Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up.

OBJECTIVE: To evaluate whether hematocrit (HCT) is associated with coronary heart disease (CHD) mortality in men over 55 years of age in Finland. METHODS: Health survey data were recorded in 1980 from 670 men, aged 55 years. The causes of deaths during a 28-year follow-up were obtained from official records. Statistical comparisons were done by Cox proportional hazard regression model after dividing the men into two groups, one with HCT<50% and the other, HCT> or =50%. RESULTS: There were altogether 412 deaths of all causes, including 140 from CHD. In men having HCT<50%, the crude CHD mortality rate per 10,000 population was 2203, while in men with HCT> or =50%, the corresponding figure was 4255. Men with HCT> or =50% were 2.4 times (95% CI 1.6-3.5) more likely to die from CHD than were men with HCT<50%. After adjusting for established coronary risk factors, the increased risk remained 1.8-fold (95 % CI, 1.1-2.7). CONCLUSIONS: Borderline polycythemia was associated with increased CHD mortality. The cut-off value in our study was > or =50%, proposing that for men over 55 years of age such HCT levels might be an additional risk factor.

Receptor-mediated binding and degradation of subfractions of human plasma low-density lipoprotein by cultured fibroblasts.

The receptor-mediated metabolism of human plasma low-density lipoprotein (LDL) subfractions was studied. LDL was isolated from healthy donors and further fractionated by density gradient ultracentrifugation into three subfractions: (I) d = 1.031-1.037, (II) d = 1.037-1.041 and (III) d = 1.041-1.047 g/ml, comprising 24 +/- 7%, 46 +/- 8% and 30 +/- 9% of the total LDL protein, respectively. As assessed by electron microscopy and gradient gel electrophoresis, the LDL particle size decreased and the relative protein content increased from fraction I towards fraction III. Fraction II had the highest (Kd 2.6 micrograms/ml) and fraction I the lowest (Kd 5.8 micrograms/ml) binding affinity to LDL receptors of human fibroblasts at 4 degrees C. The rate of receptor-mediated degradation of fraction II was also higher than that of the other two fractions at 37 degrees C. These results suggest that LDL subfractions have different rates of receptor-mediated catabolism depending on particle size or composition, and therefore their metabolic fate and atherogenic properties may also differ.

Paraoxonase gene polymorphisms and coronary reactivity in young healthy men.

This study examined the relationships between paraoxonase genotypes, coronary artery reactivity, and indices of low-density lipoprotein oxidation in healthy men. Impairment in coronary flow reserve, as assessed by positron emission tomography, is associated with lipoprotein oxidation, which is affected by high-density lipoprotein bound enzyme, paraoxonase. Paraoxonase has two common polymorphisms (M/L55 and R/Q192) that change the activity of the enzyme. Forty-nine healthy men (mean age 35 +/- 4 years) were divided by paraoxonase genotype into low (Q192/Q192, or M55/M55, M55/L55) and high-active (R192/Q192, R192/R192, or L55/L55) groups and related to the myocardial blood flow, to the susceptibility of low-density lipoprotein to oxidation, and the autoantibody titer against oxidized low-density lipoprotein. The blood flow was measured by positron emission tomography at rest and during adenosine infusion. The low-active Q192/Q192 genotype was associated with higher resting blood flow corrected for rate-pressure product compared to the high-active R192/R192 and R192/Q192 genotypes (P=0.011). The blood flow stimulated by adenosine was not significantly different in the low- and high-active genotype groups. Paraoxonase genotypes had no effect on low-density lipoprotein susceptibility to oxidation or autoantibody formation against oxidized low-density lipoprotein. Genotypes of paraoxonase may not clearly contribute to the early changes in coronary reactivity. Coronary vasomotor tone at rest appears to be modulated by paraoxonase R/Q192 polymorphism through mechanism(s) unrelated to low-density lipoprotein oxidation.

HDL enhances oxidation of LDL in vitro in both men and women.

