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Biomedical subjects

L H Kuller

Publications and source records attributed to L H Kuller.

At least 127 records · Page 7Linked to original sources
PubMed1998

Carotid atherosclerosis in premenopausal and postmenopausal women and its association with risk factors measured after menopause.

BACKGROUND AND PURPOSE: In women, symptoms of coronary artery disease are delayed by 10 to 15 years in comparison with men, most likely because of the protective effect of ovarian hormones. This report compares the prevalence and degree of carotid atherosclerosis between 292 premenopausal women and 294 women at 5 to 8 years after menopause. METHODS: Scans were performed in the same laboratory over the same time period for both groups. Intima-media thickness (IMT) was averaged across the common, bulb, and internal carotids. The plaque index summarized degree of focal plaque based on the size and number of plaques throughout both carotid systems. RESULTS: Mean IMT was 0.69 mm for premenopausal women and 0.77 mm for postmenopausal women (P < 0.001). Prevalence of plaque was 25% among premenopausal women and 54% among postmenopausal women (P < 0.001). In both premenopausal and postmenopausal women, risk factors measured before menopause were associated with carotid atherosclerosis. Premenopausal risk factors independently associated with IMT were higher pulse pressure (P < 0.001), triglycerides (P = 0.002), body mass index (P < 0.001), and study group (a surrogate for both age and menopausal status; P < 0.001). Premenopausal risk factors independently associated with focal plaque were ever smoking (P = 0.002), higher pulse pressure (P = 0.028), higher LDL (P = 0.003), age at baseline (P = 0.050), and study group (P < 0.001). CONCLUSIONS: Subclinical carotid atherosclerosis can be observed in middle-aged women. Risk factors measured before menopause are clearly associated with subclinical disease measured both concurrently and at 5 to 8 years after menopause.

Adult↗
PubMed1998

Stress-induced pulse pressure change predicts women's carotid atherosclerosis.

BACKGROUND AND PURPOSE: Individuals who exhibit large increases in blood pressure and heart rate during mental stress may be at risk for accelerated atherosclerosis. This report evaluates the association between stress-induced hemodynamic responses and carotid atherosclerosis in 254 healthy postmenopausal women. METHODS: The magnitude of change in blood pressure and heart rate from rest to public speaking and mirror image tracing, two stressful tasks, was measured. Average intima-media thickness (IMT) and focal plaque in the common carotid artery, bulb, and internal carotid artery were measured with the use of duplex ultrasonography on average 2.3 years later. RESULTS: The average IMT was 0.77 mm, with a range of 0.60 to 1.37; 52.5% had at least one plaque. Correlational analysis showed that greater IMT was associated with greater pulse pressure change during mental stress (r = 0.17, P < 0.01). Statistical adjustments for possible confounders (age, hormone replacement therapy use, resting pulse pressure, smoking status, and triglyceride levels) did not alter the results. The plaque index was associated with greater pulse pressure change during the mirror image tracing task (odds ratio = 1.47, P = 0.01) for women with a plaque score of > or = 2 versus 1 or 0, adjusted for possible confounders. CONCLUSIONS: Mental stress-induced pulse pressure changes may influence the development of early atherosclerosis in the carotid artery of women. Widening of pulse pressure during stress, as well as at rest, may be a marker of compromised compliance in the vessel wall.

Arteriosclerosis↗
PubMed1998

Smoking cessation, weight gain, and changes in cardiovascular risk factors during menopause: the Healthy Women Study.

OBJECTIVES: The relationship between smoking cessation, subsequent weight gain, and cardiovascular disease risk factors from premenopause to postmenopause was studied. METHODS: Healthy Women Study participants were assessed for changes in coronary heart disease risk factors from a premenopausal baseline assessment to first- and second-year postmenopausal assessments. RESULTS: Although ex-smokers gained substantially more weight than nonsmokers and smokers, they did not experience a greater increase in cardiovascular risk factors. In fact, the results indicated a trend toward ex-smokers' high-density lipoprotein cholesterol levels increasing slightly more than those of nonsmokers and smokers. CONCLUSIONS: Smoking cessation in perimenopausal to postmenopausal women is associated with greater weight gain but appears to be modestly associated with certain positive changes in cardiovascular risk factors.

Alcohol Drinking↗
PubMed1998

The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population.

