Area characteristics and individual-level socioeconomic position indicators in three population-based epidemiologic studies.

PURPOSE: There is growing interest in incorporating area indicators into epidemiologic analyses. Using data from the 1990 U.S. Census linked to individual-level data from three epidemiologic studies, we investigated how different area indicators are interrelated, how measures for different sized areas compare, and the relation between area and individual-level social position indicators. METHODS: The interrelations between 13 area indicators of wealth/income, education, occupation, and other socioenvironmental characteristics were investigated using correlation coefficients and factor analyses. The extent to which block-group measures provide information distinct from census tract measures was investigated using intraclass correlation coefficients. Loglinear models were used to investigate associations between area and individual-level indicators. RESULTS: Correlations between area measures were generally in the 0.5--0.8 range. In factor analyses, six indicators of income/wealth, education, and occupation loaded on one factor in most geographic sites. Correlations between block-group and census tract measures were high (correlation coefficients 0.85--0.96). Most of the variability in block-group indicators was between census tracts (intraclass correlation coefficients 0.72--0.92). Although individual-level and area indicators were associated, there was evidence of important heterogeneity in area of residence within individual-level income or education categories. The strength of the association between individual and area measures was similar in the three studies and in whites and blacks, but blacks were much more likely to live in more disadvantaged areas than whites. CONCLUSIONS: Area measures of wealth/income, education, and occupation are moderately to highly correlated. Differences between using census tract or block-group measures in contextual investigations are likely to be relatively small. Area and individual-level indicators are far from perfectly correlated and provide complementary information on living circumstances. Differences in the residential environments of blacks and whites may need to be taken into account in interpreting race differences in epidemiologic studies.

Health-associated changes in drinking: a period prevalence study of the Atherosclerosis Risk In Communities (ARIC) cohort (1987-1995).

BACKGROUND: Several investigators have suggested that drinking cessation occurs because of poor health which may bias studies on the benefit or risk of alcohol consumption. METHODS: Drinking status, level of alcohol consumption, and two measures of health (perceived health and physician diagnosed chronic disease status) were determined from exams 1 (1987-1989) and 3 (1993-1995) on 12,562 African- and European-American participants, who were aged 45-64 years at exam 1 in the ARIC Study. For those in good health at exam 1, logistic regression analyses were used to model the association between health decline and drinking change at exam 3. RESULTS: Among the total population, drinking cessation was significantly more common among those who reported poor health at exam 3, and nondrinkers were unlikely to begin drinking regardless of exam 3 health. Using different measures of health status resulted in associations whose strength and significance varied with ethnicity and, in some cases, by gender. CONCLUSION: While the current data do not prove that the health decline occurred prior to drinking cessation, our findings support the hypothesis that poor health results in drinking changes which could potentially bias studies of alcohol's benefit and risk even when lifetime abstainers are used as the reference group.

Anger proneness predicts coronary heart disease risk: prospective analysis from the atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Increased research attention is being paid to the negative impact of anger on coronary heart disease (CHD). METHODS AND RESULTS: This study examined prospectively the association between trait anger and the risk of combined CHD (acute myocardial infarction [MI]/fatal CHD, silent MI, or cardiac revascularization procedures) and of "hard" events (acute MI/fatal CHD). Participants were 12 986 black and white men and women enrolled in the Atherosclerosis Risk In Communities study. In the entire cohort, individuals with high trait anger, compared with their low anger counterparts, were at increased risk of CHD in both event categories. The multivariate-adjusted hazard ratio (HR) (95% CI) was 1.54 (95% CI 1.10 to 2.16) for combined CHD and 1.75 (95% CI 1.17 to 2.64) for "hard" events. Heterogeneity of effect was observed by hypertensive status. Among normotensive individuals, the risk of combined CHD and of "hard" events increased monotonically with increasing levels of trait anger. The multivariate-adjusted HR of CHD for high versus low anger was 2.20 (95% CI 1.36 to 3.55) and for moderate versus low anger was 1.32 (95% CI 0.94 to 1.84). For "hard" events, the multivariate-adjusted HRs were 2.69 (95% CI 1.48 to 4.90) and 1.35 (95% CI 0.87 to 2.10), respectively. No statistically significant association between trait anger and incident CHD risk was observed among hypertensive individuals. CONCLUSIONS: Proneness to anger places normotensive middle-aged men and women at significant risk for CHD morbidity and death independent of the established biological risk factors.

