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1.
J Pediatr Ophthalmol Strabismus ; 56(6): 397-401, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31743409

RESUMO

PURPOSE: To determine whether amblyopia interferes with cognitive functions requiring visuospatial processing, measured by the Tower of London (ToL) test. METHODS: The current study was based on a sub-cohort from the population-based Gutenberg Health Study and included 1,569 participants aged 35 to 44 years. Amblyopia was defined as a visual acuity of 0.63 or worse (worse eye) in the presence of an amblyogenic factor; prevalence was 5%. There were three groups: participants with amblyopia (n = 78), participants with a visual acuity of 0.63 or worse (worse eye) without amblyopia (n = 65), and participants with a visual acuity of better than 0.63 (worse eye) (n = 1,426). Visuospatial planning ability was measured by the ToL test (touch-screen version), and the performance score ranged from 0 to 24, depending on the number of correctly solved problems. The authors used linear regression models to investigate the association between amblyopia and ToL test scores, adjusting for age, sex, and socioeconomic status. RESULTS: The mean ± standard deviation of ToL test performance was 15.31 ± 3.29 in participants with a visual acuity of better than 0.63, 14.56 ± 3.76 in the amblyopic group, and 15.14 ± 3.65 in participants with a visual acuity of 0.63 or worse without amblyopia. In a linear regression model, sex, and socioeconomic status significantly predicted planning performance (P <.0001), whereas amblyopic status did not (P = .20). CONCLUSIONS: Amblyopia may affect visuospatial perception, but no such relationships could be found for higher cognitive functions that strongly depend on visuospatial processing. Thus, in adulthood, individuals with amblyopia are unaffected in their visuospatial cognitive abilities, as required by the ToL test. [J Pediatr Ophthalmol Strabismus. 2019;56(6):397-401.].

2.
Ocul Surf ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31734512

RESUMO

PURPOSE: To test whether Schirmer test (ST) results are associated with topical or systemic medication and to evaluate the distribution of tear fluid quantity in a 3-min and 5-min ST. METHODS: The Gutenberg Health Study is a population-based, prospective, observational cohort study in Germany. ST was assessed in a sub-cohort of 1,999 participants. ST was performed under topical anesthesia for 5 min (ST-5) or of 3 min (ST-3). Anthropometric factors, systemic diseases, use of systemic and eye medications were recorded. We used multivariable quantile regression analysis to assess the influence on ST measurements. RESULTS: The length of wetting of the Schirmer strips for ST-5 was 23.2 ±â€¯9.31 mm for right and 22.9 ±â€¯9.0 mm for left eyes. In ST-3, the measurements were 20.0 mm in right and 19.1 mm in left eyes. The clinical cut off of 10 mm for ST-5 corresponded with an 8 mm cut off for ST-3. There was an association of smaller ST-5 measures with male sex, higher age, socioeconomic status and season (all p < 0.001), but not with diabetes or smoking. The use of prostaglandin or beta-blocker eye drops or oral non-steroidal anti-inflammatory drugs, drugs for peptic ulcer and gastro-oesophageal reflux disease, thyroid hormones, progesterone and estrogen combination drugs, and hypnotics and sedatives showed an association with smaller ST-5. CONCLUSIONS: For the first time we describe the distribution of tear fluid quantity by ST in a very large cohort of the general population. Furthermore, we found associations of ST measures with topical and systemic medication.

3.
Invest Ophthalmol Vis Sci ; 60(14): 4943-4950, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31770434

RESUMO

Purpose: This study analyzed whether low birth weight is linked to prevalence and incidence of age-related maculopathy (AMD) in adulthood. Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in Germany. GHS participants at an age from 35 to 74 years were included. An ophthalmologic examination with fundus photography was carried out. Fundus photographs were graded according to the Rotterdam Grading Scheme for AMD at baseline and at the 5-year follow-up examination. Participants were divided into three different birth weight groups (low: <2500 g; normal: 2500-4000 g; and high: >4000 g). Poisson regression analysis with adjustment for several confounders was used to assess associations between birth weight and AMD prevalence (overall, early, late AMD) and 5-year cumulative incidence. Results: Overall, 6492 participants were included (3538 female, aged 50.7 ± 10.4 years). Prevalence of total AMD was highest in the low birth weight group (11.2%; 40/358) compared to the normal birth weight group (6.5%; 346/5328) and the high birth weight group (8.4%; 68/806). Low birth weight was associated with overall AMD prevalence (prevalence ratio [PR] = 1.54, P = 0.006), and in particular with early AMD prevalence (PR = 1.52; P = 0.01). No association was observed between low birth weight and cumulative 5-year incidence of AMD. Conclusions: Our analyses indicate that low birth weight may lead to higher prevalence of retinal diseases in later life, as we observed for AMD. Our results are limited due to missing data and loss to follow-up, but may be a first hint that AMD has one of its origins in early life.

