Screening mammography under age 50.
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Biomedical subjects
Publications and source records attributed to S Shea.
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CONTEXT: Moderate alcohol consumption has been shown to be protective for coronary heart disease, but the relationship between moderate alcohol consumption and ischemic stroke is more controversial. OBJECTIVE: To determine the association between alcohol consumption and risk of ischemic stroke. DESIGN: Population-based case-control study conducted between July 1993 and June 1997. SETTING: Multiethnic population in northern Manhattan, New York, NY, aged 40 years or older. PATIENTS AND OTHER PARTICIPANTS: Cases (n = 677) had first ischemic stroke and were matched to community controls (n = 1139) derived through random digit dialing by age, sex, and race/ethnicity. Mean +/- SD age of cases was 70.0+/-12.7 years; 55.8% were women; 19.5% were white, 28.4% black, and 50.7% Hispanic. MAIN OUTCOME MEASURE: First ischemic stroke (fatal or nonfatal). RESULTS: Moderate alcohol consumption, up to 2 drinks per day, was significantly protective for ischemic stroke after adjustment for cardiac disease, hypertension, diabetes, current smoking, body mass index, and education (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.39-0.67). This protective effect of alcohol consumption was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. In a quadratic model of stroke risk, increased risk of ischemic stroke was statistically significant among those consuming 7 or more drinks per day (OR, 2.96; 95% CI, 1.05-8.29). CONCLUSIONS: Moderate alcohol consumption was independently associated with a decreased risk of ischemic stroke in our elderly, multiethnic, urban subjects, while heavy alcohol consumption had deleterious effects. Our data support the National Stroke Association Stroke Prevention Guidelines regarding the beneficial effects of moderate alcohol consumption.
Cytoskeletal rearrangements and a membrane lipid phase transition (liquid crystalline to gel) occur in platelets on cooling from 23 to 4 degrees C. A consequence of these structural alterations is irreversible cellular damage. We investigated whether platelet membrane integrity could be preserved by (a) previously studied combinations of a calcium chelator (EGTA) and microfilament stabilizer (cytochalasin B) with apparent benefit in protecting platelets from cooling injury or (b) agents of known benefit in protecting membranes and proteins from freezing injury. Platelet function and activation before and after freezing or cooling were measured by agglutination with ristocetin, aggregation with thrombin or ADP, platelet-induced clot retraction (PICR), and expression of P-selectin. Platelets were loaded with 10 nM fluorescein diacetate. After freezing or cooling, the preparations were centrifuged and the supernatant was measured for fluorescein. For cooling experiments, fresh platelets were chilled at 4 degrees C for 1 to 21 days with or without the combination of 80 microM EGTA/AM and 2 microM cytochalasin B (EGTA/AM-CytoB) and then warmed rapidly at 37 degrees C. For freezing experiments, 5% dimethyl sulfoxide (Me2SO) or 5 mM glycerol were added to fresh platelets. The preparations were then frozen at -1 degrees C/min to -70 degrees C and then thawed rapidly at 37 degrees C. Platelet membrane integrity, as measured by supernatant levels of fluorescein, correlated inversely with platelet function. Chilling platelets at 4 degrees C with EGTA/AM-CytoB showed a gradual loss of membrane integrity, with maximum loss reached on day 7. The loss of membrane integrity preceded complete loss of function as demonstrated by PICR. In contrast, platelets chilled without these agents had complete loss of membrane integrity and function after 1 day of storage. Freezing platelets in Me2SO resulted in far less release of fluorescein than did freezing with or without other cryoprotectants (P < 0.001). This result correlated with enhanced function as demonstrated by PICR and supports earlier observations that Me2SO protects platelet membranes from freezing injury. Release of fluorescein into the surrounding medium reflected loss of membrane integrity and function in both cooled and frozen platelets. Membrane cytoskeletal rearrangements are linked to membrane changes during storage. These results may be generally applicable to the study of platelet storage.
