Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People.

BACKGROUND: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. METHODS AND RESULTS: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. CONCLUSIONS: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

Comparison of different risk scores for Parkinson disease in a population-based 10-year study.

BACKGROUND AND PURPOSE: Different algorithms aiming to identify individuals at risk of Parkinson disease (PD) have been proposed. Comparative studies of these scores and their recent updates in the general elder population are needed. METHODS: We have previously applied the "basic" PREDICT-PD algorithm, designed for remote screening, and the original and updated Movement Disorder Society (MDS) criteria for prodromal PD to the longitudinal population-based Bruneck study cohort. We have now additionally employed the "enhanced" PREDICT-PD algorithm (which includes motor assessment, olfaction, probable rapid eye movement sleep behaviour disorder status, pesticide exposure, and diabetes as additional factors). Risk scores were calculated based on comprehensive baseline assessments (2005) in 574 subjects aged 55-94 years (290 females), and cases of incident PD were identified at 5-year (n = 11) and 10-year follow-up (n = 9). We analysed the association of the different log-transformed risk scores with incident PD at follow-up (calculated per 1-SD unit change). RESULTS: The enhanced PREDICT-PD algorithm was associated with incident PD over 10-years of follow-up, yielding higher odds for incident PD (odds ratio [OR] = 4.61, 95% confidence interval [CI] = 2.68-7.93, p < 0.001) compared with the basic PREDICT-PD score (OR = 2.38, 95% CI = 1.49-3.79, p < 0.001). The updated MDS prodromal criteria yielded a numerically higher OR of 7.13 (95% CI = 3.49-14.54, p < 0.001) in comparison with the original criteria as well as the enhanced PREDICT-PD algorithm, with overlapping 95% CIs. CONCLUSIONS: The enhanced PREDICT-PD algorithm was significantly associated with incident PD. The consistent performance of both the enhanced PREDICT-PD algorithm and the updated MDS prodromal criteria compared to their original versions supports their use in PD risk screening.

Stroke Care Pathway ensures high-quality stroke management in the COVID-19 pandemic.

The aim of our study was to assess whether a well-established federal state-wide Stroke Care Pathway delivering high quality stroke care can cope with the COVID-19 pandemic and associated measures to contain the virus spread. The retrospective analysis is based on a prospective, quality-controlled, population-based registry of all stroke patients in the Tyrol, a federal state of Austria and one of the early hot-spots of COVID-19 in Europe. Patient characteristics, pre-hospital management, intra-hospital management and post-hospital were analysed. All residents of the Tyrol suffering ischemic stroke in 2020 (n = 1160) and four pre-COVID-19 years (n = 4321) were evaluated. In 2020, the annual number of stroke patients was the highest in this population-based registry. When local hospitals were overwhelmed with SARS-CoV-2-patients, stroke subjects were temporarily allocated to the comprehensive stroke centre. Stroke severity, quality metrics of stroke management, serious complications, and post-stroke mortality did not differ between 2020 and the four comparator years. Notably, iv. thrombolysis-rate was similar (19.9% versus 17.4%, P = 0.25) and endovascular stroke treatment even better (5.9% versus 3.9%, P = 0.003) but resources for in-patient rehabilitation were limited (25.8% versus 29.8%, P = 0.009). Concluding, a well-established Stroke Care Pathway was able to maintain high-quality acute stroke care even when challenged by a global pandemic.

Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease.

BACKGROUND: Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). METHODS: The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). RESULTS: Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. CONCLUSIONS: Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.

Bariatric surgery prevents carotid wall thickness progression.

BACKGROUND: Bariatric surgery is a treatment option for patients with severe obesity and improves parameters of cardiovascular and/or metabolic disease. Carotid intima media thickness (C-IMT) is a surrogate measure of subclinical atherosclerosis. Previous studies showed short to mid-term arrest and even regression of C­IMT progression following bariatric surgery. We aimed to investigate the long-term effect of weight loss on C­IMT progression 10 years after bariatric surgery in comparison to a population-based control cohort. METHODS: In total, 21 eligible patients were examined preoperatively, at 5 and 10 years after bariatric surgery. Anthropometric parameters, plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), insulin, and glucose were assessed at all three study visits. C­IMT was measured via B­mode scans of the common carotid artery. C­IMT progression was measured in an age-matched and BMI-matched cohort selected from the population-based Bruneck study to compare with changes in C­IMT progression after bariatric surgery. RESULTS: C­IMT remained stable over the 10-year observation period after bariatric surgery. The control cohort showed a significant C­IMT progression over 10 years. The difference in C­IMT progression over 10 years was significant (p < 0.01) between both cohorts. CONCLUSION: Weight loss induced by bariatric surgery halts the natural progression of C­IMT over a 10-year observation period.

