Neurofibromatosis type 1 is not associated with subarachnoid haemorrhage

BackgroundThe prevalence of intracranial aneurysms (IAs) has been proposed to be elevated in the patients with neurofibromatosis type 1 (NF1). Our aims were to determine the prevalence of NF1 in a large Finnish population based cohort of IA patients and, on the other hand, the occurrences of subarachnoid haemorrhage and unruptured intracranial aneurysms in a nationwide population-based cohort of NF1 patients and its matched ten-fold control cohort.MethodsThe Kuopio IA Database (www.kuopioneurosurgery.fi) includes all ruptured and unruptured IA cases admitted to the Kuopio University Hospital (KUH) from its defined Eastern Finnish catchment population since 1980. In this registry-based study, we cross-linked the Kuopio IA database with the Finnish national registry covering all hospital diagnoses. The NF1 diagnoses of the 4543 patients with either saccular of fusiform IA were identified from 1969 to 2015 and verified from patient records. Our second approach was to analyze the occurrence of aneurysmal subarachnoid haemorrhage (aSAH) and unruptured IAs in a nationwide population-based database of 1410 NF1 patients and its ten-fold matched control cohort (n = 14030) using national registry of hospital diagnoses between 1987 and 2014.Results One NF1 patient was identified among the 4543 IA patients. Three verified IA cases (one unruptured IA and two aSAH cases) were identified in the cohort of 1410 NF1 patients, with similar occurrences in the control cohort.Conclusions We found no evidence in our population-based cohorts to support the conception that NF1 is associated with IAs. Our results indicate that the incidence of aSAH is not elevated in patients with NF1. Further studies are required to confirm that there is no association between NF1 and unruptured IAs

Sex Difference and Rupture Rate of Intracranial Aneurysms : An Individual Patient Data Meta-Analysis

Background and Purpose: In previous studies, women had a higher risk of rupture of intracranial aneurysms than men, but female sex was not an independent risk factor. This may be explained by a higher prevalence of patient- or aneurysm-related risk factors for rupture in women than in men or by insufficient power of previous studies. We assessed sex differences in rupture rate taking into account other patient- and aneurysm-related risk factors for aneurysmal rupture. Methods: We searched Embase and Pubmed for articles published until December 1, 2020. Cohorts with available individual patient data were included in our meta-analysis. We compared rupture rates of women versus men using a Cox proportional hazard regression model adjusted for the PHASES score (Population, Hypertension, Age, Size of Aneurysm, Earlier Subarachnoid Hemorrhage From Another Aneurysm, Site of Aneurysm), smoking, and a positive family history of aneurysmal subarachnoid hemorrhage. Results: We pooled individual patient data from 9 cohorts totaling 9940 patients (6555 women, 66%) with 12 193 unruptured intracranial aneurysms, and 24 357 person-years follow-up. Rupture occurred in 163 women (rupture rate 1.04%/person-years [95% CI, 0.89-1.21]) and 63 men (rupture rate 0.74%/person-years [95% CI, 0.58-0.94]). Women were older (61.9 versus 59.5 years), were less often smokers (20% versus 44%), more often had internal carotid artery aneurysms (24% versus 17%), and larger sized aneurysms (>= 7 mm, 24% versus 23%) than men. The unadjusted women-to-men hazard ratio was 1.43 (95% CI, 1.07-1.93) and the adjusted women/men ratio was 1.39 (95% CI, 1.02-1.90). Conclusions: Women have a higher risk of aneurysmal rupture than men and this sex difference is not explained by differences in patient- and aneurysm-related risk factors for aneurysmal rupture. Future studies should focus on the factors explaining the higher risk of aneurysmal rupture in women.Peer reviewe

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

BACKGROUND: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. METHODS: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. FINDINGS: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced. INTERPRETATION: Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies. FUNDING: EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research

Outcome after clipping and coiling for aneurysmal subarachnoid hemorrhage in clinical practice in Europe, Usa, and Australia

