Time spent in a better cardiovascular health and risk of cardiovascular diseases and mortality: a prospective cohort study.

BACKGROUND: The protective effect of a higher ideal cardiovascular health (CVH) score on cardiovascular diseases (CVDs) and mortality is well recognized. However, little is known regarding the length of favorable CVH status associated with CVDs and mortality. This study aimed to examined whether the duration of better (ideal or intermediate) CVH is associated with risk of developing CVDs and mortality. METHODS: This prospective cohort study used data from 83,536 individuals from 2006 to 2020 who were enrolled in the Kailuan Study. The CVH scores of individuals were assessed at visits 1, 2, 3, and 4, respectively. The years spent in better CVH were estimated for each individual as the number of examination cycles (0-4) in which the participant was in that CVH score ≥ 8 multiplied by 2 (the mean year interval of each visit). The primary outcomes are CVD events and all-cause mortality. RESULTS: After a median follow-up period of 7.48 years, 5486 (7.07%) cases of incident CVD events and 7669 (9.18%) deaths occurred. Compared with participants in " ≤ 4 years" group, those who maintained for > 4 years had less likely to develop adverse outcomes (CVD events: hazard ratio (HR): 0.60, 95% confidence interval (CI 0.56-0.63; all-cause mortality: HR: 0.77, 95% CI 0.74-0.81). The number of years spent in better CVH was nonlinearly correlated with CVD events or mortality (all Ps for nonlinear < 0.05). The results indicated that maintaining more than 6 years in a better CVH status was associated with a decreased risk of CVD events or mortality. CONCLUSION: Our study indicates that individuals maintaining more than 6 years in better CVH could increase cardiometabolic benefits and a lower risk of all-cause mortality.

Ideal cardiovascular health metrics and life expectancy free of cardiovascular diseases: a prospective cohort study.

Objectives: Whether cardiovascular health (CVH) metrics impact longevity with and without cardiovascular diseases (CVDs) has not been well established. This study aimed to investigate the association between CVH metrics and life expectancy in participants free of CVD events. We hypothesized that ideal CVH status was associated with increased life expectancy and assessed the effect of CVH status as a prevention target of longevity in the framework of predictive, preventive, and personalized medicine (PPPM/3PM). Methods: A total of 92,795 participants in the Kailuan study were examined and thereafter followed up until 2020. We considered three transitions (from non-CVD events to incident CVD events, from non-CVD events to mortality, and from CVD events to mortality). The multistate lifetable method was applied to estimate the life expectancy. Results: During a median follow-up of 13 years, 12,541 (13.51%) deaths occurred. Compared with poor CVH, ideal CVH attenuated the risk of incident CVD events and mortality without CVD events by approximately 58% and 27%, respectively. Women with ideal CVH at age 35 had a 5.00 (3.23-6.77) year longer life expectancy free of CVD events than did women with poor CVH metrics. Among men, ideal CVH was associated with a 6.74 (5.55-7.93) year longer life expectancy free of CVD events. Conclusion: An ideal CVH status is associated with a lower risk of premature mortality and a longer life expectancy, either in the general population or in CVD patients, which are cost-effective ways for personalized medicine of potential CVD patients. Our findings suggest that the promotion of a higher CVH score or ideal CVH status would result in reduced burdens of CVD events and extended disease-free life expectancy, which offered an accurate prediction for primary care following the concept of PPPM/3PM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-023-00322-8.

Outcome after endovascular treatment for acute ischemic stroke by underlying etiology: Tertiary experience and meta-analysis.

