Malcolm Kohler

University of Zurich, Zürich, ZH, Switzerland

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Publications (52)254.08 Total impact

  • Article: Leukoaraiosis on MRI in Patients with Minimally Symptomatic Obstructive Sleep Apnoea.
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    ABSTRACT: Background: Obstructive sleep apnoea (OSA) is associated with hypertension, nocturnal blood pressure (BP) surges, and increased risk of stroke. It may therefore also be associated with a higher risk of developing leukoaraiosis. Only few data about the prevalence of leukoaraiosis in patients with OSA, and any association between degrees of severity of either condition, exist. Methods: We studied patients who were part of a clinical trial (MOSAIC) in minimally symptomatic OSA. All patients had brain MRI (T2, FLAIR) at baseline. A single observer assessed the images for the presence and severity of leukoaraiosis (ARWMC-score). We related the extent of leukoaraiosis to the severity of OSA (measured by oxygen desaturation index [ODI]) and the presence of other vascular risk factors. Results: 183 patients (156 men, 85.2%; mean age ± SD = 57.7 ± 7.4 years; median oxygen desaturation index = 9.6, interquartile range = 4.6-16.0) took part in the study. Although 135 (74%) patients had some leukoaraiosis, this was generally mild. We confirmed the well-known risk factor associations between leukoaraiosis, increasing age (p < 0.0001) and hypertension (p = 0.003), but we did not find any association between OSA and leukoaraiosis (p = 0.33), despite both conditions being associated with increasing current BP and a history of hypertension. Conclusion: Our data confirm the well-known association between leukoaraiosis, age and increasing BP. However, we found no association between OSA and leukoaraiosis despite some shared risk factor associations. Our findings suggest that OSA is not a strong independent risk factor for leukoaraiosis. Confounding by hypertension may explain any apparent association in previously reported studies of patients with severer OSA.
    Cerebrovascular Diseases 04/2013; 35(4):363-369. · 2.72 Impact Factor
  • Article: Determinants of endothelial function in patients with COPD.
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    ABSTRACT: COPD is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. This cross-sectional study aims to determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxemia and physical activity on endothelial function in COPD.In stable COPD patients assessments of endothelial function by flow-mediated dilatation (FMD), cardiovascular risk (Pocock-score), airflow obstruction (FEV1), systemic inflammation (hsCRP, Interleukin-6), oxidative stress (malondialdehyde), sympathetic activation (baroreflex-sensitivity), hypoxemia (Pa,O2), hypercapnia (Pa,CO2), physical activity (steps per day) and exercise capacity (6-minutes walking distance) were performed. Associations between FMD and potential determinants were assessed in univariate and multivariate analysis.106 patients (35% GOLD stage I/II, 25% III, 40% IV) were included. In multivariate analysis FEV1 was positively associated with FMD, independent of other significant FMD determinants from univariate analysis (gender, smoking, combined inhaled long-acting β-adrenergic and steroid medication, heart rate, baroreflex-sensitivity, Pa,CO2) and adjusted for potential confounders (cardiovascular risk, age). In addition, the FMD and FEV1 association was modified by physical activity.The findings of this study demonstrate that the severity of airflow obstruction is a significant determinant of endothelial function in patients with COPD. A high level of physical activity seems to have a favourable effect on this association.
    European Respiratory Journal 02/2013; · 5.89 Impact Factor
  • Article: Effects of obstructive sleep apnoea on heart rhythm.
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    ABSTRACT: Symptomatic obstructive sleep apnoea (OSA) has been proven to be a risk factor for hypertension and vascular dysfunction, and has been proposed to be causally related with cardiac arrhythmias and sudden cardiac death.Searches of bibliographical databases revealed that several mechanisms seem to underpin the association between OSA and cardiac arrhythmias: intermittent hypoxia associated with autonomic nervous system activation and increased oxidative stress, which may lead to cardiac cellular damage and alteration in myocardial excitability; recurrent arousals, resulting in sympathetic activation and coronary vasoconstriction; and increased negative intrathoracic pressure which may mechanically stretch the myocardial walls and thus promote acute changes in myocardial excitability as well as structural remodelling of the myocardium. Findings from cross-sectional studies suggest a high prevalence of cardiac arrhythmias in patients with OSA and a high prevalence of OSA in those with cardiac arrhythmias. Preliminary evidence from uncontrolled interventional studies suggests that treatment of OSA may prevent cardiac arrhythmias.In conclusion, there is preliminary evidence that OSA is associated with the development of cardiac arrhythmias. Data from randomized-controlled studies are needed to definitely clarify the role of OSA in arrhythmogenesis.
