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Biomedical subjects

R A Kronmal

Publications and source records attributed to R A Kronmal.

At least 19 recordsLinked to original sources
PubMed1992

Analysing the relationship between change in a risk factor and risk of disease.

There are numerous examples in the epidemiologic literature of analyses that relate the change in a risk factor, such as serum cholesterol, to the risk of an adverse outcome, such as heart disease. Many of these analyses fit some type of regression model (such as logistic regression or the Cox model for survival time data) that includes both the change in the risk factor and the baseline value as covariates. We show that this method of adjusting for the baseline level can produce misleading results. The problem occurs when the true value of the risk factor relates to the outcome, and the measured value differs from the true value due to measurement error. We may find the observed change in the risk factor significantly related to the outcome when there is in fact no relationship between the true change and the outcome. If the question of interest is whether a person who lowers his level of the risk factor by means of drugs or lifestyle changes will thereby reduce his risk of disease, then we should consider an association due solely to measurement error as spurious. We present a method that adjusts for the measurement error in a linear regression analysis and show that an analogous adjustment applies asymptotically to logistic regression. As in other errors-in-variables problems, this analysis depends on knowledge of the relative variances of the random variation, the true baseline value, and the true change. Since the magnitudes of these variances are usually unknown and sometimes unknowable (the distinction between true change and measurement error being ambiguous), we recommend a sensitivity analysis that examines how the analysis results depend on the assumptions concerning the variances. The commonly used analysis method corresponds to the extreme case in which there is no measurement error. We use data from the Framingham Study and simulations to illustrate these points.

Bias↗
PubMed1992

Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators.

BACKGROUND AND OBJECTIVES: The relation between cardiac mortality and antiarrhythmic drug administration has not been fully determined. This relation was analyzed in 1,330 patients enrolled in the Stroke Prevention in Atrial Fibrillation Study, a randomized clinical trial comparing warfarin, aspirin and placebo for the prevention of ischemic stroke or systemic embolism in patients with nonvalvular atrial fibrillation. METHODS: Patients who received antiarrhythmic drug therapy for atrial fibrillation in this study were compared with patients not receiving antiarrhythmic agents. The relative risk of cardiac mortality, including arrhythmic death, in patients receiving antiarrhythmic drug therapy was determined and adjusted for other cardiac risk factors. RESULTS: In patients receiving antiarrhythmic drug therapy, cardiac mortality was increased 2.5-fold (p = 0.006, 95% confidence interval [CI] 1.3 to 4.9) and arrhythmic death was increased 2.6-fold (p = 0.02, 95% CI 1.2 to 5.6). Among patients with a history of congestive heart failure, those given antiarrhythmic medications had a relative risk of cardiac death of 4.7 (p less than 0.001, 95% CI 1.9 to 11.6) compared with that of patients not so treated; the relative risk of arrhythmic death in the treated group was 3.7 (p = 0.01, 95% CI 1.3 to 10.4). Patients without a history of congestive heart failure had no increased risk of cardiac mortality (relative risk 0.70, 95% CI 0.2 to 3.1) during antiarrhythmic drug therapy. After exclusion of 23 patients with documented ventricular arrhythmias and adjustment for other variables predictive of cardiac death, patients receiving antiarrhythmic drugs were not at increased risk of cardiac death or arrhythmic death. However, in patients with a history of heart failure who received antiarrhythmic drug therapy, the relative risk of cardiac death was 3.3 (p = 0.05, 95% CI 0.99 to 11.1) and that of arrhythmic death was 5.8 (p = 0.009, 95% CI 1.5 to 21.7) compared with the risk in patients not taking antiarrhythmic medications. CONCLUSIONS: Although antiarrhythmic drug therapy was not randomly determined in this trial, the data suggest that in patients with atrial fibrillation and a history of congestive heart failure, the risk of such therapy may outweigh the potential benefit of maintaining sinus rhythm.

Anti-Arrhythmia Agents↗
PubMed1992

Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group.

