Serum lipoprotein in active rheumatoid arthritis and other chronic inflammatory arthritides. I. Relativity to inflammatory activity.

Lipoprotein metabolism was investigated in 69 patients with untreated active rheumatoid arthritis (n = 48) and in seronegative spondylarthropathies (n = 21). The patients had high inflammatory activity as measured by erythrocyte sedimentation rate and C-reactive protein (CRP). Serum cholesterol and cholesterol levels in the very-low-density lipoprotein (VLDL), low-density lipoprotein, and high-density lipoprotein fractions were reduced by 20% to 30% compared with healthy controls; and triglyceride levels in VLDL and high-density lipoprotein were reduced by 10% to 30%. There were significant correlations between the inflammatory activity and certain lipoprotein lipids, ie, between CRP and VLDL triglycerides, VLDL cholesterol, and serum triglycerides. The fractional elimination rate (K2) measured by an intravenous fat tolerance test was 30% higher in the patients than in the controls despite reduced tissue lipoprotein lipase activities. There was correlation between CRP and the K2 value. These findings suggest that it is the degree of inflammatory activity that governs the altered lipoprotein metabolism in untreated active chronic inflammatory arthritides. The relationships between CRP and VLDL and between CRP and K2 suggest that the VLDL particles may be altered by inflammatory process, and that the increased elimination may take place through the "scavenger pathway."

Serum triglycerides are a risk factor for myocardial infarction but not for angina pectoris. Results from a 10-year follow-up of Uppsala primary preventive study.

At a follow-up 7-10 years after a health survey of men born in 1920-1924 in the municipality of Uppsala, 31 of the participants (n = 2322) had died from ischaemic heart disease (IHD). In response to a letter to all men alive in 1980, 106 men declared that they had had a myocardial infarction (MI) (verified or suspected). In 58 cases MI was verified from the hospital records. 28 other men had had typical central chest pain (angina pectoris) only. In another 20 men other diagnoses explained the chest pain for which they were treated in hospital. The health screening values for S-cholesterol and S-triglycerides, blood pressure and smoking habits were analysed in relation to the occurrence of IHD. In this prospective study, smoking, hypertension, S-cholesterol and S-triglycerides were identified as risk factors for fatal and non-fatal MI. The risk factor values were similar in subjects suffering from angina pectoris only to those in subjects who also developed ECG and/or transferase changes, with the exception of S-triglyceride concentration, which was normal in the group with angina pectoris. The subjects who had a fatal MI had a significantly higher blood pressure than those with non-fatal MIs, but otherwise these two groups did not differ. The results emphasize the importance of scrutinizing questionnaire data with regard to chest pain and of selection of end-points when risk factor patterns are described for cardiovascular diseases.

Metabolic effects of a change in antihypertensive treatment.

Twenty hypertensive men, aged 58 to 62 years, who had been treated with a combination of different drugs for many years, had their therapy changed in a stepwise manner to a combination of 50 mg of atenolol per day and 2 to 15 mg of prazosin per day. The effects of each change of treatment were assessed separately five to six months after the change. Serum lipids and high-density lipoprotein concentrations were determined, and an intravenous glucose tolerance test was performed at the start of the study and after each change. In the group in which therapy was changed from a diuretic to prazosin, serum cholesterol and triglyceride concentrations decreased significantly by 11 and 42 percent, respectively, but in the group in which therapy was changed from hydralazine to prazosin, there were no alterations in serum lipids or lipoproteins. The changes in therapy had no overall effects on glucose or insulin parameters evaluated with an intravenous glucose tolerance test. However, prazosin was associated with an increase in the fasting blood glucose level and a decrease in the peak insulin value after glucose injection, both of which were dose-related effects. The data indicate that the glucose turnover was at least as good after a switch from diuretic to prazosin treatment as before at lower insulin values. In those patients in whom therapy was switched from propranolol to 50 mg of atenolol per day, the serum triglyceride concentration decreased by about 10 percent, whereas in the group in which therapy was changed from 100 to 50 mg of atenolol per day, there were no serum lipid or lipoprotein alterations. The results show that a combination of 50 mg of atenolol per day and prazosin has metabolic advantages over combined diuretic and propranolol treatment. Such advantages may be of importance in the long-term treatment of hypertensive patients.

Risk factors for the development of hypertension: a 10-year longitudinal study in middle-aged men.

