The association of prealbumin, transferrin, and albumin with immunosenescence among elderly males.

OBJECTIVE: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored. METHODS: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups. RESULTS: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells and significant increases in the percentage of CD8+ cells, CD8+CD28- cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells, and negative correlation with proportions of CD8+ cells, CD8+CD28- cells. CONCLUSIONS: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males.

The relationship between Chlamydia pneumoniae infection and CD4/CD8 ratio, lymphocyte subsets in middle-aged and elderly individuals.

Chlamydia pneumoniae (C. pneumoniae) is a common respiratory pathogen associated with many inflammatory diseases. There are few data concerning the lymphocyte subsets in middle-aged and elderly individuals with C. pneumoniae infection. A total of 191 patients were included in this study. The study population was categorized into the middle-aged group (40-64 years old) and the elderly group (65-89 years old). Lymphocyte subsets in peripheral blood were examined with multi-colored flow cytometry. Immunological monitoring included lymphocyte subsets, C. pneumoniae IgG and IgM serology. In the middle-aged group, 69.83% individuals presented IgG positivity, which was associated with the inverted CD4/CD8 ratio. Individuals with C. pneumoniae IgG positivity also presented an increased percentage of CD8+CD28- cells and a decreased CD4/CD8 ratio when compared to weakly-positive individuals. In the elderly group, C. pneumoniae IgG positivity was associated with a significant increase in the percentage of CD3+CD56+CD45+ (NKT) cells. In conclusion, altered lymphocyte homeostasis was shown in middle-aged individuals with C. pneumoniae IgG positivity. The senescent phenotypes of T cells might be associated with C. pneumoniae infection in middle-aged individuals.

The predictive value of lymphocyte-to-monocyte ratio in the prognosis of acute coronary syndrome patients: a systematic review and meta-analysis.

BACKGROUND: The association between the lymphocyte-to-monocyte ratio (LMR) and prognosis in the patients with acute coronary syndrome (ACS) is not fully understood. We performed this systematic review and meta-analysis to evaluate the correlation between LMR and mortality or major adverse cardiac events (MACE) in patients with ACS. METHODS: A systematic search was performed in PubMed, MEDLINE, EMBASE, the Cochrane Library, Scopus, and Web of science. The association between LMR and mortality/MACE was analyzed in patients with ACS. The search was updated to April 15, 2020. RESULTS: A total of 5 studies comprising 4343 patients were included in this meta-analysis. The results showed that lower LMR predicted higher short-term mortality/MACE (hazard ratio [HR] = 3.44, 95% confidence interval [CI]: 1.46-8.14, P <  0.05) and long-term mortality/MACE (HR = 1.70, 95% CI: 1.36-2.13, P <  0.05). In the subgroup analysis, there was still statistical significance of long-term mortality/MACE in all subgroups. CONCLUSIONS: This study suggested that lower LMR value might be associated with higher short-term and long-term mortality/MACE in ACS patients. Especially for younger ACS patients, low LMR was more closely associated with poor prognosis.

Neutrophil to high-density lipoprotein ratio has a superior prognostic value in elderly patients with acute myocardial infarction: a comparison study.

BACKGROUND: The importance of the lipid-related biomarkers has been implicated in the pathological process and prognosis of acute myocardial infarction (AMI). Our work was conducted to discuss and compare the predictive ability of the neutrophil to high-density lipoprotein cholesterol (HDL-C) ratio (NHR) with other existing prognostic indices, for instance, the monocyte to HDL-C ratio (MHR) and the low-density lipoprotein cholesterol (LDL-C) to HDL-C ratio (LDL-C/HDL-C) in elderly patients with AMI. METHODS: Our population was 528 consecutive elderly AMI patients (65-85 years) who were enrolled from Tongji Hospital and grouped according to the cutoff points which were depicted by the receiver operating characteristic (ROC). The Kaplan-Meier curves were plotted with the survival data from the follow-up to investigate the difference between cutoff point-determined groups. Moreover, we assessed the impact of NHR, MHR, LDL-C/HDL-C on the long-term mortality and recurrent myocardial infarction (RMI) with Cox proportional hazard models. RESULTS: Mean duration of follow-up was 673.85 ± 14.32 days (median 679.50 days). According to ROC curve analysis, NHR ≥ 5.74, MHR ≥ 0.67, LDL-C/HDL-C ≥ 3.57 were regarded as high-risk groups. Kaplan-Meier analysis resulted that the high-NHR, high-MHR and high-LDL-C/HDL-C groups presented higher mortality and RMI rate than the corresponding low-risk groups in predicting the long-term clinical outcomes (log-rank test: all P < 0.050). In multivariate analysis, compared with MHR and LDL-C/HDL-C, only NHR was still recognized as a latent predictor for long-term mortality (harzard ratio [HR]: 1.96, 95% confidence interval [CI]: 1.02 to 3.75, P = 0.044) and long-term RMI (HR: 2.23, 95% CI: 1.04 to 4.79, P = 0.040). Furthermore, the positive correlation between NHR and Gensini score (r = 0.15, P < 0.001) indicated that NHR was relevant to the severity of coronary artery to some extent. CONCLUSIONS: NHR, a novel laboratory marker, might be a predictor of the long-term clinical outcomes of elderly patients with AMI, which was superior to MHR and LDL-C/HDL-C.

