Medical care and biomarker-based assessment of mortality in two cohorts of patients with chronic coronary syndrome 10 years apart.

BACKGROUND: This study aimed to describe the characteristics and mortality of two cohorts of patients with chronic coronary syndrome (CCS) recruited with identical study designs in the same rehabilitation clinics but approximately 10 years apart. METHODS: The KAROLA cohorts included patients with CCS participating in an inpatient cardiac rehabilitation programme in Germany (KAROLA-I: years 1999/2000, KAROLA-II: 2009-2011). Blood samples and information on sociodemographic factors, lifestyle, and medical treatment were collected at baseline, at the end of rehabilitation, and after one year of follow-up. A biomarker-based risk model (ABC-CHD model) and Cox regression analysis were used to evaluate cardiovascular (CV) and non-CV mortality risk. RESULTS: We included 1130 patients from KAROLA-I (mean age 58.7 years, 84.4% men) and 860 from KAROLA-II (mean age 60.4 years, 83.4% men). Patients in the KAROLA-I cohort had significantly higher concentrations of CV biomarkers and fewer patients were taking CV medications, except for statins. The biomarker-based ABC-CHD model provided a higher estimate of CV death risk for patients in the KAROLA-I cohort (median 3-year risk, 3.8%) than for patients in the KAROLA-II cohort (median 3-year risk, 2.7%, p-value for difference < 0.001). After 10 years of follow-up, 91 (8.1%) patients in KAROLA-I and 45 (5.2%) in KAROLA-II had died from a CV event. CONCLUSIONS: Advances in disease management over the past 20 years may have led to modest improvements in pharmacological treatment during cardiac rehabilitation and long-term outpatient care for patients with CCS. However, modifiable risk factors such as obesity have increased in the more recent cohort and should be targeted to further improve the prognosis of these patients.

The Longer, the Better? An Empirical Study of the Extent and Mechanisms of Attenuating Biomarker Associations in Cardiovascular Patient Cohorts.

BACKGROUND: Identifying novel risk markers in cardiovascular patients remains a research priority. Longer follow-up generally is considered favorable in such studies, but associations of interest may become attenuated with increasing follow-up. This issue has not been adequately addressed in the context of patient cohorts. The current study analyzed the extent and mechanisms of attenuating associations in a cardiovascular patient cohort. METHODS: The associations of numerous biomarkers with all-cause mortality were estimated by multiple Cox regression in the Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung (KAROLA) prospective cohort study of 1204 patients who had participated in an inpatient rehabilitation program after an acute coronary syndrome (ACS) or coronary bypass operation. Hazard ratios were estimated based on the entire follow-up period (13 years), and after truncation at previous follow-up times (3, 4.5, 6, 8, 10 years). RESULTS: For the majority of markers, a clear and sometimes very pronounced attenuation of the hazard ratios could be observed with increasing follow-up duration. Differential attrition generally was not a sufficient explanation for this phenomenon, whereas further analyses suggested a role for reverse causality for some of the markers. Power analyses showed that the relationship of follow-up duration and statistical power can be counterintuitive in the presence of realistic amounts of attenuation. CONCLUSIONS: The attenuation of estimates of association in patient cohorts is a much more substantial and complex issue than currently appreciated. This has important implications for the design and interpretation of prognostic, as well as etiologic, studies which may be particularly relevant in the case of patient cohorts defined by an initial acute event.

Assessing quality of life in a clinical study on heart rehabilitation patients: how well do value sets based on given or experienced health states reflect patients' valuations?

