Lipid metabolism and classification of hyperlipaemias. / Metabolismo lipídico y clasificación de las hiperlipemias.

This chapter summarises, and updates, lipid metabolism. Both pathways, exogenous metabolisms route via the chylomicrons, and the endogenous pathway of very low-density lipoproteins (VLDL) and low-density lipoproteins (LDL). The reverse cholesterol metabolism will also be mentioned. It also includes the current classification of hyperlipidaemias or hyperlipoproteinaemias, with a reminder of the phenotype classification, and further developments of the aetiological classification. Both parts have updated references, with which knowledge of this vast subject can be expanded.

PheProb: probabilistic phenotyping using diagnosis codes to improve power for genetic association studies.

Objective: Standard approaches for large scale phenotypic screens using electronic health record (EHR) data apply thresholds, such as ≥2 diagnosis codes, to define subjects as having a phenotype. However, the variation in the accuracy of diagnosis codes can impair the power of such screens. Our objective was to develop and evaluate an approach which converts diagnosis codes into a probability of a phenotype (PheProb). We hypothesized that this alternate approach for defining phenotypes would improve power for genetic association studies. Methods: The PheProb approach employs unsupervised clustering to separate patients into 2 groups based on diagnosis codes. Subjects are assigned a probability of having the phenotype based on the number of diagnosis codes. This approach was developed using simulated EHR data and tested in a real world EHR cohort. In the latter, we tested the association between low density lipoprotein cholesterol (LDL-C) genetic risk alleles known for association with hyperlipidemia and hyperlipidemia codes (ICD-9 272.x). PheProb and thresholding approaches were compared. Results: Among n = 1462 subjects in the real world EHR cohort, the threshold-based p-values for association between the genetic risk score (GRS) and hyperlipidemia were 0.126 (≥1 code), 0.123 (≥2 codes), and 0.142 (≥3 codes). The PheProb approach produced the expected significant association between the GRS and hyperlipidemia: p = .001. Conclusions: PheProb improves statistical power for association studies relative to standard thresholding approaches by leveraging information about the phenotype in the billing code counts. The PheProb approach has direct applications where efficient approaches are required, such as in Phenome-Wide Association Studies.

Detection rates and sites of unruptured intracranial aneurysms according to sex and age: an analysis of MR angiography-based brain examinations of 4070 healthy Japanese adults.

OBJECTIVIE: The purpose of this study was to evaluate the detection rate and occurrence site according to patient sex and age of unruptured intracranial aneurysms detected through MRI and MR angiography (MRA). METHODS: A total of 4070 healthy adults 22 years or older (mean age [± SD] 50.6 ± 11.0 years; 41.9% women) who underwent a brain examination known as "Brain Dock" in the central Tokyo area between April 2014 and March 2015 were checked for unruptured saccular aneurysm using 3-T MRI/MRA. The following types of cases were excluded: 1) protrusions with a maximum diameter < 2 mm at locations other than arterial bifurcations, 2) conical protrusions at arterial bifurcations with a diameter < 3 mm, and 3) cases of suspected aneurysms with unclear imaging of the involved artery. When an aneurysm was definitively diagnosed, the case was included in the aneurysm group. The authors also investigated the relationship between aneurysm occurrence and risk factors (age, sex, smoking history, hypertension, diabetes, and hyperlipidemia). RESULTS: One hundred eighty-eight aneurysms were identified in 176 individuals (detection rate 4.32%), with the detection rate for women being significantly higher (6.2% vs 3.0%, p < 0.001). The average age in the aneurysm group was significantly higher than in the patients in whom aneurysms were not detected (53.0 ± 11.1 vs 50.5 ± 11.0 years). The detection rate tended to increase with age. The detection rates were 3.6% for people in their 30s, 3.5% for those in their 40s, 4.1% for those in their 50s, 6.9% for those in their 60s, and 6.8% for those in their 70s. Excluding persons in their 20s and 80s­age groups in which no aneurysms were discovered­the detection rate in women was higher in all age ranges. Of the individuals with aneurysms, 12 (6.81%) had multiple cerebral aneurysms; no sex difference was observed with respect to the prevalence of multiple aneurysms. Regarding aneurysm size, 2.0­2.9 mm was the most common size range, with 87 occurrences (46.3%), followed by 3.0­3.9 mm (67 [35.6%]) and 4.0­4.9 mm (20 [10.6%]). The largest aneurysm was 13 mm. Regarding location, the internal carotid artery (ICA) was the most common aneurysm site, with 148 (78.7%) occurrences. Within the ICA, C1 was the site of 46 aneurysms (24.5%); C2, 57 (30.3%); and C3, 29 (15.4%). The aneurysm detection rates for C2, C3, and C4 were 2.23%, 1.23%, and 0.64%, respectively, for women and 0.68%, 0.34%, and 0.21%, respectively, for men; ICA aneurysms were significantly more common in women than in men (5.27% vs 2.20%, p < 0.001). Multivariate logistic regression analysis revealed that age (p < 0.001, OR 1.03, 95% CI 1.01­1.04), female sex (p < 0.001, OR 2.28, 95% CI 1.64­3.16), and smoking history (p = 0.011, OR 1.52, 95% CI 1.10­2.11) were significant risk factors for aneurysm occurrence. CONCLUSIONS: In this study, both female sex and older age were independently associated with an increased aneurysm detection rate. Aneurysms were most common in the ICA, and the frequency of aneurysms in ICA sites was markedly higher in women.

