Search PubMed⌕ Search

Biomedical subjects

J E Eichner

Publications and source records attributed to J E Eichner.

At least 19 recordsLinked to original sources

Angiotensin-converting enzyme gene polymorphism in a cohort of coronary angiography patients.

An association between a polymorphism of the angiotensin-converting enzyme (ACE) gene and myocardial infarction (MI) in men has been previously reported. The present study examines the association between ACE genotype, atherosclerosis, MI, hypertension and other cardiovascular risk factors in Caucasian men (n=576) and women (n=124) who have undergone coronary angiography. Gene frequencies are also reported for African-American men (n=56). Genotype determination was based on the presence (allele I) or absence (allele D) of a 287 nucleotide Alu sequence in intron 16 of the ACE gene. Genotype frequencies for DD, ID and II were: 30.9, 47.7, 21.4% for Caucasian men; 28.2, 48.4, 23.4% for Caucasian women; and 30.4, 46.4, 23.2% for African-American men. There were no statistically significant associations between ACE genotype and number of plaques (> or =10% obstruction), lipid variables, or body mass index (BMI) for Caucasian men. Caucasian women with the DD genotype had on average fewer plaques, but this was accounted for by their younger ages. In Caucasian males, the DD genotype independently contributed to the presence of hypertension (odds ratio=1.8, 95% CI 1.1-2.9) after adjusting for age and BMI. In Caucasian males with total cholesterol levels less than 200 mg/dl (n=237), the DD (odds ratio=2.5, 95% CI 1.2-5.4) and ID genotypes (odds ratio=2.2, 95% CI 1.1-4.4) were associated with a history of MI.

Black or African American↗

Hypertension treatment patterns in American Indians: the strong heart study.

Pharmacologic treatment patterns for hypertensive American Indians from 13 communities in Arizona, Oklahoma, South Dakota, and North Dakota were assessed. Participants (2254 women and 1384 men, aged 48 to 79 years) completed a clinical examination between July 1993 and December 1995. The mean of two blood pressure (BP) measurements and detailed medication histories were obtained. The observed prevalence of hypertension was 46.7% (n=1698). In participants taking antihypertensive medications (n=1114), four principal drug classes were evaluated: diuretics, calcium channel blocking agents, beta-blocking agents, and angiotensin-converting enzyme (ACE) inhibitors. Among treated hypertensive participants, 71.4%, 24.6%, and 4.0% received one, two, and three medications, respectively. Among single drug regimens, ACE inhibitors (n=340) were used most often (49.4%), with calcium channel blocking agents and diuretics accounting for 24.2% and 19.9%, respectively. Although multiple drug class therapies varied, the combination of a diuretic and ACE inhibitor (n=120) accounted for 47.4% of dual therapy use. Hypertension control (SBP < 140 mm Hg, DBP < 90 mm Hg) rates were highest for those on dual therapies (65.4%), followed by participants on single (53.8%) and triple (43.6%) therapies. Among monotherapies, diuretics exhibited the best overall hypertension control rate in both diabetics (63.0%) and nondiabetics (68.0%), versus 47% to 61% for other remaining agents. The frequent use of ACE inhibitors, used singly or in combination, reflects the high prevalence of diabetes among American Indians. ACE inhibitors, combined with diuretics, were particularly useful in achieving BP control in this population.

Age Factors↗

Predictions of coronary artery stenosis by artificial neural network.

Data from angiography patient records comprised 14 input variables of a neural network. Outcomes (coronary artery stenosis or none) formed both supervisory and output variables. The network was trained by backpropagation on 332 records, optimized on 331 subsequent records, and tested on final 100 records. If 0.40 was chosen as the output distinguishing stenosis from no stenosis, 81 patients who had stenosis would have been identified, while 9 of 19 patients who did not have stenosis might have been spared angiography. The results demonstrated that artificial neural networks could identify some patients who do not need coronary angiography.

Adult↗

Role of factor V Leiden mutation in patients with angiographically demonstrated coronary artery disease.

