Vascular risk factors and longitudinal changes on brain MRI: the ARIC study.

OBJECTIVE: To evaluate associations between vascular risk factors and changes in burden of infarcts, ventricular size (VS), sulcal widening (SW), and white matter hyperintensities (WMH) in an initially middle-aged, biracial cohort from the Atherosclerosis Risk in Communities (ARIC) study. METHODS: Initial brain magnetic resonance (MR) scans and evaluations for vascular risk factors were performed in 1,812 ARIC participants in 1994-1995. In 2004-2006, 1,130 ARIC participants underwent repeat MR scans. MR scans were rated using a validated 9-point scale for VS, SW, and WMH. Infarcts were recorded. Multiple logistic regression analysis was used to assess associations between vascular risk factors and change between MR scans of one or more grades in VS, SW, WMH, or appearance of new infarcts, controlling for age, sex, and race. RESULTS: At baseline, the 1,112 participants with usable scans (385 black women, 200 black men, 304 white women, 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models, diabetes at baseline was associated with incident infarcts (odds ratio [OR] 1.95, 95% confidence interval [CI] 1.29-2.95) and worsening SW (OR 2.10, 95% CI 1.36-3.24). Hypertension at baseline was associated with incident infarcts (OR 1.73, 95% CI 1.23-2.42). In subjects with the highest tertile of fasting blood sugar and systolic blood pressure at baseline, the risk of incident infarcts was 3.68 times higher (95% CI 1.89-7.19) than those in the lowest tertile for both. CONCLUSION: Both atrophic and ischemic imaging changes were driven by altered glycemic and blood pressure control beginning in midlife.

Compensation or displacement of physical activity in middle-school girls: the Trial of Activity for Adolescent Girls.

OBJECTIVE: The 'activitystat' hypothesis suggests that increases in moderate-to-vigorous physical activity (MVPA) are accompanied by a compensatory reduction in light physical activity (LPA) and/or an increase in inactivity to maintain a consistent total physical activity level (TPA). The purpose of this study was to identify the evidence of compensation in middle-school girls. SUBJECTS: Participants were 6916, 8th grade girls from the Trial of Activity for Adolescent Girls (TAAG). DESIGN: Inactivity and physical activity were measured over 6- consecutive days using accelerometry (MTI Actigraph). A within-girl, repeated measures design was used to assess associations between physical activity and inactivity using general linear mixed models. RESULTS: Within a given day, for every one MET-minute more of inactivity, there was 3.18 MET-minutes (95% confidence interval (CI): -3.19, -3.17) less of TPA (activity >2 METS) on the same day. Daily inactivity was also negatively associated with TPA on the following day. Each additional minute of MVPA was associated with 1.85 min less of inactivity on the same day (95% CI: -1.89, -1.82). Daily MVPA was also negatively associated with inactivity the following day. CONCLUSION: Our results, based on 6 days of observational data, were not consistent with the 'activitystat' hypothesis, and instead indicated that physical activity displaced inactivity, at least in the short term. Longer intervention trials are needed, nevertheless our findings support the use of interventions to increase physical activity over discrete periods of time in middle-school girls.

Retinal microvascular abnormalities and cognitive decline: the ARIC 14-year follow-up study.

BACKGROUND: Because retinal and cerebral arterioles share similar pathologic processes, retinal microvascular changes are expected to be markers of cerebral small vessel disease (SVD). To better understand the role of SVD in cognitive function, we investigated the relationship between retinal microvascular abnormalities and longitudinal changes in cognitive function in a community-based study. METHODS: A total of 803 participants underwent 4 cognitive assessments between 1990-1992 and 2004-2006, using the Word Fluency (WF) test, Digit Symbol Substitution (DSS), and Delayed Word Recall as well as retinal photography in 1993-1995. Covariate adjusted random effects linear models for repeated measures were used to determine the associations of cognitive change with specific retinal vascular abnormalities. RESULTS: Individuals with retinopathy showed declines in executive function and psychomotor speed, with 1) an average decline in WF of -1.64 words per decade (95% confidence interval [CI] -3.3, -0.02) compared to no decline in those without retinopathy +0.06 (95% CI -0.6, 0.8) and 2) a higher frequency of rapid decliners on the DSS test. CONCLUSION: Signs of retinal vascular changes, as markers of the cerebral microvasculature, are associated with declines in executive function and psychomotor speed, adding to the growing evidence for the role of microvascular disease in cognitive decline in the elderly.