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Lipoprotein (a) (Lp(a)) is an established cardiovascular risk factor in adults. We sought to evaluate whether raised Lp(a) levels were predictive of a family history of early cardiovascular disease (CVD) in children already at increased risk for premature atherosclerosis because of elevated low-density lipoprotein (LDL) cholesterol levels. Lp(a) and serum lipid levels were measured in 69 children and offspring with established moderate to severe hypercholesterolemia (serum cholesterol > 170 mg/dL) who were aged 10.7 +/- 4.3 years (range 1.5 to 21 years) and had been referred to a pediatric lipid center. The children represented families with a positive (n = 27) or negative (n = 42) history for premature CVD (<55 years of age in parent or grandparent). In all children, Lp(a) levels ranged from 1 to 140 mg/dL, with a median of 29 mg/dL. Mean total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol levels were 234 mg/dL, 166 mg/dL, and 45 mg/dL, respectively. There was no difference in median Lp(a) levels between the children with a positive family history and those with a negative family history (29.9 mg/dL vs 29.0 mg/dL, respectively). In contrast, children with a positive family history showed significantly higher LDL cholesterol levels (186 +/- 61 mg/dL vs 153 +/- 52 mg/dL, P = .02). Thus, in this group of hypercholesterolemic children, LDL cholesterol but not Lp(a) levels were associated with a family history of premature CVD. Further studies are needed to identify additional specific risk factors associated with the development of CVD in this population.
The aims of our study were to assess the validity and reliability of a telephone survey instrument designed to measure vascular disease risk factors and to assess whether these measurements were influenced by age, gender, race/ethnicity, or other sociodemographic variables. Subjects were sampled and interviewed using random digit dialing methodology from the multiethnic community of northern Manhattan. For the validity study, 261 consecutive subjects were clinically assessed in-person within 60 days of the telephone interview. A retest reliability study of the telephone interview was conducted in 92 randomly selected subjects within 30 days of the initial interview. The telephone interview instrument had a sensitivity of more than 55% and a specificity of 74% or greater for various vascular disease risk factors. Sensitivity, specificity, and positive predictive value did not vary significantly or systematically among whites, blacks, and Hispanics, but subjects with access to health care were more likely to provide valid data. The reliability substudy indicated a good reliability for the telephone interview. These results support the validity of telephone interviews for estimating the prevalence of vascular risk factors in urban populations.
OBJECTIVES: This study examined the prevalence, social correlates, and clustering of cardiovascular disease risk factors in a predominantly Black, poor, urban community. METHODS: Associations of risk factor prevalences with sociodemographic variables were examined in a population-based sample of 695 men and women aged 18 to 65 years living in Central Harlem. RESULTS: One third of the men and women were hypertensive, 48% of the men and 41% of the women were smokers, 25% of the men and 49% of the women were overweight, and 23% of the men and 35% of the women reported no leisure-time physical activity over the past month. More than 80% of the men and women had at least 1 of these risk factors, and 9% of the men and 19% of the women had 3 or more risk factors. Income and education were inversely related to hypertension, smoking, and physical inactivity. Having 3 or more risk factors was associated with low income and low education (extreme odds ratio [OR] = 10.2, 95% confidence interval [CI] = 3.0, 34.5 for education; OR = 3.7, CI = 1.6, 8.9 for income) and with a history of unstable work or of homelessness. CONCLUSIONS: Disadvantaged, urban communities are at high risk for cardiovascular disease. These results highlight the importance of socioenvironmental factors in shaping cardiovascular risk.
BACKGROUND: The epsilon4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. METHODS: We reviewed clinical diagnoses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sensitivity and specificity of the clinical diagnosis or the presence of an APOE epsilon4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard. The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to generate receiver-operating-characteristic curves plotting sensitivity against the false positive rate. RESULTS: Of the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer's disease, and the diagnosis was confirmed pathologically in 1770 patients at autopsy. Sixty-two percent of patients with clinically diagnosed Alzheimer's disease, as compared with 65 percent of those with pathologically confirmed Alzheimer's disease, had at least one APOE epsilon4 allele. The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and specificity of the APOE epsilon4 allele were 65 and 68 percent, respectively. The addition of information about the APOE genotype increased the overall specificity to 84 percent in patients who met the clinical criteria for Alzheimer's disease, although the sensitivity decreased. The improvement in specificity remained statistically significant in the multivariate analysis after adjustment for differences in age, clinical diagnosis, sex, and center. CONCLUSIONS: APOE genotyping does not provide sufficient sensitivity or specificity to be used alone as a diagnostic test for Alzheimer's disease, but when used in combination with clinical criteria, it improves the specificity of the diagnosis.
