Meta-analysis Of Prospective Cohort Studies Research Articles

Predictors of cognitive impairment in Parkinson's disease: a systematic review and meta-analysis of prospective cohort studies.

Cognitive impairment is a debilitating manifestation in Parkinson's disease (PD). We sought to investigate predictors of PD-CI (PD with cognitive impairment). We systematically searched PubMed and Cochrane Library for prospective cohort studies and pooled estimates via random-effects models. Primary analyses for all types of cognitive impairments and subgroup analyses by separate outcomes were conducted. A total of 28,009 studies were identified, of which 57 studies with 31 factors were included in the meta-analysis. In the primary analysis, 13 factors were associated with PD-CI, comprising advanced age [relative risk (RR) = 1.07, 95% confidence interval (CI) = 1.03-1.12], age at onset (RR = 4.43, 95% CI = 1.87-10.54), postural-instability-gait disorder (RR = 3.76, 95% CI = 1.36-10.40), higher Hoehn and Yahr stage (RR = 1.83, 95% CI = 1.35-2.47), higher UPDRS III score (RR = 1.04, 95% CI = 1.01-1.08), rapid eye movement sleep behavior disorder (RR = 3.72, 95% CI = 1.20-11.54), hallucinations (RR = 3.09, 95% CI = 1.61-5.93), orthostatic hypotension (RR = 2.98, 95% CI = 1.41-6.28), anxiety (RR = 2.59, 95% CI = 1.18-5.68), APOE ε2 (RR = 6.47, 95% CI = 1.29-32.53), APOE ε4 (RR = 3.04, 95% CI = 1.88-4.91), electroencephalogram theta power > median (RR = 2.93, 95% CI = 1.61-5.33), and alpha power < median (RR = 1.77, 95% CI = 1.07-2.92). In the subgroup analysis, MAPT H1/H1 genotype increased the risk of dementia in PD. Sixty-four studies were included in the systematic review, of which 12 factors were additionally correlated with PD-CI using single studies. Advanced age, genetic variation in APOE and MAPT, gait disturbance, motor assessments, non-motor symptoms, and electroencephalogram may be promising predictors for PD-CI.

Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis

ObjectiveTo evaluate the association between egg intake and cardiovascular disease risk among women and men in the United States, and to conduct a meta-analysis of prospective cohort studies.DesignProspective cohort study,...

Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies

Previous findings on the associations of legume and soy intake with the risk of type 2 diabetes are conflicting. We aimed to summarize the longitudinal associations between legume and soy intake and risk of type 2 diabetes. We searched for relevant prospective cohort studies in PubMed, EMBASE, and Ovid up to August 2019. Study-specific, multivariable-adjusted RRs and 95% CIs were pooled by random-effects models. We identified 15 unique cohorts including 565,810 individuals and 32,093 incident cases. The summary RRs (95% CIs) of incident type 2 diabetes were 0.95 (0.79, 1.14; NS) for total legumes, 0.83 (0.68, 1.01; NS) for total soy, 0.89 (0.71, 1.11; NS) for soy milk, 0.92 (0.84, 0.99) for tofu, 0.84 (0.75, 0.95) for soy protein, and 0.88 (0.81, 0.96) for soy isoflavones, respectively. High heterogeneity was found for total legumes (I2=84.8%), total soy (I2=90.8%), and soy milk (I2=91.7%). Potential sources of heterogeneity were not evident for total legumes or soy milk, whereas for total soy, geographic location (Asia, United States; P=0.04) and study quality (high, moderate, or low; P = 0.02) significantly predicted heterogeneity. In dose-response analysis, significant linear inverse associations were observed for tofu, soy protein, and soy isoflavones (all P < 0.05). Overall quality of evidence was rated as moderate for total legumes and low for total soy and soy subtypes. Dietary intakes of tofu, soy protein, and soy isoflavones, but not total legumes or total soy, are inversely associated with incident type 2 diabetes. Our findings support recommendations to increase intakes of certain soy products for the prevention of type 2 diabetes. However, the overall quality of evidence was low and more high-quality evidence from prospective studies is needed. This trial was registered as PROSPERO CRD42019126403 (https://www.crd.york.ac.uk/PROSPERO).

Environmental factors, serum biomarkers and risk of atrial fibrillation: an exposure-wide umbrella review of meta-analyses.