Risk of dementia hospitalisation associated with cardiovascular risk factors in midlife and older age: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Cardiovascular risk factors are associated with a higher risk of developing dementia. Studies in older populations, however, have often failed to show this relationship. We assessed the association between cardiovascular risk factors measured in midlife and risk of being hospitalised with dementia and determined whether this association was modified by age and ethnicity. METHODS: We studied 11 151 participants in the population-based Atherosclerosis Risk in Communities cohort, aged 46-70 (23% African-Americans) in 1990-2, when participants underwent a physical exam and cognitive testing. Hospitalisations with dementia were ascertained through December 2004. RESULTS: During follow-up, 203 cases of hospitalisation with dementia were identified. Smoking (hazard ratio (HR), 95% CI 1.7, 1.2 to 2.5), hypertension (HR, 95% CI 1.6, 1.2 to 2.2) and diabetes (HR, 95% CI 2.2, 1.6 to 3.0) were strongly associated with dementia, in Caucasians and African-Americans. These associations were stronger when risk factors were measured at a younger age than at an older age. In analyses including updated information on risk factors during follow-up, the HR of dementia in hypertensive versus non-hypertensive participants was 1.8 at age <55 years compared with 1.0 at age 70+ years. Parallel results were observed for diabetes (HR 3.4 in <55, 2.0 in >or=70), smoking (4.8 in <55, 0.5 in >or=70) and hypercholesterolaemia (HR 1.7 in <55, 0.9 in >or=70) CONCLUSION: In this prospective study, smoking, hypertension and diabetes were strongly associated with subsequent risk of hospitalisation with dementia, particularly in middle-aged individuals. Our results emphasise the importance of early lifestyle modification and risk factor treatment to prevent dementia.

Cerebral MRI findings and cognitive functioning: the Atherosclerosis Risk in Communities study.

OBJECTIVE: To examine the association between prevalent cerebral abnormalities identified on MRI and cognitive functioning in a predominantly middle-aged, population-based study cohort. METHODS: Cerebral MRI was performed on 1,538 individuals (aged 55 to 72) from the Atherosclerosis Risk in Communities (ARIC) cohort, with no history of stroke or TIA, at study sites in Forsyth County, NC, and Jackson, MS. White matter hyperintensities (WMHs), ventricular size, and sulcal size were graded by trained neuroradiologists on a semiquantitative, 10-point scale. Cognitive functioning was assessed using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). RESULTS: High ventricular grade was independently associated with significantly lower scores on the DWRT and DSST and greater risk (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.51 to 3.56) of impaired scores (i.e., < or =10th percentile) on the DWRT. High sulcal grade was associated with a modest decrement in scores on the DWRT. The presence of coexisting high grade WMHs and silent infarcts was independently associated with lower scores on all cognitive tests and greater risk of impaired functioning on the DSST (OR 2.91, 95% CI: 1.23 to 6.89) and WFT (OR 2.28, 95% CI 1.03 to 5.08). The presence of two or more high-grade abnormalities was associated with increased risk of impaired functioning on all cognitive tests (DWRT: OR 2.23, 95% CI 1.40 to 3.55; DSST: OR 2.06, 95% CI 1.13 to 3.76; WFT: OR 2.07, 95% CI 1.23 to 3.49) independent of multiple covariates and silent infarcts. CONCLUSION: Common changes in brain morphology are associated with diminished cognitive functioning in middle-aged and young-elderly individuals.

Does ticlopidine reduce reocclusion and other adverse events after successful balloon angioplasty of occluded coronary arteries? Results from the Total Occlusion Study of Canada (TOSCA).

