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.

Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age.

Recommendations for control of high blood pressure (BP) emphasize lifestyle modification, including weight loss, reduced sodium intake, increased physical activity, and limited alcohol consumption. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern also lowers BP. The PREMIER randomized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups. Participants with above-optimal BP through stage 1 hypertension were randomized to an Advice Only group or one of two behavioural interventions that implement established recommendations (Est) or established recommendations plus DASH diet (Est plus DASH). The primary outcome was change in systolic BP at 6 months. The study population was 810 individuals with an average age of 50 years, 62% women, 34% African American (AA), 95% overweight/obese, and 38% hypertensive. Participants in all the three groups made lifestyle changes. Mean net reductions in systolic (S) BP in the Est intervention were 1.2 mmHg in AA women, 6.0 in AA men, 4.5 in non-AA women, and 4.2 in non-AA men. The mean effects of the Est Plus DASH intervention were 2.1, 4.6, 4.2, and 5.7 mmHg in the four race-sex subgroups, respectively. BP changes were consistently greater in hypertensives than in nonhypertensives, although interaction tests were nonsignificant. The Est intervention caused statistically significant BP reductions in individuals over and under age 50. The Est Plus DASH intervention lowered BP in both age groups, and significantly more so in older individuals. In conclusion, diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk.

Is diabetes an independent risk factor for mortality after myocardial infarction? The ARIC (Atherosclerosis Risk in Communities) Surveillance Study.

We investigated the age-, gender- and race-specific 1-year case fatality rates of diabetic and non-diabetic individuals with a myocardial infarction. Data were obtained from the Atherosclerosis Risk in Communities (ARIC) Surveillance Study, which monitors both hospitalized myocardial infarction and coronary heart disease (CHD) deaths in residents aged 35-74 years in four communities in the USA. The study population comprised 3242 hospitalized myocardial infarctions (HMIs) in diabetic subjects and 9826 HMIs in non-diabetic individuals between 1987 and 1997. Age-adjusted and gender- and race-specific odds ratios (OR) for 1-year case fatality comparing diabetic to non-diabetic patients were 2.0 (95% CI, 1.6-2.4) for white men and 1.4 (95% CI, 1.1-1.8) for white women. Further adjustment for severity of HMI, history of previous MI, stroke and hypertension, and therapy variables showed significantly higher case fatality in white diabetic men than in non-diabetic white men (OR=1.5; 95% CI, 1.2-1.9), but no significant association in the other race-gender groups. The age-adjusted odds of out of hospital death was significantly higher among white diabetic men (OR=1.7; 95% CI, 1.2-2.3), white women (OR=2.3; 95% CI, 1.4-3.8), and African-American women (OR=2.9; 95% CI, 1.5-5.9) as compared to their non-diabetic counterparts. In conclusion, diabetes is an independent factor for mortality within one year following a myocardial infarction among white men, and following out-of hospital coronary death in white men and women and in African-American women. It is possible that these differences could be explained, at least in part, by a less than optimal medical management of the high cardiovascular risk profile of these patients after hospital discharge.

Retinal microvascular abnormalities and incident stroke: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Retinal microvascular abnormalities reflect damage from hypertension and other vascular processes. We examined the relation of such abnormalities to incident stroke. METHODS: A cohort of 10358 men and women (aged 51 to 72 years) living in four US communities underwent retinal photography and standard grading for retinal microvascular abnormalities. The calibres of all retinal arterioles and venules were measured after digital conversion of the photographs, and a summary arteriole-to-venule ratio (AVR) was calculated as an index of arteriolar narrowing (smaller AVR indicates greater narrowing). Cases of incident stroke admitted to hospital were identified and validated by case record reviews. FINDINGS: Over an average of 3.5 years, 110 participants had incident strokes. After adjustment for age, sex, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, most retinal microvascular characteristics were predictive of incident stroke, with adjusted relative risks of 2.58 (1.59-4.20) for any retinopathy, 3.11 (1.71-5.65) for microaneurysms, 3.08 (1.42-6.68) for soft exudates, 2.55 (1.27-5.14) for blot haemorrhages, 2.26 (1.00-5.12) for flame-shaped haemorrhages, and 1.60 (1.03-2.47) for arteriovenous nicking. The relative risk of stroke increased with decreasing AVR (p=0.03). The associations were similar for ischaemic strokes specifically, and for strokes in individuals with hypertension, either with or without diabetes. INTERPRETATION: Retinal microvascular abnormalities are related to incident stroke. The findings support a microvascular role in the pathogenesis of stroke. They suggest that retinal photography may be useful for cerebrovascular-risk stratification in appropriate populations.

