[Dyslipidemia and cardiovascular risk in type 2 diabetes mellitus patients with associated diabetic nephropathy]. / Dislipemia y riesgo cardiovascular en el paciente diabético tipo 2 con nefropatía diabética asociada.

BACKGROUND: Diabetes patients with concomitant diabetic nephropathy are especially destined to cardiovascular complications due to the presence of microalbuminuria or proteinuria, that are potent inductors of dyslipidaemia. METHODS: We have studied 98 type 2 diabetes mellitus patients, 61 male and 37 female, mean age 63 +/- 13 year old, all of them with overt proteinuria (above 500 mg/day), divided into 4 groups: G-I (n = 13): patients with t. cholesterol > 6.25 mmol/l treated with fibric-acid derivatives; G-II (n = 52): hypercholesterolemic patients treated with statins; G-III (n = 20): hypercholesterolemic patients with no lipid-lowering intervention; G-IV (n = 13): normocholesterolemic patients (control group). Lipidic profile, proteinuria and renal function have being compared after 1, 3 and 5 years. RESULTS: Base-line characteristics of the patients were similar when regarding age, onset of diabetes or nephropathy. Only proteinuria was higher in statins-treated group (p < 0.05). Fibric-acid derivatives were more effective on hypertriglyceridaemia while statins were more effective lowering LDL cholesterol. A gemfibrocyl-treated patient presented a rhabdomyolysis episode. Statins were safe and well tolerated. Nine patients (19%) in G-II, 2 patients (10%) in G-III and 1 patient (7%) in G-IV achieved end-stage renal failure. Five-year cardiovascular mortality and all-cause mortality rate were 23%/23% in G-I, 13%/19% in G-II, 20%/25% in G-III and 31%/31% in G-IV. The difference was statistically significant when comparing normocolesterolemic versus statin-treated patients (p < 0.05). CONCLUSION: Lipid-lowering therapy could probably delay but not avoid the progression of diabetic nephropathy. Since dyslipidaemia is closely related to the progression of cardiovascular disease and mortality, an aggressive lipid-lowering therapy is recommended, irrespectively of its potential effect on diabetic nephropathy.

Fluvastatin and low-density lipoprotein oxidation in hypercholesterolemic renal transplant patients.

BACKGROUND: Hyperlipidemia contributes to the development and progression of vascular disease in organ transplant patients. Oxidative modification of low-density lipoproteins (LDLs) has been suggested as a key event in early atherogenesis. METHODS: We conducted a pilot study in renal transplanted patients with persistent hypercholesterolemia above 6.5 mmol/liter. We studied the LDL oxidation before and after one year of fluvastatin treatment. Twenty patients (12 males and 8 females, 46 +/- 10 years old) who received a kidney transplant 24 +/- 18 months before the study were treated with fluvastatin (20 mg/day for 12 weeks). Patients with a total cholesterol under 6.3 mmol/liter continued to receive 20 mg/day for another 40 weeks (group I, N = 10). Nine patients with a total cholesterol above 6.3 mmol/liter received 40 mg/day for a further 40 weeks (group II). RESULTS: Cyclosporine levels did not experience a significant variation. Total and LDL cholesterol decreased significantly in both groups (21.7 and 27.9% in group I, 18.3 and 27.2% in group II, respectively). The lag-phase time, which was significantly enlarged before fluvastatin treatment in the patients with respect to the controls (N = 18, 82 +/- 45 vs. 50 +/- 8 min) was shortened after one year of fluvastatin treatment (64 +/- 24 vs. 50 +/- 8 min, P = 0.04). Fluvastatin was stopped in only one patient because of nausea and vomiting. Transaminases and creatin-phospho-kinase were not altered. All of the patients maintained a functioning graft during the study period. CONCLUSIONS: Fluvastatin significantly reduced total and LDL cholesterol, without interferences with cyclosporine A through levels. Fluvastatin has not demonstrated an antioxidant effect in our renal hypercholesterolemic transplant patients.

