Introduction
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an important marker of cardiovascular risk and a new target for therapeutic interventions. We aimed to study the influence of metformin on the level of circulating PCSK9 in patients with stable coronary artery disease (SCAD) and type 2 diabetes (T2DM) or metabolic syndrome (MetS), receiving moderate doses of statins used in routine clinical practice.
Material and methods
The study included 80 patients with T2DM or MetS receiving rosuvastatin for at least three months prior the study. MetS was diagnosed based on the Global Consensus Definition of the International Diabetes Federation (IDF). Serum level of PCSK9 was measured with an ELISA kit.
Results
Patients with T2DM or MetS, who took part in the research, were divided into 2 groups – those who received metformin prior the main study (21 patients – 1
st
group) and patients who did not (59 patients – 2
nd
group). Addition of metformin to the 3-month statin therapy of the 2nd group patients, divided into subgroup A (
n
= 27) with the addition of metformin and subgroup B (
n
= 29) without one, did not significantly affect the level of lipids. However, the level of circulating PCSK9 in subgroup A patients decreased, compared to subgroup B (
p
< 0.01). At the same time, ongoing metformin and rosuvastatin therapy in the 1
st
group patients was not accompanied by a further decrease of the PCSK9 level.
Conclusions
The addition of metformin to ongoing rosuvastatin therapy did not significantly affect serum lipid levels, but stabilized the level of circulating PCSK9, compared with the group without metformin treatment.
IntroductionThe aim was to study the pharmacogenetic determinants of switching simvastatin-intolerant ethnic Uzbek patients with coronary artery disease (CAD) to rosuvastatin treatment.Material and methodsThe study included 50 patients with CAD, who demonstrated statin-induced adverse liver symptoms, accompanied by an elevation in transaminase level (3-fold or more in 37 cases) or statin-induced adverse muscle symptoms, accompanied by elevations in serum (CK > 3 times above the upper limit of normal (ULN)) in simvastatin treatment with a dose of 10–20 mg/day. The control group consisted of 50 patients without side effects. Patients were genotyped for polymorphisms in the genes coding for the cytochrome P450 (CYP) metabolic enzymes CYP3A5(6986A>G), CYP2C9(430C>T), CYP2C9(1075A>C), and hepatic influx and efflux transporters SLCO1B1(521T>C) and BCRP(ABCG2, 421C>A) by means of the PCR-RFLP method.ResultsWhen the 50 patients of the case group were switched to the starting rosuvastatin dose of 5 mg, intolerance symptoms were not observed in 29 (58%) versus 21 with adverse symptoms. In this case-control study, the groups differed significantly only in the prevalence of the *3/*3 genotype CYP3A5 (OR = 5.25; 95% CI: 1.6–17.8; p = 0.014).ConclusionsIn a considerable proportion of ethnic Uzbek patients with CAD and simvastatin intolerance symptoms, serious side effects when switching to a starting dose of rosuvastatin were not observed, and it should be noted that in most cases (72.4%) this phenomenon was observed among the carriers of *3/*3 genotype of the CYP3A5 (6986A> G) gene.
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