OBJECTIVES: Ticlopidine reduces stent thrombosis and other adverse events among patients receiving coronary stents. Whether ticlopidine is beneficial after balloon angioplasty is unknown. Our purpose was to compare the clinical outcome of patients undergoing balloon angioplasty treated with both aspirin and ticlopidine versus aspirin alone. METHODS AND RESULTS: We performed a databank analysis of the Total Occlusion Study of Canada (TOSCA), a randomized trial with angiographic follow-up comparing the frequency of reocclusion after angioplasty of a subtotal or total coronary occlusion in patients receiving >/=1 heparin-coated Palmaz-Schatz stent versus balloon angioplasty alone. In TOSCA, 102 patients undergoing balloon angioplasty were treated with both aspirin and ticlopidine (generally for 15-30 days) and 94 were treated with aspirin alone, by physician preference. After 6 months, failure to sustain patency (less than Thrombolysis in Myocardial Infarction [TIMI] grade 3 flow on follow-up angiography) occurred in 23% of patients on ticlopidine and aspirin versus 16% of patients on aspirin alone (P =.21); the frequency of target vessel revascularization was also similar in the 2 groups (32% vs 25%, P =.27). Myocardial infarction was infrequent in both groups (2.0% vs 1.1%, respectively, P not significant). Patients treated with aspirin and ticlopidine had more adverse angiographic and procedural characteristics, including longer lesions and treatment lengths. Multivariate analysis to adjust for these and other differences failed to reveal a benefit of ticlopidine in maintaining patency and reducing adverse clinical events. CONCLUSIONS: After balloon angioplasty of a subtotal or total coronary occlusion, no reduction in adverse events was observed among patients in whom ticlopidine was added to aspirin, even after adjustment for clinical and lesion characteristics.

Are father surrogates a risk factor for child maltreatment?

Most research on the effect of father figures in the home on the incidence of child maltreatment has been cross-sectional and has focused on sexual abuse. This prospective study's purpose is to determine if the presence of a father surrogate in the home affects the risk of a subsequent child maltreatment report. In a longitudinal sample of at-risk children, North Carolina's Central Registry for Child Abuse and Neglect was used to determine the maltreatment history of children from birth to age 8 years. Children who had a father surrogate living in the home were twice as likely to be reported for maltreatment after his entry into the home than those with either a biological father (odds ratio = 2.6, 95 % confidence interval = 1.4-4.7) or no father figure in the home (odds ratio = 2.0, 95% confidence interval = 1.1-3.5).

Depression, heart rate variability, and acute myocardial infarction.

BACKGROUND: Clinical depression is associated with an increased risk for mortality in patients with a recent myocardial infarction (MI). Reduced heart rate variability (HRV) has been suggested as a possible explanation for this association. The purpose of this study was to determine if depression is associated with reduced HRV in patients with a recent MI. METHODS AND RESULTS: Three hundred eighty acute MI patients with depression and 424 acute MI patients without depression were recruited. All underwent 24-hour ambulatory electrocardiographic monitoring after hospital discharge. In univariate analyses, 4 indices of HRV were significantly lower in patients with depression than in patients without depression. Variables associated with HRV were then compared between patients with and without depression, and potential confounds were identified. These variables (age, sex, diabetes, and present cigarette smoking) were entered into an analysis of covariance model, followed by depression status. In the final model, all but one HRV index (high-frequency power) remained significantly lower in patients with depression than in patients without depression. CONCLUSIONS: We conclude that greater autonomic dysfunction, as reflected by decreased HRV, is a plausible mechanism linking depression to increased cardiac mortality in post-MI patients.

Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL density subfractions: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Despite consensus on the need for blood cholesterol reductions to prevent coronary heart disease (CHD), available evidence on optimal cholesterol levels or the added predictive value of additional lipids is sparse. METHODS AND RESULTS: After 10 years follow-up of 12 339 middle-aged participants free of CHD in the Atherosclerosis Risk in Communities Study (ARIC), 725 CHD events occurred. The lowest incidence was observed in those at the lowest LDL cholesterol (LDL-C) quintile, with medians of 88 mg/dL in women and 95 mg/dL in men, and risk accelerated at higher levels, with relative risks (RRs) for the highest quintile of 2.7 in women and 2.5 in men. LDL-C, HDL-C, lipoprotein(a) [Lp(a)], and in women but not men, triglycerides (TG) were all independent CHD predictors, providing an RR, together with blood pressure, smoking, and diabetes, of 13.5 in women and 4.9 in men. Lp(a) was less significant in blacks than whites. Prediction was not enhanced by HDL-C density subfractions or apolipoproteins (apo) A-I or B. Despite strong univariate associations, apoB did not contribute to risk prediction in subgroups with elevated TG, with lower LDL-C, or with high apoB relative to LDL-C. CONCLUSIONS: Optimal LDL-C values are <100 mg/dL in both women and men. LDL-C, HDL-C, TG, and Lp(a), without additional apolipoproteins or lipid subfractions, provide substantial CHD prediction, with much higher RR in women than men.

