Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, is associated with insulin resistance (IR) and the risk of venous and arterial thrombotic cardiovascular disease (CVD) in the general population, and may behave as an acute-phase reactant. PAI-1 activity was measured in 124 patients with chronic renal disease, and its relationship with alterations in metabolic, lipid, and cytokine parameters and the prevalence of CVD complications was explored. Patients with chronic renal disease not requiring dialysis were divided into a low proteinuric ([LP]n = 30) or high proteinuric ([HP]n = 31) group and compared with patients on continuous ambulatory peritoneal dialysis ([CAPD]n = 32) or hemodialysis([HD]n = 31) and with 31 healthy controls. Patients on HD had significantly lower PAI-1 activity than HP, CAPD, and control groups, but no group had significantly higher values than the controls (AU/mL: 7.4 +/- 3.8 HD, 11.2 +/- 8.4 CAPD, 9.4 +/- 5.4 LP, 12.1 +/- 8.0 HP, 11.4 +/- 6.6 controls, P = .04). Interleukin-6 (IL-6), the mediator of the acute-phase response, was determined in a subset of patients and was significantly increased in HD, CAPD, and LP groups compared with the controls (median, pg/mL: 4.6 HD, 4.0 CAPD, 2.9 LP, 2.4 HP, and 1.5 controls, P < .001), but did not correlate with PAI-1. PAI-1 independently correlated with body mass index (BMI), triglycerides, and lipoprotein(a) [Lp(a)] in stepwise regression for all patients. Dividing the whole patient group by tertiles of triglycerides and BMI, increased PAI-1 was confined to the subgroup of patients with both obesity (BMI > 26.7 kg/m2) and hypertriglyceridemia (triglycerides > 2.5 mmol/L). These data suggest that PAI-1 activity in chronic renal disease and dialysis was more strongly associated with the common metabolic abnormalities of obesity and hypertriglyceridemia than with renal disease status, dialysis, or a chronic inflammatory state. This study does not support but does not exclude a major role for increased PAI-1 activity in CVD risk in chronic renal disease.
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PMID:Plasminogen activator inhibitor-1 activity in chronic renal disease and dialysis. 900 66

It has been shown that the incidence of recurrent stenosis following successful percutaneous transluminal coronary angioplasty (PTCA) is correlated with serum Lipoprotein(a) [Lp(a)] levels. The aim of the present study was to examine the influence of Lp(a) on restenosis after primary successful femoropopliteal PTA. One hundred and thirty nine consecutive patients with peripheral arterial occlusive disease (PAOD) and successful femoropopliteal PTA were studied. Follow-up included clinical examination and non-invasive laboratory testing (pulse volume recordings, ankle-brachial arterial pressure measurement) in every patient before and after 1, 3, 6 and 12 months following intervention. Duplex sonography was performed 1 year after PTA. Suspicion of restenosis (> or = 50% diameter reduction) was verified by angiography. Lp(a) was determined using ELISA technique (mg/dl). Twelve months after successful PTA no restenosis was found in 82 patients (59%: group A). The one-year recurrence rate of 41% (group B) was due to significant restenosis in 35 patients (25%) and reocclusion in 22 patients (16%). The corresponding mean values +/- S.E.M. for Lp(a) were as follows: group A, 28 +/- 5.3; group B 59 +/- 11 (P < 0.01). Women showed a higher frequency of recurrences (55%) versus men (30%, P < 0.01) also corresponding with a high Lp(a) level (51.8 +/- 8 versus 32.7 +/- 5; P < 0.05). Furthermore Lp(a) aggravated the well known increased risk for recurrence in multiple stenoses or occlusions of > or = 5 cm in length. There were no significant differences between groups A and B with respect to age, diabetes, hyperlipidaemia, obesity and cigarette smoking. The results support the view that Lp(a) is an independent risk factor for recurrence after PTA in the femoropopliteal area. It might also be a causal basis for the higher incidence of recurrences in female PAOD patients.
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PMID:Elevated lipoprotein(a) and increased incidence of restenosis after femoropopliteal PTA. Rationale for the higher risk of recurrence in females? 900 1