    European Respiratory Journal 12/2012; · 5.89 Impact Factor
  • Article: Effect of acetazolamide and autoCPAP therapy on breathing disturbances among patients with obstructive sleep apnea syndrome who travel to altitude: a randomized controlled trial.
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    ABSTRACT: Many patients with obstructive sleep apnea syndrome (OSA) living near sea level travel to altitude, but this may expose them to hypoxemia and exacerbation of sleep apnea. The treatment in this setting is not established. To evaluate whether acetazolamide and autoadjusted continuous positive airway pressure (autoCPAP) control breathing disturbances in OSA patients at altitude. Randomized, placebo-controlled, double-blind, crossover trial involving 51 patients with OSA living below an altitude of 800 m and receiving CPAP therapy who underwent studies at a university hospital at 490 m and resorts in Swiss mountain villages at 1630 m and 2590 m in summer 2009. Patients were studied during 2 sojourns of 3 days each in mountain villages, 2 days at 1630 m, 1 day at 2590 m, separated by a 2-week washout period at less than 800 m. At altitude, patients either took acetazolamide (750 mg/d) or placebo in addition to autoCPAP. Primary outcomes were nocturnal oxygen saturation and the apnea/hypopnea index; secondary outcomes were sleep structure, vigilance, symptoms, adverse effects, and exercise performance. Acetazolamide and autoCPAP treatment was associated with higher nocturnal oxygen saturation at 1630 m and 2590 m than placebo and autoCPAP: medians, 94% (interquartile range [IQR], 93%-95%) and 91% (IQR, 90%-92%) vs 93% (IQR, 92%-94%) and 89% (IQR, 87%-91%), respectively. Median increases were 1.0% (95% CI, 0.3%-1.0%) and 2.0% (95% CI, 2.0%-2.0). Median night-time spent with oxygen saturation less than 90% at 2590 m was 13% (IQR, 2%-38%) vs 57% (IQR, 28%-82%; P < .001). Acetazolamide and autoCPAP resulted in better control of sleep apnea at 1630 m and 2590 m than placebo and autoCPAP: median apnea/hypopnea index was 5.8 events per hour (5.8/h) (IQR, 3.0/h-10.1/h) and 6.8/h (IQR, 3.5/h-10.1/h) vs 10.7/h (IQR, 5.1/h-17.7/h) and 19.3/h (IQR, 9.3/h-29.0/h), respectively; median reduction was 3.2/h (95% CI, 1.3/h-7.5/h) and 9.2 (95% CI, 5.1/h-14.6/h). Among patients with OSA spending 3 days at moderately elevated altitude, a combination of acetazolamide and autoCPAP therapy, compared with autoCPAP alone, resulted in improvement in nocturnal oxygen saturation and apnea/hypopnea index. clinicaltrials.gov Identifier: NCT00928655.
    JAMA The Journal of the American Medical Association 12/2012; 308(22):2390-8. · 30.03 Impact Factor
  • Article: Severity of Peripheral Arterial Disease is Associated With Aortic Pressure Augmentation and Subendocardial Viability Ratio.
