Effects of dexamethasone on functional and pathological changes in rat bronchi caused by high acute exposure to chlorine

OBJECTIVE: To assess month-to-month variability of total cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), calculated low-density lipoprotein-cholesterol (LDL-C), apolipoprotein A1, apolipoprotein B, and lipoprotein (a), as well as factors that could influence variability, including recent acute infection in an adolescent population. METHODS: Sixty-three high school students had fasting lipids and lipoproteins measured at 4 separate times during the school year and another venipuncture 3 to 7 days after recovery from an acute infection. Erythrocyte sedimentation rate was also measured. Coefficients of variation were calculated for each study variable. The influence of recent infection on variability was assessed. RESULTS: The 50th and 95th percentiles, respectively, for the coefficient of variation for each variable were as follows: total cholesterol, 7.3% and 13.6%; triglycerides, 22% and 47.3%; HDL-C, 7.9% and 16.8%; LDL-C, 12.1% and 25%; apolipoprotein A1, 6.3% and 15.2%; apolipoprotein B, 9.5% and 17.2%; and lipoprotein (a), 19.3% and 40%. Recent infection significantly lowered HDL-C (4 mg/dL; P < .0001) and apolipoprotein A1 (7 mg/dL; P < .005). CONCLUSIONS: Clinicians evaluating lipids and lipoproteins serially should expect significant visit-to-visit variation in triglycerides and calculated LDL-C values. Assessment of HDL-C and apolipoprotein A1 should not be done within 2 weeks of an acute infection. Apolipoproteins B and A1 have slightly less variability than their respective lipoprotein cholesterol values (LDL-C and HDL-C).     

Relationship between renal plasma flow response to angiotensin II and blood pressure in a population-based sample

OBJECTIVE: The positive short-term effects of postmenopausal hormone replacement therapy (HRT) on serum lipids are well known, but it has been suggested that they vanish with time. Cholecalciferol (vitamin D3) is widely used to prevent postmenopausal osteoporosis but the influence of vitamin D3 on serum lipids is poorly known. The long-term effects of HRT and vitamin D3 on the concentrations of serum lipids were studied in a population-based prospective 3-year study. DESIGN AND METHODS: 464 women were randomized into four treatment groups: (i) HRT (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), (ii) Vit D3 (vitamin D3 300 IU/day), (iii) HRT+Vit D3 (both as above), (iv) placebo (calcium lactate 500 mg/day). RESULTS: 320 women completed the study. After three years of treatment, serum concentrations of low density lipoprotein (LDL) cholesterol decreased in the HRT group (10.1%, P<0.001) and the HRT+Vit D3 group (5.9%, P=0.005), increased in the Vit D3 group (4.1%, P=0.035) but remained unchanged in the placebo group. The concentrations of total cholesterol decreased by 5.8% in the HRT group (P<0.001) and by 3.3% in the HRT+Vit D3 group (P=0.023), but did not change in the other two groups. Serum concentrations of high density lipoprotein (HDL) cholesterol decreased in the Vit D3 group (5.2%, P=0.001), HRT+Vit D3 group (3.7%, P=0.046), and the placebo group (4.5%, P=0.006) but did not change significantly in the HRT group. The HDL/LDL ratio increased in the HRT group (10.5%, P=0.006) and decreased in the Vit D3 group (10.5%, P<0.001) whereas no changes occurred in the other two groups. In addition, serum triglycerides increased similarly in all groups (14.0-18.8%, P<0.05-0.001). CONCLUSIONS: Our results confirm the positive long-term effect of HRT with sequential estradiol valerate and cyproterone acetate on serum lipid concentrations. In addition, the results suggest that vitamin D3 supplementation may have unfavorable effects on lipids in postmenopausal women. Pure vitamin D3 treatment was associated with increased serum LDL cholesterol. Furthermore, the beneficial effects of HRT on serum LDL cholesterol content were reduced when estradiol valerate was combined with vitamin D3. However, the relevance of these associations to cardiovascular morbidity remains to be established.     