Objective: To investigate the effect of two major etiologies [intracranial atherosclerotic stenosis (ICAS) and cardioembolism (CE])] on outcomes of acute ischemic stroke (AIS) patients due to large vessel occlusion (LVO) after endovascular thrombectomy (EVT). Methods: Anterior circulation AIS patients receiving EVT were retrospectively analyzed. Clinical and laboratory data were collected. Clinical outcomes including favorable outcome (90-day modified Rankin Scale 0-2), mortality, intracranial hemorrhage (ICH) and symptomatic ICH (sICH) were compared. A systematic review and meta-analysis was also performed. Results: A total of 302 AIS patients were included and divided into the ICAS group (86 patients) and the CE group (216 patients). Patients in the ICAS group were younger (62[18.0] vs. 68[19.0] years, p < 0.001), more likely to have smoking (52.3% vs. 26.9%, p < 0.001) and drinking (52.3% vs. 23.1%, p < 0.001) history, and more frequently required rescue therapy (80.2% vs. 4.6%, p < 0.001) compared to the CE group. However, favorable outcome (aOR 0.722, 95%CI 0.372-1.402, p = 0.336) and mortality (aOR 1.522, 95%CI 0.606-3.831, p = 0.371) were not significantly different between the two groups before and after adjustment. The incidence of sICH and ICH were comparable between the two groups before and after adjustment. Systematic review and meta-analysis consisted of 8 eligible studies (7 previous studies and this current study), incorporating 552 ICAS patients and 1,402 CE patients. Favorable outcome was slightly more likely in the ICAS group compared to the CE group (54.2% vs. 46.3%, OR 1.40, 95%CI 1.00-1.96, I 2 = 53.2%). Moreover, the ICAS group had a lower rate of mortality (14.3% vs. 22.2%, OR 0.63, 95%CI 0.46-0.87, I 2 = 0.0%) and ICH (19.5% vs. 31.9%, OR 0.60, 95%CI 0.42-0.84, I 2 = 0.0%) than the CE group, while the two groups were similar in sICH rate (5.9% vs. 6.7%, OR 0.94, 95%CI 0.55-1.60, I 2 = 6.3%). Conclusion: Etiology was not considered as an important factor in functional outcome, despite the differences in baseline characteristics and technical EVT approach. The current study of anterior circulation AIS-LVO patients supports that outcomes for those with ICAS are not significantly different from those with CE.

Patterns and implications of artery remodeling based on high-resolution vessel wall imaging in symptomatic severe basilar artery stenosis.

Background: Knowledge regarding the influence of arterial remodeling patterns on plaque characteristics and postoperative outcomes in patients with severe basilar artery (BA) stenosis after endovascular treatment is lacking. The purpose of this study was to investigate plaque characteristics, remodeling patterns, and perioperative outcomes in patients with severe BA stenosis. Methods: A prospective cohort study was conducted on symptomatic patients with severe BA stenosis who underwent high-resolution MRI before endovascular treatment. The remodeling index, plaque burden, and area of stenosis were evaluated for each plaque. Based on the remodeling index calculated by high-resolution MRI, remodeling patterns were classified as negative remodeling (NR) or non-negative remodeling (non-NR). Baseline demographics, plaque features, and treatment characteristics were compared between the NR and non-NR groups. Correlations between the remodeling index, plaque burden, and stenosis severity were also examined. Results: In total, 140 eligible patients were included and analyzed, including 91 non-NR cases and 49 NR cases. A strong correlation existed between the remodeling index and plaque burden (r=0.973, P<0.001), and a marginal correlation was observed between the remodeling index and degree of stenosis by area (r=-0.261, P=0.0019). There was no significant difference between the two groups in terms of perioperative complications related to ischemic events and new ischemic cerebral lesions (NICLs). Conclusions: Under the current submaximal angioplasty and/or stenting treatment paradigms, remodeling patterns may not influence the outcome of ischemic events and NICLs. However, the remodeling index is strongly associated with plaque burden, which may provide insight for the evaluation of severe BA stenosis. Further research is warranted.

Clinical Significance and Influencing Factors of Microvascular Tissue Reperfusion After Macrovascular Recanalization.

