The distributions of plasma lipids, lipoproteins, and apoproteins of 14 524 female and male black and white participants 45 to 64 years old in the Atherosclerosis Risk in Communities (ARIC) Study are presented. All specimens were analyzed at a central laboratory. Mean total cholesterol levels increased with increasing age across all ages from 204 to 229 mg/dL (12%) in women and from 208 to 213 mg/dL (2%) in men. Triglyceride levels increased with age in women, remained stable in men, and were higher in whites than blacks. High-density lipoprotein (HDL) cholesterol levels were higher in black and white women (range, 57 to 59 mg/dL) compared with black men (49 to 52 mg/dL) or white men (42 to 43 mg/dL). Cholesterol associated with HDL was distributed in a relatively constant proportion between HDL] (70% to 76%) and HDL 2 (24% to 30%) for all race/sex groups. Low-density lipoprotein (LDL) cholesterol levels increased with age in black (14.7%) and white (17.1%) women and in black (4.4%) and white (3.7%) men; more than 50% of all participants had LDL cholesterol levels > 130 mg/dL. Apoprotein A-I and B levels followed the same trends as HDL cholesterol and LDL cholesterol levels, respectively. Lipoprotein(a) [Lp(a)J levels were twice as high in blacks as in whites, and women's Lp(a) levels were higher than men's Lp(a) levels for each race. Menopause was associated with elevated total cholesterol, LDL cholesterol, apoprotein B, and Lp(a) levels, and hormone replacement medication use in postmenopausal subjects was associated with higher HDL cholesterol, triglyceride, and apoprotein A-I levels and lower LDL cholesterol, apoprotein B, and Lp(a) levels. (Arteriosclerosis and Thrombosis 1993;13:1139-1158) KEYWORDS • epidemiology • sex • lipoproteins • race C ardiovascular diseases are currently the leading causes of death and disability in both women and men in the United States. 12 Epidemiological evidence from more than 40 prospective studies has shown strong independent relations between various classes of cholesterol-containing particles in the plasma and the incidence of coronary heart disease.310 These data, plus additional evidence from animal and cellular research, leave little doubt that plasma lipids, especially cholesterol, are fundamentally involved in the atherogenic process.The Atherosclerosis Risk in Communities (ARIC) Study is a prospective epidemiological study to investigate the etiology of atherosclerosis and its clinical sequelae and variation in cardiovascular risk factors, medical care, and disease by race, sex, geographical community, and time. 11The ARIC Study was designed to recruit 4000 black and white representative individuals between the ages of 45 and 64 in each of four communities. Thus, the ARIC Study provides an opportunity for examining lipid and lipoprotein levels among men, women, blacks, and whites. The last study detailing plasma lipid and lipoprotein distributions among several US communities was performed by the Lipid Research Clinics Program.8 ' 911 At the same time, the National ...

a]), can each be implicated with a specific component of these disease processes. The apoB moiety is similar in molecular weight and amino acid composition to apoB in low-density lipoprotein (LDL), the major carrier of cholesterol in the blood.

SUMMARY. We tested the effects of low doses of a dihydropyridine calcium antagonist, PN 200110, on endothelium-dependent vascular relaxation in rabbits fed a 1% cholesterol diet. The drug was given orally, 1 mg/day, and control rabbits received placebo. Plasma total cholesterol after 10 weeks, was similar in the placebo-and PN 200110-treated groups. The respective values averaged 2140 ± 116 (n = 14; mean ± SEM) and 2012 ± 115 mg/dl (n = 13). In placebo-treated rabbits, sudanophilic aortic lesions covered 52 ± 5% of the intimal surface, and the aortic cholesterol concentration was 72 ± 6 mg/g protein. Corresponding values in aortas from PN 200110-treated rabbits were significantly lower [36 ± 5% (P < 0.03) and 52 ± 3 mg/g protein (P < 0.03)]. Maximal endothelium-dependent cholinergic relaxation of aortic strips in untreated (n = 14) and treated cholesterol-fed rabbits (n = 13) differed significantly (P < 0.01) and averaged 31 ± 4% and 61 ± 7% of the value in normocholesterolemic controls (n = 13). We conclude that cholesterol feeding suppresses endothelium-dependent relaxation evoked by acetylchoUne, and that PN 200110 reduces the severity of atherosclerosis and impairment of endothelium-dependent relaxation. (CircRes 58: 305-309, 1986) RECENT studies indicate that calcium antagonists such as nifedipine (Henry and Bentley, 1981; Panagotopoulios and Nayler, 1984;Willis et al., 1985;Miyazaki et al., 1985), verapamil (Rouleau et al., 1983;Blumlein et al., 1984), nicardipine (Willis et al., 1985), diltiazem (Ginsburg et al., 1983), and flunarizine (Ginsburg et al., 1983) may suppress atherogenesis in cholesterol-fed rabbits. In addition, experiments with arterial smooth muscle cells in culture suggest that calcium antagonists may inhibit cell migration (Nakao et al., 1983), influence the uptake and catabolism of lipoproteins (Stein et al., 1985), and promote the depletion of intracellular cholesteryl ester stores (Etingin and Hajjar, 1985). Anti-atherosclerotic effects of calcium antagonists may be related to those of LaCl 3 and calcium-chelating agents (Kramsch et al., 1981), since these agents are known to inhibit calcium-dependent reactions. Organic or inorganic calcium antagonists and chelating agents appear to exert their antiatherogenic effects without altering circulating lipoproteins, but detailed analyses of circulating lipids and lipoproteins in animals treated with these drugs have not been reported (Henry, 1985).One important question is whether calcium antagonists protect against the effects of hypercholesterolemia by lowering arterial pressure (Henry and Bentley, 1981). Therefore, in this study, we treated cholesterol-fed rabbits with a calcium antagonist in a dosage that exerted no hypotensive effect. In addition, since endothelial injury may play an important role in atherogenesis, we addressed the question whether atherogenesis in cholesterol-fed rabbits is associated with impaired endothelial function. Recent studies have demonstrated that cholinergic relaxation of isolated arteries depends upon ...

Apolipoprotein[a], the highly glycosylated, hydrophilic apoprotein of lipoprotein[a] (Lp[a]), is generally considered to be a multimeric homologue of plasminogen, and to exhibit atherogenic/thrombogenic properties. The cDNA-inferred amino acid sequence of apo[a] indicates that apo[a], like plasminogen and some zymogens, is composed of a kringle domain and a serine protease domain. To gain insight into possible positive functions of Lp[a], we have examined the apo[a] primary structure by comparing its sequence with those of other proteins involved in coagulation and fibrinolysis, and its secondary structure by using a combination of structure prediction algorithms. The kringle domain encompasses 11 distinct types of repeating units, 9 of which contain 114 residues. These units, called kringles, are similar but not identical to each other or to PGK4. Each apo[a] kringle type was compared with kringles which have been shown to bind lysine and fibrin, and with bovine prothrombin kringle 1. Apo[a] kringles are linked by serine/threonine- and proline-rich stretches similar to regions in immunoglobulins, adhesion molecules, glycoprotein Ib-alpha subunit, and kininogen. In comparing the protease domains of apo[a] and plasmin, apo[a] contains a region between positions 4470 and 4492 where 8 substitutions, 9 deletions, and 1 insertion are apparent. Our analysis suggests that apo[a] kringle-type 10 has a high probability of binding to lysine in the same way as PGK4. In the only human apo[a] polymorph sequenced to date, position 4308 is occupied by serine, whereas the homologous position in plasmin is occupied by arginine and is an important site for proteolytic cleavage and activation. An alternative site for the proteolytic activation of human apo[a] is proposed.