Predictors of improvement in left ventricular function after percutaneous revascularization of occluded coronary arteries: a report from the Total Occlusion Study of Canada (TOSCA).

BACKGROUND: The Total Occlusion Study of Canada (TOSCA) is a multicenter, randomized trial evaluating the effect of stenting with > =1 heparin-coated stent on long-term patency after percutaneous coronary intervention by balloon angioplasty of occluded coronary arteries. The purpose of the current study was to compare the effect of stenting and balloon angioplasty on global left ventricular ejection fraction (LVEF) and regional wall motion and to examine what clinical and angiographic factors may have an effect on left ventricular function in this setting. METHODS AND RESULTS: Analysis at the core angiographic laboratory of paired baseline and follow-up left ventricular angiograms, as well as target vessel patency, was possible in 244 of 410 cases. An improvement in LVEF was observed in the entire group (59.4% +/- 11% to 61.0% +/- 11%, P =.003). The LVEF change was +1.84 +/- 7.54 in the stent group (P =.009) and 1.28 +/- 8.16 in the percutaneous transluminal coronary angioplasty group (P =.085). There was no significant intergroup difference. Patients with duration of occlusion < or =6 weeks had an improvement in LVEF (+2.98 +/- 8.68, P =.0006), whereas those with an occlusion duration of > 6 weeks had no improvement (+0.48 +/- 7.01, P not significant). Multivariate analysis revealed baseline LVEF <60%, duration of occlusion < or =6 weeks, and Canadian Cardiology Society angina class I or II to be independent predictors of improvement in LVEF. CONCLUSIONS: The restoration of coronary patency of nonacute occluded coronary arteries is associated with a small but significant improvement in regional and global left ventricular function, especially in patients with recent occlusions and depressed left ventricular function. In spite of significant effect on long-term patency, stenting of nonacute coronary occlusions does not result in significantly better left ventricular function compared with balloon angioplasty in this setting.

A prospective study of coronary heart disease and the hemochromatosis gene (HFE) C282Y mutation: the Atherosclerosis Risk in Communities (ARIC) study.

Increased iron stores may play a role in the development of coronary heart disease (CHD) by increasing lipoprotein oxidation. Recently, mutations have been discovered in the gene (HFE) for hereditary hemochromatosis, an autosomal recessive condition of disordered iron metabolism, absorption, and storage. It is possible that people who carry HFE mutations have increased risk of CHD. We used a prospective case-cohort design (243 CHD cases and 535 non-cases) to determine whether the HFE C282Y mutation was associated with incident CHD in a population-based sample of middle-aged men and women. The frequencies of homozygosity and heterozygosity for the C282Y mutation in the ARIC study population were 0.2% (one homozygous person) and 6%, respectively. The C282Y mutation was associated with nonsignificantly increased risk of CHD (relative risk=1.60, 95% CI 0.9-2.9). After adjusting for other confounding risk factors (age, race, gender, ARIC community, smoking status, diabetes status, hypertension status, LDL cholesterol, HDL cholesterol, and triglycerides), the association became stronger (relative risk=2.70, 95% CI 1.2-6.1). However, a sensitivity analysis showed that this estimate of relative risk was somewhat unstable due to few subjects in some strata. Our prospective findings suggest that individuals carrying the HFE C282Y mutation may be at increased risk of CHD.

Psychosocial characteristics after acute myocardial infarction: the ENRICHD pilot study. Enhancing Recovery in Coronary Heart Disease.

