Cardiovascular Profile Research Articles

Cardiovascular Adverse Events Associated with Monoclonal Antibody Products in Patients with COVID-19.

Little is known about cardiovascular safety profiles for monoclonal antibody products that received the FDA Emergency Use Authorization for COVID-19. In this study, data from the FDA Adverse Event Reporting System from the first quarter of 2020 to the second quarter of 2022 were used to investigate cardiovascular safety signals associated with seven monoclonal antibody products (casirivimab + imdevimab, bamlanivimab, bamlanivimab + etesevimab, sotrovimab, tocilizumab, bebtelovimab, tixagevimab + cilgavimab) in COVID-19 patients. Disproportionality analyses were conducted using reporting odds ratio and information component to identify safety signals. About 10% of adverse events in COVID-19 patients were cardiovascular adverse events. Four monoclonal antibody products (casirivimab + imdevimab, bamlanivimab, bamlanivimab + etesevimab, and bebtelovimab) were associated with higher reporting of hypertension. Tocilizumab was associated with higher reporting of cardiac failure and embolic and thrombotic event. Casirivimab + imdevimab and bamlanivimab were also associated with higher reporting of ischemic heart disease. No cardiovascular safety signals were identified for sotrovimab and tixagevimab + cilgavimab. The results indicate differential cardiovascular safety profiles in monoclonal antibodies. Careful monitoring of cardiovascular events may be considered for certain COVID-19 patients at risk when they are treated with monoclonal antibodies.

South Africa - the African-PREDICT Study.

The high prevalence of hypertension (one of the main risk factors for cardiovascular disease) in the sub-Saharan African region has been reported, and its management remains a challenge. Although the challenge in controlling hypertension has been attributed to noncompliance with existing guidelines and best practices, lack of evidence-based guidelines, resources and poor access to healthcare; the full understanding of pathophysiology in the development of hypertension may be necessary for effective prevention and treatment strategies in the region. Due to lack of pathophysiologic understanding, the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT) was then initiated to fulfill this need. African-PREDICT is an ongoing longitudinal study which started in 2013, and is expected to continue for the next 10-20 years. A total of 1,202 young black (n=606) and white (n=596) South African men and women (aged 20-30 years) who were screened to be healthy and clinically normotensive are included in this study. At each data collection phase (baseline and each 5-year follow-up) of the study, detailed measures of health behaviours, cardiovascular profile and organ damage will be taken. In addition, biological sampling for determining novel early markers or predictors will be performed. The research results reported from the African-PREDICT study will contribute to a clear understanding of early cardiovascular disease development in young and healthy black and white individuals.

Machine learning in a real-world PFO study: analysis of data from multi-centers in China

PurposeThe association of patent foreman ovale (PFO) and cryptogenic stroke has been studied for years. Although device closure overall decreases the risk for recurrent stroke, treatment effects varied across different studies. In this study, we aimed to detect sub-clusters in post-closure PFO patients and identify potential predictors for adverse outcomes.MethodsWe analyzed patients with embolic stroke of undetermined sources and PFO from 7 centers in China. Machine learning and Cox regression analysis were used.ResultsUsing unsupervised hierarchical clustering on principal components, two main clusters were identified and a total of 196 patients were included. The average age was 42.7 (12.37) years and 64.80% (127/196) were female. During a median follow-up of 739 days, 12 (6.9%) adverse events happened, including 6 (3.45%) recurrent stroke, 5 (2.87%) transient ischemic attack (TIA) and one death (0.6%). Compared to cluster 1 (n = 77, 39.20%), patients in cluster 2 (n = 119, 60.71%) were more likely to be male, had higher systolic and diastolic blood pressure, higher body mass index, lower high-density lipoprotein cholesterol and increased proportion of presence of atrial septal aneurysm. Using random forest survival (RFS) analysis, eight top ranking features were selected and used for prediction model construction. As a result, the RFS model outperformed the traditional Cox regression model (C-index: 0.87 vs. 0.54).ConclusionsThere were 2 main clusters in post-closure PFO patients. Traditional cardiovascular profiles remain top ranking predictors for future recurrence of stroke or TIA. However, whether maximizing the management of these factors would provide extra benefits warrants further investigations.

Cardiovascular Risk Factors in Patients with Congenital Hemophilia: A Focus on Hypertension.

Aging hemophiliacs face cardiovascular disease. Lots of evidence has been gathered that hemophiliacs have a more unfavorable cardiovascular profile than the general population does, especially due to the increased prevalence of hypertension (HTN). Among the existing scattered evidence, our study provides the most comprehensive and systematized analysis of the determinants of HTN in hemophiliacs. We discussed the contribution to the HTN substrate of hemophilia-specific factors, such as type, severity and the presence of inhibitors. The complex mechanism of kidney dysfunction in relation to hematuria and viral infections was meticulously addressed. Furthermore, we highlighted the new pathogenic concepts of endothelial dysfunction and the association between HTN and hemophilic arthropathy. The clustering of cardiovascular risk factors is common in hemophiliacs, and it enhances the negative vascular effect of HTN and aggravates HTN. It usually leads to an increased risk for coronary and cerebrovascular events. Our work provides reliable evidence to guide and improve the management of HTN in hemophiliacs.

