Atherosclerotic Risk Markers Research Articles

Pre-Prediabetes: Insulin Resistance is Associated with Cardiometabolic Risk in Non-obese Patients (STOP DIABETES).

To examine if insulin resistance is associated with markers of glycemic, cardiometabolic and atherosclerotic risk in non-obese, non-prediabetic individuals compared to insulin sensitive subjects matched for BMI, gender, and age. Of 1860 patients from STOP DIABETES study, 624 had normal fasting plasma glucose, body mass index < 30, and HbA1c < 5.7%. All received oral glucose tolerance test (OGTT). Insulin sensitivity was quantitated using Matsuda index: <25th percentile = Insulin Resistant (IR) (n=151) and ≥ 25th percentile = Insulin Sensitive (IS) (n=473). Measures of dysglycemia and cardiometabolic risk were compared between insulin resistant subjects (n=151) and subset of insulin sensitive individuals who were matched for BMI, gender, age (n=151). Carotid intima media thickness (CIMT) and carotid plaque were measured in 65 IR and 76 IS individuals. Compared to matched insulin sensitive patients, insulin resistant non-obese subjects demonstrated increased indicators of glycemic and cardiometabolic risk including: increased 60-minute plasma glucose and percentage of patients with 60-minute plasma glucose > 155mg/dL; increased 120-minute plasma glucose; unrecognized impaired glucose tolerance (IGT) and type 2 diabetes (T2D), decreased disposition index; increased systolic and diastolic blood pressure; elevated plasma triglycerides; reduced HDL cholesterol; increased triglyceride/HDL ratio and hs-CRP. The presence, size, and number of carotid plaques was greater in the insulin resistant group. Approximately 1 in 4 non-obese patients in this population with normal fasting glucose and HbA1c were insulin resistant. In these non-obese subjects, insulin resistance was associated with multiple indicators of dysglycemia and cardiometabolic risk.

Association Between Remnant Cholesterol and Contrast-Induced Nephropathy in Patients Undergoing Coronary Angiography and/or Percutaneous Coronary Intervention.

Contrast-induced nephropathy (CIN) is an acute renal complication that can occur after the use of iodinated contrast media. Remnant cholesterol (RC) is one of the markers of atherosclerotic cardiovascular disease risk. We evaluated the impact of RC on CIN and clinical outcomes after coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). Consecutive patients (n = 3332) undergoing CAG and/or PCI were assessed in this retrospective study. Patients were divided into four groups based on baseline RC levels. In the quartile analysis, RC were associated with a higher risk of CIN, especially when RC ≤0.20 or ≥0.38mmol/L (P < .05). However, after adjustment, the association of RC with CIN was not significant. There was a significant correlation between RC and repeated revascularization in patients undergoing PCI (P < .001) and driven primarily by the highest quartile level. After adjustment, this remained statistically significant (adjusted odds ratio (aOR) 4.06; 95% CI 2.10-7.87; P < .001). This is the first large study to show a possible association between RC and the risk of CIN after CAG and/or PCI; however, this finding was not further confirmed after adjustment. The complex clinical risk profile of patients, rather than RC itself, may contribute to the risk of CIN in this high-risk subgroup.

Evaluation of the eye findings of young male patients diagnosed with acute coronary syndrome compared to healthy individuals by optical coherence tomography angiography

Abstract Funding Acknowledgements Type of funding sources: None. Background It was aimed to evaluate retinal microvascular functions in optic coherence tomography - angiography (OCT-A) as a marker of atherosclerotic risk in young male patients followed up with Acute Coronary Syndrome (ACS). Methods This is a prospective study conducted in patients followed in our clinic with the diagnosis of ACS. Thirty male patients diagnosed with ACS and 30 healthy controls were included in the study. The patients in the ACS group underwent eye examination within the first 72 hours and selected parameters of the macular and circumpapillary vasculature, including macular vessel densities, foveal avascular zone, optic disc, were measured using OCT-A. The same measurements were made for those included in the similar age group in the control group and analyzed. Results In OCT-A measurements, the superficial and deep capillary plexus densities were found to be low in the ACS group, and the low superficial capillary plexus (SCP) density, especially in the perifoveal region, was noted (49.9-52.2, p:0.008). In addition, the foveal avascular zone was found to be higher in the ACS group (0.27-0.24, p:0.039). As expected, HDL values were lower and WBC and neutrophil values were higher in ACS patients (p&amp;lt;0.001). In addition, left ventricular ejection fraction (LVEF) was significantly lower in the ACS group compared to the control group (LVEF: 49.7%-63.1%, p&amp;lt;0.001, respectively). Conclusions Our results support the negative effects of atherosclerosis on retinal microvasculature in the newly diagnosed ACS group without known comorbidity and eye problems. Based on these findings, it was thought that the use of OCT-A in ophthalmic screening may be useful in predicting the atherosclerotic process.

