E ffekty lipid-lowering therapy 2

In the concept of a multifactor approach, the most important is the correction of lipid metabolism disorders, which, as already mentioned, makes the most important contribution to the risk of complications. By impaired lipid metabolism, we mean an increase in the level of total cholesterol (cholesterol), cholesterol cholesterol of low-density lipoproteins (LDL), triglycerides (TG), and a decrease in cholesterol cholesterol of high-density lipoproteins (HDL). In large epidemiological studies, a direct relationship was found between cholesterol level and mortality from coronary heart disease [71,72], and also that a decrease in the level of LDL cholesterol leads, in turn, to a decrease in the risk of developing coronary heart disease [73,74]. Today, the most effective and safest drug-based lipid-lowering therapy is statins. They reduce LDL cholesterol by 20–60%, TG – by 10–40%, and HDL cholesterol increases by 5–15% . Prolonged use of statins leads to a significant reduction in the risk of cardio and cerebrovascular complications [76]. At the same time, the effectiveness of statins has been proven not only in patients with coronary artery disease, but also without coronary artery disease. The ASCOT-LLA (Anglo-Scandinavian Cardiac Outcomes Trial – Lipid Lowering Arm) study proved the effectiveness of statins for the prevention of cardiovascular complications in patients with hypertension and moderate hypercholesterolemia [77]. This fact is reflected in the recommendations of GFCF for the diagnosis and treatment of atherosclerosis, where statin administration is recommended not only for treating patients with various clinical manifestations of atherosclerosis, but also for treating patients without clinical manifestations of atherosclerosis and with a high risk of CVD death according to the SCORE scale. Thus, indications for lipid-lowering therapy are greatly expanded, as a means of not only secondary, but also primary prophylaxis.

At the same time, statins have a number of additional pleiotropic effects, which include the ability to improve endothelial function, reduce blood viscosity, and also have an anti-inflammatory, hypotensive effect. One of the most important effects of statins is an improvement in endothelial function [78,79]. It is with the improvement of endothelial function in the application of statins that their hypotension effect has been identified, which has been identified in a number of studies in recent years [80,81]. In this regard, the data of our own double-blind, randomized, placebo-controlled clinical study are of interest, the purpose of which was to study the hypotensive effect of pravastatin in patients with mild hypertension and HCS. The 12-week study included 52 male patients aged 35–60 years,who were randomly assigned to 3 groups. Group I received a placebo – 16 people, Group II – Pravastatin – 40 mg per day – 18 people and Group III – prolonged non-dihydropyridine calcium antagonist – diltiazem (altiazem PP ® ) – 180 mg per day – 18 people.

The treatment with pravastatin showed a significant decrease in the average daily GAD by 6.2 mm Hg. (p <0.001), the average daily dad – 5.4 mm Hg. Art. (p <0.001). At the same time, against the background of receiving a placebo, there was no change in the average daily GARDEN (total –0.1 mm Hg, p> 0.05), nor the average daily DBP (total –0.3 mm Hg. Art. , p> 0.05). At the same time, pravastatin provided a significant reduction in the average daily GARDEN and DBP compared with placebo. At the same time, it was slightly inferior in its hypotensive effect.

As for the hypolipidemic effect of pravastatin, the decrease in total cholesterol was 29.2 ± 3.3% of the initial level (p <0.001), LDL cholesterol – 37.7 ± 4.4% of the initial level (p <0.001) , increase in HDL cholesterol levels – 30.1 ± 5.7% from the initial level (p <0.001).

Interestingly, the degree of decline in cholesterol levels did not correlate with the degree of decline in either GARDEN or DBP. Thus, the hypotensive effect of pravastatin was not dependent on its hypolipidemic action.

Pravastatin’s hypotensive effect made an additional contribution to reducing the total coronary risk, calculated on the basis of the computerized model of the West German study PROCAM STUDY [82]. The main components of this formula are: age, CAD, level of total cholesterol or LDL cholesterol, HDL cholesterol, TG, smoking status, type 2 diabetes, history of coronary artery disease, myocardial infarction, history of coronary artery disease.

Taking into account only the hypolipidemic effect, the total risk was significantly reduced (–69%) and amounted to 7.2%, while taking into account the hypotensive effect, it reached 6.3%. Thus, the antihypertensive effect of pravastatin makes an additional contribution to the reduction in total coronary risk .

Perhaps the additional antihypertensive effect of pravastatin, which is a consequence of the improvement in endothelial function, can be attributed to the WOSCOPS (West of Scotland Coronary Prevention Study) study on primary ischemic heart disease prevention, where the efficacy of pravastatin in the treatment of 6550 people with lipid metabolism disorders was evaluated [83] . The reduction in coronary risk (combined endpoints – nephatal MI, coronary artery disease, coronary angioplasty, CABG) was significantly higher (by 12%) than expected, calculated on the basis of the Framingham model, which takes into account the level of total cholesterol.

With long-term statin therapy, it is necessary to take into account not only their hypopidemic effect, but also the hypotensive effect, which makes an additional contribution to the reduction in total coronary risk.

Since endothelial dysfunction is the cause of the disruption of the structure and normal functioning of the vessels of the microvasculature [84], it would be logical to assume that statins have a favorable effect on the microcirculation system, which is the basis for adequate organ and tissue perfusion. There are only a few data from foreign studies on the effect of statins on microcirculation. . No studies on this topic have been conducted in Russia. We have undertaken a study to study the effect of a new statin called Rosuvastatin (Crestor, AstraZeneca, UK) on the microcirculatory bed in patients with dyslipidemia and mild and moderate hypertension. The study involved 25 patients with cholesterol levels above 5.0 mmol / l and LDL cholesterol above 3.0 mmol / l and the level of the GARDEN 140–179 mm Hg. and dad 90–109 mm Hg For 12 weeks, patients took 10 mg of rosuvastatin without dose adjustment. The state of the microcirculatory bed was studied using laser Doppler flowmetry.

In general, the favorable effect of rosuvastatin on the microcirculatory bed has been established. At the same time, positive shifts were observed in various pathological types of microcirculation – in spastic and hyperemic. In the case of the spastic type of microcirculation, when the microcirculatory bed is depleted in blood, an increase in blood flow occurs during the treatment with Krestor, as evidenced by the increase in the microcirculation index. The same is evidenced by the decrease in the reserve of capillary blood flow (RSC), which is a consequence of the increase in the number of functioning capillaries. In the hyperemic type of microcirculation, when there is an overflow of the vascular bed, there is a decrease in blood flow, as evidenced by a decrease in the microcirculation index. In these patients, an increase in RCC is observed, which plays a positive role, since it facilitates unloading of the overfilled precapillary link.

At the same time, in both groups, a decrease in peripheral vascular resistance was observed, as evidenced by a significant increase in myospheric amplitudes. As a result, blood flow to the capillaries increases and organ and tissue perfusion improves.

Thus, in general, during the treatment with Crestor, patients with DLP and mild and moderate hypertension have seen favorable changes in the microcirculation system.

Another positive effect of rosuvastatin on the vessels was also revealed – a significant decrease in the SBP – by 8 mm Hg. Art., DBP – at 6 mm Hg. Art.

The study confirmed the pronounced hypolipidemic effect of Crestor.

Thus, the new hypolipidemic drug rosuvastatin has not only a pronounced hypolipidemic effect, but also a positive effect on the vessels, contributing to microcirculation and a decrease in blood pressure in patients with dyslipidemia and mild and moderate arterial hypertension . Of course, the indicated vascular effects of Crestor can positively affect the effectiveness of the prevention of CCO during long-term therapy with this statin.

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