BACKGROUND: Oxidative modification of low-density lipoprotein (LDL) is a key event in the oxidation hypothesis of atherogenesis. Some in vitro experiments have previously suggested that high-density lipoprotein (HDL) co-incubated with LDL prevents Cu2+-induced oxidation of LDL, while some other studies have observed an opposite effect. To comprehensively clarify the role of HDL in this context, we isolated LDL, HDL2 and HDL3 from sera of 61 free-living individuals (33 women and 28 men). RESULTS: When the isolated LDL was subjected to Cu2+-induced oxidation, both HDL2 and HDL3 particles increased the rate of appearance and the final concentration of conjugated dienes similarly in both genders. Oxidation rate was positively associated with polyunsaturated fatty acid content of the lipoproteins in that it was positively related to the content of linoleate and negatively related to oleate. More saturated fats thus protected the lipoproteins from damage. CONCLUSION: We conclude that in vitro HDL does not protect LDL from oxidation, but is in fact oxidized fastest of all lipoproteins due to its fatty acid composition, which is oxidation promoting.

Exercise enhances vasorelaxation in experimental obesity associated hypertension.

OBJECTIVE: Regular exercise is recommended for the non-pharmacological treatment of hypertension, but the mechanisms underlying the lowering of blood pressure remain controversial. Therefore, we studied the effects of 22-week-long training on blood pressure, arterial reactivity, and metabolic abnormalities in a model of genetic obesity and moderate hypertension. METHODS: Obese and lean Zucker rats were subjected to treadmill exercise from 8 to 30 weeks of age. Blood pressures were measured by the tail-cuff method, and urine was collected in metabolic cages. At the end of the study, the samples for biochemical determinations were taken, and reactivity of isolated mesenteric and carotid arterial rings was examined in standard organ chambers. RESULTS: The exercise prevented the elevation of blood pressure which was observed in non-exercised obese Zucker rats, and also reduced blood pressure in the lean rats. The relaxations of norepinephrine-preconstricted mesenteric and carotid arterial rings to acetylcholine and nitroprusside were clearly improved by exercise in the obese rats. In the lean rats exercise enhanced vasorelaxation to nitroprusside in the mesenteric and carotid rings, and to acetylcholine in the carotid preparations. The exercise-induced improvement of endothelium-mediated dilatation to acetylcholine was abolished by nitric oxide synthesis inhibition with NG nitro-L-arginine methyl ester, but not by cyclooxygenase inhibition with diclofenac or functional inhibition of endothelium-dependent hyperpolarization by precontractions with KCl. The urinary excretion of the systemic prostacyclin metabolite (2,3-dinor-6-ketoprostaglandin F1 alpha) was increased two-fold by exercise in the obese and lean rats, whereas that of the thromboxane A2 metabolite (11-dehydrothromboxane B2) remained unaffected. Treadmill training reduced blood glucose, cholesterol, and triglycerides, but did not affect the high levels of insulin in obese Zucker rats. CONCLUSIONS: These results suggest that the antihypertensive effect of long-term exercise in experimental obesity related hypertension is associated with improved vasodilatation. This is expressed as enhanced relaxation via endogenous and exogenous nitric oxide, and increased endothelial prostacyclin production. The improved control of arterial tone after training could be attributed to the alleviation of hyperlipidemia and insulin resistance, whereas hyperinsulinaemia per se remained unaffected.

Ubiquinol-10 and total peroxyl radical trapping capacity of LDL lipoproteins during aging: the effects of Q-10 supplementation.

Evidence is rapidly accumulating that oxidative modification of low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. In this study we measured the total peroxyl radical trapping capacity of human plasma LDL phospholipids (TRAPLDL) with a luminescent method. The study was carried out with 70 healthy volunteers, aged 28-77. In males an age-related decrease in TRAPLDL was observed. In the age group under 50 years the mean TRAPLDL was 31.36 +/- 1.45 pmol peroxyl radicals/nmol Pi; among those over 50 years it was significantly lower at 26.67 0.94 pmol/nmol Pi. As regards the components of TRAPLDL, the concentration of LDL-ubiquinol did not change and a non-significant decrease in the LDL-tocopherol concentration was detected with age. In females, the mean TRAPLDL, LDL-ubiquinol-10 and tocopherol concentrations did not differ between the age groups. When 17 of the participants were given coenzyme Q10 (Q10) supplementation, 100 mg/day, a highly significant increase in LDL-ubiquinol concentration was detected. Our results indicate that LDL antioxidant defenses tend to decrease with age in the Finnish male population. The decline is most significant in males under 50 years; in older age groups the values remain stable at a low level. Q10 supplementation doubles the number of ubiquinol-10-containing LDL molecules and may therefore have an inhibitory effect on LDL oxidation.

