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K M Anderson

Publications and source records attributed to K M Anderson.

At least 109 records · Page 6Linked to original sources
PubMed1992

Maximum likelihood estimation for interval-censored data using a Weibull-based accelerated failure time model.

The accelerated failure time regression model is most commonly used with right-censored survival data. This report studies the use of a Weibull-based accelerated failure time regression model when left- and interval-censored data are also observed. Two alternative methods of analysis are considered. First, the maximum likelihood estimates (MLEs) for the observed censoring pattern are computed. These are compared with estimates where midpoints are substituted for left- and interval-censored data (midpoint estimator, or MDE). Simulation studies indicate that for relatively large samples there are many instances when the MLE is superior to the MDE. For samples where the hazard rate is flat or nearly so, or where the percentage of interval-censored data is small, the MDE is adequate. An example using Framingham Heart Study data is discussed.

Age Factors↗
PubMed1991

Influence of contemporary versus 30-year blood pressure levels on left ventricular mass and geometry: the Framingham Heart Study.

To determine whether long-term blood pressure levels correlate with left ventricular mass, echocardiographic measurements were performed in 152 men and 299 women who were participants in the Framingham Heart Study. All subjects were free of obesity and cardiovascular and pulmonary disease, were not taking antihypertensive medications and had echocardiographic studies that were adequate for estimating left ventricular mass. Thirty-year average systolic blood pressure was correlated with left ventricular mass (corrected for height) (r = 0.27, p less than 0.001 in men; r = 0.31, p less than 0.001 in women). Multivariate linear regression analyses taking into account age and body mass index showed 30-year average systolic blood pressure to be a significant independent predictor of left ventricular mass (p less than 0.01 in men and women). Systolic blood pressure at echocardiography was not independently associated with left ventricular mass when 30-year systolic blood pressure was entered into the multivariate model. The prevalence of left ventricular hypertrophy was associated with 30-year average systolic blood pressure (odds ratio for every 20-mm Hg increase in blood pressure: 3.20, p less than 0.05 in men; 3.27, p less than 0.001 in women). The increase in left ventricular mass associated with 30-year average systolic blood pressure reflected changes in left ventricular wall thickness but not in left ventricular internal dimension. Thirty-year average diastolic blood pressure was also correlated with left ventricular mass but to a lesser degree than was systolic blood pressure (r = 0.18, p less than 0.05 in men; r = 0.18, p less than 0.01 in women).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

The impact of obesity on left ventricular mass and geometry. The Framingham Heart Study.

OBJECTIVE: --To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. DESIGN: --Survey. SETTING: --Population-based epidemiologic study. PARTICIPANTS AND METHODS: --M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study. Measured height and weight were used to calculate body-mass index, a measure of obesity. RESULTS: --Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension (P less than .01 for all). Body-mass index was associated with prevalence of echocardiographic left ventricular hypertrophy, particularly in subjects with a body-mass index exceeding 30 kg/m2. CONCLUSIONS: --Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension.

Adult↗
PubMed1991

Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study).

Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p less than 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p less than 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p less than 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p less than 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease.

Von Hippel Lindau disease (VHL) is a hereditary syndrome, associated with tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The availability of a genetic test for the early and reliable detection of individuals carrying the defective gene would be beneficial for VHL patients and their relatives, since many of the manifestations of VHL can be successfully treated if detected in their early stages, while the complications of undetected disease can be devastating. We have previously shown that the VHL gene maps to chromosome 3p. To provide genetic markers for the development of a reliable diagnostic test, and to further narrow and eventually clone the VHL defect, we have generated DNA markers for chromosome 3p. With these markers, we have performed a multipoint genetic linkage analysis in 28 VHL pedigrees, comprising 470 individuals, 164 of whom were affected with VHL. Here we report the identification of tightly linked markers, including flanking markers that bracket the VHL gene to a small region on chromosome 3p25-p26. This finding has several major implications. While visceral cysts of the kidney, pancreas, and epididymis are commonly found in VHL and are considered diagnostic criteria for this disorder, they also occur in the general population. The presence of cysts, unaccompanied by other more typical lesions such as retinal and cerebellar hemangioblastoma, may therefore represent a major diagnostic problem, leading to errors in the assessment of disease status. The application of flanking markers for the VHL gene for presymptomatic diagnostic testing confirms that epididymal cysts are indeed not suitable as a diagnostic criterion in this disorder. Pheochromocytomas occur nonuniformly in VHL families and may also be associated with other hereditary tumor syndromes; our genetic studies imply that the phenotype in VHL families with and without pheochromocytomas is caused by defects within the same gene. The absence or presence of this tumor type is therefore due to the pleiotropic expression of a single gene rather than to the existence of several different genes for VHL. The region on chromosome 3p13-p14 known to contain several chromosomal translocation breakpoints in families with "pure familial renal cell carcinoma" is quite proximal to the VHL locus in 3p25-p26 we have identified. Chromosome 3p may therefore contain two loci for renal cell carcinoma: one gene (or genes) in 3p13-p14 and the VHL gene in 3p25-p26, whose aberration is also associated with other typical manifestations of VHL. Since renal cell carcinoma, pheochromocytoma, and visceral cysts can occur sporadically even in young people and may also be associated with other tumor syndromes, the availability of flanking markers for the VHL gene will be useful in identifying VHL gene carriers, particularly among those individuals at risk in whom these are the only manifestations of disease. The isolation and characterization of the VHL gene, based on the identification of flanking markers, will have important implications for diagnosis and treatment of patients with VHL, as well as for a much larger number of individuals having the sporadic counterparts of VHL-associated tumor types.