BACKGROUND AND PURPOSE: This article describes the prevalence of extracranial carotid atherosclerosis assessed by ultrasonography, its association with risk factors, and its relation to symptomatic coronary disease and stroke in men and women aged > or = 65 years. METHODS: Maximum percent stenosis, maximum common carotid artery wall thickness, and maximum internal carotid artery wall thickness were assessed using duplex ultrasound in 5,201 men and women aged > or = 65 years in the Cardiovascular Health Study, a study of the risk factors and natural history of cardiovascular disease in the elderly. Existing coronary disease and stroke were assessed by physical examination and participant history. RESULTS: Detectable carotid stenosis was present in 75% of men and 62% of women, although the prevalence of > or = 50% stenosis was low, 7% in men and 5% in women. Maximum stenosis and maximum wall thickness measurements increased with age and were uniformly greater at all ages in men than in women (p < 0.00001). Established risk factors for atherosclerosis (hypertension, smoking, diabetes) and indications of vascular disease (left ventricular hypertrophy, major electrocardiographic abnormality, bruits, and history of heart disease or stroke) related to all three carotid artery measures in the elderly. Of the three ultrasound measures, the best correlate for a history of coronary disease was maximum internal carotid artery wall thickness. For stroke the best correlate was common carotid artery wall thickness. Multiple logistic regression models of prevalent coronary heart disease and stroke that included the ultrasound findings indicated, after adjustment for age and sex, that maximum internal wall thickness and maximum common carotid wall thickness were significant correlates of both. Maximum stenosis did not add significantly to the correlation. CONCLUSIONS: In the elderly the incidence of carotid atherosclerosis was high, although the frequency of severe disease was low. The prevalence and severity of carotid atherosclerosis continued to increase with age even in the late decades of life, and more disease was found in men than in women at all ages. Known risk factors for atherosclerosis continued to relate to carotid abnormalities in the later decades of life, both in symptomatic and asymptomatic subjects.

Aged↗
PubMed1991

The intrauterine device and pelvic inflammatory disease: the Women's Health Study reanalyzed.

The Women's Health Study (WHS) was a large, widely accepted and influential case-control study of the relationship between the use of intrauterine contraceptive devices (IUDs) and pelvic inflammatory disease (PID). The data were collected at 16 hospitals in 9 cities across the U.S.A. from October 1976 through August 1978. The first paper on this research was published in 1981 and concluded that IUDs increase the risk of PID. The report cited an estimated RR (relative risk) of PID for current IUD users vs nonIUD users of 1.6 with a 95% confidence interval of (1.4, 1.9). However, careful examination of the report reveals that the data support conclusions antithetical to those at which the author arrived. When the second report on the WHS was published in 1983, it was anticipated that many of the shortcomings of the first report would be corrected, but they were not. In 1983 we undertook a complete reanalysis of the same WHS data using more appropriate criteria and the results were compared to the first two published reports. The reanalysis revealed an RR of 1.02 (0.86, 1.21) for current IUD users compared to noncontraceptors. The conclusion of the WHS should have been that IUDs do not increase the risk of PID.

Adult↗
PubMed1991

The Cardiovascular Health Study: design and rationale.

The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of coronary heart disease and stroke in adults aged 65 years and older. The main objective of the study is to identify factors related to the onset and course of coronary heart disease and stroke. CHS is designed to determine the importance of conventional cardiovascular disease (CVD) risk factors in older adults, and to identify new risk factors in this age group, especially those that may be protective and modifiable. The study design called for enrollment of 1250 men and women in each of four communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Eligible participants were sampled from Medicare eligibility lists in each area. Extensive physical and laboratory evaluations were performed at baseline to identify the presence and severity of CVD risk factors such as hypertension, hypercholesterolemia and glucose intolerance; subclinical disease such as carotid artery atherosclerosis, left ventricular enlargement, and transient ischemia; and clinically overt CVD. These examinations in CHS permit evaluation of CVD risk factors in older adults, particularly in groups previously under-represented in epidemiologic studies, such as women and the very old. The first of two examination cycles began in June 1989. A second comprehensive examination will be repeated three years later. Periodic interim contacts are scheduled to ascertain and verify the incidence of CVD events, the frequency of recurrent events, and the sequellae of CVD.

Aged↗
PubMed1990

Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients.

The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial.

Angina Pectoris↗
PubMed1990

Risk ratios and risk differences in estimating the effect of risk factors for cardiovascular disease in the elderly.

This article reviews the nature of the effects of hypertension, smoking and cholesterol on the incidence of cardiovascular disease and emphasizes how these effects vary by age. In the Methods section, we discuss briefly the concepts of additive and multiplicative statistical models as tools for summarizing data. In the results section, we summarize available data on the association between incident stroke and coronary heart disease in the elderly and each of these major risk factors. The traditional multiplicative model parsimoniously characterizes the individual and joint effects of age and high blood pressure in terms of risk ratios; but, for smoking and cholesterol, an additive model appears to be the most parsimonious. We discuss the consequences of these observations for the study and prevention of cardiovascular disease in the elderly.

Adult↗
PubMed1989

Interannual variation of the incidence of Haemophilus influenzae type b meningitis.

We conducted a population-based retrospective cohort study to define the annual age-specific incidence of Haemophilus influenzae type b meningitis for birth to 5-year-old residents of King County, Washington, from January 1977 through December 1986. We found naturally occurring wide interannual variations in incidence. The standard deviations of the age-specific incidence during the eight years before the introduction of H influenzae vaccine varied from 26% to 115% of the mean. If short-term changes in incidence were used to assess the efficacy of an H influenzae vaccine (which is less than 100% efficacious and not administered to all susceptible children), the conclusions could be erroneous. To avoid this bias, long-term cohort studies, case/control studies using concurrent controls, or large clinical trials are better choices. We found no significant change in overall incidence during the ten-year study period.

