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Biomedical subjects

J A Herd

Publications and source records attributed to J A Herd.

At least 19 recordsLinked to original sources

Effects of fluvastatin on coronary atherosclerosis in patients with mild to moderate cholesterol elevations (Lipoprotein and Coronary Atherosclerosis Study [LCAS]).

Despite the potential for reduced morbidity and mortality, aggressive intervention against mild to moderate hypercholesterolemia in patients with coronary heart disease (CHD) remains controversial and infrequently practiced. Eligible patients in the 2.5-year Lipoprotein and Coronary Atherosclerosis Study were men and women aged 35 to 75 years with angiographic CHD and mean low-density lipoprotein (LDL) cholesterol of 115 to 190 mg/dl despite diet. Patients (n = 429; 19% women) were randomized to fluvastatin 20 mg twice daily or placebo. One fourth of patients were also assigned open-label adjunctive cholestyramine up to 12 g/day because prerandomization LDL cholesterol remained > or = 160 mg/dl. The primary end point, assessed by quantitative coronary angiography, was within-patient per-lesion change in minimum lumen diameter (MLD) of qualifying lesions. Across 2.5 years, mean LDL cholesterol was reduced by 23.9% in all fluvastatin patients (+/- cholestyramine) (146 to 111 mg/dl) and by 22.5% in the fluvastatin only subgroup (137 to 106 mg/dl). Primary end point analysis (340 patients) showed significantly less lesion progression in all fluvastatin versus all placebo patients, deltaMLD -0.028 versus -0.100 mm (p <0.01), and for fluvastatin alone versus placebo alone, deltaMLD -0.024 versus -0.094 mm (p <0.02). A consistent angiographic benefit with treatment was seen whether baseline LDL cholesterol was above or below 160 or 130 mg/dl. Beneficial trends with treatment were also consistently seen in clinical event rates but were not statistically significant. Thus, lipid lowering by fluvastatin in patients with mildly to moderately elevated LDL cholesterol significantly slowed CHD progression.

Adult

Comparison of preoperative characteristics of men and women undergoing coronary artery bypass grafting (the Post Coronary Artery Bypass Graft [CABG] Biobehavioral Study).

A cohort of 759 coronary artery bypass grafting (CABG) patients (269 women and 490 men) was enrolled in the prospective POST CABG Biobehavioral Study at 5 clinical centers in the United States and Canada. Sociodemographic and medical data were obtained by interview and from medical charts. Health-related quality of life and psychosocial data were ascertained preoperatively by interview and questionnaire for those patients whose condition allowed preoperative assessment and was compared among patients from hospitals enrolling both male and female patients (143 women and 267 men). Women enrolled in the Biobehavioral Study were older than men (65.4 +/- 9.0 vs 61.8 +/- 9.7 years, p < 0.001) and more likely to have a preoperative medical condition which precluded biobehavioral evaluation (47% vs 34%, p < 0.001). Women were less likely to be high school graduates (59% vs 74%, p < 0.001), were less likely to be earning > or = $25,000 per year (39% vs 69%, p < 0.001), and were married less often at the time of surgery (59% vs 85%, p < 0.001). Fewer women than men were able to perform basic self-care activities (p < 0.001) and social activities (p < 0.001). Women were also less able to perform the more demanding activities required for independent living, recreation, and maintaining a household (p < 0.001). Women were also more anxious (p = 0.01) and reported more depressive symptoms (p < 0.001) than men. These data suggest that plans for perioperative and convalescent care for women undergoing CABG should take into account their less favorable medical and psychosocial status relative to men.

Activities of Daily Living

In normal postmenopausal women physiologic estrogen replacement therapy fails to improve exercise tolerance: a randomized, double-blind, placebo-controlled, crossover trial.

OBJECTIVE: Our purpose was to test whether estrogen replacement therapy could increase exercise tolerance in postmenopausal women. STUDY DESIGN: A randomized, double-blind, placebo-controlled, crossover study in 31 healthy postmenopausal women who received 12 weeks of physiologic estrogen replacement therapy (micronized estradiol, 2 mg/day) and were evaluated with modified Balke exercise treadmill tests. RESULTS: Serum estradiol levels increased significantly during replacement therapy in this cohort of female volunteers with a mean age of 59 years, and resting heart rate was lower in women receiving estrogen replacement (p < 0.05). However, neither the heart rate nor the blood pressure responses to exercise was different, nor was the total exercise time, rate of oxygen uptake, or maximal oxygen uptake increased after estradiol treatment. Similarly, ventilatory parameters were unaffected by estradiol. The slope of the respiratory exchange ratio was slightly but significantly different (p < 0.05) while volunteers received estrogen replacement therapy. CONCLUSION: Estrogen replacement therapy, which achieves serum estradiol concentrations in the physiologic range for 12 weeks, fails to increase exercise tolerance or improve cardiovascular response to exercise in postmenopausal women.

