Moyses Szklo

Coronary calcium as a predictor of coronary events in four racial or ethnic groups.

BACKGROUND In white populations, computed tomographic measurements of coronary-artery calcium predict coronary heart disease independently of traditional coronary risk factors. However, it is not known whether coronary-artery calcium predicts coronary heart disease in other racial or ethnic groups. METHODS We collected data on risk factors and performed scanning for coronary calcium in a population-based sample of 6722 men and women, of whom 38.6% were white, 27.6% were black, 21.9% were Hispanic, and 11.9% were Chinese. The study subjects had no clinical cardiovascular disease at entry and were followed for a median of 3.8 years. RESULTS There were 162 coronary events, of which 89 were major events (myocardial infarction or death from coronary heart disease). In comparison with participants with no coronary calcium, the adjusted risk of a coronary event was increased by a factor of 7.73 among participants with coronary calcium scores between 101 and 300 and by a factor of 9.67 among participants with scores above 300 (P<0.001 for both comparisons). Among the four racial and ethnic groups, a doubling of the calcium score increased the risk of a major coronary event by 15 to 35% and the risk of any coronary event by 18 to 39%. The areas under the receiver-operating-characteristic curves for the prediction of both major coronary events and any coronary event were higher when the calcium score was added to the standard risk factors. CONCLUSIONS The coronary calcium score is a strong predictor of incident coronary heart disease and provides predictive information beyond that provided by standard risk factors in four major racial and ethnic groups in the United States. No major differences among racial and ethnic groups in the predictive value of calcium scores were detected.

Neighborhood of Residence and Incidence of Coronary Heart Disease

BACKGROUND Where a person lives is not usually thought of as an independent predictor of his or her health, although physical and social features of places of residence may affect health and health-related behavior. METHODS Using data from the Atherosclerosis Risk in Communities Study, we examined the relation between characteristics of neighborhoods and the incidence of coronary heart disease. Participants were 45 to 64 years of age at base line and were sampled from four study sites in the United States: Forsyth County, North Carolina; Jackson, Mississippi; the northwestern suburbs of Minneapolis; and Washington County, Maryland. As proxies for neighborhoods, we used block groups containing an average of 1000 people, as defined by the U.S. Census. We constructed a summary score for the socioeconomic environment of each neighborhood that included information about wealth and income, education, and occupation. RESULTS During a median of 9.1 years of follow-up, 615 coronary events occurred in 13,009 participants. Residents of disadvantaged neighborhoods (those with lower summary scores) had a higher risk of disease than residents of advantaged neighborhoods, even after we controlled for personal income, education, and occupation. Hazard ratios for coronary events in the most disadvantaged group of neighborhoods as compared with the most advantaged group--adjusted for age, study site, and personal socioeconomic indicators--were 1.7 among whites (95 percent confidence interval, 1.3 to 2.3) and 1.4 among blacks (95 percent confidence interval, 0.9 to 2.0). Neighborhood and personal socioeconomic indicators contributed independently to the risk of disease. Hazard ratios for coronary heart disease among low-income persons living in the most disadvantaged neighborhoods, as compared with high-income persons in the most advantaged neighborhoods were 3.1 among whites (95 percent confidence interval, 2.1 to 4.8) and 2.5 among blacks (95 percent confidence interval, 1.4 to 4.5). These associations remained unchanged after adjustment for established risk factors for coronary heart disease. CONCLUSIONS Even after controlling for personal income, education, and occupation, we found that living in a disadvantaged neighborhood is associated with an increased incidence of coronary heart disease.

Association of Hormone-Replacement Therapy with Various Cardiovascular Risk Factors in Postmenopausal Women

Background Most epidemiologic studies of cardiovascular disease in postmenopausal women suggest that estrogen-replacement therapy has a protective effect. The effects of the use of estrogen combined with progestin are less well studied. Methods To examine the associations of hormone-replacement therapy with concentrations of plasma lipids and hemostatic factors, fasting serum concentrations of glucose and insulin, and blood pressure, we studied 4958 postmenopausal women participating in a population-based investigation. Using cross-sectional data, we classified the women into four groups according to their use of hormone-replacement therapy: current users of estrogen alone, current users of estrogen with progestin, nonusers who had formerly used these hormones, and nonusers who had never used them. Results Current users had higher mean levels of high-density lipoprotein cholesterol, its subfractions high-density lipoprotein2 and high-density lipoprotein3, and apolipoprotein A-I than nonusers, and lower me...

