•Metals are crucial determinants and predictors of premature death in Chinese adults.•Selenium and thallium may reduce the risks of all-cause and CVD mortality.•Molybdenum and vanadium would confer ...risks for all-cause and CVD mortality.•Plasma metal score provides in-depth characterization of multiple metal exposures.•Plasma metal score would improve the predictive ability for further mortality risk.
Exposure to metals/metalloids from both the natural environment and anthropogenic sources have a complex influence on human health. However, relatively few studies have explored the relations of exposure to multiple metals/metalloids with mortality. Therefore, this prospective study aims to examine the relations of multiple metal/metalloids exposures with all-cause and cardiovascular disease (CVD) mortality.
A total of 6155 participants within the Dongfeng-Tongji (DF-TJ) cohort were involved in this analysis, which were followed for mortality until December 31, 2018. We applied inductively coupled plasma mass spectrometry (ICP-MS) to measure baseline plasma concentrations of 23 metals. We utilized Cox regression models to calculate the hazard ratios (HRs) for all-cause and CVD mortality associated with metal concentrations. We proposed plasma metal score to assess the simultaneous exposure to multiple metals through summing each metal concentration weighted by the regression coefficients with all-cause mortality.
During the follow-up (mean duration, 9.8 years), we ascertained 876 deaths, including 416 deaths of CVD (157 deaths of coronary heart disease and 259 deaths of stroke). In the multiple-metals model, after adjusting for potential confounders, plasma copper, molybdenum, and vanadium were positively associated with all-cause mortality, whereas manganese, selenium, and thallium were negatively associated with the risk of all-cause mortality, with adjusted HRs (95% Confidence Interval, CI) of the fourth quartiles were 1.73 (1.42–2.11, P-trend < 0.001) for copper, 1.33 (1.09–1.63, P-trend = 0.005) for molybdenum, 1.43 (1.16–1.77, P-trend < 0.001) for vanadium, 0.74 (0.58–0.94, P-trend = 0.005) for manganese, 0.68 (0.56–0.83, P-trend < 0.001) for selenium, and 0.74 (0.59–0.92, P-trend = 0.002) for thallium, respectively. Positive associations were observed between plasma copper, molybdenum, vanadium concentrations and CVD mortality, whereas negative associations were found for plasma selenium and thallium concentrations with CVD mortality in the multiple-metals model. Compared with the first quartiles, the HRs of fourth quartiles were 1.94 (1.45–2.58, P-trend < 0.001) for copper, 1.72 (1.26–2.35, P-trend < 0.001) for molybdenum, 1.81 (1.32–2.47, P-trend < 0.001) for vanadium, 0.67 (0.50–0.89, P-trend = 0.003) for selenium, and 0.58 (0.41–0.81, P-trend < 0.001) for thallium, respectively. The plasma metal score was significantly associated with higher risks of all-cause and CVD death in dose–response fashions. When compared with the first quartiles of plasma metal score, the HRs of fourth quartiles were 2.16 (1.76–2.64; P-trend < 0.001) for all-cause mortality and 3.00 (2.24–4.02; P-trend < 0.001) for CVD mortality.
The study indicated that several plasma metals/metalloids were key determinants and predictors of all-cause and CVD death in the Chinese population. Our findings highlighted the importance to comprehensively assess and monitor multiple metals/metalloids exposures.
Metals exposure from natural environment and pollution have been linked to cardiovascular disease (CVD). However, whether associations existing between plasma multiple metals and incident ...cardiovascular disease in patients with type 2 diabetes (T2D) is unknown.
We conducted a prospective cohort study to investigate whether plasma levels of metals are associated with incident CVD risk in patients with T2D.
In a prospective study of 3897 type 2 diabetes embedded in the Dongfeng–Tongji cohort, fasting blood samples were collected in 2008 at baseline and in 2013 in the first follow-up period. Plasma concentrations of 23 metals were measured by inductively coupled plasma mass spectrometry (ICP-MS). The associations between plasma metal concentrations and CVD risk in patients with T2D were investigated with Cox proportional hazards models.
