Catarina I. Kiefe

γ-Glutamyltransferase Is a Predictor of Incident Diabetes and Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: γ-Glutamyltransferase (GGT), which maintains cellular concentrations of glutathione, may be a marker of oxidative stress, and GGT itself may produce oxidative stress. We performed a prospective study to examine whether serum GGT predicts diabetes and hypertension. Methods: Study participants were 4844 black and white men and women 18–30 years of age in 1985–1986; they were reexamined 2, 5, 7, 10, and 15 years later. Year 0 GGT cutpoints were 12, 17, 25, and 36 U/L (overall 25th, 50th, 75th, and 90th percentiles; the laboratory cutpoints for abnormal are 40 U/L in women and 50 U/L in men). We deleted 32 participants with prevalent diabetes and 140 participants with prevalent hypertension from the respective incidence analyses. Results: After adjustment for study center, race, sex, and age in proportional hazards regression, the hazard ratios across year 0 GGT categories were 1.0, 1.6, 1.7, 4.0 (95% confidence interval, 2.0–8.1), and 5.5 (2.7–11.1) for 15-year incident diabetes and 1.0, 1.2, 1.7 (1.2–2.2), 2.3 (1.7–3.2), and 2.3 (1.7–3.2) for hypertension. Additional adjustment for year 0 alcohol consumption, body mass index, cigarette smoking, and physical activity attenuated this relationship, but GGT remained a significant predictor. Conclusions: Serum GGT within a range regarded as physiologically normal is associated with incident diabetes and hypertension. Considering known functionality of GGT, these associations are consistent with a role for oxidative stress in risk for diabetes and hypertension.

The volume of primary angioplasty procedures and survival after acute myocardial infarction. National Registry of Myocardial Infarction 2 Investigators.

BACKGROUND There is an inverse relation between mortality from cardiovascular causes and the number of elective cardiac procedures (coronary angioplasty, stenting, or coronary bypass surgery) performed by individual practitioners or hospitals. However, it is not known whether patients with acute myocardial infarction fare better at centers where more patients undergo primary angioplasty or thrombolytic therapy than at centers with lower volumes. METHODS We analyzed data from the National Registry of Myocardial Infarction to determine the relation between the number of patients receiving reperfusion therapy (primary angioplasty or thrombolytic therapy) and subsequent in-hospital mortality. A total of 450 hospitals were divided into quartiles according to the volume of primary angioplasty. Multiple logistic-regression models were used to determine whether the volume of primary angioplasty procedures was an independent predictor of in-hospital mortality among patients undergoing this procedure. Similar analyses were performed for patients receiving thrombolytic therapy at 516 hospitals. RESULTS In-hospital mortality was 28 percent lower among patients who underwent primary angioplasty at hospitals with the highest volume than among those who underwent angioplasty at hospitals with the lowest volume (adjusted relative risk, 0.72; 95 percent confidence interval, 0.60 to 0.87; P<0.001). This lower rate, which represented 2.0 fewer deaths per 100 patients treated, was independent of the total volume of patients with myocardial infarction at each hospital, year of admission, and use or nonuse of adjunctive pharmacologic therapies. There was no significant relation between the volume of thrombolytic interventions and in-hospital mortality among patients who received thrombolytic therapy (7.0 percent for patients in the highest-volume hospitals vs. 6.9 percent for those in the lowest-volume hospitals, P=0.36). CONCLUSIONS Among hospitals in the United States that have full interventional capabilities, a higher volume of angioplasty procedures is associated with a lower mortality rate among patients undergoing primary angioplasty, but there is no association between volume and mortality for thrombolytic therapy.

Association of Age and Sex With Myocardial Infarction Symptom Presentation and In-Hospital Mortality

CONTEXT Women are generally older than men at hospitalization for myocardial infarction (MI) and also present less frequently with chest pain/discomfort. However, few studies have taken age into account when examining sex differences in clinical presentation and mortality. OBJECTIVE To examine the relationship between sex and symptom presentation and between sex, symptom presentation, and hospital mortality, before and after accounting for age in patients hospitalized with MI. DESIGN, SETTING, AND PATIENTS Observational study from the National Registry of Myocardial Infarction, 1994-2006, of 1,143,513 registry patients (481,581 women and 661,932 men). MAIN OUTCOME MEASURES We examined predictors of MI presentation without chest pain and the relationship between age, sex, and hospital mortality. RESULTS The proportion of MI patients who presented without chest pain was significantly higher for women than men (42.0% [95% CI, 41.8%-42.1%] vs 30.7% [95% CI, 30.6%-30.8%]; P < .001). There was a significant interaction between age and sex with chest pain at presentation, with a larger sex difference in younger than older patients, which became attenuated with advancing age. Multivariable adjusted age-specific odds ratios (ORs) for lack of chest pain for women (referent, men) were younger than 45 years, 1.30 (95% CI, 1.23-1.36); 45 to 54 years, 1.26 (95% CI, 1.22-1.30); 55 to 64 years, 1.24 (95% CI, 1.21-1.27); 65 to 74 years, 1.13 (95% CI, 1.11-1.15); and 75 years or older, 1.03 (95% CI, 1.02-1.04). Two-way interaction (sex and age) on MI presentation without chest pain was significant (P < .001). The in-hospital mortality rate was 14.6% for women and 10.3% for men. Younger women presenting without chest pain had greater hospital mortality than younger men without chest pain, and these sex differences decreased or even reversed with advancing age, with adjusted OR for age younger than 45 years, 1.18 (95% CI, 1.00-1.39); 45 to 54 years, 1.13 (95% CI, 1.02-1.26); 55 to 64 years, 1.02 (95% CI, 0.96-1.09); 65 to 74 years, 0.91 (95% CI, 0.88-0.95); and 75 years or older, 0.81 (95% CI, 0.79-0.83). The 3-way interaction (sex, age, and chest pain) on mortality was significant (P < .001). CONCLUSION In this registry of patients hospitalized with MI, women were more likely than men to present without chest pain and had higher mortality than men within the same age group, but sex differences in clinical presentation without chest pain and in mortality were attenuated with increasing age.