Association between fetuin-A and prognosis of CAD: A systematic review and meta-analysis.

BACKGROUND: Fetuin-A is an anti-inflammation and anti-calcification factor involved in the course of coronary artery disease (CAD). But the association between serum fetuin-A level and the prognosis of CAD patients was still controversial. To clarify the association between serum fetuin-A level and the prognosis of CAD patients, we conducted the present meta-analysis. METHODS: The included studies should be potentially relevant prospective studies published in English language before January 2019. The target population of the present meta-analysis was restricted to patients with CAD. The results of studies must report hazard ratio (HR) or Kaplan-Meier survival curve for all-cause mortality or incidence of secondary cardiovascular disease (CVD) events. The pooled HRs were analysed by the method of meta-analysis. RESULTS: A total of four prospective studies, including 4256 participants with CAD disease, were chosen to be included. The pooled HR for all-cause mortality was 0.57 (95% CI: 0.37-0.87), showing a statistically significant association between high serum fetuin-A level and low all-cause mortality in CAD patients. For the incidence of secondary CVD events, the pooled HR was 0.86 (95% CI: 0.60-1.23), indicating no statistically significant association between serum fetuin-A level and incidence of secondary CVD events in CAD patients. CONCLUSION: High serum fetuin-A level associated with lower all-cause mortality in patients with CAD. No association between serum fetuin-A level and incidence of secondary CVD events was found in patients with CAD.

Correlation between impedance cardiography and 6 min walk distance in atrial fibrillation patients.

BACKGROUND: The correlation between impedance cardiography (ICG) and 6 min walk distance (6MWD) in atrial fibrillation (AF) patients remains unknown. METHODS: We recruited 49 subjects in the study (21 AF patients and 28 patients without AF) and estimated hemodynamic parameters: cardiac output (CO), stroke volume (SV), stroke volume index (SVI), left stroke work (LSW), left stroke work index (LSWI), stroke systemic vascular resistance (SSVR), stroke systemic vascular resistance index (SSVRI); 6MWD, left ventricle ejection fraction (LVEF), NT-pro brain natriuretic peptide (NT-pro BNP) for the two groups. RESULTS: The AF group have apparently lower CO (2.26 ± 0.14 VS 4.11 ± 0.20 L/min, p = 0.039) and distinctly higher SVR (677.60 ± 69.10 VS 344.41 ± 22.98 dynes/cm(5), p = 0.001), SSVRI (396.97 ± 36.80 VS 199.01 ± 11.72 dynes/cm(5)/m(2), p < 0.001) than the control group. NT-pro BNP (1409.48 ± 239.90 VS 332.59 ± 68.85 pg/ml, p = 0.001) in the AF group was significantly higher than the control group and 6MWD (264.33 ± 14.55 VS 428.79 ± 29.98 m, p < 0.001) in the AF group was lower than the control group. There was no significant difference in LVEF between the two groups (62.67 ± 7.62 % VS 63.93 ± 5.03 %, p = 0.470). Pearson correlation analysis revealed that CO (R = 0.494, p = 0.023), SV (R = 0.633, p = 0.002), LSW (R = 0.615, p = 0.003) and LSWI (R = 0.491, p = 0.024) significantly correlated positively with 6MWD in AF patients. CONCLUSIONS: AF patients had lower cardiac output, shorter 6MWD and higher NT-pro BNP than patients with sinus rhythm. The cardiac output measured by impedance cardiography significantly correlated positively with 6MWD in AF patients.