BACKGROUND: Quality of life as an endpoint in a clinical study may be sensitive to the value set used to derive a single score. Focusing on patients' actual valuations in a clinical study, we compare different value sets for the EQ-5D-3L and assess how well they reproduce patients' reported results. METHODS: A clinical study comparing inpatient (n = 98) and outpatient (n = 47) rehabilitation of patients after an acute coronary event is re-analyzed. Value sets include: 1. Given health states and time-trade-off valuation (GHS-TTO) rendering economic utilities; 2. Experienced health states and valuation by visual analog scale (EHS-VAS). Valuations are compared with patient-reported VAS rating. Accuracy is assessed by mean absolute error (MAE) and by Pearson's correlation ρ. External validity is tested by correlation with established MacNew global scores. Drivers of differences between value sets and VAS are analyzed using repeated measures regression. RESULTS: EHS-VAS had smaller MAEs and higher ρ in all patients and in the inpatient group, and correlated best with MacNew global score. Quality-adjusted survival was more accurately reflected by EHS-VAS. Younger, better educated patients reported lower VAS at admission than the EHS-based value set. EHS-based estimates were mostly able to reproduce patient-reported valuation. Economic utility measurement is conceptually different, produced results less strongly related to patients' reports, and resulted in about 20 % longer quality-adjusted survival. CONCLUSION: Decision makers should take into account the impact of choosing value sets on effectiveness results. For transferring the results of heart rehabilitation patients from another country or from another valuation method, the EHS-based value set offers a promising estimation option for those decision makers who prioritize patient-reported valuation. Yet, EHS-based estimates may not fully reflect patient-reported VAS in all situations.

A web-based peer-modeling intervention aimed at lifestyle changes in patients with coronary heart disease and chronic back pain: sequential controlled trial.

BACKGROUND: Traditional secondary prevention programs often fail to produce sustainable behavioral changes in everyday life. Peer-modeling interventions and integration of peer experiences in health education are a promising way to improve long-term effects in behavior modification. However, effects of peer support modeling on behavioral change have not been evaluated yet. Therefore, we implemented and evaluated a website featuring patient narratives about successful lifestyle changes. OBJECTIVE: Our aim is to examine the effects of using Web-based patient narratives about successful lifestyle change on improvements in physical activity and eating behavior for patients with coronary heart disease and chronic back pain 3 months after participation in a rehabilitation program. METHODS: The lebensstil-aendern ("lifestyle-change") website is a nonrestricted, no-cost, German language website that provides more than 1000 video, audio, and text clips from interviews with people with coronary heart disease and chronic back pain. To test efficacy, we conducted a sequential controlled trial and recruited patients with coronary heart disease and chronic back pain from 7 inpatient rehabilitation centers in Germany. The intervention group attended a presentation on the website; the control group did not. Physical activity and eating behavior were assessed by questionnaire during the rehabilitation program and 12 weeks later. Analyses were conducted based on an intention-to-treat and an as-treated protocol. RESULTS: A total of 699 patients were enrolled and 571 cases were included in the analyses (control: n=313, intervention: n=258; female: 51.1%, 292/571; age: mean 53.2, SD 8.6 years; chronic back pain: 62.5%, 357/571). Website usage in the intervention group was 46.1% (119/258). In total, 141 trial participants used the website. Independent t tests based on the intention-to-treat protocol only demonstrated nonsignificant trends in behavioral change related to physical activity and eating behavior. Multivariate regression analyses confirmed belonging to the intervention group was an independent predictor of self-reported improvements in physical activity regularity (ß=.09, P=.03) and using less fat for cooking (ß=.09, P=.04). In independent t tests based on the as-treated protocol, website use was associated with higher self-reported improvements in integrating physical activity into daily routine (d=0.22, P=.02), in physical activity regularity (d=0.23, P=.02), and in using less fat for cooking (d=0.21, P=.03). Multivariate regression analyses revealed that using the website at least 3 times was the only factor associated with improved lifestyle behaviors. CONCLUSIONS: Usage of the lebensstil-aendern website corresponds to more positive lifestyle changes. However, as-treated analyses do not allow for differentiating between causal effects and selection bias. Despite these limitations, the trial indicates that more than occasional website usage is necessary to reach dose-response efficacy. Therefore, future studies should concentrate on strategies to improve adherence to Web-based interventions and to encourage more frequent usage of these programs.

