Search

Background: Previous epidemiological studies regarding the association between chronic periodontitis (CP) and carotid intima‐media thickness (cIMT) and subclinical atherosclerosis have been inconclusive. Objective: The aim of this study was to determine whether CP is associated with subclinical atherosclerosis in a large population‐based cohort study conducted in northern Germany (the Hamburg City Health study). Methods: Baseline data from 5781 participants of the Hamburg City Health Study with complete oral health and carotid ultrasound data (50.7% female, mean age: 62.1 ± 8.4 years) were evaluated. A standardized duplex sonography of the carotid artery was performed with measurement of carotid intima‐media thickness (cIMT) and atherosclerotic plaques. Oral health was assessed by recording the decayed, missing, and filled teeth (DMFT) index, clinical attachment loss (CAL), bleeding on probing (BOP), and the dental plaque index (PI). Correlations were tested for statistical significance by means of descriptive statistics and multivariate regression analyses. Results: Moderate and severe CP were associated with the prevalence of cIMT ≥ 1 mm (none or mild CP: 5.1%, moderate CP: 6.1%, severe CP: 10%) and mean cIMT (none or mild CP: 0.72 mm, moderate CP: 0.75 mm, severe CP: 0.78 mm) in bivariate analyses (p <.001). Additionally, severe and moderate CP were associated with higher prevalence of carotid atherosclerotic plaques (plaque = yes: none or mild CP: 23.9%, moderate CP: 29%, severe CP: 40.2%,). After adjustment for age, sex, smoking, diabetes, hypertension, educational level, hypercholesterolemia, and hsCRP, severe CP still correlated significantly with cIMT and the prevalence of cIMT ≥1 mm and/or presence of carotid atherosclerotic plaques. Conclusion: In this study, severe CP was associated with increased cIMT and higher prevalence of carotid plaques independent of common risk factors. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is an increasingly common problem in primary care, but little is known about its prevalence and the distribu tion of AF risk factors in the general population. Methods: We determined the prevalence of AF and the distribution of known AF risk factors among persons participating in the population-based Gutenberg Health Study. To this end, we used interview data about the medical diagnosis of AF and electrocardiograms (ECGs) that were performed for the study in 5000 persons aged 35 to 74. The response rate was 60.4%. Results: There were 5000 persons in the study sample (age 52.2 ± 11 years; 50.6% were women). The prevalence of AF, weighted for the age and sex distribution of the general population, was 2.5%. AF was found to be more common in older persons, with a more pronounced increase in men: whereas its prevalence was 0.7% in 35- to 44-year-old men, the corresponding figure for the age group 65- to 74 was as high as 10.6%. Twenty five participants (15.5% of AF cases) received their initial diagnosis of AF on the basis of the study ECG. Compared to persons without AF, persons with AF were older and more commonly male, and they had a higher burden of cardiovascular risk factors. 14.3% of persons with AF had none of the well-established risk factors for AF (systolic blood pressure, antihypertensive medication, increased body-mass-index, heart failure). 42.7% of persons with AF were not taking either anticoagulants or platelet inhibitors. Conclusion: These data indicate that the prevalence of AF in the middle-aged general population is 2.5% overall, and higher in the elderly. AF is thus a significant public health problem, and greater awareness of it is needed. [ABSTRACT FROM AUTHOR]

The article discusses empirically derived reference values from a large-scale, epidemiologic study of the distribution of echocardiographic measurements of the left ventricle (LV), conducted using state-of-the-art imaging technology and methods. The study involved a population-based sample of 5000 mid-Europeans from the Gutenberg Heart Study in Germany, including apparently healthy individuals and those with prevalent disease. Researchers found that age had a stronger association with LV metrics in women than in men.

