HDL Abnormalities Research Articles

Abstract 17070: Dyslipidemia Prevalence Among a Diverse Cohort of Childhood, Adolescent and Young Adult Cancer Survivors

Background: In the general population, dyslipidemia impacts 36% of adults between the ages of 20 and 29 years. Among survivors of childhood, adolescent, and young adult-onset cancer (C-AYAs), the prevalence of dyslipidemia in racially diverse cohorts as well as our understanding of which measured fats are most commonly abnormal are limited. Question: Among a diverse group of C-AYAs, what is the prevalence of dyslipidemia and which fats are most contributory? Methods: Individuals diagnosed with cancer at age ≤39 years and treated with anthracycline based chemotherapy between 2010-2022 were identified. Depending on age at time of collection, post-treatment lipid panels were analyzed according to AAP (<20 years) or ACC/AHA (≥20 years) guidelines. Non-fasting panels were included, in accordance with ACC/AHA guidelines. The prevalence of dyslipidemia and median values for measured fats were determined. Non-parametric testing was used to examine associations between dyslipidemia, age, and race. Results: Among a diverse (40% Black, 52% White) cohort of C-AYAs (227 total) with a median current age of 25 years (interquartile range (IQR) 20-36 years) and median total doxorubicin isotoxic equivalents of 200mg/m 2 (IQR 120-300 mg/m 2 ), the prevalence of dyslipidemia was 55%. Prevalence of dyslipidemia was not associated with race (Black 55%, White 64%, Other 44%, p=0.281) or age (<20 years 51%, ≥20 years 64%, p = 0.055). Among Black and White subjects, HDL was most commonly abnormal (Black 42%, White 38%), followed by triglycerides (TG) (Black 29%, White 41%). Median TG levels were significantly lower among Black individuals ≥20 years compared with White individuals (117 mg/dL vs 143 mg/dL, p = 0.030). Conclusions: Among a diverse group of C-AYAs, dyslipidemia was highly prevalent even at a younger age (<20 years). Race was not associated with prevalence of dyslipidemia. Dyslipidemia was primarily driven by HDL and TG abnormalities, fats associated with metabolic syndrome.

Hyperlipidaemia and cardioprotection: Animal models for translational studies.

Hyperlipidaemia is a well-established risk factor for cardiovascular diseases and therefore, many animal model have been developed to mimic the human abnormal elevation of blood lipid levels. In parallel, extensive research for the alleviation of ischaemia/reperfusion injury has revealed that hyperlipidaemia is a major co-morbidity that attenuates the cardioprotective effect of conditioning strategies (preconditioning, postconditioning and remote conditioning) and that of pharmacological interventions by interfering with cardioprotective signalling pathways. In the present review article, we summarize the existing data on animal models of hypercholesterolaemia (total, low density and HDL abnormalities) and hypertriglyceridaemia used in ischaemia/reperfusion injury and protection from it. We also provide recommendations on preclinical animal models to be used for translations of the cardioprotective strategies into clinical practice. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.23/issuetoc.

HDL Dysfunction Caused by Mutations in apoA-I and Other Genes that are Critical for HDL Biogenesis and Remodeling.

The "HDL hypothesis" which suggested that an elevation in HDL cholesterol (HDL-C) levels by drugs or by life style changes should be paralleled by a decrease in the risk for Cardiovascular Disease (CVD) has been challenged by recent epidemiological and clinical studies using HDL-raising drugs. HDL components such as proteins, lipids or small RNA molecules, but not cholesterol itself, possess various atheroprotective functions in different cell types and accumulating evidence supports the new hypothesis that HDL functionality is more important than HDL-C levels for CVD risk prediction. Thus, the detailed characterization of changes in HDL composition and functions in various pathogenic conditions is critically important in order to identify new biomarkers for diagnosis, prognosis and therapy monitoring of CVD. Here we provide an overview of how HDL composition, size and functionality are affected in patients with monogenic disorders of HDL metabolism due to mutations in genes that participate in the biogenesis and the remodeling of HDL. We also review the findings from various mouse models with genetic disturbances in the HDL biogenesis pathway that have been generated for the validation of the data obtained in human patients and how these models could be utilized for the evaluation of novel therapeutic strategies such as the use of adenovirus-mediated gene transfer technology that aim to correct HDL abnormalities.

