RESUMEN
BACKGROUND: Radiological screening for intracranial aneurysms (IAs) may identify other relevant intracranial findings. We investigated their prevalence on MR in persons screened for IAs. METHODS: We included all persons who were screened for the presence of IAs with brain MRI/MRA between 1996 and 2022 because of a family history of aneurysmal subarachnoid haemorrhage (aSAH) or autosomal dominant polycystic kidney disease (ADPKD). We reviewed radiology reports of initial and repeated brain MR to identify additional intracranial findings that needed follow-up or treatment, or carried a risk of becoming symptomatic. RESULTS: We included 766 persons (positive family history of aSAH: n = 681; ADPKD: n = 85) who had 1446 MRI/MRAs. At initial screening, 49 additional relevant intracranial findings were reported in 47 persons (6.1%, 95% CI 4.7-8.1%). Of all included persons, 338 (44%) underwent one (n = 154) or more (n = 184) follow-up screenings (total MRI/MRAs at follow-up: n = 680). In 15/338 persons (4.4%, 95% CI 2.7-7.2%), 16 new additional relevant findings were reported at a median follow-up duration of 10 years (IQR 5-12). CONCLUSIONS: Persons who are counselled for screening for IAs should be informed that there is a six percent chance of identifying an additional finding that requires follow-up or treatment, or may become symptomatic. Additionally, after 10-year follow-up screening there is a four percent chance of identifying a new additional relevant finding. The impact of such findings on quality of life needs further study.
RESUMEN
BACKGROUND: The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors. AIMS: The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA. METHODS: We conducted a sex-specific two-sample Mendelian randomization study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e. aSAH and unruptured IA combined) as outcomes. RESULTS: We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (p-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (p-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (p-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men. CONCLUSIONS: Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.
RESUMEN
Background: The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors. Aims: The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA. Methods: We conducted a sex-specific two-sample Mendelian randomisation study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e., aSAH and unruptured IA combined) as outcomes. Results: We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (P-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (P-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (P-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men. Conclusions: Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.
Asunto(s)
Estudio de Asociación del Genoma Completo , Aneurisma Intracraneal , Análisis de la Aleatorización Mendeliana , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/genética , Hemorragia Subaracnoidea/sangre , Femenino , Masculino , Aneurisma Intracraneal/genética , Aneurisma Intracraneal/epidemiología , Factores Sexuales , Medición de Riesgo , Factores de Riesgo , Incidencia , Predisposición Genética a la Enfermedad , Disparidades en el Estado de Salud , PrevalenciaRESUMEN
BACKGROUND AND OBJECTIVES: Current benefits of invasive intracranial aneurysm treatment to prevent aneurysmal subarachnoid hemorrhage (aSAH) rarely outweigh treatment risks. Most intracranial aneurysms thus remain untreated. Commonly prescribed drugs reducing aSAH incidence may provide leads for drug repurposing. We performed a drug-wide association study (DWAS) to systematically investigate the association between commonly prescribed drugs and aSAH incidence. METHODS: We defined all aSAH cases between 2000 and 2020 using International Classification of Diseases codes from the Secure Anonymised Information Linkage databank. Each case was matched with 9 controls based on age, sex, and year of database entry. We investigated commonly prescribed drugs (>2% in study population) and defined 3 exposure windows relative to the most recent prescription before index date (i.e., occurrence of aSAH): current (within 3 months), recent (3-12 months), and past (>12 months). A logistic regression model was fitted to compare drug use across these exposure windows vs never use, controlling for age, sex, known aSAH risk factors, and health care utilization. The family-wise error rate was kept at p < 0.05 through Bonferroni correction. RESULTS: We investigated exposure to 205 commonly prescribed drugs between 4,879 aSAH cases (mean age 61.4, 61.2% women) and 43,911 matched controls. We found similar trends for lisinopril and amlodipine, with a decreased aSAH risk for current use (lisinopril odds ratio [OR] 0.63, 95% CI 0.44-0.90, amlodipine OR 0.82, 95% CI 0.65-1.04) and an increased aSAH risk for recent use (lisinopril OR 1.30, 95% CI 0.61-2.78, amlodipine OR 1.61, 95% CI 1.04-2.48). A decreased aSAH risk in current use was also found for simvastatin (OR 0.78, 95% CI 0.64-0.96), metformin (OR 0.58, 95% CI 0.43-0.78), and tamsulosin (OR 0.55, 95% CI 0.32-0.93). By contrast, an increased aSAH risk was found for current use of warfarin (OR 1.35, 95% CI 1.02-1.79), venlafaxine (OR 1.67, 95% CI 1.01-2.75), prochlorperazine (OR 2.15, 95% CI 1.45-3.18), and co-codamol (OR 1.31, 95% CI 1.10-1.56). DISCUSSION: We identified several drugs associated with aSAH, of which 5 drugs (lisinopril and possibly amlodipine, simvastatin, metformin, and tamsulosin) showed a decreased aSAH risk. Future research should build on these signals to further assess the effectiveness of these drugs in reducing aSAH incidence. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that some commonly prescribed drugs are associated with subsequent development of aSAH.