Cell Line↗
PubMed1991

Duration of the QT interval and total and cardiovascular mortality in healthy persons (The Framingham Heart Study experience).

The baseline electrocardiograms of 5,125 original subjects of the Framingham Heart Study were measured to examine the relation of the QT interval corrected for heart rate (QTc) to risk of total mortality, sudden cardiac death, and death due to coronary artery disease over a 30-year follow-up period. Quintiles of QTc (seconds) less than or equal to 0.36, 0.36 to 0.38, 0.39 to 0.40, 0.41 to 0.43 and greater than or equal to 0.44 were studied in relation to these outcomes. There were no significant differences in the risk of total mortality, sudden cardiac death or death due to coronary artery disease according to QTc. A similar lack of significant association between QTc and these 3 outcomes was observed among all persons studied and in the 2 sexes after using a multiple regression analysis to control for several potentially confounding characteristics including age, gender, cigarette smoking, serum total cholesterol, systolic systemic blood pressure and Framingham relative weight. The results of this study fail to demonstrate an association between baseline QTc and overall mortality, and deaths due to sudden cardiac events or coronary artery disease in a large population-based cohort of essentially healthy persons in whom pathologic forms of QTc prolongation are uncommon.

Adult↗
PubMed1991

Cardiovascular disease risk profiles.

This article presents prediction equations for several cardiovascular disease endpoints, which are based on measurements of several known risk factors. Subjects (n = 5573) were original and offspring subjects in the Framingham Heart Study, aged 30 to 74 years, and initially free of cardiovascular disease. Equations to predict risk for the following were developed: myocardial infarction, coronary heart disease (CHD), death from CHD, stroke, cardiovascular disease, and death from cardiovascular disease. The equations demonstrated the potential importance of controlling multiple risk factors (blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking, glucose intolerance, and left ventricular hypertrophy) as opposed to focusing on one single risk factor. The parametric model used was seen to have several advantages over existing standard regression models. Unlike logistic regression, it can provide predictions for different lengths of time, and probabilities can be expressed in a more straightforward way than the Cox proportional hazards model.

Adult↗
PubMed1991

Twelve-year incidence of coronary heart disease in middle-aged adults during the era of hypertensive therapy: the Framingham offspring study.

PURPOSE: To provide information on the incidence of coronary heart disease (CHD) in the offspring of the original cohort from the Framingham Heart Study. PATIENTS AND METHODS: From 1972 to 1974, offspring of the original participants in the Framingham Heart Study underwent a baseline examination for standard cardiovascular risk factors. At entry into the study, these offspring were 30 to 59 years old and free of CHD. They were followed for 12 years, during which time 156 of 1,663 men and 55 of 1,714 women developed CHD. RESULTS: In a multivariate proportional hazards model, CHD was significantly associated with age, lower high-density lipoprotein cholesterol (HDL-C) levels, and number of cigarettes smoked. Fasting glucose levels and low-density lipoprotein cholesterol (LDL-C) were highly associated with CHD in men, but borderline in women, while triglycerides and very-low-density lipoprotein cholesterol were not significantly associated with CHD after adjustment for HDL-C and glucose. Blood pressure medication was used in half of the hypertensive individuals, and systolic pressure was associated with CHD in women only. CONCLUSIONS: This study confirms the importance of the common CHD risk factors of cigarette smoking and LDL-C, and extends the prognostic role of HDL-C in a middle-aged cohort. The impact of blood pressure, with or without use of hypertensive medications, was reduced in this study, and the data suggest that this attenuation was due to successful treatment.

Adult↗
PubMed1991

Heart rate adjustment of exercise-induced ST segment depression. Improved risk stratification in the Framingham Offspring Study.

