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.

No abstract

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.

A bnormal lipids and hypertension are both risk factors for coronary artery disease.1 " 9 Both aggregate in families 10 -13 with proven genetic transmission of certain lipid abnormalities.14 - 21 In an effort to find subsets of hypertensive individuals who may have specific genetic syndromes, we examined 131 individuals from 58 Utah sibships having two or more siblings with the onset of hypertension before age 60. The most striking concordant abnormalities in these sibships were high density lipoprotein (HDL) cholesterol levels below the age-and sexspecific 10th percentile 3.9 times more often than expected, and triglyceride and low density lipoprotein (LDL) cholesFrom the Departments of Internal Medicine, Pathology, and Human Genetics, University of Utah School of Medicine, Salt Lake City, Utah.This work was supported by Grants HL 24855 and HL 21088 from the National Heart, Lung, and Blood Institute.Address for reprints: Dr. Steven C. Hunt, Cardiovascular Genetics, 410 Chipeta Way, Room 161, Salt Lake City, UT 84108.Received July 15,1988; revision accepted Decembers, 1988. terol levels above the 90th percentile 3.0 and 1.9 times, respectively, more often than expected. 22Hypertension before age 60 occurring in two or more siblings who also have some lipid abnormality was descriptively referred to as "familial dyslipidemic hypertension" (FDH). It seems to occur in 15% or more of patients with hypertension and in at least one half of patients with early familial hypertension. 22In this report, apolipoproteins (apo) A-l and B, low density lipoprotein (LDL) subtractions, fasting plasma insulin levels, and detailed anthropometric measures were analyzed to more fully characterize patients with FDH and to investigate whether FDH might be a mixture of hypertensive patients with two or more dyslipidemic syndromes. MethodsDetails of patient selection and hypertension validation have been given previously. 22 The families were selected

Effects of endotoxin on the pulmonary hemodynamics of dogs and cats have been studied in intact animals, open chest animals with and without control of cardiac output by an extracorporeal venous reservoir—pump system, and in isolated perfused continuously weighed lungs. Pulmonary artery pressure increased without a rise in left atrial pressure in all preparations following the injection of endotoxin. Pulmonary artery wedge and small pulmonary vein pressures uniformly increased. Total pulmonary vascular, pulmonary arterial and pulmonary venous resistances were calculated in five perfused lungs. The absolute increase in pulmonary venous resistance was greater than in the arterial resistance in four of the five studies and was relatively greater in every instance. There was a consistent increase in lung weight associated with these hemodynamic changes. Analysis of the determinants of lung weight changes has provided evidence to support the conclusion that the pulmonary vascular response to endotoxin administration is characterized predominantly by constriction of pulmonary venules and/or small veins.

No abstract

Studies were made in 5 monkeys, 7 rabbits, and 33 cats of the effect of gram-negative endotoxin on aortic, pulmonary artery (PAP), and portal venous (PVP) pressures; and on changes in weight of a short segment of intestine. Studies of blood pooling were also made in 12 cats. The responses in these species were compared with those previously observed in the dog. Although variable degrees of hypotension developed at one time or another in all animals following injection of endotoxin, the early precipitous hypotension that characteristically occurs in the dog was observed only in the cat. However, in this species the dramatic fall in pressure could be ascribed to pulmonary vascular constriction and acute right ventricular hypertension and failure, and not to splanchnic pooling. PAP also became elevated in the monkey and the rabbit, but usually was of lesser magnitude and did not appear to explain the development of the relatively late hypotension that occurred in these species. The absence of significant increases in gut weight and the minor increments in PVP in all animals indicate that in none of these species is hepatic vein constriction and splanchnic pooling a significant mechanism in producing early shock as it is in the dog. Pathologic gross and microscopic studies in the monkey and gross examinations in the other species supported this conclusion.

Sodium-lithium countertransport was measured in July 1980-December 1982 in 841 persons from 48 Utah families prone to hypertension. Mean countertransport in 54 hypertensive adults (0.32 +/- 0.01 standard error of the mean) was significantly higher than in 511 normotensive adults (0.26 +/- 0.005, p less than 0.001) but with much overlap between the two groups. This difference was observed in both men and women. Only 26% of the subjects with essential hypertension had values above 0.40 (considered "high" by most other published reports). High values were seen in only 2% of 276 youths under age 18 years in contrast to 11% of the normotensive adults (p less than 0.001). Among normotensive adults, countertransport was higher in men than women, and correlated with weight, diastolic blood pressure, and age (all significant at p less than 0.01). None of these findings were seen in youths. In multivariate analyses, only weight continued to be significantly correlated with countertransport. The difference between countertransport levels in hypertensive vs. normotensive adults remained significant even after adjusting for weight. While confirming other reports of higher mean sodium-lithium countertransport in persons with essential hypertension, this study shows much overlap of values between groups and potential confounding effects of weight. When the authors compared their results with studies that show little overlap between hypertensive and normotensive adults, they found that the data for the normotensive adults in this study are similar to those reported in the other studies, but that the hypertensive adults include a larger percentage of individuals with low countertransport values.