Remnant cholesterol, preinflammatory state and chronic kidney disease: association and mediation analyses.

Blood lipid management is a key approach in the prevention of chronic kidney disease (CKD). Remnant cholesterol (RC) plays an important role in the development of multiple diseases via chronic inflammation. The aim of our study was to determine the relationship between RC and CKD and explore the role of inflammation in this relationship. The 7696 subjects from the Chinese Health and Nutrition Survey were divided into four subgroups according to the quartile of RC. The estimated glomerular filtration rate was calculated using the CKD Epidemiology Collaboration equation. Fasting RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Logistic regression analysis was employed to evaluate the relationships between RC and CKD. Mediation analysis was undertaken to identify potential mediators of high-sensitivity C-reactive protein (hs-CRP) and white blood cells (WBCs). Of all participants, the mean age was 51 years, and the male accounted for 47.8%. The multivariable-adjusted odds ratios (95% CIs) for the highest versus lowest quartile of remnant cholesterol were 1.40 (1.10-1.78, p for trend = 0.006) for CKD. RC and preinflammatory markers have combined effect on CKD. The preinflammatory state, presented by increased hs-CRP or WBCs, partially mediated the association between RC and CKD with proportion of 10.14% (p = 0.002) and 11.65% (p = 0.012), respectively. In conclusion, this study suggested a positive relationship between RC and CKD, which was partially mediated by preinflammatory state. These findings highlight the importance of RC and inflammation in renal dysfunction.IMPACT STATEMENTWhat is already known on this subject?: Dyslipidemia plays an important role in the development of chronic kidney disease (CKD). Remnant cholesterol (RC), as a triglyceride-rich particle, can contribute to target organ damage, primarily through inflammatory pathways. However, the relationship between RC and CKD in the community-dwelling population, particularly the role of inflammation, is not yet fully understood.What do the results of this study add?: This study shows that RC was significantly associated with CKD. RC and preinflammatory status exhibit a combined effect on CKD. Preinflammatory state, presented by increased high-sensitivity C-reactive protein or white blood cells, partially mediated the association between RC and CKD.What are the implications of these findings for clinical practice and/or further research?: The study provides us with a better understanding of the role of RC and inflammation in kidney dysfunction and raises the awareness of RC in the management of CKD.

The role of remnant cholesterol beyond low-density lipoprotein cholesterol in diabetes mellitus.

BACKGROUND: Previous research has linked elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) with diabetes mellitus (DM). The present study aims to estimate the RC-related DM risk beyond LDL-C, and to investigate the extent to which the association of RC and DM is mediated via insulin resistance and inflammation. METHODS: We enrolled 7308 individuals without previous history of DM into the present study from the China Health and Nutrition Survey. Fasting RC was calculated as total cholesterol minus LDL-C and high-density lipoprotein cholesterol. Subjects were divided into four groups according to their LDL-C (100 mg/dL) and RC (24 mg/dL) levels to evaluate the role of LDL-C vs. RC on DM. A logistic regression analysis was then employed to evaluate the relationships between the discordant/concordant LDL-C and RC and DM. A mediation analysis was undertaken to identify potential mediators. RESULTS: Of all the participants, a total of 625 (8.55%) patients were newly diagnosed with DM. Compared to the high LDL-C/low RC group, the low LDL-C/high RC group was more common in DM patients. After a multivariate adjustment, elevated LDL-C and RC were associated with DM. Moreover, the low LDL-C/high RC group and the high LDL-C/low RC group manifested a 4.04-fold (95% CI 2.93-5.56) and 1.61-fold (95% CI 1.21-2.15) higher risk of DM, relative to those with low LDL-C/low RC. The subgroup analysis indicated that low LDL-C/high RC was more likely to be related to DM in females. Similar results were also shown when the sensitivity analyses were performed with different clinical cut-points of LDL-C. Insulin resistance and inflammation partially mediated the association between RC and DM. CONCLUSIONS: Our findings provided evidence for RC beyond the LDL-C associations with DM that may be mediated via insulin resistance and the pro-inflammatory state. In addition, women are more susceptible to RC exposure-related DM.

Inflammatory Risk Status Shapes the Association Between Uric Acid and Cognitive Function in Non-Hyperuricemia Middle Aged and Elderly.

