Improvement in LDL-cholesterol levels of patients with familial hypercholesterolemia: can we do better? Analysis of results obtained during the past two decades in 1669 French subjects.

BACKGROUND: Heterozygous Familial Hypercholesterolemia (heFH) is an autosomal disease that affects about 1/500 people. It is characterized by markedly elevated plasma LDL-cholesterol (C) levels and an increased risk of cardiovascular disease (CVD). The aim of this study was to measure changes in LDL-C levels in heFH patients over two decades, and to evaluate if patients achieved LDL-C targets. METHODS: Data from 1669 heFH patients in five academic French centers were recorded between 1988 and 2011. RESULTS: The mean LDL-C concentrations under medical care improved between 1988 and 2011 (245 mg/dL before 1995, 164 mg/dL after 2009; p < 0.0001). However, mean LDL-C level and the number of patients treated with statins (79.3%) have not improved since 2005. In patients registered and treated after 2005 (n = 616), only 10.4% reached target LDL-C levels of <100 mg/dL. Indeed, 29.4% (n = 181) were treated with a maximal therapy (statins with a potency of >45% LDL-C reduction plus at least another lipid-lowering agent). Despite maximal treatment, only 18.8% of these heFH patients (n = 34/181) reached target LDL-C levels of <100 mg/dL. In addition, 75.3% of patients with CVD did not reach the LDL-C of <100 mg/dL. CONCLUSION: This study demonstrates that after significant improvement over the past two decades, the mean LDL-C levels in heFH French patients has remained stable since 2005. We also show that most heFH patients are not achieving their recommended LDL-C goals: this highlights the need for improved treatment and for new therapeutics in this population.

Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28 days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180 mg/dL (10.0 mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140 mg/dL (7.77 mmol/L) during follow-up. The recommended blood glucose target is 140-180 mg/dL (7.7-10 mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c) ≥ 8%) or severe/repeated hypoglycaemia.

Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimalizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180mg/dL (10.0mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140mg/dL (7.77mmol/L) during follow-up. The recommended blood glucose target is 140-180mg/dL (7.7-10mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c)≥8%) or severe/repeated hypoglycaemia.

[Paraneoplastic limbic encephalitis with positive anti-RI antibodies and mediastinal seminoma]. / Encéphalite limbique paranéoplasique avec anticorps anti-RI et séminome médiastinal.

We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis.

Spontaneous hypoglycaemia in the presence of both anti-insulin antibody and anti-insulin receptor antibody.

Beside insulinoma, alternative causes of hyperinsulinaemic hypoglycaemia include the rare autoimmune syndrome related to spontaneous autoantibodies either to insulin or to insulin receptor. We describe a case of hypoglycaemia with high insulinemia in which insulinoma could not be evidenced. Surprisingly, we found in the patient's serum both insulin autoantibodies and insulin receptor autoantibodies. Available data eventually supported the predominant role of insulin autoantibodies rather than insulin receptor autoantibodies in the mechanism of hypoglycaemia of this patient. Insulin antibodies were present in high titre. Most of the insulin in serum was bound to the insulin antibodies and free insulin was slightly increased. HLA typing displayed DR4 haplotype, known to be strongly linked to the insulin autoimmune syndrome. The patient's serum was able to inhibit insulin binding to its receptor in a cultured cell line overexpressing insulin receptors both in experiments with native serum and with serum depleted from insulin antibodies. However, we could not demonstrate that the insulin receptor antibodies had insulin mimicking effect. We have no obvious explanation for the presence of these two antibodies in the same patient. Possible hypotheses might involve an idiotype-anti-idiotype mechanism or a poly-autoimmune disease.

Combination of apolipoprotein E2 and lipoprotein lipase heterozygosity causes severe hypertriglyceridemia during pregnancy.

Pregnancy is a physiological condition where plasma triglyceride levels are moderately increased. This results from raised synthesis of very-low-density lipoproteins (VLDL) in response to elevated estrogen levels. The occurrence of marked hypertriglyceridemia (HTG) is rare and may result from combination of heterozygote mutation in the lipoprotein lipase (LPL) gene and apolipoprotein E2 isoform, as reported in this case. This observation illustrates the interaction between genetic and environmental factors, since pregnancy may disclose a silent LPL deficiency. The risk of acute pancreatitis threatens both the mother and fetus lives. Early recognition of severe HTG and appropriate management are essential for a successful pregnancy outcome.

PPAR delta: an uncompletely known nuclear receptor.

