High-dose Aspirin Research Articles

Abstract 15758: Platelet Aggregation is Elevated in Psoriasis and Associated With Cardiovascular Risk

Introduction: Psoriasis is associated with increased CV risk the mechanisms and prevention of which are not fully known. We evaluated the platelet phenotype (implicated in atherothrombosis) and in vitro response to aspirin in patients with psoriasis and its association with vascular stiffness and coronary atherosclerosis. Methods: Patients with psoriasis (n = 64, age 47.9 ± 15 years, 65% male), percent body surface area (BSA) of psoriasis 3%, were compared to controls (n = 40, age 40.8 ± 16 years, 45% male). Percent platelet aggregation in response to agonists adenosine diphosphate (ADP), collagen (Col), and arachidonic acid (AA - with and without aspirin) was measured in freshly isolated platelet-rich plasma via light transmission aggregometry (LTA). Vascular stiffness (via pulse wave velocity [PWV]) and CT coronary angiography were each performed as readouts of CV risk. Results: Compared to controls, psoriasis patients were older, of Caucasian ethnicity (Figure 1A), and overweight, but otherwise similar. Platelet aggregation after treatment with Col (p=0.01), ADP (p < 0.01), and AA (p = 0.05) were all higher in psoriasis vs. control (Figure 1B-D). Platelet aggregation after activation with high dose AA was similar between groups (Figure 1E) however co-incubation with high dose AA plus aspirin displayed incomplete platelet inhibition of psoriasis platelets vs. controls (Figure 1F). Platelet aggregation to low dose AA and high dose AA plus aspirin co-incubation were each higher in those with enhanced vascular stiffness (figure 1G/1H) and the presence of coronary plaque (Figure 1I/1J). Conclusion: Platelet aggregation is consistently elevated in psoriasis across a variety of agonists, incompletely inhibited by aspirin, and associated with biomarkers of CV risk such as vascular stiffness and the presence of coronary plaque. These findings highlight the need to evaluate various anti-platelet strategies to reduce atherothrombotic risk in patients with psoriasis.

Abstract 18486: Recurrent Pericarditis Following Atrial Fibrillation Ablation: Unmasking Latent Tuberculosis Infection

Background: Tuberculous pericarditis is rare in the United States but can lead to serious sequelae in the absence of diagnosis and treatment. We report a case of recurrent pericarditis following catheter ablation of atrial fibrillation (AF) due to reactivation of latent TB infection. Case Summary: A 52-year-old male with no past medical history underwent a difficult trans-septal puncture & cryo-balloon PV isolation, complicated by acute pericarditis and pericardial effusion with cardiac tamponade. He underwent pericardiocentesis with removal of 260cc bloody fluid. He had resolution of chest pain with ibuprofen, but experienced recurrence after 3 months and was given a longer NSAID course. Two months later, he presented with chest pain along with night sweats & low-grade fever. He had an elevated C-reactive protein, and echocardiography revealed thickened pericardium & constrictive physiology. He received high-dose aspirin, prednisone, and colchicine for recurrent pericarditis. Extensive Infectious Disease & Rheumatology work-up ruled out autoimmune & viral etiologies but his T-Spot TB test was positive. He denied personal or contact history of TB except travel to Asia 20 years ago. CT scan ruled out pulmonary TB infection. A 6-month course of Rifampin was prescribed. He experienced a 4th episode of pericarditis while tapering off prednisone, and restarted prednisone, Ibuprofen, and colchicine. Additionally, Rilonacept was prescribed. After completing 6-months of Rifampin and Rilonacept, he had significant improvement and no further recurrences on 1 year follow up. Discussion: Pericarditis is a common complication of catheter ablation, often resulting from direct injury. We report a case of recurrent pericarditis, initially believed to be a traumatic complication of AF ablation. However, investigation revealed underlying latent pericardial TB infection. Appropriate treatment led to complete resolution without sequelae.

