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Biomedical subjects

J E Hokanson

Publications and source records attributed to J E Hokanson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Lipoprotein classes and coronary disease regression.

Lowering LDL cholesterol (LDL-C) levels to reduce or prevent coronary artery disease (CAD) progression and cardiac events in hypercholesterolemic subjects is now widely accepted. The clinical benefit of lowering LDL-C has recently been extended to individuals with normal or mildly elevated LDL-C. Recent analyses of large primary and secondary CAD prevention trials, however, clearly demonstrated that reducing LDL-C levels does not entirely account for the coronary event reduction associated with lipid-lowering therapy. Growing and compelling evidence is emerging on the role of triglyceride-rich lipoproteins (VLDL and IDL), high density lipoproteins (HDL), and small, dense LDL, as well as non lipid risk factors, in the regression or stabilization of atherosclerotic plaques of mild/moderate severity, which are associated with clinical cardiac events. Enzymes involved in the tight metabolic interrelationship between triglyceride-rich lipoproteins, small, dense LDL and HDL levels may represent potential therapeutic targets for CAD prevention by favourably altering lipoprotein composition and physical properties in addition to the current therapeutic focus on lipoprotein levels.

Anticholesteremic Agents↗
PubMed1998

Common variants in the promoter of the hepatic lipase gene are associated with lower levels of hepatic lipase activity, buoyant LDL, and higher HDL2 cholesterol.

Increased hepatic lipase (HL) activity is associated with small, dense, low density lipoprotein (LDL) and low high density lipoprotein2 (HDL2) cholesterol (-C) levels. A polymorphism in the promoter region of the HL gene (LIPC) is associated with HDL-C levels. To test whether this association is mediated by differences in HL activity between different LIPC promoter genotypes, the LIPC promoter polymorphism at position -250 (G-->A), HL activity, LDL buoyancy, and HDL-C levels were studied in white normolipidemic men and men with coronary artery disease (CAD). The less common A allele (frequency=0.21 and 0.25 in normal and CAD subjects, respectively) was associated with lower HL activity (P<0.005 by ANOVA) and buoyant LDL particles (P</=0.01) in both groups. Normal and CAD subjects heterozygous for the A allele had lower HL activity (by 24% and 29%, respectively) and significantly more buoyant LDL particles. Homozygosity for this allele (AA) was associated with an even lower HL activity in normal (-26%) and CAD (-46%) subjects. The A allele was associated with higher HDL2-C in CAD patients (P=0.007); heterozygotes and homozygotes for the A allele had a 92% and a 140% higher HDL2-C level (P<0.01) than did GG individuals. In a small number of normolipidemic subjects, the same trend in HDL2-C was seen. In a univariate analysis, the LIPC genotype accounted for 20% to 32% of the variance in HL levels among normal subjects and CAD patients, respectively. After adjustment for HL, the association between LIPC genotype and LDL buoyancy was no longer significant, suggesting that the effect of LIPC genotype on LDL buoyancy is mediated by its effects on HL activity. The LIPC A allele was more frequent in Japanese-Americans and African-Americans than in whites. In summary, these results suggest that variants in the LIPC promoter may significantly contribute to the variance in levels of HL activity and consequently, to the prevalence of the atherogenic small, dense, LDL particles and low HDL2-C levels.

Adult↗
PubMed1997

Lipoprotein lipase gene variants and risk of coronary disease: a quantitative analysis of population-based studies.

