Coronary reactivity, homocysteine and methylenetetrahydrofolate reductase gene variation in young men during pravastatin therapy.
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.
Nieminen
Tuomo
T
Department of Pharmacological Sciences, Medical School, FI-33014 University of Tampere, Finland. tuomo.nieminen@iki.fi
Knuuti
Juhani
J
Hämelahti
Päivi
P
Kähönen
Mika
M
Laaksonen
Reijo
R
Janatuinen
Tuula
T
Vesalainen
Risto
R
Nuutila
Pirjo
P
Jokela
Hannu
H
Lehtimäki
Terho
T
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
D000924:Anticholesteremic Agents; D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000241:Adenosine; D017035:Pravastatin