Cross-Over Studies

The Lipoprotein and Coronary Atherosclerosis Study (LCAS): design, methods, and baseline data of a trial of fluvastatin in patients without severe hypercholesterolemia.

Few direct clinical data are available regarding whether cholesterol-lowering therapy should be extended to patients with coronary heart disease (CHD) and normal or only slightly elevated plasma cholesterol concentrations. The one published angiographic trial designed to examine this question found no benefit. Additional prospective data will be provided by the Lipoprotein and Coronary Atherosclerosis Study (LCAS), a randomized, double-blind, placebo-controlled trial of fluvastatin therapy (20 mg twice daily) monitored by both quantitative coronary angiography (QCA) and, in a subset of patients, positron-emission tomography (PET). Eligible subjects in LCAS were men and women 35-75 years of age with low-density lipoprotein (LDL) cholesterol of 115-190 mg/dL on stable dietary therapy and with angiographic evidence by caliper measurement of at least one coronary atherosclerotic lesion causing 30-75% diameter stenosis. Among the 429 patients randomized (mean age 58.8, 81% male), mean baseline LDL cholesterol was only 145.6 mg/dL. Any patient with mean prerandomization LDL cholesterol of 160 mg/dL or higher also received open-label adjunctive cholestyramine. The primary endpoint is within-patient per-lesion change in minimum lumen diameter (MLD) as measured by QCA at baseline and 2.5-year follow-up. All evaluable lesions had MLD at least 0.8mm less than the reference lumen diameter at either baseline or follow-up and MLD at least 25% of the reference lumen diameter at baseline. Data obtained on myocardial perfusion changes (99 patients underwent initial PET), special lipid particles, and coagulation factors may help define which patients with CHD and relatively low LDL cholesterol will benefit from lipid-lowering treatment.

Adult

Effect of gemfibrozil on levels of lipoprotein[a] in type II hyperlipoproteinemic subjects.

Plasma lipoprotein[a] (Lp[a]) levels are highly correlated with angiographically demonstrable coronary heart disease, and elevated Lp[a] is an independent risk factor for atherosclerosis. Previous studies have provided evidence that the levels of Lp[a] and triglyceride are related, suggesting that Lp[a] might be altered by gemfibrozil, a drug well known for its efficacy in reducing plasma triglycerides. Accordingly, 18 type IIa and 16 type IIb hyperlipoproteinemic males aged 35-58 were treated for 3 months with 600 mg of gemfibrozil twice daily. The efficacy of the drug in altering lipid and lipoprotein levels was different in the two type groups. In type IIa and IIb subjects the respective changes in median levels were: total cholesterol, -7.5 and -8.5% triglycerides, -35.6 and -54.4%; HDL-cholesterol, +9.0 and +11.0%; and Lp[a], -17.2 and +6.1%. Before and after gemfibrozil treatment, 7 type IIa and 10 type IIB subjects were given a 100 g/2 m2 oral-fat load; triglycerides and Lp[a] were measured post-prandially at 0, 2, 4, 6, 8, and 10 h. The differences between before- and after-gemfibrozil post-prandial curve integrated areas (PPCIA) were compared for triglycerides and Lp[a]. The changes in median PPCIA for triglycerides in types IIa and IIB were -54% and -53%, and for Lp[a] were -8% and +8%, respectively. These results indicate i) that the levels of Lp[a] are about 2 times higher in type IIa than IIb subjects, and ii) that although gemfibrozil elicits a rather uniform decrease in fasting and post-prandial triglyceride levels in type IIa and IIb patients, the drug causes heterogeneous changes in Lp[a], suggesting that different metabolic mechanisms may be dominant in subjects showing opposing effects.

Adult

Evidence that a low-fat diet reduces the occurrence of non-melanoma skin cancer.