Effects of three-months folate supplementation on early vascular abnormalities in hyperhomocysteinemic patients with epilepsy

BackgroundEpilepsy has been associated with an increased risk of cardiovascular events. Anti-seizure medication (ASM) may contribute to vascular risk by several mechanisms, including increased homocysteine levels. This study aims to assess the global vascular burden in hyperhomocysteinemic people with epilepsy (PWE) on long‐term ASM before and after folic acid supplementation and in subgroups of PWE treated with single enzyme-inducing or single non-enzyme inducing ASM. MethodsOne hundred and seventy-four hyperhomocysteinemic (HHcy) PWE who met the inclusion criteria were enrolled. Carotid Doppler ultrasonography, FMD and ultrasound assessment of the brachial artery properties at the baseline and after 90 days of folic acid supplementation were performed. The vascular biomarkers MMP-9 and TIMP-1 were also detected. ResultsAfter folic acid supplementation, in HHcy patients homocysteine levels reduced from 26.8 ± 10.5 to 20.2 ± 5.3 μmol/L, carotid Intima-Media-Thickness reduced from 0.83+0.06 mm to 0.79±0.05 mm, and FMD, distensibility coefficient and β-stiffness improved (p < 0.05). Moreover, MMP-9 and TIMP-1 reduced after supplementation (p < 0.05). PWE treated with a single enzyme-inducing ASM showed an impairment of vascular parameters compared to patients treated with non-enzyme inducing ASM. ConclusionsThe results highlight the importance of assessing homocysteine levels and estimating the cardiovascular risk of PWE, preferring non-enzyme inducing ASM in high cardiovascular-risk patients. An adequate correction of homocysteine levels with folate supplementation should be considered to improve the cardiovascular profile.

Diabetic foot in primary and tertiary (DEFINITE) Care: A health services innovation in coordination of diabetic foot ulcer (DFU) Care within a healthcare cluster - 18-month results from an observational population health cohort study.

Diabetic Foot in Primary and Tertiary (DEFINITE) Care is an inter-institutional and multi-disciplinary team (MDT) health systems innovation programme at a healthcare cluster in Singapore. We aim to achieve coordinated MDT care across primary and tertiary care for patients with diabetic foot ulcers (DFU), within our public healthcare cluster - an integrated network of seven primary care polyclinics and two acute care tertiary hospitals (1700-bed and 800-bed) with a total catchment population of 2.2 million residents. Results from prospective DEFINITE Care is referenced against a retrospective 2013-2017 cohort, which was previously published. Cardiovascular profile of the study population is compared against the same population's profile in the preceding 12 months. Between June 2020 and December 2021, there were 3475 unique patients with DFU with mean age at 65.9 years, 61.2% male, mean baseline HbA1c at 8.3% with mean diabetes duration at 13.3 years, mean diabetes complication severity index (DCSI) at 5.6 and mean Charlson Comorbidity Index (CCI) at 6.8. In the 12-months preceding enrolment to DEFINITE Care, 35.5% had surgical foot debridement, 21.2% had minor lower extremity amputation (LEA), 7.5% had major LEA whilst 16.8% had revascularisation procedures. At 18-months after the implementation of DEFINITE Care programme, the absolute minor and major amputation rates were 8.7% (n=302) and 5.1% (n=176), respectively, equating to a minor and major LEA per 100000 population at 13.7 and 8.0, respectively. This represents an 80% reduction in minor amputation rates (P < .001) and a 35% reduction in major amputation rates (P=.005) when referenced against a retrospective 2013-2017 cohort, which had minor and major LEA per 100000 population at 68.9 and 12.4, respectively. As compared to the preceding 12 months, there was also a significant improvement in cardiovascular profile (glycemic and lipid control) within the DEFINITE population, with improved mean HbAc1 (7.9% from 8.4%, P < .001), low-density lipoprotein (LDL) levels (2.1 mmol/L from 2.2, P < .001), total cholesterol (3.9 mmol/L from 4.1, P < .001) and triglycerides levels (1.6 mmol/L from 1.8, P=.002). Multivariate analysis revealed a history of minor amputation in the preceding 12 months to be an independent predictor for major and minor amputation within the study period of 18 months (Hazard Ratio 3.4 and 1.8, respectively, P < .001). In conclusion, within DEFINITE care, 18-month data showed a significant reduction of minor and major LEA rates, with improved medical optimisation and cardiovascular profile within the study population.

The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion.

