Predictive value of Type D personality for impaired endothelial function in patients with coronary artery disease.

BACKGROUND: Type D personality (high negative affectivity and social inhibition) is associated with cardiovascular events and coronary plaque severity. Whether Type D is also related to functional vasomotion abnormalities is unknown. We examined concurrent and predictive associations of Type D with endothelial dysfunction in patients with coronary artery disease (CAD). METHODS: At baseline, 180 CAD patients (90% men; M = 58.0 years) completed Type D (DS14) and depression scales, and entered a 12-week exercise program. Flow-mediated dilation (FMD) of the brachial artery and circulating CD34+/KDR+/CD45+dim endothelial progenitor cells (EPCs) were assessed at baseline, 3 months, and 12 months. Logistic regression and linear mixed models were used to analyze endothelial function. RESULTS: Type D personality was associated with decreased FMD across baseline, 3 months, and 12 months (mixed model analysis, p = 0.04), after adjustment for clinical characteristics, exercise training and depression. There was no significant association between Type D and decreased EPCs (p = 0.07). Age and smoking were other significant correlates of FMD and EPCs. Using a FMD <5.5% cut-off, Type D patients more often had endothelial dysfunction at baseline (24/37 = 65%) than non-Type Ds (63/143 = 44%); OR = 3.03, 95% CI 1.04-8.80. This significant Type D effect was confirmed in prospective analyses of endothelial dysfunction at 12 months (OR = 3.43, 95% CI 1.01-11.64), and in subgroup analyses of male patients. CONCLUSIONS: Type D personality was associated with impaired endothelial function in men with CAD. This association was robust across time, independent from depressive symptoms, and supports the notion that Type D has an adverse effect on cardiovascular health in patients with CAD.

Test-Retest Reliability of Maximal and Submaximal Gas Exchange Variables in Patients With Coronary Artery Disease.

PURPOSE: Gas exchange variables derived from cardiopulmonary exercise tests (CPETs) need to be reliable for evaluating interventions and clinical decision making. Whereas peak oxygen uptake ((Equation is included in full-text article.)O2) has shown to be a highly reliable parameter in patients with coronary artery disease (CAD), little is known about the reproducibility of these parameters in patients with CAD. Therefore, the purpose of this study was to confirm the reliability of peak (Equation is included in full-text article.)O2 and to investigate the reliability of submaximal CPET variables in patients with CAD. METHODS: Eighty-five patients with CAD (57.6 ± 8.5 years; 79 males) performed 2 CPETs within 10 days before starting a rehabilitation program. Reliability of peak and submaximal exercise variables was assessed by using intraclass correlation coefficients (ICC), coefficients of variation, Pearson correlation coefficients, paired t tests, and Bland-Altman plots. RESULTS: Maximal and submaximal exercise parameters showed adequate reliability. Overall, there was a good correlation across both testing occasions (r = 0.63-0.95; P < .05 for all). Peak (Equation is included in full-text article.)O2 (ICC, 0.95; 95% CI, 0.92-0.97) demonstrated excellent reliability. Of the submaximal exercise variables, oxygen uptake efficiency slope (OUES) was as reliable as peak (Equation is included in full-text article.)O2 (ICC, 0.97; 95% CI, 0.95-0.98). The ventilation/carbon dioxide production ((Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2) slope showed very good test-retest reliability (ICC, 0.87; 95% CI, 0.80-0.91) and the (Equation is included in full-text article.)O2/work rate slope showed good reliability (ICC, 0.76; 95% CI, 0.64-0.85). CONCLUSIONS: Both peak (Equation is included in full-text article.)O2 and OUES show excellent test-retest reliability. Accordingly, in the case of no or unreliable peak (Equation is included in full-text article.)O2 data, we suggest using OUES to evaluate cardiorespiratory fitness in patients with CAD.

Peak oxygen uptake, ventilatory efficiency and QRS-duration predict event free survival in patients late after surgical repair of tetralogy of Fallot.