Lipoprotein associated- phospholipase A2 in STEMI vs. NSTE-ACS patients: a marker of cardiovascular atherosclerotic risk rather than thrombosis.

A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included and divided according to presentation for non ST-segment elevation-ACS or ST-segment elevation Myocardial Infarction (STEMI). Lp-PLA2 activity was assessed in blood samples drawn at admission using the Diazyme Lp-PlA2 Activity Assay. We included in our study 117 patients, of whom 31 (26.5%) presented with STEMI. STEMI patients were significantly younger (p = 0.05), displayed a lower rate of hypertension (p = 0.002), previous MI (p = 0.001) and PCI (p = 0.01) and used less frequently statins (p = 0.01) and clopidogrel (p = 0.02). White blood cells and admission glycemia were increased in STEMI (p = 0.001, respectively). The prevalence and severity of CAD was not different according to ACS types, but for a higher prevalence of thrombus (p < 0.001) and lower TIMI flow (p = 0.002) in STEMI. The levels of Lp-PlA2 were significantly lower in STEMI as compared to NSTE-ACS patients, (132 ± 41.1 vs. 154.6 ± 40.9 nmol/min/mL, p = 0.01). In fact, the rate of patients with Lp-PlA2 above the median (148 nmol/min/mL) was significantly lower in STEMI patients as compared to NSTE-ACS (32.3% vs. 57%, p = 0.02, adjusted OR[95% CI] = 0.20[0.06-0.68], p = 0.010). Moreover, a direct linear relationship was observed between Lp-PlA2 and LDL-C (r = 0.47, p < 0.001), but not with inflammatory biomarkers. The present study shows that among ACS patients, the levels of Lp-PlA2 are inversely associated with STEMI presentation and thrombotic coronary occlusion, being instead increased in NSTE-ACS patients, therefore potentially representing a marker of more aggressive chronic cardiovascular disease with an increased risk of recurrent cardiovascular events.

Blood Markers of Inflammation, Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease.

Recent studies point toward a significant impact of cardiovascular processes and inflammation on Parkinson's disease (PD) progression. The aim of this study was to assess established markers of neuronal function, inflammation, and cardiovascular risk by high-throughput sandwich immune multiplex panels in deeply phenotyped PD. Proximity Extension Assay technology on 273 markers was applied in plasma of 109 drug-naive at baseline (BL) patients with PD (BL, 2-, 4-, and 6-year follow-up [FU]) and 96 healthy control patients (HCs; 2- and 4-year FU) from the de novo Parkinson's cohort. BL plasma from 74 individuals (37 patients with PD, 37 healthy control patients) on the same platform from the Parkinson Progression Marker Initiative was used for independent validation. Correlation analysis of the identified markers and 6 years of clinical FU, including motor and cognitive progression, was evaluated. At BL, 35 plasma markers were differentially expressed in PD, showing downregulation of atherosclerotic risk markers, eg, E-selectin and ß2 -integrin. In contrast, we found a reduction of markers of the plasminogen activation system, eg, urokinase plasminogen activator. Neurospecific markers indicated increased levels of peripheral proteins of neurodegeneration and inflammation, such as fibroblast growth factor 21 and peptidase inhibitor 3. Several markers, including interleukin-6 and cystatin B, correlated with cognitive decline and progression of motor symptoms during FU. These findings were independently validated in the Parkinson Progression Marker Initiative. We identified and validated possible PD plasma biomarker candidates for state, fate, and disease progression, elucidating new molecular processes with reduced endothelial/atherosclerotic processes, increased thromboembolic risk, and neuroinflammation. Further investigations and validation in independent and larger longitudinal cohorts are needed. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Significance of Insignificant Left Main Disease

Significance of Insignificant Left Main Disease

Exercise and Carotid Properties in the Young-The KiGGS-2 Study.

