Biomarkers in Cardiovascular Disease—Chances and Risks

Primary hyperparathyroidism (PHPT) seems to be associated with different cardiovascular diseases (CVDs). We evaluated the association of PHPT with major CV risk factors (CVRFs) and CVDs by using artificial intelligence (AI) tools. An observational and retrospective study was conducted using data from the electronic health records (EHRs) of the Hospital Universitario Puerta de Hierro Majadahonda (Spain). Of a total of 699,157 patients over 18 years of age studied (54.7% females), 6515 patients (0.9%; 65.4% women; mean age 67.6 ± 15.9 years) had a diagnosis of PHPT. The overall frequencies of hypertension, dyslipidemia, diabetes mellitus, and smoking habit in the cohort of patients with PTHP were all significantly (p < 0.001) higher than those found in patients without a diagnosis of PTHP. The total frequency of stroke, ischemic heart disease, atrial fibrillation, deep vein thrombosis, and pulmonary embolism in the cohort of PHPT patients were significantly (p < 0.001) higher than that found in patients without the diagnosis of PHPT. A multivariate regression analysis showed that PHPT was significantly (p < 0.001) and independently associated with all the CVDs evaluated. Our data show that there is a significant association between the diagnosis of PHPT and the main CVRFs and CVDs in our hospital population. Full article

Background and Objectives: Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder characterized by glucose intolerance during pregnancy. The triglyceride glucose (TyG) index, a marker of insulin resistance, and coronary flow reserve (CFR), a measure of coronary microvascular function, are emerging as potential indicators of cardiovascular risk. This study aims to investigate the association between CFR and the TyG index in GDM patients. Materials and Methods: This cross-sectional study of 87 GDM patients and 36 healthy controls was conducted. The participants underwent clinical assessments, blood tests, and echocardiographic evaluations. The TyG index was calculated as ln(triglycerides × fasting glucose/2). CFR was measured using Doppler echocardiography during rest and hyperemia induced by dipyridamole. Results: The study included 87 individuals in the GDM group and 36 individuals in the control group. There was no significant difference in age between the two groups (34.1 ± 5.3 years for GDM vs. 33.1 ± 4.9 years for the control, p = 0.364). The TyG index was significantly higher in the GDM group compared to the controls (p < 0.001). CFR was lower in the GDM group (p < 0.001). A negative correlation between the TyG index and CFR was observed (r = −0.624, p < 0.001). Linear regression revealed the TyG index as an independent predictor of reduced CFR. Conclusions: The study findings reveal a significant association between the TyG index and CFR in GDM patients, suggesting their potential role in assessing cardiovascular risk. Full article

The liver fibrosis score reflects the degree of hepatic scarring and has been reported to be associated with cardiovascular disease. Using a coronary artery computed tomography angiography registry at the Fukuoka University Hospital (FU-CCTA registry), we investigated the association between major adverse cardiovascular events (MACEs) and the liver fibrosis score (fibrosis-4 index (FIB-4I)) in 612 patients who underwent CCTA to screen for coronary artery disease and performed a prognosis survey for up to 5 years. The primary endpoint was MACEs (all-cause mortality, acute myocardial infarction, ischemic stroke, coronary revascularization). FIB-4I in all patients and in patients with hypertension (HTN) was significantly higher in the MACE group than in the non-MACE group. The event-free survival rate of MACEs targeting only patients with HTN was significantly lower in patients with a high risk of liver fibrosis (FIB-4I values of 2.67 or higher) than in those with a low or intermediate risk (less than 2.67). However, no significant difference was observed in all patients or in patients without HTN. Finally, FIB-4I and body mass index were independent factors associated with MACEs in patients with HTN. In conclusion, the liver fibrosis score may be an independent predictor of MACEs in hypertensive patients undergoing CCTA. Full article

The lipid profile is affected following menstrual cessation (MC). We aimed to evaluate the effects of goserelin-induced MC and subsequent menstrual restoration (MR) on lipid metabolism. Premenopausal women with histologically verified endometriosis (n = 15) received goserelin monthly for 6 months (6mο), resulting in MC, and were followed-up for another 6 months after MR (12mο). Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein a ([Lp(a)] and lipidomics were measured at baseline, 6mo and 12mo. Shotgun quantitative deep lipidomics were determined at the level of lipid class category, subclass, species, and fatty acyl chain lengths and degree of saturation. TC (p = 0.006), LDL-C (p = 0.028), HDL-C (p = 0.002), and apoA1 (p = 0.013) increased during goserelin-induced MC and remained practically unchanged during MR. TG, apoB, and Lp(a) did not change. From the deep lipidomics analysis, multivariate statistical analysis demonstrated profound alterations in lipid species with MC, whereas no statistically valid models could be fitted for the restoration period. In conclusion, GnRH-analog-induced MC alters lipid profiles at various levels, from standard blood lipid and lipoprotein profiles to several lipid species as detected by lipidomics analysis. Changes largely persist for at least 6 m after MR. Full article

Cardiovascular diseases (CVD) are the leading cause of death in most developed countries. MicroRNAs (miRNAs) are highly investigated molecules not only in CVD but also in other diseases. Several studies on miRNAs continue to reveal novel miRNAs that may play a role in CVD, in their pathogenesis in diagnosis or prognosis, but evidence for clinical implementation is still lacking. The aim of this study is to clarify the diagnostic potential of miRNAs in some CVDs. Full article

Liver fibrosis scores, indicative of hepatic scarring, have recently been linked to coronary artery disease (CAD). We investigated the association between CAD and the fibrosis-4 index (FIB-4I) in patients who underwent coronary computed tomography angiography (CCTA). This study included 1244 patients who were clinically suspected of having CAD. The presence or absence of CAD was the primary endpoint. FIB-4I was higher in the CAD group than in the non-CAD group (1.95 ± 1.21 versus [vs.] 1.65 ± 1.22, p < 0.001). FIB-4I was also higher in the hypertension (HTN) group than in the non-HTN group (1.90 ± 1.32 vs. 1.60 ± 0.98, p < 0.001). In all patients, high FIB-4I (≥2.67) was a predictor of presence of CAD (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.30–2.83, p = 0.001), and low FIB-4I (≤1.29) was proven to be a predictor of absence of CAD (OR: 0.65, 95% CI: 0.48–0.88, p = 0.006). In the HTN group, high and low FIB-4I levels, were found to be predictors for CAD (OR: 2.01, 95% CI: 1.26–3.21, p < 0.001 and OR: 0.65, 95% CI: 0.45–0.94, p < 0.022, respectively), in particular. FIB-4I may serve as a diagnostic indicator of the presence or absence of CAD in hypertensive patients undergoing CCTA. Full article