Connshing syndrome (CoSh) (adrenal-related synchronous aldosterone (A) and cortisol (C) excess) represents a distinct entity among PA (primary hyperaldosteronisms) named by W. Arlt et al. in 2017, but the condition has been studied for more than 4 decades. Within the last few years, this is one of the most dynamic topics in hormonally active adrenal lesions due to massive advances in steroids metabolomics, molecular genetics from CYP11B1/B2 immunostaining to genes constellations, as well as newly designated pathological categories according to the 2022 WHO classification. In gross, PA causes 4-10% of all high blood pressure (HBP) cases, and 20% of resistant HBP; subclinical Cushing syndrome (SCS) is identified in one-third of adrenal incidentalomas (AI), while CoSh accounts for 20-30% to 77% of PA subjects, depending on the tests used to confirm autonomous C secretion (ACS). The clinical picture overlaps with PA, hypercortisolemia being mild. ACS is suspected in PA if a more severe glucose and cardiovascular profile is identified, or there are larger tumours, ACS being an independent factor risk for kidney damage, and probably also for depression/anxiety and osteoporotic fractures. It seems that one-third of the PA-ACS group harbours mutations of C-related lines like PRKACA and GNAS. A novel approach means we should perform CYP11B2/CYP11B1 immunostaining; sometimes negative aldosteronoma for CYP11B1 is surrounded by micronodules or cell clusters with positive CYP11B1 to sustain the C excess. Pitfalls of hormonal assessments in CoSh include the index of suspicion (check for ACS in PA patients) and the interpretation of A/C ratio during adrenal venous sample. Laparoscopic adrenalectomy is the treatment of choice. Post-operative clinical remission rate is lower in CoSh than PA. The risk of clinically manifested adrenal insufficiency is low, but a synthetic ACTH stimulating testing might help to avoid unnecessary exposure to glucocorticoids therapy. Finally, postponing the choice of surgery may impair the outcome, having noted that long-term therapy with mineralocorticoids receptors antagonists might not act against excessive amounts of C. Awareness of CoSh improves management and overall prognosis.

Abstract 14702: The Burden of Cardiac Adverse Events Associated With Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitors: A Large Pharmacovigilance Database Analysis

Introduction: Anaplastic Lymphoma Kinase tyrosine kinase inhibitors (ALK TKIs) have played a pivotal role in the management of Metastatic Non-Small-Cell Lung Cancer (NSCLC). ALK rearrangements are associated with improved survival compared to the standard first-line therapy. However, the cardiovascular safety profile of these agents remains understudied. Methods: We interrogated the Food and Drug Administration’s Adverse Event Reporting System (FAERS) database for the reported cardiac adverse events (AE) of: crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The number of cardiac AEs reported for ALK TKIs were compared with all the other drugs between 2011-2022. Disproportionality analysis was performed using Reporting Odds Ratio (ROR). Results: We identified a total of 20,337 AEs for ALK TKIs, of which 1191 were cardiac AEs. The most frequently reported cardiac AEs associated with ALK TKIs were pericardial diseases (271), followed by bradyarrhythmia (253) and heart failure (HF) (245). HF reporting was significantly higher with lorlatinib (ROR 2.9; CI 95% 2.0-4.1). Ceretinib was associated with significantly higher reporting of pericardial diseases (ROR 28.3; CI 95% 22.6-35.3), and other tachyarrhythmias (ROR 8.9; CI 95% 5.7-13.8). Alectinib was associated with significantly higher reporting of bradyarrhythmias (ROR 9.7, CI 95% 7.8-12.1). Conclusion: Cardiovascular AEs were disproportionately higher with ALK TKIs for pericardial diseases and bradyarrhythmias with ceretinib and alectinib respectively. Larger prospective studies are needed to identify high-risk groups that would benefit from robust cardiovascular surveillance.

Abstract 15594: Decreasing the High Risk of Ponatinib-Induced Cardiovascular Toxicity in Chronic Myeloid Leukemia

Introduction: Cardiovascular (CV) toxicity of cancer therapeutics is a growing problem. Ponatinib is one of the most cardiotoxic Tyrosine Kinase Inhibitors (TKIs) and is used as a highly effective TKI against ABL T315I mutation in Chronic Myeloid Leukemia (CML). Long-term exposure to ponatinib increases CV events including myocardial infarction, heart failure, stroke, peripheral vascular disease and venous thrombosis. There is need of novel therapeutics to provide treatment for CML while avoiding CV toxicity. Hypothesis: Using in vitro and in vivo models of CV toxicity can make possible to reengineer ponatinib to minimize its toxicity. Methods: We developed new safer analogues of ponatinib using fragment-based approach. Their anti-tumor efficacy was tested in 2 different CML cell lines and CML patient samples. We assayed for myocardial toxicity by measuring contractile function in human iPSC-cardiomyocytes (hiPSC-CMs) using high-throughput functional imaging, for vascular toxicity by measuring vasculogenesis in human microvascular endothelial cells (HMVECs), and for bone marrow toxicity by colony formation assay in human bone marrow cells (HBMCs). Finally, we confirmed the safer CV profile and adequate anti-tumor efficacy in an in vivo xenograft mouse model of CML. Results: The new analogues inhibited T315I BCR-ABL kinase activity similar to ponatinib and suppressed T315I mutant CML tumor growth in vitro and in vivo . Compared to ponatinib, the new compounds showed markedly decreased adverse effects on contractility of hiPSC-CMs, vasculogenesis in HMVECs and bone marrow toxicity in HBMCs in vitro . The therapeutic window was increased in vivo , leading to regression of human T315I mutant CML xenografts comparable to ponatinib but without increased levels of cardiac troponin. Additionally, we identified multiple kinases, including FGFR1, that were inhibited by ponatinib but not the analogues, suggesting that there is a specific set of kinases responsible for ponatinib toxicity. Conclusions: This study demonstrates that chemical reengineering can generate novel, CV-safe TKIs that retain effective therapeutic properties against CML carrying ABL T315I mutation, but that exhibit minimal CV toxicity compared to ponatinib.