BACKGROUND: Simple heart rate adjustment of ST segment depression during exercise (delta ST/HR index) and the pattern of ST depression as a function of heart rate during exercise and recovery (the rate-recovery loop) have been shown to improve the ability of the exercise electrocardiogram to detect the presence of coronary heart disease (CHD), but the performance of these methods for the prediction of future coronary events remains to be examined. METHODS AND RESULTS: We compared the delta ST/HR index and the rate-recovery loop with standard electrocardiographic criteria for prediction of CHD events in 3,168 asymptomatic men and women in the Framingham Offspring Study who underwent treadmill exercise electrocardiography and who, at entry, were free of clinical and electrocardiographic evidence of CHD. After a mean follow-up of 4.3 years, there were 65 new CHD events: four sudden deaths, 24 new myocardial infarctions, and 37 incident cases of angina pectoris. When a Cox proportional hazards model with adjustment for age and sex was used, a positive exercise electrocardiogram by standard criteria (greater than or equal to 0.1 mV horizontal or downsloping ST segment depression) was not predictive of new CHD events (chi 2 = 0.40, p = 0.52). In contrast, stratification according to the presence or absence of a positive delta ST/HR index (greater than or equal to 1.6 microV/beat/min) and a positive (counterclockwise) rate-recovery loop was associated with CHD event risk (chi 2 = 9.45, p less than 0.01) and separated subjects into three groups with varying risks of coronary events: high risk, when both tests were positive (relative risk 3.6; 95% confidence interval, 2.4-5.4); intermediate risk, when either the delta ST/HR index or the rate-recovery loop was positive (relative risk, 1.9; 95% confidence interval, 1.3-2.8); and low risk, when both tests were negative. After multivariate adjustment for age, sex, smoking, total cholesterol level, fasting glucose level, diastolic blood pressure, and electrocardiographic evidence of left ventricular hypertrophy, the combined delta ST/HR index and rate-recovery loop criteria remained predictive of coronary events (chi 2 = 5.45, p = 0.02). CONCLUSIONS: Heart rate adjustment of ST segment depression by the delta ST/HR index and the rate-recovery loop during exercise electrocardiography can improve prediction of future coronary events in asymptomatic men and women.

Adult↗
PubMed1991

Differential sensitivity of arteriolar alpha 1- and alpha 2-adrenoceptor constriction to metabolic inhibition during rat skeletal muscle contraction.

Our previous studies in rat skeletal muscle have determined that neural constriction of large arterioles, which regulate blood flow and peripheral resistance, is mediated by alpha 1-adrenoceptors, whereas small arterioles, which determine effective capillary density, depend on alpha 2-receptors. During physical exercise, metabolic vasodilators from contracting skeletal muscle oppose neural vasoconstriction. By mechanisms that are not understood, adrenergic constriction of small arterioles is particularly sensitive to metabolic inhibition during imbalances in oxygen supply versus demand. This sensitivity may result from the reliance of small arterioles on alpha 2-receptors and a greater sensitivity of alpha 2 constriction to metabolic dilators. We previously demonstrated selective attenuation of arteriolar alpha 2 constriction during a reduction in the oxygen supply/demand ratio subsequent to decreased skeletal muscle perfusion. In the present study, intravital microscopy of rat cremaster skeletal muscle was used to examine the effect of increased oxygen demand on adrenergic constriction of arterioles. The effect of multiple frequencies of skeletal muscle contraction (via genitofemoral nerve stimulation) on alpha 1 (norepinephrine + rauwolscine) and alpha 2 (norepinephrine + prazosin) constriction was used to evaluate neural-metabolic interactions over a wide range of metabolic conditions. Low-frequency (less than or equal to 2 Hz) skeletal muscle contraction attenuated only alpha 2 constriction; contractions greater than or equal to 4 Hz attenuated alpha 1 constriction and further reduced alpha 2 constriction. Comparison of the frequency of contraction necessary to produce inhibition of 20% of maximal dilation indicated that alpha 2 constriction was approximately 10-fold more sensitive than alpha 1 constriction to "metabolic" inhibition. High-frequency, but not low-frequency, contraction also inhibited intrinsic tone. These data suggest that release of dilator substances during moderate exercise may preferentially attenuate alpha 2 constriction to produce small arteriolar dilation and increased capillary density. In contrast, metabolic signals associated with higher frequency muscle contraction may inhibit both intrinsic tone and large arteriolar alpha 1 tone so that blood flow and oxygen delivery increase to match the elevated oxygen demand of more heavily exercising muscle.

Animals↗
PubMed1991

Mood and clinical status in patients with multiple myeloma.

