P.M.J. Stuyt

Increased removal of remnants of triglyceride-rich lipoproteins on a diet rich in polyunsaturated fatty acids.

Abstract. We studied the effect of two diets, one rich in polyunsaturated and the other in saturated fatty acids, on the postprandial processing of exogenous and endogenous triglyceride‐rich lipoproteins (chylomicrons, very‐low‐density lipoproteins, and their remnants).

The relevance of a protein-enriched low density lipoprotein as a risk for coronary heart disease in relation to other known risk factors

The significance of a decreased low density lipoprotein cholesterol/apolipoprotein B ratio (LDL-chol/LDL apo B), or protein-enriched LDL, to predict atherosclerosis was studied in 121 males with angiographically defined coronary artery disease (CAD) and compared to 98 male controls, without history or complaints of vascular disease. Controls were selected for similar age, smoking habits and relative body weight characteristics compared to the CAD group. Covariance analysis with adjustment for hyperlipoproteinemia, apoprotein E phenotype, smoking, age and relative body weight revealed that high density lipoprotein (HDL)-cholesterol was the only parameter that differed significantly between both groups. By logistic regression analysis HDL-cholesterol had the highest predictive power for the development of CAD. The LDL-chol/LDL apo B ratio appeared significantly different between controls and CAD patients (3.1 +/- 0.7 vs. 2.9 +/- 0.6 mmol/g, P less than 0.05), indicating a predominance of subjects with protein-enriched LDL in the CAD group. However, within the group of CAD patients with normal LDL-cholesterol levels no clear distinction could be found between patients with normal and increased LDL apo B levels. Furthermore, it appeared that the LDL-chol/LDL apo B ratio correlated significantly with age (p = -0.24), serum triglycerides (p = -0.24), and HDL-cholesterol (p = 0.24). Thus, the LDL-chol/LDL apo B ratio cannot be considered an independent risk factor for CAD. When adjusted for age, smoking habits and relative body weight the significance of protein-enriched LDL as a risk factor for coronary heart disease diminishes, and HDL-cholesterol appears to be the best indicator for CAD.

A comparative study of the effects of acipimox and clofibrate in type III and type IV hyperlipoproteinemia

Acipimox, an analogue of nicotinic acid, is a hypolipidemic drug with antilipolytic activity. Ten patients with type III and 10 with type IV hyperlipoproteinemia participated in a comparative open cross-over study of the effect of acipimox (750 mg/day) and clofibrate (2 g/day) on lipoproteins, apoliproproteins and postheparin lipase activities during 6 weeks. During acipimox treatment 2 type III patients complained of flushing, resulting in one drop-out. In the type III patients serum cholesterol decreased 30% (P less than 0.01) during treatment with acipimox and 24% (P less than 0.01) with clofibrate, and serum triglycerides 48% (P less than 0.01) and 34% (P less than 0.01), respectively. In the type IV patients serum cholesterol remained unchanged and serum triglycerides decreased 34% (P less than 0.05) and 35% (P less than 0.01), respectively. HDL cholesterol increased during treatment with both drugs in both groups between 6 and 15% (P less than 0.05) mainly due to a rise in HDL3 cholesterol (d greater than 1.100 g/ml). LDL cholesterol increased significantly during treatment with clofibrate, but not with acipimox. There were no or slight changes in the apoproteins A and B. Postheparin lipoprotein lipase increased during clofibrate treatment and hepatic lipase decreased during acipimox treatment. We concluded that acipimox in a dose of 750 mg/day has a similar hypolipidemic effect as 2 g clofibrate daily in type III and IV hyperlipoproteinemia.

Apolipoprotein E phenotypes, serum lipoproteins and apolipoproteins. in angiographically assessed coronary heart disease