4.
Acta Ophthalmol ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680456

RESUMO

PURPOSE: We aimed to determine the prevalence of characteristics and pathologies of the vitreo-macular interface within the general population. METHODS: The Gutenberg Health Study is a population-based study in Germany, including an ophthalmological examination with refraction, biometry and optical coherence tomography (OCT) imaging. Characteristics of the vitreo-macular interface were graded on volume scans including visibility of an epiretinal membrane, full-thickness macular hole, lamellar hole and pseudohole. Overall and age-specific prevalences including 95% confidence intervals [95%-CI] were calculated. Association analyses were conducted to determine systemic and ocular factors that are associated with epiretinal membranes (the most common pathology) using multivariable logistic regression. RESULTS: A total of 1890 people aged 40-80 years were included in the study. Of these, 4.7% (95%-CI: 3.8%-5.8%) had an epiretinal membrane in at least one eye, 0.1% a full-thickness macular hole, 0.6% a lamellar hole and 0.6% a pseudohole. The presence of an epiretinal membrane was associated with higher age, myopic refractive error and prior retinal laser therapy, but not with gender, body height, body weight, smoking, prior cataract surgery or intraocular pressure. CONCLUSIONS: Epiretinal membranes are more frequent in older and myopic subjects and in those with prior retinal laser therapy.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31612355

RESUMO

Antiphospholipid antibodies (aPL) are heterogeneous and there is evidence that binding specificity determines which cellular effects they can trigger. We have therefore hypothesised that the induction of tissue factor (TF) in monocytes and endothelial cells by aPL depends on their binding specificity. To further investigate this, we have analyzed the ability of three human monoclonal aPL with distinctly different binding specificities to induce transcription and cell surface expression of TF in monocytes and endothelial cells. Results with human monoclonal aPL were validated with IgG-fractions obtained from patients with APS. We confirmed previous results that a lipid reactive human monoclonal aPL rapidly induced TF transcription and cell surface expression in monocytes and endothelial cells. A monoclonal aPL reactive against ß2 glycoprotein I (ß2GPI) induced TF with a delayed time course. This was fully dependent on the induction of tumor necrosis factor alpha (TNFα) secretion as capture of TNFα by adalimumab prevented TF induction. This pattern was confirmed with patient IgG fractions. Both lipid reactive and anti-ß2GPI induced TF transcription. Unexpectedly, this activity of anti-ß2GPI was mediated fully by TNFα which was secreted in response to incubation with anti-ß2GPI. The role of TNFα in mediating TF induction by anti-ß2GPI may have wider implications for APS pathogenesis.

6.
JCI Insight ; 4(23)2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31600170

RESUMO

BACKGROUNDThe presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown.METHODSTo identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry.RESULTSWe identified a genome-wide significant (P < 5 × 10-8) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discovery and replication cohorts identified rs1545300 as the lead SNP at the KCND3 locus (OR 0.82 per minor T allele, P = 7.7 × 10-12) but did not reveal additional loci. Colocalization analyses indicate causal effects of KCND3 gene expression levels on ERP in both cardiac left ventricle and tibial artery.CONCLUSIONSIn this study, we identified for the first time to our knowledge a genome-wide significant association of a genetic variant with ERP. Our findings of a locus in the KCND3 gene provide insights not only into the genetic determinants but also into the pathophysiological mechanism of ERP, discovering a promising candidate for functional studies.FUNDINGThis project was funded by the German Center for Cardiovascular Research (DZHK Shared Expertise SE081 - STATS). For detailed funding information per study, see the Supplemental Acknowledgments.