Two hundred ninety patients with a recent diagnosis of multiple myeloma were studied psychologically at the time of initial treatment. Physician- and patient-completed psychosocial scales were correlated with physical variables used to measure tumor load and physical status. A logistic regression model was used to analyze objective response to treatment. Indirect measures of response to treatment were obtained, and factors influencing survival duration were studied using a Cox regression model. If physical variables were controlled, there were no significant correlations between psychologic scores on entry and response to treatment or survival duration. Thus, the notion that mood influences disease outcome once the disease process has begun in patients with multiple myeloma is not supported by this data set.

Adult↗
PubMed1991

A nonproportional hazards Weibull accelerated failure time regression model.

We present a study of risk factors measured in mean before age 50 and subsequent incidence of heart disease over 32 years of follow-up. The data are from the Framingham Heart Study. The standard accelerated failure time model assumes the logarithm of time until an event has a constant dispersion parameter and a location parameter that is a linear function of covariates. Parameters are estimated by maximum likelihood. We reject a standard Weibull model for these data in favor of a model with the dispersion parameter depending on the location parameter. This model suggests that the cumulative hazard ratio for two individuals shrinks towards unity over the follow-up period. Thus, not only the standard Weibull, but also the semiparametric proportional hazards (Cox) model is inadequate for this data. The model improvement appears particularly valuable when estimating the difference in predicted outcome probabilities for two individuals.

Adult↗
PubMed1991

QRS interval fails to predict coronary disease incidence. The Framingham Study.

The Framingham Study cohort of 5209 white men and women was examined to determine the long-term incidence of manifestations of new coronary heart disease as a function of QRS interval on subjects' baseline electrocardiograms (recorded at the 9th biennial examination). Over 18 years of follow-up, age-adjusted incidence of myocardial infarction, angina pectoris, and coronary death appeared unrelated to baseline QRS prolongation in both sexes, by Cox regression. Subjects with left bundle-branch block fared no worse than those with right pattern. These relations held whether or not subjects with baseline electrocardiographic abnormalities other than intraventricular block were excluded from consideration. In sum, QRS duration is an unimportant predictor of coronary disease in this Framingham population.

Adult↗
PubMed1990

Prognostic use of a QRS scoring system after hospital discharge for initial acute myocardial infarction in the Framingham cohort.

Myocardial infarct size is an important risk factor for survival after acute myocardial infarction (AMI). The purpose of this study was to determine the prognostic value of myocardial infarct size, as estimated by the Selvester 54-criteria/32-point QRS scoring system, in the Framingham cohort. During the first 30 years of the Framingham Heart Study, a total of 384 participants developed an AMI requiring hospitalization; from this group, 243 patients met the following inclusion criteria: (1) no electrocardiographic changes due to a previous infarction, (2) survival greater than 3 days after discharge from the AMI hospitalization and (3) no electrocardiographic evidence of conduction disturbances or ventricular hypertrophy at the time of their final in-hospital electrocardiogram. Univariate and multivariate analyses were performed to test the association of the QRS score, and other associated risk factors, with time until coronary heart disease-related death. QRS score was found to be significantly associated with outcome (p = 0.03), as was the systolic blood pressure before infarction (p greater than 0.001). Both univariate and multivariate analysis showed that a history of systolic hypertension was the variable most strongly associated with coronary heart disease-related death. Thus, identification of AMI survivors at high risk for subsequent mortality can be improved by routine blood pressure measurement before AMI, and QRS scoring of the electrocardiogram taken at hospital discharge.

Adult↗
PubMed1990

Physical activity and risk of large bowel cancer in the Framingham Study.

We examined the relation between self-reported physical activity and large bowel cancer in a prospective cohort of men and women who participated in the Framingham Study. Self-assessments of physical activity were available from the fourth biennial examination on a total of 1906 men and 2308 women aged 30 to 62 yr in 1954. The cohort was followed for up to 28 yr and yielded 152 cases (73 men, 79 women) of large bowel cancer. Inactivity was associated with an increased risk of large bowel cancer among men but not among women. The relative risk estimates for large bowel cancer among men in the middle and lowest tertiles of a physical activity index (compared with the highest tertile) were 1.4 (95% confidence intervals, 0.8-2.6) and 1.8 (1.0-3.2), respectively. Among women the comparable estimates were 1.2 (0.7-2.1) and 1.1 (0.6-1.8), respectively. These findings were unchanged after adjustment for body mass index, serum cholesterol, alcohol, and other potentially confounding variables. The narrow range of physical activity and the minimal heavy activity reported by women in this cohort may have limited our ability to detect an association between physical activity and large bowel cancer among women.

Adult↗