Alcohol intake and risk of stroke: A dose–response meta-analysis of prospective studies

Background

Alcohol intake is inconsistently associated with the risk of stroke morbidity and mortality. The purpose of this study was to summarize the evidence regarding this relationship by using a dose–response meta-analytic approach.

Methods

We performed electronic searches of PubMed, EMBASE, and the Cochrane Library to identify relevant prospective studies. Only prospective studies that reported effect estimates with 95% confidence intervals (CIs) of stroke morbidity and mortality for more than 2 categories of alcohol intake were included.

Results

We included 27 prospective studies reporting data on 1,425,513 individuals. Low alcohol intake was associated with a reduced risk of total stroke (risk ratio [RR], 0.85; 95% CI: 0.75–0.95; P = 0.005), ischemic stroke (RR, 0.81; 95% CI: 0.74–0.90; P < 0.001), and stroke mortality (RR, 0.67; 95% CI: 0.53–0.85; P = 0.001), but it had no significant effect on hemorrhagic stroke. Moderate alcohol intake had little or no effect on the risks of total stroke, hemorrhagic stroke, ischemic stroke, and stroke mortality. Heavy alcohol intake was associated with an increased risk of total stroke (RR, 1.20; 95% CI: 1.01–1.43; P = 0.034), but it had no significant effect on hemorrhagic stroke, ischemic stroke, and stroke mortality.

Conclusions

Low alcohol intake is associated with a reduced risk of stroke morbidity and mortality, whereas heavy alcohol intake is associated with an increased risk of total stroke. The association between alcohol intake and stroke morbidity and mortality is J-shaped.     

Dietary saturated fat intake and risk of stroke: Systematic review and dose–response meta-analysis of prospective cohort studies

Background and aimsBecause of the conflicting research results, the association between saturated fatty acid (SFA) consumption and the risk of stroke remains controversial. We conducted a meta-analysis to evaluate potential dose–response relation between SFA intake and stroke.Methods and resultsPubMed, Embase, the Cochrane Library Central Register of Controlled Trials, and Web of Science were searched. Summary relative risks (RRs) of the highest vs. the lowest category of SFA intake and their 95% confidence intervals (CIs) were pooled by random-effects models. Linear or nonlinear dose–response trend estimations were evaluated with data from categories of SFA consumption in each study. Fourteen studies involving a total of 598,435 participants were eligible for high vs. low meta-analysis, and 12 studies involving a total of 462,268 participants were eligible for the dose–response relation assessment. Higher dietary SFA intake was associated with a decreased overall risk for stroke (RR, 0.87; 95% CI, 0.78–0.96; I² = 37.8%). A linear relation between SFA and stroke was explored (P = 0.01), the pooled RR of stroke per 10 g/day increase in SFA intake was 0.94 (95% CI, 0.89–0.98; P = 0.01).ConclusionThis meta-analysis further demonstrated that a higher consumption of dietary SFA is associated with a lower risk of stroke, and every 10 g/day increase in SFA intake is associated with a 6% relative risk reduction in the rate of stroke. Further research is needed to explore the influence of specific SFA types and different macronutrient replacement models of SFA on the stroke risk.     

A J-shaped relation of BMI and stroke: Systematic review and dose–response meta-analysis of 4.43 million participants

Background and aim

Many studies have shown increased risk of stroke with greater adiposity as measured by body mass index (BMI), but questions remain about the shape of the dose–response relation. We conducted a systematic review and meta-analysis of prospective studies to clarify the strength and shape of the dose–response relation between BMI and risk of stroke.

Breastfeeding and the maternal risk of type 2 diabetes: A systematic review and dose–response meta-analysis of cohort studies

Background and aimsBreastfeeding has been associated with reduced risk of maternal type 2 diabetes in some cohort studies, but the evidence from published studies have differed with regard to the strength of the association. To clarify this association we conducted a systematic review and dose–response meta-analysis of breastfeeding and maternal risk of type 2 diabetes.Methods and resultsWe conducted a systematic review and dose–response meta-analysis of prospective studies of breastfeeding and maternal risk of type 2 diabetes. We searched the PubMed, Embase and Ovid databases up to September 19th 2013. Summary relative risks were estimated using a random effects model. Six cohort studies including 10,842 cases among 273,961 participants were included in the meta-analysis. The summary RR for the highest duration of breastfeeding vs. the lowest was 0.68 (95% CI: 0.57–0.82, I² = 75%, p_{heterogeneity} = 0.001, n = 6). The summary RR for a three month increase in the duration of breastfeeding per child was 0.89 (95% CI: 0.77–1.04, I² = 93%, p_{heterogeneity} < 0.0001, n = 3) and the summary RR for a one year increase in the total duration of breastfeeding was 0.91 (95% CI: 0.86–0.96, I² = 81%, p_{heterogeneity} = 0.001, n = 4). There was little difference in the summary estimates whether or not BMI had been adjusted for. The inverse associations appeared to be nonlinear, p_nonlinearity < 0.0001 for both analyses, and in both analyses the reduction in risk was steeper when increasing breastfeeding from low levels.ConclusionThis meta-analysis suggests that there is a statistically significant inverse association between breastfeeding and maternal risk of type 2 diabetes.     

