The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany.
We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD) 59.1 (7.6) years, 7.0% diagnosed diabetes, 5.3% previously undetected diabetes) from the population-based Heinz Nixdorf Recall study. Diabetes was assessed by self-report, medication, and blood glucose. High depressive symptoms were assessed using CES-D. We calculated odds ratios and their corresponding 95% confidence interval, using multiple logistic regression analyses.
Cumulative 5-year incidences (95% CI) of high depressive symptoms in participants with diagnosed, undetected, and without diabetes were 7.1 (4.2–10.9), 4.1 (1.8–8.0), and 6.5 (5.6–7.4), respectively. The age-sex-adjusted OR for developing high depressive symptoms was 1.22 (0.74–2.03) in participants with diagnosed compared to those without diabetes, and 1.00 (0.59–1.68) after adjustment for BMI, physical activity, education, stroke, and myocardial infarction. The age-sex adjusted OR for developing high depressive symptoms in participants with previously undetected diabetes compared to those without diabetes was 0.72; 0.35–1.48; and fully adjusted 0.62; 0.30–1.30.
We found no significant associations, maybe due to low power. However, our results are in line with a recent meta-analysis suggesting that risk of developing high depressive symptoms in patients with diagnosed diabetes may be moderately higher than in those without diabetes, and that comorbidity may explain in part this association. In participants with previously undetected diabetes, this first longitudinal study indicates that the risk is not increased or may even be decreased. These results support the hypothesis that high depressive symptoms develop due to diabetes-related burden and comorbidity and not due to hyperglycemia or hyperinsulinaemia.
Atherosclerosis is the primary cause of coronary heart disease (CHD), preceding the onset of cardiovascular disease by decades in most cases. Here we examine the association between single nucleotide polymorphisms (SNPs) integrated on Metabochip and coronary artery calcification (CAC), a valid risk factor for CHD, in an unselected, population-based German cohort.
The Metabochip is a custom iSELECT array containing >195,000 SNPs that was designed to support large-scale follow-up of putative associations for metabolic and cardiovascular-associated traits. We used generalized linear regression models to explore the impact of Metabochip SNPs on quantitative CAC in 4,329 participants.
The 9p21 variant, rs1537373, was most strongly associated (Beta = 0.30; 95% confidence interval (CI) = 0.21-0.39; p = 4.05x10-11) with quantitative CAC. The second strongest association with CAC was with rs9349379 in the phosphatase and actin regulator 1 gene, PHACTR1, (Beta = 0.30; 95% CI = 0.22-0.40; p = 4.67x10-11). Both SNPs remained nominally significant in dichotomized analyses for the presence of any CAC (odds ratiors1537373 (OR) = 1.19; 95% CI = 1.07-1.31; p = 0.001 and ORrs9349379 = 1.26; 95% CI = 1.14-1.40); p = 1.5x10-5). Fine mapping of the 9p21 and PHACTR1 gene region revealed several other SNPs that were strongly associated with CAC.
We demonstrate that SNPs near 9p21 and in PHACTR1 that have previously been shown to be associated with CHD are strongly associated with CAC in the Heinz Nixdorf Recall Study cohort. Our findings suggest that the 9p21 and 6q24 loci might be involved in cardiac outcome via promoting development of atherosclerosis in the coronary arteries.
Coronary heart disease; Coronary artery calcification; Cohort study; Polymorphism; Metabochip
Patients with diabetes mellitus (DM) have an increased risk for periprocedural complications and adverse cardiac events after percutaneous coronary intervention. We addressed the potential for coronary microvascular obstruction and restenosis in patients with and without DM undergoing stenting for saphenous vein bypass graft (SVG) stenosis under protection with a distal occlusion/aspiration device.
SVG plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Percent diameter stenosis was determined from quantitative coronary angiography before, immediately after and 6 months after stent implantation. Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Total calcium, several vasoconstrictors, and tumor necrosis factor (TNF)α in particulate debris and coronary aspirate plasma were determined.
