Dyslipidemia in South Asians living in a western community

An increased prevalence of coronary heart disease (CHD) has been well documented in the South Asian population living worldwide. The prevalence of certain traditional CHD risk factors, like diabetes mellitus and tobacco use, have been on the rise in this ethnic group and likely contribute to the increase in CHD prevalence. Still, a disproportionate excess of CHD exists, and this may be linked to novel CHD risk factors. We have reviewed the prevalence of CHD in South Asians and its association to both traditional and novel CHD risk factors. We present a literature review of traditional and novel CHD risk factors, and incorporate the results of a cross-sectional study investigating the prevalence of these factors in a South Asian population residing in the United States with no prior diagnosis of CHD. The total cholesterol (TC) (mean ± standard deviation) was 193.72 ± 33.76 mg/dL, high-density lipoprotein (HDL) was 42.20 ± 12.11 mg/dL, and low-density lipoprotein (LDL) was 124.88 ± 27.22 mg/dL. The mean triglyceride level was 166.60 mg/dL. The prevalence of elevated TC (>200 mg/dL) was 41.3% and elevated LDL (>130 mg/dL) 40.7%. There was a significant difference between men and women in the prevalence of reduced HDL (<40 mg/dL) (67.3% vs. 49.4%), elevated triglycerides (>130 mg/dL) (56.4 vs. 30.4%), and small-dense LDL particles (53.6% vs. 27.8%). Considerably higher prevalence of novel CHD risk factors has been noted in the South Asian population. The CHD risk may increase significantly when these novel factors co-exist with traditional CHD risk factors.     

Familial hypercholesterolemia with extensive coronary artery disease and tuberous and tendinous xanthomas: A case report and mutation analysis

This is a case report of a 38-year-old Syrian refugee male with early-onset extensive atherosclerosis. The physical and laboratory examination were remarkable with severe xanthomas in the upper and lower extremities and with low-density lipoprotein cholesterol (LDL-C) 417 mg/dL, total cholesterol 495 mg/dL, high-density lipoprotein cholesterol 30 mg/dL, and triglycerides 242 mg/dL. LDL-C level responded poorly to the high-dose statin treatment. The genetic analysis indicated that the patient had a large homozygous deletion in LDL receptor gene including the exons 7–14. A 12-kb deletion had occurred between the 2 Alu repetitive sequences that were oriented in opposite directions, one in intron 6 and the other in intron 14. This deletion eliminated exons 7–14, which exactly corresponded to the entire exon sequence coding the epidermal growth factor precursor homology domain. This deletion in LDL receptor was previously reported. This rare case of homozygous familial hypercholesterolemia presenting with multiple large and widely distributed xanthomas implicates the need for novel treatment options in familial hypercholesterolemia patients. The case is a Syrian refugee and emphasizes the urgent need to address orphan disease in refugee populations throughout the world.     

HDL deficiency due to a new insertion mutation (ApoA-INashua) and review of the literature

A 61-year-old white man of European ancestry with significant coronary heart disease since age 42 years and marked high-density lipoprotein (HDL) deficiency (HDL cholesterol 1 mg/dL) was evaluated. His fasting low-density lipoprotein cholesterol level was 42 mg/dL, and his triglycerides were 417 mg/dL on therapy with rosuvastatin 40 mg/day, ezetimibe 10 mg/day, fenofibrate 145 mg/day, and extended-release niacin 2 g/day. Further analysis of his plasma revealed an apolipoprotein (apo) A-I level of 23.5 mg/dL (approximately 20% of normal), and the absence of small alpha-4 HDL, medium alpha-3 HDL, and very large alpha-1 HDL, with only very small pre-beta-1 HDL and large alpha-2 HDL being present. APOA-I gene sequencing revealed a novel heterozygous in-frame insertion mutation with duplication of nucleotides 1535 through 1552 inserted at position 1553, causing a new amino acid glycine at codon 157 and a duplication of amino acids alanine, arginine, alanine, histidine, and leucine at codons 158–162. This novel apoA-I mutation results in the formation of apoA-I that appears to have abnormal lipid binding properties, resulting in impaired reverse cholesterol transport, probable enhanced clearance, and premature coronary heart disease.     

