Effects of antihypertensive drugs on coronary artery disease risk: a meta-analysis

1. The effects of antihypertensive drugs on lipids may also influence their effect on coronary artery disease (CAD). However, the clinical significance of these effects and the extent to which they persist during long-term therapy is uncertain. 2. We performed a meta-analysis on 23 randomized trials published between 1988 and 1994 that compared the effects of atenolol, celiprolol (a beta-blocker with beta 2-adrenoceptor intrinsic sympathomimetic activity), enalapril, nifedipine and doxazosin on plasma cholesterol, low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides and blood pressure (BP). 3. Predicted changes in CAD risk were calculated by incorporating the results for these parameters into the Framingham equations. 4. While there were no differences in antihypertensive efficacy between the drugs, atenolol significantly (P < 0.05) reduced HDL-C and increased total cholesterol, LDL-C and triglycerides compared with celiprolol, enalapril, doxazosin and nifedipine. 5. The magnitude of the effects on lipids was not significantly influenced by the duration of therapy (up to 3 years for atenolol and doxazosin and up to 2 years for celiprolol). 6. The improvement in Framingham equation point scores (systolic BP formula) was significantly (P < 0.05) less for atenolol (-0.54; confidence intervals (CI) -0.29-(-0.78)) than for celiprolol (-1.69; CI -0.68-2.70), doxazosin (-1.67; CI -1.11-(-2.23)), enalapril (-1.43; CI 0.23-(-3.07)) and nifedipine (-1.91; CI -1.22-(-2.59)). Similar results were obtained for the Framingham diastolic BP formula. 7. These results suggest that the adverse effects of atenolol ]on plasma lipids do not improve with prolonged therapy and are theoretically great enough to reduce its efficacy in reducing CAD by approximately two thirds compared with antihypertensive drugs that do not adversely affect plasma lipids. However it must be emphasized that these are theoretical effects. In order to determine the actual differences between these drugs on CAD end points, studies using these end points are required.     

Quality of life before and during antihypertensive treatment: a comparative study of celiprolol and atenolol

BACKGROUND: The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of the prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. OBJECT: We compared the effect on quality of life of a standard cardioselective beta-blocker atenolol to the effect of celiprolol as a representative of a new class of selective beta-blockers with vasodilatory properties. One-hundred-thirty-two patients with mild to moderate hypertension were eligible to enter a 28-week double-blind parallel-group study, consisting of a 4-week run-in period on placebo and a 24-week period on dosage-adjusted treatment with either atenolol or celiprolol. RESULTS: Both systolic and diastolic blood pressure were assessed, as was quality of life perception by a selected test battery including the Quality of Life Questionnaire of Bulpitt and Fletcher [1990]. During celiprolol treatment, supine blood pressure fell from 167/101 (range 120-200/95-116) to 150/92 mm Hg (p < 0.0001). This antihypertensive effect was at least as good with celiprolol as with atenolol. Quality of life perception was comparable for the 2 drugs, although some adverse effects were more frequent during atenolol than during celiprolol, particularly after prolonged treatment. Also patient compliance was better for celiprolol than for atenolol. CONCLUSIONS: Our results show that the selective beta-blocker with vasodilatory property celiprolol is at least as effective as atenolol and that it has additional advantage in terms of enhancement of some quality of life variables.     

Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group

BACKGROUND: Previous studies often of short duration have raised concerns that antihypertensive therapy with diuretics and beta-blockers adversely alters levels of other cardiovascular disease risk factors. METHODS: The Systolic Hypertension in the Elderly Program was a community-based, multicenter, randomized, double-blind, placebo-controlled clinical trial of treatment of isolated systolic hypertension in men and women aged 60 years and older. This retrospective analysis evaluated development of diabetes mellitus in all 4736 participants in the Systolic Hypertension in the Elderly Program, including changes in serum chemistry test results in a subgroup for 3 years. Patients were randomized to receive placebo or treatment with active drugs, with the dose increased in stepwise fashion if blood pressure control goals were not attained: step 1, 12.5 mg of chlorthalidone or 25.0 mg of chlorthalidone; and step 2, the addition of 25 mg of atenolol or 50 mg of atenolol or reserpine or matching placebo. RESULTS: After 3 years, the active treatment group had a 13/4 mm Hg greater reduction in systolic and diastolic blood pressure than the placebo group (both groups, P<.001). New cases of diabetes were reported by 8.6% of the participants in the active treatment group and 7.5% of the participants in the placebo group (P=.25). Small effects of active treatment compared with placebo were observed with fasting levels of glucose (+0.20 mmol/L [+3.6 mg/dL]; P<.01), total cholesterol (+0.09 mmol/L [+3.5 mg/dL]; P<.01), high-density lipoprotein cholesterol (-0.02 mmol/L [-0.77 mg/dL]; P<.01) and creatinine (+2.8 micromol/L [+0.03 mg/dL]; P<.001). Larger effects were seen with fasting levels of triglycerides (+0.9 mmol/L [+17 mg/dL]; P<.001), uric acid (+35 micromol/L [+.06 mg/dL]; P<.001), and potassium (-0.3 mmol/L; P<.001). No evidence was found for a subgroup at higher risk of risk factor changes with active treatment. CONCLUSIONS: Antihypertensive therapy with low-dose chlorthalidone (supplemented if necessary) for isolated systolic hypertension lowers blood pressure and its cardiovascular disease complications and has relatively mild effects on other cardiovascular disease risk factor levels.     

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.     

Total cholesterol and high-density lipoprotein levels as risk factors for increased intraocular pressure

PURPOSE: To determine whether high-density lipoprotein and total cholesterol levels were risk factors for increased intraocular pressure in patients with chronic open-angle glaucoma or ocular hypertension. METHODS: We measured total cholesterol, high-density lipoprotein, and total cholesterol/high-density lipoprotein ratio in 25 patients with open-angle glaucoma or ocular hypertension who had taken no glaucoma medications for four weeks. We individually matched these patients to 25 control subjects who had no history of open-angle glaucoma or ocular hypertension, on the basis of age, race, gender, and history of vascular disease or diabetes mellitus. RESULTS: We found no statistical difference in the high-density lipoprotein (P = .702) or total cholesterol (P = .177) levels or total cholesterol/high-density lipoprotein ratio between groups (P = .178, paired t test). CONCLUSION: This study indicates that increased high-density lipoprotein and total cholesterol levels are not risk factors for increased intraocular pressure.     

Metabolic and endocrine effects of the desogestrel-containing oral contraceptive Mircette

OBJECTIVE: The purpose was to evaluate the metabolic effects of Mircette (brand of desogestrel/ethinyl estradiol and ethinyl estradiol), a low-estrogen, desogestrel-containing oral contraceptive. STUDY DESIGN: Women taking Mircette were evaluated to determine its effects on lipid profiles (n = 74), carbohydrate metabolism (n = 25), and endocrine parameters (n = 53). RESULTS: During cycles 3 and 6 of Mircette treatment, changes from baseline included mean increases in serum triglycerides and very low-density lipoprotein cholesterol ranging between 50% and 60%. Smaller mean increases were observed at these time points in high-density lipoprotein cholesterol subfraction 2 (range between 17% and 25%), total cholesterol (<10%), high-density lipoprotein cholesterol (range between 10% and 15%), and high-density lipoprotein cholesterol subfraction 3 (range between 9% and 13%), with only nominal changes (<6%) in low-density lipoprotein cholesterol and lipoprotein. Patients receiving Mircette showed no mean changes in fasting plasma glucose or serum insulin levels but did have modest increases in glucose and insulin levels after a glucose challenge. Mircette treatment suppressed follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and progesterone to levels consistent with inhibition of ovulation and increased concentrations of thyroid- and cortisol-binding globulins. CONCLUSIONS: Overall, Mircette treatment was associated with expected effects on the pituitary-ovarian axis, triglycerides, and serum binding proteins; a modest decline in glucose tolerance; and a favorable effect on lipid profiles as a result of increases in total high-density lipoprotein cholesterol and high-density lipoprotein cholesterol subfraction 2 in the absence of changes in total cholesterol or low-density lipoprotein cholesterol.     