A group of middle-aged men (n = 2322) were examined at a health screening which included an intravenous glucose tolerance test (IVGTT) with insulin determinations, and were then re-examined approximately 10 years later. At the first survey, 19.6% of the participants had hypertension, defined as diastolic blood pressure greater than or equal to 95 mmHg or were receiving drug treatment for hypertension. At follow-up survey, the corresponding figure was 34.7%. Baseline blood pressures were the strongest predictors of future development of hypertension. In the absence of baseline blood pressures, fasting and late insulin levels at IVGTT, difference in body mass index between the surveys and heredity for hypertension were significant risk factors for hypertension. When a difference in diastolic blood pressure was used as an independent variable, the only significant risk factor was the difference in body mass index. Thus, insulin resistance (as reflected by fasting, late insulin levels and body mass index) seems to be related to the development of hypertension.

A comparison of the hypotensive and metabolic effects of 50 and 100 mg atenolol per day.

Nine patients who had been treated for hypertension for many years with atenolol in a dose of 100 mg/day took part in this 18-month study, during which the dosage alternated between 50 and 100 mg/day for two-month periods. Blood pressure, heart rate, serum triglycerides and cholesterol and high density lipoprotein (HDL) lipids were checked at the end of each period. Altogether 27 and 32 measurements were made at the 50 and 100 mg dose levels respectively. Heart rate was lower by three beats/min (p less than 0.05) at the higher dose, but blood pressure and serum lipids and HDL cholesterol were not significantly different at the two dose levels.

Unaltered lipoprotein and carbohydrate metabolism during treatment with contraceptive subdermal implants containing ST-1435.

Nine healthy, fertile women were treated for six months with subdermal contraceptive implants of two different sizes containing a potent progestogen, ST-1435. Lipoprotein cholesterol and triglyceride concentrations were not influenced by the treatment. Similarly, the main apolipoproteins in low- and high-density lipoproteins were not changed, which further supports the interpretation that the lipoprotein metabolism is not affected by this type of treatment. An oral glucose tolerance test (OGTT) including insulin determinations was performed in five of the volunteers with the largest implants. Blood glucose and insulin concentrations during the OGTT remained unchanged during treatment, indicating that the treatment with ST-1435 did not affect carbohydrate metabolism.

Pharmacodynamics of a contraceptive vaginal ring releasing norethindrone and estradiol: ovarian function, bleeding control and lipoprotein patterns.

A new contraceptive vaginal ring (CVR), releasing approximately 700 micrograms of norethindrone (NET) and approximately 140 micrograms of estradiol (E2) daily, was studied in eleven women for a total of 61 21-day cycles. Ovarian function, as judged by plasma progesterone (P) and E2 levels, and plasma NET levels were studied by weekly blood samples in 30 cycles. The lipoprotein pattern was studied before, after two and six months of treatment and one month after completed treatment. The CVR gave rise to stable plasma NET levels which however varied considerably between individuals. Signs of luteal activity/ovulation were encountered in 4/30 cycles, all in subjects with the lowest NET plasma levels. E2 levels above 250 pmol/l, indicating follicular activity, were encountered in 22/30 cycles. Breakthrough bleeding and spotting appeared in 40/61 cycles and in 12 per cent of the treatment days. Bleeding control was significantly better in the same subjects when using a CVR releasing levo-Norgestrel and E2. Serum and HDL cholesterol concentrations decreased significantly by 10-12 per cent during treatment. The ratios between apolipoproteins A-I and A-II on one hand and HDL cholesterol on the other increased significantly and the ratio apolipoprotein A-I:A-II decreased significantly, indicating a change in the lipoprotein composition. These changes are qualitatively similar but quantitatively not as pronounced as with the more extensively studied 1-Ng/E2 CVR. The difference in clinical performance and in the effects on the lipoprotein pattern between the presently studied CVR and the 1-Ng/E2 CVR is most likely the result of not using equipment doses of gestagen in the CVRs.