The German CaRe high registry for familial hypercholesterolemia - Sex differences, treatment strategies, and target value attainment.

Background and aims: Familial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. Methods: We evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. Results: Among the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. Conclusions: FH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

Cardiac troponin T measured by a high-sensitivity assay predicts recurrent cardiovascular events in stable coronary heart disease patients with 8-year follow-up.

BACKGROUND: The clinical relevance of slightly increased circulating troponin concentrations in patients with stable coronary heart disease (CHD) several weeks after an acute event or CABG has not been fully evaluated. METHODS: Baseline plasma concentrations of troponin T were measured with a high-sensitivity assay (hs-cTnT) (Roche Elecsys) in a cohort of 1050 CHD patients from 30 to 70 years of age. The prognostic value of hs-cTnT on a combined cardiovascular disease (CVD) end point after adjustment for covariates was determined with Cox proportional hazards modeling. RESULTS: The median hs-cTnT concentration was 10.9 ng/L (interquartile range, 5.1-18.9 ng/L). Increased hs-cTnT concentrations were associated with an older age, history of hypertension and diabetes, more advanced coronary artery disease, and other CHD risk factors. Furthermore, hs-cTnT concentration was strongly correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cystatin C (ρ = 0.61, and ρ = 0.32, respectively; both P values <0.0001). During a median follow-up of 8.1 years, 150 patients (14.3%) experienced a secondary CVD event. In a multivariate model, hs-cTnT was associated with a hazard ratio (HR) for secondary events of 2.83 (95% CI, 1.68-4.79) when the extreme quartiles were compared. Further adjustment for cystatin C, NT-proBNP, and C-reactive protein attenuated this association only slightly (HR, 2.27; 95% CI, 1.31-3.95); P for trend < 0.002). ROC curve analysis of a clinical model that added hs-cTnT to a baseline model showed nonsignificant improvement in the area under the curve (0.69 vs 0.67), whereas the net reclassification improvement was 17.2% (P = 0.029). CONCLUSIONS: Slightly increased hs-cTnT concentrations in stable CHD patients are associated with several cardiovascular disorders and predict long-term CVD events.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 2.

BACKGROUND: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. METHODS: Generation of evidence and search of literature have been described in part 1. RESULTS: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. CONCLUSIONS: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.

Serum vitamin D and risk of secondary cardiovascular disease events in patients with stable coronary heart disease.

BACKGROUND: Recent longitudinal analyses suggested that low levels of serum 25-hydroxyvitamin D (25-OH-D) predict incident cardiovascular disease in initially healthy populations. Because the prognostic value of vitamin D for the occurrence of secondary cardiovascular events remains unclear, we examined the association of baseline 25-OH-D levels with prognosis in patients with stable coronary heart disease (CHD). METHODS: Serum 25-OH-D levels from 1,125 CHD patients of 2 German clinics undergoing a 3-week rehabilitation program after an acute cardiovascular event were measured, and participants were followed for up to 8 years. We used multivariate Cox regression analysis to model cardiovascular event incidence (fatal and nonfatal, including myocardial infarction, stroke, and death due to cardiovascular diseases) and all-cause mortality according to 25-OH-D quartiles, categories based on cut points of 15 and 30 ng/mL, or continuous vitamin D concentrations. RESULTS: During follow-up, 148 cardiovascular events and 121 deaths were recorded. Elevation of risk for the lowest quartile or category in comparison to the highest category was weak and nonsignificant for both incidence (hazard ratio [HR](quartile1) = 1.15 [0.72-1.84], HR(<15 ng/mL) = 1.17 [0.61-2.23]) and mortality (HR(quartile1) = 1.29 [0.77-2.14], HR(<15 ng/mL) = 1.87 [0.91-3.82]) in unadjusted Cox regression analysis and disappeared entirely after adjustment for potential confounders (cardiovascular events: HR(quartile1) = 0.84 [0.47-1.50], HR(<15 ng/mL) = 0.90 [0.41-1.96]; mortality: HR(quartile1) = 0.63 [0.33-1.21], HR(<15 ng/mL) = 0.93 [0.39-2.21]). Models treating vitamin D as a continuous variable likewise suggested no significant associations. CONCLUSIONS: Unlike previous population-based studies, our analysis in high-risk patients with stable CHD does not support a prognostic value of baseline-25-OH-D levels for secondary cardiovascular event incidence or all-cause mortality.