Body weight change and carotid artery wall thickness. The Atherosclerosis Risk in Communities (ARIC) Study.

The impact of weight change in adulthood on cardiovascular disease is controversial. This study examined the association of change in body weight, from young adulthood to middle age, with average carotid artery intimal-medial wall thickness by B-mode ultrasound measured in middle age. Participants were 13,282 men and women aged 45-64 years from the baseline examination of the Atherosclerosis Risk in Communities (ARIC) Study (1987-1989). Weight change was calculated as the difference between weight at the baseline examination and self-reported weight at age 25. White men gained a mean of 9.7 kg; black men, 10.1 kg; white women, 12.0 kg; and black women, 20.8 kg. Weight change was positively, albeit modestly, associated with intimal-medial thickness in black men and white men and in white women, but not in black women. Adjusted for age, examination center, smoking, education, sports activity level, height, and body mass index at age 25, the differences in intimal-medial thickness associated with a 10-kg increment in weight change were 0.016 (95% confidence interval 0.010 to 0.022) mm in white men, 0.008 (95% confidence interval 0.001 to 0.015) mm in black men, 0.013 (95% confidence interval 0.009 to 0.017) mm in white women, and 0.002 (95% confidence interval -0.002 to 0.006) mm in black women. These findings support the hypothesis that weight gain in adulthood promotes atherosclerotic changes in white men and women and in black men.

Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987-1989.

As part of the Atherosclerosis Risk in Communities (ARIC) Study assessment of the etiology and sequelae of atherosclerosis, a standardized questionnaire on transient ischemic attack (TIA) and nonfatal stroke and a computerized diagnostic algorithm simulating clinical reasoning were developed and tested at the four ARIC field centers: Forsyth County, North Carolina; Minneapolis, Minnesota; Jackson, Mississippi; and Washington County, Maryland. The diagnostic algorithm used participant responses to a series of questions about six neurologic trigger symptoms to identify symptoms of TIA or stroke and their vascular distribution. Among 12,205 ARIO participants reporting their lifetime occurrence of one or more symptoms probably due to cerebrovascular causes, nearly half (47%) reported the sudden onset of at least one symptom sometime prior to their ARIC examination. Of those with at least one symptom, only 12.9% were classified by the computer algorithm as having symptoms of TIA or stroke. Dizziness/loss of balance was the most frequently reported symptom (36%); 1.2% of these persons were classified by the algorithm as having a TIA/stroke event. Positive symptoms of speech dysfunction were classified most often (77.%) as being symptoms of TIA or stroke. Symptoms suggesting TIA were reported more frequently than symptoms suggesting stroke by both sexes. TIA or stroke-like phenomena were more frequent (p < 0.001) in females (7%) than in males (5%) and increased with age in both sexes (p = 0.13 for females; p = 0.02 for males). In Forsyth County, TIA and stroke symptoms were greater in African Americans than in Caucasians (p = 0.05, controlling for sex). The association of algorithmically defined symptoms of TIA or stroke with traditional cerebrovascular risk factors is the subject of a companion paper.

Association of transient ischemic attack/stroke symptoms assessed by standardized questionnaire and algorithm with cerebrovascular risk factors and carotid artery wall thickness. The ARIC Study, 1987-1989.

The baseline examination (1987-1989) for the Atherosclerosis Risk in Communities (ARIC) Study was conducted in 15,792 free-living residents aged 45-64 years in four geographically dispersed US communities. A questionnaire on symptoms of transient ischemic attack (TIA) and stroke was evaluated by computer algorithm for 12,205 of these participants. Data were also collected on lipoprotein levels, hemostasis, hematology, anthropometry, blood pressure, medical history, lifestyle, socioeconomic status, and medication use. Noninvasive high resolution B-mode ultrasonographic imaging was used to determine carotid arterial intimal-medial wall thickness (IMT). The cross-sectional relation between the prevalence of TIA/stroke symptoms and putative risk factors was assessed by logistic regression, controlling for age and community. Odds ratios for TIA/stroke symptoms were significantly elevated (p < or = 0.01) for diabetes mellitus, current smoking, hypertension, lower levels of education, income, and work activity, and higher levels of lipoprotein(a), IMT, hemostasis factor VIII, and von Willebrand factor. However, the relations with education and carotid IMT were not present for black Americans. In whites, the relations of TIA/stroke symptoms to IMT were nonlinear. Only at extreme levels of IMT were symptoms substantially more frequent: For example, men with an IMT greater than 1.17 mm or women with an IMT greater than 0.85 mm had approximately twice the odds of having positive TIA/stroke symptoms as those with lower IMTs. The authors plan in future analyses to address the issue prospectively, as well as to examine the relation with magnetic resonance imaging-defined outcomes and clinically defined incident stroke.

