Risk Of Aortic Dissection Research Articles

Abstract Mo050: Fluoroquinolones and the Risk of Aortic Aneurysm or Aortic Dissection: Evidence From a Nationwide Nested Case-Control Study Paralleled With Matched Experimental Models

Background and Aims: Fluoroquinolones (FQ) have been linked to aortic aneurysms and dissections (AA/AD), resulting in an official warning. However, recent large-scale epidemiological studies have reported lack of FQ-AA/AD association. This study aimed to scrutinize FQ-AA/AD risk by implementing a combined epidemiological and experimental approach. Methods: Danish nationwide registers (2003-2021) were used for a nested case-control analysis. FQ-AA/AD risk was evaluated in a main and high-risk FDA cohort. Further, mortality and aortic interventions linked to FQ were investigated in patients with aortic disease. Additionally, ciprofloxacin (100 mg/kg/day, 2x2 weeks) was administered to wild-type, hypertensive or Marfan mice. Aortic diameters and pulse wave velocity (PWV) were measured longitudinally to investigate aortic remodelling. Results: The main cohort comprised 5.10 million individuals with 58,919 cases and 1,767,510 sampled controls. Compared with amoxicillin exposure. FQ exposure was not associated with increased AA/AD risk (30-day hazard ratios (HR) 1.00 [95% confidence intervals (CI): 0.74-1.34]; 90-day HR 1.07 [CI 0.94-1.22]; 1-year HR 0.95 [0.90-1.01]). In a high-risk cohort, there was no FQ-AA/AD association (30-day HR 0.83 [0.61-1.12]; 90-day HR 0.99 [0.86-1.15]; 1-year HR 0.97 [0.90-1.05]). In patients with aortic disease, FQ were not associated with increased aortic interventions or mortality (30-day HR 0.98 [0.79-1.22]; 90-day HR 1.06 [0.95-1.19]). Additionally, ciprofloxacin did not affect aortic diameters or PWV in wild type, hypertensive, and Marfan mice, while differences between models proved the sensitivity of the methodology. Conclusion: The data clearly do not support the current precautions and warnings pertaining to risks of aortopathies and FQ should not be discouraged when clinically indicated.

Association of triglyceride-glucose index with the risk of incident aortic dissection and aneurysm: a large-scale prospective cohort study in UK Biobank

BackgroundTriglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated.MethodsThis study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI.ResultsOver a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08–1.35), 1.21 (95% CI 1.08–1.35), and 1.30 (95% CI 1.16–1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20–1.52).ConclusionsTyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

Causal Relationships between Lipid-Lowering Drug Target and Aortic Disease and Calcific Aortic Valve Stenosis: A Two-Sample Mendelian Randomization.

