Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group.

BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years. METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.     

Clinical correlates of ventricular and sulcal size on cranial magnetic resonance imaging of 3,301 elderly people. The Cardiovascular Health Study. Collaborative Research Group

To identify potential risk factors for and clinical manifestations of ventricular and sulcal enlargement on cranial magnetic resonance imaging (MRI), 3,301 community-dwelling people 65 years or older without a history of stroke or transient ischemic attack underwent extensive standardized evaluations and MRI. In the multivariate model, increased age and white matter grade on MRI were the dominant risk factors for ventricular and sulcal grade. For ventricular grade, other than race, for which non-Blacks had higher grades, models for men and women shared no other factors. For sulcal grades, models for men and women shared variables reflecting cigarette smoking and diabetes. Clinical features were correlated more strongly with ventricular than sulcal grade and more strongly for women than men. Significant age-adjusted correlations between ventricular grade and the Digit-Symbol Substitution Test were found for men and women. Prospective studies will be needed to extend findings of this cross-sectional analysis.     

Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group

BACKGROUND: Episodic inflammation in the CNS during the early stages of MS results in progressive disability years later, presumably due to myelin and axonal injury. MRI demonstrates ongoing disease activity during the early disease stage, even in some patients who are stable clinically. The optimal MRI measure for the destructive pathologic process is uncertain, however. METHODS: In this post-hoc study, MRI scans were analyzed from patients with relapsing MS participating in a placebo-controlled trial of interferon beta-1a. The brain parenchymal fraction, defined as the ratio of brain parenchymal volume to the total volume within the brain surface contour, was used to measure whole brain atrophy. The relationship between disease features and brain atrophy and effect of interferon beta-1a were determined. RESULTS: MS patients had significant brain atrophy that worsened during each of 2 years of observation. In many patients, brain atrophy worsened without clinical disease activity. Baseline clinical and MRI abnormalities were not strongly related to the rate of brain atrophy during the subsequent 2 years. Treatment with interferon beta-1a resulted in a reduction in brain atrophy progression during the second year of the clinical trial. CONCLUSIONS: Patients with relapsing-remitting MS have measurable amounts of whole brain atrophy that worsens yearly, in most cases without clinical manifestations. The brain parenchymal fraction is a marker for destructive pathologic processes ongoing in relapsing MS patients, and appears useful in demonstrating treatment effects in controlled clinical trials.     

老年患者急性脑梗死与颈动脉粥样硬化的关系探讨

目的 分析老年人颈动脉粥样硬化（CAS）与脑梗死的关系。方法对106例老年急性脑梗死患者（ACI组,年龄〉65岁）和102例无缺血性脑血管病的对照组进行颈动脉超声检查,评价粥样硬化斑块的位置、稳定性、造成的颈动脉狭窄情况,并分析三者与脑梗死的关系。结果ACI组颈动脉斑块检出率为87．02％,显著高于对照组检出率15．02％（P〈0．005）。ACI组中,中型及重型脑梗死患者的不稳定斑块检出率（51／86）显著高于轻型脑梗死患者（5／20）（P〈0．025）。结论颈动脉粥样硬化是脑梗死的独立危险因素。     

Antiarrhythmic drugs and polyneuropathy. The Collaborative Group for the Study of Polyneuropathy.

A total of 151 patients on chronic treatment with amiodarone and other antiarrhythmic drugs were subjected to standard clinical and electrophysiological investigation to assess the prevalence and specificity of polyneuropathy. Twenty two untreated patients with cardiac disorders and 246 normal subjects served as controls. Abnormal electrophysiological findings supporting the diagnosis of polyneuropathy were present in 38 subjects (25%) given antiarrhythmic drugs, with even distribution among drugs, and four untreated patients (18%). Concurrent clinical abnormalities were present in five treated patients (one each with amiodarone, propafenone, and flecainide, and two with multiple drugs). Therefore, electrophysiological abnormalities are a common, although non-specific, feature in patients taking antiarrhythmic drugs. Amiodarone users do not seem at higher risk of polyneuropathy than subjects treated with other drugs or even untreated patients with cardiac disorders.     

High-risk carotid plaques and incident ischemic stroke in patients with atrial fibrillation in the Cardiovascular Health Study

Background and purpose

Whether carotid artery disease could improve stroke risk stratification tools in patients with atrial fibrillation (AF) remains uncertain. This study was undertaken to investigate the risk of ischemic stroke associated with occlusive and nonocclusive carotid atherosclerotic disease in patients with AF in the prospective population-based Cardiovascular Health Study.

Methods

We included participants aged ≥65 years with AF. We used multivariable Cox regression analysis to explore the risk of ischemic stroke associated with the percentage of carotid stenosis, plaque irregularity, echogenicity, and vulnerability (markedly irregular, ulcerated, or hypoechoic plaques).

Results

A total of 1398 participants were included (55.2% female, 61.7% aged 65–74 years). The maximum carotid stenosis was <50%, 50%–99%, and 100% in 94.5%, 5%, and 0.5% of participants, respectively. High-risk plaques based on echogenicity and plaque irregularity were found in 25.6% and 8.9% of participants, respectively. After a median follow-up of 10.9 years (interquartile range = 7.5–15.6), 298 ischemic strokes were recorded. There was no difference in the incidence of ischemic stroke according to the degree of carotid artery stenosis (p = 0.44), plaque echogenicity (low vs. high risk, p = 0.68), plaque irregularity (low vs. high risk, p = 0.55), and plaque vulnerability (p = 0.86). The CHA₂DS₂-VASc score was associated with an increased risk of ischemic stroke (adjusted hazard ratio = 1.28, 95% confidence interval = 1.18–1.40, p < 0.001). Both maximum grade of stenosis and plaque vulnerability were not associated with incident ischemic stroke (all p > 0.05).