The purpose of this study is to quantify the magnitude of the association between common variants in the lipoprotein lipase gene and coronary disease, based on published population-based studies. Fourteen studies, representing 15,708 subjects, report allelic distribution for lipoprotein lipase gene variants among coronary disease patients and control subjects. Patient outcomes included clinical coronary disease events and documented coronary disease based on angiography. Allele frequencies are estimated for disease and non-disease groups within each study. A 2 x 2 contingency table is used to compute individual study odds ratios and 95% confidence intervals, relating the presence of the rare allele to disease status. Mantel-Haenszel-stratified analysis of each allelic variant results in a summary odds ratio and 95% confidence interval for the association between each rare allele in the lipoprotein lipase gene and coronary disease. The lipoprotein lipase D9N allele has a summary odds ratio of 1.59 (95% confidence interval 1.03-2.55), indicating a 59% increase in risk of coronary disease for carriers with this allelic variant. The lipoprotein lipase N291S allele showed no association with coronary disease (summary odds ratio 0.93, 95% confidence interval 0.73-1.19). The summary odds ratio for lipoprotein lipase S447Ter allele is 0.81 (95% confidence interval 0.65-1.0), indicating a marginal negative association between this variant and coronary disease. The common lipoprotein lipase Pvu II polymorphism shows no relation to coronary disease (summary odds ratio 0.90, 95% confidence interval 0.80-1.01). The rare allele of the lipoprotein lipase HindIII polymorphism is negatively associated with coronary disease (summary odds ratio 0.84, 95% confidence interval 0.73-0.96). The lipoprotein lipase D9N allele is associated with high levels of triglyceride and low levels of high-density lipoprotein. Similar atherogenic lipid levels are observed in subjects with structural mutations lipoprotein lipase C188E and P207L. Carriers of the S447Ter allele have low levels of triglyceride. The lipoprotein, lipase gene variants which decrease lipoprotein lipase catalytic activity are associated with familial combined hyperlipidemia, but not the elevation of apolipoprotein B seen in this disorder. In conclusion, allelic variants in the lipoprotein lipase gene are associated with altered lipid levels and differential coronary disease risk.

Alleles↗
PubMed1996

Oxidation-specific epitopes in human coronary atherosclerosis are not limited to oxidized low-density lipoprotein.

BACKGROUND: Previous small studies have demonstrated positive immunohistochemical staining in rabbit and human atherosclerotic plaques by antibodies that recognize oxidized low-density lipoprotein (OxLDL), but none have examined a large number of human coronary arteries or evaluated whether epitopes recognized by these antibodies might be present on plaque proteins other than OxLDL. METHODS AND RESULTS: Immunohistochemistry was performed on atherosclerotic (n = 87) and nonatherosclerotic (n = 51) coronary arterial segments from 20 patients by use of monoclonal antibodies that recognize epitopes on macrophages, smooth muscle cells, apolipoprotein (apo) B, and OxLDL. Staining with the OxLDL antibody (Ox5) was much more prevalent in atherosclerotic than in control segments. Extracellular Ox5 staining colocalized with apo B, but cell-associated Ox5 staining occurred in the absence of cell-associated apo B staining, which suggests that cell-associated epitopes for Ox5 were on proteins other than LDL. Epitopes for Ox5 formed in vitro on two readily available non-apo B proteins, human serum albumin and apo A-I, when these proteins were incubated under conditions of oxidant stress with polyunsaturated but not monounsaturated fatty acids; furthermore, an antioxidant inhibited Ox5 epitope formation. Thus, epitopes for Ox5 can form on proteins other than apo B. Also, phorbol ester-treated macrophages cultured in apo B-free medium developed epitopes for Ox5. CONCLUSIONS: These findings are consistent with the hypothesis that atherosclerosis is associated with oxidative modification of proteins in addition to LDL, particularly cell-associated proteins, and that the antiatherosclerotic effects of antioxidants seen in some studies may not be solely due to prevention of LDL oxidation.

Adult↗
PubMed1996

Paraoxonase genotypes, lipoprotein lipase activity, and HDL.

Paraxonase, an enzyme associated with the high density lipoprotein (HDL) particle, hydrolyzes paraoxon, the active metabolite of the insecticide parathion. Several studies have shown that paraxonase levels in humans have a distribution characteristic of two alleles, one with low activity and the other with high activity. Paraoxonase also has arylesterase activity, which does not exhibit activity polymorphism and can therefore serve as an estimate of enzyme protein. Although the ability of paraoxon to irreversibly inhibit lipoprotein lipase (LPL) has been exploited experimentally for many years, the role of plasma paraoxonase in lipoprotein metabolism is unknown. Seventy-two normal individuals were examined for paraoxonase genotypes, plasma paraoxonase and arylesterase activities, postheparin LPL and hepatic lipase (HL) activities, and lipoprotein levels to determine whether (1) paraoxonase activity or genotype determines lipoprotein levels via an effect on LPL or HL activity or (2) variation in LPL and HL activities determines HDL levels and indirectly affects paraoxonase activity and protein levels in plasma. In the entire group, paraoxonase activity was related to arylesterase activity and genotype. Whereas arylesterase activity was correlated with HDL cholesterol (HDL-C) and apolipoproteinA-I (apoA-I) levels, neither arylesterase nor paraoxonase was correlated with LPL or HL activity. Furthermore, LPL activity was positively correlated and HL inversely correlated with HDL cholesterol and apoA-I levels, whereas LPL was inversely correlated with triglyceride levels. The paraoxonase genotypes of the study group were 30 individuals homozygous for the low-activity allele, 38 heterozygotes, and 4 individuals homozygous for the high-activity allele. Paraoxonase genotype accounted for approximately .75 of the variation in paraoxonase activity. Paraoxonase activity was linearly related to arylesterase activity within each subgroup. No difference in either LPL or HL activity was seen as a function of paraoxonase genotype, nor were differences seen in plasma triglyceride or HDL-C by genotype by ANOVA. The relation between LPL and HL and components of HDL in the paraoxonase genotypic subgroups in general reflected the associations seen in the group as a whole. Multivariate analysis showed that LPL, HL, and arylesterase, a measure of paraoxonase mass, were independent predictors of HDL cholesterol, while paraoxonase genotype or activity was not. Thus, variation in LPL and HL appears to be significantly related to HDL cholesterol and apoA-I levels. The levels of HDL are a major correlate of paraoxonase protein levels, while paraoxonase genotype is the major predictor of plasma paraoxonase activity.