内源性高甘油三酯血症患者血浆VLDL、LDL及HDL对血凝的影响

目的：研究内源性高甘油三酯血症(HTG)患血浆极低密度脂蛋白(VLDL)、低密度脂蛋白(LDL)及高密度脂蛋白(HDL)是否发生了氧化修饰及其对血凝的影响。方法：对2l例内源性高甘油三酯血症患与2l例年龄性别相近的正常人的血脂、脂质过氧化物进行了分析。用一次性密度梯度超速离心法分离血浆VLDL、LDL及HDL，测定这三种脂蛋白的234nm光吸收、相对电泳迁移率(REM)和硫代巴比妥酸反应物质(TBARS)，分别将这三种脂蛋白加入由正常人新鲜混合血浆构成的反应系统中，按试剂盒分别测定凝血酶原时间(PT)及活化部分凝血酶原时间(APIT)。结果：内源性HTG患血浆TG含量平均升高2．73倍，HDLC下降l.7l倍，同时LPO升高1．22倍;HTG组VLDL、LDL及HDL的REM、234nm光吸收值、TBARS含量均较对照组显增加(P＜0．01)，表明内源性HTG患血浆VLDL、LDL及LDL均发生了氧化修饰生成Ox—VLDL、Ox-LDL.PT及APTT在分别加入HTG组的VLDL、LDL及HDL后均比加入相应正常组脂蛋白明显缩短(P均＜0．05)。相关分析表明，HTG组血浆VLDL及HDL相对电泳迁移率(REM)与PT呈负相关(P＜0．01)。结论：HTG患血浆VLDL、LDL及HDL发生了氧化修饰，并使PT及APTT明显缩短。     

Lipid measurements in the management of cardiovascular diseases: Practical recommendations a scientific statement from the national lipid association writing group

Lipoprotein measurements are pivotal in the management of patients at risk for atherosclerotic coronary heart disease (CHD) with myocardial infarction and coronary death as the main outcomes, and for atherosclerotic cardiovascular disease (ASCVD), which includes CHD and stroke. Recent developments and changes in guidelines affect optimization of using lipid measures as cardiovascular biomarkers. This scientific statement reviews the pre-analytical, analytical, post-analytical, and clinical aspects of lipoprotein measurements. Highlights include the following: i) It is acceptable to screen with nonfasting lipids. ii) non-high-density lipoprotein HDL-cholesterol (non-HDL-C) is measured reliably in either the fasting or the nonfasting state and can effectively guide ASCVD prevention. iii) low density lipoprotein cholesterol (LDL-C) can be estimated from total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) measurements. For patients with LDL-C>100 mg/dL and TG ≤150 mg/dL it is reasonable to use the Friedewald formula. However, for those with TG 150-400 mg/dL the Friedewald formula for LDL-C estimation is less accurate. The Martin/Hopkins method is recommended for LDL-C estimation throughout the range of LDL-C levels and up to TG levels of 399 mg/dL. For TG levels ≥400 mg/dL LDL-C estimating equations are currently not recommended and newer methods are being evaluated. iv) When LDL-C or TG screening results are abnormal the clinician should consider obtaining fasting lipids. v) Advanced lipoprotein tests using apolipoprotein B (apoB), LDL Particle Number (LDL-P) or remnant cholesterol may help to guide therapeutic decisions in select patients, but data are limited for patients already on lipid lowering therapy with low LDL-C levels. Better harmonization of advanced lipid measurement methods is needed. Lipid measurements are recommended 4-12 weeks after a change in lipid treatment. Lipid laboratory reports should denote desirable values and specifically identify extremely elevated LDL-C levels (≥190 mg/dL at any age or ≥160 mg/dL in children) as severe hypercholesterolemia. Potentially actionable abnormal lipid test results, including fasting triglycerides (TG) ≥500 mg/dL, should be reported as hypertriglyceridemia. Appropriate use and reporting of lipid tests should improve their utility in the management of persons at high risk for ASCVD events.     