Effectiveness and Safety of Enteric-Coated vs Uncoated Aspirin in Patients With Cardiovascular Disease

Clinicians recommend enteric-coated aspirin to decrease gastrointestinal bleeding in secondary prevention of coronary artery disease even though studies suggest platelet inhibition is decreased with enteric-coated vs uncoated aspirin formulations. To assess whether receipt of enteric-coated vs uncoated aspirin is associated with effectiveness or safety outcomes. This is a post hoc secondary analysis of ADAPTABLE (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness), a pragmatic study of 15 076 patients with atherosclerotic cardiovascular disease having data in the National Patient-Centered Clinical Research Network. Patients were enrolled from April 19, 2016, through June 30, 2020, and randomly assigned to receive high (325 mg) vs low (81 mg) doses of daily aspirin. The present analysis assessed the effectiveness and safety of enteric-coated vs uncoated aspirin among those participants who reported aspirin formulation at baseline. Data were analyzed from November 11, 2019, to July 3, 2023. ADAPTABLE participants were regrouped according to aspirin formulation self-reported at baseline, with a median (IQR) follow-up of 26.2 (19.8-35.4) months. The primary effectiveness end point was the cumulative incidence of the composite of myocardial infarction, stroke, or death from any cause, and the primary safety end point was major bleeding events (hospitalization for a bleeding event with use of a blood product or intracranial hemorrhage). Cumulative incidence at median follow-up for primary effectiveness and primary safety end points was compared between participants taking enteric-coated or uncoated aspirin using unadjusted and multivariable Cox proportional hazards models. All analyses were conducted for the intention-to-treat population. Baseline aspirin formulation used in ADAPTABLE was self-reported for 10 678 participants (median [IQR] age, 68.0 [61.3-73.7] years; 7285 men [68.2%]), of whom 7366 (69.0%) took enteric-coated aspirin and 3312 (31.0%) took uncoated aspirin. No significant difference in effectiveness (adjusted hazard ratio [AHR], 0.94; 95% CI, 0.80-1.09; P = .40) or safety (AHR, 0.82; 95% CI, 0.49-1.37; P = .46) outcomes between the enteric-coated aspirin and uncoated aspirin cohorts was found. Within enteric-coated aspirin and uncoated aspirin, aspirin dose had no association with effectiveness (enteric-coated aspirin AHR, 1.13; 95% CI, 0.88-1.45 and uncoated aspirin AHR, 0.99; 95% CI, 0.83-1.18; interaction P = .41) or safety (enteric-coated aspirin AHR, 2.37; 95% CI, 1.02-5.50 and uncoated aspirin AHR, 0.89; 95% CI, 0.49-1.64; interaction P = .07). In this post hoc secondary analysis of the ADAPTABLE randomized clinical trial, enteric-coated aspirin was not associated with significantly higher risk of myocardial infarction, stroke, or death or with lower bleeding risk compared with uncoated aspirin, regardless of dose, although a reduction in bleeding with enteric-coated aspirin cannot be excluded. More research is needed to confirm whether enteric-coated aspirin formulations or newer formulations will improve outcomes in this population. ClinicalTrials.gov Identifier: NCT02697916.

Management Patterns and Outcomes After Traumatic Brain Injury With Associated Blunt Cerebrovascular Injury.

Although blunt cerebrovascular injuries (BCVIs) are relatively common in patients with traumatic brain injuries (TBIs), uncertainty remains regarding optimal management strategies to prevent neurological complications, morbidity, and mortality. Our objectives were to characterize common care patterns; assess the prevalence of adverse outcomes, including stroke, functional deficits, and death, by BCVI grade; and evaluate therapeutic approaches to treatment in patients with BCVI and TBI. Patients with TBI and BCVI treated at our Level I trauma center from January 2016 to December 2020 were identified. Presenting characteristics, treatment, and outcomes were captured for univariate and multivariate analyses. Of 323 patients with BCVI, 145 had Biffl grade I, 91 had grade II, 49 had grade III, and 38 had grade IV injuries. Lower-grade BCVIs were more frequently managed with low-dose (81 mg) aspirin ( P < .01), although all grades were predominantly treated with high-dose (150-600 mg) aspirin ( P = .10). Patients with low-grade BCVIs had significantly fewer complications ( P < .01) and strokes ( P < .01). Most strokes occurred in the acute time frame (<24 hours), including 10/11 (90.9%) grade IV-related strokes. Higher BCVI grade portended elevated risk of stroke (grade II odds ratio [OR] 5.3, grade III OR 12.2, and grade IV OR 19.6 compared with grade I; all P < .05). The use of low- or high-dose aspirin was protective against mortality (both OR 0.1, P < .05). In patients with TBI, BCVIs impart greater risk for stroke and other associated morbidities as their severity increases. It may prove difficult to mitigate high-grade BCVI-related stroke, considering most events occur in the acute window. The paucity of late time frame strokes suggest that current management strategies do help mitigate risks.

