Publications by authors named "Elisabeth Steinhagen-Thiessen"

179 Publications

Association of sex-specific differences in lipoprotein(a) concentrations with cardiovascular mortality in individuals with type 2 diabetes mellitus.

Cardiovasc Diabetol 2021 08 18;20(1):168. Epub 2021 Aug 18.

Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.

Background: Compared to individuals without type 2 diabetes mellitus, the relative increase in cardiovascular mortality is much higher in women than in men in individuals with type 2 diabetes mellitus.

Methods: We evaluated data from 7443 individuals (3792 women, 50.9%), aged 20 to 81 years, from two independent population-based investigations, SHIP-0 and MONICA/KORA S3. We analyzed the longitudinal sex-specific associations of lipoprotein(a) with cardiovascular mortality in individuals with and without type 2 diabetes mellitus using Cox regression.

Results: During a median follow-up of 20.5 years (136,802 person-years), 657 participants (404 men and 253 women) died of cardiovascular causes. Among individuals without type 2 diabetes mellitus, men had a significantly higher risk for cardiovascular mortality compared to women in unadjusted model and after adjustment. On the other hand, in participants with type 2 diabetes mellitus, the risk for cardiovascular mortality was not different between men and women in the unadjusted model and after adjustment for age, body mass index, low-density lipoprotein-cholesterol, fasting status and study sample (SHIP-0, MONICA/KORA S3). Further adjustment for lipoprotein(a) concentrations had no impact on the hazard ratio (HR) for cardiovascular mortality comparing men versus women in individuals without type 2 diabetes mellitus [HR: 1.94; 95% confidence interval (CI) 1.63 to 2.32; p < 0.001]. In individuals with type 2 diabetes mellitus, however, further adjustment for lipoprotein(a) led to an increased risk for cardiovascular mortality in men and a decreased risk in women resulting in a statistically significant difference between men and women (HR: 1.53; 95% CI 1.04 to 2.24; p = 0.029).

Conclusions: Women are described to have a stronger relative increase in cardiovascular mortality than men when comparing individuals with and without type 2 diabetes mellitus. Higher lipoprotein(a) concentrations in women with type 2 diabetes mellitus than in men with type 2 diabetes mellitus might partially explain this finding.
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http://dx.doi.org/10.1186/s12933-021-01363-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375146PMC
August 2021

The size of apolipoprotein (a) is an independent determinant of the reduction in lipoprotein (a) induced by PCSK9 inhibitors.

Cardiovasc Res 2021 Jul 26. Epub 2021 Jul 26.

Université de La Réunion, INSERM UMR 1188 DéTROI, Sainte-Clotilde, France.

Aims: Lipoprotein (a) [Lp(a)] is a lipoprotein species causatively associated with atherosclerosis. Unlike statins, PCSK9 inhibitors (PCSK9i) reduce Lp(a), but this reduction is highly variable. Levels of Lp(a) are chiefly governed by the size of its signature protein, apolipoprotein (a) [apo(a)]. Whether this parameter determines some of the reduction in Lp(a) induced by PCSK9i remains unknown. We aimed to investigate if the Lp(a) lowering efficacy of PCSK9i is modulated by the size of apo(a), which is genetically determined by the variable number of KIV domains present on that protein.

Methods And Results: The levels of Lp(a) and the size of apo(a) were assessed in plasma samples from 268 patients before and after treatment with PCSK9i. Patients were recruited at the Outpatient Lipid Clinic of the Charité Hospital (Berlin) between 2015 and 2020. They were hypercholesterolemic at very high CVD risk with LDL-cholesterol levels above therapeutic targets despite maximally tolerated lipid-lowering therapy. Patients received either Alirocumab (75 or 150 mg) or Evolocumab (140 mg) every 2 weeks. Apo(a), apoB100, and apoE concentrations as well as apoE major isoforms were determined by liquid chromatography high-resolution mass spectrometry. Apo(a) isoforms sizes were determined by Western Blot. PCSK9i sharply reduced LDL-cholesterol (-57%), apoB100 (-47%) and Lp(a) (-36%). There was a positive correlation between the size of apo(a) and the relative reduction in Lp(a) induced by PCSK9i (r = 0.363, p = 0.0001). The strength of this association remained unaltered after adjustment for baseline Lp(a) levels and all other potential confounding factors. In patients with two detectable apo(a) isoforms, there was also a positive correlation between the size of apo(a) and the reduction in Lp(a), separately for the smaller (r = 0.350, p = 0.0001) and larger (r = 0.324, p = 0.0003) isoforms. The relative contribution of the larger isoform to the total concentration of apo(a) was reduced from 29% to 15% (p < 0.0001).

Conclusions: The size of apo(a) is an independent determinant of the response to PCSK9i. Each additional kringle domain is associated with a 3% additional reduction in Lp(a). This explains in part the variable efficacy of PCSK9i and allows to identify patients who will benefit most from these therapies in terms of Lp(a) lowering.

Translational Perspective: Unlike statins, PCSK9 inhibitors reduce the circulating levels of the highly atherogenic Lipoprotein (a). The underlying mechanism remains a matter of considerable debate. The size of apo(a), the signature protein of Lp(a), is extremely variable (300 to more than 800 kDa) and depends on its number of kringle domains. We now show that each increase in apo(a) size by one kringle domain is associated with a 3% additional reduction in Lp(a) following PCSK9i treatment and that apo(a) size polymorphism is an independent predictor of the reduction in Lp(a) induced by these drugs. In an era of personalized medicine, this allows to identify patients who will benefit most from PCSK9i in terms of Lp(a) lowering.
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http://dx.doi.org/10.1093/cvr/cvab247DOI Listing
July 2021

Sociohistorical Change in Urban Older Adults' Perceived Speed of Time and Time Pressure.

J Gerontol B Psychol Sci Soc Sci 2021 Jun 28. Epub 2021 Jun 28.

Department of Psychology, Humboldt University Berlin, Germany.

Objectives: Perceptions of time are shaped by sociohistorical factors. Specifically, economic growth and modernization often engender a sense of acceleration. Research has primarily focused on one time perception dimension (perceived time pressure) in one subpopulation (working-age adults), but it is not clear whether historical changes extend to other dimensions (e.g., perceived speed of time) and other subpopulations, such as older adults who are no longer in the workforce and experience age-related shifts in time perception. We therefore examined sociohistorical and age-related trends in two dimensions of time perception in two cohorts of urban older adults.

