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Anti-Spike IgG antibodies against SARS-CoV-2, which are elicited by vaccination and infection, are correlates of protection against infection with pre-Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti-Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS-CoV-2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS-CoV-2 infection ascertained by self-report or seroconversion of anti-Nucleocapsid antibodies. At the time of their earliest available anti-Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8-55.2), with 45.3% being female, 41.3% having a prior SARS-CoV-2 infection, and 75.5% having received at least one dose of a COVID-19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS-CoV-2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7-12.4). The age- and sex-adjusted hazard ratio for SARS-CoV-2 associated with having twice the anti-Spike IgG antibody titer was 0.875 (95% credible interval 0.868-0.881) overall, 0.842 (0.827-0.856) during 2021, and 0.884 (0.877-0.891) during 2022 (all p < 0.001). The associations were similar in females and males (Pinteraction = 0.673) and across age (Pinteraction = 0.590). Higher anti-Spike IgG antibody titers were associated with reduced risk of incident SARS-CoV-2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti-Spike IgG antibody continues to be a suitable correlate of protection against newer SARS-CoV-2 variants.
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Anticuerpos Antivirales , COVID-19 , Inmunoglobulina G , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Inmunoglobulina G/sangre , Masculino , Femenino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/epidemiología , Adulto , Estudios Retrospectivos , Glicoproteína de la Espiga del Coronavirus/inmunología , Austria/epidemiología , Vacunas contra la COVID-19/inmunología , Seroconversión , Teorema de BayesRESUMEN
Objective: Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events. Methods: We obtained genetic associations with HDPs from a genome-wide association study and used individual-participant-data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian Randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype. Results: Our primary analysis included 221,155 ever pregnant women (mean age 56.8 [SD 7.9]) with available genetic data. Odds ratios for CVD were 1.20 (1.02-1.41) and 1.24 (1.12-1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings to those of nulligravidae and men. Conclusions: Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels, and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.
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Enfermedades Cardiovasculares , Eclampsia , Hipertensión Inducida en el Embarazo , Preeclampsia , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/complicaciones , Estudio de Asociación del Genoma Completo , Hipertensión Inducida en el Embarazo/epidemiología , Hipertensión Inducida en el Embarazo/genética , Preeclampsia/epidemiología , Preeclampsia/genética , Factores de Riesgo , Análisis de la Aleatorización MendelianaRESUMEN
BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 µm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 µm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
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Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Factores de Riesgo de Enfermedad Cardiaca , Infarto del Miocardio/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Carotid intima-media thickness and carotid plaque are well-established imaging markers used to capture different stages of the atherosclerotic disease process. We aimed to quantify to which extent carotid intima-media thickness predicts incidence of first-ever carotid plaque. MATERIALS AND METHODS: Two independent reviewers conducted a comprehensive literature search of PubMed and Web of Science. To be eligible for inclusion, prospective studies were required to involve participants free of carotid plaque at baseline and report on the association of baseline carotid intima-media thickness with development of first-ever carotid plaque. Study-specific relative risks and 95% confidence intervals were collected and pooled using random-effects meta-analysis. RESULTS: We identified seven relevant prospective studies involving a total of 9341 participants. Individuals were recruited between 1987 and 2012, average age at baseline was 54 years, and 63% were female. Studies reported on 1288 incident first-ever carotid plaques, occurring over an average maximum follow-up of 8.7 years. When individuals in the top fourth of baseline carotid intima-media thickness distribution were compared with those in the bottom fourth, the pooled relative risk for incidence of first-ever carotid plaque was 1.78 (95% confidence interval: 1.53-2.07, P < .001, I2 = 2.8%). The strength of association was not modified by mean baseline age, proportion of female participants, length of follow-up, year of baseline, and geographical location of the studies. CONCLUSIONS: In general population studies, elevated baseline carotid intima-media thickness is associated with incidence of carotid plaque in individuals free of carotid plaque at baseline.
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Enfermedades de las Arterias Carótidas/epidemiología , Grosor Intima-Media Carotídeo , Placa Aterosclerótica/epidemiología , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Humanos , IncidenciaRESUMEN
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.
