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S C Hunt

Publications and source records attributed to S C Hunt.

At least 109 records · Page 6Linked to original sources
PubMed1991

Are there interactions and relations between genetic and environmental factors predisposing to high blood pressure?

An overview of published observations suggests that both genetic predisposition and environment work together to produce hypertension in most persons. High blood pressure before age 55 occurs 3.8 times more often among persons with a strong positive family history of high blood pressure. Much of the total variability in blood pressure in modern populations seems attributable to genetic factors. Estimates of the proportion of the variance attributable to all genetic factors (heritability [H2]) vary from 25% in pedigree studies to 65% in twin studies for sitting diastolic blood pressure. Several biochemical traits associated with high blood pressure are highly genetic (H2, 78-84%) and may help elucidate the pathophysiology of high blood pressure. While pertinent environmental factors such as salt intake, alcohol use, and amount of exercise also correlate significantly among relatives, only 7% of the total variance of diastolic blood pressure seems attributable to all shared environmental factors in family households. Thus most familial aggregation of high blood pressure appears to be due to genes rather than shared family environment. Practical benefit may result from identifying familial predisposition in multiple siblings with high blood pressure before age 55 and lipid abnormalities (labeled "familial dyslipidemic hypertension"). About 12% of high blood pressure patients have familial dyslipidemic hypertension and also have high risk of early coronary heart disease. Hyperinsulinemia and central obesity as well as high triglycerides and low high density lipoprotein cholesterol are prominent features of familial dyslipidemic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1991

Blood pressure and blood lipids in relation to body size in hypertensive and normotensive adults.

The relationship between relative fatness and subcutaneous fat distribution was examined in a sample of 124 hypertensive and 402 normotensive individuals. We explored the interactions between relative weight, adiposity, and preferred sites of fat accumulation in relation to disease risk, as measured by hypertensive status, blood pressure levels, and blood lipid concentrations (total cholesterol, triglyceride and HDL cholesterol). The participants were classified into quintiles of age-adjusted weight, body mass index (BMI), waist-to-hip ratio (WHR), subscapular skinfold, and a relative fat pattern index (RFPI). The mean values for blood pressure and blood lipids at each quintile of the anthropometric indices were compared by sex and hypertensive status. In the normotensive men and women, blood pressure and blood lipids levels were strongly associated with all indices of body size and adiposity. However, among hypertensive men and women the associations between blood pressure and blood lipids with anthropometric indices were significantly different across quintiles of distribution for the different indices. Our study suggests that in medicated hypertensives blood pressure and blood lipid levels can be present in the very lean and unrelated to body size, or they can be strongly associated with ponderosity and fat distribution. The difference in blood pressure and blood lipid levels from the second to the third quintiles on any one of the anthropometric indices considered is greater that the difference between the top quintiles.

Adipose Tissue↗
PubMed1990

Changes in sodium-lithium countertransport correlate with changes in triglyceride levels and body mass index over 2 1/2 years of follow-up in Utah.

We have previously reported from a cross-sectional study that plasma total cholesterol, triglycerides, and HDL-C were significantly and independently correlated with Na(+)-Li+ countertransport. These original participants were rescreened 2 1/2 years later (range of 20-58 months), with lipid, blood pressure, and Na(+)-Li+ countertransport measurements from both visits on 906 normotensive adults. The correlation found between age- and sex-adjusted triglyceride levels and Na(+)-Li+ countertransport at visit 1 (r = 0.34, p less than 0.0001) was reconfirmed at visit 2 (r = 0.32, p less than 0.0001). The Na(+)-Li+ countertransport correlations with HDL-C (r = -0.11, p less than 0.01) and body mass index (r = 0.24, p less than 0.0001) also remained at visit 2. After 30 months, there were significant increases of triglyceride, body mass index, blood pressure, and Na(+)-Li+ countertransport levels, and significant decreases of HDL-C and total cholesterol levels, after adjusting the changes in these variables between visit 2 and visit 1 for age, sex, time between the two visits, and the visit 1 level of the variable. Increases in triglycerides, cholesterol, and body mass index were significantly correlated with increases in Na(+)-Li+ countertransport (r = 0.23, r = 0.19, and r = 0.21, respectively). The correlations of the lipid and lipoprotein changes with Na(+)-Li+ countertransport changes were independent of body mass index and blood pressure changes. We conclude that increasing plasma triglyceride levels and body mass index are associated with increasing Na(+)-Li+ countertransport levels in both cross-sectional and longitudinal data.

Adolescent↗
PubMed1990

Interactions between diabetes and family history of coronary heart disease and other risk factors for coronary heart disease among adults with diabetes in Utah.