OBJECTIVE: Patients with repaired tetralogy of Fallot (ToF) have an increased long-term risk of cardiovascular morbidity and mortality. Risk stratification in this population is difficult. Initial evidence suggests that cardiopulmonary exercise testing (CPET) may be helpful to risk-stratify patients with repaired ToF. METHODS AND RESULTS: We studied 875 patients after surgical repair for ToF (358 females, age 25.5 ± 11.7 year, range 7-75 years) who underwent CPET between 1999 and 2009. During a mean follow-up of 4.1 ± 2.6 years after CPET, 30 patients (3.4%) died or had sustained ventricular tachycardia (VT). 225 patients (25.7%) had other cardiac related events (emergency admission, surgery, or catheter interventions). On multivariable Cox regression-analysis, %predicted peak oxygen uptake (V˙O2 %) (p=0.001), resting QRS duration (p=0.030) and age (p<0.001) emerged as independent predictors of mortality or sustained VT. Patients with a peak V˙O2 ≤ 65% of predicted and a resting QRS duration ≥ 170 ms had a 11.4-fold risk of death or sustained VT. Ventilatory efficiency expressed as V˙E/V˙CO2 slope (p<0.001), peak V˙O2 % (p=.001), QRS duration (p=.001) and age (p=0.046) independently predicted event free survival. V˙E/V˙CO2 slope ≥ 31.0, peak V˙O2 % ≤ 65% and QRS duration ≥ 170 ms were the cut-off points with best sensitivity and specificity to detect an unfavorable outcome. CONCLUSIONS: CPET is an important predictive tool that may assist in the risk stratification of patients with ToF. Subjects with a poor exercise capacity in addition to a prolonged QRS duration have a substantially increased risk for death or sustained ventricular tachycardia, as well as for cardiac-related hospitalizations.

Usefulness of cardiopulmonary exercise testing to predict the development of arterial hypertension in adult patients with repaired isolated coarctation of the aorta.

BACKGROUND: Patients who underwent surgery for aortic coarctation (COA) have an increased risk of arterial hypertension. We aimed at evaluating (1) differences between hypertensive and non-hypertensive patients and (2) the value of cardiopulmonary exercise testing (CPET) to predict the development or progression of hypertension. METHODS: Between 1999 and 2010, CPET was performed in 223 COA-patients of whom 122 had resting blood pressures of <140/90 mmHg without medication, and 101 were considered hypertensive. Comparative statistics were performed. Cox regression analysis was used to assess the relation between demographic, clinical and exercise variables and the development/progression of hypertension. RESULTS: At baseline, hypertensive patients were older (p=0.007), were more often male (p=0.004) and had repair at later age (p=0.008) when compared to normotensive patients. After 3.6 ± 1.2 years, 29/120 (25%) normotensive patients developed hypertension. In normotensives, VE/VCO2-slope (p=0.0016) and peak systolic blood pressure (SBP; p=0.049) were significantly related to the development of hypertension during follow-up. Cut-off points related to higher risk for hypertension, based on best sensitivity and specificity, were defined as VE/VCO2-slope ≥ 27 and peak SBP ≥ 220 mmHg. In the hypertensive group, antihypertensive medication was started/extended in 48/101 (48%) patients. Only age was associated with the need to start/extend antihypertensive therapy in this group (p=0.042). CONCLUSIONS: Higher VE/VCO2-slope and higher peak SBP are risk factors for the development of hypertension in adults with COA. Cardiopulmonary exercise testing may guide clinical decision making regarding close blood pressure control and preventive lifestyle recommendations.

Predictors of mid-term event-free survival in adults with corrected tetralogy of Fallot.

