The aim of this study was to investigate whether and what carotid plaque characteristics predict systemic cardiovascular outcomes in patients with clinically established atherosclerotic disease.
...Advancements in atherosclerosis imaging have allowed assessment of various plaque characteristics, some of which are more directly linked to the pathogenesis of acute cardiovascular events compared to plaque burden.
As part of the event-driven clinical trial AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes), subjects with clinically established atherosclerotic disease underwent multicontrast carotid magnetic resonance imaging (MRI) to detect plaque tissue composition and high-risk features. Prospective associations between MRI measurements and the AIM-HIGH primary endpoint (fatal and nonfatal myocardial infarction, ischemic stroke, hospitalization for acute coronary syndrome, and symptom-driven revascularization) were analyzed using Cox proportional hazards survival models.
Of the 232 subjects recruited, 214 (92.2%) with diagnostic image quality constituted the study population (82% male, mean age 61 ± 9 years, 94% statin use). During median follow-up of 35.1 months, 18 subjects (8.4%) reached the AIM-HIGH endpoint. High lipid content (hazard ratio HR per 1 SD increase in percent lipid core volume: 1.57; p = 0.002) and thin/ruptured fibrous cap (HR: 4.31; p = 0.003) in carotid plaques were strongly associated with the AIM-HIGH endpoint. Intraplaque hemorrhage had a low prevalence (8%) and was marginally associated with the AIM-HIGH endpoint (HR: 3.00; p = 0.053). High calcification content (HR per 1 SD increase in percent calcification volume: 0.66; p = 0.20), plaque burden metrics, and clinical risk factors were not significantly associated with the AIM-HIGH endpoint. The associations between carotid plaque characteristics and the AIM-HIGH endpoint changed little after adjusting for clinical risk factors, plaque burden, or AIM-HIGH randomized treatment assignment.
Among patients with clinically established atherosclerotic disease, carotid plaque lipid content and fibrous cap status were strongly associated with systemic cardiovascular outcomes. Markers of carotid plaque vulnerability may serve as novel surrogate markers for systemic atherothrombotic risk.
Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This ...study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy.
In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors.
Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year,
= 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2,
= 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4,
= 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0,
< 0.001).
Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH.
URL: https://www.
gov; Unique identifier: NCT01178320.
Magnetic resonance elastography (MRE) is an imaging technique for noninvasively and quantitatively assessing tissue stiffness, akin to palpation. MRE is further able assess the mechanical properties ...of tissues that cannot be reached by hand including the brain. The technique is a three-step process beginning with the introduction of shear waves into the tissue of interest by applying an external vibration. Next, the resulting motion is imaged using a phase-contrast MR pulse sequence with motion encoding gradients that are synchronized to the vibration. Finally, the measured displacement images are mathematically inverted to compute a map of the estimated stiffness. In the brain, the technique has demonstrated strong test-retest repeatability with typical errors of 1% for measuring global stiffness, 2% for measuring stiffness in the lobes of the brain, and 3–7% for measuring stiffness in subcortical gray matter. In healthy volunteers, multiple studies have confirmed that stiffness decreases with age, while more recent studies have demonstrated a strong relationship between viscoelasticity and behavioral performance. Furthermore, several studies have demonstrated the sensitivity of brain stiffness to neurodegeneration, as stiffness has been shown to decrease in multiple sclerosis and in several forms of dementia. Moreover, the spatial pattern of stiffness changes varies among these different classes of dementia. Finally, MRE is a promising tool for the preoperative assessment of intracranial tumors, as it can measure both tumor consistency and adherence to surrounding tissues. These factors are important predictors of surgical difficulty. In brief, MRE demonstrates potential value in a number of neurological diseases. However, significant opportunity remains to further refine the technique and better understand the underlying physiology.
•Magnetic resonance elastography (MRE) noninvasively measures tissue stiffness.•MRE can reliably measure global and regional stiffness in the brain in vivo.•Brain stiffness is sensitive to physiological and pathological processes.•Intracranial MRE can be used for preoperative assessment of tumors.•Further work is needed to refine technique and better understand biological basis.
