Publications by authors named "Philipp Wild"

295 Publications

Cigarette Smoking Is Related to Endothelial Dysfunction of Resistance, but Not Conduit Arteries in the General Population-Results From the Gutenberg Health Study.

Front Cardiovasc Med 2021 19;8:674622. Epub 2021 May 19.

Department of Cardiology-Cardiology I, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort. 15,010 participants (aged 35-74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit and resistance arteries was determined by flow-mediated dilation (FMD) of the brachial artery, reactive hyperemia index (RHI) using peripheral arterial tonometry, as well as by reflection index (RI) derived from digital photoplethysmography, respectively. Among all subjects, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Mean cumulative smoking exposure was 22.1 ± 18.1 pack-years in current smokers and mean years since quitting was 18.9 ± 12.7 in former smokers. In multivariable linear regression models adjusted for typical confounders, smoking status, pack-years of smoking, and years since quitting smoking were independently associated with RHI and RI, while no association was found for FMD. Overall, no clear dose-dependent associations were observed between variables, whereby higher exposure tended to be associated with pronounced resistance artery endothelial dysfunction. Cigarette smoking is associated with altered endothelial function of resistance, but not conduit arteries. The present results suggest that smoking-induced endothelial dysfunction in different circulatory beds may exhibit a differential picture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.674622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169997PMC
May 2021

Face masks effectively limit the probability of SARS-CoV-2 transmission.

Science 2021 May 20. Epub 2021 May 20.

State Environmental Protection Key Laboratory of Formation and Prevention of Urban Air Pollution Complex, Shanghai Academy of Environmental Sciences, Shanghai 200233, China.

Airborne transmission by droplets and aerosols is important for the spread of viruses. Face masks are a well-established preventive measure, but their effectiveness for mitigating SARS-CoV-2 transmission is still under debate. We show that variations in mask efficacy can be explained by different regimes of virus abundance and related to population-average infection probability and reproduction number. For SARS-CoV-2, the viral load of infectious individuals can vary by orders of magnitude. We find that most environments and contacts are under conditions of low virus abundance (virus-limited) where surgical masks are effective at preventing virus spread. More advanced masks and other protective equipment are required in potentially virus-rich indoor environments including medical centers and hospitals. Masks are particularly effective in combination with other preventive measures like ventilation and distancing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.abg6296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168616PMC
May 2021

Distribution of estimated glomerular filtration rate and determinants of its age dependent loss in a German population-based study.

Sci Rep 2021 May 13;11(1):10165. Epub 2021 May 13.

Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131, Mainz, Germany.

Glomerular filtration rate (GFR) declines with age by approx. 1 ml/min/m per year beginning in the third decade of life. At 70 years of age > 40 ml/min/m of GFR will be lost. Thus, factors affecting loss of GFR have significant public health implications. Furthermore, the definition of chronic kidney disease based on GFR may not be appropriate for the elderly. We analyzed factors affecting absolute and relative change of eGFR over a 5 year period in 12,381 participants of the Gutenberg Health Study. We estimated GFR at baseline and after 5 years of follow-up by two different equations. Association with the decline of estimated GFR (eGFR) was assessed by multivariable regression analysis. We confirmed a median loss of eGFR per year of approx. 1 ml/min/m. Aside from albuminuria systolic blood pressure was most strongly associated with faster decline of eGFR followed by echocardiographic evidence of left ventricular diastolic dysfunction and reduced ejection fraction. White blood cell count showed a moderate association with eGFR loss. Diastolic blood pressure, serum uric acid and serum albumin were associated with slower GFR decline in multivariable analysis. Sensitivity analysis with exclusion of individuals taking diuretics, antihypertensive, antidiabetic, or lipid lowering drugs confirmed these associations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-89442-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119940PMC
May 2021

Work-life conflict and cardiovascular health: 5-year follow-up of the Gutenberg Health Study.

PLoS One 2021 7;16(5):e0251260. Epub 2021 May 7.

Institute and Policlinic of Occupational and Social Medicine (IPAS), Faculty of Medicine Carl Gustav Carus, TU Dresden, Germany.

Introduction: Work-life conflicts (WLC) may impact health, but few studies prospectively consider the impact of WLC on objective outcomes such as cardiovascular disease. Using data from the Gutenberg Health Study (GHS), we examined if WLC at baseline was associated with an increased five-year incidence of cardiovascular events (myocardial infarct, stroke, atrial fibrillation, peripheral artery disease, coronary artery disease, chronic heart failure, sudden cardiac death). We also considered if WLC was associated with incident hypertension and arterial stiffness and if the effects of WLC on cardiovascular health differ for men and women.

Methods: A working subsample of the 15,010 GHS cohort participants completed the Copenhagen Psychosocial Questionnaire, which included five "work-privacy conflict" questions at baseline and at the five-year follow-up. Relative risks for incident hypertension due to increased WLC at baseline (WLC scores exceeding 60 out of 100) were estimated with Poisson regression in the subgroup of participants without hypertension at baseline (n = 2426). Categories of WLC at baseline and follow-up were also used to examine the risk of hypertension due to chronic/recurrent WLC. In this subgroup, we also examined the association between WLC as a continuous score ranging from 0 to 100 with change to arterial stiffness after five years using linear regression. Hazard ratios were estimated for incident cardiovascular events in a larger subsample of participants without prevalent cardiovascular disease at baseline (n = 3698) using Cox regression. We used various multivariable regression models to adjust for sex, age, socioeconomic status, occupational, household, and cardiovascular risk factors.

Results: We found no association between WLC and incident hypertension or increased arterial stiffness. The fully-adjusted relative risk for WLC >60 at baseline and hypertension was 0.93 (95% 0.74-1.17). The risk of hypertension due to chronic/recurrent WLC >60 was increased but not statistically significant (RR = 1.13, 95% CI 0.83-1.54). Overall, hazard ratios for incident cardiovascular events were also not increased. However, stratifying the results by sex resulted in a hazard ratio of 1.47 (95% CI 0.54-3.98) for incident cardiovascular disease among women in the fully adjusted model.

