Biomedical subjects

I Holme

Publications and source records attributed to I Holme.

At least 55 records · Page 3Linked to original sources

PubMed1996

[Statin therapy of individuals with high risk for coronary disease].

After the release of the results from the West of Scotland Prevention study (WOSCOPS) some questions have been raised with respect to validity of its finding on all cause mortality, which was reduced by 22% with pravastatin treatment (p = 0.051) compared with placebo. Also, since WOSCOPS was a primary preventive study its results could affect a large proportion of Norwegian men. Thus, it can also be asked whether statin treatment should be preferred to standard, specific treatment for certain diseases, e.g. hypertension, if economic restrictions by the government make it necessary to make priorities. For example, expensive drugs are now given free to many diabetics and hypertensives, who should probably be treated with statins, almost regardless of their cholesterol level. The total social costs of medication could then exceed accepted budgets and could lead to restrictions. The author discusses the validity of the WOSCOPS findings on all cause mortality, and compares the results obtained in this study with those randomised trials and other statin trials. Finally, a comparison is made between results from two metaanalyses: one of randomised hypertension trials and one of all randomised statin trials. It is concluded that more favourable results are obtained from the latter. Caution should be shown, however, when interpreting such a comparison.

Anticholesteremic Agents↗

PubMed1996

Exercise-induced increase in lipoprotein (a).

In the Oslo Diet and Exercise Study (ODES) 219 healthy middle-aged physically inactive persons with moderately deranged risk factor levels (increased bodyweight, diastolic blood pressure, serum cholesterol, triglycerides, decreased HDL-cholesterol) were randomized to 4 intervention groups: dietary intervention, exercise, diet + exercise and control. The purpose of the study was to test if these interventions maintained for a year, isolated or in combination, would change coronary risk factor levels as compared to control. One of the risk factors included was lipoprotein (a) (Lp(a)). The hypothesis to be tested was if physical exercise would be associated with increased levels of Lp(a) as a result of intervention. Those who exercised increased their Lp(a) levels with 15.4 (S.E. = 8.0) mg/l as compared to no exercise (P < 0.05). Also, dietary intervention tended to increase Lp(a), but the increase did not reach statistical significance. There was no detectable interaction on the effect on Lp(a) of the two intervention modalities. A dose-response relationship was found between change in the exercise-specific variables heart rate and peak oxygen uptake, and Lp(a)-change and this dose-response was most pronounced in the exercise group. Change in Lp(a) was associated to change in several lifestyle related variables such as alcohol intake and waist circumference, pointing to the possibility that Lp(a), at least in some subpopulations, is more amenable to change through lifestyle alterations than reported so far.

Adult↗

PubMed1996

Relationship between total mortality and cholesterol reduction as found by meta-regression analysis of randomized cholesterol-lowering trials.

All randomized trials of cholesterol lowering except those without information on total mortality or cholesterol reduction were included in this meta-analysis. Its purpose was to review the relationship between log odds ratio of total mortality in active vs. control group and degree of cholesterol reduction, adjusting for appropriate covariates such as type of trial (single or multifactor), risk level in the control group, and type of treatment. Analysis revealed that risk level in the control group was particularly important to adjust for because it correlated both to degree of cholesterol reduction (r = 0.48) and to log OR of total mortality (r = -0.38, single-factor trials) and thus confounded the cholesterol mortality association. After adjustment, a borderline significant association was found between degree of absolute cholesterol reduction and total mortality log OR. Type of treatments also seemed to be associated with log OR, mostly through excess risk in hormone-treated patients. There was no statistically significant indication that fibrate trials had inferior results as compared to other drug trials. Meta-analysis estimates of global treatment effects can be misleading in the guidance for creating appropriate recommendations regarding cholesterol reduction. More emphasis must be put on how cholesterol is reduced and how much.

Anticholesteremic Agents↗

PubMed1996

Association of cardiac autonomic function and the development of hypertension: the ARIC study.