Association of desphospho-uncarboxylated matrix gla protein with incident cardiovascular disease and all-cause mortality: Results from the prospective Bruneck Study.

BACKGROUND AND AIMS: Matrix Gla protein (MGP), a vitamin K-dependent protein, is a potent inhibitor of vascular calcification. Desphospho-uncarboxylated MGP (dp-ucMGP), a marker of vitamin K insufficiency, has been shown to predict cardiovascular disease (CVD) and all-cause mortality in high-risk populations. Whether the increased risk associated with dp-ucMGP also applies to the general, and especially, the elderly population has not yet been fully elucidated. METHODS AND RESULTS: Plasma dp-ucMGP was measured in 684 individuals aged 50-89 years of the prospective population-based Bruneck Study (baseline evaluation in 2000). Baseline median dp-ucMGP was 478.4 (IQR 335.0-635.2) pmol/L. Over a median follow-up of 15.5 years, 163 CVD events occurred and 235 participants died. Age-/sex-adjusted hazard ratios (HRs) per 1-SD higher level of loge transformed dp-ucMGP were 1.30 (95%CI: 1.09-1.55; p=0.004) for incident CVD and 1.36 (95%CI: 1.17-1.57; p<0.001) for all-cause mortality. After multivariable adjustment, the associations remained significant with HRs of 1.23 (95%CI: 1.02-1.47, p=0.029) for CVD and 1.40 (95%CI: 1.20-1.64; p<0.001) for all-cause mortality. The associations remained virtually unchanged after additional adjustment for dietary quality as measured with the Alternative Healthy Eating Index. We found no association of dp-ucMGP with myocardial infarction and sudden cardiac deaths, but a strong association with other vascular deaths and non-vascular/non-cancer deaths. CONCLUSIONS: This study shows a significant association of plasma dp-ucMGP with incident CVD and a significant and even stronger association with all-cause mortality. Clinical trials are needed to investigate whether vitamin K substitution results in improved health outcomes.

Ultrasound-detected inflammation is more common in clinically manifest hand osteoarthritis than in painless bony enlarged finger joints: subanalysis of the population-based Bruneck study.

Purpose: The aim of this article is to examine the extent of structural and inflammatory lesions by ultrasound in elderly subjects with hand osteoarthritis (HOA) fulfilling the ACR classification criteria (Group A), in subjects with painless enlarged finger joints (Group B), and in individuals without clinical abnormalities at hands (Group C). Methods: This study was nested within the population-based, prospective Bruneck study; 293 subjects of ⩾65 years of age were assessed. Clinical and ultrasound assessment was conducted at wrists and finger joints. Gray scale synovitis (GSS), Power Doppler (PD), osteophytes, and erosions were scored semiquantitatively (0-3). The Short Form Score for the Assessment and Quantification of Chronic Rheumatic Affections of the Hands (SF-SACRAH), the Health Assessment Questionnaire (HAQ), and the Functional Index for Hand Osteoarthritis (FIHOA) were retrieved. Results: Most subjects had ⩾1 ultrasound abnormality, of which osteophytes were the most prevalent finding in all groups (Group A: 100%, Group B: 99.4%, and Group C: 93.9%). GSS and PD-signals were more common in Group A than in Group B (94% versus 67% and 33% versus 13%, respectively). In Group C, GSS was observed in 39.4% of subjects. In subjects with HOA, the SF-SACRAH correlated with osteophyte scores (corrcoeff = 0.48), and the FIHOA correlated with the osteophyte (corrcoeff = 0.42) and PD scores (corrcoeff = 0.33). Conclusion: GSS and PD were more frequent in patients with symptomatic HOA than in cases with painless bony enlargements and subjects without clinical joint abnormalities. Functional restriction in HOA is associated with structural and inflammatory ultrasound changes.

