Stress, Anxiety and Depressive Symptoms are Predictors of Worse Outcomes in Outpatients With Arterial Hypertension and Coronary Heart Disease: Results of 1.5 Years Follow-up From the COMETA Multicenter Study.

Aim      To study associations between the risk of severe adverse cardiovascular outcomes (SACVO) and all-cause death with psychosocial risk factors (PS RFs), such as stress, anxiety and depressive symptoms, low level of education, low income, social isolation, and type D personality, in patients with arterial hypertension (AH) and ischemic heart disease (IHD) managed in primary health care institutions in a multi-year prospective study.Material and methods  PS RFs were assessed in patients with AH or IHD, who participated in a multi-year prospective COMETA study, using the Hospital Anxiety and Depression Scale (HADS), DS-14 questionnaire, and a visual analogue scale (VAS) for assessment of stress level. Associations of PS FRs with SACVO and all-cause death after a 1.5-year follow-up were analyzed using multivariate Cox regression models.Results At 1.5 years after patients were included in the study, it was possible to obtain data for 2,538 patients (age at baseline, 66.6 ± 7.8 years, 28.1% men), 106 of whom died during that period. The incidence of SACVO was 40.0 per 1000 person-years. According to the results of multivariate regression analysis, a very high level of anxiety symptoms (HADS-A≥14) was significantly associated with SACVO (odds ratio (OR), 1.81; 95% confidence interval (CI), 1.04-3.15; p=0. 02). The composite endpoint that included all-cause death and/or SACVO was significantly associated with a high (VAS score ≥8) stress level (OR, 1.53; 95% CI, 1.00-2.33; p=0.04) and a very high (HADS-D≥14) level of depressive symptoms (OR, 2.11; 95% CI, 1.22-3.62; p=0.02). A low level of education adjusted for gender and age increased the likelihood of SACVO by 1.7 (95% CI, 1.19-2.43) times. No significant associations were found between the analyzed outcomes and type D personality or with social isolation.Conclusion      In patients with AH or IHD, the presence of high-grade stress and severe depressive symptoms increased the likelihoods of all-cause death and SACVO while a low level of education and severe anxiety symptoms were associated with SACVO. The study results showed that PS RFs for cardiovascular diseases keep the PS RF prognostic significance in the conditions of modern treatment of AH and IHD. Due to the negative impact on the prognosis, PS RFs should be taken into account when taking measures for secondary prevention of AH and IHD.

[Psychosocial Aspects in Cardiac Rehabilitation: From Theory to Practice. A Position Paper From the Cardiac Rehabilitation Section of The European Association of Cardiovascular Prevention and Rehabilitation of the European Society of Cardiology].

A large body of empirical research shows that psychosocial risk factors (PSRFs) such as low socio-economic status, social isolation, stress, type-D personality, depression and anxiety increase the risk of incident coronary heart disease (CHD) and also contribute to poorer health-related quality of life (HRQoL) and prognosis in patients with establishedCHD. PSRFs may also act as barriers to lifestyle changes and treatment adherence and may moderate the effects of cardiac rehabilitation (CR). Furthermore, there appears to be a bidirectional interaction between PSRFs and the cardiovascular system. Stress, anxiety and depression affect the cardiovascular system through immune, neuroendocrine and behavioural pathways. In turn, CHD and its associated treatments may lead to distress in patients, including anxiety and depression. In clinical practice, PSRFs can be assessed with single-item screening questions, standardised questionnaires, or structured clinical interviews. Psychotherapy and medication can be considered to alleviate any PSRF-related symptoms and to enhance HRQoL, but the evidence for a definite beneficial effect on cardiac endpoints is inconclusive. A multimodal behavioural intervention, integrating counselling for PSRFs and coping with illness should be included within comprehensive CR. Patients with clinically significant symptoms of distress should be referred for psychological counselling or psychologically focused interventions and/or psychopharmacological treatment. To conclude, the success of CR may critically depend on the interdependence of the body and mind and this interaction needs to be reflected through the assessment and management of PSRFs in line with robust scientific evidence, by trained staff, integrated within the core CR team.

Data-driven healthcare: from patterns to actions.

The era of big data opens up new opportunities in personalised medicine, preventive care, chronic disease management and in telemonitoring and managing of patients with implanted devices. The rich data accumulating within online services and internet companies provide a microscope to study human behaviour at scale, and to ask completely new questions about the interplay between behavioural patterns and health. In this paper, we shed light on a particular aspect of data-driven healthcare: autonomous decision-making. We first look at three examples where we can expect data-driven decisions to be taken autonomously by technology, with no or limited human intervention. We then discuss some of the technical and practical challenges that can be expected, and sketch the research agenda to address them.