Metformin Reduces Tumor Growth in a Murine Flank Schwannoma Model.

Metformin and aspirin reduce vestibular schwannoma (VS) growth. There have been reported associations between patients with VS prescribed metformin and decreased tumor volumetric growth. Aspirin has also been associated with decreased VS growth in animal studies. Rat schwannoma cell lines were grown and implanted into 50 athymic nude mice. Tumors were grown to 5 mm, and then mice were injected with either low- or high-dose metformin, aspirin, or saline daily. Tumors were measured until 14 days elapsed or mice demonstrated symptoms such as ulceration, inability to walk, or passed away. There were no significant differences in day 0 tumor sizes between the control and the treatment groups ( p = 0.73). In the low-dose, but not high-dose groups, day 7 volumes were significantly different for both metformin ( p = 0.04) and aspirin ( p = 0.02) compared with placebo. Mean tumor growth rates were 126.6 ± 65.6 mm 3 /day for saline compared with 73.7 ± 29.5 mm 3 /day for low-dose metformin ( p = 0.03) and 68.7 ± 34.8 mm 3 /day for low-dose aspirin ( p = 0.016). There were no significant differences in tumor sizes ( p = 0.59) or growth rates ( p = 0.75) between low-dose metformin and aspirin groups. Low-dose groups had treatment stopped at 14 days, with continued monitoring demonstrating significant increases in tumor growth off treatment for both aspirin ( p = 0.006) and metformin ( p = 0.048). Metformin treatment significantly reduced VS growth to a similar level as aspirin. Furthermore, when removing both metformin and aspirin treatment, tumor growth significantly increased.

Pericardial diseases in pregnancy.

Pericardial effusion is the most common manifestation of pericardial diseases during pregnancy. This effusion is benign, mild, or moderate, well tolerated, and with spontaneous resolution after delivery; no specific treatment is required. Acute pericarditis is the second most common condition, usually requiring medical therapy during pregnancy. Cardiac tamponade and constrictive pericarditis are rare in pregnancy. Pre-pregnancy counselling is essential in women of childbearing age with recurrent pericarditis to plan pregnancy in a phase of disease quiescence and to review therapy. High-dose aspirin or non-selective nonsteroidal anti-inflammatory drugs, such as ibuprofen and indomethacin, can be used up to the 20th week of gestation. Low-dose prednisone (2.5 to 10 mg/day) can be administered throughout pregnancy. All of these medications, apart from high-dose aspirin, may be used during lactation. Colchicine is compatible with pregnancy and breastfeeding, and it can be continued throughout pregnancy in order to prevent recurrences. Appropriate follow-up with a multidisciplinary team with experience in the field is recommended throughout pregnancy to ensure good materno-fetal outcomes.

Aspirin chemoprevention in colorectal cancer: network meta-analysis of low, moderate, and high doses.

Colorectal cancer is the third most common cancer, with nearly 2 million cases worldwide and just under 1 million deaths in 2020. Several trials have demonstrated that aspirin has the potential to reduce the incidence and/or recurrence of colorectal cancer; however, the optimal aspirin dose is unclear. Relevant studies were identified by searching MEDLINE, Embase and the Cochrane Library from database inception to 2 February 2022. Data from RCTs in which the incidence of colorectal cancer in patients without active colorectal cancer assigned to aspirin versus control were included. Two investigators independently identified studies and abstracted data. Study quality was assessed using Cochrane Collaboration risk-of-bias 2 tool. The study was performed according to PRISMA guidelines. Aspirin dose was stratified into low (50-163 mg/day), mid (164-325 mg/day), and high (500-1200 mg/day). Thirteen articles representing 11 RCTs (92 550 participants) were included, with studies assessing aspirin as primary prophylaxis in general or high-risk populations, and as secondary prophylaxis for metachronous colorectal cancer. There was a statistically significant reduction in colorectal cancer incidence in the high-dose aspirin group compared with the group that received no aspirin or placebo (OR 0.69, 95 per cent credible interval 0.50 to 0.96; surface under the cumulative ranking 0.82). There was no statistically significant difference between mid- and low-dose aspirin versus no aspirin/placebo. In this network meta-analysis of RCTs, high-dose aspirin was associated with a reduction in colorectal cancer incidence. However, this was based on a limited number of trials. This study did not show a statistically significant risk reduction in colorectal cancer incidence with mid- or low-dose aspirin.