Effect of the novel antiplatelet agent cilostazol on plasma lipoproteins in patients with intermittent claudication

Cilostazol is an antiplatelet agent and vasodilator marketed in Japan for treatment of ischemic symptoms of peripheral vascular disease. It is currently being evaluated in the United States for treatment of symptomatic intermittent claudication (IC). Cilostazol has been shown to improve walking distance in patients with IC. In addition to its reported vasodilator and antiplatelet effects, cilostazol has been proposed to have beneficial effects on plasma lipoproteins. We examined the effect of cilostazol versus placebo on plasma lipoproteins in 189 patients with IC. After 12 weeks of therapy with 100 mg cilostazol BID, plasma triglycerides decreased 15% (P<0.001). Cilostazol also increased plasma high density lipoprotein cholesterol (HDL-C) (10%) and apolipoprotein (apo) A1 (5.7%) significantly (P<0.001 and P<0.01, respectively). Both HDL3 and HDL2 subfractions were increased by cilostazol; however, the greatest percentage increase was observed in HDL2. Individuals with baseline hypertriglyceridemia (>140 mg/dL) experienced the greatest changes in both HDL-C and triglycerides with cilostazol treatment. In that subset of patients, HDL-C was increased 12.2% and triglycerides were decreased 23%. With cilostazol, there was a trend (3%) toward decreased apoB as well as increased apoA1, resulting in a significant (9.8%, P<0.002) increase in the apoA1 to apoB ratio. Low density lipoprotein cholesterol and lipoprotein(a) concentrations were unaffected. Cilostazol treatment resulted in a 35% increase in treadmill walking time (P=0.0015) and a 9.03% increase in ankle-brachial index (P<0.001). These results indicate that in addition to improving the symptoms of IC, cilostazol also favorably modifies plasma lipoproteins in patients with peripheral arterial disease. The mechanism of this effect is currently unknown.     

The accuracy and precision of four infrared aural canal thermometers during cardiac surgery

Hormone replacement therapy has been shown to decrease the risk of coronary heart disease (CHD) in menopausal women. In this cross-sectional study, we addressed the following question: What effects would combined oral hormone replacement therapy have on plasma lipid and lipoprotein profiles independent of the other known CHD risk factors? We analyzed the plasma lipoproteins of two groups of menopausal women who were randomly selected from a large database of individuals. One group (n = 10) was not taking any hormone replacement therapy (NO HRT), while the second group (n = 8) was taking a daily dose of 0.625 mg conjugated estrogen and 2.5 mg medroxyprogesterone orally (PremPro, Wyeth-Ayerst, Philadelphia, PA) for at least 6 months (HRT). The two groups were not different in age, body weight, percent body fat, body mass index (BMI), waist to hip ratio, blood pressure, or insulin and glucose levels. High-density lipoprotein (HDL)-cholesterol was significantly higher (P < .05) in the HRT group. The total cholesterol (TC) to HDL-cholesterol ratio was significantly lower for HRT versus NO HRT (P < .05). Apolipoprotein (apo) A-1, the apo A-1/B ratio, and lecithin:cholesterol acyltransferase (LCAT) activity were significantly higher in HRT (P < .05). Lipoprotein subclass profiles measured by nuclear magnetic resonance (NMR) spectroscopy showed an increase in larger HDL subpopulations (H3 and H4) in HRT (P < .05), which are considered antiatherogenic. No differences were seen in the cholesterol concentration or size of low-density lipoprotein (LDL) subpopulations in HRT compared with NO HRT. These results indicate that the combined estrogen and progesterone treatment leads to beneficial effects on plasma lipoproteins. The beneficial effects include (1) increases in HDL-cholesterol and predominance of HDL2, (2) no adverse effects on LDL subpopulation distribution, and (3) increases in apo A-1 levels and LCAT activity, which indicate an improvement in reverse cholesterol transport.     

Exercise, smoking cessation, and short-term changes in serum lipids in women: a preliminary investigation

PURPOSE: This study investigated the combined effects of exercise and smoking cessation on serum lipids. METHODS: Eighteen female smokers quit smoking using standard behavioral methods combined with exercise (N = 9) or with a nonexercise contact time control (N = 9). The smoking cessation program for both groups consisted of 12 weekly 1-h behavioral modification sessions held over 12 wk. Exercise training consisted of three supervised 45-min sessions per week for 12 wk. Contact control consisted of three health education lectures/discussions per week for 12 wk. Fitness (estimated VO2 peak), dietary variables, and fasting serum lipids and lipoproteins were assessed before and at the end of treatment. VO2 peak increased in the exercise subjects compared with the controls. RESULTS: Total caloric intake as well as total fat and carbohydrate increased significantly after smoking cessation in the controls, but there were no dietary changes in the exercise group. high density lipoprotein (HDL)-C2 increased (7.6 mg x dL(-1), P < 0.01) in the exercise group, whereas the increases in HDL and its subfractions did not attain statistical significance in the contact control group. Total cholesterol, low density lipoprotein (LDL)-C, and triglycerides did not change in either group. CONCLUSIONS: We conclude that exercise training magnifies the increase in HDL-C that usually occurs with smoking cessation.     

