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Conservation of amino acid sequence of VP8 and cleavage region of 84-kDa outer capsid protein among rotaviruses recovered from asymptomatic neonatal infection.

Within the past few years, rotavirus strains were recovered from four discrete prolonged outbreaks of infection in newborn nurseries in which affected infants failed to develop significant symptoms. The virus strains recovered from each outbreak belonged to a different human rotavirus serotype and thus each of the four human rotavirus serotypes was associated with asymptomatic infection of neonates. Marked conservation of sequence was observed among the fourth genes of the nursery rotavirus strains in a previous study using RNA X RNA hybridization, while a different conserved set of fourth gene sequences was identified among virulent human rotaviruses representing the four known serotypes. In the present study, this sequence dimorphism was further evaluated by comparing the sequence of the region of the fourth gene of virulent and asymptomatic human rotaviruses that codes for the VP8 protein, downstream cleavage sites, and the NH2 terminus of VP5. The corresponding sequences of a simian rotavirus were also determined. The fourth segment (+) strand RNA has a 5' conserved nontranslated sequence of nine nucleotides and encodes a VP8 protein of 240 amino acids in human rotavirus strains and 241 amino acids in simian rotavirus strains. Human and simian rotaviruses exhibit many similarities in this region of their genome, including identical NH2-terminal amino acid sequences, conservation of arginine at the two trypsin cleavage sites, and the position of a cysteine residue. Alignment of amino acid sequences of the VP8 protein, the downstream cleavage region, and the NH2 terminus of VP5 of asymptomatic and virulent human rotavirus strains indicates a high degree of homology (96% or more) among the asymptomatic viruses (serotypes 1, 2, 3, and 4), while homology between asymptomatic strains and virulent viruses is considerably less (68-72%). A high degree of conservation of amino acid sequence (92-97%) is also observed among three of the virulent strains (serotypes 1, 3, and 4). At 48 positions in the protein sequence of VP8, the cleavage region, and the NH2 terminus of VP5, an amino acid is conserved among asymptomatic rotaviruses, while a different amino acid is conserved among virulent rotaviruses. Notably, three of these differences are located within the cleavage region between VP8 and VP5. These findings suggest that the fourth genes of virulent and asymptomatic human rotavirus strains represent two lines of divergent evolution from a common ancestor. Also, it is possible that this sequence dimorphism may be responsible in part for the difference in virulence between these two groups of human rotaviruses.

Amino Acid Sequence↗

Clinicopathologic features of asymptomatic gastric adenocarcinoma patients in Korea.

OBJECTIVE: The aim of this study was to analyze the characteristics of patients diagnosed with gastric adenocarcinoma without the presence of symptoms and to evaluate the usefulness of screening programs for gastric cancer in Korea. METHODS: We retrospectively analyzed the characteristics of 1277 gastric adenocarcinoma patients at Seoul National University Hospital (SNUH) (665 in 1996; 612 in 2001) by dividing them into two groups according to the presence or absence of symptoms (symptomatic group vs asymptomatic group). RESULTS: The proportion of asymptomatic patients increased from 1996 (4.7%) to 2001 (17.2%) (P < 0.001). Gastroscopy was the most commonly used screening tool (77.4% in 1996, 95.2% in 2001). The proportion of early gastric cancer (EGC) in the asymptomatic group was higher than in the symptomatic group (74.2% vs 25.9% in 1996, 78.1% vs 35.7% in 2001) (P < 0.001). The curative operation rate was significantly higher in the asymptomatic group. The asymptomatic group had a higher 5-year survival rate (87.7%) than the symptomatic group (51.6%) (P < 0.01). Complementary data from a screening program at the SNUH showed that 19 gastric cancer cases (0.76%) were detected out of 2501 endoscopic examinations; of these, 78.9% (15/19) were early gastric cancer cases, which is in agreement with our results. CONCLUSION: Patients with asymptomatic gastric adenocarcinoma had fewer advanced lesions, a greater chance for curative operation and a higher survival rate than symptomatic patients. An increase in the number of asymptomatic patients contributed to the increase in overall EGC from 1996 to 2001. These results seemed to support the usefulness of gastroscopy as a screening test for gastric cancer in Korea, where the incidence of gastric cancer is high.