BACKGROUND: The association between uric acid (UA) and cognitive function still remains controversial. Moreover, the role of inflammation in the above association is also unclear. OBJECTIVE: We aimed to determine the association between UA and cognitive function among non-hyperuricemia adults, and in particular, whether the association was shaped by different inflammation levels. METHODS: From the China Health and Retirement Longitudinal Study (CHARLS), 7,272 participants aged 45 and above were enrolled in 2011. Cognitive function measurement included orientation and attention, episodic memory, and visuospatial ability. Fasting blood samples were collected to measure levels of UA and high-sensitivity C-reactive protein (hs-CRP). Generalized estimating equation models were used to evaluate the effect of UA on cognitive function in all participants and those at different levels of hs-CRP (hs-CRP <3 mg/L or ≥3 mg/L). RESULTS: Among non-hyperuricemia adults (mean age: 58.08, 49.59% males) for a median of 7 years follow-up, participants with higher levels of UA had better cognitive function score compared to those with lower UA levels (ß: 0.09, 95% confidence interval [CI]: 0.01-0.17, p = 0.023). And this association was significant under low-grade inflammation levels condition (ß:0.10, 95% CI: 0.10-0.19, p = 0.024), but not in high-grade inflammation levels condition. Further, the cognitive function benefit of elevated UA existed only in people with persistent low-grade inflammation levels at a longitudinal perspective (ß: 0.14, 95% CI: 0.01-0.27, p = 0.039). CONCLUSIONS: Elevated UA levels were associated with better cognitive function in non-hyperuricemia population, especially for those at low inflammation levels.

Remnant cholesterol, iron status and diabetes mellitus: a dose-response relationship and mediation analysis.

BACKGROUND: Remnant cholesterol (RC) is recognized as a risk factor for diabetes mellitus (DM). Although iron status has been shown to be associated with cholesterol metabolism and DM, the association between RC, iron status, and DM remains unclear. We examined the relationship between RC and iron status and investigated the role of iron status in the association between RC and DM. METHODS: A total of 7308 patients were enrolled from the China Health and Nutrition Survey. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. Iron status was assessed as serum ferritin (SF) and total body iron (TBI). DM was ascertained by self-reported physician diagnosis and/or antidiabetic drug use and/or fasting plasma glucose ≥ 126 mg/dL and/or glycated haemoglobin ≥ 6.5%. General linear models were used to evaluate the relationships between RC and iron status. Restricted cubic splines were used to assess the association between RC and DM. Mediation analysis was used to clarified the mediating role of iron status in the association between the RC and DM. RESULTS: The average age of the participants was 50.6 (standard deviation = 15.1) years. Higher RC was significantly associated with increased SF (ß = 73.14, SE = 3.75, 95% confidence interval [CI] 65.79-80.49) and TBI (ß = 1.61, SE = 0.08, 95% CI 1.44-1.78). J-shape relationships were found in the association between RC levels with DM, as well as iron status with DM. Significant indirect effects of SF and TBI in the association between RC and DM were found, with the index mediated at 9.58% and 6.37%, respectively. CONCLUSIONS: RC has a dose-response relationship with iron status. The association between RC and DM was mediated in part by iron status. Future studies are needed to confirm these findings and further clarify the underlying mechanism.

Association between remnant cholesterol, metabolic syndrome, and cardiovascular disease: post hoc analysis of a prospective national cohort study.

BACKGROUND: Epidemiologic evidence suggested that remnant cholesterol (RC) is associated with the occurrence of cardiovascular disease (CVD). In recent years, RC has been connected with different types of cardiometabolic disorders. We aim to clarify the relationship among RC, metabolic syndrome (MetS) and subsequent CVD. METHODS: We enrolled 7471 individuals into our study from China Health and Nutrition Survey in 2009 and followed participants till 2015. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol minus high-density lipoprotein cholesterol. CVD was defined as myocardial infarction and stroke. Multivariate logistic regression and Cox regression models were used to evaluate the association between RC and MetS as well as CVD. We further investigated whether the association between RC and CVD was mediated by MetS. RESULTS: Of all subjects, 24.73% were diagnosed with MetS and 2.74% developed CVD. Multivariate logistic regression analysis elucidated that per-tertile-increase in RC was associated with MetS after adjusting all the confounder factors, (odds ratio: 3.49, 95% confidence interval CI 3.21-3.79, P for trend < 0.001). And per-tertile-increase RC had a significant increased risk of CVD (hazard ratio: 1.26, 95% CI 1.06-1.50, P for trend = 0.008). Meanwhile, we found that RC level is associated with the prevalence of all the components of MetS. Significant indirect effects of RC between MetS and CVD were found, with the index mediated at 48.46% of the association. CONCLUSIONS: Our study provides the evidence that RC level is independently associated with the prevalence of MetS and each component of MetS. MetS partially mediated the association between RC level and CVD risk.

Effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction.

OBJECTIVE: Evidence of therapy for dysfunctional coronary circulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) is limited. This study was performed to compare the effects of atorvastatin and rosuvastatin on dysfunctional coronary circulation. METHODS: This retrospective study enrolled 597 consecutive patients with STEMI who underwent pPCI in 3 centers from June 2016 to December 2019. Dysfunctional coronary circulation was defined by the thrombolysis in myocardial infarction (TIMI) grade and the TIMI myocardial perfusion grade (TMPG). Logistic regression analysis was used to evaluate the impact of different statin types on dysfunctional coronary circulation. RESULTS: The incidence of TIMI no/slow reflow did not differ between the two groups, but the incidence of TMPG no/slow reflow was significantly lower in the atorvastatin than rosuvastatin group (44.58% vs. 57.69%, respectively). After multivariate adjustment, the odds ratio with 95% confidence interval of rosuvastatin was 1.72 (1.17-2.52) for after pretreatment TMPG no/slow reflow and 1.73 (1.16-2.58) for after stenting TMPG no/slow reflow. Atorvastatin and rosuvastatin showed no significant differences in clinical outcomes during hospitalization. CONCLUSIONS: Compared with rosuvastatin, atorvastatin was associated with better coronary microcirculatory perfusion in patients with STEMI who underwent pPCI.

D-Dimer Is Associated With Coronary Microvascular Dysfunction in Patients With Non-obstructive Coronary Artery Disease and Preserved Ejection Fraction.

Background: Coronary microvascular dysfunction (CMVD), an important etiology of ischemic heart disease, has been widely studied. D-dimer is a simple indicator of microthrombosis and inflammation. However, whether an increase in D-dimer is related to CMVD is still unclear. Materials and Methods: This retrospective study consecutively enrolled patients with myocardial ischemia and excluded those with obstructive coronary artery. D-dimer was measured at admission and the TIMI myocardial perfusion grade (TMPG) was used to distinguish CMVD. Patients were divided into the two groups according to whether the D-dimer was elevated (>500 ng/ml). Logistic models and restricted cubic splines were used to explore the relationship between elevated D-dimer and CMVD. Results: A total of 377 patients were eventually enrolled in this study. Of these, 94 (24.9%) patients with CMVD had older age and higher D-dimer levels than those without CMVD. After full adjustment for other potential clinical risk factors, patients with high D-dimer levels (>500 ng/ml) had a 1.89-times (95% CI: 1.09-3.27) higher risk of CMVD than patients with low D-dimer levels. A non-linear relationship was found between concentrations of D-dimer and CMVD. With increased D-dimer level, the incidence of CMVD increased and then remained at a high level. Stratified analysis was performed and showed similar results. Conclusion: Elevated D-dimer level is associated with the incidence of CMVD and potentially serves as a simple biomarker to facilitate the diagnosis of CMVD for patients with angina.

Triglyceride-glucose index is associated with quantitative flow ratio in patients with acute ST-elevation myocardial infarction after percutaneous coronary intervention.

Background: The triglyceride-glucose (TyG) index is a novel marker representing the degree of insulin resistance (IR) and is closely related to cardiovascular diseases. However, the association between the TyG index and vascular function in patients with acute ST-elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI) remains unknown. Materials and methods: This study was a post hoc analysis of a multicenter, prospective cohort study. In this study, patients with STEMI who underwent PCI were included, and coronary angiography data were analyzed by Quantitative coronary angiography (QCA) and quantitative flow ratio (QFR). In addition, the TyG index was calculated as follows: Ln [fasting triglyceride (mg/dl) × fasting blood glucose (mg/dl) × 1/2]. According to the post-PCI QFR, patients were divided into two groups: post-PCI QFR ≤ 0.92 group and post-PCI QFR > 0.92 group. Construction of logistic regression model to explore the relationship between the TyG index and post-PCI QFR. Results: A total of 241 STEMI patients were included in this study. Compared with patients in the post-PCI QFR > 0.92 group, the TyG index was higher in the post-PCI QFR ≤ 0.92 group. Logistic regression model showed that after adjusting for other confounding factors, the TyG index was positively correlated with the risk of post-PCI QFR ≤ 0.92 (OR = 1.697, 95% CI 1.171-2.460, P = 0.005). Restricted cubic splines showed the cutoff value of TyG index associated with post-PCI QFR ≤ 0.92 risk was 9.75. Conclusion: The TyG index was associated with the risk of post-PCI QFR ≤ 0.92 in STEMI patients. The risk of post-PCI QFR ≤ 0.92 increased when the TyG index exceeded 9.75.

