Small Risk Research Articles

Effects of Oral Macrocyclic Lactone Heartworm Preventatives on Retinal Function and Chromatic Pupillary Light Reflex in Healthy Companion Dogs.

Determine the effect of oral macrocyclic lactone heartworm-preventative medications on retinal function and chromatic pupillary light reflex (cPLR) in healthy dogs. Cross-sectional retrospective: 60 dogs (n = 33 females) with heartworm medication administration status and electroretinogram (ERG) data available. Prospective clinical study: 25 dogs (n = 10 females) had ERG performed, 18 of which had cPLR performed. Retrospective: ERG amplitudes/peak times were compared between dogs that had or had not received oral heartworm preventatives. Bivariate and multiple variable linear regression models were used to evaluate relationships between ERG testing and heartworm preventive administration status, age, and sex. ERG and cPLR testing were performed at a baseline visit (minimum 14 days since last preventative administration), and a second visit where ERG/cPLR testing was performed 4 h after oral preventative administration. Mixed effects models and Mann-Whitney U statistics were performed. Retrospective: There was no association between heartworm preventive administration status and ERG amplitudes or peak times (all p-values > 0.12). Heartworm preventative had no effect on light- and dark-adapted ERG amplitudes or peak times (all p-values > 0.56). Similarly, there was no effect on baseline pupil size (p = 0.83), nor on cPLR (p = 0.32). No significant effects of oral macrocyclic lactones on retinal/cPLR function at preventative doses were identified. While small effects on retinal/cPLR function cannot be completely ruled out, it remains unlikely that these medications cause clinically significant visual deficits at prescribed doses, and proven antiparasitic benefits likely far outweigh small potential ophthalmic risks of administration.

A Systematic Review of Community-Based Exercise Interventions for Adults with Intellectual Disabilities

Background: Adults with intellectual disabilities are a particularly inactive sub-population who experience disproportionally poorer health and social exclusion when compared with the wider general population. This systematic review aimed to identify whether community-based exercise interventions were theoretically underpinned, whether they had an active single- or multi-exercise component, and how the interventions were objectively and/or subjectively measured, as well as deducing if they improved the health of this population. Method: A systematic search of five databases was conducted up to May 2024. The study was registered in PROSPERO and followed PRISMA reporting guidelines. Study methodological quality was appraised using the Critical Appraisal Skills Programme. Risk of bias was determined using the Cochrane collaboration tools ROB 2 and ROB 2 CRT. Articles were eligible for inclusion if they recruited adults with intellectual disability, were community-based, had an active exercise component and measured physical activity (PA) levels as an outcome measure. Results: In total, 9034 records were identified, with five studies meeting the eligibility criteria. All studies used a feasibility RCT or RCT methodology and all focused on weight loss or PA levels as the primary outcome measure. Two studies focused on walking as a single exercise, two combined walking with nutrition/weight loss, and one combined walking with aerobics. One multi-component walking and aerobics intervention led to statistically significant improvements in PA. Multi-component community-based exercise interventions led to statistically significant improvements in body composition measures. No studies showed statistically significant improvements in quality of life. Risk of bias was rated moderate to high across all included studies. Conclusions: Caution should be taken in drawing firm conclusions due to the small number of included studies, small sample sizes and high risk of bias. Multi-component community-based interventions are more effective at improving PA levels in adults with intellectual disabilities than walking-only studies. Future studies should be theoretically underpinned and explore the use of peer and student models of social support. The use of fitness facilities such as leisure centres and gyms requires further exploration in this population.