Oxidized low-density lipoprotein is chemotactic for arterial smooth muscle cells in culture.

The effects of human native and Cu2(+)-oxidized low-density lipoprotein (LDL) were tested on the migration of cultured bovine aortic smooth muscle cells (SMCs) in blind-well chambers. LDL oxidation was controlled by measuring the formation of conjugated dienes and lipid hydroperoxides, and by agarose gel electrophoresis. Oxidized LDL stimulated SMC migration, and the effect was dose-dependent up to 200 microgram/ml. The stimulation was chemotactic in nature. Native LDL was without significant activity. The results suggest that oxidized LDL may contribute to the migration of medial SMCs into the intima during atherogenesis.

The effect of short-term fasting, apolipoprotein E gene polymorphism, and sex on plasma lipids.

The effect of 1 wk of supervised fasting on plasma lipid concentrations in subjects with different apolipoprotein E (apo E) phenotypes was studied in 58 healthy free-living volunteers. The participants consumed an 870-kJ(208 kcal)/d liquid diet containing fruit and berry juices, tea, and water. The decline in plasma total cholesterol during 1 wk of fasting was 0.46 mmol/L in women and 0.35 mmol/L in men. The decreases were significant in both women and men. The response patterns of plasma total cholesterol were not significantly different between the sexes. In men, the changes in plasma low-density-lipoprotein cholesterol during the fast differed significantly (P = 0.0181) between the apo E phenotypes, whereas in women there were no differences due to phenotype (P = 0.695). The magnitude of the change in plasma triacylglycerol during the fast was different between the sexes (P = 0.0099). The changes in plasma triacylglycerols differed significantly between apo E phenotype groups in men (P = 0.0295) but not in women (P = 0.0661). Statistical comparison between different apo E phenotypes was performed with and without the small apo E3,2+E2,2 group, with essentially similar results. During fasting, plasma high-density-lipoprotein cholesterol concentrations decreased slightly but not significantly. The study shows significant differences in the associations of apo E alleles and sex on plasma lipid responses during fasting and illustrates the importance of gene-diet interactions in the regulation of lipid metabolism in humans.

Plasma apolipoprotein B in middle-aged Finnish men. Evidence for a regional gradient of apo B and lack of negative correlation between apo B and dietary linoleate in hyperapobetalipoproteinemia.

Plasma apolipoprotein B (apo B) concentrations were determined in 178 randomly selected 40-49-year-old men from Eastern and Southwestern Finland and compared with the concentrations of plasma lipids and the fatty acid composition of plasma and adipose tissue determined previously from the same populations. The plasma apo B concentrations ranged from 50 to 209 mg/dl. Although men from the two regions had similar mean concentrations of plasma triglyceride, total cholesterol and high density lipoprotein (HDL)-cholesterol, men from Eastern Finland had significantly higher mean apo B levels (139 +/- 25 mg/dl) and a lower ratio of total cholesterol to apo B (1.85 +/- 0.25) than the Southwestern men (125 +/- 33 mg/dl and 2.05 +/- 0.40, respectively). In the whole population, apo B and total cholesterol had significant negative correlations with the percentages of linoleate in the fatty acids of plasma and adipose tissue, which are known to reflect the quality of dietary fat. As the percentages of linoleate have previously been shown to be lower in the Eastern population, part of the regional difference in apo B is obviously explained by differences in the quality of dietary fat. On the other hand, men (n = 59) who had high plasma apo B (greater than 130 mg/dl) but low density lipoprotein (LDL)-cholesterol within the reference values (less than 5.17 mmol/l) showed no correlation between linoleate and apo B. This suggests that other factors than dietary fat determine the concentration of apo B in this group of men.