PIP: A new contraceptive vaginal ring (CVR), releasing approximately 700 mcg of norethindrone (NET) and approximately 140 mcg estradiol (E2) daily, was studied in 11 women for a total of 61 21-day cycles. Ovarian function, as judged by plasma progesterone (P) and E2 levels, and plasma NET levels were studied by weekly blood samples in 30 cycles. The lipoprotein pattern was studied before, after 2 and 6 months of treatment, and 1 month after compledted treatment. The CVR gave rise to stable plasma NET levels which, however, varied considerably between individuals. Signs of luteal activity/ovulation were encountered in 4 of 30 cycles, all in subjects with the lowest NET plasma levels. E2 levels above 250 pmol/1, indicating follicular activity, were encountered in 22 of 30 cycles. Breakthrough bleeding and spotting appeared in 40 of 61 cycles and in 12% of the treatment days. Bleeding control was significantly better in the same subjects when using a CVR releasing levonorgestrel and E2. Serum and high density lipoprotein cholesterol (HDL) concentrations decreased significantly by 10-12% during treatment. The ratios between apolipoproteins A-I and A-II on the one hand and HDL cholesterol on the other increased significantly and the ratio of apolipropotein A-I: A-II decreased significantly, indicating a change in the lipoprotein composition. These changes are qualitatively similar but quantitatively not as pronounced as with the more extensivley studied levonorgestrel/E2 CVR. the difference in clinical performance and in the effects on the lipoprotein pattern between the presently studied CVR and the levonorgestrel/E2 CVR is most likely the result of not using equipotent doses of gestagen in the CVRs.

Sensitivity to insulin during treatment with atenolol and metoprolol: a randomised, double blind study of effects on carbohydrate and lipoprotein metabolism in hypertensive patients.

OBJECTIVE: To compare the effects of metoprolol and atenolol on carbohydrate and lipid metabolism and on insulin response to an intravenous glucose load. DESIGN: Randomised, double blind, double dummy, controlled crossover trial. SETTING: University Hospital, Uppsala, Sweden. PATIENTS: 60 Patients with primary hypertension (diastolic blood pressure when resting supine 95-119 mm Hg on at least two occasions during four to six weeks of treatment with placebo) randomised to receive either metoprolol (n = 30) or atenolol (n = 30) during the first treatment period. INTERVENTIONS: Placebo was given for a run in period of four to six weeks. Metoprolol 100 mg twice daily or atenolol 25 mg twice daily was then given for 16 weeks. The two drugs were then exchanged and treatment continued for a further 16 weeks. END POINT: Evaluation of effects of treatment with metoprolol and atenolol on glucose, insulin, and lipid metabolism and glucose disposal mediated by insulin. MEASUREMENTS AND MAIN RESULTS: Reduction of blood pressure was similar and satisfactory during treatment with both drugs. Glucose uptake mediated by insulin was measured during a euglycaemic hyperinsulinaemic clamp to evaluate patients' sensitivity to insulin. Glucose uptake decreased from 5.6 to 4.5 mg/kg/min when patients were taking metoprolol and from 5.6 to 4.9 mg/kg/min when they were taking atenolol. Both drugs caused a small increase in fasting plasma insulin and blood glucose concentrations and glycated haemoglobin concentration. Despite decreased sensitivity to insulin the increase in insulin concentration in response to an intravenous glucose tolerance test was small, suggesting inhibition of release of insulin. Very low density lipoprotein and low density lipoprotein triglyceride concentrations were increased with both drugs and high density lipoprotein cholesterol concentration was decreased. Low density lipoprotein cholesterol concentration was not affected. CONCLUSIONS: Long term use of metoprolol and atenolol causes metabolic abnormalities that may be related to the increased incidence of diabetes in patients with hypertension who are treated pharmacologically. These results may help to explain why the two drugs have failed consistently to reduce the incidence of coronary heart disease in several large scale studies.

Do antihypertensive drugs precipitate diabetes in predisposed men?

OBJECTIVE: To evaluate the influence of antihypertensive treatment and metabolic characteristics on the development of diabetes mellitus in middle aged men. DESIGN: Prospective study over an average of nine years. SETTING: Community based health survey of middle aged men carried out at the University of Uppsala. SUBJECTS: Seventy three hypertensive men aged 49-54 and 65 normotensive controls matched for body mass index, glucose disappearance rate (k value) at an intravenous glucose tolerance test, and serum triglyceride and cholesterol concentrations. INTERVENTIONS: Hypertensive group was treated with beta blockers, thiazides, hydralazine, or combinations of these drugs. Treatment was not randomised. MEASUREMENTS AND MAIN RESULTS: Intravenous glucose tolerance, fasting blood glucose and serum lipid and insulin concentrations, body weight and height, three skinfold measurements, and blood pressure were recorded both during an initial health screening survey in 1970-3 and at a follow up survey in 1980-3. In the period between the two surveys 12 hypertensive men and two controls developed diabetes. Review of values obtained at the initial survey showed that the hypertensive men who developed diabetes or impaired glucose tolerance could be distinguished from those hypertensive men who did not by virtue of a higher fasting serum insulin concentration (26.1 v 15.2 mU/l (confidence interval of difference -15.2 to -6.2)), a lower peak serum insulin concentration (78.9 v 94.3 mU/l (confidence interval of difference -1.1 to 41.1)), and a lower k value (1.29 v 1.68 (confidence interval of difference -0.02 to 0.68)). The insulin index (peak insulin concentration divided by fasting insulin concentration), however, decreased significantly in the hypertensive men over time irrespective of whether they developed diabetes but did not change in the controls. Furthermore, the serum triglyceride concentration increased in the treated group and decreased in the controls. CONCLUSION: A severalfold difference in the incidence of diabetes between treated hypertensive and non-treated, normotensive men may be a consequence of the treatment, which may be particularly deleterious in men predisposed to diabetes.