P-444. Cerebral Small Vessel disease risk in people with HIV and substance use disorder

Abstract Background Cerebral small vessel disease (CSVD) is associated with an increased risk of stroke, dementia, and death. The risk of CSVD in people with HIV (PWH) is twice the general population but the CSVD risk in PWH with substance abuse is poorly defined. With national surveys showing approximately two-thirds of PWH admitting to using an illicit drug in their lifetime, the evaluation of CSVD risk in this population is needful.Table 1:Demographic and Clinical information of CSVD in PWH with substance use disorder (N=23) Methods We retrospectively analyzed brain magnetic resonance imaging (MRI) findings of PWH attending our ambulatory HIV needle exchange clinic. Brain MRIs done in the previous 5 years before study analysis were included. CSVD was determined by Cerebral small vessel disease score (0 to 4), assigning 1 point each for the following: (i) presence of lacunar infarct, (ii) microbleeds, (iii) prominent perivascular spaces, and (iv) white matter hyperintensities. The findings suggestive of CSVD such as age-related white matter changes and chronic microvascular ischemia were also included in the CSVD assessment. Substance use disorder (uncontrolled use of a substance despite harmful consequences) was determined to be present if this was included on the patient diagnosis list.Table 2:Cerebral Small Vessel disease Score in PWH with substance use disorder. 5 participants had a CSVD score of 0 but "age related white matter disease" on Brain MRI Results 51 patients (PWH with substance use disorder) were included in the analysis. 23 participants out of this group had brain MRI imaging out of which 12 (52.2%) had CSVD. The mean age was 50 years. The demographic and clinical data of the cohort are shown in Table 1. The CSVD score ranged from 0 to 3 with an average score of 1. Table 2 illustrates the CSVD score of the cohort. 5 participants had a CSVD score of 0 but a brain MRI report of “age-related white matter changes”. The Pearson Correlation between age and CSVD score was 0.057 with a p-value of 0.86. Conclusion 52% of PWH who use substance have CSVD on MRI brain imaging. This could translate to an increased risk of stroke, cognitive impairment, and death if not recognized early and aggressively addressed. CSVD score provides objective quantification of CSVD but age-related white matter changes, which are not captured on this score may be equally important especially as PWH continues to age. A systematic approach for screening for CSVD in PWH with substance use disorder is warranted to minimize the unfavorable outcomes associated with this cohort. Disclosures All Authors: No reported disclosures

Myocardial Infarction Following Epinephrine Administration in Anaphylaxis: A Case Report

Anaphylaxis is a severe, acute hypersensitivity reaction that can lead to rapid deterioration and potentially fatal outcomes if untreated. Common symptoms include shortness of breath, angioedema, and hypotension. Despite the high incidence, mortality rates remain low due to the first-line treatment, epinephrine, and its well-established effectiveness in anaphylaxis management. Epinephrine acts as an alpha- and beta-adrenergic agonist, effectively increasing blood pressure and relieving airway obstruction. However, epinephrine can rarely induce cardiovascular events. Here, we present a case of a 55-year-old male with a known history of hypertension, ischemic heart disease, and smoking. Presented to the ED with a severe allergic reaction, he was given epinephrine, which resulted in the development of myocardial infarction. The literature suggests a small but significant risk of cardiotoxicity linked to epinephrine, with intramuscular (IM) administration being preferable over intravenous (IV) due to lower associated risks. While the risk of cardiovascular events exists, timely epinephrine administration is crucial for preventing severe anaphylactic outcomes. Clinicians must be mindful of the adverse effects of epinephrine and carefully assess and monitor the patients, particularly those at risk of cardiovascular events.

BHSeP4 Recurrent omphalitis after open mesh repair ofumbilical hernia: misdiagnosis or complication?

Abstract The use of prosthetic mesh has become the standard practice for repairing all types of hernia due to its low recurrence rate. However, there is a small risk of mesh migration and erosion into the bowel, which can result in major morbidities. One treatment option for this condition is a surgical resection of the affected segment of the bowel, along with the removal of the mesh. We report on a 62-year-old male who had a mesh that migrated through his small bowel 16 years after his hernia repair. This patient developed recurrent umbilical discharge, pain and was treated in the community for recurrent omphalitis by GP. Delayed diagnosis led to chronic enterocutaneous fistula, which was treated with laparotomy, en bloc resection of small bowel/umbilicus/old hernia mesh, along with retrorectus mesh reconstruction of abdominal wall.