7.
J Am Heart Assoc ; 8(20): e012509, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31583936

RESUMO

Background Endothelial dysfunction is a consequence of type 2 diabetes mellitus, but it is unclear whether endothelial dysfunction of conductance versus resistance vessels may also precede type 2 diabetes mellitus development. Methods and Results In a population-based cohort of 15 010 individuals from the GHS (Gutenberg Health Study) (aged 35-74 years at enrollment in 2007-2012), we identified 1610 cases of incident pre-diabetes mellitus and 386 cases of incident type 2 diabetes mellitus by hemoglobin A1c (HbA1c) and/or medical history between 2012 and 2017. Endothelial function of conductance and resistance vessels was measured by flow-mediated dilation and digital volume plethysmography-derived reactive hyperemia index, respectively. Multivariable regression modeling was used to estimate ß coefficients of HbA1c levels at follow-up and relative risks of incident (pre-)diabetes mellitus. Reactive hyperemia index was independently associated with HbA1c after multivariable adjustment for baseline HbA1c, sex, age, socioeconomic status, arterial hypertension, waist/height ratio, pack-years of smoking, non-high-density lipoprotein/high-density lipoprotein ratio, physical activity, family history of myocardial infarction/stroke, prevalent cardiovascular disease, medication use, and C-reactive protein (ß=-0.020; P=0.0029). The adjusted relative risk per SD decline in reactive hyperemia index was 1.08 (95% CI, 1.02-1.15; P=0.012) for incident pre-diabetes mellitus and 1.16 (95% CI, 1.01-1.34; P=0.041) for incident type 2 diabetes mellitus. Flow-mediated dilation independently increased the relative risk for developing pre-diabetes mellitus by 8% (95% CI, 1.02-1.14; P=0.012), but it was not independently associated with incident type 2 diabetes mellitus (relative risk, 1.01; 95% CI, 0.86-1.19; P=0.92) and with HbA1c (ß=-0.003; P=0.59). Conclusions Endothelial dysfunction of resistance rather than conductance vessels may precede the development of (pre-)diabetes mellitus. Assessment of endothelial function by digital volume plethysmography may help to identify subjects at risk for development of type 2 diabetes mellitus.

8.
Blood ; 134(14): 1119-1131, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31434703

RESUMO

Antiphospholipid antibodies (aPLs) with complex lipid and/or protein reactivities cause complement-dependent thrombosis and pregnancy complications. Although cross-reactivities with coagulation regulatory proteins contribute to the risk for developing thrombosis in patients with antiphospholipid syndrome, the majority of pathogenic aPLs retain reactivity with membrane lipid components and rapidly induce reactive oxygen species-dependent proinflammatory signaling and tissue factor (TF) procoagulant activation. Here, we show that lipid-reactive aPLs activate a common species-conserved TF signaling pathway. aPLs dissociate an inhibited TF coagulation initiation complex on the cell surface of monocytes, thereby liberating factor Xa for thrombin generation and protease activated receptor 1/2 heterodimer signaling. In addition to proteolytic signaling, aPLs promote complement- and protein disulfide isomerase-dependent TF-integrin ß1 trafficking that translocates aPLs and NADPH oxidase to the endosome. Cell surface TF pathway inhibitor (TFPI) synthesized by monocytes is required for TF inhibition, and disabling TFPI prevents aPL signaling, indicating a paradoxical prothrombotic role for TFPI. Myeloid cell-specific TFPI inactivation has no effect on models of arterial or venous thrombus development, but remarkably prevents experimental aPL-induced thrombosis in mice. Thus, the physiological control of TF primes monocytes for rapid aPL pathogenic signaling and thrombosis amplification in an unexpected crosstalk between complement activation and coagulation signaling.

9.
N Engl J Med ; 380(26): 2529-2540, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31242362

RESUMO

BACKGROUND: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. METHODS: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. RESULTS: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. CONCLUSIONS: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.).


Assuntos
Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Medição de Risco/métodos , Troponina/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Troponina I/sangue
10.
Clin Res Cardiol ; 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31168641