Adenocarcinoma↗

Relationship of clinical diabetes and asymptomatic hyperglycemia to risk of coronary heart disease mortality in men and women.

This epidemiologic study explored the sex differential in risk of death from coronary heart disease in persons with or without clinically diagnosed diabetes or asymptomatic hyperglycemia. Use was made of 9-year follow-up data from the Chicago Heart Association Detection Project in Industry for 11,220 white men and 8,030 white women aged 35-64 years at entry to the Project (November 1967-January 1973). Both clinically diagnosed diabetes and asymptomatic hyperglycemia were associated with an increased risk of death from coronary heart disease. The extent of this association was greater in women than in men in regard to relative risk. However, absolute excess risk for both diabetics and those with asymptomatic hyperglycemia was larger for men than for women. Clinical diabetes appeared to be an independent risk factor for coronary heart disease in both men and women based on multivariate Cox regression analyses. On the other hand, for men, no significant independent effect of asymptomatic hyperglycemia was apparent. Women with asymptomatic hyperglycemia had significantly higher coronary heart disease death rates than normoglycemic women, with adjustment for major coronary heart disease risk factors; in multivariate analyses, the relationship of asymptomatic hyperglycemia to risk of coronary heart disease was of borderline significance (p = 0.054). This study indicates the independent associations of diabetes and possibly asymptomatic hyperglycemia with coronary heart disease mortality, with greater relative significance in women than in men.

Adult↗

Gonorrhea case-finding among asymptomatic men seeking ambulatory care: a cost effectiveness analysis.

Case-finding for gonorrhea in asymptomatic men is generally not performed in primary care settings and often not performed when men are seen for other reasons in clinics for sexually transmitted diseases. We performed a cost-effectiveness analysis of case-finding among asymptomatic men seeking ambulatory care, using culture of the first-voided urine and treatment of culture-positive patients with tetracycline. The analysis demonstrated that care-finding is increasingly cost-effective as the probability of asymptomatic gonorrhea becomes greater. Over a reasonable expected range of the probability of asymptomatic gonorrhea (0.1-15%) in such settings, the additional cost to avert one additional day of morbidity ranged from $47,000 to $260; the additional cost to avert one additional case of residual asymptomatic infection ranged from $26,000 to $140; and the additional cost to avert one additional case of pelvic inflammatory disease in a contact ranged from $250,000 to $1,400. We conclude that the cost-effectiveness of case-finding for gonorrhea among asymptomatic men compares favorably with that of other medical interventions when the probability of infection is relatively high (perhaps greater than or equal to 5%). In order to make use of such information, physicians in ambulatory care settings require better information about the probability of gonorrhea in asymptomatic men who differ in their medical histories and socioeconomic and ethnic backgrounds.

Ambulatory Care↗

Treatment of asymptomatic myocardial ischemia.

BACKGROUND: Asymptomatic myocardial ischemia is commonly observed in patients with coronary artery disease. Numerous studies have shown that patients with asymptomatic ischemia are at higher risk for adverse outcome than those without ischemia. Several recent studies have investigated the therapeutic options available in the management of patients with asymptomatic myocardial ischemia. METHODS: Recently published randomized controlled trials investigating the treatment of asymptomatic myocardial ischemia were reviewed. RESULTS: The controlled trials suggest that (1) asymptomatic ischemia can be suppressed to various degrees using pharmacologic therapy or revascularization, (2) beta-blockers are in general superior to calcium channel blockers or nitrates in relieving asymptomatic ischemia, and (3) revascularization is superior to pharmacologic therapy. CONCLUSIONS: A growing body of evidence suggests that in patients with coronary artery disease, treatment of asymptomatic ischemia may result in improved outcome. However, because of significant limitations in the published studies, additional studies with large sample sizes and broader inclusion criteria are needed.