Validation of death certificate diagnosis for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study.

The validity of the death certificate in identifying coronary heart disease deaths was evaluated using data from the community surveillance component of the Atherosclerosis Risk in Communities Study (ARIC). Deaths in the four ARIC communities of Forsyth Co., NC; Jackson, MS; Minneapolis, MN; and Washington Co., MD were selected based on underlying cause of death codes as determined by the rules of the ninth revision of the International Classification of Diseases (ICD-9). Information about the deaths was gathered through informant interviews, physician or coroner questionnaires, and medical record abstraction, and was used to validate the cause of death. Sensitivity, specificity, and positive predictive value of the death certificate classification of CHD death (ICD-9 codes 410-414 and 429.2) were estimated by comparison with the validated cause of death based on physician review of all available information. Results from 9 years of surveillance included a positive predictive value 0.67 (95% CI 0.66-0.68), sensitivity of 0.81 (95% CI 0.79-0.83), and a false-positive rate (1-specificity) of 0.28 (95% CI 0.26-0.30). Comparing CHD deaths as defined by the death certificate with validated CHD deaths indicated that the death certificate overestimated CHD mortality by approximately 20% in the ARIC communities. Within subgroups, death certificate overestimation was reduced with advancing age (up to age 74), was consistent over time, was not dependent on gender, and exhibited considerable variation among communities.

Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study.

The objective of this study was to describe associations of retinal arteriolar abnormalities with clinical and subclinical manifestations of atherosclerosis and a broad group of risk factors for vascular disease. A biracial population of 8772 adults (aged 48 to 72 years) living in 4 communities was examined from 1993 to 1995 were studied for that purpose. Retinal arteriovenous nicking and focal arteriolar narrowing were determined by light-box grading of a 45 degrees fundus photograph by use of a standardized protocol. Diameters of arterioles and venules were measured in digitized photographs, and a summary arteriolar-to-venular ratio was derived as an index of generalized arteriolar narrowing. Focal arteriolar narrowing was associated only with hypertension. Generalized arteriolar narrowing was associated with carotid plaque but not with any other evidence of atherosclerosis, either clinical (cardiovascular disease or stroke) or subclinical (carotid or popliteal artery thickness or lower limb obstructive disease), or with plasma cholesterol. It was also associated with smoking, with inflammatory markers (white blood cell count, fibrinogen, and reduced albumin), and with the triglyceride and high density lipoprotein cholesterol changes associated with inflammation. Arteriovenous nicking was inconsistently associated with subclinical atherosclerosis. It was not associated with cardiovascular disease, stroke, or plasma cholesterol. Arteriovenous nicking was associated with markers of inflammation and vascular endothelial dysfunction (von Willebrand factor and factor VIII). Arteriolar narrowing and nicking appear to be related to hypertension and inflammatory factors. Nicking may also be related to endothelial dysfunction. Results suggest that these arteriolar changes are pathologically distinct from atherosclerosis. Including their measurement in population studies may permit evaluation of the independent contribution of arteriolar disease to various ischemic diseases of the heart, brain, and other organs.

Trends in severity of hospitalized myocardial infarction: the atherosclerosis risk in communities (ARIC) study, 1987-1994.