Conclusions: Although our results were not statistically significant, they indicate that WLC is negatively impacting the cardiovascular health of women. While these results need to be confirmed with additional research and a longer follow-up, interventions to prevent WLC will promote health and could be especially beneficial for women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251260PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104925PMC
May 2021

Homoarginine and methylarginines independently predict long-term outcome in patients presenting with suspicion of venous thromboembolism.

Sci Rep 2021 May 5;11(1):9569. Epub 2021 May 5.

Department of Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC-MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of "frailty" and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88986-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100302PMC
May 2021

Homoarginine and methylarginines independently predict long-term outcome in patients presenting with suspicion of venous thromboembolism.

Sci Rep 2021 May 5;11(1):9569. Epub 2021 May 5.

Department of Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Endogenous arginine derivatives homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethyarginine (SDMA) are independent mortality predictors in atherosclerotic cardiovascular disease (CVD). Our study reports the first analysis, whether homoarginine, ADMA and SDMA predict venous thromboembolism (VTE) recurrence and overall mortality in patients with suspected acute VTE. We assessed serum levels of homoarginine, ADMA and SDMA by LC-MS/MS in 865 individuals from a prospective consecutive cohort of patients with clinical suspicion of VTE. The median follow-up time for mortality was 1196 days. VTE was confirmed by imaging in 418 patients and excluded in 447 patients. Low levels of homoarginine and high levels of ADMA or SDMA independently predicted all-cause mortality after adjustment for sex, age, oral anticoagulants, body mass index, arterial hypertension, diabetes mellitus, smoking, dyslipidemia, chronic heart failure, history of stroke, creatinine and cancer both in patients with VTE and without VTE. Interestingly, none of those parameters was predictive for VTE recurrence. We provide the first report that low circulating levels of homoarginine and high circulating levels of ADMA and SDMA independently predict all-cause mortality in patients with suspected VTE. These parameters might serve as markers of "frailty" and should be considered for future risk stratification approaches in this clinical population. Taking into account that homoarginine supplementation is protective in animal models of CVD and safe in healthy human volunteers, our study provides the basis for future homoarginine supplementation studies in patients with suspected VTE to investigate possible direct protective effects of homoarginine in this population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-88986-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100302PMC
May 2021

The impact of platelet indices on clinical outcome in heart failure: results from the MyoVasc study.

ESC Heart Fail 2021 May 3. Epub 2021 May 3.

Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Aims: Platelet indices have been associated with traditional cardiovascular risk factors, cardiovascular diseases and all-cause mortality. This study aimed to investigate the role of platelet count, mean platelet volume (MPV) and platelet-to-leukocyte ratio, including platelet-to-monocyte and platelet-to-lymphocyte ratio with cardiac function, heart failure (HF) phenotypes and clinical outcome, worsening of HF.

Methods And Results: Univariate and multivariable linear and Cox regression analyses were used to investigate the associations between platelet indices, cardiac function and worsening of HF in 3250 subjects enrolled in the MyoVasc study. Higher MPV, lower platelet count, lower platelet-to-leukocyte and platelet-to-monocyte ratios have been associated with reduced left ventricular ejection fraction (beta estimate [β]  = -0.05 [-0.09; -0.02], β  = 3.4 [1.2; 5.6], β  = 1.4 [1.1; 1.8], β  = 28 [20; 36]) and increased E/E' ratio (β  = 0.04 [0.003; 0.07], β  = -3.1 [-5.3; -0.92], β  = -0.83 [-1.2; -0.46], β  = -20 [-28; -12]), independent of age and sex. Cox regression demonstrated an increased risk for worsening of HF in subjects with MPV > 75th percentile (hazard ratio [HR] = 1.47 [1.16; 1.87]), platelet count < 25th percentile (HR = 1.36 [1.07; 1.74]), platelet-to-leukocyte < 25th percentile (HR = 1.53 [1.20; 1.95]), platelet-to-monocyte < 25th percentile (HR = 1.38 [1.08; 1.77]) and platelet-to-lymphocyte > 75th percentile (HR = 1.50 [1.17; 1.93]) ratios, independent of potential confounders. MPV > 75th percentile and platelet count < 25th percentile were strongly related to outcome in HFpEF vs. HFrEF (P for difference = 0.040). Platelet-to-leukocyte ratios were associated with worse outcome in both HF phenotypes, without a significant difference between HFpEF and HFrEF.

Conclusions: Platelet indices are linked with worse cardiac function and adverse clinical outcome, independent of subjects' underlying cardiovascular profile. This study emphasizes their important value to provide additional information on pathophysiology and risk stratification in HF syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ehf2.13390DOI Listing
May 2021

Noninvasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population.

Cardiovasc Res 2021 Mar 16. Epub 2021 Mar 16.

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany (PSW); Center for Cardiology-, Cardiology I (VHS, NA, AL, TG, TM).

Aims: Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality.

Methods And Results: In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased event-free survival with higher mean brachial artery diameter and baseline pulse amplitude and better survival with higher mean flow-mediated dilatation and peripheral arterial tonometry ratio (all Plog rank<0.05). In multivariable-adjusted Cox regression analyses only baseline pulse amplitude was inversely related to mortality ((hazard ratio) per standard deviation increase, 0.86, 95% confidence interval, 0.79-0.94; P = 0.0009). After exclusion of individuals with prevalent cardiovascular disease the association was no longer statistically significant in multivariable-adjusted models (hazard ratio 0.91, 95% confidence interval 0.81-1.02; P = 0.11). None of the vascular variables substantially increased the C-index of a model comprising clinical risk factors.

Conclusions: In our cohort, noninvasive measures of peripheral vascular structure and function did not reveal clinically relevant associations with incident cardiovascular disease or mortality. Whether determination of pulse amplitude by peripheral arterial tonometry improves clinical decision-making in primary prevention needs to be demonstrated.

