Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors.
BACKGROUND
Although recommended as initial therapy for patients with dyslipidemia who are taking human immunodeficiency virus protease inhibitors (HIV PIs), the effects of pravastatin on lipoproteins and arterial reactivity have not been elucidated. The purpose of this study was to determine the effects of pravastatin on lipoprotein subfractions and endothelial function in patients with dyslipidemia who are receiving HIV PIs.


METHODS
This was a placebo-controlled, double-blind, crossover study comparing pravastatin (40 mg) to placebo in 20 patients who were taking HIV PIs. Lipoprotein subfractions were measured with nuclear magnetic resonance spectroscopic analysis. Flow-mediated vasodilation (FMD) of the brachial artery was evaluated with high-resolution ultrasound scanning.


RESULTS
At baseline, subjects had an increased concentration of low-density lipoprotein (LDL) particles (1756 +/- 180 nmol/L), which tended to be small (19.9 +/- 0.2 nm), a low concentration of large high-density lipoproteins (HDL; 0.94 +/- 0.07 mmol/L), and an increased concentration of large very low-density lipoproteins (VLDL; 1.90 +/- 0.58 mmol/L). FMD was impaired (4.5% +/- 1.1%). Compared with placebo, pravastatin resulted in a 20.8% reduction in LDL particles (P =.030), a 26.7% reduction in small LDL (P =.100), and a 44.9% reduction in small VLDL (P =.023). Total and non-HDL cholesterol levels decreased by 18.3% (P <.001) and 21.7% (P <.001), respectively. FMD tended to increase in patients receiving pravastatin (0.7% +/- 0.6%); however, the difference between treatment phases was not statistically significant (P =.080).


CONCLUSIONS
This is the first double-blind, placebo-controlled study of the effects of statin therapy on lipids, lipoprotein subfractions, and endothelial function in patients taking HIV PIs. Pravastatin reduced concentrations of atherogenic lipoproteins, particularly those most associated with future coronary events.
Stein
James H
JH
University of Wisconsin Atherosclerosis Imaging Research Program, University of Wisconsin Medical School, Madison 53792, USA.
Merwood
Michelle A
MA
Bellehumeur
Jennifer L
JL
Aeschlimann
Susan E
SE
Korcarz
Claudia E
CE
Underbakke
Gail L
GL
Mays
Maureen E
ME
Sosman
James M
JM
D000328:Adult; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy; D015228:Hypertriglyceridemia / Q000150:complications / Q000188:drug therapy; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D017035:Pravastatin / Q000009:adverse effects / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects
D017320:HIV Protease Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D018894:Reverse Transcriptase Inhibitors; D014280:Triglycerides; D002784:Cholesterol; D017035:Pravastatin