Leisure, home, and occupational physical activity and cardiovascular risk factors in postmenopausal women. The Postmenopausal Estrogens/Progestins Intervention (PEPI) Study

OBJECTIVE: To examine the associations between self-reported leisure, home, and occupational physical activity and selected cardiovascular risk factors. METHODS: A cross-sectional analysis of baseline data from the Postmenopausal Estrogen/Progestins Intervention Trial was performed in 851 women aged 45 to 64 years. Outcomes were levels of high-density lipoprotein cholesterol, insulin (2 hours after challenge), fibrinogen, systolic blood pressure. Race-stratified models were adjusted for age, smoking, alcohol, and previous noncontraceptive estrogen use. Models were also run with body mass index as an additional covariate. RESULTS: In white women, leisure physical activity was positively associated with levels of high-density lipoprotein cholesterol (P = .001) and inversely associated with levels of insulin (P = .04) and fibrinogen (P = .02). Compared with high-density lipoprotein cholesterol levels in the inactive and light leisure physical activity groups, moderate (P < .001) and heavy (P = .004) leisure activities were associated with higher high-density lipoprotein cholesterol levels. High-density lipoprotein cholesterol levels in the heavy leisure physical activity group were significantly higher than those in the moderate group (P = .01). Compared with lesser levels of leisure physical activity, significantly lower mean values of fibrinogen (P = .02) and insulin (P = .01) were associated with the highest-intensity leisure physical activity. Home physical activity was positively related to high-density lipoprotein cholesterol level (P = .01); relative to lower levels of home physical activity, the heavy home physical activity group demonstrated significantly higher mean high-density lipoprotein cholesterol levels. The effects of leisure and home physical activities were independent of each other. systolic blood pressure did not vary by leisure, occupational, or home physical activity. CONCLUSION: The unique relationships between type of physical activity and cardiac risk factors underscore the necessity of including multiple domains of activity in epidemiologic studies of epidemiologic studies of physical activity in women.     

The relationship between blood pressure and biochemical risk factors in a general population

The relationship between blood pressure, ponderal index, sex, blood glucose, haemoglobin, serum uric acid, calcium cholesterol and creatinine, and albumin has been examined in 698 subjects aged between 44 and 49 years from the register of a group general practice. Sixty per cent of the variation in systolic pressure could be explained by statistically significant associations with diastolic pressure, sex, blood glucose, serum calcium, and cholesterol. The diastolic blood pressure (not corrected for systolic pressure) was significantly related only to ponderal index, haemoglobin in men, and cholesterol in women. Pulse pressure was also positively related to the risk factors blood glucose, serum cholesterol, and calcium. The possibility is discussed that one or more of these variables reduce aortic compliance and that the serum calcium contributes to this end. Diastolic, but not systolic pressure, had a prime association with relative weight, obesity being only basically associated with an increase in diastolic pressure.     

Risk factors associated with alterations in carotid intima-media thickness in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis

BACKGROUND: The possibility that calcium antagonists exert an anti-atherosclerotic action at least partly independently of the blood-pressure-lowering effect is supported by results of a large number of experimental studies and can now be investigated by quantitative B-mode ultrasound imagining of the carotid artery walls. DESIGN: The European Lacidipine Study on Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multinational trial comparing effects of 4-year treatment based on the long-acting, highly lipophilic calcium antagonist lacidipine with those of treatment based on the beta-blocker atenolol on the development of carotid artery wall alterations in patients (aged 45-75 years) with mild-to-moderate hypertension (systolic blood pressure 150-210 mmHg and diastolic blood pressure 95-115 mmHg). While the intervention study is progressing, this article summarizes baseline data obtained from the whole cohort of 2259 patients randomly allocated to treatment. METHODS: Baseline ultrasound data were obtained from two replicate examinations performed shortly before random allocation to treatment by certified sonographers at 23 referral centres and read at the ultrasound coordinating centre at the Wake Forest University School of Medicine. Intima-media thickness was measured at up to 12 different sites in the carotid artery tree and expressed as the mean of the maxima at these sites (Mmax), the mean of the maxima at four sites in the distal common carotid artery and bifurcation (CBMmax) and the maximum intima-media thickness (Tmax). Baseline demographic and clinical measurements were performed by investigators in 410 peripheral clinical units and 24 h ambulatory blood pressure monitorings read and validated by members of a centralized unit at the University of Milan. The statistical analysis centre at the Technische Universit?t München received and analysed all baseline data, by calculating means +/- SD, medians and ranges and performing correlation (Spearman correlation coefficients) and multiple regression analyses. RESULTS: Prevalence of carotid artery wall alterations among the hypertensive patients randomly allocated to treatment in the ELSA was very high: 82% had Tmax > or = 1.3 mm ('plaques' according to protocol) and 17% had Tmax > or = 1.0 and < 1.3 mm ('thickening'), with a median of two plaques per patient. We found significant correlations between ultrasound measurements and the following demographic and clinical variables: age, sex, systolic blood pressure and pulse pressure (both clinic and ambulatory), concentrations of total, high-density lipoprotein and low-density lipoprotein cholesterol and triglycerides, smoking habit and duration of hypertension. We found no significant correlation to diastolic blood pressure and glucose concentration. A multiple regression analysis indicated significant variables in the following rank order: age, 24 h ambulatory pulse pressure, sex, low-density lipoprotein cholesterol concentration, triglyceride concentration, smoking and clinic systolic blood pressure. CONCLUSIONS: Analysis of baseline data from the ELSA has shown that there is an extremely marked prevalence of carotid artery wall alterations among mild-to-moderate, middle-aged hypertensive patients. In addition to age, systolic blood pressure and pulse pressure, particularly if they are accurately measured by ambulatory monitoring, play a major role, somewhat greater than those of sex, low-density lipoprotein cholesterol concentration and smoking, in influencing intima-media thickness.     

Inositolphosphoglycans and diacyglycerol are possible mediators in the glycogenic effect of GLP-1(7-36)amide in BC3H-1 myocytes

The objective of this study is to examine the influence of lipid profiles and blood pressure on the development of microvascular complications in adolescents with insulin-dependent diabetes mellitus (IDDM) in a matched pairs study. Patients with early background retinopathy (n = 21) or microalbuminuria (n = 15) and their respective statistical twins participated in the study. Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting triglycerides, glycosylated haemoglobin A1c (HbA1c), and systolic and diastolic blood pressure during 3 years prior to the development of early background retinopathy or incipient nephropathy were examined. The multivariate discriminant analysis demonstrated glycaemic control and HDL cholesterol to be the most important variables related to the development of retinal lesions (84% correctness), and diastolic blood pressure to be associated with microalbuminuria (57% correctness). In addition to poor glycaemic control, different factors seem to be important for the early retinal or renal lesions of juvenile IDDM.     

Effects of bunazosin and atenolol on serum lipids and apolipoproteins in a randomised trial

The effects of bunazosin and atenolol on serum lipids and lipoproteins after 6 months of treatment were compared in this multicentric, double-blind, randomised trial. A total of 174 patients with mild to moderate essential hypertension from 15 hospitals in Germany and Poland was included in the study. Eighty-seven were treated with the alpha-receptor blocker bunazosin and the same number with the beta-blocker atenolol. Systolic and diastolic blood pressure decreased significantly in both groups, whereas only atenolol decreased pulse rate. In the bunazosin group HDL-cholesterol was significantly increased after 6 months of treatment, whereas all other analysed parameters remained unchanged. In the atenolol group total cholesterol, LDL-cholesterol, total triglycerides, apolipoprotein E, VLDL-cholesterol and VLDL-triglycerides were significantly increased after 6 months of therapy. There was a significant difference between bunazosin and atenolol for total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, VLDL-triglycerides and apolipoprotein B levels. As a consequence, there was a significant difference in the atherogenic index of both groups. We conclude that bunazosin is favorable in the treatment of high blood pressure, because the coronary risk is not negatively influenced as shown for atenolol.     

