Uncontrolled Risk Factors Research Articles

Abstract 4134911: Coronary Artery Calcium Predicts Cardiovascular Events in Individuals with Controlled Atherosclerotic Risk Factors: A Multi-Cohort Study

Background: There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control. Methods: Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events. Results: The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC > 100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC > 100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC > 100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control. Conclusion: There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.

Comprehensive risk factor management through a dedicated secondary prevention clinic: experience from hamilton, Ontario

Abstract Introduction and Background Atherosclerotic cardiovascular diseases (ASCVD) remain a major source of morbidity and mortality. Modifiable ASCVD risk factors can be effectively treated, however, there is a lack of systematic implementation of secondary prevention therapies in ASCVD patients. We established a comprehensive secondary prevention program for patients with ASCVD to provide care for all modifiable risk factors in an integrated manner. Methods Patients with established coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral vascular disease (PVD) who had one or more uncontrolled risk factors, were referred to the center(s). Patients were assessed between November 2022 and October 2023. Uncontrolled risk factors were defined as dyslipidemia (LDL > 70 mg/dL [1.8 mmol/L]), hypertension (defined as BP >130/80 mmHg), diabetes (HbA1c >6.5%), chronic kidney disease (eGFR <60 ml/min/1.73m2) obesity (BMI >30 kg/m2) and current tobacco use. Data was collected at the initial visit and subsequent follow-up visits. Results A total of 274 patients were seen, with 85% were referred for CAD. Median age was 62 years,72% were men. The most common uncontrolled modifiable risk factor was hypertension (62% of patients), followed by dyslipidemia (60%) and obesity (50%). 39% of patients had diabetes, with 57% on a SGLT2i, 16% on a GLP-1 agonist and with 23% with HbA1c >8%. Blood pressure was above 140/90 mm Hg in 41% of patients, 20% were current smokers and 75% of patients had two or more uncontrolled risk factors. At the first visit, 56% of patients had a pharmacological intervention. The most common was for management of dyslipidemia, followed by diabetes and then hypertension. 17.8%(n=49) patients had a change in statin,13.8% (n= 38) patients were started on Ezetmibe, 9.1%(n=25) on Icosapent Ethyl, and 16.4% (n= 45) on a PCSK9i inhibitor (monoclonal antibody or Inclisiran). Among patients with diabetes, 5.1%(n=14) patients were started on a GLP-1 agonist and 2.5%(n=7) were started on a SGLT2i. 2.9%(n=8) patients were started on Varenicline and 2.9%(n=8) were started on NRT. Mean LDL (with LDL >1.8 at baseline) at visit 1 was at 3.03 ± 1.1 (n=157) mmol/dl, which reduced to 2.05 ± 0.9 (n=77) mmol/dl by 2nd visit and to 1.90 ± 1.3 (n=32) mmol/dl by visit 3. Average SBP (SBP >130 at baseline) at visit 1 was 143.3 ± 13.4 (n=114) mm Hg, this was subsequently reduced to 126.4 ± 14.0 (n=58) mm Hg at visit 2 and further reduced to 123.2 ± 14.7 (n=31) mm Hg by visit 3. Discussion and Impact: In our tertiary Cardiac Care center there are a significant number of patients with established ASCVD that remain on inadequate treatment for secondary prevention. Addressing these risk factors in a timely and integrated fashion in one clinic improves the implementation of guideline directed therapies for management of secondary risk factors in ASCVD and is expected to result in improved outcomes.

Traditional and non-traditional cardiovascular risk factor profiles in young patients with coronary artery disease

Study objectiveThere is an increasing trend in myocardial infarction (MI) hospitalizations in young individuals. The prevalence of modifiable cardiovascular risk factors is high in this population. This study aims to assess the prevalence of traditional and non-traditional cardiovascular risk factors among young patients with coronary artery disease (CAD) including novel lipid and dietary biomarkers with a focus on potential gender differences. DesignThe Young Heart study is a prospective, single-center pilot cohort study. Baseline data included medical history, medications, and lifestyle factors. We also collected blood samples for lipid profile, lipoprotein (a), high-sensitivity C-reactive protein (hsCRP), and trimethylamine N-oxide (TMAO). ParticipantsA total of 60 patients aged <60 years with CAD (on coronary CT or invasive angiogram) were included in the study. ResultsThe median age was 51 years and predominantly male (70 %). Baseline assessment revealed a high prevalence of hypertension (76.7 %), hyperlipidemia (91.7 %), and obstructive CAD (88.3 %). 36.7 % had diabetes, 28.3 % had prediabetes, and 38.3 % had prior MI. Uncontrolled risk factors were prevalent, including increased waist circumference (54.6 %), metabolic syndrome (60.0 %), and LDL ≥70 mg/dL (47.5 %), Lp(a) ≥75 nmol/L (47.5 %). Furthermore, 41.7 % had hsCRP ≥2 mg/L, and 28.3 % had suboptimal TMAO levels. 70.0 % of patients were on guideline-directed doses of statins. ConclusionYoung patients with CAD demonstrated a substantial burden of traditional and non-traditional cardiovascular risk factors. The study findings highlight the need for targeted interventions to improve risk factor control and optimize lifestyle behaviors. Further investigation is warranted to assess the impact of these interventions on cardiovascular outcomes.