Association of a Multiancestry Genome-Wide Blood Pressure Polygenic Risk Score With Adverse Cardiovascular Events.

Traditional cardiovascular risk factors and the underlying genetic risk of elevated blood pressure (BP) determine an individual's composite risk of developing adverse cardiovascular events. We sought to evaluate the relative contributions of the traditional cardiovascular risk factors to the development of adverse cardiovascular events in the context of varying BP genetic risk profiles. Genome-wide polygenic risk score (PRS) was computed using multiancestry genome-wide association estimates among US adults who underwent whole-genome sequencing in the Trans-Omics for Precision program. Individuals were stratified into high, intermediate, and low genetic risk groups (>80th, 20-80th, and <20th centiles of systolic BP [SBP] PRS). Based on the ACC/AHA Pooled Cohort Equations, participants were stratified into low and high (10 year-atherosclerotic cardiovascular disease [CVD] risk: <10% or ≥10%) cardiovascular risk factor profile groups. The primary study outcome was incident cardiovascular event (composite of incident heart failure, incident stroke, and incident coronary heart disease). Among 21 897 US adults (median age: 56 years; 56.0% women; 35.8% non-White race/ethnicity), 1 SD increase in the SBP PRS, computed using 1.08 million variants, was associated with SBP (β: 4.39 [95% CI, 4.13-4.65]) and hypertension (odds ratio, 1.50 [95% CI, 1.46-1.55]), respectively. This association was robustly seen across racial/ethnic groups. Each SD increase in SBP PRS was associated with a higher risk of the incident CVD (multivariable-adjusted hazards ratio, 1.07 [95% CI, 1.04-1.10]) after controlling for ACC/AHA Pooled Cohort Equations risk scores. Among individuals with a high SBP PRS, low atherosclerotic CVD risk was associated with a 58% lower hazard for incident CVD (multivariable-adjusted hazards ratio, 0.42 [95% CI, 0.36-0.50]) compared to those with high atherosclerotic CVD risk. A similar pattern was noted in intermediate and low genetic risk groups. In a multiancestry cohort of >21 000 US adults, genome-wide SBP PRS was associated with BP traits and adverse cardiovascular events. Adequate control of modifiable cardiovascular risk factors may reduce the predisposition to adverse cardiovascular events among those with a high SBP PRS.

Association of Sex and Race With Incident Peripheral Artery Disease Among Veterans With Normal Ankle-Brachial Indices

Reported risk of incident peripheral artery disease (PAD) by sex and race varies significantly and has not been reported in national cohorts among individuals free of baseline PAD. To evaluate the association of sex and race, as well as prevalent cardiovascular risk factors, with limb outcomes in a national cohort of people with normal baseline ankle-brachial indices (ABIs). This cohort study was conducted using data from participants in the Veterans Affairs Birth Cohort Study (born 1945-1965), with follow-up data between January 1, 2000, and December 31, 2016. Baseline demographics were collected from 77 041 participants receiving care from the Veterans Health Administration with baseline ABIs of 0.90 to 1.40 and no history of PAD. Data were analyzed from October 2019 through September 2022. Sex, race, diabetes, and smoking status. Incident PAD, defined as subsequent ABI less than 0.90, surgical or percutaneous revascularization, or nontraumatic amputation. Of 77 041 participants with normal ABIs (73 822 [95.8%] men; mean [SD] age, 60.2 [5.9] years; 13 080 Black [18.2%] and 54 377 White [75.6%] among 71 911 participants with race and ethnicity data), there were 6692 incident PAD events over a median [IQR] of 3.9 [1.7-6.9] years. Incidence rates were lower for women than men (incidence rates [IRs] per 1000 person-years, 7.4 incidents [95% CI, 6.2-8.8 incidents] vs 19.2 incidents [95% CI, 18.7-19.6 incidents]), with a lower risk of incident PAD (adjusted hazard ratio [aHR], 0.49 [95% CI, 0.41-0.59]). IRs per 1000 person-years of incident PAD were similar for Black and White participants (18.9 incidents [95% CI, 17.9-20.1 incidents] vs 18.8 incidents [95% CI, 18.3-19.4]). Compared with White participants, Black participants had increased risk of total PAD (aHR, 1.09 [95% CI, 1.02-1.16]) and nontraumatic amputation (aHR, 1.20 [95% CI, 1.06-1.36]) but not surgical or percutaneous revascularization (aHR, 1.10 [95% CI, 0.98-1.23]) or subsequent ABI less than 0.90 (aHR, 1.04 [95% CI, 0.95-1.13]). Diabetes (aHR, 1.62 [95% CI, 1.53-1.72]) and smoking (eg, current vs never: aHR, 1.76 [95% CI, 1.64-1.89]) were associated with incident PAD. Incident PAD was rare among individuals without a history of smoking or diabetes (eg, among 632 women: IR per 1000 people-years, 2.1 incidents [95% CI, 1.0-4.5 incidents]) despite an otherwise-high-risk cardiovascular profile (eg, 527 women [83.4%] with hypertension). This study found that the risk of PAD was approximately 50% lower in women than men and less than 10% higher for Black vs White participants, while the risk of nontraumatic amputation was 20% higher among Black compared with White participants.