OBJECTIVE: To examine whether a potential marker for type 2 diabetes (family history) is related to CAD in type 1 diabetic subjects. The two major types of primary diabetes, type 1 and type 2, are both associated with an increased risk of developing coronary artery disease (CAD). However, the etiology and associated risk factors may differ by type of diabetes. In type 2 diabetes, CAD is likely to be linked with the insulin resistance associated with the type 2 "process," while CAD in type 1 diabetes has, so far, been more closely linked to renal disease. Because the etiologies of type 1 and type 2 diabetes are different, it is possible that some CAD in type 1 diabetes may be related to the coexistence of type 2 diabetes susceptibility (i.e., insulin resistance). RESEARCH DESIGN AND METHODS: We evaluated the interrelationships between family history of type 2 diabetes (age at onset > 30 years, no insulin for 1st year) and presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications study (n = 658). RESULTS: A first-degree family history of type 2 diabetes was reported in 112 subjects, and CAD was present in 119 subjects. Those subjects reporting a family history of type 2 diabetes were significantly older, had a longer duration of type 1 diabetes, had higher triglyceride and LDL cholesterol levels, and had a borderline significantly increased Beck depression inventory. Sex differences in CAD risk factors were also noted. Using logistic regression analysis, the odds ratio (95% CI) for the presence of CAD in association with a family history of NIDDM was 1.89 (1.27-2.84). The odds ratio (95% CI) after adjusting for disease duration, triglycerides, hypertension, Beck depression, and nephropathy status was 1.45 (0.87-2.28). CONCLUSIONS: We conclude that a family history of type 2 diabetes is a risk factor for CAD in type 1 diabetic subjects. This supports the concept that insulin resistance may contribute to development of CAD in type 1 diabetes.

Adult↗
PubMed1998

Factor V Leiden is not a risk factor for arterial vascular disease in the elderly: results from the Cardiovascular Health Study.

Coagulation factor V Leiden is a risk marker for venous thrombosis. For arterial thrombosis no large study to date has included population-based elderly patients. The Cardiovascular Health Study is a longitudinal study of 5,201 men and women over age 65. With 3.4-year follow-up, we studied 373 incident cases of myocardial infarction (MI), angina, stroke. or transient ischemic attack (TIA), and 482 controls. The odds ratios for each event with heterozygous factor V Leiden were: MI, 0.46 (95% CI 0.17 to 1.25); angina, 1.0 (95% CI 0.45 to 2.23); stroke, 0.77 (95% CI 0.35 to 1.70): TIA, 1.33 (95% CI 0.5 to 3.55); any outcome, 0.83 (95% CI 0.48 to 1.44). Adjustment for cardiovascular risk factors did not change relationships. In older adults factor V Leiden is not a risk factor for future arterial thrombosis.

Adult↗
PubMed1998

Correlates of antithrombin, protein C, protein S, and TFPI in a healthy elderly cohort.

The majority of fatal acute myocardial infarctions occur in the elderly. Since these events are predominantly thrombotic, we studied the cross-sectional associations of the anticoagulant proteins Antithrombin, Protein C, Protein S. and Tissue Factor Pathway Inhibitor (TFPI) in a subgroup (n = 400) of the Cardiovascular Health Study (a study of healthy men and women > or = 65 years) free of clinical cardiovascular disease (CVD). We did not observe any strong age-associated trends, although Protein C was lower in older women (p < or = 0.001), and TFPI was higher in older men (p < or = 0.01). The inhibitors were highly intercorrelated, and were associated with increased levels of inflammation-sensitive proteins (e.g., fibrinogen. plasminogen), lipids (especially total and LDL-cholesterol), and coagulation factors, such as Factors VIIc, IXc, and Xc. None was associated with the procoagulant markers Prothrombin Fragment F1-2 or Fibrinopeptide A. Only TFPI was associated with subclinical atherosclerosis: ankle-arm index and internal carotid artery stenosis, p trend < or = 0.01; and carotid wall thickness, p trend < or = 0.05. In multivariate analysis the independent predictors of TFPI were levels of fibrinogen; the fibrinolytic marker plasmin-antiplasmin complex; LDL-cholesterol; and carotid wall thickness (R2 for the model = 0.35). In summary, the inhibitors did not appear to increase with age, and were predominantly associated with inflammation markers and lipids. Since markers of thrombin production do increase with age, we hypothesize that an age-related hemostatic imbalance may ensue, with associated increased thrombotic risk. Only TFPI was associated with subclinical CVD, suggesting that it may more closely reflect endothelial damage.

Aged↗
PubMed1998

Maintenance of cardiovascular risk factor changes among middle-aged women in a lifestyle intervention trial.