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Aterosclerosis/diagnóstico , Anciano , Enfermedades Cardiovasculares/epidemiología , Grosor Intima-Media Carotídeo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Análisis de la Onda del Pulso , Proyectos de Investigación , Medición de Riesgo , Factores de RiesgoRESUMEN
Hemoglobin levels are commonly assessed to prevent causing or worsening of anemia in prospective blood donors. We compared head-to-head the accuracy of different technologies for measuring hemoglobin suitable for use in mobile donation units. We included 144 persons donating platelets at the Central Institute for Blood Transfusion and Immunology in Innsbruck, Austria. Hemoglobin levels were measured in venous blood using the portable hemoglobinometer HemoCue Hb-801 and noninvasively using OrSense NBM-200, and compared to values obtained with the Sysmex XN-430, an automated hematology analyzer employing the sodium lauryl sulphate method, which is broadly used as reference method in everyday clinical practice. Mean age of participants was 34.2 years (SD 13.0); 34.0% were female. Hemoglobin values measured with HemoCue were more strongly correlated with the Sysmex XN-430 (r = 0.90 [95% CI: 0.87-0.93]) than measured with OrSense (r = 0.49 [0.35-0.60]). On average, HemoCue overestimated hemoglobin by 0.40 g/dL (0.31-0.48) and OrSense by 0.75 g/dL (95% CI: 0.54-0.96). When using OrSense, we found evidence for higher overestimation at higher hemoglobin levels (proportional bias) specifically in females but not in males (Pdifference = .003). Sensitivity and specificity for classifying donors according to the hemoglobin donation thresholds were 99.2% (95% CI: 95.3%-100.0%) and 43.8% (23.1%-66.8%) for HemoCue vs 95.3% (89.9%-98.0%) and 12.5% (2.2%-37.3%) for OrSense. Areas under the receiver operating characteristic curves were higher using HemoCue vs OrSense both in females (0.933 vs 0.547; P = .044) and males (0.948 vs 0.628; P < .001). HemoCue Hb-801 measures hemoglobin more accurately than OrSense NBM-200 in the setting of mobile blood donation units. Our findings are particularly relevant for females, having in mind that anemia is more prevalent in females than in males.
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Donantes de Sangre , Hemoglobinas , Humanos , Femenino , Donantes de Sangre/estadística & datos numéricos , Masculino , Hemoglobinas/análisis , Adulto , Persona de Mediana Edad , Hemoglobinometría/métodos , Hemoglobinometría/instrumentación , Hemoglobinometría/normas , Anemia/sangre , Anemia/diagnóstico , Adulto Joven , AustriaRESUMEN
BACKGROUND: To provide updated estimates on SARS-CoV-2 antibody seroprevalence and average antibody titres for Central Europe. METHODS: In repeat cross-sectional investigations (1 May 2022 to 9 March 2023) involving 28,768 blood donors in the Federal State of Tyrol, Austria (participation rate: 87.0%), we measured Spike receptor-binding domain (RBD) and Nucleocapsid IgG antibodies (37,065 and 12,645 samples), and estimated monthly seroprevalences and geometric mean titres. RESULTS: Median age of participants was 45.4 years (range 18-70); 43.2% were female. Spike RBD IgG antibody seroprevalence was 96.3% (95% CI: 95.6-96.9%) in May 2022, 97.4% (96.7-98.0%) in December 2022, and 97.9% (96.4-98.8%) in March 2023. Among seropositive participants, geometric mean titres increased from 1400 BAU/mL (95% CI: 1333-1471) in May 2022 to 1821 BAU/mL (1717-1932) in December 2022, and dropped to 1559 BAU/mL (1405-1729) by March 2023. Furthermore, titres differed markedly by vaccination status and history of infection, with being the highest in participants with booster vaccination and prior infection. In autumn 2022, Nucleocapsid IgG antibody seroprevalence ranged from 36.5% (35.0-38.1) in September to 39.2% (37.2-41.2) in December 2022. CONCLUSION: Seroprevalence of SARS-CoV-2 antibodies in blood donors from Tyrol, Austria, was remarkably stable from May 2022 to March 2023. In contrast, average Spike RBD IgG antibody titres peaked in December 2022.