Weight, height, waist circumference: association with knee osteoarthritis findings from the osteoarthritis initiative.

Global prevalence of knee osteoarthritis is more than 300 million. Uncontrollable risk factors include age, sex, and height. Controllable risk factors include trauma, weight, and waist circumference. Our goal was to determine the association between knee osteoarthritis and anthropometric measures that include weight, height, and waist circumference. Using 4,602 participants (45-79 years) from the Osteoarthritis Initiative, we analyzed the association between knee osteoarthritis and anthropometry collectively and by sex. We calculated female and male tertiles (3 groups) for anthropometry. Anthropometric measures were correlated with knee osteoarthritis (P ≤ 0.05) except the correlation between height and activities and height and quality of life. When comparing female weight tertiles, there were associations (P's < 0.001) between knee osteoarthritis and weight, but when comparing male weight tertiles, these associations were primarily between the lowest weight and highest weight groups. There were significant associations between knee osteoarthritis and height among female tertiles, with no differences among male tertiles. There were knee osteoarthritis/waist circumference tertile associations (P's < 0.001) for the lowest and highest waist circumference groups. Higher weight in female participants was a stronger predictor of increases in knee osteoarthritis discomforts when compared to waist circumference, while weight and waist circumference were almost equivalent in predicting increases in knee osteoarthritis for male participants. Height did not predict increases in knee osteoarthritis with the exception of female symptoms and quality of life. Quality of life for both sexes was the most unfavorable with female participants reporting a more unfavorable quality of life than male participants.

Cardiovascular Disease Risk Factor Control Following Release From Carceral Facilities: A Cross-Sectional Study.

Incarceration is a social determinant of cardiovascular health but is rarely addressed in clinical settings or public health prevention efforts. People who have been incarcerated are more likely to develop cardiovascular disease (CVD) at younger ages and have worse cardiovascular outcomes compared with the general population, even after controlling for traditional risk factors. This study aims to identify incarceration-specific factors that are associated with uncontrolled CVD risk factors to identify potential targets for prevention. Using data from JUSTICE (Justice-Involved Individuals Cardiovascular Disease Epidemiology), a prospective cohort study of individuals released from incarceration with CVD risk factors, we examine the unique association between incarceration-specific factors and CVD risk factor control. Participants (N=471), with a mean age of 45.0±10.8 (SD) years, were disproportionately from racially minoritized groups (79%), and poor (91%). Over half (54%) had at least 1 uncontrolled CVD risk factor at baseline. People released from jail, compared with prison, had lower Life's Essential 8 scores for blood pressure and smoking. Release from jail, as compared with prison, was associated with an increased odds of having an uncontrolled CVD risk factor, even after adjusting for age, race and ethnicity, gender, perceived stress, and life adversity score (adjusted odds ratio 1.62 [95% CI, 1.02-2.57]). Release from jail is associated with poor CVD risk factor control and requires tailored intervention, which is informative as states design and implement the Centers of Medicare & Medicaid Services Reentry 1115 waiver, which allows Medicaid to cover services before release from correctional facilities.

Evaluation of Cardiovascular Risk in People with Type 1 Diabetes: A Comprehensive and Specific Proposed Practical Approach.

People living with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in this population. CVD risk increases with each uncontrolled risk factor, even in individuals with good glycaemic control. Recommendations for assessing CVD risk in the T1D population are extended from those for type 2 diabetes (T2D) even though the physiopathology and underlying mechanisms of atherosclerosis in T1D are poorly understood and differ from those in T2D. Unlike the assessment of microvascular complications, which is well established in T1D, this is far from being the case for the comorbidities and risk associated with CVD. Aside from classical cardiovascular comorbidities, carotid ultrasound can be useful to stratify CVD risk. The utilization of specific risk scales such as the Steno Type 1 Risk Engine can help to more accurately classify cardiovascular risk in these individuals. The cornerstones of the management of cardiovascular risk in T1D are the promotion of the Mediterranean diet, tight glycaemic control (glycated haemoglobin (HbA1c) < 7%), blood pressure < 130/80mmHg in most patients, and low-density lipoprotein (LDL) cholesterol < 100mg/dL in moderate-risk individuals, < 70mg/dL in high-risk individuals, and < 55mg/dL in very high-risk individuals. Conventional medical follow-up of patients with T1D should be individualized (approximately 2-3 visits per year), and a carotid ultrasound evaluation is recommended every 5 years in the absence of significant preclinical atherosclerosis or more often in those with severe preclinical atherosclerosis. Antithrombotic therapy is recommended in those receiving secondary prevention, those with stenosis > 50% in any arterial bed, and those with an impaired ankle-brachial index. This document is a proposal of a practical approach for the evaluation, classification, and management of CVD risk in individuals living with T1D.

