Prevalence of intracranial artery stenosis in a general population using 3D-time of flight magnetic resonance angiography.

BACKGROUND: Data on prevalence of intracranial artery stenosis (ICAS) in Western populations is sparse. The aim of the study was to assess the prevalence and risk factors for ICAS in a mainly Caucasian general population. METHODS: We assessed the prevalence of ICAS in 1847 men and women aged 40 to 84 years who participated in a cross-sectional population-based study, using 3-dimensional time-of-flight 3 Tesla magnetic resonance angiography. ICAS was defined as a focal luminal flow diameter reduction of ≥50 %. The association between cardiovascular risk factor levels and ICAS was assessed by multivariable regression analysis. RESULTS: The overall prevalence of ICAS was 6.0 % (95 % confidence interval (CI) 5.0-7.2), 4.3 % (95 % CI 3.1-5.7) in women and 8.0 % (95 % CI 6.3-10.0) in men. The prevalence increased by age from 0.8 % in 40-54 years age group to 15.2 % in the 75-84 years age group. The majority of stenoses was located to the internal carotid artery (52.2 %), followed by the posterior circulation (33.1 %), the middle cerebral artery (10.8 %) and the anterior cerebral artery (3.8 %). The risk of ICAS was independently associated with higher age, male sex, hypertension, hyperlipidemia, diabetes mellitus, current smoking and higher BMI. CONCLUSIONS: The prevalence of ICAS in a general population of Caucasians was relatively high and similar to the prevalence of extracranial internal carotid artery stenosis in previous population-based studies.

Anatomical variations in the circle of Willis are associated with increased odds of intracranial aneurysms: The Tromsø study.

PURPOSE: Studies on patients suggest an association between anatomical variations in the Circle of Willis (CoW) and intracranial aneurysms (IA), but it is unclear whether this association is present in the general population. In this cross-sectional population study, we investigated the associations between CoW anatomical variations and IA. METHODS: We included 1667 participants from a population sample with 3 T MRI time-of-flight angiography (40-84 years, 46.5% men). Saccular IAs were defined as protrusions in the intracranial arteries ≥2 mm, while variants of the CoW were classified according to whether segments were missing or hypoplastic (< 1 mm). We used logistic regression, adjusting for age and IA risk factors, to assess whether participants with incomplete CoW variants had a greater prevalence of IA and whether participants with specific incomplete variants had a greater prevalence of IA. RESULTS: Participants with an incomplete CoW had an increased prevalence of IA (OR, 2.3 [95% CI 1.05-5.04]). This was mainly driven by the variant missing all three communicating arteries (OR, 4.2 [95% CI 1.7-1 0.3]) and the variant missing the P1 segment of the posterior cerebral artery (OR, 3.6 [95% CI 1.2-10.1]). The combined prevalence of the two variants was 15.4% but accounted for 28% of the IAs. CONCLUSION: The findings suggest that an incomplete CoW is associated with an increased risk of IA for adults in the general population.

Prevalence of unruptured intracranial aneurysms: impact of different definitions - the Tromsø Study.

BACKGROUND: Management of incidental unruptured intracranial aneurysms (UIAs) remains challenging and depends on their risk of rupture, estimated from the assumed prevalence of aneurysms and the incidence of aneurysmal subarachnoid haemorrhage. Reported prevalence varies, and consistent criteria for definition of UIAs are lacking. We aimed to study the prevalence of UIAs in a general population according to different definitions of aneurysm. METHODS: Cross-sectional population-based study using 3-dimensional time-of-flight 3 Tesla MR angiography to identify size, type and location of UIAs in 1862 adults aged 40-84 years. Size was measured as the maximal distance between any two points in the aneurysm sac. Prevalence was estimated for different diameter cutoffs (≥1, 2 and 3 mm) with and without inclusion of extradural aneurysms. RESULTS: The overall prevalence of intradural saccular aneurysms ≥2 mm was 6.6% (95% CI 5.4% to 7.6%), 7.5% (95% CI 5.9% to 9.2%) in women and 5.5% (95% CI 4.1% to 7.2%) in men. Depending on the definition of an aneurysm, the overall prevalence ranged from 3.8% (95% CI 3.0% to 4.8%) for intradural aneurysms ≥3 mm to 8.3% (95% CI 7.1% to 9.7%) when both intradural and extradural aneurysms ≥1 mm were included. CONCLUSION: Prevalence in this study was higher than previously observed in other Western populations and was substantially influenced by definitions according to size and extradural or intradural location. The high prevalence of UIAs sized <5 mm may suggest lower rupture risk than previously estimated. Consensus on more robust and consistent radiological definitions of UIAs is warranted.

Neuroanatomical correlates of verbal fluency in early Alzheimer's disease and normal aging.