Translational Perspective: In our large middle-aged community cohort with more than 15,000 individuals, median age 55 years (25th/75th percentile 46/65), 49.5% women noninvasively measured peripheral vascular function using flow-mediated dilation after upper arm occlusion or fingertip peripheral arterial tonometry was not relevantly associated with incident cardiovascular disease or mortality in multivariable-adjusted analyses. An interaction of the association of peripheral arterial tonometry with mortality by prevalent cardiovascular disease was observed. Routine measurement of flow-mediated dilation or peripheral arterial tonometry in our community cohort to screen for high risk of cardiovascular disease or mortality was not effective.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cvr/cvab087DOI Listing
March 2021

Risk factors, physical and mental health burden of male and female pathological gamblers in the German general population aged 40-80.

BMC Psychiatry 2021 03 4;21(1):123. Epub 2021 Mar 4.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.

Background: Gambling Disorder (GD) has been associated with considerable mental and physical health risks in clinical samples. The paper determines risk factors, mental and physical health burden of probable GD for both men and women in the general population.

Methods: In the Gutenberg Health Study, a population-based sample of N = 11,875 aged 40-80 years was analyzed regarding lifetime probable GD prevalence (measured with the Lie/ Bet Questionnaire) and a wide array of health variables including standardized measures of depression, anxiety, and somatic symptoms.

Results: Probable GD lifetime prevalence was 2.1%, with higher rates among 1st generation migrants (5.5%; vs. non-migrants 1.6%), men (3.0%; vs. women 1.2%), and the sample's youngest age decade (40-49 y., 3.1%). Lifetime probable GD was associated with current work-related, family and financial stressors as well as unhealthy behavior (smoking, extended screen time), and lifetime legal offenses. In men, but not in women, increased rates of imprisonment, mental and somatic symptoms were found.

Conclusions: GD is a major public health problem with serious social, mental and physical health burden. Epidemiological findings underscore the preponderance of GD among 1st generation migrants and men. Findings are consistent with a vicious cycle of family, work related and financial stress factors, and mental and physical burden, particularly in men. Demographic risk factors may help to target specific prevention and treatment efforts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-021-03110-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931586PMC
March 2021

Promotion of Arterial Stiffness by Childhood Cancer and Its Characteristics in Adult Long-Term Survivors.

J Am Heart Assoc 2021 Feb 24;10(5):e015609. Epub 2021 Feb 24.

Preventive Cardiology and Preventive Medicine Centre for Cardiology University Medical Centre of the Johannes Gutenberg-University Mainz Mainz Germany.

Background Vascular alterations induced by antineoplastic treatment might be considered as a possible underlying mechanism of increased cardiovascular sequelae in childhood cancer survivors (CCSs). We aimed to evaluate arterial stiffness among long-term CCSs and to compare the data against a population-based sample. Methods and Results Arterial stiffness was assessed by digital photoplethysmography (stiffness index; m/s) among 1002 participants of the CVSS (Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer) study, diagnosed with neoplasia (1980-1990) before an age of 15 years. A population-based sample from the GHS (Gutenberg Health Study) (n=5252) was investigated for comparison. All subjects underwent a comprehensive, standardized clinical examination in the same study center. CCSs had higher stiffness index (β=0.66 m/s; 95% CI, 0.51-0.80 m/s) in multivariable linear regression analysis after adjustment for cardiovascular risk factors compared with the population sample of comparable age range. Stiffer vessels were found among CCSs also in absence of arterial hypertension (β=0.66; 95% CI, 0.50-0.81) or history of chemotherapy/radiotherapy (β=0.56; 95% CI, 0.16-0.96) in fully adjusted models. Moreover, stiffness index differed by tumor entity, with highest values in bone and renal tumors. Almost 5.2-fold higher prevalence of stiffness index values exceeding age-specific, population-based reference limits was observed among CCSs compared with GHS participants. Conclusions This is the first study demonstrating increased arterial stiffness among long-term CCSs. The data suggest that vascular compliance might differ in survivors of childhood cancer from the established development concept for arterial stiffness in the population; cancer growth and antineoplastic treatment might be relevant determinants of the pathobiological features. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02181049.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.015609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174251PMC
February 2021

Similarities and Differences of Mental Health in Women and Men: A Systematic Review of Findings in Three Large German Cohorts.

Front Public Health 2021 5;9:553071. Epub 2021 Feb 5.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center, Johannes Gutenberg-University Mainz, Mainz, Germany.

In Germany, large, population-based cohort studies have been implemented in order to identify risk and protective factors for maintaining health across the life span. The purpose of this systematic review is to analyse findings from three large ongoing cohorts and to identify sex-specific prevalence rates, risk and protective factors for mental health. Published studies from the Cooperative Health Research in the Region Augsburg (KORA), the Study of Health in Pomerania (SHIP) and the Gutenberg Health Study (GHS)), representing the southern, north-eastern and middle parts of Germany, were identified through searches of the databases PubMed and Web of Science. A total of 52 articles was identified from the start of each cohort until June 2019. Articles reporting prevalence rates of mental health [ = 22], explanatory factors for mental health [ = 25], or both [ = 5] were identified. Consistent across cohorts, higher prevalence rates of internalizing disorders were found for women and more externalizing disorders for men. Risk and protective factors for mental health included social factors, lifestyle, physical health, body mass index (BMI), diabetes, genetic and biological factors. In all areas, differences and similarities were found between women and men. The most evident were the sex-specific risk profiles for depression with mostly external risk factors for men and internal risk factors for women. Gender was not assessed directly, therefore we examined whether socioeconomic and family-related factors reflecting gender roles or institutionalized gender could be used as a proxy for gender. Overall, this systematic review shows differences and similarities in prevalence rates and determinants of mental health indicators between women and men. They underline the importance of focussing on sex specific approaches in mental health research and in the development of prevention measures. Current research on mental health still lacks focus on gender aspects. Therefore, an increased focus on sex and gender in mental health research is of great importance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpubh.2021.553071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892592PMC
May 2021

Impact of diesel exposure on human health: the saga continues ….

