The Effect of Vitamin Supplementation on Subclinical Atherosclerosis in Patients without Manifest Cardiovascular Diseases: Never-ending Hope or Underestimated Effect?

Micronutrients, especially vitamins, play an important role in the evolution of cardiovascular diseases (CVD). It has been speculated that additional intake of vitamins may reduce the CVD burden by acting on the inflammatory and oxidative response starting from early stages of atherosclerosis, when the vascular impairment might still be reversible or, at least, slowed down. The current review assesses the role of major vitamins on subclinical atherosclerosis process and the potential clinical implications in patients without CVD. We have comprehensively examined the literature data for the major vitamins: A, B group, C, D, and E, respectively. Most data are based on vitamin E, D and C supplementation, while vitamins A and B have been scarcely examined for the subclinical atherosclerosis action. Though the fundamental premise was optimistic, the up-to-date trials with vitamin supplementation revealed divergent results on subclinical atherosclerosis improvement, both in healthy subjects and patients with CVD, while the long-term effect seems minimal. Thus, there are no conclusive data on the prevention and progression of atherosclerosis based on vitamin supplementation. However, given their enormous potential, future trials are certainly needed for a more tailored CVD prevention focusing on early stages as subclinical atherosclerosis.

Artificial Neural Network Models for Accurate Predictions of Fat-Free and Fat Masses, Using Easy-to-Measure Anthropometric Parameters.

Abdominal fat and fat-free masses report a close association with cardiometabolic risks, therefore this specific body compartment presents more interest than whole-body masses. This research aimed to develop accurate algorithms that predict body masses and specifically trunk fat and fat-free masses from easy to measure parameters in any setting. The study included 104 apparently healthy subjects, but with a higher-than-normal percent of adiposity or waist circumference. Multiple linear regression (MLR) and artificial neural network (ANN) models were built for predicting abdominal fat and fat-free masses in patients with relatively low cardiometabolic risks. The data were divided into training, validation and test sets, and this process was repeated 20 times per each model to reduce the bias of data division on model accuracy. The best performance models used a maximum number of five anthropometric inputs, with higher R2 values for ANN models than for MLR models (R2 = 0.96-0.98 vs. R2 = 0.80-0.94, p = 0.006). The root mean square error (RMSE) for all predicted parameters was significantly lower for ANN models than for MLR models, suggesting a higher accuracy for ANN models. From all body masses predicted, trunk fat mass and fat-free mass registered the best performance with ANN, allowing a possible error of 1.84 kg for predicting the correct trunk fat mass and 1.48 kg for predicting the correct trunk fat-free mass. The developed algorithms represent cost-effective prediction tools for the most relevant adipose and lean tissues involved in the physiopathology of cardiometabolic risks.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Metabolic Phenotypes-The Game Changer in Quality of Life of Obese Patients?

BACKGROUND: The present study aimed to investigate the association of obesity phenotypes and quality of life (QoL) scales and their relationship with fat mass (FM) parameters. METHODS: This study categorized 104 subjects into 4 obesity phenotypes based on BMI and metabolic syndrome status: metabolically healthy obese (MHO), metabolically unhealthy obese (MUO), metabolically healthy non-obese (MHNO), and metabolically unhealthy non-obese (MUNO). Body composition was measured by dual-energy X-ray absorptiometry (DEXA) and metabolic profile was characterized by blood samples. All subjects completed the SF-36 item Short Form Health Survey Questionnaire. RESULTS: Comparing the four obesity phenotypes, significant results were reported for Bodily Pain between MHNO/MUNO (p = 0.034), for Vitality between MHO/MUO (p = 0.024), and for Mental Component Score between MHO/MUO (p = 0.026) and MUO/MUNO (p = 0.003). A more thorough inside-groups analysis yielded a positive and moderate to high correlation between FM parameters and QoL scales in MHO and MHNO, while a negative and weak to moderate correlation was observed in MUO and MUNO. CONCLUSION: This study reported an inverse U-shaped relationship between FM and QoL in obesity phenotypes, suggesting that metabolic status is a key factor involved in modulating QoL and therefore challenging the idea of obesity as a main driver of low QoL. We recommend the inclusion of FM percentage in the definition of obesity phenotypes in future research, to better evaluate QoL of obesity phenotypes.

Circulating Biomarkers for Laboratory Diagnostics of Atherosclerosis-Literature Review.

Atherosclerosis is still considered a disease burden with long-term damaging processes towards the cardiovascular system. Evaluation of atherosclerotic stages requires the use of independent markers such as those already considered traditional, that remain the main therapeutic target for patients with atherosclerosis, together with emerging biomarkers. The challenge is finding models of predictive markers that are particularly tailored to detect and evaluate the evolution of incipient vascular lesions. Important advances have been made in this field, resulting in a more comprehensible and stronger linkage between the lipidic profile and the continuous inflammatory process. In this paper, we analysed the most recent data from the literature studying the molecular mechanisms of biomarkers and their involvement in the cascade of events that occur in the pathophysiology of atherosclerosis.

