Multiple Cardiovascular Risk Factors Research Articles

Coronary microvascular dysfunction in postmenopausal minipigs with multiple risk factors

Abstract Background Coronary microvascular angina occurs in both men and women, however, the majority of patients are postmenopausal women with multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia. No treatment is available for coronary microvascular dysfunction, requiring more in depth knowledge on the mechanisms underlying this syndrome in this expanding group of patients. Purpose Here we studied microvascular function in vivo and and in vitro in isolated small coronary arteries, in post-menopausal miniswine with multiple cardiovascular risk factors. Methods DM (streptozotocin), hypercholesterolemia (HC, high fat, high sugar diet), CKD (renal artery embolization) and menopause (ovariectomy, OVX) were induced in 5 adult female minipigs (1.5-2 years old, ~40kg, DM+HC+CKD+OVX) for 6 months, while 11 healthy age- and weight-matched female minipigs on normal pig chow served as controls (Normal). At sacrifice, coronary flow reserve (CFR) in response to intracoronary infusion of adenosine was measured under anesthesia. Isolated small coronary arteries were used to study the endothelium-dependent response to bradykinin in the presence and absence of eNOS blockade with LNAME, and cyclooxygenase inhibition by indomethacin, and endothelium-independent response to the nitric oxide (NO) donor, SNAP. Results 6 months of sustained hyperglycemia (17.5±1.0 in DM+HC+CKD+OVX vs 8.2±0.9 mmol/l in Normal, P<0.05 by t-test), hypercholesterolemia (15.4±2.0 vs 1.7±0.1 mmol/l, P<0.05), renal dysfunction (NGAL: 205±72 vs 67±5 ng/ml, P<0.05) and low progesterone levels (13.1±5.7 in DM+HC+CKD+OVX vs 92.0±30.0 nmol/l in Normal, P=0.1) were accompanied by systemic inflammation (TNFα: 62±7 vs 47±1 pg/ml, P<0.05). CFR was significantly reduced in DM+HC+CKD+OVX as compared to the healthy animals (panel A). Coronary small arteries from DM+HC+CKD+OVX animals showed impaired endothelium-dependent vasodilation to bradykinin (panel B), which was mediated by a loss of NO (panels C & D). The loss of NO was partly compensated for by activation of the cyclooxygenase pathway, as indomethacin blunted the dilation to bradykinin in the DM+HC+CKD+OVX animals, but had no effect on the dilation to bradykinin in Normals (panels C & D). Endothelium-independent dilation to SNAP was also impaired in DM+HC+CKD+OVX animals, indicating blunted vascular smooth muscle responsiveness to nitric oxide (panel E). Conclusion Postmenopausal minipigs with multiple risk factors, displayed severe coronary microvascular dysfunction as evidenced by a significantly reduced coronary flow reserve and both reduced NO sensitivity/ production, indicating endothelial and smooth muscle cell dysfunction. Loss of NO-mediated vasodilation was partially compensated by activation of cyclooxygenase pathway. Such perturbations may contribute to reduced myocardial perfusion that is often observed in post-menopausal women with multiple cardiovascular risk factors.

Absence of coronary artery disease in high-risk sickle cell anemia patients: a new illustration supporting the protective effect of Bilirubin against atherosclerosis?

