Acute Cardiovascular Events Research Articles

Cardiovascular Disease and Sex

One of the primary causes of death worldwide is cardiovascular disease (CVD). Women typically have a lower incidence of CVD than men, however after acute cardiovascular events, women have a higher mortality and worse prognosis. Different CVDs, such as coronary heart disease, stroke, heart failure, and aortic diseases, exhibit these sex variances. These differences have raised serious concerns so sex consideration is significant for the prevention, diagnosis, treatment, and management of CVD. In order to highlight the need of taking sex differences into account when determining cardiovascular risk, this study seeks to offer an overview of sex-related differences in numerous common CVDs as well as an analysis of potential factors linked with the disparities. Future studies should focus on how to define and include sex-related indicators into the methods currently used for cardiovascular risk assessment and management.

Role of galectin-3 in vascular calcification.

Vascular calcification is an abnormal process in which bone specific hydroxyapatite crystals are actively deposited on the vascular wall mediated by phenotypic differentiated smooth muscle cells and other mesenchymal cells under various pathological conditions. It is one of the important characteristics in the occurrence and development of atherosclerosis, prevalent in patients with type 2 diabetes and advanced chronic kidney disease, especially those requiring maintenance hemodialysis, with severely threatening human health. Previous studies have shown that the early diagnosis and control of vascular calcification is of great significance for cardiovascular risk stratification, prevention of acute cardiovascular events, which can greatly improve the prognosis and quality of life of patients. Galectins are a family of lectin superfamily. It is widely distributed in various animals and plays an important role in many physiological and pathological processes, such as cell adhesion, apoptosis, inflammatory response, tumor metastasis and so on. Many biomarker-and association-related studies and Preclinical-mechanistic studies have suggested that galactose-specific lectin-3 (galectin-3) plays an important role in vascular calcification and vascular intimal calcification (VIC) calcification induced by Wnt/βcatenin signaling pathway, NF-κB signaling pathway and ERK1/2 signaling pathway. This paper mainly expounds the role and mechanism of galectin-3 in vascular calcification under different pathological conditions including atherosclerosis, diabetes and chronic kidney disease.

Influenza Vaccination as Prevention Therapy for Stable Coronary Artery Disease and Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials

BackgroundInfluenza can cause a significant burden on patients with coronary artery disease. This meta-analysis assessed the effectiveness of influenza vaccination in patients with acute coronary syndrome and stable coronary artery disease. MethodsWe searched the Cochrane Controlled Register of Trials (CENTRAL), Embase, MEDLINE, www.ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform from inception to September 2021. Estimates were summarized using the Mantel-Haenzel method and a random-effects model. To assess heterogeneity the I² statistic was used. ResultsFive randomized trials, comprising 4187 patients, were included, 2 of which included patients with acute coronary syndrome and 3 that included patients with stable coronary artery disease and acute coronary syndrome. Influenza vaccination significantly reduced the risk for all-cause mortality (relative risk [RR] = 0.56; 95% confidence interval [CI], 0.38-0.84), cardiovascular mortality (RR = 0.54; 95% CI, 0.37-0.80), major acute cardiovascular events (RR = 0.66; 95% CI, 0.49-0.88), and acute coronary syndrome (RR = 0.63; 95% CI, 0.44-0.89). On subgroup analysis, influenza vaccination remained effective for these outcomes in acute coronary syndrome but did not meet statistical significance in coronary artery disease. Furthermore, influenza vaccination did not reduce the risk for revascularization (RR = 0.89; 95% CI, 0.54-1.45), stroke or transient ischemic attack (RR = 0.85; 95% CI, 0.31-2.32), or heart failure hospitalization (RR = 0.91; 95% CI, 0.21-4.00). ConclusionsInfluenza vaccine is a cheap and effective intervention to reduce the risk for all-cause mortality, cardiovascular mortality, major acute cardiovascular events, and acute coronary syndrome among coronary artery disease patients, especially in those with acute coronary syndrome.

