Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have analysed the fatty acid composition of serum cholesterol esters (CE), phospholipids (PL) and triglycerides (TG) and of adipose tissue (AT) lipids in 72 males and chronic renal failure (CRF). Sixteen patients were treated with protein-poor diet. 16 with hemodialysis. The results have been related to clinical aspects of the disease and to abnormalities in serum lipid and lipoprotein concentrations. The major findings were high relative content of oleic acid and a low relative content of linoleic acid in all lipids in the diet-treated group compared to both controls and to the untreated and dialysed patients. Tendencies in the same directions were seen also in the untreated subjects, significant for oleic and linoleic acid in CE and for oleic acid in PL. These changes did not correlate to serum of lipoprotein lipids, or to serum creatinine concentrations in patients not on diet or dialysis, indicating that other factors are more important in modifying the fatty acid metabolism in CRF. The composition of the protein-poor diet, which was rich in fat but low in linoleic acid in relation to oleic acid, is probably a major factor explaining our findings in the diet-treated group. Since low levels of linoleic acid in plasma and AT lipids have been suggested to be a risk factor for atherosclerosis, more attention should be paid to the content and composition of dietary fat in order to prevent the occurrence of such low levels.
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PMID:Fatty acid composition of serum and adipose tissue lipids in males with chronic renal failure. Relations to serum lipoproteins and clinical factors. 707 24

Disturbances in lipid metabolism and accelerated atherosclerosis are well-known phenomena of chronic renal insufficiency. The disturbance in lipid metabolism has been repeatedly described as secondary type IV hyperlipoproteinemia according to the classification of Fredrickson. The classification of Fredrickson, however, does not take into account the role of the alpha-lipoproteins (the HDL lipoproteins and HDL cholesterol). Hence, HDL cholesterol was determined and correlated to other routine parameters of lipid metabolism in 66 patients with different degrees of renal insufficiency. Furthermore, an intravenous fat tolerance test was performed in 14 patients with terminal renal insufficiency. Beside the well-known hypertriglyceridemia with cholesterol values near the upper limits of normal, a significant reduction in HDL cholesterol was found, showing a significant inverse correlation to plasma creatinine values. Patients with advanced or terminal renal insufficiency additionally showed a significant inverse correlation between HDL cholesterol and plasma triglycerides. The disappearance rate of intravenously administered fat emulsion (which corresponds to the clearance rate of chylomicrons and VLDL) was diminished in azotaemic patients, showing a significant inverse correlation between HDL cholesterol and disappearance rate in the intravenous FTT. Beside hypertriglyceridemia, the diminished HDL cholesterol values represent an additional risk factor for the genesis of accelerated atherosclerosis. The diminished k value demonstrates a diminished activity of lipoprotein lipase as cause of hypertriglyceridemia, whereby the positive correlation between the k value and HDL cholesterol and the inverse correlation between HDL cholesterol and triglycerides suggest a causal relationship between the decreased activity of lipoprotein lipase and diminished HDL cholesterol levels.
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PMID:[High-density-lipoprotein and renal insufficiency (author's transl)]. 708 Apr 95

Fenofibrate is an efficient serum lipid-lowering drug with few clinical side effects. The drug was further evaluated in a study comprising 56 patients, which combined a dose-response trial with a subsequent comparison between the optimal fenofibrate dose and a clofibrate dose of 2 g/day. When the fenofibrate dose was gradually increased (200-300-400 mg/day), a reduction of the elevated lipoproteins within each type of hyperlipoproteinaemia was found. During the dose-response part of the therapy a transient serum creatinine rise was observed, which disappeared at the 400 mg/day level. The highest dose, 400 mg/day, proved to have the best lipid-lower effects. On this therapy the elevated LDL-cholesterol fell by 28% in type IIA + B patients, and the elevated VLDL-TG by 65% in type IIB + IV patients. The HDL/VLDL + LDL-cholesterol ratio increased significantly in all groups, in particular in type IV patients (from 0.19 to 0.28, P less than 0.001). Fenofibrate and clofibrate were each given for 2 months in random order, and the effects on lipoproteins compared. Significant differences were: higher HDL-cholesterol in type IIA on clofibrate, lower LDL-cholesterol in type IIB on fenofibrate, lower TG and cholesterol in both VLDL an LDL in type IV on fenofibrate, combined with higher HDL-cholesterol on this drug. Thus, fenofibrate seems to be an efficient lipid lowering drug with 400 mg/day as an optimal dosage under our conditions.
Atherosclerosis
PMID:Fenofibrate therapy of hyperlipoproteinaemia. A dose-response study and a comparison with clofibrate. 722 66