Method: Using propensity score matching for age and education, samples were drawn from the Berlin Aging Study (1990-1993, n = 256, Mage = 77.49) and the Berlin Aging Study-II (2009-2014, n = 248, Mage = 77.49). Cohort differences in means, variances, covariance, and correlates of perceived speed of time and time pressure were examined using multigroup SEM.

Results: There were no cohort differences in the perceived speed of time, but later-born cohorts reported more time pressure than earlier-born cohorts. There were no significant age differences, but perceptions of speed of time were more heterogeneous in the 1990s than in the 2010s. Cohorts did not differ in how time perceptions were associated with sociodemographic, health, cognitive, and psychosocial correlates.

Discussion: These findings document sociohistorical trends toward greater perceived time pressure and reduced heterogeneity in perceived speed of time among later-born urban adults. Conceptualizations of social acceleration should thus consider the whole adult life span.
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http://dx.doi.org/10.1093/geronb/gbab094DOI Listing
June 2021

Cohort profile: follow-up of a Berlin Aging Study II (BASE-II) subsample as part of the GendAge study.

BMJ Open 2021 06 23;11(6):e045576. Epub 2021 Jun 23.

Department of Psychology, Humboldt University of Berlin, Berlin, Berlin, Germany.

Purpose: The study 'Sex- and gender-sensitive prevention of cardiovascular and metabolic disease in older adults in Germany', the GendAge study, focuses on major risk factors for cardiovascular and metabolic diseases and on the development of major outcomes from intermediate phenotypes in the context of sex and gender differences. It is based on a follow-up examination of a subsample (older group) of the Berlin Aging Study II (BASE-II).

Participants: The GendAge study assessments took place between 22 June 2018 and 10 March 2020. A total of 1100 participants (older BASE-II subsample, aged ≥65 years) with baseline data assessed at least by one of the BASE-II partner sites were investigated in the follow-up. These participants had a mean age of 75.6 years (SD ±3.8), with a mean follow-up at 7.4 years (SD ±1.5).

Findings To Date: Data from different domains such as internal medicine, geriatrics, immunology and psychology were collected, with a focus on cardiometabolic diseases and in the context of sex and gender differences. Diabetes mellitus type 2 was reported by 15.6% and 8.6% of men and women, respectively. In contrast, this disease was diagnosed in 20.7% of men and 13.3% of women, indicating that a substantial proportion of almost 30% was unaware of the disease. Echocardiography revealed that left ventricular ejection fraction was higher in women than in men, in agreement with previous reports.

Future Plans: A gender questionnaire assessing sociocultural aspects implemented as part of the follow-up described here will allow to calculate a gender score and its evaluation based on the newly collected data. At the same time, the other BASE-II research foci established over the past 10 years will be continued and strengthened by the BASE-II transition into a longitudinal study with follow-up data on the older subsample.

Trial Registration Number: DRKS00016157.
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http://dx.doi.org/10.1136/bmjopen-2020-045576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8230995PMC
June 2021

[Diagnostics and treatment of statin-associated muscle symptoms].

Internist (Berl) 2021 Aug 18;62(8):827-840. Epub 2021 Jun 18.

Lipidambulanz, Klinik für Endokrinologie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Deutschland.

Statins are among the most frequently prescribed drugs in Germany. Their benefits in lowering cardiovascular risk are beyond dispute. Nevertheless, many patients complain of side effects from statin therapy, including statin-associated muscle symptoms (SAMS) in particular. Despite their relative frequency, it is difficult to objectively diagnose them, as the time until appearance of first symptoms, the nature of the complaints and the severity of muscle problems vary widely. This narrative review summarizes the causes of SAMS as well as new possibilities regarding their diagnosis and therapy.
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http://dx.doi.org/10.1007/s00108-021-01059-0DOI Listing
August 2021

Association between meal-specific daily protein intake and lean mass in older adults: results of the cross-sectional BASE-II study.

Am J Clin Nutr 2021 09;114(3):1141-1147

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Department of Endocrinology, Diabetes and Metabolism, Berlin Institute of Health, Berlin, Germany.

Background: Adequate total and meal-specific protein intake is considered an important prerequisite to preserve appendicular lean mass (ALM) in older adults and to prevent sarcopenia.

Objectives: We analyzed the meal-specific protein intake across the main meals between participants with normal vs. low ALM to BMI ratio (ALMBMI).

Methods: 782 participants [59.6% men; median 69 (IQR: 65, 71) y] of the Berlin Aging Study II have been included in this analysis. ALM was assessed by dual X-ray absorptiometry. Low lean mass was defined as ALMBMI using recommended sex-specific cut-offs. A 5-day nutritional protocol was used to assess total and meal-specific protein intake.

Results: Median total protein intake was 0.89 (IQR: 0.74, 1.05) g/kg/d body weight (BW) in participants with low ALMBMI and 1.02 (IQR: 0.86, 1.21) g/kg BW in participants with normal ALMBMI (P < 0.001). Daily protein intake at breakfast was similar in both groups [0.23 (95% CI: 0.20, 0.26) vs. 0.24 (95% CI: 0.23, 0.26) g/kg BW; P = 0.245]. Subjects with low ALMBMI reported a lower protein intake at lunch and dinner compared with those with normal ALMBMI [0.29 (95% CI: 0.27, 0.32) vs. 0.35 (95% CI: 0.34, 0.36) g/kg BW; P = 0.001 and 0.32 (95% CI: 0.30, 0.35) vs. 0.36 (95% CI: 0.35, 0.37) g/kg BW; P = 0.027, respectively]. In a stepwise regression model, a higher total protein intake was positively associated with ALMBMI [ß = 0.10 (95% CI: 0.07, 0.13) P < 0.001]. The protein intake at dinner was positively associated with ALMBMI [ß = 0.14 (95% CI: 0.08, 0.19) P < 0.001] irrespective of protein intake at breakfast and lunch. This association disappeared after additional adjustment for total protein intake.

Conclusion: Our data highlight an association of total protein intake and ALMBMI in older adults. Although current data support an association of high ALMBMI with protein intake at dinner in particular, this was not independent from total protein intake and the findings do not allow a conclusion on causality.
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http://dx.doi.org/10.1093/ajcn/nqab144DOI Listing
September 2021

Vitamin D insufficiency is associated with metabolic syndrome independent of insulin resistance and obesity in young adults - The Berlin Aging Study II.

Diabetes Metab Res Rev 2021 Apr 22:e3457. Epub 2021 Apr 22.

Department of Nutrition and Gerontology, German Institute for Human Nutrition Potsdam Rehbrücke, Nuthetal, Germany.