Eur J Prev Cardiol 2020 Apr 9. Epub 2020 Apr 9.

Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2047487320915335DOI Listing
April 2020

Quality of Life 3 and 12 Months Following Acute Pulmonary Embolism: Analysis From a Prospective Multicenter Cohort Study.

Chest 2021 Jun 3;159(6):2428-2438. Epub 2021 Feb 3.

Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address:

Background: Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE).

Research Question: What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE?

Study Design And Methods: The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact of baseline characteristics using multivariable mixed effects linear regression were studied; also assessed was the course of generic QoL as evaluated by using the EuroQoL Group 5-Dimension 5-Level utility index and the EuroQoL Visual Analog Scale.

Results: In 620 patients (44% women; median age, 62 years), overall disease-specific QoL improved from 3 to 12 months, with a decrease in the median PEmb-QoL score from 19.4% to 13.0% and a mean individual change of -4.3% (95% CI, -3.2 to -5.5). Female sex, cardiopulmonary disease, and higher BMI were associated with worse QoL at both 3 and 12 months. Over time, the association with BMI became weaker, whereas older age and previous VTE were associated with worsening QoL. Generic QoL also improved: the mean ± SD EuroQoL Group 5-Dimension 5-Level utility index increased from 0.85 ± 0.22 to 0.87 ± 0.20 and the visual analog scale from 72.9 ± 18.8 to 74.4 ± 19.1.

Interpretation: In a large cohort of survivors of acute PE, the change of QoL was quantified between months 3 and 12 following diagnosis, and factors independently associated with lower QoL and slower recovery of QoL were identified. This information may facilitate the planning and interpretation of clinical trials assessing QoL and help guide patient management.

Clinical Trial Registration: German Clinical Trials Registry (Deutsches Register Klinischer Studien: www.drks.de); No.: DRKS00005939.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chest.2021.01.071DOI Listing
June 2021

Association of Global Longitudinal Strain With Clinical Status and Mortality in Patients With Chronic Heart Failure.

JAMA Cardiol 2021 Apr;6(4):448-456

German Center for Cardiovascular Research (DZHK), partner site Rhine-Main, Mainz, Germany.

Importance: Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited.

Objective: To assess the factors associated with GLS and its prognostic value in patients with chronic HF.

Design, Setting, And Participants: The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participants with stages A to D HF according to American Heart Association (AHA) criteria were examined at a dedicated study center. Echocardiography was performed with GLS measurement by independent reviewers. Data were analyzed from September 2, 2019, to January 15, 2020.

Main Outcomes And Measures: All-cause and cardiac mortality were recorded by structured follow-up and validated via death certificates.

Results: In the study sample, data on GLS were available on 2440 individuals, of whom 2186 (mean [SD] age, 65.0 [10.5] years; 1418 [64.9%] men) were classified as having AHA HF stages A to D. Mean (SD) GLS worsened across AHA stages from stage A (n = 434; -19.44 [3.15%]) to stage B (n = 629; -18.01 [3.46%]) to stages C/D (n = 1123; -15.52 [4.64%]). Age (β = -0.27; 95% CI, -0.47 to -0.067; per decade, P = .009), female sex (β = -1.2; 95% CI, -1.6 to -0.77; per decade, P < .001), obesity (β = 0.64; 95% CI, 0.25-1.0; P = .001), atrial fibrillation (β = 1.2; 95% CI, 0.69-1.6; P < .001), myocardial infarction (β = 1.5; 95% CI, 1.00-2.1; P < .001), and estimated glomerular filtration rate (β = -0.53; 95% CI, -0.73 to -0.32; per SD, P < .001) were independently associated with GLS in multivariable regression analysis. Global longitudinal strain was associated with the severity of HF as reflected by N-terminal prohormone B-type natriuretic protein (NT-proBNP) levels after additionally adjusting for cardiac structure and function (P < .001). During follow-up, GLS was associated with all-cause mortality (hazard ratio [HR] per SD, 1.55; 95% CI, 1.19-2.01; P < .001) and cardiac death (HR per SD, 2.32; 95% CI, 1.57-3.42; P < .001) independent of image quality, observer variability, clinical profile, HF medications, NYHA class, and cardiac structure and function. After further adjustment for the NT-proBNP level, GLS remained associated with cardiac death (HR per SD, 1.60; 95% CI, 1.07-2.41; P = .02) but not all-cause mortality (HR per SD, 1.26; 95% CI, 0.95-1.66; P = .11).

Conclusions And Relevance: In patients with chronic HF, GLS was associated with clinical and cardiac status, reflected neurohormonal activation, and was associated with cardiac mortality independent of clinical and cardiac status. These findings suggest that GLS may serve as a useful tool to improve risk stratification in patients with HF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamacardio.2020.7184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859875PMC
April 2021

Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism.

Blood 2021 May;137(19):2681-2693

Preventive Cardiology and Preventive Medicine, Center for Cardiology.

Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE patients (n = 96) against those of patients with DVT-associated PE (n = 276) or isolated DVT (n = 160). This resulted in the identification of shared molecular processes between PE phenotypes, as well as an isolated PE-specific protein signature. Shared processes included upregulation of inflammation, response to oxidative stress, and the loss of pulmonary surfactant. The isolated PE-specific signature consisted of 5 proteins: interferon-γ, glial cell line-derived neurotrophic growth factor, polypeptide N-acetylgalactosaminyltransferase 3, peptidyl arginine deiminase type-2, and interleukin-15 receptor subunit α. These proteins were orthogonally validated using cis protein quantitative trait loci. External replication in an independent population-based cohort (n = 5778) further validated the proteomic results and showed that they were prognostic for incident primary isolated PE in individuals without history of VTE (median time to event: 2.9 years; interquartile range: 1.6-4.2 years), supporting their possible involvement in the early pathogenesis. This study has identified molecular overlaps and differences between VTE phenotypes. In particular, the results implicate noncanonical pathways more commonly associated with respiratory and atherosclerotic disease in the acute pathophysiology of isolated PE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2019004571DOI Listing
May 2021

Cost saving analysis of specialized, eHealth-based management of patients receiving oral anticoagulation therapy: Results from the thrombEVAL study.

