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Abstract Background This study aimed to analyze the associations of cardiometabolic index (CMI) with diabetic statuses and insulin resistance (IR) using data from the National Health and Nutrition Examination Survey (NHANES) and examined the potential mediating role of inflammation in these correlations. Methods This study enrolled 9477 participants across four NHANES cycles from 2011 to 2018. The primary outcomes of the study included the risk of having prediabetes, diabetes and the level of the homeostasis model assessment of IR (HOMA-IR). Other outcomes including the levels of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), oral glucose tolerance test (OGTT) results, fasting insulin, the risk of oral hypoglycemic medicine use, insulin use, and retinopathy were also collected and analyzed. Logistic regression model, subgroup analysis, restricted cubic spine (RCS), and Pearson correlation coefficients were conducted to assess the associations of CMI with diabetic statuses and IR. The mediating role of inflammation was evaluated to investigate the potential mechanism of the associations between CMI and diabetic statuses. Results Among included participants, the CMI levels in normal participants, prediabetes and diabetes in this study were 0.48, 0.73 and 1.07. After multivariable adjustment, CMI was positively associated with the risk of prediabetes (OR = 1.49, 95% CI = 1.24–1.79), diabetes (OR = 2.14, 95% CI = 1.82–2.50) and the level of HOMA-IR (β = 2.57, 95% CI = 2.14–3.01). Besides, an increased CMI was correlated with higher levels of FBG, HBA1c, OGTT results and fasting insulin as well as the greater risk of oral hypoglycemic medicine use and insulin use. The RCS showed an inverted L-shaped association of CMI with prediabetes and diabetes (P for non-linearity

Abstract Background This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations. Methods A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2. Results The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality. Conclusion Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.

Abstract Background Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. Methods INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). Results Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045–3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253–4.364, P = 0.008). Conclusion This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.

Abstract Background Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. Methods HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Results Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p 0.99) in comparison to the other groups (log-rank p

Abstract Background Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH. Methods Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed. Results WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother. Conclusions The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.

Abstract Background The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. Methods A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. Results During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818–34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. Conclusion Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Abstract Background Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. Methods CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography‑derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). Results Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014–2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066–4.261; P = 0.032). Conclusion TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

Abstract Background Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients. Methods A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73–0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan–Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE. Results A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P

Abstract Background Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). Methods CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. Results Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR

ObjectiveCoronary microvascular dysfunction (CMD) may associate with adverse cardiovascular events in obese patients. Coronary angiography-derived index of microcirculatory resistance (caIMR) is proposed as a less-invasive and pressure-wire-free index to assess CMD. We aimed to investigate the impact of coronary microvascular function assessed by caIMR in patients with overweight and chronic coronary syndrome (CCS).MethodsCCS patients who underwent coronary angiography between 2015 to 2018 were included. Overweight was defined as BMI≥24.0kg/m². Impaired coronary microvascular function was defined as caIMR≥25U. The patients were classified according to BMI and caIMR. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier and Cox regression analyses evaluated the association between caIMR and MACE.ResultsTwo hundred and eighty-two CCS patients were enrolled. Among these, 169 (59.93%) were overweight. Impaired coronary microvascular function was higher in overweight patients than in patients with normal weight (49.70% vs. 38.05%; P=0.035). During 35 months of follow-up, 33 MACE had occurred. Among the total CCS population, MACE was higher in patients with high caIMR than in low caIMR (18.11% vs. 6.45%, P=0.003). In subgroups analysis, MACE was higher in overweight patients with high caIMR than low caIMR (20.24% vs. 7.06%, P=0.014), while there were no significant differences in normal-weight patients. Multivariate Cox analysis demonstrated that caIMR≥25 was independently associated with MACE in overweight patients (HR, 2.87; 95% CI, 1.12-7.30; P=0.027) but not in the normal-weight patients. In addition, caIMR showed a significant predictive value for adverse outcomes in overweight patients and provided an incremental prediction when added to a prediction model with BMI.ConclusionsImpaired coronary microvascular function assessed by caIMR was common and is an independent predictor of MACE in overweight patients with CCS.

Background. White blood cell count to mean platelet volume ratio (WMR) and neutrophil-to-platelet ratio (NPR) have been demonstrated as prognostic inflammatory biomarkers of the acute coronary syndrome. We aimed to evaluate the prognostic value of WMR and NPR among myocardial infarction with nonobstructive coronary arteries (MINOCA) patients. Method. A total of 274 MINOCA patients were enrolled. Baseline clinical data, blood cell panel, and biochemical parameters were evaluated. The patients were classified according to the medians of WMR and NPR. The primary endpoint of the present study was major adverse cardiovascular events (MACE). Multivariable Cox regression analysis was used to assess the effect of independent variables of WMR and NPR on the dependent variable (MACE). Result. The median values of WMR and NPR were 701 and 0.03, respectively. During the median follow-up of 28 months, a total of 58 incidences of MACE occurred. The MACE rate was more frequent in high WMR and high NPR patients. In Kaplan-Meier analysis, the incidence of MACE was higher in WMR>701 and NPR>0.03 (long-rank P=0.004 and P=0.002, respectively). The combined high WMR and high NPR showed a significantly higher rate of MACE (long-rank P=0.001). Cox regression analysis showed that the combined high WMR and high NPR were independent predictors of long-term MACE with the highest hazard ratio (HR, 2.511; 95% CI, 1.271 to 4.960; P=0.008). Conclusion. High WMR and NPR separately or in combination were correlated with increased risk of MACE among MINOCA patients, suggesting WMR and NPR may assist as a reliable inflammatory marker in risk prediction of MINOCA patients.

Abstract Worldwide, more health care facilities are adapting the use of electronic health record (EHR). Healthcare providers (HCP) have different perceptions toward the use of EHR. To investigate the perception of three classes of HCP in Saudi Arabia toward using EHR, a questionnaire (targeting satisfaction, easiness, and benefits of use as major perception indicators) was prepared. The questionnaire was assessed by an expert panel for content validity. The questionnaire internal consistency was examined using Cronbach's alpha. 108 physicians, physical therapists (PT) and respiratory care therapists (RT) from different hospitals in Saudi Arabia answered the questionnaire. Most of respondents perceived EHR systems as beneficial and made work easier. Most HCP were satisfied with the use of EHR, however, with the use of EHR more time was needed to finish the work. Age, experience, job, and job rank of HCP are of different importance in determining responses, perception, and obstacles of using EHR. Moreover, the perception of using EHR seems to be field specific. There is a positive perception among Saudi Arabia HCP about EHR use.

The human gut microbiome has been implicated in a host of bodily functions and their regulation, including brain development and cognition. Neuroinflammation is a relatively newer piece of the puzzle and is implicated in the pathogenesis of many neurological disorders. The microbiome of the gut may alter the inflammatory signaling inside the brain through the secretion of short-chain fatty acids, controlling the availability of amino acid tryptophan and altering vagal activation. Studies in Korea and elsewhere highlight a strong link between microbiome dynamics and neurocognitive states, including personality. For these reasons, re-establishing microbial flora of the gut looks critical for keeping neuroinflammation from putting the whole system aflame through probiotics and allotransplantation of the fecal microbiome. However, the numerosity of the microbiome remains a challenge. For this purpose, it is suggested that wherever possible, a fecal microbial auto-transplant may prove more effective. This review summarizes the current knowledge about the role of the microbiome in neuroinflammation and the various mechanism involved in this process. As an example, we have also discussed the autism spectrum disorder and the implication of neuroinflammation and microbiome in its pathogenesis.