Association of postprandial triglyceride and retinyl palmitate responses with asymptomatic carotid artery atherosclerosis in middle-aged men and women. The Atherosclerosis Risk in Communities (ARIC) Study.

Blood lipid alterations after a fatty meal may be atherogenic, but there is little information regarding their associations with disease independent of fasting lipids. Asymptomatic atherosclerosis cases (n = 229) and 373 control subjects free of atherosclerosis, as defined by carotid intima-media thickness on ultrasound images, were given a fatty meal with vitamin A, followed by 3.5- and 8-hour measurements of triglycerides (TGs), TG-rich lipoprotein TGs, apoproteinB48, and retinyl palmitate. Among white men and women but not among blacks, case status was associated with greater postprandial responses of TGs and TG-rich lipoprotein TGs, but only in nonobese persons (body mass index < 30 kg/m2). The associations were strong and significant after controlling for coronary risk factors (odds ratio, approximately 2.0) and fasting TGs (odds ratio, 1.5). Associations with other postprandial lipid measurements did not persist after controlling for fasting lipids. Elevated postprandial TGs appear to be an independent risk factor for carotid intimal thickening in nonobese whites. The lack of such a relation in obese subjects and the lipid profile they manifest suggest that postprandial TGs must be accompanied by accumulation of TG-rich lipoprotein remnants to be atherogenic.

Formation of two microtubule-nucleating sites which perform differently during centrosomal reorganization in a mouse cochlear epithelial cell.

This report provides evidence for the formation of a cell surface-associated centrosome with two spatially discrete microtubule-nucleating sites that perform differently; the minus ends of microtubules remain anchored to one site but escape from the other. Centrosomal reorganization in the cells in question, outer pillar cells of the organ of Corti, indicates that its pericentriolar material becomes intimately associated with the plasma membrane at the two nucleating sites. Two large microtubules bundles assemble in each cell. A beam which includes about 1,300 microtubules spans most of the cell apex. It is positioned at right angles to a pillar with about 4,500 microtubules which is oriented parallel to the cell's longitudinal axis. The beam's microtubules elongate from, and remain attached to, a centrosomal region with two centrioles which acts as a microtubule-nucleating site. However, the elongating microtubules do not radiate from the immediate vicinity of the centrioles. During beam assembly, the minus ends of the microtubules are concentrated together close to the plasma membrane (less than 0.2 micron away in many cases) at a site which is located to one side of the cell apex. High concentrations of the pillar's microtubules elongating from one particular site have not been detected. Analyses of pillar assembly indicate that the following sequence of events occurs. Pillar microtubules elongate from an apical cell surface-associated nucleating site, which becomes more distantly separated from the centriolar locality as cell morphogenesis progresses. Microtubules do not accumulate at this apical nucleating site because they escape from it. They migrate down to lower levels in the cell where the mature bundle is finally situated and their plus ends are captured at the cell base.

Reorganization of the centrosome and associated microtubules during the morphogenesis of a mouse cochlear epithelial cell.

Reorganization of centrosomal microtubule-organizing centres and the minus ends of microtubules occurs as the centrosomal ends of large microtubule bundles are repositioned and anchored to cell junctions in certain epithelial cells called inner pillar cells in the mouse organ of Corti. The microtubule bundle that assembles in each cell consists of two distinct microtubule arrays that run closely alongside each other. Both arrays are attached to the cell surface at their upper and lower ends. One of the arrays spans the entire length of a cell but the other is confined to its lower portion. Initially, about 3,000 microtubules elongate downwards from an apically situated centrosome in each cell. Subsequently, the minus ends of these microtubules, and the centrosome and its two centrioles, migrate for about 12 microns to the tip of a laterally directed projection. Then, a meshwork of dense material accumulates to link microtubule minus ends and the centrosome to cell junctions at the tip of the projection. Pericentriolar satellite bodies, which form after the initial burst of microtubule nucleation, may represent a condensed and inactive concentration of microtubule-nucleating elements. Surprisingly, as a cell matures, about 2,000 microtubules are eliminated from the centrosomal end of the microtubule bundle. However, about 2,000 microtubules are added to the basal portion of each bundle at levels that are remote with respect to the location of the centrosome. Possibly, these microtubules have escaped from the centrosome. If this is the case, then both the plus and minus ends of most of the errant microtubules are captured by sites at the cell surface where the ends are finally anchored. Alternatively, each cell possesses at least one other major microtubule-nucleating site (which does not possess centrioles) in addition to its centrosome.

