Identification of risk factors and prodromal markers for Parkinson’s disease (PD) and the understanding of the point in time of first occurrence is essential for the early detection of incident PD. ...In this three-center longitudinal, observational study, we evaluated the specific risk for PD associated with single or combinations of risk factors and prodromal markers. In addition, we evaluated which risk factors and prodromal markers emerge at which time before the diagnosis of PD. Of the 1,847 at-baseline PD-free individuals ≥50 years, 1,260 underwent the 5-year follow-up assessment. There were 21 cases of incident PD during the study period. Enlarged hyperechogenic substantia nigra was the most frequent baseline sign in individuals developing PD after 3 years (80.0 %) and 5 years (85.7 %) compared to healthy controls (17.5 %) followed by the occurrence of mild parkinsonian signs and hyposmia. Evaluation of the signs at the first follow-up assessment showed that individuals developing PD after two additional years showed the same pattern of signs as individuals who developed PD 3 years after baseline assessment.
OBJECTIVE:--High serum uric acid levels lead to gout and have been reported to be associated with an increased risk of hypertension, obesity, metabolic syndrome, type 2 diabetes, and cardiovascular ...disease. Recently, the putative fructose transporter SLC2A9 was reported to influence uric acid levels. The aim of the present study was to examine the association of four single nucleotide polymorphisms within this gene with uric acid levels and to determine whether this association is modified by obesity. RESEARCH DESIGN AND METHODS--Four single nucleotide polymorphisms within SLC2A9 (rs6855911, rs7442295, rs6449213, and rs12510549) were genotyped in the population-based prospective Bruneck Study (n = 800) and in a case-control study from Utah including 1,038 subjects recruited for severe obesity and 831 control subjects. RESULTS:--We observed highly significant associations between all four polymorphisms and uric acid levels in all study groups. Each copy of the minor allele decreased age- and sex-adjusted uric acid levels by 0.30-0.35 mg/dl on average, which translates to a relative decrease of 5-6% with P values ranging from 10⁻⁹ to 10⁻¹¹ in the combined analysis. An extended adjustment for BMI, creatinine, gout medication, and alcohol intake improved P values to a range of 10⁻¹⁴ to 10⁻²⁰. The association was more pronounced in women and the population-based Bruneck Study and was significantly modified by BMI, with stronger effect sizes in individuals with high BMI. CONCLUSIONS:--Genetic variants within SLC2A9 have significant effects on uric acid levels and are modified by sex and BMI.
Introduction: Identifying the cause of ischemic stroke in young adults is often difficult. Our objective was to compare the etiologic diagnostic strategy for ischemic stroke in young adults between 2 ...European centers and investigate the influence of workup variations in the diagnosed etiologies. Patients and Methods: We included patients aged 18-55 years admitted for ischemic stroke or transient ischemic attack to the stroke units of Santa Maria Hospital in Lisbon, Portugal, and Innsbruck University Hospital in Innsbruck, Austria, between 2014 and 2016. Etiology and diagnostic procedures were compared between centers. Results: We included 156 patients from Innsbruck University Hospital and 110 patients from Santa Maria Hospital. Search for intracranial large-vessel disease was performed mainly by computed tomography/magnetic resonance angiography in Innsbruck (83.9% versus 52.7%; P < .01) and by transcranial Doppler in Lisbon (91.8% versus 43.2%; P < .01). Transoesophageal echocardiography was preferred in Innsbruck for detecting paradoxical embolism (80.0% versus 68.2%; P < .05), whereas in Lisbon contrast transcranial Doppler was preferred (80.9% versus 3.9%; P < .01). For investigation of other causes, Lisbon patients were more commonly screened for thrombophilia (100.0% versus 92.3%; P < .05) and autoimmune disorders (91.7% versus 44.5%; P < .01) while in Innsbruck consultation by other specialists was more frequent (51.6% versus 10.0%; P < .01). No significant differences were found in etiologies between centers. Conclusion: The differences in diagnostic workup did not influence etiologic diagnosis. Extensive laboratory testing does not seem to influence diagnosis of stroke of other determined cause, emphasizing the importance of a clinically-oriented approach for the etiologic diagnosis of stroke in young adults.