Abstract PO4-12-07: INSTITUTIONAL EXPERIENCE IN PATIENTS WITH EARLY BREAST CANCER WHO RECEIVED CARDIOTOXIC THERAPY IN CARDIONCOLOGY UNIT

Abstract Introduction: Early breast cancer (eBC) is the most frequent malignancy diagnosed in women worldwide; fortunately, survival is increasing related to early diagnosis and the incorporation of new drugs. In this scenario, preventing long-term toxicities become essential. Cardiac adverse events related to anthracyclines or trastuzumab such as reduction in left ventricular (LV) systolic function and clinical heart failure (HF), are well known and are the leading cause of morbidity in breast cancer survivors. Cardioprotective strategies and early diagnoses of asymptomatic cardiac dysfunction are essential to optimized management and prevention of overt cardiovascular (CV) disease. We made a specific cardiac assessment within an Oncocardiology multidisciplinary Unit in patients receiving anticancer therapies. We present the experience in patients with eBC treated with anthracyclines, trastuzumab or both in the past five years. Materials and Methods: We conducted an institutional, interventional, prospective study in patients who received anthracyclines, trastuzumab or both according to the standard of care (SoC) in eBC. Basal CV risk stratification included lipid profile, glycated haemoglobin, high-sensitive troponin T (hs-TnT) and N-terminal ProB-type natriuretic peptide (NT-ProBNP) was done. Image assessment was done by echocardiogram (echo), including myocardial deformation assessed by speckle tracking (STRAIN). Follow-up was done according to anthracycline or trastuzumab therapy with echo and cardiac biomarkers during the systemic therapy and at the end of anticancer treatment, 1, 2 and 5 years after. Patients with uncontrolled CV risks factors according to local protocol, asymptomatic cardiac dysfunction defined as decreased strain (&amp;gt;15% compared with baseline) or increased cardiac biomarkers (Hs-TnT &amp;gt;14 at baseline or x3 basal value during the follow-up; NT-ProBNP &amp;gt; 300 in patients with &amp;lt; 50y; &amp;gt; 600 in patients between 50-75-y or &amp;gt;900 in patients &amp;gt; 75 years or older) or patients who develop heart failure during the treatment or follow-up were referred to cardiologist. Results: between 2018 and 2022, 1125 patients were diagnosed with eBC in our institution, and 435 patients received systemic treatment with anthracyclines, trastuzumab or both. During the study period, 165 of these patients were referred to the cardio-oncologist. 60% received treatment with anthracyclines, 36% with trastuzumab and 4.1% with both. The median age was 58(±23.2), 60% had previous CV risk factors. The main reason to refer patients to the cardio-oncologist was asymptomatic cardiac dysfunction and uncontrolled CV risk factors. (Table 1). 60% of patients initiated angiotensin-converting-enzyme inhibitors or Beta-blockers, and only two patients stopped anticancer therapy due to severe cardiac dysfunction. The period of high risk of developing cardiotoxicity was the first year after the end of treatment. Conclusion: multidisciplinary evaluation within a cardio-oncology unit is useful to optimize CV risk factors and to detect asymptomatic cardiac dysfunction in patients receiving cardiotoxic drugs. Table 1. Main reasons to refer patients to cardiologist. Citation Format: Tamara Martos, Laia Carla Belarte-Tornero, Mireia Ble, Eva Gimeno, Laura Sanhauja, Felicidad Martines-Medina, Maria Martinez-García, Maria Castro-Henriques, Joan Albanell, Sonia Servitja. INSTITUTIONAL EXPERIENCE IN PATIENTS WITH EARLY BREAST CANCER WHO RECEIVED CARDIOTOXIC THERAPY IN CARDIONCOLOGY UNIT [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-07.

Catheter Ablation for Atrial Fibrillation—Influence of Modifiable Risk Factors and Ablation Modality on Procedural Efficacy and Safety