Purpose: Age-related changes affect vitamin D absorption and metabolism. Low 25-hydroxyvitamin D concentrations have been reported as risk factor for the development of metabolic syndrome (MetS). However, recent evaluations suggest this association might be explained by obesity or insulin resistance (IR) in subjects with MetS. Our aim was to analyze associations between vitamin D insufficiency and MetS in a young cohort without diabetes and two senior cohorts with and without diabetes.

Methods: Four hundred sixteen young and 1357 older BASE-II participants were analyzed. Type 2 diabetes (T2D) was defined according to European Society of Cardiology (ESC) guidelines, MetS as suggested by International Diabetes Federation/American Heart Association/National Heart, Lung and Blood Institute (IDF/AHA/NHLBI 2009). Vitamin D insufficiency was defined as 25-hydroxyvitamin D concentrations <50 nmol/L. Among other confounders, BMI and IR were taken into account.

Results: MetS was prevalent in 7.7% of the young and in 35.6% of the older BASE-II participants and T2D occurred in 12.7% of the older participants. In young subjects without diabetes, vitamin D insufficiency was associated with an independent 3.2-fold increased odds of having MetS (OR: 3.2 CI: 1.0-8.7; p = 0.042). However, in the older participants, this association was lost once BMI was taken into account among those with diabetes, and once IR was taken into account among those without diabetes.

Conclusion: Independent associations between vitamin D insufficiency and MetS were only found among young subjects without diabetes. In the older adults, BMI annihilated these associations among subjects without diabetes as did HOMA-IR among subjects with diabetes.
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http://dx.doi.org/10.1002/dmrr.3457DOI Listing
April 2021

Cis-epistasis at the LPA locus and risk of cardiovascular diseases.

Cardiovasc Res 2021 Apr 20. Epub 2021 Apr 20.

Estonian Genome Center, Institute of Genomics, University of Tartu, 51010, Tartu, Estonia.

Aims: Coronary artery disease (CAD) has a strong genetic predisposition. However, despite substantial discoveries made by genome-wide association studies (GWAS), a large proportion of heritability awaits identification. Non-additive genetic-effects might be responsible for part of the unaccounted genetic variance. Here we attempted a proof-of-concept study to identify non-additive genetic effects, namely epistatic interactions, associated with CAD.

Methods And Results: We tested for epistatic interactions in ten CAD case-control studies and UK Biobank with focus on 8,068 SNPs at 56 loci with known associations with CAD risk. We identified a SNP pair located in cis at the LPA locus, rs1800769 and rs9458001, to be jointly associated with risk for CAD (odds ratio [OR]=1.37, p = 1.07 × 10-11), peripheral arterial disease (OR = 1.22, p = 2.32 × 10-4), aortic stenosis (OR = 1.47, p = 6.95 × 10-7), hepatic lipoprotein(a) (Lp(a)) transcript levels (beta = 0.39, p = 1.41 × 10-8), and Lp(a) serum levels (beta = 0.58, p = 8.7 × 10-32), while individual SNPs displayed no association. Further exploration of the LPA locus revealed a strong dependency of these associations on a rare variant, rs140570886, that was previously associated with Lp(a) levels. We confirmed increased CAD risk for heterozygous (relative OR = 1.46, p = 9.97 × 10-32) and individuals homozygous for the minor allele (relative OR = 1.77, p = 0.09) of rs140570886. Using forward model selection, we also show that epistatic interactions between rs140570886, rs9458001, and rs1800769 modulate the effects of the rs140570886 risk allele.

Conclusions: These results demonstrate the feasibility of a large-scale knowledge-based epistasis scan and provide rare evidence of an epistatic interaction in a complex human disease. We were directed to a variant (rs140570886) influencing risk through additive genetic as well as epistatic effects. In summary, this study provides deeper insights into the genetic architecture of a locus important for cardiovascular diseases.

Translational Perspective: Genetic variants identified by GWAS studies explain about a quarter of the heritability of coronary artery disease by additive genetic effects. Our study demonstrates that non-additive effects contribute to the genetic architecture of the disease as well and identifies complex interaction patterns at the LPA locus, which affect LPA expression, Lp(a) plasma levels and risk of atherosclerosis. This proof-of-concept study encourages systematic searches for epistatic interactions in further studies to shed new light on the aetiology of the disease.
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http://dx.doi.org/10.1093/cvr/cvab136DOI Listing
April 2021

Efficacy and safety of volanesorsen in patients with multifactorial chylomicronaemia (COMPASS): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Diabetes Endocrinol 2021 05 30;9(5):264-275. Epub 2021 Mar 30.

Department of Medicine, University California San Diego, La Jolla, CA, USA. Electronic address:

Background: Volanesorsen is an antisense oligonucleotide that targets hepatic apolipoprotein C-III synthesis and reduces plasma triglyceride concentration. The aim of this study was to explore the safety and efficacy of volanesorsen in patients with multifactorial chylomicronaemia syndrome.

Methods: The COMPASS trial was a randomised, placebo-controlled, double-blind, phase 3 study done at 38 international clinical sites in Canada, France, Germany, the Netherlands, UK, and USA. Eligible patients were aged 18 years or older with multifactorial severe hypertriglyceridaemia or familial chylomicronaemia syndrome, who had a BMI of 45 kg/m or less and fasting plasma triglyceride of 500 mg/dL or higher. Patients were randomly assigned (2:1) with an interactive response system using an allocation sequence and permuted block randomisation to receive subcutaneous volanesorsen (300 mg) or a matched volume of placebo (1·5 mL) once a week for 26 weeks. After 13 weeks of treatment, dosing was changed to 300 mg of volanesorsen or placebo every 2 weeks for all patients, except those who had completed 5 months or more of treatment as of May 27, 2016. Participants, investigators, sponsor personnel, and clinical research staff were all masked to the treatment assignments. The primary outcome was percentage change from baseline to 3 months in fasting triglyceride in the full analysis set (all patients who were randomly assigned and received at least one dose of study drug and had a baseline fasting triglyceride assessment). This trial is registered with ClinicalTrials.gov, NCT02300233 (completed).