First Dutch guidelines on lipedema using the international classification of functioning, disability and health.

Introduction Lipedema is a chronic, progressive condition that can result in considerable disability. In 2011, the Dutch Society of Dermatology and Venereology organized a task force to create guidelines on lipedema, using the International Classification of Functioning, Disability and Health of the World Health Organization. Guideline development Clinical questions on significant issues in lipedema care were proposed, involving (1) making the diagnosis of lipedema; (2) clinimetric measurements for early detection and adequate follow-up; and (3) treatment. A systematic review of literature published up to June 2013 was conducted. Based on available evidence and experience of the task force, answers were formed and recommendations were stated. The guidelines define criteria to make a medical diagnosis of lipedema, a minimum data set of (repeated) clinical measurements that should be used to ensure early detection and an individually outlined follow-up plan, pillars on which conservative treatment should be based and recommendations on surgical treatment options. Conclusions Little consistent information concerning either diagnostics or therapy can be found in the literature. It is likely that lipedema is frequently misdiagnosed or wrongly diagnosed as only an aesthetic problem and therefore under- or mis-treated. Treatment is divided into conservative and chirurgic treatment. The only available technique to correct the abnormal adipose tissue is surgery. Recommendations To ensure early detection and an individually outlined follow-up, the committee advises the use of a minimum data set of (repeated) measurements of waist circumference, circumference of involved limbs, body mass index and scoring of the level of daily practice and psychosocial distress. Promotion of a healthy lifestyle with individually adjusted weight control measures, graded activity training programs, edema reduction, and other supportive measures are pillars of conservative therapy. Tumescent liposuction is the treatment of choice for patients with a suitable health profile and/or inadequate response to conservative and supportive measures.

The Effects of Sleeve Gastrectomy and Gastric Bypass on Branched-Chain Amino Acid Metabolism 1 Year After Bariatric Surgery.

BACKGROUND: Weight loss, early after Roux-en-Y gastric bypass (GB) surgery, is associated with reduced concentrations of plasma branched-chain amino acids (BCAAs) and improved insulin sensitivity. Herein, we evaluated whether changes in BCAAs and insulin sensitivity persist with weight stabilization (1 year) after GB or sleeve gastrectomy (SG). METHODS: We prospectively examined 22 severely obese patients (mean age 40.6 ± 2.1 years, BMI 38.8 ± 1.3 kg/m(2), and 59.1 % female) who underwent SG (n = 12) or GB (n = 10) for morbid obesity. Body fat composition was measured with dual X-Ray absorptiometry and abdominal fat volume with computed tomography. BCAAs and acylcarnitines were profiled using liquid chromatography with tandem mass spectrometry. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance (HOMA-IR) formula. RESULTS: At 1-year follow-up, the decrease in BMI, body weight, total fat mass (TFM), fat free mass, and visceral adipose tissue (VAT) was similar between SG and GB. HOMA-IR was associated with BCAA concentrations, and both were decreased equally in both surgical groups. In multivariate analysis with BCAAs, TFM, and VAT as independent factors, only VAT remained significantly associated with insulin resistance. CONCLUSIONS: The metabolic benefits from bariatric surgery, including the changes in BCAA profile, are comparable between SG and GB. The reduction in BCAAs and improvement in the AC profiles after bariatric surgery persists up to 12 months after surgery and may not be surgical related but is influenced primarily by the amount of weight loss, in particular the reduction in visceral adiposity.