Background: Carotid intima-media thickness (cIMT) and stiffness (cS) are predictive markers of early vascular aging and atherosclerotic risk. This study assessed, whether exercise has protective effects on carotid structure and function or on vascular risk in the young.Methods: Volume and change of exercise (recreational and organized sports participation) of German adolescents and young adults was assessed within the prospective population-study KiGGS at KiGGS-Wave-1 (2009–2012) and KiGGS-Wave-2 (2014–2017) using standardized self-reporting questionnaires. CIMT and cS were measured by real-time B-mode ultrasound sequences with semi-automated edge-detection and automatic electrocardiogram-gated quality control in 2,893 participants (14–28 years, 49.6% female). A cumulative index for atherosclerotic risk (CV-R) included z-scores of mean arterial pressure, triglycerides, total/HDL-cholesterol-ratio, body mass index, and HbA1c.Results: At KiGGS-Wave-2 cross-sectional CV-R but not cS and cIMT was lower in all exercise-groups compared to “no exercise” (B = −0.73, 95%-CI = −1.26 to 0.19, p = 0.008). Longitudinal volume of exercise was negatively associated with CV-R (B = −0.37, 95%-CI = −0.74 to 0.00, p = 0.048) but not with cS and cIMT. Cross-sectional relative risk of elevated CV-R but not cS and cIMT was lower in all exercise-groups compared to “no exercise” (RR = 0.80, 95%-CI = 0.66 to 0.98, p = 0.033). High exercise volumes were associated with lower relative risk of elevated CV-R (RR = 0.80, 95%-CI = 0.65–0.97, p = 0.021) and cS in tendency but not with cIMT.Conclusions: Increased levels of exercise are associated with a better cardiovascular risk profile in young individuals, but not with cS and cIMT. Our study confirms previous recommendations on exercise in this age group without demonstrating a clear benefit on surrogate markers of vascular health.

Effectiveness of statin treatment in reducing red cell distribution width and mean platelet volume in patients with stable coronary artery disease: A retrospective study

Objectives: Mean platelet volume (MPV) has been shown to be a predictor of platelet activation and plays a crucial role in the pathogenesis of atherosclerosis. Red cell distribution width (RDW) is a measure of the variability of erythrocyte volumes and might reflect underlying chronic inflammation. Both MPV and RDW are related to increased risk for cardiovascular disease. Since statins have pleiotropic effects, we aim to investigate the effect of statins on this possible hematologic markers of atherosclerotic risk in stable coronary artery disease (CAD). Materials and Methods: One hundred and twenty-one statin-naive patients who had undergone coronary angiography for stable CAD between June 2012 and June 2013 were retrospectively enrolled in this study. Patients were treated with atorvastatin or rosuvastatin. The lipid profile and hematological parameters were measured at baseline and after statin treatment. Results: One hundred and twenty-one patients were included in the study. The mean age was 60.5 ± 9 years and 38% of patients were women. Out of 121 patients, 106 (87.6%) patients received atorvastatin therapy and 15 (12.4%) patients received rosuvastatin therapy. After a median follow-up period of 36 days, statin treatment markedly reduced low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels (P = 0.0001, for all). For hematological parameters, only RDW significantly decreased after statin treatment (P = 0.0001). The Δ RDW were not associated with Δ LDL-C (r = 0.03; P = 0.72), ΔTG (r = 0.06; P = 0.49) and Δ TC levels (r = 0.05; P = 0.55). Statins had no effect on MPV levels (P = 0.32). Conclusions: Statin therapy significantly reduces the RDW levels in stable CAD irrespective of cholesterol levels, which might confirm the anti-inflammatory effect of statins. However, the association between decreased RDW levels and prognosis in stable CAD has to be established by multi-center, prospective studies in large populations.

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients. MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured. ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation. ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.

Mild Mitochondrial Uncoupling Decreases Experimental Atherosclerosis, A Proof of Concept.