Kawasaki Disease in Children

Kawasaki Disease (KD), previously defined as mucocutaneous lymph node syndrome, is a febrile illness caused by inflammation of the body's medium-sized blood vessels. Tomisaku Kawasaki first described it in 1967 as a self-limited acute vasculitic syndrome of unknown etiology. Intravenous immunoglobulin (IV) and high-dose oral aspirin should be begun within 10 days of disease onset along with aspirin.

Case report: corticosteroid as an alternative therapy for Kawasaki disease

Background: Kawasaki disease is an acute febrile illness with systemic vasculitis and predominantly causes acquired heart disease. The etiology is still unknown, and there is no specific diagnostic test. The diagnosis was made using clinical criteria, laboratory and echocardiographic findings. It is characterized by fever, bilateral non-exudative conjunctivitis, erythema of lips and oral mucosa, rash, cervical lymphadenopathy, edema and erythema of the hand and foot. The initial treatment for both complete and incomplete Kawasaki disease is a single high dose of intravenous immunoglobulin (IVIG) and aspirin. The place of corticosteroids in the initial therapy is still controversial. Case Description: A 3-year-old boy presented with a 7-day history of high fever and not relieved by antipyretic, which was followed by a maculopapular rash on his trunk and extremities, vomiting, reduced appetite, red on her lips and eyes who aspirin, IVIG and corticosteroid treated as initial therapy. He showed clinical improvement and did not have cardiovascular complications. Conclusion: We report a case of Kawasaki disease in a 3-year-old boy. This case highlighted that adding corticosteroids to IVIG and aspirin as initial therapy might improve outcomes in Kawasaki disease and could be selected as a treatment modality to treat Kawasaki disease.

Comparison of low-dose (162mg) and high-dose (650mg) Aspirin prophylaxis following total joint arthroplasty: a prospective cohort study.

A prospective cohort of patients with THA and total knee arthroplasty was conducted at two tertiary centres. Symptomatic VTE within 90 days of index arthroplasty was the primary outcome; gastrointestinal bleeding (GIB) and mortality were secondary outcomes. The final analysis included 312 consecutive patients: 158 in the LD group and 154 in the HD group. Two groups were similar regarding preoperative data, including sex, age, BMI, smoking, diabetes mellitus, Hgb and platelet count, and type of surgery. The LD group had one deep vein thrombosis (0.6%), and the HD group had two (1.3%) (P=0.62). Neither group had PTE. Therefore, VTE rates are the same as deep vein thrombosis rates and similar between the groups (0.6% vs. 1.3%, P=0.62)Regarding GIB due to anticoagulant therapy, no patient in the LD group reported GIB, whereas two (1.3%) patients in the HD group reported GIB within 90 days of arthroplasty. GIB rates did not differ significantly between groups (P=0.24). Considering VTE + GIB combined, the HD groups showed a higher rate of complications (N=4, 2.6%) than the LD groups (N=1, 0.6%) but not statistically significant (P=0.21). Prophylactic administration of Aspirin with low doses (81mg BID) and high doses (325mg BID) for six weeks is equally effective at reducing VTE in total joint arthroplasty patients and had similar adverse effects. Therapeutic Level II.

Coronary Artery Involvement in Kawasaki Disease-Echocardiographic Evaluation of Cases in a Tertiary Care Hospital

