Effects of postmenopausal hormone replacement therapy on insulin resistance

Postmenopausal hormone replacement therapy (HRT) protects women from the risk of cardiovascular system disease, osteoporosis, and dementia. There are conflicting reports about the effects of HRT on insulin resistance. The purpose of this study was to investigate the effects of HRT on insulin resistance with the hyperinsulinemic euglycemic clamp technique, the most sensitive technique measuring insulin resistance. Conjugated estrogen (0.625 mg/d) and medroxyprogesterone acetate (5 mg/d) were given to 15 postmenopausal women with insulin resistance. After 3 mo of HRT, the M value (total glucose consumption) increased 28% (p<0.001), low-density lipoprotein (LDL) cholesterol decreased 12.9% (p<0.044), high-density lipoprotein (HDL) cholesterol increased 17% (p<0.009), total cholesterol decreased 9.1% (p<0.016), and serum insulin decreased 33% (p<0.022) compared to baseline values before HRT was started. No significant changes in glucose, C-peptide, and triglyceride levels were observed. Whereas there were no differences regarding glucose, total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels between the insulin-resistant (n=15) and non-insulin-resistant women (n=24) (p>0.05), there were significant differences in M value, insulin, and C-peptide levels between these groups (p<0.05). We believe that HRT with this combination may protect postmenopausal women from coronary artery disease (CAD) through its beneficial effects on insulin resistance, hyperinsulinemia, and lipid levels, which are considered to be important factors in CAD pathogenesis.     

Effects of Withdrawal of Xuezhikang, an Extract of Cholestin, on Lipid Profile and C-reactive Protein: A Short-Term Time Course Study in Patients with Coronary Artery Disease

Objective C-reactive protein (CRP) is considered a risk factor for coronary artery disease. In addition to its lipid-lowering properties, statin decreases the level of CRP. Abrupt cessation of statin therapy during treatment could increase CRP level independently of the elevation of serum lipids and the incidence of cardiac events in patients with atherosclerotic heart disease. Xuezhikang (XZK), an extract of cholestin, has a marked modulating effect on lipid and CRP concentrations in different study time course. However, no attention has been paid to the changes of lipid profile and CRP concentrations after withdrawal of XZK treatment. This study was designed to explore short-term time course effects on lipid profile and CRP concentrations after withdrawal of XZK treatment in coronary heart disease patients. Materials and methods Seventy-five consecutive patients with documented coronary heart disease were randomly divided into three groups: 1. Pretreatment with XZK 1,200 mg daily for 6 weeks and then replaced by placebo (XZK discontinued group; n = 25); 2. Treatment with XZK 1,200 mg daily throughout the study (XZK continued group; n = 25); or 3. Placebo (no XZK group; n = 25). Lipid levels (total cholesterol, HDL-C, LDL-C and triglycerides) and CRP were assessed before receiving the XZK therapy, 1 day before discontinuation of XZK, and on days 1, 2, 3, 7 and 14 after discontinuation of XZK, respectively. Results After 6-week XZK treatment, the fasting total cholesterol, LDL-C, triglyceride and median hs-CRP concentrations decreased, whereas HDL-C concentration increased significantly (p < 0.001, respectively). At day 14 after discontinuation of XZK therapy, total cholesterol (15%), LDL-C (17%) and triglyceride (20%) significantly increased (p < 0.001, respectively), whereas HDL-C level (15%) significantly decreased (p < 0.05). The median level of CRP increased by 11, 65, 128, 103 and 101% on the first, second, third, seventh, and fourteenth day after withdrawal of XZK therapy (p > 0.05, <0.05, <0.001, <0.001, <0.001, compared with 1 day before withdrawal of XZK therapy, respectively). There was a prominent rebound of CRP concentration 3 days after discontinuation of XZK therapy. At this time point, hs-CRP concentration was higher than in the placebo group (p < 0.05). Seven to 14 days after discontinuation of XZK therapy, the hs-CRP concentration declined to a similar level as in the placebo group. No significant correlation was seen between the changes in hs-CRP and lipid profile at all time points. Conclusions The level of hs-CRP increases on the second day after withdrawal of XZK and there is a prominent rebound 3 days after discontinuation of XZK therapy. The increase of CRP ends within 7 days, where lipids increase at 14 days after discontinuation of XZK therapy. The results may be clinically important for patients with coronary artery disease.     