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OBJECTIVE: Observational studies show that hypertensive disorders of pregnancy (HDPs) are related to unfavourable maternal cardiovascular disease (CVD) risk profiles later in life. We investigated whether genetic liability to pre-eclampsia/eclampsia and gestational hypertension is associated with CVD risk factors and occurrence of CVD events. METHODS: We obtained genetic associations with HDPs from a genome-wide association study and used individual participant data from the UK Biobank to obtain genetic associations with CVD risk factors and CVD events (defined as myocardial infarction or stroke). In our primary analysis, we applied Mendelian randomisation using inverse-variance weighted regression analysis in ever pregnant women. In sensitivity analyses, we studied men and nulligravidae to investigate genetic liability to HDPs and CVD risk without the ability to experience the underlying phenotype. RESULTS: Our primary analysis included 221 155 ever pregnant women (mean age 56.8 (SD 7.9) years) with available genetic data. ORs for CVD were 1.20 (1.02 to 1.41) and 1.24 (1.12 to 1.38) per unit increase in the log odds of genetic liability to pre-eclampsia/eclampsia and gestational hypertension, respectively. Furthermore, genetic liability to HDPs was associated with higher levels of systolic and diastolic blood pressure and younger age at hypertension diagnosis. Sensitivity analyses revealed no statistically significant differences when comparing the findings with those of nulligravidae and men. CONCLUSIONS: Genetic liability to HDPs is associated with higher CVD risk, lower blood pressure levels and earlier hypertension diagnosis. Our study suggests similar findings in ever pregnant women, nulligravidae and men, implying biological mechanisms relating to HDPs are causally related to CVD risk.
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Estudio de Asociación del Genoma Completo , Hipertensión Inducida en el Embarazo , Análisis de la Aleatorización Mendeliana , Humanos , Femenino , Embarazo , Hipertensión Inducida en el Embarazo/genética , Hipertensión Inducida en el Embarazo/epidemiología , Persona de Mediana Edad , Masculino , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/epidemiología , Reino Unido/epidemiología , Medición de Riesgo/métodos , Predisposición Genética a la Enfermedad , Factores de Riesgo , Preeclampsia/genética , Preeclampsia/epidemiología , Preeclampsia/diagnóstico , Adulto , Factores de Riesgo de Enfermedad Cardiaca , Polimorfismo de Nucleótido SimpleRESUMEN
Background: High-sensitivity cardiac troponin T (hs-cTnT) is associated with cardiovascular disease (CVD) risk in general and various high-risk populations. Objectives: The purpose of this study was to precisely characterize the association of hs-cTnT with CVD risk in patients following acute ischemic stroke or transient ischemic attack. Methods: We conducted post hoc analyses of data from the STROKE-CARD trial (NCT02156778), a pragmatic randomized controlled trial of a disease management program in patients with acute ischemic stroke or transient ischemic attack (ABCD2 score ≥3). We measured hs-cTnT on admission (Roche Elecsys, detection limit 5 ng/L) and quantified HRs for a composite CVD outcome (ie, stroke, myocardial infarction, CVD death) adjusted for age, sex, prior coronary heart disease, prior heart failure, diabetes, smoking, systolic blood pressure, and low- and high-density-lipoprotein cholesterol. Results: Among 1,687 patients (mean age, 69.3 ± 13.7 years; 40.7% female), hs-cTnT was detectable in 80.7%. Median hs-cTnT was 10 ng/L (IQR: 6-18 ng/L). Over a median follow-up of 12.1 months, 110 patients had a CVD event. The association of hs-cTnT level with CVD risk was of log-linear shape, with a multivariable-adjusted HR of 1.40 (95% CI: 1.15-1.70; P < 0.001) per 1-SD higher log-transformed hs-cTnT value. The strength of association was similar when further adjusted for other potential confounders and across clinically relevant subgroups. Corresponding outcome-specific HRs were 1.33 (95% CI: 1.06-1.68; P = 0.016) for stroke, 1.28 (95% CI: 0.69-2.37; P = 0.430) for myocardial infarction, 1.98 (95% CI: 1.43-2.73; P < 0.001) for CVD death, and 1.93 (95% CI: 1.54-2.41; P < 0.001) for all-cause death. Conclusions: High hs-cTnT is associated with increased CVD risk in ischemic stroke and transient ischemic attack patients.
