Dose-Response Association of Low and Normal Ankle Brachial Index With the Risk of Cardiovascular Disease Morbidity and Mortality.

We quantitatively evaluated the dose-response association of low and normal ankle brachial index (ABI) with the risk of morbidity and mortality from cardiovascular diseases (CVDs). PubMed, Embase, and Web of Science were systematically searched for cohort studies. Random effects or fixed effects models were used to estimate the pooled relative risks (RRs) and 95% confidence intervals (95% CIs). Generalized least squares regression was used to assess study-specific dose-response associations per 0.1 ABI decrease. Restricted cubic splines were used to evaluate linear or nonlinear trends. Twelve cohort studies (57 031 participants) were included in this meta-analysis. For low vs normal ABI levels, the pooled RRs were 2.03 (95% CI, 1.72-2.41; I2 = 52.9%; pheterogeneity=0.030) and 2.29 (95% CI, 1.98-2.64; I2 = 39.5%; pheterogeneity =0.158) for CVD morbidity and CVD mortality, respectively. For per 0.1 ABI decrease from 1.40 the risk for CVD morbidity and CVD mortality increased by 8% (1.08, 95% CI 1.04-1.11) and 11% (1.11, 95% CI 1.07-1.15), respectively. Restricted cubic splines showed inverse linear associations for CVD morbidity and CVD mortality. As a non-invasive index, lower ABI was significantly associated with the increased risk of morbidity and mortality from CVDs in an inverse linear manner.

Integrated analysis of probability of type 2 diabetes mellitus with polymorphisms and methylation of SLC30A8 gene: a nested case-control study.

To estimate the associations between single-nucleotide polymorphisms (SNPs) and methylation of SLC30A8 gene and T2DM risk, and the interactions among SNPs, methylation, and environmental factors on T2DM risk. We genotyped 9 SNPs and tested methylation at 46 CpG loci of SLC30A8 in the baseline DNA of 290 T2DM cases and 290 matched controls nested in the Rural Chinese Cohort Study. A conditional logistic regression model was used to estimate the associations between SNPs and SLC30A8 methylation and T2DM risk. Multifactor Dimensionality Reduction analysis was used to estimate the effect of interactions among SNPs, methylation, and environment on T2DM risk. Probability of T2DM was decreased with rs11558471 (GG vs. AA, OR = 0.55, 95% CI 0.32, 0.96), with rs13266634 (TT vs. CC, OR = 0.55, 95% CI 0.32, 0.94), with rs3802177 (AA vs. GG, OR = 0.54, 95%CI 0.31, 0.94), and its probability was increased with rs2466293 of SLC30A8 (GA vs. AA, OR = 1.63, 95% CI 1.08-2.47). Its probability was also significantly associated with methylation of CG9 and CG45 (OR = 0.56 [95% CI 0.33-0.97] and 1.61 [95%CI 1.03--2.51]). T2DM probability was significantly associated with the interaction effect between rs2466293 and hypertension (p = 0.045). T2DM probability was also significantly associated with the combination effects of rs2466293 with BMI, hypertension, and hypertriglyceridemia, with the combination effects of hypertriglyceridemia with rs11558471, rs13266634, and methylation of CG45.

Joint effect of physical activity and blood lipid levels on all-cause and cardiovascular disease mortality: The Rural Chinese Cohort Study.

BACKGROUND AND AIMS: We aimed to evaluate the joint effect of physical activity (PA) and blood lipid levels on all-cause and cardiovascular disease (CVD) mortality. METHODS AND RESULTS: We analyzed 17,236 participants from the Rural Chinese Cohort Study. Cox's proportional-hazards regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) between the joint effect of PA and blood lipid levels and risk of all-cause and CVD mortality. Restricted cubic splines were used to estimate the dose-response relationship of PA with risk of all-cause and CVD mortality. During a median follow-up of 6.01 years there were 1106 deaths (484 from CVD) among participants. For all-cause mortality, compared with the group with dyslipidemia and extremely light PA (ELPA), the HRs with dyslipidemia and light PA (LPA), moderate PA (MPA), and heavy PA (HPA) were 0.56 (95% CI 0.45-0.70), 0.59 (0.46-0.75), and 0.59 (0.45-0.78), respectively, while the HRs of groups with normal lipid levels and ELPA, LPA, MPA, and HPA were 0.88 (0.72-1.04), 0.59 (0.48-0.73), 0.53 (0.41-0.67), and 0.38 (0.29-0.50), respectively. We observed similar effects on CVD mortality. Restricted cubic splines showed a curvilinear relationship between PA and risk of all-cause and CVD mortality with normal lipid levels and with dyslipidemia. CONCLUSION: Higher PA reduces the risk of all-cause and CVD mortality. Higher levels of PA are needed in the population.