Glycogen storage disease type Ia: Linkage of glucose,glycogen, lactic acid,triglyceride, and uric acid metabolism

A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m². Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease.     

Treatment options for the management of hypertriglyceridemia: Strategies based on the best-available evidence

A severe elevation in triglycerides (TG; ≥500 mg/dL) increases the risk for pancreatitis. TG levels ≥200 mg/dL are associated with a greater risk of atherosclerotic coronary heart disease (CHD). However, no outcomes trials exist to assess the efficacy of TG lowering for preventing pancreatitis in patients with severe hypertriglyceridemia. Similarly, no completed prospective outcomes trial exists to support or refute a reduction in CHD risk resulting from lipid-altering therapy in patients specifically selected for the presence of hypertriglyceridemia. This review examines the available evidence for the use of statins, omega-3 fatty acids, fibrates, and niacin in the management of hypertriglyceridemic patients. Results from CHD outcomes trials support statins as the first-line lipid-altering drug therapy to reduce CHD in hypercholesterolemic patients, and subgroup analyses suggest statins are efficacious in hypertriglyceridemic patients with fasting TG levels <500 mg/dL. Omega-3 fatty acids and fibrates are reasonable first drug options for patients with TG ≥500 mg/dL and often are used to lower TG levels with the objective of reducing pancreatitis risk, although a statin or niacin may also be reasonable options. Combination lipid drug therapy may be needed to achieve both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals for CHD prevention in patients with elevated TG levels, particularly those with TG ≥500 mg/dL. Additional clinical outcomes data are needed to provide a more evidence-based rationale for clinical lipid management of hypertriglyceridemic patients.     

Deficiency of hepatic lipase activity in post-heparin plasma in familial hyper-alpha-triglyceridemia

Hyper-alpha-triglyceridemia is a rare dyslipoproteinemia characterized by a pronounced increase in the concentration of triglycerides in the plasma high density lipoprotein (HDL) fraction. One case with this condition, an apparently healthy 61-year-old man, has been studied. Additional lipoprotein abnormalities were present, such as abnormally cholesterol-rich very low density lipoproteins (VLDL) with retarded electrophoretic mobility (beta-VLDL) and triglyceride enrichment of low density lipoproteins (LDL). The patient's plasma concentration of apolipoproteins A-I, A-II and B were normal and those of C-I, C-II, C-III and E were elevated. No abnormal forms of the soluble apolipoproteins of VLDL and high density lipoproteins (HDL) were found after analysis by isoelectric focusing. Lecithin:cholesterol acyltransferase activities, plasma cholesterol esterification rates and lipid transfer protein activities were normal. Post-heparin plasma activity of hepatic lipase was virtually absent and that of lipoprotein lipase was reduced by 50%. In plasma of this patient, HDL was almost exclusively present as large triglyceride-rich particles corresponding in size to particles of the HDL2 density fraction. The only brother of the patient also had hyper-alpha-triglyceridemia together with the other lipoprotein abnormalities described for the index case and deficiency of postheparin plasma activity of hepatic lipase. The findings presented below support the hypothesis that one primary function of hepatic lipase is associated with degradation of plasma HDL2. Deficiency of this enzyme activity thus causes accumulation of HDL2 in plasma leading to hyper-alpha-triglyceridemia. The results further suggest that the abnormal chemical and electrophoretic properties of VLDL and LDL in plasma from the patient, reminiscent of type III hyperlipoproteinemia, are secondary to the lack of the action of hepatic lipase on the HDL particles.     