Age Factors↗
PubMed1989

Anomalous coronary arteries: location, degree of atherosclerosis and effect on survival--a report from the Coronary Artery Surgery Study.

Limited information is available about clinical presentation, degree of atherosclerosis and effect on overall survival in a large series of patients with coronary artery anomalies. From the National Heart, Lung, and Blood Institute Multicenter Coronary Artery Surgery Study (CASS), detailed coding of coronary angiograms was available in 24,959 patients. Of these patients, 73 (0.3%) had major coronary artery anomalies: 70 had one coronary anomaly and 3 had two coronary anomalies. The most common anomaly involved the circumflex coronary artery (60%). In 69% of these, the circumflex artery arose from a separate ostium in the right coronary sinus, and in 31% it originated as a branch of the right coronary artery. The most common anomalous course was anterior or posterior to the great vessels but not between the great vessels. The major exception to this finding was an anomalous right coronary artery; 7 of 15 such arteries coursed between the great vessels. Anomalous circumflex coronary arteries had a significantly greater degree of stenosis than that in nonanomalous arteries in age- and gender-matched control patients (p = 0.02). Despite this difference, at 7 years there was no significant difference in survival by location or degree of stenosis in the anomalous artery.

Adult↗
PubMed1989

The impact of Haemophilus influenzae type b meningitis on nutritional status.

We investigated the immediate impact and long-term effects of Haemophilus influenzae type b meningitis on nutritional status and growth in 111 children. Mean weight change during 10 d of hospitalization was a loss of less than 1%. Follow-up median weight-for-height percentiles increased after admission (p less than 0.01). Percentile values were as follows: admission, 45th; 1 mo, 60th; 3 mo, 60th; and 6 mo, 68th. Forty-three percent of the cases were greater than 75th percentile of weight-for-height at 6 mo after disease. An additional follow-up assessment of weight-for-height indicated that 43% of a representative sample subset of 49 were still obese 1.17-5.5 y after disease. Significant differences in median concentrations of serum prealbumin were found between days 1 (128 mg/L) and 5 (199 mg/L, p less than 0.0001) and days 5 and 10 (214 mg/L, p less than 0.02). Median erythrocyte glutathione reductase activity coefficients increased between days 1 (1.16) and 5 (1.20, p less than 0.01). The mean free erythrocyte protoporphyrin-heme ratio increased between days 5 (10.78 X 10(-6)) and 10 (14.22 X 10(-6), p less than 0.01). We conclude that there were transient adverse changes in nutritional status. Obesity appears to occur after disease.

Acute Disease↗
PubMed1989

Anemia during Haemophilus influenzae type b meningitis: lack of an effect of chloramphenicol.

We sought to determine whether chloramphenicol would worsen or mitigate the anemia associated with Haemophilus influenzae type b meningitis if administered in doses which produce 'therapeutic' serum concentrations. Seventy-four cases of H. influenzae meningitis were stratified by chloramphenicol cumulative doses (mg/kg body weight) of less than 300 and greater than 300. There was no significant difference in the decrease in blood hemoglobin concentration or in the increase in the FEP:Heme ratio between the two study groups. Plasma iron and transferrin saturation values indicated iron deficiency at days 1 and 5 of hospitalization; by day 10 mean values were within the normal range. These data suggest that H. influenzae type b meningitis, not chloramphenicol therapy in the presence of monitoring is causing the observed anemia.

Anemia↗
PubMed1988

Beneficial six-year outcome of smoking cessation in older men and women with coronary artery disease. Results from the CASS registry.

We investigated the effects of cigarette smoking and cessation of smoking in a cohort of 1893 men and women from the Coronary Artery Surgery Study (CASS) registry who were 55 years of age or older and had angiographically documented coronary artery disease. The six-year mortality rate was greater among continuing smokers (n = 1086) than among those who quit smoking during the year before enrollment in the study and abstained throughout the study (n = 807) (relative risk, 1.7 [95 percent confidence limits, 1.4, 2.0]). Continuing smokers were also at higher risk of either myocardial infarction or death (1.5 [1.2, 1.7]). There was no diminution of the beneficial effect with increasing age. The relative risks of death were 1.7 (1.4, 2.1) and 1.6 (1.1, 2.3) for the groups 55 to 64 years old and 65 or older, respectively, and 1.6 (1.4, 1.9) for comparable subgroups among CASS subjects 35 to 54 years of age. When subjects were arrayed according to risk quartile, the benefits of smoking cessation were greatest in those at moderate risk. We conclude that smoking cessation lessens the risk of death or myocardial infarction in older as well as younger persons with coronary artery disease.