Background: The measurement and identification of plasma biomarkers can support the estimation of risk and diagnosis of deep vein thrombosis (DVT) associated with the use of a peripherally inserted central catheter (PICC). Objectives: This systematic review and meta-analysis aimed to identify the association between the levels of potential biomarkers that reflect the activation of the blood system, long-term vascular complications, inflammatory system, and the occurrence of PICC-related DVT. Methods: Seven electronic databases (Embase, Web of Science, Medline, Scopus, Cinahl, Cochrane Central Register of Controlled Trials, and ERIC) were searched to identify literature published until December 2022. Studies were required to report: (I) adult and pediatric patients, outpatient or admitted to clinical, surgical, or ICU with PICC; (II) patients with PICC-related DVT and patients without PICC-related DVT as a comparator; and (III) at least one biomarker available. The Newcastle–Ottawa Scale was used to evaluate the quality of the studies. Study precision was evaluated by using a funnel plot for platelets level. We provided a narrative synthesis and meta-analysis of the findings on the biomarkers’ outcomes of the studies. We pooled the results using random effects meta-analysis. The meta-analysis was conducted using Review Manager software v5.4. This systematic review is registered in PROSPERO (CRD42018108871). Results: Of the 3564 studies identified (after duplication removal), 28 were included. PICC-related DVT was associated with higher D-dimers (0.37 μg/mL, 95% CI 0.02, 0.72; p = 0.04, I² = 92%; p for heterogeneity < 0.00001) and with higher platelets (8.76 × 10⁹/L, 95% CI 1.62, 15.91; p = 0.02, I² = 41%; p for heterogeneity = 0.06). Conclusions: High levels of D-dimer and platelet were associated with DVT in patients with PICC. However, biomarkers such as APTT, fibrinogen, FDP, glucose, hemoglobin, glycated hemoglobin, INR, prothrombin time, prothrombin fragment 1.2, the thrombin–antithrombin complex, and WBC were not related to the development of DVT associated with PICC. Full article

Background: low-density lipoprotein cholesterol (LDL-C) is a strong cardiovascular risk factor, but the methods used to correctly determine it are is still questioned. The aim of this study was to compare the direct determination of LDL-C levels, obtained with the Roche cobas c system, with LDL-C values calculated through Sampson’s and Friedewald’s equations in very high-risk patients with triglycerides concentrations of less than 2.25 mmol/L (<200 mg/dL). Methods: in 127 consecutive patients with a recent diagnosis of acute coronary syndrome and triglycerides of less than 2.25 mmol/L, plasma LDL-C was measured directly and calculated with Sampson’s and Friedewald’s equations before hospital discharge, and the data were compared. Results: median LDL values obtained with the Friedenwald and Sampson equations and with direct determination were 2.31 (IQR 1.59–3.21), 2.36 (IQR 1.66–3.26) and 2.64 (IQR 1.97–3.65) mmol/L, respectively. Direct measurements were higher by 0.35 and 0.40 mmol/L when compared to the levels calculated with Sampson’s or Friedewald’s equations, respectively (p < 0.01). The correlation between the two equations was almost perfect (rho 0.997) but decreased when the directly determined data were compared to those calculated with Sampson’s equation (rho 0.954) or Friedewald’s method (rho 0.939). Conclusion: direct determination generated higher values of LDL-C concentration through a probable systematic overestimation. Full article

(1) Background. One of the causes of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is thrombus formation in situ followed by lysis, resulting in a morphologically normal angiogram but with an underlying prothrombotic state that is potentially predisposed to recurrence. Recent studies have shown that a subset of MINOCA patients may have thrombophilic conditions at screening. Objective: To compare the prothrombotic trend in MINOCA patients with that of subjects with MI and obstructive coronary arteries (MIOCA) by testing for known congenital thrombophilias and markers of coagulation activation. (2) Materials and methods. Screening included congenital thrombophilias (factor V Leiden; assessment of protein C, protein S, and antithrombin III) and eight genes. Of these, four genes represented the folate pathway enzymes: MTHFR 677 C>T (rs1801133), MTHFR 1298 A>C (rs1801131), MTR 2756 A>G (rs1805087), and MTRR 66 A>G (rs1801394). The other four genes represented the blood coagulation system: F13 (163 G>T) rs5985, F1 (−455 G>A) rs1800790, GP IIb–IIIa (1565 T>C) rs5918, and PAI-I (−675 5G>4G) rs1799889. Additionally, we examined the levels of homocysteine and lipoprotein (LP) (a). (3) Results. Our study included 269 patients: 114 MINOCA patients and 155 MIOCA patients with lesions of one coronary artery. The frequencies of polymorphisms in the genes of the blood coagulation system and the folate pathway did not differ between the groups. The following genes were associated with in-hospital mortality in the MINOCA group: MTHFR 1298 A>C rs1801131 (OR 8.5; 95% CI 1.67–43.1) and F1 (−455 G>A) rs1800790 (OR 5.8; 95% CI 1.1–27.8). In the MIOCA group, the following genes were associated with in-hospital mortality: MTHFR 1298 A>C rs1801131 (OR 9.1; 95% CI 2.8–28.9), F1 (−455 G>A) rs1800790 (OR 11.4; 95% CI 3.6–35.9), GP IIb–IIIa (1565 T>C) rs5918 (OR 10.5; 95% CI 3.5–30.8), and PAI-I (−675 5G>4G) rs1799889 (OR 12.9; 95% CI 4.2–39.7). We evaluated long-term outcomes (case fatality rate, recurrent MI, and stroke) over a period of 12 months in both groups. The variables associated with these outcomes were laboratory parameters, such as protein C deficiency, hyperhomocysteinemia, and a content of LP (a) > 30 mg/dL. However, we did not reveal the prognostic value of polymorphisms of the studied genes representing the blood coagulation system and the folate pathway. (4) Conclusion. We established no statistically significant differences between the MINOCA and MIOCA groups in the prevalence of congenital thrombophilias and the prevalence of folate pathway enzyme genes and blood coagulation system genes. The MTHFR 1298 A>C (rs1801131) and F1 (−455 G>A) rs1800790 genes were associated with in-hospital mortality in both groups. More significant prognostic factors in both groups during the one-year period were protein C deficiency, hyperhomocysteinemia, and LP (a) > 30 mg/dL. Full article

Acute heart failure and cardiogenic shock are frequently occurring and deadly conditions. In patients with those conditions, endotoxemia related to gut injury and gut barrier dysfunction is usually described as a driver of organ dysfunction. Because endotoxemia might reciprocally alter cardiac function, this phenomenon has been suggested as a potent vicious cycle that worsens organ perfusion and leading to adverse outcomes. Yet, evidence beyond this phenomenon might be overlooked, and mechanisms are not fully understood. Subsequently, even though therapeutics available to reduce endotoxin load, there are no indications to treat endotoxemia during acute heart failure and cardiogenic shock. In this review, we first explore the evidence regarding endotoxemia in acute heart failure and cardiogenic shock. Then, we describe the main treatments for endotoxemia in the acute setting, and we present the challenges that remain before personalized treatments against endotoxemia can be used in patients with acute heart failure and cardiogenic shock. Full article

