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Luc Van Bortel

Publications and source records attributed to Luc Van Bortel.

11 recordsLinked to original sources
PubMed2006

Expert consensus document on arterial stiffness: methodological issues and clinical applications.

In recent years, great emphasis has been placed on the role of arterial stiffness in the development of cardiovascular diseases. Indeed, the assessment of arterial stiffness is increasingly used in the clinical assessment of patients. Although several papers have previously addressed the methodological issues concerning the various indices of arterial stiffness currently available, and their clinical applications, clinicians and researchers still report difficulties in selecting the most appropriate methodology for their specific use. This paper summarizes the proceedings of several meetings of the European Network for Non-invasive Investigation of Large Arteries and is aimed at providing an updated and practical overview of the most relevant methodological aspects and clinical applications in this area.

Adult↗
PubMed2006

Ethnic differences in arterial stiffness and wave reflections after cigarette smoking.

BACKGROUND: Smoking increases plasma nicotine. Nicotine releases catecholamines and alters arterial distensibility. The nicotine intake per cigarette is greater and serum cotinine levels, the proximate metabolite of nicotine, are higher in Blacks than in Whites. We tested the hypothesis that cigarette smoking increases the pulse wave velocity (PWV), a marker of arterial stiffness, and the augmentation index (AI), a measure of wave reflection, more in Blacks than in Whites. METHODS: We matched Black (n = 30) and White (n = 30) smokers for age, gender, body mass index and height. We determined carotid-femoral PWV (PWVCF) and carotid-radial PWV (PWVCR) (Complior), the AI derived from the aortic pressure waveform (applanation tonometry, Sphygmocor), blood pressure, heart rate (HR) and cotinine levels before and after cigarette smoking. We also performed measurements in 16 participants after sham smoking. RESULTS: Smoking increased the AI, PWVCF and PWVCR in the whole population (all P < 0.05, n = 60). Increases in the AI and PWV were positively related to serum cotinine levels (all P < 0.05). Smoking increased serum cotinine (P = 0.01) and mean blood pressure (P = 0.03) more, but raised the HR to a lesser extent, in Blacks [+8 +/- 4 versus +13 +/- 6 beats/min in Whites (mean +/- SD), P = 0.01]. Blacks disclosed larger increases in AI adjusted for HR (Blacks, +7.2 +/- 8 versus Whites, +4.4 +/- 8%; P = 0.03), PWVCF (Blacks, +1.1 +/- 0.2 versus Whites, +0.6 +/- 0.3 m/s; P < 0.01) and PWVCR (Blacks, +1.4 +/- 0.1 versus Whites, +0.7 +/- 0.4 m/s; P < 0.01) normalized for the mean blood pressure. No changes were observed with sham smoking. CONCLUSIONS: Smoking acutely increases the PWV and AI in Blacks more than in Whites. Differences in nicotine metabolism and beta-adrenergic sensitivity could explain these findings.

Adult↗
PubMed2005

Carotid tonometry versus synthesized aorta pressure waves for the estimation of central systolic blood pressure and augmentation index.

OBJECTIVE: To assess the interchangeability of carotid tonometry and synthesized aorta pressure waveforms for estimating central systolic blood pressure (SBP) and augmentation index (AIx). METHODS: Tonometry waveforms were acquired with a custom built hardware and software platform in 276 subjects (179 men/97 women; aged 45.5 +/- 5.7 years; mean +/- standard deviation) at the radial (P(wf,ra)), brachial (P(wf,ba)), and carotid artery (P(wf,ca)). The P(wf,ba) was calibrated using systolic (SBP(ba)) and diastolic (DBP(ba)) sphygmomanometer pressure. The DBP(ba) and calculated mean (MAP(ba)) brachial pressure were subsequently used for calibration of P(wf,ra) and P(wf,ca). A central pressure waveform (P(wf,sao)) was synthesized from P(wf,ra) using a generalized pressure transfer function (TFF). The AIx and SBP were measured on P(wf,ra), P(wf,ca), and P(wf,sao). RESULTS: The SBP(ra), SBP(ca), and SBP(sao) were 138.5 +/- 16.8, 130.0 +/- 16.2, and 131.1 +/- 16.6 mm Hg, respectively. The SBP(ra) correlated well with the SBP(ca) (r = 0.93) and the SBP(sao) (r = 0.94), as did the SBP(ca) and the SBP(sao) (r = 0.97) with a mean bias of 1.35 +/- 3.90 mm Hg. The AIx derived from P(wf,ra), P(wf,ca), and P(wf,sao) were -20.8% +/- 14.5%, 12.4% +/- 13.9%, and 20.0% +/- 11.7%, respectively. The correlation between radial and carotid, and radial and central AIx was 0.72 and 0.94, respectively. The correlation between AIx derived from P(wf,ca) and P(wf,sao) was 0.75 with a bias of 11.0% +/- 14% (all correlations P < .001). CONCLUSIONS: The use of a generalized TFF in combination with well-calibrated radial pressure curves yields estimates of SBP in good agreement with carotid tonometry. Although AIx derived from a measured radial pressure curve correlates surprisingly closely with AIx measured on a synthesized aortic pressure curve, the correlation with a directly measured AIx on carotid signals is relatively poor.