[Efficacy of hygienic and dietary therapy in coronary patients with isolated hypoalphalipoproteinemia]. / Eficacia de las medidas higiénico-dietéticas en el tratamiento de la hipoalfalipoproteinemia aislada en pacientes con enfermedad arterial coronaria.

OBJECTIVE: Hypoalphalipoproteinemia (HA) is a relatively frequent disorder found in patients with coronary artery disease (CAD). It is associated to a greater risk of suffering recurrent coronary episodes and of mortality caused by this disease. METHODS: We selected 60 patients with previous CAD and isolated HA (HDLc concentration < 0.9 mmol/L, and desirable lipidic profile) that were consecutively seen in a specialized lipid clinic. Subjects were randomly included in the two groups of cases (group of intervention) and controls. Cases were treated with non-pharmacological measures which included changes in lifestyle and dietary habits. Control subjects were referred to their general practitioners in order to receive conventional medical care. RESULTS: It was demonstrated a significant increase in the HDLc concentration in both groups, being greater the improvement in the group of intervention, but the differences in the increase in the HDLc between both groups were not significant. Fibrinogen was lower in the patients of the group of intervention, especially in those patients that gave up smoking. CONCLUSION: Changes in lifestyle and dietary habits are useful to correct the low HDLc plasma levels and to reduce fibrinogen levels in those patients with CAD and HA.

Cardiovascular risk factors associated with clinically isolated and diffuse atherosclerosis in Spanish patients with coronary artery disease.

BACKGROUND: Patients with coronary artery disease (CAD) associated with peripheral (PAD) or cerebrovascular disease (CVD), a condition called diffuse atherosclerosis, have a higher risk of death than patients with isolated CAD. The prevalence of diffuse atherosclerosis and the atherogenic risk factors associated with this condition in our geographic area have not been described previously. METHODS: A cohort of 2597 patients (62 +/- 10.8 years, 665 women) consecutively admitted at Bellvitge Hospital because of acute coronary syndromes were studied. CAD patients were divided in two groups with diffuse and located atherosclerosis according to whether they had or they had not an associated PAD or CVD. Baseline history, physical data and lipid profile were recorded in each patient according to a standardized questionnaire. RESULTS: A total of 370 patients (14.2%) had diffuse atherosclerosis. Among them, there were more men and women older than 55 years than among those with isolated CAD. Patients with diffuse atherosclerosis were more frequently hypertensive, diabetic and former smokers than those with isolated CAD (60.5% vs. 49.4%, P < 0.01; 37.4% vs. 24.5%, P < 0.01; and 47% vs. 35.7%, P < 0.01, respectively). There were no significant differences in the mean values of total cholesterol (TC), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C) and triglycerides between both groups of patients, but patients with diffuse atherosclerosis had a lower HDL-C/TC ratio, with borderline statistical significance (0.18 +/- 0.06 vs. 0.19 +/- 0.06, P = 0.06). Using multiple logistic regression analysis, the variables associated with diffuse atherosclerosis in men were age greater than 55 years (OR 1.97, CI 1.33-2.93), hypertension (OR 1.50, CI 1.14-2.20), diabetes (OR 1.78, CI 1.20-2.70), smoking (former smokers) (OR 2.09, CI 1.36-3.24) and HDL-C/TC < 0.20 (OR 1.60, CI 1.18-2.17); and in women hypertension (OR 3.43, CI 1.48-7.94) and diabetes (OR 2.58, CI 1.55-4.80). CONCLUSIONS: Clinically overt diffuse atherosclerosis is a relatively common disease. Older patients and those with hypertension, diabetes or low HDL-C/TC ratio are more likely to have diffuse atherosclerosis than those without these conditions.

Low levels of high density lipoprotein cholesterol in patients with active sarcoidosis.