To determine the influence of the apolipoprotein E polymorphism on the occurrence of coronary artery disease (CAD) and on serum lipids, lipoproteins and apolipoproteins we studied 145 patients with angiographically defined CAD and compared them with 153 control subjects without history or complaints of vascular disease and with 35 subjects without significant stenosis on coronary arteriography. Subjects with hypertension, diabetes mellitus and endocrine or metabolic disorders were excluded. Covariance analysis and logistic regression analysis were performed with adjustment for age, sex, smoking habits and relative body weight. There were no significant differences for the apoE phenotypes on risk of cardiovascular disease. The CAD group had significantly higher mean values of serum cholesterol and triglycerides, very-low-density lipoprotein (VLDL)-cholesterol and VLDL-triglycerides, low-density lipoprotein (LDL)-cholesterol and apoprotein B; they had lower high-density lipoprotein (HDL)-cholesterol and apo A-I. The combination of LDL-cholesterol, apoA-I and VLDL-cholesterol was the best model in predicting cardiovascular disease. ApoE phenotype group E3/E2 had significantly lower values for serum cholesterol, LDL-cholesterol, and apoB and higher levels of apoE in comparison with the phenotype groups E3/E3 and E4/E3. The combination of LDL-cholesterol, cholesterol, apoE and VLDL-triglycerides was the best model in predicting the apoE phenotype. Thus, taking other risk factors into account, the apoE phenotype is not an independent risk factor for CAD; the apoE polymorphism influences lipoprotein levels and possibly, in that way, indirectly also the risk for CAD.

Serum lipids, lipoproteins and apolipoprotein E phenotypes in relatives of patients with type III hyperlipoproteinaemia

Abstract. Eighty‐six relatives of nineteen probands with type III hyperlipoproteinaemia were studied to determine the occurrence of hyperlipidaemia and to investigate the relation between apo E phenotypes, the occurrence of hyperlipidaemia, and the composition of the very low density lipoprotein (VLDL) fraction. Thirty‐nine relatives were hyperlipidaemic: four type IIa or IIb, nine type III and twenty‐six type IV. The predisposition for hyperlipidaemia was independent of the apo E phenotype.

Studies on the relationship between the cholesterol content in total high density lipoprotein and its subfractions, HDL2 and HDL3 in normo- and hyperlipidemic subjects.

Total high density lipoprotein (HDL) cholesterol and cholesterol in its main subfractions, HDL2 and HDL3, were determined in 160 normo- and 90 hyperlipidemic subjects by density gradient ultracentrifugation (range of HDL-cholesterol: 0.05-2.85 mmol/l). Both in the normolipidemics and in the combined group HDL3-cholesterol (HDL3-chol) as well as HDL2-cholesterol (HDL2-chol) showed a parabolic relationship with total HDL-chol. The results indicate, that at low total HDL-chol values almost all cholesterol is present in the HDL3 fraction, which shows a linear increase with total HDL-chol from 0 to 0.75 mmol/l. At a further increase of total HDL-chol, cholesterol is increasingly isolated in the HDL2-fraction, especially when HDL3-chol has reached its maximum (about 1.25 mmol/l). Thus, the magnitude of the absolute intra-individual variation of either HDL3-chol or HDL2-chol (in mmol/l) is related to the total HDL-chol concentration. Given the strong correlation between cholesterol in both HDL-subfractions with total HDL-chol and the inverse relationship of total HDL-chol with the risk for coronary heart disease, a rise in HDL3-chol or in HDL2-chol may be equally favorable.

Long-term treatment of type III hyperlipoproteinemia with clofibrate

In this retrospective study we report the results of treatment with clofibrate during at least 7 years in 9 patients with severe type III hyperlipoproteinemia. Initial treatment consisted of a diet, restricted in fat and calories, because of insufficient response additional therapy with 2 g clofibrate daily was given. Serum cholesterol decreased significantly from 14.3 +/- 4.4 mmol/l (mean +/- SD), on diet therapy, to average annual values ranging from 9.0 +/- 4.9 to 7.9 +/- 2.0 and serum triglycerides decreased significantly from 5.6 +/- 1.9 to average annual values from 3.8 +/- 1.8 to 2.0 +/- 0.7, despite a slight gain in bodyweight. Serious side-effects did not occur. After several years of treatment with clofibrate the drug was withdrawn temporarily. Serum lipids increased significantly in all patients to a level, not different from that before the start of drug therapy. It is concluded that clofibrate is a strong hypolipidemic drug for the treatment of type III hyperlipoproteinemia, which does not lose efficacy even after 7 years of use.