Atrial fibrillation (AF) is the most common cardiac arrhythmia. We designed an umbrella review to systematically assess the epidemiological credibility of the associations of non-genetic factors with risk of AF. We searched PubMed and EMBASE from inception to December 31, 2018 to identify systematic reviews and meta-analyses of observational studies for the association of non-genetic factors with risk of AF. For each meta-analysis, we used the random-effects model, and we estimated the 95% confidence and prediction intervals. We also assessed between-study heterogeneity, small-study effects and excess significance bias. We identified 34 eligible papers that examined 51 associations of 42 unique non-genetic factors with risk of AF. Eighteen associations remained statistically significant at P value < 1 × 10-6. Thirty-one associations presented large or very large between-study heterogeneity. Eight associations presented evidence for small-study effects and 13 associations had evidence for excess significance bias. Ten associations, i.e. corrected QT interval, alcohol consumption (highest vs. lowest category, per 1 drink/day increase), body mass index (> 30 units vs. < 30 units, per 5 units increase), waist circumference, body weight, type 2 diabetes mellitus, and smoking (ever vs. never, per 10 cigarettes/day increase) were supported by convincing or highly suggestive evidence in meta-analyses of prospective cohort studies. Type 2 diabetes mellitus, markers of adiposity, alcohol consumption, smoking, and corrected QT interval constitute credible risk factors of AF. Our proposed grading may guide the design of future studies, including Mendelian randomization studies, to assess whether these associations are causal.

Alcohol Consumption by Beverage Type and Risk of Breast Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Alcohol intake has been shown to increase the risk of breast cancer. However, the dose-response analysis of different alcoholic beverages (spirits, wine and beer) is not clear. Our meta-analysis aims to provide a dose-response estimation between different alcohols and breast cancer risk. Search of PubMed and Web of Science and manual searches were conducted up to 1 December 2018, and summary relative risks (RRs) and attributable risk percentage (ARP) for alcohol intake on the development of breast cancer were calculated. Dose-response meta-analysis modeled relationships between drinking type and breast cancer risk. Sources of heterogeneity were explored, and sensitivity analyses were conducted to test the robustness of findings. In total, 22 cohort studies and 45,350 breast cancer cases were included. Current drinkers for ER+ had an increased risk compared with never drinkers. In dose-response analysis, there was a statistically significant linear trend with breast cancer risk increasing gradually by total alcohol and wine dose: when adding 10g per day, the risk increased by 10.5% (RR=1.10, 95%CI=1.08-1.13) in total alcohol and 8.9% (RR=1.08, 95%CI=1.04-1.14) in wine. For postmenopausal women, the risk increases by 11.1% (RR=1.11, 95%CI=1.09-1.13) with every 10g of total alcohol increase. Furthermore, the breast cancer alcohol-attributed percentage is higher in Europe than in North America and Asia. The effect of drinking on the incidence of breast cancer is mainly manifested in ER+ breast cancer. Quantitative analysis showed total drinking had a significant risk for breast cancer, especially for postmenopausal women. However, for different alcohols, just wine intake has the similar results.

Tea consumption and colorectal cancer risk: a meta-analysis of prospective cohort studies.

Data from in vitro and animal studies support the preventive effect of tea(Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94-1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90-1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86-1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82-1.00, P < 0.05) compared to the female studies that adjusted for coffee intake (RR = 0.97; 95% CI 0.87-1.09, P > 0.05). Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female.

Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies

Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989–1993, 2000–2001, 2006–2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose–response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose–response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645

Prognostic Value of NT-proBNP After Ischemic Stroke: A Systematic Review and Meta-analysis of Prospective Cohort Studies

Background: Many studies have evaluated the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and its prognostic value in ischemic stroke. However, a widespread consensus has not been reached. Therefore, we completed a meta-analysis to evaluate the prognostic significance of NT-proBNP for mortality and functional outcome in patients with ischemic stroke. Methods: We performed a systematic search and review using the PubMed and EMBASE databases to identify literature that reported a correlation between NT-proBNP and mortality and functional outcome in ischemic stroke patients. Results: Eleven studies inclusive of 10,498 patients met the inclusion criteria. Elevated plasma NT-proBNP levels were associated with increased risk of mortality in ischemic stroke patients (all-cause mortality: odds ratio [OR] = 2.43, 95% confidence interval [CI] 1.62-3.64, P < .001, I2=74.3%; cardiovascular mortality: OR = 2.01, 95% CI 1.55-2.61, P < .001, I2 = 42.6%). In addition, unfavorable functional outcomes were observed in patients with higher levels of NT-proBNP (OR = 1.68, 95% CI 1.13-2.50, P = .01, I2 = 90.8%) after ischemic stroke. Conclusions: This meta-analysis demonstrates that NT-proBNP could be a predictor of mortality and functional outcome in ischemic stroke patients.