Asunto(s)
Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Incidencia , Adulto , Anciano , Medicamentos bajo Prescripción/uso terapéutico , Medicamentos bajo Prescripción/efectos adversos , Estudios de Casos y Controles , Aneurisma Intracraneal/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND: Unhealthy dietary habits are an important risk factor for cardiovascular disease (CVD) and adopting a healthy diet is a central recommendation in CVD prevention. This study assessed the dietary habits of patients with established CVD, their compliance to dietary guidelines, and the relationship between guideline-compliance and recurrent cardiovascular event risk. METHODS: 2656 patients with established CVD from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART) prospective cohort study, were included between 1996 and 2022. Data on dietary intake was retrospectively collected for all participants in December 2022 using a 160-item food frequency questionnaire. Compliance with dietary guidelines was quantified using an amended version of the Dutch Healthy Diet 2015 (DHD-15) index (range: 0-135). Cox proportional hazard models were used to quantify the relationship with cardiovascular events (stroke and myocardial infarction). RESULTS: Among 2656 CVD patients (77% male, mean age 59 ± 9 years), median energy intake was 1922 [IQR: 1536-2351] kcal/day. The median DHD-15 index was 81.7 [IQR 71.2-92.0], with high compliance scores for recommendations on legumes and fish, and low scores for recommendations on whole grains, red meat, processed meat, and dairy. A higher DHD-15 score was associated with lower stroke risk (HR 0.78, 95% CI 0.66-0.92 per 10-point increase) but not with myocardial infarction. CONCLUSION: Compliance with dietary guidelines was suboptimal in patients with established CVD. High compliance was associated with a clinically significant reduction in stroke risk in patients with established CVD, emphasizing the importance of dietary counseling.
Asunto(s)
Enfermedades Cardiovasculares , Conducta Alimentaria , Política Nutricional , Cooperación del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Enfermedades Cardiovasculares/prevención & control , Cooperación del Paciente/estadística & datos numéricos , Estudios Prospectivos , Anciano , Países Bajos , Estudios de Cohortes , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVES: Arterial calcification is thought to protect against rupture of intracranial aneurysms, but studies in a representative population of intracranial aneurysm patients have not yet been performed. The aim was to compare the prevalence of aneurysm wall calcification and intracranial carotid artery calcification (ICAC) between patients with an unruptured intracranial aneurysm (UIA) and a ruptured intracranial aneurysm (RIA). MATERIALS AND METHODS: We matched 150 consecutive UIA patients to 150 RIA patients on age and sex. Aneurysm wall calcification and ICAC were quantified on non-contrast enhanced computed tomography images with the modified Agatston score. We compared the prevalence of aneurysm wall calcification, ICAC, and severe ICAC (defined as a modified Agatston score in the fourth quartile) between UIA and RIA patients using univariate and multivariate conditional logistic regression models adjusted for aneurysm characteristics and cardiovascular risk factors. RESULTS: Aneurysm wall calcification was more prevalent in UIA compared to RIA patients (OR 5.2, 95% CI: 2.0-13.8), which persisted after adjustment (OR 5.9, 95% CI: 1.7-20.2). ICAC prevalence did not differ between the two groups (crude OR 0.9, 95% CI: 0.5-1.8). Severe ICAC was more prevalent in UIA patients (OR 2.0, 95% CI: 1.1-3.6), but not after adjustment (OR 1.0, 95% CI: 0.5-2.3). CONCLUSIONS: Aneurysm wall calcification but not ICAC was more prevalent in UIAs than in RIAs, which corresponds to the hypothesis that calcification may protect against aneurysmal rupture. Aneurysm wall calcification should be further assessed as a predictor of aneurysm stability in prospective cohort studies. CLINICAL