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Biomedical subjects

A A Kroon

Publications and source records attributed to A A Kroon.

At least 19 recordsLinked to original sources

An implantable carotid sinus baroreflex activating system: surgical technique and short-term outcome from a multi-center feasibility trial for the treatment of resistant hypertension.

OBJECTIVES: To assess perioperative outcomes and blood pressure (BP) responses to an implantable carotid sinus baroreflex activating system being investigated for the treatment of resistant hypertension. METHODS: We report on the first seventeen patients enrolled in a multicenter study. Bilateral perivascular carotid sinus electrodes (CSL) and a pulse generator (IPG) are permanently implanted. Optimal placement of the CSL is determined by intraoperative BP responses to test activations. Acute BP responses were tested postoperatively and during the first four months of follow-up. RESULTS: Prior to implant, BP was 189.6+/-27.5/110.7+/-15.3 mmHg despite stable therapy (5.2+/-1.8 antihypertensive drugs). The mean procedure time was 202+/-43 minutes. No perioperative strokes or deaths occurred. System tests performed 1 or up to 3 days postoperatively resulted in significant (all p < or = 0.0001) mean maximum reduction, with standard deviations and 95% confidence limits for systolic BP, diastolic BP and heart rate of 28+/-22 (17, 39) mmHg, 16+/-11 (10, 22) mmHg and 8+/-4 (6, 11) BPM, respectively. Repeated testing during 3 months of therapeutic electrical activation demonstrated a durable response. CONCLUSIONS: These preliminary data suggest an acceptable safety of the procedure with a low rate of adverse events and support further clinical development of baroreflex activation as a new concept to treat resistant hypertension.

Adult↗

Ambulatory blood pressure, asymptomatic cerebrovascular damage and cognitive function in essential hypertension.

Prolonged exposure to elevated blood pressure (BP) can lead to both structural (white matter lesions (WML) or infarctions) and functional changes in the brain. We studied in previously diagnosed essential hypertensive individuals if diurnal BP variation and ambulatory BP (ABP) profile (daytime, night time and 24-h BP averages) were related to evidence of WML, the presence of 'silent' infarcts, and cognitive performance. A group of 86 patients (mean age 57.4+/-10 years, range 40-80) were first screened for hypertension-related organ damage and underwent 24-h ABP monitoring, magnetic resonance imaging (MRI) of the brain, and a comprehensive neurocognitive assessment. Age and ABP profile were related to more periventricular, but not subcortical, WML and to presence of lacunar infarctions on MRI. After correction for demographical group differences, no association was found between night time dipping of BP on the one hand and both WML load and cognitive parameters (verbal memory, sensorimotor speed, cognitive flexibility) on the other. The presence of lacunar infarctions, however, predicted lower performance on verbal memory. Furthermore, daytime and 24-h pulse pressure averages were associated with pWML, whereas systolic BP and mean arterial pressure (MAP) for daytime, night-time and 24-h periods were higher in patients with lacunar infarctions. Notwithstanding the large variability of WML in this sample, the evidence of a connection between diurnal BP variation and early target organ damage in the brain was not convincing. However, the ABP profile may be predictive of cerebral lesion type.

Adult↗

Early increased levels of matrix metalloproteinase-9 in neonates recovering from respiratory distress syndrome.