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Cardiovascular disease is the leading cause of death in women worldwide. Nonetheless, there exist several uncertainties in the prediction, diagnosis, and treatment of cardiovascular disease in women. A cornerstone in the prediction of cardiovascular disease is the implementation of risk scores. A variety of pregnancy- and reproductive-factors have been associated with lower or higher risk of cardiovascular disease. Consequently, the question has been raised, whether these female-specific factors also provide added value to cardiovascular risk prediction. In this review, we provide an overview of the existing literature on sex differences in the association of established cardiovascular risk factors with cardiovascular disease and the relation between female-specific factors and cardiovascular risk. Furthermore, we systematically reviewed the literature for studies that assessed the added value of female-specific factors beyond already established cardiovascular risk factors. Adding female-specific factors to models containing established cardiovascular risk factors has led to little or no significant improvement in the prediction of cardiovascular events. However, analyses primarily relied on data from women aged ≥40 years. Future investigations are needed to quantify whether pregnancy-related factors improve cardiovascular risk prediction in young women in order to support adequate treatment of risk factors and enhance prevention of cardiovascular disease in women.
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BACKGROUND: Correlates of protection could help to assess the extent to which a person is protected from SARS-CoV-2 infection after vaccination (so-called breakthrough infection). We aimed to clarify associations of antibody and T-cell responses after vaccination against COVID-19 with risk of a SARS-CoV-2 breakthrough infection and whether measurement of these responses enhances risk prediction. METHODS: We did an open-label, phase 4 trial in two community centres in the Schwaz district of the Federal State of Tyrol, Austria, before the emergence of the omicron (B.1.1.529) variant of SARS-CoV-2. We included individuals (aged ≥16 years) a mean of 35 days (range 27-43) after they had received a second dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine. We quantified associations between immunological parameters and breakthrough infection and assessed whether information on these parameters improves risk discrimination. The study is registered with the European Union Drug Regulating Authorities Clinical Trials Database, 2021-002030-16. FINDINGS: 2760 individuals (1682 [60·9%] female, 1078 [39·1%] male, mean age 47·4 years [SD 14·5]) were enrolled into this study between May 15 and May 21, 2021, 712 (25·8%) of whom had a previous SARS-CoV-2 infection. Over a median follow-up of 5·9 months, 68 (2·5%) participants had a breakthrough infection. In models adjusted for age, sex, and previous infection, hazard ratios for breakthrough infection for having twice the immunological parameter level at baseline were 0·72 (95% CI 0·60-0·86) for anti-spike IgG, 0·80 (0·70-0·92) for neutralising antibodies in a surrogate virus neutralisation assay, 0·84 (0·58-1·21) for T-cell response after stimulation with a CD4 peptide pool, and 0·77 (0·54-1·08) for T-cell response after stimulation with a combined CD4 and CD8 peptide pool. For neutralising antibodies measured in a nested case-control sample using a pseudotyped virus neutralisation assay, the corresponding odds ratio was 0·78 (0·62-1·00). Among participants with previous infection, the corresponding hazard ratio was 0·73 (0·61-0·88) for anti-nucleocapsid Ig. Addition of anti-spike IgG information to a model containing information on age and sex improved the C-index by 0·085 (0·027-0·143). INTERPRETATION: In contrast to T-cell response, higher levels of binding and neutralising antibodies were associated with a reduced risk of breakthrough SARS-CoV-2 infection. The assessment of anti-spike IgG enhances the prediction of incident breakthrough SARS-CoV-2 infection and could therefore be a suitable correlate of protection in practice. Our phase 4 trial measured both humoral and cellular immunity and had a 6-month follow-up period; however, the longer-term protection against emerging variants of SARS-CoV-2 remains unclear. FUNDING: None.