RELEVANCE STATEMENT: Calcification of the intracranial aneurysm wall was more prevalent in unruptured than ruptured intracranial aneurysms after adjustment for cardiovascular risk factors. Calcification may therefore protect the aneurysm against rupture, and aneurysm wall calcification is a candidate predictor of aneurysm stability. KEY POINTS: Aneurysm wall calcification was more prevalent in patients with unruptured than ruptured aneurysms, while internal carotid artery calcification was similar. Aneurysm wall calcification but not internal carotid artery calcification is a candidate predictor of aneurysm stability. Cohort studies are needed to assess the predictive value of aneurysm wall calcification for aneurysm stability.
RESUMEN
Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.
Asunto(s)
Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Registros Electrónicos de Salud , Países Bajos/epidemiología , Modelos de Riesgos Proporcionales , Aneurisma Intracraneal/epidemiología , Aneurisma Intracraneal/diagnóstico , Bases de Datos Factuales , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/diagnósticoRESUMEN
BACKGROUND AND OBJECTIVES: Gene-gene interactions likely contribute to the etiology of multifactorial diseases such as cerebral venous thrombosis (CVT) and could be one of the main sources of known missing heritability. We explored Factor XI (F11) and ABO gene interactions among patients with CVT. METHODS: Patients with CVT of European ancestry from the large Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) international collaboration were recruited. Codominant modelling was used to determine interactions between genome-wide identified F11 and ABO genes with CVT status. RESULTS: We studied 882 patients with CVT and 1,205 ethnically matched control participants (age: 42 ± 15 vs 43 ± 12 years, p = 0.08: sex: 71% male vs 68% female, p = 0.09, respectively). Individuals heterozygous (AT) for the risk allele (T) at both loci (rs56810541/F11 and rs8176645/ABO) had a 3.9 (95% CI 2.74-5.71, p = 2.75e-13) increase in risk of CVT. Individuals homozygous (TT) for the risk allele at both loci had a 13.9 (95% CI 7.64-26.17, p = 2.0e-15) increase in risk of CVT. The presence of a non-O blood group (A, B, AB) combined with TT/rs56810541/F11 increased CVT risk by OR = 6.8 (95% CI 4.54-10.33, p = 2.00e15), compared with blood group-O combined with AA. DISCUSSION: Interactions between factor XI and ABO genes increase risk of CVT by 4- to 14-fold.
Asunto(s)
Sistema del Grupo Sanguíneo ABO , Factor XI , Trombosis de la Vena , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sistema del Grupo Sanguíneo ABO/genética , Epistasis Genética/genética , Factor XI/genética , Galactosiltransferasas , Predisposición Genética a la Enfermedad/genética , Trombosis Intracraneal/genética , Polimorfismo de Nucleótido Simple , Trombosis de la Vena/genéticaRESUMEN
Haemorrhagic stroke is a severe condition with poor prognosis. Biological sex influences the risk factors, presentations, treatment, and patient outcomes of intracerebral haemorrhage, aneurysmal subarachnoid haemorrhage, and vascular malformations. Women are usually older at onset of intracerebral haemorrhage compared with men but have an increased risk of aneurysmal subarachnoid haemorrhage as they age. Female-specific factors such as pregnancy, eclampsia or pre-eclampsia, postmenopausal status, and hormone therapy influence a woman's long-term risk of haemorrhagic stroke. The presence of intracranial aneurysms, arteriovenous malformations, or cavernous malformations poses unique clinical dilemmas during pregnancy and delivery. In the absence of evidence-based guidelines for managing the low yet uncertain risk of haemorrhagic stroke during pregnancy and delivery in women with vascular malformations, multidisciplinary teams should carefully assess the risks and benefits of delivery methods for these patients. Health-care providers should recognise and address the challenges that women might have to confront when recovering from haemorrhagic stroke.