β-VLDL accumulation in familial dysbetalipoproteinemia is associated with increased exchange or diffusion of chylomicron lipids to apo B-100 containing triglyceride-rich lipoproteins

To gain more insight into the accumulation of beta-very low density lipoprotein (beta-VLDL) in familial dysbetalipoproteinemia (FD), we followed the courses of the levels of retinyl palmitate (rp), alpha-tocopherol (alpha-T) and apolipoprotein (apo) B-48 in various lipoprotein fractions for up to 48 h in eight patients with FD and six normolipidemic control subjects after an oral fat load (50 g fat/m2 containing 150000 IU of rp and 5000 IU of alpha-T). Alpha-T was added because of its rapid transfer to other lipoproteins. Fasting apo B-48 concentration in FD was normal to strongly elevated, dependent on the fasting lipid concentrations. 3 h after fat loading, total apo B-48 content did not abnormally increase; while the apo B-100 content in the triglyceride-rich lipoprotein fraction remained stable. The levels of both vitamins increased considerably, especially in the remnant fraction (Sf 15-100), which in due course exclusively contained apo B-100 in most hyperlipidemic patients. This, together with the observation that peaks for rp and alpha-T were observed 3-6 h later than for apo B-48 strongly suggests that both vitamins transfer or diffuse rapidly towards the apo B-100 containing VLDL. RP is thus more a marker for this process, which also comprises chylomicron lipids, than a specific marker for chylomicrons. This process, first described here, appears decisive in the pathogenesis of FD.

Relations between policy for medical teaching and basic need satisfaction in teaching

Policy initiatives that aim to elevate the position of medical teaching to that of medical research could influence the satisfaction of three basic psychological needs related to motivation for medical teaching. To explore relations between the satisfaction of three basic psychological needs towards medical teaching and two policy initiatives for medical teaching: (Junior) Principal Lecturer positions [(J)PL positions] and Subsidized Innovation and Research Projects in Medical Education (SIRPMEs). An online questionnaire was used to collect data about medical teaching in the setting of a university hospital. We adapted the Work-related Basic Need Satisfaction scale (Van den Broeck et al. in J Occup Organ Psychol, 83(4):981–1002, 2010), in order to measure feelings of autonomy, competence, and relatedness in teaching. We examined the relations between (J)PL positions and SIRPMEs and the satisfaction of three basic psychological needs. A total of 767 medical teachers participated. The initiatives appear to be related to different beneficial outcomes in terms of feelings of autonomy, competence, and relatedness in medical teaching. Either a (J)PL position is obtained by teachers who feel competent and related towards medical teaching, or obtaining a (J)PL position makes teachers feel more competent and related towards teaching, or these relations could be interacting. Also, either a SIRPME is obtained by teachers who feel competent and autonomous towards medical teaching, or obtaining a SIRPME makes teachers feel more competent and autonomous towards teaching, or these relations could be interacting. Additional research needs to scrutinize the causal or interacting relations further and to determine optimal conditions for these policy initiatives more specifically. Implications for future research are discussed.

Apo E polymorphism and the removal of remnants of triglyceride-rich lipoproteins in normolipidemic subjects during a carbohydrate-rich diet

The role of the apo E polymorphism in the removal of remnants of very low density lipoproteins and chylomicrons was studied after a carbohydrate-rich diet in 10 healthy normolipidemic volunteers with different apo E phenotypes during 7 days. The cholesterol concentration in the heparin-sepharose bound part of the VLDL + IDL fraction (d < 1.019 g/ml) was taken as an estimate of the remnant concentration. Before and after carbohydrate-rich diet retinyl palmitate, mixed with cream, was consumed by each subject the evening before the fasting venepuncture to quantify the removal of chylomicron remnants. After the diet there was a comparable mean rise in the three groups in serum and in very low density lipoprotein triglycerides of about 30% and 50%, respectively. The concentration of remnants of very low density lipoproteins increased slightly in all subjects. The concentration of retinyl palmitate in the d < 1.019 g/ml fraction was 20% lower than before this diet in the E-2 homozygous subjects. In the other two groups, however, 25 to 80% higher retinyl palmitate levels were found. It is concluded, that after a carbohydrate-rich diet there is only a slight increase of very low density lipoprotein remnants, independent of the apo E polymorphism. The removal of chylomicron remnants, however, seems to be facilitated in E-2 homozygous subjects, in contrast to a slower removal in the groups with other apo E phenotypes.