Sci Rep 2021 Jan 28;11(1):2577. Epub 2021 Jan 28.

Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Langenbeckstraße 1, Mainz, 55131, Germany.

To evaluate the cost-saving of a specialized, eHealth-based management service (CS) in comparison to regular medical care (RMC) for the management of patients receiving oral anticoagulation (OAC) therapy. Costs of hospitalization were derived via diagnosis-related groups which comprise diagnoses (ICD-10) and operation and procedure classification system (OPS), which resulted in OAC-related (i.e. bleeding/ thromboembolic events) and non-OAC-related costs for both cohorts. Cost for anticoagulation management comprised INR-testing, personnel, and technical support. In total, 705 patients were managed by CS and 1490 patients received RMC. The number of hospital stays was significantly lower in the CS cohort compared to RMC (CS: 23.4/100 py; RMC: 68.7/100 py); with the most pronounced difference in OAC-related admissions (CS: 2.8/100 py; RMC: 13.3/100 py). Total costs for anticoagulation management amounted to 101 EUR/py in RMC and 311 EUR/py in CS, whereas hospitalization costs were 3261 [IQR 2857-3689] EUR/py in RMC and 683 [504-874] EUR/py in CS. This resulted in an overall cost saving 2368 EUR/py favoring the CS. The lower frequency of adverse events in anticoagulated patients managed by the telemedicine-based CS compared to RMC translated into a substantial cost-saving, despite higher costs for the specialized management of patients.Trial registration: ClinicalTrials.gov, unique identifier NCT01809015, March 8, 2013.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-82076-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844022PMC
January 2021

Inflammation predicts new onset of depression in men, but not in women within a prospective, representative community cohort.

Sci Rep 2021 Jan 26;11(1):2271. Epub 2021 Jan 26.

Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Untere Zahlbacher Str. 8, 55131, Mainz, Germany.

Depression has been associated with increased inflammation. However, only few large-scale, prospective studies have evaluated whether inflammation leads to new cases of depression and whether this association can be found in men and women. Longitudinal data of N = 10,357 adult participants with no evidence of depression at baseline (based on Patient Health Questionnaire (PHQ-9), lifetime diagnoses, and current antidepressant medication) were evaluated for depression 5 years later. Multivariate logistic regression models were used to predict the onset of depression based on C-reactive protein (CRP) and white blood cell count (WBC). We used interaction terms and separate analyses in men and women to investigate gender-dependent associations. Based on both markers, inflammation was predictive of new cases of depression 5 years later, even when adjusting for sociodemographic, physical health, health behavior variables, and baseline depression symptoms. As established by interaction terms and separate analyses, inflammatory markers were predictive of depression in men, but not in women. Additional predictors of new onset of depression were younger age, loneliness, smoking (only in men), cancer and less alcohol consumption (only in women). The study indicates gender differences in the etiology of depressive disorders within the community, with a greater role of physical factors in men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-81927-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838404PMC
January 2021

Sex-related differences in D-dimer levels for venous thromboembolism screening.

Acad Emerg Med 2021 Jan 26. Epub 2021 Jan 26.

Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio, USA.

Background: D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized that the accuracy of D-dimer tests may be enhanced by using appropriate cutoff values that reflect sex-related differences in D-dimer levels.

Methods: This research is a secondary analysis of a multicenter, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pretest probability based on Wells criteria ≤ 6 for pulmonary embolism (PE) and ≤ 2 for deep vein thrombosis (DVT). VTE diagnoses were based on computed tomography, ventilation perfusion scanning, or venous ultrasound. D-dimer levels were tested for statistical difference across groups stratified by sex and diagnosis. Multivariable regression was used to investigate sex as a predictor of diagnosis. Sex-specific optimal D-dimer thresholds for PE and DVT were calculated from receiver operating characteristic analyses. A Youden threshold (D-dimer level coinciding with the maximum of sensitivity plus specificity) and a cutoff corresponding to 95% sensitivity were calculated. Statistical difference for cutoffs was tested via 95% confidence intervals from 2,000 bootstrapped samples.

Results: We included 3,586 subjects for analysis, of whom 61% were female. Race demographics were 63% White, 27% Black/African American, and 6% Hispanic. In the suspected PE cohort, 6% were diagnosed with PE, while in the suspected DVT cohort, 11% were diagnosed with DVT. D-dimer levels were significantly higher in males than females for the PE-positive group and the DVT-negative group, but males had significantly lower D-dimer levels than females in the PE-negative group. Regression models showed male sex as a significant positive predictor of DVT diagnosis, controlling for D-dimer levels. The Youden thresholds for PE patients were 0.97 (95% CI = 0.64 to 1.79) mg/L and 1.45 (95% CI = 1.36 to 1.95) mg/L for females and males, respectively; 95% sensitivity cutoffs for this group were 0.64 (95% CI = 0.20 to 0.89) and 0.55 (95% CI = 0.29 to 1.61). For DVT, the Youden thresholds were 0.98 (95% CI = 0.84 to 1.56) mg/L for females and 1.25 (95% CI = 0.65 to 3.33) mg/L for males with 95% sensitivity cutoffs of 0.33 (95% CI = 0.2 to 0.61) and 0.32 (95% CI = 0.18 to 0.7), respectively.

Conclusion: Differences in D-dimer levels between males and females are diagnosis specific; however, there was no significant difference in optimal cutoff values for excluding PE and DVT between the sexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acem.14220DOI Listing
January 2021

Sex-related differences in D-dimer levels for venous thromboembolism screening.

Acad Emerg Med 2021 Jan 26. Epub 2021 Jan 26.

Department of Emergency Medicine, University of Cincinnati, Cincinnati, Ohio, USA.

Background: D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized that the accuracy of D-dimer tests may be enhanced by using appropriate cutoff values that reflect sex-related differences in D-dimer levels.