Proprotein convertase subtilisin/kexin type 9 (PCSK9), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cholesteryl ester transfer protein (CETP) and apolipoprotein C3 (APOC3) are pivotal regulators of lipid metabolism, with licensed drugs targeting these genes. The use of lipid-lowering therapy via the inhibition of these genes has demonstrated a reduction in the risk of cardiovascular disease. However, concerns persist regarding their potential long-term impact on aortic diseases and calcific aortic valve disease (CAVS). This study aims to investigate causal relationships between genetic variants resembling these genes and aortic disease, as well as calcific aortic valve disease using Mendelian randomization (MR). We conducted drug-target Mendelian randomization employing summary-level statistics of low-density lipoprotein cholesterol (LDL-C) to proxy the loss-of-function of PCSK9, HMGCR, CETP and APOC3. Subsequently, we investigated the association between drug-target genetic variants and calcific aortic valve stenosis and aortic diseases, including thoracic aortic aneurysm (TAA), abdominal aortic aneurysm (AAA), and aortic dissection (AD). The genetically constructed variants mimicking lower LDL-C levels were associated with a decreased risk of coronary artery disease, validating their reliability. Notably, HMGCR inhibition exhibited a robust protective effect against TAA (odds ratio (OR): 0.556, 95% CI: 0.372-0.831, p = 0.004), AAA (OR: 0.202, 95% CI: 0.107-0.315, p = 4.84 10-15), and AD (OR: 0.217, 95% CI: 0.098-0.480, p = 0.0002). Similarly, PCSK9, CETP and APOC3 inhibition proxies reduced the risk of AAA (OR: 0.595, 95% CI: 0.485-0.730, p = 6.75 10-7, OR: 0.127, 95% CI: 0.066-0.243, p = 4.42 10-10, and OR: 0.387, 95% CI: 0.182-0.824, p = 0.014, respectively) while showing a neutral impact on TAA and AD. Inhibition of HMGCR, PCSK9, and APOC3 showed promising potential in preventing CAVS with odds ratios of 0.554 (OR: 0.554, 95% CI: 0.433-0.707, p = 2.27 10-6), 0.717 (95% CI: 0.635-0.810, p = 9.28 10-8), and 0.540 (95% CI: 0.351-0.829, p = 0.005), respectively. However, CETP inhibition did not demonstrate any significant benefits in preventing CAVS (95% CI: 0.704-1.544, p = 0.836). The consistency of these findings across various Mendelian randomization methods, accounting for different assumptions concerning genetic pleiotropy, enhances the causal inference. Our MR analysis reveals that genetic variants resembling statin administration are associated with a reduced risk of AAA, TAA, AD and CAVS. HMGCR, PCSK9 and APOC3 inhibitors but not CETP inhibitors have positive benefits of reduced CAVS. Notably, PCSK9, CETP and APOC3 inhibitors exhibit a protective impact, primarily against AAA, with no discernible benefits extending to TAA or AD.

Genetic predisposition to type 2 diabetes mellitus and aortic dissection: a Mendelian randomisation study.

This Mendelian randomization (MR) study aimed to explore the causal relationship between the genetic predisposition to type 2 diabetes mellitus (T2DM) and aortic dissection (AD), and to assess associations with genetically predicted glycemic traits. The study sought to verify the inverse relationship between T2DM and AD using a more robust and unbiased method, building on the observational studies previously established. The study employed a two-sample and multivariable MR approach to analyze genetic data from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) with 74,124 cases and 824,006 controls, and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) involving up to 196,991 individuals. For AD data, FinnGen Release 10 was used, including 967 cases and 381,977 controls. The research focused on three foundational MR assumptions and controlled for confounders like hypertension. Genetic instruments were selected for their genome-wide significance, and multiple MR methods and sensitivity analyses were conducted. The study revealed no significant effect of genetic predisposition to T2DM on the risk of AD. Even after adjusting for potential confounders, the results were consistent, indicating no causal relationship. Additionally, glycemic traits such as fasting glucose, fasting insulin, and HbA1c levels did not show a significant impact on AD susceptibility. The findings remained stable across various MR models and sensitivity analyses. In contrast, genetic liability to T2DM and glycemic traits showed a significant association with coronary artery disease (CAD), aligning with the established understanding. Contrary to previous observational studies, this study concludes that genetic predisposition to T2DM does not confer protection against AD. These findings underscore the imperative for further research, particularly in exploring the preventative potential of T2DM treatments against AD and to facilitate the development of novel therapeutic interventions.

HDL-C mediates the causal relationship between serum urate and aortic aneurysm: a Mendelian randomization study

Background and purpose: Studies have indicated a close relationship between serum urate and an increased risk of aortic aneurysm or aortic dissection. However, the causality between them and the mediators of this association have not been identified. This study employs bidirectional and multivariable Mendelian randomization (MR) to investigate the causality between serum urate and aortic aneurysm or dissection and identify mediators of this relationship. Methods: We first investigated the causal association between serum urate and aortic aneurysm or aortic dissection using two-sample bidirectional MR, with the inverse-variance-weighted method as the principal analysis technique. Subsequently, we applied multivariable MR to determine probable mediators. Results: Genetically serum urate levels were linked to an increased risk of aortic aneurysm (odds ratio [OR]: 1.160, 95% confidence interval [95% CI]: 1.011–1.332, P = 0.034), with high-density lipoprotein cholesterol (HDL-C) mediating this causal relationship, accounting for 10.2% of the effect. No causal relationship was found between serum urate and aortic dissection. Conclusions: Serum urate is a risk factor for aortic aneurysm, and this causal relationship is mediated through HDL-C. Monitoring HDL-C levels in patients with hyperuricemia is essential to prevent and slow the progression of aortic aneurysm.