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Vacunas contra la COVID-19 , COVID-19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticuerpos Neutralizantes , Austria/epidemiología , Vacuna BNT162 , Infección Irruptiva , COVID-19/prevención & control , Vacunas contra la COVID-19/uso terapéutico , Inmunidad Celular , Inmunoglobulina G , SARS-CoV-2RESUMEN
Background Observational studies have shown that women with an early menopause are at higher risk of stroke compared with women with a later menopause. However, associations with stroke subtypes are inconsistent, and the causality is unclear. Methods and Results We analyzed data of the UK Biobank and EPIC-CVD (European Prospective Investigation Into Cancer and Nutrition-Cardiovascular Diseases) study. A total of 204 244 postmenopausal women without a history of stroke at baseline were included (7883 from EPIC-CVD [5292 from the subcohort], 196 361 from the UK Biobank). Pooled mean baseline age was 58.9 years (SD, 5.8), and pooled mean age at menopause was 47.8 years (SD, 6.2). Over a median follow-up of 12.6 years (interquartile range, 11.8-13.3), 6770 women experienced a stroke (5155 ischemic strokes, 1615 hemorrhagic strokes, 976 intracerebral hemorrhages, and 639 subarachnoid hemorrhages). In multivariable adjusted observational Cox regression analyses, the pooled hazard ratios per 5 years younger age at menopause were 1.09 (95% CI, 1.07-1.12) for stroke, 1.09 (95% CI, 1.06-1.13) for ischemic stroke, 1.10 (95% CI, 1.04-1.16) for hemorrhagic stroke, 1.14 (95% CI, 1.08-1.20) for intracerebral hemorrhage, and 1.00 (95% CI, 0.84-1.20) for subarachnoid hemorrhage. When using 2-sample Mendelian randomization analysis, we found no statistically significant association between genetically proxied age at menopause and risk of any type of stroke. Conclusions In our study, earlier age at menopause was related to a higher risk of stroke. We found no statistically significant association between genetically proxied age at menopause and risk of stroke, suggesting no causal relationship.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Femenino , Humanos , Persona de Mediana Edad , Hemorragia Cerebral , Análisis de la Aleatorización Mendeliana , Menopausia , Posmenopausia , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/genética , Estudios Observacionales como AsuntoRESUMEN
Aims: Current guidelines recommend measuring carotid intima-media thickness (IMT) at the far wall of the common carotid artery (CCA). We aimed to precisely quantify associations of near vs. far wall CCA-IMT with the risk for atherosclerotic cardiovascular disease (CVD, defined as coronary heart disease or stroke) and their added predictive values. Methods and results: We analysed individual records of 41 941 participants from 16 prospective studies in the Proof-ATHERO consortium {mean age 61 years [standard deviation (SD) = 11]; 53% female; 16% prior CVD}. Mean baseline values of near and far wall CCA-IMT were 0.83 (SD = 0.28) and 0.82 (SD = 0.27) mm, differed by a mean of 0.02â mm (95% limits of agreement: -0.40 to 0.43), and were moderately correlated [r = 0.44; 95% confidence interval (CI): 0.39-0.49). Over a median follow-up of 9.3 years, we recorded 10 423 CVD events. We pooled study-specific hazard ratios for CVD using random-effects meta-analysis. Near and far wall CCA-IMT values were approximately linearly associated with CVD risk. The respective hazard ratios per SD higher value were 1.18 (95% CI: 1.14-1.22; I² = 30.7%) and 1.20 (1.18-1.23; I² = 5.3%) when adjusted for age, sex, and prior CVD and 1.09 (1.07-1.12; I² = 8.4%) and 1.14 (1.12-1.16; I²=1.3%) upon multivariable adjustment (all P < 0.001). Assessing CCA-IMT at both walls provided a greater C-index improvement than assessing CCA-IMT at one wall only [+0.0046 vs. +0.0023 for near (P < 0.001), +0.0037 for far wall (P = 0.006)]. Conclusions: The associations of near and far wall CCA-IMT with incident CVD were positive, approximately linear, and similarly strong. Improvement in risk discrimination was highest when CCA-IMT was measured at both walls.
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Background The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development. Methods and Results We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques). Conclusions Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
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Enfermedades de las Arterias Carótidas , Placa Aterosclerótica , Humanos , Femenino , Persona de Mediana Edad , Masculino , Grosor Intima-Media Carotídeo , Estudios Prospectivos , Factores de Riesgo , Arteria Carótida Común/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/epidemiologíaRESUMEN
In response to a large outbreak of the SARS-CoV-2 Beta (B.1.351) variant in the district Schwaz, Austria, a rapid mass vaccination campaign with BNT162b2 was carried out in spring 2021, immunizing more than 70% of the adult population within one week. Subsequent analysis revealed that the mass vaccination was associated with a significant reduction in new SARS-CoV-2 infections compared to control districts. Here, we aimed to evaluate both SARS-CoV-2-specific T- and B-cell responses at 35 ± 8 and 215 ± 7 days after the second dose in 600 study subjects who participated at both time points. Overall, a robust antibody and T-cell response was measured at day 35, which waned over time. Nevertheless, all persons preserved seropositivity and T cell response could still be detected in about half of the participants at day 215. Further, antibody response correlated negatively with age; however, in persons who experienced SARS-CoV-2 infection prior to study enrolment, the serum levels of both S- and N-specific antibodies surprisingly increased with age. In contrast, there was no correlation of T cell response with age. We could not detect any sex-related difference in the immune responses. SARS-CoV-2 infections prior to study enrolment or incident infections before day 215 resulted in higher antibody levels and T cell responses at day 215 compared to study participants with no history of infection. Collectively, our data support that vaccination with BNT162b2 against COVID-19 provides a durable immune response and emphasize the usefulness of vaccination even after a natural infection.
