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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., (Copyright © 2021 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

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.

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 80s—age groups in which no aneurysms were discovered—the 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, 2.0–2.9 mm was the most common size range, with 87 occurrences (46.3%), followed by 3.0–3.9 mm (67 [35.6%]) and 4.0–4.9 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 1.01–1.04), female sex (p < 0.001, OR 2.28, 95% CI 1.64–3.16), and smoking history (p = 0.011, OR 1.52, 95% CI 1.10–2.11) 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.

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.

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.

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.

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., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

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., (Published by Elsevier Inc.)

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.

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.

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.

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.

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.

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.

Hyperlipidaemia is a major risk factor for cardiovascular disease. The drugs of choice for the treatment of hyperlipidaemia are either fibrates, in the case of hypertriglyceridaemia, or statins, in the case of hypercholesterolaemia. Recently, it has been shown that some of the most prescribed fibrates cause hyperhomocysteinemia, which itself has been recognised as a cardiovascular risk factor. In particular, fenofibrate and bezafibrate lead to a 20 - 40% elevation of plasma levels of the atherogenic amino acid homocysteine, thereby possibly counteracting the desired cardiovascular protection. The most likely mechanism for this increase is an alteration of creatine-creatinine metabolism and changes in methyl transfer. Gemfibrozil does not increase homocysteine. Statins have no effect on the plasma homocysteine concentration. The increase of plasma homocysteine after fenofibrate can be lowered by the concurrent administration of folic acid and vitamins B(12) and B(6). Thus, patients with hypertriglyceridaemia can either be concurrently treated with fenofibrate and vitamins or with gemfibrozil.

Xanthomas are cutaneous lesions due to a local accumulation of spumous cells in the dermal tissue or the tendons. Histologically, they are characterized by the presence of histiocytes, fibroblasts, macrophages and Touton cells full of lipids. Xanthomas may be found on any part of the body and are usually yellow-orange in color. They may or may not be associated to hyperlipoproteinemia which may be genetic or secondary. A blood test and a complete physical examination are necessary in case such a lesion is discovered. When there is no hyperlipemia some types of xanthomas may be associated to rare diseases. Xanthomas are classified according to their clinical features.

The authors investigated the effect of atorvastatin (40 mg qd) on low-density lipoprotein (LDL) particle distribution in patients with dyslipidemias of type IIA (n = 55) and IIB (n = 21). Atorvastatin therapy induced a significant decrease in total and LDL cholesterol in both patient groups. A significant reduction in triglyceride values, which was more profound in type IIB patients, was also observed. In type IIA patients, LDL-3 was the predominant subfraction. Atorvastatin therapy induced a significant reduction in total LDL mass in this group of patients that was mainly due to the reduction in large and intermediate subspecies (LDL-1 to LDL-3), whereas the mass of dense LDL particles (LDL-4 and LDL-5) remained unchanged. As a consequence, the percentage contribution of dense subfractions to the total LDL mass increased significantly after atorvastatin therapy. The dense LDL-4 subfraction was the predominant one in type IIB patients. In this group, atorvastatin therapy resulted in a significant reduction in the total LDL mass, which was due to the reduction in all LDL subfractions. Thus, the percentage mass distribution of LDL particles remained unaffected. These results suggest that the effect of atorvastatin on LDL subfractions is affected by the underlying genetic defect.