Number of parity and the risk of non-Hodgkin lymphomas: a dose–response meta-analysis of observational studies

Background: Epidemiological reports have shown that parity is associated with a risk of developing non-Hodgkin lymphomas (NHL). However, the findings have been inconsistent.

Methods: We searched the EMBASE and PubMed databases for eligible studies up to 10 March 2016. Category and generalized least square regression models were used to perform data analyses.

Results: In total, five cohort and seven case–control studies were identified. Categorical analyses indicated that parity number has little association with NHL and its subtypes. In dose–risk analyses, there were no relationships between parity and NHL risk (p_{for association}?=?0.064; n?=?10). The summarized risk ratio (RR) was 0.97 (95% confidence interval (CI): 0.95–1.00; I²?=?57.8%; p_{heterogeneity}?=?0.014; Power?=?0.79) for each additional live birth increase. Similarly, for B-cell NHL, there was a null association between parity and NHL risk (p_{for association}?=?0.121; n?=?5). The combined RR was 0.96 (95% CI?=?0.90–1.03; I²?=?63.7%; p_{heterogeneity}?=?0.026; Power?=?0.71) for each additional live birth. For follicular NHL, there was still a non-significant association identified (p_{for association}?=?0.071; n?=?4), the pooled RR was 1.00 (95% CI?=?0.95–1.07; I²?=?17.3%; p_{heterogeneity}?=?0.305; Power?=?0.26) per additional live birth.

Conclusions: Our data identified little evidence suggesting that high parity is a protective factor against the development of NHL, including its B-cell and follicular subtypes.     

Dose–response relationship of serum uric acid levels with risk of stroke mortality

Introduction

Results from the recent meta-analysis suggested that higher serum uric acid (SUA) levels are positively associated with risk of stroke. However, the relationship of SUA levels with risk of stroke is still unclear.

Materials and methods

Data from prospective cohort studies on SUA levels and risk of stroke mortality was used. Dose–response relationship was assessed by restricted cubic spline model and multivariate random effect meta-regression.

Results

A non-linear relationship (P_{for non-linearity} = 0.004) of SUA levels with risk of stroke mortality was found for men, and the relative risk (RR) with 95% confidence interval (CI) of stroke mortality was 1.00 (0.99–1.01), 0.99 (0.94–1.04), 0.98 (0.91–1.06), 1.00 (0.90–1.12), 1.17 (1.09–1.24) and 1.52 (1.33–1.78) for 2, 3, 4, 5, 6 and 7 mg/dL of SUA levels, respectively. For women, the departure from linearity was not significant (P_{for non-linearity} = 0.67), and the RR (95 %CI) of stroke mortality was 1.02 (0.99–1.04), 1.10 (0.97–1.20), 1.15 (0.96–1.37), 1.25 (1.09–1.44), 1.39 (1.28–1.50) for 2, 3, 4, 5, 6 mg/dL of SUA levels, respectively.

Conclusions

Different dose–response relationships of SUA levels with risk of stroke mortality might exist for men and for women. Dose–response relationship of SUA levels with risk of stroke incidence needs to be explored.     

Dairy products consumption and the risk of hypertension in adults: An updated systematic review and dose–response meta-analysis of prospective cohort studies

AimsWith an increase in the number of published prospective cohort studies, we sought to summarize the relationship between dairy products consumption and the risk of hypertension (HTN).Data synthesisWe searched PubMed, Web of Science, Embase, Science direct, and Scopus. Pooled RRs and 95% CIs were calculated using a random effects model. The certainty of the evidence was assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE). Sixteen studies were included in the current meta-analysis. We found an inverse association between total dairy products (RR = 0.90; 95% CI: 0.87, 0.94; n = 16), low-fat dairy products (RR = 0.86; 95% CI: 0.77, 0.96; n = 8), milk (RR = 0.94; 95% CI: 0.90, 0.99; n = 11), and fermented dairy (RR = 0.95; 95% CI: 0.91, 0.99; n = 8) consumption and the risk of HTN. However, in subgroup analysis, despite a significant association for total dairy products in women, Americans, longer and larger studies, and self-reported HTN, no associations were found in males, Europeans, or Asians, and studies which followed participants for <10 years or had <3000 participants or measured HTN. Dose–response analysis revealed a non-linear association between total dairy products and milk consumption and the risk of HTN, but a linear association for low-fat dairy products.ConclusionsHigher dairy products consumption was associated with reduced risk of HTN. This association was dependent on sex, geographical region of study, and the stage of HTN. However, the certainty of the evidence was graded either as low or very low.     

