Plasma fibrinogen and risk of vascular recurrence after ischaemic stroke: An individual participant and summary-level data meta-analysis of 11 prospective studies.

INTRODUCTION: Inflammation is an emerging target for secondary prevention after stroke and randomised trials of anti-inflammatory therapies are ongoing. Fibrinogen, a putative pro-inflammatory marker, is associated with first stroke, but its association with major adverse cardiovascular events (MACE) after stroke is unclear. MATERIALS AND METHODS: We did a systematic review investigating the association between fibrinogen and post-stroke vascular recurrence. Authors were invited to provide individual-participant data (IPD) and where available we did within-study multivariable analyses with adjustment for cardiovascular risk factors and medications. Adjusted summary-level data was extracted from published reports from studies that did not provide IPD. We pooled risk ratios (RR) by random-effects meta-analysis by comparing supra-median with sub-median fibrinogen levels and performed pre-specified subgroup analysis according to timing of phlebotomy after the index event. RESULTS: Eleven studies were included (14,002 patients, 42,800 follow-up years), of which seven provided IPD. Fibrinogen was associated with recurrent MACE on unadjusted (RR 1.35, 95% CI 1.17-1.57, supra-median vs sub-median) and adjusted models (RR 1.21, 95% CI 1.06-1.38). Fibrinogen was associated with recurrent stroke on univariate analysis (RR 1.19, 95% CI 1.03-1.39), but not after adjustment (RR 1.11, 95% CI 0.94-1.31). The association with recurrent MACE was consistently observed in patients with post-acute (⩾14 days) fibrinogen measures (RR 1.29, 95% CI 1.16-1.45), but not in those with early phlebotomy (<14 days) (RR 0.98, 95% CI 0.82-1.18) (Pinteraction = 0.01). Similar associations were observed for recurrent stroke. DISCUSSION AND CONCLUSION: Fibrinogen was independently associated with recurrence after stroke, but the association was modified by timing of phlebotomy. Fibrinogen measurements might be useful to identify patients who are more likely to derive benefit from anti-inflammatory therapies after stroke.

Development and validation of a lifetime prediction model for incident type 2 diabetes in patients with established cardiovascular disease: the CVD2DM model.

AIMS: Identifying patients with established cardiovascular disease (CVD) who are at high risk of type 2 diabetes (T2D) may allow for early interventions, reducing the development of T2D and associated morbidity. The aim of this study was to develop and externally validate the CVD2DM model to estimate the 10-year and lifetime risks of T2D in patients with established CVD. METHODS AND RESULTS: Sex-specific, competing risk-adjusted Cox proportional hazard models were derived in 19 281 participants with established CVD and without diabetes at baseline from the UK Biobank. The core model's pre-specified predictors were age, current smoking, family history of diabetes mellitus, body mass index, systolic blood pressure, fasting plasma glucose, and HDL cholesterol. The extended model also included HbA1c. The model was externally validated in 3481 patients from the UCC-SMART study. During a median follow-up of 12.2 years (interquartile interval 11.3-13.1), 1628 participants with established CVD were diagnosed with T2D in the UK Biobank. External validation c-statistics were 0.79 [95% confidence interval (CI) 0.76-0.82] for the core model and 0.81 (95% CI 0.78-0.84) for the extended model. Calibration plots showed agreement between predicted and observed 10-year risk of T2D. CONCLUSION: The 10-year and lifetime risks of T2D can be estimated with the CVD2DM model in patients with established CVD, using readily available clinical predictors. The model would benefit from further validation across diverse ethnic groups to enhance its applicability. Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle.

In this study, we developed and externally validated the CVD2DM model, which predicts the 10-year and lifetime risk of type 2 diabetes (T2D) in individuals who already have cardiovascular disease (CVD). The key findings are as follows: The CVD2DM model is the first model to estimate the risk of developing T2D applicable in all patients with atherosclerotic CVD. The model is based on several factors available in clinical practice, such as age, fasting plasma glucose, family history of diabetes, and body mass index. It was developed in 19 281 patients from the UK Biobank. The model performed well in 3481 patients from the UCC-SMART study.Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle.