Findings: Between Feb 5, 2015, and Jan 24, 2017, 408 patients were screened for eligibility. 294 were excluded and 114 randomly assigned to receive either volanesorsen (n=76) or placebo (n=38). One patient in the volanesorsen group discontinued before receiving the study drug. The total number of dropouts was 28 (four in the placebo group and 24 in the treatment group). Volanesorsen reduced mean plasma triglyceride concentration by 71·2% (95% CI -79·3 to -63·2) from baseline to 3 months compared with 0·9% (-13·9 to 12·2) in the placebo group (p<0·0001), representing a mean absolute reduction of fasting plasma triglycerides of 869 mg/dL (95% CI -1018 to -720; 9·82 mmol/L [-11·51 to -8·14]) in volanesorsen compared with an increase in placebo of 74 mg/dL (-138 to 285; 0·83 mmol/L [-1·56 to 3·22]; p<0·0001). In the key safety analysis, five adjudicated events of acute pancreatitis occurred during the study treatment period, all in three of 38 patients in the placebo group. The most common adverse events were related to tolerability and included injection-site reactions (average of 24% of all volanesorsen injections vs 0·2% of placebo injections), which were all mild or moderate. One participant in the volanesorsen group had a platelet count reduction to less than 50 000 per μL and one patient had serum sickness, both of which were regarded as serious adverse events.

Interpretation: Volanesorsen significantly reduced triglyceride concentrations in patients with multifactorial chlyomicronaemia and might reduce acute pancreatitis events in these patients.

Funding: Ionis Pharmaceuticals and Akcea Therapeutics.
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http://dx.doi.org/10.1016/S2213-8587(21)00046-2DOI Listing
May 2021

Validation of a Laser Ranged Scanner-Based Detection of Spatio-Temporal Gait Parameters Using the aTUG Chair.

Sensors (Basel) 2021 Feb 13;21(4). Epub 2021 Feb 13.

Assistance Systems and Medical Device Technology, Carl von Ossietzky University Oldenburg, 26129 Oldenburg, Germany.

This article covers the suitability to measure gait-parameters via a Laser Range Scanner (LRS) that was placed below a chair during the walking phase of the Timed Up&Go Test in a cohort of 92 older adults (mean age 73.5). The results of our study demonstrated a high concordance of gait measurements using a LRS in comparison to the reference GAITRite walkway. Most of aTUG's gait parameters demonstrate a strong correlation coefficient with the GAITRite, indicating high measurement accuracy for the spatial gait parameters. Measurements of velocity had a correlation coefficient of 99%, which can be interpreted as an excellent measurement accuracy. Cadence showed a slightly lower correlation coefficient of 96%, which is still an exceptionally good result, while step length demonstrated a correlation coefficient of 98% per leg and stride length with an accuracy of 99% per leg. In addition to confirming the technical validation of the aTUG regarding its ability to measure gait parameters, we compared results from the GAITRite and the aTUG for several parameters (cadence, velocity, and step length) with results from the Berg Balance Scale (BBS) and the Activities-Specific Balance Confidence-(ABC)-Scale assessments. With confidence coefficients for BBS and velocity, cadence and step length ranging from 0.595 to 0.798 and for ABC ranging from 0.395 to 0.541, both scales demonstrated only a medium-sized correlation. Thus, we found an association of better walking ability (represented by the measured gait parameters) with better balance (BBC) and balance confidence (ABC) overall scores via linear regression. This results from the fact that the BBS incorporates both static and dynamic balance measures and thus, only partly reflects functional requirements for walking. For the ABC score, this effect was even more pronounced. As this is to our best knowledge the first evaluation of the association between gait parameters and these balance scores, we will further investigate this phenomenon and aim to integrate further measures into the aTUG to achieve an increased sensitivity for balance ability.
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http://dx.doi.org/10.3390/s21041343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918763PMC
February 2021

BDNF serum concentrations in 2053 participants of the Berlin Aging Study II.

Neurobiol Aging 2021 05 2;101:221-223. Epub 2021 Feb 2.

Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Klinik und Poliklinik für Psychiatrie und Psychotherapie, Berlin, Germany.

Serum BDNF concentrations in 2053 participants of the Berlin Aging Study II (BASE-II; 1572 individuals from the older age group [60-85 years], 481 individuals from the younger-age reference group [22-37 years]) were studied. There was no effect of age, sex, body mass index, self-reported depression, or BDNF Val66Met variant on serum BDNF concentrations. Multiple linear regression analysis failed to detect significant relationships of Digit Symbol Substitution Test score and Consortium to Establish a Registry for Alzheimer's Disease memory score to BDNF levels. However, we detected a positive correlation between platelet counts and BDNF levels (r = 0.303, p < 0.001). Our findings do not support an effect of aging, self-reported depression, or the Val66Met variant on serum BDNF concentrations. The role of thrombocytes in the biology of serum BDNF merits further study.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.01.020DOI Listing
May 2021

Low muscle strength and increased arterial stiffness go hand in hand.

Sci Rep 2021 Feb 3;11(1):2906. Epub 2021 Feb 3.

Department of Endocrinology and Metabolism, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Low handgrip strength and increased arterial stiffness are both associated with poor health outcomes, but evidence on the relationship between handgrip strength and arterial stiffness is limited. In this cross-sectional analysis of combined baseline datasets from the LipidCardio and Berlin Aging Study II cohorts we aimed to examine whether handgrip strength (HGS) is associated with arterial stiffness. 1511 participants with a median age of 68.56 (IQR 63.13-73.08) years were included. Arterial stiffness was assessed by aortal pulse wave velocity (PWV) with the Mobil-O-Graph device. Handgrip strength was assessed with a handheld dynamometer.The mean HGS was 39.05 ± 9.07 kg in men and 26.20 ± 7.47 kg in women. According to multivariable linear regression analysis per 5 kg decrease in handgrip strength there was a mean increase in PWV of 0.08 m/s after adjustment for the confounders age, sex, coronary artery disease, systolic blood pressure, body mass index, cohort, and smoking. Thus, there was evidence that low handgrip strength and increased arterial stiffness go hand in hand. Arterial stiffness can possibly create the missing link between low handgrip strength and increased cardiovascular morbidity and mortality. Causality and direction of causality remain to be determined.
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http://dx.doi.org/10.1038/s41598-021-81084-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859241PMC
February 2021

T cell phenotypes associated with insulin resistance: results from the Berlin Aging Study II.

Immun Ageing 2020 Dec 21;17(1):40. Epub 2020 Dec 21.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Department of Endocrinology and Metabolism, Berlin Institute of Health, Chariteplatz 1, 10117, Berlin, Germany.

Background: Obesity is associated with chronic low-grade inflammation leading to metabolic and cardiovascular diseases, but a subset of obese individuals is considered insulin sensitive (IS). The underlying pathophysiologic mechanisms remain elusive and clinical studies on the relationship between inflammatory markers and metabolically healthy obesity (MHO) are scarce.