Peroxisome proliferator-activated receptors (PPAR) mediate some of the transcriptional effects of fatty acids and control many physiological functions, especially in the field of development and metabolism. Three isotypes are known, alpha, gamma, and B/delta. Roles of PPAR alpha and PPARgamma are now quite well-known, particularly since their pharmacologic ligands have been marketed, respectively the lipid-normalizing class of fibrates and the antidiabetic class of thiazolidinediones (glitazones). However, functions of PPARdelta are uncompletely known to date, but some recent data enlight its role in the regulation of fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. Overexpression of PPARdelta using a transgenic murine model promotes an increase of muscle oxidative capability. This is accompanied by a redistribution of fatty acid flux, redirected from adipose tissue towards skeletal muscle. Finally, adipose mass is reduced, due to a decreased adipocyte size. These data strongly suggest that PPARdelta play a major role in the metabolic adaptations to western diet characterized by an excessive amount of saturated fat. Considering the metabolic properties of the two other PPAR isotypes, alpha and gamma, it is likely that the three PPAR isotypes have complementary effects in the pathophysiology of obesity and metabolic syndrome. Future therapeutical perspectives in this field should consider combined treatment, adding delta agonists (for all that their safety will be established) to the already available alpha and gamma agonists.

Reverse cholesterol transport, high density lipoproteins and HDL cholesterol: recent data.

Unlike LDL cholesterol, which is a major cardiovascular risk factor, HDL cholesterol plays an important anti-atherogenic role through reverse cholesterol transport from peripheral cells to the liver. Some recent biochemical and epidemiological data shed light on this key function. In the hereditary Tangier disease with disseminated lipid storage, the main biochemical feature is a dramatically low level of HDL cholesterol. Different mutations in the ATP-binding cassette transporter A1 (ABCA1) gene have been recently described, which interfere with cellular cholesterol efflux. This results in low HDL plasma level, and defective reverse cholesterol transport to the liver. Moreover, selective hepatic uptake of HDL cholesteryl esters by SR-B1, a class B scavenger receptor, also plays a key role. In the follow-up of the PROCAM Study, the relative risk of coronary events is high in a cluster of patients with increased total cholesterol/HDL-cholesterol ratio. In the prospective secondary prevention VA-HIT study, the relative risk of coronary events in patients with low HDL cholesterol levels is decreased of 22% with a treatment by gemfibrozil. If the present available range of drugs targeted at increasing HDL cholesterol levels is rather narrow, future therapies will be encouraging, especially with agonists of PPARs.

[Clinical relevance of homocysteine monitoring in the diabetic patient]. / Faut-il doser l'homocystéine chez le patient diabétique?

Accelerated atherosclerosis is common in diabetes mellitus, although its extent is not always related to its strong association with classical cardiovascular risk factors. Diabetic patients, especially with type 2 diabetes, are prone to cardiovascular disease which is the leading cause of death in this population. Recent clinical studies among general population have shown that an even mild increase of homocysteinemia play an important role in the progression of atherosclerosis, either in coronary or peripheral arteries. An increasing amount of in vitro data is providing evidence that excess of homocysteine has a toxic effect on the arterial wall. This aminoacid thus appears to be not only a risk marker but also an emerging cardiovascular risk factor. The measurement of plasma homocysteine contributes to the identification, among the diabetic population, of patients at high cardio-vascular risk, with the aim of improving their global management. Moreover the addition of group B vitamins provides an easy and low-cost treatment to lower hyperhomocysteinemia.

[Clinical, epidemiologic, and biochemical findings on the reverse cholesterol transport (cholesterol-HDL)]. / Données cliniques, épidémiologiques et biochimiques sur le système de retour du cholestérol (cholestérol-HDL).

Contrary to high plasma levels of low-density lipoprotein cholesterol (LDL-C), closely linked with coronary heart disease (CHD), high-density lipoprotein cholesterol (HDL-C) play an antiatherogenic role, through the reverse cholesterol transport from peripheral cells to the liver. New data in the pathophysiology of a rare genetic dyslipidemia, the Tangier disease, characterized by very low HDL-C levels and premature CHD, have shed light on this complex mechanism. In this disease, cholesterol efflux from peripheral cells is dramatically reduced, and this has been recently shown to be caused by mutations in an ATP-binding cassette transporter, which normally stimulates cholesterol efflux. Reverse cholesterol transport is therefore greatly decreased. Epidemiological data have revealed that 15% to 30% of coronary patients have low HDL-C levels. However, this is often combined with high triglycerides levels, and this association is frequently found in diabetic patients, especially prone to CHD. HDL-C has been repeatedly shown to be an inverse predictor of CHD. This has been enhanced by recent interventional studies (Veterans Affairs HDL Intervention Study, Bezafibrate Infarction Prevention Study) which have provided strong evidence that pharmacological increase of HDL-C, in combination with decrease in triglycerides level, reduces incidence of CHD.