Conclusions

Neither the degree of carotid stenosis nor the presence of vulnerable plaques was associated with incident ischemic stroke in this cohort of individuals with AF. This suggests that carotid disease was probably not a significant contributor to ischemic stroke in this population.     

Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study.

BACKGROUND AND PURPOSE: To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study. METHODS: Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility. RESULTS: The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small. CONCLUSIONS: The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.     

Ultrasound findings in spontaneous carotid artery dissection. The value of duplex sonography

Extracranial and transcranial Doppler and duplex sonographic findings in six patients with internal carotid artery dissection proven by angiography is reported. Extracranial Doppler analysis showed occlusion without a recordable signal from the internal carotid artery at any level or stenosis with accelerated flow in the high cervical segment. Transcranial Doppler findings demonstrated the hemodynamic consequences of the internal carotid artery occlusion or stenosis with collateral flow across the circle of Willis and also showed the dampened pulse wave of the middle cerebral artery ipsilateral to the dissection. In duplex sonography, the indirect signs indicating internal carotid artery dissection were a patent carotid bifurcation and proximal internal carotid artery segment but with no or only a short systolic flow signal. Atherosclerotic wall changes were absent, an important finding that suggests nonatherosclerotic stenosis or occlusion. Direct signs making the diagnosis likely were a tapering of the internal carotid artery lumen distal to the bulb, an irregular membrane crossing the vessel lumen, and the demonstration of a true lumen with flow and a false one without flow. While cerebral angiography is still considered the gold standard, ultrasound may become the primary modality for early diagnosis. Doppler and duplex examinations help to indicate angiography and are the methods of choice for follow-up investigations. They clearly demonstrate spontaneous recanalization with normalization of carotid circulation or, in case of persistent occlusion, improvement of collateral blood supply. Sequential examinations may prove helpful to determine the duration of anticoagulant treatment.     

Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study

Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.     

Lyme borreliosis in Bell's palsy. Long Island Neuroborreliosis Collaborative Study Group.

Lyme borreliosis (LB) causes a range of neurologic manifestations, the most common of which is facial nerve paralysis. To evaluate nervous system LB, we organized a neurologic collaborative study group in Suffolk County, NY, a region of high LB incidence. Between July and September 1989, LB serologies were performed on all patients with new-onset Bell's palsy. Seven of 32 had serologic evidence of LB at onset. One, initially seronegative, was highly seropositive 5 weeks later. In the five in whom we examined CSF, there was no evidence of intrathecal synthesis of specific antibody. In highly endemic areas, LB may be responsible for 1/4 of cases of Bell's palsy. Rarely, the palsy may occur prior to the development of a measurable antibody response, indicating a need for follow-up serologic testing.     

The role of carotid atherosclerosis in Alzheimer's disease progression

The aim of this 12-month prospective study was to establish whether severe internal carotid artery stenosis is associated with faster progression of the cognitive impairment in patients with Alzheimer's disease (AD). Four hundred and eleven patients with AD underwent extracranial carotid Doppler ultrasound evaluation. Cerebrovascular reactivity to hypercapnia was measured by means of the breath-holding index (BHI) in those with severe carotid artery stenosis using transcranial Doppler ultrasonography. Cognitive status was quantified with the Mini Mental State Evaluation (MMSE). Ninety-eight patients had severe carotid artery stenosis, 41 right (group 1), and 57 left (group 2), while 313 had no significant stenosis (group 3). Group 1 and 2 patients showed an increased probability compared with group 3 patients to develop severe dementia (MMSE scores < 21) during the 12-month follow-up period: OR 2.36 (95% CI: 1.14-4.87) and OR 4.90 (95% CI: 2.65-9.04), respectively (p < 0.05, multiple logistic regression analysis). A BHI value ipsilateral to the stenosis < 0.69 predicted a worse MMSE score at 12 months irrespective of the side of the stenosis. These findings suggest that severe internal carotid artery stenosis can be considered as a marker of a faster rate of progression of the cognitive decline in AD. They also indicate that cerebral hemodynamic evaluation could be applied to identify patients at higher risk of rapid cognitive decline, who may benefit from aggressive treatment, and warrant investigation of the advantages of carotid revascularization procedures in these patients.     

The role of plasma lipids in carotid bifurcation atherosclerosis

The severity of coronary artery atherosclerosis correlates with increased plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides and with decreased plasma concentrations of high-density lipoprotein cholesterol (HDL-C). The role of plasma lipoproteins in the pathogenesis of cerebral atherosclerosis, however, is less clear. Several investigators report that lipoprotein abnormalities correlate inversely with the incidence of cerebral infarction. We analyzed risk factors for carotid bifurcation atherosclerosis in 121 consecutive patients who underwent cerebral angiography. This analysis revealed a significant positive correlation between the plasma TC/HDL-C ratio and the extent of carotid bifurcation atherosclerosis (p = 0.01). The extent of atherosclerosis correlated inversely with plasma concentrations of HDL-C (p = 0.02). Triglyceride concentration correlated positively with the extent of atherosclerosis with marginal significance (p = 0.07). LDL-C and TC concentrations did not correlate with bifurcation atherosclerosis (p greater than 0.1). Only 4% of the variation in the extent of bifurcation atherosclerosis was explicable on the basis of plasma lipoprotein concentrations.     

Plasma total homocysteine levels and cranial magnetic resonance imaging findings in elderly persons: the Cardiovascular Health Study

BACKGROUND: An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI). DESIGN: In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins B(6) and B(12) and methylenetetrahydrofolate reductase genotype. RESULTS: After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P =.04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B(6) and B(12) (odds ratio, 3.2; 95% confidence interval, 0.81-13.10; P =.07 for linear trend). CONCLUSION: We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade.