Publications by authors named "Philipp S Wild"

258 Publications

Galectin-3 for prediction of cardiac function compared to NT-proBNP in individuals with prediabetes and type 2 diabetes mellitus.

Sci Rep 2021 Sep 24;11(1):19012. Epub 2021 Sep 24.

German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, Mainz, Germany.

Use of galectin-3 for assessing cardiac function in prediabetes and type 2 diabetes mellitus (T2DM) needs to be established. Within the Gutenberg Health Study cohort (N = 15,010, 35-74 years) patient characteristics were investigated regarding galectin-3 levels. Prognostic value of galectin-3 compared to NT-proBNP concerning cardiac function and mortality was assessed in individuals with euglycaemia, prediabetes and T2DM in 5 years follow-up. Higher galectin-3 levels related to older age, female sex and higher prevalence for prediabetes, T2DM, cardiovascular risk factors and comorbidities. Galectin-3 cross-sectionally was related to impaired systolic (β - 0.36, 95% CI - 0.63/- 0.09; P = 0.008) and diastolic function (β 0.014, 95% CI 0.001/0.03; P = 0.031) in T2DM and reduced systolic function in prediabetes (β - 0.34, 95% CI - 0.53/- 0.15; P = 0.00045). Galectin-3 prospectively related to systolic (β - 0.656, 95% CI - 1.07/- 0.24; P = 0.0021) and diastolic dysfunction (β 0.0179, 95% CI 0.0001/0.036; P = 0.049), cardiovascular (hazard ratio per standard deviation of galectin-3 (HR) 1.60, 95% CI 1.39-1.85; P < 0.0001) and all-cause mortality (HR 1.36, 95% CI 1.25-1.47; P < 0.0001) in T2DM. No relationship between galectin-3 and cardiac function was found in euglycaemia, whereas NT-proBNP consistently related to reduced cardiac function. Prospective value of NT-proBNP on cardiovascular and all-cause mortality was higher. NT-proBNP was superior to galectin-3 to assess reduced systolic and diastolic function.
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http://dx.doi.org/10.1038/s41598-021-98227-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463561PMC
September 2021

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

PLoS One 2021 21;16(9):e0255893. Epub 2021 Sep 21.

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

Purpose: We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany.

Methods: The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corneal thickness, intraocular pressure (IOP), socio-economic status, smoking, BMI, systolic and diastolic arterial blood pressure, HbA1c, HDL-C, LDL-C, triglyceride, and lipid modifying agents.

Results: A total of 9,850 right and 9,745 left eyes of 9,858 subjects (59.2±10.8 years), 49.0% females were included in this cross-sectional analysis. 21.1% of men (95%-CI: 20.0%- 22.3%) had a corneal arcus in at least one eye, and 16.9% (95%-CI: 15.9%- 18.0%) of women. In multivariable analyses, the presence of corneal arcus was associated with male gender (OR = 0.54 for female, p<0.0001), higher age (OR = 2.54 per decade, p<0.0001), smoking (OR = 1.59, p<0.0001), hyperopia (OR = 1.05 per diopter, p<0.0001), thinner cornea (OR = 0.994 per μm, p<0.0001), higher IOP (OR = 1.02, p = 0.039), higher HDL-C-level (OR = 2.13, p<0.0001), higher LDL-C-level (OR = 1.21, p<0.0001), and intake of lipid modifying agents (OR = 1.26, p = 0.0001). Arcus was not associated with socio-economic status, BMI, arterial blood pressure, and HbA1c.

Conclusions: Corneal arcus is a frequent alteration of the cornea in Germany and is associated with ocular parameters and systemic parameters of dyslipidemia.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255893PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454945PMC
September 2021

Disturbed Glucose Metabolism and Left Ventricular Geometry in the General Population.

J Clin Med 2021 Aug 27;10(17). Epub 2021 Aug 27.

German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main, 55131 Mainz, Germany.

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH).

Methods: 15,010 subjects (35-74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up.

Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) over prediabetes (17.8%) to T2DM (23.8%). Prediabetes and T2DM were associated with increased LV mass index (prediabetes: β1.3 (95% CI 0.78-1.81), < 0.0001; T2DM: β2.37 (95% CI 1.81; 2.92), < 0.0001) independent of age, sex, and cardiovascular risk factors (CVRF). The frequency of LVH was related to the presence of T2DM (prevalence ratio (PR)T2DM 1.2 (95% CI 1.06-1.35), = 0.0038). T2DM was related to mortality independent of age, sex, and CVRF regardless of LVH (hazard ratio (HR)T2DM-LVH 2.67 (95% CI 1.94-3.66), < 0.0001; HRT2DM-noLVH 1.59 (95% CI 1.29-1.96), < 0.0001), prediabetes was only associated with outcome in individuals with LVH independent of age and sex (HRprediabetes-LVH 1.51 (95% CI 1.01-2.25), = 0.045). Neither T2DM nor prediabetes were predictors of incident LVH after adjustment for clinical covariates.

Conclusions: Prediabetes and T2DM promote alterations of cardiac geometry. T2DM and particularly the coprevalence of T2DM with LVH substantially reduce life expectancy. These findings highlight the need for new therapeutic and screening approaches to prevent and detect cardiometabolic diseases at an early stage.
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http://dx.doi.org/10.3390/jcm10173851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432105PMC
August 2021

Mortality risk among 5-year survivors of childhood cancer in Germany-Results from the CVSS study (Cardiac and Vascular late Sequelae in long-term Survivors of childhood cancer study).

Int J Cancer 2021 Aug 25. Epub 2021 Aug 25.

Division of Childhood Cancer Epidemiology, Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 individuals was used to estimate cause-specific mortality for all deceased persons. Compared to the population of (former) West Germany, we observed an excess overall mortality risk (SMR = 9.53, 95% confidence interval [CI] = 8.62-10.51). After correcting for missing cause of death information, an increased cancer mortality (SMR = 43.50, 95% CI = 25.79-73.50) in the 5-year survivors was detected. Cardiac death was ascertained in 14 individuals, resulting in an SMR of 10.85 (95% CI = 2.80-32.02) after correcting for missing values. In conclusion, childhood cancer survivors diagnosed in Germany in 1980 to 1990 have a higher mortality risk overall and an elevated risk of dying from cancer and cardiac causes in particular. The results are consistent with those of international cohort studies. However, the reported results are based on few cases and individuals with secondary cancers were excluded.
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http://dx.doi.org/10.1002/ijc.33772DOI Listing
August 2021

Five-year cumulative incidence and progression of age-related macular degeneration: results from the German population-based Gutenberg Health Study (GHS).

Graefes Arch Clin Exp Ophthalmol 2021 Aug 23. Epub 2021 Aug 23.

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

Purpose: Age-related macular degeneration (AMD) is a major cause of visual impairment and blindness. This study evaluates the incidence and progression of AMD in a large German cohort.

Methods: The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany that includes 15,010 participants between 35 and 74 years of age. The baseline examination, including fundus photography, was conducted between 2007 and 2012, and the 5-year follow-up examination was performed between 2012 and 2017. AMD grading of fundus photographs was performed according to the Rotterdam Eye Study classification. The 5-year cumulative incidence and progression of AMD were calculated. Poisson regression analysis was conducted to investigate factors associated with the cumulative incidence and progression of AMD.

Results: Six-thousand-eight-hundred-eighty-eight participants (49.8%, n = 3427 female) were included in the analysis. AMD prevalence was 8.5% [95% CI: 7.9-9.2%] at baseline and 10.3% [95% CI: 9.6-11.1%] at follow-up. The cumulative 5-year-incidence was 2.0% [1.7-2.4%]. AMD progression within 5 years was seen in 18.1% [95% CI: 15.1-21.5%] of the participants. AMD incidence and AMD progression were associated with higher age, for each 10-year increase in age, the risk of AMD doubles (RR = 2.30), and the risk of progression of the disease is increased by 1.6. while AMD incidence also with pseudophakic status.

Conclusions: In summary, this population-based sample provides substantial epidemiologic data from a large German cohort, including data on progression and cumulative incidence of macular degeneration in younger age groups. AMD progression over 5 years is common in the German population, 18.1% of subjects with AMD showed progression in at least one eye in this time frame and is associated with higher age. Nevertheless, although usually defined to occur over the age of 50, in this cohort AMD occurred in 0.5% and AMD progression occurred in 5.4% of those already affected in the youngest age group before 50 years of age.
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http://dx.doi.org/10.1007/s00417-021-05312-yDOI Listing
August 2021

FEV Predicts Cardiac Status and Outcome in Chronic Heart Failure.

Chest 2021 Aug 17. Epub 2021 Aug 17.

Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany; Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address:

Background: COPD is an established predictor of clinical outcome in patients with chronic heart failure (HF). However, little evidence is available about the predictive value of FEV in chronic HF.

