Meta-analysis Of Prospective Cohort Studies Research Articles

Association between Adherence to the Mediterranean Diet and Risk of Type 2 Diabetes: An Updated Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Despite earlier meta-analyses on the association between adherence to a Mediterranean diet (MD) and risk of diabetes, there is no comprehensive and updated study assessing this issue. Furthermore, no earlier study has examined the nonlinear dose-response relation between consumption of an MD and risk of diabetes. The current systematic review and meta-analysis was conducted to investigate the linear and nonlinear dose-response relation between MD and incidence of diabetes. Using relevant keywords, electronic searches for prospective studies were conducted in ISI Web of Science, PubMed, and Scopus until January 2022. The reported HRs or ORs in the primary studies were regarded as RRs. The overall effect was calculated using a random-effects model that accounts for between-study variability. The potential nonlinear dose-response associations were tested using a 2-stage hierarchical regression model. Based on 16 prospective studies (with 17 effect sizes), we found that the greatest adherence to the MD was significantly associated with a reduced risk of diabetes (pooled RR: 0.83; 95% CI: 0.77, 0.90; I2 = 79%, P ≤ 0.001). Based on linear dose-response analysis, each 1-score increase in the Mediterranean diet score was associated with a 3% decreased risk of diabetes (HR = 0.97; 95% CI: 0.96, 0.98; P < 0.001). A nonlinear relation (P-nonlinearity = 0.001) was also observed between MD score and risk of type 2 diabetes. Even modest adherence to the MD was linked to a decreased incidence of type 2 diabetes. The protocol is also registered in the International Prospective Register Of Systematic Reviews (PROSPERO) database (https://www.crd.york.ac.uk/PROSPERO/; registration ID: CRD 42021265332).

Metabolomics and Type 2 Diabetes Risk: An Updated Systematic Review and Meta-analysis of Prospective Cohort Studies.

BACKGROUNDDue to the rapidly increasing availability of metabolomics data in prospective studies, an update of the meta evidence on metabolomics and type 2 diabetes risk is warranted.PURPOSETo conduct an updated systematic review and meta-analysis of plasma, serum, and urine metabolite markers and incident type 2 diabetes.DATA SOURCESWe searched PubMed and Embase until 6 March 2021.STUDY SELECTIONWe selected prospective observational studies where investigators used high-throughput techniques to investigate the relationship between plasma, serum, or urine metabolites and incident type 2 diabetes.DATA EXTRACTIONBaseline metabolites per-SD risk estimates and 95% CIs for incident type 2 diabetes were extracted from all eligible studies.DATA SYNTHESISA total of 61 reports with 71,196 participants and 11,771 type 2 diabetes cases/events were included in the updated review. Meta-analysis was performed for 412 metabolites, of which 123 were statistically significantly associated (false discovery rate–corrected P < 0.05) with type 2 diabetes risk. Higher plasma and serum levels of certain amino acids (branched-chain, aromatic, alanine, glutamate, lysine, and methionine), carbohydrates and energy-related metabolites (mannose, trehalose, and pyruvate), acylcarnitines (C4-DC, C4-OH, C5, C5-OH, and C8:1), the majority of glycerolipids (di- and triacylglycerols), (lyso)phosphatidylethanolamines, and ceramides included in meta-analysis were associated with higher risk of type 2 diabetes (hazard ratio 1.07–2.58). Higher levels of glycine, glutamine, betaine, indolepropionate, and (lyso)phosphatidylcholines were associated with lower type 2 diabetes risk (hazard ratio 0.69–0.90).LIMITATIONSSubstantial heterogeneity (I2 > 50%, τ2 > 0.1) was observed for some of the metabolites.CONCLUSIONSSeveral plasma and serum metabolites, including amino acids, lipids, and carbohydrates, are associated with type 2 diabetes risk.

