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Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 55 records · Page 3Linked to original sources
PubMed1997

Estrogen replacement therapy and prognosis after first myocardial infarction.

The effects of estrogen replacement therapy on prognosis in women with established coronary disease remain uncertain. The authors conducted a retrospective cohort study of 726 women (mean age, 66.2 years) who survived first myocardial infarction to hospital discharge from 1980 through 1991, while enrolled at Group Health Cooperative of Puget Sound in western Washington State. Estrogen replacement therapy after myocardial infarction (122 women) was ascertained from computerized pharmacy records. Reinfarctions (n = 135) and deaths (n = 183) through 1993 were identified, and relative risks were calculated. The relative risk for reinfarction associated with current estrogen replacement therapy after myocardial infarction, adjusting for age and time since infarction, was 0.64 (95% confidence interval (CI) 0.32-1.30), and that for past estrogen replacement therapy was 0.90 (95% CI 0.62-1.31). The relative risk for all-cause mortality associated with current estrogen replacement therapy was 0.50 (95% CI 0.25-1.00), and that for past estrogen replacement therapy was 0.79 (95% CI 0.56-1.09). While estrogen users were less likely than nonusers to have a history of diabetes or congestive heart failure, adjustment for these and additional prognostic factors altered risk estimates only slightly. Estrogen replacement therapy after first myocardial infarction was not associated with increased risk of reinfarction or mortality. This study provides reassurance regarding the safety of estrogen replacement therapy after myocardial infarction in women.

Adult↗
PubMed1997

The efficacy and six-week tolerability of simvastatin 80 and 160 mg/day.

The hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin is the most effective of the currently approved hypolipidemic drugs and has been shown to reduce mortality and coronary morbidity in patients with coronary artery disease. For these patients the United States National Cholesterol Education Program advocates reducing low-density lipoprotein (LDL) cholesterol to <100 mg/dl. However, in some patients this cannot be achieved using monotherapy with simvastatin 40 mg/day, the current maximal recommended dose. To evaluate the effectiveness of extending the dosage range, 156 subjects with LDL cholesterol >160 mg/dl and triglycerides (TG) <350 mg/dl were randomized to simvastatin at doses of 40, 80, and 160 mg/day in a 26 week, double-blind, 3-period, complete block crossover study. Each active treatment period was 6 weeks in duration with intervening 2 week washout periods. Median reductions from baseline in LDL cholesterol were 41%, 47%, and 53% in the 40-, 80-, and 160-mg groups, respectively. The corresponding reductions in plasma TG were 21%, 23%, and 33%. High-density lipoprotein (HDL) cholesterol increased by 6% to 8% in each group. One patient (0.7%) taking 160 mg developed myopathy; 1 patient (0.7%) taking 80 mg, and 3 (2.1%) taking 160 mg had transaminase elevations > 3 times the upper limit of normal. No new or unexpected adverse effects were observed. We conclude that simvastatin at doses of 80 and 160 mg/day provides additional efficacy with a low short-term incidence of adverse effects; our results support the continued investigation of simvastatin at these doses.

Adult↗
PubMed1997

17beta-Estradiol, progesterone, and testosterone inversely modulate low-density lipoprotein oxidation and cytotoxicity in cultured placental trophoblast and macrophages.

OBJECTIVES: We have previously shown that low-density lipoprotein oxidation is diminished by 17beta-estradiol and enhanced by progesterone and testosterone. In these experiments we wished to learn whether sex hormone effects on low-density lipoprotein oxidation alter placental cell viability in primary tissue culture. STUDY DESIGN: Primary tissue culture of human term placental cells was performed. RESULTS: Addition of 17beta-estradiol decreased low-density lipoprotein oxidation (measured as lipid peroxides, thiobarbituric acid-reacting substances, and low-density lipoprotein electrophoretic mobility) and placental cell toxicity (measured as chromium 51 release) with maximum reductions of 28% (macrophages) (p < 0.05) and 26% (trophoblasts) (p < 0.01). Conversely, progesterone and testosterone increased low-density lipoprotein oxidation and chromium 51 release, the latter a maximum of 28% and 18%, respectively, for progesterone and testosterone in macrophages (p < 0.05 in both instances) and 23% in trophoblasts (p < 0.05, testosterone only). Collectively, cytotoxicity was proportional to low-density lipoprotein oxidation and estradiol, progesterone, and testosterone concentrations. CONCLUSIONS: Estradiol inhibits placental macrophage- and trophoblast-mediated low-density lipoprotein oxidation and cytotoxicity, whereas progesterone and testosterone promote these effects. Sex steroid hormones may modulate the effects of oxidative stress on placental function in pregnancy.