A study on the effect of aspirin on clinical symptoms, laboratory indices, and outcomes in patients with COVID-19

Introduction: Low-dose aspirin is one of the most widely used secondary prevention agents for cardiovascular disease and stroke. An unstable risk factor for chronic cardiovascular disease is a viral infection. Evidence suggests that the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could increase the risk of acute cardiovascular events by inducing systemic inflammatory responses and instability in coronary plaques. Objectives: The present study aimed to examine the impact of aspirin on clinical symptoms, laboratory indices, and clinical outcomes in patients with COVID-19. Patients and Methods: After reviewing the documents of hospitalized patients at the Dr. Shariati hospital in Isfahan, Iran, while case and control groups were selected using a cross-sectional method based on aspirin use and non-use. Following a random selection of the reference population (131 medical records of patients with COVID-19 who had aspirin use and 131 of the group of patients with COVID-19 without aspirin use). Medical records of patients with cardiovascular disease, diabetes, cardiovascular disease with diabetes, and patients without underlying disease were evaluated. After matching the two groups based on age, gender, and medical history, the examination and results were recorded in a questionnaire. Results: The results showed that during treatment, no significant difference between the case and control groups regarding clinical symptoms, laboratory results, the need for bilevel positive airway pressure (BiPAP), and mechanical ventilation (P=0.0111 and P=0.089, respectively) were observed. Moreover, no significant difference in the outcome, including improvement and death was detected (P=0.962). Likewise, no significant difference in hospitalization duration between the aspirin and control groups was seen (P=0.289). Conclusion: Our study on a group of COVID-19 patients showed, aspirin is ineffective on clinical symptoms, laboratory indices, and outcomes, however our results further investigation by multi-centric investigations.

Cardiorespiratory fitness, body mass index, cardiovascular disease, and mortality in young men: A cohort study.

We examined the association between cardiorespiratory fitness (CRF), body mass index (BMI), incidence of major acute cardiovascular events (MACE), and all-cause mortality (ACM). We conducted a retrospective cohort study involving 212,631 healthy young men aged 16 to 25 years who had undergone medical examination and fitness testing (2.4 km run) from 1995 to 2015. Information on the outcomes of major acute cardiovascular events (MACE) and all-cause mortality (ACM) were obtained from the national registry data. During 2,043,278 person-years of follow-up, 371 first MACE and 243 ACM events were recorded. Compared against the first run-time quintile, adjusted hazard ratios (HR) for MACE in the second to fifth quintiles were 1.26 (95% CI 0.84-1.91), 1.60 (95% CI 1.09-2.35), 1.60 (95% CI 1.10-2.33), and 1.58 (95% CI 1.09-2.30). Compared against the "acceptable risk" BMI category, the adjusted HRs for MACE in the "underweight," "increased risk," and "high-risk" categories were 0.97 (95% CI 0.69-1.37), 1.71 (95% CI 1.33-2.21), and 3.51 (95% CI 2.61-4.72), respectively. The adjusted HRs for ACM were increased in participants from the fifth run-time quintile in the "underweight" and "high-risk" BMI categories. The combined associations of CRF and BMI with MACE showed elevated hazard in the "BMI≥23-fit" category, which was more pronounced in the "BMI≥23-unfit" category. The hazards for ACM were elevated across the "BMI<23-unfit," "BMI≥23-fit," and "BMI≥23-unfit" categories. Lower CRF and elevated BMI were associated with increased hazards of MACE and ACM. A higher CRF did not fully compensate for elevated BMI in the combined models. CRF and BMI remain important targets for public health intervention in young men.

Impact of Vitamin D Supplementation on the Clinical Outcomes and Epigenetic Markers in Patients with Acute Coronary Syndrome.

Vitamin D has recently been found to influence the renin-angiotensin system (RAS); it can reduce the effects of renin-angiotensin system inhibitors (RASI) by decreasing plasma renin. This study examines the effect of vitamin D supplements on cardiac fibrosis markers, echocardiographic parameters, and epigenetic markers in patients with established acute coronary syndrome (ACS). It also looks at the incidence of vitamin D receptor (VDR) gene polymorphisms Apa I (rs7975232), Bsm I (rs1544410), Taq I (rs731236), and Fok I (rs2228570) and its association with the development of secondary major acute cardiovascular events (MACE) and heart failure (HF). A randomized controlled trial in which patients were divided into two groups was performed. Group 1 comprised of 125 ACS patients who received ACS standard therapy alone, while Group 2 consisted of 125 ACS patients who received ACS standard therapy plus vitamin D according to their vitamin D levels. Patients were monitored for 24 months to find subsequent MACE and HF. Vitamin D therapy for ACS patients resulted in a substantial decline in end systolic and end diastolic volumes (p = 0.0075 and 0.002, respectively), procollagen type III N-terminal peptide (PIIINP) and soluble ST2 levels (p = 0.007 and 0.001, respectively), as well as in ejection fraction and vitamin D level (p = 0.0001 and 0.008, respectively). In addition, vitamin D treatment was linked to a significant decline in the levels of noncoding RNA, such as mir361, lncRNA MEG3, and lncRNA Chaer (p = 2.9 × 10-4, 2.2 × 10-6, and 1.2 × 10-5, respectively). Furthermore, patients who suffered MACE had significantly higher levels of the Bsm I CC and Fok I GG genotypes (p = 4.8 × 10-4 and 0.003, respectively), while patients with HF had significantly higher levels of the Taq I AA genotype (p = 4.2 × 10-7). Supplementing ACS patients with vitamin D has been demonstrated to limit cardiac fibrosis and echocardiographic parameters, as well as epigenetic markers. Additionally, MACE and HF among ACS patients may be related to genetic variations among VDR gene polymorphisms.

