Biomedical subjects

S C Hunt

Publications and source records attributed to S C Hunt.

At least 127 records · Page 7Linked to original sources

PubMed1988

Familial dyslipidemic hypertension. Evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension.

Population-based sibships with essential hypertension diagnosed before the age of 60 years are being screened in Utah to find two or more hypertensive siblings with the same biochemical abnormality as a clue to an inherited cause for their specific type of hypertension. Among 131 hypertensive subjects in 58 sibships, concordant abnormalities in fasting serum lipid concentrations were observed in two or more siblings in 48% of the sibships. After adjusting for effects of antihypertensive medications, abnormal values reported in only 10% of the Lipid Research Clinics data were observed in 30% of patients for serum triglycerides, 19% for serum low-density lipoprotein cholesterol, and 39% for high-density lipoprotein cholesterol. More than one lipid level was abnormal in almost all concordant sibships, suggesting an association between hypertension and a syndrome of mixed lipid abnormalities, probably familial combined hyperlipidemia (renamed "familial combined dyslipidemia" because of common low high-density lipoprotein cholesterol levels). We conclude that familial dyslipidemic hypertension may be a specific syndrome with lipid abnormalities more severe than blood pressure elevations.

Adult↗

PubMed1988

The inheritance of intraerythrocytic sodium level.

Intraerythrocytic sodium level (RBC Na) was measured on 1,800 normotensive members of 64 Utah pedigrees ascertained through hypertensive or normotensive probands, sibs with early stroke death, or brothers with early coronary disease. Likelihood analysis provided evidence that RBC Na was determined by four alleles at a single locus. Each allele was recessive to all alleles associated with a lower mean level. The four resultant distributions occurred in the frequencies: 0.8%, 89.3%, 9.7%, and 0.2% with corresponding means (mmol/1 RBC) of 4.32, 6.67, 9.06, and 12.19, respectively. The major locus explained 29.0% of the variance in RBC Na; polygenic inheritance explained another 54.6%. A higher frequency of the genotypes for high RBC Na in pedigrees when the proband was hypertensive than normotensive provided evidence that this major locus increases susceptibility to hypertension.

Adolescent↗

PubMed1988

Lifestyle and blood pressure levels in male twins in Utah.

Healthy male monozygotic (MZ) and dizygotic (DZ) twin pairs (MZ pairs = 77; DZ pairs = 88) were studied to assess the effect of dietary intake, physical activity, physical fitness, body mass index (BMI), sum of the triceps and subscapular skinfold measurements, alcohol and caffeine consumption, and smoking patterns on blood pressure. Data on physical activity, detailed dietary intake, medical history, and demographics were obtained from a questionnaire. A bicycle ergometer was used to estimate level of fitness; other medical information was ascertained from physical examination. After normalizing the study variables, intraclass correlations for BMI and the sum of the triceps and subscapular skinfold measurements were higher in MZ than in DZ twin pairs (BMI: MZ r = 0.76, DZ r = 0.48; skinfolds: MZ r = 0.73, DZ r = 0.28), as were VO2max(MZ r = 0.63, DZ r = 0.25) and post-bike heart rate (MZ r = 0.69, DZ r = 0.19). Both systolic (SBP) and diastolic blood pressure (DBP) had high heritability estimates (SBP = 0.60, and DBP = 0.66). Using factor analysis, four major lifestyle factors were identified and categorized as: 1) dietary intake; 2) a factor heavily weighted by cigarette smoking, alcohol and caffeine consumption; 3) fatness; 4) physical activity and physical fitness. Adjustment for these factors did not alter heritability estimates for either SBP or DBP.

Blood Pressure↗

PubMed1988

A digoxin-like factor associates with erythrocyte sodium concentration, sodium transport, and ouabain binding.

To investigate what effects a circulating digoxin-like factor (DLF) might have on sodium metabolism, we examined data collected on 1,327 individuals screened in the Cardiovascular Genetics Clinic at the University of Utah. This sample included 639 unmedicated adults, 582 youths under age 18, and 106 medicated hypertensive individuals, all on an unrestricted diet when attending clinic. No individuals look digitalis. A digoxin assay detected measurable levels of plasma DLF in 13.4% of the youths, 17.2% of the normotensive adults, and 25.5% of the hypertensive adults. In all three groups of individuals, those with a measurable DLF had a significantly lower erythrocyte ouabain sensitive sodium efflux rate constant (adjusted for age, sex and body mass) than those with no measurable DLF (p less than 0.01). Normotensive and hypertensive adults with measurable DLF also had an increased erythrocyte intracellular sodium level. Either the number of ouabain binding sites and/or the apparent affinity for ouabain were reduced for those with DLF levels in all three groups. There was a small nonsignificant increase in blood pressure for the normotensive adults and youths with a measurable DLF. We conclude that plasma DLF is associated with reduced ouabain sensitive sodium transport and increased intracellular sodium concentration, possibly due to changes in the number of or the competition for the Na+ - K+ ATPase sites.