Adrenergic beta-Antagonists↗

Scoliosis in young men with spondylolysis or spondylolisthesis. A comparative study in symptomatic and asymptomatic subjects.

While an increased incidence of scoliosis in symptomatic spondylolysis and spondylolisthesis has been established previously, a comparison of its occurrence in symptomatic and asymptomatic individuals has not been performed. The present study is a comparison of symptomatic and asymptomatic young men with analysis as to the incidence of scoliosis. Idiopathic scoliosis was not found and all cases were due to spasm scoliosis or olisthetic scoliosis with the spasm type being much more common. Scoliotic curves were divided into mild (0-9 degrees) and moderate (10-20 degrees). No case of a curve greater than 20 degrees was seen. Scoliosis incidence in asymptomatic individuals without a pars break was 6.65%. In the groups of: (1) asymptomatic unilateral spondylolysis, (2) asymptomatic bilateral spondylolysis, (3) symptomatic bilateral spondylolysis, and (4) asymptomatic spondylolisthesis the scoliosis incidence was similar, ranging from 13.3-23.8%. These figures are significantly higher than those seen in the asymptomatic subjects without a pars break, but they are in the same range as in symptomatic patients without a pars break, suggesting that muscle spasm is the principal cause of the scoliosis.

Adolescent↗

The natural history of asymptomatic thoracic disc herniations.

STUDY DESIGN: Magnetic resonance imaging was used to determine the natural history of asymptomatic thoracic disc herniations. OBJECTIVES: To determine whether thoracic disc herniations change in size over time. SUMMARY OF BACKGROUND DATA: Based on previous work by the authors of the present study, the incidence of asymptomatic thoracic disc herniations is approximately 37%. The natural history of thoracic disc herniations is unknown. The natural history of lumbar and cervical disc herniations in symptomatic individuals who become asymptomatic has been shown in multiple studies frequently to result in a decrease in size of the herniation. METHODS: Twenty patients with 48 asymptomatic thoracic herniations previously diagnosed with magnetic resonance imaging underwent repeat magnetic resonance imaging using sagittal T1-weighted spine echo and axial multiplanar gradient refocused images at each thoracic disc level from T1 to T12 for a mean follow-up period of 26 months. Midsagittal canal diameter was recorded, and disc herniation square area was measured using a computer-assisted digitizing program. Disc herniations were categorized according to percentage of canal compromise. The change in size of the disc herniations over time was analyzed. RESULTS: All patients remained asymptomatic during the follow-up period. A total of 48 disc herniations were identified from the original magnetic resonance images. There were 21 small (0-10% canal compromise) disc herniations, 20 medium (> 10-20%) disc herniations, and seven large (> 20%) disc herniations. Of the 21 small disc herniations, 18 showed no significant change in size, whereas three showed a measurable increase in size. Of the 20 medium-sized disc herniations, 16 showed either a small or no change in size, one showed a significant increase in size, and three showed a significant decrease in size. Of the seven large disc herniations, three demonstrated no change in size, and four demonstrated a significant decrease in size. In addition, five new disc herniations were detected in four patients; one was small, and four were moderate in size. CONCLUSIONS: Based on the results of this study, the authors believe that asymptomatic disc herniations may well exist in a state of relative flux, yet exhibit little change in size and remain asymptomatic. There was a trend, however, for small disc herniations either to remain unchanged or increase in size and for large disc herniations often to decrease in size.

Adult↗

Cervical range of motion discriminates between asymptomatic persons and those with whiplash.