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    ABSTRACT: J Clin Hypertens (Greenwich). 2012; 14:855-860. ©2012 Wiley Periodicals, Inc. Peripheral arterial disease (PAD) is associated with increased cardiovascular mortality that correlates with peripheral perfusion impairment as assessed by the ankle-brachial arterial pressure index (ABI). Furthermore, PAD is associated with arterial stiffness and elevated aortic augmentation index (AIx). The purpose of this study was to investigate whether ABI impairment correlates with AIx and subendocardial viability ratio (SEVR), a measure of cardiac perfusion during diastole. AIx and SEVR were assessed by radial applanation tonometry in 65 patients with stable PAD (Rutherford stage I-III) at a tertiary referral center. AIx corrected for heart rate and SEVR were tested in a multivariate linear and logistic regression model to determine the association with ABI. Mean ABI was 0.8±0.2, AIx 31%±7%, and SEVR 141%±26%. Multiple linear regression with AIx as a dependent variable revealed that AIx was significantly negatively associated with ABI (β=-11.5; 95% confidence interval [CI], -18.6 to -4.5; P=.002). Other variables that were associated with AIx were diastolic blood pressure (β=0.2; 95% CI, 0.1-0.4; P<.001), height (β=-46.2; 95% CI, -62.9 to -29.4; P<.001), body mass index (β=-0.4; 95% CI, -0.8 to -0.1; P=.023), and smoking (β=3.6; 95% CI, 0.6-6.6; P=.019). Multiple regression with SEVR as a dependent variable showed a significant correlation with ABI (β=33.2; 95% CI, 2.3-64.1; P=.036). Severity of lower limb perfusion impairment is related to central aortic pressure augmentation and to subendocardial viability ratio. This may be a potential pathophysiologic link that impacts cardiac prognosis in patients with PAD.
    Journal of Clinical Hypertension 12/2012; 14(12):855-60. · 1.83 Impact Factor
  • Article: Sympathetic overactivity and cardiovascular disease in patients with chronic obstructive pulmonary disease (COPD).
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    ABSTRACT: Cardiovascular disease plays an important role regarding the morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). Sympathetic overactivity has been suggested to underpin the association between COPD and the development of cardiovascular disease. However, the pathophysiological basis by which sustained sympathetic overactivity affects cardiovascular function in patients with COPD is complex and incompletely understood. Different simple and more sophisticated measures of sympathetic activity, such as assessment of heart rate, blood pressure variability, and baroreflex sensitivity, provide information on the potential dysregulation of the autonomous nervous system. This review summarizes the findings from studies in animal models and humans on the potential relationship between COPD, sympathetic overactivity, and cardiovascular disease. There is preliminary evidence of sympathetic overactivity in COPD. However, direct evidence of a cause-effect relationship between sympathetic overactivity and cardiovascular disease from studies in COPD patients is lacking. Data from large cohorts of COPD patients and well-designed interventional studies looking at the relationship between COPD and autonomic nervous system function are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD.
    Discovery medicine 12/2012; 14(79):359-68.
  • Article: Elevated Levels of Endothelial Cell-Derived Microparticles following Short-Term Withdrawal of Continuous Positive Airway Pressure in Patients with Obstructive Sleep Apnea: Data from a Randomized Controlled Trial.
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    ABSTRACT: Background: Obstructive sleep apnea has been associated with impaired endothelial function; however, the mechanisms underlying this association are not completely understood. Cell-derived microparticles may provide a link between obstructive sleep apnea and endothelial dysfunction. Objectives: This randomized controlled trial aimed to examine the effect of a 2-week withdrawal of continuous positive airway pressure (CPAP) therapy on levels of circulating microparticles. Methods: Forty-one obstructive sleep apnea patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continuing therapeutic CPAP, for 2 weeks. Polysomnography was performed and circulating levels of microparticles were analyzed by flow cytometry at baseline and 2 weeks. Results: CPAP withdrawal led to a recurrence of obstructive sleep apnea. Levels of CD62E+ endothelium-derived microparticles increased significantly in the CPAP withdrawal group compared to the continuing therapeutic CPAP group (median difference in change +32.4 per µl; 95% CI +7.3 to +64.1 per µl, p = 0.010). CPAP withdrawal was not associated with a statistically significant increase in granulocyte, leukocyte, and platelet-derived microparticles when compared with therapeutic CPAP. Conclusions: Short-term withdrawal of CPAP therapy leads to a significant increase in endothelium-derived microparticles, suggesting that microparticle formation may be causally linked to obstructive sleep apnea and may promote endothelial activation.