The term "horse-racing effect" refers to a positive correlation between the slope at which blood pressure increases with age and blood pressure level at a baseline. Previous studies have reported such an effect in adults, while studies in children have found a negative correlation (termed "the Jenss effect"). These studies used analytic methods in which it was assumed that the blood pressure slopes were constant or the blood pressure profiles were linear. In this study, the authors used a components-of-variance approach that did not require this assumption in order to model serial blood pressure measurements made in 216 US preschool children (mean age at first analyzable blood pressure observation, 58.9 months) at 6-13 visits over a 3-year period (1986-1989). Measurements were made using an automated blood pressure monitor. Values from the second and third measures at each visit were averaged to obtain each observation. Data from 2,203 blood pressure observations were available for analysis. For the full group, over the mean period of observation of 21.1 months, the mean rate of increase was 3.45 mmHg/year for systolic blood pressure and 0.06 mmHg/year for diastolic blood pressure. In the authors' model, 33 percent of the total marginal variability in systolic blood pressure was attributed to random error (visit-to-visit variability); average (constant) subject-specific difference from the population slope accounted for 42 percent, and a nonlinear component of variability around the subject-specific average accounted for the remaining 25 percent. All three components were statistically significant. Models which assumed that the slopes were constant did not fit these data, and fitting these models to the data led to an artifactual negative correlation between subject-specific slopes and intercepts. An implication of this is that the concepts of "horse-racing" and "the Jenss phenomenon," which have been operationalized by testing the covariance of the subject-specific slopes and intercepts using models which assume that the blood pressure slopes are constant over time, should not be applied to data that contain this nonlinear component of variance.
Stroke mortality is reported to be greater in blacks than in whites, but stroke incidence data for blacks and Hispanics are sparse. The aim of this study was to determine and compare stroke incidence rates among whites, blacks, and Hispanics living in the same urban community. A population-based incidence study was conducted to identify all cases of first stroke occurring in northern Manhattan, New York City, between July 1, 1993, and June 30, 1996. The population of this area was approximately 210,000 at that time, based on 1990 US Census data. Surveillance for hospitalized and nonhospitalized stroke consisted of daily screening of all admissions, discharges, and computed tomography logs at Columbia-Presbyterian Medical Center, the only hospital in the region, and review of discharge lists from outside hospitals, telephone surveys of random households, and contacts with community physicians, Visiting Nurses' Services, and community agencies. Stroke incidence increased with age and was greater in men than in women. The average annual age-adjusted stroke incidence rate at age > or =20 years, per 100,000 population, was 223 for blacks, 196 for Hispanics, and 93 for whites. Blacks had a 2.4-fold and Hispanics a twofold increase in stroke incidence compared with whites. Cerebral infarct accounted for 77 percent of all strokes, intracerebral hemorrhage for 17 percent, and subarachnoid hemorrhage for 6 percent. These data from the Northern Manhattan Stroke Study suggest that part of the reported excess stroke mortality among blacks in the United States may be a reflection of racial/ethnic differences in stroke incidence.
Prerandomization run-in periods are being used to select or exclude patients in an increasing number of clinical trials, but the implications of run-in periods for interpreting the results of clinical trials and applying these results in clinical practice have not been systematically examined. We analyzed illustrative examples of reports of clinical trials in which run-in periods were used to exclude noncompliant subjects, placebo responders, or subjects who could not tolerate or did not respond to active drug. The Physicians' Health Study exemplifies the use of a prerandomization run-in period to exclude subjects who are nonadherent, while recent trials of tacrine for Alzheimer disease and carvedilol for congestive heart failure typify the use of run-in periods to exclude patients who do not tolerate or do not respond to the study drug. The reported results of these studies are valid. However, because the reported results apply to subgroups of patients who cannot be defined readily based on demographic or clinical characteristics, the applicability of the results in clinical practice is diluted. Compared with results that would have been observed without the run-in period, the reported results overestimate the benefits and underestimate the risks of treatment, underestimate the number needed to treat, and yield a smaller P value. The Cardiac Arrhythmia Suppression Trial exemplifies the use of an active-drug run-in period that enhances clinical applicability by selecting a group of study subjects who closely resembled patients undergoing active clinical management for this problem. Run-in periods can dilute or enhance the clinical applicability of the results of a clinical trial, depending on the patient group to whom the results will be applied. Reports of clinical trials using run-in periods should indicate how this aspect of their design affects the application of the results to clinical practice.
