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Biomedical subjects

T E Strandberg

Publications and source records attributed to T E Strandberg.

At least 55 records · Page 3Linked to original sources
PubMed1995

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. From that period cardiovascular disease (CVD) risk factors were available in 3313 men. In the beginning of the 1970s these men were invited to join a multifactorial primary prevention trial of CVD. Six groups were formed: (I) healthy participants in a high risk intervention group (n = 612), and (II) their randomised control group (n = 610); (III) a non-participant low risk group (n = 593); (IV) an excluded group with signs of CVD (n = 563); (V) a refused group (n = 867); and (VI) dead (n = 68). Groups I and II participated in the five year prevention trial which started in 1974. Other groups were followed up through registers, with no personal contact. MEASUREMENTS: Cardiovascular risk factors during the 1960s. Mortality follow up using national registers up to 31 December, 1992. MAIN RESULTS: Baseline risk factors were lowest in the low risk group, highest in the excluded group, intermediate and comparable in other groups. Eighteen-year (1974-1992) mortality (per 1000) was 79.3, 106.6, 155.2, 179.9, and 259.3 in the low risk, control, intervention, refused, and excluded groups, respectively (P < 0.001). In the whole population of 3313 men, the 28-year (1964-1992) total (n = 577) and coronary deaths (n = 199) were significantly predicted by smoking, blood pressure, and cholesterol; cancer deaths (n = 163) by smoking only; and violent deaths (n = 83) by none of the risk factors. One-hour postload glucose was significantly associated with total mortality in the intervention group only. When the intervention and control groups were included in the same model, the effect of group on total mortality tended to be dependent on the 1 h blood glucose value (P = 0.06 for the group by 1 h glucose interaction term). CONCLUSION: The traditional risk factors (smoking, blood pressure, and cholesterol) are significantly associated with 28-year mortality in this high social class population with previous health education. Conversely, a "clustering" of low risk factors predicted low total, coronary, and cancer mortality. The findings on 1 h blood glucose suggest that factors related to glucose tolerance explain in part the excess mortality in the intervention group compared with the control group.

Adult↗
PubMed1992

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. Despite this discouraging mortality finding multifactorial prevention with simultaneous reduction of several coronary risk factors sounds useful provided that pharmacological prevention could be selected to give more benefit than harm.

Antihypertensive Agents↗
PubMed1991

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. Posttrial mortality follow-up was continued up to December 31, 1989. SETTING: Institute of Occupational Health, Helsinki, Finland, and Second Department of Medicine, University of Helsinki. PARTICIPANTS: In all, 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s. In 1974, 1222 of these men who were clinically healthy, but with CVD risk factors, were entered into the primary prevention trial; 612 were randomized to an intervention and 610 to a control group. INTERVENTIONS: During the 5-year trial, the subjects of the intervention group visited the investigators every fourth month. They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic (mainly clofibrate and/or probucol) and antihypertensive (mainly beta-blockers and/or diuretics) drugs. The control group was not treated by the investigators. MAIN OUTCOME MEASURES: Total mortality, cardiac mortality, mortality due to other causes. RESULTS: Total coronary heart disease risk was reduced by 46% in the intervention group as compared with the control group at end-trial. During 5 posttrial years, the risk factor and medication differences were largely leveled off between the groups. Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group (relative risk [RR], 1.45; 95% confidence interval [CI], 1.01 to 2.08; P = .048); there were 34 and 14 cardiac deaths (RR, 2.42; 95% CI, 1.31 to 4.46; P = .001), two and four deaths due to other CVD (not significant), 13 and 21 deaths due to cancer (RR, 0.62; 95% CI, 0.31 to 1.22; P = .15), and 13 and one deaths due to violence (RR, 13.0; 95% CI, 1.70 to 98.7; P = .002), respectively. Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality. CONCLUSION: These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s) of methods used in the primary prevention of cardiovascular diseases.

Antihypertensive Agents↗
PubMed1991

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. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING: Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS: In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS: By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES: Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS: Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION: In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.

