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Biomedical subjects

J Eckfeldt

Publications and source records attributed to J Eckfeldt.

At least 19 recordsLinked to original sources
PubMed2002

Pharmacogenetic approaches to hypertension therapy: design and rationale for the Genetics of Hypertension Associated Treatment (GenHAT) study.

The Genetics of Hypertension Associated Treatment (GenHAT) study will determine whether variants in hypertension susceptibility genes interact with antihypertensive medication to modify coronary heart disease (CHD) risk in hypertensives. GenHAT is an ancillary study of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial, ALLHAT, a double-blind, randomized trial of 42 418 hypertensives, 55 years of age or older, with systolic or diastolic hypertension and one or more risk factors for cardiovascular disease. About 50% are non-white, and about half are female. ALLHAT completes follow-up in March 2002. GenHAT is typing variants in hypertension genes; completion of genotyping is scheduled for 2003. Analysis of gene-treatment interactions in relation to outcomes include CHD, stroke, heart failure, and blood pressure lowering. To our knowledge, GenHAT is the largest pharmacogenetic study ever conducted. An added strength is its ability to link gene-treatment interactions with important clinical outcomes across diverse ethnic and gender groups.

Humans↗
PubMed2000

A genome scan for renal function among hypertensives: the HyperGEN study.

Decreased renal function is often a complication of hypertension. Although it has been suggested that the response of the kidney to hypertension has an underlying genetic component, there is limited information suggesting that specific genetic regions or candidate genes contribute to the variability in creatinine clearance, a commonly used measure of kidney function. As part of the Hypertension Genetic Epidemiology Network (HyperGEN) study, creatinine clearance measurements were assessed in a large biracial sample of hypertensive siblings (466 African American subjects and 634 white subjects in 215 and 265 sibships, respectively). All participants were hypertensive before the age of 60 years, and the mean age of the siblings was 52 years among the African American subjects and 61 years among the white subjects. Two residual models were created for creatinine clearance: a minimally adjusted model (which included age and age(2)) and a fully adjusted model (which included age, age(2), lean body mass, pulse rate, pulse pressure, hormone-replacement therapy, educational status, and physical activity). Standardized residuals were calculated separately for men and women in both racial groups. The heritability of the residual creatinine clearance was 17% and 18% among the African American and white subjects, respectively. We conducted multipoint variance components linkage analysis using GENEHUNTER2 and 387 anonymous markers (Cooperative Human Linkage Center screening set 8). The best evidence for linkage in African American subjects was found on chromosome 3 (LOD = 3.61 at 214.6 cM, 3q27) with the fully adjusted model, and the best evidence in white subjects was found on chromosome 3 (LOD = 3.36 at 115.1 cM) with the minimally adjusted model. Positional candidate genes that are contained in and around the region on chromosome 3 (214.6 cM) that may contribute to renal function include enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (EHHADH) and apolipoprotein D (ApoD). These findings suggest there may be genetic regions related to the variability of creatinine clearance among hypertensive individuals.

Black or African American↗
PubMed2000

Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.

Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking.

Biomarkers↗
PubMed2000

No evidence of linkage between the very-low-density lipoprotein receptor gene and fasting serum insulin or homeostasis model assessment insulin resistance index: the National Heart, Lung, and Blood Institute Family Heart Study.

A major gene effect on the fasting insulin level and insulin resistance has been suggested in previous studies. Several candidate genes for insulin resistance in rare syndromes have been proposed. However, there has been limited success in finding genes for common forms of insulin resistance. There is accumulating evidence of a relationship between insulin resistance and a disturbance of free fatty acid (FFA) metabolism. The very-low-density lipoprotein (VLDL) receptor, which is associated with FFA metabolism, could serve as a possible candidate gene for insulin resistance. We performed linkage analyses between the VLDL receptor gene and fasting insulin and the homeostasis model assessment (HOMA) insulin resistance index (fasting insulin x fasting glucose/22.5) in 1,050 sibpairs participating in the phase II physical examination of the National Heart, Lung, and Blood Institute Family Heart Study (FHS). Data analyses were completed using the SIBPAL component of the SAGE software package (SAGE, Statistical Analysis for Genetic Epidemiology, Version 3.1; Computer program package available from the Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, 1997). We did not find evidence for linkage of the fasting insulin or the HOMA insulin resistance index with a polymorphic marker at the VLDL locus (P = .316 and .402, respectively). Adjustment of fasting insulin and the HOMA insulin resistance index for the body mass index (BMI) did not change the results (P = .319 and .472, respectively). In conclusion, no evidence was found for a linkage between a locus controlling the fasting insulin level or HOMA insulin resistance index and a VLDL polymorphism in the present study. Additional adjustment of fasting insulin or the HOMA insulin resistance index for the BMI did not change the linkage results significantly.