16-week-old Wistar, alloxan diabetic rats exhibited progressive elevations in levels of serum glucose, total triglycerides, cholesterol and creatinine over a period of 8 weeks; hyperglycemia preceded hyperlipidemia and hypercreatininemia and hypertriglyceridemia preceded hypercholesteremia. Age-matched control rats failed to develop any signs of hyperglycemia or hypercreatininemia, but did develop both hypercholesterolemia and hypertriglyceridemia at 24 weeks of age. This suggests that the progressive cardiovascular derangements (e.g., atherosclerosis, hypertension) noted in experimental diabetes mellitus and in the normal aging (and maturation) process may be brought about by distinctly different biochemical processes.
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PMID:Sequential changes in serum glucose, triglycerides and cholesterol in aging of normal and alloxan-diabetic rats. 723 69

The effect on kidney function fo treatment of cardiac failure with ACE-inhibitors was examined retrospectively in a material of 87 consecutive patients. Furthermore, it was evaluated whether concomitant treatment with diuretics or existing generalised atherosclerosis as indicated by ongoing treatment with nitrates could be a risk factor concerning reduction of kidney function. In 11.9% of the patients an increase in S-creatinine of > 30% was observed during the first weeks of treatment. It was only necessary to stop treatment in two of these patients. In the remainder S-creatinine decreased again during ongoing treatment. In another 10.7% of patients an increase of 20-30% in S-creatinine was observed. Seventy-two point six percent of the patients had unchanged kidney function during treatment with an ACE-inhibitor. Ongoing treatment with diuretics did not seem to be a risk factor for developing reduced kidney function, whereas significantly more patients on treatment with nitrates, indicating generalised atherosclerosis, developed reduced kidney function during treatment with ACE-inhibitors. It is recommended to control kidney function before, one to two weeks and two to three months following initiation of treatment with ACE-inhibitors and to pay special attention to patients with generalised atherosclerosis.
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PMID:[Renal function during treatment of chronic renal failure with angiotensin converting enzyme inhibitors]. 748 50

Several published reports describe an abnormal circadian blood pressure profile in chronic renal failure subjects. Factors other than renal failure, including age, diagnosis of diabetes mellitus, autonomic dysfunction, and race, also may affect circadian blood pressure profiles. To further elucidate the relationship between renal function and circadian blood pressure variation, we compared day/night circadian blood pressure changes in three groups of male veteran hypertensive patients: group A, creatinine clearance (CC) > 80 mL/min, n = 20; group B, CC 20 to 80 mL/min, n = 19; and group C, CC < 20 mL/min, n = 14. We use postural changes in catecholamines, renin, and aldosterone as a measure of autonomic function. No significant difference in day/night percent change in systolic, diastolic, mean arterial pressure (MAP), or heart rate was seen by renal function group. Regression analysis using age, diagnosis of diabetes mellitus, postural hormonal changes, and creatinine clearance found race to be the only significant predictor of the day/night percent change in MAP (P < 0.05). Compared with whites, black subjects had higher nocturnal heart rates (P = 0.01); smaller day/night heart rate changes (P = 0.03); significantly higher diastolic blood pressure (P = 0.01); and a trend toward smaller day/night change in diastolic blood pressure (P = 0.06). In conclusion, renal function level does not influence day/night blood pressure changes. The blunting or reversal of the normal circadian blood pressure pattern seen in some chronic renal failure hypertensive subjects may be attributable to the association between chronic renal failure and cofactors associated with abnormal circadian blood pressure, including black race and possibly severity of atherosclerosis.
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PMID:Circadian blood pressure variation versus renal function. 748 22

Levels of lipoprotein(a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant low-density lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P < 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes.
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PMID:Levels of lipoprotein(a), apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial. 755 61

Hyperhomocysteinemia occurs frequently in end-stage renal disease (ESRD), but its prevalence in comparison with traditional cardiovascular disease (CVD) risk factors is unknown. Fasting total plasma homocysteine, potential determinants of plasma homocysteine (i.e., plasma B-vitamins and serine), total and HDL cholesterol, glucose, and creatinine, were determined in 24 ESRD patients on dialysis, and 24 age, gender, and race matched Framingham Offspring Study controls with normal renal function. Presence of clinical CVD and CVD risk factors was established by standardized methods. Mean plasma homocysteine was markedly higher in the ESRD patients versus controls (22.7 vs. 9.5 mumol/l). ESRD patients were 33 times more likely than controls to have hyperhomocysteinemia (> 15.8 mumol/l) (95% confidence interval, 5.7-189.6). Hyperhomocysteinemia persisted in the ESRD patients despite normal to supernormal B-vitamin status. Plasma serine levels below the tenth percentile of the control distribution were found in 75% of the ESRD patients. Oral serine supplementation caused a 37% increase in mean plasma serine, but had no effect on plasma homocysteine in four ESRD patients with supernormal plasma folate, low plasma serine, and hyperhomocysteinemia. Given its unusually high prevalence, improved management of hyperhomocysteinemia might reduce CVD sequelae in ESRD.
Atherosclerosis 1995 Apr 07
PMID:Hyperhomocysteinemia and traditional cardiovascular disease risk factors in end-stage renal disease patients on dialysis: a case-control study. 760 81