The Effect of Enalapril and Timolol on Blood Lipids: A Randomized Multicenter Hypertension Study in General Practice in Norway

In a 24-week randomized, single-blind study Timolol (n=63) and Enalapril (n=57) proved to be potent and safe antihypertensive drugs. However, the effect on lipid metabolism was fundamentally different, despite the fact that the effect on total serum cholesterol did not significantly differ between the two groups. Enalapril had no adverse effect on any lipid fractions, while Timolol increased very low (VLDL) + low (LDL) density lipoprotein cholesterol by 7.6% (p<0.001) and total triglycerides by 34.5% (p<.001), and decreased the favorable high density lipoprotein (HDL) cholesterol by 11.3% (p<0.001). Thus, the ratio HDL/VLDL + LDL cholesterol was reduced by 17.1 % (p<0.001). Enalapril reduced uric acid by 3.4% (NS), while Timolol increased uric acid by 4.0% (p<0.05). The difference between the groups was statistically significant (p<0.01). The first steps in any attempt to solve the hypertension-coronary dilemma should be to take into consideration all pharmacologic effects of antihypertensive drugs.     

Comparison of Bezafibrate and Simvastatin in the Treatment of Dyslipidaemia in Patients with NIDDM

Fibrates and HMG CoA reductase inhibitors are commonly used in the treatment of diabetic dyslipidaemia. However, these two groups of drugs have not been compared in diabetic patients in a randomized controlled trial. Therefore, a multicentre study was performed in 73 subjects with non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and combined hyperlipidaemia (serum cholesterol 6.2–10.0 mmol l⁻¹, serum triglycerides 2.3–10.0 mmol l⁻¹), comparing the efficacy of 400 mg bezafibrate with 10 mg simvastatin in a double-blind fashion. Treatment with bezafibrate during 12 weeks reduced serum triglycerides significantly more than simvastatin (−41 % vs −22 %, p < 0.001) and increased HDL cholesterol more (bezafibrate: + 17 % vs simvastatin: + 9 %, p < 0.05). LDL cholesterol levels decreased by 14 % (p < 0.001) during simvastatin and increased by 21 % (p < 0.01) during bezafibrate. This increase in LDL cholesterol was positively correlated with fasting serum triglycerides (p < 0.001) and was associated with a reduction of the serum apolipoprotein B concentration, suggesting an increase in LDL particle size. Metabolic control of diabetes (fasting glycaemia; HbA_1c) and insulin secretion (C-peptide levels) were unaffected by both treatments. The incidence of side-effects during treatment was similar for both drugs. Thus, 400 mg bezafibrate mainly increases HDL cholesterol and lowers serum triglycerides but at the expense of an increase in LDL cholesterol; 10 mg simvastatin lowers LDL cholesterin more effectively but has a smaller effect on HDL cholesterol and triglycerides. © 1997 John Wiley & Sons, Ltd.     

Evidence of higher insulin resistance in NIDDM patients with ischaemic heart disease

Summary Prospective studies have shown a relationship between hyperinsulinaemia, an indirect index of insulin resistance, and IHD in men with normal glucose tolerance. In NIDDM this association is less clear possibly due to the poor significance of insulin and C-peptide concentrations as an index of insulin resistance. Therefore, only a direct measurement of insulin sensitivity could clarify the possible relationship between insulin resistance and IHD in NIDDM. We have evaluated insulin sensitivity, by means of an ITT, and some risk factors for IHD in 72 men with NIDDM, 36 with and 36 without IHD, attending our out-patient Diabetic Clinic. The two groups were of similar age, duration of diabetes, glycaemic control and body composition. Subjects with IHD were more insulin resistant (K_ITT index 2.45±0.18 vs 3.12±0.13% per min, in patients with and without IHD, respectively, p<0.004), had higher total (p=0.011) and LDL serum cholesterol levels (p=0.010) and greater prevalence of hypertension (p=0.001) compared to subjects without IHD. Using step-wise logistic regression analysis, insulin resistance (odds ratio 2.57, 95% CI 1.87–3.28, p=0.008), hypertension (odds ratio 8.17, 95% CI 6.86–9.48, p=0.002), total serum cholesterol levels (odds ratio 1.02, 95% CI 1.005–1.035, p=0.015) and BMI (0.79, 95% CI 0.67–0.97, p=0.049) were independently associated with IHD. After adjustment for age and duration of diabetes, only insulin sensitivity was directly related to the age of onset of IHD, independently from other clinical and metabolic parameters (p<0.015). In conclusion: in NIDDM, patients with IHD are more insulin resistant compared to subjects without IHD. Insulin resistance is associated with IHD, independently from other cardiovascular risk factors. A higher insulin resistance seems to be related to an earlier clinical onset of IHD.Abbreviations NIDDM non-insulin-dependent diabetes mellitus - IHD ischaemic heart disease - ITT insulin tolerance test - CI confidence interval - ACE angiotensin-converting-enzyme     