Risk factors for incident cardiovascular events among adults in low- and middle-income countries: A systematic review and meta-analysis of prospective cohort studies

The relative contributions of risk factors for cardiovascular events at a population level has received little attention in low- and middle-income countries (LMICs). We estimated the population attributable fraction (PAF) of risk factors associated with incident cardiovascular events in LMICs. We searched six databases for relevant articles, supplemented with a manual search of reference lists. Articles included in the meta-analyses were those based on prospective community-based cohorts and incorporating adjusted hazard ratios (HR) or relative risks with 95% confidence intervals (95% CI) for associations between risk factors and a composite cardiovascular and/or stroke endpoint. Pooled HRs and 95% CI were calculated using the random effects model. We assessed heterogeneity using the I2 test and study quality using the Newcastle-Ottawa Scale. We calculated the PAF of each associated risk factor. The protocol was registered in PROSPERO (CRD42019122741). We identified 18 cohorts from LMICs with 1,125,846 participants, 77,045 composite cardiovascular events and 42,216 strokes. Substantial proportions of incident cardiovascular events were attributable to hypertension (HR [95% CI], 2.23 [2.01–2.48], PAF = 28%); current smoking (1.44 [1.31–1.58], PAF = 10%); and diabetes mellitus (1.93 [1.67–2.23], PAF = 8%). Other risk factors identified included number of children, depression, bone mineral density, and air pollution. A substantial proportion of incident cardiovascular events were linked to traditional metabolic and behavioural modifiable risk factors. However, other novel risk factors also appear to contribute. Targeting of these established and novel risk factors has the potential to reduce the burden of CVD in LMICs.

Total, red and processed meat consumption and human health: an umbrella review of observational studies

Meat consumption has represented an important evolutionary step for humans. However, modern patterns of consumption, including excess intake, type of meat and cooking method have been the focus of attention as a potential cause of rise in non-communicable diseases. The aim of this study was to investigate the association between total, red and processed meat with health outcomes and to assess the level of evidence by performing a systematic search of meta-analyses of prospective cohort studies. Convincing evidence of the association between increased risk of (i) colorectal adenoma, lung cancer, CHD and stroke, (ii) colorectal adenoma, ovarian, prostate, renal and stomach cancers, CHD and stroke and (iii) colon and bladder cancer was found for excess intake of total, red and processed meat, respectively. Possible negative associations with other health outcomes have been reported. Excess meat consumption may be detrimental to health, with a major impact on cardiometabolic and cancer risk.

DNA methylation changes associated with prenatal mercury exposure: A meta-analysis of prospective cohort studies from PACE consortium.

Mercury (Hg) is a ubiquitous heavy metal that originates from both natural and anthropogenic sources and is transformed in the environment to its most toxicant form, methylmercury (MeHg). Recent studies suggest that MeHg exposure can alter epigenetic modifications during embryogenesis. In this study, we examined associations between prenatal MeHg exposure and levels of cord blood DNA methylation (DNAm) by meta-analysis in up to seven independent studies (n=1462) as well as persistence of those relationships in blood from 7 to 8 year-old children (n=794). In cord blood, we found limited evidence of differential DNAm at cg24184221 in MED31 (β=2.28×10-4, p-value=5.87×10-5) in relation to prenatal MeHg exposure. In child blood, we identified differential DNAm at cg15288800 (β=0.004, p-value=4.97×10-5), also located in MED31. This repeated link to MED31, a gene involved in lipid metabolism and RNA Polymerase II transcription function, may suggest a DNAm perturbation related to MeHg exposure that persists into early childhood. Further, we found evidence for association between prenatal MeHg exposure and child blood DNAm levels at two additional CpGs: cg12204245 (β=0.002, p-value=4.81×10-7) in GRK1 and cg02212000 (β=-0.001, p-value=8.13×10-7) in GGH. Prenatal MeHg exposure was associated with DNAm modifications that may influence health outcomes, such as cognitive or anthropometric development, in different populations.

Sleep duration and atrial fibrillation risk in the context of predictive, preventive, and personalized medicine: the Suita Study and meta-analysis of prospective cohort studies.