Transplantation of kidneys from older donors is being advocated to expand the organ donor pool. However, the prevalence of atherosclerosis and age-induced renal structural alterations account for the variable function of allografts procured from these older donors. Pretransplant biopsies are sometimes used to evaluate kidneys from older donors, but to date there are no defined criteria correlating the extent of structural alterations in these kidneys to subsequent function. We investigated the effect of glomerulosclerosis, a marker for nephrosclerosis, on graft outcome. Sixty-five baseline biopsies of kidney allografts were retrospectively analyzed to identify a referent point of glomerulosclerosis that correlated with inferior graft outcome. Age and death from nontraumatic cerebrovascular injuries were the main correlates for donor glomerulosclerosis (P < 0.001). Allografts with poor function at 6 months defined as serum creatinine > 2.5 mg/dl (n = 13) or nephrectomy (n = 4) had a mean of 20% glomerulosclerosis at the time of implantation compared with only 2% sclerosis in allografts with good function (P < 0.05). Delayed graft function occurred in 22% and 33% of recipients with no glomerulosclerosis and those with less than 20% glomerulosclerosis, respectively. In contrast, patients receiving kidneys with > 20% sclerosis had an 87% incidence of delayed function (P < 0.05). Moreover, graft loss occurred in 7% of recipients of kidneys with less than 20% sclerosis and in 38% of recipients with > 20% sclerosis (P < 0.04). Measurements of serum creatinine in the donors did not distinguish the different degrees of glomerulosclerosis found on biopsy. Our data indicate that donor glomerulosclerosis greater than 20% increases the risk of delayed graft function and poor outcome of transplanted kidneys. Therefore, we advocate the use of routine biopsies of kidneys from older (> 50 yrs) donors and those donors with nontraumatic cerebrovascular accidents, despite seemingly normal preprocurement serum creatinine.
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PMID:Glomerulosclerosis as a determinant of posttransplant function of older donor renal allografts. 765 61

Microalbuminuria was recently proposed as a novel atherogenic risk factor. The pathophysiological link between microalbuminuria and atherosclerosis may be mediated through an increased generalized transvascular leakage of albumin. To investigate this hypothesis, urinary albumin excretion and clearance and systemic transvascular albumin leakage (TERalb) were measured in 23 patients with severe clinical atherosclerosis and 25 healthy controls. In addition, renal clearances of three other endogenous plasma proteins (IgG, IgG4, and beta 2-microglobulin) and of creatinine were measured. Measurements of urine and serum proteins were done by enzyme-linked immunosorbent assays. TERalb was measured by the fractional disappearance rate of 125I-albumin from the total intravascular compartment in 1 hour after intravenous injection. Glomerular filtration rate was estimated as creatinine clearance. Urinary albumin excretion (geometric means [95% confidence intervals], 10.5 [6.1 to 18.3] versus 5.7 [4.7 to 6.9] micrograms/min; P < .05), fractional urinary albumin clearance (2.8 [1.6 to 4.8] x 10(-6) versus 1.3 [1.0 to 1.6] x 10(-6); P < .05), and TERalb (6.0 [5.5 to 6.5] versus 5.1 [4.5 to 5.8] %/h; P < .05) were higher in patients than in control subjects. Glomerular charge selectivity (ratio of IgG clearance to IgG4 clearance) was lower in patients than in control subjects (1.5 [1.1 to 2.0] versus 2.3 [2.0 to 2.6]; P < .05). These alterations were independent of blood pressure, glomerular filtration rate, tubular function, and smoking status. It is concluded that atherosclerotic vascular disease is associated with renal and systemic transvascular leakiness for albumin. Theoretically, such leakiness may in addition allow for an increased lipid insudation into the large vessel wall, thereby linking microalbuminuria to atherogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and systemic transvascular albumin leakage in severe atherosclerosis. 767 Sep 45


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