Measurement of low-density lipoprotein cholesterol in assessment and management of cardiovascular disease risk.

The deposition of cholesterol in the arterial wall by the infiltration of low-density lipoproteins (LDLs) is a key step in the development of atherosclerosis. In this Commentary, we discuss recent recommendations for clinical laboratory measurement of low-density lipoprotein cholesterol (LDL-C) and its utility both for assessing cardiovascular disease risk and as a tool in the management of patients receiving lipid-lowering therapy.

Scientific evidence to support a vitamin E and heart disease health claim: research needs.

In addition to epidemiologic studies suggesting a benefit for high intakes of alpha-tocopherol, studies following supplementation in humans have clearly shown that alpha-tocopherol decreases lipid peroxidation, platelet aggregation, and functions as a potent anti-inflammatory agent. However, prospective human clinical trials with alpha-tocopherol alone and in combination with other antioxidants have been largely negative. In this review, we critically appraise the various clinical trials and provide recommendations for future research.

Comparison of an immunoprecipitation method for direct measurement of LDL-cholesterol with beta-quantification (ultracentrifugation).

A direct LDL cholesterol assay was evaluated using immunoprecipitation (Sigma Diagnostics, St. Louis, MO) with beta-quantification obtained by ultracentrifugation. Excellent intra- and interassay coefficients of variation were obtained (< 4.5%). There was a good correlation (r = 0.88, P < .0001) between the two methods for low-density lipoprotein cholesterol (LDL-C) in 249 samples with triglyceride levels ranging from 13 mg/dL to 2,236 mg/dL and LDL cholesterol levels ranging from 28 mg/dL to 290 mg/dL. Similar correlations were seen for patients with triglyceride levels < 400 mg/dL (r = 0.89, n = 174) and > or = 400 mg/dL (r = 0.89, n = 75). However, using the Friedewald equation, there was a good correlation only in samples with triglyceride levels < 400 mg/dL. No significant differences were found between LDL-C quantitated by the direct LDL assay and beta quantification for patients with dysbetalipoproteinemia (Type III disorder). However, calculated LDL values using the Friedewald equation were found to be significantly higher when compared to beta-quantification in patients with the Type III disorder. There was a slight but significant decrease in LDL-C determined by direct LDL cholesterol assay for non-fasting versus fasting serum (4.7%) despite a strong correlation between these samples (r = 0.98, P < .0001). In addition, freezing samples for 30 days resulted in a significant decrease in levels (15.1%). Thus, this direct LDL cholesterol assay is recommended in place of beta-quantification in hypertriglyceridemic samples (TG > or = 400 mg/dL) and to monitor LDL cholesterol levels in patients with Type III dyslipidemia, because it is less time consuming, more cost-effective and can be adapted to the clinical laboratory.

A critical assessment of the effects of aminoguanidine and ascorbate on the oxidative modification of LDL: evidence for interference with some assays of lipoprotein oxidation by aminoguanidine.

Several lines of evidence support a role for oxidized low density lipoprotein (LDL) in the genesis of the atherosclerotic lesion. Hence, the effect of compounds with antioxidant properties on LDL oxidation assumes great significance. Ascorbate, a potent water-soluble chain-breaking antioxidant, has been shown to inhibit LDL oxidation. Aminoguanidine (AMG) is a pharmacological inhibitor of advanced non-enzymatic glycosylation. Recently it has been suggested that aminoguanidine might have an inhibitory effect on LDL oxidation, but total lipid peroxidation assayed by conjugated diene formation was not inhibited. Thus, in this study, we compared the effect of aminoguanidine with ascorbate to obtain a better appreciation of the effect of AMG on Cu(2+)-catalyzed LDL oxidation. Oxidative modification of LDL was monitored by assaying intermediates and end products of lipid peroxidation, conjugated dienes (CD), lipid peroxides (LPO), and relative electrophoretic mobility (REM). Apolipoprotein B-100 modification (increased fluorescence, fragmentation on SDS-PAGE, and 125I-labeled LDL degradation by human macrophages) was also measured. Ascorbate (100 microM) inhibited LDL oxidation by > 95%, as evidenced by all of the selected indices. Aminoguanidine (20 mM) substantially decreased thiobarbituric acid-reactive substances (TBARS) activity and lipid peroxide formation, but only partially prevented the increase of REM (-55%), apoB fluorescence (-39%), and degradation by macrophages (-54%). Unlike ascorbate, AMG failed to preserve alpha-tocopherol in LDL, prevent apoB-100 fragmentation, or inhibit conjugated diene formation during LDL oxidation. Furthermore, incubation of AMG with already oxidized LDL resulted in a significant decrease in TBARS activity and LPO, and 26.9% decrease in the REM of LDL.(ABSTRACT TRUNCATED AT 250 WORDS)

An assessment of posterior pituitary function in patients with Sheehan's syndrome.

Antidiuretic hormone (ADH) function was assessed in a group of 16 patients with Sheehan's syndrome and 17 controls. All patients were on adequate cortisone and thyroxine replacement therapy before testing. During the dehydration test the patients revealed an impairment of ADH function. The maximum urine osmolalities and the urine-plasma osmolality ratios were significantly lower in the patients with Sheehan's syndrome compared to controls (maximum urine osmolalities 633 +/- 38 (SEM) and 873 +/- 29 (SEM) mOsm/kg, respectively, P less than 0.001; urine-plasma osmolality ratios 2.15 +/- 0.14 (SEM) and 3.01 +/- 0.10 (SEM), respectively, P less than 0.001). Plasma osmolalities were significantly higher in the patients (296.1 +/- 1.2 (SEM) and 290 +/- 0.9 (SEM), respectively, P less than 0.001). The patients took a longer period to achieve these maximum urine osmolalities. Three of the patients with Sheehan's syndrome were diagnosed as having diabetes insipidus since their maximum urine osmolalities were below 600 mOsm/kg and following desmopressin all three had an increment in urine osmolality which exceeded 9%. In addition these three patients had a maximum urine-plasma osmolality ratio below 1.9. Thus, it appears the patients with Sheehan's syndrome have an impairment of ADH function which manifests in some as diabetes insipidus.

Fasting plasma glucose and glycosylated haemoglobin levels in the assessment of diabetic control in non-insulin-dependent diabetes in the young.

Response to diet and drug therapy was assessed in a group of 85 Indian patients with non-insulin-dependent diabetes in the young (NIDDY). There was a significant decrease in fasting plasma glucose (FPG) values on therapy (pretreatment 13.3 +/- 0.5 mmol/l; post-treatment 9,7 +/- 0,4 mmol/l) (P less than 0,001). Prior to therapy the majority of patients had either moderate (40%) or severe (59%) diabetes; on therapy, the majority had either mild (21%) or moderate (62%) diabetes. Estimation of glycosylated haemoglobin (Hb A1) levels revealed that control was excellent (Hb A1 less than 10%) in 47% of patients and excellent or adequate (Hb A1 less than 12%) in 78%. Hb A1 levels correlated significantly with the FPG value (r = 0,78; P less than 0,001). In 8 patients with iron deficiency anaemia the HB a1 level did not fall within the correlation norms between Hb A1 and FPG. Treatment of the anaemia restored the correlative norms. Hb A1 levels were significantly higher in patients with microvascular complications (12,1 +/- 0,8%) than in those without any vascular complications (10,3 +/- 0,3%) (P less than 0,01).