Independent and joint associations of non-exercise cardiorespiratory fitness and obesity with risk of type 2 diabetes mellitus in the Rural Chinese Cohort Study.

BACKGROUND AND AIMS: An association between cardiorespiratory fitness (CRF) and type 2 diabetes mellitus (T2DM) has not been established in the Chinese population. This study aimed to estimate the independent and joint associations of CRF and obesity with T2DM incidence in the rural Chinese population. METHODS AND RESULTS: We conducted a prospective study of 11,825 non-T2DM subjects among rural Chinese adults. Cox regression models were used to estimate the independent and joint associations between CRF and obesity exposure on T2DM. Restricted cubic splines were used to model the dose-response association. During a median follow-up of 6.01 years, 835 participants developed T2DM. In comparison to quartile 1 of CRF, the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of quartiles 2, 3, 4 were 0.75 (0.61-0.91), 0.54 (0.43-0.68), and 0.42 (0.32-0.55), respectively. When stratified by sex, the results were similar. Joint analyses showed that overweight/obesity-unfit individuals had a 2.28 times higher risk of developing T2DM than the normal weight-fit referent (HR 2.28, 95% CI 1.84-2.83; Pinteraction <0.001). The risk for the overweight/obesity-fit category (HR 1.61, 95% CI 1.21-2.15) was larger than for the normal weight-unfit category (HR 1.38, 95% CI 0.97-1.95) versus the normal weight-fit referent. Similar joint associations for waist circumference and CRF with T2DM were also observed. CONCLUSION: A negative association was observed between CRF and risk of T2DM. Overweight/obese or abdominal obesity and unfit participants showed the highest risks of T2DM. It is therefore strongly recommended that fitness-enhancing be encouraged for the prevention of T2DM, especially among obesity participants.

Metabolic Score for Visceral Fat: a novel predictor for the risk of type 2 diabetes mellitus.

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12 237 non-T2DM participants aged over 18 years from the Rural Chinese Cohort Study of 2007-2008 were included at baseline and followed up during 2013-2014. The cox proportional hazards regression was used to calculate hazard ratios (HR) and 95 % CI for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6·01 (95 % CI 5·09, 6·06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR for the highest v. lowest METS-VF quartile was 5·97 (95 % CI 4·28, 8·32), with a per 1-sd increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose-response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0·0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age or BMI.

Fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus, and hypertension in adults: a meta-analysis of observational studies.

Recent studies have reported conflicting associations of fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus (T2DM) and hypertension, and a meta-analysis is not available. We aimed to explore the association between fried-food consumption and risk of overweight/obesity, T2DM and hypertension in adults through a meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published up to 17 June 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. In comparing the highest to lowest fried-food intake, the pooled RRs (95% CIs) were 1.16 (1.07-1.25; I2 = 71.0%, Pheterogeneity < 0.001) for overweight/obesity (cohort: 1.19 [0.97-1.47], n = 2; cross-sectional: 1.14 [1.03-1.27], n = 9), 1.07 (0.90-1.27; 84.7%) for T2DM (cohort: 1.01 [0.89-1.15], n = 9; case-control: 2.33 [1.80-3.01], n = 1), and 1.20 (1.05-1.38; I2=91.8%) for hypertension (cohort: 1.06 [0.98-1.15], n = 8; cross-sectional: 2.16 [0.59-7.87], n = 3). Our meta-analysis indicates fried-food consumption is associated with increased risk of overweight/obesity and hypertension but not T2DM in adults, but the findings should be interpreted with caution due to high heterogeneity and unstable subgroup analyses of this meta-analysis. More studies are warranted to investigate the total fried-food consumption and these health outcomes.