Research Question: Is pulmonary function related to the progression of chronic HF?

Study Design And Methods: The MyoVasc study (ClinicalTrials.gov Identifier: NCT04064450) is a prospective cohort study of HF. Information on pulmonary and cardiac functional and structural status was obtained by body plethysmography and echocardiography. The primary study end point was worsening of HF.

Results: Overall 2,998 participants (age range, 35-84 years) with available FEV data were eligible for analysis. Linear multivariate regression analysis revealed an independent relationship of FEV (per -1 SD) with deteriorated systolic and diastolic left ventricle (LV) function as well as LV hypertrophy under adjustment of age, sex, height, cardiovascular risk factors (CVRFs), and clinical profile (LV ejection fraction: β-estimate, -1.63% [95% CI, -2.00% to -1.26%]; E/E' ratio: β-estimate, 0.82 [95% CI, 0.64-0.99]; and LV mass/height: β-estimate, 1.58 [95% CI, 1.07-2.10]; P < .001 for all). During a median time to follow-up of 2.6 years (interquartile range, 1.1-4.1 years), worsening of HF occurred in 235 individuals. In Cox regression model adjusted for age, sex, height, CVRF, and clinical profile, pulmonary function (FEV per -1 SD) was an independent predictor of worsening of HF (hazard ratio [HR], 1.44 [95% CI, 1.27-1.63]; P < .001). Additional adjustment for obstructive airway pattern and C-reactive protein mitigated, but did not substantially alter, the results underlining the robustness of the observed effect (HR, 1.39 [95% CI, 1.20-1.61]; P < .001). The predictive value of FEV was consistent across subgroups, including individuals without obstruction (HR, 1.55 [95% CI, 1.34-1.77]; P < .001) and nonsmokers (HR, 1.72 [95% CI, 1.39-1.96]; P < .001).

Interpretation: FEV represents a strong candidate to improve future risk stratification and prevention strategies in individuals with chronic, stable HF.

Trial Registry: ClinicalTrials.gov; No.: NCT04064450; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.07.2176DOI Listing
August 2021

Rationale, design and baseline characteristics of the MyoVasc study: A prospective cohort study investigating development and progression of heart failure.

Eur J Prev Cardiol 2021 Aug;28(9):1009-1018

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

Background: Heart failure (HF) is a poly-aetiological syndrome with large heterogeneity regarding clinical presentation, pathophysiology, clinical outcome and response to therapy. The MyoVasc study (NCT04064450) is an epidemiological cohort study investigating the development and progression of HF.

Methods: The primary objective of the study is (a) to improve the understanding of the pathomechanisms of HF across the full spectrum of clinical presentation, (b) to investigate the current clinical classifications of HF, and (c) to identify and characterize homogeneous subgroups regarding disease development using a systems-oriented approach. Worsening of HF, that is, the composite of transition from asymptomatic to symptomatic HF, hospitalization due to HF, or cardiac death, was defined as the primary endpoint of the study. During a six-year follow-up period, all study participants receive a highly standardized, biannual five-hour examination in a dedicated study centre, including detailed cardiovascular phenotyping and biobanking of various biomaterials. Annual follow-up examinations are conducted by computer-assisted telephone interviews recording comprehensively the participants´ health status, including subsequent validation and adjudication of adverse events.

Results: In total, 3289 study participants (age range: 35 to 84 years; female sex: 36.8%) including the full range of HF stages were enrolled from 2013 to 2018. Approximately half of the subjects (n=1741) presented at baseline with symptomatic HF (i.e. HF stage C/D). Among these, HF with preserved ejection fraction was the most frequent phenotype.

Conclusions: By providing a large-scale, multi-dimensional biodatabase with sequential, comprehensive medical-technical (sub)clinical phenotyping and multi-omics characterization (i.e. genome, transcriptome, proteome, lipidome, metabolome and exposome), the MyoVasc study will help to advance our knowledge about the heterogeneous HF syndrome by a systems-oriented biomedicine approach.

Trial Registration: ClinicalTrials.gov; NCT04064450.
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http://dx.doi.org/10.1177/2047487320926438DOI Listing
August 2021

Chronic venous insufficiency, cardiovascular disease, and mortality: a population study.

Eur Heart J 2021 Aug 13. Epub 2021 Aug 13.

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

Aims : Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce.