Dietary cholesterol consumption and incidence of type 2 diabetes mellitus: A dose–response meta-analysis of prospective cohort studies

Background and aimThe purpose of this meta-analysis was to evaluate the dose–response relationship between dietary cholesterol (DC) consumption and the incidence of type 2 diabetes mellitus (T2DM).Methods and resultsProspective studies with the endpoint of T2DM were included. The Random-effect model weighted by inverse variance was used. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics. Restricted cubic splines regression models were used to estimate the dose–response relationship. 11 prospective studies comprising of 355 230 subjects were included. Compared to lowest DC consumption, highest DC consumption was associated with an increased risk of T2DM (RR 1.15, 95% CI 1.03 to 1.28, P = 0.012; chi-squared = 31.41, I-squared 58.6%, P _{heterogeneity} = 0.003). Subgroup analyses have shown that this positive association was more evident in western countries than in eastern countries (RR 1.19, 95% CI 1.06 to 1.36 VS 1.34, 95% CI 0.84 to 1.29; P _{subgroup difference} = 0.02). For 100 mg/d increment in DC intake, the pooled RR was 1.05, (95% CI 1.04 to 1.07, P_linearity = 0.000, P_nonlinearity = 0.02), 1.06 (95% CI 1.04 to 1.07, P_linearity=0.000), and 1.01 (95% CI 0.98 to 1.05, P_linearity = 0.525) for the incidence of T2DM, in western and eastern countries, respectively.ConclusionsOur study suggests that there is a positive dose–response association between DC consumption and the incidence of T2DM, especially in western countries.Systematic review registrationPROSPERO CRD42020216318.     

Can metformin use reduce the risk of stroke in diabetic patients? A systematic review and meta-analysis

Background and aimStroke and cardiovascular diseases are major causes of death and disability, especially among diabetic patients. Some studies have shown that metformin has been effective in preventing cardiovascular diseases. In this study, we aim to evaluate the effect of metformin on stroke in type 2 diabetic patients.MethodsA comprehensive search was conducted in Medline, Embase, Scopus, and Web of Science databases from their inception till 1st July 2022. Randomized clinical trials (RCT) and cohort studies were included. Two independent researchers screened the records, extracted the data, and assessed the risk of bias and certainty of evidence. Findings were reported as risk ratio (RR) and 95% confidence interval (CI). All statistical analyses were performed using the STATA 17.0 software package.ResultsAnalysis of 21 included studies with 1,392,809 patients demonstrated that metformin monotherapy was effective in reducing stroke risk in both RCTs (RR = 0.66, 95% CI: 0.50, 0.87 p = 0.004) and cohort studies (RR = 0.67, 95% CI: 0.55, 0.81, p < 0.0001). However, combined administration of metformin with other antihyperglycemic agents had no significant effect on stroke risk reduction in either the RCTs (RR = 0.92, 95% CI: 0.69, 1.22 p = 0.558) or the cohort studies (RR = 0.79, 95% CI: 0.59, 1.06, p = 0.122).ConclusionLow to moderate level of evidence in RCTs showed that metformin monotherapy could reduce stroke risk in type 2 diabetic patients. However, the preventive effect of metformin in stroke was not observed in patients who received a combination of metformin plus other hypoglycemic agents.     

Acid control with esomeprazole and lansoprazole: A comparative dose–response study