Background and Objectives: In-stent restenosis (ISR) is a major problem in patients undergoing percutaneous coronary intervention. The prognostic nutritional index (PNI) is a nutritional status score used in the literature to determine the prognosis of coronary artery disease. In this study, we aimed to investigate the effect of preprocedural PNI values on the risk of ISR in patients with stable coronary artery disease who underwent successful percutaneous coronary intervention. Materials and Methods: This retrospective study included 809 patients. Stent restenosis was evaluated in the follow-up coronary angiography of the patients due to stable angina pectoris or acute coronary syndrome. The patients were divided into two groups based on those with (n = 236) and without (n = 573) in-stent restenosis, and their nutritional status was compared with PNI. The PNI values before the first angiography of the patients were calculated. Results: The mean PNI score was significantly lower in patients with ISR than in those without ISR (49.5 vs. 52.3, p < 0.001). Concerning the results of the Cox regression hazard model for predictors of ISR, PNI was significantly associated with the development of ISR (HR = 0.932, 95% CI: 0.909–0.956, p < 0.001). In addition, stent type, stent length, and diabetes mellitus were associated with the development of ISR. Conclusions: A low PNI value indicates poor nutritional status, which is thought to accelerate inflammation processes and cause atherosclerosis and ISR. Full article

Acutely decompensated chronic heart failure (adCHF) is among the most important causes of in-hospital mortality. R-wave peak time (R_pT) or delayed intrinsicoid deflection was proposed as a risk marker of sudden cardiac death and heart failure decompensation. Authors want to verify if QR interval or R_pT, obtained from 12-lead standard ECG and during 5-min ECG recordings (II lead), could be useful to identify adCHF. At hospital admission, patients underwent 5-min ECG recordings, obtaining mean and standard deviation (_SD) of the following ECG intervals: QR, QRS, QT, JT, and T peak–T end (Te). The R_pT from a standard ECG was calculated. Patients were grouped by the age-stratified Januzzi NT-proBNP cut-off. A total of 140 patients with suspected adCHF were enrolled: 87 (mean age 83 ± 10, M/F 38/49) with and 53 (mean age: 83 ± 9, M/F: 23/30) without adCHF. V_5-, V_6- (p < 0.05) R_pT, and QR_SD, QRS_SD, QT_SD, JT_SD, and Te_SDp < 0.001 were significantly higher in the adCHF group. Multivariable logistic regression analysis demonstrated that the mean of QT (p < 0.05) and Te (p < 0.05) were the most reliable markers of in-hospital mortality. V₆ R_pT was directly related to NT-proBNP (r: 0.26, p < 0.001) and inversely related to a left ventricular ejection fraction (r: 0.38, p < 0.001). The intrinsicoid deflection time (obtained from V_5-6 and QR_SD) could be used as a possible marker of adCHF. Full article

(1) Background: The early screening strategy for type A acute aortic syndrome (A-AAS) patients has always been challenging. (2) Methods: From September 2020–31 March 2022, 179 consecutive patients with suspected A-AAS were retrospectively reviewed. We assessed the diagnostic value of the use of handheld echocardiographic devices (PHHEs) by emergency medicine (EM) residents either alone or in combination with serum acidic calponin in this patient group. (3) Results: The direct sign of PHHE had a specificity (SP) of 97.7%. The sign of ascending aortic dilatation showed SE = 77.6%, SP = 68.5%, PPV = 48.1% and NPV = 89%. SE, SP, PPV and NPV of a positive PHHE direct sign were 55.6%, 100%, 100% and 71.4% in 19 hypotension/shock patients with suspected A-AAS, respectively. The area under curve (AUC) of acidic calponin combined with an ascending aorta diameter >40 mm was 0.927, with an SE and SP of 83.7% and 89.2%, respectively. These two combined indicators significantly improved the diagnostic efficiency of A-AAS compared with either of them alone (p = 0.017; standard error 0.016, Z value 2.39; p = 0.001, standard error 0.028, Z value 3.29). (4) Conclusion: EM resident-performed PHHE was highly indicative of A-AAS in patients presenting with shock or hypotension. An ascending aorta diameter > 40 mm combined with acidic calponin demonstrated acceptable diagnostic accuracy as a rapid first-line triage tool to identify patients with suspected A-AAS. Full article

Background and Objectives: Coronary artery disease (CAD) is the foremost cause of adult disability and mortality. There is an urgent need to focus on the research of new approaches for the prevention and treatment of CAD. Materials and Methods: The effects of peptides isolated from the blood plasma of CAD patients on endothelial cell secretion using the in vitro model have been tested. Human endothelial progenitor cells (HEPCs) were incubated for 24 h with peptides isolated from the plasma of healthy subjects or patients with stable angina, progressive unstable angina, and myocardial infarction. The contents of some soluble anticoagulant as well as procoagulant mediators in HEPC culture treated with peptide pools were then compared. Results and Conclusion: The results show that peptides from the plasma of patients with myocardial infarction promote endothelial cells to release both von Willebrand factor and endothelin-1, increasing vasoconstriction and shifting hemostatic balance toward a prothrombotic state. In contrast, peptides from the plasma of patients with progressive unstable angina suppress the secretion of endothelin-1 by HEPCs, while the secretion of both von Willebrand factor and tissue plasminogen activator was increased. As can be seen from the results obtained, disease derived peptides may contribute to the homeostasis of living organisms or the progression of pathological processes. Full article

Preeclampsia (PE) is characterized by the new onset of hypertension (HT) and proteinuria beyond the 20th week of gestation. We aimed to find the best predictor of PE and find out if it is different in women with or without HT. Consecutively attended pregnant women were recruited in the first trimester of pregnancy and followed-up. Laboratory and office and 24 h-ambulatory blood pressure (BP) data were collected. PE occurred in 6.25% of normotensives (n = 124). Both office mean BP and 24 h-systolic BP in the first trimester were higher in women with versus those without PE (p ≤ 0.001). In women with chronic hypertension (cHT), PE occurred in 55%; office SBP (p = 0.769) and 24 h-SBP (p = 0.589) were similar between those with and those without PE. Regarding biochemistry, in cHT, plasma urea and creatinine were higher in PE women than in those without cHT (p = 0.001 and p = 0.004 for the differences in both parameters). These differences were not observed in normotensives. In normotensives, mean BP was the best predictor of PE [ROC curve = 0.91 (95%CI 0.82–0.99)], best cut-off = 80.3 mmHg. In cHT, plasma urea and creatinine were the best predictors of PE, with ROC curves of 0.94 (95%CI 0.84–1.00) and 0.93 (95%CI 0.83–1.00), respectively. In the first trimester of pregnancy, the strongest predictor of PE in normotensive women is office mean BP, while in cHT, renal parameters are the strongest predictors. Otherwise, office BP is non-inferior to 24 h ambulatory BP to predict PE. Full article