Methods: In this cross-sectional analysis, we included a sample of 437 older participants (60-84 years) from the Berlin Aging Study II (BASE-II). Peripheral blood mononuclear cells were isolated, immune cell subsets were analyzed with multiparameter flow cytometry and systemic cytokine levels were measured. Immune cell parameters were correlated with metabolic measures and multiple linear regression analysis was conducted and adjusted for various demographic and clinical factors.

Results: We found that frequencies of naïve and memory CD4 and CD8 T cells inversely correlated with measures for insulin sensitivity in the older population. Moreover, the percentages of naïve CD4 and CD8 T cells were significantly higher, whereas activated T cells and IL-6 levels were lower in IS compared to insulin resistant (IR) obese individuals. The percentages of naïve CD4 and CD8 T cells were predictive for impaired insulin sensitivity (ß = 0.16, p = 0.01 and ß = 0.11, p = 0.04), and the association of naïve CD4 T cells with insulin sensitivity persisted after multivariate adjustment (ß = 0.14, p = 0.02).

Conclusions: These findings support the hypothesis that parameters of systemic inflammation can differentiate IS from IR obese individuals that are at higher risk for cardiometabolic diseases and may have clinical implications with regard to obesity treatment stratification.

Trial Registration: DRKS00009277 . Registered 31 August 2015 - Retrospectively registered.
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http://dx.doi.org/10.1186/s12979-020-00211-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7751110PMC
December 2020

Is Healthy Neuroticism Associated with Chronic Conditions? A Coordinated Integrative Data Analysis.

Collabra Psychol 2020 12;6(1). Epub 2020 Aug 12.

University of Melbourne Academic Unit for Psychiatry of Old Age and National Ageing Research Institute, Kew & Parkville, Australia.

Early investigations of the neuroticism by conscientiousness interaction with regards to health have been promising, but to date, there have been no systematic investigations of this interaction that account for the various personality measurement instruments, varying populations, or aspects of health. The current study - the second of three - uses a coordinated analysis approach to test the impact of the neuroticism by conscientiousness interaction on the prevalence and incidence of chronic conditions. Using 15 pre-existing longitudinal studies ( > 49,375), we found that conscientiousness did not moderate the relationship between neuroticism and having hypertension ( = 1.00,95%[0.98,1.02]), diabetes ( = 1.02[0.99,1.04]), or heart disease ( = 0.99[0.97,1.01]). Similarly, we found that conscientiousness did not moderate the prospective relationship between neuroticism and onset of hypertension ( = 0.98,[0.95,1.01]), diabetes ( = 0.99[0.94,1.05]), or heart disease ( = 0.98[0.94,1.03]). Heterogeneity of effect sizes was largely nonsignificant, with one exception, indicating that the effects are consistent between datasets. Overall, we conclude that there is no evidence that healthy neuroticism, operationalized as the conscientiousness by neuroticism interaction, buffers against chronic conditions.
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http://dx.doi.org/10.1525/collabra.267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566654PMC
August 2020

Treatment with PCSK9 inhibitors induces a more anti-atherogenic HDL lipid profile in patients at high cardiovascular risk.

Vascul Pharmacol 2020 12 25;135:106804. Epub 2020 Sep 25.

Institut National de la Santé et de la Recherche Médicale (INSERM), UMR 1048, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France; University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.

Background: Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9-I) have been reported to cause a moderate increase in high-density lipoprotein (HDL) cholesterol in human studies. We thus evaluated the effect of two approved PCSK9-I on the concentration and lipid composition of HDL particle subclasses.

Subjects And Methods: 95 patients (62.8 ± 10.3 years old, 58% men), with or without statin and/or ezetimibe treatment and eligible for PCSK9-I therapy, received either evolocumab (140 mg) or alirocumab (75 or 150 mg). Their HDL particle profiles were measured by NMR spectroscopy at baseline and after 4 weeks of PCSK9-I treatment.

Results: PCSK9-I treatment increased the level of HDL-C by 7%. The level of medium-sized HDL particles (M-HDL-P) increased (+8%) while the level of XL-HDL-P decreased (-19%). The lipid core composition was altered in the smaller S- and M-HDL-P, with a reduction in triglycerides (TG) and an enrichment in cholesterol esters (CE), whereas the for the larger XL- and L-HDL-P the relative CE content decreased and the TG content increased. Ezetimibe therapy differentially impacted the HDL particle distribution, independently of statin use, with an increase in S-HDL-P in patients not receiving ezetimibe.

Conclusions: As S- and M-HDL-P levels are inversely related to cardiovascular risk, PCSK9-I treatment may result in a more atheroprotective HDL particle profile, particularly in patients not concomitantly treated with ezetimibe.
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http://dx.doi.org/10.1016/j.vph.2020.106804DOI Listing
December 2020

Mutation spectrum and polygenic score in German patients with familial hypercholesterolemia.

Clin Genet 2020 11 2;98(5):457-467. Epub 2020 Sep 2.

Department of Endocrinology and Metabolism, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Autosomal-dominant familial hypercholesterolemia (FH) is characterized by increased plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and a substantial risk to develop cardiovascular disease. Causative mutations in three major genes are known: the LDL receptor gene (LDLR), the apolipoprotein B gene (APOB) and the proprotein convertase subtilisin/kexin 9 gene (PCSK9). We clinically characterized 336 patients suspected to have FH and screened them for disease causing mutations in LDLR, APOB, and PCSK9. We genotyped six single nucleotide polymorphisms (SNPs) to calculate a polygenic risk score for the patients and 1985 controls. The 117 patients had a causative variant in one of the analyzed genes. Most variants were found in the LDLR gene (84.9%) with 11 novel mutations. The mean polygenic risk score was significantly higher in FH mutation negative subjects than in FH mutation positive patients (P < .05) and healthy controls (P < .001), whereas the score of the two latter groups did not differ significantly. However, the score explained only about 3% of the baseline LDL-C variance. We verified the previously described clinical and genetic variability of FH for German hypercholesterolemic patients. Evaluation of a six-SNP polygenic score recently proposed for clinical use suggests that it is not a reliable tool to classify hypercholesterolemic patients.
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http://dx.doi.org/10.1111/cge.13826DOI Listing
November 2020

Relationship between Lipoprotein (a) and cognitive function - Results from the Berlin Aging Study II.

Sci Rep 2020 06 30;10(1):10636. Epub 2020 Jun 30.

