Critical Appraisal of C-Reactive Protein Throughout the Spectrum of Cardiovascular Disease

Figures & data

Figure 1 CRP in the pathogenesis of atherosclerosis and atherothrombosis.

Abbreviations: AT-1, angiotensin-1; CRP, C-reactive protein; EC, endothelial cells; ET-1, endothelin-1; ICAM-1, intercellular adhesion molecule-1; IL, interleukin; LDL, low-density lipoprotein; NO: nitric oxide; PAI-1, plasminogen activator inhibitor-1; TF, tissue factor; VCAM-1, vascular cell adhesion molecule-1; WBC: white blood cells.

Table 1 Prognostic value of CRP in primary prevention

Study	n	Endpoint	Cutoff	Risk estimates
Ridker, Rifai, et al 2000	28	Death/MI/stroke/revasc	>8.5 mg/L vs <0.6 mg/L	RR=1.5
	263
Harris et al 1999	1293	Death	≥2.78 mg/L	RR=1.6
Ridker et al 1997	543	MI	≥2.11 mg/L vs ≤0.55 mg/L	RR=2.9
		Ischemic stroke	≥2.11 mg/L vs ≤0.55 mg/L	RR=1.9
Tracy et al 1997	5201	MI	>2.79 mg/L vs <0.97 mg/L	RR=2.67
Ridker, Hennekens, et al 1998	122	Death/MI/stroke/revasc	>7.3 mg/L vs <1.5 mg/L	RR=4.8
		MI/stroke	>7.3 mg/L vs <1.5 mg/L	RR=7.3
Ridker, Glynn, et al 1998	144	PAD	2.1 mg/L vs 0.55 mg/L	RR=2.1
Koeing et al 1999	936	CV Death/MI	6.6 mg/L vs 0.4 mg/L	RR=2.4
Danesh et al 2000	1531	CHD	>2.4 mg/L vs <0.9 mg/L	RR=2.13
Mendall et al 2000	1395	CHD	<0.83 mg/L vs >3.87 mg/L	p=ns
		CV Death		p=ns
		All cause mortality		p=0.0033
Danesh et al 2004	6428	CHD	>2.0 mg/L vs <0.78 mg/L	RR=1.45

Abbreviations: CHD, coronary artery disease; CRP, C-reactive protein; CV Death, fatal acute myocardial infarction or sudden death; MI, myocardial infarction; Revasc, revascularization; RR, relative risk; PAD, peripheral arterial disease.

Table 2 Prognostic value of CRP in acute coronary syndromes

Study	n	Endpoint	Cutoff	Risk estimates
Short term
Liuzzo et al 1994	31	Death/MI/urg. revasc	3.0 mg/L	RR=2.6
Morrow et al 1998	437	Death	15.5 mg/L	RR=16.1
Rebuzzi et al 1998	102	MI	3 mg/L	RR=6.0
Verheggen et al 1999	211	Refractory angina	6 mg/L	OR=2.19
Oltrona et al 1997	140	Death/MI/revasc	10 mg/L	p=ns
Montalescot et al 1998	68	Death/MI/angina/revasc	5 mg/L	p=ns
Mid term
Ridker et al 2005	3,745	Death/MI	2 mg/L	RR=1.4
Muller et al 2002	1,042	Death	10 mg/L	OR=4.1
Heeschen et al 2000	447	Death/MI	10 mg/L	RR=2.0
Lindhal et al 2000	917	Death	10 mg/L	RR=2.6
Ferreiros et al 1999	194	Death/MI/refractory angina	15 mg/L	HR=3.16
Biasucci et al 1999	53	UA	3 mg/L	OR=8.6
Toss et al 1997	965	Death/MI	>10 mg/L vs <2.0 mg/L	RR=3.5
Haverkate et al 1997	2,121	Sudden death/MI	3.6 mg/L	RR=2.0

Abbreviations: CRP, C-reactive protein; HR, hazard ratio; MI, myocardial infarction; Mid-term, in-hospital, 3–37 months; OR, odds ratio; RR, relative risk; Short term, in-hospital, 3 months; UA, unstable angina; urg. revasc, urgent revascularization.

Table 3 Prognostic value of CRP after percutaneous coronary intervention

Study	n	Endpoint	Cutoff	Risk estimates
Heeschen et al 2000	447	Restenosis	10 mg/L	RR=3.0
Muller et al 2002	1042	Death	10 mg/L	OR=4.1
Chew et al 2001	727	Death/MI (30 days)	3.0 mg/L	OR=3.68

Abbreviations: CRP, C-Reactive protein; MI, myocardial infarction; OR, odds ratio; RR, risk ratio.

Table 4 Reported independent prognostic value of CRP in other clinical situations

Clinical situation	Event(s)
Atrial fibrillation	AF development, LA thrombus, success of ECV
Myocarditis	NYHA functional class, overall prognosis
Heart transplant vasculopathy	Survival
Aortic stenosis	Disease progression

Abbreviations: AF, atrial fibrillation; CRP, C-reactive protein; LA, left atrium; ECV, electrical cardioversion; NYHA, New York Heart Association.

Table 5 Treatment effect on hs-CRP levels

Study	n	Treatment	Effect	Clinical setting	p value
Ridker, Hennekens, et al 1999	472	Pravastatin 40 mg	↓ 17.4%	Secondary prevention	0.007
		Placebo	↑ 4.2%
Kinlay et al 2003	2402	Atorvastatin 80 mg	↓ 83%	Unstable	<0.0001
		Placebo	↓ 74%
Ridker et al 2005	3745	Atorvastatin 80 mg	↓ 89%	Unstable	<0.001
		Pravastatin 40 mg	↓ 82%
Nissen et al 2005	502	Atorvastatin 80 mg	↓ 36%	Stable and unstable	<0.001
		Pravastatin 40 mg	↓ 3%
Bogaty 2004	35	Rofecoxib 25 mg	↓ 59%	Stable	0.03
		Placebo	↑ 35%
Monakier 2004	34	Rofecoxib 25 mg	↓ 98%	Unstable	<0.02
		Placebo	↑ 100%
Fliser 2004	199	Olmesartan 20 mg	↓ 15.1%	Hypertension	<0.05
Després et al 2005	1036	Rimonabant 20 mg	↓18%	Overweight	0.020
		Placebo	↓7.5%
Wannamethee et al 2002	3628	Physical activity	↓ 18%	Stable (elderly men)	0.0005
Mattusch et al 1999	14	Endurance training	↓ 31%	Healthy subjects	<0.05
Chrysohoou et al 2004	3042	Mediterranean diet	↓ 20%	Stable	0.015

Abbreviations: hs-CRP, high sensitivity C-reactive protein.

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