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Objective: To assess the efficacy of non pharmacological primary prevention of hypertension., Methods: Analysis of all the available trials with a minimal one-year follow-up and one recently study with 8 weeks follow-up. The outcomes consisted in blood pressure changes and incidence of hypertension at the end of the study., Results: Five reviewed randomized controlled trials with a minimal one year follow-up and one recently study with eight weeks follow-up assessed the following intervention: advice about sodium restriction, weight reduction, physical exercise and relaxation, a diet rich in fruits vegetables and low fat dairy foods. All the results were available according to the "intention to treat principle". The feasibility appeared to be initially good, but decreased with time, confirming the difficulty of long term prevention. The prevention effect was mild with a decrease in hypertension incidence of a few percent (2%) and blood pressure decrease of only a few mmHg reduction (mean of 3 mmHg). Three community studies were reviewed. The prevention interventions were carried out on entire populations. The feasibility was bad (great number of lost-follow-up). The results on the blood pressure incidence were available in only one study and the blood pressure decrease estimates were heterogeneous, so the results cannot be generalized., Conclusion: The primary prevention of hypertension shows disappointing results when the intervention duration is above one year. It leaves little hope for a significant effect on blood pressure dependent cardiovascular events.

This study describes the relationship between nitroglycerin, isosorbide dinitrate, sodium nitroprusside, and carbonic anhydrase I, as well as the involvement of this carbonic anhydrase I in vasodilation. Two groups of coronary patients and a group of rabbits underwent treatment with the above-mentioned vasodilating drugs. The activity of red blood cell carbonic anhydrase was monitored and determined by the stopped-flow method. The results show that these drugs inhibit the activity of the isozyme in parallel to their vasodilating effect. The results of this study lead to the hypothesis that through the pH modifications induced by these vasodilators by the inhibition of carbonic anhydrase I, the isozyme may be involved in the regulation of vascular tonus.

Interleukin 6 (IL-6) and interleukin 8 (IL-8) are present in the human arterial atherosclerotic wall as cellular and extracellular deposits in the connective tissue matrix. Quantitative determinations of IL-6 by ELISA showed mean values of 27.6 +/- 3.3 ng/100 mg protein in normal intima, 37.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 25.7 +/- 4.3 ng/100 mg total extracted protein in media. IL-8 levels were 3.5 +/- 0.6 ng/100 mg protein in normal intima, 11.3 +/- 2.1 ng/100 mg protein in fibrous plaque and 8.5 +/- 1.4 ng/100 mg total extracted protein in media. Fibrous plaques presented statistically significant higher levels of both IL-6 and IL-8. IL-6 and IL-8 gene transcripts were present in human iliac fibrous plaque and media prelevated at surgery indicating that a local production by the cells of the arterial wall participate to their accumulation. We also tested the role of complement activation in induction of IL-6 and IL-8 protein synthesis as well as the subsequent activation of endothelial cells. Only IL-8 was induced by complement activation and this may contribute to increased IL-8 levels found in the atherosclerotic wall. When exposed to terminal complement complexes, endothelial cells in culture also showed an increase of both DNA-synthesis and p70 S6 kinase activity indicating that complement is able to induce not only IL-8 synthesis but also cell activation. The presence of IL-6 and IL-8 in the arterial wall where complement activation also occurred, clearly show the involvement of inflammatory events in initiation and progression of atherosclerosis.

The neoantigens of the C5b-9 complement complex, IgG, C3, C4, S-protein/vitronectin, fibronectin, and macrophages were localized on 17 samples of breast cancer and on 6 samples of benign breast tumors using polyclonal or monoclonal antibodies and the streptavidin-biotin-peroxidase technique. All the tissue samples with carcinoma in each the TNM stages presented C5b-9 deposits on the membranes of tumor cells, thin granules on cell remnants, and diffuse deposits in the necrotic areas. When chemotherapy and radiation therapy preceded surgery, C5b-9 deposits were more intense and extended. The C5b-9 deposits were absent in all the samples with benign lesions. S-protein/vitronectin was present as fibrillar deposits in the connective tissue matrix and as diffuse deposits around the tumor cells, less intense and extended than fibronectin. IgG, C3, and C4 deposits were present only in carcinoma samples. The presence of C5b-9 deposits is indicative of complement activation and its subsequent pathogenetic effects in breast cancer.