The Regulation of Post-prandial Cellular Cholesterol Metabolism in Type 2 Diabetic and Non-diabetic Subjects

The purpose of the study was to determine the effect of diabetes on the regulation of postprandial cholesterol metabolism. Four groups of patients (n = 8 for each group) were examined: Type 2 diabetic patients with and without hypercholesterolemia and nondiabetic subjects with and without hypercholesterolaemia. Serum lipoproteins, lipoprotein composition, cellular cholesterol, and cellular cholesterol synthesis were measured before and 4 h after a high calorie meal. The BMI for the hypercholesterolaemic diabetic patients of 31.5 ± 0.95 (SEM) was significantly higher than that for the control group of 26.2 ± 1.0 (p < 0.01). Fasting triglyceride levels were significantly higher in the normocholesterolaemic and hypercholesterolaemic diabetic patients and in the hypercholesterolaemic non-diabetic subjects (1.45 ± 0.22, 2.27 ± 0.34, and 1.58 ± 0.18 mmol l^?1, respectively) compared with normocholesterolaemic non-diabetic subjects (0.75 ± 0.12 mmol l^?1: p < 0.01). The normocholesterolaemic and hypercholesterolaemic diabetic subjects had significantly lower fasting serum high density lipoprotein (HDL) (1.06 ± 0.08 and 1.04 ± 0.06 mmol l^?1) compared to the corresponding non-diabetic groups (1.29 ± 0.11 and 1.45 ± 0.17 mmol l^?1, p < 0.05). The esterified/free cholesterol ratio of very low density lipoprotein (including chylomicrons VLDL-C) decreased postprandially in all groups with an overall decrease of 1.33 to 0.83 (p < 0.01). Fasting cellular cholesterol in mononuclear leucocytes from normocholesterolaemic diabetic patients was similar to that for hypercholesterolaemic diabetic (36.8 ± 1.2 vs 40.6 ± 5.5 mg g^?1 protein) and non-diabetic subjects (36.7 ± 6.8 mg g^?1 protein) and significantly greater than cholesterol in cells from control subjects (29.7 ± 1.5 mg g^?1 protein, p < 0.05). In cells from control subjects only, there was a significant postprandial increase in cholesterol to 39.4 ± 5.2 mg g^?1 protein (p < 0.05) and a corresponding postprandial reduction in cholesterol synthesis from 149 ± 34 to 102 ± 33 nmol g^?1 cell protein (p < 0.05). These results demonstrate a lack of correlation between serum and cellular cholesterol in diabetic patients and an inability to suppress cellular cholesterol synthesis postprandially in these patients. The differences may, in part, explain the increased deposition of cholesterol in atheromatous plaques in normocholesterolaemic diabetic patients.     

Serum lipid profile in fibromyalgia women

The etiology and pathogenic mechanisms of fibromyalgia (FM) syndrome are unknown. A number of studies have shown that there is an association between some of the musculoskeletal system diseases and hyperlipidemia. The aims of this study were (1) to compare the serum lipid profile among FM and healthy women and (2) to investigate the relationship between serum lipid levels and FM findings. One hundred sixty-four women (82 women with FM as study group and 82 healthy women as control group) were enrolled in the study. The mean serum total cholesterol and low-density lipoprotein cholesterol (LDL-c) were found significantly higher in the FM group than that in the control group (p<0.05). However, There was no statistically significant difference in the mean serum triglyceride, high-density lipoprotein cholesterol (HDL-c), and very low-density lipoprotein cholesterol (VLDL-c) values between the two groups (p>0.05). In the FM group, we could not find a significant correlation between the serum lipid profile values and the FM parameters (p>0.05).     