Objective: To compare non-HDL cholesterol (HDLc) and apolipoprotein B (apoB) in the identification of nonconventional high-risk dyslipidemic phenotypes in type 2 diabetic patients., Research Design and Methods: Total cholesterol and triglycerides, HDLc, LDL cholesterol, non-HDLc, apolipoprotein B (apoB), and LDL size were determined in 122 type 2 diabetic patients (68% male, aged 59.6 +/- 9.7 years, and HbA(1c) 7.5% [range 5.2-16.0]). They were then classified as normo- and hypertriglyceridemic if their triglyceride concentrations were below/above 2.25 mmol/l, as normo/hyper-non-HDLc if non-HDLc concentrations were below/above 4.13 mmol/l, and as normo- and hyperapoB if apoB concentrations were below/above 0.97 g/l. Both classifications were compared (concordance assessed with the kappa index), and low HDLc and LDL phenotype B were identified in each category., Results: A total of 26 patients were hypertriglyceridemic and 96 were normotriglyceridemic. All hypertriglyceridemic subjects had increased non-HDLc, whereas 24 had increased apoB (kappa= 0.95). In the normotriglyceridemic group, 44 had increased non-HDLc, 68 had increased apoB, and 25 of the 52 patients with normal non-HDLc had increased apoB (kappa= 0.587). Low HDLc and LDL phenotype B were similarly distributed into the equivalent categories., Conclusions: Non-HDLc and apoB are equivalent risk markers in hypertriglyceridemic patients, but apoB identifies additional patients with high-risk dyslipidemic phenotypes in normotriglyceridemic type 2 diabetic patients.

The seminal studies of Brown and Goldstein (Science 1986;232:34-47) coupled with the findings of the Framingham study revolutionized our understanding of the metabolic basis for vascular disease. These studies led to the widespread use of the coronary risk lipid profile, which uses the total cholesterol/high-density lipoprotein (HDL) ratio (or low-density lipoprotein [LDL]/HDL ratio) in predicting risk for vascular disease and as a tool for therapeutic management of patients at risk for vascular disease. However, although these methods are predictive of coronary artery disease (CAD) in general, it is also well known that the extent of occlusive disease and CAD varies greatly between individuals with similar cholesterol and HDL lipid profiles. For this reason, the National Cholesterol Education Program Expert Panel revised these guidelines and now recommends monitoring LDL and HDL cholesterol in the context of coronary heart disease risk factors and "risk equivalents." In addition, more recent findings indicate that specific alterations in individual lipoprotein subclasses may account for the variations in CAD in subjects with similar lipid profiles. For example, a preponderance of small, dense LDL particles correlates with a marked increase in risk for myocardial infarction independent of LDL levels. In particular, the association of small, dense LDL with elevated triglycerides (large, less dense VLDL) and reduced HDL has been defined as the atherogenic lipoprotein profile, and the key metabolic defect driving this profile may be elevated levels of triglycerides, specifically large, less dense VLDL. In an attempt to explain the physiologic basis for lipoprotein variations, this review describes the basic metabolic scheme underlying the traditional view of lipoprotein metabolism and physiology. It then examines the identity and role of the various lipoprotein subfractions in an attempt to distill a working model of how lipoprotein abnormalities might account for vascular disease in general and the metabolic syndrome in particular.

Coronary heart disease (CHD) remains the leading cause of death in the United States. It is now well established that cholesterol is an important, reversible risk factor for CHD. This article provides a brief background on classification of the dyslipidemias, then discusses current recommendations for the evaluation and treatment of hyperlipidemia. Other risk factors currently being investigated as they relate to the development of CHD are discussed.

Objectives: In recent years, the therapeutic implications of dyslipidemias have been clarified in large-scale epidemiologic surveys, and the validity of pharmacotherapy has been established. We investigated the practical realities of pharmacotherapy for dyslipidemias at a community hospital in Japan., Methods: Medical chart surveys were performed retrospectively on 451 dyslipidemic outpatients who visited a community hospital in Japan in July 1997. We collected clinical data from medical charts regarding selected drugs for dyslipidemias, serum lipid levels before drug treatment and after one year of treatment, and risk factors for coronary heart disease (CHD)., Results: Regardless of dyslipidemia phenotype, approximately 80% of patients were administered statins. The possibility was raised that physicians recorded risk factors in medical charts incompletely, particularly with regard to family CHD history, smoking, and obesity. Based on Japanese and us guidelines for dyslipidemias, low-density lipoprotein (LDL) cholesterol levels fully satisfied the requirements for initiating pharmacotherapy in the present study. However, the higher the risk of CHD, the lower the percentage of subjects who met the treatment goals defined by both guidelines. Only 23% of patients at high risk for CHD controlled LDL cholesterol sufficiently based on Japanese guidelines., Conclusion: To optimize pharmacotherapy for dyslipidemias, medical staff should assess risk factors for CHD more completely and attempt to achieve full control of serum lipids, particularly in patients at high risk for CHD.