An Epidemiological Survey of Cachexia in Advanced Cancer Patients and Analysis on Its Diagnostic and Treatment Status.

Recently, an international consensus diagnostic criterion for cancer cachexia was proposed. The aim of the study is to assess the prevalence of cachexia in patients with advanced cancer and to assess the current status of the diagnosis and management of cancer cachexia. A total of 390 patients with advanced cancer were included. There were 140 patients with cachexia and the prevalence was 35.9%. The prevalence was highest in pancreatic cancer (88.9%), followed by gastric cancer (76.5%) and esophageal cancer (52.9%). Sixty-three patients with cancer cachexia have CT scans available for muscle mass evaluation and 98.4% were sarcopenic. Cachectic patients have a significantly lower overall quality of life and a higher symptom burden. According to oncology physicians, only 33 patients were considered to have cancer cachexia. The false negative rate amounted to 76.4%. The positive rate was related to the body mass index and Eastern Cooperative Oncology Group performance status of the patients. There were few types of pharmacological approaches for cancer cachexia and more than half of cachectic patients did not receive any anticachexia treatment. These results indicate that the prevalence of cachexia in advanced cancer patients was high. However, cancer cachexia was rarely recognized and clinical management for cancer cachexia was very inadequate.

Effects of neferine on Kv4.3 channels expressed in HEK293 cells and ex vivo electrophysiology of rabbit hearts.

AIM: Neferine is an isoquinoline alkaloid isolated from seed embryos of Nelumbo nucifera (Gaertn), which has a variety of biological activities. In this study we examined the effects of neferine on Kv4.3 channels, a major contributor to the transient outward current (I(to)) in rabbit heart, and on ex vivo electrophysiology of rabbit hearts. METHODS: Whole-cell Kv4.3 currents were recorded in HEK293 cells expressing human cardiac Kv4.3 channels using patch-clamp technique. Arterially perfused wedges of rabbit left ventricles (LV) were prepared, and transmembrane action potentials were simultaneously recorded from epicardial (Epi) and endocardial (Endo) sites with floating microelectrodes together with transmural electrocardiography (ECG). RESULTS: Neferine (0.1-100 µmol/L) dose-dependently and reversibly inhibited Kv4.3 currents (the IC50 value was 8.437 µmol/L, and the maximal inhibition at 100 µmol/L was 44.12%). Neferine (10 µmol/L) caused a positive shift of the steady-state activation curve of Kv4.3 currents, and a negative shift of the steady-state inactivation curve. Furthermore, neferine (10 µmol/L) accelerated the inactivation but not the activation of Kv4.3 currents, and markedly slowed the recovery of Kv4.3 currents from inactivation. Neferine-induced blocking of Kv4.3 currents was frequency-dependent. In arterially perfused wedges of rabbit LV, neferine (1, 3, and 10 µmol/L) dose-dependently prolonged the QT intervals and action potential durations (APD) at both Epi and Endo sites, and caused dramatic increase of APD10 at Epi sites. CONCLUSION: Neferine inhibits Kv4.3 channels likely by blocking the open state and inactivating state channels, which contributes to neferine-induced dramatic increase of APD10 at Epi sites of rabbit heart.

Speckle tracking echocardiography assessment of global and regional contraction dysfunction in the mice model of pressure overload.

Speckle tracking echocardiography (STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge (G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group (n=10), mild trans-aortic banding (TAB) group (n=14) and severe TAB group (n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening (FS), left ventricular (LV) mass, and left ventricular end diastolic diameter (LVEDD) (P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures (P>0.05 for both). STE analysis revealed that longitudinal strain (LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups (P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group (P<0.05). Radial strain (RS) and circumferential strain (CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group (P<0.05 for both) from the postoperative week 1 (P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6 (P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.

Ability of ambulatory ECG-based T-wave alternans to modify risk assessment of cardiac events: a systematic review.