The effect of proteoglycans, collagen and lysyl oxidase on the metabolism of low density lipoprotein by macrophages.

To study the interactions of lipoproteins, connective tissue components and cells, mouse peritoneal macrophages were incubated in the presence of human low density lipoproteins (LDL) that had been complexed with pig aortic proteoglycans (PG) or incubated in the presence of soluble collagen and/or lysyl oxidase, which catalyses the formation of cross-linkages in collagen and elastin by oxidising epsilon-amino groups of lysine residues to aldehydes. Soluble and insoluble PG-LDL complexes increased the incorporation of [3H]oleate into cellular cholesteryl esters (CE) 1.6- and 2.8-fold, respectively, while LDL incubated with collagen and lysyl oxidase had no effect compared to control LDL. As judged on the basis of incubations with fucoidin, spermine and 125I-labelled lipoproteins, the mechanism of internalisation of the PG-LDL complexes is different from that of acetylated LDL or dextran sulphate-LDL complexes. The formation of PG-LDL complexes in the arterial intima may lead to an increased uptake of lipoproteins by intimal macrophages during the early phase of atherogenesis.

Antibodies to cytoskeletal proteins in sera of patients with angiographically assessed coronary artery disease.

Circulating autoantibodies to various components of the arterial wall have been reported in atherosclerosis. To examine the occurrence of autoantibodies to cytoskeletal proteins in coronary artery disease (CAD) we studied 56 patients with angiographically demonstrable CAD and compared them with 37 controls without CAD. Enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum samples. In coronary patients, antibody absorbance values at least two standard deviations above the mean for the controls were considered positive. The following numbers of positive antibody absorbances were found in the group of 56 patients: actin IgG, 6 (10.7%); cytokeratin-18 IgG, 3 (5.4%), IgA, 2 (3.6%); myosin IgA, 11 (19.6%); desmin IgG, 13 (23.2%), IgM, 3 (5.4%); vimentin IgG, 2 (3.6%), IgM, 7 (12.5%), IgA, 6 (10.7%). The specificity of desmin IgG was tested with Western blotting against extracts of human internal mammary artery. The positive antibody absorbances to one or several cytoskeletal proteins in the patients were not found to correlate with the clinical symptoms of CAD. Our results suggest an association between autoantibodies to cytoskeletal proteins, particularly to those for desmin, with angiographically assessable CAD.

Postprandial plasma lipoprotein changes in relation to apolipoprotein E phenotypes and low density lipoprotein size in men with and without coronary artery disease.

Postprandial lipoprotein metabolism may play a role in the etiology of premature coronary artery disease (CAD). To determine whether apolipoprotein E (apo E) polymorphism and the size of low density lipoprotein (LDL) influence postprandial lipemia we studied 39 healthy men and 35 men with CAD. Venous blood samples were obtained before an oral fat load and 3, 5 and 7 h thereafter. Total cholesterol and high density lipoprotein (HDL) cholesterol concentrations did not change in either group during the fat load, but triglycerides increased more markedly in CAD patients compared with controls independently of apo E phenotypes. There was a positive correlation between the size of LDL and the concentration of HDL cholesterol (r = 0.541, P < 0.001); conversely, an inverse correlation was observed between LDL size and the level of fasting triglycerides (r = -0.582; P < 0.001). The patients with CAD had significantly smaller LDL particles (25.89 +/- 0.56 nm) than in controls (26.21 +/- 0.63 nm) (P < 0.05). The increase in triglyceride levels during the fat load was highest in CAD patients with a small size of LDL particles (< 25.5 nm) and lowest in controls with large LDL (> 25.5 nm). Our results suggest that the magnitude of the triglyceride response is a better indicator of CAD risk than the fasting triglyceride concentration. The best model in our logistic regression analysis selected as significant risk factors the change of triglyceride concentration from the baseline at 5 h after a fat meal and HDL cholesterol. This model classified 83% of the subjects correctly.