Objective: The objective of the present study was to compare the effects of a 16-week pharmacotherapy with fenofibrate (200 mg) or pravastatin (initially 20 mg for 8-weeks and, if necessary, increased to 40 mg) on low density lipoprotein (LDL) particle size assessed by gradient gel electrophoresis among patients with type IIa dyslipidemia., Methods: For that purpose, type IIa dyslipidemic patients (cholesterol, 7.45+/-1.18 (S.D.) mmol/l; LDL cholesterol, 5.57+/-1.16 mmol/l; triglycerides (TGs), 1.66+/-0.43 mmol/l) were randomized to either fenofibrate (n=36) or pravastatin (n=43) therapy for 16 weeks. Fasting plasma lipoprotein levels as well as the LDL peak particle size (using 2-16% polyacrylamide gel electrophoresis) were assessed at baseline and after the 16-week treatment period., Results: Whereas significant improvements in the plasma lipoprotein-lipid variables were observed with both fenofibrate and pravastatin treatments, LDL peak particle size was only significantly increased with fenofibrate therapy (+2.11+/-5.18 A, P<0.05). Among patients under fenofibrate therapy, changes in TG levels were negatively associated with changes in LDL peak particle size (r=-0.54, P<0.0007), whereas no such association was found in pravastatin-treated patients. The prevalence of patients with small, dense LDL particles (as defined by LDL particle diameter <255.5 A) was reduced from 69.4 to 30.6% (P<0.05) among fenofibrate-treated patients as opposed to 81.4 to 72.1% (NS) in patients who received pravastatin., Conclusion: As pravastatin treatment had no effect on LDL size, it is suggested that the additional effect of fenofibrate therapy on LDL size may contribute to reduce the risk of coronary heart disease (CHD) beyond what can be expected from the reduction in LDL cholesterol concentration in type IIa dyslipidemic patients.

Coronary artery disease is the leading cause of morbidity and mortality in the United States. Studies increasingly indicate that atherosclerotic lesions are evident in the vasculature by late adolescence, and that hyperlipidemias are a common and remediable contributor to their development. Hence, health care providers dealing with adolescents must be familiar with contemporary concepts about the etiology, classification, and management of hyperlipidemias in children and adolescents. This chapter briefly reviews lipid metabolism, emphasizing lipoprotein composition, key components, enzymes, cellular receptors, transport, uptake, and fate. This framework provides a rational classification with exclusion and treatment of secondary causes such as obesity, poorly controlled diabetes, hypothyroidism, and oral contraceptive therapy, followed by currently recommended approaches to the primary hyperlipidemias, which affect at least 1:500 persons. Guidelines for screening adolescents at risk and incremental treatment with diet and lipid-lowering medications, including statins, are reviewed in the context of current national recommendations.

Background: Electronically available data, both administrative, such as outpatient encounter diagnostic data, and clinical, such as problem lists, are being used increasingly for outcome and quality assessment, risk adjustment, and clinical reminder systems., Objective: To determine the accuracy of outpatient primary care diagnostic information recorded in administrative and clinical files in a Veterans Affairs VISTA (Veterans Health Information Systems and Technology Architecture) database compared with medical chart notes., Study Design: Cross-sectional medical chart review of 148 patients attending a general medicine clinic at a university-affiliated Veterans Affairs hospital for 9 diagnoses relevant to the choice of drug therapy for hypertension., Patients and Methods: An administrative file of encounter diagnoses, for a 2-year period, and a clinical file of the problem list maintained by the clinician were the sources of electronic diagnoses. We compared these sources with diagnoses abstracted by medical chart review. We estimated the sensitivity and specificity of each electronic data source for detecting medical chart note diagnoses., Results: The sensitivity for 8 of the 9 study diagnoses was greater than 80% in the administrative file and 49% in the clinical problem list. The specificity was good for the administrative file (91% to 100%) and even better for the clinical file (98% to 100%)., Conclusions: Outpatient encounter diagnoses relevant to hypertension recorded as electronic data had high specificity, and some codes had high sensitivity when collected over multiple visits. The administrative file was more sensitive but less specific than the clinical file. Administrative vs clinical files can be selected to minimize either the false-negative or the false-positive designations, respectively, as dictated by the needs of the quality assessment review.

