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Coronary Artery Calcium Score and Polygenic Risk Score for the Prediction of Coronary Heart Disease Events.
Khan, SS, Post, WS, Guo, X, Tan, J, Zhu, F, Bos, D, Sedaghati-Khayat, B, van Rooij, J, Aday, A, Allen, NB, et al
JAMA. 2023;(20):1768-1777
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Abstract
IMPORTANCE Coronary artery calcium score and polygenic risk score have each separately been proposed as novel markers to identify risk of coronary heart disease (CHD), but no prior studies have directly compared these markers in the same cohorts. OBJECTIVE To evaluate change in CHD risk prediction when a coronary artery calcium score, a polygenic risk score, or both are added to a traditional risk factor-based model. DESIGN, SETTING, AND PARTICIPANTS Two observational population-based studies involving individuals aged 45 years through 79 years of European ancestry and free of clinical CHD at baseline: the Multi-Ethnic Study of Atherosclerosis (MESA) study involved 1991 participants at 6 US centers and the Rotterdam Study (RS) involved 1217 in Rotterdam, the Netherlands. EXPOSURE Traditional risk factors were used to calculate CHD risk (eg, pooled cohort equations [PCEs]), computed tomography for the coronary artery calcium score, and genotyped samples for a validated polygenic risk score. MAIN OUTCOMES AND MEASURES Model discrimination, calibration, and net reclassification improvement (at the recommended risk threshold of 7.5%) for prediction of incident CHD events were assessed. RESULTS The median age was 61 years in MESA and 67 years in RS. Both log (coronary artery calcium+1) and polygenic risk score were significantly associated with 10-year risk of incident CHD (hazards ratio per SD, 2.60; 95% CI, 2.08-3.26 and 1.43; 95% CI, 1.20-1.71, respectively), in MESA. The C statistic for the coronary artery calcium score was 0.76 (95% CI, 0.71-0.79) and for the polygenic risk score, 0.69 (95% CI, 0.63-0.71). The change in the C statistic when each was added to the PCEs was 0.09 (95% CI, 0.06-0.13) for the coronary artery calcium score, 0.02 (95% CI, 0.00-0.04) for the polygenic risk score, and 0.10 (95% CI, 0.07-0.14) for both. Overall categorical net reclassification improvement was significant when the coronary artery calcium score (0.19; 95% CI, 0.06-0.28) but was not significant when the polygenic risk score (0.04; 95% CI, -0.05 to 0.10) was added to the PCEs. Calibration of the PCEs and models with coronary artery calcium and/or polygenic risk scores was adequate (all χ2<20). Subgroup analysis stratified by the median age demonstrated similar findings. Similar findings were observed for 10-year risk in RS and in longer-term follow-up in MESA (median, 16.0 years). CONCLUSIONS AND RELEVANCE In 2 cohorts of middle-aged to older adults from the US and the Netherlands, the coronary artery calcium score had better discrimination than the polygenic risk score for risk prediction of CHD. In addition, the coronary artery calcium score but not the polygenic risk score significantly improved risk discrimination and risk reclassification for CHD when added to traditional risk factors.
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A Proinflammatory Diet May Increase Mortality Risk in Patients with Diabetes Mellitus.
Tan, J, Liu, N, Sun, P, Tang, Y, Qin, W
Nutrients. 2022;(10)
Abstract
This was an observational study based on the National Health and Nutrition Examination Survey (NHANES) and National Death Index (NDI) 2009-2014 which aimed to validate whether a proinflammatory diet may increase mortality risk in patients with diabetes mellitus. Dietary inflammatory potential was assessed by dietary inflammatory index (DII) based on 24 h dietary recall. Mortality follow-up information was accessed from NDI, which was then merged with NHANES data following the National Center for Health Statistics (NCHS) protocols. For 15,291 participants from the general population, the average DII was 0.37 ± 1.76 and the prevalence rate of diabetes was 13.26%. DII was positively associated with fasting glucose (β = 0.83, 95% CI: 0.30, 1.36, p = 0.0022), glycohemoglobin (β = 0.02, 95% CI: 0.01, 0.03, p = 0.0009), and the risk of diabetes (OR = 1.05, 95% CI: 1.01, 1.09, p = 0.0139). For 1904 participants with diabetes and a median follow-up of 45 person-months, a total of 178 participants with diabetes died from all causes (mortality rate = 9.34%). People with diabetes who adhered to a proinflammatory diet showed a higher risk of all-cause mortality (HR = 1.71, 95%CI: 1.13, 2.58, p = 0.0108). In summary, DII was positively associated with diabetes prevalence and a proinflammatory diet may increase mortality risk in patients with diabetes mellitus.