STUDY DESIGN: A comparative study of cervical range of motion in asymptomatic persons and those with whiplash. OBJECTIVES: To compare the primary and conjunct ranges of motion of the cervical spine in asymptomatic persons and those with persistent whiplash-associated disorders, and to investigate the ability of these measures of range of motion to discriminate between the groups. SUMMARY OF BACKGROUND: Evidence that range of motion is an effective indicator of physical impairment in the cervical spine is not conclusive. Few studies have evaluated the ability to discriminate between asymptomatic persons and those with whiplash on the basis of range of motion or compared three-dimensional in vivo measures of range of motion in asymptomatic persons and those with whiplash-associated disorders. METHODS: The study participants were 89 asymptomatic volunteers (41 men, 48 women; mean age 39.2 years) and 114 patients with persistent whiplash-associated disorders (22 men, 93 women; mean age 37.2 years) referred to a whiplash research unit for assessment of their cervical region. Range of cervical motion was measured in three dimensions with a computerized, electromagnetic, motion-tracking device. The movements assessed were flexion, extension, left and right lateral flexion, and left and right rotation. RESULTS: Range of motion was reduced in all primary movements in patients with persistent whiplash-associated disorder. Sagittal plane movements were proportionally the most affected. On the basis of primary and conjunct range of motion, age, and gender, 90.3% of study participants could be correctly categorized as asymptomatic or as having whiplash (sensitivity 86.2%, specificity 95.3%). CONCLUSIONS: Range of motion was capable of discriminating between asymptomatic persons and those with persistent whiplash-associated disorders.

Adolescent↗

Molecular analysis of bacteria in asymptomatic and symptomatic endodontic infections.

The purpose of the present study was to use terminal restriction fragment length polymorphism analysis and the 16S rRNA gene clone library to investigate the diversity of the microbiota associated with asymptomatic and symptomatic endodontic infections and to compare the bacterial community structure in these two clinical conditions. Samples were taken from asymptomatic endodontic infections associated with chronic periradicular lesions and from symptomatic infections clinically diagnosed as acute abscesses. 16S rRNA genes from DNA isolated from clinical samples were used to construct clone libraries or were subjected to terminal restriction fragment length polymorphism analysis. Sequence analysis of 186 clones revealed 42 taxa; 23 (55%) were uncultivated phylotypes, of which seven were unique to endodontic infections. Clone sequencing and terminal restriction fragment length polymorphism analysis revealed that the most commonly detected taxa were Fusobacterium nucleatum (including terminal restriction fragment types 1 and 2), Peptostreptococcus micros/Peptostreptococcus sp. oral clone AJ062/BS044/FG014, Prevotella species, Dialister species, Mogibacterium species, Lachnospiraceae oral clone 55A-34, Filifactor alocis, Megasphaera sp. oral clone CS025/BS073, and Veillonella sp. oral clone BP1-85/Veillonella dispar/V. parvula. Bacteroides-like sp. oral clone X083/Bacteroidales oral clone MCE7_20 and Dialister sp. oral clone BS016/MCE7_134 were detected only in asymptomatic teeth. On the other hand, F. nucleatum terminal restriction fragment type 2, Prevotella intermedia, Dialister pneumosintes, and some phylotypes were exclusively detected in symptomatic samples. Bacterial profiles of symptomatic endodontic infections generated by terminal restriction fragment length polymorphism analysis were clearly different from those of asymptomatic infections. Overall, the average number of terminal restriction fragments in symptomatic samples was significantly larger than in asymptomatic samples. Molecular analysis of the microbiota associated with symptomatic or asymptomatic endodontic infections indicates that the endodontic bacterial diversity is greater than previously described by culture methods and that the structure of the microbiota differ significantly between asymptomatic and symptomatic infections.

Adolescent↗

Electrophysiologic evaluation of asymptomatic patients with the Wolff-Parkinson-White pattern.