Lipoprotein distribution of apolipoprotein C-III and its relationship to the presence in plasma of triglyceride-rich remnant lipoproteins.

The distribution of apolipoprotein C-III (apoC-III) between high-density lipoprotein (HDL) and apoB-containing lipoproteins has been used in lipid-lowering angiographic trials to establish a link between impaired triglyceride (TG)-rich lipoprotein (TRL) metabolism and the progression of coronary artery disease. To investigate the extent to which plasma lipoprotein apoC-III levels reflect the presence in plasma of potentially atherogenic remnant lipoproteins, we studied 4 groups of subjects: (1) normolipidemic (NL, n = 10), (2) hypercholesterolemic (HC, type IIa, low-density lipoprotein cholesterol [LDL-C] > 3.4 mmol/L, n = 10), (3) hypertriglyceridemic (HTG, type IV, TG > 2.3 mmol/L, n = 10), and (4) combined hyperlipidemic (CHL, type IIb, TG > 2.3 mmol/L, LDL-C > 3.4 mmol/L, n = 10). The apoC-III level was measured in plasma lipoproteins separated either by density (ultracentrifugation) or by size (fast protein liquid chromatography [FPLC]), and was compared with 4 parameters reflecting remnant lipoprotein levels (ie, very-low-density lipoprotein cholesterol [VLDL-C], intermediate-density lipoprotein cholesterol [IDL-C], remnant-like particle cholesterol [RLP-C], and intermediate-sized lipoprotein [ISL] apoE). Our results demonstrate that (1) increased amounts of apoC-III associated with plasma VLDL, TRL, or apoB-containing lipoproteins (LpB), as well as increased levels of TRL remnant lipoproteins, are a characteristic of HTG patients rather than patients with increased LDL, and (2) plasma levels of apoC-III in VLDL, TRL, or LpB, as well as the HDL apoC-III to LpB apoC-III ratios, are strongly correlated with circulating levels of TRL, although these apoC-II parameters more closely reflect the balance between TRL TG production and lipolysis than the extent of plasma TRL remnant accumulation.

Evolución de la psicoterapia grupal en la asistencia psiquiátrica: la Batería "Bel-Air" / Group psychotherapy in psychiatric care: the Bel-Air Evaluation Battery

En el presente trabajo se revisa, en primer lugar, la literatura sobre la eficacia global de las psicoterapias de grupo en relación con las individuales y luego se comparan los resultados de las terapias grupales duraderas con las breves y de las de diferentes orientaciones teóricas (dinámica, cognitivo-comportamental y psícoeducativa) entre sí y en pacientes con distintos diagnósticos. Algunos estudios meta-analíticos muestran un "efecto talla" ("effect size") similar al que se puede obtener en los estudios de eficacia de los psicofármacos. Hay algunos trabajos de revisión que afirman que no existen claras ventajas de unas variedades respecto de otras pero otros estudios, en cambio, privilegian ya sea las unas o las otras. Después discutimos el grado de objetividad de las investigaciones en el campo y de los instrumentos que se han utilizado con más frecuencia. Finalizamos describiendo la Batería "Bel-Air" de evaluación que utilizamos en el Departamento de Psiquiatría de la Facultad de Medicina de la Universidad de Ginebra. Consta de tres instrumentos adaptados de otros conocidos en la literatura: Una lista corta de síntomas (The Brief Symptoms Inventory, BSI), La Escala de Funcionamiento Global (GBS), El Cuestionario de Estrategias de Enfrentamiento de ("Coping index" de K. Sherrer y U. Scherrer) y El Cuestionario de Clima Grupal (adaptado de McKezie, 1990). Hemos añadido también dos instrumentos de creación propia. El cuestionario de evaluación de las relaciones con los demás (ERA, Fredenrich & Zinetti, 2000, en prensa) y el Cuestionario de Funciones sociales (QFS). Todos estos instrumentos permiten medir características comunes a grupos de muy diverso tipo en un tiempo corto. En cada grupo específico, se pueden naturalmente añadir otros instrumentos específicos para distintas patologías para otras variables. (AU)

Plasma kinetics of apoC-III and apoE in normolipidemic and hypertriglyceridemic subjects.