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COVID-19 , SARS-CoV-2 , Adulto , Anticuerpos Antivirales , Formación de Anticuerpos , Austria , Vacuna BNT162 , COVID-19/prevención & control , Estudios de Seguimiento , Humanos , Vacunación Masiva , VacunaciónRESUMEN
Background Breastfeeding has been robustly linked to reduced maternal risk of breast cancer, ovarian cancer, and type 2 diabetes. We herein systematically reviewed the published evidence on the association of breastfeeding with maternal risk of cardiovascular disease (CVD) outcomes. Methods and Results Our systematic search of PubMed and Web of Science of articles published up to April 16, 2021, identified 8 relevant prospective studies involving 1 192 700 parous women (weighted mean age: 51.3 years at study entry, 24.6 years at first birth; weighted mean number of births: 2.3). A total of 982 566 women (82%) reported having ever breastfed (weighted mean lifetime duration of breastfeeding: 15.6 months). During a weighted median follow-up of 10.3 years, 54 226 CVD, 26 913 coronary heart disease, 30 843 stroke, and 10 766 fatal CVD events were recorded. In a random-effects meta-analysis, the pooled multivariable-adjusted hazard ratios comparing parous women who ever breastfed to those who never breastfed were 0.89 for CVD (95% CI, 0.83-0.95; I2=79.4%), 0.86 for coronary heart disease (95% CI, 0.78-0.95; I2=79.7%), 0.88 for stroke (95% CI, 0.79-0.99; I2=79.6%), and 0.83 for fatal CVD (95% CI, 0.76-0.92; I2=47.7%). The quality of the evidence assessed with the Grading of Recommendations Assessment, Development, and Evaluation tool ranged from very low to moderate, which was mainly driven by high between-studies heterogeneity. Strengths of associations did not differ by mean age at study entry, median follow-up duration, mean parity, level of adjustment, study quality, or geographical region. A progressive risk reduction of all CVD outcomes with lifetime durations of breastfeeding from 0 up to 12 months was found, with some uncertainty about shapes of associations for longer durations. Conclusions Breastfeeding was associated with reduced maternal risk of CVD outcomes.
Asunto(s)
Enfermedades Cardiovasculares , Enfermedad Coronaria , Diabetes Mellitus Tipo 2 , Accidente Cerebrovascular , Lactancia Materna , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & control , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Persona de Mediana Edad , Embarazo , Estudios Prospectivos , Factores de RiesgoRESUMEN
Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Median age of participants was 45.3 years (IQR: 30.9−55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8−86.0%) to 95.8% (94.9−96.4%), and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271−296) to 1437 (1360−1518) BAU/mL. The percentages of participants in categories with undetectable levels and detectable levels at <500, 500−<1000, 1000−<2000, 2000−<3000, and ≥3000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2−19.9; p-value < 0.001). In conclusion, anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.
