Dataset Information

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

ABSTRACT: OBJECTIVE:Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs. APPROACH AND RESULTS:In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examination and carotid ultrasound in 2002 to 2006 and returned for a repeat brain MRI in 2007 to 2011. Common carotid arterial stiffness was assessed using a standardized protocol and expressed as carotid arterial strain, distensibility coefficient, and Young elastic modulus. Modified Poisson regression was applied to relate carotid arterial stiffness parameters to CMB incidence. During a mean follow-up of 5.2 years, 463 people (18.4%) developed new CMBs, of whom 292 had CMBs restricted to lobar regions and 171 had CMBs in a deep or infratentorial region. After adjusting for age, sex, and follow-up interval, arterial stiffness measures were associated with incident CMBs (risk ratio per SD decrease in carotid arterial strain, 1.11 [95% confidence interval, 1.01-1.21]; per SD decrease in natural log-transformed distensibility coefficient, 1.14 [1.05-1.24]; and per SD increase in natural log-transformed Young elastic modulus, 1.13 [1.04-1.23]). These measures were also significantly associated with incident deep CMBs (1.18 [1.02-1.37]; 1.24 [1.08-1.42]; and 1.23 [1.07-1.42]) but not with lobar CMBs. When further adjusted for blood pressure and other baseline vascular risk factors, carotid plaque, prevalent CMBs, subcortical infarcts, and white matter hyperintensities, the associations persisted. CONCLUSIONS:Our findings support the hypothesis that localized increases in carotid arterial stiffness may contribute to the development of CMBs, especially in a deep location attributable to hypertension.

SUBMITTER: Ding J

PROVIDER: S-EPMC4514556 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

Ding Jie J Mitchell Gary F GF Bots Michiel L ML Sigurdsson Sigurdur S Harris Tamara B TB Garcia Melissa M Eiriksdottir Gudny G van Buchem Mark A MA Gudnason Vilmundur V Launer Lenore J LJ

Arteriosclerosis, thrombosis, and vascular biology 20150625 8

<h4>Objective</h4>Age and high blood pressure are major risk factors for cerebral microbleeds (CMBs). However, the underlying mechanisms remain unclear and arterial stiffness may be important. We investigated whether carotid arterial stiffness is associated with incidence and location of CMBs.<h4>Approach and results</h4>In the prospective, population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik study, 2512 participants aged 66 to 93 years underwent a baseline brain MRI examinatio ...[more]

PMID: 26112009

Similar Datasets

Project description:IMPORTANCE:The spatial distribution of cerebral microbleeds (CMBs), which are asymptomatic precursors of intracerebral hemorrhage, reflects specific underlying microvascular abnormalities of cerebral amyloid angiopathy (lobar structures) and hypertensive vasculopathy (deep brain structures). Relatively little is known about the occurrence of and modifiable risk factors for developing CMBs, especially in a lobar location, in the general population of older people. OBJECTIVE:To investigate whether lifestyle and lipid factors predict new CMBs in relation to their anatomic location. DESIGN, SETTING, AND PARTICIPANTS:We enrolled 2635 individuals aged 66 to 93 years from the population-based Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study in a brain imaging study. Participants underwent a baseline magnetic resonance imaging (MRI) examination of the brain from September 1, 2002, through February 28, 2006, and returned for a second MRI examination from April 1, 2007, through September 30, 2011. EXPOSURES:Lifestyle and lipid factors assessed at baseline included smoking, alcohol consumption, body mass index, and serum levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides. MAIN OUTCOMES AND MEASURES:Incident CMBs detected on MRIs, which were further categorized as exclusively lobar or as deep. RESULTS:During a mean follow-up of 5.2 years, 486 people (18.4%) developed new CMBs, of whom 308 had lobar CMBs only and 178 had deep CMBs. In the multivariate logarithm-binomial regression model adjusted for baseline cardiovascular risk factors, including blood pressure, antihypertensive use, prevalent CMBs, and markers of cerebral ischemic small-vessel disease, heavy alcohol consumption (vs light to moderate consumption; relative risk [RR], 2.94 [95% CI, 1.23-7.01]) was associated with incident CMBs in a deep location. Baseline underweight (vs normal weight; RR, 2.41 [95% CI, 1.21-4.80]), current smoking (RR, 1.47 [95% CI, 1.11-1.94]), an elevated serum level of high-density lipoprotein cholesterol (RR per 1-SD increase, 1.13 [95% CI, 1.02-1.25]), and a decreased triglyceride level (RR per 1-SD decrease in natural logarithm-transformed triglyceride level, 1.17 [95% CI, 1.03-1.33]) were significantly associated with an increased risk for lobar CMBs exclusively but not for deep CMBs. CONCLUSIONS AND RELEVANCE:Lifestyle and lipid risk profiles for CMBs were similar to those for symptomatic intracerebral hemorrhage and differed for lobar and deep CMBs. Modification of these risk factors could have the potential to prevent new-onset CMBs, particularly those occurring in a lobar location.