Methods: This research is a secondary analysis of a multicenter, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pretest probability based on Wells criteria ≤ 6 for pulmonary embolism (PE) and ≤ 2 for deep vein thrombosis (DVT). VTE diagnoses were based on computed tomography, ventilation perfusion scanning, or venous ultrasound. D-dimer levels were tested for statistical difference across groups stratified by sex and diagnosis. Multivariable regression was used to investigate sex as a predictor of diagnosis. Sex-specific optimal D-dimer thresholds for PE and DVT were calculated from receiver operating characteristic analyses. A Youden threshold (D-dimer level coinciding with the maximum of sensitivity plus specificity) and a cutoff corresponding to 95% sensitivity were calculated. Statistical difference for cutoffs was tested via 95% confidence intervals from 2,000 bootstrapped samples.

Results: We included 3,586 subjects for analysis, of whom 61% were female. Race demographics were 63% White, 27% Black/African American, and 6% Hispanic. In the suspected PE cohort, 6% were diagnosed with PE, while in the suspected DVT cohort, 11% were diagnosed with DVT. D-dimer levels were significantly higher in males than females for the PE-positive group and the DVT-negative group, but males had significantly lower D-dimer levels than females in the PE-negative group. Regression models showed male sex as a significant positive predictor of DVT diagnosis, controlling for D-dimer levels. The Youden thresholds for PE patients were 0.97 (95% CI = 0.64 to 1.79) mg/L and 1.45 (95% CI = 1.36 to 1.95) mg/L for females and males, respectively; 95% sensitivity cutoffs for this group were 0.64 (95% CI = 0.20 to 0.89) and 0.55 (95% CI = 0.29 to 1.61). For DVT, the Youden thresholds were 0.98 (95% CI = 0.84 to 1.56) mg/L for females and 1.25 (95% CI = 0.65 to 3.33) mg/L for males with 95% sensitivity cutoffs of 0.33 (95% CI = 0.2 to 0.61) and 0.32 (95% CI = 0.18 to 0.7), respectively.

Conclusion: Differences in D-dimer levels between males and females are diagnosis specific; however, there was no significant difference in optimal cutoff values for excluding PE and DVT between the sexes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/acem.14220DOI Listing
January 2021

Missing value imputation in proximity extension assay-based targeted proteomics data.

PLoS One 2020 14;15(12):e0243487. Epub 2020 Dec 14.

Institute of Organismic and Molecular Evolution, Johannes Gutenberg University Mainz, Mainz, Germany.

Targeted proteomics utilizing antibody-based proximity extension assays provides sensitive and highly specific quantifications of plasma protein levels. Multivariate analysis of this data is hampered by frequent missing values (random or left censored), calling for imputation approaches. While appropriate missing-value imputation methods exist, benchmarks of their performance in targeted proteomics data are lacking. Here, we assessed the performance of two methods for imputation of values missing completely at random, the previously top-benchmarked 'missForest' and the recently published 'GSimp' method. Evaluation was accomplished by comparing imputed with remeasured relative concentrations of 91 inflammation related circulating proteins in 86 samples from a cohort of 645 patients with venous thromboembolism. The median Pearson correlation between imputed and remeasured protein expression values was 69.0% for missForest and 71.6% for GSimp (p = 5.8e-4). Imputation with missForest resulted in stronger reduction of variance compared to GSimp (median relative variance of 25.3% vs. 68.6%, p = 2.4e-16) and undesired larger bias in downstream analyses. Irrespective of the imputation method used, the 91 imputed proteins revealed large variations in imputation accuracy, driven by differences in signal to noise ratio and information overlap between proteins. In summary, GSimp outperformed missForest, while both methods show good overall imputation accuracy with large variations between proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243487PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735586PMC
January 2021

[Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results].

Z Psychosom Med Psychother 2020 Dec;66(4):355-375

Klinik und Poliklinik für Psychosomatische Medizin und Psychotherapie Universitätsmedizin Mainz Johannes Gutenberg-Universität Mainz Deutschland.

Main questions from the Gutenberg Health Study (GHS) related to psychosomatic medicine are presented: (1) Prevalence and incidence of mental illnesses, (2) Sex-specific risk- and protective factors for mental health, (3) Interplay between psychological and somatic diseases and (4) methodical-psychometric developments. The GHS is an ongoing, prospective and interdisciplinary cohort study in Mainz. The comprehensive examinations include psychological characteristics and clinical and laboratory tests. 15010 respondents were selected in the baseline study from 2007 until 2012 and re-examined after 2.5 years and 5 years. Of the first 5000 respondents in the baseline study 413 women (8.7 %) and 276 men (5.8 %) indicated depressive symptoms (PHQ-9 > = 10). After five years, half of the participants with depressive symptoms at baseline also indicated depressive symptoms five years later. Risk factors for men were a lack of social support, for women smoking and Type D personality. The proportion of new cases of depression at follow-up was 4.4 %. Risk factors were symptoms of anxiety, Type D, smoking and comorbid cancer. Protective were age and social support. Findings on the association of physical and mental disorders and their behavioral and biological links (atherosclerosis, inflammation) are presented. Prospective assessment of biological, psychological and social parameters offers the possibility to study their interplay in the development of mental and somatic illnesses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13109/zptm.2020.66.4.355DOI Listing
December 2020

Incidence of Retinal Detachment in Germany: Results from the Gutenberg Health Study.

Ophthalmologica 2021 16;244(2):133-140. Epub 2020 Nov 16.

Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Purpose: To investigate the incidence of retinal detachment in the German population and to assess potential risk factors.

Methods: The Gutenberg Health Study is a population-based cohort study in Mainz, Germany, including subjects (n = 15,010) with an age range from 35 to 74 years at baseline examination. Study participants underwent a comprehensive ophthalmological examination including distant-corrected visual acuity, refraction and slit-lamp examination at baseline examination. A computer-assisted telephone interview was conducted after 2.5 and 5 years, and health events were recorded. The 5-year cumulative incidence of retinal detachment was computed for the study sample and stratified on age decades. Risk factors were analyzed using logistic regression including age, sex, spherical equivalent, pseudophakia and prior laser retinal therapy.