Metabolic Score for Visceral Fat: A reliable indicator of visceral obesity for predicting risk for hypertension.

OBJECTIVES: The aim of this study was to investigate the association of the Metabolic Score for Visceral Fat (METS-VF) with the risk for hypertension and to compare the ability of the METS-VF, the metabolic score for insulin resistance, visceral adiposity index, waist-to-height ratio, waist circumference, and body mass index to predict hypertension incidence based on a large prospective study of rural Chinese individuals. METHODS: In all, 10 297 non-hypertensive adults (≥18 y of age) from a rural Chinese cohort study in 2007 and 2008 were included at baseline and followed up in 2013 and 2014. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between baseline METS-VF and hypertension risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict hypertension incidence. RESULTS: We identified 2071 hypertension cases during follow-up. After adjusting for multivariable confounding factors, the adjusted ORs (95% CIs) for the highest versus lowest METS-VF quartile overall and for men and women were 3.84 (3.23-4.56), 3.25 (2.48-4.24), and 4.14 (3.30-5.20), respectively. Also, per-SD increase in METS-VF was positively associated with hypertension risk overall and for men and women. Similar results were found in the sensitivity and subgroup analyses. Finally, the AUC value for hypertension was higher for METS-VF than the other five indices overall and for men and women. CONCLUSIONS: The present study indicated that METS-VF was positively associated with hypertension incidence and performed better in predicting hypertension risk than five other indices, which suggests that METS-VF is a reliable predictor of hypertension in the Chinese population.

How sleep duration mediated childhood trauma and Internet addiction of the vocational college population in urban areas of south China.

Background: Internet Addiction is positively associated with a range of psychological risk factors such as childhood trauma and sleep disorders. However, it remains unclear if sleep duration mediates the association between childhood trauma and Internet addiction. Methods: We enrolled 14,263 students from Shenzhen Polytechnic College, China. Sleep duration, Internet addiction and childhood maltreatment were assessed in these students by self-report measures, Internet Addiction Test (IAT) and Childhood Trauma Questionnaire (CTQ), respectively. With bootstrap approach and path analysis, the mediating role of sleep duration in the association between childhood trauma and Internet addiction was analysed. Results: The Internet-addicted group exhibited a higher level of the emotional abuse (EA) score, physical abuse (PA) score, sexual abuse (SA) score, a lower level of emotional neglect (EN) score and sleep duration compared with the control group (all p < 0.001). The CTQ total score and subscores showed a positive correlation with IAT scores both for males (r = 0.199, p < 0.001 for the total score, r = 0.356, p < 0.001 for EA, r = 0.270, p < 0.001 for PA, r = 0.249, p < 0.001 for SA, and r = 0.132, p < 0.001 for PN) and females (r = 0.127, p < 0.001 for the total score, r = 0.335, p < 0.001 for EA, r = 0.187, p < 0.001 for PA, r = 0.189, p < 0.001 for SA, and r = 0.065, p < 0.001 for PN). The CTQ subcores were negatively related to sleep duration both for males (r = -0.177, p < 0.001 for EA, r = -0.180, p < 0.001 for PA and r = 0.182, p < 0.001 for SA) and females (r = -0.137, p < 0.001 for EA, r = -0.105, p < 0.001 for PA, and r = -0.182, p < 0.001 for SA) and sleep duration was negatively correlated with IAT scores both in males (r = -0.120, p < 0.001) and females (r = -0.108, p < 0.001). Further, the path analysis suggested that EA and SA mediated significantly to the Internet addiction when all types of childhood trauma were examined in one model (both p < 0.001). Conclusion: In the current study, a great proportion of students met criteria for Internet addiction. Sleep duration mediated a significant proportion of the indirect effect between EA/SA and Internet addiction. The findings may help with prevention and intervention of Internet addiction in the future. The limitation of this study was that it was a cross-sectional study and not controlling for other mental disorders. Future large-scale longitudinal studies will be needed to further clarify the relationship between childhood abuse and Internet addiction and the mediation role of sleep duration.