During an average of 6.2 years follow-up, 1114 participants developed CVD. In the single-metal models adjusting for established cardiovascular risk factors, plasma zinc and selenium levels were negatively and strontium was positively associated with incident CVD risk in patients with T2D. Similar results were obtained in the multiple-metal model, the HRs (95% CIs) for zinc, selenium, and strontium comparing extreme quartiles were 0.78 (95% CI: 0.65–0.93; P trend = 0.011), 0.76 (95% CI: 0.64–0.91; P trend = 0.001), and 1.51 (95% CI: 1.26–1.81; P trend <0.001), respectively. In the joint association analyses of two metals, individuals with high plasma levels of zinc and selenium had significantly lower risk of incident CVD in patients with T2D than those with low levels (HR = 0.77, 95% CI: 0.65–0.91).
The present study suggested that plasma levels of zinc and selenium had an inverse association with incident CVD risk in patients with T2D, while strontium had a positive correlation. Plasma zinc and selenium combinedly decreased incident CVD risk in patients with T2D. Further research is still needed to verify these findings in other populations.
•We investigate the association between plasma levels of metals and incident CVD risk in patients with T2D.•Plasma zinc and selenium were negatively and strontium was positively associated with incident CVD risk among T2D cases.•Plasma zinc and selenium combinedly greatly decreased incident CVD risk in patients with T2D.
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.
Background Metabolomics studies have identified various metabolic markers associated with stroke risk, yet much uncertainty persists regarding heterogeneity in these associations between different ...stroke subtypes. We aimed to examine metabolic profiles associated with incident stroke and its subtypes in Chinese adults. Methods and Results We performed a nested case–control study within the Dongfeng‐Tongji cohort, including 1029 and 266 incident cases of ischemic stroke (IS) and hemorrhagic stroke (HS), respectively, with a mean follow‐up period of 6.1±2.3 years. Fifty‐five metabolites in fasting plasma were measured by ultra‐high‐performance liquid chromatography–mass spectrometry. We examined the associations of metabolites with the risks of total stroke, IS, and HS, with a focus on the comparison of associations of plasma metabolite with IS and HS, using conditional logistic regression. We found that increased levels of asymmetrical/symmetrical dimethylarginine and glutamate were significantly associated with elevated risk of total stroke (odds ratios and 95%, 1.20 1.08–1.34 and 1.22 1.09–1.36, respectively; both Benjamini‐Hochberg‐adjusted P <0.05). When examining stroke subtypes, asymmetrical/symmetrical dimethylarginine was nominally associated with both IS and HS (odds ratios 95% CIs: 1.16 1.03–1.31 and 1.39 1.07–1.81, respectively), while glutamate was associated with only IS (odds ratios 95% CI: 1.26 1.11–1.43). The associations of glutamate with IS risk were significantly stronger among participants with hypertension and diabetes than among those without these diseases (both P for interaction <0.05). Conclusions This study validated the positive associations of asymmetrical/symmetrical dimethylarginine and glutamate with stroke risk, mainly that of IS, in a Chinese population, and revealed a novel unanimous association of with both IS and HS. Our findings provided potential intervention targets for stroke prevention.
Background
Carotid atherosclerosis, especially the rupture of unstable plaques, plays an important role in the development of stroke. A novel lipid ratio, the non-high-density lipoprotein cholesterol ...(non-HDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio, contains both atherogenic and anti-atherogenic particle information, and has been shown to be associated with carotid atherosclerosis. However, there is no data on evaluating the association between non-HDL-C/HDL-C ratio and carotid plaque stability.
Methods
This study was carried out on 27,436 urban workers aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017. Carotid plaque stability was assessed using ultrasonography. Multinomial logistic regression models were used to explore the relationship between the non-HDL-C/HDL-C ratio and carotid plaque stability by odds ratios (
ORs
) and 95% confidence intervals (
CIs
). Subgroup and sensitivity analyses were performed to verify the robustness of the results.
Results
Carotid plaque was detected in 7,161 (26.1%) participants, with stable and unstable plaque accounting for 3,277 (11.9%) and 3,884 (14.2%), respectively. The prevalence of stable carotid plaque substantially increased with increasing non-HDL-C/HDL-C ratio quartile levels (
p
for trend < 0.001) and with a similar association for unstable carotid plaque (
p
for trend < 0.001). The mean non-HDL-C/HDL-C ratios (mean ±
SD
) of non-carotid plaque (2.9 ± 1.1), stable carotid plaque (3.2 ± 1.2), and unstable carotid plaque (3.4 ± 1.4) gradually increased (
p
< 0.001). In multinomial logistic regression,
ORs
(95%
CIs
) for the highest vs. lowest quartile of the non-HDL-C/HDL-C ratio were 1.70 (1.48–1.95) between stable carotid plaques and no carotid plaque, 2.34 (2.06–2.67) between unstable carotid plaques and no carotid plaque, and 1.38 (1.18–1.61) between unstable carotid plaques and stable carotid plaque, after adjusting for common cardiovascular risk factors. The results of subgroup analysis and sensitivity analysis were similar.