Patients with transient ischemic attack (TIA) and stroke have an increased risk for subsequent cardiac events including myocardial infarction (MI), which might be associated with a worse clinical ...outcome. Rapid identification of stroke patients at higher risk for MI might foster intensified cardiac monitoring or certain therapeutic strategies. However, information regarding acute MI as a complication of stroke in the very acute phase is limited. Moreover, there are no systematic data on the occurrence of MI following intracerebral hematoma. We thus aimed to assess the frequency, clinical characteristics and short-term outcome of patients suffering from acute MI in the stroke unit setting.
We analyzed 46,603 patients from 32 Austrian stroke units enrolled in the prospective Austrian Stroke Unit Registry because of TIA/acute stroke over a 6-year period (January 1, 2007 to January 13, 2013). A total of 41,619 patients (89.3%) had been treated for TIA/ischemic stroke and 4,984 (10.7%) for primary intracerebral hemorrhage (ICH). Acute MI was defined according to clinical evaluation, ECG findings and laboratory assessments. Patients with evidence for MI preceding the cerebrovascular event were not considered.
Overall, 421 patients (1%) with TIA/ischemic stroke and 17 patients (0.3%) with ICH suffered from MI during stroke unit treatment for a median duration of 3 days. Patients with TIA/ischemic stroke and MI were significantly older, clinically more severely affected and had more frequently vascular risk factors, atrial fibrillation and previous MI. Total anterior circulation and left hemispheric stroke syndromes were more often observed in MI patients. Patients with MI not only suffered from worse short-term outcome including a higher mortality (14.5 vs. 2%; p < 0.001) at stroke unit discharge, but also acquired more stroke complications like progressive stroke and pneumonia. Multivariate analyses identified previous MI and stroke severity at admission (according to the National Institutes of Health and Stroke Scale score) as factors independently associated with the occurrence of MI on the stroke unit.
While quite rare in the acute phase after stroke, MI is associated with a poor short-term outcome including a higher mortality. Patients with previous MI and severe stroke syndromes appear to be at particular risk for MI as an early complication in the stroke unit setting. Further studies are needed to determine whether increased vigilance and prolonged (cardiac) monitoring or certain therapeutic approaches could improve the outcome in these high-risk patients.
Background Little is known about plasma apolipoprotein profiles in very preterm-born and term-born preschool children compared with the adult population. This is of particular interest because ...apolipoprotein composition might contribute to cardiometabolic outcome in later life. Methods and Results Children aged 5 to 7 years born at term or with <32 weeks of gestation were included. Apolipoprotein concentrations were measured in plasma collected after an overnight fast using multiple-reaction monitoring-based mass spectrometry. Twelve apolipoproteins were measured in 26 former term and 38 former very preterm infants. Key findings were confirmed by assessing apolipoprotein levels using antibody-based assays. Comparing children born term and preterm, apolipoprotein A-I, A- IV , C- II , and C- III were significantly higher in the latter group. Term-born children showed plasma levels of apolipoprotein C- II and C- III quantitatively similar to the adult range (Bruneck study). Hierarchical clustering analyses suggested that a higher proportion of apolipoprotein C- III and C- II reside on high-density lipoprotein particles in children than in adults given the marked correlations of apolipoprotein C- III and C- II with high-density lipoprotein cholesterol and apolipoprotein A-I in children but not adults. High-density lipoprotein cholesterol concentrations were similar in children and adults but the pattern of high-density lipoprotein cholesterol-associated apolipoproteins was different (lower apolipoprotein A-I and C-I but higher A- II , A- IV , and M). Conclusions Our study defines apolipoprotein profiles in preschoolers and reports potential effects of prematurity. Further large-scale studies are required to provide evidence whether this apolipoprotein signature of prematurity, including high apolipoprotein C- II and C- III levels, might translate into adverse cardiometabolic outcome in later life.