Short and long sleep durations are common behaviors that could predict several cardiovascular diseases. However, the association between sleep duration and atrial fibrillation (AF) risk is not well-established. AF is preventable, and risk prevention approaches could reduce its occurrence. Investigating whether sleep duration could predict AF incidence for possible preventive interventions and determining the impact of various lifestyle and clinical characteristics on this association to personalize such interventions are essential. Herein, we investigated the association between sleep duration and AF risk using a prospective cohort study and a meta-analysis of epidemiological evidence. Data of 6898 people, aged 30-84years, from the Suita Study, were analyzed. AF was diagnosed during the follow-up by ECG, medical records, checkups, and death certificates, while a baseline questionnaire was used to assess sleep duration. The Cox regression was used to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) of AF risk for daily sleep ≤ 6 (short sleep), ≥ 8 (long sleep), and irregular sleep, including night-shift work compared with 7h (moderate sleep). Then, we combined our results with those from other eligible prospective cohort studies in two meta-analyses for the short and long sleep. In the Suita Study, within a median follow-up period of 14.5years, short and irregular sleep, but not long sleep, were associated with the increased risk of AF in the age- and sex-adjusted models: HRs (95% CIs) = 1.36 (1.03, 1.80) and 1.62 (1.16, 2.26) and the multivariable-adjusted models: HRs (95% CIs) = 1.34 (1.01, 1.77) and 1.63 (1.16, 2.30), respectively. The significant associations between short and irregular sleep and AF risk remained consistent across different ages, sex, smoking, and drinking groups. However, they were attenuated among overweight and hypertensive participants. In the meta-analyses, short and long sleep durations were associated with AF risk: pooled HRs (95% CIs) = 1.21 (1.02, 1.42) and 1.18 (1.03, 1.35). No signs of significant heterogeneity across studies or publication bias were detected. Short, long, and irregular sleep could be associated with increased AF risk. In the context of predictive, preventive, and personalized medicine, sleep duration should be considered in future AF risk scores to stratify the general population for potential personalized lifestyle modification interventions. Sleep management services should be considered for AF risk prevention, and these services should be individualized according to clinical characteristics and lifestyle factors. The online version contains supplementary material available at 10.1007/s13167-022-00275-4.

Association of weight status and the risks of diabetes in adults: a systematic review and meta-analysis of prospective cohort studies.

Obesity is a known risk factor for type 2 diabetes mellitus (T2DM); however, the associations between underweight and T2DM and between weight status and prediabetes have not been systematically reviewed. We aimed to estimate the relative risks (RRs) of prediabetes/T2DM in underweight/overweight/obesity relative to normal weight. PubMed, Embase, Web of Science, and Cochrane Library were searched from inception to December 8, 2021. Prospective cohort studies with a minimum 12-month follow-up period reporting the association between baseline body mass index (BMI) categories and risk of prediabetes/T2DM in adults were included. Study quality was assessed using the Newcastle-Ottawa Scale. The main analyses of T2DM risk were performed using the ethnic-specific (Asian/non-Asian) BMI classification and additional analyses of prediabetes/T2DM risk by including all eligible studies. Random-effects models with inverse variance weighting were used. Subgroup analyses and meta-regression were conducted to explore the potential effects of pre-specified modifiers. The study protocol was registered with PROSPERO (CRD42020215957). Eighty-four articles involving over 2.69 million participants from 20 countries were included. The pooled RR of prediabetes risk was 1.24 (95% CI: 1.19-1.28, I2 = 9.7%, n = 5 studies) for overweight/obesity vs. normal weight. The pooled RRs of T2DM based on the ethnic-specific BMI categories were 0.93 (95% CI: 0.75-1.15, I2 = 55.5%, n = 12) for underweight, 2.24 (95% CI: 1.95-2.56, I2 = 92.0%, n = 47) for overweight, 4.56 (95% CI: 3.69-5.64, I2 = 96%, n = 43) for obesity, and 22.97 (95% CI: 13.58-38.86, I2 = 92.1%, n = 6) for severe obesity vs. normal weight. Subgroup analyses indicated that underweight is a protective factor against T2DM in non-Asians (RR = 0.68, 95% CI: 0.40-0.99, I2 = 56.1%, n = 6). The magnitude of the RR of T2DM in overweight/obesity decreased with age and varied by region and the assessment methods for weight and T2DM. Overweight/obesity was associated with an increased prediabetes/T2DM risk. Further studies are required to confirm the association between underweight and prediabetes/T2DM, particularly in Asian populations.

Eggconsumption and risks of all-cause and cause-specific mortality: a dose-response meta-analysis of prospective cohort studies.