Serum lipoprotein(a) [Lp(a)] concentrations in chronic renal failure patients were investigated in relation to the degree of renal insufficiency, treatment by maintenance hemodialysis, and correction of uremia by renal transplantation with or without cyclosporin immunosuppression. Fast serum levels of Lp(a) (mg/100 mL) were determined in 34 chronic renal failure patients not in need of maintenance dialysis (16 with serum creatinine 2.0-4.0 mg/100 mL; 18 with serum creatinine higher than 4.0 mg/100 mL), 40 patients treated by hemodialysis, 55 successful renal transplant recipients (28 under cyclosporin treatment and 27 receiving no cyclosporin), and 34 healthy controls. Age and sex distributions were similar among groups. Pregnant women; non-White individuals; subjects with obesity, diabetes, nephrotic syndrome, and hepatic and thyroid diseases; and those treated with oral contraceptives or lipid-lowering drugs were excluded from the study. Compared to controls, median Lp(a) was increased in nondialyzed renal failure patients (11 vs. 47.5 p < 0.001) and this was the only lipid abnormally observed in the group. There was no significant difference in Lp(a) levels between nondialized renal failure patients with serum creatinine 2.0-4.0 and > 4.0 mg/100 mL (47 vs. 49, NS). Moreover, Pearson correlation coefficient (r = 0.01, NS) showed that Lp(a) values were not related to serum creatinine in nondialyzed patients, In hemodialysis subjects Lp(a) concentrations (median = 29) were intermediate between those observed in nondialyzed patients and controls but the differences were not significant. Lp(a) levels in renal transplant patients treated with cyclosporin (median = 6) and not receiving cyclosporin (median = 13) were similar and did not differ from controls. Serum Lp(a) increases and attains maximum levels with mild/moderate reduction in renal function, and does not seem to change through late renal failure stages or in relation to the introduction of maintenance hemodialysis treatment. Correction of uremia by successful renal transplant caused normalization of Lp(a) levels regardless of the use of cyclosporin. Increased Lp(a) levels may be the earliest and more consistent lipid alteration seen in predialysis renal failure.
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PMID:Early elevation of lipoprotein(a) levels in chronic renal insufficiency. 904 61

Coronary heart disease (CHD) is more common in patients with chronic renal failure and is a major cause of death after renal transplantation. Elevated serum levels of lipoprotein(a) (Lp(a)) are a known risk factor for CHD in the general population and levels have been reported to be increased in renal transplant recipients. It has been suggested that cyclosporin may elevate Lp(a) levels. We therefore measured the serum concentration of Lp(a) in 50 renal transplant recipients who were receiving cyclosporin alone as immunosuppressive therapy and 50 who were treated with azathioprine and prednisolone, but not cyclosporin. The patients attended two renal transplant centres, one where cyclosporin alone was used as immunosuppressive treatment when possible and another where many patients commenced on azathioprine and prednisolone remain on this medication rather than cyclosporin. Patients in each group were matched for age and sex, but the time since transplantation was greater in those not receiving cyclosporin. Transplant function, obesity and the underlying cause of renal disease were similar in both groups of patients. Median Lp(a) concentration in the cyclosporin monotherapy group was 32.0 (range <0.8-140.3) mg/dl and was significantly (p < 0.05) greater than that of the azathioprine and prednisolone group which was 18.3 (range <0.8-167.7) mg/dl. The serum high-density lipoprotein (HDL) cholesterol concentration, which was 1.24 +/- 0.39 mmol/l (mean +/- SD) in patients receiving cyclosporin, was significantly (p < 0.05) less than that of those treated with azathioprine and prednisolone in whom it was 1.41 +/- 0.40 mmol/l. The lower level in those on cyclosporin was due to a decrease in the HDL2 subfraction. Serum lipid and lipoprotein concentrations were otherwise similar in the two groups of patients. The serum level of Lp(a) after renal transplantation may be influenced by the choice of immunosuppressive therapy.
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PMID:Influence of immunosuppressive therapy on lipoprotein(a) and other lipoproteins following renal transplantation. 906 48