The study sought to determine whether coagulation factor V Leiden (FV Leiden) plays a role in the pathogenesis of coronary artery disease and/or myocardial infarction. Association of FV Leiden with venous thromboembolism is well established in the literature, but the role of the mutation in arterial thrombotic events is controversial. Some studies have documented an association between the mutation and myocardial infarction and stroke in juveniles. Few studies have explored its possible contribution to coronary atherosclerosis. We screened FV genotype in 850 predominantly white coronary angiography patients. Coronary artery disease risk factors and history of myocardial infarction were then analyzed by genotype. The FV Leiden mutation occurred in 54 (6.4%) patients. There was one homozygote; a 37-year-old, white male smoker with a history of myocardial infarction. Gene frequencies for white males and females were similar: 0.965 for the normal allele and 0.035 for FV Leiden. Gene frequencies for both genders were in Hardy-Weinberg equilibrium. FV Leiden was not a useful predictor (p=0.23) of the presence of clinically defined atherosclerosis (> or = 50% stenosis) in a logistic regression model adjusting for age, lipoprotein (a), total cholesterol, triglycerides, high density lipoprotein cholesterol, and fibrinogen. In addition, there was no difference in frequency of FV Leiden among those with and without medical histories of myocardial infarction (p=0.51). Allelic frequencies of FV Leiden in this patient group do not differ significantly from those reported for white populations. The FV Leiden mutation in its heterozygous state is not independently associated with coronary artery disease or myocardial infarction.

Coronary Angiography↗

Genetic variation in alpha 2HS-glycoprotein is related to calcaneal broadband ultrasound attenuation in older women.

Calcaneal broadband ultrasound attenuation (BUA) is an independent predictor of hip and vertebral fractures. BUA is under genetic control, but the specific genes contributing to BUA are not well defined. We examined the relationship between genetic variation in alpha2HS-glycoprotein (AHSG), an abundant noncollagenous protein of bone matrix, and calcaneal BUA. Genetic polymorphism in AHSG was determined in 222 Caucasian women (age 66-92) enrolled in the Pittsburgh Study of Osteoporotic Fractures clinical center by isoelectric focusing of serum samples. Calcaneal BUA and bone mineral density (BMD) were measured on the same foot with a Walker Sonix UBA 575(+) and single X-ray absorptiometry. Hip and spine BMD were determined with a Hologic QDR-1000 densitometer using dual-energy X-ray absorptiometry. AHSG polymorphism was not significantly related to hip, lumbar spine, or calcaneal BMD. Compared with the homozygous AHSG*2 women, calcaneal BUA was 13% lower in heterozygous (P < 0.05) and 16% lower in homozygous AHSG*1 women (P < 0.05). This relationship persisted after controlling for age, weight, height, walks for exercise, and calcaneal BMD. Current and self-reported height were also lowest in homozygous AHSG*1 women, intermediate in heterozygous women, and highest among homozygous AHSG*2 subjects. These results suggest that the AHSG polymorphism may contribute to the genetic influence on calcaneal BUA and stature.

Aged↗

Iron measures in coronary angiography patients.

Excess iron has been postulated as a risk factor for coronary artery disease (CAD) because of its presence in atherosclerotic lesions, its ability to oxidize low density lipoprotein cholesterol (LDLc), and its promotion of oxygen reperfusion damage after an ischemic event. Whether iron, indirectly measured by its storage protein ferritin and its transport protein transferrin, is related to CAD was examined in a consecutive series of white male (n = 457) and female (n = 114) cardiac patients. Atherosclerosis measures were analyzed in patients grouped by tertiles of ferritin. A similar analysis was done with tertiles of transferrin. Contrary to expectations, men in the third tertile of ferritin had a smaller mean number of stenoses than men in the two lower tertiles (4.9 versus 5.6 and 5.9; P = 0.027); otherwise, there were no statistically significant differences in either number of lesions or extent of arterial narrowing based on tertiles of either measure. Separate multiple logistic regression models with age, fibrinogen, LDLc and triglycerides as covariates provided no evidence that ferritin (odds ratio = 0.88 with 95% C.I. = 0.72-1.07 for men and odds ratio = 0.79 with 95% C.I. = 0.54-1.16 for women) or transferrin (odds ratio = 0.60 with 95% C.I. = 0.31-1.16 for men and odds ratio = 1.33 with 95% C.I. 0.52-3.42 for women) were important correlates of the presence of atherosclerosis in this study.

Coronary Angiography↗

Activated factor VII levels in patients with angiographically confirmed coronary artery disease.

We have examined factor VIIa levels in consecutive consenting patients undergoing coronary angiography (n = 702) to determine if levels are related to the presence of coronary arterial narrowing and to the degree and extent of that narrowing. Both men and women with clinically defined coronary artery disease (> or = 50% stenosis in at least 1 vessel) had factor VIIa levels that were similar to men and women with less stenosis or normal coronary arteries.

