Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review.

The incidence and prevalence of cardiac and cerebrovascular diseases are constantly increasing, with chronic coronary syndrome and ischemic stroke as the leading causes of morbidity and mortality worldwide. According to current knowledge, the heart-brain axis is more than a theoretical concept, with many common pathophysiological mechanisms involved in the onset and evolution of both coronary and cerebral ischemia. Moreover, the focus is on the prevention and early intervention of risk factors in searching for targeted and personalized medical treatment. In this context, this narrative review aims to offer, in a didactic and practice-oriented manner, an up-to-date overview of the role played by lipid-derived biomarkers (from low-density lipoprotein cholesterol to oxylipin and apolipoproteins) in chronic coronary syndrome and ischemic stroke. Firstly, the authors highlight, via relevant epidemiological data, the significant burden of chronic coronary syndrome and ischemic stroke in the general population, thus explaining the need for updated information on this topic. Subsequently, the most important lipid-derived biomarkers and their multiple roles in the pathogenesis of these two disorders are listed. Currently available and experimental targeted therapies based on these lipid-derived biomarkers are presented in the final part of this paper, representing this manuscript's original and novel input.

Infective Endocarditis during Pregnancy-Keep It Safe and Simple!

The diagnosis of infective endocarditis (IE) during pregnancy is accompanied by a poor prognosis for both mother and fetus in the absence of prompt management by multidisciplinary teams. We searched the electronic databases of PubMed, MEDLINE and EMBASE for clinical studies addressing the management of infective endocarditis during pregnancy, with the aim of realizing a literature review ranging from risk factors to diagnostic investigations to optimal therapeutic management for mother and fetus alike. The presence of previous cardiovascular pathologies such as rheumatic heart disease, congenital heart disease, prosthetic valves, hemodialysis, intravenous catheters or immunosuppression are the main risk factors predisposing patients to IE during pregnancy. The identification of modern risk factors such as intracardiac devices and intravenous drug administration as well as genetic diagnostic methods such as cell-free deoxyribonucleic acid (DNA) next-generation sequencing require that these cases be addressed in multidisciplinary teams. Guiding treatment to eradicate infection and protect the fetus simultaneously creates challenges for cardiologists and gynecologists alike.

Determinants of Arterial Stiffness in Patients with Morbid Obesity. The Role of Echocardiography and Carotid Ultrasound Imaging.

Background and objective: Morbid obesity is accompanied by an increased cardiovascular (CV) risk, which justifies a multidisciplinary, integrative approach. Arterial stiffness has a well-defined additional role in refining individual CV risk. Given that echocardiography and carotid ultrasound are usual methods for CV risk characterization, we aimed to identify the imaging parameters with a predictive value for early-onset arterial stiffness. Material and methods: We conducted a study in which 50 patients (divided into two equal groups with morbid obesity and without obesity), age and gender matched, untreated for cardiovascular risk factors, were addressed to bariatric surgery or non-inflammatory benign pathology surgery. Before the surgical procedures, we evaluated demographics, anthropometric data and biochemical parameters including adipokines (chemerin, adiponectin). Arterial stiffness was evaluated using the Medexpert ArteriographTM TL2 device. Transthoracic echocardiography and carotid ultrasound were also performed. We also analyzed adipocyte size and vascular wall thickness in intraoperative biopsies. Results: Left ventricle (LV) mass index (p = 0.2851), LV ejection fraction (LVEF) (p = 0.0073), epicardial adipose tissue thickness (p = 0.0001) as echocardiographic parameters and carotid intima-media thickness (p = 0.0033), relative wall thickness (p = 0.0295), wall to lumen thickness ratio (p = 0.0930) and carotid cross-sectional area (p = 0.0042) as ultrasound parameters were significant measures in our groups and were assessed in relation to adipocyte size, blood vessel wall thickness and adipokines serum levels. Statistical analysis revealed directly proportional relationships between LV mass index (p = 0.008), carotid systolic thickness of the media (p = 0.009), diastolic thickness of the media (p = 0.007), cross-sectional area (p = 0.001) and blood vessel wall thickness. Carotid relative wall thickness positively correlates with adipocyte size (p = 0.023). In patients with morbid obesity, chemerin and adiponectin/chemerin ratio positively correlates with carotid intima-media thickness (p = 0.050), systolic thickness of the media (p = 0.015) and diastolic thickness of the media (p = 0.001). The multiple linear regression models revealed the role of epicardial adipose tissue thickness and carotid cross-sectional area in predicting adipocyte size which in turn is an independent factor for arterial stiffness parameters such as pulse wave velocity, subendocardial viability ratio and aortic augmentation index. Conclusions: Our results suggest that epicardial adipose tissue thickness, carotid intima-media thickness, relative wall thickness and carotid cross-sectional area might be useful imaging parameters for early prediction of arterial stiffness in patients with morbid obesity.

