Population-based cohort studies.
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Case-Control Studies↗
Biomedical subjects
M Szklo
Publications and source records attributed to M Szklo.
Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987-1993.
Few studies have determined whether greater carotid artery intima-media thickness (IMT) in asymptomatic individuals is associated prospectively with increased risk of coronary heart disease (CHD). In the Atherosclerosis Risk in Communities Study, carotid IMT, an index of generalized atherosclerosis, was defined as the mean of IMT measurements at six sites of the carotid arteries using B-mode ultrasound. The authors assessed its relation to CHD incidence over 4-7 years of follow-up (1987-1993) in four US communities (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; and Washington County, Maryland) from samples of 7,289 women and 5,552 men aged 45-64 years who were free of clinical CHD at baseline. There were 96 incident events for women and 194 for men. In sex-specific Cox proportional hazards models adjusted only for age, race, and center, the hazard rate ratio comparing extreme mean IMT (> or = 1 mm) to not extreme (< 1 mm) was 5.07 for women (95% confidence interval 3.08-8.36) and 1.85 for men (95% confidence interval 1.28-2.69). The relation was graded (monotonic), and models with cubic splines indicated significant nonlinearity. The strength of the association was reduced by including major CHD risk factors, but remained elevated at higher IMT. Up to 1 mm mean IMT, women had lower adjusted annual event rates than did men, but above 1 mm their event rate was closer to that of men. Thus, mean carotid IMT is a noninvasive predictor of future CHD incidence.
Age Distribution↗
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.
Black or African American↗
"Epidemiological practices in assessing small effects": conclusions from a conference held in Berlin/Potsdam, Germany, 10-13 October 1995.
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Epidemiologic Factors↗
Diabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: The Cardiovascular Health Study.
This report describes the relation among diabetes, blood pressure, and prevalent cardiovascular disease, and echocardiographically measured left ventricular mass and filling (transmitral valve flow) velocities in the Cardiovascular Health Study, a cohort of 5201 men and women > or = 65 years of age. Ventricular septal and left posterior wall thicknesses were greater in diabetic than in nondiabetic subjects, showing a significant linear trend (p = 0.025 for ventricular septal thickness in both sexes combined, p = 0.002 for posterior wall thickness) with increased duration of diabetes. Increased wall thickness of the ventricular septum or the left posterior wall was not associated with prevalent coronary heart disease (CHD) in the cohort. Increased left ventricular mass was associated with diabetic persons not reporting CHD and with all subjects with CHD regardless of glucose tolerance status. After adjusting for body weight, blood pressure, heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as measured by glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination) remained an independent predictor of increased left ventricular mass among men and women (174.2 gm in diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in normal women, p = 0.043 for both sexes combined). Both early and late diastolic transmitral peak flow velocities were higher with increased duration of diabetes, but the calculated ratio of the early peak flow velocity to the late velocity (E/A ratio) did not differ significantly between subjects with historical diabetes and those with normal fasting glucose (both genders combined, p = 0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination were significant independent predictors of the late transmitral peak flow velocity and its integrated flow-velocity curve but not for the integral of the early peak flow velocity or the E/A ratio. Diabetes is associated with abnormal left ventricular structure and function in elderly persons. This association persists after adjustment for body weight, blood pressure, heart rate, and reported coronary or cerebrovascular disease.
Aged↗
Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults.
PURPOSE: Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic disease. To examined the relationship between vitamin intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of 322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects without evidence of this disease. METHODS: All of these individuals were selected from a probability sample of 15,800 men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: Plasma homocyst(e)ine was inversely associated with intakes of folate, vitamin B6, and vitamin B12 (controls only for this vitamin)--the three key vitamins in homocyst(e)ine metabolism. Among nonusers of vitamin supplement products, on average each tertile increase in intake of these vitamins was associated with 0.4 to 0.7 mumol/L decrease in plasma homocyst(e)ine. An inverse association of plasma homocyst(e)ine was also found with thiamin, riboflavin, calcium, phosphorus, and iron. Methionine and protein intake did not show any significant association with plasma homocyst(e)ine. CONCLUSIONS: In almost all analyses, cases and controls showed similar associations between dietary variables and plasma homocyst(e)ine. Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 mumol/L lower than that among nonusers. Further studies to examine possible causal relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular disease are needed.
Analysis of Variance↗
Cytomegalovirus infection, lipoprotein(a), and hypercoagulability: an atherogenic link?