AIM: Matrix metalloproteinases (MMPs) play an eminent role in airway injury and remodelling. We explored the hypothesis that pulmonary MMP levels would differ early after birth (2-4 days) between infants with resolving respiratory distress syndrome (RDS) and infants developing chronic lung disease of prematurity (CLD). METHODS: Thirty-two prematurely born infants (gestational age < or =30 weeks) diagnosed with RDS were included. In 13 infants RDS resolved while 19 developed CLD. MMP-2 and MMP-9 in bronchoalveolar lavage (BAL) fluids collected on postnatal days 2, 4, 7 and 10 were analyzed by zymography and densitometry. Immunochemistry was performed on BAL cells and lung tissue to identify cellular sources of MMP-9 in RDS and CLD. RESULTS: Median MMP-9 levels increased significantly on day 2 in BAL fluid from patients with resolving RDS (median values MMP-9 = 42.0 arbitrary units (AU)) compared to CLD patients (MMP-9 = 5.4 AU). MMP-9 and neutrophil lipocalin-associated MMP-9 (NGAL) were significantly higher on day 4 in BAL fluid from resolving RDS (MMP-9 = 65.8 AU; NGAL = 16.1 AU) compared to CLD (MMP-9 = 25.4 AU; NGAL = 2.0 AU), Levels of MMP-9 and NGAL increased subsequently on days 7 and 10 in CLD. No differences in MMP-2 levels were detected between RDS and CLD. Neutrophils, macrophages and alveolar type-II epithelial cells were identified as potential sources of MMP-9. CONCLUSION: Our findings indicate differences in early MMP-9 BAL fluid levels between resolving RDS and developing CLD, which may relate to the ability to raise an early and adequate response to the initial injury.

Acute-Phase Proteins↗

C-reactive protein, atherosclerosis and kidney function in hypertensive patients.

Previous studies have shown a relationship between coronary or carotid atherosclerosis and C-reactive protein (CRP) concentrations. In the present investigation, we evaluated the relationship between high-sensitivity CRP (hsCRP) concentrations and the presence of atherosclerotic lesions in the renal arteries and/or abdominal aorta. In 95 hypertensive patients who underwent intra-arterial DSA on suspicion of renovascular disease, blood was sampled during the procedure for measurement of hsCRP. The presence of atherosclerotic lesions was assessed at the level of the renal arteries and the abdominal aorta. Haemodynamically significant renal artery stenosis was diagnosed when 50% or more stenosis was observed. Patients with fibromuscular disease (n = 8) or incomplete data (n = 4) were excluded from analysis. The results revealed that the median hsCRP concentrations were significantly higher among the 57 patients with atherosclerosis of the aorta and/or renal arteries compared to those in the 26 patients without any angiographic lesions (4.6 vs 1.7 mg/l; P < 0.005). Moreover, in patients with renal artery stenosis, levels of hsCRP were higher when the degree of stenosis exceeded 50%. However, the association between hsCRP and the presence of atherosclerosis appeared to be confounded by serum creatinine, creatinine clearance, age and gender. In the whole group a significant inverse relationship was found between creatinine clearance and hsCRP (P < 0.05). In conclusion, hsCRP concentrations are related to atherosclerotic lesions in the renal arteries and the abdominal aorta. While this supports the view that atherosclerotic renal artery stenosis is part of a systemic inflammatory vascular disease, increased concentrations of CRP may also coincide with decreased renal function.

Adult↗

Comparison of randomization techniques for clinical trials with data from the HOMERUS-trial.

BACKGROUND: Several methods of randomization are available to create comparable intervention groups in a study. In the HOMERUS-trial, we compared the minimization procedure with a stratified and a non-stratified method of randomization in order to test which one is most appropriate for use in clinical hypertension trials. A second objective of this article was to describe the baseline characteristics of the HOMERUS-trial. METHODS: The HOMERUS population consisted of 459 mild-to-moderate hypertensive subjects (54% males) with a mean age of 55 years. These patients were prospectively randomized with the minimization method to either the office pressure (OP) group, where antihypertensive treatment was based on office blood pressure (BP) values, or to the self-pressure (SP) group, where treatment was based on self-measured BP values. Minimization was compared with two other randomization methods, which were performed post-hoc: (i) non-stratified randomization with four permuted blocks, and (ii) stratified randomization with four permuted blocks and 16 strata. In addition, several factors that could influence outcome were investigated for their effect on BP by 24-h ambulatory blood pressure monitoring (ABPM). RESULTS: Minimization and stratified randomization did not lead to significant differences in 24-h ABPM values between the two treatment groups. Non-stratified randomization resulted in a significant difference in 24-h diastolic ABPM between the groups. Factors that caused significant differences in 24-h ABPM values were: region, centre of patient recruitment, age, gender, microalbuminuria, left ventricular hypertrophy and obesity. CONCLUSION: Minimization and stratified randomization are appropriate methods for use in clinical trials. Many outcome factors should be taken into account for their potential influence on BP levels. Recommendation. Due to the large number of potential outcome factors that can influence BP levels, minimization should be the preferred method for use in clinical hypertension trials, as it has the potential to randomize more outcome factors than stratified randomization.