Association between clinical factors and high-risk plaque features, such as, thin or ruptured cap, intraplaque hemorrhage, presence of lipid-rich necrotic core (LRNC), and increased LRNC volume as ...assessed by magnetic resonance imaging (MRI), was examined in patients with established vascular disease in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides (AIM-HIGH) trial. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents, and MRI-modified American Heart Association lesion type by a core laboratory. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced American Heart Association type-VI lesions with possible surface defect, intraplaque hemorrhage, or mural thrombus. Type-VI lesions were associated with older age (odds ratio OR = 2.6 per 5 years increase, p <0.001). After adjusting for age, these lesions were associated with history of cerebrovascular disease (OR = 4.1, p = 0.01), higher levels of lipoprotein(a) (OR = 2.0 per 1 SD increase, p = 0.02), and larger percent wall volume (PWV OR = 4.6 per 1 SD increase, p <0.001) but, were negatively associated with metabolic syndrome (OR = 0.2, p = 0.02). Presence of LRNC was associated with the male gender (OR = 3.2, p = 0.02) and PWV (OR = 3.8 per 1 SD, p <0.001); however, it was negatively associated with diabetes (OR = 0.4, p = 0.02) and high-density lipoprotein cholesterol levels (OR = 0.7 per 1 SD, p = 0.02). Increased percent LRNC was associated with PWV (regression coefficient = 0.36, p <0.001) and negatively associated with ApoA1 levels (regression coefficient = −0.20, p = 0.03). In conclusion, older age, male gender, history of cerebrovascular disease, larger plaque burden, higher lipoprotein(a), and lower high-density lipoprotein cholesterol or ApoA1 level have statistically significant associations with high-risk plaque features. Metabolic syndrome and diabetes showed negative associations in this population.
Carotid artery stenosis is a well-established risk factor of ischemic stroke, contributing to up to 10%-20% of strokes or transient ischemic attacks. Many clinical trials over the last 20 years have ...used measurements of carotid artery stenosis as a means to risk stratify patients. However, with improvements in vascular imaging techniques such as CT angiography and MR angiography, ultrasonography, and PET/CT, it is now possible to risk stratify patients, not just on the degree of carotid artery stenosis but also on how vulnerable the plaque is to rupture, resulting in ischemic stroke. These imaging techniques are ushering in an emerging paradigm shift that allows for risk stratifications based on the presence of imaging features such as intraplaque hemorrhage (IPH), plaque ulceration, plaque neovascularity, fibrous cap thickness, and presence of a lipid-rich necrotic core (LRNC). It is important for the neurosurgeon to be aware of these new imaging techniques that allow for improved patient risk stratification and outcomes. For example, a patient with a low-grade stenosis but an ulcerated plaque may benefit more from a revascularization procedure than a patient with a stable 70% asymptomatic stenosis with a thick fibrous cap. This review summarizes the current state-of-the-art advances in carotid plaque imaging. Currently, MRI is the gold standard in carotid plaque imaging, with its high resolution and high sensitivity for identifying IPH, ulceration, LRNC, and inflammation. However, MRI is limited due to time constraints. CT also allows for high-resolution imaging and can accurately detect ulceration and calcification, but cannot reliably differentiate LRNC from IPH. PET/CT is an effective technique to identify active inflammation within the plaque, but it does not allow for assessment of anatomy, ulceration, IPH, or LRNC. Ultrasonography, with the aid of contrast enhancement, is a cost-effective technique to assess plaque morphology and characteristics, but it is limited in sensitivity and specificity for detecting LRNC, plaque hemorrhage, and ulceration compared with MRI. Also summarized is how these advanced imaging techniques are being used in clinical practice to risk stratify patients with low- and high-grade carotid artery stenosis. For example, identification of IPH on MRI in patients with low-grade carotid artery stenosis is a risk factor for failure of medical therapy, and studies have shown that such patients may fair better with carotid endarterectomy (CEA). MR plaque imaging has also been found to be useful in identifying revascularization candidates who would be better candidates for CEA than carotid artery stenting (CAS), as high intraplaque signal on time of flight imaging is associated with vulnerable plaque and increased rates of adverse events in patients undergoing CAS but not CEA.
Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging ...and an individual's sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that have been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (P<.0001), frontal lobes (P<.0001), occipital lobes (P=.0005), parietal lobes (P=.0002), and the temporal lobes (P<.0001) of the brain. No significant linear correlation between brain stiffness and age was observed in the cerebellum (P=.74), and the sensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011±0.002kPa in cerebrum stiffness with a theoretical median age value (76years old) of 2.56±0.08kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23kPa and 0.09kPa stiffer than males of the same age, respectively. This study confirms that as the brain ages, there is softening; however, the changes are dependent on region. In addition, stiffness effects due to sex exist in the occipital and temporal lobes.
•Changes in brain stiffness as a function of age and sex were investigated, in vivo.•This study observed that in this older population, as the brain ages, there is softening.•Brain stiffness changes with respect to age are dependent on brain region.•Stiffness effects due to sex exist in the occipital and temporal lobes.•Age and sex need to be considered when designing future brain MRE studies.
To retrospectively evaluate the complications of diagnostic cerebral catheter angiography in 19,826 consecutive patients.
This HIPAA-compliant study had institutional review board approval, with ...waiver of informed consent. Demographic, procedural, and complication data in 19 826 consecutive patients undergoing diagnostic cerebral angiography at one institution from 1981 through 2003 were retrospectively reviewed. Neurologic, systemic, and local complications were recorded on the basis of clinical follow-up results after each angiographic examination. Events that occurred within 24 hours of angiography were considered to be complications of the procedure. Multivariable analysis was employed to identify patient and procedural factors significantly associated with neurologic complications.
Neurologic complications occurred in 522 examinations (2.63%), and 27 of these (0.14%) were strokes with permanent disability. Twelve deaths occurred (0.06%). Access-site hematoma was the most common complication overall (4.2%). Factors independently associated with an increased risk of neurologic complication included the indication of atherosclerotic cerebrovascular disease (odds ratio OR, 2.494), the indication of subarachnoid hemorrhage (OR, 2.523), and the comorbidity of frequent transient ischemic attack (OR, 1.674). Factors independently associated with a decreased risk of neurologic complication were increasing chronologic year in which the procedure was performed (OR, 0.659 per 5-year interval) and involvement of a trainee in the procedure (OR, 0.710).
In this review, diagnostic catheter cerebral angiography was found to have relatively low complication rates.
Objective
To describe the treatment and outcomes of patients with primary central nervous system (CNS) vasculitis.
Methods
We retrospectively studied a cohort of 163 consecutive patients with primary ...CNS vasculitis who were seen at the Mayo Clinic over a 29‐year period. We analyzed treatments, treatment responses, and factors predictive of outcomes.
Results
A favorable response was observed in 85% of patients treated with prednisone alone and in 80% of patients treated with prednisone and cyclophosphamide. Relapses were observed in 27% of patients, and 25% of patients had discontinued therapy by the time of the last followup visit. Treatment with prednisone alone was associated with more frequent relapses (odds ratio OR 2.90), while large vessel involvement (OR 6.14) and cerebral infarcts at the time of diagnosis (OR 3.32) were associated with a poor response to treatment. Prominent gadolinium‐enhanced cerebral lesions or meninges were linked with continued treatment at the last followup encounter (OR 2.28). Higher disability scores at the last followup visit were associated with increasing age at the time of diagnosis (OR 1.44) and cerebral infarctions (OR 3.74), while lower disability scores were associated with gadolinium‐enhanced cerebral lesions or meninges (OR 0.35) and cerebral amyloid angiopathy (OR 0.24). Increased mortality was associated with increasing age at diagnosis (hazard ratio HR 1.39), diagnosis by angiography (HR 3.28), cerebral infarction (HR 4.44), and large vessel involvement (HR 4.98), while reduced mortality was associated with gadolinium‐enhanced cerebral lesions or meninges (HR 0.20).
Conclusion
The majority of patients with primary CNS vasculitis responded to treatment. Recognition of findings at diagnosis that predict the course or outcome may aid in decision‐making regarding therapy.
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