Meta-analysis Of Prospective Cohort Studies Research Articles

Dose-response relationship between physical activity and the morbidity and mortality of cardiovascular disease among individuals with diabetes: A meta-analysis of prospective cohort studies.

Diabetes, a chronic condition affecting various organs, is frequently associated with abnormal lipid metabolism, notably increased cholesterol and triglyceride levels. These lipid abnormalities are closely linked to the development and advancement of cardiovascular disease (CVD). Although regular physical activity (PA) has consistently shown benefits in reducing CVD risk in the general population, its precise influence on CVD risk among diabetic patients remains uncertain, particularly regarding dose-response relationships. This study aimed to summarize the evidence from prospective studies on the association between PA and CVD morbidity and mortality in individuals with diabetes, and to explore the optimal levels for public health recommendation. We systematically reviewed prospective cohort studies in PubMed, EMBASE, and Web of Science up to December 2022, with inclusion criteria specifying the studies published in English and included adult participants diagnosed with diabetes. A random-effects model was used to pool the relative risk (RR) with the corresponding 95% confidence interval (CI) comparing the highest with the lowest PA categories in each study for qualitative evaluation. In addition, linear and spline regression analyses were used to estimate dose-response associations. The meta-analysis included 12 prospective cohort studies, involving a total of 109,820 participants with diabetes. The combined results revealed that higher levels of PA were associated with a reduced risk of CVD. The RR of CVD for the highest compared with the lowest PA category was 0.62 (95% CI, 0.51-0.73). In addition, there were four studies describing leisure-time physical activity (LTPA) and the pooled RR was 0.68 (95% CI, 0.52-0.83) for the highest versus the lowest activity. The linear regression model revealed that each 10 MET-h/week of incrementally higher PA was associated with a 19.0% (95% CI, 11.6%-25.7%) and a 6.9% (95% CI, 4.5%-9.3%) reduction in CVD morbidity and mortality. Additionally, spline regression curves showed nonlinear relationships between PA levels and the risk of CVD and CVD mortality (both P-nonlinearity <0.001), with a limited reduction in CVD risk and some further reduction in CVD mortality above 20 MET-h per week of PA levels. For patients with diabetes, especially type 2 diabetes, there was a dose-response relationship between increased PA and reduced risk of CVD morbidity and mortality. The observed PA threshold is consistent with the recommended level for the general population. Gradually moving from inactivity to a guideline-recommended PA level could therefore significantly reduce the burden of CVD in patients with diabetes.

Effects of whole grains on glycemic control: a systematic review and dose-response meta-analysis of prospective cohort studies and randomized controlled trials

PurposeWhole grains have recently been promoted as beneficial to diabetes prevention. However, the evidence for the glycemic benefits of whole grains seems to conflict between the cohort studies and randomized control trials (RCTs). To fill the research gap, we conducted a meta-analysis to determine the effects of whole grains on diabetes prevention and to inform recommendations.MethodsWe searched PubMed, Clarivate Web of Science, and Cochrane Library until March 2024. We used the risk ratio (RR) of type 2 diabetes to represent the clinical outcomes for cohort studies, while the biomarkers, including fasting blood glucose and insulin, HbA1C, and HOMA-IR, were utilized to show outcomes for RCTs. Dose-response relationships between whole grain intakes and outcomes were tested with random effects meta-regression models and restricted cubic splines models. This study is registered with PROSPERO, CRD42021281639.ResultsTen prospective cohort studies and 37 RCTs were included. Cohort studies suggested a 50 g/day whole grain intake reduced the risk of type 2 diabetes (RR = 0.761, 95% CI: 0.700 to 0.828, I2 = 72.39%, P < 0.001) and indicated a monotonic inverse relationship between whole grains and type 2 diabetes rate. In RCTs, whole grains significantly reduced fasting blood glucose (Mean difference (MD) = -0.103 mmol/L, 95% CI: -0.178 to -0.028; I2 = 72.99%, P < 0.01) and had modest effects on HbA1C (MD = -0.662 mmol/mol (-0.06%), 95% CI: -1.335 to 0.010; I2 = 64.55%, P = 0.05) and HOMA-IR (MD = -0.164, 95% CI: -0.342 to 0.013; I2 = 33.38%, P = 0.07). The intake of whole grains and FBG, HbA1C, and HOMA-IR were significantly dose-dependent. The restricted spline curves remained flat up to 150 g/day and decreased afterward. Subgroup analysis showed that interventions with multiple whole-grain types were more effective than those with a single type.ConclusionOur study findings suggest that a daily intake of more than 150 g of whole grain ingredients is recommended as a population approach for diabetes prevention.