OBJECTIVES: Patients who underwent corrective surgery for tetralogy of Fallot (TOF) have increased long-term risk of cardiovascular morbidity and mortality. Yet, limited information is available on how to evaluate the risk in this population. Therefore, the aim of this study was to investigate the prognostic value of aerobic exercise capacity, along with other related parameters, at medium-term follow-up in adult patients with tetralogy of Fallot. METHODS AND RESULTS: Between 2000 and 2003, 92 adults (age 26.2 +/- 7.8 years; 63 male) with corrected TOF or TOF-type morphology underwent a cardiopulmonary exercise test (CPET) until exhaustion and echocardiography. During a mean follow-up of 7.3 +/- 1.2 years (range 0.9 to 9.3 years), 2 patients died and 26 patients required at least 1 cardiac-related intervention at a mean age of 28.9 +/- 7.9 years. Event-free survival tended to be higher in patients with the classical type of TOF (P = 0.061). At multivariate Cox analysis, age at CPET [hazard ratio (HR): 1.13, P = 0.006], age at correction (HR: 0.82, P = 0.037), right ventricular (RV) function (HR: 4.94, P = 0.001), QRS duration (HR: 1.02, P = 0.007), percentage of predicted peak oxygen uptake (peak VO2%) (HR: 0.96, P=0.029) and ventilatory efficiency slope (VE/VCO2 slope) (HR: 1.13, P = 0.021) were significantly related to the incidence of death/cardiac-related intervention during medium follow-up. CONCLUSIONS: Early corrective surgery and a well-preserved RV are associated with a better outcome in adults with corrected TOF. Furthermore, CPET provides important prognostic information; peak VO2% and VE/VCO2 slope are independent predictors for event-free survival in patients with corrected TOF.

In adults with atrial switch operation for transposition of the great arteries low physical activity relates to reduced exercise capacity and decreased perceived physical functioning.

OBJECTIVE: Patients with Mustard/Senning repair for transposition of the great arteries (d-TGA) have an impaired exercise capacity, but information about physical activity levels is scarce. The aim of the study was to come to a better understanding of the interrelationships between determinants of exercise capacity, physical activity and self-perceived health status. METHODS AND RESULTS: We studied 39 d-TGA patients who underwent echocardiography and exercise testing, and who completed questionnaires about physical activity and perceived health status. All results were compared with normal values. Stepwise multiple regression analysis was used to assess the determinants of peak V02% and exercise duration. Peak VO2 averaged 64 +/- 14.1% of the predicted normal values, which is significantly lower than expected (P < 0.0001). Physical activity measures as well as perceived general health were significantly lower compared to a reference population (P < 0.05). Peak heart rate and peak oxygen pulse explained together 90% of the variability in exercise duration (model F = 162.72; P < 0.0001). Type of surgery, total energy expenditure and right ventricular contractility were independent predictors of peak VO2% explaining 43% of the variability (model F = 8.75; P = 0.0002). CONCLUSIONS: Impaired peak exercise performance in d-TGA patients results mainly from the inability to increase stroke volume and heart rate at higher exercise intensities. Senning repair and a well-preserved right ventricular function are related to a better peak V02%. Furthermore, an active lifestyle has a positive effect on exercise capacity and perceived physical functioning. Therefore it might be indicated to encourage d-TGA patients to adopt a more physically active lifestyle.

A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study.

BACKGROUND: It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. METHODS: 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO(2) scores. RESULTS: Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were significantly associated with the increase in peakVO(2) after training. CONCLUSIONS: In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO(2).

The CAREGENE study: genetic variants of the endothelium and aerobic power in patients with coronary artery disease.

OBJECTIVES: Aerobic phenotypes show a wide variability to similar aerobic training stimuli, which can be partly attributed to heritability. Endothelial function affects aerobic power. Various physiological pathways may influence the endothelial function. Therefore, we aimed to examine whether polymorphisms of the eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are associated with aerobic power or with its response to physical training in patients with coronary artery disease (CAD). METHODS: 935 biologically unrelated Caucasian patients with CAD who had exercised until exhaustion during graded bicycle testing at baseline and after completion of 3 months of training were included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise performance). Polymorphisms were detected using the invader assay and MassARRAY technology. Haplotype analysis was performed on the polymorphisms of the eNos gene, the VEGF gene and the NAD(P)H-oxidase gene. RESULTS: Physical training significantly increased aerobic power by 24.2 +/- 0.6% (P < 0.001). Associations of P < 0.05 were found between aerobic power and the eNOS 273C>T variant and the catalase -262C>T variant and aerobic power response. Haplotypes of the eNOS polymorhisms were predictive of aerobic power and its response to training (P < 0.05). After Bonferroni correction of multiple testing no significant differences remained. CONCLUSION: We believe that genetic factors are very important in the explanation of the great variability of aerobic power and its response. However, after Bonferroni-correction, differences in these polymorphisms remained no longer statistically significant.

