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ABSTRACT: The concept of chronotropic incompetence may have to be fine-tuned in an era of proven benefit of heart rate reducing therapy. It is illustrated in three patients with heart failure referred for heart transplantation evaluation. In patients one and two, symptoms of heart failure and exercise capacity improved by reducing the dose of the beta-blocking agent (case 1 and 2) and, in patient three, by additionally lowering the dose of amiodarone. Patient three showed reduced exercise tolerance, particularly during cycling albeit not during walking. Exercise tolerance during cycling improved after adaptation of the rate response parameters of his pacemaker. In conclusion, the three cases illustrate that chronotropic incompetence is a clinical reality, while a correct history taking and specific measures can solve the problem, reduce the complaints and even avoid more aggressive therapeutic options such as orthotopic transplantation.
Acta cardiologica 04/2013; 68(2):205-7. · 0.61 Impact Factor
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ABSTRACT: Background: Statins can cause tubular proteinuria by inhibiting tubular reabsorption of urinary proteins. To distinguish between microalbuminuria originating from glomerular leakage of albumin and tubular microalbuminuria due to statin therapy, the alpha-1-microglobulin/albumin ratio is evaluated in patients taking statins and compared tountreated patients.
Methods: Ten apparently healthy subjects were given 40 mg of simvastatin and tested for urinary alpha-1-microglobulin, albumin, creatinine and cystatin C, up to 24 hours after administration. Additionally, urine samples of 76 statin-treated and 456 untreated patients presenting with micro-albuminuria (albuminuria range between 20 and 200 mg/L) were tested for alpha-1-microglobulin and albumin. Alpha-1-microglobulin/albumin ratios were compared. In 50 patients on statin therapy, total cholesterol was measured.
Results: In the ten apparently healthy subjects, a significant temporary increase of alpha-1-microglobulin, albumin and alpha-1-microglobulin/albumin ratio was observed after statin intake. In the group of 532 patients showing micro-albuminuria, those treated with statins showed a significantly higher mean urinary alpha-1-microglobulin/albumin ratio then untreated patients. Urinary albumin concentrations were significantly higher in patients taking simvastatin than in patients on rosuvastatin treatment and they were also higher in patients on statin therapy with a total serum cholesterol concentration below 3.88 mmol/L than in patients with a total serum cholesterol concentration above 5.17 mmol/L.
Conclusion: Tubular proteinuria, caused by the use of statins, can be distinguished from glomerular proteinuria by a higher urinary alpha-1-microglobulin/albumin ratio.
Clinical Chemistry and Laboratory Medicine 01/2013; · 2.15 Impact Factor
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ABSTRACT: Background: C-reactive protein (CRP) is able to bind phospholipids in the presence of calcium. We wanted to investigate the reaction of CRP with various commercial fat emulsions and to explore the impact of CRP agglutination on serum CRP levels.
Materials and Methods: Serum specimens were mixed with Intralipid® 20% (soybean oil- based fat emulsion), Structolipid® (structured oil-based fat emulsion), Omegaven® (fish oil-based fat emulsion) or SMOFlipid® (mixed soybean oil-, olive oil- and fish oil-based emulsion) in Tris-Calcium buffer (pH 7.5). After 30 min of incubation at 37°C, CRP-phospholipid complexes were turbidimetrically quantified and flow cytometric analysis was performed. Similarly, CRP complexes were monitored in vivo, following administration of fat emulsion.
Results: CRP was able to agglutinate phospholipid containing lipid droplets present in the soybean oil-based fat emulsion and the structured oil-based fat emulsion. To a lesser extent, agglutination was observed for fish oil containing fat emulsions, whereas no agglutination could be noticed towards the mixed soybean oil-, olive oil- and fish oil-based emulsion. Results for propofol containing emulsions were comparable. Agglutination correlated with phospholipid content of the emulsions. When in vivo agglutination occurred, plasma CRP values dropped due to consumption of CRP by phospholipid-induced agglutination.
Conclusions: In this in vitro experiment we demonstrated agglutination of CRP with phospholipids in various fat emulsions. Research studies are required in patients to determine which effects occur with various intravenous fat emulsions.