A link between cytomegalovirus (CMV) infection and atherosclerosis has been suggested by experimental, clinical, and epidemiologic studies. We investigated the association between CMV antibody titers in serum collected in 1974 in 300 adult residents in Washington County, Md, and hemostatic parameters in plasma collected in 1987 through 1989, when these individuals participated in the baseline examination of the Atherosclerosis Risk in Communities Study. The cross-sectional association of CMV serum antibodies and hemostatic parameters was also explored in another set of Atherosclerosis Risk in Communities cases and controls. In the longitudinal analyses, CMV titers in 1974 were directly associated with 1987 through 1989 plasma levels of von Willebrand factor, factor VIII, and protein C and negatively associated with activated partial thromboplastin time. In the cross-sectional analyses, CMV titers were directly related to antithrombin III and fibrinogen levels. When the association between CMV antibodies and atherosclerosis was examined in stratified analyses, a significant association was restricted to individuals with high levels of lipoprotein(a) and fibrinogen. These results are compatible with previous evidence suggesting that CMV virus might have procoagulant properties. The possible synergism of CMV infection and resulting hypercoagulability with reduced fibrinolysis due to increased lipoprotein(a) levels deserves further investigation.
Antibodies, Viral↗
A prospective study of coronary heart disease in relation to fasting insulin, glucose, and diabetes. The Atherosclerosis Risk in Communities (ARIC) Study.
OBJECTIVE: To determine the association of coronary heart disease (CHD) incidence with diabetes, fasting serum glucose, and insulin in a biracial cohort of middle-aged men and women. RESEARCH DESIGN AND METHODS: We examined a population-based sample (n = 13,446 free of baseline CHD) from four U.S. communities in 1987-1989. We defined diabetes on the basis of baseline fasting glucose concentration (> or = 7.8 mmol/l), medical history, and current medications. A central laboratory measured fasting insulin with a nonspecific radioimmunoassay. After 4-7 years, 209 men and 96 women developed CHD. RESULTS: After adjustment for sociodemographic characteristics, smoking status, ethanol intake, sports participation, and hormone replacement therapy, the relative risk of CHD for people with diabetes versus those without diabetes was 3.45 (95% CI 2.16-5.50) among women and 2.52 (1.78-3.56) among men. Relative risks of CHD with diabetes were somewhat lower in blacks than non-blacks, but because diabetes was more than twice as prevalent in blacks, the percentage of CHD cases attributable to diabetes (population attributable risk) was 27% for black women, 15% for non-black women, 8% for black men, and 12% for non-black men. Among people without diabetes, fasting glucose was not independently associated with CHD incidence. Among women without diabetes, there was a positive association between fasting insulin and CHD; multivariable adjusted relative risks of CHD across quintiles of fasting insulin were 1.00, 0.76, 2.08, 2.08 and 2.82 (P for linear trend = 0.02). However, among men without diabetes, fasting insulin and CHD were not associated. CONCLUSIONS: Diabetes conveys a high risk of CHD in black and non-black middle-aged men and women. Fasting insulin, however, is a CHD risk factor only among women in this cohort.
Black or African American↗
Estrogen replacement therapy and cognitive functioning in the Atherosclerosis Risk in Communities (ARIC) Study.
The association of estrogen replacement therapy (ERT) with cognitive functioning was assessed in 6,110 women aged 48-67 years participating in the Atherosclerosis Risk in Communities (ARIC) study, a multicenter longitudinal investigation. ERT was evaluated in relation to results of three cognitive tests (the Delayed Word Recall (DWR) Test, the Digit Symbol Subtest of the Wechsler Adult intelligence Scale-Revised (DSS/WAIS-R), and the Word Fluency (WF) Test) using data from the first follow-up visit of the cohort (1990-1992). No consistent associations were seen between ERT and either the DWR test or the DSS/WAIS-R after adjusting for age, education, and additional covariates previously found to be associated with cognitive function scores. Among surgically menopausal women aged 48-57 years, adjusted mean WF scores were slightly greater in ERT current users (mean WF 35.9) than in never users (mean WF 33.5) (p < 0.02); and within current users, adjusted WF scores increased with duration of ERT use. However, the finding that ERT was associated with a slightly higher level of performance on only one of three measures offers little support for the hypothesis that ERT has a major protective effect on cognitive function in women less than 68 years of age. The generalizability of these findings to older women who are more likely to experience cognitive decline and who may be using ERT for longer periods of time is limited by the relatively young age of the cohort.