Activation of estrogen receptor α inhibits TLR4 signaling in macrophages and alleviates the instability of atherosclerotic plaques in the postmenopausal stage

Acute cardiovascular events increase significantly in postmenopausal women. The relationship between estrogen receptor (ER) and plaque stability in the postmenopausal stage remains to be elucidated. We aimed to explore whether ERα activation improves plaque instability in the postmenopausal stage. Here, we report that postmenopausal women showed increased macrophage activation and plaque instability with increased MCP-1, MMP9, TLR4, MYD88 and NF-κB p65 and decreased ERα and TIMP1 expression in the vascular endothelium. Moreover, ovariectomy in LDLR-/- mice resulted in a significant increase in plaque area and necrotic core area, as well as a significant decrease in collagen content and an increase in macrophage accumulation in the artery. Ovariectomy also reduced serum estrogen levels and ERα expression and upregulated TLR4 and MMP9 expression in arteries in LDLR-/- mice. Estrogen or phytoestrogen therapy upregulated the expression level of ERα in ovariectomized mice and increased plaque stability by inhibiting macrophage accumulation and TLR4 signaling. In vitro, LPS incubation of RAW264.7 cells resulted in a significant decrease in ERα and TIMP1 expression and an increase in TLR4 activation, and estrogen or phytoestrogen treatment increased ERα and TIMP1 expression and inhibited TLR4 activation and MMP9 expression in LPS-treated RAW264.7 cells. Compared to control siRNA transfected RAW264.7 cells, TLR4 siRNA promoted TIMP1 expression in RAW264.7 cells with LPS incubation, but did not affect ERα expression in RAW264.7 cells with or without LPS treatment. The ERα inhibitor MPP abolished the regulatory effect of estrogen or phytoestrogen on LPS-induced RAW264.7 cells. In conclusion, the present study demonstrates that decreased ERα expression promotes macrophage infiltration and plaque instability in the postmenopausal stage, and activation of ERα in the postmenopausal stage alleviates atherosclerotic plaque instability by inhibiting TLR4 signaling and macrophage-related inflammation.

Dual-omics reveals temporal differences in acute sympathetic stress-induced cardiac inflammation following α1 and β-adrenergic receptors activation.

Sympathetic stress is prevalent in cardiovascular diseases. Sympathetic overactivation under strong acute stresses triggers acute cardiovascular events including myocardial infarction (MI), sudden cardiac death, and stress cardiomyopathy. α1-ARs and β-ARs, two dominant subtypes of adrenergic receptors in the heart, play a significant role in the physiological and pathologic regulation of these processes. However, little is known about the functional similarities and differences between α1- and β-ARs activated temporal responses in stress-induced cardiac pathology. In this work, we systematically compared the cardiac temporal genome-wide profiles of acute α1-AR and β-AR activation in the mice model by integrating transcriptome and proteome. We found that α1- and β-AR activations induced sustained and transient inflammatory gene expression, respectively. Particularly, the overactivation of α1-AR but not β-AR led to neutrophil infiltration at one day, which was closely associated with the up-regulation of chemokines, activation of NF-κB pathway, and sustained inflammatory response. Furthermore, there are more metabolic disorders under α1-AR overactivation compared with β-AR overactivation. These findings provide a new therapeutic strategy that, besides using β-blocker as soon as possible, blocking α1-AR within one day should also be considered in the treatment of acute stress-associated cardiovascular diseases.