Oral contraceptives and rheumatoid arthritis: results from a primary care-based incident case-control study

The influence of celiprolol (beta1- and beta2-adrenoceptor partial agonist), propranolol (beta1- and beta2-adrenoceptor antagonist), and atenolol (beta1-adrenoceptor antagonist) on heart-rate variability (HRV) was assessed from Holter records in 12 normal volunteers. A combination of summary statistics and nonlinear procedures was used to assess HRV and autonomic balance. Under double-blind and randomised conditions (Latin-square design), subjects received placebo, celiprolol (200 and 800 mg), propranolol (160 mg), atenolol (50 mg), and combinations of these agents. Single oral doses of medication (at weekly intervals) were administered at 22:30 h with sleeping heart rates (HRs) recorded overnight. Compared with placebo, celiprolol (200 and 800 mg) increased the sleeping HR, the HR effect of celiprolol was different from the bradycardia after propranolol, 160 mg, and atenolol, 50 mg. Dose-response effects on HR with celiprolol were evident in the presence of atenolol, unlike those with propranolol that abolished the HR increase between celiprolol, 200 mg and 800 mg. These data were consistent with beta1-selective adrenoceptor agonism with 200 mg but agonism at both the beta1- and beta2-adrenoceptor with celiprolol, 800 mg. The action of the drugs on short-term HRV indices (rMSSD and pNN50) closely followed their effects on HR. The longer-term HRV indices (global SD, SDANN) were reduced by celiprolol but increased by propranolol and atenolol. At a fixed HR, the data dispersion (SDNN5) was higher with propranolol compared with celiprolol; however, the dispersion was not merely an HR-dependent phenomenon. A novel nonlinear approach (quadrant analysis) revealed the sequencing of cardiac accelerations and decelerations after the high correlation between adjacent intervals had been removed. Celiprolol increased the frequency of consecutive cardiac accelerations; the duration between and variance of these beat-to-beat differences shortened after celiprolol but lengthened with increased variance after propranolol and atenolol. These results demonstrated reduced HRV indices and a shift toward sympathetic dominance after the beta-adrenoceptor agonist celiprolol contrasting with increased HRV indices and parasympathetic dominance after the beta-adrenoceptor antagonists propranolol and atenolol. The implications of these findings for the treatment of patients with cardiovascular disease warrant further study.     

Lipids, lipoproteins and apolipoproteins in normal newborns

BACKGROUND: In Chile, there is a high prevalence of cardiovascular diseases. Because atherosclerosis starts in childhood, it is important to assess serum lipid levels in children. AIM: To measure serum lipid levels in normal Chilean newborns. SUBJECTS AND METHODS: A sample of umbilical cord venous blood was obtained from 156 normal newborns (76 male) immediately after delivery. Total and HDL cholesterol, triglycerides, apoprotein A1, B and lipoprotein (a) were measured. RESULTS: Mean values for total cholesterol in males, females and in the total sample were 60.6, 67.8 and 64 mg/dl respectively. The figures for HDL cholesterol were 24.9, 29.3 and 27 mg/dl, for LDL cholesterol were 28.3, 32.4 and 30 mg/dl, for triglycerides were 37.5, 30.3 and 35 mg/dl, for apoprotein A1 were 69, 79 and 74 mg/dl, for apoB were 23, 25 and 24 mg/dl and for lipoprotein (a) were 1.58, 1.79 and 1.69 mg/dl. Total cholesterol, HDL cholesterol, triglycerides and apoprotein A1 were significantly different between sexes. Percentiles 5 and 95 for total cholesterol were 37 and 111, for HDL cholesterol were 14 and 40, for LDL cholesterol were 13 and 57, for triglycerides were 20 and 69, for apoprotein A1 were 53 and 101, for apoprotein B were 11 and 48 and for lipoprotein (a) were 1.3 and 2.1 mg/dl. Five percent of children had apoprotein B values over 48 mg/dl. CONCLUSIONS: The detection of high levels of apoprotein B in newborns, could allow the early identification of individuals with high cardiovascular risk.     