Asunto(s)
Accidente Cerebrovascular Hemorrágico , Humanos , Femenino , Factores de Riesgo , Embarazo , Accidente Cerebrovascular Hemorrágico/epidemiologíaRESUMEN
BACKGROUND AND PURPOSE: Coma is an independent predictor of poor clinical outcomes in cerebral venous thrombosis (CVT). We aimed to describe the association of age, sex, and radiological characteristics of adult coma patients with CVT. METHODS: We used data from the international, multicentre prospective observational BEAST (Biorepository to Establish the Aetiology of Sinovenous Thrombosis) study. Only positively associated variables with coma with <10% missing data in univariate analysis were considered for the multivariate logistic regression model. RESULTS: Of the 596 adult patients with CVT (75.7% women), 53 (8.9%) patients suffered coma. Despite being a female-predominant disease, the prevalence of coma was higher among men than women (13.1% vs. 7.5%, p = 0.04). Transverse sinus thrombosis was least likely to be associated with coma (23.9% vs. 73.3%, p < 0.001). The prevalence of superior sagittal sinus thrombosis was higher among men than women in the coma sample (73.6% vs. 37.5%, p = 0.01). Men were significantly older than women, with a median (interquartile range) age of 51 (38.5-60) versus 40 (33-47) years in the coma (p = 0.04) and 44.5 (34-58) versus 37 (29-48) years in the non-coma sample (p < 0.001), respectively. Furthermore, an age- and superior sagittal sinus-adjusted multivariate logistic regression model found male sex (odds ratio = 1.8, 95% confidence interval [CI] = 1.0-3.4, p = 0.04) to be an independent predictor of coma in CVT, with an area under the receiver operating characteristic curve of 0.61 (95% CI = 0.52-0.68, p = 0.01). CONCLUSIONS: Although CVT is a female-predominant disease, men were older and nearly twice as likely to suffer from coma than women.
Asunto(s)
Coma , Humanos , Masculino , Femenino , Coma/etiología , Coma/epidemiología , Adulto , Persona de Mediana Edad , Trombosis Intracraneal/epidemiología , Trombosis Intracraneal/complicaciones , Estudios Prospectivos , Trombosis de la Vena/epidemiología , Trombosis de la Vena/complicaciones , Trombosis de los Senos Intracraneales/epidemiología , Trombosis de los Senos Intracraneales/complicaciones , Factores Sexuales , Factores de Edad , PrevalenciaRESUMEN
AIMS: Identifying patients with established cardiovascular disease (CVD) who are at high risk of type 2 diabetes (T2D) may allow for early interventions, reducing the development of T2D and associated morbidity. The aim of this study was to develop and externally validate the CVD2DM model to estimate the 10-year and lifetime risks of T2D in patients with established CVD. METHODS AND RESULTS: Sex-specific, competing risk-adjusted Cox proportional hazard models were derived in 19 281 participants with established CVD and without diabetes at baseline from the UK Biobank. The core model's pre-specified predictors were age, current smoking, family history of diabetes mellitus, body mass index, systolic blood pressure, fasting plasma glucose, and HDL cholesterol. The extended model also included HbA1c. The model was externally validated in 3481 patients from the UCC-SMART study. During a median follow-up of 12.2 years (interquartile interval 11.3-13.1), 1628 participants with established CVD were diagnosed with T2D in the UK Biobank. External validation c-statistics were 0.79 [95% confidence interval (CI) 0.76-0.82] for the core model and 0.81 (95% CI 0.78-0.84) for the extended model. Calibration plots showed agreement between predicted and observed 10-year risk of T2D. CONCLUSION: The 10-year and lifetime risks of T2D can be estimated with the CVD2DM model in patients with established CVD, using readily available clinical predictors. The model would benefit from further validation across diverse ethnic groups to enhance its applicability. Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle.