Beyond the Acute Phase: Long-Term Impact of COVID-19 on Functional Capacity and Prothrombotic Risk-A Pilot Study.

Background and Objectives: Assessment of the prothrombotic, proinflammatory, and functional status of a cohort of COVID-19 patients at least two years after the acute infection to identify parameters with potential therapeutic and prognostic value. Materials and Methods: We conducted a retrospective, descriptive study that included 117 consecutive patients admitted to Iasi Pulmonary Rehabilitation Clinic for reassessment and a rehabilitation program at least two years after a COVID-19 infection. The cohort was divided into two groups based on the presence (n = 49) or absence (n = 68) of pulmonary fibrosis, documented through high-resolution computer tomography. Results: The cohort comprises 117 patients, 69.23% females, with a mean age of 65.74 ± 10.19 years and abnormal body mass index (31.42 ± 5.71 kg/m2). Patients with pulmonary fibrosis have significantly higher levels of C-reactive protein (CRP) (p < 0.05), WBC (7.45 ± 7.86/mm3 vs. 9.18 ± 17.24/mm3, p = 0.053), neutrophils (4.68 ± 7.88/mm3 vs. 9.07 ± 17.44/mm3, p < 0.05), mean platelet volume (MPV) (7.22 ± 0.93 vs. 10.25 ± 0.86 fL, p < 0.05), lactate dehydrogenase (p < 0.05), and D-dimers (p < 0.05), but not ferritin (p = 0.470), reflecting the chronic proinflammatory and prothrombotic status. Additionally, patients with associated pulmonary fibrosis had a higher mean heart rate (p < 0.05) and corrected QT interval (p < 0.05). D-dimers were strongly and negatively correlated with diffusion capacity corrected for hemoglobin (DLCO corr), and ROC analysis showed that the persistence of high D-dimers values is a predictor for low DLCO values (ROC analysis: area under the curve of 0.772, p < 0.001). The results of pulmonary function tests (spirometry, body plethysmography) and the 6-minute walk test demonstrated no significant difference between groups, without notable impairment within either group. Conclusions: Patients with COVID-19-related pulmonary fibrosis have a persistent long-term proinflammatory, prothrombotic status, despite the functional recovery. The persistence of elevated D-dimer levels could emerge as a predictive factor associated with impaired DLCO.

The Role Played by Novel Inflammatory Markers in Assessment of Peripheral Artery Disease.