Production of small high-density lipoprotein particles after stimulation of in vivo lipolysis in hypertriglyceridemic individuals: studies before and after triglyceride-lowering therapy

In hypertriglyceridemic states, triglyceride enrichment of high-density lipoprotein (HDL) may play an important role in decreasing the HDL cholesterol and apolipoprotein (apo) A-1 plasma concentration. We have shown previously that HDL particles are transformed into small HDLs when lipolysis is stimulated in vivo or in vitro, and this process is more marked if the HDL is triglyceride-rich. The present study was conducted to determine whether the susceptibility of HDL to transformation can be altered by triglyceride-lowering therapy in humans. Seventeen moderately hypertriglyceridemic individuals (nine with type II diabetes mellitus and eight moderately hypertriglyceridemic nondiabetic subjects) were studied before and after 3 months of triglyceride-lowering therapy with gemfibrozil. Since no significant differences in postprandial and postheparin HDL metabolism were detected between type II diabetic and nondiabetic subjects, results are reported for the two groups combined (N = 17). Fasting HDL was triglyceride-rich with a preponderance of HDL3, and became more enriched with triglycerides postprandially. Heparin administration resulted in a rapid decrease in plasma and HDL triglycerides and an increase in plasma and HDL free fatty acids (FFAs). Postheparin, there was a reduction in HDL size and an increase in the proportion of small (HDL3c) HDL particles (HDL3c constituted 7.1% +/- 1.8% of total HDL preheparin and 26.6% +/- 3.8% postheparin, P < .001). Triglyceride-lowering treatment resulted in a decrease in fasting triglycerides (-54%, P < .001) and HDL triglyceride content (-36%, P = .002), an increase in fasting HDL cholesterol (19%, P = .004), and proportionately fewer (13.2% +/- 2.1%, P < .001) HDL3c particles formed postheparin. Postheparin HDL size correlated inversely with the fasting triglyceride level (r = -.55, P < .001) and HDL triglyceride concentration (r = -.34, P = .02). These results show that the postprandial increase in triglyceride levels in hypertriglyceridemic subjects is associated with increased production of small HDL particles when lipolysis is stimulated, and that lipid-lowering therapy can contribute to favorably reduce this postprandial production of small HDL particles. Further studies are needed to clarify how these abnormalities ultimately lead to a decrease of plasma HDL cholesterol and apo A-1 in hypertriglyceridemic states.     

Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia

We have investigated the effects of two fibric acid derivatives, bezafibrate mono (400 mg daily) and gemfibrozil (600 mg b.d.), in 29 patients with type IIb hyperlipoproteinaemia. All patients received placebo and each drug for 8 weeks in randomised order in a double-blind, cross-over study designed to evaluate any different effects of the drugs on serum lipoproteins, cholesteryl ester transfer protein (CETP), cholesteryl ester transfer activity (CETA), plasma fibrinogen, plasminogen activator inhibitor-I (PAI-1) or paraoxonase. Serum cholesterol decreased (P < 0.05) with gemfibrozil, but the effect of bezafibrate on serum cholesterol did not achieve statistical significance (placebo 8.34 +/- 1.05 (mean +/- S.D.), gemfibrozil 7.70 +/- 1.23 and bezafibrate 7.8 +/- 1.37 mmol/l). Both drugs decreased the serum triglyceride concentration (both P < 0.001) (placebo 4.39 (3.13-5.75) (median (interquartile range)), bezafibrate 2.26 (1.89-3.89) and gemfibrozil 2.00 (1.30-3.30) mmol/l) and very low density lipoprotein (VLDL) cholesterol (both P < 0.001) (placebo 1.18 (0.74-2.30), bezafibrate 0.59 (0.34-0.85) and gemfibrozil 0.48 (0.34-0.68) mmol/l). Discontinuous gradient ultracentrifugation (DGU) revealed that Sf 60-400 (large VLDL) decreased by more than 50% and Sf 20-60 (small VLDL) by more than 30% with each of the drugs (both P < 0.001), neither of which affected the composition of these lipoproteins. Gemfibrozil decreased the concentration of Sf 12-20 lipoprotein (intermediate density lipoprotein; IDL) by 23% (P < 0.01), whereas the effect of bezafibrate on this lipoprotein did not achieve statistical significance. Neither drug altered the concentration of apolipoprotein B or of total Sf 0-12 lipoproteins (low density lipoprotein, (LDL)). Both, however, significantly increased the quantity of free cholesterol in Sf 0-12 lipoproteins (P < 0.05). Overall the concentration of triglycerides decreased significantly in all lipoproteins isolated by DGU (Sf 0-12, Sf 12-20, Sf 20-60, Sf 60-400) on gemfibrozil treatment, but only in Sf 20-60 and Sf 60-400 on bezafibrate (all P < 0.05). Both drugs also increased serum high density lipoprotein (HDL) cholesterol (placebo 1.15 +/- 0.29, bezafibrate 1.27 +/- 0.38 (P < 0.01) and gemfibrozil 1.26 +/- 0.49 (P < 0.05) mmol/l) and HDL3 cholesterol concentration (placebo 0.59 +/- 0.12, bezafibrate 0.72 +/- 0.23 (P < 0.001) and gemfibrozil 0.70 +/- 0.24 (P < 0.01) mmol/l). Serum apolipoprotein A1 (apo A1) was increased (P < 0.05) by bezafibrate compared to gemfibrozil (placebo 103 +/- 26, bezafibrate 111 +/- 28 and gemfibrozil 102 +/- 25 mg/dl) and CETA from HDL to VLDL and LDL was decreased (P < 0.05) by bezafibrate compared to placebo, but the apparent decrease with gemfibrozil did not achieve statistical significance (placebo 39.6 +/- 17.7, bezafibrate 32.3 +/- 14.7 and gemfibrozil 33.8 +/- 15.0 nmol/ml/h). Neither drug affected the circulating concentration of CETP. Plasma fibrinogen was increased (P < 0.05) by gemfibrozil (placebo 4.16 (3.38-4.71) and gemfibrozil 4.65 (4.05-5.77) g/l) and was significantly lower (P < 0.001) on bezafibrate (3.60 (3.18-4.54) g/l) than on gemfibrozil treatment. There was a significant (P < 0.05) increase in PAI-1 activity with bezafibrate and a similar trend with gemfibrozil (placebo 41.2 (25.6-64.5), bezafibrate 50.5 (35.1-73.9) and gemfibrozil 48.5 (31.5-5.4 U/l). Neither fibrate influenced plasma concentrations of PAI-1 nor were the activities of lecithin:cholesterol acyl transferase or paraoxonase affected. The major difference in the action of the two drugs on lipoprotein metabolism was the greater effect of gemfibrozil in decreasing the overall serum concentration of Sf 12-20 lipoproteins and the triglycerides in Sf 12-20 and 0-12 lipoproteins. Bezafibrate, however, increased serum apo A1 concentration and significantly decreased CETA. The two drugs also had different effects on the plasma fibrinogen levels, which increased with gemfibrozil and tended to decrea     

Major locus influencing plasma APO-A1 levels also controls plasma HDL3-C concentrations

Elevated plasma levels of apolipoprotein A1 (APO-A1) and high-density lipoprotein cholesterol (HDL-C) are important protective factors for atherosclerosis and coronary heart disease. Using the data on plasma concentrations of APO-A1, and HDL-C particles HDL2-C and HDL3-C in 970 Israeli individuals belonging to 228 pedigrees, we tested the hypothesis that a major locus influencing interindividual variation in APO-A1 levels also controls interindividual variation in HDL3-C and HDL2-C levels. Univariate and bivariate complex segregation analyses, as implemented in two statistical packages (MAN-3 and PAP-4.0) were applied to test the hypothesis. The results of the analysis clearly indicated the possibility of major gene involvement in the determination of plasma concentration variation of each of the 3 study variables. The results provide strong evidence in support of our hypothesis that HDL3-C genetic variation fully depends on the APO-A1 major locus. In particular, environmental and sporadic models were strongly rejected (P < 0.001) in bivariate analysis. The hypothesis of no pleiotropic effect of the putative APO-A1 locus on HDL3-C transmission was also unequivocally rejected (P < 0.001), while the bivariate Mendelian model was accepted (P > 0.05). The results of bivariate analysis of APO-A1 effect on HDL2-C were not clear. They indicated the possibility of the existence of slight genetic covariation between the two variables, and as yet we were unable to decipher the mode of covariation with the applied models.     

Immunosorbent assay based on recombinant hemagglutinin protein produced in a high-efficiency mammalian expression system for surveillance of measles immunity

Raloxifene has been shown to have estrogen agonist effects on bone and cholesterol metabolism while having estrogen antagonist effects on mammary gland and uterus. Reported here are the results of a study to determine whether raloxifene had the estrogen agonist effect of inhibiting coronary artery atherogenesis and to compare its effects with those of traditional conjugated equine estrogens (CEE) treatment. Ovariectomized (surgically postmenopausal) cynomolgus monkeys were fed a moderately atherogenic diet and treated with a placebo, raloxifene (1 mg/kg x day), raloxifene (5 mg/kg x day), or CEE (Premarin) at a dose that mimicked that of 0.625 mg/day in women. The effects of raloxifene on plasma lipid concentrations were generally comparable to those reported in postmenopausal women treated with raloxifene: reductions in low density lipoprotein cholesterol concentrations and no significant effects on high density lipoprotein cholesterol. We found no evidence that raloxifene had an estrogen agonist effect on coronary arteries. Treatment with CEE resulted in about a 70% reduction in coronary artery plaque size relative to that in the placebo group, whereas neither the low nor the high dose of raloxifene had an effect on coronary artery plaque size. The low dose raloxifene group had about 2 times more atherosclerosis and the high dose group had about 3 times more atherosclerosis than the CEE group.     