In this study, we developed and externally validated the CVD2DM model, which predicts the 10-year and lifetime risk of type 2 diabetes (T2D) in individuals who already have cardiovascular disease (CVD). The key findings are as follows: The CVD2DM model is the first model to estimate the risk of developing T2D applicable in all patients with atherosclerotic CVD. The model is based on several factors available in clinical practice, such as age, fasting plasma glucose, family history of diabetes, and body mass index. It was developed in 19 281 patients from the UK Biobank. The model performed well in 3481 patients from the UCC-SMART study.Informing patients about their T2D risk could motivate them further to adhere to a healthy lifestyle.
RESUMEN
AIMS: The efficacy of a healthy lifestyle in secondary prevention of cardiovascular disease (CVD) is well established and a first-line recommendation in CVD prevention guidelines. The aim of this study was to assess if they are also cost-effective in patients with established CVD. METHODS: A cost-utility analysis (CUA) was performed comparing a combined Mediterranean diet and physical activity intervention to usual care in CVD patients. The CUA had a healthcare perspective and lifetime horizon. Costs and utilities were estimated using a microsimulation on a cohort of 100,000 CVD patients sampled from the UCC-SMART study (N = 8,947, mean age 62 ±8.7 years and 74% male). Cost-effectiveness was expressed as incrementalcost-effectiveness ratio (ICER), incremental net health benefit (INHB) and incremental net monetary benefit (INMB). RESULTS: Mediterranean diet and physical activity yielded 2.0 incremental quality-adjusted life years (QALYs) and cost reductions of 1,236 per person compared to usual care, resulting in an ICER of -626/QALY (95%CI -1,929 to 2,673). At a willingness-to-pay of 20,000/QALY, INHB was 2.04 (95%CI 0.99-3.58) QALY and INMB was 40,757 (95%CI 19,819-71,605). The interventions remained cost-effective in a wide range of sensitivity analyses, including worst-case scenarios and scenarios with reimbursement for food and physical activity costs. CONCLUSION: In patients with established CVD, a combined Mediterranean diet and physical activity intervention was cost-saving and highly cost-effective compared to usual care. These findings strongly advocate for the incorporation of lifestyle interventions as integral components of care for all CVD patients.
Lifestyle optimization, including physical activity and healthy diet, is a central recommendation for preventing recurrent cardiovascular events. In this study, we assessed if improving physical activity habits and adherence to a heart-healthy Mediterranean diet would also be a cost-effective option. The results were remarkable - following the Mediterranean diet and engaging in physical activity was expected to result in an increase of 2.0 quality-adjusted life years (QALYs, equal to a life year in perfect health) and cost savings. This means that lifestyle optimization in secondary CVD prevention improves population health, while reducing overall health care costs. These findings underscore the importance of implementing lifestyle changes in the care for all individuals with CVD. A health lifestyle is not only effective in improving health but also a prudent financial decision. Key messages A combined Mediterranean diet and physical activity intervention is expected to result in two additional QALYs and three additional life years free of recurrent cardiovascular events per patient with with established CVDTargeting a healthy lifestyle is expected to lead to costs savings compared to usual care, due to the low costs of the intervention and the high efficacy in preventing recurrent cardiovascular events.Lifestyle optimization in secondary CVD prevention was shown to result in a dominant incremental cost-effectiveness ratio (ICER) of -626/QALY, which strongly advocates for healthy policy targeted at implementing lifestyle interventions in regular care for CVD patients.