The Importance of HDL-Cholesterol and Fat-Free Percentage as Protective Markers in Risk Factor Hierarchy for Patients with Metabolic Syndrome.

This research focused on establishing a hierarchy concerning the influence of various biological markers and body composition parameters on preventing, diagnosing and managing Metabolic Syndrome (MetS). Our cross-sectional cohort study included 104 subjects without any atherosclerotic antecedent pathology, organized in two groups (with and without MetS). All participants underwent clinical and anthropometric measurements, DEXA investigation and blood tests for all MetS criteria, together with adiponectin, leptin, insulin, uric acid and CRP. Based on mathematical logic, we calculated a normalized sensitivity score to compare the predictive power of biomarkers and parameters associated with MetS, upon the prevalence of MetS. Patients with MetS report higher levels of uric acid (p = 0.02), CRP (p = 0.012) and lower levels of adiponectin (p = 0.025) than patients without MetS. The top three biological markers with the highest predictive power of the prevalence of the disease are HDL, insulin, and adiponectin:leptin ratio, and the top three body composition parameters are trunk fat-free percentage, waist-height ratio and trunk fat percentage. Their high sensitivity scores differentiate them from all the other markers analysed in the study. Our findings report relevant scores for estimating the importance of cardiometabolic risks in the prevalence of MetS. The high rank of protective markers, HDL and trunk fat-free percentage, suggest that positive effects have a stronger association with the prevalence of MetS, than negative ones do. Therefore, this risk stratification study provides important support for prevention and management programs regarding MetS.

A Rising Star of the Multimarker Panel: Growth Differentiation Factor-15 Levels Are an Independent Predictor of Mortality in Acute Heart Failure Patients Admitted to an Emergency Clinical Hospital from Eastern Europe.

(1) Background: Acute heart failure (HF) represents one of the most common yet extremely severe presentations in emergency services worldwide, requiring prompt diagnosis, followed by an adequate therapeutic approach, and a thorough risk stratification. Natriuretic peptides (NPs) are currently the most widely implemented biomarkers in acute HF, but due to their lack of specificity, they are mainly used as ruling-out criteria. Growth differentiation factor-15 (GDF-15) is a novel molecule expressing different pathophysiological pathways in HF, such as fibrosis, remodeling, and oxidative stress. It is also considered a very promising predictor of mortality and poor outcome. In this study, we aimed to investigate the GDF-15's expression and particularities in patients with acute HF, focusing mainly on its role as a prognosis biomarker, either per se or as part of a multimarker panel. (2) Methods: This unicentric prospective study included a total of 173 subjects, divided into 2 subgroups: 120 patients presented in emergency with acute HF, while 53 were ambulatory-evaluated controls with chronic HF. At admission, all patients were evaluated according to standard clinical echocardiography and laboratory panel, including the assessment of GDF-15. (3) Results: The levels of GDF-15 were significantly higher in patients with acute HF, compared to controls [596 (305−904) vs. 216 (139−305) ng/L, p < 0.01]. GDF-15 also exhibited an adequate diagnostic performance in acute HF, expressed as an area under the curve (AUC) of 0.883 [confidence interval (CI) 95%: 0.828−0.938], similar to that of NT-proBNP (AUC: 0.976, CI 95%: 0.952−1.000), or troponin (AUC: 0.839, CI 95%: 0.733−0.944). High concentrations of GDF-15 were significantly correlated with mortality risk. In a multivariate regression model, GDF-15 was the most important predictor of a poor outcome, superior to NT-proBNP or troponin. (4) Conclusions: GDF-15 proved to be a reliable tool in the multimarker assessment of patients with acute HF. Compared to the gold standard NT-proBNP, GDF-15 presented a similar diagnostic performance, doubled by a significantly superior prognostic value, making it worth being included in a standardized multimarker panel.

ECG and Biomarker Profile in Patients with Acute Heart Failure: A Pilot Study.

Background: Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. Methods: In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. Results: NT-proBNP level was significantly higher in patients with AHF (p < 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). Conclusions: The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

Risk factors associated with intra-stent restenosis after percutaneous coronary intervention.