OBJECTIVE: To determine lipoprotein abnormalities in patients diagnosed with sarcoidosis and their relation to disease activity. METHODS: We studied 90 patients with biopsy-proven sarcoidosis who had not been treated with corticosteroids (44 with active disease and 46 with inactive disease) and 147 control subjects. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, HDL2-cholesterol, HDL3-cholesterol, apolipoprotein A-I, apolipoprotein B, and triglyceride concentrations. RESULTS: Patients with active sarcoidosis had significantly low HDL-cholesterol concentrations (1.15 +/- 0.27 mmol/l) as compared with inactive sarcoid patients (1.40 +/- 0.34 mmol/l) and with the healthy control subjects (1.49 +/- 0.34 mmol/l) (p = 0.00001). The decrease in the HDL-cholesterol concentrations seen in patients with active disease was due mainly to the cholesterol bound to HDL2 subfraction. Apolipoprotein A-I concentrations were significantly reduced in the patients with active disease (1.18 +/- 0.32 g/l) compared to the healthy controls (1.38 +/- 0.27 g/l) (p = 0.003). There were no significant differences in cholesterol, triglyceride, LDL-cholesterol or apolipoprotein B values among the three groups. Multivariate logistic regression analysis showed that HDL-cholesterol was the only variable independently associated with disease activity (Regression Coefficient b = -0.03; S.E. = 0.008; p = 0.0005). CONCLUSION: The decrease in HDL-cholesterol that is observed in patients with sarcoidosis is limited to those with active disease.

An enzyme-linked immunosorbent assay method to measure human apolipoprotein E levels using commercially available reagents: effect of apolipoprotein E polymorphism on serum apolipoprotein E concentration.

A sensitive and specific enzyme-linked immunosorbent assay (ELISA) for human apolipoprotein E (apo E) quantification using commercially available reagents is described. The assay is a noncompetitive, sandwich ELISA in which the wells were coated with a monoclonal EO1 antibody anti-human apo E and detected with a polyclonal antibody-peroxidase conjugate anti-apo E. The mean apo E concentration in 168 middle-aged subjects randomly selected from general population was 51.7 +/- 12.4 mg/liter. Apo E levels were highly correlated with apo E phenotypes. Apo E polymorphism, which shows a modulating effect in the catabolism of apo E containing lipoproteins, may explain a large fraction, 18.5%, of the variability of serum apo E levels in middle-aged population. Isoforms apo E2 and apo E4 have an opposite effect on the regulation of serum apo E concentrations. Individuals that express apo E2 isoform present higher apo E levels (65.5 mg/liter for apo E2/E3), whereas the average of individuals with apo E4 is lower (42.8 mg/liter for apo E4/E3) than general population.

Diagnostic accuracy evaluation using ROC curve analysis.

The diagnostic accuracy of a biochemical quantity is inversely related to the overlapping zone between the values of the population suffering from a disease and the population which does not. The ROC curves are an indirect measure of the overlapping zone between both populations. Specimens (plasma and urine) taken from 928 patients with symptoms of acute abdominal pain were used and the catalytic concentration of alpha-amylase, pancreatic alpha-amylase and triacylglycerol lipase (determined by two methods) were measured. Definitive diagnosis was obtained by following the directives of expert groups on the evaluation of diagnostic tests. Diagnostic accuracy was characterized by calculating the diagnostic sensitivity and specificity, by representing the ROC curves and by quantifying the areas under the ROC curves. The catalytic concentration of pancreatic alpha-amylase in plasma was the quantity with a greater area under the ROC curve (A = 0.9740) and then the one which had greatest diagnostic accuracy. If we considered the upper limit of the reference interval to be the cut-off value, the catalytic concentration of pancreatic alpha-amylase in plasma had a diagnostic sensitivity and specificity values of 0.96 and 0.88 respectively for the acute pancreatitis.

Multicentre evaluation of the Boehringer Mannheim/Hitachi 911 Analysis System.

