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Studies of the pathobiologic consequences of high blood pressure in childhood, as well as those following blood pressure levels into young adulthood, indicate that early intervention in the natural history of essential hypertension is warranted. In an exploratory study of the concept, 95 children out of 1604 (aged 8 to 18 years), who persistently scored higher than the 90th percentile for blood pressure over a 4-month period, considering the race, sex, and height of the children, were studied. Five series of replicate measurements with 30 total observations were obtained. Children with evidence of secondary hypertension were excluded. The study children were randomly divided into treatment (n = 48) and high-comparison (n = 47) groups. Treatment consisted of low-dose combined drug therapy (propranolol and chlorthalidone) with an educational program directed towards hypertension and dietary and exercise modification. Monthly follow-up was continued for 30 months. Significant systolic (-3.59 mm Hg) and diastolic (-1.73 mm Hg) changes were noted up to 30 months (p less than 0.05) with minimal side effects. Furthermore, analyses suggested that the blood pressure change, at least in the first month, was mostly attributable to drug therapy. Moreover, the mechanism of blood pressure change appeared to be race-specific, with whites having pulse rate changes and blacks having significant weight changes, which were associated with blood pressure change. This trial shows further research is warranted to determine optimum approaches for early treatment of essential hypertension to prevent future hypertensive disease.

This paper presents a computer program for estimating transition probabilities between states in a stochastic model for an illness-death process which incorporates time-dependent covariates. Parameters are estimated by the method of maximum likelihood using the Newton-Raphson iterative procedure. The program provides the standard normal deviate statistics as well as the value of the maximum of the likelihood function which can be used on repeated applications to test hypotheses concerning coefficients associated with covariates. Although this program is demonstrated by using a model with two 'illness' states and two 'death' states, it is also suitable for analyzing data with models involving fewer states, such as the analysis of survival time with covariates assuming a proportional hazard model.

The relationship between increase in height and changes in levels of serum lipids and lipoproteins in adolescent males were examined through a biracial sample of 397 individuals, ages 8-12 years, who were reexamined 5 years after the initial screening. Significant negative correlations were observed between height change and changes in levels of serum total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) after controlling for age, initial cholesterol level, height, weight, Tanner stage, and changes in Tanner stage and weight. There was significant inverse association between height change and change in the level of HDL-C in black males, while there was significant inverse association between height change and change in the level of LDL-C in white males. These associations were independent of age, sexual maturation, and weight. Thus, changes in levels of serum lipids and lipoproteins in males during adolescence are partly associated with the growth spurt in height.

The influence of partial replacement of starch by sucrose on dietary cholesterol-induced serum lipoprotein responses was examined in 10 male cynomolgus monkeys (Macaca fascicularis). In a crossover design two semipurified diets provided either starch or starch and sucrose (1:1) as carbohydrate (49% by calories) with 0.4 mg cholesterol/kcal. Six weeks of starch + sucrose diet resulted in significantly reduced levels (mean +/- SE, mg/dl) of serum total cholesterol (264 +/- 9 vs 244 +/- 8) and apo B (110 +/- 6 vs 96 +/- 6) when compared with starch diet, whereas serum triglyceride levels remained similar between diets. With respect to changes in lipids and apolipoproteins (A-I or B) of very low (VLDL), low (LDL), intermediate (IDL), and high (HDL) density lipoproteins, starch + sucrose diet significantly increased VLDL-apo B (+34%), and decreased LDL-cholesterol (-18%) and LDL-apo B (-15%) as compared with starch alone; no differences were found in IDL and HDL between diets. The relative proportion of starch to sucrose in a diet appears to influence the magnitude of response of lipoproteins to dietary cholesterol.

Levels of high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apo A-I) may provide independent information concerning cardiovascular disease risk. Therefore, possible correlates of HDL-C and apo A-I levels were studied in 2827 5- to 17-year-olds from a biracial community, and the possible differences in these relationships were assessed. The characteristics examined included sexual maturation, plasma levels of glucose and insulin, obesity, reported oral contraceptive use, alcohol consumption, and cigarette smoking. In addition, levels of endogenous sex hormones (testosterone, estrogen, and progesterone) were measured in 515 adolescent males. HDL-C and apo A-I levels showed different (p less than 0.001) relationships with both obesity and oral contraceptive use. Increases in subscapular skinfold thickness corresponded more closely to decreases in HDL-C, rather than apo A-I, levels; the relationship with HDL-C was probably mediated by triglyceride levels. In contrast, oral contraceptive use was associated with increases in mean levels of apo A-I (8 mg/dl, whites; 16 mg/dl, blacks), but with only very small changes in HDL-C. (High-estrogen oral contraceptives were related most closely to increases in levels of both HDL-C and apo A-I). Levels of both HDL-C and apo A-I were similarly related to sexual maturation and levels of testosterone (negatively in boys), cigarette smoking (negatively), and alcohol intake (positively). Since levels of apo A-I independently of HDL-C may indicate an increased risk of cardiovascular disease, characteristics related to apo A-I levels should be further examined.

A general model for the illness-death stochastic process with covariates has been developed for the analysis of survival data. This model incorporates important baseline and time-dependent covariates in order to make an appropriate adjustment for the transition and survival probabilities. The follow-up period is subdivided into small intervals and a constant hazard is assumed for each interval. An approximation formula is derived to estimate the transition parameters when the exact transition time is unknown. The method developed is illustrated with data from a study on the prevention of the recurrence of a myocardial infarction and subsequent mortality, the Beta-Blocker Heart Attack Trial (BHAT). This method provides an analytical approach with which the effectiveness of the treatment can be compared between the placebo and propranolol treatment groups with respect to fatal and nonfatal events simultaneously.