Effect of serum uric acid on the risk of aortic aneurysm and dissection: A mendelian randomization analysis

Aortic aneurysm and dissection (AAD) are severe vascular diseases with high mortality rates. However, the causal relationship between serum uric acid levels and the occurrence of AAD remains a subject of controversy. To address this issue, we conducted a two-sample Mendelian randomization (MR) analysis to investigate whether there is a causal association between these factors. We obtained single-nucleotide polymorphisms (SNPs) data related to serum uric acid levels from the FinnGen study and data on AAD from the UK Biobank. Various two-sample MR methods, including inverse variance weighted (IVW) analysis, MR-Egger regression analysis, weighted median analysis, and contamination mixture method, were employed to assess the causal relationship between serum uric acid and the risk of AAD. Sensitivity analysis was conducted to evaluate the stability and reliability of the results. The findings revealed a positive association between serum uric acid levels and the risk of aortic aneurysm (AA) (odds ratio [OR] = 1.200, 95 % confidence interval [CI]: 1.020–1.400, P = 0.0239). However, no significant correlation was observed between serum uric acid levels and the occurrence of aortic dissection (AD) (OR = 0.893, 95 % CI = 0.602–1.326, P = 0.576). Our study, which employed MR analysis, identified a positive association between serum uric acid levels and the risk of AA. However, we did not observe a significant correlation with AD.

The aortic paradox: a nationwide analysis of 523 994 individual echocardiograms exploring fatal aortic dissection.

Increasing aortic dilation increases the risk of aortic dissection. Nevertheless, dissection occurs at dimensions below guideline-directed cut-offs for prophylactic surgery. Currently, there are no large-scale population imaging data assessing aortic dimensions before dissection. Patients within the National Echo Database of Australia were stratified according to absolute, height-indexed, and body surface area (BSA)-indexed aortic dimensions. Fatal thoracic aortic dissections (ICD-10-AM Code I71) were identified via linkage with the National Death Index. A total of 524 994 individuals were assessed, comprising patients with normal aortic dimensions (n = 460 992), mild dilation (n = 53 402), moderate dilation (n = 10 029), and severe dilation (n = 572). A total of 274 992 (52.4%) were males, with a median age of 64 years and a median follow-up time of 6.9 years. Eight hundred and ninety-nine fatal aortic dissections occurred (normal diameter = 610, mildly dilated aorta = 215, moderately dilated = 53, and severely dilated = 21). Using normal aortas as the reference population, odds of fatal dissection increased with aortic diameter [mild = odds ratio (OR) 3.05, 95% confidence interval (CI) 2.61-3.56; moderate = OR 4.0, 95% CI 3.02-5.30; severe = OR 28.72, 95% CI 18.44-44.72]. Due to the much larger number of patients without severe aortic dilation, 97.7% of fatal aortic dissections occurred in non-severely dilated aortas. Following sensitivity analysis, severe aortic dilation was responsible for at most 24.4% of fatal aortic dissections. The results were robust for absolute, height-indexed, or BSA-indexed aortic measurements. Although severe aortic dilatation is associated with a near-30-fold increase in fatal dissections, severely dilated aortas are implicated in only 2.3-24.4% of fatal dissections. This highlights the 'aortic paradox' and limitations of current guidelines. Future studies should seek to refine risk predictors in patients without severe aortic dilation.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization

BackgroundIn observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization.Materials and methodsWe performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately.ResultsThe IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836–0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12–44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607–0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta.ConclusionMendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.Graphical abstract