Serum lipid changes during acitretin (etretin) treatment of psoriasis and palmo-plantar pustulosis.

The effects of acitretin (free acid of etretinate) on the serum lipoprotein pattern and on the fat elimination in serum of 8 patients with psoriasis and 4 with palmo-plantar pustulosis were studied. The drug was given for 12 weeks; the average daily dose was 40 mg. Lipoprotein analyses and an intravenous fat tolerance test (IVFTT) were performed on three occasions (before, after 8 weeks' treatment, as well as 8 weeks after the end of the treatment). Acitretin increased the triglyceride concentration of the very low density lipoproteins by about 50% (p less than 0.02) and reduced the cholesterol of the high density lipoproteins significantly (p less than 0.001), leading to an increased low density/high density lipoprotein cholesterol ratio (p less than 0.02). The IVFTT indicated a lowering of the fat elimination capacity. All changes reverted to the original values after an 8-week wash-out period. The data suggest that the effects of acitretin on the lipoprotein metabolism resemble those of etretinate and isotretinoin.

Lack of effect of a purified bran preparation in men with low HDL cholesterol.

In 21 men who had been on a lipid-lowering diet for several years, the serum triglyceride and cholesterol levels had become normal on that treatment. In spite of this they all had low levels of cholesterol in the high density lipoproteins (HDL). In an effort to normalize this they were given a purified concentrated bran product (FiberformR, 3.5 g) three times daily for 6 weeks. The cross-over study was double-blind, placebo-controlled, and with a wash-out period between the treatment periods. There were no statistically significant changes in body weight, serum triglycerides and cholesterol or HDL triglycerides and cholesterol in association with the bran treatment. It is concluded that wheat bran in moderately large doses that are convenient to take does not offer a therapeutic alternative for increasing subnormal HDL cholesterol levels in normocholesterolaemic men.

Serum lipoprotein and lipoprotein lipase in overweight, type II diabetics during and after supplemented fasting.

Poorly controlled, obese, Type II diabetics were studied before, during, and 3 months after a weight reduction program that used supplemented fasting (200 kcal or 0.9 MJ/day). During fasting, the very low density lipoprotein (VLDL) triglycerides (TG) decreased, as did the adipose tissue lipoprotein lipase (AT-LPLA) and skeletal muscle lipoprotein lipase (SM-LPLA) activities. Three months later VLDL TG remained low (-59%), while high density lipoprotein cholesterol was higher (+11%) and blood glucose control improved compared with values on admission. The fractional removal rate (K2) at the i.v. fat tolerance test (IVFTT) and the SM-LPLA were unchanged, while AT-LPLA (expressed per gram of wet weight, but not as whole-body AT-LPLA) increased by 25%. There were no significant correlations between AT-LPLA and the lipoprotein TG concentrations or K2-IVFTT, although there were significant positive correlations between SM-LPLA and K2-IVFtt, both on admission and after body weight stabilization. This may indicate that SM-LPLA is more directly related to the capacity to remove lipoprotein TG, at least in obese diabetic patients. K2-IVFTT was inversely correlated to the VLDL TG and cholesterol concentrations both before and 3 months after fasting. Because both SM-LPLA and K2-IVFTT were unchanged after body weight reduction, the change in VLDL TG may be mainly due to a reduced rate of lipoprotein synthesis.

Effects of dietary supplementation with n-6 and n-3 long-chain polyunsaturated fatty acids on serum lipoproteins and platelet function in hypertriglyceridaemic patients.

