| Background and objectivesCardiovascular disease(CVD)was a major cause of premature death and disability both in China and worldwide.Suboptimal diet is an important risk factor for CVD.Insufficient consumption of fruit and vegetable ranked the second and fourth,respectively,among all dietary factors associated with cardiometabolic deaths in China.Previous studies have proved that increased fruit and vegetable consumption was associated with decreased risk of CVD and all-cause mortality.However,the optimal level of fruit and vegetable consumption is unknown.Furthermore,CVD is a complex disease which can be affected by both genetic and environmental factors.Previous studies failed to investigate the interaction effect between genetic risk and fruit and vegetable consumption in the risk of CVD.Therefore,based on data from the project of Prediction for Atherosclerotic Cardiovascular Disease Risk in China(China-PAR),this study aimed to prospectively examine the associations of fruit and vegetable consumption,combined or separately,with the risk of CVD and all-cause mortality;and to explore whether there was an interaction between genetic risk and fruit and vegetable consumption in the risk of stroke.MethodsThe study population came from three prospective cohorts of the China-PAR project,including the China Multicenter Collaborative Study of Cardiovascular Epidemiology-1998(China MUCA-1998),the International Collaborative Study of Cardiovascular Disease in Asia(InterASIA),and the Community Intervention of Metabolic Syndrome in China&Chinese Family Health Study(CIMIC).These three cohorts were established in 1998,2000-2001 and 2007-2008,separately.The first follow-up survey was carried out through 2007 to 2008 for both China MUCA-1998 and InterASIA cohorts.The last follow-up visits of all three cohorts were conducted from 2012 to 2015.Participants with loss to follow-up,missing information on fruit and vegetable consumption or diagnosed with CVD or cancer at baseline survey were excluded,leaving 100728 participants for association analysis.Participants with blood samples in ChinaMUCA-1998 and InterASIA cohorts and randomly selected subpopulations in CIMIC cohort were tested for genotypes.In gene-diet interaction analysis,weighted genetic risk score(GRS)of stroke was calculated among 40205 eligible participants with gene information.At baseline,participants were interviewed and underwent physical examinations and laboratory tests.Self-reported information on fruit and vegetable consumption was collected by questionnaire.Consumption frequencies and amounts were converted into an estimate of daily consumption of fruit and vegetable.Total consumption of fruit and vegetable was the sum consumption of total fruit and total vegetable.We selected single nucleotide polymorphisms(SNPs)that were of genome-wide significance in association with stroke and its related traits based on previous genome-wide association studies(GWASs).Information about each SNP was extracted from summary statistics of the GWAS for stroke conducted by Biobank Japan(including 17671 stroke cases and 192383 controls).We selected about 22 SNPs significantly associated with stroke among East Asian population,and further calculated the weighted genetic risk score(GRS)of stroke.Outcomes were ascertained by interviewing study participants or their proxies,and checking hospital records and/or death certificates.All these records were reviewed and confirmed by the end-point committee.The major outcomes were incident CVD(nonfatal acute myocardial infarction,coronary heart disease(CHD)-related mortality,and fatal or nonfatal stroke),CVD mortality,and all-cause mortality.According to the quartiles of daily consumption of fruit and vegetable,combined or separately,the participants were grouped into four categories.Cox proportional hazard models were used to estimate hazard ratios(HRs)and 95%confidence intervals(CIs)for CVD incidence,CVD mortality and all-cause mortality with the lowest quartile as the reference.Restricted cubic spline(RCS)function models were used to explore the dose-response relationship between fruit and vegetable consumption and the risk of CVD and all-cause mortality.Among participants with information about fruit and vegetable consumption at both two surveys during 2007-2008 and 2012-2015,multivariable logistic regression models were used to evaluate the association between fruit and vegetable consumption change and CVD risk,estimating odds ratios(ORs)and 