Effects of fosinopril and pravastatin on carotid intima-media thickness in subjects with increased albuminuria.
OBJECTIVE
Elevated urinary albumin excretion (UAE) is associated with an increased carotid intima-media thickness (IMT). Because angiotensin-converting enzyme inhibitors as well as statins have been shown to lower UAE and the progression of IMT, we assessed the effects of fosinopril and pravastatin on carotid IMT in subjects with an increased UAE (15 to 300 mg/24 h).


METHODS
IMT was measured at the posterior wall of the left common carotid artery using radio-frequency signal analysis obtained by M-mode ultrasonography. 642 subjects were double-blind randomized to fosinopril 20 mg or matching placebo and to pravastatin 40 mg or matching placebo and were available for intention-to-treat analysis.


RESULTS
Mean age was 51+/-11 years, 65% were male, the median UAE was 22.5 (15.5 to 40.8) mg/24 h, and the mean IMT at baseline was 0.77+/-0.18 mm. The overall progression rate of IMT in 4 years was 0.037+/-0.006 mm. No significant difference in IMT progression was found between fosinopril, pravastatin, or matching placebo. IMT after 4 years was predicted by IMT at baseline, age, gender, pulse pressure, and low-density lipoprotein cholesterol levels. Furthermore, a higher incidence of clinical events was observed in subjects with an IMT >1 mm after a mean follow-up of 46+/-7 months (hazard ratio, 3.13; 95% confidence interval, 1.59 to 6.16; P=0.001).


CONCLUSIONS
In subjects with an increased UAE, treatment with fosinopril and pravastatin showed no significant effect on carotid IMT. Furthermore, an IMT <1 mm at baseline is an important indicator for event-free survival.
Asselbergs
Folkert W
FW
Department of Clinical Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. f.w.asselbergs@thorax.azg.nl
van Roon
Arie M
AM
Hillege
Hans L
HL
de Jong
Paul E
PE
Gans
Reinold O B
RO
Smit
Andries J
AJ
van Gilst
Wiek H
WH
D000419:Albuminuria / Q000150:complications*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000473:pathology; D004311:Double-Blind Method; D005260:Female; D017328:Fosinopril / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use; D011237:Predictive Value of Tests; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*; D017540:Tunica Media / Q000187:drug effects* / Q000473:pathology*
D017035:Pravastatin; D017328:Fosinopril