Tumor necrosis factor-alpha (TNF-alpha) was demonstrated in human normal and atherosclerotic aorta, iliac and femoral arteries by immunohistochemistry using monoclonal and polyclonal antibodies. TNF was present in the cells of the arterial wall and as granular and diffuse extracellular deposits in the connective tissue matrix. Quantitative determinations of TNF by ELISA showed mean values of 21.7 +/- 0.7 ng/100 mg total extracted protein in normal intima, 38.2 +/- 0.5 in intimal thickenings, 25.5 +/- 1.1 in fibrous plaques and 16.8 +/- 0.2 ng/100 mg total extracted protein in media. Intimal thickenings presented the highest amounts of TNF with a statistically significant difference when compared to normal intima (P less than 0.05) and media (P less than 0.01). TNF-alpha concentrations in arterial eluates were about 200 times higher than in the corresponding serum samples. Western blotting analysis confirmed TNF-alpha eluted from the arterial wall to be about 17 kDa similar to human recombinant TNF-alpha. TNF-alpha in human atherosclerotic wall could be actively involved in the inflammatory events associated with atherosclerosis.

The study included 62 patients with atherosclerosis obliterans of the lower extremities, of whom 47 in stage II, 5 in stage III and 10 in stage IV of the disease. In 22 patients were present single arterial obliteration, in 30 patients multiple, layered arterial obliterations, in 8 distal arterial obliterations and 2 a diffuse atherosclerosis of the lower extremities. Patients were examined in admission to the clinic, after the treatment performed at the clinic and at various intervals, during 2-4 years. The segmental arterial pressure, the pressure index and the ultrasonogram recorded with the Cardior electrocardiograph were followed-up. The arterial pressure and the pressure indices returned to normal values only after invasive procedures. The medical treatment can bring about the clinical regression and stabilization of the disease, as well as the improvement of the ultrasonogram. For the choice of therapeutic means, the pressure index is the best criterion, since it correlates with the severity of the disease. In the case of a pressure index 0.75, the medical treatment or the transluminal dilatation is preferred, whereas at an index of 0.7 the surgical revascularisation is considered necessary. Other ultrasonic parameters were also taken into account, such as the systolic passage time and the maximum velocity, which are less important in the attainment of the mentioned aims.(ABSTRACT TRUNCATED AT 250 WORDS)

Decay-accelerating factor (DAF) is an intrinsic membrane inhibitor that regulates the activity of C3 and C5 convertases of the classical and alternative complement pathways. Using two monoclonal antibodies, IC6 and IA10, DAF was localized by immunohistochemistry using streptavidin-biotin-peroxidase complex or silver-intensified immunogold techniques in aortic, iliac and femoral samples obtained at surgery and autopsy from 32 patients. DAF was localized on the cells and in the connective tissue matrix of the arterial wall. Fibrous plaques and intimal thickenings presented larger amounts than fatty streaks, intimae and normal areas. By Western blotting analysis, DAF extracted from the arterial wall had a molecular weight of about 67 kDa. Using a double-labeling technique, DAF and C5b-9 complexes were co-localized on nucleated cells and on cell debris. The cells isolated after enzyme digestion of the arterial wall were tested for the protective role of DAF to complement-mediated damage. When DAF of the sensitized cells was blocked by monoclonal antibodies, complement-mediated cell lysis was enhanced from 10-15% to 60-70%. The effect of anti-DAF antibodies was dose-dependent. DAF blocking in the absence of antibodies used for sensitization led to a lysis under 10%. These data suggest a protective role of DAF against autologous complement activation, however insufficient to prevent complement activation in the human atherosclerotic wall.

Concentration and preferential retention of immunoglobulins and complement components were studied in comparison with other plasma proteins in 42 human aortae with atherosclerosis. Saline and acid extracted IgG, IgA, IgM, C1q, C3c, C4, C9, C3A, C-reactive protein, alpha 1-antitrypsin, alpha 2-macroglobulin, albumin, transferrin and fibrinogen were quantitatively determined using the radial immunodiffusion. The fibrous plaques and their adjacent areas contained higher levels of each protein than intima with only fatty streaks. No significant differences were found between the fibrous plaques and their adjacent areas presenting intimal thickenings. Saline eluted IgG and IgA were significantly higher in the fibrous plaque intima than in intimal samples with fatty streaks and were the only proteins detected in the acid eluates. The complement components were present in all saline eluates, while C-reactive protein was found in 23 samples. Crossed immunoelectrophoretic studies showed the activation of saline C3 and C4. In 8 cases serum levels of the studied proteins were compared with their concentration in saline eluates obtained from intima and media. The immunoglobulins and complement components presented higher intima/serum and lower media/intima retention ratios than the other studied proteins suggesting their preferential retention in the intima. The presence of immune related proteins in the atherosclerotic intima and their preferential retention might be explained not only by an altered permeability but also in relation to their function.