95%CIs.Moreover,participants were divided into 3 genetic risk or fruit and vegetable consumption groups:low/low(in the bottom quintile of GRS/in the bottom tertile of fruit and vegetable consumption),intermediate/middle(in the second to fourth quintile of GRS/in the middle tertile of fruit and vegetable consumption),and high/high(in the top quintile of GRS/in the top tertile of fruit and vegetable consumption).Cox proportional hazard model was used to evaluate the association between GRS and the risk of stroke.In gene-diet interaction analysis associated with stroke risk,the test for interaction between GRS and fruit and vegetable consumption was performed using likelihood ratio test.ResultsOf 100728 participants,the average age was 51.53 years old,40.20%were male.The median(interquartile range)consumption of total fruit and vegetable,total fruit as well as total vegetable were 450.00(271.43-571.43)g/d,50.00(17.86-142.86)g/d,and 350.00(250.00-500.00)g/d,respectively.After a median follow-up of 7.31 years,3677 CVD events,1483 CVD deaths and 5466 all-cause deaths were documented.Total fruit and vegetable consumption was inversely associated with CVD and all-cause mortality,and the multivariable adjusted HR(95%CI)that compared the top vs bottom quartiles of total fruit and vegetable consumption were 0.85(0.77-0.95)for CVD incidence,0.85(0.75-0.95)for stroke incidence,0.87(0.80-0.95)for all-cause mortality,0.76(0.65-0.90)for CVD mortality,and 0,70(0.57-0.85)for stroke mortality.Nonlinear relationships of total fruit and vegetable consumption with CVD incidence and mortality were observed,and the estimate risks decreased with the elevated consumption at the range of 0-600g/d,with no further decrease at the consumption exceeding 600g/d.However,there was no evidence for nonlinear association between total fruit and vegetable consumption and all-cause mortality.We further conducted the analyses separately by fruit and vegetable consumption.Total fruit consumption was also associated with a lower risk of CVD and all-cause mortality,and the multivariable adjusted HR(95%CI)that compared the top vs bottom quartiles of total fruit consumption were 0.82(0.74-0.91)for CVD incidence,0.79(0.70-0.89)for stroke incidence,0.81(0.74-0.89)for all-cause mortality,0.75(0.63-0.89)for CVD mortality,and 0.66(0.54-0.82)for stroke mortality.No significant associations were observed between total vegetable consumption and CVD and all-cause mortality after multivariate adjustment.And no significant associations were found between fruit and vegetable consumption,combined or separately,and CHD risk.Compared with low consumption of fruit and vegetable at both baseline and follow-up,maintaining high consumption of fruit and vegetable were associated with decreased risk of CVD,with multivariable adjusted OR(95%CI)of 0.82(0.72-0.94)for total fruit and vegetable,0.73(0.61-0.87)for total fruit,and 0.84(0.73-0.96)for total vegetable.A higher GRS was associated with an increased risk of stroke.The risk of stroke was 38%higher among participants at the intermediate genetic risk(HR:1.38;95%CI:1.17-1.61)than those at the lowest genetic risk,and 65%higher among participants at the highest genetic risk group(HR:1.65;95%CI:1.37-1.98).We found no statistically significant interplay between GRS and fruit and vegetable consumption in the risk of stroke.Compared with participants with lowest genetic risk and highest consumption of fruit and vegetable,participants with highest genetic risk and lowest consumption had the highest risk of stroke,with HR(95%CI)of 2.04(1.49-2.78)(for total fruit and vegetable),2.34(1.74-3.13)(for total fruit)and 1.61(1.20-2.17)(for total vegetable),respectively.Moreover,compared with low fruit consumption,high fruit consumption was associated with decreased risk in stroke across low,intermediate,and high genetic risk categories with the HRs of 0.64(95%CI:0.45-0.92),0.68(95%CI:0.57-0.81),and 0.60(95%CI:0.45-0.78),respectively.ConclusionHigher consumption of fruit and vegetable was significantly associated with reduced risk of CVD and all-cause mortality,and threshold effects were observed between fruit and vegetable consumption and CVD risk.Moreover,the association between fruit consumption and stroke was independent of genetic risk.This study provides evidence for promoting increased fruit and vegetable consumption to prevent CVD in China,and has important scientific significance for reducing the burden of CVD. |
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