Relationship Between Hyperuricemia and Cardiovascular Disease Risk Factors in a Chinese Population: A Cross-Sectional Study.

BACKGROUND: To study the relationship between hyperuricemia and cardiovascular diseases (CVDs) risk factors in a Chinese population. MATERIAL AND METHODS: Data analyzed in this study were from the Chinese Hyperuricemia and Gout Database. Indicators of serum uric acid (SUA) level, height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), smoking status, alcohol consumption, blood glucose, cholesterol, and triglycerides were measured. T test, one-way analysis of variance, Pearson's correlation, multivariate linear regression, and multivariate logistic regression were used. RESULTS: Compared with normouricemic men, hyperuricemic men had greater height (P<0.01), weight (P<0.001), body mass index (BMI) (P<0.001), SBP (P<0.01), DBP (P<0.001), cholesterol (P<0.01), and triglyceride (P<0.001). Compared with normouricemic women, hyperuricemic women were older (P<0.01) and had greater weight (P<0.05), BMI (P<0.01), SBP (P<0.01), DBP (P<0.05), glucose (P<0.05), and triglyceride (P<0.001). In men, an increase of 1 mg/dL in SUA was associated with a 0.279 kg/m2 increase in BMI (P<0.001), a 2.438 mg/dL increase in cholesterol (P<0.05), a 10.358 mg/dL increase in triglyceride (P<0.001), and a 3.1 mg/dL decrease in glucose (P<0.01). In women, an increase of 1 mg/dL SUA was associated with a 0.168 kg/m2 increase in BMI (P<0.01) and a 3.708 mg/dL increase in triglyceride (P<0.01). After adjustment, SUA was strongly associated with obesity and hyperlipidemia in both sexes. CONCLUSIONS: Elevated serum uric acid concentration was strongly associated with obesity and hyperlipidemia in both men and women. These results indicated that, among hyperuricemia patients, we should pay more attention to the possibility of cardiovascular complications. These results might provide a novel target or a possible new treatment for cardiovascular diseases by lowering the level of serum uric acid.

[Grade III lipemia retinalis in a 14-year-old girl]. / Lipémie rétinienne grade III chez une fille de 14 ans.

A case of grade III lipemia retinalis is reported in a 14-year-old girl presenting to the emergency department with fatigue and somnolence. Diabetic ketoacidosis diagnostic of type 1 diabetes mellitus and severe hypertriglyceridemia (23,508 mg/dL) were found on routine blood tests. The patient was admitted to the hospital, kept NPO, and intravenous insulin was started. Her symptoms rapidly improved as did the lipid panel and fundus exam. Cases of lipemia retinalis described in the literature typically occur at a blood triglyceride level above 2,000-2,500 mg/dL. A high level of chylomicrons is responsible for the milky appearance of the serum and retinal vessels. Once the blood triglyceride level decreases significantly, the fundus appearance usually returns to normal.

A bootstrapping algorithm to improve cohort identification using structured data.

Cohort identification is an important step in conducting clinical research studies. Use of ICD-9 codes to identify disease cohorts is a common approach that can yield satisfactory results in certain conditions; however, for many use-cases more accurate methods are required. In this study, we propose a bootstrapping method that supplements ICD-9 codes with lab results, medications, etc. to build classification models that can be used to identify cohorts more accurately. The proposed method does not require prior information about the true class of the patients. We used the method to identify Diabetes Mellitus (DM) and Hyperlipidemia (HL) patient cohorts from a database of 800 thousand patients. Evaluation results show that the method identified 11,000 patients who did not have DM related ICD-9 codes as positive for DM and 52,000 patients without HL codes as positive for HL. A review of 400 patient charts (200 patients for each condition) by two clinicians shows that in both the conditions studied, the labeling assigned by the proposed approach is more consistent with that of the clinicians compared to labeling through ICD-9 codes. The method is reasonably automated and, we believe, holds potential for inexpensive, more accurate cohort identification.