We used a unique data base containing medical family history information from representative Utah families to investigate interactions between diabetes and family history of coronary heart disease and other risk factors for coronary heart disease. We compared nonrelated individuals reported to have had diabetes mellitus diagnosed over the age of 19 (948) with 2150 nondiabetic individuals. Among both men and women, diabetes and family history of early coronary heart disease magnified the risk for coronary heart disease, so that in diabetic individuals with a positive family history of coronary heart disease, about 74% of the coronary heart disease could be attributed to interaction. Relative to nondiabetics without a family history of early coronary heart disease, nondiabetics with family history had a relative risk of 4.5 (2.3-8.7), diabetics without a family history had a relative risk of 2.8 (1.6-4.9), and diabetics with a family history had a relative risk of 21.3 (9.1-50.0). Smoking also interacted with diabetes; among smoking diabetics, 47% of early heart disease may be attributable to interaction between smoking and diabetes. Smoking entailed the highest risk for diabetic women. Hypertension and diabetes appeared to act additively, with little interaction. Among women, family history of diabetes was a risk factor for coronary heart disease with a relative risk of 2.5 (1.0-6.4), whereas for men the relative risk was estimated to be 0.4 (0.2-1.1).

Adult↗
PubMed1990

Genetics of hypertension: what we know and don't know.

Human arterial hypertension is likely a multifactorial trait resulting from multiple measurable monogenes, blended polygenes, shared family environment, and individual environment. Familial aggregation of hypertension and familial correlation of blood pressure appears to be more due to genes than to shared family environment. Total genetic heritability of 80% with some recessive major gene effects have been found for several traits associated with hypertension including urinary kallikrein excretion, intraerythrocytic sodium, and sodium-lithium countertransport. Other interesting factors regarding hypertension genetics include: non-modulation of the renin angiotensin system, intralymphocytic sodium, ionized calcium, and several genetic markers such as haptoglobin, HLA, and MNS blood type. Probably the most clinically useful information regarding the genetics of hypertension is evolving in several studies reporting a strong association of hypertension with dyslipidemia, diabetes, and obesity.

Environment↗
PubMed1990

Multigenic human hypertension: evidence for subtypes and hope for haplotypes.

Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension.

Blood Pressure↗
PubMed1990

Concordant dyslipidemia, hypertension and early coronary disease in Utah families.

A detailed family history questionnaire collected from families of 35,000 sixteen year old high school students in Utah was used to identify population-bases sibships with two or more living adults affected with hypertension under age 60 or coronary artery disease before age 55. Detailed clinical and biochemical evaluations performed during a four-hour visit to a research clinic provided data to test for concordant abnormalities in siblings with either early hypertension or early coronary heart disease. A new syndrome, familial dyslipidemic hypertension (FDH), was found in 48% of the hypertensive sibships. In these FDH subjects, 68% had HDL-cholesterol below the 10th percentile, 49% had triglyceride level above the 90th percentile, and 27% had LDL levels above the 90th percentile. When compared to normolipidemic hypertensive subjects, persons with FDH had significantly elevated fasting plasma insulin levels, increased subscapular skinfold thickness, increased knee width and wrist circumference, and increased levels of VLDL cholesterol and apolipoprotein B. In coronary sibships, concordant abnormalities for lipids were consistent with familial combined hyperlipidemia in 30-40% of sibships, FDH in 15-45% of sibships, and low HDL-C (with normal cholesterol) in 10%. Concordant normal lipids were found in only 15% of sibships. These data suggest that inherited metabolic abnormalities likely explain some co-aggregation of hyperinsulinemia, obesity, hypertension, and early coronary heart disease. Current knowledge also suggests these metabolic abnormalities could be treated or prevented with appropriate modification in lifestyle factors such as diet and exercise as well as through the use of prescription medications.

Adolescent↗
PubMed1990

Population-based frequency of dyslipidemia syndromes in coronary-prone families in Utah.

The frequency of familial dyslipidemia syndromes was determined from blood tests in 33 objectively ascertained families with early coronary heart disease (CHD) (two or more siblings with CHD by the age of 55 years). Three fourths of persons with early CHD in these families had 90th percentile lipid abnormalities (cholesterol level at or above the 90th percentile, triglyceride level at or above the 90th percentile, and/or high-density lipoprotein cholesterol (HDL-C) level at or less than the 10th percentile). The HDL-C and triglyceride abnormalities were twice as common as low-density lipoprotein-cholesterol abnormalities. The most common syndromes found were familial combined hyperlipidemia (36% to 48% of families with CHD), familial dyslipidemic hypertension (21% to 54% of families with CHD), and isolated low levels of HDL-C (15%), with overlapping familial dyslipidemic hypertension with familial combined hyperlipidemia and low-level HDL-C. Well-defined monogenic syndromes were uncommon: familial hypercholesterolemia being 3% and familial type III hyperlipidemia, 3%. Another 15% of families with CHD had no lipid abnormalities at the 90th percentile. Physicians should learn to recognize and treat these common familial syndromes before the onset of CHD by evaluating family history and all three standard blood lipid determinations. Failure to recognize and treat them leaves affected family members at high risk of premature CHD.