Objective: Despite improvements in the technology of catheter ablation of atrial fibrillation (AF), recurrences are still a major problem, even after a successful procedure. The uric acid/albumin ratio (UAR), which is an inexpensive and simple laboratory parameter, has recently been introduced in the literature as a predictor of adverse cardiovascular events. Hence, we aimed to investigate the relationship between the UAR and AF recurrence after catheter ablation. Methods: A total of 170 patients who underwent successful catheter ablation for AF were included. The primary outcome was the late recurrence after treatment. The recurrence (+) and recurrence (−) groups were compared for clinical, laboratory and procedural characteristics as well as the predictors of recurrence assessed by regression analysis. Results: In our study population, 53 (26%) patients developed AF recurrence after catheter ablation. Mean UAR was higher in the recurrence (+) group compared to recurrence (−) group (2.4 ± 0.9 vs. 1.8 ± 0.7, p < 0.01). In multivariable regression analysis, left atrial diameter (HR: 1.08, 95% CI: 1.01–1.16, p = 0.01) and UAR (HR:1.36, 95% CI: 1.06–1.75, p = 0.01) were found to be independent predictors of recurrence. In ROC analysis, the UAR > 1.67 predicted recurrence with a sensitivity of 77% and a specificity of 57% (AUC 0.68, p < 0.01). Conclusion: For the first time in the literature, the UAR were found to be correlated independently with AF recurrence after catheter ablation. Full article

Background: The remnant-like particle cholesterol (RLP-C) has been demonstrated to be associated with residual cardiovascular risk. The meta-analysis aimed to evaluate the impact of baseline RLP-C on the incidence of major cardiovascular adverse events (MACEs) in patients with coronary artery disease (CAD). Methods: A systematic literature search was performed in PubMed and Embase electronic databases from the inception of the databases through 1 October 2022. Studies evaluating the association between baseline RLP-C and the risk of MACEs in patients with CAD were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by a random-effect method (RLP-C analyzed as a categorical variable) and a fixed-effects model (RLP-C analyzed as a continuous variable). Results: Ten studies including 18,053 subjects were finally included in this meta-analysis. In our pooled analysis, compared to CAD patients with the lowest RLP-C category, the CAD patients with the highest RLP-C category had a significantly higher risk of future MACEs during follow-up (HR 1.79, 95% CI, 1.42–2.26, I² = 60.31%, p < 0.01), which was consistent with outcomes of meta-analysis with the RLP-C analyzed as a continuous variable (HR 1.40, 95% CI, 1.28–1.53, I² = 38.20%, p < 0.01). The sensitivity analysis confirmed the robustness of the results, and no significant publication bias was identified. Conclusion: The present meta-analysis suggests that the RLP-C was associated with an increased risk of long-term MACEs in patients with CAD at baseline. It is necessary to conduct randomized controlled trials to explore whether reducing the RLP-C level is conducive to reducing residual cardiovascular risk, even coronary plaque regression. Full article

Background: The growing cardiovascular disease (CVD) epidemic calls for further research to identify novel biomarkers for earlier detection and as potential therapeutic targets. Biomarkers Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMP-2, and MMP-9) are linked to proatherogenic and proinflammatory pathways of CVD development, the majority of which are coronary artery disease (CAD) and stroke. We evaluated potential factors affecting these four biomarkers and established their association with CVD. Methods: This is a cross-sectional analysis using a nested case-control design involving 580 participants aged 21–75 years from the prospective multi-ethnic cohort study. A total of 290 CVD cases and 290 age-and sex-matched controls were identified. All participants underwent interviews, health screenings, and provided blood samples, including biomarkers RANTES, EMMPRIN, and MMPs. CVD was defined based on previous medical history. Results: The average age of the participants was 55.7(SD = 10.3) years of age, and 34.6% were female. Arrhythmia history and low-density lipoprotein (LDL) levels were significant factors of logEMMPRIN (β = −0.124 [−0.245, −0.003] and β = 0.111 [0.0, 0.191], respectively). Only female sex (β = 0.189 [0.078, 0.300]) for logRANTES and age (β = 0.033 [0.010, 0.055]) for logMMP-2 and logMMP-9 were significant. The Indian ethnicity (β = 0.192 [0.048, 0.335]) and highly sensitive C-reactive protein (hs-CRP) levels (β = 0.063 [0.011, 0.116]) were statistically significant for logMMP-9. No association was detected between biomarkers and CVD. Conclusions: In this multi-ethnic study cohort, RANTES was associated with sex, EMMPRIN was associated with a history of arrhythmia and LDL levels, MMP-2 with age, and MMP-9 with ethnicity and hs-CRP levels. The biomarker serum levels were not associated with CVD. Full article

Background: Galectin-3 (Gal-3) is considered a potential cardiovascular inflammatory marker that may provide additional risk stratification for patients with acute heart failure. It is unknown whether mild therapeutic hypothermia (MTH) impacts Gal-3 levels. Therefore, this biomarker study aimed to investigate the effect of MTH on Gal-3. Methods: In the randomized SHOCK-COOL trial, 40 patients with cardiogenic shock (CS) complicating acute myocardial infraction (AMI) were randomly assigned to the MTH (33 °C) or control group in a 1:1 ratio. Blood samples were collected on the day of admission/day 1, day 2, and day 3. Gal-3 level kinetics throughout these time points were compared between the MTH and control groups. Additionally, potential correlations between Gal-3 and clinical patient characteristics were assessed. Multiple imputations were performed to account for missing data. Results: In the control group, Gal-3 levels were significantly lower on day 3 than on day 1 (day 1 vs. day 3: 3.84 [IQR 2.04–13.3] vs. 1.79 [IQR 1.23–3.50] ng/mL; p = 0.049). Gal-3 levels were not significantly different on any day between the MTH and control groups (p for interaction = 0.242). Spearman’s rank correlation test showed no significant correlation between Gal-3 levels and sex, age, smoking, body mass index (BMI), and levels of creatine kinase-MB, creatine kinase, C-reactive protein, creatinine, and white blood cell counts (all p > 0.05). Patients with lower Gal-3 levels on the first day after admission demonstrated a higher risk of all-cause mortality at 30 days (hazard ratio, 2.67; 95% CI, 1.11–6.42; p = 0.029). In addition, Gal-3 levels on day 1 had a good predictive value for 30-day all-cause mortality with an area under the receiver operating characteristic curve of 0.696 (95% CI: 0.513–0.879), with an optimal cut-off point of less than 3651 pg/mL. Conclusions: MTH has no effect on Gal-3 levels in patients with CS complicating AMI compared to the control group. In addition, Gal-3 is a relatively stable biomarker, independent of age, sex, and BMI, and Gal-3 levels at admission might predict the risk of 30-day all-cause mortality. Full article