[Tyrolean stroke pathway]. / Schlaganfallpfad Tirol.

Background: Recent advances in acute stroke therapy have been shown to improve clinical outcome and therefore reduce long-term disability. Acute therapy procedures in stroke have a limited time frame after onset of symptoms; thus, rapid emergency management is critical. The Tyrolean Stroke Pathway was developed to optimize the entire treatment pathway from stroke onset to outpatient rehabilitation. Objectives: The description of the Tyrolean Stroke Pathway as an example to optimize the entire treatment pathway of stroke patients in a central European alpine region with a focus on prehospital management. Materials and methods: In four subprojects from the prehospital phase up to outpatient rehabilitation, the project optimized intersections between different phases of care and evaluated the care processes using quality assurance measures. Results: After implementation, thrombolysis rates doubled and functional outcome of stroke patients after 3 months improved and complications, e.g., pneumonia, declined. Access to rehabilitation improved, particularly because of the establishment of quality assured and funded outpatient rehabilitation. Conclusions: The project showed that a holistic standardized stroke pathway from acute management up to outpatient rehabilitation can be successfully implemented in clinical routine. The project improved the entire health care pathway of stroke patients. The Stroke Action Plan for Europe 2018-2030 recommends to have national plans for stroke that encompass the entire chain of care.

Neutrophil-Derived Protein S100A8/A9 Alters the Platelet Proteome in Acute Myocardial Infarction and Is Associated With Changes in Platelet Reactivity.

OBJECTIVE: Platelets are central to acute myocardial infarction (MI). How the platelet proteome is altered during MI is unknown. We sought to describe changes in the platelet proteome during MI and identify corresponding functional consequences. Approach and Results: Platelets from patients experiencing ST-segment-elevation MI (STEMI) before and 3 days after treatment (n=30) and matched patients with severe stable coronary artery disease before and 3 days after coronary artery bypass grafting (n=25) underwent quantitative proteomic analysis. Elevations in the proteins S100A8 and S100A9 were detected at the time of STEMI compared with stable coronary artery disease (S100A8: FC, 2.00; false discovery rate, 0.05; S100A9: FC, 2.28; false discovery rate, 0.005). During STEMI, only S100A8 mRNA and protein levels were correlated in platelets (R=0.46, P=0.012). To determine whether de novo protein synthesis occurs, activated platelets were incubated with 13C-labeled amino acids for 24 hours and analyzed by mass spectrometry. No incorporation was confidently detected. Platelet S100A8 and S100A9 was strongly correlated with neutrophil abundance at the time of STEMI. When isolated platelets and neutrophils were coincubated under quiescent and activated conditions, release of S100A8 from neutrophils resulted in uptake of S100A8 by platelets. Neutrophils released S100A8/A9 as free heterodimer, rather than in vesicles or extracellular traps. In the community-based Bruneck study (n=338), plasma S100A8/A9 was inversely associated with platelet reactivity-an effect abrogated by aspirin. CONCLUSIONS: Leukocyte-to-platelet protein transfer may occur in a thromboinflammatory environment such as STEMI. Plasma S100A8/A9 was negatively associated with platelet reactivity. These findings highlight neutrophils as potential modifiers for thrombotic therapies in coronary artery disease.

Associations of Gait Disorders and Recurrent Falls in Older People: A Prospective Population-Based Study.