The relevance of impaired microvascular tissue reperfusion despite successful macrovascular angiographic reperfusion (no-reflow) in acute ischemic stroke (AIS) remains controversial. In this study, we aimed to investigate the impact of tissue optimal reperfusion (TOR) and its influencing factors. From December 1, 2020 to December 1, 2021, AIS patients with successful recanalization (modified Thrombolysis in Cerebral Infarction score [mTICI] ≥ 2b) after mechanical thrombectomy (MT) were retrospectively reviewed. Computed tomography perfusion was performed before and after MT. Successful reperfusion was assessed by TOR, defined as > 90% reduction of the Tmax > 6 s lesion volumes between baseline and early follow-up perfusion profiles. The impact of TOR on functional outcomes after successful recanalization and influencing factors for TOR were both investigated. Sixty-three patients were included, including 44 cases in the TOR group and 19 cases in the non-TOR group. The TOR group had a higher rate of favorable outcome (aOR 4.366, 95%CI 1.159-16.445, p = 0.030) and NIHSS improvement (aOR 5.089, 95%CI 1.340-19.322, p = 0.017) than the non-TOR group. Multivariable logistic regression showed baseline glucose (OR 0.648, 95%CI 0.492-0.854, p = 0.002) and mTICI 2c/3 (OR 10.984, 95%CI 2.220-54.343, p = 0.003) predicted TOR in model 1; in model 2, postoperative glucose (OR 0.468, 95%CI 0.278-0.787, p = 0.004) and mTICI 2c/3 (OR 9.436, 95%CI 1.889-47.144, p = 0.006) were predictive. TOR was strongly associated with good functional outcomes after successful recanalization of MT. Higher mTICI grade and lower perioperative glucose level may predict microvascular tissue reperfusion.

Prevalence, awareness, treatment and control of type 2 diabetes and its determinants among Mongolians in China: a cross-sectional analysis of IMAGINS 2015-2020.

OBJECTIVES: This study aims to estimate the prevalence, awareness, treatment and control rates of type 2 diabetes (T2D) and pre-diabetes as well as to identify its associated factors among Mongolians living in the Inner Mongolia Autonomous Region, China. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: This sample included 11 361 Mongolian participants from the Inner Mongolian Healthy Aging Intervention Study, a population-based screening project consisting of 141 255 adults aged above 35 years in Inner Mongolia from 2015 to 31 December 2020. OUTCOME MEASURES: The prevalence and 95% CIs of T2D and pre-diabetes were calculated. Factors associated with the prevalence, awareness, treatment and control of T2D were explored by a binomial logistic regression. RESULTS: A total of 17.2% (95% CI 16.5% to 17.9%) of the sample had T2D, of whom 34.0% (95% CI 31.9% to 36.1%) were aware of their diagnosis, 24.7% (95% CI 22.8% to 26.6%) were taking prescribed antidiabetic medications, 6.7% (95% CI 5.6% to 7.8%) had achieved control and 27.5% (95 % CI 26.7% to 28.3%) had pre-diabetes. The prevalence of T2D increased with increasing age, male, lower education level, smoking, obesity and a history of hypertension or dyslipidaemia (all p<0.05). CONCLUSIONS: T2D is highly prevalent, with suboptimal awareness, treatment and control rates, and an escalating health challenge among the Mongolian population. Broad-based strategies, including diabetes prevention education, better screening and affordable treatment, should be implemented to raise awareness, treatment and control rates of T2D in Inner Mongolia.

Outcomes after endovascular thrombectomy for acute ischemic stroke patients with active cancer: A systematic review and meta-analysis.

Background: Active cancer (AC) is a known risk factor for stroke and a common comorbidity among patients being considered for treatment with endovascular thrombectomy (EVT). This systematic review and meta-analysis aimed to evaluate the current evidence for the feasibility, efficacy, and safety of EVT for patients with AC. Methods: MEDLINE, EMBASE, and the Cochrane Library were searched for relevant randomized controlled trials (RCTs) and observational studies which met the inclusion criteria for EVT in patients with AC. Studies were excluded due to the mismatch of data format, article type, and group design. The risk of bias was assessed through different scales according to the study design. I 2 statistics were used to evaluate the heterogeneity. Funnel plots were used to evaluate publication bias. Results: A total of six studies and 3,657 patients were included. Compared to without active cancer (WC) patients, patients with AC had a significantly higher proportion of in-hospital mortality (OR 3.24; 95% CI, 1.03-10.15). The estimated rate of favorable outcome of six studies was lower in patients with AC than in patients with WC (OR 0.47; 95% CI, 0.35-0.65). For 90-day mortality of four studies, the AC group had a higher proportion when compared with the WC group (OR 3.87; 95% CI, 2.64-5.68). There was no difference between rate of six studies of successful recanalization (OR 1.24; 95% CI, 0.90-1.72) and four studies of symptomatic ICH (OR 1.09; 95% CI, 0.61-1.97) comparing AC and WC. Conclusion: Patients with AC are less likely to have a favorable outcome and have a higher risk of mortality after EVT. Further studies are warranted for this unique patient population.