The effect of a low-fat diet on occurrence of non-melanoma skin cancer was examined in a 2-year dietary intervention trial. A total of 101 skin-cancer patients were randomized either to a control group that consumed, on average, 38% of caloric intake as fat, and in which no changes in dietary habits were introduced, or to a low-fat dietary-intervention group, in which patients were instructed to limit their calories from fat to 20% of total caloric intake. Patients were examined at 4-month intervals by dermatologists blinded to their dietary assignments. Nutrient analyses, conducted at each of the 4-month follow-up visits, indicated that the % calories of fat consumed in the intervention group had been reduced to 21% at 4 months and remained below this level throughout the 2-year period. There were no significant differences in total calories consumed, or in mean body weights, between the control and the intervention groups. Nor were there significant group differences in P/S ratios until month 24. Numbers of new skin cancers treated at each examination were analyzed in 8-month periods of the 2-year study. Comparisons of skin-cancer occurrences revealed no significant changes in the control group from baseline values. However, cancer occurrence in the low-fat intervention group declined after the first 8-month period and reached statistical significance by the last 8-month period. Patients in this group had significantly fewer cancers in the last 8-month period than did patients in the control group. In addition, there was a significant reduction in the number of patients developing skin cancer in the last 8-month period, as compared with the first 8-month period, within the low-fat intervention group. There were no significant changes in the control group. These data indicate that a low-fat diet can significantly reduce occurrence of a highly prevalent form of cancer.

Carcinoma

Effects of beef and chicken consumption on plasma lipid levels in hypercholesterolemic men.

BACKGROUND: The recommendation to lower saturated fat intake is often interpreted as requiring the elimination of beef to control or lower serum cholesterol levels. The study hypothesis was that the Step I Diet (8% to 10% of energy intake from saturated fatty acids) containing beef would have the same effect on plasma lipid levels of hypercholesterolemic men as a like diet containing chicken. METHODS: Thirty-eight free-living hypercholesterolemic (otherwise healthy) men completed a 13-week dietary intervention study. Subjects consumed their usual diets for 3 weeks, followed by a 5-week stabilization diet (18% of energy intake from saturated fatty acids), before randomization to one of two test diets for 5 weeks. The test diets contained either 85 g of cooked beef (8% fat) or 85 g of cooked chicken (7% fat) per 4184 kJ and had 7% to 8% of energy from saturated fatty acids. All food was supplied during the stabilization and test diets. RESULTS: The beef and chicken test diets both produced significant decreases in average plasma total cholesterol level (0.54 mmol/L [7.6%] for beef and 0.70 mmol/L [10.2%] for chicken) and low-density lipoprotein cholesterol level (0.46 mmol/L [9%] for beef and 0.55 mmol/L [11%] for chicken). Changes in average levels of plasma total cholesterol, high-density lipoprotein cholesterol, triglyceride, and low-density lipoprotein cholesterol were not statistically different (smallest P = .26) between the beef and chicken test diets. The average triglyceride level did not change for either test diet group. CONCLUSIONS: In this short-term study, comparably lean beef and chicken had similar effects on plasma levels of total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride. We concluded that lean beef and chicken are interchangeable in the Step I Diet.

Adult

Baseline characteristics of subjects in the Lipoprotein and Coronary Atherosclerosis Study (LCAS) with fluvastatin.

A total of 429 subjects (79 women and 350 men), aged 35-75 years, have been enrolled in a randomized clinical trial of fluvastatin therapy for hypercholesterolemia. The progression and regression of atherosclerotic lesions will be assessed by quantitative angiography and positron emission tomography (PET) after 2.5 years of treatment. Patients were included in the trial if they had angiographically documented lesions that occluded 30-75% of the diameter of a major coronary vessel. Of the 429 subjects, 99 were also studied by PET at rest and during static exercise of sustained handgrip combined with administration of dipyridamole. All subjects were instructed in an American Heart Association/National Cholesterol Education Program (AHA/NCEP) Step I or Step II diet. Of the total, 107 subjects (25%) had low density lipoprotein cholesterol (LDL-C) > or = 160 mg/dL and were given cholestyramine, 8 g/day. All subjects were randomized to placebo or fluvastatin, the newest 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor to be introduced into the U.S. market. Fluvastatin is entirely synthetic and is similar in efficacy to the other available HMG-CoA reductase inhibitors. Its pharmaceutical profile (i.e., low systemic exposure) makes fluvastatin a good candidate for use in combination lipid-lowering therapy. The majority of subjects were recruited through a community campaign and the remainder through cardiac catheterization laboratories and the medical records of hospitals in the Texas Medical Center. Approximately 8,500 prospects from the community campaign were screened and 272 were randomized, a conversion rate of approximately 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Effect of a low-fat diet on the incidence of actinic keratosis.