BACKGROUND: Recurrent falls represent a major source of serious adverse health outcomes in the general older population. Gait impairment has been linked to recurrent falls, but there are only limited long-term data on this association. OBJECTIVES: The objective of the study was to investigate the association of gait disorders (GDs) and gait tests with future falls in an existing longitudinal population-based cohort. METHOD: The study was performed in participants of the Bruneck Study cohort 2010 aged 60-97 years, with prospective 5-year follow-up. At baseline, participants underwent a clinical gait assessment (to determine neurological and non-neurological GDs according to an established classification) and were also evaluated by quantitative and semiquantitative gait tests (Hauser Index, Tinetti balance and gait test, and gait speed). Logistic regression analysis adjusted for age and sex was used to determine the relationship of baseline variables with incident recurrent falls at 5-year follow-up. RESULTS: Of 328 included participants, 22 (6.7%) reported recurrent falls at follow-up. Baseline presence of GDs was associated with recurrent falls at follow-up (odds ratio [OR] 4.2; 95% confidence interval [CI] 1.6-11.1; p = 0.004), and this effect was largely driven by neurological GDs (OR 5.5; 95% CI 1.7-17.4; p = 0.004). All 3 simple gait tests were predictive for incident falls (Hauser Index, p = 0.002; Tinetti test, p = 0.006; and gait speed, p < 0.001). CONCLUSIONS: Clinical assessment of GDs and gait tests both had independent significant predictive value for recurrent falls over a 5-year follow-up period. This highlights the potential of such assessments for early fall risk screening and timely implementation of fall-preventive measures.

Long-term life history predicts current gut microbiome in a population-based cohort study.

Extensive scientific and clinical microbiome studies have explored contemporary variation and dynamics of the gut microbiome in human health and disease1-3, yet the role of long-term life history effects has been underinvestigated. Here, we analyzed the current, quantitative microbiome composition in the older adult Bruneck Study cohort (Italians, Bruneck, n = 304 (male, 154; female, 150); age 65-98 years) with extensive clinical, demographic, lifestyle and nutritional data collected over the past 26 years4. Multivariate analysis of historical variables indicated that medication history, historical physical activity, past dietary habits and specific past laboratory blood parameters explain a significant fraction of current quantitative microbiome variation in older adults, enlarging the explanatory power of contemporary covariates by 33.4%. Prediction of current enterotype by a combination of past and contemporary host variables revealed good levels of predictability (area under the curve (AUC), 0.78-0.83), with Prevotella and dysbiotic Bacteroides 2 being the best predicted enterotypes. These findings demonstrate long-term life history effects on the microbiota and provide insights into lifestyle variables and their role in maintaining a healthy gut microbiota in later life.

PCSK9 Activity Is Potentiated Through HDL Binding.

Rationale: Proprotein convertase subtilisin/kexin type 9 (PCSK9) circulates in a free and lipoprotein-bound form, yet the functional consequence of the association between PCSK9 and high-density lipoprotein (HDL) remains unexplored. Objective: This study sought to interrogate the novel relationship between PCSK9 and HDL in humans. Methods and Results: Comparing lipoprotein and apolipoprotein profiles by nuclear magnetic resonance and targeted mass spectrometry measurements with PCSK9 levels in the community-based Bruneck (n=656) study revealed a positive association of plasma PCSK9 with small HDL, alongside a highly significant positive correlation between plasma levels of PCSK9 and apolipoprotein-C3, an inhibitor of lipoprotein lipase. The latter association was replicated in an independent cohort, the SAPHIR study (n=270). Thus, PCSK9-HDL association was determined during the postprandial response in two dietary studies (n=20 participants each, 8 times points). Peak triglyceride levels coincided with an attenuation of the PCSK9-HDL association, a loss of apolipoprotein-C3 from HDL and lower levels of small HDL as measured by nuclear magnetic resonance. Crosslinking mass spectrometry (XLMS) upon isolated HDL identified PCSK9 as a potential HDL-binding partner. PCSK9 association with HDL was confirmed through size-exclusion chromatography and immuno-isolation. Quantitative proteomics upon HDL isolated from patients with coronary artery disease (n=172) returned PCSK9 as a core member of the HDL proteome. Combined interrogation of the HDL proteome and lipidome revealed a distinct cluster of PCSK9, phospholipid transfer protein, clusterin and apolipoprotein-E within the HDL proteome, that was altered by sex and positively correlated with sphingomyelin content. Mechanistically, HDL facilitated PCSK9-mediated low-density lipoprotein receptor degradation and reduced low-density lipoprotein uptake through the modulation of PCSK9 internalisation and multimerisation. Conclusions: This study reports HDL as a binder of PCSK9 and regulator of its function. The combination of -omic technologies revealed postprandial lipaemia as a driver of PCSK9 and apolipoprotein-C3 release from HDL.

Dietary spermidine improves cognitive function.