P1175 Handheld ultrasound devices are an accurate alternative to cart-based ultrasound for IBD disease activity assessment

Abstract Background Intestinal ultrasound has revolutionised inflammatory bowel disease (IBD) care, as a quick, cost-effective, accurate and reliable tool for assessing IBD activity. Recently high-quality handheld ultrasound devices (HHUS) have emerged, representing a more accessible, cheaper alternative to expensive and cumbersome cart-based ultrasounds (CBUS), however their accuracy for IUS has not been studied. We aimed to assess the accuracy of HHUS compared to CBUS in a real-world IBD population. Methods We prospectively recruited patients attending outpatient IBD clinics in a tertiary centre from 18 July to 1 October 2024. Patients were first scanned by IUS trainees or clinicians certified by the Gastroenterological Network of Intestinal Ultrasound using 1-2 HHUS (Clarius™ L15 HD3 (CL) and/or GE™ Vscan Air CL (GE) using linear and convex probes as needed) and then CBUS. We collected baseline demographics, standard ultrasound parameters, disease activity classification, concordance with CBUS, and the predicted impact on clinical management. Qualitative statistical analyses and diagnostic accuracy calculations were performed. Results We performed IUS on 101 patients (49% ulcerative colitis, 52% Crohn’s disease, 46% male, median age 39 years, median BMI 23.4 kg/m2), using CL in 69 (total segments 260) and GE in 57 (total segments 220). The demographics and scan results are detailed in Table 1. Overall concordance for disease activity status (classified as "active" or "inactive") with CBUS was 93% for CL and 91% for GE, and 100% and 95% respectively for patients with a BMI >25 kg/m2. There were 5 discordant scans each for CL (7%) and GE (9%) mostly related to discrepancies in bowel wall thickness in either the sigmoid colon or terminal ileum (there was a discrepant Doppler result in 1 case), in which 4 cases for both GE and CL reported high clinician confidence with the results. It was anticipated that the discordant result would negatively impact management in 4 (5.8%) cases for CL and 3 (5.2%) cases for GE. Overall sensitivity and specificity were high in both CL (85% and 100%) and GE (76% and 100%) and remained reasonably high for all segments (see Figure 1). Conclusion Both CL and GE HHUS represent viable alternatives to CBUS, with high diagnostic accuracy for IUS in IBD patients with normal and high BMIs. Given significantly lower costs, use of HHUS could improve access to IUS in IBD care internationally. There is a small risk that rare discordant results could negatively impact management, however this risk could be mitigated by interpreting IUS findings in the context of other disease activity markers and considering a repeat IUS using CBUS where there is uncertainty regarding findings.

Treatment of Hyperthyroidism in Graves' Disease Complicated by Thyroid Eye Disease.

Thyroid eye disease (TED) is the most consequential extrathyroidal manifestation or complication of Graves' disease (GD). Treatment of hyperthyroidism in GD complicated by TED is challenging. Antithyroid drugs (ATDs) and thyroidectomy do not change the natural course of TED, while radioactive iodine (RAI) is associated with a small but well-documented risk of TED de novo occurrence or its progression/worsening. In the presence of mild TED, any treatment for hyperthyroidism can be used, but should RAI treatment be selected, steroid prophylaxis (short course of low-dose prednisone) is strongly recommended if TED is of recent onset and/or risk factors for progression exist. In moderate-to-severe and active TED, ATDs are the preferred treatment but thyroidectomy is a valid option. RAI ablation is generally avoided, but it might be used when the clinical situation calls for it but with extreme caution if an aggressive treatment for TED with high-dose glucocorticoids (with or without orbital radiotherapy) is administered concomitantly. In moderate-to-severe and inactive TED, all three treatments for hyperthyroidism are acceptable, and steroid prophylaxis in RAI-treated patients should be given when risk factors for TED progression are identified. Management of sight-threatening TED represents the absolute priority, and hyperthyroidism should be controlled with ATDs until TED has been cured.