Association of hypertriglyceridemic waist-to-height ratio and its dynamic status with risk of type 2 diabetes mellitus: The Rural Chinese Cohort Study.

AIMS: To evaluate the risk of type 2 diabetes mellitus (T2DM) in a prospective study with hypertriglyceridemic waist-to-height ratio (HWHtR) and its dynamic status. METHODS: We collected data for 12,248 participants ≥18 years in this study. Cox's proportional-hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM risk by baseline HWHtR. Multiple logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs for T2DM risk by transformation in HWHtR. RESULTS: We identified 839 T2DM cases during a median follow-up of 5.92 years. Compared with normal TG level and normal WHtR, T2DM risk was increased with high TG level and high WHtR (aHR 2.04, 95% CI 1.49-2.79). Similar results were observed in subgroup analyses by sex and age. During follow-up, T2DM risk was increased with stable high TG level and high WHtR (aOR 4.45, 95% CI 2.76-7.17) compared with stable normal TG level and normal WHtR. The results above were robust in sensitivity analyses. CONCLUSIONS: HWHtR phenotype and its dynamic status were associated with risk of T2DM. Our study suggests that primary prevention and avoiding the appearance of the HWHtR phenotype in the rural Chinese population may reduce the T2DM risk.

Association between shift work and risk of metabolic syndrome: A systematic review and meta-analysis.

AIMS: A comprehensive assessment of the association of shift work with risk of metabolic syndrome (MetS) through a systematic review and meta-analysis has not been reported. We aimed to evaluate the relationship from observational studies. DATA SYNTHESIS: We searched PubMed, Embase, and Web of Science databases from inception to December 16, 2020. Articles were chosen according to established inclusion criteria. Studies with data on men and women and different types of shift work were treated as independent studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled by using random-effects models with heterogeneity (I2) > 50%; otherwise, a fixed-effects model was used. A total of 7192 articles was searched from PubMed, Embase and Web of science. Finally, we included 23 articles (38 studies) in this meta-analysis. The pooled RRs and 95% CI of MetS risk with shift work, 1-shift work, 2-shift work, and 3-shift work versus non-shift work were 1.30 (95% CI 1.19-1.41), 0.95 (95% CI 0.82-1.11), 1.19 (95% CI 0.91-1.56) and 1.17 (95% CI 1.00-1.37), respectively. The results from subgroup analyses stratified by sex, age, and region supported our overall findings that shift work is a risk factor for MetS. CONCLUSIONS: This meta-analysis suggests that shift work increases risk of MetS. Higher risk of MetS was found in the shift workers who were 2-shift or 3-shift or women or Asian workers.

Long-term association of ambient air pollution and hypertension in adults and in children: A systematic review and meta-analysis.

AIMS: The association of long-term ambient air pollution and hypertension has been inconsistently reported. We performed an updated systematic review and meta-analysis to assess the association between long-term exposure to ambient air pollution and risk of hypertension in adults and in children. METHODS: PubMed, EMBASE, and Web of Science were searched up to August 7, 2020 for published articles examining the association of long-term exposure to ambient air pollution, including particulate matter (PM; ultrafine particles, PM1, PM1-2.5, PM2.5, PM2.5-10 and PM10), nitrogen dioxide (NO2), nitrogen oxides (NOx), sulfur dioxide (SO2), ozone (O3), carbon monoxide (CO) and hypertension. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for hypertension with each 10-µg/m3 increase in air pollutants were calculated by random-effects models. RESULTS: We included 57 studies (53 of adults and 4 of children) in the meta-analysis. Risk of hypertension was significantly increased in adults with each 10-µg/m3 increase in exposure to PM2.5 (OR 1.10, 95% CI 1.07-1.14; I2 = 93.1%; n = 37), PM10 (1.04, 1.02-1.07; I2 = 44.8%; n = 22), and SO2 (1.21, 1.08-1.36; I2 = 96.6%; n = 3). Hypertension was not significantly associated with PM1 (n = 2), PM2.5-10 (n = 16), NO2 (n = 27), or NOx (n = 17). In children, the summary ORs (95% CIs) for each 10-µg/m3 increase in PM2.5, PM10, SO2 and O3 were 2.82 (0.51-15.68; I2 = 83.8%; n = 2), 1.15 (1.01-1.32; I2 = 0; n = 2), 8.57 (0.13-575.58; I2 = 94.2%; n = 2), and 1.26 (0.81-1.09, I2 = 91.6%; n = 2), respectively. CONCLUSIONS: Long-term ambient air pollution is a potential risk factor for hypertension in adults. More studies are needed to explore the effects of long-term air pollution on hypertension in children.