RESUMO

BACKGROUND: Choroidal thickness is associated with several cardiovascular parameters in case-control studies including patients with manifest disease. So far, it was unclear whether underlying cardiovascular risk factors or the continuum of heart failure may lead to alterations of the choroid. Therefore, our hypothesis was to test in a population-based study, whether choroidal thickness is associated with cardiovascular risk factors and heart disease. METHODS: A population-based cross-sectional study was carried out in Germany. A comprehensive medical examination including assessment of cardiovascular risk factors, echocardiography and ophthalmological examinations with spectral-domain optical coherence tomography of the choroid was performed. Subfoveal choroidal thickness as well as left ventricular ejection fraction (LVEF) and a surrogate marker for left ventricular end-diastolic pressure (E/e') were measured. Linear regression analyses were carried out to determine the relationship between subfoveal choroidal thickness and age, sex, body mass index, systolic blood pressure, dyslipidemia, HbA1c level, hematocrit, estimated glomerular filtration rate (eGFR), LVEF, E/e' and left ventricular mass index adjusted for ocular parameters. RESULTS: 1.742 subjects (48% females) with a mean age 59.3 ± 10.6 years were included in this study. Mean subfoveal thickness was 252 ± 77 µm (right eyes) and 255 ± 77 µm (left eyes). Unadjusted linear regression analysis revealed that subfoveal choroidal thickness is associated with sex, age, systolic blood pressure, hematocrit, eGFR, left ventricular end-diastolic pressure, left ventricular mass index (all p < 0.001) and dyslipidemia (p = 0.009). Adjusted linear regression only revealed age as associated parameter (p < 0.001). CONCLUSIONS: We did find evidence for an association between subfoveal choroidal thickness and cardiovascular risk factors which was mediated by aging.

11.
Thromb Haemost ; 119(8): 1347-1357, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31183847

RESUMO

In contrast to overanticoagulation, evidence on risk factors and outcome of subtherapeutic oral anticoagulation (OAC) with vitamin K-antagonists (VKAs) under optimum care is limited. We investigated the clinical phenotype, anticoagulation control, and clinical outcome of 760 VKA patients who received OAC therapy by a specialized coagulation service in the thrombEVAL study (NCT01809015). During 281,934 treatment days, 278 patients experience ≥ 1 episode of subtherapeutic anticoagulation control and had lower quality of OAC therapy compared to 482 patients without subtherapeutic international normalized ratio: 67.6%, interquartile range (IQR) 54.9%/76.8% versus 81.0%, IQR 68.5%/90.4%; p < 0.001. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, and treatment characteristics, female sex (hazard ratio [HR], 1.4, 95% confidence interval [CI], 1.0/1.9; p = 0.03), diabetes (HR, 1.4, 95% CI, 1.0/2.0; p = 0.03), and living alone (HR, 1.5, 95% CI, 1.1/2.1; p = 0.009) were independent risk factors of subtherapeutic anticoagulation control, whereas atrial fibrillation (HR, 0.6, 95% CI, 0.4/0.9; p = 0.02) and self-management of OAC therapy (HR, 0.2, 95% CI, 0.1/0.6; p = 0.001) were protective. In addition, active smoking (HR, 1.7, 95% CI, 0.9/3.0; p = 0.086) and living in a nursing home (HR, 1.6, 95% CI, 0.8/3.2; p = 0.15) indicated an elevated risk at the borderline of statistical significance. For the prediction of recurrent subtherapeutic anticoagulation, living alone was the only independent risk factor (HR, 1.7, 95% CI, 1.1/2.5; p = 0.013). The present study suggests that women, diabetics, and patients living alone experience an increased risk of low-quality VKA therapy and might potentially benefit from treatment with direct-acting anticoagulants.

12.
Biomarkers ; 24(6): 549-555, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31159594

RESUMO

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis (p < 0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity. Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.

13.
Dtsch Arztebl Int ; 116(17): 289-295, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31196384

RESUMO

BACKGROUND: The distribution of visual impairment is an indicator of the health status of the population and for the frequency of diseases of the eye. METHODS: The Gutenberg Health Study (GHS) is a population-based cohort study in Germany concerning adults aged 35 to 74. 15 010 subjects from the Mainz-Bingen region underwent general medical and ophthalmological examination, with measurement of the distance-corrected visual acuity in each eye separately. As per the World Health Organization criteria, visual impairment was defined as an acuity below 0.3 in the better eye, and blindness as an acuity below 0.05. All patients who were found to be visually impaired or blind underwent further individual study with clinical history-taking, split-lamp examination, and fundus photography. RESULTS: Data from 14 687 subjects were evaluated. The mean age of the partici- pants was 55.0 years (standard deviation, 11.1 years). The prevalence of visual im- pairment was 0.37% (95% confidence interval [0.28; 0.49]) (n = 55) and was higher in women (0.44%) than in men (0.31%). Blindness was present in 0.05% [0.03; 0.11] (n = 8) of the subjects. The prevalence of visual impairment from age 65 on- ward was 0.79%, three times higher than in the younger age groups. 54.5% of the visually impaired subjects had multiple underlying ophthalmological pathologies. CONCLUSION: The causes of visual impairment are manifold. Loss of vision is often the combined effect of multiple pathological factors. The etiology of visual impair- ment is thus a more complex matter than is commonly assumed.