Cell Death↗
PubMed1997

Nutritional intake of women and men on the NCEP Step I and Step II diets.

OBJECTIVE: Restriction of dietary fat and cholesterol are recommended for treating hyperlipidemia, but may alter vitamin or mineral intakes. We evaluated changes in nutrients of individuals taught the National Cholesterol Education Program (NCEP) Step II diet. METHODS: Subjects participated in a randomized controlled trial of the cholesterol-lowering effect of the NCEP Step II diet. Eligibility criteria included elevated fasting plasma LDL-cholesterol, no lipid-altering medications, and diet not already fat-modified. Subjects attended eight weekly dietitian-led classes. Four-day food records collected 6 months post-intervention were compared to baseline records. RESULTS: Of 409 subjects with complete data, 123 met Step I and 166 met Step II diet criteria. Intakes of micronutrients associated with fruits and vegetables (beta-carotene and vitamin A, vitamin C, folic acid, magnesium, and potassium) increased on both diets. Patterns of decreased mean intake and/or fewer subjects consuming 2/3 Recommended Dietary Allowance were seen for calcium, vitamin E, and zinc. CONCLUSIONS: NCEP Step I and II diets generally match or exceed unmodified diet for vitamin and mineral content. Premenopausal women do not appear to be at increased risk of low iron intake. Vitamin E intake decreases, although the significance is unknown in the context of lower fat intake and increased intake of other antioxidants. Diet counseling and materials should encourage sources of calcium for women, and zinc for both women and men.

Adult↗
PubMed1997

Biological and lifestyle factors, and lipid and lipoprotein levels among Japanese Americans in Seattle and Japanese men in Japan.

BACKGROUND: It has been previously shown that Japanese Americans in Seattle have significantly higher cholesterol levels than native Japanese. The present study examines the association of biological and lifestyle factors with plasma lipid and lipoprotein levels among Japanese Americans (JA) and native Japanese (NJ) to determine if these associations are consistent between these high and low cholesterol populations. METHODS: Study samples consisted of 710 JA male and 728 JA female volunteers living in the Seattle area and a random sample of 3833 NJ male urban workers who participated in parallel cardiovascular disease screening and lifestyle surveys for 1989-1994. Multiple regression analysis was conducted to examine the association of lifestyle and biological factors with lipid and lipoprotein levels. RESULTS: Alcohol consumption was positively and linearly associated with high density lipoprotein cholesterol (HDL-C) levels and negatively associated with both low density lipoprotein cholesterol (LDL-C) levels and the ratio of total cholesterol (TC)/HDL-C (P < 0.05 to P < 0.001) among JA males and JA females and NJ males. Current smoking habit was observed to be negatively associated with HDL-C levels and positively with TC/HDL-C ratio and log TG levels (logarithmic transformation of triglyceride values) (P < 0.05 to P < 0.001) among all three groups. Body mass index (BMI) was negatively associated with HDL-C levels and positively associated with log TG and TC/HDL-C ratio among all three groups (P < 0.05 to P < 0.001). Moderate alcohol consumption was negatively associated with log TG levels among JA males and females (P < 0.05), whereas heavy alcohol consumption was positively associated with log TG levels in NJ males (P < 0.001). Smoking was positively associated with TC and LDL-C levels (P < 0.05) among JA males, whereas a negative association (P < 0.05) was observed in NJ males. CONCLUSION: Overall, the fitted models were consistent between JA males and females and NJ males with the exception of smoking on TC and LDL-C. The results suggest that moderate alcohol consumption favourably influences lipid profiles in both high and low cholesterol populations. The results also indicate that light alcohol consumption is associated with decreased triglyceride levels, whereas heavy alcohol consumption is associated with increased triglyceride levels.

Adult↗
PubMed1997

Lipoprotein lipid response to the National Cholesterol Education Program step II diet by hypercholesterolemic and combined hyperlipidemic women and men.

