Perova Nv

Association of high-density-lipoprotein cholesterol with mortality and other risk factors for major chronic noncommunicable diseases in samples of US and Russian men

Previous reports from the Russian Lipid Research Clinics (LRC) study showed no association between the level of high-density-lipoprotein (HDL) cholesterol and mortality from coronary heart disease (CHD), while US LRC data indicated a strong negative association between HDL cholesterol and CHD mortality. This report investigated the association of HDL cholesterol and mortality in these same population samples with follow-up extended to 12 years. The association between HDL cholesterol and mortality remained inverse and significant in the US sample. In the Russian sample, high levels of HDL cholesterol were associated with higher risk of all-cause and cancer mortality, although adjustment for known risk factors reduced the strength of the association. The association between HDL cholesterol and CHD mortality was negative in the Russian sample, although the strength of the association was less than that for the US sample. Extended follow-up reduced the difference in the association between HDL cholesterol and mortality between the two countries; however, important differences remained. Further research will be required to clearly determine the cause for their differences.

Comparative study of the activity and composition of HDL3 in Russian and American men.

Previous studies conducted within the framework of the Lipid Research Clinics Program showed a strong inverse correlation between high-density lipoprotein cholesterol (HDL-C) level and coronary heart disease (CHD) risk in American male populations, whereas in Russian populations such a correlation was less pronounced. It was assumed that HDL was less protective of CHD in Russian than in American males. This study compared the functional activity and lipid composition of HDL3 isolated from the blood plasma of men with low, normal, and high HDL-C levels from Moscow (Russia) and Seattle (United States) populations. Results obtained showed that American HDL3, irrespective of the plasma HDL-C level, had higher activity in stimulating both [3H]cholesterol and cholesterol mass efflux from cholesterol-loaded fibroblasts and in suppressing cellular cholesterol esterification when compared with Russian HDL3. American HDL3 remained more active than Russian HDL3, even when apolipoprotein E-containing particles were removed from HDL3 by heparin-Sepharose affinity chromatography. Russian and American 125I-HDL3 had similar binding to high-affinity cell-surface sites, but Russian HDL3 had a higher nonspecific binding component compared with American HDL3. This study demonstrates for the first time potential functional differences between HDL particles isolated from Russian and American populations. The lower activity of Russian HDL3 in promoting cellular cholesterol efflux may partly explain the higher CHD risk in the Russian population compared with the American one.

Number of glucocorticoid receptors in lymphocytes and their sensitivity to hormone action

The study demonstrated a decreased level of glucocorticoid receptors (GR) in peripheral blood lymphocytes from hypercholesterolemic subjects, and an elevated level in patients with acute myocardial infarction. In the lymphocytes with a high GR number, dexamethasone inhibited [3H]-thymidine and [3H]-acetate incorporation into DNA and cholesterol, respectively, in the same manner as in the control cells. On the other hand, a decreased GR number resulted in a less efficient dexamethasone inhibition of the incorporation of labeled compounds. These data showed that the sensitivity of lymphocytes to glucocorticoids changed only with a decrease of GR level.

Effects of simvastatin on the phospholipid composition of high-density lipoproteins in patients with hypercholesterolemia.

We studied the phospholipid composition of high-density lipoproteins in patients with hypercholesterolemia before and after treatment with simvastatin. Individual phospholipids were separated by thin-layer chromatography on glass plates coated with silica gel. It was found that apart from hypolipidemic effect, simvastatin changed the concentration and phospholipid composition of high-density lipoproteins, which improved their cholesterol-accepting and cholesterol-transporting properties.

Phospholipid composition of high-density lipoproteins reflects lipolysis of triglyceride-rich lipoproteins during hyperlipidemia.

We studied phospholipid composition of high-density lipoproteins in patients with normo- and hypertriglyceridemia treated with various hypolipidemic preparations (simvastatin and fenofibrate). Both preparations changed phospholipid composition of high-density lipoproteins and improved their functional activity. The differences in the phospholipid composition of high-density lipoproteins were probably related to lipolysis of triglyceride-rich lipoproteins catalyzed by lipoprotein lipase and, in particular, hepatic lipase.

Simvastatin and Preparation of Polyunsaturated Phospholipids Produce Similar Changes in the Phospholipid Composition of High-Density Lipoproteins during Hypercholesterolemia

We studied the phospholipid composition of high-density lipoproteins in patients with coronary heart disease and hypercholesterolemia treated with simvastatin (Zocor, inhibitor of the key enzyme of cholesterol synthesis) and preparation of polyunsaturated phospholipids (lipostabil forte). Simvastatin produced a hypolipidemic effect and modulates the phospholipid composition of high-density lipoproteins (similarly to lipostabil forte). These changes contribute to functional activity of high-density lipoproteins in the reverse cholesterol transport.

EFFECT OF ENDUR-ACINE ON PLASMA ACTIVITY OF CHOLESTEROL ESTER TRANSFER PROTEIN IN SUBJECTS WITH HYPERCHOLESTEROLEMIA

The activity of cholesterol ester transfer protein was measured in the plasma of hypercholesterolemic patients before and after treatment with endur-acine, a new prolonged-action preparation of nicotinic acid. The activity was measured by a substrate-independent radioisotope method. It was found that improvement of the lipid-apoprotein parameters of the plasma after the treatment was accompanied by a reduced activity of cholesterol ester transfer protein.