Cardiovascular disease poses a significant threat to the quality of human life. Metabolic abnormalities caused by excessive caloric intake have been shown to lead to the development of cardiovascular diseases. Ceramides are structural molecules found in biological membranes; they are crucial for cell survival and lipid metabolism, as they maintain barrier function and membrane fluidity. Increasing evidence has demonstrated that ceramide has a strong correlation with cardiovascular disease progression. Nevertheless, it remains a challenge to develop sphingolipids as therapeutic targets to improve the prognosis of cardiovascular diseases. In this review, we summarize the three synthesis pathways of ceramide and other intermediates that are important in ceramide metabolism. Furthermore, mechanistic studies and therapeutic strategies, including clinical drugs and bioactive molecules based on these intermediates, are discussed. Full article

(1) Background: There are few diagnostic and therapeutic targets for myocardial remodeling in the salvageable non-infarcted myocardium. (2) Methods: Hub genes were identified through comprehensive bioinformatics analysis (GSE775, GSE19322, and GSE110209 from the gene expression omnibus (GEO) database) and the biological functions of hub genes were examined by gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, the differential expression of hub genes in various cell populations between the acute myocardial infarction (AMI) and sham-operation groups was analyzed by processing scRNA data (E-MTAB-7376 from the ArrayExpress database) and RNA-seq data (GSE183168). (3) Results: Ten strongly interlinked hub genes (Timp1, Sparc, Spp1, Tgfb1, Decr1, Vim, Serpine1, Serpina3n, Thbs2, and Vcan) were identified by the construction of a protein–protein interaction network from 135 differentially expressed genes identified through comprehensive bioinformatics analysis and their reliability was verified using GSE119857. In addition, the 10 hub genes were found to influence the ventricular remodeling of non-infarcted tissue by modulating the extracellular matrix (ECM)-mediated myocardial fibrosis, macrophage-driven inflammation, and fatty acid metabolism. (4) Conclusions: Ten hub genes were identified, which may provide novel potential targets for the improvement and treatment of AMI and its complications. Full article

(1) Objective: To reveal the correlation between the hemoglobin-to-red cell distribution width ratio (HRR) and all-cause mortality (ACM) among the septic patients with atrial fibrillation. (2) Methods: Specific clinical information was collected from the Medical Information Mart for Intensive IV (MIMIC-IV) database. The optimal cut-off value of HRR was calculated through ROC curve analysis conducted by using the maximum Youden index for the prediction of survival status. In addition, univariable and multivariable Cox regressive analyses were carried out to assess the prognostic significance of HRR and the Kaplan-Meier (K-M) analysis was conducted to draw the survival curves. Then, the 1:1 propensity score matching (PSM) method was adopted to improve the reliability of research result while balancing the unintended influence of underlying confounders. (3) Results: There were 9228 patients participating in this retrospective cohort study. The optimal cut-off value of the HRR was determined as 5.877 for in-hospital mortality. The PSM was performed to identify 2931 pairs of score-matched patients, with balanced differences exhibited by nearly all variables. According to the K-M analysis, those patients with a lower HRR than 5.877 showed a significantly higher level of in-hospital mortality, 28-day mortality, and 90-day mortality, compared to the patients with HRR ≥ 5.877 (p < 0.001). After the adjustment of possible confounders, those patients whose HRR was below 5.877 had a significantly higher level of in-hospital mortality than the patients with HRR ≥ 5.877, as revealed by the multivariable Cox regression analysis (HR = 1.142, 95%CI: 1.210–1.648, p < 0.001). Similarly, the ACM remained substantially higher in those patients with a lower HRR than in the patients with higher HRR after PSM. (4) Conclusion: A lower HRR (<5.877) was evidently associated with an increased risk of ACM, which made it applicable as a prognostic predictor of clinical outcomes for those septic patients with atrial fibrillation. Full article

Background and Objectives: It is very important to analyze how body mass index (BMI) and psychological well-being (PWB) combination may be differentially associated with mortality risk. The aim of this study was to evaluate the additional prognostic value of the combined status of BMI and PWB for the estimation of all-cause and cardiovascular disease (CVD) mortality risk in the adult Lithuanian urban population. Materials and Methods: Initial data were collected within the framework of the international cohort HAPIEE study from 2006 to 2008. A random sample of 7115 individuals aged 45–72 years was screened. The response rate was 65%. Deaths were evaluated by the death register of Kaunas city (Lithuania) in a follow-up study until 31 December 2020. The mean (SD) duration of the follow-up for the endpoints period was 12.60 (2.79) years. PWB was evaluated by a CASP-12 questionnaire. Results: The findings from the Cox proportional hazards regression multivariable analysis showed that the combinations of underweight plus lower PWB and severe obesity plus lower PWB increased all-cause mortality risk in men (respectively hazard ratio (HR) = 5.65 and HR = 1.60) and in women (respectively HR = 6.02 and HR = 1.77); and increased the risk of mortality from CVD in men (respectively HR = 6.69 and HR = 2.19) compared with responders with normal weight plus higher PWB. The combination of severe obesity plus higher PWB significantly increased the risk of all-cause and CVD mortality risk in men. The combinations of normal weight plus lower PWB and overweight plus lower PWB significantly increased the risk of all-cause mortality risk in men. Conclusions: The combination of severe obesity independently on lower or higher PWB and the combination of underweight plus lower PWB is a strong predictor for all-cause and CVD mortality risk in men and a strong predictor for all-cause mortality risk in women. Full article

Obstructive sleep apnea (OSA) is a common sleep disorder leading to increased risk of developing cardiovascular diseases (CVDs) by supporting a low-grade chronic inflammation as one of the pathological mechanisms. The continuous positive airway pressure (CPAP) device is used as an effective treatment for moderate and severe OSA. Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), white blood cell–mean platelet volume ratio (WMR), C-reactive protein–albumin ratio (CAR) and fibrinogen–albumin ratio (FAR) are new potential inflammatory biomarkers that are widely available and were shown to be possibly favorable screening or follow-up tools for moderate- or severe-grade OSA, as well as indirect indicators for cardiovascular risk. Our study evaluated the impact of CPAP therapy in patients with severe OSA and acceptable therapy adherence on NLR, PLR, WMR, FAR and CAR. Of 57 patients who were initially enrolled and had no exclusion criteria, 37 had a satisfactory CPAP adherence (usage of ≥4 h per night) after a minimum of 6 months of therapy. There was a statistically significant difference in NLR (2.122 ± 0.745 before therapy vs. 1.888 ± 0.735 after therapy) and FAR (86.445 ± 18.763 before therapy vs. 77.321 ± 19.133 after therapy) suggesting a positive effect of the CPAP therapy on chronic inflammatory states, thereby possibly reducing cardiovascular risk. Full article