Patients with and without DM had similar plaque volume, but larger necrotic core and greater particulate debris release in patients with than without DM (20.3±2.7 vs. 12.7±2.6% and 143.9±19.3 vs. 75.1±10.4 mg, P<0.05). The TNFα concentration in particulate debris and coronary aspirate plasma was higher in patients with than without DM (15.9±6.6 vs. 5.1±2.4 pmol/mg and 2.2±0.7 vs. 1.1±0.2 pmol/L, P<0.05), whereas total calcium and vasoconstrictors were not different. Patients with DM had a greater percent diameter stenosis 6 months after stent implantation than those without DM (22.17±5.22 vs. 6.34±1.11%, P<0.05). The increase in TNFα immediately after stent implantation correlated with restenosis 6 months later (r=0.69, P<0.05).
In diabetics, particulate debris and coronary aspirate plasma contained more TNFα, which might reflect the activity of the underlying atherosclerotic process.
URL: http://www.clinicaltrials.gov/ct2/results?term=NCT01430884; unique identifier: NCT01430884
Coronary disease; Diabetes mellitus; Ischemia; TNFα; Vasoconstriction
Unfavorable work characteristics, such as low job control and too high or too low job demands, have been suggested to increase the likelihood of physical inactivity during leisure time, but this has not been verified in large-scale studies. The authors combined individual-level data from 14 European cohort studies (baseline years from 1985–1988 to 2006–2008) to examine the association between unfavorable work characteristics and leisure-time physical inactivity in a total of 170,162 employees (50% women; mean age, 43.5 years). Of these employees, 56,735 were reexamined after 2–9 years. In cross-sectional analyses, the odds for physical inactivity were 26% higher (odds ratio = 1.26, 95% confidence interval: 1.15, 1.38) for employees with high-strain jobs (low control/high demands) and 21% higher (odds ratio = 1.21, 95% confidence interval: 1.11, 1.31) for those with passive jobs (low control/low demands) compared with employees in low-strain jobs (high control/low demands). In prospective analyses restricted to physically active participants, the odds of becoming physically inactive during follow-up were 21% and 20% higher for those with high-strain (odds ratio = 1.21, 95% confidence interval: 1.11, 1.32) and passive (odds ratio = 1.20, 95% confidence interval: 1.11, 1.30) jobs at baseline. These data suggest that unfavorable work characteristics may have a spillover effect on leisure-time physical activity.
cohort studies; exercise; physical activity; psychosocial factors; working population
Until now, insomnia has not been much of interest in epidemiological neighbourhood studies, although literature provides evidence enough for insomnia-related mechanisms being potentially dependent on neighbourhood contexts. Besides, studies have shown differences in sleep along individual social characteristics that might render residents more vulnerable to neighbourhood contextual exposures. Given the role of exposure duration and changes in the relationship between neighbourhoods and health, we studied associations of neighbourhood unemployment and months under residential turnover with insomnia by covering ten years of residential history of nearly 3,000 urban residents in the Ruhr Area, Germany.
Individual data were retrieved from the Heinz Nixdorf Recall Study, a population-based study of randomly chosen participants from adjacent cities, which contains self-rated insomnia symptoms and individual social characteristics. Participants’ residential addresses were retrospectively assessed using public registries. We built individually derived exposure measures informing about mean neighbourhood unemployment rates and months under high residential turnover. These measures were major predictors in multivariate logistic regressions modelling the association between social neighbourhood characteristics and insomnia in the whole sample and subgroups defined by low income, low education, social isolation, and change of residence. Traffic-related noise, age, gender, economic activity, and education were considered as covariates.
Nearly 12 per cent of the participants complained about insomnia. Associations of neighbourhood unemployment with insomnia were more consistent than those of residential turnover in the whole sample (adjusted OR 1.42, 95% CI 1.00-2.03 for neighbourhood unemployment and OR 1.33, 95% CI 0.78-2.25 for residential turnover in the highest exposure categories). In low-income and socially isolated participants, neighbourhood unemployment odds of reporting insomnia were particularly elevated (adjusted OR 2.90, 95% CI 1.39-6.02 and OR 3.32, 95% CI 1.11-9.96, respectively). Less educated participants displayed relatively high odds of reporting insomnia throughout all upper neighbourhood unemployment exposure categories. Change of residence weakened associations, whereas undisrupted exposure sharpened them by trend.