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Blood prognostic predictors of treatment response for patients with papillary thyroid cancer.
Liu, X, Huang, Z, He, X, Zheng, X, Jia, Q, Tan, J, Fan, Y, Lou, C, Meng, Z
Bioscience reports. 2020;(10)
Abstract
BACKGROUND Papillary thyroid cancer (PTC) is a very common malignant disease with high morbidity. We needed some pretreatment indicators to help us predict prognosis and guide treatment. We conducted a study about some pretreatment prognostic indicators. METHODS This clinical study recruited 705 postoperative PTC patients (211 males, 494 females). Clinical data before radioactive iodine (RAI) treatment were collected. Patients' response to therapy were classified into two categories: 'Good Prognosis Group' (GPG) and 'Poor Prognosis Group' (PPG), according to '2015 American Thyroid Association Guidelines'. Differences of indicators between different prognosis groups were compared. Odds ratios (ORs) were calculated by univariate/multiple binary logistic regression models. Difference of body mass index (BMI) changes before and after RAI treatment between different prognosis groups was also compared. RESULTS A total of 546 (77.45%) belonged to GPG, and 159 (22.55%) belonged to PPG. Platelet (PLT), neutrophil (NEUT), PLT subgroups, and combination of red blood cell distribution width (RDW) and BMI (COR-BMI) were different between two prognosis groups. The significance of the difference between the two groups of BMI disappeared after the Bonferroni correction. PLT and PLT subgroups had detrimental effects on the risk of PPG; T stage had a positive effect on the risk of PPG. PLT subgroup showed a detrimental effect on the risk of PPG when we included additional covariates. CONCLUSIONS We found that lower pretreatment PLT levels may indicate a poor prognosis for PTC. The relationship between platelet-derived growth factor (PDGF) and radiation sensitivity may be the key to this association.
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Cerebral and Renal Oxygenation in Infants Undergoing Laparoscopic Gastrostomy Tube Placement.
Muñoz, A, Tan, J, Hopper, A, Vannix, R, Carter, H, Woodfin, M, Blood, A, Baerg, J
The Journal of surgical research. 2020;:83-89
Abstract
AIM: The aim of this study was to evaluate the effects of a carbon dioxide pneumoperitoneum on cerebral and renal oxygenation and oxygen extraction, in a cohort of infants from the neonatal intensive care unit, undergoing laparoscopic gastrostomy. METHODS After institutional review board approval, between February 2018 and June 2019, infants 0-3 mo corrected age, undergoing laparoscopic gastrostomy tube placement, were included. Strict exclusion criteria created a homogeneous cohort. Cerebral and renal tissue oxygen saturation (rSO2) by near-infrared spectroscopy, skin surface oxygen saturation (SpO2), by pulse oximetry, and amplitude-integrated electroencephalography were measured. Monitoring was divided into preoperative, intraoperative and postoperative time periods. Cerebral and renal fractional tissue oxygen extraction was calculated using arterial (SpO2) and tissue oxygen saturation (rSO2): (SpO2-rSO2SpO2)X100. Data were averaged into one-minute epochs and significant changes from baseline during the intraoperative and postoperative periods were detected using one-way analysis of variance with repeated measures. RESULTS This pilot study examined sixteen infants, born at a median gestational age of 34.2 wk (range: 23.0-40.6) with a median corrected age of 42.9 wk (range: 40.0-46.3) at operation. None had seizure activity or altered sleep-wake cycles. No statistically significant variations in cerebral and renal tissue oxygenation and extraction were observed. Pulse oximetry did demonstrate significant variation from baseline on analysis of variance, but post hoc analysis did not identify any one specific time point at which this difference was significant. CONCLUSIONS During a short infant laparoscopic procedure, no significant alteration in cerebral or renal oxygenation or oxygen extraction was observed. No seizure activity or changes in infant sleep-wake cycles occurred.