Lifetime and 10-year cardiovascular risk prediction in individuals with type 1 diabetes: The LIFE-T1D model.

AIMS: To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. MATERIALS AND METHODS: A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. RESULTS: During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. CONCLUSIONS: The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation.

Covert Cerebrovascular Changes in People With Heart Disease: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: To determine the prevalence of silent brain infarction (SBI) and cerebral small vessel disease (CSVD) in adults with atrial fibrillation (AF), coronary artery disease, heart failure or cardiomyopathy, heart valve disease, and patent foramen ovale (PFO), with comparisons between those with and without recent stroke and an exploration of associations between heart disease and SBI/CSVD. METHODS: Medline, Embase, and Cochrane Library were systematically searched for hospital-based or community-based studies reporting SBI/CSVD in people with heart disease. Data were extracted from eligible studies. Outcomes were SBI (primary) and individual CSVD subtypes. Summary prevalence (95% confidence intervals [CIs]) were obtained using random-effects meta-analysis. Pooled prevalence ratios (PRs) (95% CI) were calculated to compare those with heart disease with available control participants without heart disease from studies. RESULTS: A total of 221 observational studies were included. In those with AF, the prevalence was 36% (31%-41%) for SBI (70 studies, N = 13,589), 25% (19%-31%) for lacune (26 studies, N = 7,172), 62% (49%-74%) for white matter hyperintensity/hypoattenuation (WMH) (34 studies, N = 7,229), and 27% (24%-30%) for microbleed (44 studies, N = 13,654). Stratification by studies where participants with recent stroke were recruited identified no differences in the prevalence of SBI across subgroups (phomogeneity = 0.495). Results were comparable across participants with different heart diseases except for those with PFO, in whom there was a lower prevalence of SBI [21% (13%-30%), 11 studies, N = 1,053] and CSVD. Meta-regressions after pooling those with any heart disease identified associations of increased (study level) age and hypertensives with more SBIs and WMH (pregression <0.05). There was no evidence of a difference in the prevalence of microbleed between those with and without heart disease (PR [95% CI] 1.1 [0.7-1.7]), but a difference was seen in the prevalence of SBI and WMH (PR [95% CI] 2.3 [1.6-3.1] and 1.7 [1.1-2.6], respectively). DISCUSSION: People with heart disease have a high prevalence of SBI (and CSVD), which is similar in those with vs without recent stroke. More research is required to assess causal links and implications for management. TRIAL REGISTRATION INFORMATION: PROSPERO CRD42022378272 (crd.york.ac.uk/PROSPERO/).

Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study.

OBJECTIVE: Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. RESEARCH DESIGN AND METHODS: Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. RESULTS: While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01). CONCLUSIONS: Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden.

Orthostatic hypotension (OH) is more common in the elderly and associated with increased mortality. However, its implications for 85-year-olds are not known. In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH. Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality. OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.

Systematic review of the use of ultrasound for venous assessment and venous thrombosis screening in spaceflight.

The validity of venous ultrasound (V-US) for the diagnosis of deep vein thrombosis (DVT) during spaceflight is unknown and difficult to establish in diagnostic accuracy and diagnostic management studies in this context. We performed a systematic review of the use of V-US in the upper-body venous system in spaceflight to identify microgravity-related changes and the effect of venous interventions to reverse them, and to assess appropriateness of spaceflight V-US with terrestrial standards. An appropriateness tool was developed following expert panel discussions and review of terrestrial diagnostic studies, including criteria relevant to crew experience, in-flight equipment, assessment sites, ultrasound modalities, and DVT diagnosis. Microgravity-related findings reported as an increase in internal jugular vein (IJV) cross-sectional area and pressure were associated with reduced, stagnant, and retrograde flow. Changes were on average responsive to venous interventions using lower body negative pressure, Bracelets, Valsalva and Mueller manoeuvres, and contralateral IJV compression. In comparison with terrestrial standards, spaceflight V-US did not meet all appropriateness criteria. In DVT studies (n = 3), a single thrombosis was reported and only ultrasound modality criterion met the standards. In the other studies (n = 15), all the criteria were appropriate except crew experience criterion, which was appropriate in only four studies. Future practice and research should account for microgravity-related changes, evaluate individual effect of venous interventions, and adopt Earth-based V-US standards.