Adult↗
PubMed1996

Compositional differences of LDL particles in normal subjects with LDL subclass phenotype A and LDL subclass phenotype B.

A predominance of small LDL particles (subclass phenotype B), as determined by gradient-gel electrophoresis is found among patients with myocardial infarction. Despite physical differences in phenotype A and B particles, differences in lipid composition of particles in these phenotypes have yet to be reported in an unselected population of males and females. The present study used lipid/apoB ratios to analyze the amount of lipid per LDL particle, isolated by density-gradient ultracentrifugation, in 70 healthy subjects. Relative to apoB, the LDL particles from phenotype B subjects were found to contain less free cholesterol (0.391 +/- 0.05 versus 0.465 +/- 0.05; mean +/- SD; P < .001), phospholipid (1.26 +/- 0.2 versus 1.43 +/- 0.2; P < .001), and cholesteryl ester (1.97 +/- 0.1 versus 2.11 +/- 0.2; P < .001) than particles from phenotype A subjects. The amount of triglyceride per LDL particle did not differ between the two phenotypes (0.410 +/- 0.1 versus 0.406 +/- 0.1; P = NS) despite higher plasma triglyceride levels in the phenotype B subjects. LDL size and buoyancy were positively correlated with particle free cholesterol, phospholipid, and cholesteryl ester but not with particle triglyceride. These data suggest that the physical properties of LDL from subjects with phenotype A and B reflect their lipid composition. The compositional differences between LDL particles of the two phenotypes may provide new insight into the increased risk of myocardial infarction in subjects with small, dense LDL.

Adult↗
PubMed1996

Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.

OBJECTIVES: Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the magnitude of the association between triglyceride and cardiovascular disease in the general population, and to determine whether this relationship is independent of high-density lipoprotein (HDL) cholesterol, using the semi-quantitative techniques of metaanalysis. METHODS AND DESIGN: Seventeen studies were selected for the analysis based on published reports of population-based, prospective studies, including 46413 men and 10864 women. To insure comparability, only studies reporting the association between fasting triglyceride levels and incident cardiovascular endpoints were included. Using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI) were calculated and standardized with respect to a 1 mmol/l increase in triglyceride. Multivariable-adjusted RRs were determined for the six studies in men and two studies in women that reported adjustments for HDL cholesterol. RESULTS: For men and women, the univariate RRs for triglyceride were 1.32 (95% Cl 1.26-1.39) and 1.76 (95% Cl 1.50-2.07), respectively, indicating an approximately 30% increased risk in men and a 75% increase in women. Adjustment of HDL cholesterol and other risk factors attenuated these RRs to 1.14 (95% Cl 1.05-1.28) and 1.37 (95% Cl 1.13-1.66), respectively, which were still statistically significant values. CONCLUSION: Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol. These finding demonstrate the necessity for clinical trials to evaluate whether lowering plasma triglyceride decreases the risk of cardiovascular disease.

