Inhibition of HMG-CoA reductase with cerivastatin lowers dense low density lipoproteins in patients with elevated fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus.
OBJECTIVE
While 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors effectively decrease LDL cholesterol, it remains controversial whether these agents also lower dense LDL, which are considered particularly atherogenic.


METHODS
We examined the effects of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor cerivastatin on lipids, lipoproteins, and apolipoproteins in 69 patients with elevated fasting glucose, impaired glucose tolerance, or type 2 diabetes, combined hyperlipoproteinemia and increased concentrations of dense LDL (apo B in LDL-5 plus LDL-6 > 25 mg/dl). The study was a multicenter, double-blind, randomized, parallel-group comparison of cerivastatin at 0.4 mg daily for 12 weeks (n = 34) and placebo (n = 35).


RESULTS
Cerivastatin significantly reduced cholesterol (- 20 %, p < 0.001), IDL cholesterol - 37 %, p < 0.001), LDL cholesterol (- 26 %, p < 0.001), apolipoprotein B (- 25 %, p < 0.001), triglycerides (- 12 %, p < 0.05), and raised HDL cholesterol (+ 7.5 %, p < 0.05) and apolipoprotein AI (+ 7.2 %, p < 0.05). Cerivastatin signficantly lowered apolipoprotein B in all LDL subfractions (- 21 to - 28 %, p < 0.05). Absolute changes were greatest in dense LDL and the change in dense LDL made the largest contribution to the change of total LDL. The change of dense LDL was highly correlated with baseline values. There was no consistent relationship between the effect of cerivastatin on triglycerides and the decrease of dense LDL.


CONCLUSIONS
The HMG CoA reductase inhibitor cerivastatin lowers total and LDL cholesterol and the concentration of dense LDL in patients with elevated fasting glucose, impaired glucose tolerance or type 2 diabetes.
Scharnagl
H
H
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-University, Graz, Austria. hubert.scharnagl@klinikum-graz.at
Winkler
K
K
Mantz
S
S
Baumstark
M W
MW
Wieland
H
H
März
W
W
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D004311:Double-Blind Method; D018149:Glucose Intolerance / Q000097:blood*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000097:blood*; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008875:Middle Aged; D010919:Placebos; D011725:Pyridines / Q000627:therapeutic use*
D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D010919:Placebos; D011725:Pyridines; C086276:cerivastatin