    Respiration 11/2012; · 2.26 Impact Factor
  • Article: Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial.
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    ABSTRACT: BACKGROUND: Continuous positive airway pressure (CPAP) for symptomatic obstructive sleep apnoea (OSA) improves sleepiness and reduces vascular risk, but such treatment for the more prevalent, minimally symptomatic disease is contentious. METHODS: This multicentre, randomised controlled, parallel, hospital-based trial across the UK and Canada, recruited 391 patients with confirmed OSA (oxygen desaturation index >7.5/h) but insufficient symptoms to warrant CPAP therapy. Patients were randomised to 6 months of auto-adjusting CPAP therapy, or standard care. Coprimary endpoints were change in Epworth Sleepiness Score (ESS) and predicted 5-year mortality using a cardiovascular risk score (components: age, sex, height, systolic blood pressure, smoking, diabetes, cholesterol, creatinine, left ventricular hypertrophy, previous myocardial infarction or stroke). Secondary endpoints included some of the individual components of the vascular risk score, objectively measured sleepiness and self-assessed health status. RESULTS: Of 391 patients randomised, 14 withdrew, 347 attended for their follow-up visit at 6 months within the predefined time window, of which 341 had complete ESS data (baseline mean 8.0, SD 4.3) and 310 had complete risk score data. 22% of patients in the CPAP group reported stopping treatment and overall median CPAP use was 2 : 39 h per night. CPAP significantly improved subjective daytime sleepiness (adjusted treatment effect on ESS -2.0 (95% CI -2.6 to -1.4), p<0.0001), objectively measured sleepiness and self-assessed health status. CPAP did not improve the 5-year calculated vascular risk or any of its components. CONCLUSIONS: In patients with minimally symptomatic OSA, CPAP can reduce subjective and objective daytime sleepiness, and improve self-assessed health status, but does not appear to improve calculated vascular risk.
    Thorax 10/2012; · 6.84 Impact Factor
  • Article: Voiceless due to herniating lung: an unusual cause of unilateral vocal cord paralysis.
    American Journal of Respiratory and Critical Care Medicine 08/2012; 186(4):391-2. · 11.08 Impact Factor
  • Article: The effects of simulated obstructive apnea and hypopnea on arrhythmic potential in healthy subjects.
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    ABSTRACT: Preliminary evidence supports an association between OSA and cardiac dysrhythmias. Negative intrathoracic pressure, as occurring during OSA, may provoke cardiac dysrhythmias. Thus, we aimed to study the acute effects of simulated apnea and hypopnea on arrhythmic potential and measures of cardiac repolarization [QT(C) and T (peak) to T (end) intervals ([Formula: see text])] in humans. In 41 healthy volunteers, ECG was continuously recorded prior, during and after simulated obstructive hypopnea (inspiration through a threshold load), simulated apnea (Mueller maneuver), end-expiratory central apnea and normal breathing in randomized order. The number of subjects with premature beats was significantly higher during inspiration through a threshold load (n = 7), and the Mueller maneuver (n = 7) compared to normal breathing (n = 0) (p = 0.008 for all comparisons), but not during end-expiratory central apnea (n = 3, p = 0.125). Inspiration through a threshold load was associated with a non-significant mean (SD) increase of the QT(C) interval [+5.4 (22.4) ms, 95 %CI -1.7 to +12.4 ms, p = 0.168] and a significant increase of the [Formula: see text] interval [+3.7 (8.9) ms, 95 %CI +0.9 to +6.6 ms, p = 0.010]. The Mueller maneuver induced a significant increase of the QT(C) interval [+8.3 (23.4) ms, 95 %CI 0.9 to +15.6 ms, p = 0.035] and the [Formula: see text] interval (+4.2 (8.2) ms, 95 %CI +1.6 to +6.8 ms, p = 0.002). There were no significant changes of the QT(C) and [Formula: see text] intervals during central end-expiratory apnea. These data indicate that simulated obstructive apnea and hypopnea are associated with an increase of premature beats and prolongation of QT(C) and [Formula: see text] intervals. Therefore, negative intrathoracic pressure changes may be a contributory mechanism for the association between OSA and cardiac dysrhythmias.