ODP462 Amiodarone Induced Thyrotoxicosis-Treatment Challenges

Abstract Amiodarone induced thyrotoxicosis (AIT) presents a diagnostic and treatment challenge. Importantly, uncontrolled thyrotoxicosis can be associated with significant morbidity and mortality. The following presentation depicts a case of AIT with persistent thyrotoxicosis despite optimal and prolonged medical therapy. The case was complicated by patient's high-risk cardiovascular profile postponing definitive therapy with thyroidectomy. Patient was a 58-year-old female with past medical history of coronary artery disease, severe systolic heart failure, atrial fibrillation, and ventricular tachycardia maintained on amiodarone therapy since 2019, who was noted to have abnormal thyroid function labs in 2021 with TSH of 0. 04 uIU/mL (0.45-5.3), free T3 of 4.6 pg/mL (2.2-4.1) and free T4 of 2.7 ng/dL (0.58-1.64) indicative of hyperthyroidism. Her evaluation included negative family history of thyroid disorder, negative thyroid antibody profile, as well as a thyroid ultrasound that demonstrated no thyroid enlargement, no nodules and normal vascularity. At the time of initial evaluation, patient was suffering from episodes of atrial fibrillation with rapid ventricular response. Patient was diagnosed with AIT (presumably type 1). Amiodarone was discontinued and patient was initiated on methimazole 10 mg twice daily. Unfortunately, three weeks after initiation of methimazole treatment, patient's clinical status deteriorated and she was hospitalized for multifactorial shock requiring multidisciplinary approach and vasopressor/ionotropic support. At that time her free T4 had risen to &amp;gt;5.6 ng/dL and free T3 peaked at 6.17 pg/mL. The most probable diagnosis was AIT type 2 and her medical therapy was augmented to methimazole 20 mg three times daily and prednisone 50 mg daily. After clinical stabilization, she was discharged home on this regimen. Unfortunately, her thyroid function tests remained persistently elevated for almost three months despite maximum medical therapy. At that point, patient was referred for thyroidectomy despite severe cardiomyopathy and high-risk surgical profile. Fortunately, her thyroid function tests began to improve prior to planned surgery and medical therapy was successfully de-escalated, precluding the need for surgical intervention. While most cases of AIT can be successfully treated with medical therapy, refractory cases can present a clinical challenge, especially in patients at high risk for thyroidectomy. Weighing the risks and benefits of each treatment plan requires a multi-disciplinary approach and close communication with all parties involved. Presentation: No date and time listed

Prediction of subclinical atherosclerosis in low Framingham risk score individuals by using the metabolic syndrome criteria and insulin sensitivity index.

Subclinical atherosclerosis can be present in individuals with an optimal cardiovascular risk factor profile. Traditional risk scores such as the Framingham risk score do not adequately capture risk stratification in low-risk individuals. The aim of this study was to determine if markers of metabolic syndrome and insulin resistance can better stratify low-risk individuals. A cross-sectional study of 101 healthy participants with a low Framingham risk score and no prior morbidities was performed to assess prevalence of subclinical atherosclerosis using computed tomography (CT) and ultrasound. Participants were compared between groups based on Metabolic Syndrome (MetS) and Insulin-Sensitivity Index (ISI-cal) scores. Twenty three individuals (23%) had subclinical atherosclerosis with elevated CT Agatston score ≥1. Presence of both insulin resistance (ISI-cal <9.23) and fulfillment of at least one metabolic syndrome criterion denoted high risk, resulting in significantly improved AUC (0.706 95%CI 0.588-0.822) over the Framingham risk score in predicting elevated CT Agatston score ≥1, with net reclassification index of 50.9 ± 23.7%. High-risk patients by the new classification also exhibited significantly increased carotid intima thickness. The overlap of insulin resistance and presence of ≥1 criterion for metabolic syndrome may play an instrumental role in identifying traditionally low-risk individuals predisposed to future risk of atherosclerosis and its sequelae.