Integrated analysis of probability of type 2 diabetes mellitus with polymorphisms and methylation of KCNQ1 gene: A nested case-control study.

BACKGROUND: To estimate the associations between single-nucleotide polymorphisms (SNPs) and methylation of KCNQ1 gene and type 2 diabetes mellitus (T2DM) risk and the interactions among SNPs, methylation, and environmental factors on T2DM risk. METHODS: We genotyped five SNPs and tested methylation at 39 CpG loci of KCNQ1 in 290 T2DM cases and 290 matched controls nested in the Rural Chinese Cohort Study. Conditional logistic regression model was used to estimate the associations between SNPs and KCNQ1 methylation and T2DM risk. Multifactor dimensionality reduction (MDR) analysis was used to estimate the effect of the interactions SNPs-SNPs, SNPs-methylation, methylation-methylation and SNPs, and methylation-environment on T2DM risk. RESULTS: Probability of T2DM was decreased with rs2283228 of KCNQ1 (CA vs AA, odds ratio [OR] = 0.65, 95% confidence interval [CI] 0.42-0.99). T2DM probability was significantly increased with rs2237895 combined with hypertriglyceridemia (OReg  = 2.76, 95% CI 1.35-5.62), with hypertension (OReg  = 2.23, 95% CI 1.25-3.98), and with body mass index (BMI; OReg  = 1.93, 95% CI 1.12-3.34). T2DM probability was associated with methylation of CG11 and CG41 (OR = 1.89, 95% CI 1.23-2.89, P = .003). It was significantly associated with the interaction between BMI, hypertriglyceridemia, and CG5 methylation (P = .028 and .028), and the combined effects of CG11 with hypertriglyceridemia and hypertension. On MDR analysis, no significant interaction was observed. CONCLUSION: T2DM probability was reduced 35% with rs2283228 polymorphism. It was associated with rs2237895 combined with hypertension, with BMI and with hypertriglyceridemia. The methylation at two CpG loci of KCNQ1 significantly increased T2DM risk by 89%.

Solid fuel use and cardiovascular events: A systematic review and meta-analysis of observational studies.

Although solid fuel use has been increasingly linked to cardiovascular events (CVEs), conclusions have been inconsistent. We systematically searched 3 databases (PubMed, Embase, and Web of Science) up to July 3, 2020, to identify English language reports that assessed the association of solid fuel use with CVEs. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to explore the potential sources of heterogeneity and to test the stability of the results. We finally included 13 observational studies (8 cohort, 3 cross-sectional, and 2 case-control studies comprising 791,220 participants) in the meta-analysis. The risk of CVEs was increased 21% with the highest versus the lowest solid fuel use (highest/lowest, RRpooled  = 1.21, 95% CI: 1.10-1.34). As for the subgroup analyses on study design, the pooled RR for cohort studies, case-control studies, and cross-sectional studies were 1.11 (95%CI: 1.03-1.19), 4.80 (95%CI: 2.22-10.39), and 1.46 (95%CI: 0.82-2.62), respectively. The results of this study suggested that high solid fuel use was associated with increased CVE risk, and that reducing the use of solid fuel will be important for improving the health of the populations in developing countries.

Cohort study evaluation of New Chinese Diabetes Risk Score: A new non-invasive indicator for predicting metabolic syndrome.