Project description:Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse wave velocity (-0.095 ± 0.043 SD/SD, P = 0.028) and carotid pulse pressure (-0.114 ± 0.045 SD/SD, P = 0.013) were associated with lower memory scores. Pulsatility index was associated with lower memory scores (-0.165 ± 0.039 SD/SD, P<0.001), slower processing speed (-0.118 ± 0.033 SD/SD, P<0.001) and worse performance on tests assessing executive function (-0.155 ± 0.041 SD/SD, P<0.001). When magnetic resonance imaging measures (grey and white matter volumes, white matter hyperintensity volumes and prevalent subcortical infarcts) were included in cognitive models, haemodynamic associations were attenuated or no longer significant, consistent with the hypothesis that increased aortic stiffness and excessive flow pulsatility damage the microcirculation, leading to quantifiable tissue damage and reduced cognitive performance. Marked stiffening of the aorta is associated with reduced wave reflection at the interface between carotid and aorta, transmission of excessive flow pulsatility into the brain, microvascular structural brain damage and lower scores in various cognitive domains.

Project description:BackgroundCarotid atherosclerosis is associated with subclinical ischemic cerebrovascular disease, but its role in hemorrhage-prone small vessel disease-represented by cerebral microbleed (CMB)-is unclear, although vascular risk factors underlie both conditions. We hypothesized that persons with carotid atherosclerosis would have higher risk of CMB, particularly in deep regions.Methods and resultsWe studied 1243 participants in the Framingham Offspring Study (aged 56.9±8.8 years; 53% women) with carotid ultrasound available on 2 occasions (1995-1998 and 2005-2008) prior to brain magnetic resonance imaging. Using multivariable logistic regression, we related baseline carotid stenosis, baseline intima-media thickness, and site-specific carotid intima-media thickness progression (at internal and common carotid locations) to the prevalence and location (lobar or deep plus mixed) of CMB. In addition, we assessed effect modification by lipid levels and use of statin and antithrombotic medications. Carotid stenosis ?25% (a marker of cerebrovascular atherosclerosis) was associated with presence of CMB overall (Odds Ratio 2.20, 95% CI 1.10-4.40) and at deep and mixed locations (odds ratio 3.60, 95% CI 1.23-10.5). Baseline carotid intima-media thickness was not associated with CMB. Progression of common carotid artery intima-media thickness among persons on hypertension treatment was associated with lower risk of deep and mixed CMB (odds ratio per SD 0.41, 95% CI 0.18-0.96).ConclusionsCumulative vascular risk factor exposure may increase the risk of CMB, especially in deep regions. The apparent paradoxical association of carotid intima-media thickness progression with lower risk of CMB may reflect benefits of intensive vascular risk factor treatment among persons with higher cardiovascular risk and deserves further investigation. If replicated, the results may have potential implications for assessment of preventive and therapeutic interventions for subclinical cerebral hemorrhage.

Dataset Information

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

Publications

Carotid arterial stiffness and risk of incident cerebral microbleeds in older people: the Age, Gene/Environment Susceptibility (AGES)-Reykjavik study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure