PRACTICE
AHA PANEL: RECOMMENDATIONS FOR USE OF HS-CRP IN CLINICAL PRACTICE
•hs-CRP independent marker of CVD risk
•Patients at intermediate risk (10–20% risk of CHD per 10 years):
–hs-CRP may help direct further evaluation, therapy in primary prevention
•Patients with stable coronary disease, acute coronary syndromes:
- hs-CRP measurement may be useful as independent marker of prognosis for recurrent events
- Inflammatory markers (cytokines, other acute-phase reactants) other than hsCRP should not be measured for the determination of coronary risk. (Class III, Level of Evidence: C)
Pearson TA et al. Circulation 2003;107:499-511.
PRACTICE
AHA Panel: Recommendations for hs- CRP Laboratory Testing
Measurements of hs-CRP:
•Should be performed twice (2 weeks apart)
•Results averaged, expressed as mg/L
•Fasting or nonfasting, in metabolically stable patients
•If level >10 mg/L, test should be repeated, patient examined for sources of infection or inflammation
Relative risk categories for hs-CRP levels:
•Low
•Average
•High
< 1 mg/L 1–3 mg/L > 3 mg/L
Pearson TA et al. Circulation 2003;107:499-511.
PRACTICE
If a patient with ACS has a high CRP or other inflammatory markers, what should be done?
PRACTICE
What Affects CRP?
Multivariate Model of Predictors of the Variance
in Log CRP: PROVE IT–TIMI 22
|
CRP at 4 Months, |
|
Risk Factor |
Median (IQR) |
P |
|
|
|
Age |
1.012 (1.01, 1.02) |
<0.0001 |
Female on HRT vs male |
2.372 (1.97, 2.85) |
<0.0001 |
Female not on HRT vs male |
1.47 (1.31, 1.65) |
<0.0001 |
Current smoker |
1.451 (1.32, 1.59) |
<0.0001 |
BMI >25 kg/m2 |
1.42 (1.27, 1.58) |
<0.0001 |
HDL-C <50 mg/dl |
1.23 (1.11, 1.36) |
0.0001 |
LDL-C 70 mg/dl |
1.198 (1.09, 1.32) |
0.0003 |
Glucose >110 mg/dl |
1.194 (1.08, 1.33) |
0.0009 |
Clinical event before month 4 |
1.354 (1.11, 1.65) |
0.0027 |
TG >150 mg/dl |
1.146 (1.05, 1.25) |
0.0030 |
Atorvastatin 80 mg |
0.728 (0.66, 0.8) |
<0.0001 |
Ray KK et al. J Am Coll Cardiol 2005;45:247A.
PRACTICE
LDL-C, CRP, and Early Clinical Benefit in
A to Z, MIRACL, and PROVE IT–TIMI 22
|
|
|
PROVE IT– |
Results at 4 Months |
A to Z |
MIRACL |
TIMI 22 |
LDL-C difference, mg/dl |
61 |
63 |
33 |
CRP difference, % |
0*/17 |
34 |
38 |
Early clinical benefit |
No |
Yes |
Yes |
*At 1 month, no difference in CRP
de Lemos JA et al. JAMA 2004;292:1307-1316. | Kinley S et al. Circulation 2003;108:1560-1566. | Cannon CP et al. N Engl J Med 2004;350:1495-1504.
PRACTICE
Clinical Relevance of Achieved LDL-C and Achieved CRP Combined after Treatment with Statin Therapy: PROVE IT–TIMI 22
Recurrent MI or Coronary Death, (%)
0,10
0,08
0,06
0,04
0,02
0,00 
0.00.5 1.0 1.5 2.0 2.5
Follow-up (Years)
LDL 70 mg/dl, CRP 2 mg/L
LDL 70 mg/dl, CRP <2 mg/L LDL <70 mg/dl, CRP 2 mg/L
LDL <70 mg/dl, CRP <2 mg/L LDL <70 mg/dl, CRP <1 mg/L
Ridker PM et al. N Engl J Med 2005;352:20-28. .
PRACTICE
Rosuvastatin in the Primary Prevention of Cardiovascular
Disease Among Patients With Low Levels
of Low-Density Lipoprotein Cholesterol and Elevated
High-Sensitivity C-Reactive Protein
Rationale and Design of the JUPITER Trial*
The primary objective of the JUPITER trial is to determine whether long-term treatment with rosuvastatin (20 mg orally per day) will reduce the rate of first major cardiovascular events…among individuals with LDL-C levels<130 mg/dL (3.36 mmol/L) who are at high vascular risk because of an enhanced inflammatory response as indicated by hsCRP levels 2 mg/L.
Circulation. 2003;108:2292-2297
THEORY
C-Reactive Protein and
Risk Stratification of Vulnerable Patients
Women’s Health Study
C-RP LDL-c
Ridker et.al. J Am Coll Cardiol 2006;47:C19 –31
PRACTICE
DOES ASPIRIN REDUCE CRP?
• |
Ikonomidis et al. Circulation |
YES |
|
1999;100:793–798. (N=80; 300 mg |
|
|
ASA) |
|
• |
Feldman et al. J Am Coll Cardiol |
NO |
|
2001;37:2036–2041. (N=24; 81 mg |
|
|
ASA) |
|
• |
Feng et al. J Thromb Thrombolysis |
NO |
|
2000;9:37–41. (N=32; 81 or 325 mg |
|
|
ASA) |
|
• |
Bermudez et al. ACT Trial. 2002. |
NO |
|
(N=140; 0, 81, 165, 325 mg ASA) |
|
PRACTICE
LARGE AND INTERMEDIATE-SIZE TRIALS OF ANTIBIOTICS FOR SECONDARY PREVENTION OF CHD
Trial |
Year |
Patients |
Indication |
Antibiotic |
Duration of |
Result |
|
|
(n) |
or setting |
|
therapy and |
|
|
|
|
|
|
follow-up |
|
ACADEMIC |
2000 |
302 |
CHD |
Azithromycin |
3 mo; 2 y |
N* |
ISAR-3 |
2001 |
1020 |
Post-PCI |
Roxithromycin |
1 mo; 6-12 |
N |
|
|
|
|
|
mo |
|
CLARIFY |
2002 |
148 |
ACS |
Clarithromycin |
3 mo; 18 mo |
Trend |
ANTIBIO |
2003 |
872 |
MI |
Roxithromycin |
6 wk; 12 mo |
N |
AZACS |
2003 |
1450 |
ACS |
Azithromycin |
5 d; 6 mo |
N |
WIZARD |
2003 |
7724 |
CHD |
Azithromycin |
3 mo; 3 y |
N |
ACES |
2005 |
4012 |
CHD |
Azithromycin |
12 mo; 4 y |
N |
PROVE-IT |
2005 |
4162 |
ACS |
Gatifloxacin |
18 mo; 24 |
N |
TIMI |
|
|
|
|
mo |
|
*N=negative
Anderson JL. N Engl J Med 2005; 352: 1706-1709.