In the past 4 years, 34 asymptomatic patients with the Wolff-Parkinson-White (WPW) pattern underwent electrophysiologic study. The effective refractory period (ERP) of antegrade conduction over the accessory pathway was 288 +/- 29 msec. In three asymptomatic patients (9%), the antegrade ERP of the accessory pathway was shorter than 250 msec. The antegrade ERP of the accessory pathway became shorter than 250 msec in an additional 12 of 22 (55%) patients after isoproterenol administration. Nineteen (56%) of the asymptomatic patients showed the absence of retrograde conduction over the accessory pathway even after isoproterenol administration. The rate of induction of orthodromic reciprocating tachycardia in the asymptomatic WPW patients was 15% (5/34), which was significantly lower than that in the symptomatic patients. These data suggest that in the asymptomatic patients, the absence of retrograde conduction over the accessory pathway is the reason they remained asymptomatic, free of reciprocating tachycardia. However, even in the asymptomatic patients, some had the accessory pathway in which antegrade ERP was shorter than 250 msec. They may result in rapid ventricular conduction over the accessory pathway when atrial fibrillation develops.

Adult↗

Asymptomatic bradyarrhythmias as a marker for sleep apnea: appropriate recognition and treatment may reduce the need for pacemaker therapy.

Sleep apnea is associated with many adverse cardiovascular sequelae, including hypertension, nocturnal angina, decreased cardiac output, and bradyarrhythmias. The purpose of this study was to determine if patients referred for pacemaker therapy with asymptomatic bradyarrhythmias have underlying sleep apnea as the etiology of their bradyarrhythmias. This study included eight patients (7 males, 1 female) referred to a cardiac electrophysiology practice for pacemaker therapy. Patients included had asymptomatic bradyarrhythmias that consisted of severe sinus bradycardia, second-degree atrioventricular block, and complete heart block. In 7 of 8 patients, the bradyarrhythmias occurred at night or during the day while asleep. No patients were conditioned athletes. Symptoms often associated with bradyarrhythmias, such as lightheadedness and syncope, were not present. However, seven patients had at least one symptom suggestive of sleep apnea, such as excessive daytime fatigue, snoring, cessation of breathing during sleep (apnea), or frequent night-time awakenings. Overnight polysomnography studies were obtained on patients who had one or more symptoms suggestive of sleep apnea. In this study 7 of 8 patients (88%) referred for pacemaker therapy with asymptomatic bradyarrhythmias were documented by polysomnography to have sleep apnea. When treated with either sleep position modification, nasal continuous positive airway pressure (nasal CPAP), or tracheostomy, all seven patients had improvement in sleep apnea symptoms and remained asymptomatic from their bradyarrhythmias without pacemaker therapy over an average follow-up period of 22 months. One patient without symptoms suggestive of sleep apnea declined pacemaker therapy and remained asymptomatic. From these results, we concluded that asymptomatic transient bradyarrhythmias may suggest a diagnosis of sleep apnea. The evaluation of a patient referred for pacemaker therapy with asymptomatic bradyarrhythmias should include questions related to sleep apnea symptoms. Establishing the diagnosis of sleep apnea may reduce the need for pacemaker therapy and permit appropriate treatment of the underlying cause of these bradyarrhythmias.

Aged↗

Increased platelet count and leucocyte-platelet complex formation in acute symptomatic compared with asymptomatic severe carotid stenosis.

