A hypolipoprotein sepsis phenotype indicates reduced lipoprotein antioxidant capacity, increased endothelial dysfunction and organ failure, and worse clinical outcomes.

OBJECTIVE: Approximately one-third of sepsis patients experience poor outcomes including chronic critical illness (CCI, intensive care unit (ICU) stay > 14 days) or early death (in-hospital death within 14 days). We sought to characterize lipoprotein predictive ability for poor outcomes and contribution to sepsis heterogeneity. DESIGN: Prospective cohort study with independent replication cohort. SETTING: Emergency department and surgical ICU at two hospitals. PATIENTS: Sepsis patients presenting within 24 h. METHODS: Measures included cholesterol levels (total cholesterol, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C]), triglycerides, paraoxonase-1 (PON-1), and apolipoprotein A-I (Apo A-I) in the first 24 h. Inflammatory and endothelial markers, and sequential organ failure assessment (SOFA) scores were also measured. LASSO selection assessed predictive ability for outcomes. Unsupervised clustering was used to investigate the contribution of lipid variation to sepsis heterogeneity. MEASUREMENTS AND MAIN RESULTS: 172 patients were enrolled. Most (~ 67%, 114/172) rapidly recovered, while ~ 23% (41/172) developed CCI, and ~ 10% (17/172) had early death. ApoA-I, LDL-C, mechanical ventilation, vasopressor use, and Charlson Comorbidity Score were significant predictors of CCI/early death in LASSO models. Unsupervised clustering yielded two discernible phenotypes. The Hypolipoprotein phenotype was characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1), higher SOFA scores, and worse clinical outcomes (45% rapid recovery, 40% CCI, 16% early death; 28-day mortality, 21%). The Normolipoprotein cluster patients had higher cholesterol levels, less endothelial dysfunction, lower SOFA scores and better outcomes (79% rapid recovery, 15% CCI, 6% early death; 28-day mortality, 15%). Phenotypes were validated in an independent replication cohort (N = 86) with greater sepsis severity, which similarly demonstrated lower HDL-C, ApoA-I, and higher ICAM-1 in the Hypolipoprotein cluster and worse outcomes (46% rapid recovery, 23% CCI, 31% early death; 28-day mortality, 42%). Normolipoprotein patients in the replication cohort had better outcomes (55% rapid recovery, 32% CCI, 13% early death; 28-day mortality, 28%) Top features for cluster discrimination were HDL-C, ApoA-I, total SOFA score, total cholesterol level, and ICAM-1. CONCLUSIONS: Lipoproteins predicted poor sepsis outcomes. A Hypolipoprotein sepsis phenotype was identified and characterized by lower lipoprotein levels, increased endothelial dysfunction (ICAM-1) and organ failure, and worse clinical outcomes.

[Primary and secondary hypocholesterolemia].

Hypocholesterolemia is characterized by serum total cholesterol that is lower than the 5th percentile for age and sex, or the cut-off value which predicts the adverse prognosis by epidemiological study. Unlike hypercholesterolemia, physicians pay less attention to the morbidity, causes and consequences of hypocholesterolemia in clinical practice. In fact, hypocholesterolemia is a common dislipidemia, and mainly results from secondary factors. The causes of primary hypocholesterolemia are some disorders owing to genetic mutation in the pathway of cholesterol absorption, biosynthesis or metabolism, including abetalipoproteinemia, hypobetalipoproteinemia, Tangier disease, chylomicron retention disease and inherited disorders of cholesterol biosynthesis. The causes of secondary hypocholesterolemia comprise anemia, hyperthyroidism, malignancy, live disease, critical illness, serious stress, malabsorption or malnutrition, acute or chronic infection, chronic inflammation, and use of some drugs. In addition, what's more important is that hypocholesterolemia can result in some adverse events, such as increased mortality, intracerebral hemorrhage, cancer, infection, adrenal failure, suicide and mental disorder. Therefore, with the practice of intensive lipid-lowering treatment and the tendency to the increased indications of statins, it's high time that physicians attached more importance to hypocholesterolemia.

The prevalence of dyslipoproteinemia in Thai patients with systemic lupus erythematosus.