[Factor analysis on the distribution of Chinese medicine syndromes in patients with hyperlipidemia in Xinjiang region].

OBJECTIVE: To investigate the distributive rule of Chinese medicine syndromes in patients with hyperlipidemia (HLE) in Xinjiang region. METHODS: Chinese medicine syndrome of HLE patients were differentiated. The common factors of diagnostic information for dominating HLE were extracted by factor analysis and the syndrome type was determined based on Chinese medicine theory and experiences of experts. RESULTS: The syndromes in HLE patients of Xinjiang region were mainly the Pi-Shen deficiency with insufficient Jin syndrome (I), the qi-blood deficiency syndrome (II), the Fei-Wei dryness syndrome (III), the phlegm-dampness obstructing Fei syndrome (IV), the dampness-heat accumulation syndrome (V), and the Gan-Shen yin-deficiency with blood-stasis syndrome (VI). Syndrome II was the most commonly encountered one (35.09%), the next were syndrome III (29.82%) and I (13.45%). Scores of the 6 syndromes, which embodied the severity of disease, were different significantly (F = 32.746, P < 0.01), the highest presented in syndrome I and the second in Syndrome VI. CONCLUSIONS: Syndrome in hyperlipidemia patients of Xinjiang region is dominantly the deficiency syndrome, combined with qi-stagnancy and blood-stasis, showing a complex state involving multiple organs and all the qi, blood and Jin-Ye in body.

Hyperlipidemia in Saudi Arabia.

OBJECTIVE: To determine the prevalence of hyperlipidemia among Saudis of both genders in rural and urban communities. METHODS: Selected Saudis in the age group of 30-70 years were studied over a 5-year period between 1995 and 2000 in Saudi Arabia. Data were obtained from history, physical examination, and analysis of fasting plasma lipids. The data were analyzed to classify individuals with hypercholesterolemia (HC) (total cholesterol > or =5.2 mmol/l), and hypertriglyceridemia (HT) (total triglycerides > or =1.69 mmol/l). Logistic regression analysis was performed to provide a risk assessment model and correlation with other coronary artery disease (CAD) risk factors. RESULTS: The number of study samples included in the final analysis was 16,819. The prevalence of HC was 54% with mean cholesterol level of 5.4+/-1.52 mmol/l. Prevalence of HC among males was 54.9% and 53.2% for females, while 53.4% among urban Saudis and 55.3% for rural Saudis. Hypertriglycemia prevalence was 40.3% with mean triglycerides level of 1.8+/-1.29 mmol/l. Males had statistically significant higher HT prevalence of 47.6% compared to 33.7% in females (p<0.0001). CONCLUSION: Hyperlipedimia is reaching higher prevalence rates in KSA. This finding may suggest that CAD will soon be a major health problem. Reduction in obesity by adopting healthier eating habits, and increasing physical activity are of considerable importance to our community.

The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia.

Hyperlipidemia is an important risk factor for atherosclerosis. Hemorheological factors contribute to morbidity and mortality in patients with dyslipidemia. We evaluated the effects of 3 antihyperlipidemic drugs (pravastatin, atorvastatin, and fenofibrate), which have different mechanisms of action and different patterns of action on lipid profiles, on erythrocyte deformability and fibrinogen levels in patients with type IIa and type IIb hyperlipidemia. Twenty-one patients ( 4 men and 17 women) with type IIa and IIb hyperlipidemia were randomized to 3 drugs (pravastatin 20 mg/d, atorvastatin 10 mg/d, fenofibrate 250 mg/d) for 8 weeks. Plasma glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) analysis were performed on a BM-Hitachi 747-200 autoanalyzer (Hitachi-Roche, Tokyo, Japan). Fibrinogen analysis was performed according to Clauss method. Erythrocyte deformability was assessed with cell transit analysis device. There was no significant difference in body mass index, lipid profile, fibrinogen level, and erythrocyte deformability index values among the groups before treatment ( P > .05). In all groups, there were statistically significant reductions in total LDL-C levels ( P < .05). The triglyceride levels were significantly reduced in the atorvastatin and fenofibrate groups ( P < .05), but not in the pravastatin group ( P > .05). There was no significant change in HDL-C levels during the treatment with statins ( P > .05), but there was a significant increase in the fenofibrate group ( P < .05). Mean erythrocyte deformability index was improved in all the groups ( P < .05). There was no significant change in fibrinogen levels during the treatment of pravastatin and atorvastatin ( P > .05), but in fenofibrate group, fibrinogen levels were significantly decreased ( P < .05). The 3 groups of antihyperlipidemic drugs have beneficial effects on the erythrocyte deformability index. Only fenofibrate has significant beneficial effects on the fibrinogen levels.