Association between Estimated Small Dense Low-Density Lipoprotein-cholesterol (sdLDL-C) and Atherosclerotic Cardiovascular Disease Risk

Resumo Fundamento Uma nova fórmula para estimar o colesterol de lipoproteínas pequenas, densas e de baixa densidade (sdLDL-C) com base nos resultados do painel lipídico padrão é proposto. Objetivos Para avaliar a associação entreestimado sdLDL-C (EsdLDL-C) e o risco de doença cardiovascular arterosclerótica (DCVA). Métodos Um total de 12.192 participantes do banco de dados do Korea National Health and Nutrition Examination Survey (KNHANES) entre 2010 e 2020 foram incluídos neste estudo transversal. EsdLDL-C foi calculada como EsdLDL-C = LDL-C- [1,43 × LDL-C - (0,14 × (ln (TG) × LDL-C)) - 8,99]. Análises de regressão logística foram utilizadas para avaliar a associação entre EsdLDL-C e risco de DCVA. As análises de subgrupos foram realizadas com base na idade, índice de massa corporal (IMC), hipertensão, e diabetes. Uma razão de possibilidades (OR) com um intervalo de confiança de 95% (IC) foi utilizado para avaliação. P<0,05 foi considerado estatisticamente significativo. Resultados Entre 12.192 participantes, 1.239 (10,16%) tinham DCVA. A média de sdLDL-C dos participantes foi estimada em 42,43±14,75 mg/dL usando a fórmula. Níveis elevados de EsdLDL-C (OR=1,33; IC 95%, 1,06-1,66) foram associados a um aumento do risco de DCVA. As análises de subgrupos descobriram que pode haver uma interação entre EsdLDL-C (Pinteração=0,001) ou não-HDL-C (Pinteração=0,015) e hipertensão no risco de DCVA. Conclusões Níveis elevados estimados de sdLDL-C foram associados ao risco de DCVA, e o sdLDL-C estimado pode ser uma alternativa à medição do sdLDL-C para avaliação do risco de DCVA.

Anterior Cruciate Ligament Reconstruction Graft Options.

Anterior cruciate ligament reconstruction is one of the most common orthopaedic sports medicine surgeries. Its prevalence in the sports medicine sphere is matched by the numerous options of different techniques. Chief among these is graft selection, which most commonly falls into 1 of 4 options: bone-patellar tendon-bone (BPTB) autograft, hamstring tendon autograft (HT), quadriceps tendon autograft, and allografts. The most frequently used allografts include BPTB, HT, tibialis anterior or posterior tendon, and Achilles tendon. Each graft option possesses unique advantages and disadvantages. BPTB autograft demonstrates the fastest incorporation via bone-to-bone healing. It also yields a lower revision rate and greater return-to-sport rate compared with HT. However, because of donor-site morbidity, anterior knee pain and kneeling pain can occur. There is also a small risk of patellar fracture as well as patellar tendon rupture. HT autograft requires a smaller incision than BPTB and preserves the extensor mechanism. Patients are at risk for knee flexion weakness, saphenous nerve injury, and potential graft loosening over time secondary to bone tunnel widening. Quadriceps tendon autograft may be harvested with minimally invasive techniques. As with HT, the all soft-tissue composition allows use in skeletally immature patients. Although early studies show promise, knee extension weakness has been documented, and long-term outcomes are less clear. Allograft possesses no donor-site morbidity and reduced surgical time; however, allografts are associated with the greatest failure rate in young athletes and a lower return-to-sport rate compared with autografts. They also incur a greater financial cost than autografts. To be proficient at performing anterior cruciate ligament reconstruction, it is important that the sports medicine surgeon be well versed in the various graft options and the ideal patient populations for whom they are best used.