Vascular endothelial growth factor and the risk of venous thromboembolism: a genetic correlation and two-sample Mendelian randomization study.

BACKGROUND: The relationship between vascular endothelial growth factor (VEGF) and the risk of venous thromboembolism (VTE) has always been one of the concerns in the medical field. However, the causal inferences from published observational studies on this issue may be affected by confounders or reverse causality. We performed a two-sample bidirectional Mendelian randomization (MR) to infer the associations between VEGF and VTE. METHODS: Summary statistics from genome-wide association studies (GWAS) for VEGF and VTE were obtained from published meta-analysis studies and the FinnGen consortium, respectively. Independent genetic variables significantly associated with exposure were selected as instrumental variables. Linkage disequilibrium score regression (LDSC) and five robust MR analytical approaches were conducted to estimate the genetic correlations and causal inference. The MR-Egger intercept, Cochran's Q, and MR pleiotropy residual sum and outlier (MR-PRESSO) were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on outcomes. Notably, replication analyses were performed using different subgroups of VTE. RESULTS: LDSC failed to identify genetic correlations between VEGF and VTE. Based on 9 SNPs, the circulating VEGF level was positively related to the risk of VTE using inverse variance weighting (IVW) method (odds ratio (OR) = 1.064, 95% confidence interval (CI), 1.009-1.122). Reverse MR analyses showed that genetic liability for VTE was not associated with increased VEGF level (ß = -0.021, 95% CI, -0.087-0.045). Pleiotropy-robust methods indicated no bias in any estimates. CONCLUSIONS: Our findings failed to detect coheritability between VEGF and VTE. The suggestive positive effect of the higher VEGF level on the VTE risk may have clinical implications, suggesting that VEGF as a possible predictor and therapeutic target for VTE prevention need to be further warranted.

Influence of pre-stroke dependency on safety and efficacy of endovascular therapy: A systematic review and meta-analysis.

Background and purpose: In the landmark trials studying endovascular thrombectomy (EVT), pre-stroke dependent (PSD) patients were generally excluded. This systematic review and meta-analysis aimed to compare the safety and efficacy of EVT between PSD and pre-stroke independent (PSI) patients. Methods: We searched CENTRAL, Embase, and Ovid MEDLINE up to 11 November 2021 for studies assessing PSD and PSI patients, which were separately defined as pre-stroke mRS score >2 or >1, and ≤2 or ≤1 accordingly. Two authors extracted data and assessed the risk of bias. A meta-analysis was carried out using the random-effects model. Adjusted OR and 95% CI were used to estimate adjusted pool effects. The main outcomes included favorable outcomes, successful recanalization, symptomatic intracranial hemorrhage, and 90-day mortality. Results: A total of 8,004 records met the initial search strategy, and ten studies were included in the final decision. Compared with PSImRS≤2, PSDmRS>2 had a lower favorable outcome (OR 0.51; 95% CI, 0.33-0.79) and higher 90-day mortality (OR 3.32; 95% CI, 2.77-3.98). No significant difference was found in successful recanalization and sICH. After adjustment, only 90-day mortality (aOR 1.99; 95% CI, 1.58-2.49) remained significantly higher in PSDmRS>2. Compared with PSImRS≤1, PSDmRS>1 had lower 90-day mortality (OR, 3.10; 95% CI, 1.84-5.24). No significant difference was found regarding the favorable outcome, successful recanalization, and sICH. After adjustment, no significant difference was found in a favorable outcome, but a higher rate of 90-day mortality (aOR, 2.13; 95% CI, 1.66-2.72) remained in PSDmRS>1. Conclusions: PSD does not innately influence the EVT outcomes regarding sICH and favorable outcomes but may increase the risk of 90-day mortality. Until further evidence is available, it is reasonable to suggest EVT for patients with PSD.

Postoperative neutrophil-lymphocyte ratio predicts unfavorable outcome of acute ischemic stroke patients who achieve complete reperfusion after thrombectomy.