Plasma levels of mannan-binding lectin (MBL)-associated serine proteases (MASPs) and MBL-associated protein in cardio- and cerebrovascular diseases.

Growing evidence suggests a prominent role of the complement system in the pathogenesis of cardio- and cerebrovascular diseases (CVD). Mannan-binding lectin-associated serine proteases (MASPs) MASP-1 and MASP-2 of the complement lectin pathway contribute to clot formation and may represent an important link between inflammation and thrombosis. MBL-associated protein MAp44 has shown cardioprotective effects in murine models. However, MAp44 has never been measured in patients with CVD and data on MASP levels in CVD are scarce. Our aim was to investigate for the first time plasma levels of MAp44 and MASP-1, -2, -3 concomitantly in patients with CVD. We performed a pilot study in 50 healthy volunteers, in stable coronary artery disease (CAD) patients with one-vessel (n = 51) or three-vessel disease (n = 53) and age-matched controls with normal coronary arteries (n = 53), 49 patients after myocardial infarction (MI) and 66 patients with acute ischaemic stroke. We measured MAp44 and MASP-1 levels by in-house time-resolved immunofluorometric assays. MASP-2 and MASP-3 levels were measured using commercial enzyme-linked immunosorbent assay kits. MASP-1 levels were highest in subacute MI patients and lowest in acute stroke patients. MASP-2 levels were lower in MI and stroke patients compared with controls and CAD patients. MASP-3 and MAp44 levels did not differ between groups. MASP or MAp44 levels were not associated with severity of disease. MASP and MAp44 levels were associated with cardiovascular risk factors including dyslipidaemia, obesity and hypertension. Our results suggest that MASP levels may be altered in vascular diseases. Larger studies are needed to confirm our results and elucidate the underlying mechanisms.

[The Swiss approach for cardiac rehabilitation]. / Der Schweizer Weg der kardiologischen Rehabilitation.

Structured cardiac rehabilitation goes back to the late 1960s also in Switzerland and in the beginning was only available in rehabilitation clinics. In 1972 the first ambulatory rehabilitation programs became available to patients in Zurich and Bern. In the following years, in addition to the increasing number of rehabilitation centers for inpatients, more and more ambulatory rehabilitation programs were developed, especially in the larger Midlands population area in German and French-speaking Switzerland. In 1985 the Swiss Working Group of Cardiac Rehabilitation (SAKR) was initiated as an official working group of the Swiss Society of Cardiology and one of its first tasks was to establish a list of the institutions for cardiac rehabilitation in Switzerland. At that time there were 42 rehabilitation programs for a population of approx. 6.5 million, 21 for inpatients and 21 ambulatory; however, 90% of the patients were in inpatient programs. In 1992 the SAKR group defined the quality criteria which were to be applied for official recognition of institutions for cardiac rehabilitation in Switzerland. Due to these criteria, plus the fact that an increasing number of rehabilitation clinics in the mountains had been closed down, the number of inpatient rehabilitation centers decreased from 21 to 11 between 1989 and 2011, whereas the number of ambulatory programs increased from 21 to 51. The ambulatory rehabilitation centers are partially organized by local medical groups; however, most have integrated their activities into the local hospitals. The trend shows a developing preference for ambulatory rehabilitation. More and more elderly, polymorbid patients, however, will still need care in inpatient programs.

Long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication.

UNLABELLED: Supervised exercise training has been shown to improve walking capacity in several studies of patients with intermittent claudication. However, data on long-term outcome are quite limited. The aim of this prospective study was to evaluate long-term effects of supervised exercise training on walking capacity and quality of life in patients with intermittent claudication. PATIENTS AND METHODS: Sixty-seven consecutive patients with intermittent claudication who completed a supervised 12-week exercise training program were asked for follow up evaluation 39 +/- 20 months after program completion. Pain-free walking distance (PWD) and maximum walking distances (MWD) were assessed by treadmill test and several questionnaires. RESULTS: Forty (60%) patients agreed to participate, 22 (33%) refused participation, and 5 (7%) died during follow-up. PWD and MWD significantly improved at completion of 12-weeks supervised exercise training as compared to baseline (PWD 114 +/- 100 vs. 235 +/- 248, p = 0.002; MWD 297 +/- 273 vs. 474 +/- 359, p = 0.001). Improvement of PWD and MWD could be maintained at follow up (197 +/- 254, p = 0.014; 390 +/- 324, p = 0.035, respectively) with non-smokers showing significantly better sustained PWD and MWD improvement as compared to baseline. Overall, walking capacity correlated with functional status of quality of life. CONCLUSIONS: Major findings of this investigation were that improvement in walking capacity is sustained after completion of supervised exercise training program with best results in patients who quitted or never smoked. Improved walking capacity is associated with increased functional status of quality of life.

