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Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 109 records · Page 6Linked to original sources
PubMed1990

Promoting adherence to low-fat, low-cholesterol diets: review and recommendations.

Evidence that lowering blood cholesterol levels reduces risk of coronary heart disease has prompted widespread recommendations that hyperlipidemic individuals undergo dietary therapy. However, the extent to which people can adopt and maintain diets to lower lipids is unclear. In our article, we review what is currently known regarding adherence to low-fat diets and present an approach to dietary counseling for lowering cholesterol that incorporates elements of behavioral self-management and social learning theory. We discuss specific recommendations for counseling hyperlipidemic patients based on the Dietary Alternatives Study. Recommendations include providing patients with an adequate knowledge base to make dietary changes, using goal setting and self-monitoring to help patients initiate dietary changes, enlisting support from the patient's family, and enhancing self-efficacy to promote long-term dietary maintenance.

Cholesterol, Dietary↗
PubMed1990

Estimating low-density lipoprotein cholesterol by the Friedewald equation is adequate for classifying patients on the basis of nationally recommended cutpoints.

We compared low-density lipoprotein cholesterol (LDL) values obtained by the Friedewald formula--i.e., total cholesterol minus high-density lipoprotein (HDL) cholesterol minus very-low-density lipoprotein (VLDL) cholesterol (estimated as triglyceride divided by 5)--with those obtained by lipoprotein fractionation, using 4736 specimens. When triglycerides were less than 2.0 g/L, greater than 90% of estimated LDL cholesterol values were acceptable, within +/- 10% of measured values. At triglyceride concentrations of 2.0-4.0 g/L and 4.0-6.0 g/L, only 72% and 39%, respectively, of the estimates were acceptable. LDL values derived from an alternative formula, estimating VLDL as triglycerides divided by 6, were even less accurate. Nevertheless, the use of estimated LDL for risk classification based on the National Cholesterol Education Program Adult Treatment Panel cutpoints of 1.30 and 1.60 g/L was considered acceptable. At triglyceride concentrations less than or equal to 5.0 g/L, 88% of classifications based on estimated LDL (using triglycerides divided by 5) were concordant with those by measured LDL. Eleven percent of classifications were shifted across one cutpoint, evenly distributed between high and low. Fewer than 1% of classifications, all with Type III hyperlipoproteinemia, were misclassified two cutpoints high. Refinements in the estimation model did not substantially improve LDL estimation or concordance of risk classification.

Adult↗
PubMed1989

In utero thrombosis and neonatal gangrene in an infant of a diabetic mother.

We report an infant of a diabetic mother (IDM) with in utero brachial artery thrombosis and neonatal gangrene to illustrate that there may be an increased risk for arterial as well as venous thrombosis in IDMs. The diagnosis of brachial artery thrombosis was made by using Doppler sonography flow studies and was confirmed with autopsy. The postnatal period was complicated by aortic and mesenteric artery thrombosis, with subsequent necrotizing enterocolitis, renal infarction, and death. Gangrene of a limb presenting at birth is rare, with 32 individuals reported in the literature, including this patient. Twenty-two percent (7/32) of the infants with peripartum limb gangrene were IDMs. This implies a marked increase in arterial thrombosis in IDMs over the general population. Changes in coagulation factors have been reported in newborn IDMs with poor control of maternal diabetes. Increased clotting and decreased fibrinolysis found in diabetics may lead to arterial thrombosis in IDMs in utero and postnatally. Use of anticoagulants in at-risk infants should be considered to prevent further thrombosis postnatally. Additionally, IDMs may be at increased risk for thrombotic complications from umbilical artery catheter. In utero thrombosis of the brachial artery may be one mechanism which leads to limb reduction defects in IDMs.

Aortic Diseases↗
PubMed1989

Drug ingestion during pregnancy: infrequent exposure in a contemporary United States sample. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group.