Adolescent↗
PubMed1995

LDL physical and chemical properties in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is characterized by elevations of triglyceride and/or cholesterol within families and an elevation in apoB. Although small dense LDL has been consistently associated with hypertriglyceridemia, small dense LDL persists despite reductions in triglyceride after treatment with gemfibrozil in FCHL. The current study evaluated potential differences in the distribution and chemical composition of LDL species in patients with FCHL and normolipidemic control subjects. LDL from FCHL patients was characterized by a relative abundance of a discrete LDL species with a mean peak analytic ultracentrifuge flotation rate (S0f) of 4.7 +/- 0.5 (SEM), a density of 1.041 +/- 0.001 g/mL, and a particle diameter of 250 +/- 1 A as assessed by gradient gel electrophoresis. The major LDL species in the control subjects had a higher mean S0f rate (6.3 +/- 0.4), was more buoyant (density, 1.037 +/- 0.001 g/mL), and was larger (diameter, 262 +/- 2 A). In addition, in a series of six LDL fractions separated by equilibrium density gradient ultracentrifugation, particle diameters were significantly smaller in all fractions from FCHL patients compared with those from control subjects. LDL particles from patients contained less free cholesterol, cholesteryl ester, and phospholipid than LDL from control subjects. The amount of triglyceride per LDL particle, however, did not differ between FCHL patients and control subjects. Differences in flotation rate and mass of the major LDL species between patients and control subjects could not be fully accounted for by differences in plasma triglyceride levels. Thus, LDL particles from FCHL patients are smaller and more dense with less cholesterol and phospholipid. Many of these differences appear to be independent of plasma triglyceride.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Levels of lipoprotein(a), apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial.

Levels of lipoprotein(a) [Lp(a)], apolipoprotein (apo) B, and lipoprotein cholesterol distribution using density-gradient ultracentrifugation were measured as part of a cross-sectional study at the final follow-up examination (mean 6.2 years) in the Diabetes Control and Complications Trial. Compared with the subjects in the conventionally treated group (n = 680), those subjects receiving intensive diabetes therapy (n = 667) had a lower level of Lp(a) (Caucasian subjects only, median 10.7 vs 12.5 mg/dl, respectively; P = 0.03), lower apo B (mean 83 vs. 86 mg/dl, respectively; P = 0.01), and a more favorable distribution of cholesterol in the lipoprotein fractions as measured by density-gradient ultracentrifugation with less cholesterol in the very-low-density lipoprotein and the dense low-density lipoprotein fractions and greater cholesterol content of the more buoyant low-density lipoprotein. Compared with a nondiabetic Caucasian control group (n = 2,158), Lp(a) levels were not different in the intensive treatment group (median 9.6 vs. 10.7 mg/dl, respectively; NS) and higher in the conventional treatment group (9.6 vs. 12.5 mg/dl, respectively; P < 0.01). No effect of renal dysfunction as measured by increasing albuminuria or reduced creatinine clearance on Lp(a) levels could be demonstrated in the diabetic subjects. Prospective follow-up of these subjects will determine whether these favorable lipoprotein differences in the intensive treatment group persist and whether they influence the onset of atherosclerosis in insulin-dependent diabetes.

Adolescent↗
PubMed1994

The visceral adiposity syndrome in Japanese-American men.

Japanese-Americans have an increased prevalence of non-insulin-dependent diabetes mellitus and coronary heart disease when compared to native Japanese. This increase has been associated with fasting hyperinsulinemia, hypertriglyceridemia, and low plasma levels of high-density lipoprotein (HDL) cholesterol. The purpose of this study was to examine the relationship of both visceral adiposity and insulin resistance to this metabolic syndrome and to the presence of a predominance of small, dense low-density lipoprotein (LDL) particles (LDL subclass phenotype B) that has been associated with increased atherogenic risk. Six Japanese-American men with non-insulin-dependent diabetes, each receiving an oral sulfonylurea, were selected. One or 2 nondiabetic Japanese-American men, matched by age and body mass index, were selected for each diabetic subject, giving a total of 9 nondiabetic men. Diabetic subjects had significantly higher fasting plasma glucose (p=0.0007) and lower insulin sensitivity (SI, p=0.018) using the minimal model technique than nondiabetic subjects matched for body mass index. Six men (2 with diabetes) had LDL phenotype A and 8 (4 with diabetes) had phenotype B. One nondiabetic subject had an intermediate low-density lipoprotein pattern. Significantly greater amounts of intra-abdominal fat (p=0.045) measured by computed tomography were found in the men with phenotype B while fasting insulin (p=0.070) and triglycerides (p=0.051) tended to be higher. free fatty acids (r=0.677), LDL density (relative flotation rate, r=-0.803), and plasma HDL-cholesterol (r=-0.717). SI was significantly correlated only with plasma free fatty acids (r=-0.546) and tended to be correlated with hepatic lipase activity (r=-0.512, p=0.061). In conclusion, these observations indicate that in non-obese Japanese-American men, the metabolic features of the so-called insulin resistance syndrome, including LDL phenotype B, are more strongly correlated with visceral adiposity than with SI. It may therefore be more appropriate to call this the visceral adiposity syndrome. Although questions concerning mechanisms still remain, we postulate that visceral adiposity plays a central role in the development of many of the metabolic abnormalities, including LDL subclass phenotype B, that occur in this metabolic syndrome.