Combined lifestyle factors, incident cancer, and cancer mortality: a systematic review and meta-analysis of prospective cohort studies

BackgroundCancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.MethodsEMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.ResultsThe HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66–0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42–0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.ConclusionsAdopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention.

Dairy Intake and Risk of Cardiovascular Disease.

Due to inconsistent findings on dairy consumption and CVD and all-cause mortality, we performed a narrative literature review to the current literature on dairy and its association with CVD. Due to their complex biochemistry, dairy consumption is a rather heterogeneous exposure. Multiple pathways have been proposed from dairy consumption and CVD. Current guidelines advocate for consumption of low-fat dairy products particularly milk, cheese, and yogurt, although the evidence for this is scant. Randomized clinical trials and large prospective studies on lipid-related cardiometabolic disease risk factors are consistent with results from most meta-analyses of prospective cohort studies, which suggest null or inverse relationship between CVD risk and mortality with dairy consumption although there is no clear dose response relationship. Most of current evidence suggests that dairy products are neutral or positive effect on human cardiovascular diseases.

Physical activity and mortality in patients with colorectal cancer: a meta-analysis of prospective cohort studies.

The association between physical activity (PA) and colorectal cancer (CRC) patients' survival is inconsistent. We conducted a systematic review and meta-analysis to summarize published articles on this issue. We performed a comprehensive search of the PubMed, Embase, and Web of Science databases for relevant articles through 28 February 2018. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Eighteen prospective cohort studies were included in the meta-analysis, with a total of 9257 cases of total mortality (TM) and 4015 cases of colorectal cancer-specific mortality (CRCSM) among 31 873 CRC survivors and 557 150 general populations. Among CRC survivors, the highest versus the lowest levels of prediagnosis PA showed decreased risks of TM (summary HR = 0.81, 95% CI: 0.76-0.87, I = 1.8%) and CRCSM (summary HR = 0.85, 95% CI: 0.77-0.98, I = 0), respectively. Significant risk reductions for TM and CRCSM were also demonstrated for postdiagnosis PA (HR = 0.63, 95% CI: 0.54-0.74; and HR = 0.64, 95% CI: 0.47-0.88, respectively). The inverse association between prediagnosis PA and cancer mortality was more pronounced for colon cancer than that for rectal cancer (P = 0.08). The summary HRs (95% CIs) of TM were 0.89 (0.83-0.97) and 0.79 (0.69-0.90) per 10 metabolic equivalent task-h/week increase in prediagnosis and postdiagnosis PA, respectively. Our meta-analysis provides comprehensive evidence that PA performed before or after cancer diagnosis is related to reduced mortality risk among CRC survivors.

Association between Intake of Sweetened Beverages with All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Background: There are inconsistent conclusions about the risk of death from the sugar and artificially sweetened beverages (SSBs and ASBs). We aimed to evaluate the association between ASBs and SSBs consumption and all-cause mortality and the dose-response relationship. Methods: We systematically searched the PubMed, Embase, Cochrane Library and Web of Science databases from their inception date to October 1st, 2019, prospective cohort studies researching the risk of all-cause mortality after various SSBs or ASBs consumption compared with the control group in non-hospitalized populations were included. Three authors screened the full-text for inclusion and performed quality assessment and data extraction. Random/fixed effects meta-analyses and dose-response analyses were performed to measure the association. We further conducted subgroup analyses to explore the source of heterogeneity and sensitivity analyses to assess the robustness of results. Three authors assessed the risk of bias and publication bias was assessed by Funnel plots and Egger’s regression test. The evidence strength was assessed by Cochrane’s GRADE approach. Findings: Across all 8 studies, 889,129 participants were included. Compared to the control group, high consumption (more than or equal to 250 ml/day) of SSBs increased the risk of all-cause mortality (hazard ratio [HR], 1.14; 95% confidence interval [95% CI], 1.05-1.25, P=0.003); similarly, high ASBs consumption has higher risk of all-cause mortality (HR, 1.14; 95% CI, 1.08-1.21, P<0.001). In contrast, low ASBs consumption (250 ml/month to 250 ml/week) showed a protect effect for the risk of all-cause mortality (HR, 0.95; 95% CI, 0.93-0.97, P<0.001).Both SSB and ASB showed a linear relationship with a 5% (2%-8%) and 10% (4%-18%) higher mortality, respectively. Interpretation: High consumption of both ASBs and SSBs showed a significant association with higher all-cause mortality; surprisingly, low ASBs consumption may relate to a decreased risk of all-cause mortality. This information may provide evidence for advancing public health policies and reducing the global burden of diseases. Funding Statement: Natural Science Foundation of Henan Province (Grant No. 182300410369), Science and Technology Innovation Talents in Universities of Henan province (16IRTSTHN021), Innovative Training Program for College Students (2019cxcy082) supported this study. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study was registered in PROSPERO, number CRD42019140581.