Nutrition in Clinical Practice 01/2013; · 1.59 Impact Factor
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Atherosclerosis 10/2012; · 3.79 Impact Factor
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Reinhart Speeckaert,
Bob Colebunders,
Johan R. Boelaert,
Lieve Brochez,
Jos Van Acker,
Filip Van Wanzeele,
Robert Hemmer,
Marijn M. Speeckaert,
Chris Verhofstede, Marc De Buyzere,
Vic Arendt,
Jean Plum,
Joris R. Delanghe
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ABSTRACT: Kaposi’s sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops
in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein,
exerts several immunomodulatory effects and is characterized by a genetic polymorphism leading to three major phenotypes (Hp
1-1, Hp 2-1 and Hp 2-2). This study investigated the influence of Hp genetic polymorphism on the development of KS in HIV-positive
patients. 661 HIV patients were enrolled in the study with a median age of 35years and a median follow-up time of 57months.
Hp phenotyping was performed using hemoglobin-supplemented starch gel electrophoresis. In case of low Hp concentration high
pressure gel permeation chromatography (HPGPC) was used. The Hp 1-1 phenotype was associated with a significant higher risk
of KS compared to the combined group of Hp 2-1 and Hp 2-2 patients (p<0.0005) which remained significant after adjustment for possible confounding variables (age, gender and AIDS status) (p<0.001). In contrast, the Hp 2-1 phenotype carried the lowest risk. These findings point to the involvement of Hp phenotypes
in the pathogenesis of KS, which may be due to a difference in skin immunosurveillance between the Hp phenotypes.
KeywordsGenetic polymorphism–Haptoglobin–HIV–Kaposi’s sarcoma
Archives for Dermatological Research 05/2012; 303(10):763-769. · 2.28 Impact Factor
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ABSTRACT: C-reactive protein (CRP), a pentraxin protein, is an established marker of acute phase reactions. There is some experimental evidence that the CRP molecule could be causative in all stages of atherosclerotic disease starting from endothelial dysfunction, continuing to plaque formation and destabilization, and to atherothrombotic complications. However, each claim of causality has elicited a counterpoint argument, and Mendelian randomization studies have confidently shown that the concentration of CRP is unlikely to be causative. Meta-analyses have attributed a 1.5-1.7-fold risk to one standard deviation increase of high-sensitive CRP (a high-sensitivity CRP assay) for major cardiovascular events after adjustments for classical risk factors. Additional adjustments for metabolic factors reduced the risk to approximately 1.2-1.4-fold, which is still significant. Of interest, high-sensitive CRP also predicted all-cause and cancer mortality. Driven by the JUPITER trial that showed a benefit on outcome for treatment with rosuvastatin in primary prevention, treatment has been recommended in patients with a moderate Framingham Risk Score with a high-sensitive CRP of >2 mg/l. However, adding CRP to risk charts and biomarker panels mostly yielded small and inconsistent improvements.
Biomarkers in Medicine 02/2012; 6(1):19-34. · 0.86 Impact Factor
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ABSTRACT: Platelet-derived chemokines are implicated in several aspects of vascular biology. However, for the chemokine platelet factor 4 variant (PF-4var/CXCL4L1), released by platelets during thrombosis and with different properties as compared to PF-4/CXCL4, its role in heart disease is not yet studied. We evaluated the determinants and prognostic value of the platelet-derived chemokines PF-4var, PF-4 and RANTES/CCL5 in patients with stable coronary artery disease (CAD).
From 205 consecutive patients with stable CAD and preserved left ventricular (LV) function, blood samples were taken at inclusion and were analyzed for PF-4var, RANTES, platelet factor-4 and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Patients were followed (median follow-up 2.5 years) for the combined endpoint of cardiac death, non-fatal acute myocardial infarction, stroke or hospitalization for heart failure. Independent determinants of PF-4var levels (median 10 ng/ml; interquartile range 8-16 ng/ml) were age, gender and circulating platelet number. Patients who experienced cardiac events (n = 20) during follow-up showed lower levels of PF-4var (8.5 [5.3-10] ng/ml versus 12 [8-16] ng/ml, p = 0.033). ROC analysis for events showed an area under the curve (AUC) of 0.82 (95% CI 0.73-0.90, p<0.001) for higher NT-proBNP levels and an AUC of 0.32 (95% CI 0.19-0.45, p = 0.009) for lower PF-4var levels. Cox proportional hazard analysis showed that PF-4var has an independent prognostic value on top of NT-proBNP.
We conclude that low PF-4var/CXCL4L1 levels are associated with a poor outcome in patients with stable CAD and preserved LV function. This prognostic value is independent of NT-proBNP levels, suggesting that both neurohormonal and platelet-related factors determine outcome in these patients.