Measuring psychosocial variables in patients with (sub) acute low back pain complaints, at risk for chronicity: a validation study of the Acute Low Back Pain Screening Questionnaire-Dutch Language Version.

STUDY DESIGN: A validation study of the Acute Low Back Pain Screening Questionnaire Dutch Language Version (ALBPSQ-DLV). OBJECTIVE: To determine internal consistency, construct and convergent validity of the ALBPSQ-DLV in a population of patients with (sub) acute low back pain (LBP) referred to primary care physical therapy in The Netherlands. SUMMARY OF BACKGROUND DATA: Viewing LBP as a multifactorial biopsychosocial syndrome enhances the need for validating instruments for screening psychosocial variables in patients with LBP. The ALBPSQ has been specifically constructed as a self-administered screening instrument, based on variables that have been suggested as a risk factor in the literature. METHODS: A total of 69 patients with (sub) acute LBP were recruited. Internal consistency of the ALBPSQ-DLV was determined by calculating Cronbach alpha. Construct validity was determined by applying exploratory factor analysis. Convergent validity was assessed by calculating Pearson's correlation coefficients between domains of ALBPSQ-DLV and Dutch language versions of the Fear Avoidance Beliefs Questionnaire, Tampa Scale for Kinesiophobia, Pain Coping Inventory, Quebec Back Pain Disability Scale, and the Visual Analogue Scale of pain intensity. RESULTS: Internal consistency of the ALBPSQ-DLV was 0.81. Values of the various subscales ranged between 0.48 and 0.88. Convergent validity was confirmed by moderate to good correlation coefficients (P = 0.01) between the scores on the subscales and the constructs of pain, disability, fear-avoidance beliefs, kinesiophobia, and coping (r = 0.38-0.64). Exploratory factor analysis, suppressing absolute values less than 0.40, revealed components which were in agreement with the various domains of the original ALBPSQ. CONCLUSION: The internal consistency and both construct and convergent validity of the ALBPSQ-DLV are well established in a Dutch population of 69 patients with (sub) acute nonspecific LBP referred to primary care physical therapy.

The TUBB1 Q43P functional polymorphism reduces the risk of cardiovascular disease in men by modulating platelet function and structure.

The discoid form of platelets is maintained by a marginal band of tightly coiled microtubules. beta1-tubulin is the major isoform within platelet and megakaryocyte microtubules. In 24.2% of 33 unrelated inherited macrothrombocytopenia patients and in 10.6% of 272 subjects of a healthy population a P for Q substitution in beta1-tubulin was found in the highly conserved residue 43. Heterozygous carriers of the Q43P variant showed a reduced platelet protein beta1-tubulin expression. Transfection of green fluorescent protein (GFP)-tagged Q43P beta1-tubulin in megakaryocytic MEG01 cells resulted in a disturbed tubulin organization. Electron microscopy revealed enlarged spherocytic platelets with a disturbed marginal band and organelle-free zones. In addition, platelets with the Q43P beta1-tubulin variant had reduced adenosine triphosphate (ATP) secretion, thrombin receptor activating peptide (TRAP)-induced aggregation and collagen adhesion. The prevalence of the Q43P beta1-tubulin variant was also 2 times higher (odds ratio, [OR] = 2.1;95% confidence interval [CI], 1.22-3.59) among control subjects than among patients with cardiovascular disease (10.4% versus 5.2%, P < .001). By analyzing this protective factor in men and women separately, this association was only found in men. This study thus presents the functional consequences of the platelet Q43P beta1-tubulin substitution that is frequent in the healthy population and may protect men against arterial thrombosis.

Cardiovascular pre-participation screening of young competitive athletes for prevention of sudden death: proposal for a common European protocol. Consensus Statement of the Study Group of Sport Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology.