Modifiable lifestyle risk factors, in particular obesity and related conditions, are important drivers of atrial fibrillation (AF), impacting the severity of symptoms and influence the efficacy and safety of treatment. The study aimed to assess the impact of modifiable lifestyle factors on the effectiveness and safety of AF ablation, and examine the procedural characteristics, efficacy, safety and cost outcomes of cryoballoon vs radiofrequency ablation, in a real-world clinical setting. Patients undergoing catheter ablation for AF (June 2017 to December 2020) were included in this retrospective analysis. Efficacy and safety outcomes were obtained from electronic medical records and state-wide databases. The primary outcome was successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy at 12 months. The study included 141 patients (mean age 60±11 years, 57% male). The average body mass index (BMI) was 29.2±5.6 kg/m2. Ablation by cryoballoon was undertaken in 59% (radiofrequency 41%). Acutely successful pulmonary vein isolation was achieved in 92%, however, only 52% (n=74) met the primary outcome (successful isolation of the pulmonary veins and freedom from AF without repeat ablation or ongoing antiarrhythmic therapy) at 12 months. Successful management of AF was more likely in patients with lower BMI (p=0.006; particularly with BMI <27 kg/m2; p=0.004) and weight (p=0.003), and in those without obstructive sleep apnoea (p=0.032). The only independent predictor of the primary outcome was BMI (β=0.25, p=0.004). Over 75% of complications occurred in those with BMI ≥27 kg/m2. Catheter ablation for AF is more likely to be unsuccessful in patients with uncontrolled risk factors, particularly obesity. Risk factor optimisation may improve procedural success and reduce the risk of procedural complications.

The effectiveness of green heart application to manage modifiable risk factors of coronary artery disease in Tehran Heart Center: Study protocol for a randomized controlled trial

The burden of cardiovascular disease (CVD) is diminishing in developed countries. However, in middle- and low-income countries the CVD death rates are growing. CVD is the most common cause of death and disability in Iran and accounts for nearly half of all mortalities in Iranians. Therefore, preventive strategies by risk factor modification are a top priority in the country.Recently, Mobile-Health (mHealth) technology has been the focus of increasing interest in improving the delivery of cardiovascular prevention, targeting a combination of modifiable risk factors.This parallel-group single-blinded randomized controlled trial study has been designed to evaluate the impact of using a mHealth application on risk factors control. Individuals aged between 25 and 75 years who have documented CVD by coronary angiography in Tehran Heart Center and have at least one uncontrolled risk factor from the three including hypertension, dyslipidemia, and current cigarette smoking will be included. We are going to randomize 1544 patients into two study arms as follows: 1- Intervention: usual care + mHealth 2- Control: usual care + paper-based recommendations and educational materials. After 3 and 6 months of follow-up, the status of risk factors will be determined through outpatient visits and face-to-face interviews for both arms. Outcome: Successful risk factor control will be measured after 3 and 6 months.Nowadays, mHealth is becoming increasingly popular, providing a good opportunity for constant monitoring of risk factors and changing health behavior in a target population. Meanwhile, providing evidence for the effectiveness of health intervention delivery using mobile technologies could help health providers encourage their at-risk population to stop smoking, control blood pressure and blood cholesterol, and participate in regular physical activity. While the burden of CVD is growing in developing countries, this type of intervention can be a cost-effective way to reduce it in these countries.

The secondary prevention of coronary heart disease in US adults 75 Years and older in daily practice: Results from the National Health and Nutrition Examination Survey 1999–2018 survey

BackgroundPharmacologic therapies, risk factor control, and lifestyle alterations were independently proven to reduce long-term cardiovascular events. However, comprehensive research examining the extent to which individuals aged 75 and above in the United States adhere to national guidelines for the secondary prevention of coronary heart disease is limited. Therefore, the primary objective of this study was to examine the current state of secondary prevention of coronary heart disease in persons 75 years of age and older in the United States and to examine the factors that contribute to inadequate drug utilization and poor control of numerous risk factors. MethodsWe identified patients over 75 years of age with coronary heart disease based on the National Health and Nutrition Examination Survey from 1999 to 2018 and analyzed the adequacy of risk factor control and adherence to lifestyle and medication recommendations to assess the effectiveness of coronary heart disease management. Logistic regression analysis was used to identify factors associated with uncontrolled risk factors or noncompliance with recommended medications. ResultsWe collected information from 1566 known coronary heart disease patients aged ≥75 years of age. The majority were at target goals for blood pressure (58.88%), low-density lipoprotein cholesterol (66.85%), and glycated hemoglobin (76.12%). Only 27.8% and 36.06% were at targets for body mass index and waist circumference, respectively. 91.95% reported smoking cessation, 85.98% followed recommended alcohol consumption, whereas only 10.34% reported sufficient physical activity. For β blockers, angiotensin -converting enzyme inhibitors/angiotensin receptor blockers, statins, and antiplatelet drugs, the utilization of indicated therapy was 54.41%, 49.36%, 54.79%, and 19.03%, respectively (6.26% for all 4 medications). The results of the logistic regression analysis demonstrated that diabetes mellitus and metabolic syndrome were critical markers of numerous uncontrolled risk variables as well as noncompliance with medication regimens. ConclusionsA vast majority of coronary heart disease patients ≥75 years in the USA exhibited suboptimal overall control of critical coronary heart disease risk factors. For this patient population, more knowledge is necessary to enable patients to receive continuous support, guidance, and counseling.