Background: The purpose of this work is to describe the objectives and design of cardiovascular magnetic resonance (CMR) imaging in the single center, prospective, population-based Hamburg City Health study (HCHS). The HCHS aims at improving risk stratification for coronary artery disease (CAD), atrial fibrillation (AF) and heart failure (HF). Methods: The HCHS will finally include 45,000 inhabitants of the city of Hamburg (Germany) between 45 and 74 years who undergo an extensive cardiovascular evaluation and collection of biomaterials. Risk-scores for CAD, AF and HF are used to create enriched subpopulations who are invited for CMR. A total number of approximately 12,362 subjects will undergo CMR and incident CAD, AF and HF will be assessed after 6 years follow-up. The standard CMR protocol includes cine-CMR, T1 and T2 mapping, aortic/mitral valve flow measurements, Late gadolinium enhancement, angiographies and measurements of aortic distensibility. A stress-perfusion scan is added in individuals at risk for CAD. The workflow of CMR data acquisition and analyses was evaluated in a pilot cohort of 200 unselected subjects. Results: The obtained CMR findings in the pilot cohort agree with current reference values and demonstrate the ability of the established workflow to accomplish the objectives of HCHS. Conclusions: CMR in HCHS promises novel insights into major cardiovascular diseases, their subclinical precursors and the prognostic value of novel imaging biomarkers. The HCHS database will facilitate combined analyses of imaging, clinical and molecular data ("Radiomics"). [ABSTRACT FROM AUTHOR]

"Medical scientists" are postgraduate investigators who are engaged in biomedical research, and either hold a biomedical PhD or are qualified in medicine but do not participate in patient care. Medical scientists constitute ~40% of staff at medical faculties and >90% at nonuniversity medical research institutions in Germany. However, medical scientists in Germany face limited long-term career prospects and a lack of dedicated training and support programmes. They also face time limits on their career progression arising from national academic employment legislation, and imminent reforms by the German government are likely to make this worse. Nevertheless, recent developments in the educational landscape including the introduction of increasingly focused MSc, pre-PhD, and doctoral programmes to train medically aware basic scientists, as well as improved general recognition of the roles and relevance of medical scientists in health research, are encouraging. Physiologists have taken essential steps to improve the recognition of medical scientists in Germany by introducing a "specialist physiologist" qualification; this initiative could be applied to support medical scientists in other fields and countries. In this review, we describe the particular challenges facing medical scientists in Germany and make recommendations that may apply to other academic systems., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background and Aims: Adverse pregnancy outcomes (APO) have been related to increased cardiovascular (CV) risk and mortality in later life. Underlying pathomechanisms for the development of CV disease in these women are not yet fully understood. In this study, we aimed to investigate the relationship between APO and individual CV risk profiles in later life., Methods: We used cross-sectional data from 10,000 participants enrolled in the Hamburg City Health Study (HCHS). We analysed self-reported APO, CV risk factors and health status, including biomarkers, electrocardiogram, echocardiography and vascular ultrasound. To examine associations, Wilcoxon rank sum test and Pearson's χ 2 -test were performed. Multivariable-adjusted regression models were calculated to determine associations., Results: N = 1970 women who reported pregnancies were included. Median age was 63 years, 8.7 % reported gestational hypertension (gHTN), 18 % excessive weight gain and 2.4 % gestational diabetes. Ten percent had delivered newborns with birth weight <2.5 kg, 14 % newborns with birth weight >4 kg. In multivariable-adjusted models, significant associations between APO, CV risk profiles and cardiac remodeling were identified. gHTN correlated with higher body mass index (BMI) (Beta 1.68, CI 95 % 0.86-2.50; p < 0.001), hypertension (OR 4.58, CI 95 % 2.79-7.86; p < 0.001), left ventricular remodeling (e.g. left ventricular mass index (Beta 4.46, CI 95 % 1.05-7.87; p = 0.010)) and myocardial infarction (OR 3.27, CI 95 % 0.94-10.07; p = 0.046)., Conclusions: In this population-based sample, APO were associated with CV risk profiles and cardiac