Twenty-seven patients with hypertriglyceridaemia were given dietary supplementation either with evening primrose oil rich in gammalinolenic acid (GLA, 18:3 n-6) (n = 13) or a marine oil concentrate containing n-3 fatty acids (n = 14) in a double-blind cross-over design during 8 + 8 weeks with olive oil as placebo. During GLA supplementation, increases in GLA and dihomogammalinolenic acid (20:3 n-6) were found in plasma lipid esters and platelet phospholipids, whereas platelet function and serum lipoproteins were unaffected. During supplementation with n-3 fatty acids there was a significant decrease in triglycerides in all lipoprotein fractions with a slight increase in high density lipoprotein and low density lipoprotein cholesterol. A marked increase in the long-chain n-3 fatty acids was found both in plasma and platelets, mainly at the expense of the n-6 fatty acids. No pronounced effects on platelet reactivity could be demonstrated. Our results confirm a triglyceride-lowering effect of n-3 fatty acids, whereas no such effect of GLA could be demonstrated.

Metabolic profile in obese women with the polycystic ovary syndrome.

Nine obese women with oligo- or ameno-rrhoea, all with clinical and endocrinological signs of polycystic ovary syndrome (PCO) were submitted to metabolic studies. Their mean weight was 96 kg and their mean plasma testosterone concentration was 3.5 nmol/l. A group of nine obese, regularly menstruating women of similar age and degree of obesity (mean body weight 102 kg) served as controls. Their mean testosterone concentration was 1.9 nmol/l. The high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations in plasma were significantly lower in women with PCO than in control women. Furthermore, in the whole group the testosterone level showed significant inverse relationships to HDL-cholesterol (r = -0.64; P less than 0.01) and apo A-I (r = -0.59; P less than 0.01). The lipoprotein lipase activity (LPLA) in adipose tissue was lower in the women with PCO than in the control group with levels similar to those found in adipose tissue in men. There was an inverse relationship between the testosterone concentration in plasma and LPLA in adipose tissue (r = -0.51; P less than 0.05). The fat cells were of similar size at different regions in the women with PCO but showed marked differences in the control subjects who had much larger cells at the femoral than the abdominal site. The results show that the hyperandrogenism in PCO affects adipose tissue LPLA which could explain the lower HDL cholesterol values in women with PCO.

Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension.

The aim of this study was to determine whether insulin sensitivity measured by the euglycaemic insulin clamp technique is lower in patients with primary hypertension than in matched healthy control subjects, and whether this sensitivity was affected after 12 weeks of antihypertensive treatment with the alpha 1-adrenoceptor blocking drug prazosin. Twelve moderately obese normoglycaemic patients (four men), with hypertension not previously treated with pharmacological agents and diastolic blood pressure above 100 mm Hg, and 12 healthy matched control subjects participated. Supine blood pressure decreased 12/5 mm Hg (p less than 0.01) and standing blood pressure 14/9 mm Hg (p = 0.001) during prazosin treatment (mean dosage 5.3 +/- 1.6 mg/day (SD]. During euglycaemic insulin clamp studies the control subjects showed a higher mean glucose uptake than the untreated hypertensive patients (7.5 +/- 1.0 and 5.8 +/- 1.9 mg.kg b.w.-1.min-1, respectively, p less than 0.01). During prazosin treatment there was no significant difference between the hypertensive patients and the control subjects in this respect (6.6 +/- 2.8 and 7.5 +/- 1.0, respectively, p = 0.21). During prazosin treatment, however, the disappearance rate of glucose decreased during the intravenous glucose tolerance test (from 1.7 +/- 0.9 to 1.3 +/- 0.6, p less than 0.02) and the area under the glucose concentration-time curve decreased by 38% (from 473 +/- 119 to 294 +/- 99, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The primary preventive study in Uppsala. Fatal and non-fatal myocardial infarction during a 10-year follow-up of a middle-aged male population with treatment of high-risk individuals.

A health survey of middle-aged men was carried out in 1970-73 in the municipality of Uppsala. Subjects with hypertension, hyperlipidaemia, reduced glucose tolerance, and smokers were invited to join various therapy groups. By 1980 this multifactorial intervention programme had thus been running for 10 years. This report describes the results of a follow-up undertaken to evaluate the efficacy of the programme. The annual rate of fatal myocardial infarction (MI) was lower among the participants (n = 2322) in the health examination as well as among participants and non-participants (n = 446) combined than among the male Swedish population of the same age (162 and 187 compared with 296 per 100 000 men, respectively). The annual rate of non-fatal MI among participants and non-participants combined was 295 per 100 000 men, which is lower than in other Swedish cities. In the hypertensive group (n = 126), six men had fatal and seven non-fatal MI. These 13 men had higher blood pressures (BPs) from the start than the other hypertensives. In addition, their BP reduction was smaller than in a control group randomly selected among the hypertensive subjects. In the hyperlipidaemic treatment group (n = 363) there were eight fatal and 10 non-fatal MIs. Nine of these events occurred in individuals who had dropped out from therapy. It is suggested that the low total mortality and the low rates of fatal and non-fatal MI in this middle-aged male population may be related to the multifactorial intervention programme, as the incidences were also low among the treated high-risk groups.