Anesthetic management for cesarean section in two parturient with ascending aortic aneurysm: a case-based discussion

BackgroundThe anesthetic management of parturients with ascending aortic aneurysm for cesarean section can be particularly challenging, primarily because of increased risk for aortic dissection or aneurysm rupture.Case presentationWe present some aspects of the anesthetic management of two parturients with ascending aortic aneurysm for cesarean sections; amongst, the use of remifentanil with its effects on patient and newborn. We emphasize the importance of a cardio-obstetric team in the context of preoperative planning of such patients. Also, we reviewed some literature on the anesthetic management with its effect on peri-operative hemodynamic stability.ConclusionMaintaining hemodynamic stability is paramount in the prevention of the rupture or dissection of ascending aortic aneurysm during labor of parturient.

Analysis of differential metabolites in serum metabolomics of patients with aortic dissection

BackgroundPathogenesis and diagnostic biomarkers of aortic dissection (AD) can be categorized through the analysis of differential metabolites in serum. Analysis of differential metabolites in serum provides new methods for exploring the early diagnosis and treatment of aortic dissection.ObjectivesThis study examined affected metabolic pathways to assess the diagnostic value of metabolomics biomarkers in clients with AD.MethodThe serum from 30 patients with AD and 30 healthy people was collected. The most diagnostic metabolite markers were determined using metabolomic analysis and related metabolic pathways were explored.ResultsIn total, 71 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism and four different metabolites considered of most diagnostic value including N2-gamma-glutamylglutamine, PC(phocholines) (20:4(5Z,8Z,11Z,14Z)/15:0), propionyl carnitine, and taurine. These four predictive metabolic biomarkers accurately classified AD patient and healthy control (HC) samples with an area under the curve (AUC) of 0.9875. Based on the value of the four different metabolites, a formula was created to calculate the risk of aortic dissection. Risk score = (N2-gamma-glutamylglutamine × -0.684) + (PC (20:4(5Z,8Z,11Z,14Z)/15:0) × 0.427) + (propionyl carnitine × 0.523) + (taurine × -1.242). An additional metabolic pathways model related to aortic dissection was explored.ConclusionMetabolomics can assist in investigating the metabolic disorders associated with AD and facilitate a more in-depth search for potential metabolic biomarkers.

Genetic aortopathies: a case-based approach to multidisciplinary program development.

The incorporation of genetic counseling and testing is essential to evaluation and management of thoracic aortic disease in patients under 60 years of age and those with family histories suspicious for heritable thoracic aortic disease and disorders associated with increased risk for acute type-A aortic dissection. As many as 20% of individuals with thoracic aortic disease under the age of 60 years have autosomal dominant patterns of inheritance. A considerable number of heritability factors remain undefined for these families. Genetic aortopathy programs require a collaborative approach including cardiovascular specialists and surgeons, medical geneticists, genetic counselors, and allied healthcare professionals. Comprehensive evaluation and management of these patients includes collection of detailed phenotypic data to inform the broader community and identify new associated and causative genes of interest, genetic modifiers, and other risk factors. These programs optimize outcomes and reduce the overall burden in the population of acute aortic dissection and related comorbidities.

A 12-year Retrospective Cohort Study of Point-of-care Ultrasound and Aortic Dissection Risk Score in Type A Aortic Dissection