Long Short Term Memory For Comparison Between Bank Syariah Indonesia And PT Bank Artos Indonesia Shares

The growth of the capital market in Indonesia has increased from year to year. Based on data from the Indonesia Central Securities Corporation (KSEI), there has been an increase in investor growth in the capital market by 2.34%, mutual funds by 2.44%, and shares by 1.34% until August 2024. The demographic of individual investors in the capital market is dominated by Generation Z who are younger than from 30 years as much as 55.07% in August 2024 (KSEI, 2024). Shares are a form of investment that has the potential for large profits but with small risks. One sector that Gen Z is interested in investing in is the financial sector. The aim of this research is to compare the share prices of Bank Syariah Indonesia and Bank PT Ban Artos Indonesia Tbk using a Neural Network with the Long Short Term Memory (LTSM) algorithm. The data used in this research is secondary data on BSI and PT Bank Artos Indonesia Tbk share prices taken from the investing.com website. The data period used is from 01 September 2021 – 01 September 2024. Based on the results of stock price forecasting using a Neural Network with the LTSM algorithm, RMSE value for both models is for BSI 75.0757 and 91.795 for PT. Bank Artos Indonesia Tbk. A comparison of the predicted share prices of PT Bank Arto Indonesia Tbk and BSI shows that BSI's share price performance is superior to that of PT Bank Arto Indonesia Tbk.

Very small risk of stroke and MI associated with triptans

Very small risk of stroke and MI associated with triptans

The Use of Novel Therapies in the Management of Haemolytic Disease of the Fetus and Newborn (HDFN): Scientific Impact Paper No. 75.

Haemolytic disease of the fetus and newborn (HDFN) is a rare condition that causes a baby to develop anaemia while growing inside the woman; or after birth. Left untreated, this may lead to stillbirth or neonatal death. HDFN is caused when the pregnant woman's antibodies cross the placenta, enter the baby's circulation, and attach to proteins called antigens (inherited from the father) on the baby's haemoglobin containing red blood cells, and cause them to break apart, causing fetal anaemia. Women routinely have their blood tested at the start of pregnancy to assess their ABO blood group and Rh antigens. There are five main Rhesus antigens: D, C, c, E, e; with anti-D being responsible for most cases of HDFN. If a woman is found to be Rh D negative; a 'non-invasive' blood test is performed to assess if the fetal blood group is the same as the woman's. If a woman is found to be Rh D negative, and the baby is found to be D positive, the baby is at risk. This is because the baby has inherited the D antigen from the father; so-called Rhesus incompatibility. Other red blood cell antibodies such as anti-Kell or anti-Duffy can also cause fetal anaemia. Women at highest risk of developing HDFN are those who have had at least one previous birth or a sensitising event (such as abdominal trauma) in a current or previous pregnancy, causing the woman and baby's blood to mix. Current treatment for haemolytic disease of the fetus involves giving fetal blood transfusions, with a small risk of early labour or pregnancy loss. If anaemia develops later in pregnancy, early delivery of the baby may be recommended; which could lead to complications of prematurity. In cases of mild HDFN, the baby may only require light therapy for neonatal jaundice. However, if the anaemia occurs earlier in pregnancy and is severe, the baby may need blood transfusions while still in the womb - and after birth may require an exchange transfusion, to remove the woman's antibodies from their circulation and to treat the anaemia. Intravenous immunoglobulin (IVIG) is a potential non-invasive method to prevent or delay the onset of severe anaemia. It is a blood product given intravenously every week to women who have been deemed at very high risk of early onset HDFN. It can be started at the end of the first trimester until birth, or until anaemia develops. This paper will discuss the evidence behind IVIG and other novel therapies during pregnancy, including the risks and the benefits. The developers of the paper include obstetricians, neonatologists and haematologists to provide different opinions on this topic.

