Prospective findings from the Dongfeng-Tongji cohort: Exposure to various metals, the expression of microRNA-4286, and the incidence of acute coronary syndrome.

Mounting evidence suggests that metal/metalloid exposure is related to the adverse health effects. Our prior investigation revealed a positive relation between the plasma level of microRNA-4286 (miR-4286) and an increased risk of developing acute coronary syndrome (ACS). However, it is a lack of studies evaluating the connection between metal/metalloid exposure and miRNA expression on ACS. In the prospective Dongfeng-Tongji cohort, we performed a nested case-control study. A total of 480 ACS and 480 controls were carefully selected based on similar age, sex, and blood collection time. Using inductively coupled plasma mass spectrometry, we assessed the plasma concentrations of 24 different metals. Quantitative real-time polymerase chain reaction was used to analyze the plasma miR-4286. We examined the relations of plasma metals with miR-4286 levels, the incidence of ACS, and the potential interactions. Using the multivariate conditional logistic regression models, we observed that the adjusted odds ratios (95% confidence intervals [CI]) for incident ACS were 1.79 (1.03, 3.12; P-trend = 0.03), 0.60 (0.41, 0.87; P-trend = 0.008), and 0.66 (0.46, 0.93; P-trend = 0.02), when comparing the extreme tertiles of aluminum, rubidium, and selenium, respectively. There was a relation between the concentration of rubidium in plasma and a decrease in the level of plasma miR-4286 (percent difference [95% CI]: -13.36% [-22.74%, -2.83%]; P-trend = 0.01). Both multiplicative (P interaction = 0.009) and additive interactions (relative excess risk due to interaction [95% CI]: 0.82 [0.59, 1.06]) were noted in our observation regarding the relationship between plasma aluminum and miR-4286 in incident ACS. The findings indicated that plasma aluminum was positively while plasma rubidium and selenium were negatively linked to an increased risk of developing ACS. Plasma aluminum exposure and plasma miR-4286 expression might synergistically affect the incident ACS risk. Controlling aluminum exposure was important for ACS prevention, especially for individuals with high expression of plasma miR-4286.

Associations between different body mass index and lung function impairment in Chinese people aged over 40 years: a multicenter cross-sectional study.

OBJECTIVE: The aim of this study was to explore the associations between different body mass index (BMI) levels and different lung function impairment (LFI) in Chinese people aged over 40 years. METHODS: We used a multi-stage stratified cluster random sampling method to investigate 3000 residents aged over 40 years from 5 areas in Hubei province of China in 2019-20. The data on questionnaire, physical measurements, and spirometry of the participants were collected. The associations of different BMI levels with different LFI were analyzed using multivariate logistic regressions after complex weighting. The spirometry data were analyzed using one-factor analysis of variance (ANOVA), and post-hoc was performed using the least significance difference (LSD)-t test. RESULTS: A total of 2860 subjects were included. The prevalence (95%CI) of obstructive lung disease (OLD), restrictive lung disease (RLD), mixed lung disease (MLD), chronic obstructive pulmonary disease (COPD), COPD mild, and COPD moderate/severe/very severe were 24.1% (95% CI: 22.2-26.2), 11.6% (95% CI: 10.3-12.9), 4.0% (95% CI: 3.3-4.8), 12.6% (95% CI: 11.0-14.1), 7.2% (95% CI: 6.0-8.4), and 5.3% (95% CI: 4.3-6.4) respectively. After multivariate adjustment, the risk of OLD, COPD, and COPD mild decreased with the increment of BMI levels (both P for trend < 0.05). When compared to the normal weight group, the overweight group and obese group were at lower risk of experiencing OLD than normal group, the ORs were 0.77 (95% CI: 0.59-0.99) and 0.59 (95% CI: 0.40-0.86) respectively. The obese group was at lower risk for people with COPD mild (OR: 0.42, 95%CI: 0.21-0.85). Participants in underweight group were more likely to experience COPD and COPD moderate/severe/very severe, the ORs were 2.82 (95% CI: 1.07-7.39) and 3.89 (95% CI: 1.28-11.87) respectively. CONCLUSION: Higher BMI levels were associated with an decreased risk of OLD and COPD. Obesity had a protective effect on lung function in OLD patients and COPD patients. However, there was no significant difference in RLD and MLD prevalence between different BMI groups.