Aged↗
No association of menopause and hormone replacement therapy with carotid artery intima-media thickness. Atherosclerosis Risk in Communities (ARIC) Study Investigators.
BACKGROUND: Cardiovascular disease is the major cause of death in older women. Information on the relation of menopause and hormone replacement therapy with carotid atherosclerosis is limited. METHODS AND RESULTS: We examined cross-sectionally the association of menopausal status, years since last menstruation, and hormone replacement therapy status with carotid artery intima-media thickness as determined by B-mode ultrasound. Female participants (n = 5436) in the Atherosclerosis Risk in Communities Study without a history of symptomatic cardiovascular disease were included in the analyses. Menopause status in 45- to 54-year-old women who had never used hormone replacement therapy was not strongly associated with carotid intima-media thickness (mean = 0.65 mm and 0.67 mm in premenopausal and postmenopausal women, respectively, adjusted for age, race, cigarette years of smoking, body mass index, sport index, systolic blood pressure, use of blood pressure medications, drinking status, diabetes, and education level). In postmenopausal women aged 55 to 64 years, women with < or = 5 years since last menstruation had an adjusted average intima-media thickness (0.74 mm) comparable to those with > 5 years since last menstruation (0.75 mm) (P > .05). Although hormone replacement therapy use was associated with a more favorable lipid and hemostasis profile than nonuse, its use was not associated with intima-media thickness in postmenopausal women aged 55 to 64 years (adjusted average = 0.74 mm for current users of estrogen alone and approximately 0.75 mm each for current users of estrogen plus progestin, former users, and never users). CONCLUSIONS: The data suggest that the well-known associations of hormone replacement therapy with reductions in atherosclerotic cardiovascular disease may be attributable more to acute physiological effects, such as hemodynamic changes or reduced thrombosis, than to atherosclerosis itself.
Carotid Arteries↗
Cohort study of cytomegalovirus infection as a risk factor for carotid intimal-medial thickening, a measure of subclinical atherosclerosis.
BACKGROUND: Animal studies as well as clinical and cross-sectional epidemiological studies in humans have suggested a possible role of cytomegalovirus (CMV) and other herpesvirus infections in the development of cardiovascular disease. METHODS AND RESULTS: The present report is based on a case-control study nested within a historical cohort. The case group comprised 150 individuals with elevated carotid intimal-medial thickness (IMT) measured by B-mode ultrasound at the first two examinations of the Atherosclerosis Risk in Communities (ARIC) Study (1987 through 1992). The control group comprised 150 age- and sex-matched individuals with low IMT. Antibody titers for CMV and herpesvirus 1 and 2 were determined in sera obtained in 1974 as part of a community-wide survey conducted in Washington County, Maryland. Case subjects had higher mean CMV antibody titers in 1974 sera than control subjects, although the difference was not statistically significant when adjusted for other cardiovascular risk factors. There was evidence of a graded relation between the odds of intimal-medial thickening and the levels of CMV antibodies that remained significant after adjustment for the main cardiovascular risk factors (P = .013). The adjusted odds ratio for a high CMV antibody titer (a positive/negative value > or = 20) compared with a positive/negative value < 4 was 5.3 (95% confidence interval, 1.5 to 18.0). CONCLUSIONS: The results from this first population-based cohort study of CMV infection and carotid IMT are compatible with the hypothesis of a causal role of CMV in atherosclerosis.
Antibodies, Viral↗
Morton Levin (1904-1995): history in the making.
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Case-Control Studies↗
Repeatability and validity of the Rose questionnaire for angina pectoris in the Atherosclerosis Risk in Communities Study.
Angina pectoris (AP) as determined by the Rose questionnaire was assessed in nearly 16,000 black and white men and women participating in the Atherosclerosis Risk in communities Study, a population study of cardiovascular disease in four communities. The questionnaire was administered at yearly intervals and estimates of repeatability were made. Validity was assessed indirectly by comparing Rose AP to risk factors, prevalent heart disease, medication use, and thickness of carotid artery walls as measured by B-mode ultrasound. Using kappa statistics for agreement of positive Rose AP determinations taken 1 year apart, white men show a higher level of agreement than white women (average kappa 0.36 for white men, 0.30 for white women), and whites show a higher level of agreement than blacks (average kappa 0.23 and 0.22 for black men and women, respectively). Rose AP that persists for more than one determination is associated with thicker carotid artery walls, greater amounts of cigarette smoking, greater prevalence of reported heart attack, and greater use of chest pain medications. A single determination of severe Rose AP is also associated with thicker carotid artery walls. These data suggest that multiple reports and the more severe grading of Rose AP (pain reported while walking on the level) are likely to indicate more severe disease; however, a single report using the Rose questionnaire appears valid, i.e., moderately associated with disease and risk factors, and appropriate for use in epidemiological studies.