Abstract WMP102: Diabetes-Related Polygenic Risk Is Associated With Poor Glycemic Control And Higher Risk Of Acute Cardiovascular Events In Stroke Survivors

Introduction: Though uncontrolled diabetes leads to recurrent cardiovascular events in stroke survivors, many don’t achieve appropriate glycemic control. We hypothesize an adverse polygenic risk profile leads to worse glycemic control and higher risk of recurrent cardiovascular events in stroke survivors. Methods: We conducted a population genetic study using data of stroke survivors enrolled in the UK Biobank and the Vitamin Intervention for Stroke Prevention (VISP) trial. In both studies, we modeled polygenic risk to diabetes through a polygenic risk score that included 462 single nucleotide polymorphisms known to associate with type 2 diabetes mellitus. Participants were stratified as low, intermediate, or high polygenic risk according to percentile values of this score (&lt;20 th , 20-80 th and &gt;80 th percentile). We used multivariable linear, logistic, and Cox regression models to test for association between polygenic risk to diabetes and 1) hemoglobin A1c (HbA1c), 2) risk of treatment-resistant diabetes (HbA1c ≥7 despite pharmacological therapy), and 3) composite risk of recurrent stroke or coronary artery disease (CAD). Results: In 5,670 stroke survivors enrolled in the UK Biobank (mean age 61, 41% females), a higher polygenic risk to diabetes was associated with higher HbA1c in both participants with and without diabetes, and with higher risk of treatment-resistant diabetes (all p&lt;0.05, see Table). In 1,750 stroke survivors (mean age 68, 35% female 34) enrolled in VISP, a higher polygenic risk to diabetes was associated with higher composite risk of recurrent stroke or CAD (p&lt;0.05, see Table). Conclusions: Among stroke survivors, a higher polygenic risk to diabetes is associated with worse glycemic control and higher risk of recurrent acute vascular events. Further research is needed to evaluate the portability of these results to non-white individuals and identify specific medications that may be more effective in patients with adverse genomic profiles.

Influence of administration time and sex on natriuretic, diuretic, and kaliuretic effects of diuretics.

Sex differences in renal function and blood pressure have been widely described across many species. Blood pressure dips during sleep and peaks in the early morning. Similarly, glomerular filtration rate, filtered electrolyte loads, urine volume, and urinary excretion all exhibit notable diurnal rhythms, which reflect, in part, the regulation of renal transporter proteins by circadian clock genes. That regulation is sexually dimorphic; as such, sex and time of day are not two independent regulators of kidney function and blood pressure. The objective of the present study was to assess the effect of sex and administration time on the natriuretic and diuretic effects of loop, thiazide, and K+-sparing diuretics, which are common treatments for hypertension. Loop diuretics inhibit Na+-K+-2Cl- cotransporters on the apical membrane of the thick ascending limb, thiazide diuretics inhibit Na+-Cl- cotransporters on the distal convoluted tubule, and K+-sparing diuretics inhibit epithelial Na+ channels on the connecting tubule and collecting duct. We simulated Na+ transporter inhibition using sex- and time-of-day-specific computational models of mouse kidney function. The simulation results highlighted significant sex and time-of-day differences in the drug response. Loop diuretics induced larger natriuretic and diuretic effects during the active phase. The natriuretic and diuretic effects of thiazide diuretics exhibited sex and time-of-day differences, whereas these effects of K+-sparing diuretics exhibited a significant time-of-day difference in females only. The kaliuretic effect depended on the type of diuretics and time of administration. The present computational models can be a useful tool in chronotherapy, to tailor drug administration time to match the body's diurnal rhythms to optimize the drug effect.NEW & NOTEWORTHY Sex influences cardiovascular disease, and the timing of onset of acute cardiovascular events exhibits circadian rhythms. Kidney function also exhibits sex differences and circadian rhythms. How do the natriuretic and diuretic effects of diuretics, a common treatment for hypertension that targets the kidneys, differ between the sexes? And how do these effects vary during the day? To answer these questions, we conducted computer simulations to assess the effects of loop, thiazide, and K+-sparing diuretics.

Cost-Effectiveness of Vonoprazan Compared With Proton Pump Inhibitors in Patients Taking Low-Dose Aspirin for Secondary Prevention of Cardiovascular Events in Japan.