remodeling in later life, suggesting early manifestations of future CV risk during pregnancy. Prospective data is needed for individual risk stratification in women with APO., Competing Interests: Declaration of competing interest All participating institutes and departments from the University Medical Center Hamburg-Eppendorf contribute with scaled budgets to the overall funding of the Hamburg City Health Study (HCHS). Moreover, HCHS has received funding from the Innovative medicine initiative (IMI) under Grant No. 116074 (European public-private-partnership), Fondation Leducq (Grant Number 16 CVD 03), euCanSHare (Grant Agreement No. 825903-euCanSHare H2020) and the Deutsche Forschungsgemeinschaft (DFG project Grant TH1106/5-1; AA93/2-1). The HCHS is further supported by Joachim Herz Foundation; Deutsche Gesetzliche Unfallversicherung (DGUV); Deutsches Krebsforschungszentrum (DKFZ); Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK); Deutsche Stiftung für Herzforschung; Seefried Stiftung; Bayer; Amgen, Novartis; Schiller; Siemens; Topcon, Unilever and by donations from the “Förderverein zur Förderung der HCHS e.V.”, and TePe® (2014). Sponsor funding has in no way influenced the content, conclusions or management of this study. E.U., K.B., G.A., P.S., C.V.R. and C.A.B. have not received any project related funding. N.M. reports personal fees from Abbott Laboratories, outside the submitted work. C.M. receives study-specific funding from the German Center for Cardiovascular Research (DZHK; Promotion of women scientists’ programme; FKZ 81X3710112), the Deutsche Stiftung für Herzforschung, the Dr. Rolf M. Schwiete Stiftung, NDD, and Loewenstein Medical unrelated to the current work. C.M. has received speaker fees from AstraZeneca, Novartis, Boehringer Ingelheim/Lilly, Bayer, Pfizer, Sanofi, Aventis, Apontis, Abbott outside this work. C.M. has participated in a Boehringer Ingelheim heart failure advisory board. S.B. is supported by the Innovative medicine initiative (IMI) under Grant No. 116074, the Fondation Leducq under Grant Number 16 CVD 03, Siemens, Bayer, Astra Zeneca, Deutsche Gesetzliche Unfallversicherung (DGUV) and Novartis for project related analyses. B.C.Z. has received an unrestricted project-related funding from BASF and Unilever for implementing a food frequency questionnaire into the interviews of the Hamburg City Health Study and reports fees from Jenapharm GmbH and BESINS Heathcare for lectures outside this work. R.B.S. has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under the grant agreement No 648131, from the European Union's Horizon 2020 research and innovation programme under the grant agreement No 847770 (AFFECT-EU) and German Center for Cardiovascular Research (DZHK e.V.) (81Z1710103 and 81Z0710114); German Ministry of Research and Education (BMBF 01ZX1408A) and ERACoSysMed3 (031L0239). Wolfgang Seefried project funding German Heart Foundation. R.B.S. has received lecture fees and advisory board fees from BMS/Pfizer and Bayer outside this work. E.U., N.M., K.B., P.S., C.V.R, G.A, C.M., C.A.B, S.B., B.C.Z. and R.B.S. report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background Risk stratification among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Thus, we evaluated the predictive value of soluble urokinase-type plasminogen activator receptor (suPAR) levels for cardiovascular mortality and nonfatal myocardial infarction in patients with CAD. Methods and Results Plasma levels of suPAR were measured in a cohort of 1703 patients with documented CAD as evidenced by coronary angiography-including 626 patients with acute coronary syndrome and 1077 patients with stable angina pectoris. Cardiovascular death and/or nonfatal myocardial infarction were defined as main outcome measures. During a median follow-up of 3.5 years, suPAR levels reliably predicted cardiovascular death or myocardial infarction in CAD, evidenced by survival curves stratified for tertiles of suPAR levels. In Cox regression analyses, the hazard ratio for the prediction of cardiovascular death and/or myocardial infarction was 2.19 ( P <0.001) in the overall cohort and 2.56 in the acute coronary syndrome cohort ( P <0.001). Even after adjustment for common cardiovascular risk factors, renal function and the biomarkers C-reactive protein, N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I suPAR still enabled a reliable prediction of cardiovascular death or myocardial infarction with a hazard ratio of 1.61 ( P =0.022) in the overall cohort and 2.22 ( P =0.005) in the acute coronary syndrome cohort. Conclusions SuPAR has a strong and independent prognostic value in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.