We established a strategy to directly measure cholesterol and triglyceride levels of each lipoprotein fraction using a combination of agarose gel electrophoresis and differential staining. The cholesterol and triglyceride levels determined by electrophoresis correlated significantly with those of ultracentrifugation. The correlation coefficients between these methods were, for cholesterol levels 0.975(very low density lipoproteins, VLDL), 0.986(low density lipoproteins, LDL) and 0.965(high density lipoproteins, HDL) and for triglyceride levels 0.994(VLDL), 0.963(LDL) and 0.959(HDL) respectively. Both intra-and inter-assays showed low values of coefficients of variation (CV) (less than 3.57%). We observed a strong linearity between staining and triglyceride concentration. An increased VLDL-cholesterol was observed in type III subjects, a result which enabled distinction between type III and type IIb or type V lipoproteinemia. The method revealed lipoprotein patterns in some samples otherwise unexpected from their corresponding serum lipid parameters. Analyses of these electrophoretic patterns thus provide an effective technique to classify types of hyperlipidemia defined by the WHO. Furthermore, quantitative measurement of chylomicrons, usually difficult, proved to be achievable, providing an additional analysis of postprandial hyperlipidemia and the exact measurement of LDL-cholesterol after diet. Consequently, we recommend this simple and easy method for clinical evaluation of abnormalities in lipoprotein profiles.

Sodium-lithium countertransport (SLC) kinetics were measured in 30 patients with type V hyperlipidemia, 30 patients with type IIB hyperlipidemia on similar treatment, and 30 age- and sex-matched healthy controls. Clinical and laboratory data including basic anthropometry and blood pressure were obtained and blood was taken for detailed lipid biochemistry, glucose, insulin, and leptin measurements. Patients with type V hyperlipidemia were normotensive but more obese than controls, had elevated triglycerides, very low-density lipoprotein, glucose, and insulin; and reduced HDL cholesterol compared with type IIb controls. The median SLC activity (0.23 v 0.21 mmol Li+/L RBC/h) and median maximal velocity (0.33 v 0.31 mmol Li+/L RBC/h) were increased, but not significantly, compared to controls. In patients with type V hyperlipidemia SLC maximal velocity correlated with log triglycerides (r2 = 0.853; P < .001) and log very low-density lipoprotein (VLDL) triglycerides (r2 = 0.947; P < .001). Sodium-lithium countertransport maximal velocity correlated weakly with the homeostasis model assessment index of insulin resistance (r2 = 0.224; P = .06). The sodium affinity of the transporter did not differ between the groups and was independent of any of clinical or biochemical parameter studied. We conclude that VLDL triglyceride is strongly correlated with SLC maximal velocity and activity in patients with type V hyperlipidemia.