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Novel mutations in mevalonate kinase cause disseminated superficial actinic porokeratosis.
Zhu, T, Tian, D, Zhang, L, Xu, X, Xia, K, Hu, Z, Xiong, Z, Tan, J
The British journal of dermatology. 2019;(2):304-313
Abstract
BACKGROUND Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is located at 12q23·2-q24·1. Subsequently, the mevalonate kinase gene (MVK) was shown to be pathogenic in DSAP. OBJECTIVES To elucidate the mechanism by which MVK mutations lead to keratinocyte apoptosis and DSAP, and to report a new missense mutation, c.566 C>T (p.A189V), in MVK in a Chinese DSAP pedigree. METHODS The half-life of wild-type (WT) MVK protein and mutants was assessed using cycloheximide treatment of cells. Dimerization of MVK was analysed by coimmunoprecipitation and glutathione S transferase pull-down assay. MVK kinase activity, production of cell cholesterol, mitochondrial complex activity and apoptosis were detected, using the corresponding commercial kits, in cells overexpressing MVK WT and mutants. RESULTS Mechanically, we demonstrated that both the pathogenic p.A189V mutant and a sporadic mutation p.H312R (c.935A>G), which we reported previously, have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Also, we found the p.H312R mutation confers on the MVK protein an inability to dimerize. Further, we demonstrated that the mutants are impaired in mitochondrial function and lead to increased apoptosis. CONCLUSIONS Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.
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Serum YKL-40 predicts long-term outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.
Yang, L, Dong, H, Lu, H, Liao, Y, Zhang, H, Xu, L, Tan, Y, Cao, S, Tan, J, Fu, S
Medicine. 2019;(12):e14920
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Abstract
Serum YKL-40, a potential inflammatory marker, is greatly increased at the early stage of ST-segment elevation myocardial infarction (STEMI). Here, we hypothesized that YKL-40 levels at admission could predict the long-term outcomes after STEMI.A total of 324 patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI) were consecutively enrolled and followed for 24 months. The baseline clinical and procedural data were recorded, and serum YKL-40 levels at admission were measured using ELISA method. The endpoint of interest was major adverse cardiac event (MACE), including all-cause death, recurrent myocardial infarction, and hospitalization for heart failure.Patients with elevated serum YKL-40 levels (≥126.8 ng/mL) were more likely to be older and smoker and to present with type 2 diabetes, advanced Killip class, multivessel disease and intra-aortic balloon pump, with increased levels of admission glucose, triglyceride, and high-sensitivity C-reactive protein and decreased level of high-density lipoprotein cholesterol. During the follow-up period, the incidence of MACE was notably higher in the high than in the low YKL-40 groups (28.4% vs 11.1%, P < .001). Kaplan-Meier curve showed that elevated YKL-40 levels were associated with reduced MACE-free survivals (log-rank P < .001). In multivariate Cox regression analysis, we found that high serum YKL-40 level was an independent predictor of MACE after controlling for clinical and angiographic variables (hazard ratio: 1.65, 95% confidence interval: 1.14-2.39, P = .008).The results of our study indicate that serum YKL-40 may be used as a biomarker to predict the long-term outcome after PCI in patients with STEMI.
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Effects of first radioiodine ablation on functions of salivary glands in patients with differentiated thyroid cancer.