Objective. To determine the level of acid control and the dose–response relationships achieved with esomeprazole and lansoprazole. These data are relevant in helping clinicians to decide on whether to increase a proton-pump inhibitor dose, or whether to switch to an alterative drug for increased acid control. Material andmethods. In an open-label, single-centre, randomized, six-way crossover study, 40 healthy subjects received esomeprazole 20, 40 and 80 mg, and lansoprazole 15, 30 and 60 mg once daily for 5 days. The mean time with intragastric pH >4 and mean 24-h median intragastric pH on day 5 were analyzed using a mixed-model ANOVA. Post-hoc analyses were completed for 0–12-h (daytime) and 12–24-h (night-time) post-dose intervals. Results. Increasing the dose of esomeprazole from 20 mg to 40 mg resulted in significantly improved acid control over 0–12, 12–24 and 0–24 h post-dose (p<0.001), but no significant improvement in acid control for either period was seen when further increasing the dose to 80 mg. Increasing the dose of lansoprazole from 15 mg to 30 mg or from 30 mg to 60 mg significantly improved acid control over 0–12 and 0–24 h (p<0.01) but not over 12–24 h. With the exception of the esomeprazole 20 mg versus lansoprazole 30 mg comparisons, and the esomeprazole 20 mg versus lansoprazole 15 mg during 12–24 h post-dose comparison, esomeprazole provided significantly greater acid control than lansoprazole at each dose level over 0–12, 12–24 and 0–24 h (p<0.05). Mean 24-h median intragastric pH was higher following esomeprazole dosing compared with lansoprazole at each dose level. Conclusions. For low-, standard- and double-dose comparisons, esomeprazole achieved greater elevation of gastric pH and better acid control in more subjects than lansoprazole. Use of esomeprazole may therefore reduce the need for dose adaptations or drug switching.     

Association of BMI with cardiovascular disease incidence and mortality in patients with type 2 diabetes mellitus: A systematic review and dose–response meta-analysis of cohort studies

AimsThe relation of body mass index (BMI) with cardiovascular disease (CVD) and mortality has been extensively investigated in the general population but is less clear in individuals with type 2 diabetes mellitus (T2DM). We performed a meta-analysis of cohort studies to quantitatively evaluate the association of BMI with CVD incidence and mortality in patients with T2DM.Data synthesisPubMed and Embase databases were searched for relevant cohort articles published up to June 8, 2020. Restricted cubic splines were used to evaluate the potential linear or non-linear dose–response associations. We identified 17 articles (21 studies) with 1,349,075 participants and 57,725 cases (49,354 CVD incidence and 8371 CVD mortality) in the meta-analysis. We found a linear association between BMI and risk of CVD incidence (P_{non-linearity} = 0.182); the pooled RR for CVD incidence was 1.12 (95% CI, 1.04–1.20) with a 5-unit increase in BMI. We found an overall nonlinear relationship between BMI and CVD mortality (P_{non-linearity} < 0.001). The lowest risk was at BMI about 28.4 kg/m², with increased mortality risk for higher BMI values; the RR with a 5-unit increase in BMI was 0.87 (95% CI, 0.79–0.96) and 1.11 (95% CI, 1.04–1.18) for BMI ≤28.4 kg/m² and BMI >28.4 kg/m², respectively.ConclusionsIn individuals with T2DM, BMI may have a positive linear association with risk of CVD incidence but a nonlinear association with CVD mortality. Our results can provide evidence for weight control and lifestyle intervention for preventing and managing cardiovascular disease in T2DM.     

Obesity and colorectal cancer risk： A meta-analysis of cohort studies

TO evaluate the association between obesity and colorectal cancer risk. METHODS： We searched PubMed, EMBASE, and the Cochrane Library up to January 1, 2007. Cohort studies permitting the assessment of causal association between obesity and colorectal cancer, with clear definition of obesity and well-defined outcome of colorectal cancer were eligible. Study design, sample size at baseline, mean follow-up time, co-activators and study results were extracted. Pooled standardized effect sizes were calculated.     

Meat and fish intake and type 2 diabetes: Dose–response meta-analysis of prospective cohort studies

AimsThis meta-analysis aimed to quantitatively examine the possible associations between total meat, red meat, processed meat, poultry and fish intakes and type 2 diabetes (T2D).MethodsRelevant articles were identified in PubMed, Embase and Web of Science databases using a search time up to January 2019. Generalized least-squares trend estimations and restricted cubic spline regression models were used for analysis.ResultsTwenty-eight articles were included in the analysis. When comparing the highest with the lowest category of meat intake, the summary relative risk of T2D was 1.33 (95% CI: 1.16–1.52) for total meat, 1.22 (95% CI: 1.16–1.28) for red meat, 1.25 (95% CI: 1.13–1.37) for processed meat, 1.00 (95% CI: 0.93–1.07) for poultry and 1.01 (95% CI: 0.93–1.10) for fish. In the dose–response analysis, each additional 100 g/day of total and red meat, and 50 g/day of processed meat, were found to be associated with a 36% (95% CI: 1.23–1.49), 31% (95% CI: 1.19–1.45) and 46% (95% CI: 1.26–1.69) increased risk of T2D, respectively. In addition, there was evidence of a non-linear dose–response association between processed meat and T2D (P = 0.004), with the risk increasing by 30% with increasing intakes up to 30 g/day.ConclusionOur meta-analysis has shown a linear dose–response relationship between total meat, red meat and processed meat intakes and T2D risk. In addition, a non-linear relationship of intake of processed meat with risk of T2D was detected.