Adultos: Enfermedades prevalentes: Hipertensión, diabetes, tabaquismo, dislipidemias / Guías para el primer nivel de atención de la salud

Organizada en cuatro módulos, cada uno dedicado a una patología, donde se analizan su epidemiología, clasificación, diagnóstico, tratamiento y otros aspectos de intervención. Incluye bibliografía al final de cada módulo

Adultos: Enfermedades prevalentes: Hipertensión, diabetes, tabaquismo, dislipidemias / Guías para el primer nivel de atención de la salud

Organizada en cuatro módulos, cada uno dedicado a una patología, donde se analizan su epidemiología, clasificación, diagnóstico, tratamiento y otros aspectos de intervención. Incluye bibliografía al final de cada módulo

Comparison of calculated and direct low density lipoprotein cholesterol determinations in a routine laboratory.

BACKGROUND: Low density lipoprotein cholesterol (LDL-C) concentrations form the basis for treatment guidelines established for hyperlipidaemic patients. LDL-C concentrations are commonly calculated using the Friedwald formula (FF) which has several limitations. Recently, direct methods for LDL-C estimation have been developed which are suitable for routine laboratories. OBJECTIVE: To compare serum LDL-C concentrations determined by a direct assay and the Friedwald formula. DESIGN: Cross-sectional study. SETTING: Mater Hospital Laboratory, Nairobi, Kenya. METHODS: The clinical performance of the two methods was evaluated by analysing 211 fresh plasma samples from fasting adult patients. The samples were divided into four groups-normolipidaemic; and Types IIa, IIb and IV hyperlipidaemias. RESULTS: The Friedwald formula (FF) correlated best with the direct assay in the normolipidaemic samples (r = 0.879; y= 0.468 + 0.852x). Direct LDL-C values were significantly lower than the FF in the Type IIa hyperlipidaemia samples (paired differences 0.38 +/- 0.62). There was only 65% agreement between the two methods in the borderline high LDL-C group of the National Cholesterol Education Program (NCEP) classification (LDL-C 3.36-4.14 mmol/L). CONCLUSION: There is lack of agreement between the FF and the Abbott direct LDL-C assay. If the two methods are used interchangeably, there may be confusion in the classification and control of lipid lowering medication for patients with hyperlipidaemia.

Locus for quantitative HDL-cholesterol on chromosome 10q in Finnish families with dyslipidemia.

Decreased HDL-cholesterol (HDL-C) and familial combined hyperlipidemia (FCHL) are the two most common familial dyslipidemias predisposing to premature coronary heart disease (CHD). These dyslipidemias share many phenotypic features, suggesting a partially overlapping molecular pathogenesis. This was supported by our previous pooled data analysis of the genome scans for low HDL-C and FCHL, which identified three shared chromosomal regions for a qualitative HDL-C trait on 8q23.1, 16q23.3, and 20q13.32. This study further investigates these regions as well as two other loci we identified earlier for premature CHD on 2q31 and Xq24 and a locus for high serum triglycerides (TGs) on 10q11. We analyzed 67 microsatellite markers in an extended study sample of 1,109 individuals from 92 low HDL-C or FCHL families using both qualitative and quantitative lipid phenotypes. These analyses provided evidence for linkage (a logarithm of odds score of 3.2) on 10q11 using a quantitative HDL-C trait. Importantly, this region, previously linked to TGs, body mass index, and obesity, provided evidence for association for quantitative TGs (P = 0.0006) and for a combined trait of HDL-C and TGs (P = 0.008) with marker D10S546. Suggestive evidence for linkage also emerged for HDL-C on 2q31 and for TGs on 20q13.32. Finnish families ascertained for dyslipidemias thus suggest that 10q11, 2q31, and 20q13.32 harbor loci for HDL-C and TGs.