Adult↗

Regional differences in cardiovascular risk factor profile cannot fully explain differences in cardiovascular morbidity in the Netherlands: a comparison of two urban areas.

BACKGROUND: Our objective was to investigate whether a region in the south of the Netherlands (Heerlen/Kerkrade) had a high burden of cardiovascular disease in comparison with a nearby region (Maastricht) and the average Dutch population, respectively. We also wanted to determine if there are interregional differences in cardiovascular risk factor profile. DESIGN: Cross-sectional study. METHODS: Data from a nationwide registry (CBS) were used to analyse cardiovascular mortality in the two regions and the average in the Netherlands. Data from a primary care morbidity registration network (RNH) were used to compare cardiovascular morbidity and cardiovascular risk factors in both regions. A standardisation procedure was carried out for age and sex. Data were analysed using logistic regression analyses. RESULTS: The overall cardiovascular mortality rate was higher in the Heerlen/Kerkrade region (7.8 per thousand) compared with Maastricht (6.1 per thousand, OR=1.3, 95% CI 1.2-1.5) and the average in the Netherlands (5.7 per thousand). Similarly, most cardiovascular morbidity rates for Heerlen/Kerkrade were more elevated compared with the RNH overall and with Maastricht. Prevalence rates of risk factors such as diabetes mellitus (7.2%, OR=1.5, 95% CI 1.3-1.7) and overweight (10.8%, OR= 2.0, 95% CI 1.8-2.2) were significantly higher in the Heerlen/Kerkrade region compared with Maastricht. There were no differences with regard to hypertension (15.2%, OR=1.0, 95% CI 0.9-1.1). CONCLUSION: Heerlen/Kerkrade is indeed a region with a high burden of cardiovascular disease. Differences in morbidity between Heerlen/Kerkrade and Maastricht cannot be fully explained by differences in cardiovascular risk factor profile.

Adult↗

Home versus Office blood pressure MEasurements: Reduction of Unnecessary treatment Study: rationale and study design of the HOMERUS trial.

The Home versus Office MEasurements, Reduction of Unnecessary treatment Study (HOMERUS) is a multicentre prospective study, primarily designed to examine in subjects with mild to moderate hypertension whether treatment decisions based on home blood pressure measurements can lead to reduction in the use of antihypertensive drugs and the associated costs, compared to office blood pressure measurements. After inclusion, 360 patients are randomized to two groups. In one group, antihypertensive therapy is based on blood pressure measured in the outpatient clinic: the office pressure (OP) group. In the other group, antihypertensive therapy is based on home blood pressure measurements: the self-pressure (SP) group. All readings, both in OP and in SP, are obtained with the same validated oscillometric device, the Omron 705 CP. Treatment decisions are taken by an independent physician at the coordinating centre, who is unaware whether the patient belongs to the SP or OP group. Following a standardized treatment schedule, blood pressure is targeted at 120-139 mmHg for systolic and 80-89 mmHg for diastolic pressure. Patients are followed for 1 year. At the start and at the end of the study, ambulatory blood pressure measurements are obtained as a reference. Microalbuminuria and echocardiography are assessed to evaluate the possible development of target organ damage. It is expected that, at the end of the trial, patients in both groups will have the same blood pressure, at the expense of more medication in the OP group. Therefore, a cost-minimization analysis will be performed first. If short-term effects appear not to be comparable for OP and SP, a cost-effectiveness analysis will be performed to assess the value of the SP strategy in comparison to standard practice. In addition, medication compliance is recorded within random subgroups of the SP and OP groups by means of Medication Event Monitoring System (MEMS) V TrackCaps.