To relate cardiac autonomic function measured by heart rate variability (HRV) with prevalent and incident hypertension at the population level, the authors examined a stratified random sample of 2,061 examinees from the biracial Atherosclerosis Risk in Communities (ARIC) cohort. Baseline, supine, resting beat-to-beat heart rate data were collected. High frequency (HF, 0.15 to 0.35 Hz), low frequency (LF, 0.025 to 0.15 Hz) spectral powers, and LF/HF ratio, estimated from spectral analysis, and standard deviation of all normal RR intervals (SDNN), calculated from time domain analysis, were used as the conventional indices of cardiac autonomic function. From this sample, 650 prevalent hypertensives were identified. Of those normotensive at baseline (n = 1,338), 64 participants developed hypertension during 3 years of follow-up. In the cross-sectional analysis, the adjusted geometric means of HF were 1.26, 1.20, and 1.00 (beat/min)2 for normotensives, untreated hypertensives, and treated hypertensives, respectively; means of LF were 3.24, 3.26, and 2.58; means of LF/HF ratio were 2.57, 2.70, and 2.56; and means of SDNN were 39, 34, and 35 (ms) respectively. In the prospective analysis, a statistically significant, graded inverse association between baseline HF and the risk of incident hypertension was observed: the adjusted incident odds ratios (95% CI) were 1.00, 1.46 (0.61, 3.46), 1.50 (0.65, 3.50) and 2.44 (1.15, 5.20) from the highest to the lowest quartile of HF. No clear pattern of association was observed for LF. Significant trends of association for LF/HF and SDNN and incident hypertension were also found. These results suggest that cardiac autonomic function is associated with prevalent hypertension, and that reduced vagal function and the imbalance of sympatho-vagal function are associated with the risk of developing hypertension.

Adult↗

PubMed1996

Improved carbohydrate metabolism after physical training and dietary intervention in individuals with the "atherothrombogenic syndrome'. Oslo Diet and Exercise Study (ODES). A randomized trial.

OBJECTIVES: To compare the single and joint effect of 1-year diet and exercise intervention on carbohydrate metabolism and associated coronary risk variables. DESIGN: Unmasked, randomized, 2 x 2 factorial intervention trial with 1-year duration for each participant. SETTING: The participants were recruited from a screening examination of 40-year-old persons in Oslo, Norway. SUBJECTS: Two hundred and nineteen sedentary men and women, with diastolic blood pressure 86-99 mmHg, HDL cholesterol < 1.20 mmol L-1, triglycerides > 1.4 mmol L-1, total cholesterol 5.20-7.74 mmol L-1 and BMI > 24. Participants were randomly allocated to control (n = 43), diet (n = 55), exercise (n = 54) and diet+exercise (n = 67). INTERVENTIONS: Exercise: supervised endurance exercise three times a week. Diet: reduce weight, increase the intake of fish and reduce total fat intake. MAIN OUTCOME MEASURES: One-year changes in insulin and glucose before and after a standardized glucose load. RESULTS: As compared with controls fasting insulin in pmol L-1 decreased significantly in the combined diet and exercise group (3.9 +/- 6.2 versus -22.6 +/- 4.7 respectively, P = 0.003). Insulin in pmol L-1 after glucose load decreased significantly in all intervention groups compared to controls (diet: -82.2 +/- 49.9 P = 0.02; exercise: -92.4 +/- 60.1 P = 0.03; diet + exercise: -179.6 +/- 46.1 P = 0.0004). Fasting glucose in mmol L-1 decreased significantly in the diet alone group (0.21 +/- 0.07 P = 0.006) and in the diet+exercise group (-0.26 +/- 0.08 P = 0.005). In a subgroup analysis of the good responders, the observed changes with respect to total cholesterol (-0.76 mmol L-1), HDL cholesterol (0.16 mmol L-1), triglycerides (-0.72 mmol L-1), systolic and diastolic blood pressure (-8.5/ -6.8 mmHg) were all statistically significant compared to the control with P < 0.001). CONCLUSIONS: Exercise and diet intervention and in particular the combination of the two, were effective in improving carbohydrate metabolism. Associated risk factors were also affected in a beneficial direction.

Adult↗

PubMed1996

The effect of acute vs chronic treatment with beta-adrenoceptor blockade on exercise performance, haemodynamic and metabolic parameters in healthy men and women.