The goal of the study was to examine the association between family status and several health-related variables, such as perceived general health, health behavior and self-reported morbidity. Data were derived from Health Surveys conducted in West Germany in the framework of the German Cardiovascular Prevention Study. 25'229 males and 26'097 females, aged 25 to 69 years, were examined. Age-adjusted prevalence odds ratios, calculated by multiple logistic regression analysis, were used as effect measure. The reference category was "married, living with partner" throughout. For most health-related variables significantly higher prevalence odds ratios, indicating unhealthy conditions, were observed for "singles", including persons never married, persons living separated, and divorced or widowed persons. Two or more unhealthy health behaviors were found most frequently for divorced persons of either sex. Age-adjusted odds ratios for self-reporting of three or more chronic diseases were 1.31 (p < 0.01) for divorced males, and 1.66 (p < 0.001) for divorced females. Both men and women who were divorced or separated were characterized by an unfavourable health profile.
Hypercholesterolemic children are increasingly being treated with lipid-lowering diets, but little research has focused on the effects of specific dietary substitutions on HDL cholesterol. We examined the relation between carbohydrate intake and HDL cholesterol in hypercholesterolemic children consuming fat-restricted diets. We obtained 3-d food records for 67 children (mean age: 5.8 +/- 2.5 y) referred for the treatment of hypercholesterolemia. Mean plasma HDL cholesterol was 1.12 +/- 0.21 mmol/L and total cholesterol was 5.99 +/- 1.39 mmol/L. Dietary intake comprised (percentage of total energy) 24.9 +/- 5.1% fat, 59.9 +/- 6.5% carbohydrate, and 16.5 +/- 3.4% protein. Carbohydrate intake included 30.7 +/- 7.4% from simple and 22.6 +/- 6.2% from complex carbohydrates. HDL cholesterol was positively correlated with intake of total fat (r = 0.44, P < 0.001) and saturated fatty acids (r = 0.43, P < 0.001) and inversely correlated with intake of total carbohydrate (r = -0.55, P < 0.001) and simple carbohydrate (r = -0.40, P < 0.001), but not with complex carbohydrate (r = -0.02). The significant inverse relation between simple carbohydrate intake and HDL cholesterol remained after intakes of saturated, monounsaturated, and polyunsaturated fatty acids; intake of complex carbohydrates; dietary cholesterol; plasma triacylglycerol; and age were adjusted for with multivariate techniques. In summary, higher dietary intake of simple carbohydrates was associated with lower HDL-cholesterol concentrations in hypercholesterolemic children consuming reduced-fat diets.
Previous studies have shown that CD4+ T cells are responsible for the great strength of cell-mediated xenograft rejection in the mouse. In vitro studies have suggested that this CD4+ response is to xenogeneic antigens that are presented indirectly. The present studies were carried out in order to determine whether the strength of cell-mediated xenograft rejection in vivo is dependent on the CD4+ indirect response. We grafted pig skin onto mice that express class II MHC antigens only on their thymic epithelial cells (II-4+ mice). These mice have normal numbers of functional peripheral CD4+ T cells; however they lack class II MHC expression on their antigen presenting cells and are thus incapable of mounting a CD4+ T cell-mediated indirect response. Xenograft survival was prolonged on these mice. Furthermore, administration of cyclosporine and anti-CD8 monoclonal antibodies to II-4+ recipients prolonged xenograft survival to at least the same extent as allograft survival, demonstrating that the strength of cell-mediated xenograft rejection resides in the CD4+ indirect response. Despite the increased survival time, xenograft rejection still occurred in the absence of the indirect pathway. Depletion of the II-4+ recipients of their CD4+ T cell population prolonged xenograft survival even further, suggesting the presence of a weaker CD4+ direct mechanism which was virtually undetectable in vitro.
Cardiovascular disease is the major cause of excess mortality among urban US blacks, but autopsy data comparing black-white differences in underlying pathological causes of cardiovascular death are lacking. We reviewed all 720 adult cases autopsied in 1991 in the New York City Medical Examiner's Office in which the coded cause of death was cardiovascular disease (International Classification of Diseases, 9th Revision, codes 391, 393 to 398, 401 to 404, 410, 411, 414 to 417, 420 to 438, and 440 to 444). After exclusion of 133 cases because race was missing or coded as other than black or white, gender was not coded, or there was an unusual circumstances of death or extreme obesity, 587 cases were available for analysis. There were 314 black and 273 white subjects. Black women were younger than white women at time of death (mean age, 54.7 versus 61.5 years; P<.001), whereas black and white men did not differ in mean age at death. Hypertensive vascular disease was the autopsy cause of death in 42% of blacks compared with 23% of whites (P<.001). Conversely, atherosclerotic heart disease was the autopsy cause of death in 64% of white subjects but only 38% of blacks. These patterns were consistent in both sexes and after adjustment for age. Hypertensive vascular disease was far more common than atherosclerotic heart disease as the cause of death at autopsy among blacks compared with whites in New York City, whereas atherosclerotic heart disease was more common in whites. These findings suggest that ineffective control of hypertension is a major factor contributing to excess cardiovascular mortality among urban blacks.
