Aim: The aim of the study was to identify whether short – term treatment with a combination of low, sub – therapeutic doses of fluvastatin and valsartan can improve the functional and structural properties of the arterial vascular wall in a clinically – relevant manner in optimally – treated patients with type 2 diabetes and thus indirectly reduce the risk of developing cardio – vascular diseases.
Hypotheses: One – month treatment with a combination of low, sub – therapeutic doses of fluvastatin and valsartan significantly improves the functional and structural properties of the arterial wall and has a positive impact on the laboratory parameters of inflammation, oxidative stress and gene expression in patients with type 2 diabetes. After therapy discontinuation, the residual effects persist for some time. After the effects are completely or almost completely diminished, treatment is repeated and the positive effects are regained.
Background: Atherosclerosis and associated cardio – vascular diseases are one of the main causes of mortality and significant morbidity in patients with type 2 diabetes. Complications in patients with diabetes occur earlier compared to healthy individuals of the same age. The process of atherosclerosis begins with endothelial dysfunction, which impacts the functional properties of the arterial vascular wall, and continues with structural changes. Changes in the structure and functioning of the arterial wall can be monitored non – invasively through ultrasound and laboratory parameters.
Renin – angiotensin inhibitors and statins are some of the most commonly used drugs in the treatment of cardio – vascular diseases. In addition to their primary effects, they also display so – called pleiotropic effects, which are independent of the primary effects. One of the most important pleiotropic effect is an improvement in endothelium functioning.
Our short – term treatment with low, sub – therapeutic doses of fluvastatin and valsartan in combination aimed to achieve an improvement of both functional and structural properties of the arterial wall. This concept has been proven effective in previous studies on healthy subjects. We decided to test the efficacy of the treatment in patients with type 2 diabetes as we believe that the proposed treatment may have significant beneficial effects on such patients, who often develop cardio – vascular complications earlier than healthy individuals.
Study design, description of methods and subjects: 40 patients with type 2 diabetes were included in a double – blind, randomized, placebo – controlled study. The patients were divided into two groups, where the first (test group) received a combination of low, sub – therapeutic doses of fluvastatin and valsartan, and the second (control group) received a placebo. At the beginning of the study, we took the medical history and performed clinical examinations of all the included patients, we took blood samples for hemogram, electrolytes, inflammation, oxidative stress parameters and gene analysis and performed ultrasound investigation of the functional and structural properties of the arteries on the neck and upper limbs of each patient. Ultrasound investigations and blood sample analysis were repeated after one month of treatment, and again three and six months after treatment discontinuation. After the effects of the treatment diminished, we repeated the therapy with fluvastatin and valsartan for one month, to test if the primary effects can be regained.
Results: We achieved a statistically significant improvement in the functional and structural properties of the arterial wall in patients with type 2 diabetes, which persisted for several months after finally diminishing, while therapy repetition regained the primary effects. We did not record statistically significant effects on the laboratory indicators of inflammation and oxidative stress, but we did demonstrate a favorable effect on the expression of some genes that impact the arterial vascular wall.
Conclusion: This study constitutes that a new, original approach can be effective in reducing the occurrence of cardio – vascular events in patients with type 2 diabetes. This is an initial study with good potential for further research.