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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1303.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Effect of Pravastatin on Low-Density Lipoprotein Oxidation and Myocardial Perfusion in Young Adults With Type 1 Diabetes

Tuula Janatuinen; Juhani Knuuti; Jyri O. Toikka; Markku Ahotupa; Pirjo Nuutila; Tapani Rönnemaa; Olli T. Raitakari

From Turku PET Centre (T.J., J.K., P.N., O.T.R.), MCA Research Laboratory (M.A.), and the Departments of Physiology, Clinical Physiology (J.O.T.), and Medicine (T.R.), Turku University Central Hospital, Turku, Finland.

Correspondence to Tuula Janatuinen, Turku PET Centre, Turku University Central Hospital, PO Box 52, FIN-20521 Turku, Finland. E-mail tuula.janatuinen{at}pet.tyks.fi

Objective— Diabetes has been associated with increased oxidative stress and impaired vascular function. Statins have been shown to reduce low-density lipoprotein (LDL) oxidizability and improve myocardial perfusion in hypercholesterolemic nondiabetic subjects. We studied whether pravastatin decreases LDL oxidation and improves myocardial perfusion in normocholesterolemic subjects with type 1 diabetes.

Methods and Results— In this randomized, double-blind study, myocardial perfusion was measured at rest and during dipyridamole stimulation with positron emission tomography and [¹⁵O]H₂O during hyperinsulinemic euglycemia in 42 patients (age 30±6 years; LDL cholesterol 2.48±0.57 mmol/L) before and after 4-month treatment with pravastatin 40 mg/d or placebo. In addition, 12 healthy nondiabetic subjects were studied. LDL oxidation was measured by determining the level of baseline diene conjugation in lipids extracted from LDL. The level of LDL oxidation was similar in the pravastatin and placebo groups before treatment (23.9±4.6 versus 25.6±9.5 µmol/L, respectively) and decreased significantly during pravastatin treatment to 19.5±5.0 µmol/L (P<0.005). Myocardial perfusion reserve was significantly lower in diabetic patients compared with controls (4.15±1.29 versus 5.31±1.86, P<0.05) and did not change after treatment. Glycemic control and insulin sensitivity remained unchanged during treatment.

Conclusion— Pravastatin treatment, resulting in decreased LDL oxidation, did not improve myocardial perfusion reserve in subjects with type 1 diabetes.

In this randomized, double-blind study, low-density lipoprotein (LDL) oxidation and myocardial perfusion were measured in 42 normocholesterolemic patients with type 1 diabetes before and after 4-month treatment with pravastatin or placebo. Pravastatin decreased LDL oxidation; however, this was not associated with improvement in myocardial perfusion reserve measured by positron emission tomography.

Key Words: pravastatin • positron emission tomography • myocardial perfusion • LDL oxidation • diene conjugation

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