Adult↗

PubMed1988

Health family trees: a tool for finding and helping young family members of coronary and cancer prone pedigrees in Texas and Utah.

We report on the feasibility and utility of a new approach for identifying the small percentage of families in the general population with strong familial predisposition to early coronary heart disease, strokes, and common familial cancers (breast, colon, lung), using the "Health Family Tree," a medical family history. A total of 24,332 "trees" were completed by parents and students in 37 high schools in 14 urban and rural communities in Texas and Utah during the years 1980-86. Completed "trees" were obtained from 68 per cent of all enrolled students. High-risk families, included 1,796 families with early coronary disease (7.5 per cent of all student families or 3.7 per cent of their parents' families), 870 stroke families (3.6 per cent), and 415 cancer prone families (1.7 per cent). Among these 3,081 high-risk families there were 8,245 family members already reported to have been diagnosed by a physician to have the familial disease of interest and 43,269 high risk unaffected siblings and offspring of these persons. The average cost per identified high-risk unaffected person was under $10. We conclude that the "Health Family Tree" is a feasible and cost-effective way to find high-risk families.

Adolescent↗

PubMed1988

Definition of genetic factors in hypertension: a search for major genes, polygenes, and homogeneous subtypes.

Essential hypertension is a heterogeneous group of disorders with different causes. This report reviews approaches taken and results found in current studies of the genetic and environmental determinants of essential hypertension. Recent observations from the University of Utah Cardiovascular Genetics Research Clinic and published data from other studies are cited. Several biochemical tests show strong associations with hypertension and substantial major gene and/or polygenic determination including: urinary kallikrein excretion, intracellular sodium concentration, sodium-lithium countertransport, plasma haptoglobin phenotypes, MN blood groups, and familial dyslipidemia.

Genes↗

PubMed1988

Genetic and epidemiological studies on electrolyte transport systems in hypertension.

In recent years several different tests of cations in human cells have been studied to detect and to define possible roles in the development of essential hypertension. The goal of this report is to summarize what has been learned in genetic and epidemiological studies of human populations. The seven tests reviewed in greatest detail include sodium-lithium countertransport, intraerythrocytic sodium, sodium (or lithium)-potassium cotransport, lithium leak, sodium-potassium ATPase pump, sodium pump sites (ouabain binding), and circulating sodium pump inhibitor ('digoxin-like factor' in some studies). Countertransport, intraerythrocytic sodium and cotransport consistently show different values in hypertensives compared to normotensives and even in normotensives with a positive family history of hypertension when compared to controls without a positive family history. Thorough genetic studies have been carried out only for sodium-lithium countertransport and intraerythrocytic sodium. Both of these tests are highly heritable with a combination of both polygenic and major gene effects. Cotransport, leak, and pump sites also seem to be quite significantly heritable whereas the ATPase pump activity and the circulating pump inhibitor seem to be largely determined by nongenetic factors. Some of the most dramatic changes in these tests have been observed during pregnancy. Significant increases are seen in countertransport, cotransport, ouabain binding sites, and digoxin-like factor. Oral contraceptives also seem to affect at least cotransport. Plasma triglyceride level and body weight are some of the strongest correlates of countertransport, cotransport, and lithium leak. Cotransport increases with higher dietary sodium intake and decreases with the use of the diuretic medication. In the current developmental stage these tests have several significant limitations. In most population studies there is a considerable overlap of test values between persons with high and normal blood pressure. There are substantial variations in the methods used by different laboratories for the same tests. They are expensive, complex and usually must be done on fresh cells. There are conflicts between the results of several different reported studies that could be due to the way in which their subjects were selected, the effects of medications or other uncontrolled variables, or even due to the differences in laboratory methodologies.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Transport↗

PubMed1987

Familial correlations from genes and shared environment for urine, plasma, and intraerythrocytic sodium.

