Nicoline Hoogerbrugge

The effect of growth hormone administration in growth hormone deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition

OBJECTIVE The effect on bone, protein, carbohydrate and lipid homeostasis as well as body composition of the administration of growth hormone to adult patients with growth hormone deficiency was studied.

Atorvastatin increases low-density lipoprotein size and enhances high-density lipoprotein cholesterol concentration in male, but not in female patients with familial hypercholesterolemia

The effects of atorvastatin (Lipitor) were evaluated in 40 patients with familial hypercholesterolemia (FH). Following a 6 week drug-free baseline period 20 male and 20 female patients were treated with atorvastatin 40 mg once daily (QD) for the initial 6 weeks increasing to 80 mg QD during the following 6 weeks. Atorvastatin 40 and 80 mg resulted in a dose related reduction in LDL cholesterol of 44 and 50% (P<0.001), respectively. The reduction of triglycerides (TG) was 35% (P<0.001) with 40 and 80 mg atorvastatin. The lipoprotein lipase and the hepatic lipase activity decreased dose independently by 13% (P<0.05) and 18% (P<0.01), respectively. In males, a dose independent increase in high-density lipoprotein (HDL) cholesterol concentration was observed of 8%, (P<0.05). In females, the HDL cholesterol concentration did not change. Baseline LDL size in the females was significantly larger than in the males, being 268+/-6 A and 264+/-8 A (P<0.05), respectively. In males LDL size increased significantly from 264+/-8 A at baseline to269+/-6 A at 40 mg (P<0.05) and to 270+/-5 A (P<0.05) at 80 mg atorvastatin. In females LDL size did not change upon treatment with atorvastatin 40 and 80 mg QD. In conclusion, atorvastatin has the ability to decrease cholesterol and triglyceride concentrations as well as the activity of both lipoprotein and hepatic lipase activity. Additionally it has a favorable effect on LDL size and HDL cholesterol concentration in male, but not in female FH patients.

Estrogen replacement decreases the level of antibodies against oxidized low-density lipoprotein in postmenopausal women with coronary heart disease☆

The effect of estrogen replacement therapy (ERT) on plasma lipid concentrations and oxidation parameters was studied in 25 hypercholesterolemic women with coronary heart disease (CHD). During ERT, the low-density lipoprotein cholesterol (LDLc) concentration decreased from 4.31 +/- 0.72 to 3.85 +/- 0.62 mmol/L (P < .01) and high-density lipoprotein cholesterol (HDLc) increased from 1.42 +/- 0.30 to 1.55 +/- 0.33 mmol/L (P < .01). The concentration of autoantibodies against oxidized LDL decreased from 25.9 +/- 22.0 to 22.7 +/- 19.9 mg/L (P < .05), indicating that ERT may have antioxidative effects in vivo. The lag time to oxidation and the LDL subclass pattern did not change. Analysis of the influence of smoking on the efficacy of ERT showed that ERT significantly affected LDLc and HDLc concentrations in 15 nonsmoking women. However, in 10 cigarette smokers, no significant changes in LDLc or HDLc levels were observed. Smoking did not affect the concentration of autoantibodies to oxidized LDL or the lag time. Medroxyprogesterone acetate ([MPA] 10 mg daily) added to ERT decreased HDLc by 9% (P < .01) but did not affect the LDLc level, LDL subclass pattern, or lag time. In conclusion, ERT may have antioxidative effects in vivo and favorably affects dyslipidemia in hypercholesterolemic women with CHD, especially when they refrain from smoking.

Patients with combined hypercholesterolemia-hypertriglyceridemia show an increased monocyte-endothelial cell adhesion in vitro: triglyceride level as a major determinant.

Hypercholesterolemia (HC) is one of the primary risk factors for atherosclerosis. Patients with familial hypercholesterolemia (FH) or combined hypercholesterolemia-hypertriglycerinemia (CHH) are at risk to develop premature atherosclerosis. Animal models have revealed that diet-induced HC in vivo leads to an increased adhesion of monocytes to the endothelium of the vessel wall. Changes in the monocytes, endothelial cells, or serum components may lead to the increased monocyte adhesion that results in atherosclerotic plaque formation. In the present study, we investigated the binding of the monocyte in an in vitro system. Incubation of freshly isolated monocytes from CHH patients with cultured human umbilical vein endothelial cells (HUVEC) gave a significant 60% increase in monocyte adhesion when compared with monocytes from healthy subjects. No such increase was observed using monocytes from nontreated FH patients. These data suggest that CHH results in in vivo alterations of the monocytes that lead to an increased in vitro adhesion to HUVEC, and that an increased level of plasma triglycerides is the major determinant, since HC alone does not induce this alteration.

Hypertriglyceridemia Enhances Monocyte Binding to Endothelial Cells in NIDDM

OBJECTIVE The mechanisms by which diabetes leads to rapidly progressive atherosclerosis are not fully understood. Adherence of monocytes to the arterial wall is an early event in the development of atherosclerotic lesions. RESEARCH DESIGN AND METHODS The binding of freshly isolated monocytes from patients with NIDDM, IDDM, and healthy control subjects to a monolayer of endothelial cells obtained from human umbilical vein was investigated. RESULTS Endothelial adherence of monocytes from normolipidemic patients with IDDM (15.8 ± 4.5%) or NIDDM (16.9 ± 4.6%) was comparable to that of monocytes from a control population (15.3 ± 3.5%). In patients with NIDDM with a serum triglyceride concentration > 2.5 mmol/l, the percentage of cells that adhere to endothelial cells in vitro was significantly increased (23.3 ± 3.1%). Glycemic control did not correlate with monocyte adherence. The presence of symptomatic atherosclerotic disease, age, or sex was not associated with a change in monocyte binding in vitro. CONCLUSIONS The results suggest that in NIDDM hypertriglyceridemia should be treated to reduce the high risk for atherosclerosis.