M80 - METABOLIC ABNORMALITIES RELATED TO TREATMENT WITH SELECTIVE SEROTONIN REUPTAKE INHIBITORS IN PATIENTS WITH SCHIZOPHRENIA OR BIPOLAR DISORDER: A GENOME WIDE ASSOCIATION STUDY

Background Patients’ tolerability and experienced efficacy of psychopharmacological drugs such as Selective Serotonin Reuptake Inhibitors (SSRIs) are influenced by both environmental and genetic factors. SSRIs are sometimes used as add-on therapy in schizophrenia and bipolar disorder. Association between use of SSRIs and metabolic abnormalities has been shown, but little is known about the genetic associations in this context. Our aim is to study genetic variations associated with individual differences in SSRI-induced metabolic side effects. Methods We conducted a genome-wide association study to identify genetic variants affecting susceptibility to SSRI-induced metabolic abnormalities by using data from the Norwegian Thematically Organized Psychosis study. Patients (n=1120) suffering from schizophrenia (n=719) or bipolar disorder (n=401) were included. SSRI exposure was expressed in dosages or serum concentrations of SSRIs (n=237). Metabolic outcome variables were: Levels of total cholesterol, low and high density lipoprotein (LDL and HDL) cholesterol, triglycerides, glucose and Body Mass Index (BMI). Single nucleotide polymorphisms (SNP) and use of SSRIs were tested for associations to outcome variables. To account for the effect of age, gender and co-medication with olanzapine, quetiapine or clozapine, these were included as covariates in the analysis. Results In preliminary analysis, we identified 31 regions associated with SSRI-induced metabolic abnormalities in outcome variables total cholesterol level, HDL- and LDL cholesterol levels and triglycerides (significance threshold: P Discussion The present findings indicate that SSRI-induced metabolic abnormalities are potentially affected by common genetic variation. Several markers were associated with triglyceride levels, with strongest signal seen for marker rs13428203, and for several markers in PRRC2A gene, previously associated with age-at-onset of insulin-dependent diabetes mellitus, as well as a possible involvement in the inflammatory process of pancreatic beta-cell destruction during development of insulin-dependent diabetes mellitus. Further, markers in APOE were associated with both total cholesterol-and LDL cholesterol levels. In addition, several variants in ACSL4 were associated with HDL cholesterol. Our findings warrant further investigation to elucidate the mechanisms involved, which may ultimately guide to the discovery of novel drug targets and predictive markers.

HDL abnormalities in nephrotic syndrome and chronic kidney disease.

Normal HDL activity confers cardiovascular and overall protection by mediating reverse cholesterol transport and through its potent anti-inflammatory, antioxidant, and antithrombotic functions. Serum lipid profile, as well as various aspects of HDL metabolism, structure, and function can be profoundly altered in patients with nephrotic range proteinuria or chronic kidney disease (CKD). These abnormalities can, in turn, contribute to the progression of cardiovascular complications and various other comorbidities, such as foam cell formation, atherosclerosis, and/or glomerulosclerosis, in affected patients. The presence and severity of proteinuria and renal insufficiency, as well as dietary and drug regimens, pre-existing genetic disorders of lipid metabolism, and renal replacement therapies (including haemodialysis, peritoneal dialysis, and renal transplantation) determine the natural history of lipid disorders in patients with kidney disease. Despite the adverse effects associated with dysregulated reverse cholesterol transport and advances in our understanding of the underlying mechanisms, safe and effective therapeutic interventions are currently lacking. This Review provides an overview of HDL metabolism under normal conditions, and discusses the features, mechanisms, and consequences of HDL abnormalities in patients with nephrotic syndrome or advanced CKD.

Metabolomics and partial least square discriminant analysis to predict history of myocardial infarction of self-claimed healthy subjects: validity and feasibility for clinical practice.