Results: 13,416 participants (age 52.2 ± 10.7 years, 48.8% female) were included in this analysis. Twenty-eight subjects had a retinal detachment in one eye, no subject had a retinal detachment in both eyes. The 5-year cumulative incidence of retinal detachment was 0.21% (95% CI 0.14-0.31%), the incidence rate was 42/100,000 person-years. Risk factors were male sex (OR 4.16, p = 0.004), pseudophakia (OR 3.93, p = 0.045) and myopia (OR 1.31 per diopter myopia, p < 0.0001), but not prior retinal laser therapy or age.

Conclusion: The incidence of retinal detachment in Germany at the age of 35-74 years is comparable to estimates from neighboring European countries. Risk factors are male sex, pseudophakia and myopia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000513080DOI Listing
November 2020

Self-reported cardiovascular health of teachers: results from the 5-year follow-up of the Gutenberg Health Study cohort.

Int Arch Occup Environ Health 2021 Feb 26;94(2):251-259. Epub 2020 Oct 26.

Institute for Teachers' Health, University Medical Center of the Johannes Gutenberg University of Mainz, Kupferbergterrasse 17-19, 55116, Mainz, Germany.

Objectives: Following an exploratory approach, we examined cardiovascular disease risk factors at baseline and the 5-year incidence proportion of self-reported doctor-diagnosed cardiovascular diseases (CVD) in teachers and other occupational groups of the Gutenberg Health Study.

Methods: Study participants lived in the region of Mainz, Germany. Data from 6510 working participants without prevalent CVD at baseline (2007-2012) were analyzed. Participants were teachers (n = 215), other professionals from the health, social or educational (HSE) fields (n = 1061) or worked outside the HSE fields (n = 5234). For occupational comparisons, we estimated prevalence ratios (PR) for each CVD risk factor at baseline with robust Poisson regression analyses. We calculated crude CVD incidence rates based on the observed 5-year CVD cumulative incidence at follow-up and estimated age-weighted incidence proportions. All analyses were stratified by sex.

Results: Male non-HSE workers showed a higher prevalence of smoking and physical inactivity than male teachers (PR 2.26; 95%-CI: 1.06-4.82/PR 1.89; 95%-CI: 1.24-2.87). In contrast, non-HSE workers and other HSE professionals were less likely to have reported an unhealthy alcohol intake than teachers. Differences were attenuated after SES-adjustment. We did not detect occupational group-specific differences in CVD incidence. However, there were only two cases of CVD among the teachers.

Conclusion: Particularly male teachers showed a healthier lifestyle regarding physical inactivity and smoking. Nevertheless, occupational-medical care practitioners and researchers need to be aware of the relatively heightened prevalence of unhealthy alcohol intake in female and male teachers, and in absolute terms, the high hypertension prevalence in male teachers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00420-020-01576-9DOI Listing
February 2021

c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans.

J Thromb Haemost 2021 01 18;19(1):147-152. Epub 2020 Nov 18.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Essentials Prekallikrein (PK) deficiency is a recessive trait with isolated aPTT prolongation. KLKB1 c.451dupT is common in Nigerians (7/600 alleles) and absent in a European group (0/600). To date, all genotyped PK-deficient patients of African ancestry were homozygous for 451dupT. Diagnostics of isolated aPTT prolongation in African descendants should include PK testing. ABSTRACT: Background Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Africans according to gnomAD (allele frequency 1.43%). Patients/Methods The most common African (c.451dupT) and European (c.1643G>A, p.Cys548Tyr) PK deficiency causing KLKB1 variants were analyzed in two population-based collectives of 300 Nigerian and 300 German subjects. Genome databases were evaluated for variant frequencies and ethnicity of the subjects. The geographic origin of PK-deficient cases due to 451dupT was assessed. Results Two of five patients with PK deficiency caused by homozygous 451dupT were African, one African American, one from Oman, and one of unknown origin. The frequency of 451dupT was 1.17% in the Nigerian collective (7/600 alleles); none had Cys548Tyr. Subjects with 451dupT were found among different Nigerian ethnicities. Both variants were absent in the European collective. Database research was compatible with these findings, even though mainly data of African Americans (451dupT: 1.12%-1.78%) was accessible. A relevant number of non-American Africans are included only in the 1000Genomes collective: 451dupT frequency was 1.29% in native Africans and 1.56% in African Caribbeans. Conclusions This study underlines the higher prevalence of PK deficiency among people with African descent compared to Europeans. In order to avoid delay of necessary surgical procedures in patients of African origin, diagnostic algorithms for isolated, unexplained, activated partial thromboplastin time prolongation in these subjects should include PK deficiency screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jth.15137DOI Listing
January 2021

Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism-Results from the thrombEVAL Study.

J Clin Med 2020 Oct 13;9(10). Epub 2020 Oct 13.

Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011-March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2-87.1%) vs. 69.5% (52.3-85.6%), < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85-465.26), = 0.0015), clinically relevant bleeding (RR 6.80 (2.52-25.76), < 0.001), hospitalizations (RR 2.54 (1.94-3.39), < 0.001) and mortality under OAC (RR 5.89 (2.40-18.75), < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81-10.33), < 0.0001), mortality (HR 5.54 (2.22-13.84), = 0.00025), thromboembolic events (HR 6.41 (1.51-27.24), = 0.012), clinically relevant bleeding (HR 5.31 (1.89-14.89), = 0.0015) and hospitalization (HR 1.84 (1.34-2.55), = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9103281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602093PMC
October 2020

Thrombin generation in cardiovascular disease and mortality - results from the Gutenberg Health Study.

Haematologica 2020 09 1;105(9):2327-2334. Epub 2020 Sep 1.

Department of Internal Medicine, (CARIM), Maastricht University Medical Center, The Netherlands.