Current dietary guidelines recommend eggs as a part of a healthy diet. However, whether egg consumption is associated with risk of mortality remains controversial. Moreover, the dose-response association of egg consumption with risk of mortality has not been determined. To determine the potential dose-response association of egg consumption with risk of mortality in the general population. The PubMed and Embase databases were searched for publications meeting eligibility criteria through November 2021. Required data were extracted by 1 reviewer and then checked for accuracy by another reviewer. A random-effects dose-response meta-regression model was used to calculate the pooled risk estimates. A restricted cubic spline model was used to test nonlinearity. The certainty of evidence was assessed using the GRADE system. Nineteen prospective cohort studies, involving 1 737 893 participants, were included. The pooled hazard ratios for an increase of 1 egg/d were 1.08 (95%CI, 1.01-1.15) for all-cause mortality, 1.07 (95%CI, 0.97-1.18) for cardiovascular disease-caused mortality, and 1.16 (95%CI, 1.04-1.30) for cancer-caused mortality. The certainty of evidence for these observations was rated as very low. Nonlinear dose-response associations were found for egg consumption and all-cause, cardiovascular disease-caused, and cancer-caused mortality. Moreover, the positive association between egg consumption and all-cause mortality was more pronounced in studies with adjustment for blood cholesterol-related covariates than those without (Pinteraction = 0.011). Greater amount of egg consumption confers higher risks of death from all causes, cardiovascular disease, and canc er in a nonlinear dose-response pattern. These findings should be treated with caution and need to be confirmed by future studies.

Dietary carbohydrate and the risk of type 2 diabetes: an updated systematic review and dose\u2013response meta-analysis of prospective cohort studies

We did this study to clarify the association between carbohydrate intake and the risk of type 2 diabetes (T2D) and potential effect modification by geographical location. PubMed, Scopus and Web of Science were searched to find prospective cohort studies of dietary carbohydrate intake and T2D risk. A random-effects dose–response meta-analysis was performed to calculate the summary hazard ratios (HRs) and 95%CIs. The quality of cohort studies and the certainty of evidence was rated using the Newcastle–Ottawa Scale and GRADE tool, respectively. Eighteen prospective cohort studies with 29,229 cases among 607,882 participants were included. Thirteen studies were rated to have high quality, and five as moderate quality. The HR for the highest compared with the lowest category of carbohydrate intake was 1.02 (95%CI: 0.91, 1.15; I2 = 67%, GRADE = low certainty). The HRs were 0.93 (95%CI: 0.82, 1.05; I2 = 58%, n = 7) and 1.26 (95%CI: 1.11, 1.44; I2 = 6%, n = 6) in Western and Asian countries, respectively. Dose–response analysis indicated a J shaped association, with the lowest risk at 50% carbohydrate intake (HR50%: 0.95, 95%CI: 0.90, 0.99) and with risk increasing significantly at 70% carbohydrate intake (HR70%: 1.18, 95%CI: 1.03, 1.35). There was no association between low carbohydrate diet score and the risk of T2D (HR: 1.14, 95%CI: 0.89, 1.47; I2 = 90%, n = 5). Carbohydrate intake within the recommended 45–65% of calorie intake was not associated with an increased risk of T2D. Carbohydrate intake more than 70% calorie intake might be associated with a higher risk.

Dietary iron intake and the risk of type 2 diabetes: a systematic review and dose-response meta-analysis of prospective cohort studies.

We aimed to assess the long-term association of total, heme, non-heme, and supplemental iron intake and risk of type 2 diabetes (T2D). PubMed, Scopus, and Web of Science were searched to October 2021. Two researchers extracted data in duplicate and rated the certainty in the estimates using the GRADE approach. Random-effects models were applied to estimate the relative risks (RRs) and 95% CIs. Dose-response associations were modeled by a one-stage weighted mixed-effects meta-analysis. Eleven prospective cohort studies 323,788 participants and 28,837 incident cases of T2D were included. High versus low category meta-analysis indicated that higher heme iron intake was associated with a 20% higher risk of T2D (95% CI 1.07, 1.35; I2 = 77%, n = 11; GRADE = moderate). Dose-response analysis indicated a positive monotonic association, wherein each 1mg/day increment in heme iron intake was related to a 16% higher risk (95% CI 1.03, 1.30). No significant relationship was detected between dietary intakes of total, non-heme, and supplemental iron and risk of T2D (GRADE = very low). In summary, higher heme iron intake was associated with a higher risk of T2D. Our results are in line with existing evidence indicating that adopting a Western-style dietary pattern, rich in dietary sources of heme iron, was associated with a higher risk of T2D. The protocol of this systematic review was registered at PROSPERO (registration number: CRD42021226835).

Dietary glycemic index, glycemic load and cancer risk: a meta-analysis of prospective cohort studies.