Max Planck Institute for Human Development, Berlin, Germany.

It has been suggested that an age-related loss of cognitive function might be driven by atherosclerotic effects associated with altered lipid patterns. However, the relationship between Lipoprotein (a) [Lp(a)] and healthy cognitive aging has not yet been sufficiently investigated. For the current analysis we used the cross-sectional data of 1,380 Berlin Aging Study II (BASE-II) participants aged 60 years and older (52.2% women, mean age 68 ± 4 years). We employed the Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-Plus test battery to establish latent factors representing continuous measures of domain specific cognitive functions. Regression models adjusted for APOE genotypes, lipid parameters and other risk factors for cognitive impairment were applied to assess the association between Lp(a) and performance in specific cognitive domains. Men within the lowest Lp(a)-quintile showed better cognitive performance in the cognitive domain executive functions and processing speed (p = 0.027). No significant results were observed in women. The results of the current analysis of predominantly healthy BASE-II participants point towards an association between low Lp(a) concentrations and better cognitive performance. However, evidence for this relationship resulting from the current analysis and the employment of a differentiated cognitive assessment is rather weak.
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http://dx.doi.org/10.1038/s41598-020-66783-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326928PMC
June 2020

PCSK9 Inhibitors in a German Single-Center Clinical Practice: Real-World Treatment of Patients at High Cardiovascular Risk Over 68 Weeks.

Am J Cardiovasc Drugs 2021 Jan;21(1):83-92

Division of Lipid Disorders, Department of Endocrinology, Charité Universitätsmedizin Berlin, Augustenburger Platz 1, Ostring 3, 13353, Berlin, Germany.

Aims: Several the use of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) for patients at high/very high cardiovascular risk who are inadequately treated with maximally tolerated lipid-lowering therapies (LLTs).

Objectives: We assessed the effectiveness and safety of the PCSK9i alirocumab and evolocumab in a single-center clinical practice for up to 68 weeks.

Methods: In this prospective, open-label study conducted in Germany, 635 enrolled patients were treated with alirocumab [75 or 150 mg every 2 weeks (Q2W)] or evolocumab (140 mg Q2W) according to European Society of Cardiology/European Atherosclerosis Society guidelines (low-density lipoprotein cholesterol [LDL-C] > 1.81/2.59 mmol/L (70/100 mg/dL), depending on cardiovascular risk]. Investigators were able to adjust LLTs, including PCSK9i, according to their own clinical judgment. The primary effectiveness endpoint was LDL-C reduction from baseline to week 68.

Results: At baseline, approximately 50% of patients were statin intolerant, and approximately 90% reported a history of cardiovascular disease. LDL-C reductions remained generally unchanged from weeks 4 to 68 in each treatment group. At week 68, LDL-C mean percentage changes from baseline were - 41.7% (alirocumab 75 mg Q2W), - 53.7% (alirocumab 150 mg Q2W), and - 54.1% (evolocumab 140 mg Q2W). LDL-C reduction was 7.1% greater in patients receiving statins than in those not receiving statins because of statin intolerance (P < 0.0001). PCSK9i consistently improved levels of other lipoproteins throughout. Overall, 47.1% of patients reported adverse events at week 68.

Conclusions: Consistent with clinical trial findings, alirocumab and evolocumab improved lipid levels in a real-world setting in patients with high baseline LDL-C levels despite receiving maximally tolerated LLTs. PCSK9i were generally well-tolerated.
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http://dx.doi.org/10.1007/s40256-020-00411-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838077PMC
January 2021

Hyperlipidemias in elderly patients: results from the Berlin Aging Study II (BASEII), a cross-sectional study.

Lipids Health Dis 2020 May 14;19(1):92. Epub 2020 May 14.

Department of Endocrinology and Metabolic Diseases (including Lipid Metabolism), Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Hyperlipidemias are common and the last decades have seen substantially growing evidence of their causative role in the development of atherosclerosis and subsequent cardiovascular diseases. Since hyperlipidemias usually do not cause direct clinical symptoms, they often remain undiagnosed until a serious cardiovascular event occurs. Especially for LDL-hypercholesteremia, there are well-established treatment options available to prevent the occurrence of atherosclerosis. However, there is a lack of knowledge regarding the proper treatment of elderly patients. The goal of this study was to assess the prevalence of hyperlipidemia in a group of young and a group of elderly community-dwelling participants and to determine to what extent treatment of hyperlipidemia should be initiated or required.

Methods: Crossectional data from a total of 2151 subjects (1657 in the elderly group, mean age 69, and 494 in the young group (control group), mean age 29) of the Berlin Aging Study II (BASE-II) were available. Medical history was assessed and recorded by trained physicians and prevalence of lipid disorders was determined with laboratory tests, including a lipid-profile.

Results: A large proportion of subjects (39%) were unaware of an existing lipid disorder. The prevalence of hyperlipidemia was more frequent in the elderly group (76%) compared to the young group (41%). Hypercholesterolemia was the most common diagnosed disorder (64%), followed by hyperlipoproteinemia(a) (18%), hypertriglyceridemia (7%) and combined hyperlipoproteinaemia (5%). Only a minority of this cohort was treated with lipid-lowering medication (17%) and of those treatment targets according to ESC guidelines were reached only in 16.5 %.

Conclusions: Hyperlipidemias appear underdiagnosed and undertreated. As the prevalence of these disorders increases with age and with regard to their role as a major modifiable risk factor for cardiovascular disease it seems to be advisable to aim for more consistent and sustainable screening and treatment of these common disorders.

Trial Registration: BASE-II registered with the clinical trial registry Deutsches Register Klinischer Studien (DRKS00009277).
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http://dx.doi.org/10.1186/s12944-020-01277-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227351PMC
May 2020

Sex differences in arterial wave reflection and the role of exogenous and endogenous sex hormones: results of the Berlin Aging Study II.

J Hypertens 2020 06;38(6):1040-1046

Lipid Clinic at the Interdisciplinary Metabolism Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health.

Background: Arterial stiffness is tightly linked to hypertension. Sex differences in hypertension and arterial stiffness have already been established, yet the role of sex hormones is not precisely defined. This study examined age and sex differences of arterial wave reflection and associations with endogenous and exogenous sex hormones in women.

Methods: Pulse wave analysis was performed with an oscillometric device in 590 male and 400 female participants of the Berlin Aging Study II. Participants have been recruited from two age-strata, 22-35 years and 60-82 years. Data on exposures and potential confounders, including medication, have been collected at baseline visit.