The significance of lipoproteins in serum binding variations of propofol

The protein binding of propofol was investigated in vitro in isolated lipoprotein fractions (very low-density lipoprotein [VLDL], low-density lipoprotein [LDL], and high-density lipoprotein [HDL]) and in serum samples from the following subjects: healthy normolipemic volunteers (n = 16), hyperlipidemic subjects diagnosed with familiar polygenic hypercholesterolemia (n = 26) showing high levels of cholesterol, and elderly subjects (n = 15). Protein binding was determined by using ultrafiltration, and the concentration of unbound propofol was measured by using liquid chromatography. Levels of total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, HDL cholesterol, albumin, and alpha1-acid glycoprotein were also measured. Propofol was extensively bound to the three lipoprotein fractions (88%+/-2% to VLDL, 93%+/-1% to LDL, and 91%+/-4% to HDL). The percentage of unbound propofol was significantly decreased (P < 0.0001) in hyperlipidemic (0.88%+/-0.20%) individuals whose levels of cholesterol and triglycerides were increased versus healthy subjects (1.26%+/-0.22%), whereas no significant difference was found in the elderly group (1.12%+/-0.23%). A positive relationship was found between serum protein binding of propofol and lipid levels. Multiple regression analysis, including all subjects, showed that changes in the levels of total cholesterol and triglycerides explained approximately 62% of the variability in the serum protein binding of propofol. These results stress the importance of triglycerides and cholesterol in the serum protein binding of propofol. We therefore suggest that these variations in lipid levels, and consequently in protein binding, may influence anesthetic practice with propofol. IMPLICATIONS: We investigated the effect of serum lipids in the protein binding of propofol. We found that propofol binds extensively to all lipoprotein fractions. Propofol binding showed a significant relationship with the serum levels of cholesterol and triglycerides.     

An 88-year-old female case of hyperalphalipoproteinemia associated with deficiency of cholesteryl-ester transfer activity]

An 88-year-old female was admitted to our hospital for examination of hyperalphalipoproteinemia. The high level of her serum high-density lipoprotein cholesterol (HDL-C, 148 mg/dl) was due to cholesterol amount of HDL2-C but not HDL3-C, and serum cholesteryl ester transfer activity (CETA) was at a non-detectable level. Despite her age, apparent atherosclerotic changes were not observed. She may be the oldest case of hyperalphalipoproteinemia, possibly due to deficiency of serum CETA.     

Antiatherogenic effects of adjuvant antiestrogens: a randomized trial comparing the effects of tamoxifen and toremifene on plasma lipid levels in postmenopausal women with node-positive breast cancer

PURPOSE: To evaluate whether a novel antiestrogen, toremifene, has similar antiatherogenic effects as tamoxifen. PATIENTS AND METHODS: Forty-nine postmenopausal patients with node-positive breast cancer were randomized in a trial that compared the effects of tamoxifen and toremifene on serum lipoproteins. Tamoxifen was given at 20 mg and toremifene at 60 mg orally per day for 3 years. Serum concentrations of apolipoprotein (apo) A-I, A-II, and B, and lipoprotein(a) [Lp(a)], cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol were measured before and after 12 months of antiestrogen therapy. RESULTS: Both antiestrogens significantly reduced serum total and LDL cholesterol and apo B levels. However, the response of HDL cholesterol to treatments was clearly different between the groups. Toremifene increased the HDL level by 14%, whereas tamoxifen decreased it by 5% (P = .001). As a consequence, both cholesterol-to-HDL and LDL-to-HDL ratios decreased more in the toremifene than tamoxifen group (P = .008 and P = .03, respectively). Toremifene also increased the apo A-I level (P = .00007) and apo A-I-to-A-II ratio (P = .018). Both tamoxifen and toremifene decreased the Lp(a) concentration significantly (change, 34% v 41%). CONCLUSION: These results provide positive evidence that toremifene has antiatherogenic properties with potency to improve all lipoproteins that are associated with increased coronary heart disease (CHD) risk.     

