Plasma lathosterol as a screening test for bile acid malabsorption due to ileal resection: correlation with 75SeHCAT test and faecal bile acid excretion.

1. Plasma lathosterol concentration, known to reflect cholesterol and bile acid synthesis, was evaluated as a screening test for bile acid malabsorption, comparing it with faecal bile acid measurements, SeHCAT test and Schilling test in 22 subjects of whom six were healthy controls and 16 had Crohn's disease with ileal resections of varying length. 2.

[Lowered cholesterol beneficial for vascular endothelium].

Although it is logical that coronary artery plaque is reduced, or at least the stenotic process is inhibited, when blood lipid concentrations are normalised, this does not suffice to explain the beneficial outcome of treatment in cases of hypercholesterolaemia. Several recent studies have yielded manifest evidence of the effects of cholesterol on endothelial function. Via chemical mechanisms the endothelium exerts significant regulatory effects-e g, on vascular contractility, and intervention in this process offers several possibilities of treating and preventing coronary artery disease.

Mortality in participants and non-participants of a multifactorial prevention study of cardiovascular diseases: a 28 year follow up of the Helsinki Businessmen Study.

Objective: To investigate pretrial risk factors and long term mortality (1964-1992) in participants and non-participants of a multifactorial primary prevention trial.

Design: A prospective study among 3313 initially healthy businessmen. During the 1960s (1964 onwards), 3490 healthy male business executives born between 1919 and 1934 participated in voluntary health checks at the Institute of Occupational Health in Helsinki.

Factors associated with calcific aortic valve degeneration in the elderly.

This study aimed at identifying factors influencing aortic valve calcification in old age. Echocardiographic and Doppler characteristics of the aortic valve were compared with possible clinical and biochemical predictors in 501 people aged 75-86 years and in 76 aged 55-71. Slight calcification was seen in 222 people (40%) and severe calcification in 72 (13%); 21 people had moderate or severe aortic stenosis.

Comparison of effects on sleep of lovastatin and pravastatin in hypercholesterolemia.

The effects on sleep of lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor administered as a lipophilic lactone prodrug, and pravastatin, an inhibitor administered in its active, hydrophilic, open-acid form, were compared by polysomnographic sleep monitoring. Twenty-four men with primary hypercholesterolemia (low-density lipoprotein 4 to 7 mmol/liter) each received 2 of the following 3 treatments in a randomized, incomplete block, crossover design study: lovastatin (40 mg/day), pravastatin (40 mg/day), and placebo. Test drug was administered once daily for 4 weeks during each half of the crossover study.

Regulation of serum cholesterol level in middle-aged and elderly men. Relation of cholesterol absorption and synthesis to lipoprotein metabolism.

The aim of the present study was to investigate cholesterol absorption and cholesterol and bile acid synthesis and relate these values of kinetics of low-density lipoprotein (LDL) apoprotein (apo) B in 50- and 75-year-old men to find out why and by which mechanism serum cholesterol level decreases with advancing age under normal home-living conditions. The daily calorie, fat, and cholesterol intakes were lower in the 75-year-old men because the physiological requirements of daily energy are reduced in old age. However, absolute body weight was identical in the two groups, indicating isocaloric energy intake.

Implications of recent results of long term multifactorial primary prevention of cardiovascular diseases.

Multifactorial primary prevention trials for reduction of cardiovascular diseases have engendered disappointing results because beneficial in-trial prevention has not been obtained consistently even when risk factor levels have been significantly improved. In addition, long term follow up studies, including post-trial periods, have revealed diminished or disappeared differences in risk factor levels between treated and control groups; total and coronary mortality differences have also been reduced or the death rates have even been increased during the post-trial period of treated group over those of control subjects in a study with a consistent coronary risk reduction during the intervention period. Reasons for this enhanced coronary mortality cannot be pointed out but drug treatment, especially beta-blocking agents in mild hypertension, should be studied more carefully.

Long-term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men.

Objective: To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases (CVD).

Design: The 5-year randomized, controlled trial was performed between 1974 and 1980. The subjects and their risk factors were reevaluated in 1985.

Glucose tolerance and blood pressure: long term follow up in middle aged men.

Objective: to investigate the role of glucose tolerance in the development of hypertension.

Design: Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors.

Metabolic variables of cholesterol during squalene feeding in humans: comparison with cholestyramine treatment.

Squalene, a key intermediate of cholesterol synthesis, is present especially in olive oil. Regulation of cholesterol metabolism by dietary squalene in man is unknown, even though olive oil users in Mediterranean areas have low serum cholesterol levels. We have investigated absorption and serum levels of squalene and cholesterol and cholesterol synthesis with the sterol balance technique and serum levels of cholesterol precursors in humans during squalene feeding (900 mg/d for 7-30 days).

Mortality rates after multifactorial primary prevention of cardiovascular diseases.