Lipoprotein(a) [Lp(a)] is formed by the assembly of LDL particles and a carbohydrate-rich protein, apolipoprotein(a) [apo(a)], which has a high degree of structural homology with plasminogen. While the majority of retrospective studies have found an association between Lp(a) level and cardiovascular disease (CVD), the few prospective studies to date have reported contradictory results. We conducted a nested case-control study using the participants in the Stanford Five-City Project, a long-term CVD prevention trial. Participants with an incident possible or definite myocardial infarction or coronary death were matched to a single control subject for age, sex, ethnicity, residence in a treatment or control city, and time of survey. This process yielded 134 case-control pairs, 90 male and 44 female, for whom plasma was available for analysis of Lp(a). Lp(a) values in nanomoles per liter were determined by an enzyme-linked immunoassay that measures Lp(a) independently of apo(a) size polymorphism. Apo(a) size isoforms were determined by SDS-agarose gel electrophoresis. Median Lp(a) level in male cases was almost double that in control subjects (41.8 versus 21.2 nmol/L; P < .01); in female cases, median Lp(a) was 34% higher than in control subjects (32.5 versus 21.2 nmol/L), but this difference was not statistically significant. Among the male cases, there was an increased frequency of small apo(a) isoforms, while no significant difference was found in apo(a) size between female cases and control subjects. The association between Lp(a) level and case-control status in men was independent of total, HDL, and non-HDL cholesterol levels, as well as apo(a) size isoform, cigarette smoking, blood pressure, and obesity. In men, the most efficient threshold value of Lp(a) concentration for separating cases and control subjects was 35 nmol/L; the odds ratio for being a case above this level compared with below was 2.84 (95% confidence interval: 1.53-5.27, P < .001). This study provides strong evidence that Lp(a) level is a prospective, independent risk factor for developing coronary artery disease in men and indicates that the size of apo(a) may also play a role. The lack of a significant association in women deserves further evaluation in larger studies.
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PMID:A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants. 908 76

We studied the relationships between regional body fat distribution and metabolic variables with lipoprotein(a) [Lp(a)] as well as the effects of weight loss on Lp(a) in 25 women and 9 men with obesity. Regional body fat distribution, as evaluated by the use of computed tomography; Lp(a); and fasting glucose, insulin, cholesterol, and triglycerides were analyzed before and after a very low-energy diet. No significant correlations were found between visceral, subcutaneous, and total fat and Lp(a) or between metabolic variables and Lp(a). All anthropometric variables significantly decreased after a very low-energy diet. Fasting glucose, insulin, triglycerides, and cholesterol significantly decreased after a very low-energy diet. No significant changes in Lp(a) concentration after a very low-energy diet were found. The correlation between the initial values of Lp(a) and changes of Lp(a) after a very low-energy diet was slightly significant (rho = 0.33, p < 0.06). In conclusion, our study shows that Lp(a) is not influenced by obesity, visceral fat, metabolic variables, or weight loss induced by a very low-energy diet.
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PMID:Effects of visceral fat and weight loss on lipoprotein(a) concentration in subjects with obesity. 928 40

Associations between a high daily insulin dose and cardiovascular risk factors, including those of the insulin-resistance syndrome, were studied in 479 Type 1 diabetic children 6 to 18 years of age. Insulin dose increased over the first two years after diagnosis of diabetes (p = 0.0001) and was significantly higher in girls (p = 0.01). For those children with diabetes duration of more than 2 years, the insulin requirement increased up to 13-14 years of age (p < 0.05) and was higher in pubertal than pre-pubertal children (p < 0.05). For girls, the requirement was higher in puberty than in post-puberty (p < 0.05) and increased with diabetes duration (p < 0.05). Triglyceride concentrations were associated positively and significantly with the insulin dose of both boys and girls, after adjustment for age, pubertal stage, diabetes duration, and metabolic control (fructosamine levels). No other consistent associations were found between insulin dose and other cardiovascular risk factors: body mass index, central adiposity, arterial blood pressures, serum total cholesterol, apoA1, apoB, Lp(a), uric acid, or urinary albumin excretion. Parental obesity, hypertension and diabetes were not related to the insulin dose of children. The results did not differ when the population was limited to the 375 children with diabetes duration of more than 2 years. It is concluded that in these Type 1 diabetic children the insulin dose for a given level of metabolic control (our surrogate measure of insulin resistance) was related to a single cardiovascular risk factor: triglyceride concentrations.
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PMID:Insulin dose and cardiovascular risk factors in type 1 diabetic children and adolescents. 959 39