BackgroundAortic dissection (AD) is a vascular emergency with time-dependent mortality. Point-of-care ultrasound (POCUS) and AD risk score (ADRS) have been proposed as diagnostic tools to risk stratify patients and reduce time to diagnosis. Study ObjectiveWe evaluate POCUS findings and ADRS in a retrospective cohort of patients with known type A AD. The objective of this study is to describe the prevalence of POCUS findings and ADRS in this population. MethodsThis is a retrospective cohort study of patients with acute type A AD as confirmed on computed tomography scan over a 12-year period from 2008 to 2020, with a subgroup analysis of patients who received POCUS in the emergency department. ADRS was calculated and POCUS findings were reviewed. Descriptive statistics were used to describe the distribution of POCUS findings. ResultsNinety-one patients met inclusion criteria. POCUS was performed in 41 but only 35 had images of adequate quality for inclusion. Of the POCUS images available, 30/35 (86%) patients had a POCUS finding consistent with dissection and 5/35 (14%) had no findings on POCUS. Twelve percent (11/91) of patients had ADRS = 0. Two patients with ADRS = 0 received POCUS, and one patient had no findings on POCUS. ConclusionAlthough POCUS provides rapid information in the diagnosis of type A AD, 14% of patients with images available for review had no findings on POCUS. Of the whole cohort, 12% had an ADRS = 0. Further studies are needed to identify an optimal diagnostic pathway for this catastrophic disease.

Evaluation of the Value of Histological Examination for the Prediction of Genetic Thoracic Proximal Aortopathies.

Background: Heritable connective tissue disorders are often accompanied by an increased risk for thoracic aortic aneurysm and dissection (TAAD). Profound knowledge of the underlying pathology may have an impact on individual treatment, systematic follow-up, and early detection by the screening of offspring. The aim of this study, based in a single high-volume tertiary center, was an analysis of the diagnostic validity of histopathologic findings in patients with TAAD due to these findings' accuracy in diagnosing heritable connective tissue disorders. Methods: Therefore, genetic testing by next-generation sequencing (NGS) was performed to evaluate the correlations. In total, 65 patients with TAAD undergoing surgical treatment before the age of 60 years or with age up to 80 years if they had offspring at the time of the procedure were included in the analysis. Results: In our cohort, no certain correlation of histological findings to the results of genetic diagnostics in patients with clinically relevant aortic pathology could be shown. Patients with histopathologic findings for heritable connective tissue disorder and a positive gene variant were 11.6 years younger than patients without mutation and without histological evidence for connective tissue disorder. Conclusions: Genetic clarification is useful to define the specific genotype of the disease of the aortic wall in the case of non-specific histological characteristics.

Cardiovascular and obstetrical outcomes among delivering patients with Marfan or Loeys-Dietz syndrome: a retrospective analysis by hospital delivery setting

BackgroundPregnancy is a high-risk time for patients with Marfan syndrome (MFS) or Loeys-Dietz (LDS) syndrome due to risk for cardiovascular complications including risk of aortic dissection. Little is known about differences in obstetric and cardiac outcomes based on delivery hospital setting (academic/academic-affiliated versus community medical centers). ObjectiveThis study aimed to evaluate obstetric and cardiac outcomes of patients with MFS or LDS based on delivery hospital setting. Study DesignThis is a secondary analysis of a retrospective, observational cohort study of singleton pregnancies among patients with a diagnosis of MFS or LDS from 1990 to 2016. Patients were identified through the Marfan Foundation, Loeys-Dietz Syndrome Foundation, or Cardiovascular Connective Tissue Clinic at Johns Hopkins Hospital. Data were obtained via self-reported obstetric history and verified by review of medical records. Nonparametric analysis was performed via Fisher's Exact Test and Wilcoxon rank-sum tests. Results273 deliveries among patients with MFS or LDS were included in this analysis. More patients who had a known diagnosis prior to delivery for either MFS or LDS delivered at an academic hospital as compared community hospital (78.6% vs. 59.9%, p=0.001). Patients with MFS or LDS who delivered at academic centers were more likely to have an operative vaginal delivery compared to those at community centers (23.7% vs 8.6%, p=0.002). When indications for cesarean delivery were assessed, connective tissue disease was the primary reason for indication for mode of delivery at community centers compared to academic centers (55.6% vs 43.5%, p=0.02). There were higher rates of cesarean for arrest of labor and/or malpresentation at community hospitals compared to academic centers (23.6% vs 5.3%, p=0.01). There were no differences between groups in regards to method of anesthesia for delivery. Among those with a known diagnosis of MFS or LDS prior to delivery, there were increased operative vaginal delivery rates at academic hospitals compared to community hospitals (27.2% vs 15.1%, p=0.03; Table 2). More patients with an aortic root measuring ≥4 cm pre-pregnancy or postpartum delivered at academic centers compared to community centers (33.0% vs. 10.2%, p=0.01), but there were no significant differences in median size of the aortic root during pregnancy or on postpartum assessment between delivery locations. Cardiovascular complications were rare: eight patients who delivered at academic centers and seven patients who delivered at community centers had an aortic dissection either in pregnancy or the postpartum period (p=0.79). ConclusionPatients with MFS/LDS and more severe aortic phenotypes were more likely to deliver at academic hospitals. Those who delivered at academic hospitals had higher rates of operative vaginal delivery. Despite lower frequencies of aortic root diameter >4.0 cm, those delivered at community hospitals had higher rates of cesarean delivery for the indication of MFS/LDS. Optimal delivery management of these patients requires further prospective research.