Disease-modifying anti-rheumatic drugs improve the cardiovascular profile in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting about 0. 5-1% of the adult population and manifesting as persistent synovitis, systemic inflammation and production of autoantibodies. Patients affected by RA not only experience chronic disease progression, but are also burdened by a 1.5-fold increased cardiovascular (CV) risk, which is comparable to the risk experienced by patients with type 2 diabetes mellitus. RA patients also have a higher incidence and prevalence of coronary artery disease (CAD). Although RA patients frequently present traditional CV risk factors such as insulin resistance and active smoking, previous studies have clarified the pivotal role of chronic inflammation-driven by proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha)-in accelerating the process of atherosclerosis and impairing the coagulation system. Over the last years, a number of studies have shown that disease-modifying anti-rheumatic drugs (DMARDs) reducing the inflammatory state in general improve the CV risk, however some drugs may carry some apparent negative effects. Thus, RA is a model of disease in which targeting inflammation may counteract the progression of atherosclerosis and reduce CV risk. Clinical and experimental evidence indicates that the management of RA patients should be tailored based on the positive and negative effects of DMARDs on CV risk together with the individual traditional CV risk profile. The identification of genetic, biochemical and clinical biomarkers, predictive of evolution and response to treatment, will be the next challenge for a precision approach to reduce the burden of the disease.

The safety of early discharge following transfemoral transcatheter aortic valve replacement under general anesthesia.

There is growing evidence of the safety of same-day discharge for low-risk conscious sedated TAVR patients. However, the evidence supporting the safety of early discharge following GA-TAVR with routine transesophageal echocardiography (TEE) is limited. To assess the safety of early discharge following transcatheter aortic valve replacement (TAVR) using General Anesthesia (GA-TAVR) and identify predictors for patient selection. We used data from 2,447 TEE-guided GA-TAVR patients performed at Cedars-Sinai between 2016 and 2021. Patients were categorized into three groups based on the discharge time from admission: 24 h, 24-48 h, and >48 h. Predictors for 30-day outcomes (cumulative adverse events and death) were validated on a matched cohort of 24 h vs. >24 h using the bootstrap model. The >48 h group had significantly worse baseline cardiovascular profile, higher surgical risk, low functional status, and higher procedural complications than the 24 h and the 24-48 h groups. The rate of 30-day outcomes was significantly lower in the 24 h than the >48 h but did not differ from the 24-48 h (11.3 vs. 15.5 vs. 11.7%, p = 0.003 and p = 0.71, respectively). Independent poor prognostic factors of 30-day outcomes had a high STS risk of ≥8 (OR 1.90, 95% CI 1.30-2.77, E-value = 3.2, P < 0.001), low left ventricle ejection fraction of <30% (OR 6.0, 95% CI 3.96-9.10, E-value = 11.5, P < 0.001), and life-threatening procedural complications (OR 2.65, 95% CI 1.20-5.89, E-value = 4.7, P = 0.04). Our formulated predictors showed a good discrimination ability for patient selection (AUC: 0.78, 95% CI 0.75-0.81). Discharge within 24 h following GA-TAVR using TEE is safe for selected patients using our proposed validated predictors.

The obesity paradox in patients with acute coronary syndromes – is it still applicable to the current era? The ACSIS registry 2000–2018

Abstract Background Obesity is a major epidemic which is associated with major cardiovascular (CV) risk factors. Nevertheless, substantial data, mostly published more than a decade ago, have demonstrated an obesity paradox, where obese patients generally have a better short- and long-term prognosis than do their leaner counterparts with the same CV profile. As for the obesity paradox in acute coronary syndrome (ACS), prior studies demonstrated that the body-mass index (BMI)-mortality association followed a “U” shape curve: it is the highest in underweight (BMI&amp;lt;19) or severely obese (BMI &amp;gt;44), and is the lowest in overweight or mildly obese patients (BMI 30–34 and BMI 35–39) [1–2]. It is not fully elucidated whether the obesity paradox is still relevant in the current era in patients with ACS. We aimed to examine temporal trends in the clinical outcomes of ACS patients by their BMI status. Methods Data from the ACSIS registry including all patients with calculated BMI data between the years 2000–2018. Patients were stratified by BMI groups to underweight, normal, overweight and obese. Clinical endpoints included 30d MACE, and 1-year mortality. Temporal trends were examined in the late (2010–2018) vs. the early period (2000–2008). Multivariable models examined factors associated with clinical outcomes by BMI status. Results Among the 13,816 patients from the ACSIS registry with available BMI data, 104 were underweight, 3921 were normal, 6224 were overweight and 3567 were obese. 1-year mortality was highest among underweight patients (24.8%), as compared to normal weight patients (10.7%) and lowest among overweight and obese patients (7.1% and 7.5% respectively; p for trend &amp;lt;0.001) [Figure 1]. 30-day MACE rates were qualitatively similar (24.3% for underweight, 13.6% for normal weight, 11.6% for overweight, and 11.7% for obese; p for trend&amp;lt;0.001). Comparing the 2 time-periods, 30-day MACE was significantly lower in the late period in all BMI groups, excluding patients who were underweight. Similarly, 1-year mortality has not changed during the years in underweight patients, and has decreased in normal weight and obese patients. Conclusions In ACS patients, during 2-decades, 30-day MACE and 1-year mortality were lower among overweight and obese patients compared with underweight and normal weight patients. During time, 30-day MACE and 1-year mortality have decreased among the majority of BMI groups, excluding the underweight patients, in which the rates were consistently high. Our findings suggest that the obesity paradox is still relevant in ACS patients in the current era. Funding Acknowledgement Type of funding sources: None.

The metabolic health of young men conceived using intracytoplasmic sperm injection.