Angina Pectoris↗
Poland and United States Collaborative Study on Cardiovascular Epidemiology. A comparison of HDL cholesterol and its subfractions in populations covered by the United States Atherosclerosis Risk in Communities Study and the Pol-MONICA Project.
HDL cholesterol (HDL-C) levels are inversely related to coronary heart disease (CHD) risk, and HDL-C distributions vary among countries. Poland is one of the few developed countries in which CHD rates are increasing at the same time that US rates have been falling, but whether these differences are explained by differences in risk factors such as HDL-C has not been determined. To examine this possibility, levels of HDL-C and its subfractions were compared in US and Polish urban and rural men and women aged 45 to 64 years. Age-adjusted HDL-C means were 0.20 mmol/L higher in urban Polish men and 0.37 mmol/L higher in rural Polish men than in their US counterparts (P < .0001); means in urban Polish women were 0.06 mmol/L higher (P < .05) and in rural Polish women 0.09 mmol/L higher (P < .001) than in their US counterparts. Adjustment for age, education, alcohol intake, smoking, BMI, heart rate, and menopause status (in women) had little effect on differences. Means of HDL2 and HDL3 levels showed similar between-country differences, although differences were minimal for HDL2 in urban men and women, and HDL3 means did not differ between rural women. BMI was inversely related to HDL-C and both subfractions in all gender-country-site strata (P < .001), and alcohol was directly related to HDL-C (P < .001) in all strata except Polish women. Cigarette smoking was negatively related to HDL-C and both subfractions in all US samples except HDL2 in urban men, whereas in Polish samples, significant associations were found only in urban women for HDL-C and in rural and urban women for HDL3. Age, heart rate, and education showed inconsistent or no association with HDL-C and its subfractions in either country. This profile of HDL-C and its subfractions in Polish samples contrasts sharply with the opposite trend in CHD mortality rates, which suggests either that other risk factors may account for the trends or that the relationship between HDL-C and CHD may differ between the two countries.
Age Factors↗
Association of the waist-to-hip ratio is different with wine than with beer or hard liquor consumption. Atherosclerosis Risk in Communities Study Investigators.
Specific alcoholic beverage associations with the waist-to-hip ratio were characterized in 12,145 African-American and white men and women ages 45-64 years. Estimated waist-to-hip ratios of those consuming more than six nonwine alcohol drinks/week and more than six wine drinks/week (vs. nondrinkers) were 0.007 larger (p < 0.001) and 0.009 smaller (p < 0.05), respectively. In similar comparisons, the odds ratios for a large waist-to-hip ratio were 1.4 (95% confidence interval 1.1-1.7) for nonwine and 0.45 (95% confidence interval 0.21-0.95) for wine intake. The opposite direction in adjusted associations for wine and nonwine (mainly beer) drinking supports the popular concept of the "beer belly."
Adipose Tissue↗
Social inequalities and atherosclerosis. The atherosclerosis risk in communities study.
The cross-sectional associations of social class indicators with coronary heart disease prevalence and subclinical atherosclerosis were investigated among 15,800 persons from four US communities between 1987 and 1989. Among persons without clinical atherosclerotic disease, ultrasound-determined intimal-medial wall thickening of the carotid arteries was used as an indicator of subclinical atherosclerosis. Odds ratios for coronary heart disease prevalence and mean differences in carotid wall thickness were investigated before and after adjustment for cardiovascular risk factors. After adjustment for age and gender, the lowest income category was associated with a threefold increase in coronary heart disease odds compared with the highest category (for whites, odds ratio (OR) = 3.4, 95% confidence interval (CI) 1.8-6.6; for blacks, OR = 3.2, 95% CI 2.2-4.8). Odds ratios increased linearly with decreasing income (p < 0.0001). Low education was also associated with increased odds of coronary heart disease after adjustment for age and gender, but the association was stronger in whites than in blacks (lowest category vs. highest: for whites, OR = 3.8, 95% CI 2.5-5.9; for blacks, OR = 1.7, 95% CI 0.9-3.1). Similar patterns were found for subclinical atherosclerosis: Carotid wall thickness increased with decreasing income and education, but trends by education were clearer in whites than in blacks. Lower occupational categories were also associated with increased coronary heart disease prevalence odds and increased carotid wall thickness. After adjustment for risk factors, associations with clinical coronary heart disease persisted but associations with carotid wall thickness disappeared, suggesting that factors related to the clinical expression of lesions may vary by social class. The process of atherogenesis and its clinical expression are patterned by social class, emphasizing the need to address social inequalities in the prevention of cardiovascular disease.