OBJECTIVE: The risk of stroke in patients with recently symptomatic carotid stenosis is considerably higher than in patients with asymptomatic stenosis. In the present study it was hypothesised that excessive platelet activation might partly contribute to this difference. METHODS: A full blood count was done and whole blood flow cytometry used to measure platelet surface expression of CD62P, CD63, and PAC1 binding and the percentage of leucocyte-platelet complexes in patients with acute (0-21 days, n = 19) and convalescent (79-365 days) symptomatic (n = 16) and asymptomatic (n = 16) severe (> or =70%) carotid stenosis. Most patients were treated with aspirin (37.5-300 mg daily) although alternative antithrombotic regimens were more commonly used in the symptomatic group. RESULTS: The mean platelet count was higher in patients with acute and convalescent symptomatic compared with asymptomatic carotid stenosis. There were no significant differences in the median percentage expression of CD62P and CD63, or PAC1 binding between the acute or convalescent symptomatic and asymptomatic patients. The median percentages of neutrophil-platelet (p = 0.004), monocyte-platelet (p = 0.046), and lymphocyte-platelet complexes (p = 0.02) were higher in acute symptomatic than in asymptomatic patients. In patients on aspirin monotherapy, the percentages of neutrophil-platelet and monocyte-platelet complexes (p = 0.03) were higher in acute symptomatic (n = 11) than asymptomatic patients (n = 14). In the convalescent phase, the median percentages of all leucocyte-platelet complexes in the symptomatic group dropped to levels similar to those found in the asymptomatic group. CONCLUSION: Increased platelet count and leucocyte-platelet complex formation may contribute to the early excess risk of stroke in patients with recently symptomatic carotid stenosis.

Acute Disease↗

Clinicopathologic relevance of asymptomatic endometrial carcinoma.

OBJECTIVE: To assess whether screening asymptomatic women is significant for early detection of endometrial carcinoma. STUDY DESIGN: We compared the clinicopathologic findings and prognoses of 21 asymptomatic patients with 427 symptomatic patients with endometrial carcinoma. RESULTS: The incidence of asymptomatic endometrial carcinoma was 4.7%. Nineteen of 21 asymptomatic patients with endometrial carcinoma were found by cytologic screening for endometrial cancer. There was a statistical difference in the histopathology and depth of myometrial invasion between the asymptomatic and symptomatic groups. However, no statistical differences were found in tumor grade, lymph node metastasis, adnexal metastasis, cervical invasion, peritoneal cytology, surgical stage and patient age. Univariate analysis showed that the presence or absence of symptoms was not related to survival. CONCLUSION: The detection of asymptomatic endometrial carcinoma is not related to a reduced mortality rate. Screening asymptomatic women for endometrial carcinoma is not recommended.

Adult↗

Asymptomatic arrhythmias in patients with symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia.

BACKGROUND: Paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia are recognized clinically when patients seek treatment for symptoms due to recurrent arrhythmias; atrial fibrillation also increases the risk of stroke. The frequency with which asymptomatic arrhythmias occur in patients with these arrhythmias is unknown. METHODS AND RESULTS: Twenty-two patients with paroxysmal atrial fibrillation (n = 8) or paroxysmal supraventricular tachycardia (n = 14) were studied for 29 days with two different ambulatory ECG-monitoring techniques to measure the relative frequency of asymptomatic and symptomatic arrhythmias. All class I antiarrhythmic drugs, calcium channel blockers, beta-blockers, and digitalis were withheld. Sustained asymptomatic arrhythmia events (defined as lasting at least 30 seconds) were documented using continuous ambulatory ECG monitoring once weekly for a total of 5 of the 29 study days; symptomatic arrhythmia events were documented using transtelephonic ECG monitoring for all 29 days of the study. In the group of patients with paroxysmal atrial fibrillation, asymptomatic arrhythmia events occurred significantly more frequently than symptomatic arrhythmia events; the mean rates, expressed as events/100 d/patient (95% confidence interval), were 62.5 (40.4, 87.3) and 5.2 (2.7, 9.0) (P < .01); the ratio of the mean rates was 12.1 (5.8, 26.4). In contrast, in the group of patients with paroxysmal supraventricular tachycardia, asymptomatic arrhythmia events were significantly less frequent than symptomatic arrhythmia events; the mean rates were 0.0 (0.0, 5.3) and 7.4 (5.0, 10.6) (P = .02). The ratio of the mean rates was 0.0 (0.0, 0.8). CONCLUSIONS: In a group of patients with paroxysmal atrial fibrillation, sustained asymptomatic atrial fibrillation occurs far more frequently than symptomatic atrial fibrillation. However, it is not known whether asymptomatic atrial fibrillation is a potential risk factor for stroke even when patients are not having symptomatic arrhythmias.