The co-localization of terminal C5b-9 complement complexes and macrophages was investigated in human arteries with atherosclerosis using a double-labeling immunohistochemical technique. Macrophages were found in all the atherosclerotic arteries, with the accumulation correlating positively with the degree of atherosclerosis. This accumulation was associated with an increase of C5b-9 deposits, as well as with an increase in the number of deposits containing both complement components and macrophages ('co-localization'). This co-localization was found to pertain both to intact macrophages and to macrophage remnants. These data suggest that C5b-9 complement complex might be formed on macrophages with subsequent promotion of inflammatory events and progression of the atherosclerotic lesions.

S-protein/vitronectin is a multifunctional glycoprotein interacting with both complement activation and coagulation pathways. Its presence was investigated in 5 femoral and 5 iliac atherosclerotic human arteries, obtained at surgery, by immunoelectron microscopy using an affinity purified rabbit IgG specific for human S-protein/vitronectin. The immunoelectron dense specific deposits were found in both intimal thickenings and fibrous plaques in association with elastic fibers, collagen bundles and cell debris in the vicinity of elastin. Cell debris embedded in the collagen matrix were S-protein/vitronectin negative. S-protein/vitronectin was also absent on intact cells, lipid droplets and cholesterol clefts. All cell debris, however, was positive for C5b-9 deposits suggesting that complement activation had occurred at these sites with or without S-protein/vitronectin interaction. S-protein/vitronectin may play a role in the arterial wall defence by restricting the extent of complement activation.

The absolute and relative bioavailability of nifedipine (1) from different formulations administered as single oral doses in healthy volunteers was determined. Serum concentrations of 1 were measured by GC. The absolute bioavailability of 1 was 53% because of presystemic metabolism. The bioavailability of Adalat (Bayer) tablets, Nifedipina (Terapia) and Corinfar (VEB Arzneimittelwerk Dresden) sugar-coated tablets was 93%, 92% and 86% (respectively) as compared with Adalat capsules. The AUC were not significantly different. The Cmax and tmax values were different, indicating that the absorption of 1 showed differences in first-order rate constants of dissolution in the above mentioned order. Despite the differences among the formulations studied, each preparation may have its merits. In a multiple dose regimen of 20 mg 1 (Nifedipina, Terapia) t.i.d., minimal therapeutic drug levels were achieved and maintained during steady state, from the 1st d of treatment.

Gamma-glutamyltransferase (gamma-GT) was found to exceed the upper normal limit in 31 of the 32 patients with liver metastases verified during surgery or at autopsy, while the level of this enzyme was normal in 25 of the 28 patients with proven neoplasma but without evidence of metastatic involvement of the liver. Particularly high values of gamma-GT activity were noted in 9 patients in whom liver metastases were accompanied by clinical jaundice. A similar behaviour was noted for alkaline phosphatase but changes affecting this enzyme were less obvious. Thus, for a mean increase of gamma-GT to levels up to seven times the upper normal limit, the level of alkaline phosphatase increased only three times. A decrease of serum pseudocholinesterase occurred in most patients with neoplasma, the process being more evident when liver metastases were present. It is concluded that an increase of gamma-GT in a patient with neoplasma could be considered as a marker of hepatic metastases, if chronic alcoholism or hepatobiliary disease can be excluded.

Decreased levels of serum cholesterol and beta-lipoproteins occurring in hyperthyroidism were found to be accompanied by an enchanced activity of pseudocholinesterase, while in patients with myxedema, the pathologically increased levels of serum cholesterol and beta-lipoproteins were associated with diminished serum pseudocholinesterase activity. The percentage of the pre-beta fraction was found to be increased in both hypo- and hyperthyroid patients, but mechanisms leading to this change are probably different in the two pathological conditions. The behaviour of cholesterol and pseudocholinesterase activity and especially the ratio between these paramameters might be used for the diagnosis of thyroid disease and for the control of therapeutic efficiency.

Serum concentration of ionic calcium and the effect of dietary salt restriction on serum total calcium was studied in patients with essential arterial hypertension. The concentration of serum ionic calcium was significantly lower than in controls in all the evolutive stages of the disease (p less than 0.005; p less than 0.005; p less than 0.001). During salt restriction serum total calcium rises significantly (p less than 0.005) as compared with the values found under a salt containing diet. It was suggested that increased chronic ingestion of sodium or restriction of dietary salt produces alterations in Na-Ca exchanges across semipermeable membrane of the smooth muscle.