Continuous assay for acid phosphatase using 1-naphthyl phosphate as a substrate

The sequential effects of an American Heart Association (AHA) Step 1 diet and subsequent weight loss on lipoprotein lipids in obese [body mass index (in kg/m2) > 27], postmenopausal women (n = 48) were determined. Subjects followed a euenergetic AHA Step 1 diet for 2 mo, followed by a weight-loss diet (deficit of 1.0-1.5 MJ/d) for 6 mo. The AHA diet lowered concentrations of total (7%), low-density-lipoprotein (LDL) (6%), and high-density-lipoprotein (HDL) (14%) cholesterol (P < 0.01). Weight loss (-5.6 +/- 0.7 kg; P < 0.01) increased plasma triacylglycerol concentrations (9%; P < 0.01) and increased HDL-cholesterol concentrations (8%; P < 0.01) compared with changes after the AHA diet, but there were no changes in total or LDL cholesterol. The combined AHA diet and weight-loss interventions lowered triacylglycerol (10%) and total (6%), LDL (6%), and HDL (7%) cholesterol. These changes correlated indirectly with the baseline concentration for each lipid. When the women were divided on the basis of initial LDL-cholesterol concentration, the AHA diet and weight-loss interventions reduced (P < 0.01) triacylglycerol (19%), total cholesterol (13%), and LDL cholesterol (14%) in the women with hypercholesterolemia but not in normocholesterolemic or midly hypercholesterolemic women. Thus, an AHA Step 1 diet and subsequent weight loss improve lipoprotein lipid profiles of obese, postmenopausal women with hypercholesterolemia. However, because it lowers HDL cholesterol, a low-fat diet without substantial weight loss may not be beneficial for improving lipoprotein lipid risk factors for coronary artery disease in obese, postmenopausal women with normal lipid profiles.     

Treatment of established postmenopausal osteoporosis with raloxifene: a randomized trial

Raloxifene is a selective estrogen receptor modulator that in experimental animals acts as an estrogen receptor antagonist in breast and endometrium but as an estrogen receptor agonist in the skeletal and cardiovascular systems. We conducted a 1-year prospective, randomized, double-blind trial in 143 postmenopausal osteoporotic women (mean +/- SD age, 68.4+/-5.0 years) with at least one prevalent vertebral fractures and low bone mineral density (BMD), comparing groups receiving raloxifene at 60 mg/day (RLX60) or 120 mg/day (RLX120) and a control group receiving supplements of 750 mg/day of calcium and 400 IU/day of vitamin D. There were no differences among groups in the occurrence of uterine bleeding, thrombophlebitis, breast abnormalities, or increased endometrial thickness (assessed by ultrasonography). As compared with controls, the changes in values over 1 year for RLX60 and RLX120, respectively, were significant for serum bone alkaline phosphatase (-14.9%, -8.87%), serum osteocalcin (-20.7%, -17.0%), and urinary C-telopeptide fragment of type I collagen/creatinine (-24.9%, -30.8%), markers of bone turnover; for serum total cholesterol (-7.0% for RLX60) and low density lipoprotein cholesterol (LDL) (-11.4% for RLX60) and for the LDL/HDL cholesterol ratio (-13.2%, -8.3%). BMD increased significantly in the total hip (1.66% for RLX60) and ultradistal radius (2.92%, 2.50%). There were nonsignificant trends toward increases over controls in BMD for lumbar spine, total body, and total hip (for RLX120). Using a >15% cutoff definition, raloxifene had no effect on incident fractures, but using a >30% cutoff, there was a dose-related reduction (p = 0.047). We conclude that raloxifene therapy is well tolerated, reduces serum lipids, and does not stimulate the uterus or breasts. It has beneficial effects on bone, although, under the conditions of this study, these appear to be of a smaller magnitude than have been reported with estrogen therapy.     

Effects of estrogen replacement therapy on the lipoprotein profile in postmenopausal women with ESRD