Coronary Angiography↗

Fibrinogen levels in women having coronary angiography.

Fibrinogen has emerged as a risk factor for coronary artery disease in men that equals cholesterol in importance. It is known to play an important role in reparative processes, and evidence is accumulating that fibrinogen/fibrin accumulates at the site of minimal vascular injury. Fibrinogen contributes significantly to blood viscosity and its adherence to endothelium may mediate progression of atheromatous lesions. This study was designed to examine a number of markers of risk in a consecutive series of cardiology patients undergoing coronary catheterizations over a 15-month period. This article examines the level of fibrinogen in relation to the number of reported coronary stenoses and disease severity in a series of Caucasian female patients (n = 101). Women were classified as diseased if they had at least 1 lesion > or = 25% in the coronary anatomy and nondiseased if they had no lesions > or = 25%. The number of reported lesions correlates significantly with fibrinogen levels (r = 0.36, p = 0.0002). Women with fibrinogen levels > or = 283 mg/dl had a 3.2-fold increased risk (95% confidence interval 1.2 to 9.1) of having at least 1 stenosis > or = 25% after adjusting for age and diabetic status. Smoking and body mass index did not differ by disease status and thus did not confound the finding. Mean fibrinogen levels showed a progressive positive association with increasing clinically defined vessel involvement (stenosis > or = 50%).

Age Factors↗

Relation of apolipoprotein E phenotype to myocardial infarction and mortality from coronary artery disease.

The apolipoprotein E polymorphism is a genetic determinant of low-density lipoprotein (LDL) cholesterol. Its status as a risk factor for coronary artery disease (CAD), either through a causal relation with LDL cholesterol level or independently, is less clearly established. Data from the Multiple Risk Factor Intervention Trial were used to examine the influence of apolipoprotein E phenotype on risk of coronary events. Of the 12,866 randomized participants, 619 were studied in a nested case-control design. CAD deaths (93) and nonfatal myocardial infarctions (113) were matched to 412 controls. The allele frequencies of apolipoprotein E in the white subset (epsilon 2 = 0.06, epsilon 3 = 0.79, and epsilon 4 = 0.15) were very similar to other nonselected white American populations, and the relation of apolipoprotein E on total and LDL cholesterol was generally similar to that seen in other studies, with the epsilon 2 allele being associated with lower and the epsilon 4 allele with higher total and LDL cholesterol. Allele frequencies were not the same for patients and control subjects. The presence of epsilon 4 was associated with an increased risk of CAD that was most evident for fatal cases. There was no relation between changes in LDL cholesterol over time during the trial and apolipoprotein E phenotypes.

Alleles↗

Apo E allele frequencies in younger (age 42-50) vs older (age 65-90) women.

Allelic variation at the apolipoprotein E (Apo E) structural locus has been shown to influence concentrations of total cholesterol and low density lipoprotein cholesterol (LDL-C). Apo E has six phenotypes resulting from three common alleles at this locus. The epsilon 2 allele is associated with lower LDL-C and the epsilon 4 allele with higher LDL-C. In the current study, we compared the epsilon allele distribution in two cohorts of white women recruited from population based listing of southwestern Pennsylvania. The "younger" cohort consisted of 473 women, age 42-50; the "older" cohort, 870 women, age 65-90. A comparison of the overall distribution of allele frequencies in the two cohorts was significantly different. The allele frequency of epsilon 4 was lower in the older cohort (0.098 vs. 0.122, P = 0.08) and the epsilon 2 allele frequency was higher (0.084 vs. 0.059, P = 0.05) in the older cohort. These observations are consistent with the hypothesis that there may be a selection against individuals with the epsilon 4 allele. However, future research is needed to confirm this observation and to compare survival in individuals by their epsilon allele.

Aged↗

Genetic variation in two bone-related proteins: is there an association with bone mineral density or skeletal size in postmenopausal women?