Algorithms↗

Who should be taking the blood pressure?

Given the variability of blood pressure, it is often difficult to make a diagnosis of hypertension or to evaluate the effect of treatment on the basis of single blood pressure readings in the office. To obtain multiple measurements one can either turn to ambulatory blood pressure monitoring or have the patient take his or her own pressure. Both approaches require the availability of reliable, validated devices. Currently, only some instruments which measure blood pressure oscillometrically at the upper arm can be recommended for self-measurements. Studies are in progress to assess the prognostic significance of self-measured blood pressure data.

Automation↗

Renovascular disease in patients with hypertension: detection with duplex ultrasound.

The aim of this study was to evaluate the accuracy of duplex ultrasound for the diagnosis of renovascular disease in a cohort of hypertensive patients. In 78 patients suspected of renovascular hypertension on clinical grounds duplex ultrasound examination of the renal arteries was performed. Renal angiography was used as the standard of reference. Duplex ultrasound was inconclusive in 11 kidneys (7%). None of the supernumerary renal arteries was detected with duplex ultrasound. The overall prevalence of significant renovascular disease (> or =50% stenosis) was 20%. Based on the combination of parameters at thresholds commonly applied in current literature: ie PSV(max) >180 cm/sec and RAR >3.5 the overall sensitivity of duplex ultrasound for detection of haemodynamically significant renovascular disease was 50.0% with a specificity of 91.3% (PPV: 87.9%; NPV: 59.1). Lowering the thresholds for both parameters improved the test results at the cost of a significant increase of false positive examinations. In a population of hypertensive patients clinically suspected of renovascular hypertension, only limited results for duplex ultrasound could be acquired in the detection of renovascular disease. This result, in combination with the wide range of sensitivities and specificities published in international literature and the relatively large number of incomplete examinations does not support the general application of duplex ultrasound as a screening procedure for detection and assessment of renovascular disease.

Adult↗

Diagnostic tests for renal artery stenosis in patients suspected of having renovascular hypertension: a meta-analysis.

PURPOSE: To summarize and compare the validity of computed tomography angiography, magnetic resonance angiography, ultrasonography, captopril renal scintigraphy, and the captopril test for diagnosis of renal artery stenosis in patients suspected of having renovascular hypertension. DATA SOURCES: For each diagnostic modality, published studies were identified by MEDLINE literature searches. STUDY SELECTION: Original studies were selected if they met the following criteria: 1) suspicion of renovascular hypertension was the indication for the test; 2) intra-arterial x-ray angiography was used as the gold standard; 3) a cutoff point for a positive test result was explicitly defined; and 4) absolute numbers of true-positive, false-negative, true-negative, and false-positive results were available or could be derived from the presented data. DATA EXTRACTION: A standard form was used to extract relevant data. DATA SYNTHESIS: Data on the accuracy of the different diagnostic methods were analyzed and compared by constructing summary receiver-operating characteristic (ROC) curves and by computing areas under the summary ROC curves. RESULTS: Although accuracy varied greatly for all diagnostic modalities, summary ROC curves found that computed tomography angiography and gadolinium-enhanced, three-dimensional magnetic resonance angiography performed significantly better than the other diagnostic tests. CONCLUSIONS: Computed tomography angiography and gadolinium-enhanced three-dimensional magnetic resonance angiography seem to be preferred in patients referred for evaluation of renovascular hypertension. However, because few studies of these tests have been published, further research is recommended.

Angiotensin-Converting Enzyme Inhibitors↗

Association between the alpha-adducin Gly460Trp polymorphism and systolic blood pressure in familial combined hyperlipidemia.