Spouse-spouse, sib-sib, and parent-offspring correlations were calculated for urinary, plasma, and intracellular sodium levels on over 1,900 persons aged 3-86 years in 98 Utah kindreds. For 36 hours prior to their clinic visit, 31% of the sample was salt-loaded with salt tablets, while the rest followed their normal diet. For those on their normal diet, urine creatine-, age-, and sex-adjusted urinary sodium excretion from a timed 12-hour overnight sample showed similar and significant correlations between spouses (r = .29), sibs less than 20 years old (r = .38), and parent-offspring pairs for offspring less than 20 years old (r = .29). This contrasted with the lower correlations between sibs 20 years of age and older (r = .10) and parent-offspring pairs for offspring 20 years of age and older (r = .13), presumed to live in different households. Adult plasma sodium sib-sib (r = .13) and parent-offspring (r = .15) correlations were similar to the urinary sodium correlations, while the spouse-spouse (r = .48), the sib-sib (r = .64), and the parent-offspring (r = .63) correlations for those presumed to live in the same household nearly doubled. Intracellular sodium correlations for the adult sibs (r = .32) and offspring (r = .36) were over twice as large as for urinary or plasma sodium, although the spouse-spouse correlation (r = .37) remained large also.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1987

Recruitment of members of high-risk Utah pedigrees.

Cardiovascular Genetics Research Projects in Utah are designed to investigate genetic and environmental determinants of early coronary disease, stroke, and hypertension in population-based pedigrees. Early coronary disease is defined as the occurrence of documented coronary death or myocardial infarction before age 55. Detailed recruitment experience is reported for 2500 persons age 3-83 years in 98 high-risk pedigrees from three ascertainment groups: 1. Descendants of sibships with two or more stroke deaths before age 75. 2. Descendants of sibships with two or more coronary deaths before age 55. 3. First- and second-degree relatives of hypertensive and normotensive probands randomly selected from the Utah Hypertension Detection and Follow-up Program. A response rate of 94% of invited adults attending the first 4-hour clinic visit for detailed screening in 1980-1983 was achieved by multiple telephone, mail, and personal contacts and rescheduling of missed clinic appointments. For the same participants, a second screening cycle in 1983-1986 showed a 91% response of invited adults. Second visit response rates were examined within subgroups according to data collected at the first clinic visit. Below average response rates included 79% of persons with fewer than 12 years of education, 84% of current smokers, and 86% of divorced persons. Above average response rates included 93% of persons attending college and 95% of persons with total family income above $25,000. There were no differences in response according to sex or age. The average cost of recruitment was $59 per person and represented about 10% of the total budget for the High-Risk Pedigree Project.

Adolescent↗

PubMed1987

Blood pressure reactivity in adult male twins.

The purpose of the present investigation was to examine possible genetic contributions to cardiovascular reactivity by contrasting patterns of association in 82 monozygotic (MZ) and 88 dizygotic (DZ) adult male twin pairs (age range = 21 to 61 years, M = 35 years). Systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded during baseline and during a mental arithmetic task (i.e., serial subtraction). The task produced significant elevations in all three cardiovascular measures (i.e., 10 mmHg SBP, 8 mmHg DBP, and 6 bpm HR, respectively). Levels of SBP and DBP reactivity were significantly correlated in MZ pairs but not in DZ pairs. Statistical tests suggest a heritability estimate of about 50% that was marginally significantly for SBP and DBP changes during the task. There was no indication of a genetic influence on HR reactivity. Resting level and static task period measures of SBP, DBP, and HR demonstrated statistically significant heritability estimates of 60% to 80%.

Adult↗

PubMed1987

Genetic studies of cation tests and hypertension.

Several tests of cation concentration and transport are being studied among members of large Utah pedigrees as part of a study of the genetic and environmental determinants of essential hypertension. Corrected urinary sodium excretion and plasma sodium concentration correlated well in spouses and siblings (r = 0.21-0.54, p less than 0.001), suggesting the effects of shared family environment (e.g., sodium intake). Intraerythrocytic sodium concentration and sodium-lithium countertransport showed no significant correlation in spouses and very significant correlations between siblings and between parents and offspring (r = 0.34-0.58, p less than 0.001), suggesting mostly genetic determination. Using maximum likelihood tests of different genetic models, both sodium-lithium countertransport and intraerythrocytic sodium showed predominantly polygenic determination (H2 = 70%) and some possible major gene determinants (H2 = 18-25%) for a total heritability of 89 to 95% for these characteristics. These data suggest both genes and shared family environment contribute to the familiality of cation tests. They also illustrate the need and utility of quantitative methods for objective analysis of pedigree data.