Sex and gender publications in brain health: a mapping review of the Asia-Pacific region.

INTRODUCTION: Reporting of sex and gender analysis in medical research has been shown to improve quality of the science and ensures findings are applicable to women and men. There is conflicting evidence on whether efforts by funding agencies and medical journals to encourage reporting of sex and gender analysis has resulted in tangible improvements. This study mapped the inclusion of sex and gender analysis in stroke and dementia research conducted in the Asia-Pacific region. METHODS: A systematic search for Asia-Pacific stroke and dementia research was conducted in PubMed and papers included from the period 2012 to 2022. Eligible studies were reviewed for inclusion of a primary sex or gender focus and categorized by type of sex and gender analysis. Author gender was determined using an algorithm and its associations with inclusion of sex and gender analysis examined. RESULTS: Total Asia-Pacific publications increased from 109 in 2012 to 313 in 2022, but the rate of studies with a primary sex or gender focus did not increase significantly (R2 = 0.06, F(1,9) = 0.59, p = 0.46). Australia, China, India, Japan and South Korea produced the most publications over the study period and were the only countries with at least 50 publications. The impact of author gender was mixed, with female first authorship associated with inclusion of sex or gender analysis and last female authorship associated with studies having a primary sex or gender focus. CONCLUSIONS: In the Asia-Pacific, brain health research is currently centered around high income countries and efforts are needed to ensure research findings are applicable through out the region. While there was a general increase in brain health publications over the last decade, the rate of sex and gender analysis was unchanged. This demonstrates that even with efforts in some countries in place, there is currently a lack of progress in the Asia-Pacific region to produce more research focusing on sex and gender analysis.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

BACKGROUND AND OBJECTIVES: Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. METHODS: Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. RESULTS: IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). DISCUSSION: Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.

Hypertension and mild cognitive impairment: state-of-the-art review.

BACKGROUND: Mid-life hypertension is associated with cognitive decline and dementia in later life. Reducing high blood pressure (BP) with antihypertensive agents is a well-researched strategy to prevent dementia and mild cognitive impairment (MCI). However, there is still limited direct evidence to support the approach, and particularly for the treatment of the very old and those with existing MCI. METHODS: This review presents an overview of the current evidence for the relationship between MCI and hypertension, and of the potential pathophysiological mechanisms related to cognitive decline and incidence dementia in relation to aging. RESULTS: Although observational data are near consistent in showing an association between mid-life hypertension and MCI and/or dementia, the evidence in relation to hypertension in younger adults and the very old (age >80 years) is much more limited. Most of the commonly available antihypertensive agents appear to provide beneficial effects in reducing the risk dementia, but there is limited evidence to support such treatment in those with existing MCI. CONCLUSIONS: Further studies are needed to determine the optimal levels of BP control across different age groups, especially in adults with MCI, and which class(es) of antihypertensive agents and duration of treatment best preserve cognitive function in those at risk of, or with established, MCI.

Mental health in the two years following hypertensive and normotensive pregnancy: The Postpartum, Physiology, Psychology and Paediatric follow-up (P4) cohort study.