Abdomen↗
PubMed1994

Epidemiology of triglycerides, small dense low-density lipoprotein, and lipoprotein(a) as risk factors for coronary heart disease.

In addition to LDL cholesterol, triglyceride; small, dense LDL (LDL subclass phenotype B); and lipoprotein(a) are emerging as important risk factors for CHD. Elevated plasma levels of each of these risk factors have consistently been associated with increased risk of CHD in case-control studies of white patients. In prospective studies, however, the association between triglycerides and CHD is generally not independent of HDL cholesterol in multivariate statistical analyses. Although the data are scarce, studies in women show that triglycerides are a stronger risk factor for CHD in women than in men. Although no prospective studies of LDL subclass phenotype B have been reported, a number of potential atherogenic mechanisms may be responsible for the association with CHD seen in the case-control studies. Similarly, few prospective studies of lipoprotein(a) have been published, all in Scandinavian men. The observational studies generally show an association between elevated lipoprotein(a) and CHD in whites but not in blacks. Each of these risk factors also has a genetic component. Of the two familial forms of hypertriglyceridemia, FCH has been associated with familial CHD in two cross-sectional studies. LDL subclass phenotype B is inherited consistent with a single major gene effect, and candidate gene linkage studies are in progress to map the chromosomal location of this proposed gene. Finally, lipoprotein(a) levels are largely attributable to variation at the apo(a) locus on chromosome 6. Whether other genetic variations explain the lack of reported associations between lipoprotein(a) and CHD in black populations remains to be determined. Understanding of these "non-LDL" lipoprotein-related risk factors will provide important information for the development of new, effective intervention strategies for the prevention of CHD.

Arteriosclerosis↗
PubMed1994

A comparison of self-esteem lability and low trait self-esteem as vulnerability factors for depression.

Self-esteem lability (SEL), defined as daily event-related variability in state self-esteem, and low trait self-esteem (TSE) were assessed among 205 male and female undergraduates who were currently depressed (CD), previously depressed (PD), and never depressed (ND). SEL scores were derived for the effect of positive, negative, and combined events on state self-esteem over 30 days. Consistent with psychodynamic and cognitive theories, SEL was found to be a better index of depression proneness than TSE. PD Ss showed higher lability on all SEL scores than ND controls but did not differ from controls on TSE. Ss were reassessed 5 months later, and new cases showed higher premorbid SEL than ND controls but did not differ from controls on premorbid TSE. SEL at Time 1 was found to increase risk for depression at Time 2 among Ss reporting high life stress at Time 2. Theoretical and methodological implications are discussed.

Adult↗
PubMed1994

Characterization of low-density lipoprotein subclasses: methodologic approaches and clinical relevance.

Emerging evidence suggests that subclasses of LDL, characterized by variations in density, size, and chemical composition of LDL particles, are of important clinical significance. Accumulating case-control studies demonstrate that a predominance of small, dense LDL particles (LDL subclass phenotype B) is associated with an increased risk of coronary heart disease, and several potential atherogenic mechanisms have been proposed. New studies also demonstrate that LDL subclass phenotype B is an integral feature of the insulin resistance syndrome. In addition to the well-documented genetic influences on LDL subclass distributions, lipid-altering drugs, diet, and exercise all appear to affect LDL subclasses. A better understanding of this combination of genetic and environmental influences could lead to the development of effective intervention strategies for the prevention of coronary heart disease.

Case-Control Studies↗
PubMed1993

Complex segregation analysis of LDL peak particle diameter.