Adult↗

PubMed1986

Testing for familial aggregation of a dichotomous trait.

Familial aggregation of a disease is usually tested using a chi square statistic on a sample of pairs of related individuals. Standard sampling designs often produce dependent observations (multiple pairs from the same family), possibly inflating the numerical value of the statistic over the value independent observations would produce. This article presents a derivation of the chi square statistic for familial aggregation, allowing for dependency because of the inclusion of the same and related persons in multiple pairs. For intraclass aggregation, the standard chi square statistic is appropriate. For interclass aggregation, an adjustment to the standard chi square statistic is needed; the adjustment depends on the disease frequency and the intraclass aggregation within each class.

Analysis of Variance↗

PubMed1986

A comparison of positive family history definitions for defining risk of future disease.

The relative risk of developing future coronary heart disease (CHD) or hypertension between positive and negative family history families is compared for different definitions of a positive family history when applied to life-table data for 94,292 persons. Having two or more first degree relatives with CHD identifies 8% of the population with relative risks of 3.3-5.9 for CHD before age 50. A quantitative family history score (FHS) compares the family's age and sex specific disease incidence to that expected in the general population and predicts future disease incidence in unaffected family members slightly better (relative risks = 3.4-6.9 for CHD before age 50). Using only one affected relative, even if affected at an early age (less than 55 years old) does not discriminate low and high risk families as well (relative risks = 1.4-3.9 for CHD before age 50). Similar results were obtained for family history of hypertension. There is an increase in future disease incidence for all ages with increasing FHS values (p less than 0.0001), which can be used as a continuous or categorical variable in analysis where family history is associated with a particular variable under study. These results provide a rational basis for choosing and applying specific definitions of a positive family history of coronary disease or hypertension in clinical, epidemiologic and genetic studies.

Adult↗

PubMed1986

Associations of three erythrocyte cation transport systems with plasma lipids in Utah subjects.

To investigate the pathophysiology of essential hypertension, detailed biochemical and clinical variables were collected and analyzed for 2091 Utah subjects aged 3 to 83 years. Three different measurements of erythrocyte cation transport were obtained: Na+-Li+ countertransport, Li+-K+ cotransport, and furosemide-insensitive Li+ efflux into MgCl2. Total plasma cholesterol, triglycerides, and high density lipoprotein cholesterol levels were obtained from fasting subjects. Levels of high density lipoprotein subfractions 2 and 3 were also obtained from 350 subjects. Standardized data collection also included blood pressure, height, weight, and presence or absence of a diagnosis or treatment of essential hypertension. In univariate analyses of all 1420 adults, each of the three transport systems showed the same significant correlations with triglyceride levels (r = 0.33-0.35, p less than 0.0001), high density lipoprotein concentration (r = -0.19 to -0.21, p less than 0.001), and weight (r = 0.22-0.28, p less than 0.0001). In multivariate regression analyses, values for each transport system were significantly higher in hypertensive subjects; values for triglycerides, high density lipoprotein, and usually, the high density lipoprotein subfractions continued to have strong significant independent associations with all three transport systems; and weight remained significantly related only to Na+-Li+ countertransport. In separate logistic regressions, plasma triglyceride levels (positively, p less than 0.001) and high density lipoprotein subfraction 3 levels (inversely, p less than 0.03) were associated with hypertension itself. In multivariate analyses among 671 children, high density lipoprotein and high density lipoprotein subfraction 3 levels showed significant (p less than 0.05) inverse correlations with Na+-Li+ countertransport and furosemide-insensitive Li+ efflux.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1986

Coronary disease and risk factors in close relatives of Utah women with early coronary death.

Familial aggregation of coronary heart disease (CHD) and specific major risk factors were determined among 639 first-degree relatives of 73 women with confirmed coronary death before age 55. They were compared with 1,151 persons in 141 control families. Of women with early coronary death, 62% had first-degree relatives with early coronary disease compared with 12% of affected control family members. In the proband families, coronary incidence rates were 2.7 times the control population rates for women (P<.001) and 1.6 times the control population rates for men (P<.05). An excess incidence of coronary disease was observed for ages 45 to 74 in both men and women.Smoking, hypertension, diagnosed hyperlipidemia and diabetes were all two to three times more common in the female probands with early coronary death than in healthy controls. Hypertension was more common in all proband relatives (both sexes with and without coronary disease). Smoking was more common among female relatives of probands when compared with the controls. These data suggest that early coronary disease in women is often familial and associated with smoking and hypertension. The familial aggregation seems to be stronger in female relatives of female probands with early CHD than in male relatives. Genetic factors or shared family life-style or both likely account for these observations.