BackgroundThe dynamics of metabolomics in establishing a prediction model using partial least square discriminant analysis have enabled better disease diagnosis; with emphasis on early detection of diseases. We attempted to translate the metabolomics model to predict the health status of the Orang Asli community whom we have little information. The metabolite expressions of the healthy vs. diseased patients (cardiovascular) were compared. A metabotype model was developed and validated using partial least square discriminant analysis (PLSDA). Cardiovascular risks of the Orang Asli were predicted and confirmed by biochemistry profiles conducted concurrently.ResultsFourteen (14) metabolites were determined as potential biomarkers for cardiovascular risks with receiver operating characteristic of more than 0.7. They include 15S-HETE (AUC = 0.997) and phosphorylcholine (AUC = 0.995). Seven Orang Asli were clustered with the patients’ group and may have ongoing cardiovascular risks and problems. This is supported by biochemistry tests results that showed abnormalities in cholesterol, triglyceride, HDL and LDL levels.ConclusionsThe disease prediction model based on metabolites is a useful diagnostic alternative as compared to the current single biomarker assays. The former is believed to be more cost effective since a single sample run is able to provide a more comprehensive disease profile, whilst the latter require different types of sampling tubes and blood volumes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13336-015-0018-4) contains supplementary material, which is available to authorized users.

Abstract 584: ApoE3[K146N/R147W] Acts as a Dominant Negative ApoE Form that Prevents Remnant Clearance and Inhibits the Biogenesis of HDL

Introduction: The K146N/R147W substitutions in human apolipoproteinE3 (apoE3) have been associated with a dominant form of type III hyperlipoproteinemia which is expressed at an early age. Methods: The effects of the K146N,R147W substitutions on the lipid and lipoprotein profiles and the HDL phenotypes were studied by adenovirus mediated gene transfer of the full length and a truncated apoE3[K146N/R147W]-202 mutant using different mouse models. Results: A low dose of adenovirus expressing the apoE3[K146N/R147W] mutant in apoE deficient or in apoA-I x apoE double deficient mice exacerbated the hypercholesterolemia and increased greatly plasma apoE and triglycerides levels. In apoE deficient mice, the apoE3[K146N/R147W] mutant displaced apoA-I from the VLDL/LDL/HDL region and resulted in the accumulation of discoidal apoE containing HDL particles in plasma. Similar doses of WT apoE3 cleared the cholesterol of apoE deficient mice without induction of hypertriglyceridemia and promoted formation of spherical HDL particles. A unique feature of the truncated apoE3[K146N/R147W]-202 mutant is that it prevented the induction of hypertriglyceridemia but did not correct the hypercholesterolemia. Other apoE-202 truncated mutants tested did not induce hypertriglyceridemia but corrected hypercholesterolemia. Infection of apoE deficient mice with adenoviruses expressing the apoE3[K146N/R147W] and lipoprotein lipase corrected the hypertriglyceridemia but did not prevent the formation of discoidal HDL particles. Infection of apoE deficient mice with adenoviruses expressing the apoE3[K146N/R147W] and lecithin:cholesterol (LCAT) acyltransferase corrected hypertriglyceridemia, normalized the plasma cholesteryl ester to total cholesterol ratio and generated spherical HDL particles. The combined data indicate that the K146N/R147W substitutions in the full length and the truncated apoE3[K146N/R147W] mutant prevent receptor mediated remnant clearance. Conclusion: The lipid/lipoprotein and HDL abnormalities observed in the different mouse models suggest that the apoE3[K146N/R147W] mutant acts a dominant negative ligand that exacerbates the dyslipidemia and also affects the activity of LCAT and thus inhibits the maturation of HDL.

Familial occurrence of abnormalities of high-density lipoprotein cholesterol

In families, well-known monogenic high-density lipoprotein cholesterol (HDL-C) disorders characterized by extreme HDL-C levels on both ends of the continuum occur in multiple HDL pathways and can confer increased risk for atherosclerotic disease. Polygenic HDL-C variants have been more difficult to identify. In many family and twin studies in different populations, HDL-C levels have been shown to be highly heritable, explaining, on average, between 40% and 60% of between-individual variation. This review of abnormal HDL in families addresses known monogenic HDL disorders and HDL-C heritability in the general population, and presents novel data on the heritability of HDL-C in families with a history of premature coronary artery disease. We conclude that levels of HDL-C and HDL abnormalities are largely under genetic control and environmental and behavioral factors alone have only a modest impact. While rare, monogenic disorders offer considerable insight into the genetics of HDL regulation. Moderate to high heritability estimates across different family populations suggest that future genetic studies will be successful in identifying HDL genetic trait loci and that translational studies will ultimately lead to therapies that optimize the cardiovascular protective benefits of HDL.

Management of mixed hyperlipidaemia

This editorial refers to ‘Efficacy and safety of the coadministration of ezetimibe with fenofibrate in patients with mixed hyperlipidaemia’† by M. Farnier et al. , on page 897 The introduction of the HMG-CoA reductase inhibitors (statins) about 15 years ago has influenced the daily practice of cardiologists and other physicians enormously with respect to preventive strategies of first and second cardiovascular events. These drugs can lower the concentration of LDL-cholesterol by 30–60% and are generally well tolerated. In the last decade, randomized trials with statins have involved more than 90 000 patients, in which the overall safety and efficacy of the statins has been firmly established. The use of statins has, therefore, become the cornerstone of drug therapy in reducing the concentration of LDL-cholesterol and thereby the risk of cardiovascular disease and stroke, even in subjects without high serum cholesterol levels. Despite the success of statins in reducing cardiovascular morbidity and mortality, a substantial number of patients continue to have clinical events, which can partly be explained by the fact that other lipoprotein particles in addition to LDL contribute to the risk of cardiovascular disease, such as abnormalities in triglyceride-rich lipoproteins (very low-density lipoproteins, chylomicrons, or their remnants) and HDL.1 This is especially the case in … *Corresponding author. Tel: +31 243618819; fax: +31 243541734. E-mail address : a.stalenhoef{at}aig.umcn.nl

The role of oxidative stress-altered lipoprotein structure and function and microinflammation on cardiovascular risk in patients with minor renal dysfunction.

Cardiovascular disease is common in patients with chronic kidney disease (CKD). As renal function fails, many patients become progressively malnourished, as evidenced by reduced levels of albumin, prealbumin, and transferrin. Malnourished patients have increased levels of C reactive protein (CRP), interleukin-6 (IL-6), and concomitant cardiovascular disease when they reach end stage. Many diseases that cause CKD, diabetes, and hypertension are also associated with cardiovascular disease. Thus the direct effect of renal failure per se directly contributing to the inflammation-malnutrition-atherosclerosis paradigm is not completely established in early stages of CKD. Some aspects of progressive renal failure, however, cause changes in plasma composition and endothelial structure and function that favor vascular injury. As renal function fails, hepatic apo A-I synthesis decreases and HDL levels fall. HDL is an important antioxidant and defends the endothelium from the effects of cytokines. Inflammation causes further structural and functional abnormalities in HDL. Apolipoprotein C III (apo C III), a competitive inhibitor of lipoprotein lipase is increased in CKD. Serum triglyceride levels increase as a result of accumulation of intermediate-density lipoprotein (IDL) comprising VLDL and chylomicron remnants. These impede vascular relaxation and are associated with cardiovascular disease. Activation of the renin angiotensin axis is a component of many renal diseases and adaptation to loss of renal mass. Angiotensin II (AngII) activates NADPH oxidases, leading to production of the superoxide anion and decreased availability of nitric oxide (NO), further impairing vascular function. H(2)O(2), produced as a consequence of superoxide dismutation, stimulates vascular cell proliferation and hypertrophy. Leukocyte-derived myeloperoxidase functions as an "NO Oxidase" in the inflamed vasculature and contributes to decreased NO bioavailability and compromised vascular reactivity. The changes in lipoprotein composition and structure as well as AngII-mediated alterations in endothelial function amplify the effect of subsequent inflammatory events.

The metabolic syndrome: a practical guide to origins and treatment: Part II.

The metabolic syndrome (MetS), a cluster of metabolic abnormalities with insulin resistance as a major characteristic, has gone by several names over the past two decades. The diagnostic criteria proposed by the Adult Treatment Program III (ATP III) of the National Cholesterol Education Program (NCEP) have led to greater awareness of the components and treatment strategies.1 Five diagnostic traits are listed in the ATP III version of the MetS (Table; referred to as the “metabolic syndrome”), and the presence of any 3 of these factors is considered sufficient for diagnosis. This practical review will consider each in turn, providing advice for cardiologists, internists, and other health care providers who are diagnosing and treating persons with the syndrome in an effort to prevent a variety of clinical outcomes. View this table: Diagnostic Criteria for the Metabolic Syndrome The major adverse consequence of the MetS is cardiovascular disease (CVD). Several of the metabolic abnormalities associated with the syndrome, in fact, are CVD risk factors. One of these abnormalities, insulin resistance, also predisposes to the development of type 2 diabetes mellitus (T2DM). In age-adjusted estimates from the National Health and Nutrition Examination Survey III in 1998 to 1994, approximately 24% of adult Americans had ≥3 of the 5 MetS criteria. Key determinants of greater prevalence were age and ethnicity. Prevalence rates were highest in Mexican Americans and were successively lower in white, African American and other racial groups.2 These published estimates included persons with diabetes mellitus who had met the 1998 fasting glucose criteria (≥126 mg/dL [8.0 mmol/L]) of the American Diabetes Association.3 This article will focus on the features of the MetS in persons without diabetes mellitus, although most persons with T2DM also have the MetS. Moreover, the therapeutic approaches to metabolic risk factors described here also can be applied to …