    Arbeitsphysiologie 07/2012; · 2.15 Impact Factor
  • Article: CrossTalk proposal: Most of the cardiovascular consequences of OSA are due to increased sympathetic activity.
    Malcolm Kohler, John R Stradling
    The Journal of Physiology 06/2012; 590(Pt 12):2813-5; discussion 2823. · 4.72 Impact Factor
  • Article: Rebuttal from malcolm kohler and john R. Stradling.
    Malcolm Kohler, John R Stradling
    The Journal of Physiology 06/2012; 590(Pt 12):2821. · 4.72 Impact Factor
  • Article: Atherosclerosis and arterial stiffness in obstructive sleep apnea--a cardiovascular magnetic resonance study.
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    ABSTRACT: Obstructive sleep apnoea (OSA) has been linked to cardiovascular risk factors, such as hypertension, and clinical cardiovascular endpoints. Our aim was to assess whether OSA is independently associated with atherosclerosis and vascular dysfunction as assessed by cardiovascular magnetic resonance (CMR). 58 patients with OSA and 39 matched control subjects without OSA underwent CMR of the aorta and carotid arteries. Carotid and aortic wall thickness and aortic distensibility were measured. Multi-weighted, high resolution CMR imaging was used for carotid atheroma characterization according to the American Heart Association (AHA) atheroma classification, modified for CMR. Carotid [1.47±0.03 mm vs. 1.26±0.05 mm, (P<0.01)] and aortic wall thickness [2.95±0.09 mm vs. 2.05±0.07 mm, (P<0.001)] were increased in patients with OSA compared to controls. Aortic distensibility was decreased in patients with OSA [3.62±0.3 vs. 4.75±0.2 mmHg(-1)×10(-3), (P<0.05)]. Prevalence of carotid plaque, average carotid atheroma class, and prevalence of high risk features of carotid atheroma were increased in patients with OSA (P<0.005 for all). On multivariate analysis, Oxygen desaturation index (ODI) emerged as an independent predictor of carotid and aortic wall thickness, but not of aortic stiffness. OSA is associated with increased carotid and aortic atheroma burden and with advanced, high risk carotid atherosclerotic plaques, but not with aortic stiffening.
    Atherosclerosis 04/2012; 222(2):483-9. · 3.79 Impact Factor
  • Article: Cardiac Autonomic Function and Cardiovascular Response to Exercise in Patients with Chronic Obstructive Pulmonary Disease
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    ABSTRACT: Background: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. Objective: To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. Methods: Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. Results: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV1%predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV1 and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV1 were independent predictors of exercise capacity in patients with COPD. Conclusions: In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.
    03/2012; 9(2):160-165.
  • Article: The effects of continuous positive airway pressure therapy withdrawal on cardiac repolarization: data from a randomized controlled trial.
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    ABSTRACT: The preliminary evidence supports an association between obstructive sleep apnoea (OSA), disturbed cardiac repolarization, and consequent cardiac dysrhythmias. The aim of the current trial was to assess the effects of continuous positive airway pressure (CPAP) therapy withdrawal on the measures of cardiac repolarization in patients with OSA. Forty-one OSA patients established on CPAP treatment were randomized to either CPAP withdrawal (subtherapeutic CPAP) or continue therapeutic CPAP for 2 weeks. Polysomnography was performed, and indices of cardiac repolarization (QT(c), TpTe(c) intervals) and dispersion of repolarization (TpTe/QT ratio) were derived from 12-lead electrocardiography (ECG) at baseline and 2 weeks. Continuous positive airway pressure withdrawal led to a recurrence of OSA. Compared with therapeutic CPAP, subtherapeutic CPAP for 2 weeks was associated with a significant increase in the length of the QT(c) and TpTe(c) intervals (mean difference between groups 21.4 ms, 95% CI 11.3-1.6 ms, P < 0.001 and 14.4 ms, 95% CI 7.2-21.5 ms, P < 0.001, respectively) and in the TpTe/QT ratio (mean difference between groups 0.02, 95% CI 0.00-0.03, P = 0.020). There was a statistically significant correlation between the change in apnoea/hypopnoea index (AHI) from baseline, and both the change in the QT(c) interval and the TpTe(c) interval (r = 0.60, 95% CI 0.36-0.77, P < 0.001 and r = 0.45, 95% CI 0.17-0.67, P = 0.003, n = 41, respectively). Continuous positive airway pressure withdrawal is associated with the prolongation of the QT(c) and TpTe(c) intervals and TpTe/QT ratio, which may provide a possible mechanistic link between OSA, cardiac dysrhythmias, and thus sudden cardiac death.