BACKGROUND: Declining mortality rates of coronary heart disease in the United States could be attributable to declining incidence, declining severity, and/or improvements in treatment. METHODS: We examined trends in severity of patients hospitalized for myocardial infarction to characterize its contribution to this decline by using data from the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: No significant change in the proportion having systolic blood pressure <100 mm Hg or an abnormal pulse at presentation was noted. The proportion with ST-segment elevation on the initial electrocardiogram increased 10% per year (P <.001), and the proportion with a diagnostic or evolving diagnostic electrocardiogram abnormality increased 4% per year (P <.01); the proportion that had a new Q-wave infarction develop remained unchanged. The mean peak creatine kinase level decreased 5% per year (P <.001), the proportion with abnormal enzyme levels decreased 10% per year (P <.001), and the proportion that met criteria for definite myocardial infarction decreased 4% per year (P <.05). The proportion that had cardiogenic shock decreased 10.9% per year (P <. 01), but the proportion that had an acute episode of congestive heart failure was stable. CONCLUSIONS: With stable hemodynamic indicators, worsening electrocardiographic indicators, and improving enzymatic indicators, these results provide mixed support for decreases in the severity of myocardial infarction.

Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. METHODS: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. MAIN OUTCOME MEASURES: Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). RESULTS: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. CONCLUSION: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.

Prehospital delay in patients hospitalized with heart attack symptoms in the United States: the REACT trial. Rapid Early Action for Coronary Treatment (REACT) Study Group.

BACKGROUND: The use of thrombolytic therapy for patients with myocardial infarction has been limited by patient delay in seeking care. We sought to characterize prehospital delay in patients hospitalized for evaluation of heart attack symptoms. METHODS AND RESULTS: The Rapid Early Action for Coronary Treatment (REACT) is a multicenter, randomized community trial designed to reduce patient delay. At baseline, data were abstracted from the medical records of 3783 patients hospitalized for evaluation of heart attack symptoms in 20 communities. The median prehospital delay was 2.0 hours; 25% of patients delayed longer than 5.2 hours. In a multivariable analysis, delay time was longer among non-Hispanic blacks than among non-Hispanic whites, longer at older ages, longer among Medicaid-only recipients and shorter among Medicare recipients than among privately insured patients, and shorter among patients who used an ambulance. CONCLUSIONS: The observed pattern of differences is consistent with the contention that demographic, cultural, and/or socioeconomic barriers exist that impede rapid care seeking.

Survival of premenopausal breast carcinoma patients in relation to menstrual cycle timing of surgery and estrogen receptor/progesterone receptor status of the primary tumor.

BACKGROUND: Premenopausal breast carcinoma patients who undergo tumor excision during the follicular phase of their menstrual cycle may have a significantly worse prognosis than those whose tumors are excised in other phases of the menstrual cycle. METHODS: Outcome was determined in a series of 112 premenopausal women with operable breast carcinoma in relation to the timing of surgery within the menstrual cycle and the estrogen receptor (ER) and progesterone receptor (PR) status of their primary tumors as determined by immunohistochemistry. RESULTS: Those patients with ER positive tumors who underwent surgery in the early and luteal phase of the cycle had a significantly better survival than women with ER negative tumors (chi-square test = 15.56; P < 0.001). This also was true for PR status (chi-square test = 18.21; P < 0.001). After follicular phase surgery, tumor receptor status had no effect on overall survival. Patients with the best prognosis had ER/PR positive tumors excised on Days 0-2 and 13-32 but even those women with ER or PR negative tumors removed during the luteal phase of their menstrual cycle fared better than patients whose tumors were removed during the follicular phase. CONCLUSIONS: There was a better survival rate for patients with both ER/PR positive and negative tumors treated during the luteal phase of the menstrual cycle. This could be the result of progesterone acting on the surrounding peritumoral normal tissue, thereby exerting a straitjacket effect and improving cohesion of the primary carcinoma. Unopposed estrogen in the follicular phase of the cycle may enable more tumor emboli to escape and successfully establish micrometastases.