BACKGROUND: Actinic keratoses are premalignant lesions and are a sensitive and important manifestation of sun-induced skin damage. Studies in animals have shown that dietary fat influences the incidence of sun-induced skin cancer, but the effect of diet on the incidence of actinic keratosis in humans is not known. METHODS: We randomly assigned 76 patients with nonmelanoma skin cancer either to continue their usual diet (control group) or to eat a diet with 20 percent of total caloric intake as fat (dietary-intervention group). For 24 months, the patients were examined for the presence of new actinic keratoses by physicians unaware of their assigned diets. RESULTS: At base line, the mean (+/- SD) percentage of caloric intake as fat was 40 +/- 4 percent in the control group and 39 +/- 3 percent in the dietary-intervention group. After 4 months of dietary therapy the percentage of calories as fat had decreased to 21 percent in the dietary-intervention group, and it remained below this level throughout the 24-month study period. The percentage of calories as fat in the control group did not fall below 36 percent at any time. The cumulative number of new actinic keratoses per patient from months 4 through 24 was 10 +/- 13 in the control group and 3 +/- 7 in the dietary-intervention group (P = 0.001). CONCLUSIONS: In patients with a history of nonmelanoma skin cancer, a low-fat diet reduces the incidence of actinic keratosis.

Basal Cell Carcinoma

Identification and management of heterozygous familial hypercholesterolemia: summary and recommendations from an NHLBI workshop.

Heterozygous familial hypercholesterolemia (hFH) is one of the most common monogenic disorders with serious health consequences, affecting approximately 1 in 500 persons in the United States. Persons with hFH generally manifest elevations of low density lipoprotein (LDL) cholesterol throughout their lives and have a markedly increased risk of death from coronary artery disease. The hypercholesterolemia of hFH is responsive to medication and diet, and, if detected early, aggressive LDL cholesterol control may prevent or substantially delay cardiovascular disease. However, evidence suggests that many persons with hFH are undetected and inadequately treated. On July 20-21, 1992, the National Heart, Lung, and Blood Institute sponsored a workshop to assess the current understanding of the diagnosis and management of hFH, to emphasize recommendations for identification and management that are known to be effective, and to identify opportunities and needs for intervention and research.

Heterozygote

Cardiovascular response to stress.

The behavioral characteristics of psychological stressors have been operationally defined. A psychological stressor is one that causes a stress response in a predictable percentage of index subjects. However, it may not always produce a stress response, and the probability of producing such a response depends on interactions between the behavioral situation and the individual involved. Thus there is a danger that a psychological stressor will be defined according to the stress response it causes rather than its structural characteristics. The characteristics that enhance the likelihood that a psychological stressor will cause a stress response are its novel, challenging, or threatening aspects that engage a subject in continuous active mental effort. The intensity of the stress response depends on the intensity of mental effort exerted to meet a challenging situation, whether or not that situation is perceived as threatening. The behavioral response to a psychological stressor also has been defined. It includes somatomotor, neuroendocrine, and cardiovascular components. The somatomotor response to stressful psychological events includes purposeful active coping to counter the challenge or threat posed by the stressor. The neuroendocrine response includes a combination of pituitary-adrenal cortical and hypothalamic-sympathetic-adrenal medullary secretions. The cardiovascular response includes a combination of increased rate and force of cardiac contraction, skeletal muscle vasodilation, venoconstriction, splanchnic vasoconstriction, renal vasoconstriction, and decreased renal excretion of sodium. Of all the modifiers that influence the stress response to a psychological stressor, family history is the one most likely to have an effect. A family history of essential hypertension increases the likelihood that a subject will respond to a psychological stressor with a cardiovascular stress response pattern. Other predisposing characteristics that increase the likelihood of a stress response include behavioral patterns of response to challenge or threat but may also include anatomic or biochemical characteristics that increase susceptibility to neurogenic activation of central aminergic mechanisms.

Animals

Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS).

