HemoCue Hb-801 Provides More Accurate Hemoglobin Assessment in Blood Donors Than OrSense NBM-200.

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.

Anti-SARS-CoV-2 IgG Seroprevalence in Tyrol, Austria, among 28,768 Blood Donors between May 2022 and March 2023.

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.

Hypertensive disorders of pregnancy and cardiovascular disease risk: a Mendelian randomisation study.

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.

Intima-media thickness at the near or far wall of the common carotid artery in cardiovascular risk assessment.

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 0.02 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.

Age at Menopause and the Risk of Stroke: Observational and Mendelian Randomization Analysis in 204 244 Postmenopausal Women.

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.

Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque: Individual Participant Data Meta-Analysis of 20 Prospective Studies.

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.

Immune response after two doses of the BNT162b2 COVID-19 vaccine and risk of SARS-CoV-2 breakthrough infection in Tyrol, Austria: an open-label, observational phase 4 trial.

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.

Assessment of Cardiovascular Risk in Women: Progress so Far and Progress to Come.

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.

Hypertensive disorders of pregnancy and cardiovascular disease risk: A Mendelian Randomisation study.

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.

Ultra-rapid rollout vaccination with BNT162b2 to reduce SARS-CoV-2 infections in the general population.

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.

Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in Tyrol, Austria: Updated Analysis Involving 22,607 Blood Donors Covering the Period October 2021 to April 2022.

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.

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.

Seroprevalence, Waning and Correlates of Anti-SARS-CoV-2 IgG Antibodies in Tyrol, Austria: Large-Scale Study of 35,193 Blood Donors Conducted between June 2020 and September 2021.

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.

Breastfeeding Is Associated With a Reduced Maternal Cardiovascular Risk: Systematic Review and Meta-Analysis Involving Data From 8 Studies and 1 192 700 Parous Women.

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.

Associations between Physical Activity, Sitting Time, and Time Spent Outdoors with Mental Health during the First COVID-19 Lock Down in Austria.

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.

Sleep quality and daytime sleepiness in epilepsy: Systematic review and meta-analysis of 25 studies including 8,196 individuals.

We sought to gain a better understanding of the relationship between epilepsy and sleep quality and daytime sleepiness by performing a literature search of PubMed for case-control studies that compared patients with epilepsy to controls and reported the Pittsburgh sleep quality index (PSQI) and/or the Epworth sleepiness scale (ESS). Study-specific mean differences in the PSQI and ESS between cases and controls were extracted from the publications and pooled using random-effects meta-analysis. Twenty-five studies (2964 cases, 5232 controls) were included. Fifteen studies reported the PSQI and 24 the ESS. Mean age was 40 years; 50.4% were women. When comparing cases to controls, the pooled mean differences in the PSQI and ESS were 1.27 (95% confidence interval (CI): 0.76, 1.78; P < 0.001; I2: 81.4%) and 0.38 (95% CI: -0.07, 0.84; P = 0.099; I2: 81.0%). Subgroup analyses revealed that mean differences in the ESS were significantly lower in studies with a higher proportion of patients with focal epilepsy (P = 0.004). In this large-scale meta-analysis patients with epilepsy had a higher PSQI, close to the pathological cut-off, compared to controls, but a similar and unremarkable ESS. Further studies are needed to investigate potential effect modifiers, such as specific antiepileptic drugs or seizure frequency.

Low-Density Lipoprotein Cholesterol Corrected for Lipoprotein(a) Cholesterol, Risk Thresholds, and Cardiovascular Events.

Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ≥190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.