Abstract 03: Cardiovascular Disease Risk Factor Control Following Release From Carceral Facilities

Background: Incarceration is a social determinant of cardiovascular disease (CVD) but is rarely addressed in clinical settings or cardiovascular prevention efforts. People who have been incarcerated are more likely to develop CVD at younger ages and have worse cardiovascular outcomes compared with the general population, even after controlling for traditional risk factors. The objective of this study is to identify incarceration-specific factors that are associated with uncontrolled CVD risk factors and identify potential targets for prevention specific to this population. Methods: Using data from Justice-Involved Individuals Cardiovascular Disease Epidemiology (JUSTICE), a prospective cohort study of individuals released from incarceration with CVD risk factors, we examine the association between incarceration-specific and psychosocial factors and CVD risk factor control, including systolic blood pressure (SBP≥140 mmHg, diastolic blood pressure (DBP)≥90, body mass index (BMI)≥40, glycosylated hemoglobin (HbA1c) ≥8%, and low-density lipoprotein cholesterol (LDL-c) ≥160). Incarceration-specific factors include the conditions of confinement (jail vs. prison, time spent in solitary confinement), the carceral health care delivery system (co-payment, medication self-management, discharge planning), and collateral sanctions following release (barriers to housing, food, employment due to criminal record). Psychosocial factors included perceived discrimination and stress, self-efficacy, and lifetime adversity. Results: The mean age of participants (N=417) was 45.2 ±SD 10.7 years and disproportionately men (92%), racially minoritized groups (80%), and poor (66% without an income). Over half (53%) had at least one uncontrolled CVD risk factor. Having been incarcerated in a jail, as compared with prison, was associated with an increased odds of having an uncontrolled CVD risk factor, even after adjusting for age, race and ethnicity, gender, perceived stress, depression symptoms, and life adversity score (AOR 1.79, 95% CI 1.08-2.94). People held in jail, as compared with prison, had higher rates of smoking, uncontrolled hypertension, fewer opportunities to manage one’s own medications while incarcerated, or receive medications prior to release. Discussion: Release from jail is associated with worse CVD risk factor control and requires tailored intervention focused on smoking cessation, hypertension control, and improved discharge planning. These data are especially informative as states design and implement the Centers of Medicare &amp; Medicaid Services new Medicaid Reentry Section 1115 Demonstration Opportunity, which allow Medicaid programs for the first time in history to cover services prior to release from correctional facilities that address chronic health conditions like cardiovascular disease and its risk factors.

Pulmonary edema in a young male with severe uncontrolled cardiovascular risk factors and pan-vascular atherosclerosis: a case report.

Cardiovascular risk factors are the cause of atherosclerotic disease, which can involve all the elastic and muscolo-elastic arteries. The etiopathogenesis of atherosclerosis is multifactorial since genetics, lifestyle, and comorbidities can be simultaneously involved. Clinical manifestations can be heterogeneous and include myocardial infarction, stroke, aortic aneurysms, renal artery stenosis, renal insufficiency, peripheral artery disease, etc. Currently, 70% of clinical events cannot be prevented with available drug therapy, statins included, and at least 10% of coronary events occur in apparently healthy individuals in the absence of major traditional risk factors. The case of a young male with a history of coronary artery disease and multiple atherosclerotic risk factors not properly treated who was admitted to the emergency department for pulmonary edema and high blood pressure is presented. During the diagnostic workup, a dramatic atherosclerotic involvement of all arterial trees emerged. Moreover, the patient presented with thrombosis of the right subclavian artery, which was treated with a heparin infusion and later complicated by cerebral hemorrhage with residual hemiplegia.

Implant Choice May Reduce the Risk of Early Mechanical Failure in Total Ankle Replacement.

Total ankle replacements (TARs) have rapidly advanced in terms of volume, technique, design, and indications. However, TARs are still at risk for early mechanical failure and revision. Prior studies have investigated potential risk factors for failure, but have been limited to smaller series or older implants. This study sought to identify risk factors for early mechanical failure in modern TAR. This is a retrospective study of a single-institution registry. Five surgeons contributed cases involving patients who underwent a primary TAR with any implant. Implants were grouped on the basis of the type of fixation. The primary outcome was early mechanical failure (revision with component removal for a non-infectious etiology, that is, subsidence, aseptic loosening, and/or malalignment). Logistic regression determined the effects of age, weight, hindfoot arthrodesis, implant type, and radiographic deformity on failure. The 731 included patients had a mean follow-up of 2.7 years. Ten percent (71 patients) had hindfoot arthrodesis. There were 33 mechanical failures (4.5%) at a mean of 1.7 years after the index surgical procedure. Our model demonstrated that hindfoot arthrodesis was associated with 2.7 times greater odds of failure (p = 0.045), every 10 kg of body weight increased the odds of tibial-sided failure by 1.29 times (p = 0.039), and implants with more extensive tibial fixation (stems or keels) lowered the odds of tibial failure by 95% (p = 0.031). In patients with uncontrollable risk factors (hindfoot arthrodesis) or risk factors that may or may not be modifiable by the patient (weight), implants with more robust tibial fixation may be able to reduce the risk of early mechanical failure. Further research is warranted to support efforts to decrease early failure in TAR. Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Abstract WP258: Younger Patients Have a Higher Likelihood of Recurrent Vessel Small Subcortical Infarct: A Post-Hoc Analysis of the SPS3 Trial