In an effort to determine if structural variation in proteins important in bone metabolism might influence bone mineral density (BMD) and thus be a determinant of susceptibility to osteoporosis in older women, the authors typed a group of 258 non-Black women (age 65-90) participating in the Study of Osteoporotic Fractures (SOF) for two polymorphic bone-related proteins, group specific component (Gc), also known as vitamin D-binding protein, and alpha 2HS glycoprotein (AHSG). These two proteins exhibit common structural variation in populations that can be detected by isoelectric focusing/immunoblotting of serum. An important function of Gc is the binding, solubilization, and transport of vitamin D sterols in the bloodstream while AHSG is a glycoprotein constituent of calcified cortical bone matrix. There are six common phenotypes of Gc and four of AHSG. Using Gc or AHSG phenotypes as categorical variables, statistical analyses were done to determine if bone mineral density of the proximal or distal radius or calcaneus differed by phenotype. Neither Gc nor AHSG phenotype demonstrated a statistically significant relationship with BMD at any site. Adjustments for age and degree of obesity did not substantively affect these results. Subsequent analyses to determine if phenotype of either of these proteins was associated with variables related to skeletal size showed an association of AHSG with height (P less than .02). This may indicate that AHSG phenotype is related to postmenopausal loss of height, or it may be a chance statistical finding.

Aged↗

The impact of the apolipoprotein E polymorphism on the lipoprotein profile in insulin-dependent diabetes: the Pittsburgh Epidemiology of Diabetes Complications Study IX.

The apolipoprotein (apo) E polymorphism has been related to differences in lipoprotein metabolism and lipid/lipoprotein concentrations in a number of studies. Whether these associations are seen in insulin-dependent diabetes mellitus (IDDM), which itself affects many of the same aspects of lipoprotein metabolism as does the apo E polymorphism, is unknown. The present study is an investigation into the influence of apo E phenotype on lipoprotein concentrations in a large group of IDDM patients (n = 433) participating in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study. The frequency of the three apo E alleles 2, 3, and 4 did not differ in this population from that reported in general white populations. Although the diabetic subjects show the same trends as seen in the general population, ie, apo E-2 is associated with lower and apo E-4 with higher low-density lipoprotein cholesterol (LDLc) compared with apo E3 (P less than .03), they also show relationships with glycemic control that influence the relative levels of lipid measures with respect to apo E phenotype. Results also raise the possibility that lipoprotein composition varies according to apo E phenotype in IDDM.

Adult↗

The relation between serum albumin levels and risk of coronary heart disease in the Multiple Risk Factor Intervention Trial.

The relation between serum albumin levels and subsequent incidence of myocardial infarction and coronary heart disease deaths was evaluated using stored serum from the Multiple Risk Factor Intervention Trial (MRFIT). There were 91 coronary heart disease deaths, 113 myocardial infarction patients, and 405 controls matched to cases within 5 years of age, treatment group, and clinic site. There was a highly significant inverse relation between serum albumin level and risk of coronary heart disease. Individuals with a baseline level of serum albumin greater than or equal to 4.7 g/dl had an odds ratio of 0.45 as compared with individuals with a baseline level of serum albumin less than 4.4 g/dl. The relation persisted after adjusting for other cardiovascular risk factors (blood pressure, smoking, and serum cholesterol). The association was stronger for coronary heart disease deaths than for surviving myocardial infarction patients, and for cigarette smokers as compared with cigarette nonsmokers. The deaths studied occurred in the time period at least 6 years after the sera had been obtained and up to 10.5 years of follow-up, and the myocardial infarctions studied occurred within the first 6.5 years of follow-up. There was no consistent relation between time and death due to coronary heart disease or myocardial infarction and albumin levels. Albumin levels are related to the acute phase reaction. Lower albumin levels may be a marker of persistent injury to arteries and progression of atherosclerosis and thrombosis. The consistent relation between albumin and coronary heart disease risk requires further evaluation.

Adult↗

A simplified method for screening the apolipoprotein E polymorphism.

A simple method for screening populations for the apolipoprotein E polymorphism which involves isoelectric focusing of delipidated samples on polyacrylamide gels of pH 4.5-5.8 followed by immunoblotting using a double-antibody technique is presented. The method is a synthesis of two previously published procedures and works well on samples that have been stored for as long as 15 years.

Adult↗

Alpha 2-HS glycoprotein phenotypes and quantitative hormone and bone measures in postmenopausal women.