BACKGROUND: Exercise-based spectral T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death (SCD) and cardiac mortality. Prior studies have indicated that ambulatory electrocardiogram (AECG)-based TWA is an important alternative platform to exercise for risk stratification of cardiac events. This study sought to review data regarding 24-hour AECG-based TWA and to discuss its potential role in risk stratification of fatal cardiac events across a series of patient risk profiles. METHODS: Prospective clinical studies of the predictive value of AECG-based TWA obtained with daily activity published between January 1990 and November 2014 were retrieved. Major endpoints included composite endpoint of SCD, cardiac mortality, and severe arrhythmic events. RESULTS: Data were accumulated from 5 studies involving a total of 1,588 patients, including 317 positive and 1,271 negative TWA results. Compared with the negative group, positive group showed increased rates of SCD (hazard ratio [HR]: 7.49, 95% confidence interval [CI]: 2.65 to 21.15), cardiac mortality (HR: 4.75, 95% CI: 0.42 to 53.55), and composite endpoint (SCD, cardiac mortality, and severe arrhythmic events, HR: 5.94, 95% CI: 1.80 to 19.63). For the 4 studies evaluating TWA measured using the modified moving average method, the HR associated with a positive versus negative TWA result was 9.51 (95% CI: 4.99 to 18.11) for the composite endpoint. CONCLUSIONS: The positive group of AECG-based TWA has a nearly six-fold risk of severe outcomes compared with the negative group. Therefore, AECG-based TWA provides an accurate means of predicting fatal cardiac events.

[A meta-analysis on the efficacy of stem cells transplantation therapy on the prevention of cardiac remodeling and main adverse cardiovascular event in patients with chronic heart failure].

OBJECTIVE: Stem cells transplantation is a promising strategy in cardiology. This meta-analysis summarizes the efficacy and safety of stem cells transplantation on top of standard medication on chronic heart failure patients. METHODS: The following databases were searched, including Cochrane Library (Issue 4, 2011), PubMed (1980 to 2011), Embase (1990 to 2011), CBM (1978 to 2011), CNKI (1994 to 2011), VIP (1989 to 2011), and WanFang Data (1998 to 2011). Search criteria:studies were screened and the quality was evaluated according to predefined inclusion and exclusion criteria. Intervention measures: the treatment group using stem cell transplantation therapy on top of standard drug treatment, while the control group using standard drug treatments. RESULTS: A total of 31 studies involving 2375 patients were included. The results show that the improvement of LVEDV in the stem cell treatment group is greater than in the control group [SMD = -11.8% (95%CI: -0.223 - 0.013), P = 0.027] and the relative-risk of cardiac events is lower in stem cell treatment group [RR = 0.77 (95%CI: 0.66 - 0.90), P < 0.01] than in control group. CONCLUSION: Stem cells therapy is effective in improving cardiac remodeling and reducing the relative-risk of cardiac events in patients with chronic heart failure.

Clinical efficacy of selenium supplementation in patients with Hashimoto thyroiditis: A systematic review and meta-analysis.

BACKGROUND: Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study investigates clinically relevant effects of selenium supplementation in patients with HT. METHODS: A systematic search was performed in PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. The latest update was performed on December 3, 2022. We investigated the changes in thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) after selenium supplementation. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: After screening and full-text assessment, 7 controlled trials comprising 342 patients were included in the systematic review. The results showed that there was no significant change in TPOAb levels (WMD = -124.28 [95% CI: -631.08 to 382.52], P = .631, I2 = 94.5%) after 3 months of treatment. But there was a significant decrease in TPOAb levels (WMD = -284.00 [95% CI: -553.41 to -14.60], P < .05, I2 = 93.9%) and TgAb levels (WMD = -159.86 [95% CI: -293.48 to -26.24], P < .05, I2 = 85.3%) after 6 months of treatment. CONCLUSIONS: Selenium supplementation reduces serum TPOAb and TgAb levels after 6 months of treatment in patients with HT, but future studies are warranted to evaluate health-related quality or disease progression.

Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study.

The age-related decline in T-cell function among elderly individuals remains unclear. We thus investigated the interrelationship between T-cell subsets and age to identify the changes in T-cell phenotypes and develop an age prediction model for the elderly population. A total of 127 individuals aged >60 years were divided into three groups (youngest-old group, 61-70 years, n = 34; middle-old group, 71-80 years, n = 53; and oldest-old group, ≥ 81 years, n = 40). The percentage of CD8+CD28- cells (P = 0.001) was highest in the oldest-old group and then followed by the middle-old group, while the youngest-old group was the lowest. Both females and males demonstrated significant decreases in the absolute counts of CD4+CD45RA+ cells (P = 0.020; P = 0.002) and CD8+CD28+ cells (P = 0.015; P = 0.005) with age. Multivariate linear regression showed that the percentage of CD8+CD28- cells (P < 0.001) was an independent predictor of aging after adjusting for sex, body mass index, hospitalization duration, smoking, drinking, chronic medical illness, and medications at admission. In conclusion, our results suggest that aging in elderly individuals is accompanied by a decrease in the counts of T-cell subpopulations. CD8+CD28- cells may be potential targets for elderly individuals in antiaging-related immunosenescence.