Conclusion
Our findings suggested that the non-HDL-C/HDL-C ratio was significantly associated with carotid plaque stability and might be a useful indicator for the early identification of high-risk carotid plaque.
The associations of sleep duration and midday napping with homocysteine (Hcy) levels, and whether these sleep behaviors modify the association between genetic predisposition and Hcy levels, has yet ...to be investigated. We included 19,426 participants without severe health conditions at baseline from the Dongfeng−Tongji cohort. In a subgroup of 15,126 participants with genetic data, a genetic risk score (GRS) based on 18 Hcy-related loci was constructed to test the gene−sleep interactions in Hcy. Hcy levels were higher in subjects with a long sleep duration (≥9 h) and midday napping (>90 min), as compared to those who reported a moderate sleep duration (7 to <8 h) and midday napping (1−30 min) (all p values < 0.05). A long sleep duration and midday napping showed a joint effect in increasing Hcy (p for trend < 0.001). Significant interactions regarding Hcy levels were observed for a long sleep duration with GRS and MTHFR rs1801133, and long midday napping with DPEP1 rs12921383 (all p values for interaction < 0.05). Overall findings indicated that a long sleep duration and midday napping were associated with elevated serum Hcy levels, independently and jointly, and amplified the genetic susceptibility to higher Hcy.
Carotid plaque plays an important role in the development of stroke. The triglyceride-glucose (TyG) index is a reliable alternative marker of insulin resistance. However, there are limited data ...regarding the relationship between TyG index and carotid plaque and its stability in nondiabetic adults.
This study was carried out on 24,895 urban workers (10,978 men and 13,917 women) aged 20 years or older who participated in a comprehensive health screening between January 2016 and December 2017 at the First Affiliated Hospital of Zhengzhou University, China. Carotid plaque was assessed using ultrasonography. TyG index was calculated as ln fasting triglyceride (mg/dL) × fasting glucose (mg/dL) /2. Logistic regression models and restricted cubic spline (RCS) models were used to estimate the association of the TyG index with carotid plaque and its stability by odds ratios (ORs) and 95% confidence intervals (CIs).
Carotid plaque was detected in 5,668 (22.8%) respondents, with stable and unstable plaque accounting for 2,511 (10.1%) and 3,158 (12.7%), respectively. There was a significant positive association between the prevalence of carotid plaque and TyG index quartile levels, and the same associations were observed for the prevalence of stable and unstable carotid plaque (
for trend <0.0001). The multivariable-adjusted ORs (95% CIs) for the highest vs. lowest quartile of TyG index were 1.30 (1.15-1.47) for carotid plaque, 1.38 (1.17-1.63) for stable carotid plaque, and 1.24 (1.07-1.43) for unstable carotid plaque. The RCS analysis showed a linear association between TyG index and carotid plaque, and linear associations were also observed between TyG index and both stable carotid plaque and unstable carotid plaque (
for linearity<0.05).
Our findings suggested that the TyG index was significantly associated with carotid plaque and might be a useful indicator for the early identification of carotid plaque in nondiabetic subjects.
ObjectivesThis study aimed to explore the distribution differences of common risk factors between coronary heart disease (CHD) and stroke in China.SettingThe China National Stroke Screening Survey is ...a cluster sampling survey based on a nationwide general community population, adopting multistage stratified sampling method and covering all 31 provinces in China mainland.ParticipantsA total number of 725 707 people aged 40 years and above were included in the study.Primary and secondary outcome measuresThe basic demographic information, lifestyle behaviour, physical examination, traditional risk factors, family history of cardiovascular disease (CVD) and CVD events were collected. Risk factors of CHD and stroke were explored and analysed in the whole investigated population to identify the common risk factors. Multivariate logistic regression analysis was used to analyse the distribution difference of risk factors between CHD and stroke.ResultsThere were 13 variables associated with CHD and stroke, in which 11 variables revealed differences in the distribution between CHD and stroke. Family history of stroke (OR: 2.30; 95% CI 2.15 to 2.45), men (OR: 1.92; 95% CI 1.80 to 2.05), rural areas (OR: 1.70; 95% CI 1.60 to 1.80), transient ischaemic attack (OR: 1.41; 95% CI 1.30 to 1.54) and hypertension (OR: 1.28; 95% CI 1.19 to 1.38) indicated significantly stronger association with stroke, while family history of CHD (OR: 0.25; 95% CI 0.23 to 0.27), atrial fibrillation (OR: 0.60; 95% CI 0.51 to 0.71), diabetes (OR: 0.76; 95% CI 0.71 to 0.81), dyslipidaemia (OR: 0.76; 95% CI 0.72 to 0.81), smoking (OR: 0.79; 95% CI 0.73 to 0.85) and overweight/obesity (OR: 0.90; 95% CI 0.86 to 0.93) had closer relationship with CHD.ConclusionsThe distribution of risk factors for CHD and stroke were substantial differences. More specific prevention and control measures should be formulated according to the distribution differences of risk factors related to CVD.
Heart failure (HF) is a potential cause of ischemic stroke (IS), and previous studies have reported an association between HF and IS. This study aimed to analyze the causal link between HF and IS ...using bidirectional and multivariable Mendelian randomization (MR) studies.
Genetic variants significantly associated with HF and IS were selected in the MR analysis from two large genome-wide association studies. Bidirectional and multivariable MR analyses were performed to evaluate the effect of HF on IS or the effect of IS on HF.
Two-sample MR analysis showed causal effects of HF on IS of all causes odds ratio (OR) = 1.555, 95% confidence interval (CI): 1.343-1.799,
= 3.35 × 10
and large artery atherosclerosis stroke (LAS) (OR = 1.678, 95% CI: 1.044-2.696,
= 3.03 × 10
), while there was a suggestive effect of HF on cardioembolic stroke (CES) (OR = 3.355, 95% CI: 1.031-10.919,
= 0.044). Genetically predicted HF was not associated with small artery occlusion stroke. Bidirectional MR analysis showed causal effects of IS of all causes (OR = 1.211, 95% CI: 1.040-1.410,
= 0.014) and CES (OR = 1.277, 95% CI: 1.213-1.344,
= 6.73 × 10
) on HF, while there were no causal effects of LAS on HF.
This MR analysis provided evidence of the causal links between genetically predicted HF and IS. Subgroup analysis highlighted the causal or suggestive relationship between genetically predicted HF and LAS or CES. The potential causal links need further investigation with genetic information about other ancestries or etiologies of HF.
C-reactive protein (CRP) is a well-recognized biomarker of inflammation, which can be used as a predictor of cardiovascular disease. Evidence have suggested exposure to multiple metals/metalloids may ...affect immune system and give rise to cardiovascular disease. However, it is lack of study to comprehensively evaluate the association of multiple metals and CRP, the interactions between metals, and the gene-metal interaction in relation to CRP levels.
To explore the associations of multiple plasma metals with serum CRP, and to test the interactions between metals, and gene-metal interactions on the levels of serum CRP.
We included 2882 participants from the Dongfeng-Tongji cohort, China, and measured 23 plasma metals and serum CRP concentrations. The genetic risk score (GRS) was calculated based on 7 established CRP-associated variants. For metals which were associated with the levels of CRP, we further tested the interactions between metals on CRP, and analyzed the gene-metal interactions on CRP.
The median level for CRP in the total population was 1.17 mg/L. After multivariable adjustment, plasma copper was positively associated with serum CRP (FDR < 0.001), whereas selenium was negatively associated with serum CRP (FDR = 0.01). Moreover, selenium and zinc attenuated the positive association between high plasma copper and CRP (P for interaction < 0.001). Participants with a higher GRS had a higher CRP level, with the increase in ln-transformed CRP per increment of 5 risk alleles were 0.64 for weighted GRS, and 0.54 for unweighted GRS (both P < 0.001). Furthermore, the genetic association with CRP was modified by copper concentration (P for interaction < 0.001).
Our results suggest that serum CRP is positively associated with plasma concentration of copper, and inversely associated with selenium. Plasma zinc, selenium and CRP genetic predisposition would modify the associations between plasma copper and serum CRP.
•We found that serum CRP was positively associated with plasma copper, and inversely associated with selenium.•The positive association of plasma copper with serum CRP appeared to be attenuated with high plasma zinc and selenium.•This is the first study that explored the potential gene-metal interactions in relation to CRP levels.•These novel findings may provide new insights to personalized prevention and interventions for inflammation.
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