Background: Kawasaki disease (KD) is the leading cause of childhood acquired heart disease. Cardiovascular manifestations can be prominent in the acute phase of the illness. Echocardiography is useful in recognizing these cardiac manifestations. We carried out a retrospective study by analyzing the data of Kawasaki disease patients in a tertiary care hospital. Methods: The prevalence of coronary artery dilatation and clinical outcome were documented. Clinical, laboratory, and echocardiographic findings were obtained at baseline and 1 week, 6 weeks after initial therapy with intravenous immunoglobulin in addition to high doses of Aspirin which reduces the risk of coronary artery aneurysm. Results: One hundred and forty-nine patients with mean age 3± 2 years old, 60% males with Kawasaki disease were included. One hundred and thirty-two patients had coronary involvement (left main coronary artery 36.37 %, left anterior descending artery 28.03%, right main coronary artery 24.25%, circumflex branch in 11.37%). Administration of intravenous immunoglobulin (IVIG) and aspirin has greatly reduced the incidence of coronary lesions in affected children. The initial cardiac findings developed over first few weeks of illness resolved in most of the cases in the subsequent echocardiogram studies after IVIG. The mean duration to normalization of abnormal echocardiography findings is 6±3 months. Conclusion: Coronary artery involvement is seen in most of children with Kawasaki disease. Intravenous gamma globulin and aspirin has been reported to reduce the likelihood of development of giant coronary artery aneurysms and appears to have a direct beneficial effect on abnormalities in cardiac function associated with the acute phase of Kawasaki disease. Cardiovasc j 2023; 15(2): 144-150

P031 Montelukast antagonising underlying systemic illness

Abstract Background/Aims Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multisystemic, autoimmune vasculitis involving small to medium-sized blood vessels. It has a well-established affiliation with atopic syndromes, typically adult-onset asthma and sinusitis. More rare associations are linked with drug side effects such as Montelukast. According to the ‘American College of Rheumatology 1990’, the following criteria yield a sensitivity of 84% in identifying a patient with EGPA. The criteria include: asthma, eosinophilia &amp;gt;10% on differential white cell count, mononeuropathy or polyneuropathy, transient pulmonary infiltrates on chest radiography, paranasal sinus abnormality, and blood vessel biopsy demonstrating extravascular eosinophilia, in a patient with symptoms of systemic vasculitis. The multisystemic involvement of EGPA makes both diagnosis and management difficult as presentations can vary. Methods We report the complex case of a 61 year-old gentleman diagnosed with EGPA. His relevant past medical history includes a diagnosis of Asthma in 2002 (managed with inhaled bronchodilators, corticosteroids, and montelukast), recurrent sinusitis, and lower respiratory tract infections. The patient presented with a one month history of abdominal cramping and bloating. This was associated with nausea, constipation, anorexia, and a week of ‘drenching’ night sweats. His full physical examination during this time was unremarkable. Results He had a normal CT Abdomen Pelvis and colonoscopy. His admission chest radiograph demonstrated bilateral parenchymal lung changes. This was followed by a CT Thorax showing bilateral upper and lower lobe bronchiectasis. Mediastinal and hilar adenopathy consistent with a diagnosis of allergic bronchopulmonary aspergillosis with associated reactive adenopathy. His laboratory investigations showed eosinophilia (21.68) and leucocytosis (32.7). In view of these results, an autoantibody screen was sent showing positive ANCA and positive anti-Myeloperoxidase antibodies(MPO titre 55). Two days into his admission he developed pain and paralysis of his right upper limb. He reported marked fatigue followed by a petechial, non-blanching, vasculitic rash on both ankles. Neurological examination reflected a subacute symmetrical sensory and motor polyneuropathy predominantly involving the right side with bilateral foot drop. MRI Brain demonstrated an established infarct in the left external capsule. He was commenced on high dose aspirin. Due to high suspicion for EGPA, methylprednisolone was commenced for 5 days, followed by tapering oral corticosteroid therapy and Rituximab therapy. A skin punch biopsy showed ‘ a vasculopathic type reaction with small vessel vasculitis, associated mixed inflammatory infiltrate which includes some eosinophils’ confirmed his diagnosis. Conclusion A topic of particular relevance to this case is the association between EGPA and montelukast. It has been hypothesised that there may be a relationship between Leukotriene Receptor Antagonist Therapy, specifically Montelukast, with the pathogenesis of EGPA. Some research suggests that treatment with Montelukast permits the decreased need for oral corticosteroids for asthma control. Therefore, suggesting that EGPA could have been masked by corticosteroid therapy. Disclosure Á. Connerton: None.