Blood Glucose↗
PubMed1990

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). The results were compared with those during cholestyramine treatment. Fecal analysis suggested that about 60% of dietary squalene was absorbed. Serum squalene levels were increased 17 times, but serum triglyceride and cholesterol contents were unchanged. The squalene feeding significantly (P less than 0.05) increased serum levels of free (1.7-2.3 times) and esterified (1.9-2.4 times) methyl sterol contents, while elevations of free and esterified delta 8-cholesterol and lathosterol levels were inconsistent. Cholestyramine treatment modestly augmented free methyl sterol levels (1.3-1.7 times), less consistently than those of esterified ones, while, in contrast to the squalene feeding, serum contents of free and esterified delta 8-cholesterol and lathosterol were dramatically increased (3.3-8 times). Neither of the treatments significantly affected serum plant sterol and cholestanol levels. The squalene feeding had no consistent effect on absorption efficiency of cholesterol, but significantly increased (paired t-test, P less than 0.05) the fecal excretions of cholesterol and its nonpolar derivatives coprostanol, epicoprostanol, and coprostanone (655 +/- 83 SE to 856 +/- 146 mg/d) and bile acids (212 +/- 24 to 255 +/- 24 mg/d), indicating an increase of cholesterol synthesis by about 50%. We suggest that a substantial amount of dietary squalene is absorbed and converted to cholesterol in humans, but this squalene-induced increase in synthesis is not associated with consistent increases of serum cholesterol levels. The clearly increased serum contents of esterified methyl sterols may reflect stimulated tissue acyl CoA: cholesterol acyltransferase (ACAT, EC 2.3.1.26) activity during squalene feeding as these sterols are not esterified in serum.

Cholestanol↗
PubMed1989

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. However, the sterol profiles were clearly different. Thus, exogenous squalene raised most significantly (up to 109-fold) free and esterified methyl sterols, and less so (up to 2-fold) demethylated C27 sterols (desmosterol and cholestenols) and also esterified cholesterol. Activation of endogenous squalene production by cholestyramine was associated with a depletion of esterified cholesterol and by a marked, up to 8-fold, increase of the free demethylated sterol precursor levels, whereas the increase of methyl sterols, up to 5-fold, was less conspicuous than during the squalene feeding. The changes were mostly insignificant for esterified sterols. The altered serum sterol profiles were quite similar to those in liver. Serum cholestenols and especially their portion of total serum precursor sterols were closely correlated with the hepatic activity of HMG-CoA reductase.

Animals↗
PubMed1989

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. The hepatic levels of sitosterol and campesterol closely correlated with each other, but not with cholesterol levels. The percentage esterification of both phytosterols was lower than that of cholesterol. The results indicate that activation of hepatic sterol production leads to depletion of hepatic plant sterols. It is suggested that poor esterification of plant sterols may contribute to this decrease.

Animals↗
PubMed1989

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). During the six years following the discontinuation of the trial, 11 deaths from cardiovascular disease occurred both in the intervention and in the control groups and three in the non-randomised low risk group. Thus, the cumulative eleven-year cardiovascular mortality rates and their 95% confidence intervals (Cl95) were 2.45% (Cl95: 1.38, 3.67) in the intervention group and 1.97% (Cl95: 1.01, 3.34) in the randomised high risk control group. In the non-randomised low risk group the mortality rate was 0.51 (Cl95: 0.01, 1.46). Multiple logistic regression analysis showed that overweight and hypercholesterolaemia, and smoking in the high risk controls, were the initial risk factors associated with the 11-year cardiovascular mortality. The latter was not accumulated in any treatment measure during the prevention period. Furthermore, despite the unfavourable effect of beta-blocking agents on total cardiac events during the intervention, beta-blockers were not associated with cardiac deaths in the 11-year follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗
PubMed1988

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. Its hypocholesterolemic action is not sufficient in all patients but this can be substantially improved by combining other hypolipidemic drugs with different mode of action. Interference with lipoprotein structure may contribute to the hypocholesterolemic action of probucol, and despite the lowering of HDL cholesterol probucol has been shown to regress peripheral cholesterol deposits. There is also tentative evidence that the drug may protect from CHD in primary prevention. The newly-discovered antioxidant property of probucol preventing harmful LDL modification in vitro might partly explain the favorable effects of probucol independently of its effects on LDL- or HDL-cholesterol levels.

Animals↗
PubMed1988

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. Studies on synthesis regulation have been partly contradictory but it is now concluded that the cellular cholesterol balance is the basic regulatory factor of intestinal cholesterol synthesis. However, the balance is affected differently in various specialized cells and parts of the small intestine. 3. Most data on synthesis regulation are derived from experimental animals but the few human studies suggest that similar regulatory factors function in man, too.