Cardiovascular risk factors and cognitive decline in middle-aged adults

Objective: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. Methods: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale–Revised and the first-letter word fluency (WF) test using letters F, A, and S. Results: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p < 0.05), and the presence of hypertension at baseline was associated with greater decline on the DSS alone (p < 0.05). The association of diabetes with cognitive decline persisted when analysis was restricted to the 47- to 57-year-old subgroup. Smoking status, carotid intima–media wall thickness, and hyperlipidemia at baseline were not associated with change in cognitive test scores. Conclusions: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

Prevalence of Type 2 Diabetes Mellitus among Persons with Hepatitis C Virus Infection in the United States

Approximately 2.7 million persons in the United States have chronic hepatitis C virus (HCV) infection (1). Chronic HCV infection may lead to cirrhosis and hepatocellular carcinoma and is a leading cause of liver transplantation in the United States (2). Hepatitis C virus infection may also cause extrahepatic illnesses, including essential mixed cryoglobulinemia, sporadic porphyria cutanea tarda, and thyroid disease, all of which may reflect interactions between HCV and the host immune system (2-7). An increased prevalence of diabetes mellitus among persons with HCV infection has also been observed (8-15). The data linking HCV infection and diabetes mellitus are derived from several recent clinic-based, casecontrol studies that leave several important questions unanswered (8-15). Most of these reports did not consider such factors as body mass index, illicit drug use, and socioeconomic status, which have been associated with both conditions and thus could confound the relationship (1, 16). In addition, because the studies were based principally in referral centers, the relationship may be restricted to persons with severe forms of the diseases. For example, since the liver is crucial to carbohydrate metabolism and glucose homeostasis, diabetes may occur more often in anti-HCVpositive persons simply because of hepatocyte dysfunction (17). Discovery of an increased prevalence of diabetes in the general population among persons with HCV infection and less severe liver disease might suggest an alternate mechanism, such as an HCV-related autoimmune process. Similarly, it has not been determined whether HCV infection results in an increased occurrence of type 1 or type 2 diabetes. Answers to these questions could shed light on the biological mechanisms involved. Both HCV infection and diabetes have been carefully evaluated in a representative sample of the general population of the United States through the Third National Health and Nutrition Examination Survey (NHANES III) (18, 19). We sought to test the hypothesis that persons with HCV infection have an increased prevalence of type 2 diabetes after adjustment for important confounding variables, including age, body mass index, poverty level, and history of drug and alcohol use. Methods Survey Design and Study Sample The NHANES III was conducted from 1988 to 1994 by the National Center for Health Statistics of the Centers for Disease Control and Prevention and is described in detail elsewhere (18, 19). In brief, the survey used a stratified, multistage probability cluster sampling design to obtain a representative sample of the U.S. civilian, noninstitutionalized population. It was designed to oversample Mexican-Americans and African-Americans; in our analysis, we used sampling weights to account for this fact. Approximately 34 000 persons who were at least 2 months of age at the time of the evaluation were sampled at 89 randomly selected locations throughout the United States. Persons selected for evaluation were interviewed at their residence by using a questionnaire that collected information on demographic characteristics, medical history, current and past medication use, and other risk behaviors. Ninety-one percent (30 818) of participants also underwent physical examination and laboratory assessment at a mobile examination center. Plasma glucose levels were measured and HCV antibody testing was performed in examined persons who were at least 20 years of age or 6 years of age, respectively. The institutional review board at the Centers for Disease Control and Prevention approved the study, and all participants provided written informed consent (18, 19). Because plasma glucose testing was performed only in persons older than 20 years of age, we restricted our analysis to persons 20 years of age or older at the time of examination. Of the 18 825 persons older than 20 years of age who were interviewed, 16 573 (88%) also had a complete physical examination and laboratory analysis and were thus deemed eligible for our analysis. Persons were included in our investigation if they had complete evaluations for diabetes and HCV infection. In particular, each household was randomly assigned to a morning, afternoon, or evening evaluation, and participants were instructed to abstain from intake other than water for a specific period of time. Of the 8158 persons assigned to a morning session, 7439 (91%) completed an 8- to 24-hour fast, whereas 2467 of 8415 (29%) persons assigned to a later appointment fasted for 8 to 24 hours. In