Results: Aumentation index (AIx) and pulse wave velocity increased with age. Mean AIx was higher in women than in men. Multivariable regression analysis showed a positive association between use of oral contraceptive pills (OCPs) and AIx controlling for confounders (age, BMI, current smoking, central blood pressure), with a significantly higher mean AIx in OCP-users compared with nonusers (mean group difference: 4.41; 95% confidence interval 1.61-7.22). Per quartile decrease in estradiol level AIx increased by 1.72 (95% confidence interval 0.43-3.00). In OCP users endogenous estradiol was largely suppressed.

Conclusion: The findings suggest important sex differences in measures of arterial wave reflection, with a higher mean AIx observed in women compared with men. OCPs may promote the development of hypertension by increasing AIx. Suppressed endogenous estradiol levels may be responsible for this increased wave reflection due to increased vasotonus of the small and medium arteries.
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http://dx.doi.org/10.1097/HJH.0000000000002386DOI Listing
June 2020

Dehydration predicts longitudinal decline in cognitive functioning and well-being among older adults.

Psychol Aging 2020 Jun 30;35(4):517-528. Epub 2020 Apr 30.

Department of Psychology.

Adequate hydration is essential for health, with even mild forms of dehydration often having negative effects on cognition and well-being. Despite evidence of higher risk for dehydration among older adults, links between dehydration and cognitive or well-being outcomes have not been established in old age. In this study, we used longitudinal data from the Berlin Aging Study II (age range 60-89) to investigate whether trajectories of cognitive functioning (digit symbol, = 1,111) and well-being (Diener satisfaction with life, = 1,066; Socio-Economic Panel Study life satisfaction, = 1,067; and Lawton morale, = 1,067) are associated with objective dehydration (osmolarity; 33% dehydrated). Our results revealed that higher dehydration was associated with steeper decline in cognitive functioning and well-being over time, and lower well-being among those with higher body mass index. These associations were independent of sociodemographic and physical health characteristics. Our findings highlight the importance of adequate hydration for preserved cognition and well-being across old age. We discuss potential mechanisms and consider practical implications arising from our results. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/pag0000471DOI Listing
June 2020

Trajectories of multiple subjective well-being facets across old age: The role of health and personality.

Psychol Aging 2020 Sep 20;35(6):894-909. Epub 2020 Apr 20.

Department of Psychology, Humboldt University Berlin.

Subjective well-being is often characterized by average stability across old age, but individual differences are substantial and not yet fully understood. This study targets physical and cognitive health and personality as individual difference characteristics and examines their unique and interactive roles for level and change in a number of different facets of subjective well-being. We make use of medical diagnoses, performance-based indicators of physical (grip strength) and cognitive functioning (Digit Symbol), and extraversion and neuroticism and apply parallel sets of multilevel growth models to multiyear well-being data obtained in the Berlin Aging Study 2 ( = 1,216; = 71; = 3.84; 51% women) and the German Socio-Economic Panel ( = 3,418; = 70; = 6.89; 51% women). Results revealed by and large average stability of life satisfaction, morale, and emotions (anger, fear, sadness, happiness) across old age. Most important for our research questions, higher morbidity, poor performance on grip strength and perceptual speed tests, lower extraversion, and higher neuroticism were each uniquely associated with lower life satisfaction, morale, and positive affect and higher negative affect. Some evidence emerged for facet-specific health-personality interaction effects in predicting affective experiences, but effects observed were not consistent across studies and of small size. We take our findings to indicate that health and personality traits constitute important individual difference characteristics for our understanding of subjective well-being in old age and that these likely do not interact with one another to shape well-being. We discuss theoretical and practical implications. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/pag0000459DOI Listing
September 2020

Plasma carotenoids, tocopherols and retinol - Association with age in the Berlin Aging Study II.

Redox Biol 2020 05 13;32:101461. Epub 2020 Feb 13.

Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany; Geriatrics Research Group, Charité - Universitätsmedizin Berlin, 13347 Berlin, Germany; Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany. Electronic address:

Regular consumption of fruits and vegetables, which is related to high plasma levels of lipid-soluble micronutrients such as carotenoids and tocopherols, is linked to lower incidences of various age-related diseases. Differences in lipid-soluble micronutrient blood concentrations seem to be associated with age. Our retrospective analysis included men and women aged 22-37 and 60-85 years from the Berlin Aging Study II. Participants with simultaneously available plasma samples and dietary data were included (n = 1973). Differences between young and old groups were found for plasma lycopene, α-carotene, α-tocopherol, β-cryptoxanthin (only in women), and γ-tocopherol (only in men). β-Carotene, retinol and lutein/zeaxanthin did not differ between young and old participants regardless of the sex. We found significant associations for lycopene, α-carotene (both inverse), α-tocopherol, γ-tocopherol, and β-carotene (all positive) with age. Adjusting for BMI, smoking status, season, cholesterol and dietary intake confirmed these associations, except for β-carotene. These micronutrients are important antioxidants and associated with lower incidence of age-related diseases, therefore it is important to understand the underlying mechanisms in order to implement dietary strategies for the prevention of age-related diseases. To explain the lower lycopene and α-carotene concentration in older subjects, bioavailability studies in older participants are necessary.
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http://dx.doi.org/10.1016/j.redox.2020.101461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7030983PMC
May 2020

Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue.

Sci Rep 2020 02 7;10(1):2158. Epub 2020 Feb 7.

Muscle Research Unit, Experimental and Clinical Research Center, a joint cooperation between the Charité Universitätsmedizin and the Max Delbrück Center for Molecular Medicine, Berlin, 13125, Germany.

Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy.
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http://dx.doi.org/10.1038/s41598-020-58668-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005895PMC
February 2020

Potentially inappropriate medication in older participants of the Berlin Aging Study II (BASE-II) - Sex differences and associations with morbidity and medication use.

PLoS One 2019 30;14(12):e0226511. Epub 2019 Dec 30.

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at the Interdisciplinary Metabolism Center, Berlin, Germany.

Introduction: Multimorbidity in advanced age and the need for drug treatment may lead to polypharmacy, while pharmacokinetic and pharmacodynamic changes may increase the risk of adverse drug events (ADEs).

Objective: The aim of this study was to determine the proportion of subjects using potentially inappropriate medication (PIM) in a cohort of older and predominantly healthy adults in relation to polypharmacy and morbidity.