There is considerable inconsistency in results regarding the association of dietary glycemic index (GI) and glycemic load (GL) with cancer risk. Wethereforeconducted this systematic review and dose-response meta-analysis of prospective cohort studies to evaluate the relationship between dietary GI/GL and cancer risk. We searched PubMed and Web of Science for prospective cohort studies of dietary GI/GL in relation to risks of all types of cancer up to 31 March 2021. We used a random-effect model to calculate summary relative risks (RR) and 95% confidence intervals (CI). The certainty of evidence was assessed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. This study was registered at PROSPERO (CRD42020215338). Overall, 55 cohorts were included in the meta-analysis. We assessed the relationship between dietary GI or GL and risks of 23 cancer types, including hormone-related cancers, cancers from digestive system, respiratory system, urinary system and other cancer sites. High GI diet increased overall risk of cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.04, 95% CI 1.01-1.07). For site-specific cancers, high GI diet increased risks of lung cancer (highest vs lowest categories, n = 5, RR 1.08, 95% CI 1.01-1.18) and breast cancer (highest vs lowest categories, n = 14, RR 1.05, 95% CI 1.01-1.09), especially for postmenopausal breast cancer (highest vs lowest categories, n = 10, RR 1.06, 95% CI 1.00-1.13), all with low certainty of evidence. Additionally, dietary GI was positively related to risk of bladder cancer with low certainty of evidence (highest vs lowest categories, n = 3, RR 1.23, 95% CI 1.09-1.40), as well as negatively related to ovarian cancer risk with very low certainty of evidence (highest vs lowest categories, n = 4, RR 0.83, 95% CI 0.69-1.00) and lymphoma risk with low certainty of evidence (highest vs lowest categories, n = 2, RR 0.84, 95% CI 0.72-0.98). Besides, we found an inverse association of dietary GL with lung cancer risk with low certainty of evidence (highest vs lowest categories, n = 5, RR 0.87, 95% CI 0.80-0.94). High dietary GI increased overall cancer risk with low certainty of evidence. For site-specific cancers, high GI diet increased the risks of breast cancer with low certainty of evidence and lung cancer with low certainty of evidence. Dietary GL was inversely associated with lung cancer risk with low certainty of evidence.

A meta-analysis of prospective cohort studies of flavonoid subclasses and stroke risk.

Epidemiological studies indicate that higher intakes of flavonoids are associated with reduced stroke risk, however, which subtypes play significant roles to protect against stroke remain unclear. A systematic literature search in PubMed and Web of Science databases was performed up to Oct. 2021. Flavonoids or their subtypes (flavanol, flavanone, flavone, flavan-3-ol, isoflavone, or anthocyanin) were paired with stoke as the search term. Multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) for the highest versus the lowest category were pooled by using a random-effects model. Dose-response analysis was implemented by using a restricted cubic spline regression model. Ten independent prospective cohort studies with 387,076 participants and 9,564 events were included. Higher intakes of flavanones were inversely associated with stroke risk (RR=0.85; 95%CI: 0.78, 0.93). Dose-response analysis showed that 50 mg/day increment of flavanones was associated with 11% reduction in stroke risk (RR=0.89; 95%CI: 0.84, 0.94). Flavan-3-ols was marginally inversely associated with stroke risk (RR=0.92; 95%CI: 0.82, 1.02). Dose-response analysis showed that 200 mg/day increment of flavan-3-ols was associated with 14% reduction in stroke risk (RR=0.86; 95%CI: 0.75, 0.98). The non-significant association was observed with respect to other flavonoid subclasses. This study demonstrated higher intakes of flavanones and flavan-3-ols were associated with a lower risk of stroke. Dietary intakes of lemon and citrus rich in flavanones and flavan-3-ols might have beneficial functions for the protection against stroke. The findings of these associations of the present study need to be confirmed in other regions and ethnic origins.

Mediterranean dietary pattern and the risk of type 2 diabetes: a systematic review and dose–response meta-analysis of prospective cohort studies

Previous meta-analyses assessed the association of adherence to the Mediterranean dietary pattern (MedDiet) with the risk of type 2 diabetes (T2D). Since then, new large-scale cohort studies have been published. In addition, dose-response relation was not previously investigated and the certainty of evidence was not assessed. We aimed to explore the dose-response relationship between adherence to the MedDiet and the risk of T2D. We did a systematic search using PubMed, Scopus, and ISI Web of Science upto April 2021 for prospective cohort studies of the relationship between adherence to the MedDiet and the risk of T2D in the general population. The summary relative risks (RR) and 95%CI were estimated by applying a random-effects model. Fourteen prospective cohort studies (410,303 participants and 41,466 cases) were included. There was an inverse association for the highest versus lowest category of adherence to the MedDiet (RR: 0.79, 95%CI 0.72, 0.88; I2 = 82%, n = 14; Risk difference: - 21 per 1000 person, 95%CI - 28, - 12; GRADE = moderate certainty), and for a 2-point increment in the MedDiet adherence score (RR: 0.86, 95%CI 0.82, 0.91; n = 13). The RR remained significant after controlling for important confounders and in almost all subgroups, especially subgroups defined by geographical region. We observed an inverse linear association between MedDiet adherence score and T2D incidence. Adherence to the MedDiet was inversely related to T2D risk in a dose-response manner. Adherence to a Mediterranean-style diet may be a good advice for the primary prevention of T2D. PROSPERO (CRD42021246589).