Aim: Atherosclerosis is responsible for high morbidity and mortality rates around the world. Local arterial oxidative stress is involved in all phases of atherosclerosis development. Mitochondria is a relevant source of the oxidants, particularly under certain risky conditions, such as hypercholesterolemia. The aim of this study was to test whether lowering the production of mitochondrial oxidants by induction of a mild uncoupling can reduce atherosclerosis in hypercholesterolemic LDL receptor knockout mice. Methods: The mice were chronically treated with very low doses of DNP (2,4-dinitrophenol) and metabolic, inflammatory and redox state markers and atherosclerotic lesion sizes were determined. Results: The DNP treatment did not change the classical atherosclerotic risk markers, such as plasma lipids, glucose homeostasis, and fat mass, as well as systemic inflammatory markers. However, the DNP treatment diminished the production of mitochondrial oxidants, systemic and tissue oxidative damage markers, peritoneal macrophages and aortic rings oxidants generation. Most importantly, development of spontaneous and diet-induced atherosclerosis (lipid and macrophage content) were significantly decreased in the DNP-treated mice. In vitro, DNP treated peritoneal macrophages showed decreased H2O2 production, increased anti-inflammatory cytokines gene expression and secretion, increased phagocytic activity, and decreased LDL-cholesterol uptake. Conclusions: These findings are a proof of concept that activation of mild mitochondrial uncoupling is sufficient to delay the development of atherosclerosis under the conditions of hypercholesterolemia and oxidative stress. These results promote future approaches targeting mitochondria for the prevention or treatment of atherosclerosis.

Association between 10-Year Atherosclerotic Cardiovascular Disease Risk and Vascular Endothelial Function in Patients with Vasospastic Angina

Background: Endothelial dysfunction is a predictor of atherosclerotic cardiovascular disease (ASCVD) and plays an important role in vasospastic angina (VA). Objectives: This study evaluated whether flow-mediated dilation (FMD) is also a good marker of 10-year ASCVD risk (10Y-ASCVDR) in patients with VA. Methods: Based on their clinical history and coronary artery diameter stenosis (DS), patients were retrospectively enrolled into VA (DS <50% and positive ergonovine provocation), minor coronary artery disease (mCAD, DS <30%), and significant coronary artery disease (sCAD, DS ≥50%) groups. Endothelial function was evaluated by FMD. Results: Each group contained 50 patients. The 10Y-ASCVDR was significantly higher in the sCAD group than in the VA and mCAD groups (10.86 ± 7.30, 4.71 ± 4.04, and 4.77 ± 4.30, respectively, p < 0.001). The FMD was significantly higher in the mCAD group than in the VA and sCAD groups (6.37 ± 4.25, 3.10 ± 2.23, and 3.07 ± 1.89, respectively, p < 0.001). A significant correlation was found between the FMD and 10Y-ASCVD in the mCAD group (r = −0.622, p < 0.001) and the sCAD group (r = −0.557, p < 0.001) but not in the VA group (r = −0.193, p = 0.179). After adjusting for potential confounders such as BMI, C-reactive protein, maximal coronary stenosis, and brachial-ankle pulse wave velocity, multivariate analysis showed that FMD was independently associated with 10Y-ASCVDR in all patients. However, when looking only at the VA group, FMD did not correlate independently with 10Y-ASCVDR. Conclusions: Unlike mCAD and sCAD, we found no correlation between 10Y-ASCVDR and endothelial function in VA. Thus, our results support that FMD is not a good marker of atherosclerotic cardiovascular risk in VA.

Evolving determinants of carotid atherosclerosis vulnerability in asymptomatic patients from the MAGNETIC observational study

MRI can assess plaque composition and has demonstrated an association between some atherosclerotic risk factors (RF) and markers of plaque vulnerability in naive patients. We aimed at investigating this association in medically treated asymptomatic patients. This is a cross-sectional interim analysis (August 2013–September 2016) of a single center prospective study on carotid plaque vulnerability (MAGNETIC study). We recruited patients with asymptomatic carotid atherosclerosis (US stenosis > 30%, ECST criteria), receiving medical treatments at a tertiary cardiac rehabilitation. Atherosclerotic burden and plaque composition were quantified with 3.0 T MRI. The association between baseline characteristics and extent of lipid-rich necrotic core (LRNC), fibrous cap (CAP) and intraplaque hemorrhage (IPH) was studied with multiple regression analysis. We enrolled 260 patients (198 male, 76%) with median age of 71-y (interquartile range: 65–76). Patients were on antiplatelet therapy, ACE-inhibitors/angiotensin receptor blockers and statins (196–229, 75–88%). Median LDL-cholesterol was 78 mg/dl (59–106), blood pressure 130/70 mmHg (111–140/65–80), glycosylated hemoglobin 46 mmol/mol (39–51) and BMI 25 kg/m2 (23–28); moreover, 125 out of 187 (67%) patients were ex-smokers. Multivariate analysis of a data-set of 487 (94%) carotid arteries showed that a history of hypercholesterolemia, diabetes, hypertension or smoking did not correlate with LRNC, CAP or IPH. Conversely, maximum stenosis was the strongest independent predictor of LRNC, CAP and IPH (p < 0.001). MRI assessment of plaque composition in patients on treatment for asymptomatic carotid atherosclerosis shows no correlation between plaque vulnerability and the most well-controlled modifiable RF. Conversely, maximum stenosis exhibits a strong correlation with vulnerable features despite treatment.