Abstract Background Sickle cell anemia (SCA) is associated with both cardiac and systemic vascular disorders, which are the leading cause of morbi-mortality. Although these patients cumulate multiple cardiovascular (CV) risk factors, along with chronic inflammation and endothelial activation, some pre-clinical studies underlined a paradoxical protection against atherosclerosis. Purpose The aim of this study was to evaluate the prevalence of coronary artery disease in a high-risk SCA population. Methods From January 2019 to December 2023, consecutive adult patients with SCA were prospectively included in the DREPACOEUR registry to specifically analyze cardiac structure and function. They all had a comprehensive CV evaluation at steady-state in day-hospital including clinical exam, cardiac imaging, rhythm monitoring along with biology analysis. Only patients that underwent coronary imaging (CT coronary angiogram) were included in this study. Results Ninety patients were included. Mean age was 44±12, 50% were male with a high prevalence of systemic hypertension (57%), obstructive sleep apnea (21%) and 10% smokers. Only one patient had history of diabetes while no dyslipidemia (or lipid lowering therapy) was reported. Heart function was mainly preserved with a mean left ventricular ejection fraction (LVEF) of 58±5%. Expectedly, patients showed low hemoglobin level 8,7±1.4g/dL with high hemolysis markers. Glomerular filtration rate was 109 [62; 122] mL/min/m² with 21% having chronic kidney disease. Plasmatic LDLc level was low (0.7±0.3g/L, with 20% <0.5g/l) while triglycerides (TG) were highly variable (1.1±0.7mg/dL). Strikingly, no patient showed signs of significant coronary artery disease, with 87% presenting a calcium score of 0, 77% had a CAD-RADS of 0 while no patient was higher than 2. Correlation and linear regression analysis were performed to find independent parameters associated with LDLc and TG. Total bilirubin was the only variable that correlated with both LDLc and TG (R= -0.37, p<0.001 and R= -0.33, p=0.001 respectively). Conclusion Despite systemic vasculopathy and chronic inflammation, ageing SCA patients showed no significant coronary artery disease. These data are in line with pre-clinical studies suggesting a lipid-lowering role of bilirubin and its protective effect against atherosclerosis.

Uric acid is associated with increased risk of myocardial infarction: results from NHANES 2009-2018 and bidirectional two-sample Mendelian randomization analysis.

Although a growing number of studies have shown that elevated uric acid (UA) levels are associated with multiple cardiovascular risk factors and progression of coronary artery disease, the causal relationship between UA and the occurrence of myocardial infarction (MI) remains uncertain. The aim of this study was to investigate the relationship between UA and the risk of MI. We screened 23,080 patients in the National Health and Nutrition Examination Survey (NHANES) database for 2009-2018 and explored the association between UA and MI risk using multivariate logistic regression model. In addition, a two-way two-sample Mendelian randomization (TSMR) analysis was performed to examine the causal relationship of UA on MI, and inverse variance-weighted (IVW) results were used as the primary outcome in this study. Sensitivity analysis and horizontal multiple validity test were also performed to verify the reliability of the results. After multivariable adjustment, individuals with the severe elevation of UA levels have a significantly increased risk of MI (OR=2.843, 95%CI: 1.296-6.237, P=0.010). In TSMR analysis, the IVW method demonstrated a significant association between UA and increased risk of MI (OR=1.333, 95%CI: 1.079-1.647, P=0.008). Results from the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO test all suggest the reliability of the IVW analysis. Reverse TSMR analysis did not indicate a causal relationship between genetic susceptibility to MI and UA levels (IVW: OR=1.001, 95%CI: 0.989-1.012, P=0.922). Based on cross-sectional study and Mendelian randomization analysis, it has been demonstrated that UA is an independent risk factor for MI. Elevated levels of UA increase the risk of MI, particularly in cases of severe elevation.

Long-term efficacy and safety of dose-dense and dose-intense ABVD without consolidation radiotherapy in patients with advanced Hodgkin lymphoma: A 15-year follow-up of the ABVDDD-DI phase II study.

We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVDDD-DI) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVDDD-DI without uneven late toxicities.

Hypothalamic Gliosis is Associated With Multiple Cardiovascular Disease Risk Factors.