The 1996 American Heart Association consensus panel recommendations stated that pre-participation cardiovascular screening for young competitive athletes is justifiable and compelling on ethical, legal, and medical grounds. The present article represents the consensus statement of the Study Group on Sports Cardiology of the Working Group on Cardiac Rehabilitation and Exercise Physiology and the Working Group on Myocardial and Pericardial diseases of the European Society of Cardiology, which comprises cardiovascular specialists and other physicians from different European countries with extensive clinical experience with young competitive athletes, as well as with pathological substrates of sudden death. The document takes note of the 25-year Italian experience on systematic pre-participation screening of competitive athletes and focuses on relevant issues, mostly regarding the relative risk, causes, and prevalence of sudden death in athletes; the efficacy, feasibility, and cost-effectiveness of population-based pre-participation cardiovascular screening; the key role of 12-lead ECG for identification of cardiovascular diseases such as cardiomyopathies and channelopathies at risk of sudden death during sports; and the potential of preventing fatal events. The main purpose of the consensus document is to reinforce the principle of the need for pre-participation medical clearance of all young athletes involved in organized sports programmes, on the basis of (i) the proven efficacy of systematic screening by 12-lead ECG (in addition to history and physical examination) to identify hypertrophic cardiomyopathy-the leading cause of sports-related sudden death-and to prevent athletic field fatalities; (ii) the potential screening ability in detecting other lethal cardiovascular diseases presenting with ECG abnormalities. The consensus document recommends the implementation of a common European screening protocol essentially based on 12-lead ECG.

Determinants of the effects of physical training and of the complications requiring resuscitation during exercise in patients with cardiovascular disease.

BACKGROUND: Benefits of cardiac rehabilitation with exercise therapy are well-established, although individual reactions are heterogeneous. The identification of determinants of training effects is useful from a prognostic point of view, but data regarding this are scarce. Furthermore, limited data exist on the determinants of complications during exercise in cardiac patients. This study aimed to investigate the determinants (1) of training effects in cardiac rehabilitation and (2) of complications requiring resuscitation during exercise activities at the hospital and during continued exercise at a sports club for cardiac patients. DESIGN: Clinical association study. METHODS: Determinants of changes in peak oxygen uptake (VO2) after 3 months of cardiac rehabilitation were determined by multiple regression analysis (n=1909). Determinants of events requiring resuscitation (n=21) were assessed by logistic regression analysis. RESULTS: Improvements in peak VO2 and exercise duration averaged 26%. Eighteen per cent of the variance in absolute improvements of peak VO2 was explained, with age and training characteristics as the strongest determinants. Twenty-one per cent of the variation in relative improvements was explained, with baseline exercise performance and training characteristics being the strongest determinants. The intake of anti-arrhythmics (odds ratio=5.5; P<0.001) and the presence of ST-segment depression (> or =1 mm) at baseline exercise testing (odds ratio=1.6; P<0.001) were predictive for serious complications. The occurrence of events requiring resuscitation was higher at the sports club (1/16,533 versus 1/29,214 patient-hours). CONCLUSIONS: Age, baseline exercise performance and training characteristics were predictive for training effects in cardiac rehabilitation. Anti-arrhythmics and ST-segment depression at baseline exercise testing were predictive for complications.

Depression and the heart: a systematic overview of definition, measurement, consequences and treatment of depression in cardiovascular disease.

Depression is an independent risk factor in the pathogenesis of cardiovascular disease and it is a prevalent disorder after cardiovascular disease associated with negative outcome in terms of mortality and morbidity. It is a dangerous condition requiring adequate screening and treatment, however, it often remains undiagnosed and thus untreated. Non-psychiatric healthcare workers, like nurses, general practitioners, physiotherapists and cardiologists are the health providers most closely involved in the management of patients with cardiovascular disease. They can play an important role in screening cardiovascular patients for depressive symptoms and in referring them for treatment. The purpose of this article therefore is to provide an evidence-based framework, aiming to educate non-psychiatric healthcare providers on depressive disorder in the context of chronic cardiovascular disease. In this paper, an overview of the definition, prevalence and consequences of depression will be discussed. Moreover, an overview of measurement methods and treatment modalities for depression will be provided. In addition, a step-by-step guide is provided in order to help non-psychiatric healthcare providers in dealing with depressed patients.