BACKGROUND: In a genome scan for familial combined hyperlipidemia (FCHL), a locus contributing to systolic blood pressure (SBP) has been identified on chromosome 4, containing the a-adducin gene (ADD1). In previous studies, an association has been found between the alpha-adducin Gly460Trp polymorphism and salt-sensitive hypertension. In this study, we investigated the association between the a-adducin Gly460Trp polymorphism and blood pressure in FCHL patients. METHODS: A total of 79 unrelated patients with FCHL and 121 unrelated controls (spouses) were recruited for the study. Blood pressure was measured in a standardized fashion, with the subject in sitting position after 10 min of rest. The alpha-adducin Gly460Trp polymorphism was detected by mutagenically separated polymerase chain reaction. RESULTS: The genotype frequencies of both FCHL patients and controls were in Hardy-Weinberg equilibrium. The alpha-adducin Gly460Trp polymorphism showed a significant association with FCHL, the number of subjects carrying a 460Trp allele was significantly higher in patients compared with controls (53% v 33%, chi2 = 8.0, P = .018). In FCHL patients carrying at least one 460Trp allele, SBP was significantly higher compared with patients homozygous for the 460Gly allele (140 mm Hg and 130 mm Hg respectively, P = .015). CONCLUSIONS: This study shows that the 460Trp allele is associated with FCHL. Furthermore, SBP is increased in patients carrying the 460Trp allele.

Adult↗

Renal clearance of endogenous leptin in hypertensive humans with or without renal artery stenosis.

In humans, the kidney is involved in leptin clearance from the body. The present study was performed to assess the renal extraction of leptin in hypertensive patients with or without renal artery stenosis. Sixty-five hypertensive subjects (39 males and 26 females) underwent catheterization of the renal artery and both renal veins with blood sampling for measuring leptin levels. Blood flow to both kidneys was measured by the xenon washout technique. From these data, renal leptin uptake and renal fractional extraction of leptin were calculated. Endogenous creatinine clearance ranged from 24 to 191 ml/min in the males and from 20 to 149 ml/min in the females. In 25 patients, radiological signs of renal artery stenosis were present. Total renal leptin uptake by both kidneys averaged 141 +/- 47 ng x min(-1) x 100 g(-1). No differences in leptin uptake were found between males and females or between patients with or without renal artery stenosis. The average renal extraction fraction of leptin was 6 +/- 2%. Renal leptin uptake and renal extraction fraction of leptin did not correlate with arterial leptin concentrations or with blood pressure, endogenous creatinine clearance, or the presence or absence of renal artery stenosis. In hypertensive patients with or without renal artery stenosis, the kidney removes only a small fraction of circulating leptin from the body within one passage. This fraction remains relatively constant despite wide variations in renal function or circulating leptin.

Adolescent↗

The rebound of lipoproteins after LDL-apheresis. Kinetics and estimation of mean lipoprotein levels.

We studied the rebound of lipoproteins in 20 hypercholesterolemic men [mean total cholesterol (TC) levels 9.6+/-1.8 mmol/l] after LDL-apheresis (LA) to determine the rate of recovery and the change in cholesterol synthesis, and to find a uniform estimation for time-averaged levels. After 10-20 months on biweekly LA using dextran sulfate cellulose columns and concomitant simvastatin administration, time-averaged levels (+/-SD) measured by integration of the area under the curve were as follows: TC 4.4+/-1.0 mmol/l, LDL cholesterol (LDL-C) 2.5+/-1.0 mmol/l, apolipoprotein B (apo B) 1. 3+/-0.3 g/l, triglycerides (TG) 1.7+/-0.7 mmol/l, HDL-C 1.1+/-0.2 mmol/l, and lipoprotein(a) [Lp(a)] 53.7+/-49.4 mg/dl. Mean acute reductions in TC, LDL-C, apo B, Lp(a), and TG were 61, 77, 75, 76, and 62%, respectively. HDL-C levels were not influenced. Median recovery half times for TC, LDL-C, apo B, and Lp(a) were 3.0, 4.0, 2. 3, and 3.5 days, respectively. The rebound of Lp(a) was identical to LDL-C, in 12 and 13 days post-treatment, respectively, whereas apo B and TC returned to pre-treatment levels in 7.5 and 10 days, respectively, due to the fast rebound of VLDL particles. Notwithstanding these differences, time-averaged levels (C(AVG)) could be estimated uniformly for the four latter parameters with the formula: C(AVG)=C(MIN)+0.73(C(MAX)-C(MIN)), where C(MAX) and C(MIN) are the immediate pre- and post-treatment levels. During long-term treatment the whole-body cholesterol synthesis was increased as measured by the ratio lathosterol to cholesterol of 3.24+/-1.49 mmol/mmol, whereas no further transient increase in the recovery period after LA was found. In conclusion, long-term LA and simvastatin therapy induced acute and chronic changes in lipids and lipoproteins showing the feasibility of biweekly treatment. It was shown that time-averaged levels, as a measure for the effective plasma levels, can be accurately estimated from pre- and post-treatment levels only.