Abstract Background Recent studies showed that lipoprotein(a) Lp(a) is a causal risk factor for cardiovascular disease (CVD). However, whether Lp(a) modifies clinical risk assessment was not ...established. Objectives This study was conducted to determine whether Lp(a) improves CVD risk prediction. Methods In 1995, Lp(a) was measured in 826 men and women (age range, 45 to 84 years) from the general community. Incidence of CVD was recorded over 15 years of follow-up. Results In models adjusted for Framingham Risk Score (FRS) and Reynolds Risk Score (RRS) variables, the hazard ratio (HR) for incident CVD was 1.37 per 1-SD higher Lp(a) level (SD = 32 mg/dl) and 2.37 when comparing the top fifth quintile with other quintiles. The addition of Lp(a) to the RRS increased the C-index by 0.016. Of the 502 subjects who remained free of CVD, 82 were correctly reclassified to a lower risk category and 49 were reclassified to a higher risk category (predicted 15-year categories: <7.5%, 7.5% to <15%, 15% to <30%, ≥30%) (p < 0.001). Of the 148 subjects who developed CVD, 18 were correctly reclassified to a higher risk category and 17 were reclassified to a lower risk category. In subjects at intermediate risk (15% to <30%), the net reclassification improvement afforded by Lp(a) was 22.5% for noncases, 17.1% for cases, and 39.6% overall. Allele-specific Lp(a) levels did not add to the predictive ability of the FRS or RRS or to Lp(a). Conclusions Elevated Lp(a) predicts 15-year CVD outcomes and improves CVD risk prediction. These findings suggest that Lp(a) levels may be used in risk assessment of subjects in the general community, particularly in intermediate-risk groups.
Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts ...cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease.
Oxidized Low-Density Lipoprotein Autoantibodies, Chronic Infections, and Carotid Atherosclerosis in a Population-Based Study
Manuel Mayr, Stefan Kiechl, Sotirios Tsimikas, Elizabeth Miller, Joanna ...Sheldon, Johann Willeit, Joseph L. Witztum, Qingbo Xu
Autoantibodies to oxidized low-density lipoprotein (OxLDL) and apolipoprotein B-100-immune complexes (ApoB-IC) were measured in the Bruneck study and correlated with antipathogen antibodies, chronic infections, and the presence and progression of carotid atherosclerosis. Significant associations were obtained for OxLDL markers with antibodies to Escherichia coliand chlamydial lipopolysaccharide, mycobacterial heat shock protein 65, Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus (p < 0.001 for most associations) and with chronic infections as defined by clinical criteria. Titers of immunoglobulin G OxLDL antibodies inversely correlated with total cholesterol, LDL cholesterol, and ApoB concentrations. However, OxLDL autoantibodies and ApoB-IC did not emerge as independent risk predictors of carotid atherosclerosis in multivariate analyses.
We investigated whether associations exist between immune reactions to oxidized low-density lipoproteins (OxLDLs), chronic infections, and carotid atherosclerosis as quantified by ultrasound.
Atherosclerosis is a chronic immuno-inflammatory disease wherein both oxidized lipids and infectious agents are incriminated as possible contributors.
We measured immunoglobulin (Ig)G and IgM autoantibody titers to copper-oxidized-LDL and malondialdehyde-LDL (OxLDL-AB), IgG and IgM apolipoprotein B-100-immune complexes (ApoB-IC), and titers of antibodies to Escherichia coliand chlamydial lipopolysaccharide (LPS), mycobacterial heat shock protein 65 (mHSP65), Chlamydia pneumoniae, Helicobacter pylori, and cytomegalovirus and evaluated their relationship to cardiovascular risk factors, chronic infections, and incident/progressive carotid atherosclerosis in the Bruneck study.
The OxLDL-AB and ApoB-IC levels remained stable over time as indicated by strong correlations between 1995 and 2000 measurements (p < 0.001 each). Significant associations existed between all OxLDL markers and antibody titers to pathogens, especially to E. coli-LPS and mHSP65. Both OxLDL-AB and ApoB-IC levels showed a rise with increasing pathogen burden. Notably, OxLDL-ABs were also elevated in subjects with chronic infection as defined by clinical criteria. Titers of IgG, but not IgM, OxLDL-AB, or ApoB-IC inversely correlated with total cholesterol, LDL cholesterol, and apoB concentrations. The IgG OxLDL markers were positively and IgM markers were inversely associated with incident and progressive carotid atherosclerosis in univariate analyses but were not independent predictors in multivariate analyses.
Our study provides evidence for an association between human oxLDL markers and chronic infections. Moreover, in this population-based study, neither IgG nor IgM OxLDL autoantibodies were independently predictive of atherosclerosis progression in the carotid arteries.
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