Atherosclerosis and left ventricular hypertrophy: persisting problems in treated hypertensive patients

OBJECTIVES: First, to determine whether hypertensive patients managed in general practice have more advanced atherosclerosis and left ventricular hypertrophy than matched normotensive patients from the same practices. Second, to investigate the associations of several potentially modifiable factors with these vascular and cardiac outcomes. DESIGN AND METHODS: We performed a case-control study of 500 hypertensive cases (systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or receiving treatment) and 506 age- (mean 61 years) and sex- (54% female) matched normotensive controls recruited from general practices. Carotid artery far wall thickness (CWT), assessed by B-mode ultrasound, and left ventricular mass (LVM), assessed by M-mode echocardiography, were the main study outcome measures. RESULTS: Mean systolic/diastolic blood pressure levels in the 399 treated cases (145/87 mmHg) were lower than those in untreated cases (158/94 mmHg) but higher than those in controls (133/82 mmHg, all P < 0.0001). Mean body mass index (BMI) and total triglyceride levels were higher and high-density lipoprotein cholesterol was lower in cases than in controls (all P < 0.0004). Mean CWT was 10% greater in cases than in controls and LVM was 14% greater (both P < 0.001), but both were similar in treated and untreated cases (P > 0.05). In multivariate analyses, blood pressure and BMI were both directly and independently related to CWT and LVM (both P < 0.0001). CONCLUSIONS: In this study, hypertensive patients managed in general practice - whether treated with antihypertensive drugs or not - had more advanced atherosclerosis and left ventricular hypertrophy than did matched normotensive patients. Efforts to lower blood pressure further and to reduce BMI could potentially reduce these differences, and this might lead to a reduction in the risk of major cardiovascular events.     

Long-term clinical follow-up after directional coronary atherectomy

We designed a prospective observational trial to study the relationship of thyroid function to cholesterol and weight changes at menopause. Subjects were participants in the ongoing Healthy Women Study, a prospective study of cardiovascular risk factor change through menopause. Healthy premenopausal women were recruited from a random sample of licensed drivers in selected ZIP codes of Allegheny County, Pennsylvania. Participants had to be 42-50 years of age, have menstruated within the last 3 months, not have had surgical menopause, have diastolic blood pressure < 100 mm Hg, and not be taking medications (including insulin, estrogen, lipid-lowering drugs, or thyroid or antihypertensive medications) at the baseline examination. The substudy included three groups of women who were premenopausal at baseline and were categorized according to change noted at follow-up regarding menopausal status and use of hormone replacement therapy (HRT). The groups comprised 95 women who remained premenopausal, 96 postmenopausal women not on HRT, and 61 postmenopausal women using HRT. The main outcome measures were baseline and follow-up measurements for serum levels of thyroid-stimulating hormone (TSH), thyroid peroxidase, and thyroglobulin, as well as serum cholesterol, total high-density lipoprotein (HDL) cholesterol, triglycerides, and calculated low-density lipoprotein (LDL) cholesterol, height, and weight. Covariates included cigarette smoking and alcohol intake. The prevalence of thyroid antibodies in this healthy population was high at both time points (range 27%-31%) and did not differ by menopausal status. The presence of thyroid antibodies was associated with increased TSH concentration. Women with antibodies at both time points had lower levels of total and LDL cholesterol compared with those with no antibodies, significant only for those women who remained premenopausal during the follow-up period. Thyroid function during menopause in this healthy population is unlikely to account for the observed changes in levels of serum lipoprotein and body weight. The presence of thyroid antibodies may be associated with lower total and LDL cholesterol, possibly through an underlying inflammatory disorder.     