Animals↗
PubMed1987

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). However, the levels of free methylated cholesterol precursors, especially lanosterols, less markedly delta 8,24 and delta 8-dimethyl sterols and monomethyl sterols, were increased after only one day's treatment, while those of esterified methyl sterols were increased inconsistently, and those of free and esterified delta 8-lathosterol, lathosterol and desmosterol were not affected at all. Cholestyramine treatment had no significant effect on ACAT in spite of a decrease in the hepatic content of esterified cholesterol and caused a marked increase in the free cholesterol precursor levels, especially in those of lathosterols. Cholestyramine given to ketoconazole-treated rats increased the hepatic levels of delta 8 and delta 7-lathosterols but not desmosterol or methylated cholesterol precursors. Ketoconazole increased and cholestyramine markedly decreased plant sterols, sitosterol and campesterol in the liver. In serum, the contents of both lanosterols and lathosterol were increased but that of cholesterol tended to be decreased by ketoconazole (-19%). The results indicate that ketoconazole impairs demethylation processes at C-14 and to some extent at C-4 in the rat liver, resulting in lowered serum cholesterol level.

Animals↗
PubMed1984

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. Simultaneously, the incorporation of 14C-acetate into nonsaponifiable sterols and the concentrations of free methyl sterols and cholesterol in the liver were elevated.

Animals↗
PubMed1983

Sterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivo.

Because bile contains substantial amounts of cholesterol precursors, e.g., squalene and different methyl sterols, the fate of biliary squalene was studied by incubating isolated jejunal loops of the rat in vivo with bile containing 3H-squalene and 14C-cholesterol. After 90 min, no radioactivity was found in plasma lipids. Closer analysis of gut epithelium revealed that both labeled compounds were preferentially taken up by the villous cells. Biliary 3H-squalene was absorbed almost completely and was further cyclized to free and esterified methyl sterols and cholesterol. Whereas squalene not cyclized to sterols stayed in the mucosa, the newly synthesized sterols were transferred to lumen. The lipid patterns of gut lumen and mucosal cells were quite different, suggesting that the transfer of the newly synthesized lipid to intestinal lumen was not due to the desquamation of epithelial cells alone. The results suggest that biliary cholesterol precursors can contribute to the cholesterol production of the jejunal villous cells bypassing the rate-limiting step of the cholesterol synthesis pathway, and to the "nonexchanging" fecal neutral sterols of the rat.

Animals↗
PubMed1983

Clofibrate decreases jejunal cholesterol synthesis and activity of postheparin plasma lipoprotein lipase in the rat.

Clofibrate treatment decreased drastically the activity of serum postheparin lipoprotein lipase of rats fed with fat-free test diet but had no effect on hepatic lipase. 3 weeks' treatment was followed by a significant fall in serum cholesterol caused by a marked decrease in HDL-cholesterol. Clofibrate decreased in vitro synthesis of cholesterol and fatty acids in jejunal villous cells but not in the crypt cells.

Animals↗
PubMed1983

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. Both the cholesterol feeding and the fast increased the total cholesterol concentrations in the villous cells, but the concentrations were unaffected by the other diets. In rats fed FFD-SO diet the cholesterol synthesis was significantly higher in the villous than in the crypt cells, although the cellular cholesterol concentrations were similar. The hepatic cholesterol synthesis from 14C-acetate was low in rats fed FFD-SO as compared with chow diet, whereas the incorporation of 14C-acetate into hepatic fatty acids and the incorporation of 3H-mevalonate into NSL were not affected by the diet. 5% cholestyramine had no significant effect on the cholesterol synthesis or cholesterol concentrations of the villous cells during high (FFD-SO diet) or low cholesterol synthesis (chow or cholesterol feeding). FFD-SO increased serum total cholesterol compared with chow diet and total fast, whereas cholestyramine and cholesterol feeding had no effect. Intraperitoneal administration of the hypocholesterolemic agent, 4-aminopyrazolopyrimidine, to fasting rats decreased markedly crypt cell cholesterol and increased cholesterol synthesis in the crypt cells and in the villous cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1982

In vitro synthesis of triglycerides and cholesterol in human gallbladder mucosa.

Triglyceride and sterol synthesis was investigated in vitro in the gallbladder mucosa from control subjects and patients with acalculous cholesterolosis. The incorporation rate of 14C-acetate was 1.6 +/- 0.2 nmol/g/h into cholesterol (sum of squalene, methyl sterols, and cholesterol) and 5.7 +/- 0.8 nmol/g/h into triglycerides. The rates were significantly correlated with each other (r = 0.667). The conversion of 3H-mevalonate into cholesterol (49 +/- 10 nmol/g/h) and triglycerides (4.7 +/- 1.2 nmol/g/h) indicated a high activity in the postmevalonate cholesterol synthesis and an active shunt pathway of mevalonate metabolism. The synthesis rates of cholesterol, triglycerides, and sterol esters were closely interrelated, were unaltered in cholesterolosis, and were not correlated with the serum, biliary, and mucosal lipid concentrations. Thus, despite marked lipid accumulation the lipid synthesis proceeds effectively in the gallbladder mucosa with cholesterolosis.

Cholesterol↗