Adult↗
PubMed2005

AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 1): pharmacokinetics.

BACKGROUND: AQUAVAN Injection (AQ) (GPI 15715; Guilford Pharmaceutical Inc., Baltimore, MD) is a water-soluble prodrug of propofol (PropofolGPI). This study aimed to explore the pharmacokinetics of AQ, PropofolGPI, and formate (a metabolite of AQ) and to compare them with the pharmacokinetics of propofol lipid emulsion (PropofolD). METHODS: After ethics committee approval, 36 healthy volunteers were randomly allocated into six cohorts (male/female: 3/3) and given a single bolus of AQ (5, 10, 15, 20, 25, or 30 mg/kg). For comparison, an equipotent dose (as measured by the Bispectral Index) of PropofolD was given to the same subjects 1 week later. For both drugs, blood samples were collected (1-480 min) to analyze AQ, PropofolGPI, PropofolD, and formate concentrations. Noncompartmental pharmacokinetic analyses were performed for all analytes. A population compartmental model was developed for AQ and PropofolGPI using NONMEM. The models were evaluated using simulations and bootstraps. RESULTS: The noncompartmental pharmacokinetic comparison revealed different dispositions of PropofolGPI and PropofolD. The maximum plasma concentration was lower for PropofolGPI than for PropofolD at equipotent doses, and apparent clearance and distribution volume were much higher for PropofolGPI than for PropofolD. Formate concentrations were similar when injecting both drugs and were not higher than baseline. Compartmental modeling revealed that the pharmacokinetic behavior of AQ and its liberated PropofolGPI was best described by a nonlinear, six-compartment model, composed of two three-compartment models connected to each other by hydrolysis of AQ to PropofolGPI. CONCLUSIONS: PropofolGPI showed different noncompartmental pharmacokinetics from PropofolD, hereby revealing the influence of the formulation. The combined model for AQ and PropofolGPI was best modeled by a nonlinear, six-compartment model.

Adolescent↗
PubMed2005

AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 2): pharmacodynamics and safety.

BACKGROUND: AQUAVAN Injection (AQ) (GPI 15715; Guilford Pharmaceuticals Inc., Baltimore, MD) is a water-soluble prodrug of propofol. The authors explored the pharmacodynamics and safety of AQ and compared it with propofol lipid emulsion (PropofolD). METHODS: After institutional review board approval, 36 volunteers with American Society of Anesthesiologists physical status of I were randomly allocated into six cohorts (male/female: 3/3 per cohort) and given a single bolus of AQ (5, 10, 15, 20, 25, or 30 mg/kg). A Bispectral Index monitor (Aspect Medical Systems Inc., Newton, MA) measured the hypnotic effect. The lowest Bispectral Index level (BISpeak) was recorded. One week later, PropofolD was given to the same subjects at 50 mg/min to reach a similar BISpeak. Heart rate, oxygen saturation measured by pulse oximetry, blood pressure, and side effects were monitored. Incidence and duration of apnea and loss (LOCverbal) and return of response to verbal command were measured. A population compartmental pharmacokinetic-pharmacodynamic model was developed for AQ using NONMEM and evaluated using simulations, leverage, and bootstrap analyses. RESULTS: In the higher dosages (cohorts 4-6), all subjects achieved LOCverbal. Similar times until LOCverbal were seen for AQ and PropofolD. A dose-related increase in duration of LOCverbal was longer for AQ than for PropofolD. AQ BISpeak occurred later than with PropofolD. Pain on injection was only present with PropofolD (12 of 36). With AQ, transient paresthesias and pruritus were seen. Hemodynamic profiles were similar for both drugs, except for an initial tachycardia after AQ administration. Dose-dependent apnea was more pronounced with PropofolD than with AQ. The AQ combined pharmacokinetic-pharmacodynamic profile was best described by a nonlinear, six-compartment pharmacokinetic model and an effect site compartment. A dependency of the ke0 value on the PropofolGPI plasma concentration was noted. CONCLUSION: Bolus administration of AQ achieves LOCverbal at a similar time as an equipotent amount of PropofolD but shows a longer time to BISpeak and prolonged pharmacodynamics. For both drugs, excellent drug safety was achieved, although there was a tendency of fewer and shorter duration of apneas for AQ.