Cholesterol, HDL↗
PubMed1989

Cross-spouse correlates of blood pressure in hypertension-prone families in Utah.

This study used a subsample of 543 married couples from a large group of families in Utah, who were originally studied to assess the genetic and environmental determinants of hypertension. Excluding individuals on medication and controlling for the major risk factors for hypertension, evidence was obtained for cross-spouse blood pressure associations equal in magnitude to self-psychosocial and demographic measures. Observed spouse-spouse similarity for blood pressures remained significant after adjustment for shared psychological factors. It is speculated that different aspects of each spouse's nonmarital environments (e.g. work, social support) have differential impacts on the marital environment and on physiologic indicators of health.

Adult↗
PubMed1989

Validity of cigarette smoking habits in three epidemiologic studies in Utah.

Utah has lower incidence and mortality for many smoking-related forms of cancer and heart disease. It is an important epidemiologic question to assess whether the population attributable risk associated with cigarette smoking in this low-risk population is biased from under-reporting because of societal pressures not to smoke. To answer this question, we compared reported cigarette use to serum cotinine values in three different epidemiologic study designs. Included in these analyses were data from men interviewed for a cross-sectional study of dietary intake and hormones, women interviewed as a part of a case-control study of cervical cancer, and men interviewed in conjunction with a cardiovascular disease and hypertension family follow-up study. Cross-sectional study participants reported accurate cigarette usage 93.8% of the time; case-control participants accurately reported cigarette use 98.5% of the time; participants interviewed in the family cohort study correctly reported usage 82.8% of the time. Most inaccurate reporting of smoking was by exsmokers being followed for a disease known to be linked to smoking. The low attributable risk of smoking related to diseases in Utah is not from underreporting of cigarette smoking, and makes Utah an ideal population to examine other risk factors for diseases where smoking increases risk.

Adolescent↗
PubMed1989

Predictive value of a short dietary questionnaire for changes in serum lipids in high-risk Utah families.

Dietary questionnaires and serum cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol determinations were completed for 1239 subjects aged greater than or equal to 20 at each of two separate screenings. The mean time between screenings was 2.5 y. After correcting for potential confounding variables, reduction of a measure of dietary cholesterol and saturated fatty acids assessed by two simple questions was a significant independent predictor of reduction in total cholesterol in serum (p less than 0.005). Initial body mass index (BMI) and change in BMI were highly significant predictors of initial values and changes in total cholesterol, triglycerides, and HDL cholesterol in serum. Reduction of dietary saturated fatty acid and cholesterol was significantly correlated with initial serum cholesterol levels, which suggest that serum cholesterol screening may be an important motivating factor for dietary change. Important public health and research implications of these findings are discussed.

Adult↗
PubMed1989

Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins.

The relative contributions of genes and shared environment to cardiovascular risk factors were studied in twins and pedigrees in 1983-1985. Sitting, standing, isometric hand grip, bicycling, and mentally stressed (serial subtraction) blood pressures were obtained from 146 male monozygous twins, 162 male dizygous twins, and 1,102 healthy adults in 67 Utah pedigrees. Fasting total plasma cholesterol, triglycerides, high density lipoprotein cholesterol (HDL), and body mass index were also measured. Heritability was estimated before and after adjusting for 12 environmental variables (measures of socioeconomic status; personality types; exercise levels; use of tobacco, alcohol, coffee, etc.) by using age-adjusted twin intraclass correlations. These heritabilities were compared with those obtained from a variance components analysis of the pedigree data separating genetic and common household effects. Sitting and standing blood pressure heritability estimates were much higher from twin than from pedigree data (39-63% in twins vs. 16-22% in pedigrees), as were those for cholesterol and triglycerides (65 and 75% from twins vs. 42 and 37% from pedigrees) and body mass index (51 vs. 21%). Estimates were similar for heritability of HDL cholesterol (51 vs. 45%). Most of the stressed blood pressure heritabilities were similar to sitting blood pressure estimates. No common household effect (except for adjusted HDL cholesterol (24%), p less than 0.01) was statistically significant for the lipids, blood pressures, or body mass index. Environmental variables correlated much better in monozygous twins and spouses than in dizygous twins, brothers, or sisters. Spouse correlations for lipids, blood pressures, and body mass index were low, with a maximum of 0.12 (p less than 0.05) for HDL cholesterol. We conclude that genes contribute much more than shared environment to the well-recognized familial correlation of blood pressures, lipids, and body mass index.

