OBJECTIVE: To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status. RESEARCH DESIGN AND METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Glucose 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.

Non-coding circular RNAs (circRNAs) have displayed dysregulated expression in several human cancers. Here, we profiled the circRNA expression of papillary thyroid carcinoma (PTC) tumors to improve our understanding of PTC pathogenesis. Microarray profiling was performed on 18 thyroid samples, consisting of six PTC tumors, six matching contralateral normal samples, and six benign thyroid lesions. After low-intensity filtering, hierarchical clustering revealed the circRNA expression patterns. Statistical analysis followed by qRT-PCR validation identified the differential circRNAs. MicroRNA (miRNA) target prediction software identified putative miRNA response elements (MREs), which were used to construct a network map of circRNA-miRNA interactions for the differential circRNAs. Bioinformatics platforms predicted cancer-related circRNA-miRNA associations and putative downstream target genes, respectively. A total of 88 circRNAs and 10 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to normal thyroid tissue, while 129 circRNAs and 226 circRNAs were significantly upregulated and downregulated, respectively, in PTC tumors relative to benign thyroid lesions. A total of 12 upregulated and four downregulated circRNAs were overlapping between the foregoing comparisons. One downregulated circRNA (hsa_circRNA_100395) showed interactive potential with two cancer-related miRNAs (miR-141-3p and miR-200a-3p). From this analysis, we identified several promising cancer-related genes that may be targets of the dysregulated hsa_circRNA_100395/miR-141-3p/miR-200a-3p axis in PTC tumors. circRNA dysregulation may play a role in PTC pathogenesis, and several key circRNAs show promise as candidate biomarkers for PTC. The hsa_circRNA_100395/miR-141-3p/ miR-200a-3p axis may be involved in the pathogenesis of PTC.

National 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. This 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). Metabolic 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. We 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. National Natural Science Foundation of China.

Background: Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. Methods: This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011–2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. Results: Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17–1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01–1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71–1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77–2.14) or former smokers (HR, 1.22; 95% CI, 0.66–2.28). Conclusions: Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.

Hypoxia enhances indoleamine 2,3-dioxygenase production in dendritic cells Hypoxia enhances indoleamine 2,3-dioxygenase production in dendritic cells

The updated definition of hypertension by the American College of Cardiology (ACC) and the American Heart Association (AHA) is an important paradigm shift and has lead to extensive discussion. We aimed to examine the association between the updated blood pressure (BP) categories and the risk of cardiovascular diseases (CVDs) with potential modifications from other cardiovascular health metrics (CVHMs). This prospective study included 91,204 participants ≥40 years recruited from 20 community sites across mainland China. Participants were followed up during 2010-2016 for CVD events including nonfatal myocardial infarction, stroke, heart failure, and cardiovascular death. BP categories were defined according to the 2017 ACC/AHA guideline and CVHMs included smoking, physical activity, diet, body-mass index, total cholesterol, and fasting glucose. Overall, 1,985 major CVD events occurred during a mean follow-up of 3.7 years. Having more ideal CVHMs significantly reduced the risk of CVD events in both stage 1 and stage 2 hypertension. Compared with participants without hypertension, participants having ≥4 ideal CVHMs were no longer associated with an increased CVD risk in stage 1 hypertension (HR=1·04; 95% CI=0·83-1·31), but less so in stage 2 hypertension (HR=1·90, 95% CI=1·70-2·13). Such pattern of association was more evident in participants aged <60 years (P for interaction <0·05). Stage 1 hypertension defined by the ACC/AHA identifies individuals at increased CVD risk, which can be attenuated by achieving more preferable cardiovascular health, especially in adults aged <60 years.