Published Online
on February 3, 2005

A more recent version of this article appeared on March 1, 2005

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Submitted on October 11, 2004
Revised on November 25, 2004
Accepted on November 30, 2004

Effects of Fosinopril and Pravastatin on Carotid Intima-Media Thickness in Subjects With Increased Albuminuria

Folkert W. Asselbergs MD, PhD^*; Arie M. van Roon PhD; Hans L. Hillege MD, PhD; Paul E. de Jong MD, PhD; Reinold O.B. Gans MD, PhD; Andries J. Smit MD, PhD; Wiek H. van Gilst PhD; on behalf of the PREVEND IT Investigators

From the Department of Clinical Pharmacology (F.W.A., W.H.v.G.), University of Groningen, Groningen, the Netherlands; the Department of Internal Medicine (A.M.v.R, R.O.B.G., A.J.S.), Trial Coordination Center (H.L.H.), and the Department of Nephrology (P.E.d.J.), University Hospital Groningen, Groningen, the Netherlands.

^* To whom correspondence should be addressed. E-mail: f.w.asselbergs{at}thorax.azg.nl.

Background and Purpose--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.

Key words: ACE inhibitors • albuminuria • carotid arteries • controlled clinical trials • statins

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