Area Characteristics and Individual-Level Socioeconomic Position Indicators in Three Population-Based Epidemiologic Studies

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

Self-Reported Experiences of Racial Discrimination and Black-White Differences in Preterm and Low-Birthweight Deliveries: The CARDIA Study

OBJECTIVES We examined the effects of self-reported experiences of racial discrimination on Black-White differences in preterm (less than 37 weeks gestation) and low-birthweight (less than 2500 g) deliveries. METHODS Using logistic regression models, we analyzed data on 352 births among women enrolled in the Coronary Artery Risk Development in Young Adults Study. RESULTS Among Black women, 50% of those with preterm deliveries and 61% of those with low-birthweight infants reported having experienced racial discrimination in at least 3 situations; among White women, the corresponding percentages were 5% and 0%. The unadjusted odds ratio for preterm delivery among Black versus White women was 2.54 (95% confidence interval [CI]=1.33, 4.85), but this value decreased to 1.88 (95% CI=0.85, 4.12) after adjustment for experiences of racial discrimination and to 1.11 (95% CI=0.51, 2.41) after additional adjustment for alcohol and tobacco use, depression, education, and income. The corresponding odds ratios for low birthweight were 4.24 (95% CI=1.31, 13.67), 2.11 (95% CI=0.75, 5.93), and 2.43 (95% CI=0.79, 7.42). CONCLUSIONS Self-reported experiences of racial discrimination were associated with preterm and low-birthweight deliveries, and such experiences may contribute to Black-White disparities in perinatal outcomes.

Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction.

BACKGROUND Although small changes in creatinine level during hospitalization have been associated with risk of short-term mortality, associations with posthospitalization end-stage renal disease (ESRD) and long-term mortality are unknown. We assessed the relationship between change in serum creatinine levels up to 3.0 mg/dL and death and ESRD among elderly survivors of hospitalization for acute myocardial infarction. METHODS Retrospective cohort study of a nationally representative sample of Medicare beneficiaries admitted with acute myocardial infarction to nonfederal US hospitals between February 1994 and July 1995. Outcomes were mortality and ESRD through June 2004. RESULTS The 87 094 eligible patients admitted to 4473 hospitals had a mean age of 77.1 years; for the 43.2% with some creatinine increase, quartiles of increase were 0.1, 0.2, 0.3 to 0.5, and 0.6 to 3.0 mg/dL. Incidence of ESRD and mortality ranged from 2.3 and 139.1 cases per 1000 person-years, respectively, among patients with no increase to 20.0 and 274.9 cases per 1000 person-years in the highest quartile of creatinine increase. Compared with patients without creatinine increase, adjusted hazard ratios by quartile of increase were 1.45, 1.97, 2.36, and 3.26 for ESRD and 1.14, 1.16, 1.26, and 1.39 for mortality, with no 95% confidence intervals overlapping 1.0 for either end point. CONCLUSION In a nationally representative sample of elderly patients discharged after hospitalization for acute myocardial infarction, small changes in serum creatinine level during hospitalization were associated with an independent higher risk of ESRD and death.

Relation of race and sex to the use of reperfusion therapy in Medicare beneficiaries with acute myocardial infarction.

BACKGROUND There are few reports describing the combined influence of the race and sex of a patient on the use of reperfusion therapy for acute myocardial infarction. METHODS To determine the relation of race and sex to the receipt of reperfusion therapy for myocardial infarction in the United States, we reviewed the medical records of 234,769 Medicare patients with myocardial infarction. From these records we identified 26,575 white or black patients who met strict eligibility criteria for reperfusion therapy. We then performed bivariate and multivariate analyses of prevalence ratios to determine predictors of the use of reperfusion therapy in four subgroups of patients categorized according to race and sex: white men, white women, black men, and black women. RESULTS Among eligible patients, white men received reperfusion therapy with the highest frequency (59 percent), followed by white women (56 percent), black men (50 percent), and black women (44 percent). After adjustment for differences in demographic and clinical characteristics, white women were as likely as white men to receive reperfusion therapy (prevalence ratio, 1.00; 95 percent confidence interval, 0.98 to 1.03). Likewise, black women were as likely as black men to receive reperfusion therapy (prevalence ratio, 1.00; 95 percent confidence interval, 0.89 to 1.13). However, black women were significantly less likely to receive reperfusion therapy than white men (prevalence ratio, 0.90; 95 percent confidence interval, 0.82 to 0.98), as were black men (prevalence ratio, 0.85; 95 percent confidence interval, 0.78 to 0.93). CONCLUSIONS After adjustment for differences in clinical and demographic characteristics and clinical presentation, differences according to sex in the use of reperfusion therapy are minimal. However, blacks, regardless of sex, are significantly less likely than whites to receive this potentially lifesaving therapy.