Aspirin prevents estrogen deficiency-induced bone loss by inhibiting osteoclastogenesis and promoting osteogenesis

BackgroundAspirin is a commonly used antipyretic, analgesic, and anti-inflammatory drug. Numerous researches have demonstrated that aspirin exerts multiple biological effects on bone metabolism. However, its spatiotemporal roles remain controversial according to the specific therapeutic doses used for different clinical conditions, and the detailed mechanisms have not been fully elucidated. Hence, in the present study, we aimed to identify the dual effects of different aspirin dosages on osteoclastic activity and osteoblastic bone formation in vitro and in vivo.MethodsThe effects of varying doses of aspirin on osteoclast and osteoblast differentiation were evaluated in vitro. The underlying molecular mechanisms were detected using quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence techniques. An ovariectomized rat osteoporosis model was used to assess the bone-protective effects of aspirin in vivo.ResultsAspirin dose-dependently suppressed RANKL-induced osteoclasts differentiation and bone resorption in vitro and reduced the expression of osteoclastic marker genes, including TRAP, cathepsin K, and CTR. Further molecular analysis revealed that aspirin impaired the RANKL-induced NF-κB and MAPK signaling pathways and prevented the nuclear translocation of the NF-κB p65 subunit. Low-dose aspirin promoted osteogenic differentiation, whereas these effects were attenuated when high-dose aspirin was administered. Both low and high doses of aspirin prevented bone loss in an ovariectomized rat osteoporosis model in vivo.ConclusionAspirin inhibits RANKL-induced osteoclastogenesis and promotes osteogenesis in a dual regulatory manner, thus preventing bone loss in vivo. These data indicate that aspirin has potential applications in the prevention and treatment of osteopenia.

The impact of aspirin exposure prior to intensive care unit admission on the outcomes for patients with sepsis-associated acute respiratory failure.

Objectives: This present study aimed to infer the association between aspirin exposure prior to ICU admission and the clinical outcomes of patients with Sepsis-associated acute respiratory failure (S-ARF). Methods: We obtained data from the Medical Information Mart for Intensive Care IV 2.0. Patients were divided into pre-ICU aspirin exposure group and Non-aspirin exposure group based on whether they took aspirin before ICU admission. The primary outcome is 28-day mortality. Augmented inverse propensity weighted was used to explore the average treatment effect (ATE) of the pre-ICU aspirin exposure. A generalized additive mixed model was used to analyze the longitudinal data of neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), oxygenation index (P/F), dynamic lung compliance (Cdyn), mechanical power (MP), and mechanical power normalized to predicted body weight (WMP) in the two groups. A multiple mediation model was constructed to explore the possible mediators between pre-ICU aspirin exposure and outcomes of patients with S-ARF. Results: A total of 2090 S-ARF patients were included in this study. Pre-ICU aspirin exposure decreased 28-day mortality (ATE, -0.1945, 95% confidence interval [CI], -0.2786 to -0.1103, p < 0.001), 60-day mortality (ATE, -0.1781, 95% Cl, -0.2647 to -0.0915, p < 0.001), and hospital mortality (ATE, -0.1502, 95%CI, -0.2340 to -0.0664, p < 0.001). In subgroup analysis, the ATE for 28-day mortality, 60-day mortality, and hospital mortality were not statistically significant in the coronary care unit group, high-dose group (over 100mg/d), and no invasive mechanical ventilation (IMV) group. After excluding these non-beneficiaries, Cdyn and P/F ratio of the pre-ICU aspirin exposure group increased by 0.31mL/cmH2O (SE, 0.21, p = 0.016), and 0.43mmHg (SE, 0.24, p = 0.041) every hour compared to that of non-aspirin exposure group after initialing IMV. The time-weighted average of NLR, Cdyn, WMP played a mediating role of 8.6%, 24.7%, and 13% of the total effects of pre-ICU aspirin exposure and 28-day mortality, respectively. Conclusion: Pre-ICU aspirin exposure was associated with decreased 28-day mortality, 60-day mortality, and hospital mortality in S-ARF patients except those admitted to CCU, and those took a high-dose aspirin or did not receive IMV. The protective effect of aspirin may be mediated by a low dynamic level of NLR and a high dynamic level of Cdyn and WMP. The findings should be interpreted cautiously, given the sample size and potential for residual confounding.