Apolipoprotein (apo) C-III and apoE play a central role in controlling the plasma metabolism of triglyceride-rich lipoproteins (TRL). We have investigated the plasma kinetics of total, very low density lipoprotein (VLDL) and high density lipoprotein (HDL) apoC-III and apoE in normolipidemic (NL) (n = 5), hypertriglyceridemic (HTG, n = 5), and Type III hyperlipoproteinemic (n = 2) individuals. Apolipoprotein kinetics were investigated using a primed constant (12 h) infusion of deuterium-labeled leucine. HTG and Type III patients had reduced rates of VLDL apoB-100 catabolism and no evidence of VLDL apoB-100 overproduction. Elevated (3- to 12-fold) total plasma and VLDL apoC-III levels in HTG and Type III patients, although associated with reduced apoC-III catabolism (i.e., increased residence times (RTs)), were mainly due to increased apoC-III production (plasma apoC-III transport rates (TRs, mean +/- SEM): (NL) 2.05 +/- 0.22 (HTG) 4.90 +/- 0.81 (P < 0.01), and (Type III) 8.78 mg. kg(-)(1). d(-)(1); VLDL apoC-III TRs: (NL) 1.35 +/- 0. 23 (HTG) 5.35 +/- 0.85 (P < 0.01), and (Type III) 7.40 mg. kg(-)(1). d(-)(1)). Elevated total plasma and VLDL apoE levels in HTG (2- and 6-fold, respectively) and in Type III (9- and 43-fold) patients were associated with increased VLDL apoE RTs (0.21 +/- 0.02, 0.46 +/- 0. 05 (P < 0.01), and 1.21 days, NL vs. HTG vs. Type III, respectively), as well as significantly increased apoE TRs (plasma: (NL) 2.94 +/- 0.78 (HTG) 5.80 +/- 0.59 (P < 0.01) and (Type III) 11.80 mg. kg(-)(1). d(-)(1); VLDL: (NL) 1.59 +/- 0.18 (HTG) 4.52 +/- 0.61 (P < 0.01) and (Type III) 11.95 mg. kg(-)(1). d(-)(1)). These results demonstrate that hypertriglyceridemic patients, having reduced VLDL apoB-100 catabolism (including patients with type III hyperlipoproteinemia) are characterized by overproduction of plasma and VLDL apoC-III and apoE.

Hypothalamic-pituitary Langerhans cell histiocytosis: a diagnostic challenge.

Four cases of hypothalamic-pituitary Langerhans cell histiocytosis (LCH) are reported, highlighting the expanding spectrum of clinical and magnetic resonance imaging (MRI) features in adults. The diagnostic challenge of hypothalamic-pituitary LCH is emphasized in cases revealed as supra-sellar tumors with panhypopituitarism or as isolated central diabetes insipidus. Diagnosis is confirmed by histological examination showing infiltration with CD1a positive histiocytes. General guidelines for diagnosis procedure are drawn out, including the neurosurgical biopsy in particular cases.

Assessment of cardiac arrhythmic risk in diabetic patients using QT dispersion abnormalities.

The purpose of this study was to assess the abnormalities and prevalence of QT dispersion in 154 diabetic patients (DP) who underwent a standard 12-lead ECG. QT interval was measured from the beginning of the QRS complex until the T wave returned to baseline. Atrial fibrillation, pacemakers and the impossibility of measuring 6 QT intervals per ECG were reasons for exclusion from the study. Diabetic patients were compared with 104 sex- and age-matched controls (C): mean age 50.7 +/- 2.3 years (DP) vs 48.4 +/- 10.1 (C) (ns); diabetes duration: 11.6 +/- 7.9 years. Seventy-eight percent of DP were non-insulin-dependent. Mean QT duration was 0.383 +/- 0.031 s (DP) vs 0.381 +/- 0.026 (C) (ns); QT dispersion (difference between the longest and shortest QT interval measurement) 0.033 +/- 0.015 s (DP) vs 0.024 +/- 0.011 (C) (p < 0.001); and QT variability 3.003 +/- 1.23% (DP) vs 2.295 +/- 0.936 (C) (p < 0.001); with a standard deviation of 0.012 +/- 0.005 s (DP) vs 0.009 +/- 0.004 (C) (ns). QT dispersion indices (dispersion, variability) were significantly increased in DP, even for short diabetes duration. Future studies should focus on QT dispersion to assess the usefulness of such indices in detecting DP at high risk of sudden death and ventricular arrhythmias.

Effects of low density and high density lipoproteins isolated from non-insulin dependent diabetic patients on prostaglandin secretion by mouse macrophage cell line P388D1.