Verbal fluency (VF) impairments occur early in Alzheimer's disease (AD) and to a lesser extent also in normal aging. However, the neural underpinnings of these impairments are not fully understood. The present study evaluated whether VF impairments in early AD and normal aging rely upon common or different neuroanatomical correlates. We examined the association between VF performance and brain structure in 18 mild AD patients and 24 healthy elderly. Linear regressions were performed between accuracy and time intervals in VF scores and structural measurements of cerebral gray matter (GM) and white matter (WM) using MRI. Results showed that semantic VF correlated exclusively with GM in cerebellum, left temporal fusiform cortex, and WM in uncinate fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Phonemic VF showed unique associations between intervals and WM in left-hemisphere tracts. The association between GM in hippocampus, subcortical structures and semantic accuracy differentiated patients from controls. Results showed that VF impairments are primarily associated with same structural brain changes in AD as in healthy elderly but at exaggerated levels. However, specific VF deficiencies and their underlying neural correlates exist and these clearly differentiate the initial stages of AD.

Estimated and Measured GFR Associate Differently with Retinal Vasculopathy in the General Population.

BACKGROUND/AIMS: Estimated glomerular filtration rate (eGFR) is used extensively in epidemiological research. Validations of eGFR have demonstrated acceptable performance, but the dependence of creatinine and cystatin C on non-GFR factors could confound associations with disease. Few studies have investigated this issue in direct comparison with measured GFR (mGFR). We compared the associations between eGFR and mGFR and retinal vasculopathy, a marker of systemic microvasculopathy. METHODS: Iohexol clearance and retinal photography were examined in the Renal Iohexol Clearance Survey in Tromsø 6, which consists of a representative sample of middle-aged persons from the general population. A total of 1,553 persons without self-reported kidney disease, cardiovascular disease or diabetes were investigated. Three eGFR equations based on creatinine and/or cystatin C from the Chronic Kidney Disease Epidemiology Collaboration were studied. Differences between eGFR and mGFR were analyzed with seemingly unrelated regression methods. RESULTS: mGFR in the lowest quartile was associated with an increased multivariable-adjusted odds ratio of retinopathy (OR 1.86, 95% CI 1.16-2.97), but not with retinal artery or vein diameters. eGFR based on cystatin C (eGFRcys) was consistently biased relative to mGFR in its associations with retinal vessel diameters across different models. eGFR based on creatinine (eGFRcrea) and eGFR based on both creatinine and cystatin C were also biased in several of these models (p < 0.05). For retinopathy, the differences between the 3 eGFR and mGFR measurements were not statistically significant. CONCLUSIONS: Low mGFR is associated with retinopathy in the general population. eGFR based on creatinine and/or cystatin C are not valid substitutes for mGFR in studies of the relationship between the retina and kidney function in healthy persons.

Subclinical cardiovascular disease is associated with a high glomerular filtration rate in the nondiabetic general population.

A reduced glomerular filtration rate (GFR) in chronic kidney disease is a risk factor for cardiovascular disease. However, evidence indicates that a high GFR may also be a cardiovascular risk factor. This issue remains unresolved due to a lack of longitudinal studies of manifest cardiovascular disease with precise GFR measurements. Here, we performed a cross-sectional study of the relationship between high GFR measured as iohexol clearance and subclinical cardiovascular disease in the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6), a representative sample of the middle-aged general population. A total of 1521 persons without cardiovascular disease, chronic kidney disease, diabetes, or micro- or macroalbuminuria were examined with carotid ultrasonography and electrocardiography. The GFR in the highest quartile was associated with an increased odds ratio of having total carotid plaque area greater than the median of non-zero values (odds ratio 1.56, 95% confidence interval 1.02-2.39) or electrocardiographic signs of left ventricular hypertrophy (odds ratio 1.62, 95% confidence interval 1.10-2.38) compared to the lowest quartile. The analyses were adjusted for cardiovascular risk factors, urinary albumin excretion, and fasting serum glucose. Thus, high GFR is associated with carotid atherosclerosis and left ventricular hypertrophy and should be investigated as a possible risk factor for manifest cardiovascular disease in longitudinal studies.

Albuminuria and carotid atherosclerosis as predictors of cognitive function in a general population.

BACKGROUND/AIMS: Albuminuria and carotid atherosclerosis are predictors of cardiovascular disease and potential predictors of cognitive decline. Our aim was to study whether albuminuria was an early predictor of cognitive function independent of carotid atherosclerosis in a general population. METHODS: The study population comprised 1,577 adults without self-reported stroke. In 1994 and 2007 all were screened for cardiovascular risk factors, urinary albumin-creatinine ratio (ACR), carotid intima-media thickness and carotid total plaque area (TPA). Endpoints were neuropsychological test results in 2007 from the digit symbol test, the finger-tapping test, the Mini Mental Status Examination and the 12-word test parts 1 and 2. Multivariate linear regression was used to assess associations. RESULTS: Higher ACR, ΔACR, intima-media thickness, TPA and ΔTPA independently predicted a lower score on the digit symbol test. Higher ΔACR and ΔTPA predicted a lower score on the finger-tapping test. Higher TPA predicted a lower score on the 12-word test part 1 (immediate recall). Smoking predicted lower scores on the digit symbol and finger-tapping tests independent of albuminuria and carotid atherosclerosis. CONCLUSIONS: Our results suggest that albuminuria, carotid atherosclerosis and smoking are independent predictors of executive function and motor tempo.