14.
Biomolecules ; 9(5)2019 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-31108918

RESUMO

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status as well as systolic and diastolic blood pressure, body mass index (BMI), LDL cholesterol, HDL cholesterol, and triglycerides. (3) Results: A significant correlation was shown for RTL, with age as a quality control in our study (effect = -0.004, p = 3.2 × 10-47). Analysis of the relation between RTL and cardiovascular risk factors showed a significant association of RTL in patients who were current smokers (effect = -0.016, p = 0.048). No significant associations with RTL were seen for cardiovascular risk factors of LDL cholesterol (p = 0.127), HDL cholesterol (p = 0.713), triglycerides (p = 0.359), smoking (p = 0.328), diastolic blood pressure (p = 0.615), systolic blood pressure (p = 0.949), or BMI (p = 0.903). In a subsequent analysis, we calculated the tertiles of RTL. No significant difference across RTL tertiles was detectable for BMI, blood pressure, lipid levels, or smoking status. Finally, we studied the association of RTL and cardiovascular risk factors stratified by tertiles of age. We found a significant association of RTL and LDL cholesterol in the oldest tertile of age (effect = 0.0004, p = 0.006). (4) Conclusions: We determined the association of relative telomere length and cardiovascular risk factors in a population setting. An association of telomere length with age, current smoking status, as well as with LDL cholesterol in the oldest tertile of age was found, whereas no associations were observed between telomere length and triglycerides, HDL cholesterol, blood pressure, or BMI.

15.
Clin Res Cardiol ; 108(12): 1313-1323, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30953178

RESUMO

BACKGROUND: Higher, but also lower resting heart rate (HR), has been associated with increased cardiovascular events and mortality. Little is known about the interplay between HR, cardiovascular risk factors, concomitant diseases, vascular (endothelial) function, neurohormonal biomarkers, and all-cause mortality in the general population. Thus, we aimed to investigate these relationships in a population-based cohort. METHODS: 15,010 individuals (aged 35-74 at enrolment in 2007-2012) from the Gutenberg Health Study were analyzed. Multivariable regression modeling was used to assess the relation between the variables and conditional density plots were generated for cardiovascular risk factors, diseases, and mortality to show their dependence on HR. RESULTS: There were 714 deaths in the total sample at 7.67 ± 1.68 years of follow-up. The prevalence of diabetes mellitus, arterial hypertension, coronary and peripheral artery disease, chronic heart failure, and previous myocardial infarction exhibited a J-shaped association with HR. Mortality showed a similar relation with a nadir of 64 beats per minute (bpm) in the total sample. Each 10 bpm HR reduction in HR < 64 subjects was independently associated with increased mortality (Hazard Ratio 1.36; 95% confidence interval 1.06-1.75). This increased risk was also present in HR > 64 subjects (Hazard Ratio 1.29; 95% confidence interval 1.19-1.41 per 10 bpm increase in HR). Results found for vascular and neurohormonal biomarkers exhibited a differential picture in subjects with a HR below and above the nadir. DISCUSSION: These results indicate that in addition to a higher HR, a lower HR is associated with increased mortality.

16.
Thromb Haemost ; 119(7): 1147-1153, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31018220

RESUMO

Antiphospholipid antibodies (aPL) have been reported to activate platelets. This is considered to be one of the pathogenic properties of aPL. Even though aPL heterogeneity is quite well established, little is known, if the ability to activate platelets is common to all aPL or depends on antigen specificity. To further study this issue, we analyzed the ability of three human monoclonal aPL with distinctly different antigenic specificities to activate platelets in vitro. The results obtained with human monoclonal aPL were validated with immunoglobulin G (IgG) fractions obtained from patients with antiphospholipid syndrome (APS). A co-factor-independent human monoclonal anticardiolipin aPL had no discernible effect on human platelets. Two monoclonal aPL reactive against ß2 glycoprotein I (ß2GPI) induced platelet aggregation, integrin αIIbß3 activation and P-selectin surface expression. These data could be confirmed with patient IgG fractions which could only induce aggregation, if they had anti-ß2GPI activity. Anti-ß2GPI aPL-induced platelet activation depended on interaction of aPL with the low affinity Fcγ-receptor IIa on the platelet surface. It was completely abolished by pretreatment of platelet-rich plasma with the mechanistic target of rapamycin (mTOR) inhibitors rapamycin or everolimus. This extends previous data showing that mTOR is involved in signaling of anti-ß2GPI in monocytes and endothelial cells. In conclusion, anti-ß2GPI aPL activate platelets while co-factor-independent anticardiolipin aPL have no effect. mTOR is involved in this signaling process which has implications beyond APS, because so far the role of mTOR signaling in platelets is incompletely explored and requires further study.