Our findings hint at multiple stressors being effective in both the neighbourhood context and individual resident, possibly reflecting precarious life situations undermining residents’ sleep and health chances. Moreover, our results suggest a temporal dependency in the association between neighbourhood and insomnia.
Insomnia; Neighbourhood unemployment; Residential turnover; Income; Education; Social isolation; Change of residence.
Tobacco smoking is a major contributor to the public health burden and healthcare costs worldwide, but the determinants of smoking behaviours are poorly understood. We conducted a large individual-participant meta-analysis to examine the extent to which work-related stress, operationalised as job strain, is associated with tobacco smoking in working adults.
Methodology and Principal Findings
We analysed cross-sectional data from 15 European studies comprising 166 130 participants. Longitudinal data from six studies were used. Job strain and smoking were self-reported. Smoking was harmonised into three categories never, ex- and current. We modelled the cross-sectional associations using logistic regression and the results pooled in random effects meta-analyses. Mixed effects logistic regression was used to examine longitudinal associations. Of the 166 130 participants, 17% reported job strain, 42% were never smokers, 33% ex-smokers and 25% current smokers. In the analyses of the cross-sectional data, current smokers had higher odds of job strain than never-smokers (age, sex and socioeconomic position-adjusted odds ratio: 1.11, 95% confidence interval: 1.03, 1.18). Current smokers with job strain smoked, on average, three cigarettes per week more than current smokers without job strain. In the analyses of longitudinal data (1 to 9 years of follow-up), there was no clear evidence for longitudinal associations between job strain and taking up or quitting smoking.
Our findings show that smokers are slightly more likely than non-smokers to report work-related stress. In addition, smokers who reported work stress smoked, on average, slightly more cigarettes than stress-free smokers.
The relationship between work-related stress and alcohol intake is uncertain. In order to add to the thus far inconsistent evidence from relatively small studies, we conducted individual-participant meta-analyses of the association between work-related stress (operationalised as self-reported job strain) and alcohol intake.
Methodology and Principal Findings
We analysed cross-sectional data from 12 European studies (n = 142 140) and longitudinal data from four studies (n = 48 646). Job strain and alcohol intake were self-reported. Job strain was analysed as a binary variable (strain vs. no strain). Alcohol intake was harmonised into the following categories: none, moderate (women: 1–14, men: 1–21 drinks/week), intermediate (women: 15–20, men: 22–27 drinks/week) and heavy (women: >20, men: >27 drinks/week). Cross-sectional associations were modelled using logistic regression and the results pooled in random effects meta-analyses. Longitudinal associations were examined using mixed effects logistic and modified Poisson regression. Compared to moderate drinkers, non-drinkers and (random effects odds ratio (OR): 1.10, 95% CI: 1.05, 1.14) and heavy drinkers (OR: 1.12, 95% CI: 1.00, 1.26) had higher odds of job strain. Intermediate drinkers, on the other hand, had lower odds of job strain (OR: 0.92, 95% CI: 0.86, 0.99). We found no clear evidence for longitudinal associations between job strain and alcohol intake.
Our findings suggest that compared to moderate drinkers, non-drinkers and heavy drinkers are more likely and intermediate drinkers less likely to report work-related stress.
Socioeconomic status (SES) is an important determinant of population health. Explanatory approaches on how SES determines health have so far included numerous factors, amongst them psychosocial factors such as social relationships. However, it is unclear whether social relationships can help explain socioeconomic differences in general subjective health. Do different aspects of social relationships contribute differently to the explanation? Based on a cohort study of middle and older aged residents (45 to 75 years) from the Ruhr Area in Germany our study tries to clarify the matter.