Blood Glucose↗
PubMed2000

Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

BACKGROUND: Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. METHODS: We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. RESULTS: During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends </=0.02). The adjusted relative risk for the highest versus lowest quartile of triglycerides was 1.65 (95% CI, 1.1, 2.5, P = 0.01) and for HDL was 0.47 (95% CI, 0.3, 0.8, P = 0.003). These associations were significant in participants with normal creatinine (defined as <1.4 mg/dL for men and <1.2 mg/dL for women), with diabetes, and without diabetes. The effect of high triglycerides was independent of plasma glucose, but was weaker and less consistent after further adjustment for fasting insulin in nondiabetics. CONCLUSIONS: High triglycerides and low HDL cholesterol, but not low-density lipoprotein cholesterol, predict an increased risk of renal dysfunction. The treatment of these lipid abnormalities may decrease the incidence of early renal disease.

Arteriosclerosis↗
PubMed1999

Lewis blood group phenotype as an independent risk factor for coronary heart disease (the NHLBI Family Heart Study).

In the Copenhagen Male Study, men with Lewis blood group phenotype Le(a-b-) were found to have increased risk for coronary heart disease (CHD); such a relation has not been confirmed in men, and has not been evaluated in women. In the NHLBI Family Heart Study, we determined the Lewis blood type of 1,620 white subjects (790 male and 830 female subjects). The Lewis(a-b-) phenotype was found in 142 subjects (8.8%), 6.3% of subjects from randomly chosen families and 9.7% of subjects from families found to be at high risk for CHD. A history of CHD was present in 39.1% of men with Le(a-b-) versus 27.2% of men with other Lewis types; for women, the corresponding numbers were 12.3% versus 9.4%, respectively. In multivariate analysis, adjusting for age, sex, and risk group, the odds ratio for CHD was 2.0 (95% confidence interval = 1.2 to 3.1) for Le(a-b-) versus other Lewis groups. Mean values for body mass index, blood pressure, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, glucose, insulin, homocysteine, and fibrinogen were not significantly different between Le(a-b-) subjects and others, but triglycerides (p = 0.002) were higher in the Le(a-b-) subjects. However, inclusion of all risk factors in multivariate analysis did not diminish the increased risk for CHD associated with the Le(a-b-) phenotype. We conclude that the Le(a-b-) phenotype is associated with an increased risk for CHD; its effect does not appear to act predominantly through conventional cardiovascular risk factors. At present, mechanisms of effect are unknown.

Adult↗
PubMed1998

Segregation analysis of plasminogen activator inhibitor-1 and fibrinogen levels in the NHLBI family heart study.

