Risk Of Aneurysmal Subarachnoid Hemorrhage Research Articles

Risk factors for aneurysmal subarachnoid hemorrhage - BMI and serum lipids: 11-year follow-up of the HUNT and the Tromsø Study in Norway

Life-style factors have been associated with the risk for aneurysmal subarachnoid hemorrhage (aSAH), but it is not clear whether body mass index (BMI) and serum lipids are associated with risk. We prospectively assessed these associations in two large population studies. A total of 65,526 participants in the Nord-Trøndelag Health Study (1995-1997) and 26,882 participants in the Tromsø Study (1994-1995) were included. Studies included measurements of body weight and height, serum lipids, and self-administered questionnaires. Participants who experienced aSAH were identified, and hazard ratios (HRs) were estimated using Cox regression analysis. During 11 years of follow-up, aSAH was diagnosed in 122 participants. Overweight (BMI 25-29.9) was negatively associated with the risk of aSAH (HR 0.7, 95% CI 0.4-1.0). There was no over all association of total serum cholesterol, HDL cholesterol, or triglycerides with the risk of aSAH, but in participants younger than 50 years, HDL cholesterol was inversely associated with the risk (HR per standard deviation increase 0.6, 95% CI 0.4-0.9). Overweight may be associated with reduced risk of aSAH, but there was no over all association of total serum cholesterol, HDL cholesterol, or triglycerides with the risk of aSAH in this prospective study.

Not Tonight, Darling, I Might Get a Headache

See related article, pages 1878–1882 Advances in neuroimaging and an increase in the number of neuroimaging procedures performed have created a new management dilemma. Unruptured intracranial aneurysms (UIA) are found in ≈2% of people undergoing digital subtraction angiography1 and in 0.4% of people undergoing an MRI.2 The best risk management strategy in these patients is not known. Such patients are at increased risk for aneurysmal subarachnoid hemorrhage (SAH), but to know how they might best be managed, we need to understand more about the natural history of UIA, about factors that might provoke rupture, and about the risks and potential successes of intervention. In recent years, the Utrecht group,3 whose most recent work appears in this issue of Stroke , has contributed greatly to our understanding of these issues. The best estimate of the risk of rupture probably comes from the prospective arm of International Study of Unruptured Intracranial Aneurysms (ISUIA),4 which suggests an annual rupture risk of ≈0.1% for aneurysms 10 mm and most are in the anterior circulation. Paradoxically, despite this apparently very low rupture risk, most aneurysmal SAH appear to be attributable to rupture of small anterior circulation aneurysms. The most rational explanation, proposed by Wiebers et al5 and strongly supported by detailed mathematical modeling,6 is that most SAH arises from recently formed rather than long-standing aneurysms, although it is …

Interleukin 6-174G>C polymorphism and risk of aneurysmal subarachnoid hemorrhage: case-control study and meta-analysis

Vascular inflammation contributes to the pathogenesis of aneurysmal subarachnoid hemorrhage (aSAH). Interleukin 6 (IL6) is a proinflammatory cytokine involved in many vascular pathologies. Two studies analyzing an association of the functional IL6 gene -174G>C promoter polymorphism with aSAH provided inconsistent results. The aim of this study was to investigate whether this IL6 polymorphism is associated with aSAH in a Polish population. We genotyped 276 aSAH patients and 581 unrelated control subjects. All were of Caucasian origin. In addition, a meta-analysis combining results of the current and previously published studies was conducted. The distribution of IL6 genotypes and alleles did not differ significantly between aSAH (GG - 29.7%, GC - 50.0%, CC - 20.2%, G - 54.7%) and control subjects (GG - 32.0%, GC - 47.3%, CC - 20.7%, G - 44.3%). In the meta-analysis, the IL6-174G>C polymorphism was not associated with aSAH risk either. We failed to find an association between the IL6 -174G>C polymorphism and aSAH in analyzed European populations.