Atherogenic lipoprotein changes in diabetic nephropathy

Cardiovascular risk is increased in patients with diabetic nephropathy. The aim of this study was to examine the relative impacts of albuminuria and renal failure, the two important features of diabetic nephropathy, on potentially atherogenic lipoprotein changes in this condition. The subjects were 160 non-diabetic healthy controls and a total of 200 type 2 diabetes patients with various degrees of nephropathy. The diabetic patients were divided into four groups by urinary albumin/creatinine ratio (U-ACR) and serum creatinine (S-Cr) levels: DM-1 ( U-ACR<30 mg/g, N=85), DM-2 ( U-ACR=30 –300 mg/g, N=48), DM-3 ( U-ACR>300 mg/g, N=29) and DM-4 ( S-Cr>177 μmol/l or 2.0 mg/dl, N=38). Lipids in very low (VLDL), intermediate (IDL), low (LDL), and high density (HDL) lipoproteins were measured following ultracentrifugation. VLDL-cholesterol (VLDL-C) was elevated (by 73–100%) in diabetic patients and it did not differ among the stages of nephropathy. IDL-C was higher as the nephropathy stage was advanced, and the elevation was significant in the DM-3 (by 75%) and DM-4 (by 131%) groups. LDL-C was not elevated in diabetic patients and was not different among the stages of nephropathy. Reduction of HDL-C was significant in DM-1, DM-2 and DM-3 (by 12–16%) and it was more exaggerated in DM-4 (by 35%). Multiple regression analyses indicated that elevated S-Cr, but not U-ACR, was an independent factor associated with raised IDL-C and lowered HDL-C in diabetic patients. These results indicate that diabetic patients with nephropathy show multiple lipoprotein changes, and that renal failure has greater impact than albuminuria on abnormalities in IDL and HDL. These lipoprotein alterations may contribute to an increased cardiovascular risk in diabetic nephropathy, especially in diabetic renal failure.

Aging and cardiovascular disease: a summary of the Eighth Münster International Arteriosclerosis Symposium.

This unique symposium focused on the remarkable increase in the older population that is occurring in many countries of the world. The international experts spoke on the effects of aging on cardiovascular disease, which is by far the most prominent cause of morbidity and mortality in the elderly. The program highlighted some of the most prominent changes that occur in the elderly and influence the toll that cardiovascular disease takes. The program was divided into four sessions: (1) the effects of aging on some of the cardiovascular risk factors; (2) the effects of aging on the heart muscle; (3) reports on recent studies of the effects of aging on morphology and function of the conduction system; and (4) a session featuring outstanding authorities on aging and the elastin, collagen, and calcium of the vessel wall, all of which are frequently added to the artery wall during aging. The speakers were carefully selected from top scholars in England, Germany, Finland, France, Italy, Japan, and the United States. Professor W.H. Hauss, who pioneered the development of the Institute for Arteriosclerosis Research at the University of Munster, Germany, and is now in his 80s, opened the symposium and introduced four prominent officials in health, education, and other German government posts, who added their words of welcome. The first session was chaired by Professor G. Assmann, who is the current director of the Arteriosclerosis Research Institute in Munster, Germany. He gave the opening presentation on genetic determinants of life expectancy, a subject on which he is a world authority. He began his presentation with a brief description of the very large PROCAM study of more than 35 000 individuals, two thirds of whom are male, being carried out at the University of Munster Arteriosclerosis Institute in Westphalia. This long-term study of the natural history …

HDLs containing apolipoproteins A-I and A-II (LpA-I:A-II) as markers of coronary artery disease in men with non-insulin-dependent diabetes mellitus.