Development and validation of an interpretable machine learning model-Predicting mild cognitive impairment in a high-risk stroke population.

Background: Mild cognitive impairment (MCI) is considered a preclinical stage of Alzheimer's disease (AD). People with MCI have a higher risk of developing dementia than healthy people. As one of the risk factors for MCI, stroke has been actively treated and intervened. Therefore, selecting the high-risk population of stroke as the research object and discovering the risk factors of MCI as early as possible can prevent the occurrence of MCI more effectively. Methods: The Boruta algorithm was used to screen variables, and eight machine learning models were established and evaluated. The best performing models were used to assess variable importance and build an online risk calculator. Shapley additive explanation is used to explain the model. Results: A total of 199 patients were included in the study, 99 of whom were male. Transient ischemic attack (TIA), homocysteine, education, hematocrit (HCT), diabetes, hemoglobin, red blood cells (RBC), hypertension, prothrombin time (PT) were selected by Boruta algorithm. Logistic regression (AUC = 0.8595) was the best model for predicting MCI in high-risk groups of stroke, followed by elastic network (ENET) (AUC = 0.8312), multilayer perceptron (MLP) (AUC = 0.7908), extreme gradient boosting (XGBoost) (AUC = 0.7691), and support vector machine (SVM) (AUC = 0.7527), random forest (RF) (AUC = 0.7451), K-nearest neighbors (KNN) (AUC = 0.7380), decision tree (DT) (AUC = 0.6972). The importance of variables suggests that TIA, diabetes, education, and hypertension are the top four variables of importance. Conclusion: Transient ischemic attack (TIA), diabetes, education, and hypertension are the most important risk factors for MCI in high-risk groups of stroke, and early intervention should be performed to reduce the occurrence of MCI.

Alternating Early Afterdepolarizations Underlying Bradycardia-Dependent Macroscopic T Wave and Discordant Mechanical Alternans.

BACKGROUND: Macroscopic T wave alternans (macro-TWA) often heralds the onset of Torsades de Pointes in patients with QT prolongation. However, the mechanisms underlying macro-TWA remain unclear. We examined the cellular and ionic basis for macro-TWA in rabbits with left ventricular hypertrophy (LVH). METHODS: The renovascular hypertension model was used to induce LVH in rabbits. Action potentials were simultaneously recorded from epicardium and endocardium together with a transmural ECG and isometric contractility in arterially perfused left ventricular wedges. Late sodium current (INa-L) was recorded in single-isolated left ventricular myocytes with the whole cell patch-clamp technique. RESULTS: Macro-TWA and accompanied mechanical alternans occurred spontaneously in 8 of 33 LVH rabbits (P<0.05, versus 0/15 in controls) and were induced by an INa-L enhancer ATX-II at 1 to 3 nM in additional 7. Macro-TWA and mechanical alternans occurred discordantly, that is, that longer QT interval and larger T wave were associated with weaker isometric contvractility. Alternating early afterdepolarizations in the endocardium caused macro-TWA in 12 of 15 LVH rabbits and, therefore, early afterdepolarization-dependent R-from-T extrasystoles and Torsades de Pointes always originated from the beats with longer QT and larger T wave during macro-TWA. INa-L density was significantly larger in LVH myocytes than that of control myocytes. Macro-TWA, mechanical alternans, R-from-T extrasystoles, and Torsades de Pointes were all abolished by INa-L blocker ranolazine or mexiletine. CONCLUSIONS: LVH enhances INa-L density and promotes alternating early afterdepolarizations in the left ventricular endocardium that manifest as macro-TWA with discordant mechanical alternans. INa-L blockade abolishes macro-TWA, mechanical alternans, early afterdepolarization-dependent R-from-T extrasystoles, and Torsades de Pointes.