Purpose: Only approximately half of anterior circulation large vessel occlusion (LVO) patients receiving endovascular treatment (EVT) have a favorable outcome. The aim of this study was to explore the association of dynamic inflammatory markers (i.e., neutrophil to lymphocyte ratios, NLR, measured at different times after EVT) as well as other potential influencing factors with unfavorable outcome among acute ischemic stroke (AIS) patients who achieved complete reperfusion after EVT. Methods: Patients treated with EVT for LVO between January 2019 to December 2021 were prospectively enrolled. Complete reperfusion was defined as modified thrombolysis in cerebral infarction (mTICI) grade 3. A modified Rankin scale at 90 days (mRS90) of 3-6 was defined as unfavorable outcome (i.e., futile reperfusion). A logistic regression analysis was performed with unfavorable outcome as a dependent variable. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) were then used to determine the diagnostic values of NLR and other relevant factors. Results: 170 patients with complete reperfusion (mTICI 3) were included in this study. Unfavorable outcome was observed in 70 (41.2%). Higher NLR within 24h (p=0.017) and at 3-7d (p=0.008) after EVT were an independent risk factors for unfavorable outcome at 3 months. In addition, older age, higher NIHSS scores, poor collaterals, and general anesthesia were independent predictors of unfavorable outcomes. When accounting for NLR, the diagnostic efficiency improved compared to conventional characteristics. Conclusion: Our findings suggest that advanced age, increased stroke severity, poor collaterals, general anesthesia, and NLR are independent predictors for an unfavorable clinical outcome following complete reperfusion after EVT. Neuroinflammation may merit particular attention in future studies.

Assessment of the Causal Effect of IgG N-Glycosylation Level on Risk of Dementia: A 2-Sample Mendelian Randomization Study.

BACKGROUND: Previous prospective studies highlighted aberrant immunoglobulin G (IgG) N-glycosylation as a risk factor for dementia [such as Alzheimer's disease (AD) and vascular dementia (VaD)]. It is unclear whether this association is causal or explained by confounding or reverse causation. OBJECTIVE: The aim is to examine the association of genetically predicted IgG N-glycosylation with dementia using 2-sample Mendelian randomization (MR). METHODS: Independent genetic variants for IgG N-glycosylation traits were selected as instrument variables from published genome-wide association studies (GWAS) among individuals of European ancestry. We extracted their corresponding summary statistics from large-scale clinically diagnosed AD GWAS dataset and FinnGen biobank VaD GWAS dataset. The inverse variance weighted (IVW) was performed to calculate the effect estimates. Meanwhile, multiple sensitivity analyses were used to assess horizontal pleiotropy and outliers. RESULTS: There were no associations of genetically predicted IgG N-glycosylation traits with the risk of AD and VaD using the IVW method (all Bonferroni corrected p > 0.0013). These estimates of four additional sensitivity analyses methods were consistent with the IVW estimates in terms of direction and magnitude. Additionally, the MR-PRESSO global test and the intercept of MR-Egger regression indicated no evidence of horizontal pleiotropy. Meanwhile, the heterogeneity test showed no significant heterogeneity using the Cochran Q statistic. The leave-one-out sensitivity analyses also did not detect any significant change. CONCLUSION: Our MR study did not support evidence for the hypothesis that IgG N-glycosylation level may be causally associated with the risk of dementia.

Genome-Wide Mapping of Plasma IgG N-Glycan Quantitative Trait Loci Identifies a Potentially Causal Association between IgG N-Glycans and Rheumatoid Arthritis.

Observational studies highlight associations of IgG N-glycosylation with rheumatoid arthritis (RA); however, the causality between these conditions remains to be determined. Standard and multivariable two-sample Mendelian randomization (MR) analyses integrating a summary genome-wide association study for RA and IgG N-glycan quantitative trait loci (IgG N-glycan-QTL) data were performed to explore the potentially causal associations of IgG N-glycosylation with RA. After correcting for multiple testing (p < 2 × 10-3), the standard MR analysis based on the inverse-variance weighted method showed a significant association of genetically instrumented IgG N-glycan (GP4) with RA (odds ratioGP4 = 0.906, 95% confidence interval = 0.857-0.958, p = 5.246 × 10-4). In addition, we identified seven significant associations of genetically instrumented IgG N-glycans with RA by multivariable MR analysis (p < 2 × 10-3). Results were broadly consistent in sensitivity analyses using MR_Lasso, MR_weighted median, MR_Egger regression, and leave-one-out analysis with different instruments (all p values <0.05). There was limited evidence of pleiotropy bias (all p values > 0.05). In conclusion, our MR analysis incorporating genome-wide association studies and IgG N-glycan-QTL data revealed that IgG N-glycans were potentially causally associated with RA. Our findings shed light on the role of IgG N-glycosylation in the development of RA. Future studies are needed to validate our findings and to explore the underlying physiological mechanisms in the etiology of RA.

