title: Coronary reactivity, homocysteine and methylenetetrahydrofolate reductase gene variation in young men during pravastatin therapy.
abstract: High plasma homocysteine (Hcy) has been linked to impaired endothelial function. We investigated whether treatment with pravastatin affects the Hcy levels. Moreover, we studied whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism affects coronary vasomotion at baseline and during the treatment with pravastatin. Fifty-one healthy, mildly hypercholesterolemic men (mean age 35+/-4 years) attended this randomised, double-blind, placebo-controlled study. The volunteers were randomised into groups with 6-month treatment with pravastatin (40 mg/day, n=25) or placebo (n=26). Coronary blood flow measurements with positron emission tomography at rest and during adenosine infusion as well as biochemical analyses were done at baseline and at the end of the treatment period. The Hcy concentration decreased significantly during the pravastatin therapy (-0.81+/-1.46 micromol/l, p=0.01), but not during placebo (0.02+/-2.39 micromol/l, p=0.97). The MTHFR polymorphism did not affect the Hcy concentration or coronary flow indices. Neither did the MTHFR polymorphism modulate the effects of pravastatin on coronary vasomotion. In conclusion, a 6-month therapy with pravastatin decreases Hcy concentration in Finnish healthy young men. The MTHFR genotype is neither a determinant of baseline coronary flow indices nor does it modulate the effect of pravastatin on coronary reactivity.
authors.affiliation: Department of Pharmacological Sciences, Medical School, FI-33014 University of Tampere, Finland. tuomo.nieminen@iki.fi
authors.forename: Tuomo
authors.initials: T
authors.lastname: Nieminen
authors.forename: Juhani
authors.initials: J
authors.lastname: Knuuti
authors.forename: Päivi
authors.initials: P
authors.lastname: Hämelahti
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.forename: Tuula
authors.initials: T
authors.lastname: Janatuinen
authors.forename: Risto
authors.initials: R
authors.lastname: Vesalainen
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Hannu
authors.initials: H
authors.lastname: Jokela
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
mesh_terms: D000241:Adenosine; D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003326:Coronary Circulation / Q000187:drug effects* / Q000235:genetics; D004311:Double-Blind Method; D006710:Homocysteine / Q000097:blood / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic; D049268:Positron-Emission Tomography; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000924:Anticholesteremic Agents; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000241:Adenosine; D017035:Pravastatin