Eleven-year mortality rates were studied in middle aged men who had participated in a randomised 5-year multifactorial primary prevention trial on cardiovascular diseases during 1974-1980. The men were given health education advice before the study. The 5-year trial markedly improved the risk factor status in the men in the intervention group (n = 612), but their 5-year incidence of total coronary events tended to be higher than in the randomised non-treated control group (n = 610) and significantly higher than in an non-randomised, non-treated low risk group (n = 593).

Effects of cholestyramine and squalene feeding on hepatic and serum plant sterols in the rat.

Hepatic and serum phytosterol concentrations were compared in the rat under basal conditions and during activated cholesterol and bile acid production due to squalene and cholestyramine feeding. Both treatments consistently decreased hepatic and serum levels of sitosterol and campesterol and, unlike esterified cholesterol, esterified plant sterols were not increased in liver during squalene feeding. Serum levels of phytosterols were decreased quite proportionately to those in the liver.

Variations of hepatic cholesterol precursors during altered flows of endogenous and exogenous squalene in the rat.

Hepatic and serum levels of cholesterol precursors were analyzed in rats under basal (control) conditions and when cholesterol synthesis was activated by feeding 1% squalene or 5% cholestyramine. Exogenous squalene stimulated the activity of acyl-coenzyme A:cholesterol acyltransferase (ACAT) but strongly inhibited the activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase; cholestyramine did not affect ACAT but increased HMG-CoA reductase several-fold, indicating enhanced production of endogenous squalene. Activation of cholesterol synthesis by the two methods markedly increased the hepatic and serum contents of cholesterol precursor sterols.

Physiological and pharmacological regulation of small intestinal cholesterol synthesis.

1. The small intestine is an important site of cholesterol synthesis in the body and at least in experimental animals, it also contributes to the circulating plasma pool of cholesterol. 2.

Probucol in long-term treatment of hypercholesterolemia.

Over 15 yr of clinical experience with probucol seems to indicate that the drug is a safe and moderately effective hypocholesterolemic drug even in long-term treatment. Adverse effects are infrequent and usually tolerable. Probucol prolongs QT-interval but this does not seem to be connected with harmful effects in man.

Effects of ketoconazole on cholesterol synthesis and precursor concentrations in the rat liver.

Ketoconazole, an antimycotic agent, given to rats for a week as 0.05% food addition had no effect on the hepatic concentrations of free and esterified cholesterol or on the activity of acyl coenzyme. A: cholesterol-acyltransferase (ACAT).

Long-term use of probucol in the multifactorial primary prevention of vascular disease.

Over 1,200 middle-aged men with no apparent vascular disease participated in a 5-year multifactorial primary prevention trial, in which 612 received dietetic, hygienic and--when indicated--pharmacologic treatment for the following risk factors: hyperlipidemia, hypertension, smoking, obesity and abnormal glucose tolerance. Pharmacologic therapy included hypolipidemic agents (mainly probucol and clofibrate) and antihypertensive drugs (mainly diuretics and beta blockers). At the end of the 5 years, results in these men were compared with findings in 610 high risk and 593 low risk control subjects, none of whom had received treatment.

Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality.

In a randomized five-year multifactorial primary prevention trial of vascular diseases, hyperlipidemias, hypertension, smoking, obesity, and abnormal glucose tolerance of the high-risk test group (n = 612 men) were treated with dietetic-hygienic measures and hypolipidemic (mainly probucol and clofibrate) and antihypertensive (mainly diuretics and beta-blockers) agents. A matched high-risk control group (n = 610) and a low-risk control group (n = 593) were not treated. The program markedly improved the risk factor status, yet the five-year coronary incidence tended to be higher in the intervention group than in the control group (3.

Diurnal variation of plasma methyl sterols and cholesterol in the rat: relation to hepatic cholesterol synthesis.

Free cholesterol of plasma low density lipoproteins (LDL) and high density lipoproteins (HDL) of the rat was high and that of plasma very low density lipoproteins (VLDL) was low during the dark period of the diurnal cycle. Variations in the esterified plasma sterols were inconsistent. Free methyl sterols were high in all lipoproteins during the dark phase.

Regulation of cholesterol synthesis in jejunal absorptive cells of the rat.

Cholesterol metabolism was studied in jejunal mucosa of the rat with special emphasis on cholesterol synthesis of villous cells, the site of intestinal lipid absorption. The type of diet and nutritional state clearly affected the cholesterologenesis of villous cells. Consequently, the incorporation of 14C-acetate into nonsaponifiable lipids (NSL; includes squalene and sterols) decreased in the following order of magnitude: 1) fat-free diet supplemented with safflower oil (FFD-SO), 2) FFD alone, 3) standard rat chow, 4) 1% cholesterol in FFD-S(, 5) total fast.