China Cardiometabolic Disease Research Articles

The mediating role of remnant cholesterol in the associations of Angiopoietin-like 8 with all-cause, CVD, and cancer death: the China Cardiometabolic Disease and Cancer Cohort (4C) study.

To investigate the potential mediating effect of remnant cholesterol (RC) in the associations between angiopoietin-like 8 (ANGPTL8) and the risk of all-cause, cardiovascular disease (CVD), and cancer death. This prospective observational study included 3278 individuals from China. Binary logistic regression and mediation analyses were conducted to investigate the mediating effect of RC in the associations between ANGPTL8 and all-cause, CVD, and cancer death. During up to 5-year follow-up, a total of 265 deaths (8.08%) were documented. Both increased levels of ANGPTL8 and RC were associated with a higher risk of death for all-cause, CVD, and cancer risk. The level of RC ≥ 33 mg/dL could identify individuals at a higher risk of death independent of low-density lipoprotein cholesterol (LDL-C) levels in Chinese general populations. Furthermore, RC significantly mediated the relationship between increased ANGPTL8 levels and higher risk of all-cause, CVD, and cancer death (proportion of mediation effect: 13.10%, 9.22%, and 6.07%, respectively, all p < 0.05). Both increased circulating levels of ANGPTL8 and RC are the risk factors for all-cause, CVD, and cancer death and RC partially mediates the association between ANGPTL8 and death risk.

A prospective cohort study investigating the association between type 2 diabetes and subsequent cardiovascular events in patients with different blood pressure, HbA1c, and lipid levels.

Globally, there has been a steady increase in the prevalence of type 2 diabetes, and the risk of cardiovascular disease has increased. The relationship between diabetes and the incidence of cardiovascular disease (CVD) at different blood pressure, glycated haemoglobin A1c (HbA1c), and lipid levels remains uncertain. This study aimed to investigate these associations within a population-based cohort. We analysed data from the Guiyang subcentre of the China Cardiometabolic Disease and Cancer Cohort Study, which enrolled participants aged 40 years and older between 2011 and 2012. Subsequently, a follow-up visit was conducted during 2014-2016 to assess incident CVD events. The analysis included a cohort of 7197 adults, of whom 590 were diagnosed with diabetes. Among all the participants, the CVD events linked to diabetes had a multivariable adjusted hazard ratio of 2.37 [95% confidence intervals (CI): 1.38-4.08]. Patients with diabetes had a greater risk of experiencing CVD events if they had high blood pressure [hazard ratios (HR): 1.24, 95% CI: 1.39-4.21] and high lipid levels (HR: 2.19, 95% CI: 1.29-3.70) compared to people with normal blood pressure (HR: 1.23, 95% CI: 0.54-2.82) and lipid levels (HR: 1.26, 95% CI: 0.47-3.41). Our analysis revealed a significant association between diabetes and an increased risk of subsequent CVD events, which can be mitigated through optimal management of the metabolic profile of cardiovascular risk factors.

Associations of Diet and Lifestyle with Mortality and Stroke: The China Cardiometabolic Disease and Cancer Cohort (4C) Study.

This study aimed to examine the individual and combined associations between dietary habits and lifestyle factors concerning all-cause mortality and stroke in Chinese adults. We conducted a nationwide, multicenter, prospective cohort study involving 10,008 participants, gathering baseline data on lifestyle, metabolic status, dietary habits, and living behaviors. Subsequently, a 10-year follow-up was performed, resulting in the inclusion of 7,612 participants in this study. We employed Spearman correlation analysis, restricted cubic spline regression, and Cox regression analysis to evaluate the connections between outcome events, dietary habits, and lifestyle. For each additional serving of pulses consumed per week, there was a slight decrease in the risk of all-cause mortality (HR: 0.91, 95% CI: 0.83-0.99). The hazard ratios for stroke were 2.24 (1.48, 3.37) for current smokers, in comparison to individuals who had never smoked. Appropriate intake of specific dietary factors and certain lifestyle habits were associated with reduced stroke: fruit drinks at 0.51 (0.34, 0.87), and animal viscera at 0.58 (0.32, 1.04). Weekly consumption of at least 21 servings of vegetables (0.72, 0.53-0.98), 0-1 serving of fried food (0.58, 0.38-0.90), and at least 1 serving of carbonated beverages (0.51, 0.28-0.92) was associated with a reduced risk of stroke. Smoking was found to be linked to an increased risk of stroke. A higher intake of fruit drinks and animal viscera was associated with a reduced risk of stroke. In contrast, a higher intake of beans was associated with a decreased risk of overall mortality. Consuming an appropriate amount of vegetables, fried foods, and carbonated drinks was found to potentially lower the risk of stroke. Collectively, these findings underscore the importance of developing tailored dietary interventions conducive to the Chinese populace's health.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5μm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case–control study