Predictive effect of different blood lipid parameters combined with carotid intima-media thickness on coronary artery disease.

Background: Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD. Methods: This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD. Results: Patients were classified into two groups based on whether CAD existed. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) [Lp (a)], apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High level of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02-1.95, P = 0.036). Conclusion: For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.

Effect of GP IIb/IIIa inhibitor duration on the clinical prognosis of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction with no-/slow-reflow phenomenon.

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) accompanied by the no-/slow-reflow phenomenon, the maintenance duration of GP IIb/IIIa inhibitor (GPI) is controversial. We compare the efficacy and safety of short- and long-term GPI infusion in STEMI patients with the no-/slow-reflow phenomenon. METHODS: From June 2016 to December 2019, we continuously included patients with on-set STEMI who underwent pPCI, accompanied by the no-/slow-reflow, during interventional procedures at Guangdong Provincial People's Hospital and Zhuhai Golden Bay Hospital. The hemorrhage events, heart function, and major adverse cardiovascular events (MACE) were compared between < 24 h and ≥ 24 h GPI duration groups. The Kaplan-Meier curve was used to estimate the 1-year MACE-free survival at different GPI utility times. RESULTS: In total, 127 patients were divided into two groups based on the duration of tirofiban use (less and more than 24 h). There was no significant difference between two groups in terms of baseline characteristics, plaque condition, and coronary physiological function. The two groups showed similar in-hospital MACE (1 [1.85%] vs. 4 [5.48%], p = 0.394) and 1-year MACE-free survival (log-rank test p = 0.9085). The 1-year MACE remained consistent between the two groups in all subgroups of different risk factors of no-/slow-reflow. There was no significant difference in heart function and in-hospital hemorrhage events (3.7% vs. 1.37%, p = 0.179). CONCLUSION: In the real world, prolonging the duration of GPI may not significantly improve the clinical outcome in patients with STEMI with no-/slow-reflow.

Emerging Trends and New Developments in Transient Elastography: A Bibliometric and Cocitation Analysis from 1999 to 2017.

Purpose: To identify and characterize the 100 most-cited articles in the field of transient elastography. Methods: The top-cited articles focusing on transient elastography from 1999 to 2017 were retrieved from Science Citation Index Expanded (SCI-E) database. The most prolific article, journal, country and continent, top-cited article in different period, international collaboration, cocitation analysis of journal were retrieved and analyzed in this article. Bibexcel 2016, Microsoft Excel 2010, and VOSviewer 1.6.5 were used to analyze bibliometric records we downloaded. Results: The 100 most-cited articles were published between 2003 and 2015. The total citations ranged from 54 to 1376 (mean, 167.52 ± 208.46; median, 89.5) and the annual citations ranged from 4.91 to 98.24 (mean, 17.21±15.68; median, 12.1). The top-cited article was published in Gastroenterology in 2005 by Castera L. et al. (n=1376). The most-cited articles in 2003-2007 (n=1380), 2008-2012 (n=599) and 2013-2017 (n=159) were located. All of the most-cited articles in three periods were focusing on the topic of noninvasive assessment of liver fibrosis. The most prolific author was de Ledinghen V. (n=21) and France (n=43) was the leading country. The most productive journal was Journal of Hepatology (n=20). The major article type was original research article. Conclusions: We undertook efforts to provide an insight into the features and evolvement of the most-cited articles in the field of transient elastography. For transient elastography, as a noninvasive assessment of liver fibrosis, its use in the evaluation of liver fibrosis is gradually mature and shows great advantages. Moreover, the field of transient elastography is in a stage of rapid development.