Methods And Results : Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40-80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was done in an independent cohort study (MyoVasc, NCT04064450). The prevalence of telangiectasia/reticular, varicose veins, and CVI was 36.5% [95% confidence interval (CI), 35.6-37.4%], 13.3% [12.6-13.9%], and 40.8% [39.9-41.7%], respectively. Age, female sex, arterial hypertension, obesity, smoking, and clinically overt cardiovascular disease were identified as clinical determinants of CVI. Higher CEAP classes were associated with a higher predicted 10-year risk for incident cardiovascular disease in individuals free of cardiovascular disease (n = 9923). During a mean follow-up of 6.4 ± 1.6 years, CVI was a strong predictor of all-cause death independent of the concomitant clinical profile and medication [hazard ratio (HR) 1.46 (95% CI 1.19-1.79), P = 0. 0003]. The association of CVI with an increased risk of all-cause death was externally validated in the MyoVasc cohort [HR 1.51 (95% CI 1.11-2.05), P = 0.009].

Conclusion : Chronic venous insufficiency is highly prevalent in the population and is associated with the presence of cardiovascular risk factors and disease. Individuals with CVI experience an elevated risk of death, which is independent of age and sex, and present cardiovascular risk factors and comorbidities.
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http://dx.doi.org/10.1093/eurheartj/ehab495DOI Listing
August 2021

Distribution of HOMA-IR in a population-based cohort and proposal for reference intervals.

Clin Chem Lab Med 2021 Oct 11;59(11):1844-1851. Epub 2021 Aug 11.

Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany.

Objectives: Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay.

Methods: The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35-74 years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteria. Age- and sex-dependent distributions of HOMA-IR and reference intervals were obtained. In a substudy three insulin assays were compared and HOMA-IR estimated for each assay.

Results: Among the 10,340 participants analyzed there were 6,590 non-diabetic, 2,901 prediabetic, and 849 diabetic individuals. Median (interquartile range [IQR]) HOMA-IR was 1.54 (1.13/2.19), 2.00 (1.39/2.99), and 4.00 (2.52/6.51), respectively. The most stringently selected reference group consisted of 1,065 persons. Median (IQR) HOMA-IR was 1.09 (0.85/1.42) with no significant difference between men and women. The 97.5th percentile was 2.35. There was a non-significant trend towards higher values with older age. Comparison of three immunoassays for insulin showed an unsatisfactory correlation among the assays and systematic differences in calculated HOMA-IR.

Conclusions: We present HOMA-IR reference intervals for adults derived by more or less stringent selection criteria for the reference cohort. In addition we show that assay specific reference intervals for HOMA-IR are required.
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http://dx.doi.org/10.1515/cclm-2021-0643DOI Listing
October 2021

Refined atrial fibrillation screening and cost-effectiveness in the German population.

Heart 2021 Aug 10. Epub 2021 Aug 10.

University of Sydney, Charles Perkins Centre, Heart Research Institute, Sydney, New South Wales, Australia.

Objective: Little is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.

Methods: We performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables.

Results: Of 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of individuals aged 65-74 years and predominantly men (86%). The classical risk factor burden was high in individuals with new AF. The median estimated stroke risk was 2.2%/year, while risk of developing heart failure was 21% over 10 years. In the 65-74 year age group, the cost per quality-adjusted life-year gained resulting from a single timepoint screening was €30 361. In simulations, the costs were highly sensitive to AF detection rates, proportion of treatment and type of oral anticoagulant. Prescreening by Nt-proBNP measurements was not cost-effective in the current setting.

Conclusions: In our middle-aged population cohort, we identified 0.2% new AF by single timepoint screening. There was a significant estimated risk of stroke and heart failure in these individuals. Cost-effectiveness for screening may be reached in individuals aged 65 years and older. The simple age cut-off is not improved by using Nt-proBNP as a biomarker to guide a screening programme.
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http://dx.doi.org/10.1136/heartjnl-2020-318882DOI Listing
August 2021

Five-year change in refractive error and its risk factors: results from the Gutenberg Health Study.

Br J Ophthalmol 2021 Aug 6. Epub 2021 Aug 6.

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

Background/aims: To examine the 5-year change in refractive error in phakic eyes and its risk factors in the general population.

Methods: The Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants from Germany aged 35-74 years at baseline examination (2007-2012). After 5 years, a follow-up examination was carried out (83% participation). 5-year change of spherical equivalent (SE) was computed as difference between follow-up and baseline objective refraction. Linear and logistic regression analysis were conducted analysing potential risk factors. Only phakic eyes at follow-up examination were included.