Hypothalamic gliosis is mechanistically linked to obesity and insulin resistance in rodent models. We tested cross-sectional associations between radiologic measures of hypothalamic gliosis in humans and clinically relevant cardiovascular disease risk factors, as well as prevalent coronary heart disease. Using brain MRI images from Framingham Heart Study participants (N=867; mean age, 55 years; 55% females), T2 signal intensities were extracted bilaterally from the region of interest in the mediobasal hypothalamus (MBH) and reference regions in the amygdala (AMY) and putamen (PUT). T2 signal ratios were created in which greater relative T2 signal intensity suggests gliosis. The primary measure compared MBH to AMY (MBH/AMY); a positive control ratio (MBH/PUT) also assessed MBH whereas a negative control (PUT/AMY) did not. Outcomes were BMI, HDL-C, LDL-C, fasting triglycerides, and the presence of hypertension (n=449), diabetes mellitus (n=66), metabolic syndrome (n=254), or coronary heart disease (n=25). Dietary risk factors for gliosis were assessed in a prospective analysis. Statistical testing was performed using linear or logistic regression. Greater MBH/AMY T2 signal ratios were associated with higher BMI (β = 21.5 [95% CI, 15.4-27.6]; P<0.001), higher fasting triglycerides (β = 1.1 [95% CI, 0.6-1.7]; P<0.001), lower HDL-C (β = -20.8 [95% CI, -40.0 to -1.6]; P=0.034), and presence of hypertension (odds ratio, 1.2 [95% CI, 1.1-1.4]; P=0.0088), and the latter two were independent of BMI. Findings for diabetes mellitus were mixed and attenuated by adjusting for BMI. Metabolic syndrome was associated with MBH/AMY T2 signal ratios (odds ratio, 1.3 [95% CI, 1.1-1.6]; P<0.001). Model results were almost uniformly confirmed by the positive control ratios, whereas negative control ratios that did not test the MBH were unrelated to any outcomes (all P≥0.05). T2 signal ratios were not associated with prevalent coronary heart disease (all P>0.05), but confidence intervals were wide. Self-reported percentages of macronutrient intake were not consistently related to future T2 signal ratios. Using a well-established study of cardiovascular disease development, we found evidence linking hypothalamic gliosis to multiple cardiovascular disease risk factors, even independent of adiposity. Our results highlight the need to consider neurologic mechanisms to understand and improve cardiometabolic health.

Thyroid hormones and oxidative stress moderated the association between urinary phthalate metabolites and cardiovascular risk factors

While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations.

Cardiovascular disease in thymic cancer patients.

Cancer patients may have increased risk for adverse cardiac events, but our understanding of cardiovascular risk in thymic cancer patients is not clear. We sought to characterize baseline cardiometabolic risk factors before thymic cancer diagnosis and the potential association between cancer treatment and subsequent cardiac events. This was a retrospective cohort study evaluating patients with thymic cancer from 2003 to 2020 compared to age- and sex-matched controls without cancer. Baseline cardiovascular risk factors, cancer characteristics, and incidence of cardiac events were collected from the health information exchange. Multivariable regression was used to examine the impact of cardiovascular risk factors and cancer therapies. We compared 296 patients with pathology-confirmed thymic cancer to 2,960 noncancer controls. Prior to cancer diagnosis, thymic cancer patients (TCPs) had lower prevalence of hypertension, dyslipidemia, and diabetes mellitus and similar rates of obesity, tobacco use, and pre-existing cardiovascular disease (CVD) compared to controls. After diagnosis, high-risk TCPs (>2 cardiovascular risk factors or pre-existing CVD) had higher risk for cardiac events (HR 3.73, 95% CI 2.88-4.83, p < 0.001). In the first 3 years after diagnosis, TCPs had higher incidence of cardiac events (HR 1.38, 95% CI 1.01-1.87, p = 0.042). High-risk TCPs who received radiotherapy or chemotherapy had higher risk of cardiac events (HR 4.99, 95% CI 2.30-10.81, p < 0.001; HR 6.24, 95% CI 2.84-13.72, p < 0.001). Compared to noncancer controls, TCPs experienced more cardiac events when adjusted for risk factors. Patients with multiple cardiovascular risk factors receiving radiotherapy or chemotherapy had higher incidence of cardiac events.

Even a low comorbidity burden predicts poor outcome in chronic heart failure.