The frequency of ventricular premature complexes and the degree of impairment of left ventricular ejection fraction are major predictors of cardiac mortality and sudden death in the year after acute myocardial infarction. Recent studies have implicated psychosocial factors, including depression, the interaction of social isolation and life stress, and type A-B behavior pattern, as predictors of cardiac events, controlling for known parameters of disease severity. However, results tend not to be consistent and are sometimes contradictory. The present investigation was designed to test the predictive association between biobehavioral factors and clinical cardiac events. This evaluation occurred in the context of a prospective clinical trial, the Cardiac Arrhythmia Pilot Study (CAPS). Five-hundred two patients were recruited with greater than or equal to 10 ventricular premature complexes/hour or greater than or equal to 5 episodes of nonsustained ventricular tachycardia, recorded 6 to 60 days after a myocardial infarction. Baseline behavioral studies, conducted in approximately 66% of patients, included psychosocial questionnaires of anxiety, depression, social desirability and support, and type A-B behavior pattern. In addition, blood pressure and pulse rate reactivity to a portable videogame was assessed. The primary outcome was scored on the basis of mortality or cardiac arrest. Results indicated that the type B behavior pattern, higher levels of depression and lower pulse rate reactivity to challenge were significant risk factors for death or cardiac arrest, after adjusting statistically for a set of known clinical predictors of disease severity. The implication of these results for future research relating behavioral factors to cardiac endpoints is discussed.

Affect

Relation of psychosocial and stress reactivity variables to ventricular arrhythmias in the Cardiac Arrhythmia Pilot Study (CAPS).

Both animal and human data implicate psychosocial distress and cardiovascular reactivity in response to challenge in the etiology of sudden cardiac death. In this study, the relation of these biobehaviorial factors to frequency of ventricular premature complexes, a predictor of sudden death was investigated. The study population was made up of patients enrolled in the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Pilot Study (CAPS). Ventricular premature complexes (VPCs) were assessed by multiple, 24-hour ambulatory electrocardiographic recordings. Patients completed trait psychosocial measures assessed at baseline and state psychosocial measures assessed periodically during a 1-year follow-up period. Psychosocial measures included self-reports of depression, anxiety, anger and type A behavior pattern. A competitive challenge using a video game was used as a stressor to elicit cardiovascular reactivity and was administered at baseline and during follow-up sessions. Cardiovascular reactivity was defined as peak level during stressor exposure minus the mean of resting levels for systolic and diastolic blood pressure and pulse rate. Results indicated that biobehavioral factors were not associated with diurnal VPC rates. Furthermore, biobehavioral factors did not predict response to antiarrhythmic therapy. Based upon the results of this study, it is speculated that the established relation between behavioral factors and sudden death may not be mediated by VPC rates.

Arrhythmias, Cardiac

Identifying families at high risk of cardiovascular disease: alternative work site approaches.

By examining coverage, concordance, and costs, this project evaluated four methods of cardiovascular disease (CVD) risk screening at a work site with 1821 central office employees of an energy company in Houston, Tex. Screening methods included a health risk appraisal mail questionnaire (HRA), an HRA plus brief physical assessment, an analysis of medical claims data, and an analysis of absenteeism data. Coverage ranged from 99% of employees for the absenteeism method to about 30% for the HRA method. Combining the first three screening methods, 18% of families had at least one member with a CVD or related diagnosis or one of four major CVD risk factors. The absenteeism method yielded 12.1% of the central office employees with 9 or more days absent. Although the absenteeism method identified high-cost families, only 9% had a heart disease or related diagnosis. This lack of concordance also occurs with other methods. For example, only 9.4% of families identified with the claims data were also identified by the HRA. Therefore, the methods identify different groups of high-risk families. Findings are discussed in relation to costs and other factors important to firms' selection of screening methods.

Absenteeism

Characterization of inheritance patterns of blood pressure in Macaca fascicularis.

A breeding colony of Macaca fascicularis was established at the New England Regional Primate Center in 1977 and continued through 1984. Characterization of the offspring of this colony at 18 and 30 months of age suggested that higher blood pressure levels are hereditary in M. fascicularis, but evidence to date cannot determine if this condition is harmful to the animals.

Animals

Medical therapy in the elderly.

Recommendations concerning nutrition and physical activity are an important part of health care in the elderly. There is increasing evidence that diet and exercise influence the development and progression of cardiovascular disease in the elderly as well as the young. Decreases in coronary risk factors can be achieved in the elderly by attention to proper diet and exercise.

Aged