Background and Objectives: Atherosclerosis is a multifactorial process in which inflammatory markers have both therapeutic and prognostic roles. Recent studies bring into question the importance of assessing new inflammatory markers in relation to the severity of peripheral artery disease (PAD), such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-C-reactive protein ratio (LCR). Materials and Methods: We conducted a retrospective and descriptive study including 652 patients with PAD, who were divided into two groups according to the severity of the ankle-brachial index value: mild and moderate obstruction (257 patients) and severe obstruction (395 patients). We evaluated demographics, anthropometric data and clinical and paraclinical parameters in relation to the novel inflammatory biomarkers mentioned above. Results: Weight (p = 0.048), smoking (p = 0.033), the number of cardiovascular risk factors (p = 0.041), NLR (p = 0.037), LCR (p = 0.041) and PLR (p = 0.019), the presence of gangrene (p = 0.001) and the number of lesions detected via peripheral angiography (p < 0.001) were statistically significant parameters in our study. For the group of patients with severe obstruction, all three inflammatory biomarkers were statistically significantly correlated with a serum low-density lipoprotein-cholesterol level, the number of cardiovascular risk factors, rest pain, gangrene and a risk of amputation. In addition, directly proportional relationships were found between NLR, PLR and the number of stenotic lesions (p = 0.018, p = 0.016). Also, NLR (area under the curve = 0.682, p = 0.010) and PLR (AUC = 0.692, p = 0.006) were predictors associated with a high risk of amputation in patients with an ABI < 0.5. Conclusions: in our study, we demonstrated the importance of assessing inflammatory markers in relation to the presence of cardiovascular risk factors through the therapeutic and prognostic value demonstrated in PAD.

Blood and Salivary Cortisol Variations in Athletes in Relation to Cardiopulmonary Exercise Testing.

Background and Objectives: Cortisol is a valuable marker for assessing the body's response to any form of stress. We conducted this study in order to evaluate the variations of salivary and serum cortisol levels in professional football players in relation to cardiopulmonary exercise testing (CPET) and their significance in potentially evaluating overtraining in athletes. Also, the question of whether salivary cortisol determination could fully substitute serum sampling was addressed. Materials and Methods: A total of 19 male professional football players were evaluated by measuring serum cortisol levels at rest (T0) and immediately after a CPET (T1) and salivary cortisol levels at rest (T0), 10 min after a CPET (T2), and 30 min after a CPET (T3). Results: T0 serum cortisol showed a statistically significant correlation with the oxygen uptake at the anaerobic threshold divided by the body weight (VO2-AT/weight), as did the T2 salivary cortisol with the maximum oxygen uptake at the anaerobic threshold (VO2-AT) and VO2-AT/weight. T0 salivary cortisol was significantly correlated with the subjects' height and the predicted O2 pulse. Conclusions: While some correlations were discovered, they are insufficient to recommend cortisol as a routine biomarker in athletes' evaluation. However, significant correlations were established between salivary and serum determinations, meaning that the non-invasive procedure could substitute venous blood sampling.

PLL-Based Readout Circuit for SiC-MOS Capacitor Hydrogen Sensors in Industrial Environments.

For proper operation in real industrial conditions, gas sensors require readout circuits which offer accuracy, noise robustness, energy efficiency and portability. We present an innovative, dedicated readout circuit with a phase locked loop (PLL) architecture for SiC-MOS capacitor sensors. A hydrogen detection system using this circuit is designed, simulated, implemented and tested. The PLL converts the MOS nonlinear small-signal capacitance (affected by hydrogen) into an output voltage proportional to the detected gas concentration. Thus, the MOS sensing element is part of the PLL's voltage-controlled oscillator. This block effectively provides a small AC signal (around 70 mV at 1 MHz) for the sensor and acquires its response. The correct operation of the proposed readout circuit is validated by simulations and experiments. Hydrogen measurements are performed for concentrations up to 1600 ppm. The PLL output exhibited voltage variations close to those discernable from experimental C-V curves, acquired with a semiconductor characterization system, for all investigated MOS sensor samples.

CPAP Influence on Readily Available Inflammatory Markers in OSA-A Pilot Study.