PURPOSE: Psychosocial factors, such as emotional distress and social isolation, have been increasingly recognized as important risk factors for patients' recovery from acute myocardial infarction (AMI). This study examined age, gender, and ethnic differences in depression and general distress, social support, and health-related quality of life after AMI. METHODS: Data came from a series of 88 patients aged 62.1 +/- 14.2 years (46% female) who were hospitalized for AMI at eight different US clinical centers participating in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) Pilot Study. Standardized psychometric measures were administered to assess three psychosocial domains: (1) depression and general distress (mental health functioning), (2) social support, and (3) health-related quality of life. Multivariate analysis of variance was used to examine the effects of age, gender, and ethnic differences in each of the three psychosocial domains. RESULTS: Female patients reported higher levels of depression and distress compared with male patients (P = .040). Gender differences in mental health functioning differed by age (P = .046), with the greatest differences observed among younger female patients. Older patients (P = .014) and female patients (P = .025) reported lower levels of social support compared with younger and male patients, respectively. Minority patients did not differ from nonminority patients in mental health functioning or social support, and there were no significant differences in post-AMI quality of life on the basis of age, gender, or ethnicity. CONCLUSIONS: The psychosocial risk profile after AMI may be different for male and female patients, and interventions may need to take account of each gender's specific needs.

Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT).

BACKGROUND: This long-term, multicenter, randomized, double-blind, placebo-controlled, 2 x 2 factorial, angiographic trial evaluated the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis in normocholesterolemic patients. METHODS AND RESULTS: There were a total of 460 patients: 230 received simvastatin and 230, a simvastatin placebo, and 229 received enalapril and 231, an enalapril placebo (some subjects received both drugs and some received a double placebo). Mean baseline measurements were as follows: cholesterol level, 5.20 mmol/L; triglyceride level, 1.82 mmol/L; HDL, 0.99 mmol/L; and LDL, 3.36 mmol/L. Average follow-up was 47.8 months. Changes in quantitative coronary angiographic measures between simvastatin and placebo, respectively, were as follows: mean diameters, -0.07 versus -0.14 mm (P:=0.004); minimum diameters, -0.09 versus -0.16 mm (P:=0. 0001); and percent diameter stenosis, 1.67% versus 3.83% (P:=0.0003). These benefits were not observed in patients on enalapril when compared with placebo. No additional benefits were seen in the group receiving both drugs. Simvastatin patients had less need for percutaneous transluminal coronary angioplasty (8 versus 21 events; P:=0.020), and fewer enalapril patients experienced the combined end point of death/myocardial infarction/stroke (16 versus 30; P:=0.043) than their respective placebo patients. CONCLUSIONS: This trial extends the observation of the beneficial angiographic effects of lipid-lowering therapy to normocholesterolemic patients. The implications of the neutral angiographic effects of angiotensin-converting enzyme inhibition are uncertain, but they deserve further investigation in light of the positive clinical benefits suggested here and seen elsewhere.

Tests for gaussian repeated measures with missing data in small samples.

For small samples of Gaussian repeated measures with missing data, Barton and Cramer recommended using the EM algorithm for estimation and reducing the degrees of freedom for an analogue of Rao's F approximation to Wilks' test. Computer simulations led to the conclusion that the modified test was slightly conservative for total sample size of N=40. Here we consider additional methods and smaller sample sizes, Nin¿12,24¿. We describe analogues of the Pillai-Bartlett trace, Hotelling-Lawley trace and Geisser-Greenhouse corrected univariate tests which allow for missing data. Eleven sample size adjustments were examined which replace N by some function of the numbers of non-missing pairs of responses in computing error degrees of freedom. Overall, simulation results allowed concluding that an adjusted test can always control test size at or below the nominal rate, even with as few as 12 observations and up to 10 per cent missing data. The choice of method varies with the test statistic. Replacing N by the mean number of non-missing responses per variable works best for the Geisser-Greenhouse test. The Pillai-Bartlett test requires the stronger adjustment of replacing N by the harmonic mean number of non-missing pairs of responses. For Wilks' and Hotelling-Lawley, an even more aggressive adjustment based on the minimum number of non-missing pairs must be used.

Maternal disciplinary practices in an at-risk population.