Association Between Cardiovascular Risk Factors and Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Association Between Cardiovascular Risk Factors and Colorectal Cancer: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Dietary Pattern, Diet Quality, and Dementia: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Diet is an important lifestyle factor that may prevent or slow the onset and progression of neurodegeneration. Some, but not all, recent studies have suggested that adherence to a healthy dietary pattern may be associated with reduced risk of dementia. In this meta-analysis, we systematically examined the associations between overall dietary patterns, assessed a priori and a posteriori, and risk of dementia. We systematically searched PubMed, Web of Science, and the Cumulative Index for Nursing and Allied Health databases from January 1, 1981 to September 11, 2019. Prospective studies published in English were included. Random-effects model was used to calculate the pooled risk ratios and 95% confidence intervals (CIs). Sixteen research articles were identified in the systematic review and 12 research articles including 66,930 participants were further included for the meta-analysis. Adherence to high diet quality or a healthy dietary pattern was significantly associated with lower risk of overall dementia (pooled risk ratio = 0.82; 95% CI: 0.70, 0.95; n = 12) and Alzheimer's disease (pooled risk ratio = 0.61; 95% CI: 0.47, 0.79; n = 6) relative to those with low diet quality or an unhealthy dietary pattern. Subgroup analyses stratified by age, sex, follow-up duration, diet quality assessment approach, study location, and study quality generated similar results. Adherence to a healthy dietary pattern was associated with lower risk of overall dementia. Further randomized controlled trials are needed to provide additional evidence about the role of a healthy diet on the development and progression of dementia.

Relation of Total Sugars, Sucrose, Fructose, and Added Sugars With the Risk of Cardiovascular Disease: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies

ObjectiveTo determine the association of total and added fructose-containing sugars on cardiovascular disease (CVD) incidence and mortality. MethodsMEDLINE, EMBASE and Cochrane Library were searched from January 1, 1980, to July 31, 2018. Prospective cohort studies assessing the association of reported intakes of total, sucrose, fructose and added sugars with CVD incidence and mortality in individuals free from disease at baseline were included. Risk estimates were pooled using the inverse variance method, and dose-response analysis was modeled. ResultsEligibility criteria were met by 24 prospective cohort comparisons (624,128 unique individuals; 11,856 CVD incidence cases and 12,224 CVD mortality cases). Total sugars, sucrose, and fructose were not associated with CVD incidence. Total sugars (risk ratio, 1.09 [95% confidence interval, 1.02 to 1.17]) and fructose (1.08 [1.01 to 1.15]) showed a harmful association for CVD mortality, there was no association for added sugars and a beneficial association for sucrose (0.94 [0.89 to 0.99]). Dose-response analyses showed a beneficial linear dose-response gradient for sucrose and nonlinear dose-response thresholds for harm for total sugars (133 grams, 26% energy), fructose (58 grams, 11% energy) and added sugars (65 grams, 13% energy) in relation to CVD mortality (P<.05). The certainty of the evidence using GRADE was very low for CVD incidence and low for CVD mortality for all sugar types. ConclusionCurrent evidence supports a threshold of harm for intakes of total sugars, added sugars, and fructose at higher exposures and lack of harm for sucrose independent of food form for CVD mortality. Further research of different food sources of sugars is needed to define better the relationship between sugars and CVD. Registrationclinicaltrials.gov, NCT01608620

Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies.

