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.

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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.