1. Variable results have been reported on the effect of beta-adrenoceptor blockers on maximal oxygen uptake (VO2 max) and exercise endurance. This may in part be due to different subject populations, but it could also be due to an adaption of metabolic and haemodynamic responses to exercise during chronic treatment with beta-adrenoceptor blockers. The present study was therefore carried out to examine the effect of acute and chronic administration of the non-selective beta-adrenoceptor blocker propranolol on both peak VO2 and exercise performance in the same subjects. Since the effect of beta-adrenoceptor blockade has not been properly investigated in women, eight healthy women were compared with seven men. Progressive bicycle exercise to exhaustion was performed after propranolol 0.15 mg kg-1 i.v. (acute) or 80 mg three times daily for 2 weeks (chronic) or placebo given according to a double-blind crossover design. 2. Mean (s.e. mean) peak VO2, was significantly reduced from 42.3 (1.6) ml min-1 kg-1 during placebo to 40.3 (1.2, P < 0.05) ml min-1 kg-1 after acute and 39.1 (1.2, P < 0.001) ml min-1 kg-1 after chronic propranolol treatment. No significant difference in peak VO2 between the two propranolol treatment regimens was observed (mean difference 1.2, 95% CI -0.1 to 2.4 ml min-1 kg-1). There was no treatment interaction with gender. 3. Cumulative work, 163 (9.3) kJ, was significantly reduced by acute, 148 (7.7, P < 0.001) kJ, and chronic, 147 (7.6, P < 0.001) kJ, administration of propranolol since the time to exhaustion was reduced by 5.3% and 5.3%, respectively. There was no significant difference between the two regimens of propranolol (mean difference 0.2, 95% CI -6.7 to 7.0 kJ) or between the sexes. Maximal knee extensor and handgrip strengths were not affected by propranolol. 4. Whereas sex did not influence ventilatory, haemodynamic or metabolic parameters, some differences were observed between acute and chronic propranolol treatment. During submaximal exercise oxygen uptake was reduced by approximately 2% and RER values increased by 0.04-0.05 after chronic treatment in contrast to no effect of acute propranolol treatment. Heart rate and systolic blood pressure were reduced significantly more after chronic compared with acute propranolol treatment; peak heart rate being 186 (2.2), 147 (2.3) and 134 (2.3) beats min-1, and peak systolic blood pressure being 189 (7), 171 (4) and 161 (4) mmHg after placebo, acute and chronic propranolol administration, respectively. Also the exercise induced rise in potassium and lactate levels were modified differentially; the rise in potassium concentration was less after chronic compared with acute propranolol treatment and lactate levels were reduced only after chronic administration of propranolol. In contrast, ventilation, which was unchanged after propranolol during submaximal exercise, was reduced to similar extent at exhaustion from 108 (6.4) to 97 (7.2) and 96 (5.9) l min-1 after acute and chronic propranolol administration, respectively. Diastolic blood pressure and subjective perception of fatigue were similar across the treatment regimens. 5. The study has demonstrated that acute and chronic administration of propranolol result in different haemodynamic and metabolic response to exercise, although endurance and peak oxygen consumption were reduced to the same extent. The response to propranolol was not significantly different between men and women.

Adrenergic beta-Antagonists↗

PubMed1996

Smoking habits and risk of fatal stroke: 18 years follow up of the Oslo Study.

STUDY OBJECTIVE: To examine the risk of fatal stroke in relation to smoking habits in men screened for the Oslo study. DESIGN: The Oslo study is a prospective, cohort study of the epidemiology and preventive aspects of cardiovascular diseases in middle aged men. Screening started in May 1972 and results after 18 years of follow up are reported. PARTICIPANTS: There were 16209 men aged 40-49 years, of whom 16173 had no stroke history. Eighty five men died from stroke, of whom 48 were daily cigarettes smokers, 7 were pipe and cigar smokers, 15 smoked cigarettes and pipe or cigars daily, 11 were previous cigarette smokers, and 4 had never smoked cigarettes. MAIN RESULTS: Results of proportional hazards regression analysis adjusted for age, diastolic blood pressure, and glucose concentration showed the following rate ratios (RR) (95% confidence interval) of smoking groups compared with those who had never smoked or had previously smoked: combined cigarette and cigar or pipe smokers, RR = 6.1 (3.0, 12.5); cigarettes only, RR = 4.1 (2.3,7.4); and pipe and/or cigars only RR = 2.2 (0.9,5.5). The overall, age adjusted risk of smoking cigarettes daily was 3.5 and was found to increase with increasing cigarette consumption. Regardless of their smoking group, stroke cases had increased diastolic (DBP) and systolic blood pressure (SBP) when compared with men who had not had a stroke. The absolute differences in DBP and SBP between stroke cases and others for never and previous cigarette smokers versus daily smokers were twice as large: DBP, 12.1 mmHg versus 6.5 mmHg respectively and SBP, 16.0 mmHg versus 7.1 mmHg respectively. A high BMI increased the risk of fatal stroke of never and previous cigarette smokers. Men being treated for hypertension at the time of screening had three times the crude risk of fatal stroke of men who were not taking hypertensive treatment. CONCLUSIONS: Daily cigarette smoking increased the risk of fatal stroke three and a half times. Combined cigarette and pipe or cigar smoking had a higher risk than smoking cigarettes only. An increased risk was found in relation to increased daily cigarette consumption.