Treatment of hypertriglyceridemia with para-aminosalicylic acid-C: A possible mechanism of action

The effect of para-aminosalicylic acid-C (PAS-C, 8 g/day) on lipid metabolism was studied on a metabolic ward in nine subjects with primary endogenous hypertriglyceridemia. During 2 wk on a basal isocaloric liquid formula diet (40% fat, 45% carbohydrate), PAS-C reduced plasma triglyceride (?41.9 ± 18.9%, p < .01, $\text{x}$ ± SD), cholesterol (?22.8 ± 12.9%, p < .005), and a very low density lipoprotein triglyceride (p < .001) and cholesterol (p < .01) levels without changing the cholesterol content of low density or high density lipoproteins. Similar effects occurred on a fat-free, 85% carbohydrate diet. Decreases in very low density lipoproteins correlated with changes in both total triglyceride (r = .99, p < .01) and cholesterol (r = .70, p < .05). Treatment with PAS-C reduced the plasma triglyceride removal rate related to lipoprotein lipase (?14.6 ± 14.1%, p < .02), but did not alter plasma postheparin lipolytic activity or the apparent Km for substrate-enzyme interaction. Kinetic data obtained during the prolonged heparin infusion fit the linearized Michaelis-Menten model for subjects with endogenous hypertriglyceridemia. The reduction in the plasma triglyceride concentration during PAS-C treatment was a function of the decrease in triglyceride removal rate (r = .74, p < .025) without alternation in the maximal removal capacity related to lipoprotein lipase. This suggests that under the steady state conditions of these studies, the decrease in plasma triglyceride concentration was due to a reduction in endogenous triglyceride production. Free fatty acid metabolism, glucose homeostasis, fat absorption, and thyroid function did not change. These results suggest that PAS-C lowers plasma triglyceride and cholesterol levels in hypertriglyceridemic subjects by reducing endogenous very low density lipoprotein production and/or secretion into the circulation.     

Current status of Type 2 (non-insulin-dependent) diabetic subjects on dialysis therapy in Japan

Summary According to a national survey of dialysis patients in Japan conducted by the Japanese Society for Dialysis Therapy, there were 1,033 patients on dialysis in the Shiga area which has a population of about 1.2 million. Of these 1,033 dialysis patients 140 were the result of diabetic nephropathy. From four hospitals affiliated to Shiga University of Medical Science the medical records of 90 diabetic subjects on dialysis therapy were reviewed and various clinical parameters were analysed and compared with those of patients with chronic glomerulonephritis. Since only one patient had Type 1 (insulin-dependent) diabetes, the remaining 89 with Type 2 (non-insulin-dependent) diabetes were used for this study. The significantly different variables between patients with Type 2 diabetes and chronic glomerulonephritis were age (60.4 vs 54.6 years,p<0.05), BMI (22.4 vs 20.6 kg/m²,p<0.001), cardiothoracic ratio (56.4 vs 53.3%,p<0.001), mean blood pressure (110 vs 117 mm Hg,p<0.05), serum creatinine (9.0 vs 11.5 mg/dl,p<0.001), serum urea-N (98.2 vs 115.5 mg/dl,p<0.001), serum total protein (6.0 vs 6.5 g/dl,p<0.001) and serum albumin (3.5 vs. 3.9 g/dl,p<0.001). Serum levels of cholesterol and triglyceride were not significantly different between two groups, though the prevalence of electrocardiogram abnormalities, oedema, neuropathy, myocardial infarction and cerebrovascular diseases was significantly higher in the Type 2 diabetic group. These results suggested that Type 2 diabetic patients with end-stage renal disease were older, more malnurished, fluid overloaded and multi-morbid as a result of vasculopathy and neuropathy. However, the analysis of causes of death in Type 2 diabetic patients (n=24) and patients with chronic glomerulonephritis (n=26) failed to provide evidence of higher risk of cardiac death in the Type 2 diabetic group compared to the group with chronic glomerulonephritis (37.5 vs 34.6%, NS). In the Type 2 diabetic patients on dialysis therapy, malnutrition, fluid overload and neuropathy appeared to be significant factors influencing the outcome of the therapy, while in patients with chronic glomerulonephritis, age and vascular morbidities were considered to be major risk factors for the prognosis.     