Obesity, strongly associated with the risk for coronary heart disease (CHD), is becoming increasingly prevalent. This study was designed to establish first whether systemic arterial compliance (SAC), an index of arterial function, is improved with weight loss and second, whether cardiovascular risk factors that improve with weight loss are reduced equally with lean meat or with an equivalent amount of plant protein in the diet. Thirty-six women, mostly overweight or obese, aged 40+/-9 years, were allocated nonrandomly to a 16-week parallel-design trial of two equienergetic diets designed to lead to weight loss, with one arm of the study emphasizing red meat and the other soybeans as the major protein source. Body weight, waist and hip circumference, and plasma lipids, glucose, insulin, and leptin levels were measured, and SAC was calculated from ultrasound measurement of aortic flow velocity and aortic root driving pressure. Subjects lost weight (9% of body weight in 16 weeks) and showed decreased plasma total and low-density lipoprotein (LDL) cholesterol (12% and 14%, P < .0001, respectively), triacylglycerol (17%, P < .05), and leptin (24%, P < .01) concentrations. However, lipoprotein(a) [Lp(a)] levels did not change significantly. Mean arterial pressure (MAP) decreased 7% and SAC increased 28% (P < .001 for both). However, only the decrease in arterial pressure correlated significantly with the reduction in the waist to hip ratio (WHR), and the improvement in SAC correlated inversely with the blood pressure reduction (P < .001 for both). Further, weight loss and the metabolic benefits of weight loss occurred equally with the meat-based and plant-based diets. We conclude that moderate weight loss in women leads to a substantial reduction in the cardiovascular risk, including SAC.
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PMID:Arterial compliance, blood pressure, plasma leptin, and plasma lipids in women are improved with weight reduction equally with a meat-based diet and a plant-based diet. 982 5

This paper provides a broad overview of the epidemiological and genetical aspects of common multifactorial diseases in man with focus on three well-studied ones, namely, coronary heart disease (CHD), essential hypertension (EHYT) and diabetes mellitus (DM). In contrast to mendelian diseases, for which a mutant gene either in the heterozygous or homozygous condition is generally sufficient to cause disease, for most multifactorial diseases, the concepts of genetic susceptibility' and risk factors' are more appropriate. For these diseases, genetic susceptibility is heterogeneous. The well-studied diseases such as CHD permit one to conceptualize the complex relationships between genotype and phenotype for chronic multifactorial diseases in general, namely that allelic variations in genes, through their products interacting with environmental factors, contribute to the quantitative variability of biological risk factor traits and thus ultimately to disease outcome. Two types of such allelic variations can be distinguished, namely those in genes whose mutant alleles have (i) small to moderate effects on the risk factor trait, are common in the population (polymorphic alleles) and therefore contribute substantially to the variability of biological risk factor traits and (ii) profound effects, are rare in the population and therefore contribute far less to the variability of biological risk factor traits. For all the three diseases considered in this review, a positive family history is a strong risk factor. CHD is one of the major contributors to mortality in most industrialized countries. Evidence from epidemiological studies, clinical correlations, genetic hyperlipidaemias etc., indicate that lipids play a key role in the pathogenesis of CHD. The known lipid-related risk factors include: high levels of low density lipoprotein cholesterol, low levels of high density lipoprotein cholesterol, high apoB levels (the major protein fraction of the low density lipoprotein particles) and elevated levels of Lp(a) lipoprotein. Among the risk factors which are not related to lipids are: high levels of homocysteine, low activity of paraoxonase and possibly also elevated plasma fibrinogen levels. In addition to the above, hypertension, diabetes and obesity (which themselves have genetic determinants) are important risk factors for CHD. Among the environmental risk factors are: high dietary fat intake, smoking, stress, lack of exercise etc. About 60% of the variability of the plasma cholesterol is genetic in origin. While a few genes have been identified whose mutant alleles have large effects on this trait (e.g., LDLR, familial defective apoB-100), variability in cholesterol levels among individuals in most families is influenced by allelic variation in many genes (polymorphisms) as well as environmental exposures. A proportion of this variation can be accounted for by two alleles of the apoE locus that increase (&epsi;4) and decrease (&epsi;2) cholesterol levels, respectively. A polymorphism at the apoB gene (XbaI) also has similar effects, but is probably not mediated through lipids. High density lipoprotein cholesterol levels are genetically influenced and are related to apoA1 and hepatic lipase (LIPC) gene functions. Mutations in the apoA1 gene are rare and there are data which suggest a role of allelic variation at or linked LIPC gene in high density lipoprotein cholesterol levels. Polymorphism at the apoA1--C3 loci is often associated with hypertriglyceridemia. The apo(a) gene which codes for Lp(a) is highly polymorphic, each allele determining a specific number of multiple tandem repeats of a unique coding sequence known as Kringle 4. The size of the gene correlates with the size of the Lp(a) protein. The smaller the size of the Lp(a) protein, the higher are the Lp(a) levels. (ABSTRACT TRUNCATED)
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PMID:Ionizing radiation and genetic risks. VI. Chronic multifactorial diseases: a review of epidemiological and genetical aspects of coronary heart disease, essential hypertension and diabetes mellitus. 987 81