Electrocardiographic signal recorded in right unipolar leads (2V1, 3V1, V1) was amplified (up to 500,000 times) averaged (256 or 512 cardiac cycles) and finally digitally filtered, in order to record His-Purkinje (HP) activity. A group of 41 patients with sinus rhythm and PR intervals ranging between 100 and 250 ms was repeatedly investigated. Distinct and highly reproducible waveforms located in the PR segment, attributable to HP activity, were recorded on the averaged unfiltered traces in 14 patients (34%). Waveforms, with an amplitude ranging between 4 and 80 microV, were positive in 13 patients and negative in one. In one patient, with atrial tachycardia with 2:1 atrioventricular block, two positive successive deflections suggested the possibility of recording the proximal and distal His activity. Externally recorded averaged unfiltered traces could be useful for the investigation of HP activity in a relatively large proportion of patients.

The relationship between macrophages and the terminal C5b-9 complement complexes was investigated in human arteries affected with atherosclerosis by using monoclonal antibodies and indirect immunoperoxidase, immunogold silver staining, and double-labeling immunohistochemical techniques. Macrophages were found in all the atherosclerotic arteries as immunoreactive deposits with a nucleus, considered as intact cells, or without a nucleus, considered as cell remnants. The double-labeling technique shows C5b-9 deposits partially colocalized on the intact macrophages or on the cell debris of macrophage origin. These data suggest that C5b-9 complement complex may be formed on activated or dying macrophages with subsequent promotion of inflammatory events and progression of the atherosclerotic lesions.

Cardiac arrhythmias, investigated in 1000 persons subjects to a submaximal exercise test, showed an incidence of 6%. The most frequent were the ventricular premature beats, related in more than half of the cases to an organic, probably ischemic, heart disease. Left bundle branch block and ventricular tachycardia were rare and indicated an organic heart disease. Several other rare arrhythmias are discussed. In patients with exercise-induced cardiac arrhythmias, an increased ratio of the tension-time index to maximal oxygen consumption indicates an uneconomical and less efficient cardiac work. The increase of the PEP and of the PEP/LEVT ratio during recovery, in the subjects exhibiting exercise-induced ventricular premature beats, also suggests a lowered cardiac efficiency. These findings support the view that cardiac arrhythmias frequently coexist with an organic, especially ischemic, heart disease.

The presence of the terminal C5b-9 complement complex in tissues indicates that complement activation has occurred in situ with subsequent membrane damage, tissue injury, and inflammatory response mediation. The terminal C5b-9 neoantigens of the complement system, S protein C3c, C3d, and apolipoprotein B deposits were localized in 20 aortic fibrous plaques, 12 aortic intimal thickenings, 8 aortic fatty streak intimae, 14 coronary fibrous plaques, 5 coronary intimal thickenings, and 8 femoral fibrous plaques, using an indirect and double-staining immunoperoxidase technique. The specific granular deposits were present from the early to the advanced stages of atherosclerosis in relation to the degree of fibrosis and necrosis. The different double-staining localization of C5b-9 and S protein may suggest local assembly of the complex as a consequence of complement activation and may sustain its role in the chronic progression of atherosclerosis.

The serum concentration of Zn and Cu were determined in 126 controls and 160 patients with atherosclerosis obliterans (AO) and 53 patients with thromboangiitis obliterans (TO). The concentration of serum Zn decreases with age both in controls and patients with AO in all the evolutive stages of the disease. In patients with TO, the concentration of serum Zn shows no correlation with age. The significantly lower values of serum Zn in controls and patients with AO over 61 yr than those below this age is attributed to the decreased Zn supply, especially to some individual cellular abnormalities. The values of serum Cu are higher in patients with AO and TO than in controls irrespective of the evolutive stage of the disease. This was related to cigarette smoking and inflammation. The Zn/Cu ratio in the serum is below 1 in patients with AO and TO and in controls over 61-yr-old. The pathogenetic role of this ratio in atherosclerosis and inflammation still remains a controversial question.