Is the metabolic health of men conceived using ICSI different to that of IVF and spontaneously conceived (SC) men? ICSI-conceived men aged 18-24 years, compared with SC controls, showed differences in some metabolic parameters including higher resting diastolic blood pressure (BP) and homeostasis model assessment for insulin resistance (HOMA-IR) scores, although the metabolic parameters of ICSI- and IVF-conceived singleton men were more comparable. Some studies suggest that IVF-conceived offspring may have poorer cardiovascular and metabolic profiles than SC children. Few studies have examined the metabolic health of ICSI-conceived offspring. This cohort study compared the metabolic health of ICSI-conceived men to IVF-conceived and SC controls who were derived from prior cohorts. Participants included 121 ICSI-conceived men (including 100 singletons), 74 IVF-conceived controls (all singletons) and 688 SC controls (including 662 singletons). Resting systolic and diastolic BP (measured using an automated sphygmomanometer), height, weight, BMI, body surface area and fasting serum metabolic markers including fasting insulin, glucose, total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol, triglycerides, highly sensitive C-reactive protein (hsCRP) and HOMA-IR were compared between groups. Data were analysed using multivariable linear regression adjusted for various covariates including age and education level. After adjusting for covariates, compared to 688 SC controls, 121 ICSI-conceived men had higher diastolic BP (β 4.9, 95% CI 1.1-8.7), lower fasting glucose (β -0.7, 95% CI -0.9 to -0.5), higher fasting insulin (ratio 2.2, 95% CI 1.6-3.0), higher HOMA-IR (ratio 1.9, 95% CI 1.4-2.6), higher HDLC (β 0.2, 95% CI 0.07-0.3) and lower hsCRP (ratio 0.4, 95% CI 0.2-0.7) levels. Compared to 74 IVF-conceived singletons, only glucose differed in the ICSI-conceived singleton men (β -0.4, 95% CI -0.7 to -0.1). No differences were seen in the paternal infertility subgroups. The recruitment rate of ICSI-conceived men in this study was low and potential for recruitment bias exists. The ICSI-conceived men, the IVF-conceived men and SC controls were from different cohorts with different birth years and different geographical locations. Assessment of study groups and controls was not contemporaneous, and the measurements differed for some outcomes (BP, insulin, glucose, lipids and hsCRP). These observations require confirmation in a larger study with a focus on potential mechanisms. Further efforts to identify whether health differences are due to parental characteristics and/or factors related to the ICSI procedure are also necessary. This study was funded by an Australian National Health and Medical Research Council Partnership Grant (NHMRC APP1140706) and was partially funded by the Monash IVF Research and Education Foundation. S.R.C. was supported through an Australian Government Research Training Program Scholarship. R.J.H. is supported by an NHMRC project grant (634457), and J.H. and R.I.M. have been supported by the NHMRC as Senior and Principal Research Fellows respectively (J.H. fellowship number: 1021252; R.I.M. fellowship number: 1022327). L.R. is a minority shareholder and the Group Medical Director for Monash IVF Group, and reports personal fees from Monash IVF Group and Ferring Australia, honoraria from Ferring Australia and travel fees from Merck Serono and MSD and Guerbet; R.J.H. is the Medical Director of Fertility Specialists of Western Australia and has equity in Western IVF; R.I.M. is a consultant for and shareholder of Monash IVF Group and S.R.C. reports personal fees from Besins Healthcare and nonfinancial support from Merck outside of the submitted work. The remaining authors have no conflicts of interest to declare. N/A.

Denture wearing status, cardiovascular health profiles, and mortality in edentulous patients: A prospective study with a 27-year follow-up

ObjectivesLife's Simple 7 (LS7) metrics provide insight into improving cardiovascular health (CVH) and help reduce mortality risks. Edentulous older adults have a higher mortality risk than dentulous ones, probably due to worse oral function. It is reported that wearing dentures will decrease the mortality risk factor by improving oral function. This prospective study aimed to investigate if denture wearing could modify the association between CVH profile and mortality risk among edentulous elderly. MethodsFrom the Third National Health and Nutrition Examination Survey (NHANES III), 1,735 edentulous older adults (mean age 69.4 years old) with CVH profiles and data on denture wearing status were selected for this study. CVH profiles according to LS7 metrics were classified into poor, intermediate, or ideal. Denture wearers were defined as those wearing complete dentures in both arches all the time or only when awake. Multivariable Cox proportional-hazards regression was conducted to estimate the association of CVH profiles with all-cause and cardiovascular mortality. Stratified analyses and the testing of interaction terms were used to evaluate the difference between the association in edentulous patients with and without dentures. ResultsA total of 1,420 (81.8%) older adults died during the 27-year follow-up, with 478 (27.6%) cases attributable to heart disease. After controlling for potential confounders, edentulous patients with an ideal CVH (LS7 = 10–14) had a lower mortality risk than those with poor CVH (LS7 = 0–4). Furthermore, we observed an effect modification by denture use (Pinteraction = 0.046), with the role of ideal CVH in mitigating mortality among the denture wearers (Hazard Ratio = 0.440 [0.329–0.588]), while no significant association among those without dentures. Similar results were achieved for cardiovascular mortality, but there was no effect modification of denture use (Pinteraction = 0.352). ConclusionIn this study, a favorable cardiovascular health profile presents a protective effect on all-cause mortality only among edentulous patients wearing dentures instead of non-wearer. Clinical SignificanceDenture usage could improve oral function (e.g., chewing, smiling, speaking, etc.) and promote general health. Effect modification found in this study indicates having ideal CVH alone cannot substantially reduce mortality risk among edentulous patients. Therefore, health care professionals should keep an eye on the elderly not wearing dentures as they are probably more at risk for adverse health outcomes. It remains unclear if denture wearing has a causal relation with lower mortality risks, and further research is needed.