Economic and Political Aspects of Egypt’s Accession to BRICS

The article focuses on the reasons why the Egyptian leadership decided to join BRICS in January 2024. The analysis of the Egyptian leadership’s public rhetoric has shown that the key motives for joining the organization are usually related to the economy: Egyptian politicians most often talk about expanding cooperation with the organization’s member countries, dedollarization and the New Development Bank. This is due to the fact that Egypt is facing serious economic problems, which relate to budget deficit, high inflation, trade deficit and devaluation of the national currency. BRICS cannot solve these Egyptian problems and is not a “silver bullet” but the benefits of joining, associated with economic cooperation and the New Development Bank, far outweigh the costs, which are limited to a small risk of deteriorating relations with the United States. BRICS does not impose rigid obligations on its members, which makes the organization attractive to countries with different political systems, allowing them to maintain balance in international relations with different actors thereof (such as the United States, China, Russia, India, European Union countries etc.)

Intranasal Dexmedetomidine Administration Precipitates Respiratory Failure in Child With Croup and Asthma.

Intranasal dexmedetomidine administration in clinically recommended doses has a small but important risk of causing catastrophic respiratory failure in the setting of preexisting severe respiratory workloads.

Does remote COVID infection in pregnancy affect the placenta and pregnancy outcomes? - Results from a prospective cohort study (PLACENTA IN COVID/ PIC study).

To study the rates of abnormal placentae and associated adverse perinatal outcomes in pregnant women who had COVID 19 infection during pregnancy, remote from delivery. To study the histopathological findings associated with these abnormal placentae. A prospective cohort study was carried out, recruiting pregnant women with singleton gestation, who had COVID 19 infection during their pregnancy, remote from delivery between August 2021 to July 2022. Ethics approval was obtained by the Institutional Review Board. Abnormal placentae were identified as those with weight <10th centile and associated histopathological findings were noted . Rates of SGA (small for gestational age) babies and stillbirths were recorded. The data was analyzed using Statistical Package for Social Sciences (SPSS) v 25. Most of the 67 women in our cohort, had mild forms of COVID 19. Half had had infection in their second trimester. Among those infected in the third trimester, 93% were symptomatic. Gestational Diabetes was the most common associated medical condition. . Abnormal placentae were seen in 40%(n=27) of women. Half of these (15) were associated with SGA babies . Distribution of medical co morbidities was comparable among those with abnormal and healthy placentae. Most, 84%, SGA babies were born to mothers who had COVID <28 weeks GA. There is a small but significant risk of SGA babies being born to women who had COVID at<28 weeks, irrespective of medical comorbidities. Close monitoring of these pregnancies is, hence warranted.

Use of active low suction pressure (subgaleal) drains in chronic subdural haematoma surgery

Subdural drains are used to reduce recurrence after surgical evacuation of chronic subdural hematoma. There is a small risk of parenchymal injury. We hypothesize that using subgaleal drains with low active suction (-50 mm Hg to -100 mm Hg) may be a safer alternative and still maintain efficacy in preventing recurrence. A retrospective review of adult patients who underwent surgical drainage of chronic subdural hematoma at our institution was performed. They were classified into 2 groups: a subdural group and a subgaleal group. We collected data on patient demographics, preoperative use of antiplatelets or anticoagulants, the type of drains used, laterality of burr-hole surgery performed and postoperative complications, and recurrence. Descriptive statistics and regression analyses were used to analyze the data. 322 patients recruited, 172 received subgaleal drains with low active suction and 150 received passive subdural drains. There was no significant difference in the rate of recurrence; there was 11. % recurrence in the subgaleal drain group and 9.3% recurrence in the subdural drain group (P= 0.660). Patients who underwent active subgaleal drain insertion had significantly fewer complications, at 2.3% compared with 8.0% in patients who had passive subdural drains (P= 0.037). The use of subgaleal drains with low active suction led to significantly lower complication rates compared with the use of subdural drains and maintained its efficacy in preventing recurrence.