Cardiovascular prevention in clinical practice (ESC and German guidelines 2007).

Preventive efforts should be guided by the patient's global cardiovascular (CV) risk. A risk stratification should be done in every person > age 35 with more than a single risk factor. Recommendations for improved lifestyle are applicable to all persons with CV risk factors: smoking cessation, daily exercise, normal body mass index, Mediterranean diet, blood pressure < 140 mmHg systolic, and LDL cholesterol < 130 mg/dl are beneficial. If the 10-year risk is > or = 20% for CV events or > or = 5% for CV death, additional drug interventions are usually necessary: acetylsalicylic acid 100 mg daily, statins to lower LDL cholesterol to < 100 mg/dl or, in diabetics with coronary artery disease, to < 70 mg/dl, blood pressure should be < 130 mmHg systolic, e.g., in patients with diabetes or renal disease. After bare-metal stent implantation clopidogrel should be given for > or = 4 weeks and after drug-eluting stents for > or = 6 months. In patients after myocardial infarction with an ejection fraction of < 40%, ACE inhibitors and beta-blocker should be started. Influenza vaccination improves prognosis in high-risk patients.

Multi-state models of transitions in depression and anxiety symptom severity and cardiovascular events in patients with coronary heart disease.

OBJECTIVE: Patients with coronary heart disease (CHD) commonly suffer from depression and anxiety, yet transitions of symptom severity and cardiovascular events (CVE) over time are not well characterized. METHODS: We included 997 patients with stable CHD from a prospective cohort study. We estimated 5- and 10-year transition probabilities of depression and anxiety symptom severity levels and fatal- and non-fatal adverse CVE. Depression and anxiety symptoms were measured with the Hospital Anxiety and Depression Scale 5 times over 13 years and categorized as no, mild, or moderate/severe symptoms. Using multi-state modeling, we calculated 5- and 10-year transition probabilities for depression and anxiety symptom severity and CVE and calculated transition intensity ratios for factors associated with symptom severity progression and regression. RESULTS: At 5 years, only approximately half of participants with moderate or severe symptom severity at baseline transitioned to no symptom severity. Patients with low physical activity (<1x/week or never) had a higher probability of worse symptom severity after 5 and 10 years and a higher probability of a CVE after 5 and 10 years regardless of their depression status at baseline compared to higher physical activity groups. Higher body mass index, <10 years of education, and lower physical activity were associated with depression symptom progression; female and lower physical activity were associated with anxiety symptom progression. CONCLUSIONS: Patients with CHD had a consistent burden of depression and anxiety symptoms. Secondary prevention strategies should target depression and anxiety and include a physical activity component.

Development and first assessment of a questionnaire for health care utilization and costs for cardiac patients.