For the analyses data from the population-based prospective Heinz Nixdorf Recall (HNR) Study is used. As indicators of SES education, equivalent household income and occupational status were employed. Social relations were assessed by including structural as well as functional aspects. Structural aspects were estimated by the Social Integration Index (SII) and functional aspects were measured by availability of emotional and instrumental support. Data on general subjective health status was available for both baseline examination (2000–2003) and a 5-year follow-up (2006–2008). The sample consists of 4,146 men and women. Four logistic regression models were calculated: in the first model we controlled for age and subjective health at baseline, while in models 2 and 3, either functional or structural aspects of social relationships were introduced separately. Model 4 then included all variables. As former studies indicated different health effects of SES and social relations in men and women, analyses were conducted with the overall sample as well as for each gender alone.
Prospective associations of SES and subjective health were reduced after introducing social relationships into the regression models. Percentage reductions between 2% and 30% were observed in the overall sample when all aspects of social relations were included. The percentage reductions were strongest in the lowest SES group. Gender specific analyses revealed mediating effects of social relationships in women and men. The magnitude of mediating effects varied depending on the indicators of SES and social relations.
Social relationships substantially contribute to the explanation of SES differences in subjective health. Interventions for improving social relations which especially focus on socially deprived groups are likely to help reducing socioeconomic disparities in health.
Real-time cardiovascular magnetic resonance (rtCMR) is considered attractive for guiding TAVI. Owing to an unlimited scan plane orientation and an unsurpassed soft-tissue contrast with simultaneous device visualization, rtCMR is presumed to allow safe device navigation and to offer optimal orientation for precise axial positioning. We sought to evaluate the preclinical feasibility of rtCMR-guided transarterial aortic valve implatation (TAVI) using the nitinol-based Medtronic CoreValve bioprosthesis.
rtCMR-guided transfemoral (n = 2) and transsubclavian (n = 6) TAVI was performed in 8 swine using the original CoreValve prosthesis and a modified, CMR-compatible delivery catheter without ferromagnetic components.
rtCMR using TrueFISP sequences provided reliable imaging guidance during TAVI, which was successful in 6 swine. One transfemoral attempt failed due to unsuccessful aortic arch passage and one pericardial tamponade with subsequent death occurred as a result of ventricular perforation by the device tip due to an operating error, this complication being detected without delay by rtCMR. rtCMR allowed for a detailed, simultaneous visualization of the delivery system with the mounted stent-valve and the surrounding anatomy, resulting in improved visualization during navigation through the vasculature, passage of the aortic valve, and during placement and deployment of the stent-valve. Post-interventional success could be confirmed using ECG-triggered time-resolved cine-TrueFISP and flow-sensitive phase-contrast sequences. Intended valve position was confirmed by ex-vivo histology.
Our study shows that rtCMR-guided TAVI using the commercial CoreValve prosthesis in conjunction with a modified delivery system is feasible in swine, allowing improved procedural guidance including immediate detection of complications and direct functional assessment with reduction of radiation and omission of contrast media.
Aortic stenosis; Transcatheter aortic valve implantation; Cardiovascular magnetic resonance; Real-time
To assess in a multicenter design the between-center reproducibility of volumetric virtual histology intravascular ultrasound (VH-IVUS) measurements with a semi-automated, computer-assisted contour detection system in coronary lesions that were consecutively stented. To evaluate the reproducibility of volumetric VH-IVUS measurements, experienced analysts of 4 European IVUS centers performed independent analyses (in total 8,052 cross-sectional analyses) to obtain volumetric data of 40 coronary segments (length 20.0 ± 0.3 mm) from target lesions prior to percutaneous intervention that were performed in the setting of stable (65%) or unstable angina pectoris (35%). Geometric and compositional VH-IVUS measurements were highly correlated for the different comparisons. Overall intraclass correlation for vessel, lumen, plaque volume and plaque burden was 0.99, 0.92, 0.96, and 0.83, respectively; for fibrous, fibro-lipidic, necrotic core and calcified volumes overall intraclass correlation was 0.96, 0.94, 0.98, and 0.99, respectively. Nevertheless, significant differences for both geometrical and compositional measurements were seen. Of the plaque components, fibrous tissue and necrotic core showed on average the highest measurement reproducibility. A central analysis for VH-IVUS multicenter studies of lesions prior to PCI should be pursued. Moreover, it may be problematical to pool VH-IVUS data of individual trials analyzed by independent centers.