addition, 562 persons who did not fast but reported use of antidiabetic medication were included in the study sample. Of the 10 468 eligible persons, 627 were excluded from analysis because of indeterminate or missing plasma glucose levels (n =212), indeterminate or missing anti-HCV information (n =290), or a history of diabetes that was unsubstantiated by hyperglycemia or use of antidiabetic medications (n =125). The remaining 9841 persons constitute the study sample (Figure 1). Figure 1. Determination of the study sample. Ascertainment of Diabetes Venous whole blood was drawn into a vacuum tube containing the glycolytic inhibitors potassium oxalate and sodium fluoride and was immediately centrifuged at 1500 g for 10 minutes, as described elsewhere (19). Plasma was frozen at 70 C and shipped to the University of Missouri Diabetes Diagnostic Laboratory, Columbia, Missouri, where plasma glucose testing was performed by using a modified hexokinase enzymatic method. During the 6 years of the survey, the within-assay and between-assay coefficients of variation were 1.6% to 3.7% (20). Type 1 and type 2 diabetes were classified according to previously defined criteria, a combination of the 1997 American Diabetes Association criteria and that used by the Early Treatment Diabetic Retinopathy Study group (21, 22). Persons were considered to have diabetes if they used insulin or oral hypoglycemic agents at the time of the survey or had a fasting plasma glucose level of 7.0 mmol/L or more ( 126 mg/dL). Persons in whom diabetes was diagnosed before 30 years of age, started receiving insulin therapy within 1 year of diagnosis, and reported insulin use at the time of the survey were categorized as having type 1 diabetes. All others who met the above criteria for diabetes were classified as having type 2 diabetes. Exposure Assessment Presence of antibody to HCV (anti-HCV) was assessed by using a second-generation enzyme immunoassay test (Abbott Laboratories, Chicago, Illinois). Positive specimens were tested in duplicate, and repeatedly positive samples were tested again by using the MATRIX assay (Abbott Laboratories). Specimens that were positive according to all three tests were considered to be anti-HCV positive. A sandwich radioimmunoassay (Abbot Laboratories, North Chicago, Illinois) was used for semiquantitative determination of hepatitis B surface antigen in human serum. Serum blood chemistries, including hematologic variables, were obtained by using a Hitachi Model 737 multichannel analyzer (Boehringer Mannheim Diagnostics, Indianapolis, Indiana) (19). Serum liver enzyme levels, including alanine aminotransferase levels, could not be determined from frozen plasma. Information on other covariates was collected during the interview and subsequent examination. Age, ethnicity, and socioeconomic status were categorized according to the survey design as suggested by the National Center for Health Statistics for analysis of NHANES III data (19). Age was analyzed in 10-year groups, and ethnicity was divided into four categories: non-Hispanic white, non-Hispanic black, Mexican-American, and other, which included other Hispanics, Asians, and Native Americans. Too few persons and potential heterogeneity in the other category prohibited its inclusion in analysis. Educational attainment and poverty level were used as proxy measures of socioeconomic status. Educational attainment was classified according to whether a participant had achieved greater than a high school diploma. Poverty level was calculated as a poverty income ratio of self-reported family income to a denominator based on poverty threshold, family size, and the calendar year of the interview. Poverty threshold values, which were standardized for inflation, were based on tables published annually by the U.S. Census Bureau (19). Participants with a poverty income ratio less than 1.0 were considered to be below the poverty level. Body mass index, measured in kg/m2, was assessed during the examination. Participants with a body mass index less than 25 kg/m2, 25 to 29.9 kg/m2, 30 to 34.9 kg/m2, and 35 kg/m2 or more were classified according to the National Heart, Lung, and Blood Institute as lean or normal, overweight, obese, or morbidly obese, respectively (23). Participants who indicated that any of their first-degree relatives had diabetes were considered to have a positive family history of diabetes. Cigarette smoking was categorized according to whether the person was a never, former, or current smoker at the time of the interview. Illicit drug use was assessed by questions about lifetime use of marijuana or cocaine (including crack cocaine), but no specific questions were asked about injection drug use. Excessive alcohol intake was defined as alcohol consumption of more than 50 g/d (approximately five drinks) during the past year. Statistical Analysis General descriptive analysis was performed to compare participants with and those without diabetes. For categorical variables, two-way tabulations calculating a Pearson chi-square statistic, corrected for complex survey design or clustered data, were used. For continuous variables, survey designcorrected t-tests were performed. Univariate and multivariate survey logistic regression techniques were used to determine the crude and adjusted odds ratios of type 2 diabetes with respect to HCV infection. Variables considered to be potential confounders in multiva

Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND Coronary artery calcium (CAC) and carotid intima-media thickness (IMT) are noninvasive measures of atherosclerosis that consensus panels have recommended as possible additions to risk factor assessment for predicting the probability of cardiovascular disease (CVD) occurrence. Our objective was to assess whether maximum carotid IMT or CAC (Agatston score) is the better predictor of incident CVD. METHODS A prospective cohort study of subjects aged 45 to 84 years in 4 ethnic groups, who were initially free of CVD (n = 6698) was performed, with standardized carotid IMT and CAC measures at baseline, in 6 field centers of the Multi-Ethnic Study of Atherosclerosis (MESA). The main outcome measure was the risk of incident CVD events (coronary heart disease, stroke, and fatal CVD) over a maximum of 5.3 years of follow-up. RESULTS There were 222 CVD events during follow-up. Coronary artery calcium was associated more strongly than carotid IMT with the risk of incident CVD. After adjustment for each other (CAC score and IMT) and age, race, and sex [corrected], the hazard ratio of CVD increased 2.1-fold (95% confidence interval [CI], 1.8-2.5) for each 1-standard deviation (SD) increment of log-transformed CAC score, vs 1.3-fold (95% CI, 1.1-1.4) for each 1-SD increment of the maximum IMT. For coronary heart disease, the hazard ratios per 1-SD increment increased 2.5-fold (95% CI, 2.1-3.1) for CAC score and 1.2-fold (95% CI, 1.0-1.4) for IMT. A receiver operating characteristic curve analysis also suggested that CAC score was a better predictor of incident CVD than was IMT, with areas under the curve of 0.81 vs 0.78, respectively. CONCLUSION Although whether and how to clinically use bioimaging tests of subclinical atherosclerosis remains a topic of debate, this study found that CAC score is a better predictor of subsequent CVD events than carotid IMT.

Arterial stiffness and the development of hypertension. The ARIC study.

Decreased elasticity in large and medium-sized arteries has been postulated to be associated with cardiovascular diseases. We prospectively examined the relation between arterial elasticity and the development of hypertension over 6 years of follow-up in a cohort of 6992 normotensive men and women aged 45 to 64 years at baseline from the biracial, population-based Atherosclerosis Risk in Communities (ARIC) Study. Arterial elasticity was measured from high-resolution B-mode ultrasound examination of the left common carotid artery as adjusted arterial diameter change (in micrometers, simultaneously adjusted for diastolic blood pressure, pulse pressure, pulse pressure squared, diastolic arterial diameter, and height), Petersons elastic modulus (in kilopascals), Youngs elastic modulus (in kilopascals), and beta stiffness index. Incident hypertension (n=551) was defined as systolic blood pressure >/=160 mm Hg, diastolic blood pressure >/=95 mm Hg, or the use of antihypertensive medication at a follow-up examination conducted every 3 years. The age-, ethnicity-, center-, gender-, education-, smoking-, heart rate-, and obesity-adjusted means (SE) of baseline adjusted arterial diameter change, Petersons elastic modulus, Youngs elastic modulus, and beta stiffness index were 397 (5), 148 (2.0), 787 (12.7), and 11.43 (0.16), respectively, in persons who developed hypertension during follow-up, in contrast to 407 (1), 124 (0.6), 681 (3.7), and 10.34 (0.05), respectively, for persons who did not. The similarly adjusted cumulative incident rates of hypertension from the highest to the lowest quartiles of arterial elasticity were 6.7%, 8.0%, 7.3%, and 9.6%, respectively, when measured by adjusted arterial diameter change (P<0.01). One standard deviation decrease in arterial elasticity was associated with 15% greater risk of hypertension, independent of established risk factors for hypertension and the level of baseline blood pressure. These results suggest that lower arterial elasticity is related to the development of hypertension.