Circulating immune complexes (CIC) were characterized for the content in IgG, IgA, IgM, C3 and C4 in patients with heart disease. The levels of IgG, IgM and C4 in PEG-precipitates of patients' sera were significantly higher than those found in controls, and the precipitation profile was similar to that of rheumatoid arthritis patients. Differences were observed in the composition of CIC: IgM was highest in association with myocarditis, and C3 predominated in cases of valvular disease. Complex-bound C4 was significantly higher in patients with myocardial infarction which developed pericarditis either early or late in the evolution of the disorder. Antimyocardial antibodies could be detected in sera and in corresponding PEG-precipitates. The bulk of the data suggests that CIC might play a pathogenetic role in various heart diseases.

The terminal C5b-9 complement complex was investigated in 15 aortic, 2 femoral fibrous plaques and 5 fatty streaks aortic intimae using indirect immunofluorescence and immunoperoxidase. All the fibrous plaques presented C5b-9 deposit-like threads in the fibrous cap and masses in the amorphous areas of the plaque. The deposits were frequently associated with other immune-related proteins such as: IgG, IgA, IgM, Clq, C3c and C4 which were simultaneously investigated. Fatty streaks intimae presented no C5b-9 and complement component deposits. Whereas the demonstration of the complement components could merely reflect a non-specific trapping, the presence of assembled C5b-9 in the damaged tissue is more indicative of the involvement of complement activation in the progression of atherosclerotic lesions.

Serum concentration of Na, K, Ca, Mg and inorganic phosphate as well as serum levels of Zn and Cu were determined in control subjects and in patients with essential arterial hypertension (EAH) divided according to the stage of the disease. No significant differences were found between the serum mean levels of Na, K, Ca, Mg, Zn and Cu in controls and in patients with EAH. A significant decrease of the serum Zn was noted in the third stage of EAH. A number of cases with hypomagnesemia and/or hypopotassemia probably caused by a long term uncontrolled therapy was also detected. The concentration of inorganic phosphate was significantly lower in patients with EAH associated with overweight than in hypertensive patients with normal body weight and in controls. It is considered that a sustained study of the complex interrelationship between electrolyte interaction and the functional aspects of the arterial wall could still contribute to a better understanding of pathogenic aspects of EAH and of its complications including those subsequent to modern diuretic therapy.

The terminal C5b-9 neoantigens of the complement complex, S-protein (Vitronectin), C3c, C3d and apolipoprotein B were localized on 16 aortic fibrous plaques, 8 aortic intimal thickenings, 4 fatty streaks intimae, 12 coronary fibrous plaques, 3 coronary intimal thickenings, 6 femoral and 5 basilar fibrous plaques, using an indirect and double-staining immunoperoxidase method. The granular specific deposits were localized in the fibrous cap and deeper parts of the plaque or in the deeper intima and inner-third media of intimal thickenings and fatty streaks intimae, in relation to the degree of atherosclerotic involvement. The different localization of C5b-9 and S-protein demonstrated by the double-staining technique is more suggestive for the assembly of the complex into the arterial wall and not for its preformed passage from circulation. The relation of these immune deposits to the degree of fibrosis and necrosis and their presence from the initial stages through to the advanced lesions could ascribe a role to the complement system in atherosclerosis.

The concentrations of IgG, IgA, IgM, Clq, C3c, C4, C9, C3A, Albumin, Transferrin, Alpha-1-antitrypsin, Alpha-2-macroglobulin were determined in the serum, aortic atherosclerotic intima and media of 8 patients. The protein levels in the intima were dependent on their serum concentration. The passage of proteins from serum to media was investigated using the ratios between their intima/serum and media/intima concentrations. Immunoglobulins and complement components displayed higher intima/serum and lower media/intima ratios than the other proteins suggesting a preferential retention of the immune related proteins in the intima. This trapping into the intima seems to be related to their function too, suggesting a certain involvement in the progression of the atherosclerotic lesions.

The paper reports on the bioavailability of niphedipine in various pharmaceutic preparations administered in a single dose of 10 mg, per os, to volunteer subjects: Niphedipine dragees (Terapia, Cluj-Napoca), Adalat capsules (Bayer); Adalat coated tablets (Bayer and Birlaşik Alman Ilac Fabricalari, Istanbul) and Corinfar dragées (VEB Arzneimittelwerk, Dresden). In the blood samples collected, niphedipine was determined by a gas-chromatographic procedure. Pharmacokinetic analysis of the experimental data was made by a digital computer. Bioavailability of niphedipine was the best with Adalat capsules. The relative bioavailability of the other products was: tablets (Adalat); 93%; dragées (Niphedipine): 92%; dragées (Corinfar 86%). Absorption speed of Niphedipine decreases in the order: capsules, tablets, indigenous and imported dragées. Statistical analysis (Student test) shows that the differences in bioavailability among the preparations are not important. Efficiently therapeutic plasmatic concentrations are maintained for about 6 hours after a single dose of 10 mg administered as tablets and dragées and for 8 hours in the case of capsules. Important differences exist between the maximum concentration of niphedipine in blood, following some differences in the absorption speed, achieved after administration of capsules, on the one hand, and of tablets and dragées on the other hand. Choosing the type of tablet depends, therefore, on the nature of the affection treated. Niphedipine (Terapia) has corresponding biopharmaceutic properties and is useful in treating hypertension and for preventing and treating anginal attacks.