OBJECTIVES: To investigate the association of the baseline New Chinese Diabetes Risk Score (NCDRS) with metabolic syndrome (MetS) risk and to evaluate the power of the baseline NCDRS to predict MetS based on the rural Chinese cohort study. METHODS: Study participants were classified by baseline quartiles of NCDRS by gender. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of MetS according to different diagnostic criteria. The receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were used to evaluate the power of the baseline NCDRS for predicting MetS according to different diagnostic criteria. RESULTS: We included 7,133 participants, and 1,651 MetS cases were identified after 6 years follow-up. After adjusting for multivariable confounding factors and with NCDRS quartile 1 as the reference, with quartile 4, the risk of MetS was increased for all participants, men and women: ORs (95% CIs) 4.03 (3.23-5.02), 3.59 (2.56-5.05) and 5.71 (4.23-7.70), respectively. Similar results were found on sensitivity analysis. The baseline NCDRS was a good predictor of MetS for all participants, men and women with MetS defined according to the diagnostic criteria of the Chinese Joint Committee on the Development of Guidelines for the Prevention and Treatment of Dyslipidemia in Adults (JCDCG). CONCLUSIONS: Our study, based on the cohort study, found that the baseline NCDRS was positively associated with risk of MetS. Furthermore, our study might provide suggestions for developing a useful and inexpensive tool for predicting MetS in the Chinese population.

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.

AIMS: The 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 SYNTHESIS: PubMed 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 (Pnon-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 (Pnon-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. CONCLUSIONS: In 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.

Association between serum level of C-reactive protein and risk of cardiovascular events based on cohort studies.

Although the association between serum level of C-reactive protein (CRP) and risk of cardiovascular events (CVEs) has been reported, the comprehensive assessment of the quantitative association of CRP level with risk of CVEs has not been reported. Our meta-analysis aims to quantitatively evaluate the association of CRP level and risk of CVEs. We searched PubMed and Embase databases for articles published up to December 6, 2019. Studies with data on men and women, different types of CVEs and multiple cohorts within a study were treated as independent studies. Generalized least-squares regression models were used to assess the quantitative association between CRP level and risk of CVEs. Restricted cubic splines were used to model the possible linear association between CRP and CVEs. We included 36 articles (60 studies; 227,715 participants) in the analysis. The pooled relative risks (RRs) of high versus low CRP level for cardiovascular disease (CVD), stroke and coronary heart disease (CHD) were 1.64 (95% confidence interval [CI], 1.49-1.82), 1.46 (95% CI, 1.35-1.58), and 1.55 (95% CI, 1.47-1.63), respectively. A linear association was found between CRP level and CVD (P = 0.429), stroke (P = 0.940), and CHD (P = 0.931); with each 1-mg/L increase in CRP level, the pooled RRs for CVD, stroke, and CHD were 1.18 (95% CI, 1.12-1.24), 1.07 (95% CI, 1.04-1.09), and 1.12 (95% CI, 1.08-1.16), respectively. This meta-analysis suggests that risk of CVEs increases with increasing serum CRP level.

Dose-Response Association Between High-Density Lipoprotein Cholesterol and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

INTRODUCTION: Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose-response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. METHODS: We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C-stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose-response associations. RESULTS: We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76-0.89; I2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69-0.82; I2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04-1.42; I2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96-1.00; I2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg's test and Egger's test for the association of HDL-C level with risk of total stroke, IS, and ICH. CONCLUSION: A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.

BMI and risk of all-cause mortality in normotensive and hypertensive adults: the rural Chinese cohort study.

OBJECTIVE: The impact of baseline hypertension status on the BMI-mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI-mortality association using a rural Chinese cohort. DESIGN: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. SETTING: Longitudinal population-based cohort. PARTICIPANTS: 17 262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. RESULTS: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤ 18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the hazard ratios for mortality in normotensive participants were 1·92 (95% CI 1·23, 3·00), 1·44 (95% CI 1·01, 2·05), 1·14 (95% CI 0·82, 1·58), 0·96 (95% CI 0·70, 1·31), 0·96 (95% CI 0·65, 1·43), 1·32 (95% CI 0·81, 2·14) and 1·32 (95% CI 0·74, 2·35), respectively, and in hypertensive participants were 1·85 (95% CI 1·08, 3·17), 1·67 (95% CI 1·17, 2·39), 1·29 (95% CI 0·95, 1·75), 1·20 (95% CI 0·91, 1·58), 1·10 (95% CI 0·83, 1·46), 1·10 (95% CI 0·80, 1·52) and 0·61 (95% CI 0·40, 0·94), respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity v. normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. CONCLUSIONS: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

Air pollution and DNA methylation in adults: A systematic review and meta-analysis of observational studies.