Ten-year incidence of elevated blood pressure and its predictors: The CARDIA Study

Few prospective studies have examined associations of lifestyle factors or variables in the insulin resistance syndrome (syndrome X) with incidence of elevated blood pressure (BP) in black subjects and women. This report estimates the 10-year incidence of high blood pressure (HBP) and high normal blood pressure (HNBP) in the biracial cohort of the Coronary Artery Risk Development in (Young) Adults Study (CARDIA), and examines lifestyle factors and four syndrome X variables, measured at baseline, as predictors. CARDIA examined 5115 black and white men and women aged 18–30 years in 1985–1986, and re-examined them at 2, 5, 7, and 10 years. The 10-year incidence of HBP was 16.4% in black men, 7.8% in white men, 13.1% in black women, and 3.2% in white women, while the 10-year incidence of HBP or HNBP was 29.5%, 16.2%, 19.2%, and 6.3%, respectively, in the four sex–race subgroups. Predictors included body mass index, waist circumference, physical activity, alcohol intake, pulse rate, cigarette smoking, education, fasting insulin, triglycerides, uric acid, and high-density lipoprotein cholesterol, as well as age and systolic BP. In univariate analyses, each of these variables was significantly related to incidence in at least one of the four sex–race groups. In multivariate analyses that included control for age and systolic pressure, independent predictors included fasting insulin in white men and women, triglycerides in white men, uric acid and pulse rate in black men, waist circumference in white men and black women, and education (inverse) in white men and black and white women. These results suggest that lower socioeconomic status, as assessed by education level, and one or more syndrome X variables, ie, fasting insulin, triglycerides, uric acid, may be associated with development of elevated BP in young adults.

Relationship of Early Life Stress and Psychological Functioning to Adult C-Reactive Protein in the Coronary Artery Risk Development in Young Adults Study

BACKGROUND Low socioeconomic status (SES) and a harsh family environment in childhood have been linked to mental and physical health disorders in adulthood. The objective of the present investigation was to evaluate a developmental model of pathways that may help explain these links and to relate them to C-reactive protein (CRP) in the Coronary Artery Risk Development in Young Adults (CARDIA) dataset. METHODS Participants (n = 3248) in the CARDIA study, age 32 to 47 years, completed measures of childhood SES (CSES), early family environment (risky families [RF]), adult psychosocial functioning (PsyF, a latent factor measured by depression, mastery, and positive and negative social contacts), body mass index (BMI), and C-reactive protein. RESULTS Structural equation modeling indicated that CSES and RF are associated with C-reactive protein via their association with PsyF (standardized path coefficients: CSES to RF, RF to PsyF, PsyF to CRP, CSES to CRP, all p < .05), with good overall model fit. The association between PsyF and CRP was partially mediated by BMI (PsyF to BMI, BMI to CRP, both p < .05). CONCLUSIONS Low childhood SES and a harsh early family environment appear to be related to elevated C-reactive protein in adulthood through pathways involving psychosocial dysfunction and high body mass index.

Chronic Disease as a Barrier to Breast and Cervical Cancer Screening

AbstractOBJECTIVE: To assess whether chronic disease is a barrier to screening for breast and cervical cancer. DESIGN: Structured medical record review of a retrospectively defined cohort. SETTING: Two primary care clinics of one academic medical center. PATIENTS: All eligible women at least 43 years of age seen during a 6-month period in each of the two study clinics (n=1,764). MEASUREMENTS AND MAIN RESULTS: Study outcomes were whether women had been screened: for mammogram, every 2 years for ages 50–74; for clinical breast examinations (CBEs), every year for all ages; and for Pap smears, every 3 years for ages under 65. An index of comorbidity, adapted from Charlson (0 for no disease, maximum index of 8 among our patients), and specific chronic diseases were the main independent variables. Demographics, clinic use, insurance, and clinical data were covariates. In the appropriate age groups for each test, 58% of women had a mammogram, 43% had a CBE, and 66% had a Pap smear. As comorbidity increased, screening rates decreased (p<.05 for linear trend). After adjustment, each unit increase in the comorbidity index corresponded to a 17% decrease in the likelihood of mammography (p=.005), 13% decrease in CBE (p=.006), and 20% decrease in Pap smears (p=.002). The rate of mammography in women with stable angina was only two fifths of that in women without. CONCLUSIONS: Among women who sought outpatient care, screening rates decreased as comorbidity increased. Whether clinicians and patients are making appropriate decisions about screening is not known.