Saline and acid eluates of intima with only fatty streaks, fibrous plaque and intima surrounding the fibrous plaque were obtained from 42 human aortae. IgG, IgA, IgM, C1q, C3c, C4, C9, C3A, C-reactive protein, alpha-1-antitrypsin, alpha-2-macroglobulin, albumin, transferrin and fibrinogen were quantitatively determined in these eluates using the radial immunodiffusion technique. Saline extracted IgG and IgA were significantly higher in the fibrous plaque and adjacent tissue than in the fatty streak intima, where IgM was the highest. IgG and IgA were only present in acid eluates. The complement components were present in all saline eluates, but only traces of C3c and C1q in some acid eluates. Statistically significant differences were found for C1q and C9. C-reactive protein was present in 23 samples. The results could suggest an involvement of immune mechanisms in the progression of the atherosclerotic lesion.

The terminal C5b-9 complex of the complement system was localized in 26 aortic, 3 iliac and 4 femoral human fibrous plaques using indirect immunofluorescence and immunoperoxidase. IgG, IgA, IgM, Clq, C3c, C4, C9 and fibrinogen were investigated simultaneously. All the fibrous plaques presented C5b-9 deposits appearing like thin threads in the fibrous cap and masses and spots in the amorphous areas. The extent and intensity were in agreement with the size of the fibrous plaques. The intimal thickenings presented less intense deposits which were absent in atherosclerosis-free samples. The C5b-9 deposits were frequently associated with immunoglobulins and complement components in the same areas. Whereas the demonstration of complement components reflected only a nonspecific trapping, the presence of assembled C5b-9 in the damaged tissues is more indicative of the involvement of complement activation in the tissue injury. The absence of C5b-9 in the atherosclerosis-free intima and its presence at lower intensity in the intimal thickenings than in the fibrous plaques suggest a pathogenic involvement in the chronic progression of the atherosclerotic lesion.

The assembly of the terminal C5b-9 complement complex is a prime mechanism of complement-induced membrane damage followed by inflammatory response mediation and subsequent extensive tissue damage. In the assembly process the terminal complement components expose neoantigenic determinants which can be recognized by specific antibodies. Using such a specific antibody, affinity-purified rabbit IgG and by means of immunoelectron microscopy, the C5b-9 neoantigens were localized on the structures of the human fibrous plaque from 3 iliac and 3 femoral arteries obtained at surgery. The immunoelectron-dense deposits were localized on the cell debris, enmeshed in the connective tissue matrix, consisting of irregular particles that frequently had the shape and size of intracellular organelles or vesicles with concentric osmiophilic lamellae. No deposits could be found on the intact cells, on the connective tissue matrix or on cholesterol and lipid deposits. The presence of C5b-9 neoantigens deposits in the fibrous plaques frequently associated with other immune-related proteins indicates that complement activation has occurred in situ and could be related to the chronic progression of the atherosclerotic lesion.

Starting from experimental observations demonstrating that a high ratio of zinc to copper led to hypercholesterolemia in rats, serum Zn and Cu levels were measured by atomic absorption spectrophotometry in 65 normolipemic controls and in 100 subjects with various types of hyperlipoproteinemia (HLP). Serum Zn levels did not significantly differ from control values in any type of HLP. However, hyperlipoproteinemic patients with obvious clinical atherosclerosis displayed significantly lower serum-Zn concentration than hyperlipo-proteinemic subjects without clinical symptoms. On the other hand, when compared to control subjects, serum Cu levels were not found to be decreased, but rather increased, in hyperlipoproteinemic patients with or without atherosclerosis. As a result, the Zn∶Cu ratio appeared to be lower than normal in hyperlipoproteinemic patients with cardiovascular disease. It is conceivable that changes of these trace elements should be rather connected to vessel injury and associated disease than to HLP which, at least in humans, is not accompanied by a high Zn∶Cu ratio.