Adult↗

Quinaprilat-induced vasodilatation in forearm vasculature of patients with essential hypertension: comparison with enalaprilat.

The aim of the present study was to assess the possible differences in hemodynamic and neurohumoral responses to local ACE inhibition in the human forearm of patients with essential hypertension with either quinaprilat or enalaprilat. Forearm vascular responses to infusion of quinaprilat or enalaprilat (0.5 microg/dL/min) into the brachial artery were studied in 12 male patients with essential hypertension. The experiments were performed in a randomized, double-blind, crossover fashion. Before and during ACE inhibition, the vasoconstrictor response to four cumulative doses of angiotensin I (Ang I) was studied. Forearm blood flow was assessed using venous occlusion plethysmography. Local quinaprilat infusion induced a more rapid (even after 15 minutes; median vasodilation quinaprilat 29% vs. enalaprilat --1%, P < 0.02) and longer lasting forearm vasodilation as compared with enalaprilat. After 15 minutes of local ACE inhibition, the vasoconstrictor response to Ang I was completely blocked by both ACE inhibitors. We conclude that in patients with essential hypertension quinaprilat induces a more rapid and longer lasting vasodilatation than enalaprilat. These effects of quinaprilat are possibly related to its higher affinity for vascular ACE. On the other hand, the fact that these effects of quinaprilat were observed despite a similar degree of ACE inhibition as during enalaprilat may suggest that quinaprilat directly stimulates another vasodilatating mechanism.

Aged↗

Renal haemodynamics and sodium excretory capacity during urapidil treatment in patients with essential hypertension.

OBJECTIVE: Since renal sympathetic nerves are involved in the regulation of sodium excretion, we investigated whether treatment with urapidil, an alpha1-adrenoceptor blocking agent which also lowers sympathetic activity, alters sodium excretory capacity in patients with essential hypertension. DESIGN: A double-blind, randomized, parallel-group study. METHODS: Studies were carried out in 26 patients who were randomized to treatment with either placebo or urapidil for 8 weeks. Before and after treatment blood pressure, renal haemodynamics and various neurohormones were measured, as well as the response of these variables to a hypertonic saline infusion. RESULTS: Urapidil had no effect on renal haemodynamics or neurohormones at rest However, as compared to placebo the saline-induced rises in renal plasma flow and glomerular filtration rate lasted longer during treatment with urapidil. Responses of renin, angiotensin II and catecholamines were not modified by urapidil. On the other hand, aldosterone was less suppressed while atrial natriuretic peptide was less stimulated following the saline load when patients had been treated with urapidil. Cumulative sodium excretion during a 3 h period from the moment of saline infusion was similar whether patients had been treated with placebo or with urapidil. CONCLUSIONS: Our data show that urapidil interferes with renal haemodynamics after sodium loading but that any tendency to promote sodium output may be offset by changes in aldosterone and atrial natriuretic peptide. We conclude that urapidil, under the circumstances tested, does not affect the sodium excretory capacity of the kidney.

Adrenergic alpha-Antagonists↗

Angiotensin II sensitivity is associated with the angiotensin II type 1 receptor A(1166)C polymorphism in essential hypertensives on a high sodium diet.