The Women's Healthy Lifestyle Project is a 5-year randomized clinical testing whether a behavioral intervention aimed at lifestyle changes in diet and physical activity can prevent the rise in weight and low-density lipoprotein cholesterol (LDL-c) observed during menopause. Cardiovascular risk factor and behavioral data from 489 participants (intervention group n = 236; control group n = 253) who attended baseline, 6-month, and 18-month clinical assessments were analyzed to determine how well initial improvements achieved at 6 months were maintained over the subsequent year of follow-up. Results indicated that the treatment effect persisted at 18 months for weight, body mass index, total cholesterol, LDL-c, systolic blood pressure (SBP), and glucose levels. Intervention participants maintained improvements in physical activity, caloric intake, dietary cholesterol, SBP, and glucose levels between 6 and 18 months, although weight, total cholesterol, and LDL-c began to rise during this period. Eighty percent of intervention participants compared to 45% of controls were at or under baseline weight at 18 months, suggesting that promoting modest weight loss may be an effective approach to preventing weight gain in these women.

Adult↗
PubMed1997

Estrogen replacement therapy and mortality among older women. The study of osteoporotic fractures.

BACKGROUND: Most previous studies of estrogen replacement therapy (ERT) and mortality have focused on younger women. Recently, it has been suggested that the effect of ERT on mortality may represent a "healthy-user" effect, ie, those with healthier lifestyles having a greater likelihood of receiving ERT. METHODS: Nine thousand seven hundred four women, 65 years or older, participated; 1258 (14.1%) reported current use of ERT for at least 1 year at entry. During an average follow-up of 6.0 years, 1054 women (11.8%) died. RESULTS: After adjusting for multiple variables, mortality rate was lower among current (relative risk [RR], 0.69; 95% confidence interval [CI], 0.54-0.87) and past users (RR, 0.79; 95% CI, 0.66-0.95), mainly due to reductions in deaths due to cardiovascular disease. The protective effect of ERT was greatest among women younger than 75 years (RR, 0.55; 95% CI, 0.40-0.76) compared with women from 75 to 84 years of age (RR, 0.93; 95% CI, 0.62-1.41) and 85 years or older (RR, 1.33; 95% CI, 0.43-4.12). The RR for overall mortality was 0.95 (95% CI, 0.68-1.32) among short-term users (1-9 years) compared with 0.55 (95% CI, 0.40-0.75) among long-term users (> or = 10 years). Deaths considered unrelated to ERT tended also to be reduced in current users younger than 75 years (RR, 0.72; 95% CI, 0.49-1.06) and current long-term users (RR, 0.75; 95% CI, 0.51-1.10). CONCLUSIONS: Estrogen replacement therapy is associated with lower overall mortality rates and reduced deaths due to cardiovascular disease. Women using ERT had healthier lifestyles, and the risk for death thought to be unrelated to ERT also tended to be lower in ERT users, suggesting in part a healthy-user effect.

Aged↗
PubMed1997

Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants.

The present study examined lifestyle and behavioral correlates of the change in total testosterone over 13 years in 66 men aged 41-61 years who were former participants of the Multiple Risk Factor Intervention Trial (MRFIT) at the Pittsburgh, Pennsylvania, center. The authors also determined in these men if changes in total testosterone are related to changes in cardiovascular disease risk factors. The mean total testosterone level was 751 (standard deviation, 248) ng/dl at baseline and decreased by 41 (standard deviation, 314) ng/dl during follow-up. The correlation between measures was r = 0.44 (p < 0.001). In multivariate analysis, higher type A coronary-prone behavior score, greater pack-years of cigarette smoking, and the MRFIT special intervention group were associated with larger decreases in total testosterone. Age, body weight, weight change, leisure time activity level, and alcohol intake were not related to the change in total testosterone. The decrease in endogenous testosterone was associated with an increase in triglycerides and a decrease in high density lipoprotein cholesterol in multivariate analysis controlling for obesity and other lifestyle covariates. There was little relation between change in testosterone and change in total and low density lipoprotein cholesterol or blood pressure. This longitudinal study confirms a gradual decline in total testosterone levels with advancing age in older men and provides evidence that lifestyle and psychosocial factors are related to this decline. Decreases in endogenous testosterone levels with age in men are associated with potentially unfavorable changes in triglycerides and high density lipoprotein cholesterol.

Adult↗
PubMed1997

Incidence of and risk factors for atrial fibrillation in older adults.

BACKGROUND: This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up. METHODS AND RESULTS: In this cohort study, 5201 adults > or = 65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF. CONCLUSIONS: The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.