BACKGROUND: The valid and reliable measurement of health service utilization, productivity losses and consequently total disease-related costs is a prerequisite for health services research and for health economic analysis. Although administrative data sources are usually considered to be the most accurate, their use is limited as some components of utilization are not systematically captured and, especially in decentralized health care systems, no single source exists for comprehensive utilization and cost data. The aim of this study was to develop and test a questionnaire for the measurement of disease-related costs for patients after an acute cardiac event (ACE). METHODS: To design the questionnaire, the literature was searched for contributions to the assessment of utilization of health care resources by patient-administered questionnaires. Based on these findings, we developed a retrospective questionnaire appropriate for the measurement of disease-related costs over a period of 3 months in ACE patients. Items were generated by reviewing existing guidelines and by interviewing medical specialists and patients. In this study, the questionnaire was tested on 106 patients, aging 35-65 who were admitted for rehabilitation after ACE. It was compared with prospectively measured data; selected items were compared with administrative data from sickness funds. RESULTS: The questionnaire was accepted well (response rate = 88%), and respondents completed the questionnaire in an average time of 27 minutes. Concordance between retrospective and prospective data showed an intraclass correlation (ICC) ranging between 0.57 (cost of medical intake) and 0.9 (hospital days) with the other main items (physician visits, days off work, medication) clustering around 0.7. Comparison between self-reported and administrative data for days off work and hospitalized days were possible for n = 48. Respective ICCs ranged between 0.92 and 0.94, although differences in mean levels were observed. CONCLUSION: The questionnaire was accepted favorably and correlated well with alternative measurement approaches. This first assessment showed promising characteristics of this questionnaire in different aspects of validity for patients with ACE. However, additional research and more extensive tests in other patient groups would be worthwhile.

Role of cytomegalovirus sero-status in the development of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes.

OBJECTIVE: We investigated prospectively the role of cytomegalovirus (CMV) sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus. BACKGROUND: There have been suggestions of an association between cytomegalovirus infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are relatively immunocompromised. METHODS: Patients aged 30-70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease between January 1999 and May 2000 were included in this analysis. CMV status at baseline was measured by serum immunoglobulin G antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months. RESULTS: Among the 1033 subjects with measured IgG antibody for CMV, 56.5% were sero-positive to CMV at baseline. During follow-up, secondary CVD events occurred among 71 (6.9%) participants. Occurrence of a secondary CVD event was more common among sero-positive than among sero-negative patients (adjusted hazard ratio, HR, 1.31, 95% confidence interval (CI) 0.80-2.20), among patients with diabetes HR 2.00 (95% CI 1.20-3.25). The risk of secondary CVD events was strongly increased among patients with both a positive CMV sero-status and diabetes (adjusted HR 2.58, 95% CI 1.32-5.10) compared to CMV negative, non-diabetic patients, whereas either conditions alone was associated with a weak and non-significant increase in risk only. CONCLUSION: Our results are consistent with a possible moderate increase in risk of secondary CVD events among patients with a positive CMV sero-status, and they indicate a strongly increased risk among CMV positive patients with diabetes.

Prognostic value of one-year course of symptoms of anxiety and depression in patients with coronary heart disease: Role of physical activity and unmet medical need.

INTRODUCTION: Symptoms of depression and anxiety contribute to determining prognosis of patients with coronary heart disease. We evaluated the association of the one-year course of symptoms of anxiety and depressive symptoms with fatal and non-fatal cardiovascular disease-events during 10-year follow-up and assessed the utilization of anti-depressant and psycholeptic medication. METHODS: Prospective cohort study in coronary heart disease patients aged 30-70 years with stable coronary heart disease. Symptoms of anxiety and depression were evaluated at baseline and follow-up using the Hospital Anxiety and Depression Scale. Associations with fatal and non-fatal cardiovascular disease events were determined by a Cox-proportional hazards model. RESULTS: Nine hundred and ninety-six patients were included in this study. Of the 862 patients with a normal depression symptom score at baseline 10.3% had an increased score at one-year follow-up. Of those with an elevated symptom score at baseline, 62.7% still had an elevated score after one year. During follow-up (median 8.9 years) fatal and non-fatal cardiovascular disease events were observed in 152 patients. One year course of depressive symptoms was associated with cardiovascular disease events during follow-up (p-value for trend 0.029); for example, patients with an increase of depressive symptoms had a hazard ratio of 1.93 (95% confidence interval 1.08-3.34) compared with patients with a normal score at baseline as well as at one-year follow-up. However, if physical activity was considered as a covariate, the HRs attenuated and the association was no longer statistically significant. The utilization of anti-depressant medication in the overall population was low (overall 2%). CONCLUSIONS: The study supports a role of the one year course of symptoms of depression for long-term prognosis of patients with known coronary heart disease, which might be partly mediated by lack of physical activity.