The beFIT study tested whether teaching the NCEP step II diet (< 30% of calories from total fat and < 7% from saturated fat) is an effective therapy in hypercholesterolemic women and men with or without elevated triglycerides after 6 months. Hypercholesterolemic subjects had two LDL cholesterol measurements above the age- and sex-specific 75th percentile, and combined hyperlipidemic subjects additionally had similarly elevated triglyceride. Subjects were randomized to receive dietary intervention (eight weekly classes) immediately or 6 months later. Follow-up visits were quarterly, with lipid measurements and 4-day food records. Subjects randomized to delayed intervention did not report diet changes or experience lipid changes; the immediate intervention group significantly reduced fat and cholesterol intake, resulting in significant LDL cholesterol lowering. Six months after diet instruction, 178 women and 231 men reported total and saturated fat intakes of approximately 25% and 7.5% kcal LDL cholesterol was significantly reduced in women (7.6% and 8.1%) and men (8.8% and 8.1%) with hypercholesterolemia and combined hyperlipidemia, respectively, but was not different by sex or lipid disorder. Candidates for drug therapy were reduced from between 27% and 37% to 20%. HDL cholesterol was significantly decreased in women (-6.4% and -4.7%) but not in men (-1.3% and -2.7%). The 6.4% reduction in hypercholesterolemic women was significantly different from that of men. The significance of the HDL cholesterol reduction in women is unknown. LDL cholesterol response was similar between women and men and between hypercholesterolemic and combined hyperlipidemic subjects. LDL cholesterol lowering by diet can significantly reduce the number of hyperlipidemic persons requiring drug therapy.

Adult↗
PubMed1997

The Northwest Lipid Research Clinic Fat Intake Scale: validation and utility.

OBJECTIVES: This paper describes the Northwest Lipid Research Clinic Fat Intake Scale, a brief dietary questionnaire to screen and monitor dietary intake related to plasma cholesterol levels. METHODS: The 12-item instrument assesses intake of foods high in fat, saturated fat, and cholesterol. Test-retest reliability was assessed on 194 men and 116 women with high cholesterol prior to a dietary intervention study. To measure validity and responsiveness to dietary change, scores were compared with 4-day food records before and after diet education classes. RESULTS: Test-retest correlation coefficients were .88 for men and .90 for women (2 weeks between scores). Scores for men and women were correlated with nutrients shown by food records at baseline (.47 and .54, total fat; .50 and .51, saturated fat) and 18 months postintervention (.52 and .58, total fat; .56 and .64, saturated fat; all Ps < .001). Mean scores decreased from about 30 to 23 (P < .001, paired t test). CONCLUSIONS: The Fat Intake Scale, a qualitative instrument, has acceptable reliability and validity for estimating the level of cholesterol-related diet components and reflects dietary modification. The format of the instrument also lends itself to patient education and goal setting.

Adult↗
PubMed1997

A double-blind, randomized, controlled trial of the effects of two eggs per day in moderately hypercholesterolemic and combined hyperlipidemic subjects taught the NCEP step I diet.

OBJECTIVE: We investigated the effect of egg feeding in 161 hypercholesterolemic (HC) or combined hyperlipidemic (CHL) free-living subjects taught the NCEP Step I Diet. METHODS: Subjects had LDL-C between 3.36 and 4.91 mmol/L (130 and 190 mg/dL). HC subjects had triglyceride concentrations < 75th %-ile, CHL > or = 75th %-ile. Six weeks after instituting the Step I Diet, subjects were randomized to two eggs or egg substitute daily for 12 weeks. RESULTS: Mean dietary intake (9-day food records) was within NCEP guidelines and 131 subjects finished with stable weight and adherence > 80%. Placebo group lipoprotein lipids were unchanged at study end for both HC (n = 35) and CHL (n = 21) subjects. Egg-fed HC subjects (n = 44) increased LDL-C nonsignificantly, 0.07 mmol/L (3 mg/dL) (p = 0.49). Egg-fed CHL subjects (n = 31) increased LDL-C 0.31 mmol/L (12 mg/dL) (p < 0.001). HDL-C increased significantly in both HC and CHL groups, 0.10 and 0.08 mmol/L (4 and 3 mg/dL, p = 0.003 and 0.02), respectively. HC and CHL subjects did not differ by apo E phenotype distribution. Postprandial triglyceride-rich lipoproteins and LDL subclass phenotype were unaffected by egg feeding in subsets of subjects. CONCLUSIONS: CHL subjects ingesting a Step I Diet in a free-living setting are sensitive to egg feeding and should benefit from dietary cholesterol restriction. The limited LDL-C rise in HC subjects resembles that seen in egg-fed normocholesterolemic subjects ingesting a Step I Diet, but requires confirmation.