The optimum management of dyslipidaemia requires a comprehensive, diagnostic work-up. This, minimally, includes: Characterisation of any hyperlipidaemic disorder present. Identification of additional risk factors so as to assess overall (global) risk of future coronary heart disease (CHD). The global risk is best assessed by a calculation combining the risk factors in the individual. In severe monogenic dyslipidaemias and in patients with confirmed pre-existing CHD the risk is usually high; in most such cases the use of lipid-modifying drugs (LMDs) is indicated. Assessment of psychosocial, economic and educational factors relevant to management. Prevention and cost-effective management of even moderately dyslipidaemic patients require appropriate modification of lifestyle: avoidance of tobacco smoking, participation in regular exercise, and a health-promoting diet. Depending on individual circumstance, vigorous, personalised intervention and expert assistance from dieticians, biokineticists and other health care personnel may determine success. The correct choice of patient for drug treatment is a key therapeutic decision and is best done after full lifestyle modification. Recent evidence confirms that appropriately prescribed LMD therapy can lower morbidity and mortality from CHD as well as all-cause mortality. Patients with the following features are candidates for LMD therapy: have clinical CHD and a low-density lipoprotein cholesterol (LDLC) level > 3.0 mmol/l despite optimum non-pharmacological intervention, or suffer from familial hypercholesterolaemia (FH) or equivalent severe, monogenic disorder, or have a 10-year risk of an acute clinical coronary event of > 20% (or > 30% risk if extrapolated to the age of 60 years) owing to the presence of the hyperlipidaemia alone or in combination with contributory risk factors. The ideal target LDLC concentration is < or = 3 mmol/l, but a reduction of at least 45% should be regarded as a minimum target in severe cases who do not reach this goal. Successful therapy requires on-going attention to compliance, therapeutic response and side-effects, and may necessitate adjustment or reinforcement. Concurrent or contributory conditions, such as smoking, hypertension and diabetes mellitus, must also be treated along with the clinically manifest CHD. Severely hyperlipidaemic, complicated or unresponsive high-risk cases should be referred to an appropriate specialist or lipid clinic. Prevention of CHD in the community should be encouraged through public and professional education, the provision of community facilities for exercise and recreation, and legislation directed at reducing the use of tobacco products and ensuring the appropriate labelling of food products.

Plasma lipids play a key role in the development of atherosclerosis. Recent trial data support early identification of asymptomatic adults with high-risk lipid profiles for primary prevention of coronary heart disease. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have been shown to reduce coronary events in both asymptomatic adults and those with known coronary heart disease. The optimal plasma low-density lipoprotein cholesterol for secondary coronary prevention remains controversial. The Second Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II), published in 1993 by the National Cholesterol Education Program, recommends guidelines for evaluation and diagnosis of lipids. Subsequently, several clinical trials have identified populations benefiting from pharmacologic intervention and new approaches to the management of lipid disorders. Consequently, these guidelines should be applied with the interval evidence in mind.

Type 2 diabetes is associated with a marked increase in the risk of coronary artery disease. Dyslipidemia is believed to be a major source of this increased risk. Several studies in diabetic patients have demonstrated a decreased incidence of coronary artery disease with the use of drugs that lower the level of low-density lipoprotein in diabetic patients, but other forms of dyslipidemia, such as hypertriglyceridemia, are believed to play a role in the etiology of coronary artery disease in diabetes. Drugs, such as fenofibrate, which improve these other forms of dyslipidemia, are being investigated in diabetic patients to determine if they decrease mortality and morbidity from coronary artery disease.

We investigated the redox dynamics of alpha-tocopherol in plasma and erythrocyte membranes in elderly patients with asymptomatic primary hyperlipidemia divided into three groups (hypercholesterolemia, hypertriglyceridemia and low high-density lipoprotein cholesterol levels) and in healthy elderly subjects to assess the antioxidative status of alpha-tocopherol. alpha-Tocopherol and alpha-tocopherolquinone were determined by high-performance liquid chromatography using a redox detection mode. In the erythrocyte membrane, there was no difference in the alpha-tocopherol concentration between hyperlipidemic and healthy subjects. The alpha-tocopherolquinone/alpha-tocopherol ratio in plasma and erythrocyte membrane, and the alpha-tocopherol in erythrocyte membrane/alpha-tocopherol in plasma ratio were significantly lower in elderly patients with hypercholesterolemia or hypertriglyceridemia. These findings suggest that the uptake ratio in erythrocyte membranes and the antioxidative activity of alpha-tocopherol in both plasma and erythrocyte membranes are decreased in elderly hyperlipidemic patients. These decreases may promote membrane lipid peroxidation or accelerate atherosclerosis.

Hyperlipidemia is a common disease that leads to considerable morbidity and mortality. It is a major risk factor for the development of atherosclerosis. Hyperlipidemia is often undertreated by medical providers. Several large, randomized trials have established the benefit of aggressive management of hyperlipidemia. Effective treatment requires a multidisciplinary approach. There are many cholesterol-lowering medications on the market. The HMG-coA-reductase inhibitors are the most efficacious and are well tolerated.