Decreased cognitive performance is a hallmark of brain aging, but the underlying mechanisms and potential therapeutic avenues remain poorly understood. Recent studies have revealed health-protective and lifespan-extending effects of dietary spermidine, a natural autophagy-promoting polyamine. Here, we show that dietary spermidine passes the blood-brain barrier in mice and increases hippocampal eIF5A hypusination and mitochondrial function. Spermidine feeding in aged mice affects behavior in homecage environment tasks, improves spatial learning, and increases hippocampal respiratory competence. In a Drosophila aging model, spermidine boosts mitochondrial respiratory capacity, an effect that requires the autophagy regulator Atg7 and the mitophagy mediators Parkin and Pink1. Neuron-specific Pink1 knockdown abolishes spermidine-induced improvement of olfactory associative learning. This suggests that the maintenance of mitochondrial and autophagic function is essential for enhanced cognition by spermidine feeding. Finally, we show large-scale prospective data linking higher dietary spermidine intake with a reduced risk for cognitive impairment in humans.

Characterization of gait variability in multiple system atrophy and Parkinson's disease.

BACKGROUND: Gait impairment is a pivotal feature of parkinsonian syndromes and increased gait variability is associated with postural instability and a higher risk of falls. OBJECTIVES: We compared gait variability at different walking velocities between and within groups of patients with Parkinson-variant multiple system atrophy, idiopathic Parkinson's disease, and a control group of older adults. METHODS: Gait metrics were recorded in 11 multiple system atrophy, 12 Parkinson's disease patients, and 18 controls using sensor-based gait analysis. Gait variability was analyzed for stride, swing and stance time, stride length and gait velocity. Values were compared between and within the groups at self-paced comfortable, fast and slow walking speed. RESULTS: Multiple system atrophy patients displayed higher gait variability except for stride time at all velocities compared with controls, while Parkinson's patients did not. Compared with Parkinson's disease, multiple system atrophy patients displayed higher variability of swing time, stride length and gait velocity at comfortable speed and at slow speed for swing and stance time, stride length and gait velocity (all P < 0.05). Stride time variability was significantly higher in slow compared to comfortable walking in patients with multiple system atrophy (P = 0.014). Variability parameters significantly correlated with the postural instability/gait difficulty subscore in both disease groups. Conversely, significant correlations between variability parameters and MDS-UPDRS III score was observed only for multiple system atrophy patients. CONCLUSION: This analysis suggests that gait variability parameters reflect the major axial impairment and postural instability displayed by multiple system atrophy patients compared with Parkinson's disease patients and controls.

STROKE-CARD care to prevent cardiovascular events and improve quality of life after acute ischaemic stroke or TIA: A randomised clinical trial.

BACKGROUND: Patients with ischaemic stroke or transient ischaemic attack (TIA) are at high risk of recurrent stroke and other cardiovascular diseases and commonly suffer from reduced quality of life. We aimed to determine whether the disease management programme STROKE-CARD can prevent cardiovascular diseases and improve quality of life in these patients. METHODS: In this pragmatic open-label two-centre randomised controlled trial with blinded outcome assessment, we randomly assigned patients with acute ischaemic stroke or TIA (ABCD2 score ≥3) in a 2:1 ratio to receive STROKE-CARD care or standard care. STROKE-CARD care is a disease management programme by a multidisciplinary stroke team that comprises a standardised 3-month visit and access to a web-based patient portal targeting risk factor management, post-stroke complications, comorbidities and cardiovascular warning signs, rehabilitation demands, and patient education, counselling, and self-empowerment. Co-primary outcomes were analysed on an intention-to-treat basis and were: (i) major cardiovascular disease events defined as nonfatal ischaemic or haemorrhagic stroke, nonfatal myocardial infarction, or vascular death occurring between hospital discharge and 12 months; and (ii) health-related quality of life at 12 months quantified with the EuroQol-5-Dimensions-3-Levels (EQ-5D-3L) overall utility score. This trial is registered with ClinicalTrials.gov, number NCT02156778. FINDINGS: Of 2149 patients enrolled between January 2014 and December 2017 (mean age 69 years, 41% female, 83% with ischaemic stroke, 17% with TIA), 1438 were assigned to STROKE-CARD care and 711 to standard care. Major cardiovascular disease events occurred in 78 patients in the STROKE-CARD care group (5.4%) and in 59 patients in the standard care group (8.3%) (hazard ratio, 0.63; 95% confidence interval: 0.45-0.88; P=0.007). STROKE-CARD care also led to a better EQ-5D-3L overall utility score at 12 months (P<0.001). Among pre-specified secondary outcomes, STROKE-CARD care improved all individual EQ-5D-3L dimensions and functional outcome on the modified Rankin Scale at 12 months. Post hoc explanatory analyses identified considerable demands for additional rehabilitation and refinement of preventive therapy regimes at the 3-month visit and high proportions of post-stroke complications and warning signs of imminent cardiovascular diseases within the first three months. INTERPRETATION: The pragmatic and easily implementable STROKE-CARD care programme reduced cardiovascular risk and improved health-related quality of life and functional outcome in patients with acute ischaemic stroke or TIA. FUNDING: Tirol Kliniken, Tyrolean Health Insurance Company, Tyrol Health Care Funds, Boehringer Ingelheim, Nstim Services, Sanofi, Bayer Healthcare.