BackgroundLong-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. ObjectivesOur study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. MethodsThis is a prospective nested case–control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score–matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. ResultsThe majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18–26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. ConclusionsThese findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Early adulthood weight change, midlife “Life’s essential 8” health status and risk of cardiometabolic diseases: a chinese nationwide cohort study

BackgroundThe association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by “Life’s Essential 8” has not been characterized. We aim to examine the associations of early adulthood weight change and midlife “Life’s Essential 8” CVH status with cardiometabolic outcomes in a Chinese cohort.MethodsThe study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in “Life’s Essential 8” was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria.Results72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife.ConclusionsOur study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

The Impact of Sedentary Behavior on Renal Function Decline in 132,123 Middle Aged and Older Adults: A Nationwide Cohort Study.

BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.

Exposure to famine in every stage of life and the risk of osteoporosis and fractures later in life: A cross-sectional study.

Data on the association between early-life famine exposure and osteoporosis and fractures remain limited and inconclusive. The aim of this study was to investigate the correlation between famine exposure and osteoporosis and fractures. We performed a cross-sectional analysis using the first follow-up survey data from the China Cardiometabolic Disease and Cancer Cohort Study from 2014 to 2016. We classified 4807 Lanzhou participants into seven groups based on their birthday (non-exposed or exposed in the fetal stage, early childhood, mid-childhood, late childhood, adolescence, or early adulthood). And we combined the non-exposed and early-adulthood exposed groups as a control group, which was called "age balanced group". This age-balanced group was used as the control group to further evaluate the risk of osteoporosis and fracture. We used multiple logistic regression to estimate the association between famine exposure and the risk of osteoporosis (T-score≤-1.8 by QUS) and self-reported fracture. In women, compared to the age-balanced group, the odds ratios (95% CI) for the risk of osteoporosis were 1.400(1.034, 1.897), 1.630(1.268, 2.095), 1.707(1.314, 2.218), 2.150(1.732.2.668) and 2.885(2.286,3.641) in the fetal stage, early childhood, mid-childhood, late childhood and adolescence famine-exposed cohorts. In men, no association between famine and osteoporosis was noted with exposed cohort compared with the age-balanced control cohort (p>0.05). Interestingly, the association between famine exposure and fractures was slightly different from the above results: in women, the odds ratios (95% CI) for fractures in mid-childhood famine exposure was 1.461(1.082,1.973), in late childhood famine exposure was 1.333(1.035,1.718) and in adolescence famine exposure was 1.607(1.239,2.085). However, compared to the age-balanced control cohort, men exposed to famine in early childhood (OR: 1.801, 95% CI: 1.010,3.211) had a higher risk of fracture. Famine exposure in different life stage has adverse effects on bone health. Famine exposure in not only the period from gestation to infancy, but also childhood and adolescence was associated with an increased risk of osteoporosis, especially in women. Exposure to famine in childhood- (mid and late) and adolescence- life period is associated with fracture in women. But, in men early-childhood famine exposure was only associated with fracture.

Data-driven subgroups of prediabetes and the associations with outcomes in Chinese adults

Prediabetes and its pathophysiology remain important issues. We aimed to examine the cluster characteristics of prediabetes and explore their associations with developing diabetes and its complications based on 12 variables representing body fat, glycemic measures, pancreatic β cell function, insulin resistance, blood lipids, and liver enzymes. A total of 55,777 individuals with prediabetes from the China Cardiometabolic Disease and Cancer Cohort (4C) were classified at baseline into six clusters. During a median of 3.1 years of follow-up, significant differences in the risks of diabetes and its complications between clusters were observed. The odds ratios of diabetes stepwisely increase from cluster 1 to cluster 6. Clusters 1, 4, and 6 have increased chronic kidney diseases risks, while the prediabetes in cluster 4, characterized by obesity and insulin resistance, confers higher risks of cardiovascular diseases compared with others. This subcategorization has potential value in developing more precise strategies for targeted prediabetes prevention and treatment.

Examining the Linear Association Between Blood Pressure Levels and Cardiovascular Diseases in the Absence of Major Risk Factors in China.