Drug ingestion in a cohort of United States women proved consistently lower than in prior United States populations. Participating were 342 insulin-dependent diabetic and 387 control subjects who were enrolled before conception (76%) or no later than 21 days after conception (24%). Drug exposures were then recorded at entry and periodically throughout organogenesis (gestational weeks 6, 8, 10). During gestational weeks 1 to 10, approximately two thirds of the subjects were exposed to no agent other than oral iron, oral vitamins, or insulin (diabetic subjects). The mean exposures in gestational weeks 1 to 10 were 0.72 +/- 1.05 (SD) for diabetic women and 0.54 +/- 0.96 for control subjects; throughout pregnancy, the mean exposures were 1.26 +/- 1.66 and 1.58 +/- 1.78, respectively. The low exposure frequency in this contemporary United States population is highly encouraging. However, it follows that collaborative cohort efforts may be necessary in order to assess teratogenicity of drugs because relatively few women are now exposed.

Abnormalities, Drug-Induced↗
PubMed1989

Review of the effects of fenofibrate on lipoproteins, apoproteins, and bile saturation: US studies.

The first well-controlled studies of fenofibrate in the United States indicate that the drug is safe and effective for the treatment of type IIa and type IIb hyperlipidemia. Fenofibrate produced a marked reduction in triglyceride (TG) levels (p less than 0.01) as well as a uniform decrease in very-low-density lipoprotein (VLDL) cholesterol levels (p less than 0.01) and a rise in high-density lipoprotein (HDL) cholesterol levels (p less than 0.01) in 227 subjects with both type IIa and IIb hyperlipidemias. Low-density lipoprotein (LDL) cholesterol levels also fell: 20.3% in type IIa and 6% in type IIb subjects. Fenofibrate also affected the structure and composition of some of the major classes of lipoproteins: increases in apolipoproteins (apo) AI and AII and decreases in apo B and apo E were consistent with reductions in TG, VLDL, and LDL and increases in HDL. Tolerance of fenofibrate was excellent, with most side effects being transitory or reversible. Thus, based on the lipid hypothesis of atherosclerosis, therapy with fenofibrate can potentially lead to significant reductions in cardiovascular disease in type IIa and type IIb hyperlipoproteinemia.

Adult↗
PubMed1989

Apoprotein measurements and their clinical application.

The apoproteins structurally are closely associated with specific lipoproteins, for example, apoprotein B with VLDL and LDL and apoprotein A-I with HDL. The levels of these apoproteins provide information about the plasma concentrations and metabolism of the lipoproteins with which they are associated. The levels of apoprotein B and apoprotein A-I and the Lp(a) lipoprotein can serve as important predictors of coronary heart disease risk and can provide information not available from blood lipid and lipoprotein lipid levels. For clinicians and public health interests, the decision to use apoprotein measurements and to estimate cardiovascular risk depends on the clinical setting, the availability of standardized apoprotein methods that can be related to age- and sex-specific population-based reference values, and the cost of the measurements. In addition, these apoproteins can be used in specific cases to answer diagnostic questions and provide information about therapeutic response.

Adult↗
PubMed1989

Fenofibrate for the treatment of type IV and V hyperlipoproteinemias: a double-blind, placebo-controlled multicenter US study.

The results of a randomized, double-blind, placebo-controlled multicenter trial of fenofibrate in the treatment of type IV/V hyperlipoproteinemia are reported. Ten study centers in the United States recruited 147 adults with a history of type IV or V hyperlipoproteinemia. After a six- to 12-week dietary stabilization period and a four-week placebo period, patients whose 12-hour fasting total plasma triglyceride levels ranged from 350 to 1,500 mg/dl were continued in the study; 55 patients with levels of 350 to 499 mg/dl were placed in group A and 92 with levels of 500 to 1,500 mg/dl in group B. Patients in each group were randomly assigned to receive 100 mg of fenofibrate or placebo three times daily for eight weeks. In both groups A and B fenofibrate-treated patients showed statistically significant reductions in levels of total cholesterol, very-low-density lipoprotein cholesterol, total triglycerides, and very-low-density lipoprotein triglycerides, and significant increases in high-density lipoprotein cholesterol; patients in group B also showed a significant increase in low-density lipoprotein cholesterol levels. Sixteen of the 75 fenofibrate-treated patients and 11 of the 72 placebo patients reported adverse events that were potentially drug related; most of these were gastrointestinal and a few reported musculoskeletal and skin reactions. It is concluded that fenofibrate is an effective and safe agent in the treatment of type IV/V hyperlipoproteinemia.