BACKGROUND. Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction, especially in younger women without cardiovascular risk factors. Patient management and diagnostics are still largely based on retrospective and observational studies. Most patients with SCAD report chest pain and have elevated biomarkers with ECG findings. SCAD can lead to cardiogenic shock, ventricular arrhythmias and cardiac arrest, and is commonly associated with fibromuscular dysplasia (FMD). Genetic associations are still in their infancy with this disease process. METHODS. An Invitae 29 gene aortopathy panel was performed on a mother with a thoracic aortic aneurysm and her daughter who presented with SCAD and was noted to have FMD. RESULTS. The patient and her mother were both noted to have a heterozygous mutation of the Biglycan (BGN) gene (Variant c.1030T > G (p.Tyr344His)) of undetermined significance. An extensive literature review was performed, including a review of the UK Biobank. This is the first case to our knowledge showing a possible link between the BGN mutation and SCAD/FMD. CONCLUSIONS. The BGN mutation has been recognized to be correlated with aortic aneurysm and aortic dissection. It has not yet been explored to be associated with SCAD/FMD. This paper highlights the potential link between the BGN gene and SCAD/FMD. Further research looking at this association is warranted. Full article

Background: Patients with acute coronary syndrome (ACS) still have a high risk of recurrence of major adverse cardiovascular and cerebrovascular events (MACCE). However, there are rare studies on the prediction of MACCE in patients with ACS using lipoprotein a [Lp(a)] combined with fibrinogen. The aim of this study was to analyze the predictive value of Lp(a) combined with fibrinogen for the long-term prognosis of patients with ACS. Methods: 804 patients with ACS admitted to 11 tertiary general hospitals in Chengdu from January 2017 to June 2019 were included in the study. According to the Lp(a) 300 mg/L, patients were assigned to the non-high Lp(a) group and high Lp(a) group. Patients were assigned to the non-high or high fibrinogen groups using the fibrinogen level of 3.08 g/L. Subsequently, patients were divided into group A, B, or C by Lp(a) combined with fibrinogen. The study endpoints were MACCE, including all-cause death, non-fatal myocardial infarction, non-fatal stroke, and revascularization. The incidences of MACCE among groups were compared. Lp(a), fibrinogen, Lp(a) combined with fibrinogen classifications were each added into the basic model to construct three new models. The C-index, net reclassification index (NRI) and integrated discrimination improvement (IDI) of the three new models were then compared. Results: The median follow-up was 16 months. During follow-up, the cumulative incidence of MACCE in group C was significantly higher than that measured in group A and B (p < 0.001). The results of the multivariate Cox regression analysis of MACCE showed that Lp(a) ≥300 mg/L with fibrinogen ≥3.08 g/L was an independent predictor of MACCE. According to the GRACE score and the statistical analyses, the basic model was constructed, which had a C-index of 0.694. The C-index, NRI, and IDI of the new model constructed using the basic model + Lp(a) combined with fibrinogen classification were 0.736, 0.095, and 0.094 respectively. Conclusions: Single Lp(a), single fibrinogen and Lp(a) combined with fibrinogen were independent predictors of MACCE in patients with ACS. The predictive value of Lp(a) combined with fibrinogen in patients with ACS was better than that of single Lp(a) and single fibrinogen. Full article

Irisin, as one of the myokines induced by exercise, has attracted much attention due to its important physiological functions such as white fat browning, the improvement in metabolism, and the alleviation of inflammation. Despite the positive role that irisin has been proven to play in the prevention and treatment of cardiovascular diseases, whether it can become a biomarker and potential target for predicting and treating cardiovascular diseases remains controversial, given the unreliability of its detection methods, the uncertainty of its receptors, and the species differences between animals and humans. This paper was intended to review the role of irisin in the diagnosis and treatment of cardiovascular diseases, the potential molecular mechanism, and the urgent problems to be solved in hopes of advancing our understanding of irisin as well as providing data for the development of new and promising intervention strategies by discussing the causes of contradictory results. Full article

Depression is one of the world’s most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother–child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine’s clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother–infant bond early in the offspring’s life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals’ cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity. Full article

Background: Statins are the most widely used drugs for decreasing elevated serum LDL-cholesterol (LDL-C) and thus for the prevention of atherosclerotic cardiovascular disease (ASCVD), but they have also some pleiotropic effects, including anti-inflammatory properties. Atherosclerosis is a low-grade inflammatory disease, and elevated ferritin is considered to be one of the markers of inflammation. Since the results of studies on the effects of statins on serum ferritin levels are conflicting, this meta-analysis was performed. Methods: A literature search was performed using major electronic databases (MEDLINE/PubMed, Scopus, Embase, and ISI Web of Science) from inception up to 5 March 2022 to find studies evaluating the effect of different statins on serum ferritin levels. The effect size was determined using weighted mean differences (WMDs) and the corresponding 95% confidence intervals (CIs). Results: The meta-analysis of nine studies (1611 patients) analyzing the effects of statins on serum ferritin levels that were included showed a significant decrease in circulating ferritin levels caused by statins. The results did not suggest any significant association between the changes in concentrations of serum ferritin and the duration of treatment with statins. Conclusions: Statin therapy decreases the circulating concentrations of ferritin, which might be beneficial for the prevention and/or progression of ASCVD. This effect might be explained by the anti-inflammatory effects and maybe some other pleiotropic effects of statins and not by their lipid-lowering effects. Full article

This study aims to provide an overview of multivariable prognostic modelling studies developed for coronary heart disease (CHD) in the general population and to explore the optimal prognostic model by comparing the models’ performance. A systematic review was performed using Embase, PubMed, Cochrane, Web of Science, and Scopus databases until 30 November 2019. In this work, only prognostic studies describing conventional risk factors alone or a combination of conventional and genomic risk factors, being developmental and/or validation prognostic studies of a multivariable model, were included. A total of 4021 records were screened by titles and abstracts, and 72 articles were eligible. All the relevant studies were checked by comparing the discrimination, reclassification, and calibration measures. Most of the models were developed in the United States and Canada and targeted the general population. The models included a set of similar predictors, such as age, sex, smoking, cholesterol level, blood pressure, BMI, and diabetes mellitus. In this study, many articles were identified and screened for consistency and reliability using CHARM and GRIPS statements. However, the usefulness of most prognostic models was not demonstrated; only a limited number of these models supported clinical evidence. Unfortunately, substantial heterogeneity was recognized in the definition and outcome of CHD events. The inclusion of genetic risk scores in addition to conventional risk factors might help in predicting the incidence of CHDs; however, the generalizability of the existing prognostic models remains open. Validation studies for the existing developmental models are needed to ensure generalizability, improve the research quality, and increase the transparency of the study. Full article