BACKGROUND: Postpartum mental illnesses and hypertensive disorders of pregnancy (HDP) are both common, and both associated with adverse maternal and child health outcomes. However, the relationship between them is unclear. This study aimed to investigate prevalence and symptom severity of depression, anxiety, and post-traumatic stress disorder (PTSD) 2-years postpartum in women with normal blood pressure (NBP) during pregnancy versus preeclampsia or gestational hypertension (GH). METHODS: Two-years follow-up of the prospective Postpartum, Physiology, Psychology and Paediatric (P4) Cohort Study was conducted in metropolitan Australia. Prevalence and symptom severity of depression (Edinburgh Postnatal Depression Scale, EPDS > 12), anxiety (7-item Generalized Anxiety Disorder scale, GAD-7 ≥ 10) and PTSD (Posttraumatic stress Diagnostic Scale, PDS/PDS-5) were measured and calculated for women with NBP, preeclampsia and GH. RESULTS: Among 365 participants (NBP: n = 271, preeclampsia: n = 75, GH: n = 19), 2-years postpartum depression prevalence was 3.9% (95% CI 2.3-6.4%): 4.4% after NBP, and 2.7% after preeclampsia (p = 0.53). Anxiety prevalence was higher after GH than NBP (15.8% versus 3.3%, p = 0.02). Prevalence of any mental illness (depression/anxiety/PTSD) was 5.9% (95% CI 3.8-8.8%); 5.6% after NBP, 4.1% after PE, and 15.8% after GH (p = 0.15). Although PTSD prevalence was low (1.4%), and similar between groups (p = 0.97), around 3 times more women after PE (8.1%), compared to NBP (2.5%), recalled childbirth as traumatic (p = 0.003). CONCLUSIONS: Preeclampsia, although associated with persistent perceptions of traumatic childbirth, did not alter the risk of mental illnesses at 2-years postpartum. GH (albeit in a small subgroup) was associated with increased anxiety scores. Larger, multicentre studies are required to clarify relationships between HDP and postpartum mental illness. TRIAL REGISTRATION: Retrospectively registered on 18/11/2013 with the Australian and New Zealand Clinical Trials Registry. REGISTRATION NUMBER: ACTRN 12613 00,126 0718.

Association Between Age at Diabetes Diagnosis and Subsequent Incidence of Cancer: A Longitudinal Population-Based Cohort.

OBJECTIVE: Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population. RESEARCH DESIGN AND METHODS: The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years. RESULTS: A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females. CONCLUSIONS: Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.

Do Dictation Privileges Add Value to Radiology Electives If Medical Students Have Access to Online Modules?

RATIONALE AND OBJECTIVES: Traditional in-person medical student radiology electives are predominantly observerships. However, during the COVID-19 restrictions, many schools across Canada and the United States moved their radiology electives to an online format with great success. To the best of our knowledge, an evaluation of student experiences at a site where the 2-week on-site elective has both dictation privileges and an online component has not been completed. MATERIALS AND METHODS: We analyzed the pre- and post-test data from the online component of a radiology elective, retrieved the total number of dictation reports, and reviewed qualitative student feedback to gauge student engagement and learning. We used a generalized linear mixed model (GLMM) to compare the difference between the student scores on pre- and postmodule section quizzes, accounting for individual and section-specific variation in performance. A second GLMM was fit to assess improvement in the cumulative test taken before and after the entire elective. Both models accounted for the potential benefit of dictation. RESULTS: Student score improved significantly on the postsection tests (ßpost = 15.9% ± 0.86% SE, P < 0.001) and on the final postelective test (ßpost = 28.1% ± 1.8% SE, P < 0.001). The effect of total number of dictated studies on final test performance was not significant (ßpost = 0.07% ± 0.07% SE, P = 0.317). CONCLUSION: This retrospective study suggests that resources should be directed to the development of mixed online/in-person electives for ideal student engagement at the senior medical student level. Further work must be completed to understand the potential benefits of, and barriers to, student dictation at the medical student level.

Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review.

Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was "ground-based environment"; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity.

Variability in home blood pressure and its association with renal function and pulse pressure in patients with treated hypertension in primary care.