Guías para el tratamiento de las dislipemias en el adulto: Adult Treatment Panel III (ATP-III) / Guidelines for dyslipemias treatment: adult treatment panel III (ATP-III)

Las guías de tratamiento para disminuir los lípidos y el riesgo de enfermedad coronaria (EC) diseñadas por el National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP-III) contienen una serie de características que las diferencian de las anteriores guías. Estos nuevos aspectos incluyen modificaciones en las concentraciones de lípidos y lipoproteínas; una mayor atención a la prevención primaria a través del empleo de las puntuaciones obtenidas en las tablas de Framingham, para definir el riesgo de aquellas personas con múltiples factores de riesgo lipídicos y no lipídicos; del mismo modo, ha sido objeto de reflexión la asociación del síndrome metabólico con el riesgo de EC. Se introduce la categoría de equivalentes de riesgo coronario, donde se incluye a personas con enfermedad aterosclerótica, diabetes mellitus o aquellas que presentan un riesgo de EC a los 10 años superior al 20 por ciento, basado en las proyecciones de Framingham; se les clasifica como pacientes de alto riesgo coronario y susceptibles de un tratamiento intensivo para reducir las concentraciones del colesterol ligado a las lipoproteínas de baja densidad (cLDL). Asimismo, se ha establecido como objetivo terapéutico secundario la mejoría del colesterol ligado a lipoproteínas de alta densidad (cHDL) en pacientes con aumento de las concentraciones de triglicéridos, una vez que se han alcanzado las metas del cLDL. El ATP-III dedica una extensa sección al tratamiento no farmacológico, que se centra en la dieta aterogénica, la obesidad y los hábitos de vida sedentarios, para recomendar un programa activo de cambios en el estilo de vida.En esta revisión se discuten algunos aspectos relacionados con: a) la evaluación del riesgo para seleccionar a pacientes susceptibles de intervención clínica, considerando los nuevos factores de riesgo emergentes y el síndrome metabólico; b) la evaluación de diversos algoritmos de evaluación del riesgo cardiovascular; c) el manejo clínico de los factores de riesgo cardiovasculares, con futuras perspectivas de objetivos del cLDL; d) atención a las características especiales de una dieta saludable cardiovascular, y e) el tratamiento de ciertas dislipemias específicas, como la elevación de triglicéridos o la dislipemia diabética (AU)

Binary classification of dyslipidemia from the waist-to-hip ratio and body mass index: a comparison of linear, logistic, and CART models.

BACKGROUND: We sought to improve upon previously published statistical modeling strategies for binary classification of dyslipidemia for general population screening purposes based on the waist-to-hip circumference ratio and body mass index anthropometric measurements. METHODS: Study subjects were participants in WHO-MONICA population-based surveys conducted in two Swiss regions. Outcome variables were based on the total serum cholesterol to high density lipoprotein cholesterol ratio. The other potential predictor variables were gender, age, current cigarette smoking, and hypertension. The models investigated were: (i) linear regression; (ii) logistic classification; (iii) regression trees; (iv) classification trees (iii and iv are collectively known as "CART"). Binary classification performance of the region-specific models was externally validated by classifying the subjects from the other region. RESULTS: Waist-to-hip circumference ratio and body mass index remained modest predictors of dyslipidemia. Correct classification rates for all models were 60-80%, with marked gender differences. Gender-specific models provided only small gains in classification. The external validations provided assurance about the stability of the models. CONCLUSIONS: There were no striking differences between either the algebraic (i, ii) vs. non-algebraic (iii, iv), or the regression (i, iii) vs. classification (ii, iv) modeling approaches. Anticipated advantages of the CART vs. simple additive linear and logistic models were less than expected in this particular application with a relatively small set of predictor variables. CART models may be more useful when considering main effects and interactions between larger sets of predictor variables.