Coronary artery disease; Intravascular ultrasound; Radiofrequency; Virtual Histology; Measurement reproducibility; Percutaneous coronary interventions
Background: Recent studies have shown an association of short-term exposure to fine particulate matter (PM) with transient increases in blood pressure (BP), but it is unclear whether long-term exposure has an effect on arterial BP and hypertension.
Objectives: We investigated the cross-sectional association of residential long-term PM exposure with arterial BP and hypertension, taking short-term variations of PM and long-term road traffic noise exposure into account.
Methods: We used baseline data (2000–2003) on 4,291 participants, 45–75 years of age, from the Heinz Nixdorf Recall Study, a population-based prospective cohort in Germany. Urban background exposure to PM with aerodynamic diameter ≤ 2.5 μm (PM2.5) and ≤ 10 μm (PM10) was assessed with a dispersion and chemistry transport model. We used generalized additive models, adjusting for short-term PM, meteorology, traffic proximity, and individual risk factors.
Results: An interquartile increase in PM2.5 (2.4 μg/m3) was associated with estimated increases in mean systolic and diastolic BP of 1.4 mmHg [95% confidence interval (CI): 0.5, 2.3] and 0.9 mmHg (95% CI: 0.4, 1.4), respectively. The observed relationship was independent of long-term exposure to road traffic noise and robust to the inclusion of many potential confounders. Residential proximity to high traffic and traffic noise exposure showed a tendency toward higher BP and an elevated prevalence of hypertension.
Conclusions: We found an association of long-term exposure to PM with increased arterial BP in a population-based sample. This finding supports our hypothesis that long-term PM exposure may promote atherosclerosis, with air-pollution–induced increases in BP being one possible biological pathway.
atherosclerosis; environmental epidemiology; hypertension; particulate matter; traffic emissions
Background: Secondhand smoke (SHS) consists of fine particulate matter, carcinogens, and various toxins that affect large parts of the population. SHS increases the risk for acute cardiovascular events and may contribute to the development of atherosclerosis.
Objectives: We investigated the association of SHS with coronary artery calcification (CAC).
Methods: In this cross-sectional analysis, we used baseline data (2000–2003) from 1,766 never-smokers without clinically manifested coronary heart disease, 45–75 years of age, from the Heinz Nixdorf Recall Study, an ongoing, prospective, population-based cohort study in Germany. Self-reported frequent SHS at home, at work, and in other places was assessed by questionnaire. CAC scores were derived based on electron-beam computed tomography. We conducted multiple linear regression analysis using exposure to SHS as the explanatory variable and ln(CAC+1) as the response variable. We conducted logistic regression to estimate the odds ratio (OR) for presence of any CAC.
Results: Frequent exposure to SHS was reported by 21.5% of participants. After adjustment for age, sex, and socioeconomic status, CAC + 1 was 21.1% [95% confidence interval (CI): –5.5%, 55.2%] higher in exposed than in unexposed participants. After adjusting for other cardiovascular risk factors, the association was attenuated (15.4%; 95% CI: –9.6%, 47.2%). SHS exposure was also associated with a CAC score > 0 (fully adjusted OR = 1.38; 95% CI: 1.03, 1.84).
Conclusions: Self-reported frequent exposure to SHS was associated with subclinical coronary atherosclerosis in our cross-sectional study population. Considering the widespread exposure and the clinical relevance of coronary atherosclerosis, this result, if confirmed, is of public health importance.
cardiovascular atherosclerosis; comparative risk assessment; environmental epidemiology; population health; secondhand smoke
Social relations have repeatedly been found to be an important determinant of health. However, it is unclear whether the association between social relations and health is consistent throughout different status groups. It is likely that health effects of social relations vary in different status groups, as stated in the hypothesis of differential vulnerability. In this analysis we explore whether socioeconomic status (SES) moderates the association between social relations and health.
