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In patients with moderate, dietary noncorrigible hyperlipoproteinemia type IIb and ischemic heart disease, treatment with nicotinic acid is limited by the side effects of the drug. In 100 patients, 6-month treatment with nicotinic acid (n = 50) or "essential" phospholipids (EPL); Lipostabil, manufacturer: Rhone-Poulenc Rorer) (n = 50) indicated comparable efficacy for both substances: Significant (p < .001) reductions of serum total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride values were similar in both groups, while nicotinic acid increased high-density lipoprotein (HDL) cholesterol significantly (p < .01) better than Lipostabil. A detailed analysis of ultracentrifugal lipoprotein profiles, hydroperoxide concentrations in LDL, and cholesterol-accepting properties of HDL in a small number of Lipostabil- and nicotinic acid-treated patients revealed favorable shifts in the lipoprotein profile, significant (p < .05) reductions of LDL hydroperoxides, and favorable increases of the most antiatherogenic HDL2b subfraction only in the Lipostabil-treated group. Clinically, both medications reduced the intensity and number of angina pectoris attacks per week (p < .05), but only Lipostabil-treated patients significantly (p < .05) increased their working capacity in the veloergometric test. Since in the nicotinic acid-treated group dropouts (nine patients, eight related to the drug) and side effects [14] exceeded those in the Lipostabil-treated group (two dropouts not related to the drug, no side effects), it is suggested that Lipostabil is a preferable alternative in the treatment of patients with moderate, dietary noncorrigible hyperlipoproteinemia IIb and ischemic heart disease.

Our review addresses the development of the cholesterol concept of atherogenesis from the classical investigations of Anitchkov and Chalatov (1913), who induced experimental cholesterol atherosclerosis in rabbits, to the present time. We conclude that based on data obtained to date relating to the presence of different classes of lipoproteins in blood, on the role of peroxidatively modified low density lipoproteins in atherogenesis, and on the involvement of various arterial and blood cells and other factors, the cholesterol concept of atherogenesis has not lost its significance. Moreover, cholesterol-lowering therapy has a leading role in the primary and secondary prevention of coronary heart disease events and other clinical manifestations of atherosclerosis.

It is shown that cholesterol may interact with some substances containing the guanidine group (guanidine itself, arginine, metformin and dodecylguanidine bromide) and with arginine-rich proteins--apoproteins A-I and E. In the latter case the interaction produces the formation of cholesterol-apoprotein complexes. Analysis of such complexes has shown that one apo A-I molecule binds 17-22 and one apo E molecule binds 30-35 sterol molecules, which approximately corresponds to the amount of arginine residues in these proteins. Formation of cholesterol-apoprotein complexes has been suggested to occur due to: (1) formation of hydrogen bond and/or ion-dipole interaction between cholesterol hydroxyl and guanidine groups of the apoprotein arginine residues and (2) hydrophobic interaction of the cholesterol aliphatic chain with nonpolar side chains of the amino acids occupying the third position from arginine in the protein molecule.

Summary: Adult Russian males (ages 40-49) have recently been shown, in collaborative Lipid Research Clinic (LRC) studies, to have substantially higher (8-10 mg/dl) plasma high-density lipoprotein cholesterol (C-HDL) than adult American males. Since C-HDL has a powerful inverse correlation with the risk of developing coronary heart disease, elucidation of the etiology of cross-cultural differences in C-HDL may be important in developing approaches to prevent or ameliorate coronary heart disease. This LRC study, using identically standardized LRC laboratories, focused on cord blood C-HDL in 423 neonates of Leningrad (USSR) and 425 neonates of Cincinnati (USA) to determine whether, like Russian adults, Russian neonates had higher C-HDL levels. Mean C-HDL levels in male and female American neonates were slightly (1-2 mg/dl), but not significantly higher (P = 0.22, 0.22) than in male and female Russian neonates, respectively. In subsets of the neonate American (260 of 425) and Russian (174 of 423) groups, mean C-HDL levels were 3 mg/dl and 3 mg/dl higher, respectively, in male and female American neonates than in their Russian counterparts, and these small mean differences were statistically significant, P < 0.025. Thus, adult Russian-American differences in C-HDL were not echoed by comparisons of neonates, using identical laboratory methods for lipoprotein determination. The within-culture, cross-sex comparisons of cord blood lipids and lipoproteins, did, however, parallel findings in older children and young adults. Both female American and Russian neonates had higher C-HDL levels than did males (P = 0.001, 0.002). Within the limits of inheritance as expressed by cord blood lipoproteins, the dichotomy between Russian and American neonates and adults for C-HDL suggests that higher adult Russian C-HDL levels may possibly reflect an aggregate of variables grouped under the term "environmental effect." Speculation: Because population studies and studies of kindreds with familial hyper-α-lipoproteinemia reveal a strong inverse correlation of C-HDL with coronary heart disease, the elucidation of the etiology of cross-cultural and cross-racial differences in C-HDL might have considerable importance in identifying "protective" environmental differences relevant to development of coronary heart disease.