Adolescent↗
PubMed1989

Epidemiology of cardiovascular disease in women and the role of sex steroid hormone use.

Women in the United States are at significant risk for CVD. After a 10- to 12-year delay in onset, the rate of increase in CAD with age in women is the same as that in men. Cardiovascular risk correlates positively with total serum cholesterol, LDL and triglyceride levels and inversely with HDL cholesterol. Triglycerides are an independent risk factor in women. The close correlation between cholesterol levels and myocardial infarction has been documented in population-based studies in men and women and in dietary and drug intervention trials in men. For every 1% decrease in cholesterol, there is a corresponding 2% decrease in cardiovascular risk in both sexes. For adults it is recommended that total cholesterol levels be less than 200 mg/dL. Fifty percent of women in the United States have cholesterol levels that exceed that number. Cholesterol screening, identification of high-risk individuals and early institution of overall risk management strategies are keys to reducing morbidity and mortality. Ideal therapeutic interventions are those that are lipid neutral or have a beneficial effect on the lipid profile.

Cardiovascular Diseases↗
PubMed1988

Incidence of spontaneous abortion among normal women and insulin-dependent diabetic women whose pregnancies were identified within 21 days of conception.

Whether pregnant women with insulin-dependent diabetes mellitus have an increased risk of spontaneous abortion is controversial. To address this question, we enrolled 386 women with insulin-dependent diabetes and 432 women without diabetes before or within 21 days after conception and followed both groups prospectively. Sixty-two diabetic women (16.1 percent) and 70 control women (16.2 percent) had pregnancy losses (odds ratio, 0.99; 95 percent confidence interval, 0.67 to 1.46). After adjustment for known risk factors for spontaneous abortion, the rate was still not significantly higher in the diabetic group (odds ratio, 0.91; 95 percent confidence interval, 0.59 to 1.40). Nonetheless, among the diabetic women, most of whom had good metabolic control, those who had spontaneous abortions had higher fasting and postprandial glucose levels in the first trimester than those whose pregnancies continued to delivery (P = 0.01 for fasting glucose levels and P = 0.005 for postprandial levels). In the small subgroup of diabetic women with poor control, who had elevated values for glycosylated hemoglobin in the first trimester, each increase of 1 SD above the normal range was associated with an increase of 3.1 percent in the rate of pregnancy loss (95 percent confidence interval, 0.6 to 5.6). We conclude that diabetic women with good metabolic control are no more likely than nondiabetic women to lose a pregnancy, but that diabetic women with elevated blood glucose and glycosylated hemoglobin levels in the first trimester have a significantly increased risk of having a spontaneous abortion.

Abortion, Spontaneous↗
PubMed1988

Lack of relation of increased malformation rates in infants of diabetic mothers to glycemic control during organogenesis.

To determine how much insulin-dependent diabetes increases a woman's risk of giving birth to a malformed infant and how that risk is influenced by metabolic control, we followed 347 diabetic and 389 control women who enrolled in the study within 21 days of conception (the early-entry group) and 279 diabetic women who entered later (the late-entry group). We detected major malformations in the infants of 4.9 percent of the early-entry diabetic women, 2.1 percent of the controls, and 9.0 percent of the late-entry diabetic women. Malformation rates were significantly higher among offspring of early-entry diabetic women than among those of controls (odds ratio, 2.45; lower one-sided 95 percent confidence limit, 1.12; P = 0.027), and higher among late-entry than among early-entry diabetic women (odds ratio, 1.91; lower one-sided 95 percent confidence limit, 1.07; P = 0.032). Mean blood glucose and glycosylated hemoglobin levels during organogenesis were not significantly higher in women whose infants were malformed. Hypoglycemia (glucose, less than or equal to 50 mg per deciliter [2.8 mmol per liter]) was not significantly more common in the same group. Hyperglycemia and glycosylated hemoglobin were not correlated with malformation. The data suggest that more sensitive measures are needed to identify the teratogenic mechanisms, or that not all malformation can be prevented by good glycemic control. Despite the increased malformation rate among infants of the early-entry diabetic women, as compared with the controls, the more favorable outcome seen in the former group as compared with the late-entry group justifies the attempt to achieve good metabolic control around the time of conception.