Several investigations have shown heterogeneity in the functional responses to angiotensin II (Ang II) in patients with essential hypertension. The present study was initiated to evaluate whether the A(1166)C polymorphism of the Ang II type 1 receptor (AT(1)R) gene contributes to this variability in Ang II responses. After 7 days of a high-sodium diet (220 mmol Na(+) per day), we measured in 42 essential hypertensive patients blood pressure, heart rate, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), active plasma renin concentration, aldosterone, and atrial natriuretic peptide (ANP) before and during Ang II infusion (increasing doses of 0.3, 1.0, and 3.0 ng/kg per minute). Calculated variables were filtration fraction and renal vascular resistance (RVR). Patients in the 3 genotype groups (AA: n=14; AC: n=17; CC: n=11) were matched for gender, age, and body mass index. At baseline, CC patients had decreased GFR (P:=0.06) and aldosterone (P:<0.05) and increased ANP (P:<0.05) compared with AA patients. Moreover, responses of ERPF, GFR, and RVR to the lowest concentration of Ang II (0.3 ng/kg per minute) were more pronounced in CC patients than in AA patients (ERPF/GFR: P:<0.05; RVR: P:=0.07), whereas maximal responses were all comparable between the groups. Heart rate was decreased at all levels of Ang II infusion in CC patients, while it did not change in AA or AC patients. There were no differences in responses of active plasma renin concentration, aldosterone, and ANP to Ang II between the 3 groups. From these data, we conclude that the C allele of the AT(1)R A(1166)C polymorphism is associated with increased sensitivity but not reactivity to Ang II. An augmented response to Ang II may well be responsible for the increased incidence of cardiovascular abnormalities found in patients with 1 or 2 C alleles.

Adult↗

The rebound of lipoproteins after LDL-apheresis. Effects on chemical composition and LDL-oxidizability.

The changes in low density lipoprotein (LDL) composition and oxidizability after LDL-apheresis (LA) using dextran sulfate cellulose columns were evaluated in 12 hypercholesterolemic men (mean+/-S.D. total cholesterol (TC) 9.7+/-1.8 mmol/l). After 10-20 months on biweekly LA combined with simvastatin 40 mg per day immediate pre-apheresis levels of TC, LDL-cholesterol, and apolipoprotein B were decreased to 5.3+/-1.3 mmol/l, 3.3+/-1.2 mmol/l, and 1.6+/-0.4 g/l, respectively, whereas apheresis induced mean acute reductions of 61, 78, and 76%, respectively. Measurements of copper-induced LDL-oxidizability in vitro showed an increased resistance against oxidation after LA until day 3 post-treatment: lag time (min) (day 0 (before LA) versus day 1 (post-LA)) 112+/-27 versus 130+/-26 (P=0.001), maximal rate of diene production (nmol/min per mg LDL) 11.1+/-2.7 versus 9.1+/-2.1 (P=0.001), and time to maximal diene production (min) 186+/-39 versus 209+/-35 (P=0. 001). Analysis of the chemical composition of LDL revealed a 25% (P<0.001) reduced content of cholesteryl esters and a decrease of the cholesterol to protein ratio of 1.20+/-0.25 to 0.70+/-0.22 (P<0. 001) through the 3rd day post-LA. Linoleic acid and arachidonic acid content of LDL decreased 11 and 18%, respectively, at the expense of palmitic acid. Vitamin E levels (mg/l) were significantly lowered due to reduction of the lipoprotein pool by apheresis; however, vitamin E content of LDL did not change in the days after apheresis when expressed per g protein or per micromol linoleic acid. The changes in fatty acid pattern were strongly associated with changes in LDL-oxidizability indices (P</=0.01). Thus, LA effectively decreased LDL pool size, inducing the presence of less buoyant lipoproteins, which were less susceptible to in vitro oxidation. This was not explained by changes in vitamin E levels, but by short-term changes in the fatty acids composition.

Apolipoproteins B↗