Adult↗

PubMed1995

Cholesterol reduction and its impact on coronary artery disease and total mortality.

A sample of 42 randomized cholesterol-lowering trials represented by 32 data points were subjected to a metaregression analysis. The logarithmic odds ratio (InOR) of total mortality outcome or incidence of coronary artery disease (CAD) were used as dependent variables and regressed against the net amount of total cholesterol reduction between treatment groups in each trial. Analyses were weighted by variance of OR. Adjustments were also made for single and multifactor trials and for total mortality risk level in the control/placebo group as well as for treatment modality. Analyses were performed both with and without inclusion of trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors as treatment modality. A statistically significant dose-response relationship was found between InOR and the amount of cholesterol reduction for both endpoints and in both groups of trials. These findings were essentially unaltered by various adjustments for potential confounders or by various sensitivity analyses. The results of the Scandinavian Simvastatin Survival Study (4S) fell close to the regression lines for both outcome measures, and inclusion of other statin trials strengthened the significance of this dose-response compared with previous metaregression analyses without inclusion of statin trials. The type of treatment was significantly associated with both endpoints. Fibrate trials did significantly worse on all-cause mortality than statin trials and other drug trials (except hormone). The baseline cholesterol level was also significantly predictive of CAD incidence as a trial outcome; efficacy increased with increased level of baseline cholesterol.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗

PubMed1995

Incidence of hypertrophic cardiomyopathy in hypothyroidism.

In 13 consecutive severely hypothyroid patients no sign of endocrine cardiomyopathy in the form of asymmetric septal hypertrophy (ASH) could be disclosed by M-mode and two-dimensional (2D) echocardiography on examination prior to thyroxine replacement therapy. In previous investigations ASH was demonstrated to be almost invariably present in untreated hypothyroidism irrespective of thyrotropin levels. Consequently application of positive inotropic and afterload reducing agents that may invoke deleterious effects in ASH has been considered hazardous in hypothyroidism even when indicated by concurrent other heart disease. Determination of exact confidence limits reveals that the proportional incidence of hypothyroid hypertrophic cardiomyopathy could not exceed 24.7% with 95% probability. We conclude that ASH is not necessarily inherent in hypothyroidism.

Adult↗

PubMed1995

Risk of fatal stroke according to blood pressure level: an 18-year follow-up of the Oslo Study.

OBJECTIVE: To determine how blood pressure level predicts the incidence of fatal stroke. DESIGN: The Oslo Study is a prospective cohort study of preventive and epidemiological aspects of cardiovascular disorders in middle-aged men. Of 25,915 men invited, 16,209 aged 40-49 years attended the screening. A 7% random sample of men aged 20-39 years were also invited to attend. METHODS: The screening started in May 1972 and the analysis presented is an 18-year follow-up for fatal strokes. Men with a history of stroke were excluded from the analyses. RESULTS: Of 16,173 men with no history of stroke 85 died from stroke. Results from Cox proportional hazards regression analysis confirm diastolic (DBP) and systolic blood pressure (SBP) as strong independent risk factors of fatal stroke, with DBP being the stronger predictor. Analyses of risk of fatal stroke by quintile values show SBP to give significantly increased risk from the third quintile (136 mmHg), and DBP from the fifth quintile (95 mmHg) relative to the first quintile. No levelling off at highest levels can be seen when analysing decile values. No J-shape of the curve was evident. Men on drug treatment for hypertension with no stroke history (n = 440) had 4.7-fold (crude) and 2.8-fold (adjusted for age and DBP) the rate of stroke mortality of men not on drug treatment for hypertension. CONCLUSION: DBP was a stronger predictor than SBP, with increasing risk from the fifth quintile of DBP and the third quintile of SBP. Men on drug treatment for hypertension at screening were at increased risk during the follow-up period, indicating that their treatment did not sufficiently reduce their risk of stroke.