Moderate physical activity may not decrease the risk of cardiovascular disease in persistently overweight and obesity adults.

BACKGROUND: Body mass index (BMI) and physical activity (PA) has been documented to be associated with cardiovascular disease (CVD). However, the evidences regarding joint phenotypes of BMI and PA trajectories with risk for CVD and all-cause mortality are still limited. METHODS: Participants from the Kailuan Study, followed up during 2006-2019 were included, with primary outcomes of CVDs (myocardial infarction or stroke) and all-cause mortality. BMI and PA were repeatedly measured at least three times, and thus joint phenotypes trajectory groups were identified by group-based trajectory modeling. Cox proportional hazards models were used to examine the associations between trajectory groups and CVDs and all-cause mortality. RESULTS: Totally 88,141 (6 trajectories) and 89,736 participants (5 trajectories) were included in the final analyses relating trajectories to CVDs and all-cause mortality, respectively. Compared with persistent normal-weight with moderate PA group, participants were associated with increased risk of CVD in persistent overweight with moderate PA trajectory group (adjusted hazard ratio [aHR]: 1.31, 95% confidence interval [CI]: 1.22-1.41) and persistent obesity with moderate PA trajectory group (aHR: 1.55, 95% CI: 1.41-1.69). While the rising to overweight with moderate PA in normal-weight status with active PA (aHR: 0.72, 95% CI: 0.65-0.79), persistent overweight with moderate PA (aHR: 0.92, 95% CI: 0.87-0.97) and decline to normal-weight in overweight status with moderate PA (aHR: 0.73, 95% CI: 0.67-0.80) trajectories group were significantly associated with decreased all-cause mortality risk. The associations remained robust among stratifying by age and sex individuals and sensitive analysis. CONCLUSIONS: The long-term trajectories analysis showed that moderate PA may not decrease the risk of CVD in persistently overweight and obesity adults.

Causal associations between COVID-19 and atrial fibrillation: A bidirectional Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies showed that coronavirus disease (2019) (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). The causal association between COVID-19 infection or its severity and susceptibility of atrial fibrillation (AF) remains unknown. METHODS AND RESULTS: The bidirectional causal relationship between COVID-19 (including COVID-19, hospitalized COVID-19 compared with not hospitalized COVID-19, hospitalized COVID-19 compared with the general population, and severe COVID-19) and AF are determined by using two-sample Mendelian randomization (MR) analysis. Genetically predicted severe COVID-19 was not significantly associated with the risk of AF [odds ratio (OR), 1.037; 95% confidence interval (CI), 1.005-1.071; P = 0.023, q = 0.115]. In addition, genetically predicted AF was also not causally associated with severe COVID-19 (OR, 0.993; 95% CI, 0.888-1.111; P = 0.905, q = 0.905). There was no evidence to support the association between genetically determined COVID-19 and the risk of AF (OR, 1.111; 95% CI, 0.971-1.272; P = 0.127, q = 0.318), and vice versa (OR, 1.016; 95% CI, 0.976-1.058; P = 0.430, q = 0.851). Besides, no significant association was observed for hospitalized COVID-19 with AF. MR-Egger analysis indicated no evidence of directional pleiotropy. CONCLUSION: Overall, this MR study provides no clear evidence that COVID-19 is causally associated with the risk of AF.

Vitamin D and Multiple Health Outcomes: An Umbrella Review of Observational Studies, Randomized Controlled Trials, and Mendelian Randomization Studies.

Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.

Protocol of the Inner Mongolian Healthy Aging Study (IMAGINS): a longitudinal cohort study.