Abstract MP30: Metabolomics Analyses Identified Factors Modifying the Association of Aspirin Use With Kidney Function

Introduction: Uncontrolled high dose aspirin use impairs kidney function. Short-term low dose aspirin treatment has also been associated with kidney function in older patients. We aimed to evaluate the association of regular aspirin use with kidney function in middle-aged adults and to identify factors modifying the association. Methods: We performed cross-sectional analyses among 1,261 participants of the 2016 Bogalusa Heart Study (BHS) visit. Regular aspirin use was self-reported and confirmed by serum biomarker, salicyluric glucuronide . Aspirin users were categorized at the median of salicyluric glucuronide levels into low and high dose users. A total of 887 known metabolites were profiled from the serum. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi equation. We tested associations of aspirin use with eGFR and examined interactions of aspirin with serum metabolites on eGFR. Age, sex, race, education, smoking, drinking, physical activity, BMI, blood pressure, and fasting glucose were adjusted in all analyses. Results: The mean age of BHS participants was 48.2, and 133 (10.5%) were self-reported aspirin users. Serum salicyluric glucuronide level was significantly correlated with self-reported aspirin usage (P=2.00х10 -21 ). After adjusting for all covariables, mean eGFR for never, low dose, and high dose aspirin users were 92.9, 90.2, and 89.9 mL/min/1.73m 2 , respectively (P for trend=0.004). After Bonferroni correction, 28 metabolites modified the associations of aspirin use with eGFR (P&lt;5.52х10 -5 ), of which, 26 increased the aspirin's nephrotoxicity effect, while behenoylsphingomyelin and tricosanoylsphingomyelin significantly attenuated the eGFR lowering effect of aspirin (Table). Conclusion: Aspirin use is associated with decreased eGFR among middle-aged adults, and this association was modified by dietary, gut microbiome, and biomarkers of kidney disease, cardiovascular disease, and cancer. The findings may help develop better use strategies for regular users.

Low- or high-dose preventive aspirin use and risk of death from all-cause, cardiovascular disease, and cancer: A nationally representative cohort study.

Background and aim: For a long time, aspirin has been recommended for the prevention of cardiovascular disease (CVD). However, results of long-term effects of aspirin use on the risk of CVD and all-cause death as well as cause-specific mortality are not consistent. This study aims to investigate the relationship between low- or high-dose preventive aspirin use and the risk of death from all-cause, CVD, and cancer among US adults aged 40years and older. Methods: A prospective cohort study was conducted by utilizing four cycles of the National Health and Nutrition Examination Survey (NHANES) and linked 2019 mortality files. Cox proportional hazard models accounting for multiple covariates were used to calculate hazard ratio (HR) and 95% confidence interval (CI) for the associations between low- or high-dose aspirin use and risk of death. Results: A total of 10,854 individuals (5,364 men and 5,490 women) were enrolled in the study. During a median follow-up of 4.8years, 924 death events including 294 CVD death and 223 cancer death were documented. We found no evidence that taking low-dose aspirin decreased the chance of dying from any cause (HR: 0.92, 95% CI: 0.79-1.06), CVD (HR: 1.03, 95% CI: 0.79-1.33), or cancer (HR: 0.80, 95% CI: 0.60-1.08). High-dose aspirin users had a higher risk of CVD death compared to participants who had never used aspirin (HR: 1.63, 95% CI: 1.11-2.41). Conclusion: Using low-dose aspirin has no effect on the risk of death from any causes, whereas taking high doses of aspirin increases the risk of CVD death.

Intracardiac Thrombi as a New Variant Cardiovascular Injury in a Previously Healthy COVID-19 Child: Case Report and Follow Up

However, with the onset of the second COVID-19 pandemic wave, single cases of acute thrombotic complications in previously healthy children began to appear. Here we describe the patient with COVID-19 time related acute intracardiac thrombus in a previously healthy 6 year old girl. The treatment according to the national pediatric protocol, included low-molecular weight heparin infusion, high-dose aspirin, methylprednisolone, and intravenous immunoglobulin was lead to dissolving without cardiac surgery. A follow up after 12 months from discharge demonstrated: physical exam, ECG, echocardiography are all normal. Our case presentation shows, that all health care providers must be informed about the full range of complications and even a mild onset of COVID-19 in children.

A Phase 2A Trial of the Safety and Tolerability of Increased Dose Rifampicin and Adjunctive Linezolid, With or Without Aspirin, for Human Immunodeficiency Virus-Associated Tuberculous Meningitis: The LASER-TBM Trial.