A first British case of fish-eye disease presenting at age 75 years: a double heterozygote for defined and new mutations affecting LCAT structure and expression.

Fish-eye disease is a familial syndrome with corneal opacification, major high density lipoprotein (HDL) deficiency in plasma, significant cholesterol esterification in plasma on non-HDL lipoproteins, generally without premature coronary disease. This first British male case from unrelated British parents had infarcts when aged 49 and 73 years but was asymptomatic at age 81 years, with plasma cholesterol 4.3-7.1 mmol/litre, triglycerides 1.8-2.2 mmol/litre, HDL cholesterol < 0.1 mmol/litre, apolipoprotein A-I < 0.16 g/litre, lipoprotein(a) 0.61 g/litre. Cholesterol esterification was impaired using HDL-3 and A-I proteoliposomes but not using VLDL/IDL/LDL. The findings are those of LCAT deficiency with the classic fish-eye disease defect. Most of the 22 reported cases were homozygous or heterozygous for a Thr-Ile mutation at codon 123 of the lecithin:cholesterol acyltransferase (LCAT) gene. This patient was a double heterozygote for this mutation and a second new incompletely defined mutation affecting LCAT expression as defined by reduced mass and activity in plasma.     

Assessment of lipoprotein profiles study (ALPS) and antioxidant activity in healthy subjects treated with AGI-1067

BackgroundAGI-1067 (succinobucol) is a phenolic derivative of probucol that inhibits the vascular oxidative-inflammatory cascade and is intended to have an improved clinical profile.ObjectiveThe Assessment of Lipoprotein Profiles (ALPS) study evaluated the effects of AGI-1067 on lipid, antioxidant, antiinflammatory and safety profiles in healthy subjects.MethodsThis was a double-blind, placebo-controlled, 12-week, multicenter trial. Eligible subjects, aged 18 to 65 years, had low-density lipoprotein cholesterol (LDL-C) ≤ 190 mg/dL, triglyceride (TG) ≤ 600 mg/dL and Framingham risk <10%. Subjects were randomized 1:1 to oral 300 mg AGI-1067 (n = 127) or matching placebo (n = 127) once daily.ResultsAGI-1067 and placebo treatment had small changes (mean) in: LDL-C (+2.98 vs −1.52 mg/dL, respectively; P = 0.057), apolipoprotein B (+1.48 vs −1.91 mg/dL; P = 0.267), high-density lipoprotein cholesterol (HDL-C) [−3.69 vs −0.29 mg/dL; P < 0.001], and apolipoprotein (Apo) A-I (−10.43 vs −6.14 mg/dL; P = 0.021). Subjects with baseline LDL-C > 130 mg/dL showed the largest decreases in HDL-C and ApoA-I, while subjects with LDL-C ≤130 mg/dL had insignificant changes in both parameters. Changes in cholesteryl ester transfer protein mass were significantly correlated (P < 0.0001) with LDL-C changes, but not HDL-C. Paraoxonase activity increased with AGI-1067 vs little change in placebo (+1.78 vs +0.15 U/L, respectively; P = 0.077). HDL particles isolated from AGI-1067 treated subjects showed significant antioxidant potency vs HDL particles from placebo subjects (thiobarbituric acid reactive substances in a LDL oxidation assay decreased −25.88% vs +7.88, respectively; P = 0.011).ConclusionThe ALPS study demonstrated that AGI-1067 had minor effects on LDL and HDL cholesterol. More dramatic effects were observed for HDL-associated paraoxonase and thiobarbituric acid reactive substances activity, suggesting that the antiatherosclerotic properties of AGI-1067 may involve an HDL antioxidant mechanism consistent with inhibition of the oxidative-inflammatory cascade, rather than involving a lipid regulating pathway.     