Background and Aims: Guidelines recommend a healthy diet as a cornerstone of cardiovascular disease (CVD) prevention. Although the Mediterranean diet (MD) is the best studied dietary pattern for CV outcomes, data on association between MD and severity of CAD are limited. Therefore, we analysed dietary data in association with the SYNTAX score in coronary artery disease (CAD) patients from the INTERCATH study., Methods: The INTERCATH study is an observational study in patients undergoing coronary angiography at the University Heart Center Hamburg. Coronary morphology is assessed by the SYNTAX score. A lifestyle questionnaire collects dietary data with food frequency questions at baseline. Based on seven dietary characteristics, we calculated an established Mediterranean diet score (MDS) with a range of 0-28 points at which 28 points reflect maximal adherence to MD. To investigate the association of MD with severity of CAD, we performed logistic regression analysis after adjustment for confounding factors., Results: Of 1121 patients, 27% were women. The median age was 70.7 years (interquartile range (IQR) 61.1,77.0). CV risk factors were distributed as expected for a CAD cohort (31.3% diabetes, 81.1% arterial hypertension, 34.0% smoking, median BMI 26.6 kg/m 2 (IQR 24.1, 30.3), median LDL-C 87 mg/dL (IQR 65.0,116,6). Of all variables included, the strongest correlation with MDS was found for log (hs-CRP) (r = -0.21, p < 0.001). Adherence to MD represented by a higher MDS was significantly associated with a reduced probability for a medium/high risk SYNTAX score of ≥23 with an odds ratio (OR) of 0.923 per point increase of MDS (95% confidence interval 0.869-0.979; p = 0.0079). This association remained significant after adjustment for cardiovascular risk factors (OR 0.934, 95% CI 0.877-0.995, p = 0.035). After further adjustment for log (hs-CRP), the association remained no longer significant (OR 0.955 (0.893-1.022, p = 0.19)., Conclusions: In this contemporary data set, we found an independent association of adherence to MD with a less complex CAD. Hs-CRP correlated significantly with adherence to MD and may be a marker of the vasoprotective effects of MD. These results strengthen the evidence for the protective effect of an MD pattern in CVD prevention., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sex differences in cardiovascular risk factors, cardiac structure and function, and disease and symptom burden in the common arrhythmia atrial fibrillation (AF) have not been investigated systematically at the population level. Cross-sectional data of 14,796 subjects (age range 35 to 74 years, 50.5% men) from the population-based Gutenberg Health Study were examined to show the distribution of cardiovascular risk factors by AF status and sex, and to determine sex-specific predictors for AF. The prevalence of AF was higher in men (4.3%) than in women (1.9%). Men had a worse cardiovascular risk factor profile, a higher prevalence of cardiovascular disease, but fewer symptoms than women. Age-adjusted Cox regressions showed sex interactions in the association of high-density lipoprotein-cholesterol, triglycerides, diabetes mellitus, coronary artery disease, myocardial infarction, generalized anxiety disorder, and heart rate with AF. After multivariable adjustment, sex interactions were seen for thickness of interventricular end-diastolic septum, odds ratio (OR) per standard deviation (SD), 95% confidence interval women: 0.9 (0.8, 1.1), men: 1.2 (1.1, 1.4), interaction p value = 0.02; left atrial diameter index, OR per SD women: 1.5 (1.3, 1.8), men: 1.9 (1.7, 2.1), interaction p value = 0.03; and myocardial infarction, OR women: 2.7 (1.3, 5.6), men: 0.7 (0.5, 1.1), interaction p value = 0.002. In conclusion, in our large cohort, we observed substantial sex differences in AF distribution and clinical characteristics including comorbidities, symptom burden, and structural cardiac changes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The atypical presentation of women with acute coronary syndrome (ACS) has been related to delayed diagnosis and treatment, which may explain worse outcome compared with men., Methods and Results: We analyzed pooled data of 2520 patients of 2 prospective cohorts in terms of differences in presentation and management of women and men suggestive of ACS. Using logistic regression, we established 2 diagnostic models and tested their diagnostic performance in both sexes separately. Sex-specific differences in management of patients with ACS were ascertained and a 2-year follow-up was performed. Women were older than men (median 67 versus 61 years, P =0.001), had more often dyspnea (22% versus 18%, P =0.024), nausea or vomiting (26% versus 16%, P =0.001) and radiating chest pain (47% versus 40%, P =0.001). Classical risk factors (smoking, diabetes mellitus, dyslipidemia or known coronary artery disease) were less frequent in women. Diagnostic models showed no significant sex-related differences in diagnostic performance in a "first contact" setting (medical history and symptoms) or after "complete triage" (including ECG and biomarkers). Women with ACS underwent coronary angiography (73.8% versus 84.3%, P <0.001) and revascularization (53.8% versus 70.1%, P <0.001) less frequently. Two-year incidence of myocardial infarction and death was similar in both sexes, but revascularization and cardiac rehospitalization were more frequent in men., Conclusions: In a large cohort of patients with suspected ACS, sex differences in clinical presentation did not impair diagnostic accuracy. Two-year outcomes were comparable. Our findings suggest a benefit of chest pain units to minimize sex differences in ACS management and prognosis., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT02355457 (BACC), NCT03227159 (stenoCardia)., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: In the Gutenberg Health Study, a random sample of the population was scanned with vascular ultrasound for early atherosclerosis. A continuous classical risk marker model (waist circumference, HbA1c, LDL/HDL ratio, pack years and pulse pressure) was compared to a model of modern biomarkers (C-reactive protein, troponin I, N-terminal pro B-type natriuretic peptide, copeptin, mid-regional pro-adrenomedullin, and asymmetric dimethylarginine) with regard to the ability of ruling out abnormal intima-media thickness (IMT), respectively, carotid plaques., Methods: Data of the first consecutive 5,000 participants (aged 35-74 years; 2,540 men, 2,460 women) were analyzed. IMT was measured at both common carotid arteries using an edge detection system. Plaques were defined as protrusion of ≥1.5 mm in common, internal and external carotid artery., Results: For classical risk factors, in comparison to a model of six modern biomarkers, regarding the variable (a) IMT>0.85 mm negative and positive predictive value (NPV and PPV) were 0.98 and 0.16 for both the classical risk factor model and the biomarker model. The second variable (b) presence of plaque could be ruled out with an NPV of 0.84 and identified with a PPV of 0.61 for classical risk factors, and 0.84 and 0.58 for biomarkers, respectively. Values were calculated using logistic regression analysis., Conclusion: Classical risk factors allow ruling out pathologic IMT and presence of carotid plaques in a population of primary prevention in a reliable way. Modern biomarkers performed almost equally well but did not provide further information.