Dietary fat intake with risk of gestational diabetes mellitus and preeclampsia: a systematic review and meta-analysis of prospective cohort studies.

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are commonly observed medical complications in pregnancy. Dietary total fat and fatty acids associated with GDM and PE risk have been examined in several epidemiological studies. In some instances, systematic reviews and meta-analyses might provide more accurate dietary recommendations. This systematic review and dose-response meta-analysis was conducted to investigate the association between dietary total fat and fatty acids and the risk of GDM and PE. Research on dietary fat intake and the risk of GDM and PE was conducted through systematic searches of the PubMed, Scopus, and Web of Science databases for articles published up to August 19, 2023. An investigation of associations between dietary intake of total fat and fatty acids and the risk of GDM and PE was performed using prospective cohort study designs. Twenty-one prospective cohort studies were considered eligible. Findings indicated that higher intakes of total fat (relative risk [RR], 1.08; 95% confidence interval [CI], 1.02-1.14), animal fat (RR, 1.56; 95%CI, 1.34-1.89), vegetable fat (RR, 1.23; 95%CI, 1.05-1.45), dietary cholesterol (RR, 1.48; 95%CI, 1.10-2.00), and omega-3 fatty acid (RR, 1.11; 95%CI, 1.02-1.20) are associated with a greater risk of GDM. However, no significant association was found between dietary total fat and fatty acids and the risk of PE. Dose-response meta-analyses suggested every 10% increment in total energy intake from total fat, 5% from animal fat, 5% from vegetable fat, and 100 mg from cholesterol was related to 15%, 12%, 7%, 14%, and 20% higher GDM risk, respectively. Overall, total fat, animal fat, vegetable fat, dietary cholesterol, and omega-3 fatty acid consumption are associated with a small but statistically significant increase in GDM risk. PROSPERO (CRD42023466844).

Risk of stroke with different levels of leisure-time physical activity: a systematic review and meta-analysis of prospective cohort studies

BackgroundLeisure-time physical activity (LTPA) protects against vascular diseases. Whether and to what extent different levels of LTPA, including lower ones, benefit stroke prevention is still unclear.MethodsWe searched prospective cohort studies,...

Association between tea consumption and risk of kidney stones: results from dose-response meta-analysis of prospective studies and Mendelian randomization analysis.

The association between tea consumption and kidney stones is inconsistent in observational studies. Thus, we performed a dose-response meta-analysis of prospective cohort studies and a two-sample Mendelian randomization (MR) analysis to identify this association. The prospective cohort studies reporting the relationship between tea consumption and kidney stones were searched from PubMed, the Cochrane Library, EMBASE, and Web of Science from inception to December 1, 2023. For MR analysis, the summary-level data for tea consumption and kidney stones were extracted from the UK Biobank available data and the 8th release of the FinnGen consortium, respectively. The inverse-variance weighted (IVW) method was the primary analytical method. In our dose-response meta-analysis, four prospective cohort studies involving 1,263,008 participants were included, and tea consumption was found to have significant associations with kidney stones (RR: 0.80, 95% CI: 0.73-0.87). We also observed a substantially linear negative relationship between tea consumption and the risk of kidney stones. In MR analysis, the IVW method indicated that tea consumption was inversely associated with kidney stones (OR: 0.71, 95% CI: 0.53-0.94). Our study confirmed a causal relationship between tea consumption and kidney stones, and higher tea consumption may reduce the risk of kidney stones.