Low-dose aspirin (LDA) is used to prevent recurrent cardiovascular (CV) events, but is associated with upper gastrointestinal (GI) bleeding; concomitant use of a proton pump inhibitor (PPI) reduces this risk. This study aimed to assess the cost-effectiveness of vonoprazan compared with PPIs (lansoprazole and esomeprazole) in patients taking LDA for secondary prevention of CV events. A Markov simulation model was developed to predict the number of GI bleeding and acute CV events using 3 strategies (vonoprazan+LDA, esomeprazole+LDA, and lansoprazole+LDA), which were translated into quality-adjusted life-years (QALYs) and costs. Transition probabilities and utilities were derived from the results of published literature, and medical costs were based on the Japanese National Health Insurance fee table and claims databases in 2020. Outcomes were projected over 30 years starting at age 65 years and discounted at 2% annually. Expected costs with esomeprazole 20 mg, lansoprazole 15 mg and vonoprazan 10 mg were JPY 1,225,657, JPY 943,930, and JPY 1,059,510, respectively. The QALY gain for vonoprazan vs. esomeprazole was 0.35, thus vonoprazan was dominant against esomeprazole. The QALY gain for vonoprazan vs. lansoprazole was 0.29 and the incremental cost-effectiveness ratio (ICER) was JPY 398,551, thus, vonoprazan was more cost-effective than lansoprazole. Vonoprazan is dominant or cost-effective compared with esomeprazole and lansoprazole in patients taking LDA for secondary prevention of CV events.

Cardiovascular Risk Assessment in Rheumatoid Arthritis: Accelerated Atherosclerosis, New Biomarkers, and the Effects of Biological Therapy.

Rheumatoid arthritis (RA), one of the most common of the chronic inflammatory autoimmune diseases (CIADs), is recognized as an independent cardiovascular risk factor. Traditional risk factors such as smoking, arterial hypertension, dyslipidemia, insulin resistance, and obesity are frequently found in RA. Given the increased risk of mortality and morbidity associated with cardiovascular disease (CVD) in RA patients, screening for risk factors is important. Moreover, there is a need to identify potential predictors of subclinical atherosclerosis. Recent studies have shown that markers such as serum homocysteine, asymmetric dimethylarginine, or carotid intima-media thickness (cIMT) are correlated with cardiovascular risk. Although RA presents a cardiovascular risk comparable to that of diabetes, it is not managed as well in terms of acute cardiovascular events. The introduction of biological therapy has opened new perspectives in the understanding of this pathology, confirming the involvement and importance of the inflammatory markers, cytokines, and the immune system. In addition to effects in inducing remission and slowing disease progression, most biologics have demonstrated efficacy in reducing the risk of major cardiovascular events. Some studies have also been conducted in patients without RA, with similar results. However, early detection of atherosclerosis and the use of targeted therapies are the cornerstone for reducing cardiovascular risk in RA patients.

Combining IVUS + OCT Data, Biomechanical Models and Machine Learning Method for Accurate Coronary Plaque Morphology Quantification and Cap Thickness and Stress/Strain Index Predictions

Assessment and prediction of vulnerable plaque progression and rupture risk are of utmost importance for diagnosis, management and treatment of cardiovascular diseases and possible prevention of acute cardiovascular events such as heart attack and stroke. However, accurate assessment of plaque vulnerability assessment and prediction of its future changes require accurate plaque cap thickness, tissue component and structure quantifications and mechanical stress/strain calculations. Multi-modality intravascular ultrasound (IVUS), optical coherence tomography (OCT) and angiography image data with follow-up were acquired from ten patients to obtain accurate and reliable plaque morphology for model construction. Three-dimensional thin-slice finite element models were constructed for 228 matched IVUS + OCT slices to obtain plaque stress/strain data for analysis. Quantitative plaque cap thickness and stress/strain indices were introduced as substitute quantitative plaque vulnerability indices (PVIs) and a machine learning method (random forest) was employed to predict PVI changes with actual patient IVUS + OCT follow-up data as the gold standard. Our prediction results showed that optimal prediction accuracies for changes in cap-PVI (C-PVI), mean cap stress PVI (meanS-PVI) and mean cap strain PVI (meanSn-PVI) were 90.3% (AUC = 0.877), 85.6% (AUC = 0.867) and 83.3% (AUC = 0.809), respectively. The improvements in prediction accuracy by the best combination predictor over the best single predictor were 6.6% for C-PVI, 10.0% for mean S-PVI and 8.0% for mean Sn-PVI. Our results demonstrated the potential using multi-modality IVUS + OCT image to accurately and efficiently predict plaque cap thickness and stress/strain index changes. Combining mechanical and morphological predictors may lead to better prediction accuracies.