Introduction: Recurrent ischemic stroke due to intracranial large artery disease occurs in up to 20% of patients and is associated with uncontrolled cardiovascular risk factors. However less is known of recurrent vessel small subcortical infarcts (rvSSI), which may be related to branch atherosclerotic disease. The aim of this study was to describe the clinical risk factors associated with rvSSI. Methods: We performed a post-hoc analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) dataset which enrolled participants between 2003 and 2007. All participants were ≥ 30 years old and had a SSI index event within the preceding 6 months of randomization, confirmed by MRI with a maximal diameter on diffusion weighted imaging (DWI) of ≤ 20 mm, and were without competing stroke mechanism (e.g. ipsilateral carotid stenosis ≥ 50%). Participants were followed over a mean duration of 4 years post-enrollment during which stroke recurrence was noted and characterized. rvSSI was defined as recurrent SSI within the same vascular distribution as an index enrolling infarct confirmed by brain MRI. Chi-squared and student’s T test were used for categorical and continuous variables, respectively. Adjusted logistic regression models were formed to calculate odds ratio. Statistical significance was ≤ 0.05. Results: Of the 3020 participants enrolled in SPS3, 1245 participants met inclusion criteria with 15 having a rvSSI (mean time post-enrollment: 427 days). Participants with rvSSI were younger (54.5 ± 10.2 years vs 61.2 ± 10.6 years, p = 0.008) and had enrollment diagnoses of obesity [BMI ≥ 30 kg/m2; 80% (12/15) vs 49% (598/1230), p = 0.016] and hyperlipidemia [87% (13/15) vs 58% (713/1230), p = 0.025]. Sex, former/current tobacco use, and known diagnoses of hypertension and diabetes mellitus did not differ. For every advancing decade of life, the likelihood of developing a rvSSI was 0.46 (95%CI 0.26 - 0.82, p = 0.008). Conclusions: Participants of the SPS3 trial who were younger in age had rvSSI more frequently with the likelihood decreasing by roughly half with advancing decade of life.

Abstract TP134: White Matter Disease and Patterns of Infarction: A Single Center Study

Background: Patterns of acute cerebral infarction can often reveal the underlying mechanism of ischemic injury. Despite the strong overlap between vascular risk factors and embolic infarct mechanisms (with multifocal infarct patterns), acute multifocal subcortical infarcts may be related to microangiopathic changes. Methods: A prospective stroke registry was queried for patients with acute infarction in &gt;1 vascular territory on diffusion-weighted imaging (unrelated to any endovascular procedure). The odds of a multi-infarct subcortical pattern (vs. cortical pattern) were estimated for patients with higher Fazekas grade (2-3) versus low grade (0-1) patients using forward stepwise logistic regression with greatest minimization of corrected Akaike information criterion including all demographic covariates. Results: Out of 746 patients with acute infarcts and complete covariate data, 226 patients (30.3%) had a multi-infarct pattern, of whom 113 (50.0%) had high grade (Fazekas 2-3) white matter disease. Compared to patients with grade 0-1 Fazekas score, those with grade 2-3 more frequently had multifocal subcortical infarcts (4.4% vs. 10%, p=0.01). Following multivariable adjustment, the odds of multifocal subcortical infarcts were greater for patients with higher Fazekas grades (adjusted odds ratio [OR] 2.9, 95% confidence interval [CI] 1.3-6.7). The higher odds of multifocal subcortical infarcts were observed in a stepwise fashion for each Fazekas grade when compared to grade 0 (adjusted OR for grade 3 10.1, 95% CI 1.2-84; grade 2 OR 9.4, 95% 1.2-75.6; grade 1 OR 4.9, 95% 0.6-40.4). Conclusions: In this single center analysis we found that white matter burden is correlated with subcortical patterns of multifocal cerebral infarction. This suggests such infarcts may be caused by uncontrolled vascular risk factors rather than a proximal embolic source when chronic white matter disease is present.

Tofacitinib use in ulcerative colitis: An expert consensus for day-to-day clinical practice.

Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advancedtherapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a usefulagent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent andthiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.