[Manifestation and course of coronary heart disease in men and women--consequences for diagnosis and treatment]. / Manifestation und Verläufe der koronaren Herzkrankheit bei Männern und Frauen--Konsequenzen für Diagnose und Therapie.

Gender related issues in manifestation, diagnosis and treatment of coronary artery disease are important but still not well recognized. Women are more likely to present late after first symptoms of myocardial infarction. Myocardial infarction is more often unrecognized. In regard to complications after myocardial infarctions ventricular tachycardia and cardiac arrest are more frequent and women are also more likely to develop heart failure or cardiogenic shock. The reason for this is most probably the fact that women presenting with myocardial infarction are of older age and have a higher incidence of co-morbidities. Thrombolysis and coronary angioplasty are less often performed in women in the setting of myocardial infarction. However there is a clear trend toward improvement of this situation during the last years. The reopening rate of occluded coronary arteries with thrombolysis and with coronary angioplasty is similar in women compared to men. Perioperative risk with aorto-coronary bypass surgery is higher in women, which can not be fully explained by higher age and co-morbidities. However 10 years survival rate after aorto-coronary bypass-surgery is similar for men and women, although occlusion of venous grafts is seen more often in women. The benefit of structured cardiac rehabilitation after an acute event is similar for younger and older women and as good as in men. Positive effects of cardiac rehabilitation include increased physical performance, reduction of body fat, improvement of lipid-profiles and an improvement of the psychosocial situation and quality of life.

Safety and exercise tolerance of acute high altitude exposure (3454 m) among patients with coronary artery disease.

OBJECTIVES: To assess the safety and cardiopulmonary adaptation to high altitude exposure among patients with coronary artery disease. METHODS: 22 patients (20 men and 2 women), mean age 57 (SD 7) years, underwent a maximal, symptom limited exercise stress test in Bern, Switzerland (540 m) and after a rapid ascent to the Jungfraujoch (3454 m). The study population comprised 15 patients after ST elevation myocardial infarction and 7 after a non-ST elevation myocardial infarction 12 (SD 4) months after the acute event. All patients were revascularised either by percutaneous coronary angioplasty (n = 15) or by coronary artery bypass surgery (n = 7). Ejection fraction was 60 (SD 8)%. beta blocking agents were withheld for five days before exercise testing. RESULTS: At 3454 m, peak oxygen uptake decreased by 19% (p < 0.001), maximum work capacity by 15% (p < 0.001) and exercise time by 16% (p < 0.001); heart rate, ventilation and lactate were significantly higher at every level of exercise, except at maximum exertion. No ECG signs of myocardial ischaemia or significant arrhythmias were noted. CONCLUSIONS: Although oxygen demand and lactate concentrations are higher during exercise at high altitude, a rapid ascent and submaximal exercise can be considered safe at an altitude of 3454 m for low risk patients six months after revascularisation for an acute coronary event and a normal exercise stress test at low altitude.

[Stress as a cardiovascular risk factor]. / Stress als kardiovaskulärer Risikofaktor.

Stress is a reaction of the organism to a stressor with various negative health consequences including the development of arteriosclerosis. Stress may cause myocardial ischemia, rhythm disturbances, platelet stimulation, increased blood viscosity through hemoconcentration as well as endothelial dysfunction and coronary vasoconstriction in the presence of arteriosclerosis of the coronary arteries. Psychosocial risk factors may also lead to the development and to clinical consequences of arteriosclerosis. The five most important psychosocial risk factors are: depression, anxiety, personality factors, social isolation and chronic life stress. Various components are responsible for the fact that life events or certain psychosocial factors can lead to a stress reaction. Psychosocial risk factors have direct pathophysiologic effects but also influence life style and behavior Various stress management intervention programs have proven to be effective. Psychosocial intervention in conjunction with cardiac rehabilitation programs has shown to reduce cardiovascular morbidity and mortality.

[Cardiovascular system and aging]. / Herz und Gefasse.