PLoS ONE 01/2012; 7(2):e31343. · 4.09 Impact Factor
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Marc De Buyzere
Journal of hypertension 12/2011; 29(12):2312-5. · 4.02 Impact Factor
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Reinhart Speeckaert,
Bob Colebunders,
Johan R Boelaert,
Lieve Brochez,
Jos Van Acker,
Filip Van Wanzeele,
Robert Hemmer,
Marijn M Speeckaert,
Chris Verhofstede, Marc De Buyzere,
Vic Arendt,
Jean Plum,
Joris R Delanghe
[show abstract]
[hide abstract]
ABSTRACT: Kaposi's sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein, exerts several immunomodulatory effects and is characterized by a genetic polymorphism leading to three major phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). This study investigated the influence of Hp genetic polymorphism on the development of KS in HIV-positive patients. 661 HIV patients were enrolled in the study with a median age of 35 years and a median follow-up time of 57 months. Hp phenotyping was performed using hemoglobin-supplemented starch gel electrophoresis. In case of low Hp concentration high pressure gel permeation chromatography (HPGPC) was used. The Hp 1-1 phenotype was associated with a significant higher risk of KS compared to the combined group of Hp 2-1 and Hp 2-2 patients (p < 0.0005) which remained significant after adjustment for possible confounding variables (age, gender and AIDS status) (p < 0.001). In contrast, the Hp 2-1 phenotype carried the lowest risk. These findings point to the involvement of Hp phenotypes in the pathogenesis of KS, which may be due to a difference in skin immunosurveillance between the Hp phenotypes.
Archives for Dermatological Research 07/2011; 303(10):763-9. · 2.28 Impact Factor
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Acta cardiologica 10/2010; 65(5):575-9. · 0.61 Impact Factor
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ABSTRACT: Carotid-femoral pulse wave velocity can be determined using different distances - either direct carotid-femoral distance or subtracted [(sternal-femoral) - (carotid-sternal)] distance - resulting in pulse wave velocity differences of up to 30%. The present study aims to present and validate a population-based model for the conversion between distances.
Three thousand one hundred and sixteen participants from the Asklepios study (n = 2510) and Hôpital Européen Georges Pompidou (n = 606) databases, in which all distance measurements were available, were randomly distributed in a model (n = 311) and validation (n = 2805) population. Model parameters for the conversion equations were selected and evaluated using multiple linear regression with stepwise selection of covariates (age, sex, weight, height, BMI and waist circumference). The proposed model was evaluated on the validation population.
The difference between direct and subtracted distances was found to be partially dependent on body height, and its inclusion in the multivariate model improved model performance by over 20%. Other combinations of adjustments did not improve model prediction. Conversion equations derived in the model population were: Estimated Direct_distance = 0.45*Subtracted_distance + 0.21*height + 0.08 and Estimated Subtracted_distance = 1.04*Direct_distance - 0.11*height - 0.02, respectively. Applying these equations for estimation of direct and subtracted distances in the validation population yielded good correspondence to measured results (r = 0.73 and 0.57, respectively), with nonsignificant mean differences between estimated and measured values. Increasing the size of the model population did not significantly change the model validity.
In cases in which not all distance measurements are available for exact conversion, the presented equations can be used to convert between distance definitions.
Journal of hypertension 11/2009; 27(12):2377-85. · 4.02 Impact Factor
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Hypertension 09/2009; · 6.21 Impact Factor
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ABSTRACT: Chlamydophila psittaci infections in humans are underestimated. We investigated the occurrence of C. psittaci in a Belgian population of 540 individuals. Data were from a population survey (n=2524) of apparently healthy community-dwelling subjects aged 35-55 years. Pharyngeal swabs and blood were taken. Individuals completed a questionnaire on professional and nonprofessional activities, smoking habits, medical history and contact frequency with different bird species. Swabs were analysed by a C. psittaci-specific and a Chlamydophila pneumoniae-specific PCR. Sera were tested by a recombinant C. psittaci major outer-membrane protein-based ELISA, a C. psittaci whole organism-based ELISA (Serion) and a micro-immunofluorescence test (Focus Diagnostics). Results confirmed our suspicion about the underestimation of psittacosis in Belgium. Psittaciformes and racing pigeons were the main infection source. Women with excessive alcohol intake defined as a mean intake of >2 units daily were more frequently infected than men. We analysed the effect of seropositivity and/or PCR positivity on inflammation (white blood cell count, high-sensitivity C-reactive protein, fibrinogen). In general, seropositivity showed a trend to slightly higher levels of inflammatory variables (all non-significant), whilst PCR positivity showed a trend to no effect or even lower inflammatory levels.