Vascular Endothelial Growth Factor Inhibitors and the Risk of Aortic Aneurysm and Aortic Dissection

Vascular endothelial growth factor pathway inhibitors (VPIs) pose a concern for aortic aneurysm (AA) and aortic dissection (AD), signaling potential vascular disease development. To investigate VPI-associated AA and AD. This case-control study with a nested design used full population data from a national claims database in Taiwan between 2011 and 2019. Eligible participants were aged 20 years or older with kidney, hepatic, gastrointestinal, or pancreatic cancer diagnosed between January 1, 2012, and December 31, 2019. The first cancer diagnosis date was defined as the cohort entry date. Cases were patients who received a diagnosis of AA or AD in hospitalizations or emergency visits between the cohort entry date and December 31, 2019. Controls were matched by ratio (up to 1:5) based on age, sex, cancer type, cohort entry date, and the index date (ie, the first AA or AD event date). Data analysis was performed between January 2022 and December 2023. Use of the oral VPIs sorafenib, sunitinib, and pazopanib between cohort entry date and index date. In the primary analysis, AA and AD were evaluated compositely, while in the secondary analyses, they were evaluated separately. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to assess the association with VPI use (sorafenib, sunitinib, and pazopanib) considering various VPI exposure windows and cumulative use. A total of 1461 cases were included (mean [SD] age, 73.0 [12.3] years; 1118 male patients [76.5%]), matched to 7198 controls. AA or AD risk increased with a VPI exposure of 100 days or less before the index date (aOR, 2.10; 95% CI, 1.40-3.15), mainly from VPI-associated AD (aOR, 3.09; 95% CI, 1.77-5.39). Longer VPI duration (68 days or more: aOR, 2.64; 95% CI, 1.66-4.19) and higher cumulative dose (61 or more defined daily doses: aOR, 2.65; 95% CI, 1.66-4.23) increased the risk. The use of the 3 study VPIs (sorafenib, sunitinib, and pazopanib) was associated with an increased risk of AA and AD in patients with cancer, essentially all of the risk from VPI-associated AD. Future studies are needed to determine the risk factors of VPI-associated AA and AD, as well as to establish a class effect.

Fluoroquinolones: Neurological Complications and Side Effects in Clinical Practice.

Fluoroquinolones, a popular antibiotic class that inhibits nucleic acid synthesis of bacteria by disrupting the activity of the enzyme's topoisomerase IV and DNA gyrase, are used to treat bacterial infections. However, the widespread use of these drugs has allowed for the development of microbial resistance in recent years. Quinolones also have many clinically relevant side effects, including psychosis, confusion, seizures, headaches, dizziness, and nausea. Common side effects include tendinitis,myopathy, depression, and fatigue. Cardiovascular side effects include increased risk of aortic aneurysm, aortic dissection, and QT interval prolongation. Overall, quinolones can be an effective choice for treating bacterial infections. Still, the side effect profile and decreased efficacy secondary to microbial resistance no longer make the quinolone class an ideal choice for many types of infection. A better understanding of the role of quinolone-mediated or neurological damage, cardiovascular impairment, and musculoskeletal involvement is imperative to determine the risks/benefits for the clinician.