E-063 Cardiothoracic surgery does not pose significant risk of aneurysmal subarachnoid hemorrhage

ObjectiveNeurologic imaging prior to cardiac surgery often identifies incidental intracranial vascular pathology. The risk of hemorrhage from these lesions during an open cardiothoracic surgical procedure is unknown, preventing appropriate patient...

Genes influencing coagulation and the risk of aneurysmal subarachnoid hemorrhage, and subsequent complications of secondary cerebral ischemia and rebleeding

BackgroundWe investigated whether genes influencing coagulation are associated with the occurrence of aneurysmal subarachnoid hemorrhage (SAH) and with secondary cerebral ischemia and rebleeding in patients with aneurysmal SAH.MethodGenotyping for factor V Leiden (G1691A), prothrombin G20210A, methylenetetetrahydrofolate reductase (MTHFR) C677T, factor XIII subunit A Val34Leu, Tyr204Phe and Pro564Leu, and factor XIII subunit B His95Arg was performed in 208 patients with aneurysmal SAH and in 925 controls. Secondary cerebral ischemia occurred in 49 (24%) patients and rebleeding in 28 (14%) during their clinical course of 3 months after the aneurysmal SAH. The risk of aneurysmal SAH was assessed as odds ratio (OR) with 95% confidence interval (95% CI). The risk of secondary cerebral ischemia and rebleeding was assessed as hazard ratio (HR) with 95% CI using Cox regression.FindingsCarriers of the subunit B His95Arg factor XIII polymorphism had an increased risk of aneurysmal SAH with 23% of the patients homozygous or heterozygous for the variant allele compared to 17% of control subjects (OR 1.5, 95% CI 1.0–2.2). For the remaining genetic variants no effect on the risk of aneurysmal SAH could be demonstrated. A clear relation with the risk of secondary cerebral ischemia and of rebleeding could not be established for any of the genetic variants.ConclusionsWe found that aneurysmal SAH patients are more often carriers of the subunit B His95Arg factor XIII polymorphism compared to controls. This suggests that carriers of the subunit B His95Arg factor XIII polymorphism have an increased risk of aneurysmal SAH. Larger studies should confirm our results. As aneurysmal SAH patients who died soon after admission could not be included in the present study, our results only apply to a population of patients who survived the initial hours after the hemorrhage. For the other studied genetic factors involved in coagulation, no association with the occurrence of aneurysmal SAH or with the occurrence of secondary cerebral ischemia or rebleeding after aneurysmal SAH could be demonstrated.

A1/A2 polymorphism of GpIIIa gene and a risk of aneurysmal subarachnoid haemorrhage

Platelet glycoproteins are involved in pathophysiology of cerebrovascular diseases. The aim of this study was to investigate the association between the GpIIIa gene A1/A2 polymorphism and a risk of aneurysmal subarachnoid haemorrhage (SAH) in a Polish population. In a case-control study we genotyped 288 Caucasian patients with aneurysmal SAH and 457 age-, gender- and race-matched controls. The GpIIIa A1/A2 polymorphism was genotyped with RFLP technique. No difference was found in the distribution of the polymorphism between the cases and controls (cases: A1A1—201 (69.8%), A1A2—83 (28.8%) and A2A2—4 (1.4%) vs. controls: A1A1—323 (70.7%); A1A2—128 (28.0%); A2A2—6 (1.3%), P > 0.05. In a multivariate analysis female gender (OR = 1.950; 95%CI: 1.308–2.907), hypertension (OR = 4.774; 95%CI: 3.048–7.478) and smoking (OR = 2.034; 95%CI: 1.366–3.030), but not GpIIIa A1/A2 polymorphism, were independent risk factors for aneurysmal SAH. The GpIIIa A1/A2 polymorphism is not a risk factor of aneurysmal SAH in a Polish population.