In the baseline examination of the Heinz Nixdorf Recall study, conducted in a dense populated Western German region (N = 4,814, response rate 56%), SES was measured by income and education. Social relations were classified by using both structural as well as functional measures. The Social Integration Index was used as a structural measure, whilst functional aspects were assessed by emotional and instrumental support. Health was indicated by self-rated health (1 item) and a short version of the CES-D scale measuring the frequency of depressive symptoms. Based on logistic regression models we calculated the relative excess risk due to interaction (RERI) which indicates existing moderator effects.
Our findings show highest odds ratios (ORs) for both poor self-rated health and more frequent depressive symptoms when respondents have a low SES as well as inappropriate social relations. For example, respondents with low income and a low level of social integration have an OR for a high depression score of 2.85 (95% CI 2.32-4.49), compared to an OR of 1.44 (95% CI 1.12-1.86) amongst those with a low income but a high level of social integration and an OR of 1.72 (95% CI 1.45-2.03) amongst respondents with high income but a low level of social integration. As reference group those reporting high income and a high level of social integration were used.
The analyses indicate that the association of social relations and subjective health differs across SES groups as we find moderating effects of SES. However, results are inconsistent as nearly all RERI scores are positive but do not reach a significant level. Also moderating effects vary between women and men and depending on the indicators of SES and social relations used. Thus, the hypothesis of differential vulnerability can only partially be supported. In terms of practical implications, psychosocial and health interventions aiming towards the enhancement of social relations should especially consider the situation of the socially deprived.
Aims: The aim of the current study was to assess cardiac structure and function as well as cardiac abnormalities in a large patient-population based multicenter study of HIV-infected subjects. Materials and methods: We enrolled 803 HIV-positive adults (83.4% men, mean age: 44.2 ± 10.3 yrs) in this prospective, cross-sectional cohort study. The study protocol included a standardized documentation of patient history, medical treatment and clinical examination. All subjects underwent a standardized transthoracic echocardiographic examination protocol including Doppler and tissue Doppler imaging. Results: Echocardiographic measurements revealed a structural dilatation of the left ventricle in 10.1% of all HIV-infected subjects. Interventricular septum and posterior wall thickness were increased in 18.0% and 11.1%, respectively, with elevated muscle mass in 14.3% male and 19.4% female patients. Of all participants 13.5% exhibited a pathologic contraction characteristic of one or more myocardial segments. Prevalence of systolic and diastolic dysfunction was 34.3% and 48.0%, respectively. However, severe forms of ventricular dysfunction were rare. Conclusions: In conclusion our results demonstrate the relevance of echocardiography in this patient-population in the era of antiretroviral therapy. Above all, left ventricular wall thickness and function should be controlled regularly in HIV-infected subjects. (ClinicalTrials.gov number, NCT01119729).
Echocardiography; HIV-Infection; AIDS; cardiomyopathy
Background. Levosimendan is an inotropic drug with unique pharmacological advantages in patients with acute heart failure. Scope of this study is to determine whether longer infusion patterns without the hypotension-inducing loading dose could justify an effective and safe alternative approach. Methods. 70 patients admitted to the emergencies with decompensated chronic heart failure received intravenously levosimendan without a loading dose up to 72 hours. Clinical parameters, BNP (Brain Natriuretic Peptide) and signal-averaged-ECG data (SAECG) were recorded up to 72 hours. Results. The 48-hour group demonstrated a statistically significant BNP decrease (P < .001) after 48 hours, which also maintained after 72 hours. The 72-hour group demonstrated a bordeline decrease of BNP after 48 hours (P = .039), necessitating an additional 24-hour infusion to achieve significant reduction after 72 hours (P < .004). SAECG data demonstrated a statistically significant decrease after 72 hours (P < .04). Apart from two deaths due to advanced heart failure, no major complications were observed. Conclusion. Prolonged infusion of levosimendan without a loading dose is associated with an acceptable clinical and neurohumoral response.