Extracellular matrix protein signature of recurrent spontaneous cervical artery dissection.

OBJECTIVE: To assess whether connective tissue disorder is evident in patients with spontaneous cervical artery dissection and therefore identify patients at risk of recurrence using a cutting-edge quantitative proteomics approach. METHODS: In the ReSect study, all patients with spontaneous cervical artery dissection treated at the Innsbruck University Hospital since 1996 were invited to attend a standardized clinical follow-up examination. Protein abundance in skin punch biopsies (n = 50) was evaluated by a cutting-edge quantitative proteomics approach (liquid chromatography-mass spectrometry) that has hitherto not been applied to such patients. RESULTS: Patients with 1-time single-vessel (n = 19) or multiple-vessel (n = 13) dissections did not differ between each other or compared to healthy controls (n = 12) in protein composition. Patients with recurrent spontaneous cervical artery dissection (n = 6), however, showed significantly different expression of 25 proteins compared to the other groups combined. Literature review and Gene Ontology term annotation check revealed that 13 of the differently expressed proteins play a major role in the structural integrity of connective tissue or are linked to connective tissue disorders. These proteins showed clustering to a collagen/elastin cluster and one consisting of desmosome related proteins. CONCLUSION: This study unravels an extracellular matrix protein signature of recurrent spontaneous cervical artery dissection. In the long run and after large-scale validation, our findings may well assist in identifying patients at risk of recurrent spontaneous cervical artery dissection and thus guide therapy.

The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.

Application of a Simple Parkinson's Disease Risk Score in a Longitudinal Population-Based Cohort.

BACKGROUND: Identifying individuals at risk of developing Parkinson's disease (PD) is critical to define target populations for future neuroprotective trials. OBJECTIVE: The objective of this study was to apply the PREDICT-PD algorithm of risk indicators for PD in a prospective community-based study (the Bruneck study), representative of the general elderly population. METHODS: PREDICT-PD risk scores were calculated based on risk factor assessments obtained at baseline (2005, n = 574 participants). Cases of incident PD were identified at 5-year and 10-year follow-ups. Participants with PD or secondary parkinsonism at baseline were excluded (n = 35). We analyzed the association of log-transformed risk scores with the presence of well-established markers as surrogates for PD risk at baseline and with incident PD at follow-up. RESULTS: A total of 20 participants with incident PD were identified during follow-up (11 after 5 years and 9 after 10 years). Baseline PREDICT-PD risk scores were associated with incident PD with odds ratios of 2.09 (95% confidence interval, 1.35-3.25; P = 0.001) after 5 years and of 1.95 (1.36-2.79; P < 0.001) after 10 years of follow-up per doubling of risk scores. In addition, higher PREDICT-PD scores were significantly correlated with established PD risk markers (olfactory dysfunction, signs of rapid eye movement sleep behavior disorder and motor deficits) and significantly associated with higher probability for prodromal PD according to the Movement Disorder Society research criteria at baseline. CONCLUSIONS: The PREDICT-PD score was associated with an increased risk for incident PD in our sample and may represent a useful first screening step in future algorithms aiming to identify cases of prodromal PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.