Patients with heart failure (HF) often have multiple cardiovascular risk factors (CVRF) and comorbidities (CMB). We evaluated the impact of additive CMB and CVRF in HF prognosis. We retrospectively analyzed ambulatory patients with systolic dysfunction between January 2012 and May 2018. Follow-up: until January 2021. Endpoint: all-cause death. CVRF analyzed: Arterial hypertension, Diabetes mellitus and smoking. CMB evaluated: coronary artery disease, non-coronary atherosclerotic disease, respiratory disease, dementia, anemia, chronic kidney disease, inflammatory/autoimmune disease, active cancer and atrial fibrillation. Classification according to the number of CVRF and/or CMB: < 2 and ≥ 2. The independent prognostic impact of CVRF/CMB burden was assessed with multivariate Cox-regression. Most patients had ≥ 2 CMB (67.9%). Regarding CVRF, 14.9% presented none, 40.2% had one and 32.1% had two. During a median 49-month follow-up, 419 (49.1%) patients died. Mortality was higher among patients with ≥2 CVRF (56.1 vs 43.4% in those with <2) and in those with ≥2 CMB (57.7 vs 31.0%). While patients with one CMB had similar mortality than those with none. Patients with ≥2 CMB had higher long-term mortality risk: HR=2.47 (95% CI: 1.95-3.14). In patients with ≥2CVRF: HR of dying = 1.39 (1.14- 1.70). When taken together there was a clear survival disadvantage for patients with ≥ 2 CVRF/CMB - adjusted HR: 2.20 (1.45-3.34). The presence of only 2 CVRF/CMB more than doubles the patients´ risk of dying. CVRF and CMB should be assessed as part of routine patient management.

Cardiac risk in elderly individuals attended by basic health units

The objective was to assess the cardiac risk of elderly individuals attending Basic Health Units (UBS) in the North and South zones of Aracaju, SE. To achieve this objective, the study employed the Framingham Risk Score, which takes into account multiple cardiovascular risk factors, including age, blood pressure, heart rate, cholesterol levels, body composition, and other pertinent indicators. It's worth noting that some of these factors can be modified, while others cannot. A total of 76 elderly individuals participated in the study ( = 67 ± 6.07 years). The highest mean values for cardiovascular risk factors were found for total cholesterol ( = 199.10 ± 43.57 mg/dL) and low density lipoprotein ( = 129.57 ± 34.85 mg/dL), followed by the systolic blood pressure ( = 124.8 ± 19.88 bpm). The cardiovascular risk of the sample group was characterized as high ( = 0.29% ± 1.5%). Furthermore, the mentioned percentage delta reflects the change in value over a specific period, providing insights into relative changes in a dynamic context. The outcome of this study was a comprehensive assessment of the cardiac risk in these UBS attendees, contributing to the understanding and appropriate treatment of cardiovascular conditions in this population.

Mediterranean diet effects on vascular health and serum levels of adipokines and ceramides.

A randomized clinical trial to evaluate the effect of a Mediterranean-style diet on vascular health indices such as endothelial function indices, serum lipid and ceramide plasma and some adipokine serum levels. We recruited all consecutive patients at high risk of cardiovascular diseases admitted to the Internal Medicine and Stroke Care ward at the University Hospital of Palermo between September 2017 and December 2020. The enrolled subjects, after the evaluation of the degree of adherence to a dietary regimen of the Mediterranean-style diet, were randomised to a Mediterranean Diet (group A) assessing the adherence to a Mediterranean-style diet at each follow up visit (every three months) for the entire duration of the study (twelve months) and to a Low-fat diet (group B) with a dietary "counselling" starting every three months for the entire duration of the study (twelve months).The aims of the study were to evaluate: the effects of adherence to Mediterranean Diet on some surrogate markers of vascular damage, such as endothelial function measured by means of the reactive hyperaemia index (RHI) and augmentation index (AIX), at the 6-(T1) and 12-month (T2) follow-ups; the effects of adherence to Mediterranean Diet on the lipidaemic profile and on serum levels of ceramides at T1 and T2 follow-ups; the effects of adherence to Mediterranean Diet on serum levels of visfatin, adiponectin and resistin at the 6- and 12-month follow-ups. A total of 101 patients were randomised to a Mediterranean Diet style and 52 control subjects were randomised to a low-fat diet with a dietary "counselling". At the six-month follow-up (T1), subjects in the Mediterranean Diet group showed significantly lower mean serum total cholesterol levels, and significantly higher increase in reactive hyperaemia index (RHI) values compared to the low-fat diet group. Patients in the Mediterranean Diet group also showed lower serum levels of resistin and visfatin at the six-month follow-up compared to the control group, as well as higher values ​​of adiponectin, lower values of C24:0, higher values of C22:0 and higher values of the C24:0/C16:0 ratio. At the twelve-month follow-up (T2), subjects in the Mediterranean Diet group showed lower serum total cholesterol levels and lower serum LDL cholesterol levels than those in the control group. At the twelve-month follow-up, we also observed a further significant increase in the mean RHI in the Mediterranean Diet group, lower serum levels of resistin and visfatin, lower values of C24:0 and of C:18:0,and higher values of the C24:0/C16:0 ratio. The findings of our current study offer a further possible explanation with regard to the beneficial effects of a higher degree of adherence to a Mediterranean-style diet on multiple cardiovascular risk factors and the underlying mechanisms of atherosclerosis. Moreover, these findings provide an additional plausible interpretation of the results from observational and cohort studies linking high adherence to a Mediterranean-style diet with lower total mortality and a decrease in cardiovascular events and cardiovascular mortality. ClinicalTrials.gov Identifier: NCT04873167. https://classic.clinicaltrials.gov/ct2/show/NCT04873167.