Weight loss and mortality in people living with HIV: a systematic review and meta-analysis

BackgroundIn the first reported cases of human immunodeficiency virus (HIV) infection, people living with HIV (PLHIV) suffered weight loss, which was an independent predictor of mortality. Highly active antiretroviral therapy (HAART) has changed this scenario for ideal weight, overweight, and even obesity. However, some PLHIV, even on HAART, continue to lose weight. Thus, the guiding question of the study was: do PLHIV hospitalized using HAART with weight loss have higher mortality than hospitalized PLHIV using HAART without weight loss?MethodA systematic review and meta-analysis of prospective cohort studies published in English, Spanish, or Portuguese, searched in the MedLine, Embase, and LILACS databases from March 2020, until October 2023, reported by MOOSE. We analyzed the methodological quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Tool for Cohort Studies; used the risk ratio (RR) to calculate the probability of hospitalized PLWH who lost weight dying, applied the random effect model and created the funnel plot. We used the inverse variance test estimated by the Mantel-Haenszel method, considering a 95% confidence interval (CI), heterogeneity (I2), total effect size (Z), and significance value of p < 0.05. We performed a sensitivity analysis with meta-regression and meta-analyses on subgroups to diagnose influence and outliers. The quality of evidence and strength of recommendation were analyzed using the Grading of Recommendations Assessment, Development, and Evaluation system (GRADE).ResultsWe included 10 of the 711 studies identified, totaling 1,637 PLHIV. The studies were from South Africa (1), Canada (1), China (1), Brazil (1), Cameroon (1), Ethiopia (1), Thailand (1), Colombia (1), and Tanzania (2), from 1996 to 2017. The average age of the participants was 33.1 years old, and the male was predominant. The leading causes of hospital admission were related to co-infections, and the average hospitalization time was 20.5 days. The prevalence of death in hospitalized PLHIV using HAART who lost weight was 57.5%, with a 1.5 higher risk of dying (RR: 1.50, 95% CI: 1.03, 2.19, p = 0.04) than hospitalized PLHIV who did not lose weight.ConclusionWe concluded, with a very low confidence level, that that weight loss significantly increased the risk of death in hospitalized PLWH using HAART.Trial Registration and fundingPROSPERO International Prospective Register of Systematic Reviews CRD42020191246 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020191246.

Olive oil intake and cardiovascular disease, cancer, and all-cause mortality: a systematic review and dose-response meta-analysis of prospective cohort studies.

Background: Currently, the reported links between olive oil intake and cardiovascular disease (CVD), cancer morbidity and mortality, and all-cause mortality are inconsistent. The aim of this meta-analysis is to study the reported correlations of olive oil intake with CVD, coronary heart disease (CHD), stroke and cancer incidence and mortality, and all-cause mortality. Methods: PubMed, Embase, and Web of Science were searched until March 7, 2024. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were estimated by the random-effects model. Nonlinear dose-response relationships were modeled with restricted cubic splines. This study has been registered at PROSPERO (CRD42023419001). Results: Overall, 30 articles covering 2 710 351 participants were identified. Higher olive oil intake was linked with a reduced risk of CVD incidence (RR: 0.85; 95% CI: 0.77, 0.93), CHD incidence (RR: 0.85; 95% CI: 0.72, 0.99), CVD mortality (RR: 0.77; 95% CI: 0.67, 0.88), and all-cause mortality (RR: 0.85; 95% CI: 0.81, 0.89). For a 10 g d-1 increment of olive oil intake, the risk of CVD incidence, stroke incidence, CVD mortality, and all-cause mortality decreased by 7%, 5%, 8%, and 8%, respectively. No association was found between olive oil intake and cancer incidence and mortality. Nonlinear relationships between olive oil intake and CVD and all-cause mortality were observed, with a reduced risk from intakes ranging from 0 to 18 g d-1 and 0 to 22 g d-1, respectively. Conclusion: Our study found that high olive oil intake was related to a lower risk of CVD and CHD incidence and CVD mortality and all-cause mortality.

Breakfast skipping and risk of all-cause, cardiovascular and cancer mortality among adults: a systematic review and meta-analysis of prospective cohort studies.