The analytical performance and practicability of the Boehringer Mannheim (BM)/Hitachi 911 analysis system have been assessed in a multicentre evaluation, which involved six laboratories from European countries. Analytes commonly used in classical clinical chemistry were tested in a core programme, which mainly followed the ECCLS guidelines. In addition, a satellite programme covered other analytes, such as proteins, drugs and urine analytes. In total, the study comprised more than 100 000 data items collected over a three-month period. The evaluation was supported with 'Computer Aided Evaluation' (CAEv) and telecommunications.Acceptance criteria for the results were established at the beginning of the study. Nearly all of the analytes met the imprecision limits: within-run imprecision (as CVs) was 2% for enzyme and substrate assays, 1% for ISE methods and 5% for immunoassays; between-day imprecision was 3l% for enzyme and substrate assays, 2% for ISE methods and 10% for immunoassays.No relevant drift effects (systematic deviation >/= 3%) were observed over eight hours. The methods were linear over a wide range. Sample-related and reagent-dependent carry-over can be reduced to a negligible amount by integration of a softwarecontrolled wash-step.Endogenous interferences were found for creatinine (Jaffé method) and uric acid assays (caused by bilirubin), for creatine kinase, creatine kinase MB isoform and gamma-glutamyltransferase (caused by haemoglobin), and for immunoglobulin A (caused by lipaemia)Accuracy was checked by an interlaboratory survey, recovery studies in control materials and method comparison studies. The survey showed that, with the exception of cholesterol and iron in two laboratories, the recovery of analytes did not deviate by more than 5%. Sixty-six of the 77 method comparisons performed met the acceptance criteria. The deviations of the remaining 11 results could be explained by differences in either calibration, application or by the use of different methods.Practicability was assessed using a questionnaire which covered all of the important aspects of an analysis system in the clinical laboratory. Twelve groups of attributes out of 14 were rater higher for the BM/Hitachi 911 than for the present situation in the laboratories concerned. Especially high scores were given for the versatility group.The acceptance criteria for the analytical performance of the BM/Hitachi 911 analysis system were fulfilled in all laboratory segments with few exceptions. The practicability exceeded the requirements in most of the attributes. The results of the study confirmed the usefulness of the system as a consolidated workstation in small- to medium-sized clinical laboratories and in STAT laboratories, or as an instrument for special analytes like proteins and drugs, or for urinalysis in large laboratories.

Biological variation data applied to the selection of serum lipid ratios used as risk markers of coronary heart disease.

The biological variation of several relative lipid quantities, calculated as the ratios between the concentrations of various serum lipids and apolipoproteins, has been estimated over a one-year period. The medians of the within-subject biological coefficient of variation, separated by sex when significant differences exist, were 15.4% for [apolipoprotein A-I]/[apolipoprotein B], 6.8% for [high-density lipoprotein (HDL)-cholesterol]/[cholesterol], 10.5% and 17.6% (women and men, respectively) for [HDL2-cholesterol]/[HDL-cholesterol], 13.6% for [HDL2-cholesterol]/[HDL3-cholesterol], 10.6% for [low-density lipoprotein (LDL)-cholesterol]/[apolipoprotein B], 10.6% and 8.7% (women and men, respectively) for [LDL-cholesterol]/[cholesterol], and 6.3% for [LDL-cholesterol]/[HDL-cholesterol]. From these data, we have calculated the critical difference for significant change detection, the index of individuality, and the goal for the between-day imprecision. Concerning within-subject biological variation, the best ratios for the detection of risk of coronary heart disease and the monitoring of intervention are [LDL-cholesterol]/[HDL-cholesterol] and [HDL-cholesterol]/[cholesterol]. The index of individuality obtained in this study indicates that the use of population-based reference values is inadequate for interpreting the ratios studied.

Results of the multicenter evaluation of the CEDIA Theophylline assay.