To investigate the role of coronary vasa vasorum (VV) neovascularization in the progression and complications of human coronary atherosclerotic plaques.
Accumulating evidence supports an important role of VV neovascularization in atherogenesis and lesion location determination in coronary artery disease. VV neovascularization can lead to intraplaque hemorrhage, which has been identified as a promoter of plaque progression and complications like plaque rupture. We hypothesized that distinctive patterns of VV neovascularization and associated plaque complications can be found in different stages of human coronary atherosclerosis.
Hearts from 15 patients (age 52±5, mean±SEM) were obtained at autopsy, perfused with Microfil™ and subsequently scanned with micro-computed tomography (micro-CT). Two-cm-segments (n=50) were histologically classified as either normal (n=12), nonstenotic plaque (<50% stenosis, n=18), or calcified (n=10) or non-calcified (n=10) stenotic plaque. Micro-CT images were analyzed for VV density (#/mm2), VV vascular area fraction (mm2/mm2) and VV endothelial surface fraction (mm2/mm3). Histological sections were stained for Mallory’s (iron), von Kossa (calcium) and glycophorin-A (erythrocyte fragments) as well as endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α).
VV density was higher in segments with non-stenotic and non-calcified stenotic plaques as compared to normals (3.36±0.45, 3.72±1.03 vs. 1.16±0.21, P<0.01). In calcified stenotic plaques VV spatial density was lowest (0.95±0.21, P<0.05 vs. non-stenotic and non-calcified stenotic plaque). The amount of iron and glycophorin A was significantly higher in non-stenotic and stenotic plaques as compared to normals, and correlated with VV density (Kendall-Tau correlation-coefficient 0.65 and 0.58 respectively, P<0.01). Moreover, relatively high amounts of iron and glycophorin A were found in calcified plaques. Further immunohistochemical characterization of VV revealed positive staining for eNOS and TNF-α but not VEGF.
Our results support a possible role of VV neovascularization, VV rupture and intraplaque hemorrhage in the progression and complications of human coronary atherosclerosis.
vasa vasorum; human coronary atherosclerosis; micro-CT; calcification; intraplaque hemorrhage
The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15,842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 × 10−8. Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2. Two other loci include ATP1B1 and PLN, genes with established electrophysiological function, whereas three map to RNF207, near LITAF and within NDRG4-GINS3-SETD6-CNOT1, respectively, all of which have not previously been implicated in cardiac electrophysiology. These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD.
Cardiovascular magnetic resonance (CMR) is considered an attractive alternative for guiding transarterial aortic valve implantation (TAVI) featuring unlimited scan plane orientation and unsurpassed soft-tissue contrast with simultaneous device visualization. We sought to evaluate the CMR characteristics of both currently commercially available transcatheter heart valves (Edwards SAPIEN™, Medtronic CoreValve®) including their dedicated delivery devices and of a custom-built, CMR-compatible delivery device for the Medtronic CoreValve® prosthesis as an initial step towards real-time CMR-guided TAVI.
The devices were systematically examined in phantom models on a 1.5-Tesla scanner using high-resolution T1-weighted 3D FLASH, real-time TrueFISP and flow-sensitive phase-contrast sequences. Images were analyzed for device visualization quality, device-related susceptibility artifacts, and radiofrequency signal shielding.
CMR revealed major susceptibility artifacts for the two commercial delivery devices caused by considerable metal braiding and precluding in vivo application. The stainless steel-based Edwards SAPIEN™ prosthesis was also regarded not suitable for CMR-guided TAVI due to susceptibility artifacts exceeding the valve's dimensions and hindering an exact placement. In contrast, the nitinol-based Medtronic CoreValve® prosthesis was excellently visualized with delineation even of small details and, thus, regarded suitable for CMR-guided TAVI, particularly since reengineering of its delivery device toward CMR-compatibility resulted in artifact elimination and excellent visualization during catheter movement and valve deployment on real-time TrueFISP imaging. Reliable flow measurements could be performed for both stent-valves after deployment using phase-contrast sequences.