Prevalence of stroke and transient ischemic attacks in the Atherosclerosis Risk in Communities (ARIC) study.

The Atherosclerosis Risk in Communities (ARIC) study is a population-based observational study of randomly sampled, census-based populations in four locations within the United States. The study was designed to determine whether there are regional differences in incidence, prevalence, and mortality rates from cardiovascular and cerebrovascular disease in populations aged 45 to 64 years. Both cohort examinations and community surveillance are included. In addition to a standardized transient ischemic attack (TIA) and stroke questionnaire and algorithm for determination of incidence and prevalence, B-scan ultrasonography is used to quantify the degree of atherosclerotic changes in the carotid artery. Initiated in late 1986, the first cohort evaluation was completed in early 1990. The third, which includes magnetic resonance imaging of the brain, is in progress and will be completed in 1996. Positive responses to the TIA/stroke questionnaire increase by decile of age, are greater in women than men, and are more frequent in African Americans than Caucasians. The baseline study using an algorithm for categorization of patient responses into vascular and other causes of TIA and stroke estimated prevalence of 5.5% in African Americans and 6.3% in Caucasians.

Microtubule rearrangement and bending during assembly of large curved microtubule bundles in mouse cochlear epithelial cells.

Mature inner pillar cells in the mammalian organ of Corti are curved through about 60 degrees, where they arch over adjacent epithelial cells and the apex of an intercellular space called the tunnel of Corti. This report deals with changes in microtubule organization that are associated with cell bending and tunnel formation during morphogenesis of the mouse organ of Corti. A large bundle of up to 3,000 microtubules assembles in each inner pillar cell. Microtubule rearrangement occurs about 5 days after bundle assembly begins. The lumen of each initially straight hollow tube-shaped microtubule bundle is occluded as the bundle becomes more compact and elliptical in cross section. This event anticipates the once-only bending which subsequently occurs between particular levels (about 9-19 microns) below the top of a bundle as it curves into its final shape about 2 days later. Microtubule rearrangement presumably facilitates bending which is effected in the plane of least mechanical resistance parallel to the short axis of a bundle's elliptical cross-sectional profile. Precocious bending of bundles has been induced about 1.5 days in advance of the natural event. Abnormal positioning of these prematurely curved bundles indicates that bending is effected by a contractile mechanism located within bundles rather than being a response to externally applied forces. The potential importance of such microtubule-associated contractions for active modulation of the vibratory response in the cochlea during hearing is considered.

A cell surface-associated centrosomal layer of microtubule-organizing material in the inner pillar cell of the mouse cochlea.

This investigation provides evidence that pericentriolar material is divorced from the immediate vicinities of centrioles and becomes functionally associated with the plasmalemma during the differentiation of a mammalian cell type. Such events occur prior to the assembly of large transcellular microtubule bundles in columnar epithelial cells called inner pillar cells in the mouse organ of Corti. The microtubules do not radiate from a typical centrosome and its centrioles. They elongate from a microtubule-organizing centre (MTOC), which is deployed as a subapical cell surface-associated layer in each cell. Most of the dense material of this layer, and the tops of most of the microtubules, are initially concentrated around the sides of a cell about 1 microns below its apical surface. In addition, a pair of centrioles is located above the layer, which acts as if it is a pericellular concentration of the pericentriolar material of a modified centrosome. Although microtubule nucleation takes place in a centrosome-like region, 13 protofilament fidelity is not exercised. Most of the microtubules have 15 protofilaments. Microtubule assembly progresses in these cells after the organ of Corti has been isolated for in vitro culture. However, large numbers of microtubules elongate from pericentriolar material juxtaposed against the centrioles. Hence, there is some reversion by the centrosomes of cultured cells to the operational configuration regarded as typical for animal tissue cells in general.