The Risk of Aneurysmal Subarachnoid Hemorrhage During Pregnancy, Delivery, and the Puerperium in the Utrecht Population

It is unclear whether the risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased during pregnancy, labor, and the puerperium. We compared the risk of aSAH during this period with the risk outside this period. We included women with aSAH between 18 and 42 years of age (n=244) from our prospectively collected database of patients with subarachnoid hemorrhage treated in the University Medical Center Utrecht, the provincial referral center, between January 1987 and April 2006. We estimated the relative risk of aSAH during pregnancy, delivery, or the puerperium by a case-crossover design and calculated a standardized incidence ratio, dividing the observed number of patients with aSAH during pregnancy, delivery, or puerperium by the expected number based on the incidence in the general population of women of the same age during the study period. Of the 244 women, 4 were pregnant, 3 in the puerperium and none in labor. The relative risk of aSAH during pregnancy, delivery, or the puerperium was 0.4 (95% CI, 0.2 to 0.9). Based on the number of women aged 18 to 42 years within the catchment area of our hospital and the number of pregnancies within the study period, the expected number of patients with aSAH during pregnancy, delivery, or the puerperium was 12, resulting in a standardized incidence ratio of 0.6 (95% CI, 0.2 to 1.1). The risk of aSAH is not increased during pregnancy, labor, and the puerperium. There is no need to advise against pregnancy in women with an increased risk of subarachnoid hemorrhage and no evidence to advise against vaginal delivery in such women.

Smoking and family history and risk of aneurysmal subarachnoid hemorrhage

Smoking and family history of aneurysmal subarachnoid hemorrhage (aSAH) are independent risk factors for aSAH. Using a population-based case-control study of hemorrhagic stroke, we hypothesized that having both a first-degree relative with a brain aneurysm or SAH (+FH) and current smoking interact to increase the risk of aSAH. Cases of aneurysmal SAH were prospectively recruited from all 17 hospitals in the five-county region around the University of Cincinnati. Controls were identified by random digit dialing. Controls were matched to cases of aSAH by age (+/-5 years), race, and sex. Conditional multiple logistic regression was used to identify independent risk factors. For deviation from the additive model, the interaction constant ratio test was used. A total of 339 cases of aSAH were matched to 1,016 controls. Compared to current nonsmokers with no first-degree relatives with aSAH (-FH), the odds ratio (OR) for aSAH for current nonsmokers with +FH was 2.5 (95% confidence interval [CI] 0.9-6.9); for current smokers with -FH, OR = 3.1 (95% CI 2.2-4.4); and for current smokers with +FH, OR = 6.4 (95% CI 3.1-13. 2). The interaction constant ratio, which measured the deviation from the additive model, was significant: 2.19 (95% CI 0.80-5.99). The lower bound of the 95% CI >0.5 signifies a departure from the additive model. Evidence of a gene-environment interaction with smoking exists for aneurysmal subarachnoid hemorrhage. This finding is important to counseling family members and for screening of intracranial aneurysm (IA) as well as the design and interpretation of genetic epidemiology of IA studies.

Interleukin 6 gene polymorphisms are not associated with aneurysmal subarachnoid haemorrhage in an Italian population

Objective:Several lines of evidence indicate a role for inflammatory processes in the development of cerebral aneurysms. Recently, polymorphisms in the promoter region of the interleukin 6 (IL6) gene were shown...

TUMOR NECROSIS FACTOR-α GENE AND CEREBRAL ANEURYSMS

The pathogenesis of intracranial aneurysms is still uncertain. In addition to atherosclerosis, immunological factors may play a role in the disease. Recent studies have suggested that tumor necrosis factor-alpha (TNF-alpha), one of the main proinflammatory cytokines, may play a key role in the formation and rupture of cerebral aneurysms. The purpose of this study is to evaluate the association of a functionally active polymorphism (-308 G<A) in the TNF-alpha gene with the risk and the clinical features of aneurysmal subarachnoid hemorrhage. A total of 171 consecutive aneurysmal subarachnoid hemorrhage patients and 144 healthy controls were involved in the study. Computed tomographic scan findings were assessed by Fisher grade; clinical neurological assessment was performed using the Hunt and Hess grading system. Patients and controls were genotyped for the-308 biallelic (G<A) polymorphism of the TNF-alpha gene. The TNF-alpha G allele was significantly more frequent in patients than in controls (chi2 = 5.59; P = 0.0181) and homozygosity for the G allele, compared with remaining genotypes, was associated with a significantly increased risk of aneurysmal subarachnoid hemorrhage (odds ratio = 2.20; 95% confidence interval = 1.29<odds ratio<3.75). Allelic and genotypic frequencies of the examined polymorphism were not significantly different in disease subgroups. The different TNF-alpha genotypes do not seem to significantly modify the main clinical features of the disease. Our data suggests that the TNF-alpha gene or a linked locus significantly modulates the risk for aneurysmal subarachnoid hemorrhage. Additional studies in different populations are warranted to confirm our findings.