Background: B cells and autoantibodies play an important role in the pathogenesis of abdominal aortic aneurysm (AAA). IgG glycosylations are highly valued as potential disease biomarkers and therapeutic targets. Methods: Lectin microarray was applied to analyze the expression profile of serum IgG glycosylation in 75 patients with AAA, 68 autoimmune disease controls, and 100 healthy controls. Lectin blots were performed to validate the differences. The clinical relevance of lectins binding from the microarray results was explored in AAA patients. Results: Significantly lower binding level of SBA (preferred GalNAc) was observed for the AAA group compared with DCs (p < 0.001) and HCs (p = 0.049). A significantly lower binding level of ConA (preferred mannose) was observed in patients with aneurysm diameter >5 cm. Significantly higher binding of CSA (preferred GalNAc) was present for dyslipidemia patients, whereas a lower binding level of AAL (preferred fucose) was observed for hypertensive patients. Patients with diabetes had lower binding levels of IRA (preferred GalNAc) and HPA (preferred GalNAc) compared with those not with DM. PTL-L (R = 0.36, p = 0.0015, preferred GalNAc) was positively associated with aneurysm diameters, whereas DSL (R = 0.28, p = 0.014, preferred (GlcNAc)2-4) was positively associated with patients’ age. Symptomatic patients had a lower binding level of ConA (p = 0.032), and patients with coronary heart disease had higher binding levels of STL (p = 0.0029, preferred GlcNAc). Patients with ILT bound less with black bean crude (p = 0.04, preferred GalNAc). Conclusions: AAA was associated with a decreased IgG binding level of SBA (recognizing glycan GalNAc). Symptomatic patients with aneurysm <5 cm had a higher binding level of ConA (preferred mannose). Coronary heart disease and elder age were associated with increased IgG bisecting GlcNAc. IgG O-glycosylation (GalNAc) may play an important role in AAA pathogenesis and progression. Full article

Objective: The aim of this study is to assess the association between epicardial adipose tissue (EAT) and coronary artery disease (CAD) via meta−analysis. Methods: Specific searches of online databases from January 2000 to May 2022 were conducted. All observational studies evaluating the association between EAT and CAD in PubMed, Web of Science, and the Cochrane Library databases were screened. A meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta−Analyses guidelines (PRISMA). In total, 21 studies encompassing 4975 subjects met the inclusion criteria, including 2377 diagnosed and assigned as the CAD group, while the other 2598 were assigned as the non−CAD group. Subjects in the CAD group were further divided into the severe stenosis group (stenosis ≥ 50%, n = 846) and the mild/moderate stenosis group (stenosis < 50%, n = 577). Results: Both the volume and thickness of EAT in the CAD group were larger compared to the non−CAD group (p < 0.00001). In a subgroup analysis within the CAD group, the severe stenosis group had a larger volume and thickness with respect to EAT when compared to the mild/moderate group (p < 0.001). Conclusions: The enlargement of EAT presented in CAD patients with an association with CAD severity. Although limited by different CAD types and measuring methods for EAT, as well as a smaller sample size, our results suggest that EAT is a novel predictor and a potential therapeutic target for CAD. Full article

Background: A risk assessment of in-stent restenosis (ISR) patients is critical for providing adequate treatment. Nevertheless, the prognostic value of high-sensitivity CRP (hs-CRP) levels on ISR has not been consistently demonstrated in clinical studies. In the current meta-analysis, we aim to assess the predictive role of hs-CRP in patients treated with stenting. Methods: We searched PubMed, Web of Science, Embase, and the Cochrane Registry through May 2022. We selected random control trials that compared the effects of different interventions, and that revealed the effects of hs-CRP. Two reviewers independently screened the articles, extracted the data, and assessed the quality of the studies according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The data were pooled using a random-effects meta-analysis. Results: Nine articles were included in the meta-analysis. A total of 1.049 patients received stent implantation, and 185 ISR events were recorded during the 1–12-month follow-up period. Baseline hs-CRP levels were not associated with the prediction of ISR among patients receiving stent implantation. The OR of hs-CRP for ISR was 1.81 (0.92–2.69). In the subgroup analysis, 6–12-month hs-CRP levels, diabetes mellitus (DM), and age ≥60(years)were associated with a higher risk of ISR. Conclusions: This meta-analysis shows that higher levels of baseline hs-CRP are not associated with an increased risk of ISR in stented patients. However, an increased risk of ISR was associated with hs-CRP levels at 6 to 12 months of follow-up, which is higher in studies with diabetes mellitus patients and the elderly. Full article

Background: The present study aimed to determine whether the polymorphisms of the 11q23.3 locus affect the risk and mortality of coronary artery disease in 5-year and 10-year observations. Methods: The study group consisted of 519 subjects: 276 patients with CAD and 243 blood donors as controls. The genotyping of polymorphisms (rs10750097, rs3741298, and rs1729410) was performed using the TaqMan-PCR method. Survival was defined as the period from the angiographic confirmation of CAD to cardiovascular death, and the endpoint was defined as death from cardiovascular causes. Results: The G allele of the rs1729410 polymorphism increased the risk of CAD (OR = 1.55, p = 0.04) and showed a synergistic correlation with overweight/obesity (additive synergy index (SI) = 11.01, p < 0.001). The carriers of the GG genotype and over-normative LDL levels increased the risk of CAD by over 12-fold higher than expected (multiplicative synergy index (SIM) = 12.34, p < 0.001). In the case of the rs10750097 variant, an effect on mortality was shown in both 5-year and 10-year periods. Conclusion: The results revealed that the rs1729410 polymorphism increases the risk of CAD in synergy with traditional risk factors, and the rs10750097 polymorphism of the 11q23.3 locus affects the risk of death in patients with CAD. Full article

(1) Background: The heart-type fatty acid-binding protein (H-FABP) is a specific myocardial biomarker and high levels indicate ischemia regardless of patient-reported symptoms. Concurrently, major adverse cardiovascular events and surgery such as coronary artery by-pass grafting (CABG) cause substantial psycho-emotional distress e.g., depression and anxiety. Comprehensive cardiac rehabilitation is, therefore, essential to both physical and psychological recovery. (2) Methods: This is a unicentric, prospective study on 120 consecutive post-CABG patients undergoing a 6-month cardiac rehabilitation program based on physical exercise, Mediterranean diet principles, and Q10 coenzyme antioxidant supplements. H-FABP levels, depression, and anxiety scores (Hamilton HAM-D and HAM-A scales) were monitored after surgery and at 6 months. (3) Results: Mean H-FABP dropped from 60.56 to 4.81. Physical ability increased from 1–2 to 4–5 METS. Mean depression and anxiety improved from 15.88 to 6.96 and from 25.13 to 15.68, respectively. Median scores went down 50% for depression and 9% for anxiety. Explored associations between H-FABP and psycho-emotional status were statistically insignificant. (4) Conclusions: patients adhered to the program and improved significantly in all studied aspects. Clinical significance is discussed in the context of countries like Romania, where such programs are limited by systemic and financial constraints. Further research directions are identified. Full article