Resting Heart Rate and Cognitive Decline: A Meta-Analysis of Prospective Cohort Studies

Several previous meta-analyses have identified an association between cognitive decline and heart rate variability, which reflects autonomic nerve activity. This systematic review and meta-analysis investigated the impact of increased resting heart rate (RHR) on the incidence of cognitive decline, including dementia. The PubMed, Embase, and PsycInfo databases were searched for relevant prospective cohort studies published before April 18, 2022. A methodological quality assessment of the included studies was conducted using the Newcastle-Ottawa Scale. Summary estimates of the incidence of cognitive decline, including dementia, were generated using a random-effects model. Potential publication bias was evaluated using Begg's funnel plots and Egger's regression tests. The meta-analysis included 7 prospective cohort studies comprising 53,621 participants. A weak significant association was observed between RHR and the risk of cognitive decline, although the analysis indicated high heterogeneity among the studies (relative risk=1.18, 95% confidence interval=1.04-1.33, I²=82.5%). Significant associations were determined between RHR and all combined types of dementia except for Alzheimer's disease and mild cognitive impairment. There was also a dose-response association between increased RHR and cognitive decline. The meta-estimate of the cognitive decline risk associated with a 10 beat-per-minute increase in RHR was 1.06, and it was 1.10 for dementia. This study found that a higher RHR was associated with an increased cognitive decline risk. Due to study limitations such as publication bias and high heterogeneity, additional studies are required to validate this finding. PROSPERO registration number CRD42021282912.

Use of oral contraceptives and risk of pancreatic cancer in women: A recalculated meta-analysis of prospective cohort studies.

In a recent systematic review and meta-analysis of observational studies, the author found potential errors in the selection and extraction processes. The recalculated summary relative risks and the results of a dose-response meta-analysis showed that oral contraceptive use may not be associated with the risk of pancreatic cancer in women.

Dietary risk factors for hip fracture in adults: An umbrella review of meta-analyses of prospective cohort studies.

To summarise the totality of evidence regarding dietary risk factors for hip fracture in adults, evaluating the quality of evidence, to provide recommendations for practice and further research. Systematic review of meta-analyses of prospective cohort studies. Systematic reviews with meta-analyses reporting summary risk estimates for associations between hip fracture incidence and dietary exposures including oral intake of a food, food group, beverage, or nutrient, or adherence to dietary patterns. Medline, Embase, Web of Science, and the Cochrane Library from inception until November 2020. The methodological quality of systematic reviews and meta-analyses was assessed using AMSTAR-2, and the quality of evidence for each association was assessed using GRADE. Results were synthesised descriptively. Sixteen systematic reviews were identified, covering thirty-four exposures, including dietary patterns (n = 2 meta-analyses), foods, food groups, or beverages (n = 16), macronutrients (n = 3), and micronutrients (n = 13). Identified meta-analyses included 6,282 to 3,730,424 participants with between 322 and 26,168 hip fractures. The methodological quality (AMSTAR-2) of all systematic reviews was low or critically low. The quality of evidence (GRADE) was low for an inverse association between hip fracture incidence and intake of fruits and vegetables combined (adjusted summary relative risk for higher vs lower intakes: 0.92 [95% confidence interval: 0.87 to 0.98]), and very low for the remaining thirty-three exposures. Dietary factors may play a role in the primary prevention of hip fracture, but the methodological quality of systematic reviews and meta-analyses was below international standards, and there was a lack of high-quality evidence. More long-term cohort studies reporting absolute risks and robust, well-conducted meta-analyses with dose-response information are needed before policy guidelines can be formed. PROSPERO CRD42020226190.