Long-term physical training in female Type 1 (insulin-dependent) diabetic patients: absence of significant effect on glycaemic control and lipoprotein levels

Summary No objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 (insulin-dependent) diabetic patients trained two to three times a week for several months. In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control. Thirteen patients completed a 5-month study; 6 were randomized to exercise training (20 min daily bicycle exercise) and 7 served as non-exercising controls. The training resulted in an 8% increase in maximal oxygen uptake (p < 0.05). No change in glycaemic control occurred during the study period in either group. In addition, serum lipid and lipoprotein levels were followed. Total cholesterol decreased during the study period irrespective of training. No effect was noted on the levels of LDL, VLDL, HDL and HDL₂ cholesterol. A significant training effect was obtained in the HDL₃ subfraction (−10%,p < 0.05). Total triglycerides were unchanged, but a decrease in the level of LDL triglycerides was observed with training (−12%,p < 0.01). It is concluded that, in female Type 1 diabetic patients, daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles.     

No excess 12-year mortality in men with impaired glucose tolerance who participated in the Malmö Preventive Trial with diet and exercise

Summary Impaired glucose tolerance (IGT) is associated with increased mortality due to ischaemic heart disease (IHD), but as it is not known whether this excess mortality can be reduced by preventing or delaying the development of non-insulin-dependent diabetes mellitus (NIDDM), a long-term NIDDM prevention trial of dietary counselling and physical exercise was launched at Malm?, Sweden, the 12-year follow-up of which is reported here. At 12-year follow-up of 6956 men who underwent health screening at 48 years of age, an IGT intervention group (n = 288) who participated in a long-term NIDDM prevention programme were compared with an IGT non-randomised routine treatment group (n = 135), a diabetic group (n = 144), and the remainder, the normal glucose tolerance (NGT) group (n = 6389). The variables studied included the levels of blood glucose, plasma insulin, blood pressure, blood lipids, lung function and maximum oxygen uptake. Subjects with IGT were characterised by overweight, poor vital capacity, hypertension, hypertriglyceridaemia and hyperinsulinaemia. The mortality rate in the IGT intervention group was similar to that in the NGT group (6.5 vs 6.2 per 1000 person years at risk) and lower than that in the IGT routine treatment group (6.5 vs 14.0, p = 0.009). In the two IGT groups taken together, intervention but not body mass index, systolic blood pressure, smoking, cholesterol or the 2-h glucose level predicted mortality. Systolic blood pressure was a predictor of IHD mortality among IGT subjects; and in the cohort as a whole, body mass index, systolic blood pressure, hypercholesterolaemica, diabetes and smoking were predictors of IHD mortality. The findings suggest that a long-term intervention programme, with an emphasis on lifestyle changes, including dietary counselling and physical exercise, will reduce mortality in subjects with IGT who are at an increased risk of both developing NIDDM and of premature death due to IHD and other causes. [Diabetologia (1998) 41: 1010–1016] Received: 20 June 1997 and in revised form: 24 April 1998     

Arterial wall cholesterol content is a predictor of development and severity of arterial thrombosis

Background: It is unclear if total cholesterol content contributes to the severity of cardiovascular events by affecting the amount of thrombosis. This study evaluated relationships between cholesterol levels and the amount of thrombosis in an atherosclerotic rabbit model of plaque disruption and thrombosis. Methods: Three groups of NZW rabbits were used: normal rabbits (Group I, n = 4); atherosclerotic rabbits (Group II, n = 4); and atherosclerotic rabbits with pharmacologically triggered thrombosis (Group III, n = 16). Atherosclerosis was induced by feeding a cholesterol enriched diet and balloon deendothelialization. At post-mortem, platelet-rich thrombus and arterial wall cholesterol were quantified and histology performed by light and electron microscopy. Results: Arterial wall cholesterol was strongly correlated to serum cholesterol in all groups (r = 0.94, p < 0.0001). There was a significant correlation between the thrombus surface area with arterial wall cholesterol in Group III (r = 0.71, p < 0.002). Serum cholesterol, arterial wall cholesterol, and thrombus surface area were all significantly correlated but only arterial wall cholesterol was an independent predictor of thrombosis. A threshold specific for this model was noted for serum and arterial cholesterol levels above which thrombosis consistently occurred. Conclusions: Arterial wall cholesterol was strongly correlated to serum cholesterol and thrombosis severity. Serum cholesterol, arterial wall cholesterol and thrombus surface area were all integrally related. Condensed Abstract A model of plaque disruption and thrombosis was used to demonstrate a correlation between serum and arterial wall cholesterol (r = 0.94; p < 0.0001); arterial wall cholesterol and the amount of thrombosis (surface area; r = 0.71, p < 0.002). A threshold of serum and arterial cholesterol was determined at which thrombosis occurred in this model.     