Childhood growth hormone treatment and metabolic and cardiovascular risk in adults born small for gestational age after growth hormone cessation in the Netherlands: a 12-year follow-up study

Childhood growth hormone treatment has been associated with increased cardiovascular mortality and morbidity in adults born small for gestational age (SGA) compared with the general population, but these risks have not been compared with untreated control groups. We aimed to investigate longitundinal metabolic and cardiovascular health in adults born SGA after cessation of growth hormone treatment. We longitudinally investigated the metabolic and cardiovascular health profile of 167 adults born SGA and previously treated with growth hormone during the 12 years after growth hormone cessation. Metabolic and cardiovascular parameters were assessed with the frequently sampled intravenous glucose tolerance test, serum lipids and blood pressure were measured, body composition was determined by dual-energy x-ray absorptiometry, and visceral fat was measured by MRI. At approximately age 30 years, we compared the metabolic and cardiovascular health profile of adults born SGA and previously treated with growth hormone (SGA-GH) with 219 untreated adults: 127 born SGA with either persistent short stature (SGA-S) or spontaneous catch-up to typical adult stature (SGA-CU), and 92 born appropriate for gestational age. During 12 years of follow-up, SGA-GH adults maintained normal β-cell function (p=0·157 for the difference from growth hormone cessation to 12-year follow-up) and showed an increase in insulin sensitivity (p=0·002), fat mass (p<0·001), total cholesterol (p<0·001), and blood pressure (p<0·001). By around age 30 years, these parameters reached similar levels to those in SGA-S adults (insulin sensitivity p=0·242; fat mass p=0·449; total cholesterol p=0·616; systolic blood pressure p=0·523; diastolic blood pressure p=0·538). By around age 30 years, SGA-GH adults also had similar metabolic and cardiovascular health parameters to adults born appropriate for gestational age, with the exception of lower lean body mass (estimated marginal mean 44·67 kg [95% CI 43·54-45·80] in SGA-GH adults vs 47·65 kg [46·39-48·92] in adults born appropriate for gestational age) and higher concentrations of adverse serum lipids, such as cholesterol (4·75 mmol/L [4·55-4·95] vs 4·33 mmol/L [4·13-4·5]), which were present in all groups born SGA. Abdominal adiposity (visceral adipose tissue p=0·107; subcutaneous adipose tissue: p=0·244), liver fat fraction (p=0·104), and blood pressure (systolic blood pressure 0·927; diastolic blood pressure: 0·737) were similar between SGA-GH adults and all control groups. At approximately age 30 years, SGA-GH adults had a similar metabolic and cardiovascular health profile to untreated adults born SGA or appropriate for gestational age, indicating long-term metabolic and cardiovascular safety of growth hormone treatment for children born SGA with short stature. Novo Nordisk.

A study of cardiovascular profile in patients with primary hypothyroidism

Introduction and Aim: Raised cardiovascular morbidity is common among patients with primary hypothyroidism. Study of electrocardiogram (ECG) and echocardiography (ECHO) and correlation with lipid profile may help in early detection of cardiovascular diseases in hypothyroidism. By this study, we aimed at studying the cardiovascular profile in patients with primary hypothyroidism and correlating ECHO and ECG changes in primary hypothyroidism with the LDL cholesterol. Materials and Methods: This was a single centre cross-sectional observational study. All patients diagnosed with primary hypothyroidism were included. The laboratory parameters pertaining to primary hypothyroidism were recorded. ECG and ECHO were noted and correlated with lipid profile. Results: Total 240 subjects were selected according to inclusion and exclusion criteria, of which males were 25% and females 75%. Mean ± SD of LDL-C among subjects having ST-T changes was 160.98 ±14.86. Mean ± SD of LDL-C among subjects having no ST-T changes was 128±10.15. Unpaired student t test was used to compare mean of lipid profile in patient having ST-T changes with patients having no ST-T changes. A strong correlation was observed between LDL cholesterol and ST-T changes in ECG (P value =0.001) Conclusion: Diastolic dysfunction is more common than systolic dysfunction in primary hypothyroidism. LDL levels were high in patients with primary hypothyroidism who had ST-T changes in electrocardiogram. Levothyroxine replacement causes decrease in Total as well as LDL cholesterol in primary hypothyroidism. ECG changes correlated with abnormal lipid profile in patients with primary hypothyroidism.