Results: Right eyes of 10 175 subjects were included. An age-related shift of refractive error was identified, namely -0.12 D for age 35-44 years, 0.25 D for age 45-54 years, 0.25 D for age 55-64 years and 0.12 D for age 65-74 years during the 5-year follow-up. Smokers had a hyperopic shift (OR=1.31; p<0.001), while baseline SE (OR=0.89 per dioptre; p<0.001) and female sex (OR=1.49; p<0.001) were linked with a myopic shift. Education, occupation and other cardiovascular parameters were not associated with change in refractive error.

Conclusions: The GHS demonstrates a parabolic shift in refractive error with a myopic shift at age 35-44 years, followed by a hyperopic shift at age 45-64 years which decreases at higher age. Smoking is associated with a hyperopic shift whereas female sex and myopic baseline SE is associated with a myopic shift. Educational level and occupation were not linked to a change in refractive error at age 35-74 years.
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http://dx.doi.org/10.1136/bjophthalmol-2021-318828DOI Listing
August 2021

Domains of Physical Activity in Relation to Stiffness Index in the General Population.

J Am Heart Assoc 2021 08 5;10(16):e020930. Epub 2021 Aug 5.

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

Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex-specific relations between domains of physical activity (PA; commuting, domestic, and leisure-time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self-reported PA was evaluated by the "Short Questionnaire to Assess Health-Enhancing Physical Activity" and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrated strong beneficial effects of repetitive activities, such as active commuting or leisure-time PA-related walking on AS in men, but not in women. Lower AS associated with endurance training was also found among men and premenopausal women. In contrast, intense occupational PA was related to stiffer vessels in men (<0.0001) and women (=0.0021) in a fully adjusted model. Combination of both, performing endurance training and having stiffness index values below median, resulted in the best survival. In contrast, subjects with elevated stiffness index at baseline without any endurance activities demonstrated the worst survival. Conclusions In this population representative sample, a differential impact of domains of self-reported PA on AS was demonstrated. Our data strengthen the importance of regular endurance PA to induce a reduction of AS, which, in turn, may improve cardiovascular prognosis. We also report deleterious effects of intense occupational PA on stiffness index, a finding that needs further confirmation by larger prospective trials.
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http://dx.doi.org/10.1161/JAHA.121.020930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475023PMC
August 2021

A targeted proteomics investigation of the obesity paradox in venous thromboembolism.

Blood Adv 2021 07;5(14):2909-2918

Preventive Cardiology and Preventive Medicine, Center for Cardiology.

The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass-related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technology. Measurements were performed in samples collected during the acute VTE event and at 12-month follow-up. An 11-protein signature (CLEC4C, FABP4, FLT3LG, IL-17C, LEP, LYVE1, MASP1, ST2, THBS2, THBS4, TSLP) for body mass in VTE patients was identified. The signature did not significantly mediate the obesity paradox (change in hazard ratio [HR]: 0.04; likelihood ratio test of nested models = 7.7; P = .74), but its main constituent protein, leptin, was inversely associated with recurrent VTE or death (adjusted HR [95% confidence interval] per standard deviation increase: 0.66 [0.46-0.94]). This relationship was significantly (P = .007) modified by markers of leptin resistance (ie, high body mass index and high circulating matrix metalloproteinase-2 levels). Although the signature did not substantially explain the obesity paradox, leptin appears to be protective against disease recurrence and death in VTE patients. This protective effect was abrogated under conditions of leptin resistance and hence was unrelated to the obesity paradox.
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http://dx.doi.org/10.1182/bloodadvances.2020003800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341360PMC
July 2021

Soluble Platelet Release Factors as Biomarkers for Cardiovascular Disease.

Front Cardiovasc Med 2021 21;8:684920. Epub 2021 Jun 21.

Departments of Biochemistry and Internal Medicine, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.

Platelets are the main players in thrombotic diseases, where activated platelets not only mediate thrombus formation but also are involved in multiple interactions with vascular cells, inflammatory components, and the coagulation system. Although reactivity of platelets provides information on the function of circulating platelets, it is not a full reflection of the activation state, which may be relevant for thrombotic risk assessment in various disease conditions. Therefore, studying release markers of activated platelets in plasma is of interest. While this type of study has been done for decades, there are several new discoveries that highlight the need for a critical assessment of the available tests and indications for platelet release products. First, new insights have shown that platelets are not only prominent players in arterial vascular disease, but also in venous thromboembolism and atrial fibrillation. Second, knowledge of the platelet proteome has dramatically expanded over the past years, which contributed to an increasing array of tests for proteins released and shed from platelets upon activation. Identification of changes in the level of plasma biomarkers associated with upcoming thromboembolic events allows timely and individualized adjustment of the treatment strategy to prevent disease aggravation. Therefore, biomarkers of platelet activation may become a valuable instrument for acute event prognosis. In this narrative review based on a systematic search of the literature, we summarize the process of platelet activation and release products, discuss the clinical context in which platelet release products have been measured as well as the potential clinical relevance.
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http://dx.doi.org/10.3389/fcvm.2021.684920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255615PMC
June 2021