Background: Numerous studies reported inconsistent association between breakfast skipping and all-cause, cardiovascular disease (CVD) and cancer mortality. Therefore, we conducted a systematic review and meta-analysis to elucidate these associations. Methods: PubMed, Embase, and Web of Science databases were searched up to July 2023 for prospective cohort studies that assessed the association between breakfast skipping and all-cause, CVD and cancer mortality in general adults. A random effect model was used to estimate the pooled hazard ratio (HR) and 95% confidence intervals (CIs), with subgroup analysis and sensitivity analysis performed. The Newcastle-Ottawa Scale (NOS) was used to assess the study and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to assess the risk of bias. Results: The final analysis included 9 cohort studies including 242 095 participants, with 6 studies for all-cause mortality, 4 studies for CVD mortality, and 2 studies for cancer mortality. Compared to regular breakfast consumption, skipping breakfast was associated with a higher risk of all-cause (HR: 1.27, 95% CI, 1.07-1.51, I2 = 77%), CVD (HR 1.28, 95% CI 1.10-1.50, I2 = 0), and cancer (HR: 1.34, 95% CI: 1.11-1.61, I2 = 0%) mortality. Sensitivity analysis revealed inconsistent results in all-cause and CVD mortality. Subgroup analysis showed significant association in studies with larger participants, longer follow-up, adjustments for energy intake, and high-quality articles. GRADE showed very low evidence for all-cause mortality and low evidence for CVD and cancer mortality. Conclusion: The findings underscore the importance of regular breakfast habits for health and longevity. However, these results require careful interpretation due to geographic limitations, potential heterogeneity, and instability.

Dietary indices underpinning front-of-pack nutrition labels and health outcomes: a systematic review and meta-analysis of prospective cohort studies

BackgroundNutrient profiling systems are increasingly used to characterize the healthfulness of foods for front-of-package (FOP) labeling, which have been proposed as an effective public health strategy to help people make healthier food choices. ObjectiveThis study aimed to review available evidence from cohort studies that evaluated the association of dietary indices underpinning FOP nutrition labels with all-cause mortality and incidence of cardiovascular diseases (CVDs) or cancer. MethodsPubMed, Web of Science, and Scopus were systematically searched up to October 2023. We included articles if they were prospective cohort studies, if the exposure was any dietary index underpinning FOP nutrition labels [e.g., the modified Food Standard Agency-Nutrient Profiling System (FSAm-NPS) and the Health Star Rating System], and if outcomes were all-cause mortality or incidence of or mortality due to CVD and cancer. Random-effects models were used to calculate the pooled hazard ratios (HRs) and 95% CIs. ResultsWe identified 11 records (7 unique prospective studies), which were included in the systematic review. The meta-analysis comprised 8 studies analyzing the FSAm-NPS dietary index (DI) as exposure. The pooled HRs associated with a 2-unit increase in the FSAm-NPS DI of all-cause mortality, CVD, and cancer risk were 1.06 (95% confidence interval [CI]: 0.99, 1.13; I2: 80%), 1.08 (95% CI: 1.00, 1.18; I2: 70%), and 1.09 (95% CI: 1.00, 1.19; I2: 77%), respectively. The Chilean Warning Label score and the Health Star Rating systems were examined by 1 study each and were significantly associated with the outcomes. ConclusionsDIs underpinning most common FOP nutrition labels and reflecting nutrient-poor diets show a tendency toward an increased incidence of CVD and cancer, but the observed effects are quite modest in magnitude. Further studies at the population level are needed to support the widely shared hypothesis that FOP labels, possibly in conjunction with other interventions, may contribute to reduce noncommunicable disease risk.This meta-analysis was registered at PROSPERO as CRD42021292625

Mechanical thrombectomy in M1 and M2 segments of middle cerebral arteries: A meta-analysis of prospective cohort studies

Mechanical thrombectomy in M1 and M2 segments of middle cerebral arteries: A meta-analysis of prospective cohort studies

Abdominal obesity and digestive system cancer: a systematic review and meta-analysis of prospective studies

