Does pravastatin increase chylomicron remnant catabolism in postmenopausal women with type 2 diabetes mellitus?

SummaryObjective  We investigated the effects of pravastatin on chylomicron remnant catabolism measured with a 13C stable isotope breath test and plasma apolipoprotein (apo) B‐48 and remnant‐like particle (RLP)‐cholesterol in postmenopausal women with type 2 diabetes mellitus.Patients and measurements  Nineteen postmenopausal women with type 2 diabetes were randomized to receive 40 mg/day pravastatin or no treatment for 6 weeks followed by a 2‐week washout period, and crossed over for a further 6 weeks. Fractional catabolic rate (FCR) of a chylomicron remnant‐like emulsion was determined from 13CO2 enrichment in the breath and plasma using isotope‐ratio mass spectrometry and multicompartmental modelling. Plasma apo B‐48 and RLP‐cholesterol concentrations were also measured as static markers of chylomicron remnant metabolism.Results  Pravastatin significantly reduced plasma concentrations of cholesterol (5·9 ± 0·3 vs. 4·8 ± 0·2 mmol/l; P < 0·001), low density lipoprotein (LDL)‐cholesterol (3·5 ± 0·2 vs. 2·6 ± 0·2 mmol/l; P < 0·001), triglyceride (2·1 ± 0·3 vs. 1·7 ± 0·2 mmol/l; P = 0·017), non‐high density lipoprotein (HDL)‐cholesterol (4·4 ± 0·3 vs. 3·3 ± 0·2 mmol/l; P < 0·001), lathosterol/total cholesterol ratio (2·6 ± 0·2 vs. 2·0 ± 0·3, P = 0·035), apo B‐100 (1·1 ± 0·1 vs. 0·8 ± 0·1 g/l; P = 0·001), apo B‐48 (4·8 ± 0·9 vs. 3·3 ± 0·6 mg/l; P = 0·016), and RLP‐cholesterol (31·4 ± 8·2 vs. 18·6 ± 4·6 mg/dl; P = 0·024). Pravastatin was also associated with an increase in sitosterol/total cholesterol ratio (2·8 ± 0·3 vs. 3·1 ± 0·3, P = 0·029). Chylomicron remnant‐like emulsion catabolism was not, however, significantly altered by pravastatin estimated by either breath or plasma clearance measurements.Conclusions  In postmenopausal women, pravastatin decreases plasma concentrations of remnant lipoproteins by a mechanism that may relate chiefly to inhibition of remnant production, but this requires further evaluation.