Monocyte to high-density lipoprotein ratio predict long-term clinical outcomes in patients with coronary heart disease: A meta-analysis of 9 studies.

BACKGROUND: A novel inflammation-related biomarker, the monocyte to high-density lipoprotein cholesterol ratio (MHR), had a great relation to the development and prognosis of coronary atherosclerotic heart disease. Current study was to investigate whether the MHR was a potential tool in predicting the mortality and major adverse cardiac events (MACEs) in patients suffering coronary heart disease (CHD) by meta-analysis. METHODS: The Cochrane Library, PubMed, MEDLINE, Scopus, EMBASE, and Web of science were searched for relevant cohort studies published prior to February 10, 2022. The association between MHR and mortality/MACEs was analyzed in patients with CHD. Hazard ratios (HR) with 95% confidence interval (CI) were calculated to estimate the strength of association. RESULTS: In the meta-analysis, a total of 9 studies of 11,345 patients with CHD were included. Compared with the low level of MHR group, the high MHR value was associated with higher long-term MACEs (HR = 1.72 95% CI 1.36-2.18, P < .001), long-term mortality (HR = 1.71, 95% CI 1.10-2.66, P = .017), and in-hospital mortality/MACEs (HR = 2.82, 95% CI = 1.07-7.41, P = .036). CONCLUSIONS: This study suggested that increased MHR value might be associated with higher long-term mortality and long-term MACEs in CHD patients. MHR might serve as a potential prognostic indicator for risk stratification in patients with CHD.

Is elevated triglyceride/high-density lipoprotein cholesterol ratio associated with poor prognosis of coronary heart disease? A meta-analysis of prospective studies.

BACKGROUND: Elevated triglycerides (TG) and reduced high-density lipoprotein cholesterol (HDL-C) are recognized as essential and independent hazard factors for total death and major adverse cardiovascular events (MACE) in patients with coronary heart disease (CHD). However, whether the increased TG/HDL-C forecasted the prognosis of CHD is still unknown. Therefore, we performed a meta-analysis to investigate the relationship between the elevated TG/HDL-C ratio and poor prognosis of CHD. METHODS: A systematic literature search was conducted in PubMed, Web of Science, EMBASE, and The Cochrane Library, until August 30, 2021. Prospective observational studies regarding the association between TG/HDL-C and long-term mortality/MACEs in CHD patients were included. RESULTS: In total, 6 independent prospective studies of 10,222 participants with CHD were enrolled in the systematic and meta-analysis. Our outcomes of the meta-analysis indicated that the elevated TG/HDL-C group had a significantly increased risk of long-term all-cause mortality (hazard ratio [HR] = 2.92, 95% confidence interval [CI]: 1.75-4.86, P < .05) and long-term MACEs (HR = 1.56, 95%CI 1.11-2.18, P < .05). CONCLUSION: In patients with CHD, the present study showed that the high TG/HDL-C was associated with increased risk of long-term all-cause mortality and MACE.

A novel mutation in the KCNH2 gene associated with short QT syndrome.

A gain of function mutation N588K in the KCNH2 gene that encodes HERG channels has been shown to underlie the SQT1 form of short QT syndrome (SQTS). We describe a different mutation in the KCNH2 gene in a Chinese family with clinical evidence of SQTS. A Chinese family with a markedly short QT interval (QTc=316 ± 9 ms, n=4) and a strong family history of sudden death was investigated. Analysis of candidate genes contributing to ventricular repolarization identified a C1853T mutation in the KCNH2 gene coding for the HERG channel, resulting in an amino acid change (T618I) that was found to 100% co-segregate with the SQTS phenotype (n=4). Whole cell voltage clamp studies of the T618I mutation in HEK-cells demonstrated a 6-fold increase in maximum steady state current (146.1 ± 16.7 vs 23.8 ± 5.5 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -78.6 ± 6.8 vs T618I -29.3 ± 1.7 mV). Kinetic analysis revealed slower inactivation rates of T618I but faster rates of recovery from inactivation. Quinidine (5 µM) and sotalol (500 µM) had similar inhibitory effects on steady currents measured at +20 mV in WT and T618I but were less effective in inhibiting tail currents of mutant channels. The altered function of T618I-HERG channels suggests that this mutation in the KCNH2 gene is responsible for the SQTS phenotype in this family. Both quinidine and sotalol may be therapeutic options for patients with the T618I HERG mutation.