Adolescent↗
PubMed2004

Arterial stiffness and wave reflections in patients with sickle cell disease.

We tested the hypothesis that lower blood pressure and increased vasodilatation reported in sickle cell disease (SCD) patients with hemoglobin SS genotype (SS) are translated by lower arterial stiffness determined by pulse wave velocity (PWV) and wave reflections assessed by augmentation index (AI). We enrolled 20 SS (8 females; 12 male) patients closely matched for age, gender, height, and body mass index to 20 subjects with hemoglobin AA genotype (AA). Carotid-femoral PWV (PWV(CF)) and carotid-radial PWV (PWV(CR)) were recorded with the Complior device. Aortic AI was derived from pressure wave analysis (SphygmocoR). PWV(CF) and PWV(CR) were lower in SS than in AA (4.5+/-0.7 m/s versus 6.9+/-0.9 m/s, P<0.0001 and 6.6+/-1.2 m/s versus 9.5+/-1.4 m/s, P<0.0001, respectively). AI was lower in SS than in AA (2+/-14% versus 11+/-8%, P=0.02). Multivariate analysis revealed that both PWV(CF) and PWV(CR) were negatively associated with hemoglobin SS type and positively related to mean arterial pressure (MAP), whereas AI was positively associated with MAP and total cholesterol (all P<0.0001). Multivariate analysis restricted to SS indicated a positive association between PWV(CF) and PWV(CR) with age but a negative association with MAP (R2=0.57 and 0.51, respectively, both P<0.001), whereas MAP and heart rate were independently associated with AI (R2=0.65, P<0.001). This study provides the first evidence that SCD is associated with both lower arterial stiffness and wave reflections. SS patients have a paradoxical negative association between PWV and MAP, suggesting that low MAP does not protect them against arterial stiffness impairment.

Adult↗
PubMed2004

Bioavailability of ibuprofen from hot-melt extruded mini-matrices.

The bioavailability of ibuprofen from hot-melt extruded mini-matrices based on ethyl cellulose and a hydrophilic excipient was tested. During the in vivo evaluation an oral dose of 300 mg ibuprofen was administered to healthy volunteers (n = 9) in a randomized cross-over study and compared with a commercially available sustained release product (Ibu-slow). The plasma samples were analysed by a validated HPLC-UV method. One mini-matrix formulation (F-1) consisted of 30% ibuprofen, 35% ethyl cellulose and 35% hydroxypropyl methylcellulose (Metolose 60 SH 50), while the second formulation (F-2) contained 60% ibuprofen, 20% ethyl cellulose and 20% xanthan gum. These mini-matrices were administered in hard gelatine capsules. Both formulations behaved in vivo as sustained release formulations with an HVD(t50% Cmax) value (time span during which the plasma concentration is at least 50% of the Cmax value) of 7.6 and 12.0 h for formulations F-1 and F-2, respectively, whereas a value of 5.2 h was obtained for Ibu-slow. Although a significantly higher Cmax and AUC(0-24 h) was seen for the reference product, the relative bioavailability of both experimental formulations was about 80%.

Adolescent↗
PubMed2004

Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

OBJECTIVE: Increased arterial stiffness is a determinant of cardiovascular mortality. Pulse wave velocity (PWV) is a direct measure of arterial stiffness. Aortic augmentation index (AI) and pulse pressure (PP) are surrogate measures of arterial stiffness. Both PWV, AI and PP increase with cardiovascular risk factors. The aim of this study was to test the validity of AI and PP as surrogate measures of arterial stiffness compared with PWV, during beta-adrenergic stimulation with Isoprenaline (Iso). DESIGN AND METHODS: A total of 41 healthy volunteers entered a randomized, double-blind, placebo-controlled, cross-over study. In random order, subjects were given intravenous infusion in equal volume of Iso 8 microg/kg per min (dissolved in glucose 5%) and placebo (glucose 5%). A wash-out period of 25 min was observed between the infusions. Measurements included blood pressure (BP), heart rate (HR), PWV, and AI. PWV were determined using complior (Complior, Artech-Medical, Paris, France). AI and aortic PP were obtained from pulse wave analysis of radial applanation tonometry, using transfer function (SphygmoCor Windows software). RESULTS: Baseline AI increased (P < 0.05) with aging, a lower height and a larger diastolic BP (DBP). Iso increased (P < 0.0001) HR, brachial SBP, brachial and aortic PP as compared with placebo. In contrast, Iso decreased (P < 0.05) AI, brachial DBP, peripheral PWV, but not aortic PWV. Decrease of AI induced by Iso was not related to PWV. In stepwise multiple regression changes in HR, brachial SBP and DBP were independent determinants of AI response to Iso (r = 0.78, P < 0.0001). CONCLUSIONS: Our findings show that AI and PP fail as surrogate measures of arterial stiffness during beta-adrenergic stimulation.