Analysis of in-hospital complications in patients with acute cardiovascular pathology and co-infection with COVID-19: a registry of one center

The aim – to analyze in-hospital mortality in pts with acute cardiovascular pathology (ACP) and a co-infection with COVID-19.Materials and methods. 139 pts with ACP who were diagnosed with COVID-19 were examined. 69 (49.6 %) pts had ACS (47 pts with AMI), 33 (23.7 %) pts – hypertensive urgency, 24 (17.3 %) pts – ADHF, 9 (6.5 %) pts – tachysystolic paroxysm of atrial fibrillation, 2 (1.4 %) pts – acute pulmonary embolism, and 2 (1.4 %) pts – syncope. The average age was 67.9±12.7 y.o., 70 (50.4 %) pts were male. Concomitant arterial hypertension was found in 87.1 %, DM – 20.9 %, CHF – 30.9 %, COPD – 9.4 % of pts, history of AMI – 20.1 % and ischemic stroke – 9.4 % of pts. In 79 (56.8 %) pts COVID-19 was diagnosed and laboratory confirmed before hospitalization (hospitalized in 5.3±3.6 days after symptoms onset). 31 (22.3 %) pts were diagnosed with COVID-19 upon admission, and 29 (20.9 %) – during their stay in the hospital. 20 (15.6 %) pts were vaccinated against COVID-19. The initial SpO2 level was 91.6±10.3 %, while more than half of pts (53.2 %) had SpO2 &lt; 95 % and almost every fourth (23.2 %) patient had SpO2 &lt; 90 %.Results and discussion. During the hospital period, 20 (14.4 %) pts died. The mortality rate was 28.0 % in pts with ADHF, 19.1 % in pts with AMI and significantly less in pts hospitalized for unstable angina, hypertensive urgency or atrial fibrillation – 5.2 % (p&lt;0.05 in comparison with pts with AMI or ADHF). The main cause of death was the development of cardiopulmonary failure – 14 (70.0 %) pts. 4 (20.0 %) pts died from AMI complications, 1 – from pulmonary embolism and 1 – from acute ischemic stroke. Two critical periods of in-hospital mortality can be distinguished: 1 – the first two days of hospitalization (mainly complications of acute cardiovascular pathology and thrombotic events); 2 – from 7 to 10 days after hospitalization (development of multiple organ failure due to hypoxia and heart failure progression). The mortality rate of patients with ACP and COVID-19 was significantly higher than that of simultaneously hospitalized patients without comorbid respiratory infection (14.4 % vs. 6.4 %, p=0.012) and patients who were hospitalized before the pandemic (14.4 % vs. 2.9 %, p&lt;0.001). Vaccinated patients were significantly less likely to develop acute kidney injury, acute hypoxic delirium, had higher average blood SpO2, and less often required non-invasive ventilation. Only 1 vaccinated patient died from the development of cardiogenic shock against the background of anterior AMI and multivessel coronary artery disease (mortality – 15.7 % in unvaccinated pts vs 5.0 % in vaccinated, p=0.076).Conclusions. Co-infection with COVID-19 worsens treatment outcomes and in-hospital mortality of patients with ACP. Vaccination significantly reduces the likelihood of complications and tends to reduce mortality.