BACKGROUND: Patients with ESRD have excessive cardiovascular morbidity and mortality. In postmenopausal women with normal renal function, estrogen replacement therapy decreases cardiovascular mortality by 50%, in part because of their beneficial effects on the lipoprotein profile. Because of similarities in the lipoprotein profile between healthy, postmenopausal women, and women with ESRD, we examined the effects of estrogen replacement on lipoproteins in 11 postmenopausal women with ESRD. METHODS: In a randomized, placebo-controlled crossover study (8 week treatment arms) using 2 mg daily of oral, micronized estradiol, 11 postmenopausal women with ESRD were treated. Neither baseline lipid nor lipoprotein abnormalities were used as entry criteria for study participation. RESULTS: Blood estradiol levels were 19 +/- 4 with placebo and 194 +/- 67 pg/ml (P = 0.024) with estradiol treatment. Total HDL cholesterol concentrations increased from 52 +/- 19 mg/dl to 61 +/- 20 mg/dl (16%), with placebo and estradiol treatments, respectively (P = 0.002). Apolipoprotein A1 increased by 24.6% (P = 0.0002) with estradiol intervention. HDL2 concentrations were 19 +/- 13 with placebo and 24 +/- 16 with estradiol treatment (P = 0.046). There were no differences in total or LDL cholesterol, other lipoprotein fractions including Lp(a), and triglycerides with 2 mg daily estradiol treatment. No significant side effects were observed. CONCLUSIONS: Therefore, using standard dosage regimens for estrogen replacement therapy in postmenopausal women with ESRD, HDL cholesterol is increased to an extent that would be expected to improve their cardiovascular risk profile. Further studies are needed to assess whether estrogen replacement therapy decreases the incidence or severity of cardiovascular disease in ESRD patients to a similar degree compared with other women.     

Fibrinolytic response in subjects with hypertriglyceridemia and low HDL cholesterol

The combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C) appears to be an excessively high risk factor for coronary artery disease (CAD). In the Helsinki study, both coronary events and mortality were decreased by gemfibrozil, especially in subjects with low HDL-C and high triglycerides (TG). On the other hand, it is known that high levels of TG can be associated with high levels of circulating plasminogen activator inhibitor (PAI), which is also a possible risk factor for CAD. The aim of the present study was to see: 1) whether the combination of low HDL-C and high TG is associated with a more impaired fibrinolytic response than in either isolated condition, and 2) whether gemfibrozil administration can improve fibrinolysis in patients with both high TG and low HDL-C. Twelve non-obese, non-diabetic subjects (eight men, four women; mean age 55 +/- 13 yrs) with low HDL-C (< 35 mg/dL men; < 45 mg/dL women) and high TG (mean 253.6 +/- 42.6 mg/dL) entered the study (Group A). Additionally fourteen comparable subjects with normal HDL-C were also investigated (Group B), plus 12 comparable subjects with isolated low HDL-C (Group C). Ten healthy people served as the control group. The following plasma fibrinolytic parameters were measured: tissue plasminogen activator antigen, PAI antigen and activity, euglobulin fibrinolytic activity (EFA) on fibrin plates, plasminogen and alpha-2-antiplasmin activities. All except the latter two values were also measured after venous occlusion (vo). In baseline conditions, patients in Groups A and B had higher EFA values before vo and higher PAI-1 antigen and alpha-2-antiplasmin levels after vo than those of controls or the subjects in Group C. The relationship between PAI antigen and PAI activity and TG was not confirmed in our population (n = 48). We also saw no interference due to HDL-C, while there was a significant relationship between EFA before vo and both TG and cholesterol. After gemfibrozil treatment (600 mg bid for 12 weeks), the lipid profiles of subjects with high TG and low HDL-C were significantly improved. There was also a slight reduction of PAI activity after vo, while the PAI-1 antigen had decreased significantly from baseline after vo (56.3 +/- 13 ng/mL before vo; 48.4 +/- 21 ng/mL after vo; P = 0.04). The higher risk of CAD in patients with low HDL-C and high TG might be in part related to impairment of fibrinolysis, which occurs in patients with isolated high TG. The close relationship existing between both TG and cholesterol levels and fibrinolytic activity confirm the key role of this latter process in the development of CAD.     

Exercise training induced alterations in prepubertal children's lipid-lipoprotein profile