Fasting blood samples taken from 93 pairs of outpatient systemic lupus erythematosus (SLE) women and matched controls were assessed for total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol. The demographic data, clinical manifestations, Mexican-SLE Disease Activity Index (MEX-SLEDAI), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index and medication prescribed in the SLE patients were reviewed. A significant elevation of TG levels was observed in the SLE patients compared to controls (mean+/-SD 113.3+/-59.5 versus 77.7+/-45.7 mg/dL, P < 0.001). The HDL-c level was also significantly lower in SLE patients than controls (mean+/-SD 49.7+/-12.7 versus 65.0+/-14.8 mg/dL, P < 0.001). The percentage of samples with low HDL-c (<35 mg/dL) was higher in the SLE group (9.7%) than controls (0%; P = 0.002). The LDL-c and TC levels were comparable in both groups. The use of antimalarial drugs was negatively associated with TC (OR 0.22, 95%CI 0.08-0.61) and LDL-c levels (OR 0.27, 95%CI 0.09-0.80). The increased prevalence of dyslipoproteinemia in SLE patients in this report has confirmed the results of previous studies and emphasized the importance of controlling this modifiable cardiovascular risk factor by the combination of lifestyle modification and medical treatments.

Apolipoprotein E2/E2 genotype in combination with mutations in the LDL receptor gene causes type III hyperlipoproteinemia.

The primary genetic cause of type III hyperlipoproteinemia is the homozygous presence of the apolipoprotein E2 allele. However, only approximately 1% of subjects with the apolipoprotein E2/E2 genotype develop type III hyperlipoproteinemia. Other factors are therefore necessary to express type III hyperlipoproteinemia. Two individuals were identified as having type III hyperlipoproteinemia (triglyceride to very low-density lipoprotein (VLDL) cholesterol ratio >0.3). However, in contrast to unchanged or slightly decreased low-density lipoprotein (LDL)-cholesterol levels typically observed in type III patients, elevated LDL-cholesterol levels were observed. The expected apolipoprotein E2/E2 isoform was confirmed by genetic analysis. To explain the elevated LDL-cholesterol level, single strand conformation polymorphism analysis was performed to screen for mutations in the LDL receptor gene. In both individuals, mutations causing an impaired LDL receptor function (2 bp insertion in exon 3 and Glu119 --> Gly mutation in exon 4) were identified. In six more unrelated individuals, these mutations combined with the common apolipoprotein E3/E3 genotype, resulted in an isolated, severe LDL-cholesterol elevation. Our results indicate that the level of LDL receptors plays an important role in remnant clearance, and that the combination of the binding-defective apolipoprotein E2 with a defective LDL receptor precipitate type III hyperlipoproteinemia.

Contribution of nonspecific laboratory test to the diagnosis of malaria in febrile travelers returning from endemic areas: value of hypocholesterolemia.

BACKGROUND: The gold standard in diagnosis of malaria is microscopic detection of malaria parasites in thin blood smears. However, the sensitivity and specificity of blood smears depend mostly on the experience of the examiner. In the traveler returning from the tropics, diagnosis of malaria may be difficult when the parasitemia is low. In this circumstance any indicator that suggests the diagnosis of malaria is of great interest. The aim of this study is to determine the value of hypocholesterolemia to the diagnosis of imported malaria. METHOD: A retrospective case-control study was performed among hospitalized patients with fever returning from a malaria-endemic area, to compare the results of routine biological parameters of 129 malaria cases with those of 92 control patients. RESULTS: Multivariate analysis, using a logistic regression model demonstrates that hypocholesterolemia was the strongest parameter associated with malaria (adjusted odds ratio [OR]: 75.22, 95% confidence interval [CI] 4.60-1227.78) and the most specific (98%, 95% CI 0.95-1.0). The most sensitive abnormality was thrombocytopenia (82%, 95% CI-0.77 0.87). With a malaria prevalence of 52% in our population study, hypocholesterolemia has the strongest positive predictive value among routine biological parameters for malaria diagnosis (96%). The combination of hypocholesterolemia and thrombocytopenia was always associated with diagnosis of malaria in this study. CONCLUSION: These results show that hypocholesterolemia is significantly associated with malaria. Therefore, in the setting of negative thin and thick blood smears, the presence of hypocholesterolemia, particularly when it is combined with thrombocytopenia, in a febrile traveler returning from a malaria-endemic area, should prompt repetition and careful analysis of blood smears to avoid misdiagnosis.

Hypolipemia associated with the wasting condition of rabbits infected with Strongyloides papillosus.

Rabbits develop a wasting condition in the intestinal stage of Strongyloides papillosus infection. Serum inflammatory cytokine and lipid profiles were investigated in five rabbits infected with S. papillosus and five uninfected pair-fed controls to ascertain whether the disease is inflammatory cytokine-mediated cachexia. Tumor necrosis factor alpha (TNF alpha) was detected in one infected animal at Day 7 after infection. Interleukin (IL)-1 was detected in three infected, and one control, animals at Day 28. IL-6 remained unchanged in both the groups. Infected animals developed hypolipemia, including hypotriglyceridemia in the intestinal stage of infection. Control animals lost body weight in the same manner as the infected animals, but had elevated cholesterols and phospholipids with normal triglyceride concentrations. The results suggested that the wasting condition has no association with cachexia induced by TNF alpha. IL-1 or IL-6, and that hepatic function for lipid synthesis is affected during the intestinal stage of S. papillosus infection.