Blood pressure variability (BPV) represents a cardiovascular risk factor, regardless of mean level of blood pressure (BP). In this post-hoc analysis from the PERson-centredness in Hypertension management using Information Technology (PERHIT) study, we aimed to explore BPV in daily home measurements in hypertensive patients from primary care, to identify factors associated with high BPV and to investigate whether estimated glomerular filtration rate (eGFR) and pulse pressure, as markers of target organ damage (TOD), are associated with BPV. For eight consecutive weeks, 454 participants reported their daily BP and heart rate in their mobile phone, along with reports of lifestyle and hypertension-related factors. Systolic BP (SBP) values were used to calculate BPV with coefficient of variation (CV) as primary estimate. Background characteristics and self-reports were tested between fifths of CV in a linear regression model, adjusted for age and sex. Associations between BPV and eGFR and pulse pressure were tested with linear and logistic regression models. Higher home BPV was associated with higher age, BP, heart rate, and smoking. BPV was lower for participants with low alcohol consumption and treatment with calcium channel blockers. There was a significant association between BPV and pulse pressure (P = 0.015), and between BPV and eGFR (P = 0.049). Participants with high BPV reported more dizziness and palpitations. In conclusion, pulse pressure and eGFR were significantly associated with home BPV. Older age, high BP, heart rate, and smoking were associated with high BPV, but treatment with calcium channel blockers and low alcohol consumption was associated with low BPV. Trial registration: The study was registered with ClinicalTrials.gov [NCT03554382].

Sex differences in risk factors for incident peripheral artery disease hospitalisation or death: Cohort study of UK Biobank participants.

BACKGROUND: Women with peripheral artery disease (PAD) often have atypical symptoms, late hospital presentations, and worse prognosis. Risk factor identification and management are important. We assessed sex differences in associations of risk factors with PAD. METHODS: 500,207 UK Biobank participants (54.5% women, mean age 56.5 years) without prior hospitalisation of PAD at baseline were included. Examined risk factors included blood pressure, smoking, diabetes, lipids, adiposity, history of stroke or myocardial infarction (MI), socioeconomic status, kidney function, C-reactive protein, and alcohol consumption. Poisson and Cox regressions were used to estimate sex-specific incidence of PAD hospitalisation or death, hazard ratios (HRs), and women-to-men ratios of HRs (RHR) with confidence intervals (CIs). RESULTS: Over a median of 12.6 years, 2658 women and 5002 men had a documented PAD. Age-adjusted incidence rates were higher in men. Most risk factors were associated with a higher risk of PAD in both sexes. Compared with men, women who were smokers or had a history of stroke or MI had a greater excess risk of PAD (relative to those who never smoked or had no history of stroke or MI): RHR 1.18 (95%CI 1.04, 1.34), 1.26 (1.02, 1.55), and 1.50 (1.25, 1.81), respectively. Higher high-density lipoprotein cholesterol (HDL-C) was more strongly associated with a lower risk of PAD in women than men, RHR 0.81 (0.68, 0.96). Compared to HDL-C at 40 to 60 mg/dL, the lowest level of HDL-C (≤40 mg/dL) was related to greater excess risk in women, RHR 1.20 (1.02, 1.41), whereas the highest level of HDL-C (>80 mg/dL) was associated with lower risk of PAD in women, but higher risk in men, RHR 0.50 (0.38, 0.65). CONCLUSIONS: While the incidence of PAD was higher in men, smoking and a history of stroke or MI were more strongly associated with a higher risk of PAD in women than men. HDL-C was more strongly associated with a lower risk of PAD in women than men.

Sex hormones and the risk of myocardial infarction in women and men: a prospective cohort study in the UK Biobank.

