Elevated ICAM-1 and MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on Inflammatory Markers study: a substudy of Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration.
BACKGROUND
Plasma levels of soluble intercellular adhesion molecule 1 (sICAM-1) and monocyte chemoattractant protein 1 (sMCP-1) are associated with increased risk for future coronary events. However, the effect of statins on these inflammatory markers has hardly been studied. We analyzed whether treatment with the different doses of atorvastatin affects sICAM-1 and sMCP-1 plasma levels in subjects at high cardiovascular risk.


METHODS
Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration was a 12-week, prospective, multicenter, open-label trial that enrolled a total of 2117 subjects with coronary heart disease (CHD), CHD equivalent (defined as diabetes, peripheral vascular disease, or cerebrovascular disease), or a 10-year CHD risk >20%. Subjects with low-density-lipoprotein cholesterol between 100 and 220 mg/dL (2.6-5.7 mmol/L) and triglycerides <600 mg/dL (6.8 mmol/L) were assigned to atorvastatin (10-80 mg/d) based on low-density-lipoprotein cholesterol at screening. The Atorvastatin on Inflammatory Markers study included statin-free patients (N = 1078).


RESULTS
At baseline, 52%, 14%, 12%, and 22% of subjects were assigned to doses of 10, 20, 40, and 80 mg, respectively. Levels of sICAM-1 [geometric mean (95% confidence interval); 283.8 (278.1-289.6) vs 131.9 (127.2-136.6) ng/mL, P < .0001] and sMCP-1 [164.1 (159.9-168.2) vs 131.1 (123.1-139.6 pg/mL, P < .0001] were increased in subjects at high cardiovascular risk compared to healthy subjects (n = 130). In the whole population, sICAM-1 and sMCP-1 levels were reduced by atorvastatin [% change (95% confidence interval); -2.2 (-3.8 to -0.6); -4.1 (-6.1 to -2); P = .006 and P = .0002, respectively]. All doses of atorvastatin diminished sICAM-1 and sMCP-1 levels in the highest quartile.


CONCLUSIONS
Short treatment with atorvastatin reduced sICAM-1 and sMCP-1 plasma levels showing anti-inflammatory effects in subjects at high cardiovascular risk.
Blanco-Colio
Luis Miguel
LM
Vascular Research Laboratory, Fundación Jimenéz Díaz, Autonoma University, Madrid, Spain.
Martín-Ventura
Jose Luis
JL
de Teresa
Eduardo
E
Farsang
Csaba
C
Gaw
Allan
A
Gensini
GianFranco
G
Leiter
Lawrence A
LA
Langer
Anatoly
A
Martineau
Pierre
P
Egido
Jesús
J
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D018932:Chemokine CCL2 / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D048909:Diabetes Complications / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D016896:Treatment Outcome
D000924:Anticholesteremic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D011758:Pyrroles; D018799:Intercellular Adhesion Molecule-1; D002784:Cholesterol; D000069059:Atorvastatin