A reverse J-shaped association of leisure time physical activity with prognosis in patients with stable coronary heart disease: evidence from a large cohort with repeated measurements.

OBJECTIVE: To study the association of self-reported physical activity level with prognosis in a cohort of patients with coronary heart disease (CHD), with a special focus on the dose-response relationship with different levels of physical activity. METHODS: Data were drawn from a prospective cohort of 1038 subjects with stable CHD in which frequency of strenuous leisure time physical activity was assessed repeatedly over 10 years of follow-up. Multiple Cox proportional hazards regression models were used to assess the association of physical activity level with different outcomes of prognosis (major cardiovascular events, cardiovascular mortality, all-cause mortality), with different sets of adjustments for potential confounders and taking into account time-dependence of frequency of physical activity. RESULTS: A decline in engagement in physical activity over follow-up was observed. For all outcomes, the highest hazards were consistently found in the least active patient group, with a roughly twofold risk for major cardiovascular events and a roughly fourfold risk for both cardiovascular and all-cause mortality in comparison to the reference group of moderately frequent active patients. Furthermore, when taking time-dependence of physical activity into account, our data indicated reverse J-shaped associations of physical activity level with cardiovascular mortality, with the most frequently active patients also having increased hazards (2.36, 95% CI 1.05 to 5.34). CONCLUSIONS: This study substantiated previous findings on the increased risks for adverse outcomes in physically inactive CHD patients. In addition, we also found evidence of increased cardiovascular mortality in patients with daily strenuous physical activity, which warrants further investigation.

Calcium, phosphate and the risk of cardiovascular events and all-cause mortality in a population with stable coronary heart disease.

OBJECTIVE: High serum calcium and phosphate levels have been linked to cardiovascular diseases and all-cause mortality but evidence from longitudinal studies is scarce, especially among patients with pre-existing coronary heart disease. The association between baseline calcium and phosphate and prognosis was examined in a cohort study of patients with stable coronary heart disease. METHODS: Serum calcium and phosphate were measured in a cohort of initially 1206 patients undergoing a 3 week rehabilitation programme after an acute cardiovascular event and subsequently being followed-up for 8 years. Multivariate Cox regression was employed to assess the association of quartiles and continuous levels of calcium and phosphate with secondary cardiovascular events and all-cause mortality. RESULTS: No significant risk elevations were observed for secondary cardiovascular event incidence in models adjusted for a variety of potential confounders. High calcium levels, however, were strongly associated with mortality risk in adjusted models (HR(Q4vsQ1)=2.39 (1.22 to 4.66)). In additional multivariable analyses, the calcium/albumin ratio was predictive for all-cause mortality (HR(Q4vsQ1)=2.66 (1.35 to 5.22)) and marginally predictive for cardiovascular event incidence (HR(Q4vsQ1)=1.74 (1.00 to 3.05)). CONCLUSIONS: Calcium and the ratio of calcium with albumin, its major binding protein, were strongly associated with all-cause mortality among patients with coronary heart disease. The underlying mechanisms and the clinical implications of these findings deserve further study.

Serum parathyroid hormone and risk of adverse outcomes in patients with stable coronary heart disease.