Aging is one of the most important cardiovascular risk factors. Age-related morphologic changes in large resistance vessels include an intima-media-thickening and increased deposition of matrix substance, ultimately leading to a reduced compliance and an increased stiffness of the vessels. Aging of the heart is mainly characterized by an increase of the left ventricular mass in relation to the chamber volume and a decrease of diastolic function. There is some controversy in regard to the question if these changes in the vessel wall are the consequence of aging or if a decrease in physical activity is a major contributor of this process. With age the cardiovascular profile is changing. Whereas smoking is less prominent, arterial hypertension and diabetes mellitus are more often encountered. Primary and secondary prevention through cardiovascular risk factor management is also very important in the aging population due to the increased risk of acute vascular complications with age. Preventive measures have to include life style factor interventions as well as optimized drug therapy. There is no scientific evidence that vascular aging can be prevented by administration of supplements such as antioxidant vitamins. Aspirin is effective for cardiovascular prevention up to a higher age. Betablockers and ACE-inhibitors are generally underused in older patients after myocardial infarctions. Statins are effective in reducing cardiovascular complications up to an age of 80 years. Myocardial infarction in elderly patients is often characterized by atypical symptoms and may be even silent. Interventional therapy in elderly patients is as successful as in younger patients but has an increased complication rate. Ambulatory cardiac rehabilitation in elderly patients leads to significant improvements of physical capacity, well-being and quality of life and may help to prevent social isolation.

Eccentric endurance training in subjects with coronary artery disease: a novel exercise paradigm in cardiac rehabilitation?

This study evaluated the effects of 8 weeks of eccentric endurance training (EET) in male subjects (age range 42-66 years) with coronary artery disease (CAD). EET was compared to concentric endurance training (CET) carried out at the same metabolic exercise intensity, three times per week for half an hour. CET ( n=6) was done on a conventional cycle ergometer and EET ( n=6) on a custom-built motor-driven ergometer. During the first 5 weeks of the training program the metabolic load was progressively increased to 60% of peak oxygen uptake in both groups. At this metabolic load, mechanical work rate achieved was 97 (8) W [mean (SE)] for CET and 338 (34) W for EET, respectively. Leg muscle mass was determined by dual-energy X-ray absorptiometry, quadriceps strength with an isokinetic dynamometer and muscle fibre composition of the vastus lateralis muscle with morphometry. The leg muscle mass increased significantly in both groups by some 3%. Strength parameters of knee extensors improved in EET only. Significant changes of +11 (4.9)%, +15 (3.2)% and +9 (2.5)% were reached for peak isometric torque and peak concentric torques at 60 degrees s(-1) and 120 degrees s(-1), respectively. Fibre size increased significantly by 19% in CET only. In conclusion, the present investigation showed that EET is feasible in middle-aged CAD patients and has functional advantages over CET by increasing muscle strength. Muscle mass increased similarly in both groups whereas muscle structural composition was differently affected by the respective training protocols. Potential limitations of this study are the cautiously chosen conditioning protocol and the restricted number of subjects.

Physical activity for primary and secondary prevention. Position paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology.

There is now clear scientific evidence linking regular aerobic physical activity to a significant cardiovascular risk reduction, and a sedentary lifestyle is currently considered one of the five major risk factors for cardiovascular disease. In the European Union, available data seem to indicate that less than 50% of the citizens are involved in regular aerobic leisure-time and/or occupational physical activity, and that the observed increasing prevalence of obesity is associated with a sedentary lifestyle. It seems reasonable therefore to provide institutions, health services, and individuals with information able to implement effective strategies for the adoption of a physically active lifestyle and for helping people to effectively incorporate physical activity into their daily life both in the primary and the secondary prevention settings. This paper summarizes the available scientific evidence dealing with the relationship between physical activity and cardiovascular health in primary and secondary prevention, and focuses on the preventive effects of aerobic physical activity, whose health benefits have been extensively documented.

Secondary prevention through cardiac rehabilitation: position paper of the Working Group on Cardiac Rehabilitation and Exercise Physiology of the European Society of Cardiology.

The purpose of this statement is to provide specific recommendations in regard to evaluation and intervention in each of the core components of cardiac rehabilitation (CR) to assist CR staff in the design and development of their programmes; the statement should also assist health care providers, insurers, policy makers and consumers in the recognition of the comprehensive nature of such programmes. Those charged with responsibility for secondary prevention of cardiovascular disease, whether at European, at national or at individual centre level, need to consider where and how structured programmes of CR can be delivered to the large constituency of patients now considered eligible for CR.

Effects of exercise training program on functional capacity and quality of life in patients with peripheral arterial occlusive disease. Evaluation of a pilot project.