Long-term use of lipid-lowering drugs slows progression of carotid atherosclerosis: the Tromso study 1994 to 2008.

OBJECTIVE: Data on the effect of lipid-lowering drugs (LLD) on carotid atherosclerosis outside clinical trials are limited. The aim of this study was to determine the effect of LLD on change in carotid intima media thickness and total plaque area in a general population. APPROACH AND RESULTS: Subjects were 1532 women and 1442 men who participated in a longitudinal population-based study with ultrasound examination of intima media thickness and total plaque area in the right carotid artery at baseline and after 13 years follow-up. Long-term use of LLD was defined as use for >5 years, any-time use of LLD was defined as use at baseline or at 6 years or at 13 years of follow-up. In multivariable models adjusted for age, sex, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, prevalent cardiovascular disease, and daily smoking, long-term use of LLD had a protective effect on progression of both intima media thickness (ß=-0.0387 mm; P=0.002) and total plaque area (ß=-0.400 mm(2); P=0.006). There was a weaker protective effect of any-time use of LLD on progression of intima media thickness (ß=-0.024 mm; P=0.046) and total plaque area (ß=-0.318 mm(2); P=0.06). CONCLUSIONS: LLD protected against progression of carotid atherosclerosis. The protective effect was strongest in long-term users.

The metabolic syndrome and progression of carotid atherosclerosis over 13 years. The Tromsø study.

BACKGROUND: The metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease. In this study, we examine if metabolic syndrome predicts progression of atherosclerosis over 13 years. METHODS: Participants were 1442 men and 1532 women in the population-based Tromsø Study who underwent carotid ultrasound examinations at baseline in the 4th (1994-5) and at follow-up in the 6th survey (2007-8). Of these, 278 men and 273 women fulfilled the criteria for the MetS, defined according to a modified version of the National Cholesterol Education Program Adult Treatment Panel III (NCEP, ATPIII). Carotid atherosclerosis was assessed as total plaque area (TPA) and mean intima-media thickness (IMT) at follow-up and as change in IMT and TPA from baseline to follow-up. Associations between MetS and its components and carotid atherosclerosis were assessed in linear regression models adjusted for age, total cholesterol and daily smoking, stratified by sex. RESULTS: IMT and TPA levels at follow-up (p < 0.0001) and progression of TPA (p = 0.02) were higher in the MetS group compared to the non-MetS group. In stepwise multivariable models, MetS was associated with TPA (ß = 0.372 mm2, p = 0.009) and IMT (ß = 0.051 mm, p < 0.0001) in men, and with IMT (ß = 0.045 mm, p = 0.001) in women after 13 years of follow-up, but not with progression of IMT or TPA. In analyses stratified by age, MetS predicted progression of IMT (ß = 0.043 mm, p = 0.046) and TPA (ß = 1.02 mm2, p = 0.002) in men below 50 years of age. Hypertension was predictive of follow-up TPA and IMT in both genders and of progression of TPA in women. Impaired glucose tolerance was associated with follow up levels of IMT and TPA as well as progression in IMT in men. None of the other components of MetS were associated with progression of atherosclerosis. CONCLUSIONS: Subjects with MetS had higher levels of IMT and TPA at follow up than those without MetS. Mets predicted progression of IMT and TPA in those below 50 years of age, but not in other age groups, indicating that MetS may be involved in the initiation of the atherosclerotic process.

Risk factors for progression of carotid intima-media thickness and total plaque area: a 13-year follow-up study: the Tromsø Study.

BACKGROUND AND PURPOSE: Data on risk factors for progression of intima-media thickness (IMT) and plaque are scarce. The objective was to determine long-term risk factors for total plaque area (TPA) and IMT as well as risk factors for progression (ΔTPA and ΔIMT). METHODS: Subjects were 1307 men and 1436 women who participated in a longitudinal population-based study with ultrasound examination of the right carotid artery at baseline and after 13 years of follow-up. Total cholesterol, high-density lipoprotein cholesterol, blood pressure, body mass index, and information about smoking habits, prevalent diabetes, and cardiovascular disease were obtained at baseline. Carotid atherosclerosis was assessed as TPA and mean IMT of plaque-free segments of the common carotid artery. Associations between z-scores of risk factors and carotid atherosclerosis were assessed in multiple linear regression models. RESULTS: In multivariable models, total cholesterol, systolic blood pressure, and smoking were stronger predictors of follow-up TPA than of IMT, whereas sex and age were stronger predictors of IMT. Total cholesterol (standardized ß=0.081), systolic blood pressure (standardized ß=0.062), and smoking (standardized ß=0.107) were significant predictors of ΔTPA, whereas only total cholesterol (standardized ß=0.084) was an independent predictor of ΔIMT. The variance explained by traditional cardiovascular risk factors was somewhat greater for TPA than for IMT. CONCLUSIONS: The cardiovascular risk factors total cholesterol, smoking, and systolic blood pressure were stronger long-term predictors of TPA and TPA progression than for IMT and IMT progression.