Adult↗
PubMed1997

A dietary and behavioral intervention designed to lower coronary heart disease. Risk factors are unaffected by variation at the APOE gene locus.

Variation at the apolipoprotein E (APOE) gene locus has demonstrated a consistent impact on lipoprotein levels. APOE typing was performed for 488 healthy, caucasian, premenopausal women participating in the Women's Healthy Lifestyle Project (WHLP) aimed at reducing total fat, saturated fat and cholesterol intake and promoting physical activity. Women in both the intervention and control groups were included in the trial. The purpose of the present study was to determine whether the magnitude of the changes in total cholesterol (Tc), low density lipoprotein cholesterol (LDLc) and high density lipoprotein cholesterol (HDLc) due to the dietary intervention were dependent on the variation in APOE. Weight, body mass index (BMI), and lipoprotein levels were measured at baseline and at a 6 month follow-up. ANOVA was used to determine whether the change in Tc and LDLc was dependent on dietary intervention and variation at APOE levels. The levels of Tc and LDLc were higher in women with the APOE*4 genotype. There were no statistically significant effects of APOE genotype and changes in Tc and LDLc (P > 0.1). Adjusted Tc and LDLc changes were comparable in the 3 APOE subgroups (Tc = -14.3, -12.9 and -11.7 mg/dl; LDLc = -12.1, -10.7 and -10.7 mg/dl, respectively as above). In conclusion, the genetic (APOE) background of premenopausal women in this study did not have a significant effect on their response to dietary intervention.

Apolipoproteins E↗
PubMed1997

Coronary heart disease mortality and adjuvant tamoxifen therapy.

BACKGROUND AND PURPOSE: Data from randomized clinical trials in Scotland and Sweden testing the efficacy of tamoxifen therapy in patients with breast cancer have suggested that the drug may also reduce the risk of coronary heart disease. In view of these findings, we examined mortality from coronary heart disease among patients with early stage breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project B-14 trial of tamoxifen therapy. METHODS: Deaths occurring among women who were randomly assigned to 5 years of either tamoxifen or placebo in the first phase of the B-14 trial were reviewed to determine the cause. Three categories of heart disease-related death were defined: 1) death from a definite fatal myocardial infarction, 2) death from definite fatal coronary heart disease/possible myocardial infarction, and 3) death from possible fatal coronary heart disease. Comparisons of the findings by treatment group were made on the basis of average annual hazard (i.e., death) rates and the corresponding relative hazard of death. RESULTS: The average annual death rate from coronary heart disease was lower for patients who received tamoxifen than for patients who received placebo, but the difference was not statistically significant. There were eight definite heart-related deaths (i.e., definite fatal myocardial infarction or definite fatal coronary heart disease/possible myocardial infarction) among the patients who received tamoxifen, yielding an average annual rate of 0.62 per 1000 patients. There were 12 definite heart-related deaths among the patients who received placebo, yielding an average annual rate of 0.94 per 1000. The corresponding relative hazard of death from definite fatal heart disease (tamoxifen versus placebo) was 0.66 (95% confidence interval = 0.27-1.61). Eleven deaths in the tamoxifen group and 10 deaths in the placebo group were classified as possible cases of fatal coronary heart disease. When these cases and the definite cases were considered together, the average annual death rate for the patients who received tamoxifen was 1.48 per 1000, and the rate for the patients who received placebo was 1.73 per 1000. The corresponding relative hazard of death was 0.85 (95% confidence interval = 0.46-1.58). CONCLUSIONS: The findings from the B-14 trial are consistent with the findings from the Scottish and the Swedish trials, suggesting that tamoxifen treatment reduces coronary heart disease among patients with breast cancer. Continued follow-up of the patients in these trials and in ongoing prevention trials is needed to accumulate enough data so that reliable conclusions can be drawn about the benefits of tamoxifen in preventing heart disease.

Adult↗
PubMed1997

Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study.