Characteristics of low density lipoprotein isolated from circulating immune complexes.

Circulating immune complexes (CIC) containing low density lipoprotein (LDL) were recently found in the blood of patients with coronary atherosclerosis. In the present study, we investigated the chemical composition and physical characteristics of the lipoprotein constituents of these CIC. CIC were isolated from the blood of atherosclerotic patients by affinity chromatography using anti-human immunoglobulin G-agarose. Low density lipoprotein of these complexes (CIC-LDL) was obtained by ultracentrifugation. CIC-LDL was compared with free circulating LDL isolated from the blood plasma of the same patients. Plasma LDL was fractionated by lectin-chromatography on RCA120-agarose to obtain desialylated LDL (atherogenic) and sialylated LDL (nonatherogenic). Both CIC-LDL and desialylated LDL, but not native (sialylated) lipoprotein, induced a 1.8- to 3-fold increase in the intracellular contents of free and esterified cholesterol of cells cultured from grossly normal areas of human aorta. The sialic acid level in CIC-LDL was 1.3- and 2.1-fold lower than in desialylated or native LDL, respectively. The neutral lipid and phospholipid contents of CIC-LDL and desialylated LDL were reduced as compared to native LDL. The levels of lipid-oxidation products, thiobarbituric acid-reactive substances and hydroperoxides, were similar in all lipoprotein preparations. However, desialylated LDL and CIC-LDL had an elevated oxysterol content. Gradient ultracentrifugation revealed that CIC-LDL particles had a higher density than native LDL. The mean diameters of native, desialylated and CIC-LDL accounted for 24.0, 21.3 and 19.5 nm, respectively. Like desialylated LDL, CIC-LDL displayed a higher electrophoretic mobility compared with that of native LDL. Thus, LDL obtained from circulating immune complexes appears to be a multiple-modified lipoprotein possessing many similarities to desialylated LDL. It was also found that the LDL content of circulating immune complexes correlates well with the desialylated LDL level in human plasma but not with the total LDL concentration. We believe that desialylated LDL predominately interacts with antibodies forming immune complexes. Taken together, our findings suggest that multiple-modified desialylated LDL is the circulating autoantigen for anti-LDL autoantibodies.

Women have a larger and less atherogenic low density lipoprotein particle size than men.

Some epidemiological studies have shown that serum total cholesterol increases with age. especially in women. On the other hand, the risk of coronary artery disease is smaller in women than in men. Earlier studies have shown that a small dense low density lipoprotein (LDL) is more atherogenic than a large LDL. We studied LDL size and apolipoprotein E (apo E) phenotypes in premenopausal and postmenopausal women and in men at the same age. In this study 342 subjects participating in a health screening study were examined. There were four subgroups: 40-year-old men (n = 85), 40-year-old women (n = 80), 70-year old men (n = 88) and 70-year-old women (n = 89). In the present study LDL size was larger (P < 0.01) in women (26.39 +/- 0.07 nm) than in men (25.95 +/- 0.07 nm). We found that LDL size correlated highly positively (r = 0.606; P < 0.001) with serum high density lipoprotein (HDL) concentration and inversely with serum triglyceride concentration (r = -0.627; P < 0.001). Measuring serum HDL cholesterol and triglycerides in health screening studies gives information indirectly about LDL size and its atherogenicity. Apo E phenotype was not significantly associated with serum triglycerides, but was associated with LDL size, LDL cholesterol, total cholesterol and HDL cholesterol. In our sample LDL size decreased and LDL cholesterol and total cholesterol increased according to the most prevalent apo E phenotypes in the order E2/3, E3/3, E3/4 and E4/4. Subjects with phenotype apo E4/4 had the smallest LDL size (25.70 +/- 0.19 nm), the highest total cholesterol (6.53 +/- 0.35 mmol/l) and the lowest HDL cholesterol values (1.28 +/- 0.04 mmol/l). We conclude that there was a significant interaction between sex and age in serum total cholesterol which was highest in older women. However, their LDL size was larger and their LDL is less atherogenic. Apo E phenotype had a significant influence on LDL size.