Adult↗
PubMed1989

Current knowledge regarding the genetics of human hypertension.

Observations over 11 years from the University of Utah Cardiovascular Genetics Research Clinic and published data from other studies are reviewed to illustrate research approaches, developing results and prospects for future studies. Strong associations with hypertension have been found for several biochemical tests that show substantial genetic determination. Suggestions of recessive major gene effects and significant polygenic background determinations have been found for several variables, including urinary kallikrein excretion, intracellular sodium concentration, sodium-lithium countertransport and sodium-potassium cotransport. Each of these variables is related in some way to sodium or potassium metabolism, or both, and may help to improve the understanding of a possibly inherited susceptibility to hypertension that is related to dietary electrolyte intake. A second major group of factors involving familial predisposition to hypertension include lipid abnormalities (increased very-low- and low-density lipoprotein cholesterol and decreased high-density lipoprotein cholesterol); increased fasting insulin levels or insulin resistance, or both; obesity (especially central or upper body obesity); and multiple environmental factors influencing these metabolic systems, including dietary fat, carbohydrate and calorie intake; physical exercise; and certain antihypertensive medications that adversely affect lipid metabolism and glucose tolerance. Some studies even suggest a possible link between these two large groups of factors (electrolyte metabolism and lipid-insulin metabolism). Hypertriglyceridaemia and hyperinsulinaemia are both significantly correlated with increased levels of several cation-flux tests. It is recommended that studies of human hypertension apply these biochemical profiles to study sibships with two or more hypertensive siblings as a cost-effective initial approach.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus↗
PubMed1989

A gene for high urinary kallikrein may protect against hypertension in Utah kindreds.

The inheritance of 12-hour overnight total urinary kallikrein excretion and its association with family history of essential hypertension were studied in 405 normotensive adults and 391 youths in 57 Utah pedigrees. Total urinary kallikrein excretion was highly familial with 51% of the total variance attributable to a dominant allele for high total urinary kallikrein excretion and 27% attributable to the combined effects of polygenes and shared family environment. An estimated 28% of the population has one or two copies of the dominant allele for high total urinary kallikrein excretion (2.3 SD units higher than the low homozygotes). About 83% of the population could be assigned to one of the two genotypic populations. Individuals with the high total urinary kallikrein excretion genotype were significantly less likely to have one or two hypertensive parents (relative odds = 0.56, p = 0.042). We conclude that a dominant allele expressed as high total urinary kallikrein excretion may be associated with decreased risk of essential hypertension. Further studies should be performed to confirm this finding and to test for interactions between this apparently protective gene and other genetic and environmental determinants of essential hypertension.

Adolescent↗
PubMed1989

Heritability estimates of pulmonary function.

To test the hypothesis that there is genetic control of pulmonary function parameters independent of that influencing height, we evaluated 74 pairs of asymptomatic, nonsmoking twins. FVC, FEV1, FEF25-75%, TLCsb, RVsb, Dsb, and D/VA were measured. Pulmonary function indices were adjusted for height using simple linear regression. Mean intrapair differences (unadjusted and adjusted for height) were compared using t tests of independent samples. Within pair, Holzinger's, and Falconer's heritability estimates were calculated using height-adjusted residual values. When total variances of a function parameter were statistically different between monozygotes and dizygotes, the among component heritability estimate was calculated and used as the best indicator of heritability. Following adjustment for height, no measure of pulmonary function which satisfied the requirements of the analysis was found to be significantly heritable.

Adult↗
PubMed1988

Family history as an independent risk factor for incident coronary artery disease in a high-risk cohort in Utah.

To test independence of family history of coronary artery disease (CAD) as a risk factor for the development of new clinical CAD, data collected at 2 clinic visits on 1,196 men and women, ages greater than 20 years, were analyzed using Cox proportional hazard method. During a mean follow-up of 2.5 years, 16 new CAD cases were observed. After adjustment for age, sex, total cholesterol, high density lipoprotein cholesterol, hypertension, diabetes, cigarette smoking and body mass index, family history remained a highly significant predictor of future CAD (p = 0.0017). Only age was a more significant covariate (p = 0.0001) than family history. Sex (p = 0.00074) and serum total cholesterol (p = 0.015) also contributed significantly to CAD incidence while high density lipoprotein cholesterol, hypertension, diabetes, body mass index and several interaction terms did not improve the prediction in this population. These results provide evidence for the existence of other heritable risk factors which appear to contribute strongly to the occurrence of early CAD in many high-risk families.

Adult↗