Serum creatinine ratio: A novel predictor of mortality after percutaneous coronary intervention in patients with normal and abnormal renal function

The occurrence of contrast induced nephropathy (CIN) is associated with increased mortality after percutaneous revascularization procedures. However, the exact correlation between various levels of creatinine elevation relative to the baseline and subsequent mortality in patients with chronic renal insufficiency (CRI) is not well established. In addition, the relationship between elevated postprocedural creatinine and ensuing mortality in patients with normal baseline renal function needs to be investigated. Methods : All percutaneous coronary intervention (PCI) patients (n = 12,997) were analyzed for any rise in serum creatinine (SCr): CRI group (BSC ≥ 1.5 mg/dl) (n = 1,853) and normal baseline renal function (NBR BSC < 1.5 mg/dl) group (n = 11,144). Patients in each group were analyzed for any elevation in SCr postprocedure and subdivided based on the SCr ratio [peak SCr/Baseline creatinine (BSC)] of <1.25, 1.25–1.5, and >1.5. The overall incidence of CIN (defined as an increment of 25% over baseline creatinine) was 5.9%: 11.3% in the CRI group versus 5.1% in normal BSC group (P < 0.01). Recursive partitioning and Cox hazard modeling were used to assess significant variables associated with mortality within 1 year. Only serum creatinine ratio (SCrR) > 1.5 correlated with increased mortality in both CRI group as well as normal BSC group. Conclusions : SCrR > 1.5 predicts mortality at 1 year after PCI. The association between SCrR > 1.5 and increased mortality at follow‐up is observed in patients with CRI as well as normal baseline renal function. SCrR may thus serve as a useful clinical tool for risk stratification and prognostication of patients after PCI. © 2009 Wiley‐Liss, Inc.     

Higher Cholesterol Level Predicts Cardiovascular Event and Inversely Associates With Mortality in Hemodialysis Patients: 10‐Year Outcomes of the Q‐Cohort Study

The prevalence of atherosclerotic diseases is higher in hemodialysis patients. The aim of the current study was to investigate associations between cholesterol level and the incidences of cardiovascular disease (CVD) and mortality in hemodialysis patients. A total of 3517 participants undergoing maintenance hemodialysis were followed up for 10 years. Total cholesterol (TC) level was divided into quartile in baseline data. The multivariate analyses were calculated by a Cox proportional hazards model. The incidences of ischemic heart disease (IHD), peripheral artery disease (PAD), and CVD were significantly positively associated with higher cholesterol levels after adjustment for confounding factors (P < 0.01, P = 0.04, and P < 0.01, respectively). Furthermore, the incidences of cancer‐associated mortality and all‐cause mortality were significantly positively associated with lower cholesterol levels after adjustment for confounding factors (both P < 0.01). The lowest TC level at all‐cause mortality risk was 179 mg/dL. From these results, higher TC predicts IHD, PAD, and CVD events, and lower TC predicts cancer‐associated mortality and all‐cause mortality in patients undergoing maintenance hemodialysis.     

Related factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia

Objective: To investigate the related factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia. Methods: One hundred and ten patients with primary hypertension and hyperhomocysteinemia (homocysteine levels >10 μmol/L) were enrolled into this study, ages from 18 years to 75 years. They were divided into the normal serum uric acid group which contained 74 cases patients (41 cases of male and 33 cases of female) and the hyperuricemia group which contained 36 cases patients (20 cases of male and 16 cases of female). Plasma concentrations of homocysteine, serum uric acid, serum folic acid, blood sugar, triglyceride, total cholesterol, serum low density lipoprotein cholesterol, serum high density lipoprotein cholesterol, blood urea nitrogen, and creatinine were detected in these patients, and the deference of them between the two groups was compared. And then the risk factors of serum uric acid with univariate analysis and multivariate analysis by logistic regression analysis were analyzed. Results: The result of multivariate analysis showed that the incidence of serum uric acid in patients with primary hypertension and hyperhomocysteinemia had significant relationships with systolic blood pressure (OR [odds ratio]: 1.132, 95%CI [confidence interval]: 1.003~1.290, p = 0.043), diastolic blood pressure (OR: 1.353 95%CI: 1.023~1.789, p = 0.034, homocysteine (OR: 1.264, 95%CI: 1.016~1.573, p = 0.035), triglyceride (OR: 9.726, 95%CI: 1.288~73.466, p = 0.027), and creatinine (OR: 1.031, 95%CI: 1.005~1.508, p = 0.018). Conclusion: The indices of systolic blood pressure, diastolic blood pressure, homocysteine, triglyceride, and creatinine were important risk factors of serum uric acid in patients with primary hypertension and hyperhomocysteinemia. It is of great significance to measure multiple risk factors in patients with primary hypertension and hyperhomocysteinemia.     