PS-BPC05-7: HEMODYNAMIC MANAGEMENT OF RESISTANT HYPERTENSION

Background: Hypertension is the most prevalent chronic disease worldwide and is related to a high probability of cardiac disease, kidney disease and cerebrovascular events. Blood pressure measurement was used in the last decades to diagnose and guide antihypertensive therapy; however blood pressure is the result of the interaction of more complex hemodynamic parameters previously reserved for experimental studies or critical care patients management using invasive methods. Since 1996 few studies have proposed the use of hemodynamic parameters to classify and guide hypertension therapy with good results. Purpose: The present study's purpose was to measure hemodynamic parameters in patients with non-controlled resistant hypertension and use it to guide pharmacologic treatment to archive control blood pressure values according to the European Society of Cardiology guidelines. Methods: A total of 84 patients between 32 and 95 years old diagnosed with non-controlled primary resistant hypertension were recruited and after previous therapy washout hemodynamic parameters were measured using noninvasive Methods: preload by central venous pressure (CVP) using inferior vena cava diameter, cardiac index and systemic vascular resistance using Lyljestrand &amp; Zander modified formula. Patients were classified into 3 basic groups depending on which parameter was above normal value: hyperdynamic (HD) for high cardiac index &gt; 3.5 L/min/m2, fluid overload (FO) for CVP &gt; 8cmH2O and high systemic vascular resistance index (HSVRi) &gt; 2500 dynes/sec/m2/cm5, also 3 combined groups were a patient had 2 simultaneous hemodynamic alterations (HD+FO, HD+HSVRi and FO+HSRVi), according to this classification pharmacotherapy was guided indicating Bisoprolol in HD group, Amlodipine to HSVR patients and Hydrochlorothiazide to FO patients, in combined groups, combined therapy was given. Patients were observed for 6 months period taking as primary endpoint blood pressure control, acute cardiovascular events and hypotension. Results: A significant reduction of hemodynamic parameters and blood pressure was observed in the first month of treatment obtaining a 100% hemodynamic and blood pressure goals in all patients in the third month of therapy without hypotension or acute cardiovascular event during this period, the HD+FO group reach goals at the 6th month of treatment without reported complications. Conclusions: In this preliminary study we observed that hemodynamic guided high blood pressure control may be a valuable tool for a better understanding, classification and treatment in patients with resistant hypertension; however larger outcome studies confirm this hypothesis.

CRP/HDL-C and Monocyte/HDL-C ratios as Predictors of Metabolic Syndrome in Patients With Type 2 Diabetes Mellitus.

Metabolic syndrome (MetS) denotes a cluster of co-occurring medical conditions associated with regulating hyperglycemia and acute cardiovascular events and complications. The escalating frequency of MetS among individuals afflicted with type 2 diabetes mellitus (T2DM) underscores its burgeoning significance as a critical public health concern and a complex clinical conundrum. Timely identification is imperative to avert the expedited progression of diabetic complications. To investigate the role of CRP/HDL-C and Monocyte/HDL ratios in predicting MetS in T2DM individuals. The study was designed as a two-year prospective study and included 80 T2DM patients divided into MetS and non-MetS groups based on MetS development over two years. The patients' serums were analyzed for complete blood count parameters, lipid profile, and C-reactive protein (CRP). Based on the laboratory test results, Monocyte/HDL-C and CRP/HDL-C ratios were calculated and analyzed. The receiver operating characteristic (ROC) curve and their corresponding areas under the curve (AUC) were used to determine prognostic accuracy. Monocyte/HDL-C ratio and CRP/HDL-C ratio were significantly higher in MetS-T2DM2 than in nonMetS-T2DM (p=0.003 and p=0.029, respectively). The results of ROC curve analysis have shown that the CRP/HDL-C ratio (AUC of 0.695) and Monocytes/HDL-C ratio (AUC of 0.645) can serve as good predictors of MetS in T2DM patients. This study confirms the reliability of the Monocytes/HDL-C and CRP/HDL-C ratios as novel, simple, low-cost, and valuable predictors of MetS development in T2DM.

Treatment with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i): Current Evidence for Expanding the Paradigm?

Background: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are low-density lipoprotein cholesterol (LDL-C)-lowering drugs that play a critical role in lipoprotein clearance and metabolism. PCSK9i are used in patients with familial hypercholesterolemia and for the secondary prevention of acute cardiovascular events in patients with atherosclerotic cardiovascular disease (CVD). Methods: We focused on the literature from 2015, the year of approval of the PCSK9 monoclonal antibodies, to the present on the use of PCSK9i not only in the lipid field but also by evaluating their effects on metabolic factors. Results: PCSK9 inhibits cholesterol efflux from macrophages and contributes to the formation of macrophage foam cells. PCSK9 has the ability to bind to Toll-like receptors, thus mediating the inflammatory response and binding to scavenger receptor B/cluster of differentiation 36. PCSK9i lower the entire spectrum of apolipoprotein B-100 containing lipoproteins (LDL, very LDLs, intermediate-density lipoproteins, and lipoprotein[a]) in high CVD-risk patients. Moreover, PCSK9 inhibitors are neutral on risk for new-onset diabetes mellitus and might have a beneficial impact on the development of nonalcoholic fatty liver disease by improving lipid and inflammatory biomarker profiles, steatosis biomarkers such as the triglyceride-glucose index, and hepatic steatosis index, although there are no comprehensive studies with long-term follow-up studies. Conclusion: The discovery of PCSK9i has opened a new era in therapeutic management in patients with hypercholesterolemia and high cardiovascular risk. Increasingly, there has been mounting scientific and clinical evidence supporting the safety and tolerability of PCSK9i.