    European Heart Journal 03/2012; 33(17):2206-12. · 10.48 Impact Factor
  • Article: Vascular dysfunction in chronic obstructive pulmonary disease: current evidence and perspectives.
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    ABSTRACT: The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and comorbidities. COPD has been associated with an increased risk for cardiovascular disease, osteoporosis, cachexia and skeletal muscle weakness. In several large prospective cohort studies, the degree of airflow limitation was an independent predictor of both fatal and nonfatal cardiovascular events, implying a causal relationship between airflow obstruction and vascular disease. The pathomechanisms responsible for this association are mostly unknown. It has been proposed that systemic inflammation, oxidative stress, hypoxia and sympathetic activation may be mechanisms in COPD leading to vascular dysfunction and cardiovascular disease. However, the current evidence of a causal relationship between COPD and vascular dysfunction is insufficient and more data from well-designed studies are urgently needed, hopefully leading to novel therapeutic and preventive approaches in the care of patients with COPD.
    Expert Review of Respiratory Medicine 02/2012; 6(1):37-43.
  • Article: Comparison of photoplethysmographic and arterial tonometry-derived indices of arterial stiffness.
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    ABSTRACT: Arterial tonometry is a method to assess arterial stiffness and has become a valuable tool in the stratification of cardiovascular risk. The arterial tonometry-derived augmentation index (AIx) is a marker of arterial stiffness and an independent predictor of mortality. As the AIx is relatively cumbersome to obtain, simpler methods such as analysis of pulse waves obtained by digital photoplethysmography have been proposed to estimate arterial stiffness. The objective of this study is to compare the usefulness of the stiffness index (SI) derived from digital photoplethysmography and the AIx derived from radial tonometry for stratification of cardiovascular risk. We studied 83 subjects with a heterogeneous cardiovascular risk profile and determined the ability of the two devices to differentiate subjects with low from subjects with high cardiovascular risk estimated by the Europe (EU)-heart score. Failure rate in both devices was similar (3.6%). AIx and SI were modestly correlated (r=0.48, P<0.001) and both indexes correlated with the EU-score (r=0.54, P<0.001) and (r=0.56, P<0.001), respectively. Both devices discriminated accurately between subjects with high cardiovascular risk (upper tertile of the EU-score) and low cardiovascular risk (lower tertile). However, only the SI differentiated significantly between subjects with intermediate risk (middle tertile) and high risk (upper tertile). Compared with the AIx, assessment of the SI derived by digital photoplethysmography is simple and possibly yields an advantage in risk stratification of subjects with intermediate and high cardiovascular risk. Therefore, digital pulse wave analysis may be a valuable tool to estimate arterial stiffness in large clinical studies.
    Hypertension Research 02/2012; 35(2):228-33. · 2.58 Impact Factor
  • Article: Cardiac autonomic function and cardiovascular response to exercise in patients with chronic obstructive pulmonary disease.