Serum lipids and thyrotropin in women with coronary artery disease

Abnormalities of thyroid function are associated with changesin lipid concentrations and in the incidence of ischaemic heartdisease. Whether lipid concentration and thyroid function arerelated when thyroid function is normal in ischaemic heart diseaseis uncertain. This study was undertaken to investigate the relationshipbetween thyroid function, serum lipids and ischaemic heart diseasein euthyroid women. Forty-six euthyroid patients were studied. Patients with diseasesknown to affect lipid levels or receiving drugs known to alterlipid or thyroid metabolism were excluded Twenty-three had ischaemicheart disease (IHD) and were matched with 23 controls. Correlationswere found between thyrotropin (TSH) and cholesterol (P=0·05)low density lipoprotein (LDL) (P=0·09) and triglyceride(P=0·009 in the IHD group but not between any serum lipidsand TSH in the control group. Analysis of covariance showeda statistically significant difference between groups of theassociation between cholesterol and TSH (P<0·05 (slope)P<0·001 (means)), LDL and TSH (P<0·005 (means))and between triglyceride and TSH (P<0·05 (means)).This study suggests that TSH within the normal range is havinga statistically significant effect on lipid levels in womenwith ischaemic heart disease.     

Analysis of Factors that Affect Short-Term Blood Pressure Variability in Patients with Chronic Renal Failure

Recent reports suggest the relationship of short-term blood pressure (BP) variability to cardiovascular target organ damage. In this study, short-term BP variability was assessed as the standard deviation of daytime and nighttime BP in 36 hospitalized patients with chronic renal failure (CRF) who underwent ambulatory BP monitoring. Positive correlations were observed between body mass index (BMI) and daytime systolic and diastolic BP variability, BMI and nighttime diastolic BP variability, cholesterol and daytime systolic BP variability, cholesterol and nighttime systolic and diastolic BP variability, nocturnal decline in BP and nighttime diastolic BP variability, and plasma concentration of norepinephrine (p-NE) and nighttime systolic BP variability. In multivariate linear regression analyses, BMI showed the strongest association with daytime and nighttime diastolic BP variability (p < .005 and p < .05). On the other hand, cholesterol and p-NE were the primary determinants of daytime and nighttime systolic BP variability, respectively (p < .01 and p < .0005). Interestingly, CRF patients with ischemic heart disease (IHD) had significantly increased daytime systolic and diastolic BP variability and nighttime systolic BP variability (p < .05 or less). Furthermore, logistic regression analysis demonstrated that nighttime systolic BP variability was an independent risk factor of IHD in patients with CRF (odds ratio 1.50 [95% confidence interval 1.01 to 2.25]; p < .05). Taken together, short-term BP variability is suggested to be affected by BMI, cholesterol, and p-NE in CRF patients. Furthermore, sympathetic nerve overactivitymay be involved in cardiovascular complications in CRF patients through the increase in nighttime systolic BP variability.     

Genetic influence of the R/Q353 genotype on factor VII activity is overwhelmed by environmental factors in Chinese patients with Type II (non-insulin-dependent) diabetes mellitus