Sex-Specific Relationship Between Parathyroid Hormone and Platelet Indices in Phenotypes of Heart Failure-Results From the MyoVasc Study.

Front Cardiovasc Med 2021 16;8:682521. Epub 2021 Jun 16.

DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, Mainz, Germany.

Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF. This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF. PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk factors, comorbidities, estimated glomerular filtration rate, and medication, were used to assess the associations between platelet indices and PTH. The results showed distinct sex-specific associations between PTH and platelet indices. A positive association between PTH and MPV was found in females with symptomatic HF with reduced ejection fraction (HFrEF) only [β = 0.60 (0.19; 1.00)]. Platelet count was inversely associated with PTH in male HFrEF individuals [β = -7.6 (-15; -0.30)] and in both males and females with HF with preserved ejection fraction (HFpEF). This study reports differential, sex-specific relationships between PTH and platelet indices in HF individuals independent of vitamin D status and clinical profile. Particularly in phenotypes of symptomatic HF, distinct associations were observed, suggesting a sex-specific mechanism involved in the interaction between PTH and platelets.
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http://dx.doi.org/10.3389/fcvm.2021.682521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245004PMC
June 2021

Cardiovascular profiling in the diabetic continuum: results from the population-based Gutenberg Health Study.

Clin Res Cardiol 2021 Jun 24. Epub 2021 Jun 24.

Department of Cardiology - Cardiology I, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstr. 1, 55131, Mainz, Germany.

Aims: To assess the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes in the general population and to investigate the associated cardiovascular burden and clinical outcome.

Methods And Results: The study sample comprised 15,010 individuals aged 35-74 years of the population-based Gutenberg Health Study. Subjects were classified into euglycaemia, prediabetes and T2DM according to clinical and metabolic (HbA1c) information. The prevalence of prediabetes was 9.5% (n = 1415) and of T2DM 8.9% (n = 1316). Prediabetes and T2DM showed a significantly increased prevalence ratio (PR) for age, obesity, active smoking, dyslipidemia, and arterial hypertension compared to euglycaemia (for all, P < 0.0001). In a robust Poisson regression analysis, prediabetes was established as an independent predictor of clinically-prevalent cardiovascular disease (PR 1.20, 95% CI 1.07-1.35, P = 0.002) and represented as a risk factor for asymptomatic cardiovascular organ damage independent of traditional risk factors (PR 1.04, 95% CI 1.01-1.08, P = 0.025). Prediabetes was associated with a 1.5-fold increased 10-year risk for cardiovascular disease compared to euglycaemia. In Cox regression analysis, prediabetes (HR 2.10, 95% CI 1.76-2.51, P < 0.0001) and T2DM (HR 4.28, 95% CI 3.73-4.92, P < 0.0001) indicated for an increased risk of death. After adjustment for age, sex and traditional cardiovascular risk factors, only T2DM (HR 1.89, 95% CI 1.63-2.20, P < 0.0001) remained independently associated with increased all-cause mortality.

Conclusion: Besides T2DM, also prediabetes inherits a significant cardiovascular burden, which translates into poor clinical outcome and indicates the need for new concepts regarding the prevention of cardiometabolic disorders.
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http://dx.doi.org/10.1007/s00392-021-01879-yDOI Listing
June 2021

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.
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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.
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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 05 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.
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http://dx.doi.org/10.1038/s41598-021-89442-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119940PMC
May 2021

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

Sci Rep 2021 05 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.
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http://dx.doi.org/10.1038/s41598-021-89442-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119940PMC
May 2021

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

ESC Heart Fail 2021 Aug 3;8(4):2991-3001. 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.
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http://dx.doi.org/10.1002/ehf2.13390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318485PMC
August 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.
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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.
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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 02 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.
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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.
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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.

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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 06 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.
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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.
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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.
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http://dx.doi.org/10.1182/blood.2019004571DOI Listing
May 2021
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