It has been suggested that inherited traits play a role in the development of osteoporosis by providing a background for the modulation of gene expression. In this study, we examine the influence of the different alleles of alpha 2-HS glycoprotein (AHSG), a protein of the bone matrix, on quantitative estrogens, estrone and estradiol, and bone measures, bone area and density. Estrogens provide a protective effect against fractures in older women and were thus included in the analyses. Isoelectric focusing of AHSG from sera followed by immunoblotting was used to type 163 white postmenopausal women participating in a clinical trial of the effects of walking on bone loss. Plasma hormones were measured by a combination of extraction, column chromatography, and radioimmunoassay; bone measures on the dominant radius were determined with computerized tomography. Analysis of variance was done on estrogen and bone measures after controlling for the effects of age and body mass index. The two major alleles of AHSG result in three phenotypes, designated AHSG 1-1, AHSG 2-1, and AHSG 2-2. The AHSG 1-1 homozygote showed a decreased concentration of estradiol, the AHSG 2-2 homozygote showed an increased concentration, and the AHSG 2-1 heterozygote was intermediate (P = 0.001). Estrone demonstrated a similar pattern in residual analysis although it did not reach statistical significance.

Aged↗

Phenotypic effects of apolipoprotein structural variation on lipid profiles. I. APO H and quantitative lipid measures in the healthy women study.

Apolipoprotein H (APO H), also known as beta 2-glycoprotein I, has been identified as a protein component of the major lipoprotein density fractions in human plasma. Recently, genetically determined structural polymorphism in white and black populations has been documented for this apolipoprotein. There are three common alleles in whites and blacks and a fourth allele found mainly in blacks. Family data confirm the autosomal codominant pattern of inheritance for the APO H structural gene. Little is known about the function of APO H, but it has demonstrated both lipid and platelet involvement. In this study we investigate the effect of APO H phenotypes on quantitative lipid measures in a group of 443 white women being followed through menopause for changes in cardiovascular risk. At baseline all women were premenopausal. None of the APO H phenotypes showed a statistically significant effect on lipid measures in this population.

Adult↗

Phenotypic effects of apolipoprotein structural variation on lipid profiles: II. Apolipoprotein A-IV and quantitative lipid measures in the healthy women study.

Apolipoprotein A-IV (APO A-IV) is a major protein component of mesenteric lymph chylomicrons and very-low-density lipoproteins. It is found in plasma predominantly unassociated with major lipoprotein fractions and in high density lipoproteins. APO A-IV exhibits structural heterogeneity owing to two codominant alleles, APO A-IV*1 and APO A-IV*2, that occur in Caucasian and black populations. In vitro experimental evidence indicates that APO A-IV may be a cofactor for the lecithin:cholesterol acyltransferase enzyme, may be involved in reverse cholesterol transport, and may play an important role in the modulation of lipoprotein lipase activity. In this study we have investigated the effect of two APO A-IV phenotypes, APO A-IV 1-1 and APO A-IV 2-1, on quantitative lipid measures in a group of 453 white women being followed through menopause for changes in cardiovascular risk. At baseline all women were premenopausal. Of the nine lipid measures, triglycerides showed a marginally significant effect caused by phenotype. The APO A-IV 2-1 heterozygotes had lower average triglycerides than the 1-1 homozygotes (P = .053).

Adult↗

Phenotypic effects of apolipoprotein structural variation on lipid profiles. IV. Apolipoprotein polymorphisms in a small group of black women from the healthy women study.

Structural variation in apolipoprotein E has been shown to influence lipid and lipoprotein concentrations. The purpose of the present study was to investigate several apolipoproteins in a group of Black women from the Healthy Women Study (HWS). HWS is a community-based prospective study of 541 premenopausal women who are being followed through the menopause to determine the influence of biological, genetic, and psychosocial phenomenon on cardiovascular risk factors. Of the 541 subjects, 48 are Black. Serum from most of these 48 Black women was used to type seven apolipoproteins (APO A-I, APO A-II, APO A-IV, APO C-II, APO D, APO E, and APO H). Five of these apolipoproteins are polymorphic in Blacks (APO A-IV, APO C-II, APO D, APO E and APO H). Only two and three individuals, respectively, were heterozygous at the APO D and APO C-II loci. APO A-IV, E, and H exhibited more variation, however, only APO E phenotypes could be used for statistical analyses. Three common phenotypes, APO E 3-2, APO E 3-3, and APO E 4-3, were used in analysis of variance on four quantitative lipid variables. Despite small numbers, the effect of APO E phenotype was apparent. The APO E 3-2 phenotype showed reduced average levels of total cholesterol, apolipoprotein B (APO B) and low-density lipoprotein cholesterol (LDLc), and the APO E 4-3 phenotype showed increased levels (P less than or equal to .0497). The APO E3-3 homozygote was intermediate on all three. Because of small numbers in the cells of APO A-IV and APO H phenotypes, these were not analyzed with respect to quantitative lipids.

Adult↗