Many studies demonstrate a J-shaped association between blood pressure and cardiovascular diseases (CVDs), but the findings are plagued by confounding from other traditional cardiovascular risk factors (CVRFs). Our aims were to examine the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels with CVD in individuals without major CVRFs and whether there were thresholds for the association. In the 4C study (China Cardiometabolic Disease and Cancer Cohort), 36 042 CVRF-free participants without CVD, diabetes, dyslipidemia, hypertension, or smoking were identified during 2011 to 2012. Among CVRF-free participants, 17 476 CVRF-preferable individuals with better glycemic (fasting glucose, <110 mg/dL; 2-hour post-load glucose, <140 mg/dL) and lipid profile (total cholesterol, <200 mg/dL; LDL [low-density lipoprotein] cholesterol, <130 mg/dL) were selected. The total person-years of follow-up for CVRF-free subjects and CVRF-preferable subjects were 130 147 and 63 573 person-years, respectively. Information on the development of major CVDs was collected during 2014 to 2016. Cox proportional hazard models were performed to estimate the risks for incident CVD by SBP and DBP groups, respectively. We found that both baseline SBP and DBP presented significantly linear associations with CVD risks in CVRF-free and CVRF-preferable participants. There is significant increase in the CVD risk among CVRF-free participants with baseline SBP level of 110 to 119 mm Hg (hazard ratio, 1.79 [95% CI, 1.19-2.71]), 120 to 129 mm Hg (hazard ratio, 2.03 [95% CI, 1.36-3.03]), and 130 to 139 mm Hg (hazard ratio, 2.15 [95% CI, 1.40-3.28]) compared with SBP <110 mm Hg. Significant increases were also observed for DBP level of 80 to 89 mm Hg (hazard ratio, 1.43 [95% CI, 1.03-1.97]) compared with DBP <70 mm Hg. Similar results were observed in CVRF-preferable participants. SBP and DBP with levels currently considered normal were significantly and linearly associated with incident CVD without thresholds above 110/70 mm Hg among Chinese adults without major CVRFs.

Amino acids, microbiota-related metabolites, and the risk of incident diabetes among normoglycemic Chinese adults: Findings from the 4C study

SummaryAlthough previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor–metabolite–diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.

Dose-response association between sedentary time and incident of diabetes in Chinese middle-aged and older adults: The 4C study

AimsTo investigate the dose-response relationship of total sedentary time with incident diabetes in Chinese middle-aged and older adults. MethodsThe present study followed 100,525 participants aged ≥ 40 years old from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was a prospective study conducted in 25 communities across mainland China. Associations between sedentary time and incident diabetes were assessed with Cox regression and restricted cubic splines. ResultsDuring a median follow-up of 3.8 years, 7,529 participants developed diabetes. After adjustment for multiple variables, high levels of sedentary time (≥ 30 h/week) was associated with increased risk for developing diabetes (hazards ratio, 1.08; 95 % confidence intervals 1.02, 1.14) compared with low levels of sedentary time (<20 h/week). Restricted cubic spline analyses revealed an inverted U-shaped relation between sedentary time with diabetes. Subgroup analyses found that the observed association remained significant in subgroup of individuals with body mass index (BMI) ≥ 25 kg/cm2 or diastolic blood pressure (DBP) ≥ 90 mm Hg. However, the significant association was diminished in participants with sufficient physical activity (PA) (P = 0.22). ConclusionsThe multicenter, population-based, prospective study suggested an inverted U-shaped relation between sedentary time with diabetes. PA alleviated the deleterious effects associated with sedentary time.

Association Between Insulin Resistance and Cardiovascular Disease Risk Varies According to Glucose Tolerance Status: A Nationwide Prospective Cohort Study.

OBJECTIVETo investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.RESEARCH DESIGN AND METHODSWe analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality.RESULTSIn participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82–1.30), 1.23 (1.07–1.42), and 1.61 (1.30–2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92–1.18), 1.12 (1.06–1.18), and 1.15 (1.09–1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2–34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15–17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44–77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters.CONCLUSIONSGlucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.

Depression Status, Lifestyle, and Metabolic Factors With Subsequent Risk for Major Cardiovascular Events: The China Cardiometabolic Disease and Cancer Cohort (4C) Study.

BackgroundWe aimed to evaluate the association between depression and major cardiovascular events and test whether the relationship between depression and cardiovascular events is influenced by lifestyle or metabolic risk factors.MethodsThe China Cardiometabolic Disease and Cancer Cohort (4C) Study was a nationwide, multicenter, prospective cohort study. About 92,869 participants without cardiovascular disease or cancer at baseline were included. Depression status was evaluated by the Patient Health Questionnaire-9 (PHQ-9). Lifestyle information was collected by the questionnaire, and metabolic risk factors including waist circumference, blood pressure, lipid profiles, and plasma glucose were measured. Major cardiovascular events including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure events were validated based on medical records.ResultsDuring an average of 3.8 years of follow-up, we detected 2,076 cardiovascular events and showed that participants with depressive symptoms had an increased risk for cardiovascular events after adjustments [hazard ratio (HR): 1.29; 95% confidence index (CI): 1.08–1.53]. Stratified on metabolic risk status, the relationship between depression and cardiovascular events tended to be stronger according to the increasing numbers of metabolic risk factors, with HR (95% CI) of 0.98 (0.72–1.35) in the category with 0–2 metabolic risk factors, 1.36 (0.996–1.87) and 1.47 (1.13–1.92) for those with 3, and 4–5 metabolic risk factors, respectively, indicating an interaction effect (P = 0.039).ConclusionDepression was independently associated with an increased risk of major cardiovascular events. The effect was particularly prominent among populations at higher metabolic risk.

