Changes in flow-mediated dilatation, cytokines and carotid arterial stenosis during aggressive atorvastatin treatment in normocholesterolemic patients.
BACKGROUND
Aggressive statin therapy to reduce low-density lipoprotein (LDL) cholesterol in patients with normal LDL-cholesterol levels reduces the incidence of future cardiovascular events and enhances atherosclerotic regression in the common carotid artery. We tried to quantify changes in flow-mediated dilatation (FMD), inflammatory cytokines, and the severity of carotid arterial stenosis, after aggressive statin administration to patients with normal LDL-cholesterol levels, and stroke or transient ischemic attack ipsilateral to carotid arterial stenosis.


METHODS
Twenty patients with at least a 50% reduction in the diameter of the carotid artery were studied. Atorvastatin 10 mg daily was prescribed for 4 months. Serial changes in the severity of carotid arterial stenosis, and brachial-artery FMD were evaluated by high-resolution ultrasound. Tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), interleukin-6 (IL-6), vascular cell adhesion molecule (VCAM), intracellular adhesion molecule (ICAM), soluble endothelin-1 (ET-1), and high-sensitivity C-reactive protein (hs-CRP), were measured before, and after 2 and 4 months of, atorvastatin treatment.


RESULTS
Atorvastatin significantly decreased plasma levels of total cholesterol and LDL-cholesterol after 1, 2 and 4 months of treatment (p < 0.01). FMD showed significant improvement after only 4 months (10.0% vs 6.8% at baseline; p = 0.019). The overall severity of carotid arterial lesions was not significantly reduced by atorvastatin. Changes in TNF-alpha, IL-1beta, IL-6 and ET-1 showed trends towards a progressive decline after atorvastatin, but none of the cytokines was reduced significantly. FMD did not correlate with the severity of carotid arterial stenosis, lipid profile, or cytokine levels.


CONCLUSIONS
Atorvastatin effectively reduced plasma concentrations of total cholesterol and LDL-cholesterol, and had beneficial effects on endothelial function, in Chinese patients with carotid arterial stenosis and normal LDL-cholesterol levels.
Hsu
Hung-Yi
HY
Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, R.O.C. 2941@vghtc.gov.tw
Wang
Pao-Yu
PY
Chen
Ying-Tsung
YT
Sheu
Wayne Huey-Herng
WH
Hu
Han-Haw
HH
Sheng
Wen-Yung
WY
D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000378:metabolism; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging / Q000601:surgery; D016893:Carotid Stenosis / Q000188:drug therapy* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism*; D004108:Dilatation, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D016232:Endothelins / Q000378:metabolism; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D011859:Radiography; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000924:Anticholesteremic Agents; D015815:Cell Adhesion Molecules; D008078:Cholesterol, LDL; D016207:Cytokines; D016232:Endothelins; D006538:Heptanoic Acids; D007375:Interleukin-1; D015850:Interleukin-6; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D002097:C-Reactive Protein; D002784:Cholesterol; D000069059:Atorvastatin