The authors ascertained cardiovascular events (myocardial infarction and angina pectoris) in 498 women with systemic lupus erythematosus seen at the University of Pittsburgh Medical Center from 1980 to 1993 (3,522 person-years). Subjects were stratified by age, and cardiovascular event incidence rates were determined. The authors compared these rates with cardiovascular event rates were determined. The authors compared these rates with cardiovascular event rates occurring over the same time period in 2,208 women of similar age participating in the Framingham Offspring Study (17,519 person-years). Age-specific rate ratios were computed to determine whether the cardiovascular events in the lupus cohort were greater than expected. The risk factors associated with cardiovascular events in women with lupus were determined. There were 33 first events (11 myocardial infarction, 10 angina pectoris, and 12 both angina pectoris and myocardial infarction) after the diagnosis of lupus: two thirds were under the age of 55 years at the time of event. Women with lupus in the 35- to 44-year age group were over 50 times more likely to have a myocardial infarction than were women of similar age in the Framingham Offspring Study (rate ratio = 52.43, 95% confidence interval 21.6-98.5). Older age at lupus diagnosis, longer lupus disease duration, longer duration of corticosteroid use, hypercholesterolemia, and postmenopausal status were more common in the women with lupus who had a cardiovascular event than in those who did not have an event. Premature cardiovascular disease is much more common in young premenopausal women with lupus than in a population sample. With the increased life expectancy of lupus patients due to improved therapy, cardiovascular disease has emerged as a significant threat to the health of these women. The impact of this problem has been underrecognized, with little focus placed on aggressive management of hypercholesterolemia and other possible risk factors.

Adolescent↗
PubMed1997

Prospective study of the determinants of age at menopause.

The authors prospectively studied the effect of demographic, reproductive, stress-related, and health behavior factors measured at study entry on age of natural menopause in 185 healthy US women. At study entry, women were 42.5-47.5 years old and premenopausal. After a baseline examination (1983-1985), women were followed for 7-9 years, during which time they reported on a monthly basis their menstrual status and whether they were taking hormones. Menopausal age was defined as age at the last menstrual period prior to stopping menstruation for 12 months (and not taking hormones). Estimated median age at menopause was 51.5 years for the whole sample. Median age at menopause was earlier for women who reported irregular menstrual cycles at study entry (50.2 years), were African-American (49.3 years), were smokers (50.6 years), or were currently on a weight reduction diet (50.5 years). Psychosocial stress was predictive of an even earlier median age at menopause in African Americans (48.4 years) and in those with irregular cycles at baseline (49.4 years). Results suggest that premenopausal women in their forties who are experiencing irregular menstrual cycles, are smokers, are dieting, or are African-American are likely to reach menopause earlier than their contemporaries. African-American women may have a different "biological clock" than white women, especially when under stress, or they may experience more stress of longer duration.

Adult↗
PubMed1997

A case-control study of hematopoietic and lymphoid neoplasms: the role of work in the chemical industry.

The present case-control study was conducted in an effort to determine if work in the chemical industry is related to excesses of certain hematopoietic and lymphoid neoplasms. Cases who died from non-Hodgkin's lymphoma, multiple myeloma, and leukemia were matched by race, gender, age, year of death, and county of residence to controls who died from cardiovascular disease. A total of 618 (309 matched pairs) white male residents of Kanawha County, WV, aged 23-96, who had died between 1965 and 1990 were identified. Conditional logistic regression was conducted and yielded an association between chemical industry work and death due to non-Hodgkin's lymphoma, multiple myeloma, and lymphoid leukemia among subjects who died at age < 65. These results are consistent with the findings of previous studies linking work in chemical manufacturing to hematopoietic and lymphoid neoplasms, and indicate that the excesses may be related to the occupational exposures in men who died at younger ages.

Aged↗
PubMed1997

The psychological consequences of weight gain prevention in healthy, premenopausal women.

OBJECTIVE: This study examined the psychological consequences of a modest weight loss in a sample of healthy women aged 44 to 50. METHOD: Five hundred and thirty-five women, with body mass indices (BMIs) ranging from 20 to 34, were randomly assigned either to an intensive behavioral lifestyle intervention or to a no-treatment control group. Women in the lifestyle intervention received weight loss goals of 5 to 15 lb, depending on baseline BMI, and attended 20 weekly group meetings during which they received information on lowering dietary fat intake and increasing physical activity levels. Psychological measures administered at baseline and at a 6-month examination assessed perceived stress, mood, dietary restraint, and binge eating behaviors. RESULTS: Intervention subjects showed significant decreases in depressive symptoms over time, relative to control subjects, and this effect was observed for normal-weight, as well as heavier, subjects. Binge eating scores for all subjects declined significantly over time, with heavier subjects in the intervention showing the greatest decrease in scores. DISCUSSION: The current study found no evidence of negative psychological sequelae of participation in a behavioral lifestyle change program, regardless of weight status. Results further suggest that participation in these types of programs may exert a positive influence on the psychological status of both normal-weight and heavier women.

Adult↗