Blood Glucose↗
PubMed1988

Cardiovascular effects of endogenous and exogenous sex hormones over a woman's lifetime.

Natural fluctuations in concentrations of physiologic sex hormones over the course of a woman's lifetime affect lipoprotein levels; such effects may be compared with those induced by exogenous hormone therapy. During the progesterone-dominated luteal phase of the menstrual cycle, high-density lipoprotein (HDL) concentrations do not fall, but low-density lipoprotein (LDL) concentrations usually decline. During pregnancy both estrogen and progesterone levels are extremely high; LDL concentration gradually increases to a maximum value at term of 50% above the nonpregnant level. Total HDL and HDL2 concentrations also increase, reaching a maximal 30% increase at 20 weeks' gestation. These physiological fluctuations have not been associated with increased arteriosclerosis. Oral contraceptives that combine C21 progestins and certain C19 progestin derivatives with estrogen have little or no effect on HDL2; however, those with a marked progestogenic or androgenic effect are more likely to lower HDL and HDL2. Increases in LDL concentration during oral contraceptive use are not consistently proportional to estrogen/progestin ratio and may reflect progestin androgenicity or a progestin-estrogen interaction. In postmenopausal women estrogen alone benefits lipoproteins, whereas cyclical administration of progestin with estrogen appears to lower HDL2-cholesterol proportionate to progestin dose. These exogenous hormone-induced changes are associated with the expected changes in arteriosclerosis risk when they have been looked for. In summary, estrogen-progestin regimens that do not affect LDL- and HDL2-cholesterol concentrations are most desirable in terms of long-term cardiovascular risk.

Arteriosclerosis↗
PubMed1988

The effects of postmenopausal estrogen therapy on the incidence of arteriosclerotic vascular disease.

Recent studies show that arteriosclerotic cardiovascular disease is associated with high low-density lipoprotein and low high-density lipoprotein cholesterol concentrations and, further, that reversal of these abnormalities can prevent cardiovascular disease. As postmenopausal estrogen therapy favorably changes low-density lipoprotein and high-density lipoprotein cholesterol concentrations, it is hypothesized that reductions in cardiovascular disease will be observed in postmenopausal women so treated. The majority of at least 23 studies support this view.

Arteriosclerosis↗
PubMed1987

Effects of fenofibrate on plasma lipoproteins in hypercholesterolemia and combined hyperlipidemia.