Adult↗

PubMed1995

Effects of lipid-lowering therapy on total and coronary mortality.

The results of several lipid-lowering randomized trials were released during the past year. The Scandinavian Simvastatin Survival Study has contributed significantly to the understanding of lipid-lowering on all-cause and coronary mortality outcome. An approximate 25% net difference in cholesterol between the simvastatin and placebo group produced a 30% reduction in total mortality in the simvastatin group (P < 0.01). No increase in noncardiovascular mortality or nonfatal diseases was observed. Although angiographic trials that study atherosclerosis are not designed to show the effect on clinical outcome, several new trials such as the Asymptomatic Carotid Artery Progression Study, the Multicentre Anti-Atheroma Study, the Canadian Coronary Atherosclerosis Intervention Trial and the Stanford Coronary Risk Intervention Project all add information that is consistent with the results from the Scandinavian Simvastatin Survival Study. The meta-analysis of randomized cholesterol-lowering trials also indicates that no excess of all-cause mortality is present when the degree of cholesterol reduction and treatment modality is adjusted. It is probable that the excess mortality from noncardiovascular causes found in unadjusted analyses is due to specific effects of hormones and fibrate drug treatments to reduce cholesterol. It is concluded that the lipid hypothesis is confirmed more solidly than ever before.

Anticholesteremic Agents↗

PubMed1995

Lowering of HDL2b by probucol partly explains the failure of the drug to affect femoral atherosclerosis in subjects with hypercholesterolemia. A Probucol Quantitative Regression Swedish Trial (PQRST) Report.

The aim of the Probucol Quantitative Regression Swedish Trial (PQRST) (n = 303) was to investigate whether probucol (0.5 g BID) added to diet and cholestyramine (8 g BID) could retard progression or induce regression of femoral atherosclerosis in hypercholesterolemic (> 6.86 mmol/L) subjects. Probucol did not induce regression over the 3-year trial period as estimated by change in lumen volume on quantitative arteriography of a 20-cm segment of the femoral artery. In this report we studied in a representative subgroup (n = 72) whether the reduction in HDL concentrations induced by probucol could explain the failure of the drug to be effective. We analyzed the effects of treatment on HDL particle size subclasses. Probucol lowered the relative level of HDL2b, comprising the largest HDL particles, by 53% and the protein concentration of HDL2b by 67%. The protein reduction in HDL was mainly confined to the apolipoprotein A-I moiety. The change in lumen volume correlated significantly with change in HDL, ie, HDL cholesterol (r = .34, P < .01), HDL2 cholesterol (r = .37, P < .01), HDL2b protein (r = .44, P < .001), and the relative HDL2b value (r = .51, P < .001). The corresponding values for relative HDL2b, distribution calculated on the active (n = 35) and placebo (n = 37) groups separately were also significant (r = .39 and .32, respectively; both P < .05). The correlation between drug-induced change in the relative HDL2b concentration and change in atherosclerosis was independent of the alteration in triglyceride concentration and could not be explained by treatment interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

PubMed1995

Probucol treatment decreases serum concentrations of diet-derived antioxidants.

The effect of probucol, which is both a cholesterol-lowering drug and an antioxidant, on the serum concentrations of diet-derived antioxidants vitamin E, beta-carotene, lycopene, and vitamin A was studied in 303 hypercholesterolemic subjects. In a 3-year, double-blind, randomized trial we investigated to determine whether combined treatment with diet, cholestyramine, and probucol could reduce the progression of femoral atherosclerosis. Serum and lipoprotein antioxidant levels were measured by reverse-phase high-performance liquid chromatography. Cholestyramine significantly lowered serum concentrations of vitamin E by 7%, beta-carotene by 40%, and lycopene by 30% (all P < .001) due to impairment of gastrointestinal absorption and to serum cholesterol lowering. Probucol reduced serum vitamin E by 14% (P < .001) secondary to cholesterol and triglyceride lowering. The carotenoids were reduced by probucol by 30% to 40% (P < .001) most probably due to reductions in lipoprotein particle size and to competition with these substances for incorporation into VLDL during its assembly in the liver. This study shows that the use of a lipid-soluble antioxidant and cholesterol-lowering drug may have unfavorable effects on blood levels of diet-derived antioxidants.