17.
Clin Chem Lab Med ; 57(5): 565-566, 2019 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-30870140
18.
Clin Res Cardiol ; 108(10): 1107-1116, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30820639

RESUMO

AIMS: The electrocardiographic pattern of early repolarization (ER) is related to increased cardiac mortality in the general population. The pathophysiological basis of ER is largely unknown. We investigated the association of echocardiographic structural and functional parameters of the left ventricle with the presence of ER in the community. METHODS AND RESULTS: The presence of ER (ER+) was assessed in 13,878 participants (mean age 54.6 years, 51.1% women) of the Gutenberg Health Study and related to left ventricular structure and function derived from standard echocardiography. The prevalence of ER was 5.0% (694/13,878), with higher prevalence in men than women (6.6% vs. 3.5%, p < 0.001). In men baseline characteristics differed including a lower BMI and a lower heart rate in ER+ individuals, whereas in women there were only minor differences. Multivariable-adjusted logistic regression analysis in men showed an association of ER with smaller diameters (left-ventricular end-diastolic diameter: OR 0.77 95% CI 0.69-0.86, p < 0.001; left-ventricular end-systolic diameter: OR 0.86 95% CI 0.78-0.95, p = 0.0035), and lower left-ventricular end-diastolic and end-systolic volume (OR 0.72 95% CI 0.65, 0.80, p < 0.001 and OR 0.80 95% CI 0.72, 0.89, p < 0.001). In women, the associations of ER with left ventricular diameters and volumes showed a similar direction, but were not as pronounced. CONCLUSION: In the community, the ER pattern predominantly occurs in men with a low heart rate and a slender habit. Furthermore, ER is not associated with higher left ventricular mass or size but rather with smaller left ventricular diameters and volumes with a regular systolic and diastolic function. Patterns were comparable in women, but less strong.

20.
JAMA Ophthalmol ; 137(5): 507-514, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30789653

RESUMO

Importance: Low birth weight is associated with altered ocular organ development in childhood, including the morphology of the eye. However, no population-based data exist about this association in adulthood. Objective: To evaluate whether low birth weight has a long-term association with anterior segment anatomy and axial length in adulthood. Design, Setting, and Participants: The Gutenberg Health Study is a population-based, observational cohort study in Germany. All participants underwent ocular biometry. Among the participants with follow-up and self-reported birth weight available, associations were assessed between low birth weight and anterior segment anatomy and axial length using multivariable linear regression analysis with adjustment for age and sex. In patients with phakia, anterior chamber depth and lens thickness were also examined. Data for this study were collected from April 27, 2012, through April 28, 2017, and analyzed from January through April 2018. Exposures: Low birth weight. Main Outcomes and Measures: Corneal curvature, central corneal thickness, white-to-white distance, anterior chamber depth, lens thickness, and axial length. Results: Overall, 11 294 eyes of 7120 participants were included (52.4% female; mean [SD] age, 56.2 [10.3] years). Most of the participants were white (98.6%). After adjustment for age and sex, an association was found between a lower birth weight and steeper corneal curvature (ß = 0.005 mm/100 g; 95% CI, 0.005-0.006 mm/100 g; P < .001), smaller white-to-white distance (ß = 0.006 mm/100 g; 95% CI, 0.005-0.007 mm/100 g; P < .001), thinner central corneal thickness (ß = 0.327 µm/100 g; 95% CI, 0.229-0.425 µm/100 g; P < .001), and shorter axial length (ß = 0.006 mm/100 g; 95% CI, 0.003-0.010 mm/100 g; P < .001). However, anterior chamber depth and lens thickness were not associated with low birth weight in participants with phakia (10 510 eyes of 5279 participants). Conclusions and Relevance: These analyses demonstrate an association between low birth weight and altered ocular geometry in adults aged 40 to 80 years, suggesting that birth weight and associated factors are crucial in anatomical ocular morphologic development. Retinopathy of prematurity and its treatment may affect ocular anatomy but could not be further analyzed in this study.

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