Background: Initial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited., Methods and Results: In 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, P(X2-Test) = 0.32. Multivariable regression analyses of the severity of depressive symptoms in relation to atrial fibrillation in cardiovascular risk factor adjusted models revealed a relation of PHQ-9 values and atrial fibrillation (odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01-1.08; P = 0.023). The association was stronger for the somatic symptom dimension of depression (OR 1.08, 95% CI 1.02-1.15; P = 0.0085) than for cognitive symptoms (OR 1.05, 95% CI 0.98-1.11; P = 0.15). Results did not change markedly after additional adjustment for heart failure, partnership status or the inflammatory biomarker C-reactive protein. Both, self-reported physical health status, very good/good versus fair/bad, (OR 0.54, 95% CI 0.41-0.70; P<0.001) and mental health status (OR 0.61 (0.46-0.82); P = 0.0012) were associated with atrial fibrillation in multivariable-adjusted models., Conclusions: In a population-based sample we observed a higher burden of depressive symptoms driven by somatic symptom dimensions in individuals with atrial fibrillation. Depression was associated with a worse perception of physical or mental health status. Whether screening and treatment of depressive symptoms modulates disease progression and outcome needs to be shown.

Aims: High-density lipoprotein (HDL) cholesterol is a strong predictor of cardiovascular mortality. This work aimed to investigate whether the presence of coronary artery disease (CAD) impacts on its predictive value., Methods and Results: We studied 3141 participants (2191 males, 950 females) of the LUdwigshafen RIsk and Cardiovascular health (LURIC) study. They had a mean ± standard deviation age of 62.6 ± 10.6 years, body mass index of 27.5 ± 4.1 kg/m&sup2;, and HDL cholesterol of 38.9 ± 10.8 mg/dL. The cohort consisted of 699 people without CAD, 1515 patients with stable CAD, and 927 patients with unstable CAD. The participants were prospectively followed for cardiovascular mortality over a median (inter-quartile range) period of 9.9 (8.7-10.7) years. A total of 590 participants died from cardiovascular diseases. High-density lipoprotein cholesterol by tertiles was inversely related to cardiovascular mortality in the entire cohort (P = 0.009). There was significant interaction between HDL cholesterol and CAD in predicting the outcome (P = 0.007). In stratified analyses, HDL cholesterol was strongly associated with cardiovascular mortality in people without CAD [3rd vs. 1st tertile: HR (95% CI) = 0.37 (0.18-0.74), P = 0.005], but not in patients with stable [3rd vs. 1st tertile: HR (95% CI) = 0.81 (0.61-1.09), P = 0.159] and unstable [3rd vs. 1st tertile: HR (95% CI) = 0.91 (0.59-1.41), P = 0.675] CAD. These results were replicated by analyses in 3413 participants of the AtheroGene cohort and 5738 participants of the ESTHER cohort, and by a meta-analysis comprising all three cohorts., Conclusion: The inverse relationship of HDL cholesterol with cardiovascular mortality is weakened in patients with CAD. The usefulness of considering HDL cholesterol for cardiovascular risk stratification seems limited in such patients.