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    ABSTRACT: Chronic obstructive pulmonary disease (COPD) is associated with impaired exercise tolerance, but it has not been established to what extent cardiac autonomic function impacts on exercise capacity. To evaluate whether there is an association between airflow limitation and cardiac autonomic function and whether cardiac autonomic function plays a role in exercise intolerance and daily physical activity (PA) in patients with COPD. Univariate and multivariate analyses were performed to evaluate the association between both 6-minute walking test (6MWT) and PA (steps per day) and pulmonary function, cardiac autonomic function (HR at rest, HRR and heart rate variability, HRV) in patients with COPD. Results: In 154 COPD patients (87 females, mean [SD]: age 62.5 [10.7] years, FEV(1) %predicted (43.0 [19.2]%), mean HR at rest was elevated (86.4 [16.4] beats/min) and HRV was reduced (33.69 [28.96] ms) compared to published control data. There was a significant correlation between FEV(1) and HR at rest (r = -0.32, p < 0.001), between HR at rest and 6MWD (r = -0.26, p = 0.001) and between HR at rest and PA (r = -0.29, p = 0.010). No correlation was found between HRV and 6MWD (r = 0.089, p = 0.262) and PA (r = 0.075, p = 0.322). In multivariate analysis both HR and FEV(1) were independent predictors of exercise capacity in patients with COPD. In patients with COPD the degree of airflow limitation is associated with HR at rest. The degree of airflow limitation and cardiac autonomic function, as quantified by HR at rest, are independently associated with exercise capacity in patients with COPD.
    COPD Journal of Chronic Obstructive Pulmonary Disease 01/2012; 9(2):160-5. · 1.79 Impact Factor
  • Article: Predicting daily physical activity in patients with chronic obstructive pulmonary disease.
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    ABSTRACT: Objectively measuring daily physical activity (PA) using an accelerometer is a relatively expensive and time-consuming undertaking. In routine clinical practice it would be useful to estimate PA in patients with chronic obstructive pulmonary disease (COPD) with more simple methods. To evaluate whether PA can be estimated by simple tests commonly used in clinical practice in patients with COPD. The average number of steps per day was measured for 7 days with a SenseWear Pro™ accelerometer and used as gold standard for PA. A physical activity level (PAL) of <1.4 was considered very inactive. Univariate and multivariate analyses were used to examine the relationship between the 6-minute walking distance (6MWD), the number of stands in the Sit-to-Stand Test (STST), hand-grip strength and the total energy expenditure as assessed by the Zutphen Physical Activity Questionnaire (TEE(ZPAQ)). ROC curve analysis was used to identify patients with an extremely inactive lifestyle (PAL<1.4). In 70 patients with COPD (21 females) with a mean [SD] FEV(1) of 43.0 [22.0] %predicted, PA was found to be significantly and independently associated with the 6MWD (r = 0.69, 95% CI 0.54 to 0.80, p<0.001), STST (r = 0.51, 95% CI 0.31 to 0.66, p = 0.001) and TEEZPAQ (r = 0.50, 95% CI 0.30 to 0.66, p<0.001) but not with hand-grip strength. However, ROC curve analysis demonstrated that these tests cannot be used to reliably identify patients with an extremely inactive lifestyle. In patients with COPD simple tests such as the 6-Minute Walk Test, the Sit-to-Stand Test and the Zutphen Physical Activity Questionnaire cannot be used to reliably predict physical inactivity.
    PLoS ONE 01/2012; 7(11):e48081. · 4.09 Impact Factor
  • Article: Neonatal cyanosis due to a new (G)γ-globin variant causing low oxygen affinity: Hb F-Sarajevo [(G)γ102(G4)Asn→Thr, AAC>ACC].
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    ABSTRACT: A baby girl, born at term, presented with severe cyanosis and received oxygen supplementation. Consecutive arterial blood gas analysis showed a pronounced right shift of the saturation curve, suggesting the presence of a hemoglobin (Hb) variant. A new (G)γ-globin variant was detected, namely HBG2:c.308G, which we have named Hb F-Sarajevo, the city from where the baby's parents originate. This A to C transversion exists in cis to the common (A)γ(T) and the resulting mutant Hb molecule exhibits very low oxygen affinity and cooperativity. Its analogue in the β-globin gene is Hb Kansas [β102(G4)Asn→Thr, AAC>ACC].
    Hemoglobin 01/2012; 36(2):109-13. · 1.30 Impact Factor