We have previously shown that low-density (LDL) and high-density (HDL) lipoprotein from healthy subjects can promote in vitro prostaglandin (PG) release by murine macrophages. In this pilot study, we have measured PG production induced by lipoproteins of six diabetic patients with poor metabolic control, compared to five healthy controls. Plasma lipoprotein levels were similar in both groups. Lipoprotein fractions were purified by sequential ultracentrifugation. After lipoprotein incubation with cells, supernatants were extracted and PG quantified by HPLC. In presence of LDL, in control subjects, there was an increase in total PG production, mainly due to thromboxane B2 (TxB2). In diabetic patients, the secretion pattern was similar. In presence of HDL, in control subjects, total PG secretion was also increased, but it was balanced between TxB2 and prostacyclin. In diabetic patients, at low HDL concentration (10 mg/l) the secretion was mainly due to TxB2, while at higher HDL concentrations (100 mg/l). the secretion was balanced between TxB2 and prostacyclin. Comparison of means of areas under curve for the two groups studied showed that LDL increased all PG secretion in diabetic patients compared to controls (P < 0.05 for PGF2alpha), while HDL increased all PG secretion in controls compared to diabetic patients, except PGF2alpha. Our work suggests a key role of LDL in TxB2 secretion in diabetic patients, which is a major proaggregant and vasoconstrictive agent. There was also an increased secretion of all PG in diabetic patients.

[Late recurrence of subacute De Quervain-Crile thyroiditis]. / Récidive tardive d'une thyroïdite subaiguë de De Quervain-Crile.

Subacute thyroiditis usually recovers completely, and recurrences are unfrequent. We report hereafter the case of a 70-year-old man with a typical diagnosis of subacute thyroiditis. He reported a similar episode 20 years earlier, followed by a mild but persistant hypothyroidism. This case reminds that recurrence of subacute thyroiditis can occur even after many years.

Plasma remnant-like particle lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects.

Remnant-like particle (RLP) lipid and apolipoprotein (apo) levels were determined in the plasma of normolipidemic and hyperlipidemic subjects, in order to investigate the relationship between RLP levels and the concentration of other plasma lipoprotein parameters. Plasma RLP fractions were isolated with the use of an immunoaffinity gel (RLP-Cholesterol Jimro II, Japan Immunoresearch Lab.), containing specific anti-apoB-100 and anti-apoA-I antibodies. Four groups of human subjects were selected, who had either matching or significantly different levels of plasma triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C): (1) normolipidemic control (NC) subjects (n = 10), (2) patients with elevated levels of LDL-C (type IIa, LDL-C (mean +/- S.E.), 4.65 +/- 0.09 mmol/l, n = 10), (3) hypertriglyceridemic (HTG) patients with elevated LDL-C (type IIb, TG: 3.86 +/- 0.36; LDL-C: 4.67 +/- 0.21 mmol/l, n = 10), and (4) HTG patients with normal LDL-C (type IV, TG: 3.71 +/- 0.39 mmol/l, n = 10). NC subjects (RLP-C: 0.22 +/- 0.01; RLP-TG: 0.24 +/- 0.03 mmol/l) had RLP apoB, apoC-III and apoE levels of 3.2 +/- 0.3, 1.8 +/- 0.3, and 1.4 +/- 0.1 mg/dl, representing 3.2 +/- 0.4, 14.5 +/- 1.4 and 32.1 +/- 2.1% of total plasma levels, respectively. RLP lipid and apolipoprotein concentrations were significantly higher in HTG groups (type IIb and IV) compared to NTG groups (NC and type IIa) (e.g. RLP-C: 0.50 +/- 0.07 and 0.58 +/- 0.11 vs. 0.22 +/- 0.01 and 0.21 +/- 0.01 mmol/l, respectively (P < 0.01); RLP apoB: 8.4 +/- 1.6 and 8.2 +/- 0.9 vs. 3.2 +/- 0.3 and 3.4 +/- 0.2 mg/dl, respectively (P < 0.01)). No significant difference in RLP levels was observed between groups having different LDL levels, and thus no correlation existed between RLP-C and LDL-C levels (r = 0.24, n.s.). RLP-C and RLP apoB levels were, however, correlated with VLDL-C and VLDL apoB (r = 0.86, P < 0.001 and r = 0.70, P < 0.001, respectively). These results demonstrate that elevated levels of both RLP lipids and apolipoproteins are characteristic of patients with increased levels of plasma triglyceride, and not patients with increased levels of LDL.