Relatively low serum lipid levels are thought to be an important factor contributing to the low incidence of ischemic heart diseases (IHD) in Japanese. It has been proven that obesity or overweight constitutes a basal condition for several risk factors in atherosclerosis. The purpose of this study is to obtain data on serum lipids and lipoprotein profiles in relation to body mass index (BMI), which will enable us to compare the nature and weight of metabolic risk factors in atherosclerosis between Japanese and people in Western countries. Data of total serum cholesterol, triglyceride, and HDL-cholesterol levels of Japanese men and women obtained from a large-scale survey in 1990 were analysed according to BMI for different age groups. Apolipoprotein A-I and B and Lp(a) were also measured in randomly selected samples and their contribution as a risk factor was estimated especially in postmenopausal women. The subjects in two age groups of men (20-39 and 40 59 years) and women (20 39 and 50-69 years) were graded into quintiles according to the BMI. The middle grades of BMI were 21.9-23.3 and 22.4-23.6 for younger and older men, and 20.0-21.1 and 22.2-23.6 for younger and older women, respectively. These values are much lower than those in Western populations, the border between the IVth and the top quintile almost corresponding to the average for Americans. Total cholesterol showed a tendency to shift into higher ranges in all age groups in both men and women as BMI increased, with the highest distribution remaining in the range of 160-199 mg/dl (4.2-5.2 mmol/l). The average cholesterol levels for the top quintile of BMI were still lower than most of the average values in Western populations. The distribution of cholesterol in higher ranges was much greater and the difference according to BMI was smaller in older women than in men. In both men and women, whether younger or older, about 90% of the subjects in the lower quintiles of BMI had triglyceride levels lower than 150 mg/dl. The distribution in the higher range of triglyceride was small in women, not only at younger ages but also in postmenopausal women at the top quintile of BMI. About 85% of the younger women with a middle grade of BMI had an HDL-cholesterol level higher than 50 mg/dl. The values in postmenopausal women were still higher than in men aged 40-59 years. Shift of the distribution curves of HDL-cholesterol according to BMI was similar in all groups and more remarkable than the change in triglyceride. The average HDL-cholesterol levels at the top quintile were almost comparable to the average values in Western countries; the difference in HDL-cholesterol levels between the two populations can mostly be explained by the difference in BMI. Smokers showed a slightly lower total cholesterol and significantly (3-4 mg/dl) lower HDL-cholesterol levels, although there was no difference in distribution of BMI between smokers and non-smokers. Relatively low total cholesterol levels even in smokers has probably contributed to the low incidence of IHD in spite of the high frequency of smoking in Japanese population. Mean Lp(a) levels showed a tendency to increase after age 40 in women. BMI itself did not have a correlation with serum Lp(a) levels. The distribution curve of Lp(a) shifted to higher levels as total cholesterol increased and the tendency was most remarkable in women around or after the menopause. It was remarkable in older women that as the total cholesterol or apo B level increased there was also an increased prevalence of abnormal ECG with a pattern of myocardial ischemia. Postmenopausal women seem to have a great risk of atherosclerosis regarding the lipid and lipoprotein profile even in the Japanese population.
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PMID:Analysis of serum lipid levels in Japanese men and women according to body mass index. Increase in risk of atherosclerosis in postmenopausal women. Research Group on Serum Lipid Survey 1990 in Japan. 1020 80


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