RESUMEN
(1) Background: Primary Familial Brain Calcification (PFBC) is a neurodegenerative disease characterized by bilateral calcifications of the basal ganglia and other intracranial areas. Many patients experience symptoms of motor dysfunction and cognitive disorders. The aim of this study was to investigate the association between the amount and location of intracranial calcifications with these symptoms. (2) Methods: Patients with suspected PFBC referred to our outpatient clinic underwent a clinical work-up. Intracranial calcifications were visualized on Computed Tomography (CT), and a Total Calcification Score (TCS) was constructed. Logistic and linear regression models were performed. (3) Results: Fifty patients with PFBC were included in this study (median age 64.0 years, 50% women). Of the forty-one symptomatic patients (82.0%), 78.8% showed motor dysfunction, and 70.7% showed cognitive disorders. In multivariate analysis, the TCS was associated with bradykinesia/hypokinesia (OR 1.07, 95%-CI 1.02-1.12, p < 0.01), gait ataxia (OR 1.06, 95%-CI 1.00-1.12, p = 0.04), increased fall risk (OR 1.04, 95%-CI 1.00-1.08, p = 0.03), and attention/processing speed disorders (OR 1.06, 95%-CI 1.01-1.12, p = 0.02). Calcifications of the lentiform nucleus and subcortical white matter were associated with motor and cognitive disorders. (4) Conclusions: cognitive and motor symptoms are common among patients with PFBC, and there is an association between intracranial calcifications and these symptoms.
RESUMEN
Purpose: Unruptured intracranial aneurysms (UIAs) can cause aneurysmal subarachnoid hemorrhage, a severe and often lethal type of stroke. Automated labeling of intracranial arteries can facilitate the identification of risk factors associated with UIAs. This study aims to improve intracranial artery labeling using atlas-based features in graph convolutional networks. Approach: We included three-dimensional time-of-flight magnetic resonance angiography scans from 150 individuals. Two widely used graph convolutional operators, GCNConv and GraphConv, were employed in models trained to classify 12 bifurcations of interest. Cross-validation was applied to explore the effectiveness of atlas-based features in node classification. The results were tested for statistically significant differences using a Wilcoxon signed-rank test. Model repeatability and calibration were assessed on the test set for both operators. In addition, we evaluated model interpretability and node feature contribution using explainable artificial intelligence. Results: Atlas-based features led to statistically significant improvements in node classification (p<0.05). The results showed that the best discrimination and calibration performances were obtained using the GraphConv operator, which yielded a mean recall of 0.87, precision of 0.90, and expected calibration error of 0.02. Conclusions: The addition of atlas-based features improved node classification results. The GraphConv operator, which incorporates higher-order structural information during training, is recommended over the GCNConv operator based on the accuracy and calibration of predicted outcomes.
RESUMEN
INTRODUCTION: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach. PATIENTS AND METHODS: Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA (N = 2140 cases), ASAH (N = 5140) or the combined group, and liability to drug usage from 23 drug classes (N up to 320,000) independent of the risk factor high blood pressure. Next, we evaluated the causality and therapeutic potential of correlated drug classes using three different Mendelian randomization frameworks. RESULTS: Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09-2.39, p = 0.018) and ASAH (OR = 1.68, 95% CI = 1.07-2.65, p = 0.024) if they used antidepressant drugs. This effect was absent in non-users. For beta-blockers, additional analyses showed that this effect was not independent of blood pressure after all. A complex and likely pleiotropic relationship was found between genetic liability to chronic multisite pain, pain medication usage (paracetamol, acetylsalicylic acid, and opioids), and IA. CONCLUSIONS: We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA.
RESUMEN
BACKGROUND: Fahr's disease and syndrome are rare disorders leading to calcification of the small arteries in the basal ganglia of the brain, resulting in a wide range of symptoms comprising cognitive decline, movement disorders and neuropsychiatric symptoms. No disease-modifying therapies are available. Studies have shown the potential of treatment of ectopic vascular calcifications with bisphosphonates. This paper describes the rationale and design of the CALCIFADE trial which evaluates the effects of etidronate in patients with Fahr's disease or syndrome. METHODS: The CALCIFADE trial is a randomised, placebo-controlled, double-blind trial which evaluates the effects of etidronate 20 mg/kg during 12 months follow-up in patients aged ≥ 18 years with Fahr's disease or syndrome. Etidronate and placebo will be administered in capsules daily for two weeks on followed by ten weeks off. The study will be conducted at the outpatient clinic of the University Medical Center Utrecht, the Netherlands. The primary endpoint is the change in cognitive functioning after 12 months of treatment. Secondary endpoints are the change in mobility, neuropsychiatric symptoms, volume of brain calcifications, dependence in activities of daily living, and quality of life. RESULTS: Patient recruitment started in April 2023. Results are expected in 2026 and will be disseminated through peer-reviewed journals as well as presentations at national and international conferences. CONCLUSIONS: Fahr's disease and syndrome are slowly progressive disorders with a negative impact on a variety of health outcomes. Etidronate might be a new promising treatment for patients with Fahr's disease or syndrome. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05662111. Registered 22 December 2022, https://clinicaltrials.gov/ct2/show/NCT01585402 .