Carotid artery intimal-medial wall thickening and plasma homocyst(e)ine in asymptomatic adults. The Atherosclerosis Risk in Communities Study.

BACKGROUND Plasma levels of homocyst(e)ine are elevated in certain patients with occlusive arterial diseases. We extended these findings to asymptomatic adults. METHODS AND RESULTS We determined plasma homocyst(e)ine levels in 287 pairs of asymptomatic adults. Cases and controls were defined on the basis of intimal-medial thickness of the carotid wall as measured by B-mode ultrasound. Study subjects had no history of atherosclerotic disease and were selected from a probability sample of 15,800 men and women between 45 and 64 years old. Subjects with thickened intimal-medial carotid walls (cases) had higher plasma homocyst(e)ine levels than controls (p < 0.001). The odds ratio for having a thickened carotid artery wall was 3.15 (p < 0.001) for subjects in the top quintile of plasma homocyst(e)ine levels (> 10.5 mumol/L) compared with those in the bottom quintile (< 5.88 mumol/L). CONCLUSIONS The present study as well as observations on the common occurrence of elevated plasma homocyst(e)ine levels in patients with occlusive arterial diseases suggest that clinical trials should be conducted to determine whether normalization of hyperhomocyst(e)inemia may prevent progression of atherosclerosis.

Poverty, race, and hospitalization for childhood asthma.

This study uses Maryland hospital discharge data for the period 1979-82 to determine whether Black children are more likely to be hospitalized for asthma and whether this difference persists after adjustment for poverty. The average annual asthma discharge rate was 1.95/1000 children aged 1-19; 3.75/1000 for Black children, and 1.25/1000 for White. Medicaid-enrolled children of both races had increased discharge rates for asthma compared to those whose care was paid for by other sources: 5.68/1000 vs 2.99/1000 for Blacks, and 3.10/1000 vs 1.11/1000 for Whites. When ecologic analyses were performed, populations of Black and White children had nearly equal asthma discharge rates after adjustment for poverty. The statewide adjusted rate was 2.70/1000 (95% CL = 1.93, 3.78) for Black children and 2.10/1000 (1.66, 2.66) for White children. Among Maryland counties and health planning districts, variation in asthma discharge rates was not associated with the supply of hospital beds or the population to primary-care physician ratio. We conclude that Black children are at increased risk of hospitalization for asthma, but that some or all of this increase is related to poverty rather than to race.

Population correlates of plasma fibrinogen and factor VII, putative cardiovascular risk factors

Recent prospective investigations have reported that higher plasma fibrinogen concentrations and higher factor VII coagulant activity are associated with greater risk of cardiovascular disease. To discover what characteristics may influence fibrinogen and factor VII, we analyzed data from the Atherosclerosis Risk in Communities Study obtained from over 12,000 men and women, aged 45-64 years, from four communities in December 1986 to June 1989. Fibrinogen was higher in blacks than whites and in women than men; in general, it increased with age, smoking, body size, diabetes, fasting serum insulin, LDL cholesterol, lipoprotein(a), leukocyte count, and menopause, and it decreased with ethanol intake, physical activity, HDL cholesterol, and female hormone use. Factor VII was higher in women than men and, in women, increased with age; in both sexes, it increased with body size, triglycerides, LDL cholesterol, and HDL cholesterol, and it decreased with ethanol intake. These findings indicate that elevations in fibrinogen and factor VII may be modifiable through appropriate lifestyle changes.