A current model suggested that the somatic symptom dimension accounts for the adverse effect of depression in patients with coronary heart disease (CHD). In order to test this model we sought to determine in a large population-based sample how symptom dimensions of depression are associated with CHD, biomarkers and traditional risk factors. The associations of cognitive and somatic symptom dimensions of depression with CHD, risk factors, endothelial function, and biomarkers of inflammation and myocardial stress were analyzed cross-sectionally in a sample of n = 5000 Mid-Europeans aged 35-74 years from the Gutenberg Health Study (GHS). Only the somatic symptom dimension of depression was associated with CHD, biomarkers (inflammation, vascular function) and cardio-vascular risk factors. When multivariable adjustment was applied by demographic and cardiovascular risk factors, the weak associations of the somatic symptom dimension with the biomarkers disappeared. However, the associations of the somatic symptom dimension with CHD, myocardial infarction, obesity, dyslipidemia and family history of myocardial infarction remained. Both dimensions of depression were independently associated with a previous diagnosis of depression and distressed personality (type D). Thus, our results partly confirm current models: Somatic, but not cognitive-affective symptom dimensions are responsible for the association between depression and CHD, inflammation, vascular function and cardiovascular risk factors in the general population. However, our findings challenge the assumptions that somatic depression might be due to inflammation or vascular dysfunction as consequence of progressed atherosclerotic disease. They rather emphasize a close interplay with life-style factors and with a family history of MI.

Aims and Background: Midregional proadrenomedullin (MR-proADM) is a protein, which exerts various effects on the cardiovascular system. Recent studies underscored its prognostic implications in patients with acute dyspnea and cardiovascular diseases. Therefore, we aimed to determine the distribution of MR-proADM in the general population and to reveal potential associations of MR-proADM with cardiovascular risk factors and measures of subclinical cardiovascular disease., Methods and Results: MR-proADM plasma concentrations were determined in individuals of the population-based cohort of the Gutenberg Health Study (N = 5000) using a commercially available fluoroimmunoassay. Individuals were enrolled between April 2007 and October 2008. Subclinical cardiovascular disease was assessed using echocardiographic and functional measures of myocardial and vascular function. The mean age of the study population was 55.5 ± 10.9 years. In the overall population we determined a median MR-proADM plasma concentration of 0.44 nmol/L in men and women. MR-proADM concentrations were elevated in individuals with hypertension, diabetes, dyslipidemia, known cardiovascular disease, heart failure, peripheral artery disease, atrial fibrillation, and history of myocardial infarction and stroke. In men, we observed a positive association of MR-proADM with reduced ejection fraction, intraventricular septal diameter, wall thickness, and echocardiographic measures of diastolic dysfunction., Conclusions: In this study, we present age-dependent reference values for MR-proADM in a representative population sample. Elevated MR-proADM plasma concentrations were strongly associated with classical cardiovascular risk factors and manifest cardiovascular diseases. Furthermore, we revealed a gender-specific association with echocardiographic measures of hypertension. MR-proADM seems to be a promising prognostic biomarker for subclinical and manifest cardiovascular disease., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: The use of biomarkers is firmly established for the assessment of cardiovascular disease. Emerging biomarkers such as midregional pro-atrial natriuretic peptide (MR-proANP) challenge established markers regarding risk prediction and stratification ability. The aim of the present study was to describe the distribution of a contemporary MR-proANP assay in a large population-representative sample and to evaluate the association with prevalent cardiac diseases and cardiovascular risk factors., Methods: MR-proANP was determined by the use of a contemporary commercially available assay (BRAHMS GmbH, Hennigsdorf, Germany) in a representative sample of 5000 participants from the large population-based Gutenberg Health Study. N-terminal pro B-type natriuretic peptide (NT-proBNP) was used as a comparator., Results: Mean age was 55.5 ± 10.9 years. Coronary artery disease (CAD) was documented in 4.6%, heart failure (HF) in 1.5% of the study participants. We observed a moderate to strong correlation of the biomarkers with age, diabetes, hypertension, smoking, renal function, prevalence of CAD and HF. Males showed lower MR-proANP concentrations than females. MR-proANP showed no relevant correlation with BMI (ρ=-0.030) and CRP (ρ=0.039). Reference limits for MR-proANP representing the 95th/97.5th/99th percentile were determined for healthy individuals with 116/132/169 pmol/mL., Conclusions: The current analysis in a large population-based sample elucidates the correlations and distribution of MR-proANP. Its concentration in healthy individuals depends on prevalent cardiovascular diseases and classical risk factors. The reported population-based reference values might be useful for distinguishing between healthy and diseased individuals, thus improving risk stratification and triaging in various clinical settings.