#2885 Thrombosis complicating the first native arteriovenous fistula: what are the risk factors?

Abstract Background and Aims The native arteriovenous fistula is considered the best vascular access for hemodialysis, whose ultimate complication is thrombosis. The risk factors for this complication are multiple. The aim of our work is to determine the risk factors for thrombosis of the first created native AVF. Method This is a retrospective descriptive study of 65 patients over 18 years of age and hemodialyzed in our department who benefited of the confection of a native arteriovenous fistula at the same hospital. Results Arteriovenous fistula thrombosis occurred in 41.53% of patients with an average age of 49.4 years and a sex ratio M/F=3.5. 59.2% of arteriovenous fistulae were distal versus 40.7% proximal, divided into humerocephalic (29.6%) and humerobasilic (11.1%). AVF thrombosis occurred after a mean duration of 3.19 years after its confection [01 months, 13 years]. 25.9% of arteriovenous fistulae had not yet been punctured. 63% of patients were smokers, 55.6% were diabetics, 74.1% were hypertensive and 66.7% were cardiac with predomination of ischemic etiology in 29.6%. 44.4% of patients had obliterative arteriopathy of the lower limbs, 25.9% of whom were amputees. Patients had been on dialysis for an average of 4.4 years [01 months, 13 years], with diabetic nephropathy predominating at 51.9%. All patients were on antiplatelet therapy and 7.4% on anticoagulation. 11.1% had perdialytic hypotension. Multivariate statistical analysis revealed a significant correlation between anemia, diabetes and the occurrence of thrombosis (respectively p = 0.03; p = 0.024). Conclusion Patients with arteriovenous fistula thrombosis have multiple cardiovascular risk factors. Diabetes and anemia remain the main predictive factors for thrombosis.

MULTIDRUG RESISTANT DYSLIPIDEMIA: A CASE REPORT

Abstract Introduction Recently introduced lipid–lowering agents (PCSK9–i, bempedoic acid) can efficiently treat statin–intolerant patients, who couldn‘t reach LDL target before. Nonetheless, there are still cases where the pharmacological management may have strong limitations. Case Report A 71 year–old woman, with multiple cardiovascular risk factors (diabetes, hypertension and familial dylipidemia, LDL–C 276) underwent heart transplantation for a hypertrophic cardiomyopathy with an evolution towards a dilated phenotype in 2005. Before the transplant, she was on low–dose statin treatment (pravastatin 10 mg/die) that was suspended years later owing to hyper–CKemia (600 U/L), despite her being totally asymptomatic. A second attempt with simvastatin/ezetimibe 40/10 mg resulted again in elevation of CK levels, associated with significant muscular pain. Thus, just ezetimibe was continued. In 2020, 15 years after the transplant, the patient underwent a coronary angiography showing a moderate coronary allograft vasculopathy (ISHLT CAV2). Specifically, a sub occlusive ostial left main coronary artery lesion was treated by percutaneous angioplasty and stent implantation. Since a lower LDL target was needed (LDL–C 55 mg/dL), Alirocumab was introduced. However, 6 months later, no significant LDL levels reduction had been observed. The shift to evolocumab led to the same result, although the patient reported full therapeutic compliance. In the suspicion of anti–drug antibodies development, we opted for Inclisiran without achieving a significant decrease in LDL–C levels. In parallel with the search for genetic mutations in the PCSK9 gene and other genes involved in cholesterol metabolism (including LDLR, APOB, and LDLRAP1 and resulting positive only for common variants in LDLR receptor), therapy with bempedoic acid was initiated, again without substantial benefit (LDL–C 118 mg/dL). Conclusion Despite cholesterol management has been simplified by the introduction of new drugs, it may still be complex in patients requiring very low LDL–C levels in some specific cases. Drugs with a LDL receptor–independent mechanism of action (e.g., evinacumab) may allow the achievement of therapeutic goals suggested by clinical guidelines.