Association between Plant-Based Dietary Patterns and Risk of Cardiovascular Disease: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

Plant-based diets, characterized by a higher consumption of plant foods and a lower consumption of animal foods, are associated with a favorable cardiovascular disease (CVD) risk, but evidence regarding the association between plant-based diets and CVD (including coronary heart disease (CHD) and stroke) incidence remain inconclusive. A literature search was conducted using the PubMed, EMBASE and Web of Science databases through December 2020 to identify prospective observational studies that examined the associations between plant-based diets and CVD incidence among adults. A systematic review and a meta-analysis using random effects models and dose–response analyses were performed. Ten studies describing nine unique cohorts were identified with a total of 698,707 participants (including 137,968 CVD, 41,162 CHD and 13,370 stroke events). Compared with the lowest adherence, the highest adherence to plant-based diets was associated with a lower risk of CVD (RR 0.84; 95% CI 0.79–0.89) and CHD (RR 0.88; 95% CI 0.81–0.94), but not of stroke (RR 0.87; 95% CI 0.73–1.03). Higher overall plant-based diet index (PDI) and healthful PDI scores were associated with a reduced CVD risk. These results support the claim that diets lower in animal foods and unhealthy plant foods, and higher in healthy plant foods are beneficial for CVD prevention. Protocol was published in PROSPERO (No. CRD42021223188).

Risk of Recurrence after Stopping Anticoagulants in Women with Combined Oral Contraceptive-Associated Venous Thromboembolism: A Systematic Review and Meta-Analysis

BackgroundAlthough combined oral contraceptives (COC) are considered a transient risk factor for venous thromboembolism (VTE), the risk of recurrence after discontinuation of anticoagulation is unclear. Few studies have focused on the risk of recurrence in this group; studies report variable results and are limited by small sample size. The risk of recurrence appears to be low, but this could relate to the young age of affected women. Deciphering the absolute VTE recurrence risk after a COC-associated VTE is crucial in helping clinicians and patients decide if anticoagulation could be discontinued after the initial treatment period.ObjectivesThe objectives of this systematic review and meta-analysis are to estimate the incidence of recurrent VTE among women with COC-associated VTE, compared with women with unprovoked VTE.MethodsWe searched the following databases: Cochrane Central Register of Controlled Trial, Cochrane Database of Systematic Reviews, Embase Classic +Embase, and Medline ALL, all from the OvidSP platform, from the database's inception to July 2020. Additional studies were identified by screening citations from included studies.Prospective cohort studies, randomized controlled trials (RCTs), and meta-analyses of prospective cohort studies or RCTs were reviewed by two authors for study inclusion (Figure 1). Studies were included if women had objectively confirmed COC-associated VTE, received a minimum of three months of anticoagulation, discontinued COC prior to or at time of discontinuation of anticoagulation, time of follow-up began after anticoagulation was stopped, and recurrent VTE data was available. Studies were excluded if patients were systematically treated with an alternative pharmacologic agent intended to reduce the risk of recurrent VTE such as aspirin. Authors of identified papers were contacted for additional data on critical variables. If there were multiple publications from a cohort, the study with the longest follow up was included.Two authors extracted study data and assessed included studies for risk of bias using the Newcastle Ottawa Scale. Meta-analysis was done using a random effects Poisson regression model. Heterogeneity was assessed using the I-squared measure.ResultsOur systematic review included 19 studies with a total of 1,537 women (5,828 patient years of follow up) with an index COC-associated VTE, and 1,974 women (7,798 patient years of follow up) with an index unprovoked VTE. Authors contributed additional unpublished data in 16 of the 19 studies. Overall, studies were at low risk of bias, with a mean of 7 stars (out of a possible 9) in the Newcastle Ottawa Scale.Among the 19 studies, the incidence rate of VTE recurrence in women with COC-associated VTE was 1.22 per patient year (95% confidence interval (CI) 0.94 to 1.59, I 2 = 6.4%, 95% prediction interval (PI) 0.81 to 1.85) (Figure 2). The incidence rate of VTE recurrence in women with an index unprovoked VTE not associated with COC was 3.89 per patient year (95% CI 2.98 to 5.07, I 2 =74.2%, 95% PI 1.37 to 11.03).The unadjusted incidence rate ratio of recurrent VTE comparing women with COC-associated events to women with unprovoked events was 0.34 (95% CI 0.26 to 0.45, I 2 = 2.6%, 95% PI 0.26 to 0.46). Only three studies had age-adjusted comparisons, but each with a different effect measure so they could not be combined, with a relative risk ratio 0.4 (95% CI 0.2 to 0.8) (also adjusted for site of VTE and congenital thrombophilia) (Eischer 2014), a hazard ratio of 0.11 (95% CI 0.01 to 0.85) (Kearon 2019), and an incidence rate ratio of 1 (95% CI 0.3 to 3.2) (Le Moigne 2013).ConclusionsThe estimated risk of VTE recurrence after a COC-associated VTE is low, and is lower compared to women with unprovoked VTE, however this comparison may be confounded by age. With only a minority of studies providing age adjusted analyses, the true difference remains unknown. Our meta-analysis is strengthened by the substantial contribution of unpublished data from individual study authors. This can help to guide clinicians and patient shared decision-making on the duration of anticoagulation. [Display omitted] DisclosuresLe Gal: LEO Pharma: Honoraria; BMS: Honoraria; Pfizer: Honoraria; Bayer: Honoraria; Aspen: Honoraria; Sanofi: Honoraria. Schulman: Boehringer-Ingelheim: Research Funding; Octapharma: Research Funding. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