Summary We studied the effects of genetic and environmental influences on factor VII coagulant activity (VIIc) in Chinese diabetic patients (263 with Type II [non-insulin-dependent] diabetes mellitus, 78 with Type I [insulin-dependent] diabetes mellitus) and 143 normal control subjects. VIIc was measured by a one-stage biological assay. The R/Q353 or Msp1 polymorphism at codon 353 of the factor VII gene was detected after Msp1 digestion of polymerase chain reaction-amplified genomic DNA. In both diabetic and control subjects the allele frequencies of the R (M1) and Q (M2) alleles were 0.96 and 0.04; the corresponding reported frequencies in Caucasians being 0.90 and 0.10: VIIc were 21 % lower in Chinese control subjects and Type I diabetic patients with R/Q, compared with R/R subjects (p < 0.001 and p < 0.05). The corresponding difference was 4 % for Type II diabetc patients (p = NS). Type II diabetic patients had higher mean VIIc levels than control subjects and Type I diabetic patients (p < 0.01); they were also older, and had higher serum creatinine and triglyceride (all p < 0.01). They also had higher VIIc levels than an age-matched older control group (p < 0.01; n = 182) in whom the genotype effect was clearly seen. On stepwise linear regression analysis, the significant independent determinants of VIIc were serum triglyceride (contributing 20 % and 25 % to variance in control subjects and diabetic patients), the R/Q353 genotype (contributing to 12 % of the variance in control subjects but only 1 % in diabetic patients), age and total cholesterol in all subjects, and in the diabetic patients female sex, urinary albumin excretion rate and serum creatinine. VIIc was higher in diabetic patients with macroangiopathy and retinopathy (both p < 0.0001). We conclude that compared with Caucasians, the Q allele frequency is significantly lower in these Chinese subjects. Plasma VIIc is determined by both genetic and environmental influences such that in Chinese Type II diabetic patients, the effect of environmental factors predominates, almost negating the influence of the R/Q353 genotype. High VIIc may contribute to the increased cardiovascular risk in Type II diabetic patients. [Diabetologia (1998) 41: 760–766] Received: 24 October 1997 and in final revised form: 28 January 1998     

C-Met Protooncogene Expression and Its Regulation by Cytokines in the Regenerating Pancreas and in Pancreatic Cancer Cells

Objective Jejunoileal (JI) bypass was a widely performed surgical procedure for morbid obesity in the 1970s. The purpose of this study was to assess cardiovascular risk factors and mortality in patients 25 years or more after this operation. Material and methods All (n=36) patients operated on for obesity with JI bypass at Haukeland University Hospital between 1971 and 1976 were evaluated. Survivors (n=28) participated in a follow-up that included clinical examination and biochemical tests. Preoperative data were compared with data at 1 year (3 years) and 25 years. Causes of death were identified for the deceased. Results For the 23 patients alive with intact JI shunts at 25 years there was a statistically significant lowering of body mass index (BMI) (p<0.01), systolic blood pressure (p<0.05), diastolic blood pressure (p<0.001) and serum cholesterol (p<0.05) compared to before the operation. There was no statistically significant change in fasting blood glucose or serum triglyceride. The serum insulin level was normal in all but one (21/22) of the patients examined. Three out of 26 patients with intact JI shunts, and 5 out of 10 patients with reversed JI shunts, had died. Conclusion For patients with intact shunts there is a persistent reduction in body weight, serum cholesterol and blood pressure, and a reduced insulin resistance 25 years after JI bypass.     

Effects of Nicotinic Acid on Concentrations of Serum Apolipoproteins B,C-I,C-II,C-III and E in Hyperlipidemic Patients

Abstract. Twenty-four patients with Type IIa, IIb, III and IV hyperlipoproteinemia (HLP) were treated with 4 g of nicotinic acid daily with the purpose to study its effect on serum apolipoprotein B, C-I, C-II, C-III and E concentrations. Triglyceride and total cholesterol concentrations of whole serum and of different serum lipoprotein fractions were also determined. Analyses were performed prior to and after a drug treatment period of 6 weeks, during which all the patients were weight stable. Treatment caused a decrease in serum concentrations of apolipoproteins C-I, C-II, C-III and E. These highly significant reductions were all positively correlated to a reduction of very low density lipoprotein triglyceride levels of serum (r-values >0.76, p<0.001). There were highly significant decreases in serum levels of apolipoprotein B and low density lipoprotein total cholesterol. These reductions were positively intercorrelated (r=0.55; p<0.01). Similar effects were observed in the different HLP types and in both sexes. Treatment resulted in normolipidemia in 12 patients, who were hypercholesterolemic (7 type IIa, 3 type IIb, 2 type III hyperlipoproteinemia) prior to treatment. The serum apolipoprotein B concentrations of these 12 patients fell after therapy to values which, however, remained abnormally high. We suggest that serum lipid adjusting treatment should aim at a normalization not only of serum lipid concentrations but also of the serum apolipoprotein B concentration in order to achieve a maximal antiatherogenic effect.