To investigate the lipoprotein effect of fenofibrate in hypercholesterolemia or combined hyperlipidemia (types II A and II B hyperlipidemias, respectively), 240 patients were recruited and 227 randomized to a double-blind randomized trial lasting 24 weeks and 192 patients continued to participate in an open-label phase for another 24 weeks. A 100-mg dose of fenofibrate or a matching placebo was given three times daily. Fenofibrate side effects in excess of placebo affected 6 percent of fenofibrate users and were confined almost entirely to skin rashes. In 180 hypercholesterolemic patients randomly assigned to receive fenofibrate versus placebo, triglyceride and very low-density lipoprotein cholesterol levels decreased 38 percent, total cholesterol levels decreased 17.5 percent, and low-density lipoprotein cholesterol levels decreased 20.3 percent with fenofibrate treatment. High-density lipoprotein cholesterol levels increased 11.1 percent with a decrease in the low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio of 27 percent. All differences were statistically significant (p less than 0.01). In combined hyperlipidemic (type II B) patients, triglyceride levels decreased by 45 percent, very low-density lipoprotein cholesterol levels decreased 52.7 percent, total cholesterol levels decreased 16 percent, low-density lipoprotein cholesterol levels decreased 6 percent, and high-density lipoprotein levels increased 15.3 percent for a low-density lipoprotein cholesterol: high-density lipoprotein cholesterol ratio decrease of 13 percent. All differences were again statistically significant (p less than 0.01). In both groups of patients, the onset of the drug effect was generally rapid, with maximal total and low-density lipoprotein cholesterol level lowering achieved within four weeks in hypercholesterolemic patients and maximal triglyceride and cholesterol level lowering in hypertriglyceridemic patients achieved in two weeks. Maximum high-density lipoprotein increases occurred after four weeks in type II A patients and 12 to 16 weeks in type II B patients. Fenofibrate is a well-tolerated drug in the fibric acid series and has putatively beneficial effects on triglyceride, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein cholesterol concentrations in both type II A and type II B hyperlipidemic patients. If the lipid hypothesis of atherosclerosis applies to the lipoprotein changes induced by fenofibrate, reductions in cardiovascular disease risk in both type II A and II B hyperlipidemic patients should result from fenofibrate treatment.

Adult↗
PubMed1987

Effect of fenofibrate treatment on plasma lipoprotein lipids, high-density lipoprotein cholesterol subfractions, and apolipoproteins B, AI, AII, and E.

In this segment of a multicenter study, 36 hypercholesterolemic patients were randomly assigned to fenofibrate or placebo treatment to assess effects on plasma concentrations of lipoprotein cholesterol and triglyceride, high-density lipoprotein-cholesterol subfractions, and apolipoproteins E, B, Al, and All. All of these factors are of known or potential value in determining the patient's risk of arteriosclerosis. Observations were made during initial screening and placebo phases, a 24-week, double-blind treatment phase, and a subsequent 24-week, open-label fenofibrate phase. There were three possible expressions of fenofibrate efficacy. Changes in lipoprotein cholesterol and total triglyceride concentrations observed in these patients were very similar to those seen with the larger multicenter cohort: total triglyceride levels decreased 38 to 46 percent, low-density lipoprotein cholesterol levels decreased 13 to 20 percent, and high-density lipoprotein cholesterol levels increased 4 to 13 percent. Triglyceride concentrations were significantly reduced (p less than 0.01) in very low-density lipoprotein (50 to 56 percent, similar to those of total triglyceride and very low-density lipoprotein cholesterol), and in low-density lipoprotein cholesterol levels (17 to 21 percent). A slight but statistically insignificant decrease in high-density lipoprotein triglyceride was observed (9 to 15 percent). High-density lipoprotein2 cholesterol levels did not change significantly, whereas high-density lipoprotein3 cholesterol levels increased 8 to 16 percent, accounting for all of the increase in high-density lipoprotein cholesterol. Apoprotein All levels increased significantly (13 to 20 percent) whereas those of apolipoprotein Al did not, consistent with an increase in high-density lipoprotein3 levels, where apolipoprotein All is more abundant relative to apolipoprotein Al than in high-density lipoprotein2. Apolipoprotein B levels decreased 20 to 26 percent and those of apolipoprotein E went from 29 to 34 percent, relative to the 16 to 20 percent decreases in very low-density lipoprotein and low-density lipoprotein triglyceride and cholesterol levels. Five patients with combined elevations of triglyceride and low-density lipoprotein cholesterol treated with fenofibrate, had reductions primarily in triglyceride, total apolipoprotein E (50 percent reduction), and apolipoprotein B (18 percent) levels. High-density lipoprotein3 cholesterol levels increased 19 percent and high-density lipoprotein2 cholesterol levels were unchanged. Low-density lipoprotein cholesterol levels declined slightly in four patients and a slight rise was observed in a fifth patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