We report on the results of the multicenter evaluation of the CEDIA Theophylline assay on Boehringer Mannheim/Hitachi analyzers in 15 clinical laboratories in Europe and U.S.A. Main items of investigation were imprecision, recovery of control sera, interlaboratory survey and method comparisons using patient samples. Imprecision was found to be comparable to other routine methods. An advantage of the CEDIA assay can be seen in the good interlaboratory transferability of results. The new test has been shown to measure very accurately particularly by comparison with HPLC procedures revealing highly correspondent results. The reagent can be used up to one month using multiple recalibration. Due to its high practicability and reliability the CEDIA Theophylline assay can be recommended as a very suitable routine method for therapeutic drug monitoring on random access analyzers like Boehringer Mannheim/Hitachi analysis systems.

[Early detection of dyslipidemias. Is the isolated determination of total cholesterol efficient?]. / Detección inicial de las dislipemias. Es eficaz la determinación aislada del colesterol total?

BACKGROUND: The aim of this study was to analyze the percentage of individuals with hypoalphalipoproteinemia and isolated hypertriglyceridemia which would not be detected if only total cholesterol were included in the initial detection of dyslipemia. METHODS: Five hundred forty-one individuals participating in a study concerning factors of cardiovascular risk were included in the present study which consisted in a survey on risk factors and a medical examination. The population studied was divided according to the concentration of total cholesterol (TC) in desirable concentrations (5.2 mmol/l), intermediate (5.2-6.2 mmol/l) and elevated (6.2 mmol/l). The concentrations of cholesterol bound to high density lipoproteins (cHDL) less than 0.9 mmol/l and of triglycerides (TG) greater than 2.3 mmol/l were considered as high risk. RESULTS: Hypoalphalipoproteinemia would not be detected in 2.9% of the population studied (IC 95%: 1.5%-4.3%) and isolated triglyceridemia in 2.4% (IC 95%: 1.1%-3.7%) if the cHDL and the TG were only determined in the individuals who had high or elevated CT concentrations and two or more cardiovascular risk factors. CONCLUSIONS: These data support the efficacy of CT as the only test for initial detection of dyslipemia and question the convenience of initial quantification of cHDL and triglycerides in all cases as some authors request.

The determination of thyroxine and thyroxine uptake with new homogeneous enzyme immunoassays using Boehringer Mannheim/Hitachi analysis systems.

New homogeneous enzyme immunoassays for the determination of thyroxine and thyroxine uptake have been developed. The CEDIA assays are based on the cloned enzyme donor immunoassay technology, which involves fragments of beta-galactosidase prepared by genetic engineering. The assays have been adapted for Boehringer Mannheim/Hitachi analysers. The CEDIA T4/T Uptake assays were evaluated in eleven clinical chemistry laboratories on various Boehringer Mannheim/Hitachi analysis systems, using a 2-point calibration. The analytical range of the T4 test was 10 to 258 nmol/l thyroxine. The T uptake test had a measuring range between 20-50%. Depending on the concentration of the analyte (samples from hypo-, eu- or hyperthyroid patients), mean coefficients of variation ranged from 1.8 to 4.8% within-run and from 4.1 to 6.5% between-run for the T4 assay. Even better coefficients of variation were obtained for the T uptake assay (1.4 to 2.3% within-run, 2.8 to 3.3% between run). The relative inaccuracy of the CEDIA assays with respect to values assigned by other tests was satisfactory in various control sera. The T4 assay was compared with one radioimmunoassay, one enzyme immunoassay and one fluorescence polarisation immunoassay. Slopes ranging from 0.9 to 1.1 and intercepts ranging from -10 to +10 nmol/l thyroxine were obtained with two exceptions. The results of the T uptake test correlated reasonably with those of other thyroxine-binding methods. No interference was observed with icteric and lipaemic sera. Haemoglobin up to 4 g/l had no significant influence. Results of the CEDIA T Uptake test are mainly used for calculation of the free thyroxine index, in which the thyroxine value is corrected for variations of thyroxine-binding protein concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)