Elevated plasminogen activator inhibitor-1 (PAI-1) and fibrinogen concentrations are risk factors for coronary heart disease. We investigated environmental, familial, and genetic influences on PAI-1 antigen and fibrinogen concentrations in 2029 adults from 512 randomly ascertained families in 4 US communities. We used maximum-likelihood segregation analysis to fit several genetic and nongenetic modes of inheritance to the data to determine whether mendelian inheritance of a major gene could best explain the familial distributions of these 2 hemostatic factors. Age- and gender-adjusted familial correlations for PAI-1 antigen level averaged 0.16 in first-degree relatives (95% CI=0.11 to 0.21); the spouse correlation was positive but not statistically significant (r=0.10, 95% CI=-0.02 to 0.23). Complex segregation analysis indicated a major gene associated with higher PAI-1 concentrations in 65% of individuals from these families. Demographic, anthropometric, lifestyle, and metabolic characteristics together explained 37% to 47% of the variation in PAI-1 antigen levels, and the inferred major gene explained an additional 17% of the variance. Positive and statistically significant age- and gender-adjusted familial correlations in first-degree relatives indicated a possible heritable component influencing plasma fibrinogen concentration (r=0. 17, 95% CI=0.13 to 0.22); however, segregation analysis did not provide statistical evidence of a major gene controlling fibrinogen level. These family data suggest that there are modest familial and genetic effects on the concentration of PAI-1.

Adult↗
PubMed1997

Family history of coronary heart disease and hemostatic variables in middle-aged adults. Atherosclerosis Risk in Communities Investigators and Family Heart Study Research Group.

Individuals with a family history of coronary heart disease (CHD) may be predisposed to atherothrombosis. To investigate this hypothesis, a family CHD risk score was computed for approximately 13,000 men and women aged 45 to 64; hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor, antithrombin III. protein C) were also measured in plasma. After adjustment for age and ethnicity, there was a statistically significant, positive association between the family risk score and four of the six hemostatic variables (fibrinogen, factor VIIc, factor VIIIc, von Willebrand factor) in women and all six hemostatic variables in men. In general, these associations were weak and substantially attenuated after adjustment for constitutional, lifestyle, and biochemical covariates. These results indicate that mean levels of selected hemostatic variables, like traditional CHD risk factors, are higher in individuals with a family history of heart disease.

Blood Coagulation↗
PubMed1996

NHLBI Family Heart Study: objectives and design.

The NHLBI Family Heart Study is a multicenter, population-based study of genetic and nongenetic determinants of coronary heart disease (CHD), atherosclerosis, and cardiovascular risk factors. In phase I, 2,000 randomly selected participants and 2,000 with family histories of CHD were identified among 14,592 middle-aged participants in epidemiologic studies. Medical histories from these individuals, their parents, and their siblings were used to calculate family risk scores that compared the number of reported and validated CHD events with the number expected based on the size, sex, and age of family members. A total of 657 families with the highest risk scores and early-onset CHD and 588 randomly sampled families had clinic examinations that included electrocardiograms, carotid artery ultrasound scans, spirometry, measurements of body size, blood pressure, lipids, lipoproteins, hemostatic factors, insulin, glucose, and routine chemistries. Additional biochemical and genetic studies are being performed on selected participants. Serum, plasma, lymphocytes, red cells, and DNA are stored for future studies, including genotyping of candidate genes and anonymous markers. Contributions of genes, shared and individual environments, and behaviors to variations in risk factors, preclinical atherosclerosis, and CHD will be estimated. Linkage studies, including the quantitative trait loci approach, are planned.

Age of Onset↗
PubMed1995

Sensitivity of HPLC and conventional bilirubin measurements in the detection of early cholestasis.

Recent studies using very sensitive high-performance liquid chromatography (HPLC) techniques have shown that conjugated bilirubin concentrations in normal human serum are about 0.006 mg/dl, much lower than the direct-reacting bilirubin concentrations reported by typical clinical laboratory techniques (up to 0.3 mg/dl). In animal models of cholestasis, we tested the concept that HPLC measurements of true serum conjugated bilirubin would provide a more sensitive indicator of cholestasis than does the conventional measurement. Serum conjugated bilirubin was not detectable (< 0.006 mg/dl) in untreated rats and guinea pigs. After bile duct ligation, the true serum conjugated bilirubin concentration in rats was significantly elevated by 10 minutes, whereas the conventional bilirubin measurement did not become significantly elevated until 120 minutes; comparable values for the guinea pig were 30 and 240 minutes, respectively. Studies of two rat models of drug-induced cholestasis, cyclosporine A and 17 alpha-ethynylestradiol, showed that measurable levels of true conjugated bilirubin appeared in the serum of cyclosporine A-treated rats but not in the estrogen-treated animals. We conclude that true serum conjugated bilirubin concentrations measured by HPLC provide an extremely sensitive means of detecting cholestasis and that such measurements could have clinical utility in detecting very early or minimal liver dysfunction.