Adrenergic beta-Agonists↗
PubMed2004

Functional analysis of the common carotid artery: relative distension differences over the vessel wall measured in vivo.

OBJECTIVES: Absolute (DeltaD) and relative (DeltaD/D) arterial diameter distension, parameters related to the elasticity of the vessel, can be measured in superficial arteries using ultrasound-based vessel "wall tracking" techniques. Currently available systems (e.g. the Wall Track System; WTS) measure the displacement of the media-adventitia transition (outer wall). We hypothesize that, given volume incompressibility of the vessel wall, DeltaD and DeltaD/D measured at the outer wall, significantly underestimate vessel distension at the lumen-intima interface (inner wall). METHODS: We measured DeltaD and DeltaD/D at both the inner and outer wall of the common carotid artery in 39 subjects (aged 18-83 years) using a new prototype "wall tracking" system based on the Vivid-7 scanner (GE Vingmed Ultrasound, Horten, Norway). In addition, DeltaD and DeltaD/D were also measured using WTS. RESULTS: As anticipated, tracking the inner wall yielded lower diastolic diameters than when tracking the outer wall (Ddia = 5.70 +/- 0.80 and 6.91+/- 0.98 mm, respectively, P < 0.0001). DeltaD (0.54+/- 0.16 versus 0.49 +/- 0.16 mm; P < 0.0001) and DeltaD/D (0.096+/- 0.030 versus 0.071+/- 0.026, P < 0.0001) were indeed larger at the inner than at the outer wall. For WTS, Ddia, DeltaD and DeltaD/D were 7.04 +/- 1.02 mm, 0.45 +/- 0.14 mm and 0.066 +/- 0.022, respectively. CONCLUSIONS: On average, DeltaD and DeltaD/D are 10 and 25% higher on the inner than on the outer wall, respectively. Follow-up studies in larger cohort trials are mandatory to assess whether tracking the inner wall yields arterial function parameters with a higher cardiovascular prognostic potential.

Adolescent↗
PubMed2004

Effect of beta-adrenergic stimulation on pulse wave velocity in black and white subjects.

BACKGROUND: Reduced beta-adrenergic sensitivity has been reported in black subjects. We hypothesized that beta-adrenergic stimulation by isoproterenol would affect pulse wave velocity (PWV), a marker of arterial stiffness, differently in black and white subjects. METHODS: Healthy normotensive black subjects (n = 21) matched for age, gender, height and body mass index with healthy normotensive white subjects (n = 20), participated in a randomized, double-blind, placebo-controlled cross-over study. The PWV was determined using an automated device at baseline and after 30 min of an equal volume infusion of isoproterenol (8 mug/kg per min) or placebo (dextrose 5%), separated by a washout period of 25 min. RESULTS: At baseline, heart rate (HR), systolic and diastolic blood pressure (SBP, DBP) and PWV were comparable in black and in white subjects. Placebo had no significant effect on haemodynamic variables. Isoproterenol increased HR, SBP and pulse pressure and decreased DBP with a comparable magnitude in both groups. Compared with placebo, isoproterenol decreased carotid-femoral PWV in white (from 5.9 +/- 1.2 to 5.7 +/- 1.1 m/s, means +/- SD, P = 0.05), but not in black subjects (from 6.2 +/- 1.3 to 6.6 +/- 1.7 m/s, P = 0.1). The difference in response between black and white subjects was significant (P = 0.04). Isoproterenol decreased carotid-radial PWV only significantly in white subjects. CONCLUSION: These results are compatible with the hypothesis of an altered beta-adrenergic sensitivity, which is expressed by a blunted effect of isoproterenol on arterial stiffness in black subjects.

Adrenergic beta-Agonists↗