Abnormalities in HDL and an increased risk of coronary artery disease (CAD) coexist in non-insulin-dependent diabetes mellitus (NIDDM). HDLs can be separated by their apolipoprotein (apo) content into particles containing apoA-I but not apoA-II (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II). The LpA-I particles have been suggested to be more effective in conferring protection against CAD than the LpA-I:A-II particles. However, data are sparse, and no studies have defined the role of these two classes of particles in NIDDM. LpA-I and LpA-I:A-II particles were quantified by a differential electroimmunoassay in four groups of men with similar age and body mass index (BMI) distributions. Group 1 consisted of 50 patients with NIDDM and angiographically verified CAD; group 2, 50 men with CAD but no diabetes; group 3, 50 men with NIDDM but no CAD; and group 4, 31 healthy men. Serum apoA-I and apoA-II concentrations were measured by immunoturbidimetry, and HDL2 and HDL3 were separated by ultracentrifugation. Concentrations of LpA-I:A-II particles in group 1 were 13.8%, 18.3%, and 26.9% lower than in groups 2 through 4, respectively. In a two-by-two factorial ANOVA, adjusted for age and BMI, the differences were significant for both CAD (P < .001) and NIDDM (P < .001), with no interaction between the factors. These results were confirmed by comparable differences in the serum concentrations of apoA-I and apoA-II. LpA-I particles were related to the presence or absence of CAD (P = .013), but the difference was lost in a multivariate analysis. A low HDL3 cholesterol concentration characterized both CAD (P = .002) and NIDDM (P = .024). HDL2 cholesterol differed significantly with regard to the presence of NIDDM (P = .033) but only borderline with respect to CAD (P = .073). ApoA-II-containing lipoproteins and HDL3 cholesterol are powerful markers of CAD in men with NIDDM.

Marked hyper-HDL 2-cholesterolemia associated with premature corneal opacity : A case report

We report here a peculiar case with premature corneal opacity and extremely high levels of HDL cholesterol in serum. The patient is a 54-year-old man who was first noticed to have marked corneal opacities at age 19. His serum HDL cholesterol level was elevated to the level of 135–160 mg/dl, while total serum cholesterol and triglyceride concentrations were 254 mg/dl and 56 mg/dl, respectively. Serum apoprotein A-I and E levels analyzed by single radial immunodiffusion method were elevated in the case. Serum lipoprotein fractions isolated by preparative ultracentrifugation revealed that increased levels of HDL cholesterol were accounted for solely by the HDL 2 fraction. HDL 2 of the patient contained relatively higher amounts of apoprotein E than normal control HDL 2. Elution profiles of lipoproteins in high performance liquid chromatography revealed that HDL 2 particles from the patient were larger in size than those from normal controls. These characteristics of HDL are in part similar to those of HDLG which appears in experimental animals after cholesterol feeding. Such abnormalities in HDL 2 fractions associated with premature corneal opacity have not been reported so far and appear to constitute a new disease entity.

血清 High Density Lipoprotein の臨床的検討

Quantitative analysis of serum apo HDL and HDL-cholesterol was carried out in 75 human subjects. The subjects consisted of the following four groups: myocardial infarction, angina pectories, arrhythmia probably due to myocardial ischemia and normal controls. To avoid possibly indefinite factors, age matched healthy men and women who have the same occupation and have been in similar circumstances were subjected as normal control.The concentration of apo HDL was measured by rocket immuno-electrophoresis using anti-HDL-serum (anti-α1-lipoprotein-serum, BEHR-INGWERKE AG). HDL-cholesterol was determined by the precipitation method using heparinmanganese chloride.Mean levels of both apo HDL and HDL-cholesterol were significantly lower in two groups of myocardial infarction and angina pectoris than those in the control group. In the group of arrhythmia apo HDL level was low, but no significant decrease of HDL-cholesterol was seen.Fourteen of 41 normal controls has low levels of HDL-cholesterol, but low levels of apo HDL were seen in only 3 control subjects.Although there was a low statistical correlation (r=0.570, p<0.001) between apo HDL and HDL-cholesterol levels, the statistics in terms of 90% confidence interval for the regression line indicated difficulties in estimating HDL-cholesterol level from apo HDL level, i. e. the levels of HDL-cholesterol and apo HDL are variable to each other under the contribution of unknown factors.In this study, apo HDL level was a valuable discriminator to characterize HDL abnormalities in myocardial infarction. These results bring forward an interesting problem in apo HDL metabolism, especially in atherosclerotic disease.