Serum hepatocyte growth factor as a possible indicator of arteriosclerosis

OBJECTIVE: To investigate the possible involvement of hepatocyte growth factor in arteriosclerotic lesions, by studying the relationship between serum concentrations of hepatocyte growth factor and grades of retinal arteriosclerosis. METHODS: We measured the blood pressure, body mass index, serum concentrations of total cholesterol, high-density lipoprotein cholesterol, triglycerides, creatinine, uric acid, total protein, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, gamma-glutamyltranspeptidase, alkaline phosphatase, and hepatocyte growth factor, erythrocyte counts, hemoglobin concentration, and hematocrit levels of 112 adults. Serum concentrations of hepatocyte growth factor were measured by a specific enzyme-linked immunosorbent assay. For each subject, photographs of both optic fundi were taken, and the grade of arteriosclerotic changes in the retinal arteries was evaluated according to Scheie's classification. RESULTS: Individuals with more advanced grades of arteriosclerotic changes had higher serum hepatocyte growth factor values (grade 0, 0.056 +/- 0.004 ng/ml, n = 86; grade 1, 0.132 +/- 0.026 ng/ml, n = 17, P < 0.01, versus grade 0; grade 2-3, 0.271 +/- 0.023 ng/ml, n = 9, P < 0.01, versus grades 0 and 1). The serum hepatocyte growth factor concentrations were also correlated significantly to the serum uric acid concentrations (r = 0.230, P = 0.015) and erythrocyte counts (r = 0.299, P = 0.001), but not to the systolic and diastolic blood pressures, and other physical and humoral parameters. CONCLUSIONS: Serum hepatocyte growth factor levels are thought to indicate the presence or development of arteriosclerotic lesions and may be a useful biochemical parameter for estimating the development of systemic arteriosclerosis irrespective of blood pressure levels.     

Pro-haemorrhagic effects of calcium antagonists: a comparison of isradipine and atenolol on ex vivo platelet function in hypertensive subjects

It has been suggested that long term treatment with calcium antagonist drugs might inhibit platelet function and lead to an anti-atheromatous effect. However recent data have also suggested that such an effect might increase mortality due to an increased incidence of gastrointestinal bleeding. We identified 43 subjects from general practice with uncomplicated mild to moderate hypertension to compare the effects of the calcium antagonist isradipine with that of the beta-blocker atenolol on platelet function, plasma beta-thromboglobulin levels, fibrinolysis, and serum lipids in a randomised double-blind parallel group study. After careful evaluation to exclude concomitant aspirin use, only 24 subjects were eligible to enter the study. While isradipine and atenolol produced comparable and clinically significant falls in blood pressure (167 +/- 2/102 +/- 1 to 153 +/- 3/91 +/- 2 mm Hg, and 165 +/- 2/101 +/- 1 to 156 +/- 4/91 +/- 2 mm Hg, respectively), neither drug produced a detectable effect on ex vivo platelet aggregation, platelet retention, or thromboxane generation with adrenaline, collagen, adenosine-di-phosphate, or platelet activating factor. However a decrease in plasma beta-thromboglobulin levels was observed which reached statistical significance (P < 0.05) after 12 weeks treatment in the isradipine but not the atenolol group. A 39% reduction with isradipine compared with 34% following atenolol treatment. Euglobulin clot lysis time was not altered by either drug. Serum cholesterol concentrations were also unaltered by drug treatment. Therapeutic doses of the calcium antagonist isradipine may produce a minor indirect effect on platelet function after several weeks of treatment. However, this is of doubtful clinical importance and may simply reflect an effect of lowered blood pressure on platelet function.     

Multiple injuries in peacetime and wartime estimate of severity of injury by the Injury Severity Score and Polytraumaschlüssel

The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.     