OBJECTIVES: To describe maternal discipline of children in at-risk families and to determine factors associated with disciplinary practices. DESIGN: Cross-sectional survey. SETTING: At-risk families in North Carolina followed up in a longitudinal study of child maltreatment. PARTICIPANTS: Maternal caregivers of 7- to 9-year-old children with factors at birth that placed them at risk. MEASUREMENTS AND RESULTS: A total of 186 maternal caregivers were interviewed. A measure, based on coding parental responses, was used to assess disciplinary practices for 5 different misbehaviors. Limit setting was the most commonly used disciplinary practice for 4 of 5 misbehaviors, with 63% of mothers reporting that this method generally worked best. Spanking was more likely used as a secondary response for each misbehavior, when the primary one had not succeeded. Conversely, teaching or verbal assertion was always less likely as a secondary response. Teaching or verbal assertion was used more commonly for lying than for any other misbehavior, limit setting for disobeying, spanking for stealing, and spanking with an object for being disrespectful. Regression modeling for the 4 most common disciplinary practices showed (P<.05) that black race, lack of Aid to Families With Dependent Children receipt, more-educated mothers, and female sex of child were associated with higher use of teaching or verbal assertion; a biological father in the home was associated with less use of limit setting; and black race and report for child maltreatment were associated with more use of mild spanking. CONCLUSIONS: In this sample, limit setting was the most common disciplinary technique. Disciplinary practices used varied depending on the type of misbehavior and other contextual factors, including child, parent, and family characteristics.

School performance in a longitudinal cohort of children at risk of maltreatment.

OBJECTIVE: Previous research has suggested that child maltreatment is associated with poor school performance. However, previous studies have largely been cross-sectional or, if longitudinal, have had small sample sizes, short follow-up periods, or have not adequately controlled for confounders. The objective of this study is to determine the relationship between child maltreatment and school performance in a cohort of children at risk of maltreatment and followed since birth. METHOD: This prospective study followed children born at risk for maltreatment with semi-annual reviews of the North Carolina Central Registry of Child Abuse and Neglect. At ages six and eight years, children's teachers were surveyed using the Achenbach Teacher Report Form and project-developed questions regarding peer status. This information, along with control variables from maternal interviews, was used in logistic regression models to determine the impact of maltreatment on academic performance, peer status, and adaptive functioning. The generalized estimating equations (GEE) method was applied to adjust variance estimates for within-person correlations of school performance measures at two points in time. RESULTS: A substantiated maltreatment report is significantly associated with poorer academic performance (p < 0.01) and poorer adaptive functioning (p < 0.001) but not with peer status. CONCLUSIONS: Understanding the consequences of maltreatment, including poor academic performance and adaptive functioning, is important in planning educational, health, and social service interventions that may help abused or neglected children succeed in school and later in life. Longitudinal analysis is the best way to establish a causal relationship between maltreatment and subsequent school problems.

Patterns of practice in emergency department management of chest pain of suspected cardiac origin: clinical utility of single stat creatine kinase (CK).

The patterns of practice and the clinical utility of a single stat creatine kinase (CK) level in the emergency department management of chest pain of suspected cardiac origin were examined by a prospective observational study using a two-part questionnaire, completed by physicians before and after availability of CK results. The results showed that of the 776 patients in the study, 135 were admitted to hospital with acute myocardial infarction (AMI), 285 were admitted for reasons other than AMI, 343 were discharged, and 13 died or were transferred to another hospital. Although initial and final diagnoses in the emergency department did not differ in 597 patients (77%), initial decisions to admit or discharge were made in only 244 (31%) patients without waiting for CK results, and in 401 (52%) cases, decisions on patient disposition were deferred. Of 218 patients who had elevated CK levels, 193 (89%) were admitted, 121 for AMI. Only five (< 1%) patients who would otherwise have been discharged were admitted because of elevated CK levels. Of the 343 discharges, 245 (71%) occurred after the physicians knew the CK results. It is concluded that emergency department physicians routinely make changes in their diagnostic and management decisions based on current information and as it becomes updated. This study also suggests that there appears to be a heavy reliance on a single CK assay, although the relative importance of this diagnostic test compared to other factors is not known. Further studies are necessary.