Markers of atherosclerotic risk in patients with non-alcoholic fatty liver disease: A preliminary study

Introduction: The prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD) is rising continuously. Cardiovascular disease is one among the leading causes of morbidity and premature mortality in patients with NAFLD. Aims and Objectives: To determine the risk of atherosclerosis in NAFLD subjects diagnosed by USG at K.S.Hegde Charitable hospital. Materials and Methods:A cross-sectional study involving 203 persons diagnosed with NAFLD were included in the study. Subjects with alcoholic liver disease, renal failure, tuberculosis, hepatitis B and/or C and those on lipid lowering drug were excluded from the study. Lipid profile was measured and Atherogenic Index of Plasma (AIP) was calculated as log (TG/HDL-c). Categorization of the subjects with respect to risk of atherosclerosis was done based on serum LDL-c, non HDL-c and AIP. Statistical analysis was done using Chi Square test and p value Results: More than normal values were observed for serum total cholesterol, LDL-c, triglyceride and non HDL-c in high percentage of NAFLD subjects (76.8%, 84.7%, 70.4% and 72.4% respectively). Serum HDL-c level was low in 53.2% subjects. 51.2% of subjects had high AIP and 23.6% had moderately high AIP. Conclusion: Results of categorization of the subjects with respect to risk of atherosclerosis based on serum LDL-c, non HDL-c and AIP showed that high percentages of subjects were in moderate and high risk categories. AIP is probably a better marker to determine the risk of atherosclerosis. Keywords: Atherogenic index of plasma, NAFLD, Non-alcoholic fatty liver disease, Lipids, Cardiovascular.

Carotid IMT and Stiffness in the KiGGS 2 National Survey: Third-Generation Measurement, Quality Algorithms and Determinants of Completeness

Carotid intima–media thickness (cIMT) and carotid stiffness (CS) are important markers of atherosclerotic risk in the young. We assessed a novel third-generation method for its applicability in large population-based epidemiologic studies to determine strengths, limitations, completeness and predictors of unsuccessful measurement. Four thousand seven hundred ninety-eight 14- to 31-y-old participants of the German KiGGS cohort, which is based on a nationally representative sample with 11-y follow-up, underwent B-mode ultrasound examinations of the left and right common carotid artery with semi-automatic edge detection and automatic electrocardiogram-gated real-time quality control based on a sophisticated snake algorithm and subpixel interpolation. Overall completeness was 98% for far wall cIMT and 89% for CS parameters. Plane-specific completeness varied from 92%–96% for far wall and from 64%–69% for near-wall cIMT. Obesity independently predicted unsuccessful cIMT and CS measurements with odds ratios of 12.67 (95% confidence interval: 5.50–29.19) and 7.30 (4.87–10.94) compared with non-overweight after adjustment for blood pressure, cholesterol, smoking, hazardous drinking, age, sex and sonographer. Inter- and intra-rater reliabilities of cIMT and CS parameters in a sample of 15 young adults were good or excellent. Third-generation cIMT and CS measurements in the young with semi-automatic edge-detection and automatic real-time quality control has been successfully standardized with high reliability and very high completeness in a national survey setting. This provides a strong methodological foundation for further validation of the predictive value of cIMT and CS for atherosclerotic risk in the young.