OBJECTIVES: There is conflicting evidence around the role of sex hormones with cardiovascular outcomes. The aim of this study was to examine the association of sex hormones with the risk of myocardial infarction (MI) in pre- and post-menopausal women, and men in the UK Biobank. METHODS: The UK Biobank is a prospective population-based cohort study, that recruited over 500,000 (aged 40-69 years) women and men between 2006 and 2010. Sex specific cox regression models, estimating hazard ratios (HRs) and women to men ratio of HRs (RHR) with respective 95% confidence intervals (CI), were used to model the association of sex hormones [oestrogen, testosterone, oestrogen: testosterone (O/T) ratio, sex hormone-binding globulin (SHBG) and the free androgen index (FAI)], measured at study baseline, with incident MI for women and men. RESULTS: Data were from 479,797 participants [264,282 (55.1%) women] without a history of MI at study baseline. Over 12.5 years of follow-up, there were 4,908 MI events in women and 10,517 in men. Neither oestrogen nor testosterone were associated with MI in women and men after multiple adjustment. For men, but not women, a unit higher log-transformed O/T ratio was associated with a lower risk of MI 0.79 (0.65, 0.95) after adjustment for traditional CVD risk factors. The corresponding women to men RHR (95% CI) was 1.24 (0.99, 1.56). Higher SHBG (per unit) was also associated with a lower risk of MI in men 0.94 (0.89, 0.99), and not in women 1.02 (0.95, 1.09) after multiple adjustment, the corresponding women to men RHR (95% CI) was 1.09 (1.00, 1.18). Higher FAI was associated with a higher risk of MI in men 1.09 (1.02, 1.15), though not in women 0.97 (0.92, 1.02), the corresponding women to men RHR was 0.89 (0.82, 0.97). Finally, there were differential effects in the association of SHBG and FAI between pre- and post-menopausal women. CONCLUSIONS: A higher O/T ratio was associated with a lower risk of MI, and a higher FAI with a higher risk of MI after adjustment for CVD risk factors in men, but not in women. Thus, hormone ratios, rather than each alone, may play an important role in modulating the effect of MI.

There are conflicting findings surrounding the association of sex hormones and myocardial infarction (MI) (heart disease). In particular, high oestradiol levels in women are often thought to be protective and explain why the rates of heart disease are lower in women than men. For men, those with low levels of testosterone are often thought to be more prone to develop heart disease in their lifetimes.Our study presents a comprehensive analysis of the association of sex hormones (in isolation and also together via their ratios), in women and men using the large-scale UK Biobank.We found that neither oestrogen nor testosterone alone were associated with heart disease in women and men after accounting for cardiovascular risk factors, but the ratio of testosterone and oestrogen was associated with a lower risk of heart disease in men, though not in women. We also saw the association of sex hormone­binding globulin (SHBG), and free androgen index (FAI) (calculated by the ratio of total testosterone level to SHBG) with heart disease was different between women and men, and between pre- and post-menopausal women.This paper highlights the complex interplay between sex hormones with heart disease in the presence of age and cardiovascular risk factors. In particular the balance (ratio) of sex hormones maybe more important, rather than each in isolation, when exploring their association with heart disease.

Certainty of Evidence Assessment in Systematic Reviews Published by High-Impact Sports Science Journals: A Meta-epidemiological Study.

BACKGROUND: Assessing certainty of evidence is a key element of any systematic review. The aim of this meta-epidemiology study was to understand the frequency and ways with which certainty of evidence is assessed in contemporary systematic reviews published in high-impact sports science journals. METHODS: We searched PubMed and relevant journal web sites from 1 August 2016 to 11 October 2022 for systematic reviews published in the top-ten highest-impact journals within the 2020 Journal Citation Report for the Sports Sciences category. Pairs of independent reviewers screened items using a priori established criteria. RESULTS: Of 1250 eligible documents, 258 (20.6%) assessed the certainty of evidence, defined as using two or more distinct domains to provide an overall rating of the trustworthiness of findings across studies. Nine methods were cited for assessing certainty, with the most common being the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach (61.6%). The proportion of systematic reviews assessing certainty of evidence appeared to increase over the 6-year timeframe analyzed. Across all reviews analyzed, a large majority addressed the domains of risk of bias, imprecision, and inconsistency of the results. Other certainty domains including indirectness/applicability were less commonly assessed. DISCUSSION: Only one in five recent contemporary systematic reviews in the field of exercise and sports science assessed certainty of evidence. Organizational and institutional education on methods for assessing evidence may help further increase uptake of these methods and improve both the quality and clinical impact of systematic reviews in the field.