Atrial Fibrillation↗

Left ventricular hypertrophy is associated with asymptomatic cerebral damage in hypertensive patients.

BACKGROUND AND PURPOSE: It has been demonstrated that left ventricular hypertrophy (LVH) confers an increased risk for major cerebrovascular events. However, it is still uncertain whether there is an association between LVH and asymptomatic cerebrovascular damage in hypertensive patients. In this study, we investigated the relation between LVH, evaluated by both echocardiography (Echo-LVH) and electrocardiography (ECG-LVH), and preclinical cerebral damage, as identified by magnetic resonance imaging. METHODS: One hundred ninety-five consecutive patients were enrolled in the study. We evaluated other risk factors such as age, sex, presence of diabetes, cholesterol levels, smoking status, heart rate, and systolic and diastolic blood pressure. Asymptomatic cerebrovascular damage was considered silent cerebral lesions: punctate lesions, lacunes, and territorial lesions. Patients were divided into 2 groups according to the presence of asymptomatic brain lesions. RESULTS: The 2 groups of patients differed only in terms of age and systolic pressure. More importantly, the prevalence of Echo-LVH (83% versus 47.7%, P<0.001) and ECG-LVH (56% versus 22%, P<0.001) was significantly higher in patients with asymptomatic brain lesions. A multivariate analysis allowed us to recognize LVH as the only independent predictor for the presence of ischemic lacunes (P<0.001). Moreover, we evaluated the impact of left ventricular geometry on asymptomatic cerebrovascular damage, and we found that hypertensives with concentric hypertrophy displayed more pronounced asymptomatic cerebrovascular damage compared with patients with eccentric hypertrophy. CONCLUSIONS: Our study demonstrates that LVH is associated with cerebral damage even in the absence of clinical symptoms. Thus, the presence of cardiac damage provides important prognostic clues about the presence of asymptomatic cerebral damage.

Age Distribution↗

Asymptomatic coronary artery disease in patients with stroke. Prevalence, prognosis, diagnosis, and treatment.

The frequency of angiographically defined asymptomatic CAD in patients with carotid disease is 40%. Although the prognosis of patients with asymptomatic 1-vessel or 2-vessel CAD is good (annual cardiac mortality rate less than 2%), the prognosis of asymptomatic 3-vessel disease or left main CAD is substantially less favorable (annual cardiac mortality 5-8%). Preliminary data from nonrandomized studies suggest that coronary artery bypass surgery significantly lowers cardiac mortality in patients with asymptomatic 3-vessel or left main CAD. Further studies are needed to determine 1) vascular risk factor profiles that are predictive of asymptomatic CAD in patients with cerebrovascular disease and 2) the prevalence of asymptomatic CAD, especially 3-vessel and left main CAD, in patients with a variety of subtypes of cerebrovascular disease (e.g., carotid disease, atherosclerotic vertebrobasilar disease, cardioembolism, penetrating artery disease, stroke of undetermined cause). If the prevalence of asymptomatic 3-vessel or left main CAD is high in a subset of patients with cerebrovascular disease, a randomized study comparing coronary artery bypass surgery with best medical therapy (anti-ischemic agents, lipid-lowering therapy, and aspirin) may be warranted.

Cerebrovascular Disorders↗

Transcranial Doppler assessment of cerebrovascular reactivity in symptomatic and asymptomatic severe carotid stenosis.