Association of education levels with the risk of hypertension and hypertension control: a nationwide cohort study in Chinese adults

BackgroundEducation attainment can improve life expectancy and guide healthy behaviours throughout an entire lifetime. A nationwide longitudinal study of the association of education status with the risk of hypertension and...

Metabolomics study reveals systematic metabolic dysregulation and early detection markers associated with incident pancreatic cancer.

Biomarkers for early detection of pancreatic cancer are in urgent need. To explore systematic circulating metabolites unbalance and identify potential biomarkers for pancreatic cancer in prospective Chinese cohorts, we conducted an untargeted metabolomics study in subjects with incident pancreatic cancer and matched controls (n=192) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We characterized 998 metabolites in baseline serum and calculated 156 product-to-precursor ratios based on the KEGG database. The identified metabolic profiling revealed systematic metabolic network disorders before pancreatic cancer diagnosis. Forty-Five metabolites or product-to-precursor ratios showed significant associations with pancreatic cancer (P < .05 and FDR < 0.1), revealing abnormal metabolism of amino acids (especially alanine, aspartate and glutamate), lipids (especially steroid hormones), vitamins, nucleotides and peptides. A novel metabolite panel containing aspartate/alanine (OR [95% CI]: 1.97 [1.31-2.94]), androstenediol monosulfate (0.69 [0.49-0.97]) and glycylvaline (1.68 [1.04-2.70]) was significantly associated with risk of pancreatic cancer. Area under the receiver operating characteristic curves (AUCs) was improved from 0.573 (reference model of CA 19-9) to 0.721. The novel metabolite panel was validated in an independent cohort with AUC improved from 0.529 to 0.661. These biomarkers may have a potential value in early detection of pancreatic cancer.

Age-specific modifiable risk factor profiles for cardiovascular disease and all-cause mortality: a nationwide, population-based, prospective cohort study.

SummaryBackgroundNational investigations on age-specific modifiable risk factor profiles for cardiovascular disease (CVD) and mortality are scarce in China, the country that is experiencing a huge cardiometabolic burden exacerbated by population ageing.MethodsThis is a nationwide prospective cohort study of 193,846 adults in the China Cardiometabolic Disease and Cancer Cohort Study, 2011-2016. Among 139,925 participants free from CVD at baseline, we examined hazard ratios and population-attributable risk percentages (PAR%s) for CVD and all-cause mortality attributable to 12 modifiable socioeconomic, psychosocial, lifestyle, and metabolic risk factors by four age groups (40-<55 years, 55-<65 years, 65-<75 years, and ≥75 years).FindingsMetabolic risk factors accounted for 52·4%, 47·2%, and 37·8% of the PAR% for CVD events in participants aged 40-<55 years, 55-<65 years, and 65-<75 years, respectively, with hypertension being the largest risk factor. While in participants aged ≥75 years, lifestyle risk factors contributed to 34·0% of the PAR% for CVD, with inappropriate sleep duration being the predominant risk factor. Most deaths were attributed to metabolic risk factors (PAR% 25·3%) and lifestyle risk factors (PAR% 24·6%) in participants aged 40-<55 years, with unhealthy diet and diabetes being the main risk factors. While in participants aged ≥55 years, most deaths were attributed to lifestyle risk factors (PAR% 26·6%-41·0%) and socioeconomic and psychosocial risk factors (PAR% 26·1%-27·7%). In participants aged ≥75 years, lifestyle risk factors accounted for 41·0% of the PAR% for mortality, with inappropriate sleep duration being the leading risk factor.InterpretationWe identified age-specific modifiable risk profiles for CVD and all-cause mortality in Chinese adults, with remarkable differences between adults aged ≥75 years and their younger counterparts.FundingNational Natural Science Foundation of China.

Non-alcoholic fatty liver disease, metabolic goal achievement with incident cardiovascular disease and eGFR-based chronic kidney disease in patients with prediabetes and diabetes

Aims/hypothesisWe aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total ‘ABCs’ metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study. MethodsWe conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. ‘ABCs’ metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR. ResultsThe multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05–1.27) for CVD events and 1.33 (95% CI, 1.20–1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21–2.18)] and CKD [1.63 (1.17–2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications. ConclusionsNAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.