This systematic review and meta-analysis aimed to investigate the association between air pollution and DNA methylation in adults from published observational studies. PubMed, Web of Science and Embase databases were systematically searched for available studies on the association between air pollution and DNA methylation published up to March 9, 2021. Three DNA methylation approaches were considered: global methylation, candidate-gene, and epigenome-wide association studies (EWAS). Meta-analysis was used to summarize the combined estimates for the association between air pollutants and global DNA methylation levels. Heterogeneity was assessed with the Cochran Q test and quantified with the I2 statistic. In total, 38 articles were included in this study: 16 using global methylation, 18 using candidate genes, and 11 using EWAS, with 7 studies using more than one approach. Meta-analysis revealed an imprecise but inverse association between exposure to PM2.5 and global DNA methylation (for each 10-µg/m3 PM2.5, combined estimate: 0.39; 95% confidence interval: 0.97 - 0.19). The candidate-gene results were consistent for the ERCC3 and SOX2 genes, suggesting hypermethylation in ERCC3 associated with benzene and that in SOX2 associated with PM2.5 exposure. EWAS identified 201 CpG sites and 148 differentially methylated regions that showed differential methylation associated with air pollution. Among the 307 genes investigated in 11 EWAS, a locus in nucleoredoxin gene was found to be positively associated with PM2.5 in two studies. Current meta-analysis indicates that PM2.5 is imprecisely and inversely associated with DNA methylation. The candidate-gene results consistently suggest hypermethylation in ERCC3 associated with benzene exposure and that in SOX2 associated with PM2.5 exposure. The Kyoto Encyclopedia of Genes and Genomes (KEGG) network analyses revealed that these genes were associated with African trypanosomiasis, Malaria, Antifolate resistance, Graft-versus-host disease, and so on. More evidence is needed to clarify the association between air pollution and DNA methylation.

Association of Cycling with Risk of All-Cause and Cardiovascular Disease Mortality: A Systematic Review and Dose-Response Meta-analysis of Prospective Cohort Studies.

BACKGROUND: Cycling has been suggested to be related to risk of all-cause and cardiovascular disease (CVD) mortality. However, a quantitative comprehensive assessment of the dose-response association of cycling with risk of all-cause and CVD mortality has not been reported. We performed a meta-analysis of cohort studies assessing the risk of all-cause and CVD mortality with cycling. METHODS: PubMed and Embase databases were searched for relevant articles published up to December 13, 2019. Random-effects models were used to estimate the summary relative risk (RR) of all-cause and CVD mortality with cycling. Restricted cubic splines were used to evaluate the dose-response association. RESULTS: We included 9 articles (17 studies) with 478,847 participants and 27,860 cases (22,415 from all-cause mortality and 5445 from CVD mortality) in the meta-analysis. Risk of all-cause mortality was reduced 23% with the highest versus lowest cycling level [RR 0.77, 95% confidence interval (CI) 0.67-0.88], and CVD mortality was reduced 24% (RR 0.76, 95% CI 0.65-0.89). We found a linear association between cycling and all-cause mortality (Pnon-linearity = 0.208); the risk was reduced by 9% (RR 0.91, 95% CI 0.86-0.96) with each five metabolic equivalent of task (MET)-h/week increase in cycling. We found an approximately U-shaped association between cycling and CVD mortality (Pnon-linearity = 0.034), with the lowest risk at approximately 15 MET-h/week of cycling. CONCLUSIONS: Our findings based on quantitative data suggest that any level of cycling is better than none for all-cause mortality. However, for CVD mortality, one must choose an appropriate level of cycling, with an approximate optimum of 15 MET-h/week (equal to 130 min/week at 6.8 MET).