Animals↗
PubMed1994

Active and passive smoking are associated with increased carotid wall thickness. The Atherosclerosis Risk in Communities Study.

BACKGROUND: Active cigarette smoking has been established as a potent risk factor for carotid atherosclerosis in clinical populations; however, neither the role of active smoking in general populations nor the impact of environmental tobacco smoke has been well described. METHODS: The association between carotid artery wall thickness and cigarette smoking was studied in 12,953 black and white men and women, aged 45 to 65 years, examined in the Atherosclerosis Risk in Communities Study. Participants were classified as current smokers (n = 3525), past smokers (n = 4315), never smokers reporting weekly exposure to environmental tobacco smoke (ETS or "passive smoking") of at least 1 hour (n = 3339), or never smokers reporting no weekly exposure to ETS (n = 1774). Carotid artery intimal-medial thickness (IMT) was measured by B-mode ultrasound. RESULTS: Increased IMT was observed in each category, in order from smallest to greatest increase: never smokers not exposed to ETS, never smokers exposed to ETS, past smokers, and current smokers. The larger IMT observed in the nonsmoking group exposed to ETS compared with the nonsmokers not exposed persisted after control for diet, physical activity, body mass index, alcohol intake, education, and major cardiovascular risk factors. Among past and current smokers, increased pack-years of exposure was associated with increased IMT. Among nonsmoking men exposed to ETS, there was a significant increase in IMT with increasing number of hours per week of ETS exposure. CONCLUSIONS: These data confirm the strong relationship between active smoking and carotid artery IMT and provide initial evidence that passive smoking exposure is related to greater IMT. Increasing exposure to cigarette smoke (either pack-years of active smoking or hours of ETS) was significantly related to increased IMT.

Aged↗
PubMed1993

The effect of fish oil supplements on blood pressure.

We conducted a double-blind, placebo-controlled crossover study to determine the effects of fish oil supplementation on blood pressure in middle-aged men. Subjects were randomly assigned to consume either 20 g of fish oil or safflower oil for 12 weeks and then consume the other oil for an additional 12 weeks after a 4-week washout period. We found no significant changes from the pretreatment value in systolic or diastolic blood pressure with the use of fish oil supplements. In addition, there were no significant differences in the posttreatment blood pressures comparing the fish and safflower oil phases of the study.

Blood Pressure↗
PubMed1993

Matrix effects and the accuracy of cholesterol analysis.

We found evidence of bias due to matrix effect in 70% of 37 instrument/reagent-specific systems analyzing the total cholesterol content of a lyophilized proficiency testing material. We used a computational method to remove bias due to matrix effect from the proficiency testing database. After correction for matrix effect bias and when compared with the reference method, 92% to 93% of results for three lyophilized proficiency testing samples analyzed in 1989 and 1990 met the 1992 National Cholesterol Education Program total error goal of 8.9%, and 94% to 95% met the Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) goal of 10%. However, compared with the definitive method for total cholesterol, the calibration bias of 41% of 37 peer groups exceeded the 1992 National Cholesterol Education Program goal for bias of 3%. Because the calibration bias of the method is incorporated into the peer group mean, use of peer group means as target values to assess result acceptability hinders advancement of the state of the art in interlaboratory comparability and the clinical effectiveness of laboratory testing. The prevalence of matrix effects has prevented successful application of accuracy-based evaluation of cholesterol test proficiency. The establishment of predictable recovery, preferably complete recovery, of cholesterol from reference materials is an important priority for cholesterol test methods. However, adjustment of proficiency testing results to remove the average bias due to matrix effects can help assess the actual state of the art in cholesterol test accuracy.

Bias↗
PubMed1990

ARIC hemostasis study--II. Organizational plan and feasibility study.