Elevated Levels of Serum Alkaline Phosphatase are Associated with Increased Risk of Cardiovascular Disease: A Prospective Cohort Study.

AIM: We aimed to investigate the associations of serum alkaline phosphatase (ALP) levels with incident cardiovascular disease (CVD), coronary heart disease (CHD), and stroke, as well as their subtypes, among men and women in a prospective cohort study. METHODS: A total of 11,408 men and 14,981 women were included to evaluate the associations between ALP levels and incident CVD. Participants were divided into four groups according to the quartiles of serum ALP levels in men and women separately. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average follow-up of 7.3 years, 7,015 incident CVDs (5,561 CHDs and 1,454 strokes) were documented. After adjustments for age, body mass index, smoking status, drinking status, diabetes, hyperlipidemia, hypertension, physical activity, aspirin usage, anticoagulants usage, menopausal status (women only), family history of CVD, estimated glomerular filtration rate, white blood cell counts, and admission batch and comparing the lowest quartile of ALP, the adjusted HRs (95% CIs) of participants in the highest quartile were 1.22 (1.11-1.34) for CVD, 1.14 (1.02-1.28) for CHD, 1.43 (1.18-1.73) for stroke, 1.31 (1.09-1.57) for acute coronary syndrome (ACS), 1.37 (1.11-1.70) for ischemic stroke, and 1.75 (1.10-2.79) for hemorrhagic stroke in men and 1.12 (1.01-1.23) for CVD, 1.10 (0.99-1.23) for CHD, 1.18 (0.92-1.51) for stroke, 1.23 (1.03-1.47) for ACS, 1.10 (0.83-1.45) for ischemic stroke, and 1.54 (0.90-2.65) for hemorrhagic stroke in women. The ALP-CVD associations remained significant even within the normal ranges of ALP levels (40-150 U/L). Moreover, linear dose-response relationships were found between ALP levels and incident CVD. CONCLUSIONS: Higher ALP levels, even within the normal range, were significantly associated with increased risks of CVD, in a dose-dependent manner. These findings suggested that regular monitoring of ALP levels may help in improving the early identification of the population at higher CVD risk.

Alternations in the gut microbiota and metabolome with newly diagnosed unstable angina.

Gut microbiota plays an important role in coronary heart disease, but its compositional and functional changes in unstable angina (UA) remain unexplored. We performed metagenomic sequencing of 133 newly diagnosed UA patients and 133 sex- and age-matched controls, and profiled the fecal and plasma metabolomes in 30 case-control pairs. The alpha diversity of gut microbiota was increased in UA patients: the adjusted odds ratios (ORs) per standard deviation increase in Shannon and Simpson indices were 1.30 (95% confidence interval, 1.01-1.70) and 1.36 (1.05-1.81), respectively. Two common species (depleted Klebsiella pneumoniae and enriched Streptococcus parasanguinis; P ≤ 0.002) and three rare species (depleted Weissella confusa, enriched Granulicatella adiacens and Erysipelotrichaceae bacterium 6_1_45; P ≤ 0.005) were associated with UA. The UA-associated gut microbiota was depleted in the pathway of L-phenylalanine degradation (P = 0.001), primarily contributed by Klebsiella pneumoniae. Consistently, we found increased circulating phenylalanine in UA patients (OR = 2.76 [1.17-8.16]). Moreover, Streptococcusparasanguinis was negatively correlated with fecal citrulline (Spearman's rs = -0.470, P = 0.009), a metabolite depleted in UA patients (OR = 0.26 [0.08-0.63]). These findings are informative to help understand the metabolic connection between gut microbiota and UA.