Adult↗
PubMed1996

Predicting participation in a dietary intervention to lower cholesterol among individuals with hyperlipidemia.

Adult men and women (N = 8,748) were given blood cholesterol tests and completed a measure of fat intake and a staging questionnaire that assessed readiness to adopt a cholesterol-lowering diet. Eligibility for the trial was based on plasma cholesterol levels and self-reported dietary intake. Of 772 eligible participants, 545 (70.6%) agreed to join. In multivariate analyses, joiners did not differ from nonjoiners by age, total cholesterol levels, or self-reported dietary fat intake. Women were more likely than men to join the study. Individuals in the preparation stage (defined on the basis of a staging algorithm derived from the transtheoretical model of change) were more likely to join the trial than were precontemplators. An understanding of the determinants of participation in a dietary intervention may be important in the enhancement of high-risk individuals' acceptance of recommendations to make dietary changes.

Adult↗
PubMed1996

Variations in plasma lipid concentration during examination stress.

The effect of psychological stress on plasma lipids was studied in 40 law students (20 men and 20 women). Plasma cholesterol, triglyceride, and apolipoprotein concentrations were examined at the beginning of the quarter and during the week before final examinations. Cortisol, blood pressure, and heart rate, and self-reports of stress and workload were also measured to verify that examinations were associated with increased stress levels. Perceived stress, perceived workload, and cortisol increased before examinations. Low density lipoprotein cholesterol (LDL-C) increased 5.8 +/- 13.9 mg/dL, and apolipoprotein B (apo B) increased 2.9 +/- 4.0 mg/dL. High density lipoprotein cholesterol decreased in women only. These changes were not due to changes in dietary intake or indexes of plasma volume. However, changes in cortisol and changes in LDL-C and apo B were associated, suggesting a neuroendocrine component to the effects. These results suggest that episodic, stressful situations may lead to potentially atherogenic changes in lipid and lipoprotein concentrations.

Journal Article↗
PubMed1995

Effect of fluvastatin on intermediate density lipoprotein (remnants) and other lipoprotein levels in hypercholesterolemia.

The accelerated atherosclerosis in diseases associated with elevated remnant lipoprotein levels has directed interest toward the response of this lipoprotein species to lipid-lowering treatment. The effect of fluvastatin--a synthetic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor--was compared with that of placebo on parameters of remnant metabolism in 57 patients with moderate hypercholesterolemia, but not heterozygous familial hypercholesterolemia, type III hyperlipidemia, or endogenous hypertriglyceridemia. Fluvastatin therapy resulted in decreases versus baseline in plasma total cholesterol, low density lipoprotein cholesterol (LDL-C) and LDL apolipoprotein (apo) B levels of 18%, 20%, and 18%, respectively (p < 0.01). Plasma parameters related to remnant metabolism were also significantly decreased: intermediate density lipoprotein by 43% and apo E by 22% (p < 0.01). The percent decrease in plasma intermediate density lipoprotein cholesterol level was twice that of LDL-C and 50% greater than the decrease seen in very low density lipoprotein cholesterol (VLDL-C), which was decreased by 28%. Total triglycerides were reduced by 11% and VLDL apo B by 24%, whereas high density lipoprotein cholesterol (HDL-C) rose significantly by 8%, HDL2-C by 24%, and HDL3-C by 3%. There were no increases in apo A-I levels compared with placebo nor any significant change in plasma lipoprotein(a) levels. The composition of LDL and VLDL particles did not appear to be altered by therapy, as assessed by the LDL-C:LDL-B, VLDL-C:VLDL-B, or triglyceride:VLDL-B ratios.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Spouse support and long-term adherence to lipid-lowering diets.

Social support is inversely associated with heart disease risk. Support may influence heart disease by encouraging health behavior change in high-risk individuals. This study examined the association between spouse support and maintenance of low-fat diets in men with hypercholesterolemia. Participants were 254 men enrolled in a 24-month randomized trial of lipid-lowering diets initiated in 1985 in Seattle, Washington. The Evaluation of Spouse Support, which assesses the extent to which spouses supported maintenance of lipid-lowering diets, was administered after the last of eight dietary classes and at 3, 12, and 24 months postinstruction. Attainment of dietary goals was determined from food records completed at the end of the class and at 3, 12, and 24 months. Compared with those in the lowest quartile, those in the highest quartile of support were more likely to attain dietary goals at 3 months (odds ratio (OR) = 4.5, 95% confidence interval (CI) 1.9-10.4), 12 months (OR = 5.5, 95% CI 2.4-12.5), and 24 months (OR = 3.9, 95% CI 1.7-9.3). Support was not associated with end-of-class dietary goal achievement. Social support may be an important factor in the maintenance of low-fat diets.