Association of Fatal Aneurysmal Subarachnoid Hemorrhage with Human Leukocyte Antigens in the Finnish Population

Human leukocyte antigens (HLA) have been reported to associate with the risk of aneurysmal subarachnoid hemorrhage (SAH) and poor outcome after SAH. Our aim was to identify HLA antigens that associate with the risk of fatal SAH in the Finnish population. Medical records of 600 cadaveric organ donors were reviewed to find organ donors that succumbed to SAH ( n = 232) or brain trauma ( n = 151). HLA antigen frequencies in these groups were compared with HLA frequenciens in a reference population of 10,000 bone marrow donors. Chi-Square test with Bonferroni correction and multiplicative logistic regression models were used and false positive result probabilities (FPRP) were calculated. Alpha-level was 0.01. HLA-A3 associated with fatal SAH ( p = 0.0014, OR 1.3 and 95%CI 1.1–1.6) and HLA-DR7 inversely associated with fatal SAH ( p = 0.0040, OR 0.3 and 95%CI 0.2–0.6). HLA-A3 but not HLA-DR7 showed also a positive trend in donors with brain trauma. FPRP was below 0.5 for HLA-A3, but clearly above 0.5 for HLA-DR7. HLA-A3 seems to associate with fatal SAH in the Finnish population. Further studies are needed to reveal the pathobiologic mechanisms for how HLA-A3 associates with the risk of fatal SAH in Finns.

The Relationships of Gender, Cigarette Smoking, and Hypertension with the Risk of Aneurysmal Subarachnoid Hemorrhage: A Case–Control Study in Nagoya, Japan

To examine the relationship of gender, cigarette smoking, and a history of hypertension to the risk of aneurysmal subarachnoid hemorrhage (SAH), using a case-control study. Case subjects consisted of a consecutive series of 201 patients with spontaneous SAH with aneurysm(s) confirmed by angiography and/or CT scan. One hospital and one community control subject was matched to each case by gender and age (+/- 2 years). Multiple conditional logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI) adjusted for potential confounders. Current smoking and a history of hypertension were each significantly associated with an increased risk of subarachnoid hemorrhage for men and women combined. There was also a non-significant trend towards synergism between these two factors with respect to an increased risk of subarachnoid hemorrhage for each gender separately and both combined. A significantly increased risk was observed for a history of hypertension (adjusted OR, 3.5; 95% CI, 1.2-14.7) among men, for current smoking alone (adjusted OR, 2.9; 95% CI, 1.1-7.7), and a history of hypertension alone (adjusted OR, 2.6; 95% CI, 1.4-5.1) among women. Trends towards gender differences and synergism emerged in the relationship of cigarette smoking and a history of hypertension of the risk of SAH provides useful information for targeting individuals/populations in programs for the primary prevention of SAH by gender.

The natural history of unruptured intracranial aneurysms

Since the publication of preliminary results from the International Study of Unruptured Intracranial Aneurysms in 1998 there has been a great deal of debate concerning the natural history of these lesions and their attendant risk of aneurysmal subarachnoid hemorrhage. Therefore, the authors reviewed a selected number of crucial studies concerning this topic to determine the best evidence-based estimate of a rupture rate for these lesions. Based on this analysis, the yearly risk of bleeding for an unruptured intracranial aneurysm is estimated to be approximately 1% for aneurysms 7 to 10 mm in diameter. This risk of rupture increases with aneurysm size and it likewise diminishes as the size of the lesion decreases. This general rule serves as a reasonable interpretation of the results reported in the current body of literature.