Pathophysiologie und Therapie von Lipidstoffwechselstörungen bei Nierenerkrankungen

Summary Nephrotic syndrome, uremia, hemodialysis, peritoneal dialysis, and renal transplantation are accompanied by alterations in lipoprotein metabolism (Table 1). In nephrotic patients, total cholesterol, LDL, VLDL and triglycerides are elevated, while HDL may be increased, normal, or decreased. The pathophysiology includes increased hepatic synthesis of VLDL and cholesterol, decreased activity of lipoprotein lipase, and increased urinary excretion of HDL (Fig. 1). The risk of coronary heart disease (CHD) is increased in nephrotic patients, and elevated LDL-cholesterol may contribute to this risk. Cholesterol lowering diet and drugs are indicated. Presently, Lovastatin and Simvastatin are the most potent cholesterol lowering drugs in nephrotic patients with good evidence of long-term safety. Most patients with impaired renal function or on hemodialysis have moderate hypertriglyceridemia due to decreased lipoprotein lipase activity (Fig. 2). HDL may be slightly decreased. Although the risk of CHD is increased in these patients, triglyceride lowering drugs are not indicated, since no benefit can be expected. Peritoneal dialysis is accompanied by elevated VLDL in addition to hypertriglyceridemia. Reabsorption of large amounts of glucose from peritoneal dialysis fluid increases the carbohydrate load and stimulates hepatic VLDL synthesis. Cholesterol lowering therapy may be advantageous, but the experience is very limited. Side effects of lipid lowering drugs may be aggravated in renal failure. Total cholesterol, LDL, VLDL, and triglycerides are elevated in 50% of patients following renal transplantation. Corticosteroides and cyclosporin are major causes of hyperlipidemia. Cholesterol lowering therapy is indicated since the incidence of CHD is increased. Lipid lowering diet, triple immunosuppression with low dose cyclosporin, azathioprim, and prednisone, or conversion from cyclosporin to azathioprim are valuable measures to reduce cholesterol. Low-dose lovastatin (20 mg/24 h) seems to be an effective and safe cholesterol lowering drug in renal transplantation, while higher doses may induce rhabdomyolysis.

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Abkürzungsverzeichnis NS Nephrotisches Syndrom - LDL Low Density Lipoprotein Cholesterin - VLDL Very Low Density Lipoprotein Cholesterin - HDL High Density Lipoprotein Cholesterin - KHK Koronare Herzerkrankung - HMG-CoA 3-Hydroxy-3-Methylglutaryl-Coenzym A - NIH National Institute of Health - GFR Glomeruläre Filtrationsrate     

Obstructive sleep apnea syndrome. Effects of therapy on dyslipidemia

Summary Objective   Dyslipidemia is frequently observed in patients with obstructive sleep apnea syndrome (OSAS). The effects of OSAS treatment on lipid levels in these patients have been examined. Patients and Methods   95 consecutive patients (aged 56.6±9.5 years) with polysomnographically verified OSAS and LDL cholesterol levels of more than 130 mg per deciliter have been included in a prospective trial. Plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, apolipoprotein B, and lipoprotein (a) levels were determined in all patients at baseline and after long term therapy. Results   Total cholesterol (249.9 ± 31.4 vs. 240.0 ± 34.1 mg/dL; p = 0.01) and LDL cholesterol levels (179.4 ± 29.4 vs. 165.5 ± 32.5 mg/dL; p < 0.001) decreased significantly after 6 months in patients effectively treated, while they did not change significantly in those OSAS patients in whom treatment proved to be ineffective. Body mass index, HDL cholesterol, triglyceride, apolipoprotein B, and lipoprotein (a) levels did not change during follow-up. Both the change of total and LDL cholesterol levels were independently associated with treatment efficacy as indicated by the change of the apnea/hypopnea index. Conclusion   The results suggest that effective treatment of sleep-disordered breathing may have significant effects on the total and LDL cholesterol levels in OSAS patients.     

Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women

OBJECTIVE: To investigate the effects of short-term administration of melatonin on lipoprotein metabolism in normolipidemic postmenopausal women. METHODS: Fifteen such women received 6.0 mg melatonin daily for 2 weeks. Blood was sampled before and after treatment. We measured concentrations of total cholesterol and total triglyceride in the plasma, as well as the levels of cholesterol, triglyceride, and protein in the very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Plasma apolipoprotein levels were determined by immunoturbidimetric assay. Activities of lipoprotein lipase, hepatic triglyceride lipase, and lecithin cholesterol acyltransferase were also determined by enzymatic analysis. RESULTS: Melatonin administration significantly increased the plasma levels of triglyceride by 27.2% (P < 0.05), of VLDL-cholesterol by 37.2% (P < 0.01), of VLDL-triglyceride by 62.2% (P < 0.001), and of VLDL-protein by 30.0% (P < 0.05). However, the plasma total cholesterol level and the concentration of lipid and protein in LDL and HDL were not significantly affected. Melatonin significantly increased the plasma levels of apolipoprotein C-II by 29.5% (P < 0.005), of C-III by 17.1% (P < 0.001), and of E by 7.6% (P < 0.05). The plasma levels of apolipoprotein A-I, A-II, and B were not altered. Melatonin significantly inhibited the activity of lipoprotein lipase by -14.1% (P < 0.05), but did not significantly affect the activities of hepatic triglyceride lipase or of lecithin cholesterol acyltransferase. CONCLUSIONS: Findings indicate that melatonin increases the plasma level of VLDL particles by inhibiting the activity of lipoprotein lipase, but may not affect the plasma levels of LDL and HDL particles in postmenopausal women with normolipidemia.     

Diagnostic certainty is sometimes certainly an error

We evaluated a low-density lipoprotein (LDL) subfraction separation method using polyacrylamide tube gel electrophoresis (PTGE) and compared it with the reference method, polyacrylamide gradient gel electrophoresis (PGGE-REF). Excellent intra-assay and interassay coefficients of variation were obtained (<4%) for PTGE. For 102 subjects, LDL subclasses correlated most significantly with triglyceride (TG) level, high-density lipoprotein (HDL) cholesterol level, total cholesterol/HDL cholesterol ratio, and non-HDL cholesterol level (P < .05). The distribution of large LDL (76%) was predominant for subjects with low TG levels (< 150 mg/dL [1.69 mmol/L]), while distribution of small LDL (79%) was predominant for subjects with high TG levels (>200 mg/dL [2.26 mmol/L]). Excellent agreement between the methods was observed (weighted kappa = 0.78). Of 51 samples classified as small, dense LDL by PGGE-REF, none were misclassified as lage LDL and 4 as intermediate LDL by PTGE (92% concordance); of 44 samples classified as small and 7 as intermediate by PTGE (77% concordance). The PTGE method is precise and compares favorably with PGGE-REF. It has the advantage of being simple, less expensive, and more suitable for use in the clinical laboratory.     

Severe acquired (secondary) high-density lipoprotein deficiency

Decreased high-density lipoprotein cholesterol (HDL-C) levels have been designated a major risk factor for cardiovascular disease, and there is considerable interest in identifying individuals with these abnormalities for appropriate management. Although low HDL-C may result from genetic factors, it is estimated that approximately 50% of cases may be secondary to other abnormal or disease states or to their treatment. Very low HDL-C levels, arbitrarily defined as <20 mg/dL, are uncommon, and are best known to result from major genetic mutations of key steps in HDL metabolism. Less well-described are secondary forms of severe HDL-C deficiency, which need to be distinguished from the primary causes. In this review, causes of severe acquired HDL-C deficiency are identified from the literature and are reviewed extensively. These include moderate to severe hypertriglyceridemia, critical illness, androgenic anabolic steroids, and acquired lecithin cholesteryl acyl transferase deficiency and liver disease. A relatively new entity referred to as the "disappearing HDL syndrome" was coined to describe the fairly rapid development of severe HDL-C deficiency in ambulant subjects with previously normal HDL-C and triglyceride levels. This may occur with peroxisome proliferation-activated receptor agonist treatment or in patients with benign or malignant paraproteinemias. Case discussions from our clinical experience are provided to illustrate to the practitioner the clinical context in which these severe acquired deficiencies of HDL occur.     