BACKGROUND AND PURPOSE: Some studies have suggested a link between impaired cerebral hemodynamics and stroke in patients with carotid stenosis. The aim of this study was to assess the effects of severe carotid stenosis on cerebrovascular reactivity and the possible changes after endarterectomy. METHODS: Using bilateral transcranial Doppler ultrasound, we studied the changes of flow velocity after hypercapnia in the middle cerebral arteries of 10 control subjects and 24 patients (13 symptomatic and 11 asymptomatic) with unilateral severe carotid stenosis before and after endarterectomy. Cerebrovascular reactivity was evaluated with the breath-holding index (BHI). RESULTS: Before endarterectomy, BHI (mean value +/- SD) was significantly lower (P < .001) in the stenotic side of symptomatic patients (0.40 +/- 0.2) than in control subjects (1.12 +/- 0.3), the stenotic side of asymptomatic patients (0.80 +/- 0.4), and the normal side of both symptomatic (0.93 +/- 0.3) and asymptomatic ultrasonics (1.03 +/- 0.2) patients. On the other hand, no significant difference in BHI was detected in control subjects, on the normal side of symptomatic and asymptomatic patients, and the stenotic side of asymptomatic patients. After endarterectomy, BHI significantly increased (P < .0001) on the stenotic side of symptomatic patients (1.06 +/- 0.2) while remaining substantially stable on the normal side of both symptomatic and asymptomatic patients and on the stenotic side of asymptomatic patients. CONCLUSIONS: These findings suggest that the study of cerebrovascular reactivity to hypercapnia may be relevant in evaluating the functional effects of carotid stenosis. Further investigations are needed to confirm the reliability of the breath-holding method in the selection of patients who might benefit most from carotid endarterectomy.

Aged↗

Temporal variability of asymptomatic embolization in carotid artery stenosis and optimal recording protocols.

BACKGROUND AND PURPOSE: Although asymptomatic embolization can be detected in patients with carotid artery stenosis, its temporal variability is unclear. An understanding of this is important in designing optimal recording protocols for future prospective studies of the predictive value of embolic signals (ES). We determined the effect of repeating and extending recording times in patients with symptomatic and asymptomatic carotid stenosis. METHODS: In 20 asymptomatic and 20 symptomatic subjects with > 60% carotid stenosis, we used transcranial Doppler ultrasound to record for ES in the ipsilateral middle cerebral artery. Three 1-hour recordings were performed on three separate days, and on one occasion (not necessarily the first) the recording was extended to 2 hours. The recordings were saved onto digital tape for subsequent blinded analysis. RESULTS: Marked temporal variability was seen in symptomatic patients in whom the cumulative proportion of subjects with ES increased from 10 (50%) after a single hour of recording to 12 (60%) and 15 (75%) after two and three recordings, respectively. Extending the recording to 2 hours increased the yield of ES-positive patients from 6 (30%) to 8 (40%). In symptomatic patients there was excellent agreement between whether patients were positive for ES during each of two consecutive 1-hour recordings (kappa = 0.78, P = 0.0003) but poor agreement between the results of two single-hour recordings performed on different days (kappa = 0.22, P = 0.27). In asymptomatic patients, 4 (20%) were ES positive during the first hour; this increased to 5 (25%) after the recording was repeated once, with no further increase after the third recording. Extending the recording to 2 hours increased the yield from 3 (15%) to 7 (35%). In contrast to symptomatic stenoses, in patients with asymptomatic stenoses there was fair agreement between whether patients were ES positive on two consecutive 1-hour recordings (kappa = 0.49, P = 0.01) or two single-hour recordings performed on different days (kappa = 0.48, P = 0.02). Symptomatic subjects were more likely to have ES (when all 1-hour recordings were considered, 24/60 versus 10/60; P = 0.0046). ES in symptomatic subjects had a higher relative intensity increase than in asymptomatic subjects (P = 0.01). CONCLUSIONS: The temporal variability of ES needs to be taken into account in the design of optimal recording protocols and comparisons of results from different studies. Extending the duration of recording beyond an hour in symptomatic stenoses is of less value, but repeating the recording on a different day will often identify additional subjects with ES. In intervention studies in symptomatic patients, the time since last symptoms must be considered. In asymptomatic stenosis, extending the duration of recording beyond an hour will increase the proportion of patients positive for ES.

Adult↗