BackgroundThe diagnostic criteria for abdominal obesity are usually waist circumference or waist-to-hip ratio. The magnitude of the risks for cancers of the digestive system and abdominal obesity is unknown. To assess whether abdominal obesity increases the risk of digestive cancer, we conducted a systematic review and meta-analysis of prospective cohort studies in a database.MethodsPubMed, Embase, and Web of Science databases were searched from their inception to December 2022. The 9-star Newcastle Ottawa Scale was used to assess study quality. Pooled relative risks and 95% confidence intervals were calculated using fixed or random effect models respectively. The stability of the results was explored by one-by-one exclusion. Subgroup analysis was conducted to explore sources of heterogeneity. Publication bias was evaluated by Begg’s and Egger’s tests.ResultsA total of 43 cohort studies were included. There were 42 and 31 studies in the meta-analysis of waist circumference and waist-to-hip ratio on digestive system cancer, respectively. The results of the meta-analysis revealed that the greater waist circumference and waist-to-hip ratio were correlated with increased incidence of digestive system cancers: waist circumference: RR 1.48, 95% CI 1.38-1.59, p < 0.001; waist-to-hip ratio: RR 1.33, 95% CI 1.28-1.38, p = 0.001. Subgroup analysis by cancer type showed that higher WC and WHR would increase the prevalence of LC, PC, GC, EC, and CRC. The sensitivity analysis was conducted by a one-by-one elimination method, and the results of the meta-analysis remained stable. It is proved that the results were robust by the trim-and-fill method.ConclusionsThere was evidence to suggest that abdominal obesity increased the incidence of digestive cancer, it is necessary to take appropriate measures to reduce abdominal obesity. Waist circumference and waist-to-hip ratio may be better predictors of digestive system cancers. However, the association between waist circumference and digestive system cancer was greater, so more attention should be paid to measuring abdominal obesity with waist circumference.

Dietary fiber intake and all-cause and cause-specific mortality: An updated systematic review and meta-analysis of prospective cohort studies

Accumulating evidence supports the effects of dietary fiber on the risk of non-communicable diseases (NCDs). However, there is no updated systematic review and meta-analysis that compares and pools the effect of different types of fiber on mortality. In this systematic review and meta-analysis, all prospective cohort studies that evaluated the relationship between dietary fiber intake and all-cause or cause-specific mortality were included. The PubMed, SCOPUS, and Web of Science databases were searched up to October 2022. Data extraction and quality assessment were performed by two researchers independently. Heterogeneity between studies was assessed using Chi-square based test. Random/fixed effect meta-analysis was used to pool the hazard ratios (HR) or relative risks (RR) and 95% confidence intervals (CI) for the association between different types of fiber and mortality. This systematic review included 64 eligible studies, with a total sample size of 3512828 subjects, that investigated the association between dietary fiber intake and mortality from all-cause, cardiovascular disease (CVD), and cancer. Random-effect meta-analysis shows that higher consumption of total dietary fiber, significantly decreased the risk of all-cause mortality, CVD-related mortality, and cancer-related mortality by 23, 26 and 22% (HR:0.77; 95%CI (0.73,0.82), HR:0.74; 95%CI (0.71,0.77) and HR:0.78; 95%CI (0.68,0.87)), respectively. The consumption of insoluble fiber tended to be more effective than soluble fiber intake in reducing the risk of total mortality and mortality due to CVD and cancer. Additionally, dietary fiber from whole grains, cereals, and vegetables was associated with a reduced risk of all-cause mortality, while dietary fiber from nuts and seeds reduced the risk of CVD-related death by 43% (HR:0.57; 95% CI (0.38,0.77)). This comprehensive meta-analysis provides additional evidence supporting the protective association between fiber intake and all-cause and cause-specific mortality rates.