II genotype of the angiotensin-converting enzyme gene increases the risk for subarachnoid hemorrhage from ruptured aneurysm.

Evidence exists in support of a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (SAH) in humans. Meta-analysis of 2 previous studies showed that the I allele of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism was a weak, but significant, risk factor for aneurysmal SAH. Moreover, a recent study has shown that the local renin-angiotensin system (RAS) is involved in the development of intracranial aneurysm. The aim of this study was to investigate the association between ACE I/D polymorphism and a risk for aneurysmal SAH in a Polish population. Ninety patients with aneurysmal SAH (mean age: 48.9+/-14.0 years) and 128 healthy controls matched for age and sex were genotyped for the ACE I/D polymorphism. Aneurysmal SAH was diagnosed by cranial computed tomography and/or lumbar puncture and digital subtraction angiography. ACE gene polymorphism was detected by polymerase chain reaction amplification of the intron 16-specific I/D fragments, 490-bp and 190-bp, respectively. The ACE genotype distribution in patients with aneurysmal SAH (II, 52.2%; ID, 15.6%; DD, 32.2%) differed significantly from controls (II, 23.4%; ID, 50.8%; DD, 25.8%) (P<0.001). A logistic regression model showed that the II genotype of ACE gene was independent from female sex and smoking as a risk factor for aneurysmal SAH (OR, 4.57; 95% CI, 2.35 to 8.90). Here we report that II genotype of ACE gene is a risk factor for aneurysmal SAH.

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study.

Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. Cases and controls did not differ with regard to menstrual and reproductive history except in age at birth of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role for HRT on risk of SAH in postmenopausal women.

Hypertension, small size, and deep venous drainage are associated with risk of hemorrhagic presentation of cerebral arteriovenous malformations.

To identify clinical and angiographic factors of cerebral arteriovenous malformations (AVMs) associated with hemorrhage to improve the estimation of the risks and help guide management in clinical decision making. We conducted a retrospective analysis of 100 consecutive adults who have presented during the past 3 years to our institution with cerebral AVMs. Angiographic and clinical parameters were evaluated using multivariate logistic regression analysis to analyze factors associated with hemorrhagic presentation. The group had a mean age of 37.8 years; 53% were men, 48% presented with intracranial hemorrhage, and 40% presented with seizures. All 10 patients with cerebellar AVMs presented with hemorrhage. The following factors were independently associated with AVM hemorrhage: history of hypertension (P = 0.019; odds ratio [OR] = 5.36), nidal diameter <3 cm (P = 0.023: OR = 4.60), and deep venous drainage (P = 0.009: OR = 5.77). Dural arterial supply (P = 0.008; OR = 0.15) was independently associated with decreased risk of bleed. Location, nidal aneurysms, patient age, and smoking were not associated with increased or decreased bleeding risk. In this study, we found small AVM size and deep venous drainage to be positively associated with AVM hemorrhage. Dural supply was associated with a decreased likelihood of hemorrhagic presentation. Hypertension was found to be the only clinical factor positively associated with hemorrhage, a finding not previously reported. Smoking, although associated with increased risk of aneurysmal subarachnoid hemorrhage, was not associated with a higher risk of AVM hemorrhage.

Does alcohol intoxication precipitate aneurysmal subarachnoid haemorrhage?

Seventy-five consecutive patients aged 15 to 55 years with aneurysmal subarachnoid haemorrhage verified by CSF examination and cerebral angiography or at necropsy were studied. In 19 cases (25%; four women and 15 men) the bleeding was preceded within 24 hours by a bout of alcohol drinking. Alcohol-related cases composed 33% and 14% of the patients in the age groups 15-40 and 41-55 years, respectively. Alcohol intoxication preceding the subarachnoid haemorrhage was two to four times as common in male and three to five times as common in female patients as alcohol intoxication in the general Finnish population of the same age and sex. Occasional alcohol intoxication seems to carry an increased risk of aneurysmal subarachnoid haemorrhage.