Low density lipoprotein receptor gene mutations in patients with clinical diagnosis of familial hypercholesterolemia.

Low density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterolemia which is associated with elevated risk of ischemic heart disease. AIM: To define LDLR gene mutations in unrelated patients with heterozygous familial hypercholesterolemia in Russia. METHODS: PCR- single-strand conformation polymorphism analysis, automated DNA sequencing, and test for the presence of the apolipoprotein (apo) B-3500 mutation known to induce hereditary defect in apo-B-100. RESULTS: We found 6 novel mutations of LDLR gene designated E8X, 230insG, 671_679dupGACAAATCT, W422R, D461Y, and V698L. We also identified three missense mutations - C139G, E207K and R395W, which were previously described in FH patients from western populations. None of the studied persons had apo-B-3500 mutation. CONCLUSION: These findings broaden knowledge on mutations responsible for development of familial hypercholesterolemia and confirm molecular heterogeneity of this disease in Russia.     

Apheresis of low density lipoproteins using a heparin-based sorbent with low antithrombin III binding capacity

A sorbent based on heparin fraction with low affinity for antithrombin III is proposed for low density lipoproteins apheresis in hypercholesterolemia. Heparin was fractionated on antithrombin III-Sepharose; fractions with high and low affinity for antithrombin III were immobilized on CNBr-activated Sepharose 4B. Both sorbents appeared to have an LDL-binding capacity essentially similar to that of the sorbent based on unfractionated heparin. However only plasmasorption on a low affinity heparin-containing sorbent did not reduce plasma antithrombin III. Hence the use of this sorbent may be advantageous over the currently applied sorbents with unfractionated heparin in the treatment of familial hypercholesterolemia.     

Effect of β-hydroxy-β-methylglutaryl coenzyme a reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver

We studied the effects of two inhibitors of β-hydroxy-β-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that β-hydroxy-β-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 143, No. 4, pp. 390–393, April, 2007     

Relationship between free-radical lipid oxidation and efficiency of coronary angioplasty in coronary patients

Low-dose (250 mg daily) oral probucol produces a significant antioxidant effect in coronary patients: increases activity of glutathione peroxidase (enzyme utilizing lipoperoxides) and reduces the content of free-radical oxidation products in the blood. Probucol therapy for 7 days before and for 6 months after coronary angioplasty significantly reduces the severity of coronary artery stenosis. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 503–506, November, 2007     

Treatment for dyslipidemias in patients with arterial hypertension

AIM: To evaluate a combination of the effects of non-drug measures and rozuvastatin on the lipid spectrum and blood pressure (BP) in patients with treated arterial hypertension (AH) concurrent with dyslipidemia. MATERIALS AND METHODS: The multicenter open-labeled prospective program included 299 patients from 19 cities and towns of Russia. Two hundred and eighty-eight patients completed phase 1 of the program; out of them 279 patients (149 males and 130 females) aged 58-80 years (56.7 +/- 8.7 years) with a mean AH history of 10.3 +/- 8.4 years. Phase 1 of the program involved 3 visits and it was over 12 weeks after rozuvastatin therapy. Phase 2 (including a visit 12 weeks following the termination of Phase 1) is being continued. RESULTS: Rozuvastatin therapy resulted in a reduction in the levels of total cholesterol (TC) by 2.5 +/- 0.8 mmol/l (p < 0.001), low-density lipoprotein (LDL) cholesterol by 2.2 +/- 0.8 mmol/l (p < 0.001), triglycerides (TG) by 0.8 +/- 0.9 mmol/l (p < 0.001), and atherogenicity index (AI) by 2.8 +/- 1.4 (p < 0.001) and an increase in the content of high-density lipoprotein (HDL) cholesterol by 0.2 +/- 0.2 mmol/l (p < 0.001), which produced the target levels of LDL cholesterol in 61% of the patients, HDL cholesterol in 70%, and TG in 73%. During unaltered antihypertensive therapy there were also decreases in body mass by 1.5 +/- 2.8 mmol/l (p < 0.001), body mass index by 0.5 +/- 1.0 kg/ m2 (p < 0.001), waist circumference by 1.0 +/- 3.2 cm (p < 0.001), and BP by 72 +/- 14.2/4.1 +/- 8.6 mm Hg (p < 0.001). There was an increase in the activity of aspartate aminotransferase and alanine aminotransferase, and creatine phosphokinase; however, this was clinically significant in none patients. CONCLUSION: Rozuvastatin significantly lowers the levels of TC, LDL cholesterol, TG, and AI and elevates the concentration of HDL cholesterol. In the majority (83%) of the patients, rozuvastatin used in a dose of 10 mg/day was sufficient to normalize the lipid profile, which makes it possible to recommend that rozuvastatin therapy should be started from this dose.     

Simvastatin (40 mg/day) in patients with hereditary hypercholesterolemia: effect on high density lipoprotein cholesterol

AIM: To study effect of simvastatin of the level of high density lipoprotein (HDL) cholesterol (CH). MATERIAL AND METHODS: Simvastatin (40 mg/day) was given for 3 months to 15 patients (3 men, 12 women, mean age 56-/+10.3 years) with hereditary type II hypercholesterolemia after washout from lipid lowering therapy. Initial level of HDL CH was below and above 1.0 mmol/l in 7 and 8 patients, respectively. Blood lipids, activity of liver enzymes and creatine kinase were determined after 1 and 3 months of therapy with simvastatin. Safety and tolerability of simvastatin were also studied. RESULTS: Simvastatin was well tolerated. In 1 patient the drug was stopped because of pain in the liver and nausea. In patients with initially low HDL CH levels of total and low density lipoprotein (LDL) CH significantly decreased by 29.6 and 36.8%, respectively, after 3 months, while level of HDL CH increased by 20% after 1 month of therapy. In patients with initially normal HDL CH levels of total and LDL CH significantly decreased by 31.1 and 32.6%, respectively, while those of triglycerides and HDL CH did not change. CONCLUSION: In patients with hereditary hypercholesterolemia 40 mg/day of simvastatin besides pronounced lowering of LDL CH level caused significant increase of HDL CH (up to 20% in 1 month) in patients with initially low level of this parameter.