Abstract 13681: Association of Serum Trimethylamine N-oxide Levels With Cardiovascular Disease and All-Cause Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Background: Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite of red meat, has emerged as a potential biomarker for CVD and all-cause mortality. It is also found in preformed amounts in fish. However, the association between serum TMAO levels and CVD outcomes remain unclear. Aim: To conduct a systematic review and dose-response meta-analysis evaluating the association between serum TMAO and CVD and all-cause mortality in prospective cohort studies. Methods: A comprehensive literature search was conducted in MEDLINE, EMBASE, and Cochrane Library up to and including March 6, 2023. A manual search through references found in reviews and meta-analyses was also conducted. Studies reporting hazard ratios (HRs) or relative risks (RRs) with 95% confidence intervals (CIs) for the association between serum TMAO levels and CVD or all-cause mortality in adults ≥ 18 years with follow-up of ≥ 1 year were included. Random-effects models were utilized for pooled risk estimates and assess the dose-response. GRADE was used to evaluate certainty of evidence. Results: 2459 papers, 44 prospective cohort studies were included involving 84771 participants included in final analysis (fig.1). Pooled analyses revealed a significant positive association between elevated serum TMAO levels and the risk of total CVD (RR 1.29 [1.16-1.44]), CVD mortality (RR 1.51 [1.23-1.87]) and all-cause mortality (RR 1.30 [1.21,1.39]). Non-significant associations were found for MI, stroke, total CHD, MI mortality and CHD mortality. All outcomes were of low to very low certainty.Dose response analysis revealed a significant linear association with all-cause mortality (RR 1.01 [95% CI 1.01, 1.02] per 2μM/L) up to a threshold of 6μM/L and total CVD (RR 1.04 [1.02-1.06]). Conclusion: This study provides evidence supporting the positive association of serum TMAO levels with increased risk of total CVD, CVD mortality and all-cause mortality. A recent review found 13/15 studies demonstrated a strong positive correlation between TMAO and fish intake, complicating the hypotheses relating TMAO in red meat and CVD risk. Thus, further assessments of diet components are needed to explore the clinical implications of the associations found in our study.

Uric acid levels and risk of cognitive impairment: Dose-response meta-analysis of prospective cohort studies.

Studying the effects of uric acid levels on cognitive function and quantifying the dose-response relationship. Based on PubMed and Embase search terms, we identified prospective cohort studies that included blood uric acid as a risk factor and cognitive impairment as a result up to September 2022. We extracted pooled relative risks (RRs) and corresponding 95% confidence intervals (CIs). Nine reports (including 488,915 participants and 5516 cognitive impairment cases) with median follow-up of 8.8-22 years were eligible for analyses. Compared with lowest category of blood uric acid concentration, the combined RR of cognitive impairment events in the highest classification was 0.81 (95% CI: 0.70-0.92, P < 0.001). Dose-response analysis of eight reports (including 484,297 participants and 5059 cognitive impairment cases) showed that there was no evidence of a curvilinear relationship between blood uric acid levels and cognitive impairment (P = 0.51 for nonlinear relationship). The summary RR of cognitive impairment for an increase of 1 mg/dL blood uric acid level was 0.98 (95% CI: 0.95-1.00; linear trend P = 0.07, I2 = 67.1%, heterogeneity P < 0.05). There was also a linear negative association between blood uric acid levels and cognitive impairment risk in the male subgroup analysis (RR = 0.97, 95% CI: 0.95-0.99, P < 0.05). Levels of blood uric acid are not related to risk of cognitive impairment. A subgroup analysis shows that the rise in blood uric acid levels in the male population is related to a decreased risk of cognitive impairment. These results need to be confirmed by further studies.

Exploring high-protein diets in the context of cardiac rehabilitation.

The review aims to explore the potential benefit and risk of high-protein diets (HPD) regarding the comorbidity of sarcopoenia and CVD in the setting of cardiac rehabilitation (CR). CR is standard care for individuals who have experienced a cardiac event, but the current practice of predominantly aerobic exercise, a lower-fat diet and weight loss poorly addresses the issue of sarcopoenia. HPD, especially when combined with resistance exercise (RE), may be valuable adjuncts to current CR practice and benefit both muscle and cardiovascular health. Meta-analyses and randomised controlled trials of HPD and CVD risk show beneficial but variable effects regarding weight loss, the lipid profile, insulin resistance and lean body mass in those living with or high risk of CVD. Meta-analyses of prospective cohort studies on hard CVD endpoints favour lower- and plant-protein diets over higher animal protein, but the evidence is inconsistent. HPD augment the strength and muscle gaining benefits of RE in older populations, but there are no published data in those living with CVD providing promising opportunities for CR research. HPD raise concern regarding renal and bone health, the microbiome, branched chain amino acids and environmental sustainability and findings suggest that plant-based HPD may confer ecological and overall health advantages compared to animal-based HPD. However, incorporating RE with HPD might alleviate certain health risks. In conclusion, a largely plant-based HPD is deemed favourable for CR when combined with RE, but further research regarding efficacy and safety in CR populations is needed.