Transendothelial migration of megakaryocytes in response to stromal cell-derived factor 1 (SDF-1) enhances platelet formation

Cerivastatin sodium, a synthetic and pure enantiomeric 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, is considered effective in the treatment of mild-to-moderate primary hyper-cholesterolemia (total cholesterol < or = 220-259 mg/dL) at a daily dose of 0.15 mg. We compared the efficacy and tolerability of a dosage of 0.3 mg/d with those of a dosage of 0.15 mg/d in patients with severe primary hypercholesterolemia (serum total cholesterol > or = 260 mg/dL). After a minimum of 4 weeks' lead-in with placebo, 73 patients with severe primary hypercholesterolemia were randomly assigned to receive either 0.15 or 0.3 mg of cerivastatin sodium once daily after the evening meal for 12 weeks. In 58 patients, the same drug was continued at a flexible dosage for an additional 36 weeks or longer to assess the long-term efficacy and tolerability of cerivastatin sodium. During the 12-week treatment period, serum total cholesterol levels decreased significantly from baseline in both dosage groups, but the percentage reduction was significantly greater in the 0.3-mg group (range, 24.4% to 25.6%) than in the 0.15-mg group (range, 19.4% to 21.6%). The percentage reduction in levels of low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B and the percentage increase in levels of high-density lipoprotein cholesterol were significantly greater in the 0.3-mg group than in the 0.15-mg group. When the results for the 0.3- and 0.15-mg groups were combined, the percentage of change in serum lipid levels at 48 weeks remained as stable as at 12 weeks. No serious adverse reactions were observed. We concluded that the higher dose of cerivastatin sodium was more effective than the lower dose, with comparable tolerability, in the treatment of patients with severe primary hypercholesterolemia.     

Low lipid concentrations in critical illness: implications for preventing and treating endotoxemia

OBJECTIVES: To determine the prevalence and clinical significance of hypolipidemia found in critically ill patients, and whether the addition of a reconstituted lipoprotein preparation could inhibit the generation of tumor necrosis factor-alpha (TNF-alpha) in acute-phase blood taken from these patients. SETTING: Surgical intensive care unit (ICU) of a large urban university hospital. DESIGN: Prospective case series. PATIENTS: A total of 32 patients with a variety of critical illnesses had lipid and lipoprotein concentrations determined. Six patients and six age- and gender-matched control subjects had whole blood in vitro studies of the effect of lipoprotein on lipopolysaccharide mediated TNF-alpha production. INTERVENTIONS: Blood samples were drawn on admission to the ICU and over a subsequent 8-day period. MEASUREMENTS AND MAIN RESULTS: Mean serum lipid and lipoprotein values obtained from patients within 24 hrs of transfer to the surgical ICU were extremely low: mean total cholesterol was 117 mg/dL (3.03 mmol/L), low-density lipoprotein cholesterol 71 mg/dL (1.84 mmol/L), and high-density lipoprotein cholesterol 25 mg/dL (0.65 mmol/L). Only the mean triglyceride concentration of 105 mg/dL (1.19 mmol/L), and the mean lipoprotein(a) concentration of 25 mg/dL (0.25 g/L) were within the normal range. During the first 8 days following surgical ICU admission, there were trends toward increasing lipid and lipoprotein concentrations that were significant for triglycerides and apolipoprotein B. Survival did not correlate with the lipid or lipoprotein concentrations, but patients with infections had significantly lower (p = .008) high-density lipoprotein cholesterol concentrations compared with noninfected patients. Lipopolysaccharide-stimulated production of TNF-alpha in patient and control blood samples was completely suppressed by the addition of 2 mg/mL of a reconstituted high-density lipoprotein preparation. CONCLUSIONS: Patients who are critically ill from a variety of causes have extremely low cholesterol and lipoprotein concentrations. Correction of the hypolipidemia by a reconstituted high-density lipoprotein preparation offers a new strategy for the prevention and treatment of endotoxemia.