The present study aimed to explore the correlations between clinical, biological, imagistic and procedural factors with the risk of intra-stent restenosis (ISR) in coronary artery disease (CAD) patients after percutaneous coronary intervention (PCI). An observational cross-sectional study was conducted in a high-volume PCI center over a period of 2 years. A total of 235 consecutive patients diagnosed with angina or acute coronary syndrome treated by PCI were included in the study. Diagnosis of ISR was documented by coronary angiography in patients with suggestive coronary symptoms and ischemic changes in non-invasive or invasive paraclinical investigations. Thus, they were assigned to two groups: With or without ISR. All patients underwent clinical and laboratory examination, providing clinical and paraclinical variables that could be considered risk factors for ISR. Current smokers [risk ratio (RR)=1.63; 95% confidence interval (95% CI): 1.25-2.13], arterial hypertension (RR=1.86; 95% CI: 1.41-2.45), diabetes (RR=1.83; 95% CI: 1.42-2.36), high C-reactive protein (CRP) levels (RR=1.44; 95% CI: 0.93-2.24), chronic kidney disease (CKD) (RR=1.90; 95% CI: 1.53-2.36) and thrombolysis in myocardial infarction (TIMI) score were found to have a significant role in estimating the risk for ISR. Moreover, the ISR group (119 patients) presented with a lower stent inflation pressure when compared to the control group (116 patients) (14.47 vs. 16.14 mmHg, P=0.004). An increased mean stent diameter used for PCI was not associated with a high ISR incidence (P=0.810) as well as complex coronary treated lesions with longer stents (mean length of 24.98 mm in patients without ISR vs. 25.22 mm in patients with ISR; P=0.311). There was an estimated two times higher risk (RR=2.13; 95% CI: 1.17-3.88) concerning multi-stenting and restenosis degree >70%. To conclude, smoking, hypertension, diabetes mellitus, high CRP levels, CKD, TIMI score, stent type, low pressure for stent implantation and multi-stenting were found to be associated with ISR in patients following PCI. Therefore, a close follow-up should be targeted in such patients.

The Relationship between Cardiovascular Risk Scores and Several Markers of Subclinical Atherosclerosis in an Asymptomatic Population.

BACKGROUND: The current cardiovascular disease (CVD) primary prevention guidelines prioritize risk stratification by using clinical risk scores. However, subclinical atherosclerosis may rest long term undetected. This study aimed to evaluate multiple subclinical atherosclerosis parameters in relation to several CV risk scores in asymptomatic individuals. METHODS: A cross-sectional, single-center study included 120 asymptomatic CVD subjects. Four CVD risk scores were computed: SCORE, Framingham, QRISK, and PROCAM. Subclinical atherosclerosis has been determined by carotid intima-media thickness (cIMT), pulse wave velocity (PWV), aortic and brachial augmentation indexes (AIXAo, respectively AIXbr), aortic systolic blood pressure (SBPao), and ankle-brachial index (ABI). RESULTS: The mean age was 52.01 ± 10.73 years. For cIMT-SCORE was more sensitive; for PWV-Framingham score was more sensitive; for AIXbr-QRISK and PROCAM were more sensitive while for AIXao-QRISK presented better results. As for SBPao-SCORE presented more sensitive results. However, ABI did not correlate with any CVD risk score. CONCLUSIONS: All four CV risk scores are associated with markers of subclinical atherosclerosis in asymptomatic population, except for ABI, with specific particularities for each CVD risk score. Moreover, we propose specific cut-off values of CV risk scores that may indicate the need for subclinical atherosclerosis assessment.

Biomarkers Utility: At the Borderline between Cardiology and Neurology.

Biomarkers are important diagnostic and prognostic tools as they provide results in a short time while still being an inexpensive, reproducible and accessible method. Their well-known benefits have placed them at the forefront of research in recent years, with new and innovative discoveries being implemented. Cardiovascular and neurological diseases often share common risk factors and pathological pathways which may play an important role in the use and interpretation of biomarkers' values. Among the biomarkers used extensively in clinical practice in cardiology, hs-TroponinT, CK-MB and NTproBNP have been shown to be strongly influenced by multiple neurological conditions. Newer ones such as galectin-3, lysophosphatidylcholine, copeptin, sST2, S100B, myeloperoxidase and GDF-15 have been extensively studied in recent years as alternatives with an increased sensitivity for cardiovascular diseases, but also with significant results in the field of neurology. Thus, given their low specificity, the values interpretation must be correlated with the clinical judgment and other available investigations.

Beyond the Finish Line: The Impact and Dynamics of Biomarkers in Physical Exercise-A Narrative Review.

The research of biomarkers continues to emerge as a developing academic field which is attracting substantial interest. The study of biomarkers proves to be useful in developing and implementing new screening methods for a wide variety of diseases including in the sports area, whether for leisure activities or professional sports. Novel research has brought into question the immune system and the limitations it may impose on sports practicing. As the well-being of athletes is a priority, the state of their immune function offers valuable information regarding their health status and their ability to continue training. The assessment of various biomarkers may contribute to a more accurate risk stratification and subsequent prevention of some invalidating or even fatal pathologies such as the sudden cardiac death. Therefore, we have reviewed several studies that included sports-related pathology or specific morphofunctional alterations for which some immune biomarkers may represent an expression of the underlying mechanism. These include the defensins, immunoglobulin A (IgA), interleukin-6 (IL-6), the tumoral necrosis factor α (TNF-α), and the white blood cells (WBC) count. Similarly, also of significant interest are various endocrine biomarkers, such as cortisol and testosterone, as well as anabolic or catabolic markers, respectively. Literature data highlight that these values are greatly influenced not only by the duration, but also by the intensity of the physical exercise; moderate training sessions actually enhance the immune function of the body, while a significant increase in both duration and intensity of sports activity acts as a deleterious factor. Therefore, in this paper we aim to highlight the importance of biomarkers' evaluation in connection with sports activities and a subsequent more adequate approach towards personalized training regimens.