Prevalence of age-related maculopathy in the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To describe the prevalence of age-related maculopathy (ARM) in blacks and whites and its relation to macrovascular disease and risk factors thereof in a population studied for cardiovascular disease risk factors and outcomes. POPULATION: A biracial population of 11532 adults (ranging from 48-72 years of age; 8984 whites and 2548 blacks) living in 4 US communities (Forsyth County, North Carolina; the city of Jackson, Miss; selected suburbs of Minneapolis, Minn; and Washington County, Maryland) were examined during the interval from 1993 to 1995. METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of 1 eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System. RESULTS: The overall prevalence of any ARM was lower in blacks (3.7%) than whites (5.6%). After controlling for age and sex, the odds ratio for any ARM in blacks compared with whites was 0.73 (95% confidence interval, 0.58-0.91; P = .006). Few associations between atherosclerosis and its risk factors and the presence of early ARM or its component lesions were found. After adjusting for age, race, and sex, carotid artery plaque (odds ratio, 1.77; 95% confidence interval, 1.18-2.65) and focal retinal arteriolar narrowing (odds ratio, 1.79; 95% confidence interval, 1.07-2.98) were associated with retinal pigment epithelial depigmentation. CONCLUSIONS: This population-based study documents the higher prevalence of early ARM in whites compared with blacks. Measures of atherosclerosis and its risk factors were generally unrelated to ARM and do not explain these racial differences.

Sex and race differences in short-term prognosis after acute coronary heart disease events: the Atherosclerosis Risk In Communities (ARIC) study.

BACKGROUND: Case fatality after myocardial infarction (MI) among patients admitted to the hospital may differ between men and women and blacks and whites. Furthermore, a different pattern of sex and race differences in case fatality may occur when coronary deaths outside the hospital are included in the analysis. The ARIC study provides community-based data to examine 28-day case fatality rates after coronary heart disease (CHD) events. METHOD AND RESULTS: Surveillance of out-of-hospital CHD deaths and hospitalized MI was conducted in 4 U.S. communities from 1987 to 1993. Hospital discharges and death certificates were sampled, medical records abstracted, and interviews conducted with witnesses of out-of-hospital deaths. MI and out-of-hospital death classifications followed a standard algorithm. Linkage of hospitalized MIs to fatality within 28 days ensured complete ascertainment of case fatality rate. Comorbidities and complications during hospital stay were compared to assess possible explanatory factors for differences in case fatality. Overall, age-adjusted 28-day case fatality (MI plus CHD) was higher in black men compared with white men (odds ratio 1.78, 95% confidence interval 1.4-2.2) and in black women compared with white women (odds ratio 1.5, 95% confidence interval 1. 2-2.0). Although men had higher overall case fatality rates than did women, this difference was not statistically significant. After a hospitalized MI, 28-day case fatality rate was not statistically significantly different between men compared with women or blacks compared with whites. CONCLUSION: Race and sex differences in case fatality after hospitalized MI were not evident in these data, although when out-of-hospital deaths were included, men and blacks were more likely than women and whites to die within 28 days of an acute cardiac event. A majority of deaths occurred before hospital admission, and additional study of possible reasons for these differences should be a priority.

Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND: Several markers of hemostatic function and inflammation have been associated with increased risk of coronary heart disease, but prospective evidence for their role in ischemic stroke is scant. METHODS AND RESULTS: The Atherosclerosis Risk in Communities (ARIC) Study measured several of these markers in more than 14 700 participants 45 to 64 years old who were free of cardiovascular disease and were followed up for 6 to 9 years for occurrence of ischemic stroke (n=191). There was no apparent association between ischemic stroke incidence and factor VIIc, antithrombin III, platelet count, or activated partial thromboplastin time. After adjustment for multiple cardiovascular risk factors, von Willebrand factor, factor VIIIc, fibrinogen, and white blood cell count were positively associated and protein C was negatively but nonsignificantly associated with ischemic stroke incidence in regression analyses based on either continuous variables or fourths of the variable distributions. The adjusted relative risk (and 95% CI) for ischemic stroke in those in the highest versus lowest fourth were: von Willebrand factor, 1.71 (1.1 to 2.7); factor VIIIc, 1.93 (1.2 to 3.1); white blood cell count, 1.50 (0.9 to 2.4); fibrinogen, 1.26 (0.8 to 2.0); and protein C, 0.65 (0.4 to 1.0). CONCLUSIONS: This study offers modest support for the hypothesis that some markers of hemostatic function and inflammation can identify groups of middle-aged adults at increased risk of stroke. These factors may play a role in the pathogenesis of ischemic stroke.

Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study.

Narrowing and other changes in retinal arterioles may reflect damage due to hypertension, which may predict stroke and other cardiovascular diseases independently of blood pressure level. Newly developed quantitative methods of assessing retinal narrowing are used to determine whether this sign is related only to current blood pressure or whether it also independently reflects the effects of previous blood pressure. Retinal photography was performed at the third examination of Atherosclerosis Risk in Communities (ARIC) Study in 1993-1995, and results are presented for the 9,300 nondiabetic participants aged 50-71 years. Generalized narrowing of smaller arterioles was strongly and monotonically related to current blood pressure in men and women, whether they were taking antihypertensive medications or not, and, independent of current blood pressure, was consistently and monotonically related to blood pressure levels measured 3 and 6 years before the retinal assessment. Arteriovenous nicking was also independently related to both current and previous blood pressures. The patterns of association suggested that these signs reflect both transient and persisting structural effects of elevated blood pressure, in agreement with the scant pathologic literature available. The findings suggest that retinal assessment may be useful for research on the microvascular contributions to clinical cardiovascular diseases.

Prospective associations of fasting insulin, body fat distribution, and diabetes with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

OBJECTIVE: We tested the hypothesis that diabetes, body fat distribution, and (in nondiabetic subjects) fasting insulin levels are positively associated with ischemic stroke incidence in the general population. RESEARCH DESIGN AND METHODS: As part of the Atherosclerosis Risk in Communities (ARIC) Study, we measured diabetes by using fasting glucose criteria, waist and hip circumferences, and fasting insulin levels with a radioimmunoassay in > 12,000 adults aged 45-64 years who had no cardiovascular disease at baseline. We followed them for 6-8 years for ischemic stroke occurrence (n = 191). RESULTS: After adjustment for age, sex, race, ARIC community, smoking, and education level, the relative risk of ischemic stroke was 3.70 (95% CI 2.7-5.1) for diabetes, 1.74 (1.4-2.2) for a 0.11 increment of waist-to-hip ratio, and 1.19 (1.1-1.3) for a 50-pmol/l increment of fasting insulin among nondiabetic subjects. Ischemic stroke incidence was not statistically significantly associated with BMI (comparably adjusted relative risk = 1.15, 95% CI 0.97-1.36). With adjustment for other stroke risk factors (some of which may mediate the effects of diabetes, fat distribution, and hyperinsulinemia), the relative risks for diabetes, waist-to-hip ratio, and fasting insulin level were 2.22 (95% CI 1.5-3.2), 1.08 (0.8-1.4), and 1.14 (1.01-1.3), respectively. CONCLUSIONS: Diabetes is a strong risk factor for ischemic stroke. Aspects of insulin resistance, as reflected by elevated waist-to-hip ratios and elevated fasting insulin levels, may also contribute to a greater risk of ischemic stroke.

Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994.

BACKGROUND AND METHODS: To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). RESULTS: The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval for the change, +0.5 to +14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. CONCLUSIONS: From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction.

Cell proliferation measured by MIB1 and timing of surgery for breast cancer.