Antioxidants↗

PubMed1995

Nonfasting serum glucose and the risk of fatal stroke in diabetic and nondiabetic subjects. 18-year follow-up of the Oslo Study.

BACKGROUND AND PURPOSE: The association between nonfasting serum glucose and stroke mortality for diabetic and nondiabetic subjects is presented for participants of the Oslo Study. METHODS: The study started in 1972; of 16,209 men aged 40 to 49 years, 16,172 had no previous history of stroke and 151 were known to be diabetic. Five diabetic and 80 nondiabetic subjects died of stroke during the 18 years of follow-up, giving a rate ratio of 7.87 (95% confidence interval [CI], 2.48 to 19.14). The rate of mortality for all causes in diabetic subjects was more than five times that of those who were nondiabetic. RESULTS: Nonfasting serum glucose was a predictor of fatal stroke in all participants (diabetic subjects included) without a history of stroke in age-adjusted univariate analysis. The relative risk was 1.13 (CI, 1.03 to 1.25) by increase of 1 mmol/L of serum glucose according to results of proportional hazards regression analysis. Accordingly, relative risk for nondiabetic subjects was 1.02 (CI, 0.83 to 1.26) with no linear trend. The rate ratio of the fifth quintile to the rest was 1.57 (CI, 0.94 to 2.56) for all participants and 1.28 (CI, 0.72 to 2.18) for nondiabetics. CONCLUSIONS: There was an interaction between glucose level and body mass index versus stroke for all participants but not for nondiabetic subjects, with an increased risk for men with above-median values of glucose and body mass index. Analysis of nondiabetic subjects failed to show glucose as a definite predictor of fatal stroke.

Adult↗

PubMed1995

Diet and exercise intervention have favourable effects on blood pressure in mild hypertensives: the Oslo Diet and Exercise Study (ODES).

The purpose of this study was to investigate the effect of 1-year diet intervention, exercise intervention and both combined on blood pressure (BP) in normotensives and mild hypertensives. Two hundred and nineteen sedentary middle aged men and women with slightly deranged coronary heart disease (CHD) risk factors were randomised to a control, a diet, an exercise and a diet + exercise group. Based on baseline diastolic BP, participants were divided into tertiles, giving baseline average BP of 141.4/96.7 in tertile 1, 130.7/87.6 in tertile 2 and 121.9/79.0 in tertile 3. The 1-year net-difference in BP between the intervention groups and the control group decreased across the tertiles; in tertile 1 being -11.2/-6.7 (p < 0.05), -11.3/-6.7 (p < 0.05 for systolic BP only) and -7.0/-5.1 (NS) in the combined, diet and exercise group respectively. Triglycerides, HDL cholesterol, and insulin variables were significantly and favourably changed, the changes being most marked in the combined group. The results show that diet and diet + exercise are about equally effective in reducing BP, and the effects may be dependent on the baseline level. Within the upper tertile of baseline BP, the decline in BP in the combined intervention and the diet group are almost comparable to those obtained with drug treatment. In addition, other important CHD risk factors were all changed in a beneficial direction.

Adult↗

PubMed1994

Influence of lipoprotein lipids, dietary fat and smoking on macrophage degradation of native and oxidized low density lipoprotein.

Relatively little is known about the biological mechanisms by which lipoproteins promote atherogenesis. It has, however, been shown that structural modification of low density lipoprotein (LDL), such as by oxidation, results in their uptake and degradation by intimal macrophages and consequently leads to formation of lipid-rich atherosclerotic lesions. The aim of the present investigation was to study the influence of dietary intake of fat, lipoprotein lipid composition, smoking and gender on macrophage degradation of LDL before and after oxidation. The study group consisted of 48 males and 56 females with hyperlipidemia taking part in the open prerandomization phase of the Probucol Quantitative Regression Swedish Trial (PQRST). Analysis including lipoprotein determinations, dietary and smoking habit interviews, LDL degradation by macrophages, LDL receptor binding and LDL thiobarbituric acid reactive substance (TBARS) levels before and after copper ion-induced oxidation was done during the pre-andomization phase of the study. Increased plasma and very low density lipoprotein (VLDL) triglyceride levels were associated with an increased macrophage degradation of native LDL, whereas no such association was found after oxidation of LDL. The dietary intake of polyunsaturated fatty acids (PUFA) was also inversely related to the degradation of native LDL by macrophages, but increased the rate at which oxidized LDL was degraded. Smoking and gender did not influence the rate of macrophage degradation of native or oxidized LDL. It is concluded that hypertriglyceridemia is associated with an increased macrophage degradation of LDL. This may represent a mechanism by which hypertriglyceridemia promotes atherosclerosis.