Surgical Management of Familial Aortic Disease

Pregnancy may increase the risk of aortic dissection in young women genetically predisposed in the third trimester and the peri-partum period. This disease must be managed with emergency. Later, aortic familial diseases must be screened in the children by genetic tests, because of the high risk of rapid developing dissection or aneurysm in the childhood, whose management is challenging. We report the cases of a pregnant woman operated for aortic dissection, and her son operated four years later for aneurysm of the ascending aorta, and aortic insufficiency. Children with familial aortic root aneurysm may have intervention of valve sparing and aortic replacement if the aortic regurgitation is minimal. But, long-term clinical and echocardiographic follow-up is mandatory.

Dietary vitamin C and vitamin E with the risk of aortic aneurysm and dissection: A prospective population-based cohort study

Background and aimsThe associations between dietary vitamin C (VC), vitamin E (VE) intake and aortic aneurysm and dissection (AAD) remain unclear. This study aimed to prospectively investigate the associations between dietary VC and VE with the incident risk of AAD. Methods and resultsA total of 139 477 participants of UK Biobank cohort were included in the analysis. Dietary VC and VE consumptions were acquired through a 24-h recall questionnaire. Cox proportional regression models were used to examine the associations between VC, VE intake and the risk of AAD. Incident AAD was ascertained through hospital inpatient records and death registers. During a median follow-up of 12.5 years, 962 incident AAD events were documented. Both dietary VC [adjusted hazard ratio (HR), 0.77; 95 % confidence intervals (CI), 0.63–0.93; P-trend = 0.008] and VE (adjusted HR, 0.70; 95 % CI, 0.57–0.87; P-trend = 0.002) were inversely associated with incident AAD when comparing the participants in the highest quartile with those in the lowest. In subgroup analyses, the associations were more pronounced in participants who were over 60 years old, participants with smoking history, hypertension or hyperlipidemia, who were under the high risk of AAD. ConclusionHigher dietary VC and VE intakes are associated with reduced risk of AAD. Our study emphasizes the importance of diet adjustment strategies targeted on VC and VE to lower the incidence rate of AAD especially in the high-risk population.

Risk assessment for aortic dissection in Turner syndrome: The role of the aortic growth rate.

The risk of aortic dissection (AoD) is increased in Turner syndrome (TS) but predicting those at risk is difficult. Based on scarce evidence, preventive aortic surgery is recommended when aortic diameter increases >5 mm/year.To investigate the aortic growth rate in TS and TS-related conditions associated with aortic growth. We also reported our experience of women who suffered aortic dissection (AoD), and who had preventive aortic replacement. 151 adult TS were retrospectively identified. Women who had more than one transthoracic echocardiogram (TTE) after age 16 years were included in the aortic growth study. Aortic diameters at sinuses of Valsalva (SoV) and ascending aorta (AA) were analysed by two experts. 70/151 women had more than one TTE (interscan interval 4.7 years). Mean aortic growth was 0.13 ± 0.59 mm/year at SoV and 0.23 ± 0.82 mm/year at AA. Known risk factors for aortic dilatation and TS-related conditions were not associated with aortic growth. 4/151 women experienced AoD (age 25±8 years): two had paired scans for aortic growth, which was 0.67 mm/year at both SoV and AA in the first woman, and 11 mm/year (SoV) and 4 mm/year (AA) in the second. Only 1/4 of women with AoD survived; she used a TS cardiac-alert card to inform emergency personnel about her risk of AoD. 5/151 had a preventive aortic replacement, but one died post-operatively. Mean aortic growth in our TS population was increased compared to non-TS women and was not associated with currently known risk factors for AoD, suggesting that aortic growth rate itself could be a useful variable to stratify who is at risk for AoD.

Association of alcohol consumption with aortic aneurysm and dissection risk: results from the UK Biobank cohort study

Association of alcohol consumption with aortic aneurysm and dissection risk: results from the UK Biobank cohort study