The quantitative association between serum/dietary magnesium and cardiovascular disease (CVD) remains unclear. We conducted a dose-response meta-analysis to evaluate the quantitative association between serum/dietary magnesium and CVD, including coronary heart disease (CHD). PubMed, China National Knowledge Infrastructure, and Web of Science were searched for publications. STATA 12.0 was used to analyze data. We used the random-effects model to reduce heterogeneity. Eighteen prospective cohort studies with 544,581 participants and 22,658 CVD cases were included. The follow-up duration was 1-28 years. The pooled relative risk (RR) of CVD for the relatively normal versus lowest serum and dietary magnesium level was 0.64 {[95% confidence interval (CI): 0.51-0.80] and 0.90 [95% CI: 0.84-0.96]}. The pooled RR of CHD for the relatively normal versus lowest serum and dietary magnesium level was 0.70 (95% CI: 0.57-0.85) and 0.86 (95% CI: 0.77-0.94). We noted a significant association between increasing serum magnesium levels (per 0.1-mg/dL increase) and risk of CVD (RR: 0.93, 95% CI: 0.88-0.97) and CHD (RR: 0.90, 95% CI: 0.84-0.96) and between dietary magnesium levels (per 100-mg/d increase) and risk of CVD (RR: 0.90, 95% CI: 0.83-0.96) and CHD (RR: 0.92, 95% CI: 0.82-0.98). Serum/dietary Mg level comparisons presented a 7%-10% decrease in CVD/CHD risk. The dose-response meta-analyses showed linear relationships between serum magnesium and CVD (Pnonlinearity = 0.833) or CHD (Pnonlinearity = 0.193) and dietary magnesium and CVD (Pnonlinearity = 0.463) or CHD (Pnonlinearity = 0.440). Increasing dietary magnesium or serum magnesium level is linearly and inversely associated with the risk of total CVD and CHD events.

Liver Enzymes and the Risk of Atrial Fibrillation: A Meta-Analysis of Prospective Cohort Studies.

Background: The association between liver enzymes and the future development of atrial fibrillation (AF) from observational studies is unclear. We, therefore, performed a meta-analysis to systematically evaluate the relationship between liver enzymes and AF risk. Methods: We searched the PubMed and Embase databases for observational cohort studies assessing the association between liver enzymes and AF risk. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Results: Five prospective studies with 282,615 participants and 7062 AF events were included. The pooled fully adjusted RRs (95% CIs) for AF were 1.10 (1.06-1.14) per 1-standard deviation change in log baseline level of gamma glutamyltransferase (GGT). No positive association was found between alanine aminotransferase (ALT, RR 1.04, 95% CI 0.90-1.20, p = 0.607) or aspartate aminotransferase (AST, RR 1.05, 95% CI 0.96-1.15, p = 0.268) and the risk of AF. Conclusions: The baseline GGT level is positively associated with the AF risk in a log-linear manner. We found no significant association between ALT or AST and the risk of AF. However, further well-designed prospective studies are needed to confirm these findings and elucidate the pathophysiological mechanisms.

Blood Pressure Variability and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis of Population-Based Cohorts.

Background and Purpose- Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia. Methods- A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models. Results- These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 [95% CI, 1.06-1.50]). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 [95% CI, 0.74-1.16]) and the presence of microbleeds (odds ratio, 1.13 [95% CI, 0.89-1.44]) were not statistically significant. Conclusions- A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.

Prognostic value of von Willebrand factor for patients with atrial fibrillation: a meta-analysis of prospective cohort studies

BackgroundIt is unknown whether an abnormal level of von Willebrand factor (vWF) is correlated with the prognosis of patients with atrial fibrillation (AF) and current findings are controversial. This meta-analysis...

Physical activity and risk of venous thromboembolism: systematic review and meta-analysis of prospective cohort studies

The inverse association between physical activity and arterial thrombotic disease is well established. Evidence on the association between physical activity and venous thromboembolism (VTE) is divergent. We conducted a systematic review and meta-analysis of published observational prospective cohort studies evaluating the associations of physical activity with VTE risk. MEDLINE, Embase, Web of Science, and manual search of relevant bibliographies were systematically searched until 26 February 2019. Extracted relative risks (RRs) with 95% confidence intervals (CIs) for the maximum versus minimal amount of physical activity groups were pooled using random effects meta-analysis. Twelve articles based on 14 unique prospective cohort studies comprising of 1,286,295 participants and 23,753 VTE events were eligible. The pooled fully-adjusted RR (95% CI) of VTE comparing the most physically active versus the least physically active groups was 0.87 (0.79–0.95). In pooled analysis of 10 studies (288,043 participants and 7069 VTE events) that reported risk estimates not adjusted for body mass index (BMI), the RR (95% CI) of VTE was 0.81 (0.70–0.93). The associations did not vary by geographical location, age, sex, BMI, and methodological quality of studies. There was no evidence of publication bias among contributing studies. Pooled observational prospective cohort studies support an association between regular physical activity and low incidence of VTE. The relationship does not appear to be mediated or confounded by BMI.