The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia.

Hoogerbrugge N, Jansen H, de Heide L, Zillikens MC, Deckers JW, Birkenhäger JC (University Hospital Dijkzigt, Rotterdam, The Netherlands). The additional effects of acipimox to simvastatin in the treatment of combined hyperlipidaemia. J Intern Med 1997; 241: 151–56.

Monocytes from patients with combined hypercholesterolemia-hypertriglyceridemia and isolated hypercholesterolemia show an increased adhesion to endothelial cells in vitro: II. Influence of intrinsic and extrinsic factors on monocyte binding

One of the primary risk factors for atherosclerosis is hypercholesterolemia. Patients with isolated hypercholesterolemia or combined hypercholesterolemia-hypertriglyceridemia are at risk to develop premature atherosclerosis. Diet-induced hypercholesterolemia in animals leads to an increased adhesion of monocytes to and transmigration through the intact endothelium of the vessel wall. In the present study, we investigated in vitro binding of freshly isolated monocytes from patients and healthy controls to a monolayer of endothelial cells obtained from human umbilical vein. All four diagnosed patient groups with isolated or combined hypercholesterolemia showed a significant increase in monocyte binding as compared with the control group (familial hypercholesterolemia [FH], +41%; polygenic hypercholesterolemia [PH] +35%; familial combined hypercholesterolemia [FCH], +47%; nonfamilial combined hypercholesterolemia-hypertriglyceridemia [CHH], +67%). In a longitudinal study it was observed that diet or medication induced a decrease in cholesterol and triglycerides; however, these therapeutic conditions did not diminish in vitro monocyte binding in the patient groups. There was no correlation between monocyte binding and plasma cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, or lipoprotein(a) within hyperlipidemic patient groups. The presence of heart and vessel disease in hyperlipidemic patients was not associated with a change in monocyte binding. The adhesion to endothelial cells of monocytes from smoking patients with combined hypercholesterolemia (27%) was significantly higher (+23%) than that of monocytes from nonsmoking patients. Cytofluorimetric analysis of monocytes from FCH and CHH patients for specific monocyte differentiation markers and integrins did not show differences as compared with monocytes from healthy controls.

Effects of atorvastatin on serum lipids of patients with familial hypercholesterolaemia

Hoogerbrugge N (University Hospital Dijkzigt, Rotterdam, the Netherlands). Effects of atorvastatin on serum lipids of patients with familial hypercholesterolaemia. J Intern Med 1998; 244: 143–7.

Growth Hormone Normalizes Low-Density Lipoprotein Receptor Gene Expression in Hypothyroid Rats

Hypothyroidism leads to a decreased activity of the low-density lipoprotein (LDL) receptor, which contributes to the hypercholesterolemia frequently seen during hypothyroidism. It is not known whether the decreased activity of the LDL receptor is directly due to the absence of thyroid hormone, or secondary to a deficiency of growth hormone (GH). Therefore, the effect of GH administration on LDL receptor activity was studied in hypothyroid rats. Following induction of hypothyroidism, the level of LDL receptor mRNA was significantly decreased in liver homogenates to 31 % +/- 6% of the control value. LDL binding to liver cell membranes and plasma membranes decreased during hypothyroidism to approximately 65% of the control value. The effect of hypothyroidism on the hepatic LDL receptor was reflected in a significantly increased half-life of (125)I-LDL of 29 hours in controls versus 48 hours in hypothyroid rats. Treatment of hypothyroid rats with human GH (hGH) resulted in normalization of both the amount of hepatic LDL receptor mRNA and LDL binding on liver cell membranes. The plasma half-life of human (125)I-labeled LDL decreased during GH substitution but did not normalize. GH treatment significantly reduced plasma LDL cholesterol levels by 36% (P < .05, n = 8), to levels that were still higher than in control animals. These data indicate that at least part of the decreased LDL receptor activity during hypothyroidism is secondary to GH deficiency.

High fat intake in hyperlipidaemic patients is related to male gender, smoking, alcohol intake and obesity

BACKGROUNDnIn individuals at high cardiovascular risk, such as patients with hyperlipidaemia, low dietary fat intake is used to reduce this risk. The aim of the present study was to identify determinants of (saturated) fat intake in hyperlipidaemic patients.nnnMETHODSnCross sectional study in a lipid clinic of a tertiary referral centre. A total of 1169 patients (714 males and 455 females) with hyperlipidemia were studied. Food frequency questionnaires were present of 1026 patients. In 615 patients a detailed diet analysis was performed. The main outcomes measures were determinants of fat intake, indicated by a regression coefficient (beta-coefficient).nnnRESULTSnThe following variables were independently related to fat intake: present smoking (beta-coefficient 3.7), male gender ((beta 1.6), familial hypercholesterolemia (beta -1.6), alcohol (beta 0.6 per glass of alcohol), body mass index (beta 0.6). No interaction between gender and smoking or between gender and alcohol intake was observed in relation to fat intake. The percentage of energy from fats were higher in males than in females, 34.2+/-8.3% and 31.7+/-8.3%, respectively (P<0.001). The higher total and saturated fat intake in males is due to a larger consumption of cheese, meat products, bread and potato products. Women had a higher relative intake of carbohydrate 48.5+/-8.7% versus 46.5+/-8.8% in males (P<0.05), due to a relatively higher intake of fruit, milk products and pastry and biscuits.nnnCONCLUSIONSnA specific gender-oriented approach may improve the results of dietary counselling of hyperlipidaemic patients.