High muscle lipoprotein lipase activity in thyrotoxic patients.

Serum lipoprotein metabolism was studied in 7 women before and after treatment for thyrotoxicosis. Of the lipoprotein lipids, the triglyceride concentration in the low density lipoproteins (LDL) (P less than 0.01) and the cholesterol concentration in both LDL (P less than 0.01) and the high density lipoproteins (HDL) (P less than 0.05) increased significantly during treatment. These changes were accompanied by increases in apolipoprotein B (P less than 0.01) and A-I (P less than 0.05) concentrations in serum. Muscle lipoprotein lipase activity (LPLA) was increased in the thyrotoxic state by 46% (P less than 0.05) compared with the value after the patients had been rendered euthyroid, but adipose tissue LPLA was only 8% higher (ns) in the former state. The capacity for removal of exogenous fat, as determined by the fractional elimination rate (K2) at an iv fat tolerance test, was 23% higher in the thyrotoxic than in the euthyroid state (ns). It is suggested that the increase in muscle LPLA in the thyrotoxic state may be due to enhanced sensitivity to catecholamines. This may contribute to the increased capacity for plasma triglyceride turnover in thyrotoxicosis.

Alcohol intemperance and sudden death.

Ten years after a health screening examination was offered to 50 year old men 32 of the 2322 participants and 12 of the 454 nonparticipants had died of ischaemic heart disease. Of these, 26 and 11 respectively had suffered sudden death, for which necropsy was performed. Half of the men who had died suddenly had been registered for alcohol intemperance up to 1973, which was four times the prevalence of such registrations in the general population. Registration at both the Swedish Temperance Board and the Bureau of Social Services was associated with an odds ratio of 3.74 for sudden death as compared with not being registered at either. Logistic analysis including the classical risk factors for ischaemic heart disease together with registration for alcohol intemperance and at the Bureau of Social Services showed only the two types of registration and systolic blood pressure to be independent risk factors. On the other hand, there was no overrepresentation of subjects entered in the registers among those surviving a myocardial infarction. For non-fatal myocardial infarction blood pressure and serum triglyceride concentration were significant risk factors and serum cholesterol concentration, smoking, and body mass index probable risk factors; the two types of registration were not independent risk factors. Alcohol intemperance is strongly associated with an increased risk of sudden death after myocardial infarction.

A comparison of the effects of bisoprolol and atenolol on lipoprotein concentrations and blood pressure.

Forty-two patients (28 men, 14 women, age range 27-65 years) with newly discovered mild to moderate hypertension were randomly allocated to treatment with either bisoprolol or atenolol for a double-blind comparison of these two beta 1-adrenoceptor blocking drugs. Two doses of each drug (10 and 20 mg/d for bisoprolol and 50 and 100 mg/d for atenolol) were given, each dose for a 3-month period, the dose to be given first being decided by random allocation of the patients. During the second 3-month period, the patient received the alternative dose. After treatment for 6 and 12 weeks with each dose, the blood pressure, heart rate, and lipoprotein concentrations were checked. Bisoprolol treatment (both 10 and 20 mg) resulted in a decrease in blood pressure in the supine position from 154/100 to 138/89 mm Hg; and atenolol treatment resulted in decreases from 161/102 to 145/90 mm Hg (50 mg/d) and 146/91 mm Hg (100 mg/d). The drugs and doses did not differ in their effect. The triglyceride content in very low density lipoproteins (VLDL) increased during treatment with bisoprolol (10 mg/d) from 1.04 to 1.31 mmol/l (p less than 0.05); during treatment with atenolol (100 mg/d) it increased from 0.90 to 1.14 mmol/l (p less than 0.05). The cholesterol content in low density lipoproteins did not change, but that in high density lipoproteins (HDL) decreased during treatment with both drugs (from 1.22 to 1.10 mmol/l with bisoprolol 20 mg/d, p less than 0.01: and from 1.21 to 1.13 mmol/l with atenolol 100 mg/d, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)