Susceptibility of LDL to oxidation is not associated with the presence of coronary heart disease or renal dysfunction in NIDDM patients.

Coronary heart disease (CHD) is the leading cause of death among patients with non-insulin-dependent diabetes mellitus (NIDDM) and the oxidation of low-density lipoprotein (LDL) may be an essential factor in the development of atherosclerotic lesions. Therefore, we studied the in vitro susceptibility of LDL to copper-induced oxidation in 72 NIDDM patients and 94 well-matched non-diabetic control subjects. There was no significant difference in the lagtime of LDL oxidation between NIDDM patients and control subjects (68.1+/-8.8 vs. 66.7+/-9.2 min, respectively, P=0.29). The plasma alpha-tocopherol/LDL-ratio was the most significant determinant of the lagtime in multiple regression analysis. High level of serum triglycerides was associated with decreased lagtime in control subjects, but not in NIDDM patients. Blood glucose balance was not associated with LDL susceptibility to oxidation in NIDDM patients. Subjects with CHD did not have LDL susceptibility to oxidation different from that of subjects without CHD in either of the study groups. Urinary albumin excretion or glomerular filtration rate was not associated with the lagtime of LDL oxidation in NIDDM patients. In conclusion, these data suggest that diabetes and hyperglycemia per se do not affect the susceptibility of LDL to oxidation. The presence of CHD or renal dysfunction were not associated with LDL susceptibility to oxidation.

Characteristics of low-density lipoprotein subfractions from patients with coronary artery disease.

BACKGROUND: The low-density lipoprotein (LDL) of patients with coronary artery disease (CAD) has been reported to enhance cholesterol ester accumulation in aortic cells. The LDL of patients with CAD also has a higher mean density than the LDL of healthy subjects, indicating a different subspecies distribution. Because these density differences may be associated with altered metabolism and atherogenicity of LDL, we studied the properties and effects of isolated LDL subfractions on cell lipid metabolism and cholesterol accumulation. METHODS: Plasma pools of patients with angiographically proven CAD (A) and healthy controls (C) were used to isolate and fractionate LDL into five subfractions (1 to 5, from the lowest to the highest density) by gradient ultracentrifugation. Each of the LDL subfractions was analyzed for particle diameter, chemical composition, sialic acid content, and their effect on lipid content and cholesterol esterification in arterial cell and macrophage cultures, respectively. RESULTS: The chemical compositions of the respective subfractions revealed no differences between patients and controls, except that the sialic acid content was reduced in dense LDL subfractions, especially in the samples from patients with CAD (fractions A3, A4, A5, and C5). LDL subfractions with reduced sialic acid content also enhanced the incorporation of [14C]-oleate into cholesterol esters in mouse peritoneal macrophage cultures (fractions A4, A5, and C5) and increased the cholesterol ester content in primary cultures of human aortic intimal cells (fractions A3, A4, A5, and C5). CONCLUSIONS: The results suggest that the dense LDL subfractions of patients with CAD are atherogenic by promoting intracellular cholesterol ester accumulation. The results also suggest that the atherogenicity is associated with reduced sialic acid content of the LDL subspecies.

Normalization of lipoprotein lipase and hepatic lipase by gemfibrozil results in correction of lipoprotein abnormalities in chronic renal failure.

Eighteen patients with chronic renal failure (serum creatinine 173-756 mumol/l) and hyperlipidemia were treated with gemfibrozil (1200 mg/day). The drug caused a significant improvement of the dyslipidemia within one week and the effect was progressive during the 28 weeks of treatment. Very-low-density lipoprotein triglycerides and very-low-density lipoprotein cholesterol decreased by about 50% and high-density lipoprotein cholesterol increased by 30%. The lipoprotein changes occurred simultaneously with a significant activation to normal levels of postheparin plasma lipoprotein and hepatic lipases. Opposite effects were observed when gemfibrozil was discontinued and the patients were given placebo. No major harmful effects were observed.

Stability of plasma total cholesterol, triglycerides, and apolipoproteins B and A-I during the early postmortem period.