BACKGROUND: In patients with peripheral arterial occlusive disease (PAOD) stage II, exercise training seems to be important to reduce symptoms and improve functional capacity. We evaluated the effects of an out-patient treatment program on walking distance (standardized treadmill testing), training exercise capacity, and disease specific quality of life (PAVK-86 questionnaire). METHODS AND RESULTS: Thirty-one patients aged 70 +/- 2 with intermittent claudicatio in stage IIa/IIb according to Fontaine (n = 18/13) underwent a supervised 12 week exercise training and education outpatient program. During course of intervention, patients demonstrated improvements in pain-free training walking distance (p < 0.001) and repetitions of tiptoe standing (p < 0.05). In standardized treadmill testing, pain-free walking distance was improved by 182% (129 +/- 19 m-->364 +/- 53 m; p < 0.001), and maximum walking distance by 76% (311 +/- 42 m-->546 +/- 63 m; p < 0.01). Before training, mean subscale scores of the PAVK-86 demonstrated distinct impairments concerning pain and functional status. After 12 weeks of intervention, with exception of the subscale complaints, all dimensions of quality of life assessed have improved significantly. The highest effect size was observed for the subscales pain, mood, and functional status. Improvement in the subscale anxiety and pain-free walking distance (treadmill test) correlated significantly (r = 0.46) as well as improvement in the subscale mood and maximum walking distance (r = 0.45). CONCLUSION: In patients with PAOD stage II considerable effects on functional capacity and important dimensions of quality of life can be achieved by a short exercise and education program.

Comparison of 99mTc-sestamibi lung/heart ratio, transient ischaemic dilation and perfusion defect size for the identification of severe and extensive coronary artery disease.

The ability to identify patients with severe coronary artery disease (CAD) by analysis of perfusion defects is limited. The lung/heart ratio (LHR) and transient ischaemic dilatation (TID) have been used for this purpose in thallium-201 scintigraphy. The value of these parameters in technetium-99m sestamibi single-photon emission tomography (SPET) imaging is controversial. In this study, therefore, we determined TID and LHR in a single-day rest/stress 99mTc-sestamibi SPET perfusion protocol and compared these measurements with perfusion defect size (PDS) and angiographic severity of CAD. Severe CAD was defined as >75% left main coronary stenosis and/or >90% proximal left anterior descending artery stenosis and/or >90% proximal stenosis in the left circumflex and right coronary arteries. LHR was determined from a stress anterior planar image recorded < or =6 min after exercise. TID ratio was derived from automatically calculated left ventricular rest/stress volumes, and PDS was measured based on semi-automated computer software (CEqual). Diagnostic accuracy and predictive values were compared between 22 patients with severe and 98 patients without severe CAD. LHRs showed a higher sensitivity (73%) for the assessment of severe CAD as compared to PDS and TID ratio (41% and 23% respectively, P<0.01), whereas specificity was highest for TID ratio [95%, P<0.01 when compared to PDS (84%) and LHR (82%)]. It is concluded that increased LHR in 99mTc-sestamibi myocardial perfusion imaging seems to yield good diagnostic accuracy in the detection of patients with severe CAD and may be derived from a single-day rest/stress study.

Approximations for trimmed Fisher procedures in research synthesis.

When combining the results of independent studies it often happens that some studies are potentially aberrant either in quality or in actual values. Because aberrant studies are often at the extremes, we may wish to trim some of the largest and smallest effects. In such a case the use of p-values may well serve as a diagnostic method. However, the use of ordered effects changes the distribution of the underlying statistics. We provide a discussion of the exact distribution of the trimmed version of the Fisher procedure. Because of the complexity of the exact distribution, several approximations are presented. These alternatives are applied to a meta-analysis on the effect of the dose of a drug on the risk of mortality.

[Patient self-monitoring of oral anticoagulation with CoaguChek]. / Patienten-Selbstkontrolle der oralen Antikoagulation mit CoaguChek.

We investigated the feasibility, quality and safety of patient self-control of oral anticoagulation. The patients were selected by their physicians on the basis of criteria such as compliance, skills and motivation. After theoretical and practical training they self-monitored and self-adjusted their anticoagulant dosage for 6 months by weekly self-measurement of their INR values using a capillary whole blood prothrombin time monitor (CoaguChek). Venous INR measurements once a month served as quality control. There were 51 study participants, who performed a median 5 INR measurements per month. 75.8% of all registered INR values were within the recommended individual INR target ranges. The coefficient of correlation between capillary (y) and venous (x) INR values was r = 0.87 (regression analysis y = 1.0 x -0.2). The concordance of capillary and venous INR values was 80% with respect to the individual INR target ranges. There were 5 minor bleeding episodes and no overt thromboembolic recurrences during the study period. In conclusion, the study demonstrated that patient self-control of oral anticoagulation is feasible and achieves a high percentage of INR values within the recommended target ranges. Therefore, self-control of oral anticoagulation can be offered to skilled and motivated patients as an alternative to physician-guided antiocogulation. However, specific training of these selected patients is necessary.