Metabolism of an artificial emulsion resembling chylomicrons in patients with multiple myeloma.

Multiple myeloma, as other neoplastic diseases, is accompanied by alterations in lipid metabolism. The metabolism of chylomicrons is unexplored in this condition, despite the importance of these lipoproteins for the energy body supply. Chylomicron metabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver. Triglyceride-rich emulsions can mimic chylomicron metabolism in man and are a useful tool to evaluate this metabolic pathway. A double-labeled chylomicron-resembling emulsion was injected into 20 patients with multiple myeloma and 30 normolipidemic healthy subjects. The plasma kinetic curves of the emulsion 3H-triglyceride and 14C-cholesteryl ester were determined in plasma samples collected over 60 minutes. The fractional clearance rate (FCR) of triglycerides in multiple myeloma was not changed compared to controls. However, FCR of cholesteryl esters was smaller in multiple myeloma (0.025 +/- 0.003 and 0.061 +/- 0.010 min(-1), respectively). These results indicate that chylomicron lipolysis is not affected in multiple myeloma, whereas remnant removal is diminished.

[How I study a patient with a low concentration of HDL cholesterol]. / Comment j'explore ... un sujet avec une concentration basse de cholestérol HDL.

A decrease in plasma HDL cholesterol concentration is considered as a major cardiovascular risk factor and is a prevalent lipid abnormality among patients with coronary heart disease. This condition is most often observed in the presence of hypertriglyceridaemia, generally linked to the insulin resistance syndrome, but may also be associated to elevated LDL cholesterol level or even be present alone (hypoalphalipoproteinaemia). The decision to treat a patient with low HDL level depends on the individual overall cardiovascular risk which should be evaluated as carefully as possible. The investigation should look for causes which may favour this metabolic condition, such as bad life habits or possible pharmacological interferences.

[Metabolic control and the prevalence of dyslipidemia in children and adolescents with insulin-dependent diabetes mellitus]. / El control metabólico y la prevalencia de dislipidemia en niños y adolescentes con diabetes mellitus insulino-dependiente.

Cholesterol, triglycerides and lipoprotein levels were assayed in serum of 152 children and teenagers with IDDM and in 228 non-diabetic siblings. A poor control of diabetes, reflected by high levels of glycosylated hemoglobin and/or high fasting blood glucose, was associated with statistically significant increases in total cholesterol, LDL-cholesterol and triglycerides, and a reduction in HDL-cholesterol. Mean total cholesterol levels in diabetic patients (171 +/- 33 mg/dL for males and 199 +/- 53 mg/dL for females) were statistically higher than those in their siblings (158 +/- 30 mg/dL and 164 +/- 33 mg/dL respectively). The prevalence of hypercholesterolemia (HC) and hypertriglyceridemia (HTG) were higher in the diabetic patients but statistically significant exclusively in females (prevalences of 40% vs 12% for HC and 30% vs 9% for HTG with a p value < 0.005). The diabetic patients in good metabolic control had similar lipid levels to those of their non-diabetic siblings. These data support the hypothesis that poor control of blood glucose is associated with atherogenic lipid profiles. The prevalence of hypercholesterolemia is impressively high in our diabetic population and indicates that all IDDM patients should have a serum lipid and lipoprotein analysis done annually; blood glucose control and dietary guidelines should be improved in these cases.

Glucose-6-phosphate: a key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia.

The glycogen storage disorders (GSD)-I, -III, -VI and -VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for atherosclerosis. The atherogenicity of triglycerides has remained controversial, while increased plasma cholesterol levels are generally accepted as a significant risk factor for coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where triglycerides are atherogenic and those which are not significantly related to early onset of atherosclerosis but may cause other disorders such as pancreatitis. Among the disorders of carbohydrate metabolism patients with diabetes mellitus frequently have enhanced plasma triglycerides associated with a higher risk for coronary heart disease, while patients with certain types of glycogen storage disease have high triglyceride levels but do not seem to have an enhanced risk for atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of glucose metabolism including GSD-I (glucose-6-phosphatase deficiency), favism (glucose-6-phosphate dehydrogenase deficiency), and diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that glucose-6-phosphate (Glc-6-P) is a central molecule in cellular glucose metabolism which critically influences pentose phosphate cycle activity and, via NADPH2-generation, regulates glutathione peroxidase activity for radical detoxification and also cholesterol and triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of membrane lipids may protect against the development of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)