Asunto(s)
Enfermedades de los Ganglios Basales , Calcinosis , Ácido Etidrónico , Enfermedades Neurodegenerativas , Humanos , Ácido Etidrónico/uso terapéutico , Actividades Cotidianas , Calidad de Vida , Enfermedades de los Ganglios Basales/complicaciones , Enfermedades de los Ganglios Basales/diagnóstico , Enfermedades de los Ganglios Basales/psicología , EncéfaloRESUMEN
The Circle of Willis (CoW) is an important network of arteries connecting major circulations of the brain. Its vascular architecture is believed to affect the risk, severity, and clinical outcome of serious neuro-vascular diseases. However, characterizing the highly variable CoW anatomy is still a manual and time-consuming expert task. The CoW is usually imaged by two angiographic imaging modalities, magnetic resonance angiography (MRA) and computed tomography angiography (CTA), but there exist limited public datasets with annotations on CoW anatomy, especially for CTA. Therefore we organized the TopCoW Challenge in 2023 with the release of an annotated CoW dataset. The TopCoW dataset was the first public dataset with voxel-level annotations for thirteen possible CoW vessel components, enabled by virtual-reality (VR) technology. It was also the first large dataset with paired MRA and CTA from the same patients. TopCoW challenge formalized the CoW characterization problem as a multiclass anatomical segmentation task with an emphasis on topological metrics. We invited submissions worldwide for the CoW segmentation task, which attracted over 140 registered participants from four continents. The top performing teams managed to segment many CoW components to Dice scores around 90%, but with lower scores for communicating arteries and rare variants. There were also topological mistakes for predictions with high Dice scores. Additional topological analysis revealed further areas for improvement in detecting certain CoW components and matching CoW variant topology accurately. TopCoW represented a first attempt at benchmarking the CoW anatomical segmentation task for MRA and CTA, both morphologically and topologically.
RESUMEN
AIMS: To quantify the relationship between self-reported, long-term lifestyle changes (smoking, waist circumference, physical activity, and alcohol consumption) and clinical outcomes in patients with established cardiovascular disease (CVD). METHODS AND RESULTS: Data were used from 2011 participants (78% male, age 57 ± 9 years) from the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease cohort who returned for a re-assessment visit (SMART2) after â¼10 years. Self-reported lifestyle change was classified as persistently healthy, improved, worsened, or persistently unhealthy. Cox proportional hazard models were used to quantify the relationship between lifestyle changes and the risk of (cardiovascular) mortality and incident Type 2 diabetes (T2D). Fifty-seven per cent of participants was persistently healthy, 17% improved their lifestyle, 8% worsened, and 17% was persistently unhealthy. During a median follow-up time of 6.1 (inter-quartile range 3.6-9.6) years after the SMART2 visit, 285 deaths occurred, and 99 new T2D diagnoses were made. Compared with a persistently unhealthy lifestyle, individuals who maintained a healthy lifestyle had a lower risk of all-cause mortality [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.36-0.63], cardiovascular mortality (HR 0.57, 95% CI 0.38-0.87), and incident T2D (HR 0.46, 95% CI 0.28-0.73). Similarly, those who improved their lifestyle had a lower risk of all-cause mortality (HR 0.52, 95% CI 0.37-0.74), cardiovascular mortality (HR 0.46, 95% CI 0.26-0.81), and incident T2D (HR 0.50, 95% CI 0.27-0.92). CONCLUSION: These findings suggest that maintaining or adopting a healthy lifestyle can significantly lower mortality and incident T2D risk in CVD patients. This study emphasizes the importance of ongoing lifestyle optimization in CVD patients, highlighting the potential for positive change regardless of previous lifestyle habits.