The importance of treating dyslipidemias based on cardiovascular risk factors is highlighted by the National Cholesterol Education Program guidelines. The first step in evaluation is to exclude secondary causes of hyperlipidemia. Assessment of the patient's risk for coronary heart disease helps determine which treatment should be initiated and how often lipid analysis should be performed. For primary prevention of coronary heart disease, the treatment goal is to achieve a low-density lipoprotein (LDL) cholesterol level of less than 160 mg per dL (4.15 mmol per L) in patients with only one risk factor. The target LDL level in patients with two or more risk factors is 130 mg per dL (3.35 mmol per L) or less. For patients with documented coronary heart disease, the LDL cholesterol level should be reduced to less than 100 mg per dL (2.60 mmol per L). A step II diet, in which the total fat content is less than 30 percent of total calories and saturated fat is 8 to 10 percent of total calories, may help reduce LDL cholesterol levels to the target range in some patients. A high-fiber diet is also therapeutic. The most commonly used options for pharmacologic treatment of dyslipidemia include bile acid-binding resins, HMG-CoA reductase inhibitors, nicotinic acid and fibric acid derivatives. Other possibilities in selected cases are estrogen replacement therapy, plasmapheresis and even surgery in severe, refractory cases.

Objective: To characterize serum lipid abnormalities in overweight and obese female patients and to quantify the relative importance of associated factors., Methods: Cross sectional study at the first visit to the out-patient department. 237 consecutive overweight and obese female patients (age 31 +/- 14 y, body mass index (BMI) 34.2 +/- 6.0 kg/m2) were studied. Evaluation included a questionnaire-based assessment of dietary and physical activity habits, determination of anthropometric indexes (BMI, abdominal/thigh ratio (A/T) and conicity index (CI)) and endocrine evaluation. Statistical analysis by factorial ANOVA and multiple regression., Results: Dyslipidaemia was present in 46% of the patients, with hypercholesterolaemia (35%) being more frequent than hypertriglyceridaemia (10%). Age but not dietary habits or physical activity patterns was significantly related to serum lipid concentrations, independently accounting for 6-10% of their variability. Pharmacological drug use resulted in increased serum triglyceride concentrations, explaining less than 5% of their variability. Serum cholesterol concentrations were not significantly related either to anthropometric or to endocrine indexes. For serum triglyceride concentrations, anthropometric indexes accounted for 6% of their variability and endocrine indexes-postprandial insulin, serum cortisol, testosterone and androstenedione together accounted for 32%., Conclusion: In mild to moderate female obesity of the peripheral type, dyslipidaemia is common. However the most common abnormality, hypercholesterolaemia is not significantly related to anthropometric or endocrine indexes, while these together account for more than one third of variability in serum triglyceride concentrations.

Background: The relationship of dyslipidemias between young offspring and their parents was examined to evaluate its usefulness in predicting lipid disorders among parents and children., Methods: Young offspring ages 5-17 years and their parents were studied in a community-based sample of 477 families. The dyslipidemias were defined as: (1) isolated high low-density lipoprotein cholesterol (LDL-C); (2) isolated high triglycerides (TG) and/or low high-density lipoprotein cholesterol (HDL-C); and (3) combined, involving both above., Results: Children of parents with a given dyslipidemia type had the highest frequency of the same disorder (P < 0.001 to P < 0.05). In discriminant analyses only the corresponding disorders in their parents were selected into the models as significant predictors after controlling parental obesity. In terms of sensitivity, 54.8, 50.0, 66.7, and 69.1% of offspring could be correctly predicted for isolated TG/HDL-C, isolated LDL-C, combined, and any type of disorder, respectively, by the corresponding disorders in both parents. Likewise, the predictability of parent's dyslipidemia from their children's disorder was also modest., Conclusion: The conjoint dyslipidemias have familial basis to provide rationale for parents or children to determine their own risk status; however, sensitivity and positive predictive values are not high enough to be useful as a selective screening tool.