CORONARY VASOSPASM ASSOCIATED WITH 5-FLUOROURACIL CHEMOTHERAPY

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: 5-Fluorouracil (5FU) is the third most commonly used chemotherapeutic agent in the treatment of solid malignancies, particularly colorectal and pancreatic neoplasms. (1,2) Coronary vasospasm associated with 5FU is a known complication. (3) Cardiotoxicity occurs in 1% to 18% of patients receiving 5FU, and the incidence of this complication is on the rise.(4) The objective of this report is to highlight the characteristics of this uncommon complication. CASE PRESENTATION: A 66-year-old male with a past medical history of coronary artery disease status-post 4-vessel coronary artery bypass graft surgery and stage 4 colon adenocarcinoma with metastasis to the liver, presented to the emergency department (ED) with complaints of sudden onset of burning deep sub-sternal chest pain with no radiation. The chest pain began approximately eight hours after his first round of 5FU, leuocorin and eloxatin (FOLFOX) chemotherapy. In the ED he was given aspirin and heparin. EKG was concerning for ST-segment elevation myocardial infarction in the inferior leads. Troponins were negative (<0.01). A subsequent left heart catheterization revealed patent grafts and normal coronary arteries. An echocardiogram showed no acute wall motion abnormalities and an ejection fraction of 65%. The 5FU was discontinued and the patient’s chest pain improved. He was discharged with sublingual nitroglycerin and diltiazem. Two weeks later, the patient returned with similar chest pain after his second cycle with 5FU, leuocorin and eloxatin (FOLFOX). The symptoms of his coronary artery vasospasm were believed to be due to 5FU chemotherapy. He was further instructed to go to the cardiovascular ICU to receive nitroglycerine infusions before each cycle of FOLFOX. Unfortunately, the patient expired two months after starting chemotherapy; from cardiopulmonary arrest secondary to sepsis. DISCUSSION: This is a case of a 66-year-old male with a past medical history of coronary artery disease and stage 4 colon adenocarcinoma on 5-Fluorouracil, leuocorin and eloxatin (FOLFOX) chemotherapy presenting for coronary vasospasm likely from 5-Fluorouracil. Cardiotoxicity related to 5FU is poorly understood. Leading theories of the mechanism of 5FU-induced coronary vasospasm seem to involve 5FU's modification of smooth muscle tone. (5,6) Patients on 5FU with coronary vasospasm may have ECG findings suggestive of occlusion, (3) similar to our patient. Treatment of affected patients is determined by confirmation of 5FU as the definitive cause of the coronary vasospasm, as well as the requirement of 5FU as the only suitable chemotherapeutic agent. If possible, care providers should consider switching to an acceptable chemotherapeutic substitute. CONCLUSIONS: In conclusion, consideration should be given for patients with coronary artery disease starting 5-Fluorouracil chemotherapy. Reference #1: 1. Grem JL. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs 2000; 18: 299-313. 2. Myers CE. The pharmacology of the fluoropyrimidines. Pharmacol Rev 1981; 33: 1-15. 3. de Forni M, Malet-Martino MC, Jailais P, et al. Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. Clin Oncol 1992; 10: 1795-1801. 4. Lestuzzi C, Vaccher E, Talamini R, et al. Effort myocardial ischemia during chemotherapy with 5-fluorouracil: an underestimated risk. Ann Oncol 2014; 25: 1059-1064. 5. Bonetti PO, Lerman LO and Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arterioscler Throb Vasc Biol 2003, 23: 168-175. 6. Reddy KG, Nair RN, Sheehan HM, et al. Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for artherosclerosis. I Am Coll Cardio! 1994; 23: 833-843. DISCLOSURES: No relevant relationships by Ahmad ababneh, source=Web Response No relevant relationships by HANAD BASHIR, source=Web Response No relevant relationships by Ahmad JABRI, source=Web Response No relevant relationships by Gauranga Mahalwar, source=Web Response

Функциональное состояние сосудистой стенки и плазменного звена гемостаза у женщин раннего постменопаузального периода на фоне длительной менопаузальной гормональной терапии