BACKGROUND AND PURPOSE: Physical activity reduces the risk of premature death and cardiovascular disease, but the relationship to stroke is less well studied. The objective of this study was to investigate the association between leisure-time physical activity and ischemic stroke in an urban, elderly, multiethnic population. METHODS: The Northern Manhattan Stroke Study is a population-based incidence and case-control study. Case subjects had first ischemic stroke, and control subjects were derived through random-digit dialing with 1:2 matching for age, sex, and race/ethnicity. Physical activity was recorded through a standardized in-person interview regarding the frequency and duration of 14 activities over the 2 prior weeks. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals after adjustment for medical and socioeconomic confounders. RESULTS: Over 30 months, 369 case subjects and 678 control subjects were enrolled. Mean age was 69.9 +/- 12 years; 57% were women, 18% whites, 30% blacks, and 52% Hispanics. Leisure-time physical activity was significantly protective for stroke after adjustment for cardiac disease, peripheral vascular disease, hypertension, diabetes, smoking, alcohol use, obesity, medical reasons for limited activity, education, and season of enrollment (OR = 0.37; 95% confidence interval=0.25 to 0.55). The protective effect of physical activity was detected in both younger and older groups, in men and women, and in whites, blacks, and Hispanics. A dose-response relationship was shown for both intensity (light-moderate activity OR = 0.39; heavy OR = 0.23) and duration (<2 h/wk OR = 0.42; 2 to <5 h/wk OR = 0.35; > or =5 h/wk OR = 0.31) of physical activity. CONCLUSIONS: Leisure-time physical activity was related to a decreased occurrence of ischemic stroke in our elderly, multiethnic, urban subjects. More emphasis on physical activity in stroke prevention campaigns is needed among the elderly.
OBJECTIVES: This study examined the effects of a school-based intervention designed to promote the consumption of low-fat white milk at lunchtime in 6 elementary schools in an inner-city, primarily Latino neighborhood. METHODS: A multifaceted intervention based on social marketing techniques was delivered at 3 randomly selected schools. The school was the unit of assignment and analysis; 6902 children were involved in the study. Milk selection and consumption were measured by sampling discarded milk and/or tallying milk carton disappearance at baseline, immediately postintervention, and at 3 to 4 months follow-up. RESULTS: Immediately postintervention, the mean proportion of sampled milk cartons that contained low-fat milk increased in the intervention schools, from 25% to 57%, but remained constant at 28% in the control schools. Differences between intervention and control schools remained significant at 3 to 4 months follow-up. The intervention was not associated with a decrease in overall milk consumption. CONCLUSIONS: A school-based intervention can lead to significant increases in student consumption of low-fat milk.
Coronary heart disease (CHD) and cancers of the breast, prostate, and colon are more common in industrialized countries than in the developing world, and to some degree, these conditions appear to share risk factors. To investigate whether there is an association between these cancers and a prior history of CHD, a hospital-based case-control study was conducted at Columbia-Presbyterian Medical Center in New York. The study was based on 252 breast cancer cases, 256 colorectal cancer cases, and 322 benign surgical controls, all of whom underwent biopsy or surgery between January 1989 and December 1992, and on 319 prostate cancer cases and 189 benign prostatic hypertrophy controls diagnosed between January 1984 and December 1986 (prior to widespread use of prostate-specific antigen screening). Medical records were reviewed on each, focusing on the preoperative anesthesia and surgical clearances. No association was found between a history of CHD and breast or colorectal cancer, but an elevated risk was found for prostate cancer (odds ratio, 2.00; 95% confidence interval, 1.18-3.39), using unconditional logistic regression with adjustment for appropriate confounders. No association was found between cigarette smoking and any of the three cancers. Aspirin use was protective for colorectal cancer (odds ratio, 0.35; 95% confidence interval, 0.17-0.73) but had no association with breast or prostate cancer. The study suggests that individuals with CHD are at elevated risk for prostate cancer but not breast or colorectal cancer. Etiological risk factors associated with CHD should be investigated with regard to prostate cancer. Patients with CHD may represent a high-risk group for prostate cancer and potential future targets for prostate cancer screening interventions.