Associations of coagulation factor X and XI with incident acute coronary syndrome and stroke: A nested case-control study.

BACKGROUND: Coagulation cascade contributes to thrombotic and hemorrhagic diseases, but it remains unclear whether coagulation factors X (FX) and XI (FXI) levels are associated with cardiovascular diseases. OBJECTIVE: To evaluate prospective associations of FX and FXI levels with incident acute coronary syndrome (ACS), stroke, and their subtypes (acute myocardial infarction, unstable angina, ischemic stroke, and hemorrhagic stroke). METHODS: We performed a nested case-control study (n = 1846) within the Dongfeng-Tongji cohort from 2013 to 2016 matched on age (within 1 year), sex, and sampling date (within 1 month) by incidence density sampling, and measured plasma FX and FXI levels by enzyme-linked immunosorbent assay. FX and FXI levels were categorized into three groups (low, <25th; middle, 25th to <75th; and high ≥75th percentiles) according to distributions, and conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: After adjustment for traditional cardiovascular risk factors, compared with middle groups, the OR (95% CI) in high levels of FX and FXI were 1.11 (0.79-1.56) and 0.96 (0.68-1.36) for incident ACS, and 1.01 (0.63-1.62) and 1.72 (1.14-2.60) for incident stroke, respectively. As for subtypes of ACS and stroke, only high FXI levels were significantly associated with incident ischemic stroke (OR 1.66, 95% CI 1.05-2.65). Moreover, all associations remained steady after additional adjustment for platelet and leukocyte. CONCLUSION: FXI levels were associated with a greater risk of incident ischemic stroke but not hemorrhagic stroke or ACS. FX levels were not associated with incident ACS or stroke.

Prospective Study on Plasma MicroRNA-4286 and Incident Acute Coronary Syndrome.

Background Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2-stage prospective nested case-control design within the Dongfeng-Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case-control pairs using quantitative real-time polymerase chain reaction. We observed that plasma miR-4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07-1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR-4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%-18.83%) increase in plasma miR-4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR-4286 (ß coefficients: 0.27 [95% CI, 0.01-0.53] and 0.27 [95% CI, 0.07-0.47] separately by inverse variance-weighted and Mendelian randomization-pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR-4286 explained 5.5% (95% CI, 0.7%-17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR-4286 was associated with an increased risk of ACS. The upregulated miR-4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.

Association of resting heart rate and its change with incident cardiovascular events in the middle-aged and older Chinese.

Whether heart rate change is associated with cardiovascular disease (CVD) in the general population is unclear. We conducted a prospective cohort study to assess the association of resting heart rate and its change with incident CVD in the middle-aged and older Chinese. Resting heart rate was measured during the baseline survey (September 2008 to June 2010) and the resurvey (2013). Incident CVD was followed up until December 31, 2016. Finally, a total of 20,828 participants were included in the analyses of baseline heart rate and 9132 participants were included in the analyses of heart rate change. The associations of baseline heart rate and heart rate change with incident CVD were assessed with multivariable Cox proportional hazards models. Compared with moderate baseline heart rate (65 to 80 bpm), low baseline heart rate (<65 bpm) was associated with higher risk of CVD (HR, 1.19; 95% CI, 1.07-1.32). Compared with stable heart rate (-5 to 15 bpm) in the moderate baseline heart rate group (65 to 80 bpm), an increase of heart rate (>15 bpm) in high baseline heart rate group (>80 bpm) (HR, 1.67; 95% CI, 1.02-2.71) or a decrease of heart rate (<-5 bpm) in low baseline heart rate group (<65 bpm) (HR, 2.48; 95% CI, 1.27-4.82) was associated with higher risk of CVD. In conclusion, low resting heart rate is associated with higher risk of CVD. Both continuous increase in high baseline heart rate and decrease in low baseline heart rate are associated with higher risk of CVD.