Correction: Effect of Milk and Cultured Milk Products on Type 2 Diabetes: A Global Systematic Review and Meta-analysis of Prospective Cohort Studies

Correction: Effect of Milk and Cultured Milk Products on Type 2 Diabetes: A Global Systematic Review and Meta-analysis of Prospective Cohort Studies

OR25-04 Factors Affecting Testosterone Concentrations In Men: Individual Participant Data Meta-analyses From The Androgens In Men Study

Abstract Disclosure: R.J. Marriott: None. K. Murray: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. B.B. Yeap: None. Different factors modulate circulating testosterone in men, impacting interpretation of reference ranges. We aimed to clarify factors associated with variations in sex hormone concentrations by conducting individual participant data (IPD) meta-analyses of prospective cohort studies of adult men with total testosterone measured using mass spectrometry. The Androgens In Men Study protocol was submitted to PROSPERO (23 July 2019), registered (20 November 2019; CRD42019139668) and published (BMJ Open 2020; 10: e034777). A systematic review (14 June-31 December 2019) identified prospective cohort studies (BMJ Open 2021; 11: e048013). IPD data were requested. Cross-sectional analyses related total testosterone (measured using mass spectrometry), sex hormone binding globulin (SHBG), luteinising hormone (LH), dihydrotestosterone (DHT) and estradiol (also measured using mass spectrometry) concentrations to sociodemographic, lifestyle, and health factors. Summary curves and effect estimates with 95% confidence intervals (CIs) were obtained using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (25,149 men). There was a non-linear association of testosterone with age, with negligible change among men aged 17-70 years (1SD increase about age 43.5, from 35.7 to 51.3 years -0.27 nmol/L, CI -0.71 to 0.18) and decreasing testosterone with age for men &amp;gt;70 years (1SD increase about age 84.5, from 76.7 to 92.3 years -1.55 nmol/L, CI -2.05 to -1.06). Testosterone was inversely associated with BMI (1SD increase about 27.5 kg/m2, from 25.5 to 29.6 kg/m2 -2.42 nmol/L, CI -2.70 to -2.13). Testosterone concentrations were lower for men who: were married/de facto (-0.57 nmol/L); undertook ≤75 minutes vigorous physical activity/week (-0.51 nmol/L); former smokers (-0.34 nmol/L); had hypertension (-0.53 nmol/L), cardiovascular disease (-0.35 nmol/L), cancer (-1.39 nmol/L), or diabetes (-1.43 nmol/L); all CIs excluded zero. SHBG increased with age (per SD increase in age 11.3 nmol/L, CI 9.0 to 13.6) and decreased with BMI (per SD increase in BMI -5.9 nmol/L, CI -6.9 to -5.0). There was little change in mean LH with age in men &amp;lt;70 years (1SD increase in age 0.10 IU/L, CI -0.08 to 0.28), but an increase in LH with age in men ≥70 years (1SD increase in age 4.14 IU/L, CI 3.71 to 4.56). DHT and estradiol were less prominently associated with these factors. Multiple factors are associated with variation in male testosterone and SHBG concentrations, with evidence of primary impairment of testicular hormone production after age 70 years. Interpretation of testosterone results in individuals needs to account for these factors, especially age &amp;gt;70 years, BMI, diabetes and cancer. Further research is needed to determine health impacts of declining testosterone in older men. Presentation Date: Saturday, June 17, 2023

THU652 Associations Of Testosterone, Dihydrotestosterone, Estradiol And Sex Hormone-binding Globulin With All-cause And Cardiovascular Mortality, And Incident Cardiovascular Events In Men: Individual Participant Data Meta-analyses