Dairy intake and the risk of pancreatic cancer: the Japan Collaborative Cohort Study (JACC Study) and meta-analysis of prospective cohort studies.

Dairy product intake was suggested to reduce the risk of gastrointestinal cancers. This study investigated the association between dairy product intake and the risk of pancreatic cancer (PAC) using a prospective cohort study and meta-analysis of prospective cohort studies. First, we included 59774 people aged 40-79 years from the Japan Collaborative Cohort Study (JACC Study). The Cox regression was used to compute the hazard ratios (HR) and 95 % CI of incident PAC for individuals who reported the highest intakes of milk, cheese and yogurt compared with not consuming the corresponding dairy products. Then, we combined our results with those from other four prospective cohort studies that were eligible after searching several databases, in a meta-analysis, using the fixed-effects model before evaluating publication bias and heterogeneity across studies. In the JACC Study, the highest v. no intakes of milk, cheese and yogurt were not associated with the reduced risk of PAC after a median follow-up of 13·4 years: HR (95 % CI) = 0·93 (0·64, 1·33), 0·91 (0·51, 1·62) and 0·68 (0·38, 1·21), respectively. The results did not significantly change in the meta-analysis: 0·95 (0·82, 1·11) for milk, 1·16 (0·87, 1·55) for cheese and 0·91 (0·79, 1·05) for yogurt. The meta-analysis showed no signs of publication bias or heterogeneity across studies. To conclude, consumption of milk, cheese and yogurt was not associated with the risk of PAC either in the JACC Study or the meta-analysis.

Coffee consumption and the risk of cerebrovascular disease: a meta-analysis of prospective cohort studies

BackgroundStroke is a crucial health threat to adults worldwide. Despite extensive knowledge of risk-factor mitigation, no primary prevention exists for healthy people. Coffee is a widely consumed beverage globally. Health benefit of coffee for several neurological diseases has been identified; however, the association between stroke risk and coffee consumption in healthy people has not been determined. We investigated the effect of coffee on stroke risk by conducting a meta-analysis of prospective cohort studies.MethodsElectronic databases, namely PubMed, BioMed Central, Medline, and Google Scholar, were searched using terms related to stroke and coffee. Articles that described clear diagnostic criteria for stroke and details on coffee consumption were included. The reference lists of relevant articles were reviewed to identify eligible studies not shortlisted using these terms. Enrolled studies were grouped into three outcome categories: overall stroke, hemorrhagic stroke, and ischemic stroke.ResultsSeven studies were included and all of them were large-scale, long-term, follow-up cohort studies of a healthy population. Upon comparing the least-coffee-consuming groups from each study, the meta-analysis revealed a reduction in the risk of overall stroke during follow-up (hazard ratio [HR] for overall stroke = 0.922, 95% confidence interval [CI] = 0.855–0.994, P = 0.035). In studies with a clear definition of hemorrhagic and ischemic stroke, coffee consumption reduced the risk of ischemic stroke more robustly than that of hemorrhagic stroke (hemorrhagic, HR = 0.895, 95% CI = 0.824–0.972, P = .008; ischemic, HR = 0.834, 95% CI = 0.739–0.876, P < .001). No obvious dose-dependent or U-shaped effect was observed.ConclusionsCoffee consumption reduces the risk of overall stroke, especially ischemic stroke. Further investigation is required to identify beneficial components in coffee, including caffeine and phenolic acids, to develop preventive medication for stroke.