A predominance of small low-density lipoprotein (LDL) particles, as determined by gradient gel electrophoresis (GGE), has been proposed to be a common genetic marker for risk of coronary heart disease. Previous analyses of the families in the Berkeley data set defined a dichotomous trait based on the LDL size distribution by GGE: subjects with a predominance of small LDL particles have LDL subclass "pattern B," while those with a predominance of large LDL particles have LDL subclass "pattern A." Using this definition, previous complex segregation analyses demonstrated a single major gene effect on pattern B with a dominant or additive mode of inheritance, and reduced penetrance in young males and premenopausal women. In the present analyses, a continuous variable denoted LDL peak particle diameter is used, reflecting the size (diameter in A) of the major LDL subclass, for comparison with the dichotomous LDL subclass pattern classification. After adjusting for age and gender, the results demonstrate a single major Mendelian gene effect, but the exact mode of inheritance could not be established. Thus, analysis of the continuous variable was not superior to that of the dichotomous classification in determining the mode of inheritance of the proposed single gene controlling LDL subclasses.

Coronary Disease↗
PubMed1993

Analyzing individual status and change with hierarchical linear models: illustration with depression in college students.

A recently developed class of multilevel or hierarchical linear models (HLM) provides an intuitive and efficient way to estimate individual growth or change curves. The approach also models the between-subjects variation of the individual change curves with treatment factors and individual attributes. Unlike other repeated measures analysis methods common in the behavioral sciences, HLM allows the fit of data with unequal numbers of repeated observations for each subject, variable timing of observations, and missing data, features which are often characteristic of data from field studies. The application of HLM for the analysis of repeated psychological measures is discussed and illustrated here with depression data for college students. Strengths and limitations of the approach are discussed.

Adaptation, Psychological↗
PubMed1993

Effect of hepatic lipase on LDL in normal men and those with coronary artery disease.

Hepatic triglyceride lipase (HL) is thought to play a role in the formation of low density lipoproteins (LDLs) from small very low density lipoproteins (VLDLs) and intermediate density lipoproteins (IDLs). To analyze the possible physiological role of HL in determining LDL buoyancy, size, and chemical composition, HL activity and LDL were studied in 21 patients with coronary artery disease (CAD) and 23 normolipidemic subjects. In both groups, LDL buoyancy and size were inversely associated with HL activity levels. The effect of HL on LDL size was comparable in CAD patients and in normolipidemic subjects. HL appeared to influence LDL lipid composition primarily by affecting the surface lipid components. The free cholesterol content of LDL particles was highly correlated with HL activity in both CAD and normolipidemic individuals. The free cholesterol to phospholipid ratio in LDL particles correlated with HL in both CAD and normolipidemic subjects. When the individuals were separated according to their LDL subclass patterns, pattern B subjects had significantly higher HL than pattern A subjects in both CAD and normolipidemic groups. The analysis of the cholesterol distribution profiles across the lipoprotein density gradient confirmed that LDL buoyancy is affected by HL. These data support the hypothesis that HL modulates the physical and compositional properties of LDL and contributes to the expression of the LDL subclass phenotype, suggesting a physiological role for HL in LDL metabolism.

Adult↗
PubMed1993

Plasma triglyceride and LDL heterogeneity in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a genetic disorder characterized by increases in plasma cholesterol and/or triglyceride, elevated apolipoprotein B, and heterogeneous low density lipoprotein (LDL). To examine the relation between plasma triglyceride concentrations and LDL heterogeneity, 13 hypertriglyceridemic FCHL patients with a predominance of small LDL (LDL subclass phenotype B) were treated with gemfibrozil. The distribution of LDL was determined using nondenaturing gradient gel electrophoresis and nonequilibrium density gradient ultracentrifugation. Mean plasma triglyceride levels decreased 55% (p < 0.01) after 3 months of treatment. Mean LDL peak particle size remained small (247 +/- 4 versus 249 +/- 5 A), and the correlation between change in plasma triglyceride concentrations and a change in LDL peak particle size was not significant. Individual changes in LDL flotation rate (Rf) were, however, inversely correlated with changes in triglyceride concentration (R = 0.60, p < 0.05). Although mean LDL Rf increased during treatment (p < 0.005) due to an increase in buoyant LDL, dense LDL remained elevated compared with that of a control population. Thus in FCHL patients, small, dense LDL persists despite decreases in plasma triglyceride concentrations.

Adult↗