Effect of a standalone rehabilitation programme for patients with peripheral arterial disease on claudication, cardiovascular risk factors and quality of life

Background/Aims There have been calls to make rehabilitation programmes more accessible to patients with peripheral arterial disease. This study aimed to evaluate the effectiveness of a standalone peripheral arterial disease rehabilitation programme on walking outcomes, quality of life and cardiovascular risk factors as primary outcomes. Secondary outcomes relating to the characteristics that may have influenced change in walking outcomes and reasons for non-attendance or non-completion were also explored. Methods In this prospective, observational, one-site study, new patients were offered a 10-week programme, consisting of exercise, education and intervention for uncontrolled cardiovascular risk factors, in line with international peripheral arterial disease guidelines. Claudication times were measured using the Gardner-Skinner protocol and quality of life was measured using VascuQol. Pre- and post-intervention data were analysed using the SPSS version 23, with Pearson's Rho, Spearman's Rho and t tests being performed as appropriate. Statistical significance was set at P&lt;0.05. Results Of the 160 referrals received, 114 patients were enrolled in the programme and 89 (78%) completed it. Reasons for non-completion were mainly either logistical (domestic commitments or return to work) or perceptions of insuitability relating to age, infirmity or severity of peripheral arterial disease. Of those who completed the programme, the median age was 66 years, 81% were men, 71% had a history of hypertension, 25% had diabetes and 37% smoked. There were significant pre–post improvements (P&lt;0.05) in initial and maximum claudication time and distance, systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein and quality of life scores. Improvements in maximum claudication times were associated with lower baseline initial claudication times, lower body mass index, some quality of life scores and male gender. Conclusions The peripheral arterial disease rehabilitation programme was effective in improving functional capacity, quality of life and some cardiovascular risk factors. Factors found to influence improvements in claudication times could be discussed with patients before and during the programme to address misperceptions, provide encouragement and improve compliance and recruitment. The safe environment of supervised exercise may have contributed to these results, prompting efforts to make exercise accessible to all patients with peripheral arterial disease.

Assessment and prediction of cardiovascular risk and associated factors among tribal population of Assam and Mizoram, Northeast India: A cross-sectional study

BackgroundCardiovascular diseases (CVD) are major health concerns and the leading cause of mortality globally. In India, tribal people are limited to rural areas and often associated with undiagnosed, uncontrolled disease risk factors. In this study, we explore the CVD risk factors and predict the ten-year CVD risk in tribal populations of Assam and Mizoram, Northeast India. MethodsThis community-based cross-sectional study was conducted in Assam and Mizoram from 2019 to 2022. The details of demographics, socioeconomic status, and anthropometric data were collected, and participants were evaluated for cardiometabolic risk factors using serum samples. To identify cardio-metabolic risk-associated factors, we performed a logistic regression analysis. The ten-year CVD risk was calculated using the Framingham general cardiovascular risk prediction equations. ResultsThe study included 1812 participants from the villages of Assam (n = 708) and Mizoram (n = 1104). It was observed that Mizoram's tribal males who were overweight, >35 years of age, with higher systolic (SBP) and diastolic blood pressure (DBP), and low levels of high-density lipoproteins (HDL) had a higher chance of developing cardiovascular disease over the next ten years. Multiple regression analysis revealed that age, gender, body mass index (BMI), smoking habits, and alcohol consumption were the risk factors that elevate SBP, DBP, blood glucose, and lipid levels and contribute to CVD risk among the tribal population. ConclusionOur findings highlight distinct risk factors contributing to cardiovascular risks within the tribal communities of Assam and Mizoram. Hence, it is essential to raise awareness among the tribal population and educate them on adopting a healthy lifestyle.

ELN Criteria for Cytoreduction Start Identify Patients with Polycythemia Vera at Higher Thrombotic Risk