Background:Within randomized clinical trials (RCTs), coiling of the ruptured aneurysm to prevent rebleeding results in better outcomes than clipping in patients with aneurysmal subarachnoid hemorrhage (aSAH). Objective: To study the association of coiling and clipping with outcome after aSAH in daily clinical practice. Methods: In this controlled, nonrandomized study, we compared outcomes after endovascular coiling and neurosurgical clipping of ruptured intracranial aneurysms in an administrative dataset of 7658 aSAH patients (22 tertiary care hospitals from Europe USA Australia; 2007-2013). Because the results contradicted those of the randomized trials, findings were further explored in a large clinical dataset from 2 European centers (2006- 2016) of 1501 patients. Results: In the administrative dataset, the crude 14-d case-fatality rate was 6.4% (95% confidence interval [CI] 5.6%-7.2%) after clipping and 8.2% (95% CI 7.4%-9.1%) after coiling. After adjustment for age, sex, and comorbidity/severity, the odds ratio (OR) for 14-d casefatality after coiling compared to clipping was 1.32 (95% CI 1.10-1.58). In the clinical dataset crude 14-d case fatality ratewas 5.7% (95% CI 4.2%-7.8%) for clipping and 9.0% (95% CI 7.3%- 11.2%) for coiling. In multivariable logistic regression analysis, the OR for 14-d case-fatality after coiling compared to clipping was 1.7 (95% CI 1.1-2.7), for 90-d case-fatality 1.28 (95% CI 0.91-1.82) and for 90-d poor functional outcome 0.78 (95% CI 0.6-1.01). Conclusion: In clinical practice, coiling after aSAH is associated with higher 14-d case-fatality than clipping and nonsuperior outcomes at 90 d. Both options need to be considered in aSAH patients. Further studies should address the reasons for the discrepancy between current data and those from the RCTs

Outcome after clipping and coiling for aneurysmal subarachnoid hemorrhage in clinical practice in Europe, Usa, and Australia

Background:Within randomized clinical trials (RCTs), coiling of the ruptured aneurysm to prevent rebleeding results in better outcomes than clipping in patients with aneurysmal subarachnoid hemorrhage (aSAH). Objective: To study the association of coiling and clipping with outcome after aSAH in daily clinical practice. Methods: In this controlled, nonrandomized study, we compared outcomes after endovascular coiling and neurosurgical clipping of ruptured intracranial aneurysms in an administrative dataset of 7658 aSAH patients (22 tertiary care hospitals from Europe USA Australia; 2007-2013). Because the results contradicted those of the randomized trials, findings were further explored in a large clinical dataset from 2 European centers (2006- 2016) of 1501 patients. Results: In the administrative dataset, the crude 14-d case-fatality rate was 6.4% (95% confidence interval [CI] 5.6%-7.2%) after clipping and 8.2% (95% CI 7.4%-9.1%) after coiling. After adjustment for age, sex, and comorbidity/severity, the odds ratio (OR) for 14-d casefatality after coiling compared to clipping was 1.32 (95% CI 1.10-1.58). In the clinical dataset crude 14-d case fatality ratewas 5.7% (95% CI 4.2%-7.8%) for clipping and 9.0% (95% CI 7.3%- 11.2%) for coiling. In multivariable logistic regression analysis, the OR for 14-d case-fatality after coiling compared to clipping was 1.7 (95% CI 1.1-2.7), for 90-d case-fatality 1.28 (95% CI 0.91-1.82) and for 90-d poor functional outcome 0.78 (95% CI 0.6-1.01). Conclusion: In clinical practice, coiling after aSAH is associated with higher 14-d case-fatality than clipping and nonsuperior outcomes at 90 d. Both options need to be considered in aSAH patients. Further studies should address the reasons for the discrepancy between current data and those from the RCTs

Concordance in Aneurysm Size at Time of Rupture in Familial Intracranial Aneurysms

Background and Purpose- Intracranial aneurysm (IA) size and location are important determinants of aneurysm rupture risk. In familial IAs there is concordance of location; however, if such concordance exists for size is unknown. We analyzed the concordance of aneurysm size at time of rupture in familial IAs. Methods- In pairs of affected relatives with aneurysmal subarachnoid hemorrhage, the ratio between the largest and the smallest aneurysm size at time of rupture was calculated. We also compared the proportion of families in which both IAs ruptured at a size 1.2, and 12 (17%) had a ratio ≥3. We found no difference between the proportion of families (n=31; 49%) who both had IA at time of rupture <7 mm (n=20; 31%) or both ≥7 mm (n=11; 18%) and the proportion of those families with one patient with an IA <7 mm and another with an IA ≥7 mm (n=33; 51%; P=0.86). Overall, the repeatability in aneurysm size at rupture within familial IAs was 0.10 (95% CI, 0-0.35). Conclusions- There is no good concordance in aneurysm size at rupture within familial IAs. These data suggest that size of a ruptured IA in a family member should not significantly impact on the management of a familial unruptured IA in a relative