Adult↗

PubMed1985

Heritability of cardiac size: an echocardiographic and electrocardiographic study of monozygotic and dizygotic twins.

Because of the uncertainty as to the extent to which cardiac size is determined by exercise training vs genetic endowment, this study investigated familial (genetic plus common family environment) vs nonfamilial influences on cardiac size. College-age monozygotic twins (group 1, 31 sets), dizygotic twins (group 2, 10 sets), siblings of like sex (group 3, six sets), and nonrelated subjects (group 4, 15 sets) underwent echocardiographic and electrocardiographic tests, measurement of maximum oxygen uptake (VO2max), and evaluation of pulmonary and body composition; mean intrapair differences of the four groups were compared. Mean intrapair differences in cardiac size varied as much for subjects in group 1 as for those in groups 2 and 3. However, subjects in groups 1, 2, and 3 had less variation (p less than .05) than those in group 4. After the initial testing, 14 pairs of monozygotic twins, five sets of dizygotic twins, and six sets of siblings underwent 14 weeks of exercise training (both members participated) and all tests were repeated. After exercise training, subjects in group 1 still had as much intrapair variability in cardiac size as those in groups 2 and 3. The data suggest cultural familial influences are more important in determining cardiac size than nonfamilial influences or even genetic influences alone.

Adult↗

PubMed1985

Effects of age, sex, and body habitus on QRS and ST-T potential maps of 1100 normal subjects.

Body surface potential maps provide more detailed regional cardiac electrophysiologic information than the standard electrocardiogram. We performed a large-scale study of a normal population to form a comparison base for evaluation of the clinical utility of this technique. We analyzed body surface maps from 1113 normal subjects from 10 to 80 years old to detail map features as a function of age, sex, and body habitus. Maps were analyzed by visual inspection and by a spatial and temporal data reduction technique that allows statistical comparison of map features. On average, both QRS and ST-T potentials decreased with increasing age. Potential pattern distributions remained constant from 10 to 40 years. Beyond age 40, larger numbers of maps from normal subjects showed depolarization patterns consistent with delayed activation of the left anterior fasicle, despite normal 12-lead electrocardiograms. Only minor QRS potential amplitude and distribution differences were noted when male and female subjects were compared within groups of similar age and body habitus. Male subjects consistently showed greater average T potential amplitudes. Slender body habitus was associated with a more horizontal "zero" potential line. In female subjects over age 40 there were more extensive low-level negative potentials recorded over the precordium during the ST segment than in men. This study defines the range of normal body surface potential maps in a large clinically normal population and provides a basis for qualitative and statistical comparison with map features of patients with disease.

Adolescent↗

PubMed1985

The relationship of lithium-potassium cotransport and the passive lithium leak to hypertension in Utah subjects.

Rate constants for lithium-potassium cotransport (kLPC) and the lithium efflux into MgCl2 with furosemide (passive lithium leak) along with sodium-lithium countertransport (SLC) were measured in erythrocytes from 351 normotensive adults age 18 and over, 220 youth under age 18 and in 27 hypertensives. The kLPC was significantly higher in the hypertensives than the adult normotensives with means and standard deviations of 13.9 +/- 9.2 vs. 8.7 +/- 5.9 10(-3)/hr (p less than 0.01). Adjusting for the significant weight (p = 0.014) and sex (p = 0.066, normotensive males higher than females) associations with kLPC in an analysis of covariance, increased the significant difference between the hypertensives and normotensives (p = 0.0004). The passive lithium leak rate constant was also higher in hypertensives than normotensives (20.2 +/- 7.6 vs. 15.5 +/- 5.3 10(-3)/hr, p less than 0.01). Weight (p=0.0003), but not sex, was related to the leak but did not account for the difference between hypertensives and normotensives (p = 0.0009). Mean blood pressure was positively associated with the lithium leak but not the kLPC or SLC values in a multivariate regression.

Adolescent↗