Upadhyaya, A, Meng, Z, Wang, P, Zhang, G, Jia, Q, Tan, J, Li, X, Hu, T, Liu, N, Zhou, P, et al
Medicine. 2017;(25):e7164
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Abstract
The aim of this study was to evaluate the effects of the first radioactive iodine (I) therapy on functions of salivary glands in patients with differentiated thyroid carcinoma (DTC).There were 36 consented patients with DTC enrolled in this study, who received 3.7 GBq (100mCi) I for ablation after total thyroidectomy. Salivary gland function was assessed using salivary gland scintigraphy in two phases, one 4 hours before and the other 6 months after I therapy (both under thyrotropin stimulation condition). Quantitative parameters including uptake fraction (UF), uptake index (UI), excretion fraction (EF), and excretion ratio (ER) were measured and compared. Blood parameters were also compared. Associations between sex and outcome of the first I therapy as well as individual salivary gland function were measured. Wilcoxon Signed Rank Sum test and χ test were used for statistical analysis.When compared between pre-ablation and post-ablation, UF of bilateral parotid and submandibular glands were significantly increased (all P < .01). UI of both submandibular glands were significantly increased (P < .05). This seemingly increased uptake function after the first I therapy was actually compensatory mechanism of salivary gland, which indicated a possible intermediate state after radiation. But salivary glands' secretory function had not changed significantly except for left submandibular gland; we demonstrated that only left submandibular gland showed significantly decreased ER (P < .05). Thyroglobulin and thyroglobulin antibody significantly decreased after I therapy (P < .05). There were no sex differences on therapeutic outcome and salivary gland dysfunctions after the first I therapy. Salivary gland of both males and females could be affected by I therapy.The first I ablative therapy may impair the salivary uptake and secretory function of patients with DTC. There was no association between sex and salivary gland dysfunction.
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Analysis of radioiodine therapy and prognostic factors of differentiated thyroid cancer patients with pulmonary metastasis: An 8-year retrospective study.
Wang, R, Zhang, Y, Tan, J, Zhang, G, Zhang, R, Zheng, W, He, Y
Medicine. 2017;(19):e6809
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To assess the efficacy of radioiodine therapy (RIT) and investigate the prognostic factors for patients with pulmonary metastasis secondary to differentiated thyroid carcinoma (DTC) through a retrospective study. A total of 80 patients with radioactive iodine-131 (I)-avid pulmonary metastasis from DTC treated with I from 2007 to 2014 at our institution entered the study. Treatment response was mainly measured by two parameters: serum thyroglobulin (Tg) levels and post-therapeutic I whole-body scan (WBS). Treatment variables were assessed for statistical significance using the univariate and multivariate analyses. A receiver-operating characteristic (ROC) curve was also plotted to verify the accuracy of predictors. Of these 80 patients, the overall effective rate was 72.5% (58/80), the rates for complete response (CR), partial response (PR), and no response (NR) were 20.0%, 52.5%, and 27.5%, respectively. Univariate analysis showed that gender, pulmonary nodule size, absence or presence of extrapulmonary distant metastases, age, and Tg level at diagnosis were significantly associated with I therapy efficacy. Binary logistic regression analysis revealed that older patients (odds ratio [OR]:1.481, 95% confidence interval [CI]: 1.457-2.091, P = .020), subjects with higher Tg levels at diagnosis (OR: 1.046, 95% CI: 1.016-1.119, P = .014), and those with extrapulmonary distant metastases (OR: 1.185, 95%CI: 1.025-1.463, P = .020) had a higher probability of poor prognosis. The optimal cutoffs for age and Tg level to predict I therapy efficacy for DTC with lung metastases were 46 years old and 55.50 ng/mL, respectively, based on ROC analysis. This study indicated that most DTC patients with pulmonary metastases can obtain partial or complete remission after RIT, while older patients with higher Tg levels at diagnosis and extrapulmonary distant metastases more likely show poor prognosis.
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Metabolic parameters in type 2 diabetic patients with varying degrees of glycemic control during Ramadan: An observational study.
