRPgt2
LDLgt70, hs-CRPlt2
LDLlt70, hs-CRPlt2
A to Z2
PROVE ITTIMI 221
Recurrent Ml or death
0
180
360
540
720
900
Follow-up (days)
Follow-up (days)

• Reproduced with permission
• Ridker PM, et al. N Engl J Med. 200535220-28
• Morrow DA, et al. Circulation. 2006114281-288.

.
8
SEARCH Study of the Effectiveness of Additional
Reductions in Cholesterol and Homocysteine
Simvastatin 80 mg Simvastatin
20 mg
folic acid 2 mg
folic acid 2 mg Vit B12 1 mg
Vit B12 1 mg
Simvastatin 80 mg Simvastatin
20 mg
placebo
placebo
N 12,064

http//www.ctsu.ox.ac.uk/projects/search
9
JUPITER Adverse Events
Ridker PM et al. N Engl J Med. 2008
3592195-2207.
10
SEARCH Myopathy Rates
http//www.ctsu.ox.ac.uk/projects/search
11
JUPITER Subgroup Analysis
N
P for interaction
Family HX of CHD
2045
0.07
No family HX of CHD
15,684
4073
0.70
BMI lt 25 kg/m2
7009
BMI 25-29.9 kg/m2
6675
BMI
30 kg/m2
Metabolic syndrome
7375
0.14
No metabolic syndrome
10,296
Framingham risk
10
8882
0.99
Framingham risk gt 10
8895
hs-CRP gt 2 mg/L only
6375
hs-CRP gt 2 mg/L only
6375
All participants
17,802
0.25
0.5
1.0
2.0
4.0
Rosuvastatin superior
Rosuvastatin inferior
Reproduced with permission Ridker PM, et al. N
Engl J Med. 20083592195-2207.
12
Summary

• Implications for primary prevention
• hs-CRP and family history added to Reynolds Risk
  Score for both men and women
• First line prevention remains diet, exercise,
  smoking cessation
• Whether or not hs-CRP/inflammation is causal,
  testing remains a valuable clinical tool for
  identifying high-risk individuals