Adult↗
PubMed1988

Prevalence and significance of atrial fibrillation in coronary artery disease (CASS Registry).

Estimates of the prevalence of atrial fibrillation (AF) in patients with coronary artery disease have varied from "frequent" to less than 2%. Data on 18,343 patients with angiographically demonstrated CAD in the Coronary Artery Surgery Study (CASS) registry were reviewed and AF was found to be present in 116 (0.6%) patients. The presence of AF was positively associated with the following clinical and angiographic variables: older age, sex (male), mitral regurgitation and functional impairment due to congestive heart failure. The number of diseased coronary arteries was negatively related to the presence of AF. Atrial fibrillation was an independent predictor of survival and its presence doubled the estimated risk over those patients without AF.

Adult↗
PubMed1987

Evaluation of the use of braces to prevent injury to the knee in collegiate football players.

Data were collected in 1984 from seventy-one schools that were members of Division I of the National College Athletic Association and in 1985 from sixty-one of these schools to assess whether the use of so-called preventive braces for the knee was associated with a decrease in either the severity or the incidence (or both) of injuries to the knee in collegiate football players. Over-all, players who wore braces on the knees had significantly more injuries to the knee than players who did not. The severity of the injuries was no different in the two groups. Based on these findings, we cannot recommend the use of these braces in an attempt to prevent injury to collegiate football players.

Adult↗
PubMed1986

Effect of age at loss of dietary control on intellectual performance and behavior of children with phenylketonuria.

We determined the effect on intellectual performance and behavior of the age at which dietary control was lost in 119 10-year-old children with phenylketonuria (PKU) who had started on a diet low in phenylalanine before the age of 65 days. The children's diets were considered to be out of control when their blood phenylalanine concentration persistently exceeded 15 mg per deciliter. The age at which control was lost was the best, and frequently the only, predictor of the child's IQ at the age of 8 or 10 years and of the deficit in the child's IQ as compared with those of his or her unaffected siblings or parents. The age at which control was lost was also the best predictor of the deficit in scores on the Wide Range Achievement Test of children with PKU at the age of eight, as compared with their unaffected siblings, and of behavior problems (Louisville Behavior Checklist). Variables that were not significant included the maximal phenylalanine concentration before dietary therapy, the age at which treatment was started, and the family's coping abilities. The greatest deficiencies in all of these outcomes were observed among children who were out of dietary control before the age of six years. The highest correlation between the IQs of the children with PKU and their respective parents was observed among the children still on the diet at the age of eight years; the lowest, among those who had poor dietary control before the age of six. These findings suggest that phenylalanine restriction should continue after the age of eight years in children with PKU.

Adolescent↗
PubMed1986

Effect of cigarette smoking on survival of patients with angiographically documented coronary artery disease. Report from the CASS registry.

Through a multicenter registry of patients in the Coronary Artery Surgery Study, we prospectively evaluated morbidity and mortality in 4,165 smokers with angiographically proved coronary artery disease, 2,675 of whom continued to smoke and 1,490 of whom quit. At five years, mortality (adjusted by Cox analysis for baseline differences) was 22% for those who continued smoking and 15% for quitters. The relative risk (also from the Cox analysis) for mortality in continuers vs quitters was 1.55 (95% confidence interval, 1.29 to 1.85). The adverse effect of smoking mainly took the form of higher frequencies of myocardial infarction--associated death and sudden death: the frequencies of these events during follow-up in continuers vs quitters were 7.9% vs 4.4% for myocardial infarction--associated death and 2.8% vs 1.5% for sudden death. This study supports the recommendation that patients with coronary artery disease should stop smoking.

Coronary Disease↗
PubMed1986

Seven year survival of patients with normal or near normal coronary arteriograms: a CASS registry study.

The effect on 7 year survival of having a normal or near normal coronary arteriogram was examined using data from the CASS registry of 21,487 consecutive coronary arteriograms taken in 15 clinical sites. Of these, 4,051 arteriograms were normal or near normal, and the patients had normal left ventricular function as judged by absence of a history of congestive heart failure, no reported segmental wall motion abnormality and an ejection fraction of at least 50%; 3,136 arteriograms were entirely normal and the remaining 915 revealed mild disease with less than 50% stenosis in one or more segments. The 7 year survival rate was 96% for the patients with a normal arteriogram and 92% for those whose study revealed mild disease (p less than 0.0001). Nine risk variables recorded at entry were analyzed for predictive value for survival: age, sex, height, weight, history of smoking, presence of absence of mild disease, electrocardiographic response to exercise, family history of coronary heart disease and a history of hypertension. Of these, age, smoking history, presence or absence of disease and a history of hypertension had predictive value.

Adult↗