Siaw, MY, Chew, DE, Toh, MP, Seah, DE, Chua, R, Tan, J, Lee, EY, Chan, SY, Lee, JY
Journal of diabetes investigation. 2016;(1):70-5
Abstract
AIMS/INTRODUCTION The changes in metabolic parameters in type 2 diabetic patients who fast during Ramadan have not been studied in Singapore. This study aimed to examine the trends of glycated hemoglobin (HbA1c), systolic blood pressure, low-density lipoprotein cholesterol, and triglycerides in diabetic patients with varying degrees of glycemic control and different types of therapeutic approaches during Ramadan. METHODS The present retrospective study used a national electronic database to examine the metabolic parameter of Malay patients with type 2 diabetes. Eligible patients were stratified into three groups based on their mean HbA1c control before Ramadan: group 1 (HbA1c ≥10%), group 2 (HbA1c 7.1-9.9%) and group 3 (HbA1c ≤7%). Patients with a glomerular filtration rate <15 mL/min were excluded. The trends of metabolic parameters were traced before, during and after Ramadan. RESULTS Of 13,565 patients examined, 5,172 patients (38.1%) were eligible for this study. Mean change of HbA1c varied from -1.4% to +0.2% during Ramadan, with the greatest reduction observed in group 1 (P < 0.001). A minimal systolic blood pressure reduction was observed in groups 2 and 3 (2 mmHg; P < 0.01). Low-density lipoprotein cholesterol and triglycerides changes were insignificant. A small, 0.1%, reduction in mean HbA1c was observed in patients taking oral antidiabetic agents during Ramadan (P < 0.001). CONCLUSIONS Blood glucose was most affected during Ramadan, particularly in patients with mean baseline HbA1c ≥10%. The type of antidiabetic agent used did not seem to contribute to glycemic changes.
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Gender and Age Impact on the Association Between Thyroid-Stimulating Hormone and Serum Lipids.
Meng, Z, Liu, M, Zhang, Q, Liu, L, Song, K, Tan, J, Jia, Q, Zhang, G, Wang, R, He, Y, et al
Medicine. 2015;(49):e2186
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The relationship between thyroid-stimulating hormone (TSH) and hyperlipidemia is still a topic of debate. We aimed to explore the impact of gender and age on the association between serum TSH and lipid profile in a large cohort of Chinese.This cross-sectional study enrolled 13,915 participants (8565 male, 5350 female), who self-reported as healthy without any known previous diseases. Clinical data including anthropometric measurements, thyroid function, and other serum parameters were collected. The associations between TSH and hyperlipidemia of males and females were analyzed separately after dividing TSH and age into subgroups. Odds ratio for hyperlipidemia was calculated by binary logistic regression models.Young males had significantly higher prevalence of hypercholesterolemia, hypertriglyceridemia, and high serum low-density lipoprotein-cholesterol than females, yet after menopause, females had higher prevalence than males. TSH was positively associated with hyperlipidemia independent of thyroid hormones. Males showed more reduced risks of hyperlipidemia in low TSH concentrations, while females demonstrated more enhanced risks of hyperlipidemia in high TSH concentrations. For instance, if TSH was lower than 0.3 μIU/mL, the risks of developing hypercholesterolemia and hypertriglyceridemia in males were only 0.198 (P < 0.01) and 0.425 (P < 0.05) of the reference TSH risks (between 2.0 and 3.0 μIU/mL), while in females the risks were 0.553 (P < 0.05) and 0.642 (P > 0.05), respectively. If TSH was higher than 4.0 μIU/mL, women displayed significantly higher risks of developing hypertriglyceridemia than the reference TSH risks (P < 0.05), yet, men did not demonstrate such significances.Our results showed thyroid hormone independent positive associations between serum TSH and lipids, which were substantially influenced by gender and age. Males demonstrated more protective effects of low TSH against hyperlipidemia, while females showed more detrimental effects of high TSH on hyperlipidemia.