Adult↗
PubMed1995

Metabolism of modified LDL by cultured human placental cells.

UNLABELLED: All major classes of normal circulating lipoproteins can be metabolized by human placental cells. However, the metabolism of abnormal or modified lipoproteins has been little studied. We therefore investigated whether placental cells metabolize acetylated low density lipoprotein (ac-LDL) or oxidatively-modified LDL (ox-LDL), both of which are metabolized by scavenger receptors, and if so, whether modified LDL stimulates progesterone secretion as does normal LDL. Placental macrophages and trophoblasts were isolated on a 40% Percoll gradient after enzymatic digestion. The cellular uptake and degradation of [125I]-ac-LDL was 20-fold higher than [125I]-LDL in both macrophages and trophoblasts. Both cell types demonstrated high affinity and saturable degradation. Similarly, increased esterification of [14C]-labelled oleic acid to cholesterol was observed when cells were incubated with ac-LDL vs. LDL. Uptake of ac-LDL by trophoblasts also was demonstrated by colocalization of fluorescently labelled ac-LDL and fluorescent antibodies specific for trophoblasts. Similar colocalization of fluorescent ac-LDL and fluorescent anti-macrophage specific epitopes was seen in macrophages. Uptake and degradation of [125I]-ac-LDL by placental cells was inhibited by increasing concentrations of unlabelled ac-LDL or fucoidin but not LDL, indicating uptake by a scavenger receptor. Both unlabelled ac-LDL and ox-LDL inhibited uptake of [125I]-labelled ox-LDL, suggesting uptake by a common mechanism. Although secretion of progesterone by trophoblasts was stimulated by incubation with LDL, progesterone secretion by trophoblasts was not stimulated by ac-LDL and only minimally stimulated by ox-LDL. CONCLUSIONS: Scavenger receptors are present in human placental trophoblasts as well as macrophages. Scavenger receptor activity greatly exceeds that of LDL receptor activity in both cell types. However, cholesterol assimilated via the scavenger receptor pathway appears to be disconnected from endocrine steroidogenesis in trophoblasts. Thus, we hypothesize that scavenger receptors function in trophoblasts to degrade modified lipoproteins and prevent toxic effects on placental cellular function and fetal growth and development.

Cells, Cultured↗
PubMed1995

Zinc intake and plasma zinc level are maintained in men consuming cholesterol-lowering diets.

OBJECTIVE: Reduced zinc intake has been reported when cholesterol-lowering diets are adopted. This study examined whether such diets compromise the zinc status of men with hypercholesterolemia. DESIGN: Zinc intake on baseline 4-day food records and baseline plasma zinc levels were compared with intake and levels 12 and 24 months after subjects adopted a low-fat, increased-fiber diet. Dietary fiber intake, supplement use, alcohol intake, and exercise were evaluated as possible confounding variables. SUBJECTS: Subjects were free-living men (n = 365) with baseline cholesterol level above the 75th percentile who were participants in a randomized trial comparing cholesterol-lowering diets with goals of 30%, 26%, 22%, and 18% of energy from fat and 300, 200, 100, and 100 mg cholesterol, respectively. STATISTICAL ANALYSES: Data were analyzed using two sample t tests, multiple linear regression, and analysis of variance. RESULTS: For all subjects combined, mean fat and cholesterol intakes approached or met the guidelines of the National Cholesterol Education Program step 2 diet, with approximately 30 g fiber per day. Density (mg/1,000 kcal) of zinc intake was unchanged from the baseline value. We found a slightly positive relationship between fiber and zinc intakes; no relationship between fiber intake and plasma zinc level; no effect of supplement use (category included all types of supplements), alcohol use, or level of exercise on plasma zinc levels; and no difference by dietary assignment in zinc intake or plasma zinc levels. APPLICATION: Zinc status does not appear to be at risk in adult men who adopt cholesterol-lowering diets. These results may not be generalized to higher-risk population groups or situations in which dietary counseling is less comprehensive.

Adult↗