Vascular reactivity is reflected by blood biomarkers and noninvasive vascular function measurement. The relation of biomarkers to flow-mediated dilation and peripheral arterial tonometry in the general population is little understood. In 5000 individuals (mean age, 56±11 years; age range, 35-74 years; 49% women) of the population-based Gutenberg Health Study we simultaneously assessed 6 biomarkers of cardiovascular function (midregional proadrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro B-type natriuretic peptide, copeptin, C-terminal proendothelin 1, and neopterin) in relation to flow-mediated dilation and peripheral arterial tonometry. Strongest partial correlations (adjusted for age and sex) were observed for baseline pulse amplitude with MR-proADM (r=0.13) and MR-proANP (r=-0.13); hyperemic response variables showed the highest correlation for MR-proADM and peripheral arterial tonometry ratio (r=-0.14). In multivariable linear regression models, strongest associations with baseline vascular function were observed for MR-proANP with baseline pulse amplitude (β per SD increase [99.17%], -0.080 [-0.115 to -0.044]; P<0.0001 after Bonferroni correction for multiple testing) and MR-proADM (-0.044 [-0.070 to -0.017]; P<0.0001), as well as MR-proANP (-0.033 [-0.057 to -0.009]; P=0.0017) and N-terminal pro B-type natriuretic peptide (-0.027 [-0.051 to -0.003]; P=0.015) with brachial artery diameter. For hyperemic response variables, highest associations were seen for peripheral arterial tonometry ratio with MR-proADM (-0.022 [-0.043 to -0.004]; P=0.043), MR-proANP (0.016 [-0.0034 to 0.035]; P=0.18), and C-terminal proendothelin 1 (-0.025 [-0.043 to -0.008]; P=0.00094]. In our large, population-based study, we identified MR-proADM and MR-proANP as circulating biomarkers of vascular function most strongly related to noninvasive measures of conduit artery and peripheral arterial performance. Whether determination of blood biomarkers helps to better understand vascular pathology and may provide prognostic information needs to be investigated in future studies.

Basic and clinical studies have suggested that inflammation predisposes to atrial fibrillation (AF). We assessed the association of 12 circulating inflammatory biomarkers (i.e., C-reactive protein, fibrinogen, interleukin-6, intercellular adhesion molecule-1, lipoprotein-associated phospholipase A2 [mass and activity], monocyte chemoattractant protein-1, myeloperoxidase, CD40 ligand, osteoprotegerin, P-selectin, and tumor necrosis factor receptor II) with incident AF in 2863 Framingham Offspring Study participants (mean age 60.7 years, SD = 9.4, 55% women). During follow-up (median 6 years), 148 participants (43% women) developed incident AF. In the multivariable proportional hazards models, the inflammatory biomarker panel was associated with incident AF (p = 0.03). With stepwise selection (p <0.01 for entry and retention), log-transformed osteoprotegerin was associated with incident AF (hazard ratio per SD 1.30, 95% confidence interval 1.08 to 1.56, p = 0.006). Adjusting for interim myocardial infarction or heart failure attenuated the association between osteoprotegerin and incident AF (hazard ratio 1.18, 95% confidence interval 0.98 to 1.43, p = 0.09). In conclusion, circulating osteoprotegerin concentration was significantly associated with incident AF in our community-based sample, possibly mediated by interim cardiovascular events.

Aims: Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation., Methods and Results: In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of < or =60 mL/min per 1.73 m(2) (n = 295) were excluded. In patients with complete follow-up information (n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically transformed, standardized cystatin C was associated with cardiovascular death [hazard ratio: 1.94, 95% confidence interval (CI): 1.59-2.37, P < 0.001]. A potential threshold effect was observed; patients in the upper quartile had a 3.87-fold (95% CI: 2.33-6.42; P < 0.001) risk of mortality compared with the pooled lower quartiles. This risk association remained robust after adjustment for potential confounders including classical risk factors and N-terminal pro B-type natriuretic peptide. Serum creatinine was not associated with the outcome in this group of patients with normal renal function., Conclusion: Results of this prospective study show that cystatin C is a potent predictor of cardiovascular mortality beyond classical risk factors in patients with CAD and normal or mildly reduced kidney function.