Arteriosclerosis↗
Population awareness and control of hypertension and hypercholesterolemia. The Atherosclerosis Risk in Communities study.
BACKGROUND: A national program for hypertension detection and control was implemented in the 1970s, whereas a similar program for control of hypercholesterolemia has been implemented in recent years. We studied the levels of awareness, treatment, and control of these conditions in US population samples during a 3-year period (1987 to 1989). METHODS: The levels of awareness, treatment (by medication), and adequate control of hypertension (systolic blood pressure, > or = 140 mm Hg; diastolic blood pressure, > or = 90 mm Hg; or antihypertensive medication) and hypercholesterolemia (serum cholesterol level, > or = 6.21 mmol/L [> or = 240 mg/dL], or lipid-lowering medication) were studied among participants in the baseline examination of the Atherosclerosis Risk in Communities Study, including 15,739 individuals aged 45 to 64 years. RESULTS: Eighty-four percent of the hypertensive subjects and 42% of the hypercholesterolemic subjects were aware of their conditions. Overall, 50% of the hypertensive subjects and only 4% of the hypercholesterolemic subjects had their conditions both treated and controlled. Rates of hypertension prevalence, awareness, and control remained stable during the 3-year study period. Hypercholesterolemia prevalence decreased from 30% in 1987 to 25% in 1989; its awareness increased from 31% to 50% during the same period. Hypertensive women were more likely than hypertensive men to be aware and treated, whereas hypercholesterolemia awareness was higher in men than in women. Hypertension awareness was highest in black women, but black hypertensive subjects were less likely than whites to be treated and to have their hypertension controlled. Black hypercholesterolemic subjects were less likely to be either aware or treated. CONCLUSIONS: After the recent implementation of the National Cholesterol Education Program, the levels of awareness, treatment, and control of hypercholesterolemia are improving at a high rate, although they are still substantially lower than those for hypertension. Further improvement is necessary, particularly among certain population groups, such as blacks.
Age Distribution↗
The relationship of active and passive smoking to carotid atherosclerosis 12-14 years later.
BACKGROUND: Active and passive smoking have been found to be associated with clinical atherosclerotic disease. To explore the effects of smoking on atherogenesis, we investigated the relationship of past and current active and passive smoking to carotid atherosclerosis in middle-aged adults. METHODS: The study population consisted of 2,073 middle-aged residents of Washington County, Maryland. Information on active smoking and exposure to environmental tobacco smoke (ETS) was obtained from a 1975 census and from the baseline visit of the Atherosclerosis Risk in Communities (ARIC) Study in 1987-1989. Carotid artery intimal-medial wall thickness, measured by B-mode ultrasound methods in 1987-1989, was used as an indicator of carotid atherosclerosis. Mean intimal-medial wall thickness (IMT) was adjusted for age, gender, cardiovascular risk factors, and education using multiple linear regression. RESULTS: The lowest mean IMT was found among never smokers who had never been exposed to ETS (mean +/- standard error: 0.706 +/- 0.013 mm). Exposure to ETS in one or both time periods was associated with increased IMT among never smokers (ETS in 1975 only: 0.731 +/- 0.022; ETS in 1987-1989 only: 0.738 +/- 0.011; ETS in both periods: 0.734 +/- 0.012). Active smoking in 1975 was also associated with increased IMT. The greatest mean intimal-medial wall thickness was found among persons who were current smokers in both time periods (0.807 +/- 0.009). CONCLUSIONS: Both past and current passive and active smoking are associated with increased carotid intimal-medial wall thickness.
Arteriosclerosis↗