ACUTE CORONARY SYNDROME IN A PATIENT WITH LEFT SUBCLAVIAN OCCLUSION AND ANTEROLATERAL CORONARY STEAL

Abstract This is a 57–year–old male patient suffering from multiple cardiovascular risk factors: obesity, arterial hypertension, dyslipidemia, type 2 diabetes mellitus, active smoker. Chronic obstructive pulmonary disease. Stage 2 chronic kidney disease. Peripheral vascular disease with previous bilateral thromboendarterectomy and percutaneous revascularization of the lower limbs. Stable angina for which three years ago he underwent Coronary Artery Bypass Graft: left internal mammary artery (LIMA) to left anterior descending artery combined with saphenous vein grafts to the main obtuse marginal branch. The patient presented with Acute Coronary Syndrome non ST–segment elevation myocardial infarction (N–STEMI), intermittent episodes of chest pain due to mild exertion in the previous days. Antero–lateral ST depression and inverted T waves, associated with a mild reduction in left ventricular systolic function due to hypokinesia of the antero–lateral walls and increased troponin values were present. Coronary angiography documented patency of the LIMA graft without evidence of any culprit lesions on the coronary branches. However, selective angiography documented a sub–occlusion of the proximal left subclavian artery (Figure 1). A computed tomography scan confirmed a hyperdense calcified plaque occluding 95% of the origin of the left subclavian artery. The patient then underwent angioplasty with stenting of the left subclavian artery (Figure 2). Subclavian coronary steal syndrome usually presents with exertional angina, but rarely can cause Acute Coronary Syndrome. During coronary angiography performed for Acute Coronary Syndrome and in the absence of detection of clear coronary culprit lesions, selective angiography of the subclavian artery may confirm the suspicion of coronary steal syndrome.

Cardiac evaluation in amiodarone-induced thyroid dysfunction with suspected cardiac ischemia?: a case report and review of the literature

BackgroundAmiodarone-induced thyroid dysfunction (AIT) is a side-effect associated with the use of Amiodarone for the treatment of refractory arrythmias. Resulting hyperthyroidism can precipitate cardiac complications, including cardiac ischemia and myocardial infarction, although this has only been described in a few case reports.Case presentationWe present here a clinical scenario involving a 66-year-old male Caucasian patient under Amiodarone for atrial fibrillation, who developed AIT. In the presence of dyspnea, multiple cardiovascular risk factors and ECG abnormalities, a transthoracic echocardiogram was performed, showing inferobasal hypokinesia. This led to further investigations through a cardiac PET-CT, where cardiac ischemia was suspected. Ultimately, the coronary angiography revealed no abnormalities. Nonetheless, these extensive cardiologic investigations led to a delay in initiating an emergency endovascular revascularization for acute-on-chronic left limb ischemia. Although initial treatment using Carbimazole was not successful after three weeks, the patient reached euthyroidism after completion of the treatment with Prednisone so that eventually thyroidectomy was not performed. Endovascular revascularization was finally performed after more than one month.ConclusionsWe discuss here cardiac abnormalities in patients with AIT, which may be due to relative ischemia secondary to increased metabolic demand during hyperthyroidism. Improvement of cardiac complications is expected through an optimal AIT therapy including medical therapy as the primary approach and, when necessary, thyroidectomy. Cardiac investigations in the context of AIT should be carefully considered and may not justify delaying other crucial interventions. If considered mandatory, diagnostic procedures such as coronary angiography should be preferred to functional testing.