Journal of Medical Microbiology 07/2009; 58(Pt 9):1207-12. · 2.50 Impact Factor
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Patrick Segers,
Dries Mahieu,
Jan Kips,
Ernst Rietzschel, Marc De Buyzere,
Dirk De Bacquer,
Sofie Bekaert,
Guy De Backer,
Thierry Gillebert,
Pascal Verdonck,
Luc Van Bortel
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ABSTRACT: Central-to-peripheral amplification of the pressure pulse leads to discrepancies between central and brachial blood pressures. This amplification depends on an individual's hemodynamic and (patho)physiological characteristics. The aim of this study was to assess the magnitude and correlates of central-to-peripheral amplification in the upper limb in a healthy, middle-aged population (the Asklepios Study). Carotid, brachial, and radial pressure waveforms were acquired noninvasively using applanation tonometry in 1873 subjects (895 women) aged 35 to 55 years. Carotid, brachial, and radial pulse pressures were calculated, as well as the absolute and relative (with carotid pulse pressure as reference) amplifications. With subjects classified per semidecade of age, carotid-to-radial amplification varied from approximately 25% in the youngest men to 8% in the oldest women. Amplification was higher in men (20+/-14%) than in women (13+/-12%; P<0.001) and decreased with age (P<0.001) in both. Amplification over the brachial-to-radial path contributed substantially to the total amplification. In univariate analysis, the strongest correlation was found with the carotid augmentation index (-0.51 in women; -0.47 in men; both P<0.001). In a multiple linear regression model with carotid-to-radial amplification as the dependent variable, carotid augmentation index, total arterial compliance, and heart rate were identified as the 3 major determinants of upper limb pressure amplification (R2=0.36). We conclude that, in healthy middle-aged subjects, the central-to-radial amplification of the pressure pulse is substantial. Amplification is higher in men than in women, decreases with age, and is primarily associated with the carotid augmentation index.
Hypertension 06/2009; 54(2):414-20. · 6.21 Impact Factor
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Marc De Buyzere
Journal of Hypertension 02/2009; 27(1):24-7. · 4.02 Impact Factor
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ABSTRACT: The assessment of cardiovascular function by means of arterial pulse wave analysis (PWA) is well established in clinical practice. PWA is applied to study risk stratification in hypertension, with emphasis on the measurement of the augmentation index as a measure of aortic pressure wave reflections. Despite the fact that the prognostic power of PWA, in its current form, still remains to be demonstrated in the general population, there is general agreement that analysis and interpretation of the waveform might provide a deeper insight in cardiovascular pathophysiology. We propose here the use of wavelet analysis (WA) as a tool to quantify arterial pressure waveform features, with a twofold aim. First, we discuss a specific use of wavelet transform in the study of pressure waveform morphology, and its potential role in ascertaining the dynamics of temporal properties of arterial pressure waveforms. Second, we apply WA to evaluate a database of carotid artery pressure waveforms of healthy middle-aged women and men. Wavelet analysis has the potential to extract specific features (wavelet details), related to wave reflection and aortic valve closure, from a measured waveform. Analysis showed that the fifth detail, one of the waveform features extracted applying the wavelet decomposition, appeared to be the most appropriate for the analysis of carotid artery pressure waveforms. What remains to be assessed is how the information embedded in this detail can be further processed and transformed into quantitative data, and how it can be rendered useful for automated waveform classification and arterial function parameters with potential clinical applications.
Medical & Biological Engineering 10/2008; 47(2):165-73. · 1.76 Impact Factor
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ABSTRACT: To assess the prognostic significance of nighttime and daytime blood pressure (BP), their ratio and the nighttime dipping pattern for mortality and recurrent cardiovascular (CV) events in patients with CV disease at baseline.
The prognostic value of ambulatory BP has not been reported in hypertensive patients with a history of CV disease.
We performed a meta-analysis on individual data of 302 patients with hypertension and CV disease from three prospective studies performed in Europe.
Age of the patients averaged 69+/-9 years; 50% were men and 62% were under antihypertensive treatment at the time of ambulatory BP monitoring. Office, daytime and nighttime BP averaged 161+/-20/86+/-12, 144+/-16/83+/-11 and 132+/-18/72+/-12 mmHg. Total follow-up time amounted to 2049 patient--years. Multivariable Cox regression analysis revealed that nighttime BP, but not daytime BP significantly predicted CV mortality (P< or =0.05) and major CV events (P< or =0.01) after adjustment for office BP and other confounders. When both nighttime and daytime BP were entered into the models, the predictive power of nighttime BP remained significant (P< or =0.05); daytime BP did not add prognostic precision to nighttime BP. The systolic nightday BP ratio predicted all outcomes, and outcome was significantly worse in reverse dippers and nondippers than in dippers, both before and after adjustment for 24-h BP (P< or =0.05).