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, chronic hypoxia and a proinflammatory phenotype. The purpose of our study was to evaluate readily available inflammatory biomarkers (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cell count (WBC), red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), WBC-to-MPV ratio (WMR) and lymphocyte-to-C-reactive protein ratio (LCR)) before and after CPAP in patients with moderate-severe OSA. We performed a prospective study that included patients with newly-diagnosed moderate-severe OSA. The control groups (patients without OSA and with mild OSA) were selected from the hospital polygraphy database. All subjects underwent routine blood panel, which was repeated in moderate-severe OSA patients after 8 weeks of CPAP. Our final study group included 31 controls, 33 patients with mild, 22 patients with moderate and 37 patients with severe OSA. CRP, ESR, NLR and WMR were correlated with OSA severity. After 8-week CPAP therapy, we documented a decrease in weight status, which remained statistically significant in both CPAP-adherent and non-adherent subgroups. Readily available, inexpensive inflammatory parameters can predict the presence of moderate-severe OSA, but are not influenced by short-term CPAP.

Value of the Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio in Predicting CPET Performance in Patients with Stable CAD and Recent Elective PCI.

Background and Objectives: Functional capacity (FC) assessed via cardiopulmonary exercise testing (CPET) is a novel, independent prognostic marker for patients with coronary artery disease (CAD). Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) are two readily available predictors of systemic inflammation and cardiovascular event risk, which could be used as cost-effective predictors of poor FC. The purpose of this study was to evaluate the utility of NLR and PLR in predicting poor FC in patients with CAD and recent elective percutaneous coronary intervention (PCI). Materials and Methods: Our cross-sectional retrospective analysis included 80 patients with stable CAD and recent elective PCI (mean age 55.51 ± 11.83 years, 71.3% male) who were referred to a cardiovascular rehabilitation center from January 2020 to June 2021. All patients underwent clinical examination, cardiopulmonary exercise testing on a cycle ergometer, transthoracic echocardiography and standard blood analysis. Results: Patients were classified according to percent predicted oxygen uptake (% VO2 max) in two groups­poor FC (≤70%, n = 35) and preserved FC (>70%, n = 45). There was no significant difference between groups regarding age, gender ratio, presence of associated comorbidities, left ventricular ejection fraction and NLR. PLR was higher in patients with poor FC (169.8 ± 59.3 vs. 137.4 ± 35.9, p = 0.003). A PLR cut-off point of 139 had 74% sensitivity and 60% specificity in predicting poor FC. After multivariate analysis, PLR remained a significant predictor of poor functional status. Conclusions: Although CPET is the gold standard test for assessing FC prior to cardiovascular rehabilitation, its availability remains limited. PLR, a cheap and simple test, could predict poor FC in patients with stable CAD and recent elective PCI and help prioritize referral for cardiovascular rehabilitation in high-risk patients.

Subendocardial Viability Ratio Predictive Value for Cardiovascular Risk in Hypertensive Patients.

Background: The subendocardial viability ratio (SEVR), also known as the Buckberg index, is a parameter of arterial stiffness with indirect prognostic value in assessing long-term cardiovascular risk. Materials and Methods: We conducted a prospective cohort study on 70 patients with uncomplicated hypertension admitted to a county medical reference hospital. We analyzed demographics, laboratory data, arterial stiffness parameters and cardiovascular risk scores (SCORE and Framingham risk scores) and aimed to identify paraclinical parameters associated with increased cardiovascular risk. Results: Of the arterial stiffness parameters, SEVR correlates statistically significantly with age, central and peripheral systolic blood pressure, as well as with heart rate. SEVR seems to have prognostic value among hypertensive patients by increasing the risk of major cardiovascular events assessed by SCORE and Framingham risk scores. SEVR correlates statistically significantly with serum fibrinogen (p = 0.02) and hemoglobin (p = 0.046). Between pulse wave velocity and lipid parameters (p = 0.021 for low-density lipoprotein cholesterol and p = 0.030 for triglycerides) a statistically significant relationship was found for the study group. The augmentation index of the aorta also correlated with serum LDL-cholesterol (p = 0.032) and the hemoglobin levels (p = 0.040) of hypertensive patients. Conclusions: Age, abdominal circumference and Framingham score are independent predictors for SEVR in our study group, further highlighting the need for early therapeutic measures to control risk factors in this category of patients.