Цель исследования: оценка изменений функциональной активности сосудистой стенки и плазменного звена гемостаза у женщин раннего постменопаузального периода на фоне длительной низкодозовой менопаузальной гормональной терапии (МГТ). Материалы и методы: Обследовано 162 женщины в ранней постменопаузе. В основную группу вошли 84 пациентки, которым была назначена низкодозовая МГТ: 1 мг 17β-эстрадиола (E2) и 2 мг дроспиренона (ДРСП) — препарат Анжелик® (Байер Фарма, Германия). Контрольную группу составили 78 женщин, не получавших МГТ. Длительность наблюдения составила 5,2 [4,8; 5,7] лет. Исследовали антитромбогенную активность сосудистой стенки, лабораторные маркеры эндотелиальной дисфункции. Результаты: Несмотря на увеличение агрегационной активности тромбоцитов и более низкие значения активности антитромбина III у женщин на фоне МГТ, не было отмечено увеличения риска развития венозного тромбоза и эмболий, ишемического инсульта и случаев острого коронарного синдрома. К окончанию наблюдения установлено снижение антиагрегационного потенциала сосудистой стенки, более выраженное у женщин группы кон-троля. У женщин, принимавших МГТ, выявлено снижение концентрации фибриногена крови к окончанию исследования. На фоне МГТ отмечено значимое возрастание уровня метаболитов оксида азота, снижение уровней эндотелина-1 и асимметричного диметиларгинина к 12 мес наблюдения, но в дальнейшем отмечено повышение их уровней, не достигшее исходных значений. Заключение: Изменения функциональной активности эндотелия свидетельствуют об отсутствии негативного влияния на эндотелий сосудов длительной низкодозовой МГТ (1 мг E2/2 мг ДРСП). Objectives: to assess changes in the functional activity of the vascular wall and plasma hemostasis in women of early postmenopausal period under long-term low-dose menopausal hormone therapy (MHT). Patients/Methods: We examined 162 women in early postmenopause. The main group included 84 patients; they were prescribed a low-dose MHT: 1 mg of 17β-estradiol (E2) and 2 mg of drospirenone (DRSP) — Angelique® (Bayer Pharma, Germany). The control group consisted of 78 women did not taking MHT. The duration of observation was 5.2 [4.8; 5.7] years. Antithrombogenic activity of the vascular wall and laboratory markers of endothelial dysfunction were examined. Results: In women taking MHT we found increasing of platelet aggregation activity and lower antithrombin III activity, but did not reveal increased risk of venous thrombosis and embolism, ischemic stroke, and cases of acute coronary syndrome. By the end of observation decreasing of antiplatelet potential of the vascular wall, more expressed in women of the control group, was noted. In women taking MHT, blood fi brinogen concentration decreased by the end of the study. After 12 months of observation in women taking MHT we revealed significant increasing of nitric oxide metabolites, decreasing of endothelin-1 and asymmetric dimethylarginine; later their levels increased but did not reach the initial values. Conclusions: Changes in endothelial functional activity showed no adverse effect of long-term low-dose MHT (1 mg E2/DRSP 2 mg) on the vascular endothelium.

Endothelial Dysfunction in Dyslipidaemia: Molecular Mechanisms and Clinical Implications.

The endothelium consists of a monolayer of Endothelial Cells (ECs) which form the inner cellular lining of veins, arteries, capillaries and lymphatic vessels. ECs interact with the blood and lymph. The endothelium fulfils functions such as vasodilatation, regulation of adhesion, infiltration of leukocytes, inhibition of platelet adhesion, vessel remodeling and lipoprotein metabolism. ECs synthesize and release compounds such as Nitric Oxide (NO), metabolites of arachidonic acid, Reactive Oxygen Species (ROS) and enzymes that degrade the extracellular matrix. Endothelial dysfunction represents a phenotype prone to atherogenesis and may be used as a marker of atherosclerotic risk. Such dysfunction includes impaired synthesis and availability of NO and an imbalance in the relative contribution of endothelialderived relaxing factors and contracting factors such as endothelin-1 and angiotensin. This dysfunction appears before the earliest anatomic evidence of atherosclerosis and could be an important initial step in further development of atherosclerosis. Endothelial dysfunction was historically treated with vitamin C supplementation and L-arginine supplementation. Short term improvement of the expression of adhesion molecule and endothelial function during antioxidant therapy has been observed. Statins are used in the treatment of hyperlipidaemia, a risk factor for cardiovascular disease. Future studies should focus on identifying the mechanisms involved in the beneficial effects of statins on the endothelium. This may help develop drugs specifically aimed at endothelial dysfunction.