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. This study aims to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, N=5000 subjects from the population-based Gutenberg Health Study were analysed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factors trigger in platelet poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted for age, cardiovascular risk factors, cardiovascular diseases and therapy, was used to assess clinical determinants of thrombin generation. Cox regression models adjusted for age, sex, cardiovascular risk factors and vitamin K antagonists investigated the association between thrombin generation parameters and total mortality. Lag time was positively associated with obesity and dyslipidaemia for both sexes (p<0.0001). Obesity was also positively associated with endogenous thrombin potential in both sexes (p<0.0001) and peak height in males (1 pM tissue factor, p=0.0048) and females (p<0.0001). Cox regression models showed an increased mortality in individuals with lag time (1 pM tissue factor, hazard ratio=1.46, [95% CI: 1.07; 2.00], p=0.018) and endogenous thrombin potential (5 pM tissue factor, hazard ratio = 1.50, [1.06; 2.13], p=0.023) above the 95th percentile of the reference group, independent of the cardiovascular risk profile. This large-scale study demonstrates traditional cardiovascular risk factors, particularly obesity, as relevant determinants of thrombin generation. Lag time and endogenous thrombin potential were found as potentially relevant predictors of increased total mortality, which deserves further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2019.221655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556497PMC
September 2020

Birth Weight and Diabetic Retinopathy: Results From the Population-Based Gutenberg Health Study (GHS).

Ophthalmic Epidemiol 2021 04 29;28(2):122-130. Epub 2020 Sep 29.

Department of Ophthalmology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

Purpose: This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population.

Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.5% at study entry, a doctor-diagnosis of diabetes, or diabetes medication. The presence of DR was determined by evaluating fundus photographs. BW was assessed by self-reports. GHS participants were divided into three different BW groups (low: <2500 g; normal: 2500-4000 g; high:>4000 g). Logistic regression analysis was conducted as uni- and multivariable analysis with adjustment for age and sex. Effect mediators were separately investigated.

Results: A total of 1,124 GHS participants (7.5% of the cohort) had diabetes at study entry. Of these, 402 subjects (35.8%) had gradable fundus photographs, reported BW data and were included into this study. Overall, 91/402 subjects (23%) had DR. With regard to BW groups, DR was descriptively more frequent in subjects with low (28.1% [95%-CI: 14.4-47.0%; n = 32]) and high BW (30.8% [95%-CI: 19.1-45.3%; n = 52]) compared to normal BW (20.8% [95%-CI: 16.5-25.7%; n = 318]). Both high and low BW were associated with DR in multivariable analysis (high: OR = 1.68, = .037; low: OR = 1.81, = .05). The BW effect was mediated by duration of diabetes in both BW groups and by arterial hypertension in the low BW group.

Conclusion: Low and high BW in persons with diabetes is related to higher risk of diabetic retinopathy. Longer duration of diabetes and higher prevalence of arterial hypertension are factors in these subjects explaining the elevated risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09286586.2020.1800753DOI Listing
April 2021

The relationship of ocular geometry with refractive error in normal and low birth weight adults.

J Optom 2021 Jan - Mar;14(1):50-57. Epub 2020 Sep 23.

Department of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.

Purpose: Low birth weight (BW) individuals have an increased risk for myopic refractive error. However, it is unclear which ocular geometric alterations lead to an increase in myopic refractive error. This study aims to evaluate the impact of ocular biometry in interaction with BW on refractive error.

Methods: Participants of the prospective, observational, population-based Gutenberg Health Study (GHS) with self-reported BW aged 40-80 years and objective refraction and optical biometry were included. Linear regression analyses were conducted to evaluate associations between spherical equivalent with corneal power, anterior chamber depth, lens thickness and axial length and its interaction with BW adjusted for age and sex. Low BW was defined as BW<2500 g and normal BW between 2500-4000 g.

Results: Overall, 5123 participants were included. Linear regression showed an interaction of axial length (B = 0.009/100 g, p = 0.002) with BW on spherical equivalent while corneal power, anterior chamber depth and lens thickness revealed no interaction with BW on refractive error. Furthermore, linear regression analysis revealed, that axial length explains 58% of variance of spherical equivalent in low BW subjects, and 54% in normal BW subjects. In contrast, corneal power explained 1% of variance of spherical equivalent in both groups.

Conclusions: Our results indicate that axial length variation explains the majority of variance in refractive error, while steeper corneal shape has no conclusive effects on refractive error. Low BW is not linked to effects of steeper corneal shape on myopic refractive error, while the effect of axial length on myopia is fractionally enlarged in those subjects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.optom.2020.08.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752971PMC
September 2020

Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies.

EBioMedicine 2020 Oct 10;60:102978. Epub 2020 Sep 10.

Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg-University Mainz, Germany; Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz, Germany; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain, Mainz, Germany.

Background: The pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.

Methods: Platelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and platelet-related variables.

Findings: VTE cases (N = 159) presented with lower platelet count and MPV vs controls (N = 140). Whole blood aggregation showed shorter collagen/Epinephrine closure times in cases, particularly within acetylsalicylic acid (ASA) users. Within ASA users, higher PRP aggregation after adenosine diphosphate (ADP), epinephrine, collagen and arachidonic acid was observed in cases vs controls. Within non-ASA and/or subjects on anticoagulants, cases presented with lower aggregation after ADP and collagen vs controls. Lower platelet-dependent TG, higher CD63 on resting and lower PAC-1 expression after collagen/ADP in-vitro stimulated platelets further characterized VTE cases vs controls, independent of therapy. Lasso regression analysis identified 26 variables associated with VTE of which 69% were platelet-related.

Interpretation: Comprehensive phenotyping of platelet function identified a large proportion of low responders to ASA in VTE cases. Lower platelet-dependent TG and lower platelet reactivity after ex-vivo stimulation characterized the "platelet exhausted syndrome" in cases. Finally, from a large array of covariates including clinical risk factors, platelet biomarkers comprised 69% of all selected variables differentiating VTE cases vs controls.

Funding: German Federal Ministry of Education and Research, CTH-Mainz and Bayer AG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.102978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494681PMC
October 2020