Coronary microvascular dysfunction in postmenopausal minipigs with multiple risk factors

Coronary microvascular angina occurs in both men and women, however, the majority of patients are postmenopausal women with multiple cardiovascular risk factors, such as diabetes mellitus (DM), chronic kidney disease (CKD) and dyslipidemia. No treatment is available for coronary microvascular dysfunction, requiring more in depth knowledge on the mechanisms underlying this syndrome in this expanding group of patients. Here we studied microvascular function in vivo and and in vitro in isolated small coronary arteries, in postmenopausal miniswine with multiple cardiovascular risk factors. DM (streptozotocin), hypercholesterolemia (HC, high fat, high sugar diet), CKD (renal artery embolization) and menopause (OVX) were induced in 5 adult female minipigs (1.5-2 years old, ±40kg, DM+HC+CKD+OVX) for 6 months, while 11 healthy female minipigs matched for age and weight, on normal pig chow served as controls (Control). At sacrifice, coronary flow reserve (CFR) in response to intracoronary infusion of adenosine was measured under anesthesia, and endothelium-dependent response to bradykinin in the presence and absence of eNOS blockade with LNAME, were studied in vitro in isolated small coronary arteries. 6 months of sustained hyperglycemia (17.5±1.0 in in DM+HC+CKD+OVX vs 8.2±0.9 mmol/l in Control), hypercholesterolemia (15.4±2.0 vs 1.7±0.1 mmol/l) and renal dysfunction (plasma total protein: 84±3 vs 72±1 g/l) were accompanied by systemic inflammation (TNFalpha: 62±7 vs 47±1 pg/ml, all p&lt;0.05 by t-test). Coronary flow reserve was significantly reduced in animals with multiple risk factors (3.4±0.4 in DM+HC+CKD+OVX) as compared to the healthy animals (4.9±0.3 in Control, p&lt;0.05). In vitro, coronary small arteries from DM+HC+CKD+OVX animals showed impaired endothelium-dependent vasodilation to bradykinin, which was mediated by a loss of nitric oxide. Conclusion: Postmenopausal minipigs with multiple risk factors, displayed severe coronary microvascular dysfunction as evidenced by a significantly reduced coronary flow reserve and endothelial dysfunction. The latter was characterized by a marked loss of nitric oxide. Such perturbations may contribute to reduced myocardial perfusion that is often observed in postmenopausal women with multiple cardiovascular risk factors. Funding: Grant 2020B008 RECONNEXT. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

MULTIDRUG RESISTANT DYSLIPIDEMIA: A CASE REPORT

Objective: Recently introduced lipid-lowering agents (PCSK9-i, bempedoic acid) can efficiently treat statin-intolerant patients, who couldn’t reach LDL target before. Nonetheless, there are still cases where the pharmacological management may have strong limitations. Design and method: A 71 year-old woman, with multiple cardiovascular risk factors (diabetes, hypertension and familial dylipidemia, LDL-C 276) underwent heart transplantation for a hypertrophic cardiomyopathy with an evolution towards a dilated phenotype in 2005. Before the transplant, she was on low-dose statin treatment (pravastatin 10 mg/die) that was suspended years later owing to hyper-CKemia (600 U/L), despite her being totally asymptomatic. A second attempt with simvastatin/ezetimibe 40/10 mg resulted again in elevation of CK levels, associated with significant muscular pain. Thus, just ezetimibe was continued. In 2020, 15 years after the transplant, the patient underwent a coronary angiography showing a moderate coronary allograft vasculopathy (ISHLT CAV2). Specifically, a sub occlusive ostial left main coronary artery lesion was treated by percutaneous angioplasty and stent implantation. Since a lower LDL target was needed (LDL-C 55 mg/dL), Results: Alirocumab was introduced. However, 6 months later, no significant LDL levels reduction had been observed. The shift to evolocumab led to the same result, although the patient reported full therapeutic compliance. In the suspicion of anti-drug antibodies development, we opted for Inclisiran without achieving a significant decrease in LDL-C levels. In parallel with the search for genetic mutations in the PCSK9 gene and other genes involved in cholesterol metabolism (including LDLR, APOB, and LDLRAP1 and resulting positive only for common variants in LDLR receptor), therapy with bempedoic acid was initiated, again without substantial benefit (LDL-C 118 mg/dL). Conclusions: Despite cholesterol management has been simplified by the introduction of new drugs, it may still be complex in patients requiring very low LDL-C levels in some specific cases. Drugs with a LDL receptor-independent mechanism of action (e.g., evinacumab) may allow the achievement of therapeutic goals suggested by clinical guidelines.