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COVID-19 , SARS-CoV-2 , Adulto , Anticuerpos Antivirales , Austria/epidemiología , Donantes de Sangre , COVID-19/epidemiología , Femenino , Humanos , Inmunoglobulina G , Masculino , Persona de Mediana Edad , Estudios SeroepidemiológicosRESUMEN
There is uncertainty about the seroprevalence of anti-SARS-CoV-2 antibodies in the general population of Austria and about the waning of antibodies over time. We conducted a seroepidemiological study between June 2020 and September 2021, enrolling blood donors aged 18-70 years across Tyrol, Austria (participation rate: 84.0%). We analyzed serum samples for antibodies against the spike or the nucleocapsid proteins of SARS-CoV-2. We performed a total of 47,363 samples taken from 35,193 individuals (median age, 43.1 years (IQR: 29.3-53.7); 45.3% women; 10.0% with prior SARS-CoV-2 infection). Seroprevalence increased from 3.4% (95% CI: 2.8-4.2%) in June 2020 to 82.7% (95% CI: 81.4-83.8%) in September 2021, largely due to vaccination. Anti-spike IgG seroprevalence was 99.6% (95% CI: 99.4-99.7%) among fully vaccinated individuals, 90.4% (95% CI: 88.8-91.7%) among unvaccinated individuals with prior infection and 11.5% (95% CI: 10.8-12.3%) among unvaccinated individuals without known prior infection. Anti-spike IgG levels were reduced by 44.0% (95% CI: 34.9-51.7%) at 5-6 months compared with 0-3 months after infection. In fully vaccinated individuals, they decreased by 31.7% (95% CI: 29.4-33.9%) per month. In conclusion, seroprevalence in Tyrol increased to 82.7% in September 2021, with the bulk of seropositivity stemming from vaccination. Antibody levels substantially and gradually declined after vaccination or infection.
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Donantes de Sangre , COVID-19 , Adolescente , Adulto , Anciano , Austria/epidemiología , COVID-19/epidemiología , Femenino , Humanos , Inmunoglobulina G , Masculino , Persona de Mediana Edad , SARS-CoV-2 , Estudios Seroepidemiológicos , Adulto JovenRESUMEN
This study aimed to determine the impact of ultra-rapid rollout vaccination on incidence of SARS-CoV-2 infection. Vaccination with BNT162b2 was provided to 66.9% of eligible residents of the Schwaz district in Tyrol, Austria, within six days per dose (first dose: 11-16 March 2021, second dose: 8-13 April 2021). Of 11,955 individuals enrolled at nine vaccination centers (median age 44.6 years; 51.3% female), 71 had incident SARS-CoV-2 over a six-month follow-up. Incidence rates per 100,000 person-weeks were 92.3 (95% confidence interval [CI]: 70.8-120.2) at weeks 1-5 and 6.4 (3.9-10.4) at ≥6 weeks after dose 1. In these two periods, effectiveness of the vaccination campaign to reduce incident SARS-CoV-2 was 58.6% (50.8%-65.2%) and 91.1% (89.6%-92.3%) in study participants and 28.3% (23.1%-33.0%) and 64.0% (61.7%-66.1%) in the Schwaz district, compared with districts with slower vaccination rollout. Therefore, the vaccination campaign in the Schwaz district illustrates the impact of accelerated vaccination rollout in controlling the pandemic.
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Measures implemented to reduce the spread of SARS-CoV-2 have resulted in a decrease in physical activity (PA) while sedentary behaviour increased. The aim of the present study was to explore associations between PA and mental health in Austria during COVID-19 social restrictions. In this web-based cross-sectional study (April-May 2020) moderate-to-vigorous physical activity (MVPA), sitting time, and time spent outdoors were self-reported before and during self-isolation. Mental well-being was assessed with the Warwick-Edinburgh Mental Well-being Scale, and the Beck depression and anxiety inventories. The majority of the participants (n = 652) were female (72.4%), with a mean age of 36.0 years and a standard deviation (SD) of 14.4. Moreover, 76.5% took part in ≥30 min/day of MVPA, 53.5% sat ≥10 h/day, and 66.1% spent ≥60 min/day outdoors during self-isolation. Thirty-eight point five percent reported high mental well-being, 40.5% reported depressive symptoms, and 33.9% anxiety symptoms. Participating in higher levels of MVPA was associated with higher mental well-being (odds ratio = OR: 3.92; 95% confidence interval = 95%CI: 1.51-10.15), less depressive symptoms (OR: 0.44; 95%CI: 0.29-0.66) and anxiety symptoms (OR = 0.62; 95%CI: 0.41-0.94), and less loneliness (OR: 0.46; 95%CI: 0.31-0.69). Participants sitting <10 h/day had higher odds of mental well-being (OR: 3.58; 95%CI: 1.13-11.35). Comparable results were found for spending ≥60 min/day outdoors. Maintaining one's MVPA levels was associated with higher mental well-being (OR = 8.61, 95%CI: 2.68-27.62). In conclusion, results show a positive association between PA, time spent outdoors and mental well-being during COVID-19 social restrictions. Interventions aiming to increase PA might mitigate negative effects of such restrictions.