The Role of the Oxidative Stress Markers in Endotelial Dysfunction at Cardiovascular Disease Patients

Although oxidative stress itself is directly associated with the occurrence of atherosclerosis, and together with endothelial dysfunction is a marker of atherosclerotic risk, none of these two markers were directly correlated with the presence of atherosclerosis. This study investigated the correlation between oxidative stress and endothelial dysfunction in people with cardiovascular disease. Furthermore, another objective of this paper is the direct study of the effect of a compound with antioxidant properties, selenium, on a model of endothelial dysfunction induced on human vascular fragments.

The impact of helical flow on coronary atherosclerotic plaque development

Background and aimsAtherosclerosis has been associated with near-wall hemodynamics and wall shear stress (WSS). However, the role of coronary intravascular hemodynamics, in particular of the helical flow (HF) patterns that physiologically develop in those arteries, is rarely considered.The purpose of this study was to assess how HF affects coronary plaque initiation and progression, definitively demonstrating its atheroprotective nature. MethodsThe three main coronary arteries of five adult hypercholesterolemic mini-pigs on a high fat diet were imaged by computed coronary tomography angiography (CCTA) and intravascular ultrasound (IVUS) at 3 (T1, baseline) and 9.4 ± 1.9 (T2) months follow-up. The baseline geometries of imaged coronary arteries (n = 15) were reconstructed, and combined with pig-specific boundary conditions (based on in vivo Doppler blood flow measurements) to perform computational fluid dynamic simulations. Local wall thickness (WT) was measured on IVUS images at T1 and T2, and its temporal changes were assessed. Descriptors of HF and WSS nature were computed for each model, and statistically compared to WT data. ResultsHF intensity was strongly positively associated with WSS magnitude (p < 0.001). Overall, coronary segments exposed to high baseline levels of HF intensity exhibited a significantly lower WT growth (p < 0.05), compared to regions with either mid or low HF intensity. ConclusionsThis study confirms the physiological significance of HF in coronary arteries, revealing its protective role against atherosclerotic WT growth and its potential in predicting regions undergoing WT development. These findings support future in vivo measurement of coronary HF as atherosclerotic risk marker, overcoming current limitations of in vivo WSS assessment.

Mining possible associations of faecal A. muciniphila colonisation patterns with host adiposity and cardiometabolic markers in an adult population.

We aimed to evaluate colonisation patterns of Akkermansia muciniphila in a Greek adult population and to investigate model-adjusted associations of A. muciniphila with host adiposity and cardiometabolic markers. Participants (n=125) underwent anthropometric, dietary, physical activity and lifestyle evaluation. Blood sampling for determination of blood lipid indices, glucose metabolism, adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), inflammation and oxidative stress parameters was also performed. Stool A. muciniphila presence and levels were determined by quantitative PCR and subjects were grouped based on bimodal distribution of levels (Low vs High). A. muciniphila was detected in 88.6% of participants. Overweight/obese (OW/OB) subjects were more prone in low bimodal levels of A. muciniphila compared to normal-weight (NW) individuals (58.75 vs 27.59%, P=0.004), with a 4-time greater likelihood after multi-adjusted logistic regression analysis (P=0.016). Levels of A. muciniphila were negatively associated with total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) ratio (log10:-0.009±0.004, P=0.033), whereas detection of this bacterium was negatively associated with both TC/HDL-C ratio (log10: -0.049±0.023, P=0.036) and low-density lipoprotein cholesterol/HDL-C ratio (-0.407±0.176, P=0.023). Furthermore, low bimodal levels of A. muciniphila were positively associated with fasting blood glucose (log10: 0.018±0.009, P=0.037). In terms of inflammation markers, levels of A. muciniphila were positively associated with soluble cluster of differentiation-14 (sCD14) (log10: 0.012±0.004, P=0.003) and faecal detection of this bacterium had a positive association with anti-inflammatory interleukin 10 levels (log10: 0.325±0.131, P=0.015). In addition, A. muciniphila levels were positively associated with total adiponectin (log10: 0.046±0.015, P=0.002), whereas low bimodal levels of A. muciniphila had an inverse relationship with this blood marker (log10: -0.131±0.053, P=0.016). In conclusion, we confirmed the previously reported association of A. muciniphila with metabolic health for the first time in a Greek urban population; furthermore, we shed some light to novel atherosclerotic risk markers with rather unexplored connections with A. muciniphila colonisation patterns in human subjects.