The Role of CT Imaging in a Fractured Coronary Stent with Pseudoaneurysm Formation.

We report a case of a 63-year-old male patient with multiple cardiovascular risk factors and previous myocardial infarction who was referred to the emergency department on September 2023 with symptoms and clinical and biological data consistent with an acute coronary event. A coronary angiography revealed severe ostial stenosis of the left anterior descending artery (LAD) and intrastent thrombotic occlusion in the first two segments of the LAD. Two drug-eluting stents were implanted and the patient was discharged when hemodynamically stable; however, three weeks later, he returned to the emergency department complaining of fever, anterior chest pain, dyspnea at rest, and high blood pressure values at home. High levels of troponin T, C-reactive protein, and NT-proBNP were detected and blood cultures showed methicillin-resistant Staphylococcus aureus. The computed tomography (CT) examination showed a saccular dilatation had developed between two fragments of a stent mounted at the level of the LAD, surrounded by a hematic pericardial accumulation. LAD pseudoaneurysm ablation and a double aortocoronary bypass with inverted saphenous vein autograft were performed and the patient showed a favorable postoperative evolution. In this case, surgical revascularization was proven to be the appropriate treatment strategy, demonstrating the need to choose an individualized therapeutic option depending on case-specific factors.

Obesity and polycystic ovary syndrome influence on intestinal permeability at fasting, and modify the effect of diverse macronutrients on the gut barrier

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.

Cardioprotective Effects of Aloysia polystachya Essential Oil on a Rat Model with Multiple Cardiovascular Risk Factors.

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A.polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A.polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A.polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A.polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A.polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

Improvements of myocardial strain and work in diabetes patients with normal ejection fraction after empagliflozin treatment.

To assess the effect of empagliflozin treatment on left ventricular (LV), right ventricular (RV) and left atrial (LA) functions in diabetes patients with normal ejection fraction. The study included a total of 128 diabetes patients with multiple cardiovascular risk factors who were subjected to a 6-month follow up from the initiation of empagliflozin treatment. Before and after treatment with empagliflozin, LV, RV and LA strain, and noninvasive myocardial work parameters were evaluated by speckle tracking echocardiography. In 128 diabetes patients (mean age 56 ± 8 years, 85 men) with multiple cardiovascular risk factors, myocardial strain and work parameters were impaired, despite the absence of significant clinical symptoms of heart failure. After 6-month treatment with empagliflozin, the absolute value of LV strain in all directions increased, represented by LV global longitudinal strain (-18.0 ± 1.7% to -19.2 ± 1.7% [mean ± SD]). The same trend in LV global work efficiency (93 [91-94] % to 94 [93-95] % [median (IQR)]), RV free-wall longitudinal strain (-24.0 ± 2.7% to -25.0 ± 2.8%), LA reservoir (31 ± 5% to 34 ± 5%) and conduit strain (-14 ± 4% to -16 ± 4%) was also observed. LV mass index (106.9 ± 16.8-103.6 ± 16.4 g/m2) and LV global wasted work (143 [111-185] mmHg% to 108 [88-141] mmHg%) decreased after treatment (P < 0.05 for all). LV volume and LA volume index remained unchanged after treatment. In the multivariable analysis, the change in LA reservoir strain (β = 0.050, P = 0.035) and baseline global longitudinal strain (β = -0.488, P < 0.001) were independent predictors of improvement in LV global longitudinal strain. This study suggests that 6-month treatment with empagliflozin improved LV, RV and LA functions in diabetes patients with normal ejection fraction.