Author/Editor     Reiner, Željko; Tedeschi-Reiner, Eugenia
Title     Vloga statinov v preprečevanju srčno-žilnih bolezni
Translated title     The role of statins in the prevention of cardiovascular diseases
Type     članek
Source     Krka Med Farm
Vol. and No.     Letnik 23, št. 33
Publication year     2002
Volume     str. 19-32
Language     slo
Abstract     The HMG-CoA reductase inhibitors, often referred to as the statins, are inhibitors of cholesterol synthesis in hepatocytes. They are specific, competitive inhibitors of the enzyme HMG-CoA reductase, which catalyses the first step in cholesterol synthesis - the conversion of HMG-CoA to mevalonate. As a result, hepatic LDL-receptor activity increases, leading to increased uptake of LDL and decreased plasma total and LDL cholesterol. Several secondary prevention studies (4S, CARE, LIPID) in the last decade have clearly demonstrated that secondary prevention of coronary heart disease (CHD) with statins should be essential treatment because it signi ficantly reduces cardiovascular morbidity and mortality and is cost-effective. There is increasing evidence, particularly from primary prevention studies (WOSCOP, AFCAPS/TexCAPS), that statins should be used in primary prevention of CHD as well, especially for high risk patients. The greater is the total and LDL cholesterol reduction, the better is the risk lowering effect. However, the beneficial effects of statins should not only be attributed to their cholesterol-lowering effects. They also reduce the enhanced susceptibility to oxidation of LDL particles, restore endothelial dysfunction, prevent arterial smooth muscle cell migration and proliferation, reduce platelet aggregation, improve impaired fibrinolysis and stabilize the plaque. Apart from these antiatherogenic effects they seem to increase bone formation, thus possibly reducing the risk of osteoporotic fractures, and may inhibit tumour cell growth as well.
Summary     Zaviralci reduktaze HMG CoA, imenovani tudi statini, zavirajo sintezo holesterola v celicah, zlasti jetrnih. To dosežejo z zaviranjem reduktaze HMG CoA, ključnega encima za začetek sinteze holesterola spremembe HMG CoA v mevalonat. Posledica je povečano število receptorjev za LDL na jetrnih celicah oziroma povečana aktivnost teh receptorjev. jetrne celice tako odstranjujejo iz krvi več delcev LDL, zaradi česar se zmanjša količina skupnega holesterola in holesterola LDL. Nekaj velikih raziskav v zadnjih desetih letih (4S, CARE, LIPID) je nedvomno pokazalo, da mora biti sekundarno preprečevanje koronarne bolezni (KB) s statini osnovni pristop, ker se na ta način lahko pomembno zmanjšata obolevnost in umrljivost zaradi srčno-žilnih bolezni. To je tudi finančno upravičeno. Vedno več podatkov, ki izhajajo iz velikih raziskav o primarnem preprečevanju KB (WOSCOP, AFCAPS/TexCAPS), dokazuje, da je statine treba dajati tudi v primarnem preprečevanju, predvsem bolnikom z velikim tveganjem. Učinek na zmanjševanje tveganja je tako večji pri osebah z nižjim skupnim holesterolom in holesterolom LDL. Koristni učinki statinov nikakor ne temelje le na uspešnem zmanjševanju količine holesterola v krvi. Zmanjšujejo tudi oksidacijo delcev LDL, odpravljajo moteno endotelno funkcijo, preprečujejo gibauje gladkomišičnih celic in njihovo razmnoževanje, zmanjšujejo agregacijo trombocitov in izboljšujejo spremenjeno fibrinolitično aktivnost, kar vse deluje protiaterogeno in stabilizira aterosklerotične lehe. Zdi se, da poleg protiaterogenih učinkov vzpodbujajo nastajanje kostne mase in morda zmanjšujejo tveganje za prelome kosti, ki so posledica osteoporoze, morda pa lahko zavirajo tudi rast tumorskih celic.
Descriptors     CARDIOVASCULAR DISEASES
CORONARY DISEASE
HYPERCHOLESTEROLEMIA
HMG-COA REDUCTASE INHIBITORS
CLINICAL TRIALS