In our previous paper, we reported the development of a blood collection and processing system (BCPS) suitable for the ARIC multicenter hemostasis study. As an additional step of preparation for the ARIC study, we incorporated this BCPS into an organizational plan to increase efficiency and minimize errors. We initially designed organizational trays for blood collection tubes and aliquot tubes and developed a coordinated step-by-step plan for the orderly processing of blood samples. Once the plan was considered workable, we carried out a pilot study to test the feasibility of this integrated organizational plan. Included in the pilot study were 95 healthy subjects randomly selected from 4 ARIC field centers, whose age and gender were comparable to those projected for the ARIC population. We determined the time lapse of filling the first tube as an index of blood flow. The overall mean time-lapse was 23 s (S.D. = 5). There was no significant difference among the field centers. We also determined the entire time lapse required for completing the sample processing. The total processing time was always less than 60 min. By performing the processing of samples in pairs, all the samples from two subjects could be completely processed in 70 min. This greatly increased the efficiency of field center operation. We evaluated the potential in vitro hemostasis activation by measuring plasma beta-thromboglobulin and platelet factor 4 levels. The geometric means of both proteins were comparable to our previously reported results. Fibrinogen, factor VII, factor VIII, von Willebrand factor, antithrombin III, protein C and activated partial thromboplastin time were analyzed.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteriosclerosis↗
PubMed1989

Fish oil supplementation does not lower plasma cholesterol in men with hypercholesterolemia. Results of a randomized, placebo-controlled crossover study.

STUDY OBJECTIVE: To determine the effects of fish oil supplementation on plasma cholesterol in middle-aged men with isolated hypercholesterolemia. DESIGN: Randomized double-blind placebo-controlled (safflower oil) two-period crossover trial with 12-week treatment periods. SETTING: Outpatient general medicine clinic at a university-affiliated Veterans Affairs hospital. PATIENTS: Thirty-eight men with plasma cholesterol between 5.68 and 7.76 mmol/L (220 to 300 mg/dL), triglyceride levels less than 3.39 mmol/L (300 mg/dL), and free of coexisting diseases. INTERVENTIONS: Fish oil and placebo (safflower oil) supplementation. After basal measurements and a 4-week lead-in period, twenty 1-g capsules of either fish oil or placebo oil were provided for 12 weeks (period 1). After a 4-week washout phase participants then received the other oil for an additional 12 weeks (period 2). MEASUREMENTS AND MAIN RESULTS: Blood was drawn at the beginning and end of each study period and analyzed for levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein A1, and apolipoprotein B. Low-density lipoprotein (LDL) cholesterol was calculated using the Friedewald equation. Total and LDL cholesterol increased from the before treatment values by 4.8% and 9.1%, respectively, after ingestion of fish oil. Compared with placebo, LDL cholesterol was significantly higher (4.5 compared with 4.1 mmol/L, P = 0.01) and triglycerides lower (1.3 compared with 1.8 mmol/L, P = 0.01) after fish oil. Total and HDL cholesterol and apolipoprotein A1 and B levels did not differ. CONCLUSIONS: Fish oil supplements do not lower plasma cholesterol levels in middle-aged men with hypercholesterolemia without elevated triglycerides. They should not be recommended as a method to lower plasma cholesterol in these patients.

Adult↗
PubMed1982

Urinary urea: are currently available methods adequate for revival of an almost abandoned test?

Measurement of urinary urea excretion has been suggested as a means of estimating nitrogen balance in hospitalized patients who are malnourished. Because proficiency-testing surveys show gross variations in mean urea as determined by various automated methods and extremely poor precision occasionally, we compared urinary urea measurements and ammonia interference in three widely used methods. The coupled urease/glutamate dehydrogenase method (used in the DuPont aca) showed positive interference from ammonia, as expected; with the diacetylmonoxime (Technicon (12/60) and the urease conductivity (Beckman ASTRA) methods we saw no such interference. Generally, interference by ammonia is less than 10%, but (rarely) it may exceed 25%. However, if urine specimens are properly diluted and potential sources of interference recognized, all three methods appear capable of providing clinically useful data.

Ammonia↗