Methods: Cross-sectional data were available from 1,382 study participants (median age 69 years, IQR 67-71, 51.3% females) of the Berlin Aging Study II (BASE-II). PIM was classified according to the EU(7)-PIM and German PRISCUS (representing a subset of the former) list. Polypharmacy was defined as the concomitant use of at least five drugs. A morbidity index (MI) largely based on the Charlson Index was applied to evaluate the morbidity burden.

Results: Overall, 24.1% of the participants were affected by polypharmacy. On average, men used 2 (IQR 1-4) and women 3 drugs (IQR 1-5). According to PRISCUS and EU(7)-PIM, 5.9% and 22.6% of participants received at least one PIM, while use was significantly more prevalent in females (25.5%) compared to males (19.6%) considering EU(7)-PIM (p = 0.01). In addition, morbidity in males receiving PIM according to EU(7)-PIM was higher (median MI 1, IQR 1-3) compared to males without PIM use (median MI 1, IQR 0-2, p<0.001).

Conclusion: PIM use occurred more frequently in women than in men, while it was associated with higher morbidity in males. As expected, EU(7)-PIM identifies more subjects as PIM users than the PRISCUS list but further studies are needed to investigate the differential impact of both lists on ADEs and outcome.

Key Points: We found PIM use to be associated with a higher number of regular medications and with increased morbidity. Additionally, we detected a higher prevalence of PIM use in females compared to males, suggesting that women and people needing intensive drug treatment are patient groups, who are particularly affected by PIM use.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0226511PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936809PMC
March 2020

Long-term gait measurements in daily life: Results from the Berlin Aging Study II (BASE-II).

PLoS One 2019 11;14(12):e0225026. Epub 2019 Dec 11.

Lipid Clinic at the Interdisciplinary Metabolism Center, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Background: Walking ability is an important prerequisite for activity, social participation and independent living. While in most healthy adults, this ability can be assumed as given, limitations in walking ability occur with increasing age. Furthermore, slow walking speed is linked to several chronic conditions and overall morbidity. Measurements of gait parameters can be used as a proxy to detect functional decline and onset of chronic conditions. Up to now, gait characteristics used for this purpose are measured in standardized laboratory settings. There is some evidence, however, that long-term measurements of gait parameters in the living environment have some advantages over short-term laboratory measurements.

Methods: We evaluated cross-sectional data from an accelerometric sensor worn in a subgroup of 554 participants of the Berlin Aging Study II (BASE-II). Data from the two BASE-II age groups (age between 22-36 years and 60-79 years) were used for the current analysis of accelerometric data for a minimum of two days and a maximum of ten days were available. Real world walking speed, number of steps, maximum coherent distance and total distance were derived as average data per day. Linear regression analyses were performed on the different gait parameters in order to identify significant determinants. Additionally, Mann-Whitney-U-tests were performed to detect sex-specific differences.

Results: Age showed to be significantly associated with real world walking speed and with the total distance covered per day, while BMI contributed negatively to the number of walking steps, maximum coherent distance and total distance walked. Additionally, sex was associated with walking steps. However, R2-values for all models were low. Overall, women had significantly more walking steps and a larger coherent distance per day when compared to men. When separated by age group, this difference was significant only in the older participants. Additionally, walking speed was significantly higher in women compared to men in the subgroup of older people.

Conclusions: Age- and sex-specific differences have to be considered when objective gait parameters are measured, e.g. in the context of clinical risk assessment. For this purpose normative data, differentiating for age and sex would have to be established to allow reliable classification of long-term measurements of gait.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0225026PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905575PMC
March 2020

Cohort differences in adult-life trajectories of internal and external control beliefs: A tale of more and better maintained internal control and fewer external constraints.

Psychol Aging 2019 Dec;34(8):1090-1108

Department of Human Development and Family Studies, Pennsylvania State University.

Life Span theory posits that sociohistorical contexts shape individual development. In line with this proposition, cohort differences favoring later-born cohorts have been widely documented for cognition and health. However, little is known about historical change in how key resources of psychosocial functioning such as control beliefs develop in old age. We pooled data from 3 independent samples: Berlin Aging Study (6 waves, = 414); Interdisciplinary Longitudinal Study of Adult Development (4 waves, = 925); and Berlin Aging Study II (4 waves, = 1,111) to construct overlapping multiyear longitudinal data from ages 61 through 85 years for cohorts born 1905 to 1953 and examine historical changes in within-person trajectories of internal and external control beliefs. Results revealed that earlier-born cohorts exhibit age-related declines in internal control beliefs regarding both desirable and undesirable outcomes, whereas later-born cohorts perceive higher internal control and maintain this advantage into old age. Earlier-born cohorts also experience steep age-related increases in external control beliefs regarding both powerful others and chance, whereas later-born cohorts perceive lower external control and were stable across old age. Education and gender disparities in control beliefs narrowed over historical time. Sociodemographic, physical health, cognitive, and social factors explained some of the differences in control beliefs, and accounted for sizable portions of cohort effects. Our results indicate that current generations of older adults perceive more and better maintained internal control and fewer external constraints. We discuss potential underlying mechanisms and consider conceptual and societal implications of our findings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/pag0000389DOI Listing
December 2019

Knowledge-based best of breed approach for automated detection of clinical events based on German free text digital hospital discharge letters.

PLoS One 2019 27;14(11):e0224916. Epub 2019 Nov 27.

Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Lipid Clinic at Interdisciplinary Metabolism Center, Berlin, Germany.

Objectives: The secondary use of medical data contained in electronic medical records, such as hospital discharge letters, is a valuable resource for the improvement of clinical care (e.g. in terms of medication safety) or for research purposes. However, the automated processing and analysis of medical free text still poses a huge challenge to available natural language processing (NLP) systems. The aim of this study was to implement a knowledge-based best of breed approach, combining a terminology server with integrated ontology, a NLP pipeline and a rules engine.

Methods: We tested the performance of this approach in a use case. The clinical event of interest was the particular drug-disease interaction "proton-pump inhibitor [PPI] use and osteoporosis". Cases were to be identified based on free text digital discharge letters as source of information. Automated detection was validated against a gold standard.

Results: Precision of recognition of osteoporosis was 94.19%, and recall was 97.45%. PPIs were detected with 100% precision and 97.97% recall. The F-score for the detection of the given drug-disease-interaction was 96,13%.

Conclusion: We could show that our approach of combining a NLP pipeline, a terminology server, and a rules engine for the purpose of automated detection of clinical events such as drug-disease interactions from free text digital hospital discharge letters was effective. There is huge potential for the implementation in clinical and research contexts, as this approach enables analyses of very high numbers of medical free text documents within a short time period.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224916PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881027PMC
March 2020
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