Introduction Recently, the European Leukemia Net (ELN) recommended cytoreduction in patients (pts) with Polycythemia Vera (PV) at low risk (LR) (age &amp;lt;60 yrs &amp; no previous thromboses) but carrying additional criteria for therapy start (CTS) ( Marchetti M et al, Lancet Haematol 2022). Little is known about: 1] efficacy of hydroxyurea (HU) in LR pts, high risk due to age &amp;gt;60 yrs (HR-AGE) or high risk due to previous thrombosis regardless of age (HR-THRO); 2] impact of CTS on thrombotic risk. Aims In a large cohort of HU-treated PV pts, we investigated if thrombotic risk was influenced by: 1] conventional risk factors for thrombosis; 2] ELN-defined complete response (CR) at 12 mos; 3] presence of CTS. Methods After IRB approval, data of 961 WHO2016-defined PV pts were retrospectively collected by 21 Hematology Centers. In April 2023, an update was performed in 10 participating Centers with specific focus on CTS at diagnosis and HU start; 504 HU-treated pts resulted eligible for this analysis. Therapy was at discretion of the treating hematologist. Pts were followed until death or data cut-off date. CTS evaluated for association with thrombosis included: persistent/progressive leukocytosis (100% increase if white blood cells (WBC) &amp;lt;10 x10 9/L or 50% increase if WBC&amp;gt;10 or WBC&amp;gt;15 at diagnosis and HU start); extreme persistent thrombocytosis (&amp;gt;1000 x10 9/L platelets (PLT) at diagnosis and HU start); progressive splenomegaly (increase of &amp;gt;5 cm from diagnosis); inadequate hematocrit (Hct) control (&amp;gt;6 PHL/yr; HCT &amp;gt;53% at diagnosis and HU start; PHL intolerance); uncontrolled cardiovascular risk factors (CVRF). Symptoms were present as the only ELN criterion in 40 patients, of whom none had thrombosis; therefore, they were not included in the analysis. Results 504 pts received HU: 81 pts were at LR and 423 (83.9%) were at HR (HR-AGE, no. 290, 57.5%; HR-THRO, no. 133, 26.4%). Median time on HU was 11.6 yrs (0.1-23.1). During HU, 53 pts had 69 thromboses (35 arterial) for an incidence rate of thrombosis (IR-thro) of 1.5 %p-y, comparably in LR and HR ( Table 1). Notably, IR-thro was equal in LR and HR-AGE (p=0.94), but significantly higher in HR-THRO pts (p=0.005 vs LR and p=0.009 vs HR-AGE). At 12 months, CR was achieved by 8.2%, 23% and 25% of LR, HR-AGE and HR-THRO pts, respectively (LR vs HR-AGE and HR-THRO, p&amp;lt;0.001 and p=0.003). Thrombosis-free survival (TFS) by landmark analysis at 12 months was significantly better in CR pts (p=0.01). Specifically, best TFS was observed in LR and HR-AGE pts with CR, while HR-THRO pts without CR had the worst TFR (p=0.009). CTS were observed in 255 (50.6%) pts: 48 LR (59.3%), 139 HR-AGE (47.9%) and 68 HR-THRO (51.1%). In the remaining LR pts, HU was triggered by mild thrombocytosis (&amp;lt;1000 x10 9/L) and/or mild leukocytosis (&amp;lt;15 x10 9/L) and/or mild splenomegaly (&amp;lt;5 cm from costal margin) and/or persistent systemic symptoms. CTS were associated to significantly increased of IR-thro in the overall cohort (p&amp;lt;0.001), in LR pts (p=0.04), in HR-AGE pts (p=0.02) and in HR-THRO pts (p=0.03) ( Table 1) . The impact of CTS was confirmed in the overall cohort both for arterial (1.30 vs 0.44 %p-y, p=0.01) and venous thrombosis (1.37 vs 0.44 %p-y, p=0.007). TFS at 5 yrs was 87% and 95% in pts with or without CTS (p&amp;lt;0.001) ( Fig.1a). In presence of CTS, TFS of LR and HR-AGE pts were comparable to HR-THRO pts without CTS ( Fig. 1b). In multivariate Cox analysis considering age&amp;gt;60 yrs, previous thrombosis, CTS, and CR to HU at 12 months, CTS and previous thrombosis remained associated with thrombotic risk (HR: 2.7, 95% CI: 1.4-5, p =0.002; HR: 2.4, 95% CI: 1.4-4.2, p =0.001). Finally, in 59 additional LR pts untreated with HU, IR-thro was 0.78 in absence of CTS, and 1.57 %p-y in presence of such criteria. Conclusions Albeit retrospective, this study shows for the first time that ELN criteria for therapy start including splenomegaly, leukocytosis, thrombocytosis, uncontrolled Hct and CVRF, identified an increased risk phenotype either in LR and HR pts treated with HU. This was confirmed also in HU-untreated pts. Also, lack of CR at 12 months was detrimental on TFS particularly in HR-THRO pts, and less significantly than CTS. These findings, that complement data from the Majic-PV trial ( Harrison CN et al, J Clin Oncol 2023), dictate better management of HU therapy, and call for greater attention to CTS and their integration into prognostic models that go beyond the two categories related only to age and thrombotic history.

Aminoglycosides-Related Ototoxicity: Mechanisms, Risk Factors, and Prevention in Pediatric Patients.

Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable risk factors are involved in the pathogenesis of aminoglycoside-related ototoxicity and, because of the irreversibility of ototoxicity, an important undertaking for preventing ototoxicity includes antibiotic stewardship to limit the use of aminoglycosides. Aminoglycosides are fundamental in the treatment of numerous infectious conditions at neonatal and pediatric age. In childhood, normal auditory function ensures adequate neurocognitive and social development. Hearing damage from aminoglycosides can therefore strongly affect the normal growth of the child. This review describes the molecular mechanisms of aminoglycoside-related ototoxicity and analyzes the risk factors and the potential otoprotective strategies in pediatric patients.