Abstract Disclosure: B.B. Yeap: None. R.J. Marriott: None. L. Antonio: None. S. Bhasin: None. A.S. Dobs: None. D.J. Handelsman: None. G.J. Hankey: None. R. Haring: None. A.M. Matsumoto: None. C. Ohlsson: None. E.S. Orwoll: None. D.M. Vanderschueren: None. G.A. Wittert: None. F.C. Wu: None. K. Murray: None. Studies examining associations of circulating sex steroids with mortality risk in men show inconsistent results for testosterone (T), with limited data for dihydrotestosterone (DHT) and estradiol (E2). We aimed to clarify associations of sex steroids, sex hormone-binding globulin (SHBG) and luteinising hormone (LH) with risks of all-cause and cardiovascular disease (CVD) mortality and incident CVD events in men, by conducting individual participant data (IPD) meta-analyses of prospective cohort studies with sex steroids measured using mass spectrometry. The Androgens In Men Study protocol was registered (PROSPERO: CRD42019139668) and published (BMJ Open 2020;10:e034777). A systematic review (completed Dec 2019) identified relevant studies (BMJ Open 2021;11:e048013). IPD were requested. Cox proportional hazards analyses related total T, SHBG, LH, DHT and E2 concentrations to risk of all-cause mortality and CVD deaths, and risk of incident CVD events. Models were adjusted for age and other sociodemographic factors, lifestyle factors, medical conditions and medications. Summary curves and hazard ratios (HRs) with 95% confidence intervals (CIs) were determined using two-stage random-effects IPD meta-analyses. Summary estimates were obtained from 11 studies (24,596 men), with median baseline age 49-76 years and 4-20 years follow-up among studies. Associations of T with all-cause and CVD mortality risk were non-linear. Risk of all-cause mortality increased for men with baseline T concentrations &amp;lt;8.7 nmol/L, and risk of CVD death increased for men with baseline T &amp;lt;5.3 nmol/L. Lower SHBG concentrations were associated with lower risk of all-cause mortality (median Quintile [Q]1 vs Q5 [Q1:Q5], 20.6 vs 68.3 nmol/L; HR=0.85, CI=0.77-0.95), and CVD death (HR=0.81, CI 0.65-1.00). Men with LH &amp;gt;10 IU/L or E2 &amp;lt;5.1 pmol/L had higher all-cause mortality, with no association of LH or E2 with CVD deaths. Associations of DHT with all-cause and CVD mortality risk were non-linear. Men with lower baseline DHT concentrations had higher risk of all-cause mortality (median Q1:Q5, 0.69 vs 2.45 nmol/L; HR=1.19, CI=1.08-1.30) and CVD deaths (HR=1.29, CI=1.03-1.61), with risk increasing for DHT &amp;gt;2.45 nmol/L. Men with baseline DHT concentrations &amp;lt;0.59 nmol/L had increased risk of incident CVD events, no other hormones were associated with this outcome. Our results suggest greater all-cause and CVD mortality risk among men with very low baseline T, higher baseline SHBG, or either lower or very high baseline DHT concentrations. There was greater risk of CVD events among men with very low baseline DHT concentrations. Potential mechanisms by which SHBG and DHT might influence mortality risk in ageing men merit further investigation. Presentation: Thursday, June 15, 2023

The associations between physical activity, sleep and sedentary behaviour, with mortality and health outcomes: A systematic review and meta-analysis of prospective cohort studies

The associations between physical activity, sleep and sedentary behaviour, with mortality and health outcomes: A systematic review and meta-analysis of prospective cohort studies

Ambulatory and home blood pressure monitoring for cardiovascular disease risk evaluation: a systematic review and meta-analysis of prospective cohort studies.

The aim of this work was to systematically review the level of evidence based on prospective cohort studies investigating the role of 24-h ambulatory blood pressure measurement (ABPM) and home blood pressure measurement (HBPM) on cardiovascular disease (CVD) risk prediction. Eight studies were included in the meta-analysis. The Der Simonian and Laird's random-effects model with standard error adjustment using the Knapp-Hartung method was used. SBP from ABPM and HBPM was significantly and positively associated with CVD risk [ combined hazard ratio per 1-SD SBP, 95% confidence interval (95% CI): 1.32, 1.19-1.45, I2 = 35.8%, and 1.30, 95% CI: 1.11-1.49, I2 = 79.1%, respectively], after adjusting for office BP levels and other potential confounders. DBP from both ABPM and HBPM was positively associated with CVD risk ( combined hazard ratio per 1-SD DBP, 95% CI: 1.15, 1.01-1.29, I2 = 73.1% and 1.21, 1.05-1.37, I2 = 84.5%, respectively). BP either from ABPM or HBPM could predict CVD risk. As so, at least one of out-of-office BP measurements have to be taken into account during the evaluation of the hypertensive population.