Background: Major surgeries suppress patients’ cellular immunity for several days, but the mechanisms underlying this T-cell dysfunction are not well understood. A decreased L-Arginine (L-Arg) level may inhibit T-cell function. Arginase 1 (Arg 1) is induced after traumatic injury, leading to molecular changes in T cells, including decreased expression of cell surface T-cell receptors (TCRs) and a loss in CD3ζ chain expression. In this study, we examined the temporal patterns of CD3ζ expression and Arg 1 activity in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: We determined the CD3ζ chain expression; the Arg 1 activity; and the leukocyte, neutrophil and lymphocyte levels of patients on the day before surgery and at 24, 48 and 72 h after surgery. Results: Fifty adult patients scheduled for elective cardiac surgery with CPB were eligible for enrolment. Arginase activity was significantly increased between the day before surgery and at 24, 48 and 72 h after surgery (p < 0.01), and CD3ζ expression was significantly decreased between the day before surgery and at 24, 48 and 72 h after surgery (p < 0.001). We observed significant leukocytosis, neutrophilia and lymphopenia after surgery. Conclusions: The decreased CD3ζ chain expression could be due to the increased Arg 1 activity secondary to the activation of neutrophils in cardiac surgery under CPB. These findings could explain the limited immune-system-mediated organ damage resulting from systemic inflammatory response to major cardiac surgery with CPB. Full article

Evidence for the association between the frailty index and cardiovascular disease (CVD) is inconclusive, and this association has not been evaluated in Chinese adults. We aim to examine the association between the frailty index and CVD among middle-aged and older Chinese adults. We conducted cross-sectional and cohort analyses using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). From 2011 to 2018, 17,708 participants aged 45 years and older were included in the CHARLS. The primary outcome was CVD events (composite of heart disease and stroke). Multivariable adjusted logistic regression and Cox proportional hazards models were used to estimate the association between the frailty index and CVD in cross-sectional and follow-up studies, respectively. A restricted cubic spline model was used to characterize dose–response relationships. A total of 16,293 and 13,580 participants aged 45 years and older were included in the cross-sectional and cohort analyses, respectively. In the cross-sectional study, the prevalence of CVD in robust, pre-frailty and frailty was 7.83%, 18.70% and 32.39%, respectively. After multivariable adjustment, pre-frailty and frailty were associated with CVD; ORs were 2.54 (95% confidence interval [CI], 2.28–2.84) and 4.76 (95% CI, 4.10–5.52), respectively. During the 7 years of follow-up, 2122 participants without previous CVD developed incident CVD; pre-frailty and frailty were associated with increased risk of CVD events; HRs were 1.53 (95% CI, 1.39–1.68) and 2.17 (95% CI, 1.88–2.50), respectively. Furthermore, a stronger association of the frailty index with CVD was observed in participants aged <55, men, rural community-dwellers, BMI ≥ 25, without hypertension, diabetes or dyslipidemia. A clear nonlinear dose–response pattern between the frailty index and CVD was widely observed (p < 0.001 for nonlinearity), the frailty index was above 0.08, and the hazard ratio per standard deviation was 1.18 (95% CI 1.13–1.25). We observed the association between the frailty index and CVD among middle-aged and elderly adults in China, independent of chronological age and other CVD risk factors. Our findings are important for prevention strategies aimed at reducing the growing burden of CVD in older adults. Full article

Background. Mineral metabolism (MM) system and N-terminal pro-brain natriuretic peptide (NT-ProBNP) have been shown to add prognostic value in patients with stable coronary artery disease (SCAD). However, the influence of NT-ProBNP on the prognostic role of MM in patients with SCAD has not been shown yet. The objective of this study is to assess the influence of NT-ProBNP on the prognostic role of MM markers in patients with SCAD. Methods: We analyzed the prognostic value of MM markers (parathormone (PTH), klotho, phosphate, calcidiol (25-hydroxyvitamin D₃), and fibroblast growth factor-23) in 964 patients with SCAD and NT-ProBNP > 125 pg/mL vs. patient with NT-ProBNP ≤ 125 pg/mL included in five hospitals in Spain. The main outcome was the combination of death, heart failure, and ischemic events (any acute coronary syndrome, ischemic stroke, or transient ischemic attack). Results: A total of 622 patients had NT-proBNP > 125 pg/mL and 342 patients had NT-ProBNP ≤ 125 pg/mL. The median follow-up was 5.1 years. In the group of NT-proBNP > 125 pg/mL, the patients were older, and there were more females and smokers than in the group of patients with normal NT-proBNP. Additionally, the proportion of patients with hypertension, atrial fibrillation, ejection fraction < 40%, cerebrovascular attack, or prior coronary artery bypass graft was higher in the high NT-proBNP group. In the high NT-proBNP patients, the predictors of poor prognosis were PTH (HR = 1.06 (1.01–1.10), p < 0.001) and NT-proBNP (HR = 1.02 (1.01–1.03), p = 0.011), along with age (HR = 1.039 (1.02–1.06), p < 0.001), prior coronary artery bypass graft (HR = 1.624 (1.02–2.59), p = 0.041), treatment with statins (HR = 0.32 (0.19–0.53), p < 0.001), insulin (HR = 2.49 (1.59–4.09), p < 0.001), angiotensin receptor blockers (HR = 1.73 (1.16–2.56), p = 0.007), nitrates (HR = 1.65 (1.10–2.45), p = 0.014), and proton pump inhibitors (HR = 2.75 (1.74–4.36), p < 0.001). In the NT-proBNP ≤ 125 pg/mL subgroup, poor prognosis predictors were plasma levels of non-high-density lipoprotein (non-HDL) cholesterol (HR = 1.01 (1.00–1.02), p = 0.014) and calcidiol (HR = 0.96 (0.92–0.99), p = 0.045), as well as treatment with verapamil (HR = 11.28 (2.54–50.00), p = 0.001), and dihydropyridines (HR = 3.16 (1.63–6.13), p = 0.001). Conclusion: In patients with SCAD and NT-ProBNP > 125 pg/mL, PTH and NT-ProBNP, which are markers related to ventricular damage, are predictors of poor outcome. In the subgroup of patients with NT-ProBNP ≤ 125 pgm/L, calcidiol and non-HDL cholesterol, which are more related to vascular damage, are the independent predictors of poor outcome. Then, in patients with SCAD, baseline NT-ProBNP may influence the type of biomarker that is effective in risk prediction. Full article