We have investigated the use of the antibody MIB1 as a proliferative and prognostic marker in breast cancer and whether changes in proliferative activity could account for differences in prognosis of premenopausal women operated on during different phases of the menstrual cycle. MIB1 expression was strongly correlated with S-phase fraction and histological grade. There was no difference in MIB1 scores between different phases of the menstrual cycle. Both MIB1 score and timing of surgery correlated significantly with duration of survival, while the two together were even stronger predictors of overall survival. Women with slowly proliferating tumours surgically removed in the luteal phase had a very good prognosis, whereas women with rapidly proliferating tumours excised at other times of the cycle had a worse prognosis.

Physical activity and incidence of coronary heart disease in middle-aged women and men.

Few studies of physical activity and coronary heart disease (CHD) have included women or blacks. We examined this association in a biracial cohort of 45- to 64-yr-old adults. We related the sports, leisure, and work indices developed by J. A. H. Baecke et al. to CHD incident events (N = 97 in women, N = 223 in men) over 4-7 yr in the Atherosclerosis Risk in Communities study. The age-, race-, and field center-adjusted relative risk of CHD was 0.73 in women and 0.82 in men per each standard deviation increment in the sports index (P < 0.05). For the leisure index, these relative risks were 0.78 for both sexes (P < 0.05). The work index was not associated with CHD. These inverse associations held for non-blacks, but there was no association between the sport or leisure indices and CHD among blacks. Vigorous sports participation was strongly inversely associated with CHD, but an independent contribution of nonvigorous activity (e.g., walking) could not be demonstrated conclusively. Adjustment for other risk factors attenuated the relative risks, as one might expect if these risk factors mediated any protective effect of physical activity. Our findings reinforce evidence that regular physical activity should protect women, as well as men, from CHD. Explanations for no association among blacks, if real, are needed.

Neighborhood environments and coronary heart disease: a multilevel analysis.

The authors investigated whether neighborhood socioeconomic characteristics are associated with coronary heart disease prevalence and risk factors, whether these associations persist after adjustment for individual-level social class indicators, and whether the effects of individual-level indicators vary across neighborhoods. The study sample consisted of 12,601 persons in four US communities (Washington County, Maryland; Forsyth County, North Carolina; Minneapolis, Minnesota; and Jackson, Mississippi) participating in the baseline examination of the Atherosclerosis Risk in Communities Study (1987-1989). Neighborhood characteristics were obtained from 1990 US Census block-group measures. Multilevel models were used to estimate associations with neighborhood variables after adjustment for individual-level indicators of social class. Living in deprived neighborhoods was associated with increased prevalence of coronary heart disease and increased levels of risk factors, with associations generally persisting after adjustment for individual-level variables. Inconsistent associations were documented for serum cholesterol and disease prevalence in African-American men. For Jackson African-American men living in poor neighborhoods, coronary heart disease prevalence decreased as neighborhood characteristics worsened. Additionally, in African-American men from Jackson, low social class was associated with increased serum cholesterol in "richer" neighborhoods but decreased serum cholesterol in "poorer" neighborhoods. Neighborhood environments may be one of the pathways through which social structure shapes coronary heart disease risk.

The poor quality of early evaluations of magnetic resonance imaging.

To study the quality of early research on the clinical efficacy of diagnostic imaging with magnetic resonance, we assessed 54 evaluations published in the first four years after introduction of this modality using ten commonly accepted criteria of research methodology. The terms sensitivity, specificity, false-positive or false-negative, accuracy, and predictive values were used infrequently. Nineteen percent of the evaluations used three terms appropriately, 48% used one or two terms, and 33% used none. Data were presented appropriately for one or more of the five terms in 59% of evaluations. A "gold standard" comparison with the results of an independent procedure, such as surgical or autopsy findings, was presented in 22% of evaluations. Results of another imaging procedure were described in 63% of evaluations. Only one evaluation clearly described a prospective study design, although 11 evaluations apparently were planned in advance. Not one evaluation contained an appropriate statistical analysis of the distributions of quantitative readings, "blinded" image readers to diagnosis or other test results, measured observer error, or randomized the order of magnetic resonance imaging and other imaging procedures. We conclude that health care professionals paying for expensive innovative diagnostic technology should demand better research on diagnostic efficacy.