Adult↗

PubMed1994

Dystonia and dyskinesia in glutaric aciduria type I: clinical heterogeneity and therapeutic considerations.

Glutaric aciduria type I (GA-I) is an inborn error in the degradation of lysine, hydroxylysine, and tryptophan due to a deficiency of glutaryl-CoA dehydrogenase. Glutaric, 3-OH-glutaric, and glutaconic acids are excreted in the urine, particularly during intercurrent illness. The enzyme may be assayed in leukocytes, cultured fibroblasts and chorionic villi. Twelve new cases, 9 months-16 years of age, are reported, comprising all known cases of GA-I in Sweden and Norway. Ten had a severe dystonic-dyskinetic disorder, one had a mild hyperkinetic disorder, and one was asymptomatic. Two children died in a state of hyperthermia. Carnitine deficiency and malnutrition developed in patients with severe dystonia and dysphagia, which necessitated substitution and gastrostomy. A slowly progressive dyskinetic disorder developed in spite of adequate early dietary treatment in one subject. Macrocephaly was found in three. Computed tomography and magnetic resonance investigations in 10 showed deep bitemporal spaces in 7. Neuropsychological testing of 8 of 12 subjects demonstrated receptive language function to be superior to expressive language and motor function. Cognitive functions were obviously less affected than motor functions. A review of 57 pooled cases showed that a severe dystonic syndrome developed in 77%, a mild extrapyramidal syndrome in 10%, and 12% were asymptomatic. This disorder may pass undetected in the cerebral palsy and mentally retarded child and adult populations. Repeated urine examinations of organic acids in the urine and enzyme assay may be necessary to confirm GA-I.

Adolescent↗

PubMed1994

Quality-adjusted meta-analysis of the hypertension/coronary dilemma.

Primary investigators of randomized drug trials in hypertension were invited to rate quality of such trials. The intention of the survey was to ask if antihypertensive drug therapy reduces incidence of coronary heart disease (CHD) in hypertensive patients. Response was obtained for 7 of the 11 invited investigators, covering 69% of patients and 75% of CHD cases. Principal component analysis was used to construct a quality score based on answers to 12 questions along visual analog scales. The score correlated well with the answer to a global question of overall quality given by the raters. No systematic tendency toward favoring one's own trial could be demonstrated, therefore, all raters have contributed to the rating. The trials with the highest rated quality to answer the research question were Systolic Hypertension in the Elderly Program (SHEP), Australian National Blood Pressure Study, Medical Research Council, Veterans Administration, and European Working Party of Hypertension in the Elderly. The large Heart Detection and Follow-up Program (HDFP) trial was rated at 11th place among the trials with a score of < 40% of the SHEP. The small trials performed in the 1960s were placed at the bottom of the ranking list. Because SHEP is the only trial without diastolic hypertension, results were given with and without SHEP results. When incorporating the quality score into a meta-analysis of CHD outcome, results were dependent on whether SHEP was included or not. For diastolic hypertension only, the effect of therapy was estimated to be about 8% for all higher quality studies, whereas inclusion of the lower quality HDFP changed it to 14%. When isolated systolic hypertension trial was pooled with the others, no major relation to quality rating was observed. A 14% CHD preventive efficacy was established when pooling the three top quality studies. This stayed unchanged until HDFP at rank 11 was included raising this estimate to 16%. Inclusion of the two latest published trials in the elderly, the Medical Research Council trial of treatment of hypertension in older adults and the Swedish Trial in Old Patients with hypertension, did not change this overall estimate of 16% (standard error = 3.8%). It is concluded that if all randomized drug trials in hypertension had the same treatment efficacy, the estimated CHD prevention would be in the range of 15%. Subgroup analyses revealed no relationship to age, but a difference in efficacy was shown depending on whether the trials were performed in the United States or elsewhere. Also, patients at higher risk levels showed better benefit than lower risk patients.

Adult↗