In this study, we investigated whether lifestyle changes were related to improved health outcomes in individuals with cardiovascular disease (CVD). We assessed self-reported lifestyle behaviours (smoking, waist circumference, alcohol consumption, and physical activity), at inclusion in the cohort and again â¼10 years later. The results emphasize the importance of making healthy lifestyle choices, even for individuals already diagnosed with CVD, and suggest that it is never too late to improve one's lifestyle.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Factores de Riesgo , Estudios Prospectivos , Estilo de VidaRESUMEN
BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (ASAH) is a complex disease with higher incidence in women compared to men and in Japan compared to other countries. It was hypothesized that ASAH is consistent with a multistep model of disease. The following assessments were made: (1) the number of steps needed for the disease to occur and (2) whether this number may be different in female versus male and in Japanese versus non-Japanese patients. METHODS: Incidence data were generated from a meta-analysis on ASAH incidence until 2017, which was supplemented with a literature search from 2017 to April 2023. Age- and sex-adjusted incidences per 10-year age groups were calculated and the logarithm of age-specific incidence against the logarithm of age was regressed with least-squares regression. RESULTS: In 2317 ASAH patients a linear relationship between logarithm of incidence and logarithm of age was found with a slope estimate of 3.13 (95% confidence interval 2.60-3.65), consistent with a four-step process. Similar estimates were found for female, male, Japanese and non-Japanese patients. CONCLUSIONS: Our results suggest that ASAH is a four-step process, also in subgroups with higher ASAH incidence. Elucidation of the exact nature of these steps can provide important clues for identification of disease mechanisms underlying ASAH.
Asunto(s)
Aneurisma Intracraneal , Hemorragia Subaracnoidea , Humanos , Masculino , Femenino , Hemorragia Subaracnoidea/epidemiología , Incidencia , Japón/epidemiologíaRESUMEN
OBJECTIVES: In patients with an unruptured intracranial aneurysm, gadolinium enhancement of the aneurysm wall is associated with growth and rupture. However, most previous studies did not have a longitudinal design and did not adjust for aneurysm size, which is the main predictor of aneurysm instability and the most important determinant of wall enhancement. We investigated whether aneurysm wall enhancement predicts aneurysm growth and rupture during follow-up and whether the predictive value was independent of aneurysm size. MATERIALS AND METHODS: In this multicentre longitudinal cohort study, individual patient data were obtained from twelve international cohorts. Inclusion criteria were as follows: 18 years or older with ≥ 1 untreated unruptured intracranial aneurysm < 15 mm; gadolinium-enhanced aneurysm wall imaging and MRA at baseline; and MRA or rupture during follow-up. Patients were included between November 2012 and November 2019. We calculated crude hazard ratios with 95%CI of aneurysm wall enhancement for growth (≥ 1 mm increase) or rupture and adjusted for aneurysm size. RESULTS: In 455 patients (mean age (SD), 60 (13) years; 323 (71%) women) with 559 aneurysms, growth or rupture occurred in 13/194 (6.7%) aneurysms with wall enhancement and in 9/365 (2.5%) aneurysms without enhancement (crude hazard ratio 3.1 [95%CI: 1.3-7.4], adjusted hazard ratio 1.4 [95%CI: 0.5-3.7]) with a median follow-up duration of 1.2 years. CONCLUSIONS: Gadolinium enhancement of the aneurysm wall predicts aneurysm growth or rupture during short-term follow-up, but not independent of aneurysm size. CLINICAL RELEVANCE STATEMENT: Gadolinium-enhanced aneurysm wall imaging is not recommended for short-term prediction of growth and rupture, since it appears to have no additional value to conventional predictors. KEY POINTS: ⢠Although aneurysm wall enhancement is associated with aneurysm instability in cross-sectional studies, it remains unknown whether it predicts risk of aneurysm growth or rupture in longitudinal studies. ⢠Gadolinium enhancement of the aneurysm wall predicts aneurysm growth or rupture during short-term follow-up, but not when adjusting for aneurysm size. ⢠While gadolinium-enhanced aneurysm wall imaging is not recommended for short-term prediction of growth and rupture, it may hold potential for aneurysms smaller than 7 mm.