SENSITIZING POTENTIAL OF TEMPORARY FILLING MATERIALS

Introduction: When treatment requires multiple visits, temporary filling materials are needed in order to seal the cavity between the appointments. Some of their substances can be contact allergens. Although the risk is very low, it should not be ignored. The aim of the study is to establish the sensitizing potential of temporary filling materials. Materials and methods: In order to confirm allergy to temporary filling materials, we used a patch test with a panel of 9 allergens – components of temporary filling materials with established strong sensitizing properties. Results: The results showed that sensitization and polysensitization to the examined dental materials are registered more often in women than men and zinc (Zn) is the most common sensitizer among the ingredients of temporary filling materials. Cross-sensitization between acrylates is also found. Conclusion: There is an extremely small risk for the ingredients of the temporary filling materials to cause oral symptoms.

A Sequential Learning Procedure for Estimating Coefficients in Linear Regression With Applications to Online Sales Examination

ABSTRACTIn this paper, we consider the problem of estimating coefficients in a linear regression model. We propose a sequential learning procedure to determine the sample size for achieving a given small estimation risk, under the widely used Gauss‐Markov setup with independent normal errors. The procedure is proven to enjoy the second‐order efficiency and risk‐efficiency properties, which are validated through Monte Carlo simulation studies. Using e‐commerce data, we implement the procedure to examine the influential factors of online sales.

The contribution of attention-deficit/hyperactivity disorder polygenic load to metabolic and cardiovascular health outcomes: a large-scale population and sibling study

Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18–90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals’ own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03–0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01–0.16%) (P < 0.05). Adjustment for shared familial factors attenuated the associations between ADHD-PGS and cardiometabolic outcomes (on average 56% effect size reduction), and significant associations only remained for metabolic disease. Overall our findings suggest that increased genetic liability for ADHD confers a small but significant risk increase for cardiometabolic health outcomes in adulthood. These associations were observable in the general population, even in individuals without ADHD diagnosis, and were partly explained by familial factors shared among siblings.

Abstract 4135082: Small dense low-density lipoprotein cholesterol and risk of peripheral artery disease

Background: High levels of small dense low-density lipoprotein (sdLDL) is a hallmark of dyslipidemia; however, studies on sdLDL cholesterol levels and risk of peripheral artery disease are sparse and results inconclusive. Hypothesis: We tested the hypothesis that higher levels of sdLDL cholesterol are associated with increased risk of peripheral artery disease in a primary prevention setting. Methods: We studied 31,036 individuals free of lipid-lowering therapy, ischemic stroke, and myocardial infarction at study entry in 2013-2017. All had fresh sample measurements of sdLDL cholesterol. During a median follow-up on 6.2 years, 155 were diagnosed with peripheral artery disease. The association was confirmed using ankle-brachial index (ABI) ≤ 0.9 as endpoint. Lastly, as comparison across different vascular beds risk estimates for myocardial infarction and ischemic stroke were calculated. Results: Higher levels of sdLDL cholesterol were associated with higher risk of peripheral artery disease and an ABI ≤ 0.9 illustrated by cubic splines multivariable adjusted for sex, systolic blood pressure, education, body mass index (BMI), diabetes, large buoyant LDL cholesterol, and age. Per 1 mmol/L (37 mg/dL) higher sdLDL cholesterol hazard ratio for peripheral artery disease was 2.01 (95% CI: 1.41-2.85) and odds ratio for an ABI ≤ 0.9 was 1.51 (95% CI: 1.07-2.14) in multivariable adjusted models. The cumulative incidence of peripheral artery disease was respectively 1.5%, 2.5%, and 3.5% for individuals having a sdLDL cholesterol in the 1 st -50 th , 51 st -90 th , and the 91 st -100 th percentiles at age 80. For the 91 st -100 th versus the 1 st -50 th percentile a hazard ratio on 2.51 (95% CI: 1.50-4.20) for peripheral artery disease, 2.18 (95% CI: 1.58-3.01) for myocardial infarction, and 1.85 (95% CI: 1.37-2.49) for ischemic stroke was found. Furthermore, the association of higher sdLDL cholesterol with increased risk of peripheral artery disease was robust in sensitivity analyses. Conclusion: Higher levels of sdLDL cholesterol were robustly associated with increased risk of peripheral artery disease in a primary prevention setting.