Evidence for the presence in human plasma of lecithin: cholesterol acyltransferase activity (beta-LCAT) specifically esterifying free cholesterol of combined pre-beta- and beta-lipoproteins. Studies of fish eye disease patients and control subjects

The present study was undertaken to test our hypothesis that two different lecithin: cholesterol acyltransferase (LCAT) activities exist in normal human plasma, one denoted alpha-LCAT esterifying the free cholesterol of high density lipoproteins (HDL) and the other denoted beta-LCAT acting on the free cholesterol of very low (VLDL) and low (LDL) density lipoproteins. Plasmas depleted of HDL were obtained by means of preparative ultracentrifugation. Incubation at 37 degrees C of these plasma fractions from control subjects and patients with fish eye disease resulted in esterification of the remaining free cholesterol of combined VLDL and LDL (pre-beta- and beta-lipoproteins) in the HDL depleted plasmas. The shapes of the cholesterol esterification rate curves were similar for whole and HDL depleted plasmas from both control subjects and fish eye disease patients. In crosswise mixed incubation experiments with isolated combined VLD and LDL and total lipoprotein depleted plasma from a control subject and a patient with fish eye disease, respectively, esterification of free cholesterol occurred. Incubation of isolated total lipoproteins in plasma from a patient with LCAT deficiency mixed with total lipoprotein depleted plasma from a fish eye disease patient as a source of LCAT caused cholesterol esterification but did not result in normalization of the LCAT deficiency HDL particles, while the amount of normal-sized LDL particles increased. The present results support the hypothesis that a beta-LCAT exists in normal human plasma.     

Usefulness of examination of the cholesterol versus triglyceride ratio for lipoprotein fractions in a patient with marked hyper-triglyceridemia

A patient consulted the emergency room with acute pancreatitis, hypertriglyceridemia, and diabetes mellitus, and was later admitted to the hospital. Serum levels of total cholesterol(TC) and total triglyceride (TTG), and the cholesterol(Chol) versus triglyceride(TG) ratio(Chol/TG) for lipoprotein fractions were examined periodically during the course of treatment using Chol/Trig Combo, which identifies Chol and TG by differential staining. On admission, the patient's TTG, pancreatic amylase and glucose levels were 4020 mg/dl, 2012 IU/l, and 242 mg/dl, respectively. Clinofibrate administration resulted in a decrease in Chol and TG values for all fractions. However, the Chol/TG ratios were unchanged(HDL of 0.2 to 0.4, VLDL of approximately 0.13, and LDL of 0.1 to 0.2: Reference values from 103 healthy students were as follows: HDL 5.8 +/- 2.0, VLDL 0.39 +/- 0.1, and LDL 4.9 +/- 1.3[Mean +/- SD].). During clinofibrate treatment, TC and TG values gradually increased. Clinofibrate was discontinued and fenofibrate administration was initiated. This was followed by a dramatic improvement in TC, TTG and Chol/TG values for both HDL and LDL. The monitoring of lipoprotein fraction values proved useful for determining the treatment regimen for this patient with hypertriglyceridemia.     

