ANICHKOV study: the effect of combined hypotensive and lipid-lowering therapy on cardiovascular complications in patients of high and very high risk.

AIM: The aim of the study was to assess cardiovascular risk in patients with elevated levels of total cholesterol and LDL-C and concomitant AH, a comparative analysis of adherence, efficacy and safety of various forms of combined therapy in outpatient practice, including promising lisinopril/amlodipine/rosuvastatin FC (Ekvamer®). MATERIALS AND METHODS: The ANICHKOV study included 702 patients in Moscow and the Moscow region over 18 years old with a -chole-sterol level ≥7.5 mmol/l and/or LDL-C ≥4.9 mmol/l from March 2017 to December 2018 based on 2 federal centers. According to the results of visit I, patients were prescribed with one of three therapy schemes. In the absence of AH, patients received scheme I -(Mertenil® at initial dosage of 10 mg/day). When history of AH existed or AH detected at visit I, patients were randomized to scheme II (Ekvamer® 5/10/10 mg/day) or III (Mertenil® 10 mg/day + Ekvator® 5/10 mg/day). During the observation, the treatment scheme remained unchanged, however, if the target levels of LDL-C and/or BP were not reached, the doses could be increased. The analysis of the main effects of the prescribed therapy were carried out for 12 months, and the frequency of MACE (CVD, ACS, stroke, or hospitalization to perform PCI) was also evaluated. RESULTS: Following the visit I, scheme I was assigned to 390 patients (55.6%), scheme II - 190 (27.1%), scheme III - 122 (17.4%). In 147 patients (20.9%), TG level was >2.3 mmol/l, which required additional fenofibrate intake in a dose of 145 mg/day. Adherence level was 89.5%, including scheme I - 91.7%, scheme II - 90.5%, scheme III - only 81.8%. In general, among compliant patients (n = 590), the decrease in TCh level was 41.0%, LDL-C - 47.4%. 16.6% of patients reached target levels of LDL-C <2.5 mmol/l, 5.6% - <1.8 mmol/l. In the fenofibrate subgroup, TG level decrease was 34.6%. During the follow-up period, 47 cases of side effects were observed in 27 patients (4.6%), that did not require modification of therapy. Systolic BP reduction in compliant patients of schemes II and III was 20 mm. Hg (13.1%), diastolic BP - 12 mm. Hg (13.6%), target BP levels (<140/90 mm. Hg) reached 83.7% and 80.8% of patients, respectively, target levels of BP and LDL-C <2.5 mmol/l reached 14.5% and 13.1% of patients, respectively, <1.8 mmol/l - 5.8% and 5.1%, respectively. During the observation period no deaths were recorded, other components of MACE were observed in 38 patients (5.8%), including 27 among compliant patients (4.6%) and 11 among non-compliant (15.9%, p<0.01). In 19 out of 38 patients (50%), hospitalization for routine PCI was the end point, ACS - in 12 (31.6%), and stroke - in 7 (18.4%). CONCLUSION: The results of the study demonstrated a sufficient hypolipidemic effect and high safety of Mertenil® and Ekvamer®. A higher adherence to the combined preparation than to two monodrugs was noted. Achieving target levels of BP and LDL-C is problematic, which dictates the expediency of using fixed combinations of drugs, especially in primary prevention.

[How surplus of palmitic fatty acid in food initiates hypertriglyceridemia, increases cholesterol of low density lipoproteins, triggers atherosclerosis and develops atheromatosis.]

In phylogenesis, the first transfer of all fatty acids to cells is implemented by high density lipoproteins. Later, unsaturated and polyene fatty acids are transferred to cell by low density lipoproteins. The insulin-depended cells absorb palmitic saturated fatty acid, oleic mono-unsaturated fatty acid and of the same name triglycerides in very low density lipoproteins. The hepatocytes secrete palmitic, oleic and linoleic very low density lipoproteins separately. In blood, under hydrolysis of triglycerides, cells absorb ligand palmitic and oleic very low density lipoproteins by force of апоЕ/В-100 endocytosis; they are not transformed into low density lipoproteins. The palmitic saturated fatty acids in the form of polyether of cholesterol turn into linoleic very low density lipoproteins from high density lipoproteins at impact of protein transferring polyene ethers of cholesterol. They transform very low density lipoproteins into low density lipoproteins of the same name; the cells absorb them by force of апоЕ/В-100 endocytosis. In physiological sense, amount of oleic very low density lipoproteins are always more than palmitic of very low density lipoproteins. Under syndrome of insulin-resistance there is no transformation of palmitic saturated fatty acid synthesized from glucose in vivo into oleic mono-saturated fatty acid. The hepatocytes secrete into blood mainly palmitic very low density lipoproteins which amount exceeds oleic very low density lipoproteins. Under slow hydrolysis in blood, main mass of palmitic very low density lipoproteins becomes palmitic low density lipoproteins. These very lipoproteins initiate hyperlipidemia, increase content of cholesterol of cholesterol-low density lipoproteins, lower cholesterol-high density lipoproteins, decrease bio-availability of polyene fatty acids for cells, trigger development of atherosclerosis and formation of atheromatosis in intima of arteries. The aphysiologic effect of surplus of palmitic saturated fatty acid in vivo and triglycerides of the same name can't be eliminated under increasing of content of ω-3 polyene fatty acids in food and effect of statines. All this is to be rationally applied in prevention of hypertriglyceridemia, atherosclerosis, atheromatosis of coronary arteries, ischemic heart disease and myocardium infarction.