The stability of plasma lipids and apolipoproteins during the early postmortem period was studied by taking four duplicate blood samples from eight cadavers 2, 6, 12, and 24 h after death. The bodies were kept at +4 degrees C. The plasma samples were analyzed for total cholesterol (TC), triglycerides (TG), apolipoprotein B (apo B), and apolipoprotein A-I (apo A-I). In TC, values rose by 6 and 11% in two cases, and in six cases diminished 3 to 15% during the first 6 h compared to values obtained 2 h postmortem. The greatest changes were a continuing rise in one case by 33% and a fall by 21% in another case during 24 h. In TG values marked changes took place including one case with a rise of 67% within 24 h. The concentrations of apo B rose by 9 to 11% in three cases and fell by 3 and 4% in two cases during 6 h, but during the whole study period a rise up to 78% occurred. In the concentrations of apo A-I, cases fell by as much as 42% in 6 h, and in one case rose by 20% during 6 h. The results indicate that unpredictable fluctuations occur in plasma lipid and apolipoprotein values within 24 h after death, and they should be interpreted cautiously if the samples have been taken after a prolonged postmortem period.

Carotid intima-media thickness after pediatric renal or liver transplantation at high-resolution B-mode ultrasonography.

In a previous study, we observed a higher incidence of dyslipidemia in pediatric renal recipients compared with liver recipients. In the present study, we measured common carotid artery intima-media thickness (IMT) in 13 pediatric renal recipients, 9 liver recipients, and 26 control individuals with median age of 11.4, 10.8, and 12.0 years, respectively. The patients were studied from 0.2 to 10.8 years after renal transplantation (RTx) or liver transplantation (LTx). An experienced radiologist (T.K.) blinded to the status of the children measured the IMT using a high-resolution B-mode ultrasonography method. In patients who underwent RTx or LTx, serum fasting lipid profile, estimates of renal and liver function, and glucose metabolism were determined. Children undergoing RTx or LTx more often had hypertension compared with the control individuals (P = .004). Before transplantation, dyslipidemia was greater in patients undergoing RTx compared with those undergoing LTx (P < .05). Children who underwent RTx, compared with those who underwent LTx or control individuals, had thicker mean IMT at the 6 sites measured (mean [SD], 0.57 [0.07], 0.51 [0.05], and 0.53 [0.06] mm, respectively; P = .02]. As a result of linear regression in renal recipients, variability of glomerular filtration rate (<60 mL/min/1.73 m(2) vs normal) accounted for 43.3% of variability of the mean of maximal IMT (B = 8.9; SE = 3.1; P = .01). Variability of pre-RTx serum triglyceride concentration (B = 1.6; SE = 0.6; P = .03) and actual triglyceride concentration (B = 10.3; SE = 2.2; P = .002) accounted for 82.2% of variability of maximal IMT. Our findings support previous data on the importance of maintenance of good graft function with sufficient but not overly efficient immunosuppression after transplantation in prevention of future cardiovascular disease.

Elevated plasma fibrinogen caused by inadequate alpha-linolenic acid intake can be reduced by replacing fat with canola-type rapeseed oil.

The effects of canola-type rapeseed oil (RSO) on serum lipids, plasma fibrinogen, lipid oxidation and fatty acids were studied in three groups of subjects, two of which had not been consuming fish in their habitual diets. Forty-two volunteers (35 women, 7 men, 16-62 years) replaced fat with RSO for 6 weeks in a parallel design. The average cholesterol and fibrinogen concentrations were 5.0 mmol/l and 2.6 g/l, respectively. The intake of alpha-linolenic acid (alpha-LLA) was doubled. Efficient competitive inhibition by alpha-LLA was seen as a decrease in long-chain (LC) n-6 PUFA at 3 weeks. Elevated fibrinogen (2.6-3.9 g/l) decreased by 0.95 g/l at 6 weeks. Docosahexaenoic acid (22:6n-3) in plasma phospholipids increased at low fibrinogen levels only. The associations and changes in plasma C18 and LC PUFA followed the competitive and metabolic principles of the body, and especially in the case of n-3 PUFA according to the recycling pathway.