BACKGROUND: Cardiovascular diseases (CVDs) remain the leading cause of premature mortality and burden of diseases in the world. The Inner Mongolia Autonomous Region is located in northern China, constitute 17.66% individuals with Mongolian, which have unique diet and lifestyles. Therefore, the Inner Mongolian Healthy Aging Study (IMAGINS) was designed to explore risk factors for chronic diseases and evaluate the effectiveness of health management on CVDs in population at high-risk. METHODS: The IMAGINS is an ongoing and prospective cohort study of men and women aged ≥35 years from Inner Mongolian Autonomous Region, northern China. This study performed in investigating risk factors for CVDs, screening and providing health management strategy for high-risk population of CVDs. The IMAGINS began in September 2015 and scheduled to recruiting and follow-up outcome until 2030. For general population, a long-term follow-up will be conducted every 5 years to collect the information above and data on clinical outcomes. For high-risk population, comprehensive health managements were performed and scheduled to follow-up annually. All IMAGINS participants are followed for incident CVDs and death. DISCUSSION: The IMAGINS is designed to increase understanding how cardiovascular-related risk factors contribute to the development of CVDs and the positive effect of health management strategy for high-risk CVD participants. Key features of this study include (i) a carefully characterized cohort between high risk of CVDs and non-high risk population; (ii) detailed measurement of CVDs risk factors and health management strategies for high risk population; (iii) long-term follow-up of CVDs and death. The IMAGINS represents a good research opportunity to investigate clinical and genetic factors in high-risk population, might providing basis for the prevention and control of non-communicable diseases.

Causal Relationship Between Lung Function and Atrial Fibrillation: A Two Sample Univariable and Multivariable, Bidirectional Mendelian Randomization Study.

Background: Observational studies have identified impaired lung function accessed by forced expiratory volume in one second (FEV1), forced vital capacity (FVC) or the ratio of FEV1 over FVC (FEV1/FVC) as an independent risk factor for atrial fibrillation (AF). However, the result may be affected by confounders or reverse causality. Methods: We performed univariable MR (uvMR), multivariable MR (mvMR) and bidirectional two-sample MR to jointly estimate the causality of lung function with AF. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, three complementary sensitive analyses approaches including MR-Egger regression, weighted median (WM) MR and Pleiotropy Residual Sum and Outlier (MR-PRESSO) in uvMR as well as mvMR-Egger and mvMR-PRESSO in mvMR were applied to control for pleiotropy. Linkage disequilibrium score (LDSC) regression was applied to estimate genetic correlation between lung function and AF. Results: All forward and reverse uvMR analyses consistently suggested absent causal relations between lung function and AF risk [forward IVW: odds ratio (OR)FEV1 = 1.031, 95% CI = 0.909-1.169, P = 0.630; ORFVC = 1.002, 95% CI = 0.834-1.204, P = 0.982; ORFEV1/FVC = 1.076, 95% CI = 0.966-1.199, P = 0.182; reverse IVW: ORFEV1 = 0.986, 95% CI = 0.966-1.007, P = 0.187; ORFVC = 0.985, 95% CI = 0.965-1.006, P = 0.158; ORFEV1/FVC = 0.994, 95% CI = 0.973-1.015, P = 0.545]. The forward MR-Egger showed that each standard deviation (SD) increase in FEV1/FVC was related to a higher AF risk (OR = 1.502, 95% CI = 1.178-1.915, P = 0.006) without heterogeneity (Q_pval = 0.064), but pleiotropy effect exist (intercept = -0.017, P = 0.012). However, this significant effect disappeared after adjustment of FEV1 and FVC (OR = 1.523, 95% CI = 0.445-5.217, P = 0.503) in mvMR. No evidence was found for independent causal effects of FEV1 and FVC on AF in mvMR analysis by using mvIVW method (ORFEV1 = 0.501, 95% CI = 0.056-4.457, P = 0.496; ORFVC = 1.969, 95% CI = 0.288-13.474, P = 0.490). Notably, the association between lung function and AF were replicated using the FinnGen cohort data. Conclusions: Our findings reported no coheritability between lung function and AF, and failed to find substantial causal relation between decreased lung function and risk of AF. However, lung function and AF were both associated with inflammation, which may be potential pathway, warranting further study.