BACKGROUND AND OBJECTIVE: Recent longitudinal studies have suggested an association of high serum parathyroid hormone levels (PTH) with elevated cardiovascular risk in the general population. This study presents analyses of the prognostic value of baseline PTH for subsequent cardiovascular events and all-cause mortality in a high-risk population with stable coronary heart disease. METHODS: Based on measurements of PTH levels in 1133 patients recruited at two German rehabilitation clinics and followed over 8 years, multivariate Cox regression analysis was performed to estimate the risk of secondary cardiovascular events (including myocardial infarction, stroke and death due to cardiovascular diseases) and all-cause-mortality according to PTH quartiles (Q1-Q4) and continuous PTH concentrations. RESULTS: During follow-up, 153 cardiovascular events and 124 deaths occurred. Age and sex-adjusted Cox regression analysis yielded statistically significant positive associations of PTH with both cardiovascular event incidence and all-cause mortality (HR (95% CI) per SD increase of PTH: 1.35 (1.21-1.51) and 1.25 (1.11-1.42), respectively). Associations remained essentially unchanged after additional adjustment for multiple cardiovascular risk factors. More detailed dose-response analyses showed strong risk elevation for above-normal levels of PTH (> 95th percentile), with essentially no association at lower levels. CONCLUSION: The results of this first detailed study in a cohort of patients with stable coronary heart disease suggest an independent predictive value of above-normal PTH for the prognosis in patients with stable coronary heart disease.

Long term effects of comprehensive cardiac rehabilitation in an inpatient and outpatient setting.

OBJECTIVES: To compare the long-term effects of comprehensive outpatient versus inpatient rehabilitation with respect to morbidity and mortality, as well as to changes in physical performance and physical activity. DESIGN: A total of 163 consecutive patients were enrolled for comprehensive cardiac rehabilitation (CCR) following a recent coronary event, to outpatient or inpatient CCR according to treatment preference because randomisation was accepted by only 4 patients. CCR was six hours per day for 4 weeks and consisted of exercise training, education, psychological support, and nutritional and occupational advice. Examinations were before, after and 12 months after CCR. Primary outcome measures were event-free survival with or without interventions, EFS-I or EFS, respectively, 12 months after rehabilitation. RESULTS: Main patient characteristics were distributed equally in the cohorts. Results were adjusted by logistic regression for age, BMI, LV-function, exercise capacity and physical activity before the event. Adjusted EFS, EFS-I , overall survival and other morbidity outcome measures did not differ significantly. During CCR, physical activity was higher in outpatients, but this difference was not maintained in the follow up. Average physical activity was increased 12 month after CR with no difference between groups. CONCLUSION: Although influenced by patient preference, participation in either inpatient or outpatient CCR led to comparable results in terms of all-cause or cardiac overall survival, event-free survival and other secondary outcome measures like cardiac morbidity, physical performance and increased physical activity.

Intervention study shows outpatient cardiac rehabilitation to be economically at least as attractive as inpatient rehabilitation.

BACKGROUND: Since the late 1990 s, cost pressure has led to a growing interest in outpatient rehabilitation in Germany where predominantly inpatient rehabilitation has been provided. Taking into account the feasibility of a randomized design, the aim of this study was to compare outpatient and inpatient cardiac rehabilitation from a societal perspective. METHOD: A comprehensive cohort design was applied. Costs during rehabilitation were measured using individual documentation of the rehabilitation centers. Economic end points were quality of life (EQ-5D), and total direct and indirect costs. A propensity score approach, integrated into a simultaneous regression framework for cost and effects, was used to control for selection bias. Bootstrap analysis was applied for assessing uncertainty in cost-effectiveness. RESULTS: A total of 163 patients were included in the study (112 inpatients, 51 outpatients). As randomization was chosen by only 2.5% of participants, the study had to be analyzed as an observational study. Direct costs during inpatient rehabilitation were significantly higher by 600 euro (+/-318; p < 0.001) compared to outpatient rehabilitation (2,016 euro +/- 354 euro vs. 1,416 euro +/- 315), while there was no significant difference in health-related quality of life. Over the 12-month follow-up period, adjusted costs difference in total cost was estimated at -2,895 euro (p = 0.102) and adjusted difference in effects at 0.018 quality-adjusted life years (QALYs) (n.s.) in favor of outpatient treatment. CONCLUSION: The ratio of mean cost over mean effect difference (incremental cost-effectiveness ratio) indicates dominance of outpatient rehabilitation, but at a considerable statistical uncertainty. However, outpatient rehabilitation cannot be rejected from an economic perspective.