The present study shows that the Medtronic CoreValve® prosthesis is potentially suited for real-time CMR-guided placement in vivo after suggested design modifications of the delivery system.
Subjective parameters such as quality of life or patient satisfaction gain importance as outcome parameters and benchmarks in health care. In many countries hospitals are now undergoing accreditation as mandatory or voluntary measures. It is believed but unproven that accreditations positively influence quality of care and patient satisfaction. The present study aims to assess in a defined specialty (cardiology) the relationship between patient satisfaction (as measured by the recommendation rate) and accreditation status.
Consecutive patients discharged from 25 cardiology units received a validated patient satisfaction questionnaire. Data from 3,037 patients (response rate > 55%) became available for analysis. Recommendation rate was used as primary endpoint. Different control variables such as staffing level were considered.
The 15 accredited units did not differ significantly from the 10 non-accredited units regarding main hospital (i.e. staffing levels, no. of beds) and patient (age, gender) characteristics. The primary endpoint "recommendation rate of a given hospital" for accredited hospitals (65.6%, 95% Confidence Interval (CI) 63.4 - 67.8%) and hospitals without accreditation (65.8%, 95% CI 63.1 - 68.5%) was not significantly different.
Our results support the notion that - at least in the field of cardiology - successful accreditation is not linked with measurable better quality of care as perceived by the patient and reflected by the recommendation rate of a given institution. Hospital accreditation may represent a step towards quality management, but does not seem to improve overall patient satisfaction.
Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85×10−8 in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84×10−7), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at ∼1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults.
Genome-wide association studies (GWAS) have successfully contributed to the detection of genetic variants involved in body-weight regulation. We jointly analysed two GWAS for early-onset extreme obesity in 2,258 individuals of European origin and followed-up the findings in 3,141 individuals. Evidence for association of markers in two new genetic loci was shown (SDCCAG8 on chromosome 1q43–q44 and between TNKS/MSRA on chromosome 8p23.1). We also re-identified variants in or near FTO, MC4R, and TMEM18 to be associated with extreme obesity. In addition, we assessed the effect of the markers in 31,182 obese, lean, normal weight, and unselected individuals from population-based samples and showed that the variants near FTO, MC4R, TMEM18, and SDCCAG8 were consistently associated with obesity. For variants of TNKS/MSRA, the obesity association was limited to children and adolescents. In summary, we detected two new obesity loci and confirmed that the currently known major common variants related to obesity overlap to a substantial degree between children and adults.
Predischarge defibrillation threshold testing is often performed a few days after ICD implantation in order to validate defibrillation thresholds obtained at the time of implant. Ventricular fibrillation is induced with such testing and causes an increase in serum Brain Natriuretic Peptide (BNP) levels. BNP is an indicator for cardiac stress. We wanted to examine the feasibility to alter the trend of BNP after predischarge testing in VVI, DDD and CRT ICD's.
We measured BNP before predischarge testing and 5, 10, 20 and 40 minutes after predischarge testing in 13 groups with each 20 patients. We evaluated patients without post shock pacing and patients with a post shock pacing frequency of 60, 70, 80, 90 and 100 bpm and a duration of 30 and 60 sec as well as a post shock pacing frequency of 80 and 90 bpm and a duration of 120 sec post shock pacing.
Patients without post shock pacing showed the highest BNP during the follow-up. The percentage values of BNP increased consistent significantly after 5 minutes compared with BNP before predischarge testing. The percentage values of BNP trend was significantly lower with a post shock pacing of 90 bpm and duration of 60 sec. In addition, we excluded a cardiac necrosis by predischarge testing because of similar values of myoglobin, cardiac troponin I and creatine kinase during the follow-up.
Our results suggested that post shock pacing with 90 bpm and duration of 60 sec as the best optimized post shock pacing frequency and duration for VVI, DDD and CRT ICD's. A reduction of cardiac stress is going to be achieved with the optimization of the post shock pacing frequency and duration.
brain natriuretic peptide; ICD; predischarge test; heart failure; optimisation