Drug regimens that include intensified antibiotics alongside effective anti-inflammatory therapies may improve outcomes in tuberculous meningitis (TBM). Safety data on their use in combination and in the context of human immunodeficiency virus (HIV) are needed to inform clinical trial design. We conducted a phase 2, open-label, parallel-design, randomized, controlled trial to assess the safety of high-dose rifampicin, linezolid, and high-dose aspirin in HIV-associated TBM. Participants were randomized (1.4:1:1) to 3 treatment arms (1, standard of care [SOC]; 2, SOC + additional rifampicin [up to 35 mg/kg/d] + linezolid 1200 mg/d reducing after 28 days to 600 mg/d; 3, as per arm 2 + aspirin 1000 mg/d) for 56 days, when the primary outcome of adverse events of special interest (AESI) or death was assessed. A total of 52 participants with HIV-associated TBM were randomized; 59% had mild disease (British Medical Research Council (MRC) grade 1) vs 39% (grade 2) vs 2% (grade 3). AESI or death occurred in 10 of 16 (63%; arm 3) vs 4 of 14 (29%; arm 2) vs 6 of 20 (30%; arm 1; P = .083). The cumulative proportion of AESI or death (Kaplan-Meier) demonstrated worse outcomes in arm 3 vs arm 1 (P = .04); however, only 1 event in arm 3 was attributable to aspirin and was mild. There was no difference in efficacy (modified Rankin scale) between arms. High-dose rifampicin and adjunctive linezolid can safely be added to the standard of care in HIV-associated TBM. Larger studies are required to determine whether potential toxicity associated with these interventions, particularly high-dose aspirin, is outweighed by mortality or morbidity benefit. NCT03927313.

Recurrent kawasaki disease with intussusception: A case report and a review of the literature

Objective: Kawasaki disease (KD) is a multisystemic vasculitic disease that occasionally presents with gastrointestinal tract symptoms.Case presentation: A 2-year-old girl diagnosed with KD 4 months prior was referred to our hospital with complaints of vomiting. She was subsequently diagnosed with intussusception, which was efficiently alleviated through air insufflation. However, despite her improved clinical status, she had a fever unresponsive to antibiotic therapy. Four days later, the patient exhibited typical symptoms of Kawasaki disease. Thus, intravenous immunoglobulin and high-dose aspirin were administrated, and the outcome was satisfactory.Conclusions: In young children who present with crying, vomiting, and passage of bloody stools, color ultrasonography should be performed promptly to avoid missed diagnosis and misdiagnosis.

Abstract 14192: Effect of Aspirin Dosing in Patients Treated With P2Y12 Inhibitors for Secondary Prevention of Cardiovascular Events

Background: The ADAPTABLE was a pragmatic randomized controlled trial that found no difference between high dose vs low dose aspirin for secondary prevention of ischemic or bleeding events. Whether concomitant P2Y12 inhibitor therapy modifies the effect of aspirin dose on clinical events remains unclear. Methods: Participants in ADAPTABLE were stratified according to baseline use of clopidogrel or prasugrel (P2Y12 group). Ticagrelor was not permitted due to a black box warning with high dose aspirin. The primary effectiveness endpoint was a composite of myocardial infarction, stroke, or death and the primary safety endpoint was hospitalization for major bleeding. We used multivariable Cox regression to compare the relative effectiveness and safety of aspirin dose within P2Y12 and non-P2Y12 groups. Results: Of the 13,815 (91.6%) participants with available data, 3,051 (22.1%) were on a P2Y12 inhibitor at baseline (clopidogrel: 93.4%; prasugrel: 6.6%). P2Y12 inhibitor use was associated with higher risk of the primary effectiveness endpoint (10.86% vs. 6.31%; adjusted HR 1.44 95% CI 1.22-1.62) but was not associated with bleeding (0.53% vs. 0.95%; adjusted HR:1.42; 95% CI 0.91, 2.22). We found no interaction in the relative effectiveness and safety of high vs. low dose aspirin by P2Y12 inhibitor use (Table, P interaction 0.09 and 0.73 for primary effectiveness and safety endpoint, respectively). Aspirin dose switching and discontinuation occurred in 28.6% of patients. Although this was more common in high dose vs. low dose aspirin, the above rates did not differ between the P2Y12 and non-P2Y12 groups. Conclusion: In this pre-specified subgroup analysis of a large, pragmatic trial, we found that the relative effectiveness and safety of high dose vs. low dose aspirin was not modified by baseline use of P2Y12 inhibitors. Decisions regarding aspirin dosing should be individualized based on clinical factors and patient preference, regardless of P2Y12 inhibitor use.