Blood transcriptome profiling as potential biomarkers of suboptimal health status: potential utility of novel biomarkers for predictive, preventive, and personalized medicine strategy.

The early identification of Suboptimal Health Status (SHS) creates a window opportunity for the predictive, preventive, and personalized medicine (PPPM) in chronic diseases. Previous studies have observed the alterations in several mRNA levels in SHS individuals. As a promising "omics" technology offering comprehension of genome structure and function at RNA level, transcriptome profiling can provide innovative molecular biomarkers for the predictive identification and targeted prevention of SHS. To explore the potential biomarkers, biological functions, and signalling pathways involved in SHS, an RNA sequencing (RNA-Seq)-based transcriptome analysis was firstly conducted on buffy coat samples collected from 30 participants with SHS and 30 age- and sex-matched healthy controls. Transcriptome analysis identified a total of 46 differentially expressed genes (DEGs), in which 22 transcripts were significantly increased and 24 transcripts were decreased in the SHS group. A total of 23 transcripts were selected as candidate predictive biomarkers for SHS. Gene Ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that several biological processes were related to SHS, such as ATP-binding cassette (ABC) transporter and neurodegeneration. Protein-protein interaction (PPI) network analysis identified 10 hub genes related to SHS, including GJA1, TWIST2, KRT1, TUBB3, AMHR2, BMP10, MT3, BMPER, NTM, and TMEM98. A transcriptome predictive model can distinguish SHS individuals from the healthy controls with a sensitivity of 83.3% (95% confidence interval (CI): 73.9-92.7%), a specificity of 90.0% (95% CI: 82.4-97.6%), and an area under the receiver operating characteristic curve of 0.938 (95% CI: 0.882-0.994). In the present study, we demonstrated that blood (buffy coat) samples appear to be a very promising and easily accessible biological material for the transcriptomic analyses focused on the objective identification of SHS by using our transcriptome predictive model. The pattern of particularly determined DEGs can be used as predictive transcriptomic biomarkers for the identification of SHS in an individual who may, subjectively, feel healthy, but at the level of subcellular mechanisms, the changes can provide early information about potential health problems in this person. Our findings also indicate the potential therapeutic targets in dealing with chronic diseases related to SHS, such as T2DM and CVD, and an early onset of neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, as well as the findings suggest the targets for personalized interventions as promoted in PPPM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-021-00238-1.

Choroidal and Retinal Thickness and Axial Eye Elongation in Chinese Junior Students.

Purpose: To explore the associations between macular choroidal and retinal thickness and axial elongation in non-myopic and myopic junior students. Methods: In this school-based longitudinal observational study, axial length was measured by optical low-coherence reflectometry, and choroidal thickness and retinal thickness were measured by spectral-domain optical coherence tomography. Myopia was defined as non-cycloplegic objective spherical equivalent refraction ≤ -0.50 diopters. Structural equation modeling and multiple linear regression models were used to analyze the associations between baseline choroidal and retinal thickness with axial elongation. Results: Out of 1307 students examined at baseline in 2017, 1197 (91.58%) returned for follow-up examination in 2018, with a median age of 12.00 years (interquartile range [IQR], 1.00) and included 667 boys (55.72%). Within a 1-year period, the median axial elongation of right eyes was 230 µm (IQR, 180) in boys and 200 µm (IQR, 160) in girls (P = 0.032). The thinner temporal choroidal thickness was associated with greater 1-year axial elongation only in myopic students (ß, -0.20; 95% confidence interval [CI], -0.37, -0.03), the thinner temporal retinal thickness was associated with greater 1-year axial elongation in both non-myopic (ß, -2.67; 95% CI, -4.52, -0.82) and myopic (ß, -0.99; 95% CI, -1.68, -0.30) students, after adjustment for sex, age, and height. Subfoveal and nasal choroidal and retinal thickness were not significantly associated with axial elongation in either non-myopic or myopic students. Conclusions: A thinner temporal choroid at age 12 years may predict greater 1-year axial elongation in myopic students, and a thinner temporal retina may predict greater 1-year axial elongation in both non-myopic and myopic students. This finding may help to identify children at risk and control axial elongation with potential preventive strategies.