A Narrative Review on Exercise and Cardiovascular Disease: Physical Activity Thresholds for Optimizing Health Outcomes

The favorable risk factor profiles and superb cardiac performance of elite long-distance runners, as well as the anti-aging effects of exercise, have likely contributed to the escalating number of adults worldwide who have embraced the notion that “more exercise is invariably better.≵ Nevertheless, vigorous-to-high-intensity physical activity (PA), particularly when unaccustomed, appears to be a trigger for acute cardiac events in individuals with known or occult atherosclerotic cardiovascular disease or structural cardiovascular abnormalities, most notably, hypertrophic cardiomyopathy. Although regular endurance exercise and moderate-to-vigorous PA provide established cardioprotective benefits, high-volume, high-intensity exercise training regimens appear to induce maladaptive cardiac remodeling in some individuals. These potential adverse cardiac adaptations include accelerated coronary artery calcification (CAC), elevated cardiac biomarker release, myocardial fibrosis, and atrial fibrillation (AF), which may be described by a reverse J-shaped curve. However, the risk for acute cardiovascular events is lower in fit/active persons compared to their unfit/inactive counterparts with the same CAC scores. Similarly, the risk of AF is the highest in habitually sedentary older adults, decreases with light-to-moderate intensity regular PA but increases with high-volume, high-intensity exercise regimens (i.e., reverse J-shaped curve). This review examines these relations and more, with specific reference to the World Health Organization exercise intensity and duration recommendations for optimal health, as well as the thresholds for other research-based exercise metrics, including steps/day and the concept of metabolic equivalents-minutes/week. The primary beneficiaries of exercise training programs and long-term goal training intensities, based on age, sex, and “good≵ fitness, are also discussed. In summary, the benefits of regular moderate-to-vigorous PA and the associated improvements in cardiorespiratory fitness far outweigh the risks for most individuals.

Prognostic value of TAPSE/sPAP ratio among patients hospitalized in ICCU for acute cardiovascular event: Insights from the ADICCT-ICCU trial

Prognostic value of TAPSE/sPAP ratio among patients hospitalized in ICCU for acute cardiovascular event: Insights from the ADICCT-ICCU trial

S-57-2: THE GUT MICROBIOME AND CARDIOVASCULAR RISK FACTORS IN HUMANS

Animal studies to date have demonstrated the functional link between gut microbiota composition and cardiovascular outcomes, with specific microbial metabolites being involved. Examples of this include trimethylamine oxide (TMAO) involved atherosclerosis and more recently, studies proving that short chain fatty acids (SCFAs) acetate, butyrate and propionate are involved in blood pressure regulation and cardiovascular outcomes in animal models. At the same time, a number of epidemiological studies have highlighted the links in humans between gut microbiome composition and both hypertension and arterial stiffness. Additional factors involved in cardiovascular disease (CVD) risk that have come from human observational studies show that circulating levels of ceramides, GlycA (a marker of glycosylated acute phase proteins) and indole propionic acid (an antioxidant predictive of insulin resistance and arterial stiffness) are all modulated by the gut microbiome and alter cardiovascular risk in general. Dietary fiber supplementation results in reduced circulating levels of both GlycA and ceramides, both of which have been proven to be predictors of major acute cardiovascular events (MACE). Changes in gut microbiome composition induced by dietary interventions accompany decreases these markers of MACE. Formal mediation analyses of such data show that the effect of gut microbiome composition on the markers of MACE is mediated by increases in circulating levels of SCFAs. Butyrate, propionate and acetate activate the short fatty acid receptors FFAR2 and FFAR3 with different affinities, which might explain the different roles that these compounds play in blood pressure regulation and CVD outcomes. Furthermore, some SCFAs but not others are involved in modulation of the endocannabinoid system. Specifically, butyrate, but not propionate or acetate, affects endocannabinoid circulating levels and is involved in the gene expression levels of enzymes that modulate degradation of endocannbinoids. Importantly, butyrate levels can be modulated by diet but also by exercise. In addition, circulating levels of different SCFAs have different bacterial and host contributions, with serum levels of acetate being negligibly determined by gut microbiota composition (Figure 1). Joining together the evidence from human observational and interventional studies and the data from animal model data helps us delineate a complex series of interconnected pathways from bacterially produced SCFAs to blood pressure regulation and other cardiovascular outcomes, which are modifiable by both diet and exercise.