Nighttime BP is the better predictor of death and recurrent CV events in hypertensive patients with a history of CV disease. The night-day BP ratio and the dipping pattern significantly predict outcome, even after adjustment for 24-h BP.
Blood pressure monitoring 09/2008; 13(6):325-32. · 1.62 Impact Factor
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ABSTRACT: Previous studies have demonstrated reduced exercise capacity in patients with diabetes mellitus. This study evaluated the relationship between fasting blood glucose (FBG) levels and exercise capacity in patients with coronary artery disease (CAD).
We evaluated 986 consecutive patients with CAD referred for bicycle spiroergometry combined with gated myocardial perfusion imaging. Maximum oxygen consumption (VO2max) and maximal watts were measured. Patients were divided into 4 FBG categories: < 100 mg/dL (n = 611), 100 to 109 mg/dL (n = 144), 110 to 125 mg/dL (n = 102), and > or = 126 mg/dL (n = 129). Differences in clinical characteristics, exercise hemodynamics, perfusion imaging, and univariate as well as multivariate predictors of exercise capacity were determined.
Maximal watts and VO2max were significantly lower (P < .0001) in patients with higher FBG levels and were related to FBG values in univariate and multivariate analyses. Left ventricular volumes and ejection fractions did not differ between the FBG categories. Myocardial perfusion imaging showed a comparable degree of ischemia in the 4 FBG groups. However, patients with higher FBG levels had higher heart rate and blood pressure values at rest resulting in a higher rate-pressure product (values in the 4 FBG groups 8299 +/- 2051, 8733 +/- 2008, 9558 +/- 2583, and 9588 +/- 2468 beat/min x mm Hg, P < .0001), suggesting increased myocardial oxygen consumption per unit time at rest.
Exercise capacity in patients with CAD is related to FBG levels. Patients with impaired fasting glucose or an FBG level > or = 126 mg/dL reached lower peak watts and lower VO2max values. This could be attributed to a higher myocardial oxygen consumption per unit time at rest and the inability to adapt their coronary flow adequately to higher metabolic demands during maximal exercise.
American heart journal 09/2006; 152(3):486-92. · 4.65 Impact Factor
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ABSTRACT: Several studies have shown that longitudinal systolic function and left ventricular filling pressures, as assessed with tissue Doppler imaging, predict exercise capacity.
The aim of this study was to evaluate whether natriuretic peptides and inflammatory parameters can independently predict maximum oxygen uptake at peak exercise (VO2max) on top of tissue Doppler imaging-derived markers.
We evaluated 142 patients (age 70 +/- 6 years, 77% men) with known or suspected coronary artery disease and a preserved left ventricular ejection fraction (> or = 50%). All patients underwent bicycle spiroergometry, and N-terminal pro-B-type natriuretic peptide levels were determined. Cytokines (IL-6 and soluble tumor necrosis factor receptors 1 and 2) and high-sensitivity C-reactive protein were measured as inflammatory markers. Tissue Doppler imaging was applied to evaluate peak long axis systolic velocities (Sm) and early mitral annulus velocities (E'). Ratio of early transmitral flow (E) to E' was assessed as marker of left ventricular filling. Analysis of variance, comparing VO2max quartiles, was used to determine univariate predictors and linear regression to determine multivariate VO2max predictors.
Average VO2max was 18.5 +/- 5.7 mL/kg per minute (range 6-36.6). Compared with the highest quartile, patients with low VO2max were more frequently women (P < .0001). N-terminal pro-B-type natriuretic peptide and cytokine levels were significantly higher in the lower VO2max categories. Longitudinal myocardial velocities increased, and E/E' decreased along with increasing VO2max. In multivariate linear regression analysis, VO2max was independently predicted by sex, glucose, Sm, E/E', and cytokine levels.
Maximum oxygen uptake at peak exercise in patients with known or suspected coronary artery disease and preserved systolic function was independently predicted by inflammatory makers on top of tissue Doppler-derived systolic and diastolic function.
American heart journal 08/2006; 152(2):297.e1-7. · 4.65 Impact Factor
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ABSTRACT: To assess the interchangeability of carotid tonometry and synthesized aorta pressure waveforms for estimating central systolic blood pressure (SBP) and augmentation index (AIx).
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).
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).
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.
American Journal of Hypertension 09/2005; 18(9 Pt 1):1168-73. · 3.18 Impact Factor