Cholesterol lipoproteins,triglycerides, rural-urban differences and prevalence of dyslipidaemia among males in Rajasthan

To develop profiles of serum cholesterol lipoproteins and triglycerides, influence of rural versus urban lifestyle in their levels and prevalence of dyslipidaemias, we studied cohorts of male population in Rajasthan. Fasting blood samples were obtained from 401 men (age range 20-73 years) randomly selected from a larger sample of 3397 during a comprehensive cardiovascular risk factor survey in rural (202 men) and urban (199 men) populations. Serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and triglycerides (TG) were determined and correlated with age and anthropometric variables. The lipid levels were classified according to US National Cholesterol Education Program (NCEP) guidelines. The mean +/- SD levels in mg/dl were, total cholesterol 170.5 +/- 40, LDL cholesterol 102.1 +/- 36, HDL cholesterol 43.6 +/- 12 and TG 124.0 +/- 50. The mean levels in rural vs. urban population were total cholesterol 165 +/- 37 vs. 176 +/- 43 (p = 0.008), LDL cholesterol 97 +/- 33 vs. 108 +/- 39 (p = 0.003), HDL cholesterol 44 +/- 13 vs. 43 +/- 12 (p = 0.44) and TG 122 +/- 46 vs 126 +/- 55 (p = 0.41). There was significant positive correlation of age and body-mass index with total and LDL cholesterol and triglycerides but not with HDL cholesterol. When classified according to the NCEP guidelines high total cholesterol (> or = 240 mg/dl) and LDL cholesterol (> or = 160 mg/dl) was in 33 (8.3%). Borderline high total cholesterol (200-239) was in 64 (16%) and borderline high LDL cholesterol (130-159) in 55 (13.7%). Borderline high triglyceride (200-400 mg/dl) was in 33 (8.2%) and severe hypertriglyceridaemia in none. Low HDL cholesterol (< 35 mg/dl) was in 96 (23.9%) and protective level of HDL cholesterol (> or = 60 mg/dl) in 47 (11.7%). In urban as compared to rural men the prevalence of hypercholesterolaemia > 200 mg/dl (28% vs 22%) and hyper LDL cholesterolaemia (26% vs 18%) were significantly more.     

Progressively decreasing plasma high-density lipoprotein cholesterol levels preceding diagnosis of smoldering myeloma

We report a case of disappearing high-density lipoprotein (HDL) syndrome caused by oxidative modification of HDL and by autoantibodies against modified HDL, with subsequent diagnosis of myeloma. An elderly Caucasian man had normal lipid levels with HDL cholesterol (HDL-C) levels in the upper 70 mg/dL range from 1999 to 2003. In 2003, his HDL-C levels began to progressively fall, and by 2011, they were undetectable (<5 mg/dL) when measured with a Beckman Synchron LX auto analyzer. Analyses of the plasma sample from 2011 using ultracentrifugation (Vertical Auto Profile), nuclear magnetic resonance, and Ace EXCEL auto analyzer have shown that HDL-C levels were easily detectable (47–54 mg/dL), although reduced compared with his pre-2003 values. Analyses of his plasma sample from 2011 also showed the presence of lipid-adducted apolipoprotein A1 (apoA1) and high titer of antibodies against the adducted apoA1. Interestingly, a negative correlation between HDL-C levels and the titer of antibodies against apoA1 adducts was found in the control cohort. Finally, we show that in the mouse system, an antibody against apoA1 increases the clearance of HDL from plasma. This case of smoldering myeloma preceded by acquired, severe HDL-C deficiency, likely because of oxidative modifications of the HDL protein leading to the formation of autoantibodies, interference with clinical measurement of HDL-C, and increased plasma clearance of HDL, adds to the list of diagnostic considerations for unexplained HDL-C decreases over time.     

Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100–150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 ± 26 mg/dl compared to 351 ± 65 mg/dl at baseline in the IMA-treated patients and 139 ± 18 mg/dl compared to 359 ± 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.Abbreviations LDL low-density lipoprotein - IMA immunoadsorption - DSA dextran sulfate cellulose adsorption - apo apolipoprotein - Lp(a) lipoprotein(a) - HDL high-density lipoprotein - ACE angiotensin-converting enzyme