PURPOSE: This study examined the effect of exercise training on prepubertal children's (ET, N = 28) lipid-lipoprotein profile, relative to a maturity matched control group (CON, N = 20). METHODS: Training for ET involved stationary cycling for 30 min, 3 times.wk-1 for 12 wk, at 79.3 +/- 1.2% (mean +/- SD) peak heart rate (HR). Controls maintained their usual lifestyle pattern. Plasma concentrations of total triacylglycerol (TG), total cholesterol (TC), and high-density lipoprotein (HDL)-cholesterol (HDL-C) were determined pre- and postintervention. Low-density lipoprotein (LDL)- cholesterol (LDL-C) was subsequently estimated from these concentrations, and the ratios TC/HDL-C and LDL-C/HDL-C were also calculated. There were no pretest differences (P > 0.05) for any of these blood analytes between groups. The following, potentially, confounding variables were also measured: peak VO2, percent body fat (%BF), dietary composition, and habitual physical activity. These variables, with pretest HDL-C, were included as covariates in two-way split plot ANCOVA analyses. Dietary variables were not included as covariates as they were not related to any of the blood analytes. RESULTS: There were no differences over time or between groups for TG and TC (P > 0.05). LDL-C decreased in ET (-10.2%) but remained unchanged in CON (0.3%) over the intervention period (P < 0.05). HDL-C increased in ET (9.3%) but decreased in CON (-8.9%) (P < 0.01). A similar, but inverted, pattern of change (P < 0.01) was revealed for both ratios, TC/HDL-C (-11.6% vs 6.3%, ET and CON, respectively), and LDL-C/HDL-C (-17.2% vs 8.0%, ET and CON, respectively). The favorable alterations in the lipid-lipoprotein profile for ET were independent of alterations in peak VO2 (group x time interaction, P < 0.05), %BF (main effect time, P < 0.01), and habitual physical activity (group x time interaction, P < 0.01). CONCLUSIONS: In conclusion, the favorable alterations in the lipoprotein profile seen in this study would suggest that it is possible to influence the prepubertal lipoprotein profile independent of alterations in confounding variables such as body composition, cardiorespiratory fitness, and habitual physical activity.     

Plasma lipoprotein and apolipoprotein levels in Taipei and Framingham

We compared the plasma lipoprotein cholesterol, triglyceride, apolipoprotein (apo) A-I, apoB, and lipoprotein(a) [Lp(a)] concentrations in a low coronary heart disease (CHD) risk population (n = 440) in Taipei with a high CHD risk population (n = 428) in Framingham matched for age, sex, and menopausal status. Taipei men had significantly lower low-density lipoprotein cholesterol (LDL-C) (-20 mg/dL, -14%, P < .01) and apoB (-7 mg/dL, -6%, P < .05) levels and significantly higher high-density lipoprotein cholesterol (HDL-C) levels (6 mg/dL, 13%, P < .01) than Framingham men. Taipei women had significantly lower LDL-C (-18 mg/dL, -15%, P < .01) and higher HDL-C (4 mg/dL, 7%, P < .01) levels than Framingham women. Median concentrations and distributions of Lp(a) by sex were similar in Taipei and Framingham. After adjusting for body mass index and smoking status, only differences in total cholesterol and LDL-C levels remained significantly different for both sexes between the two populations (P < .01). Gender differences for lipids within populations were similar. After adjusting for age, body mass index, and smoking status, women in both Taipei and Framingham had significantly lower mean triglyceride, LDL-C, and apoB levels and significantly higher HDL-C and apoA-I levels than men. Postmenopausal women in Taipei had significantly higher mean total cholesterol, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) levels than premenopausal women (P < .05), whereas in Framingham postmenopausal women had significantly higher total cholesterol, triglyceride, LDL-C, and apoB levels than premenopausal women (P < .05). Our data are consistent with the concept that plasma lipoprotein cholesterol levels (especially LDL-C) but not apolipoprotein values explain some of the twofold difference in age-adjusted CHD mortality between these two populations.     

Effects of docosahexaenoic acid on serum lipoproteins in patients with combined hyperlipidemia: a randomized, double-blind, placebo-controlled trial

OBJECTIVE: The objective of this study was to evaluate the effects of daily dietary supplementation with 1.25 g or 2.5 g of docosahexaenoic (DHA), in the absence of eicosapentaenoic acid (EPA), on serum lipids and lipoproteins in persons with combined hyperlipidemia (CHL) [serum low-density lipoprotein cholesterol (LDL-C) 130 to 220 mg/dL and triglycerides 150 to 400 mg/dL]. METHODS: After a 6-week dietary stabilization period, subjects entered a 4-week single-blind placebo (vegetable oil) run-in phase. Those with adequate compliance during the the run-in were randomized into one of three parallel groups (placebo, 1.25, or 2.5 g/day DHA) for 6 weeks of treatment. Supplements were administered in a triglyceride form contained in gelatin capsules. Primary outcome measurements were plasma phospholipid DHA content, serum triglycerides, high-density lipoprotein cholesterol (HDL-C). LDL-C and non-HDL-C. RESULTS: The DHA content of plasma phospholipids increased dramatically (2 to 3 fold) in a dose-dependent manner. Significant (p < 0.05) changes were observed in serum triglycerides (17 to 21% reduction) and HDL-C (6% increase) which were of similar magnitude in both DHA groups. Non-HDL-C [+1.6 (NS) and +5.7% (p < 0.04)] and LDL-C [+9.3% (NS) and +13.6% (p < 0.001)] increased in the DHA treatment groups. All lipid effects reached an apparent steady state within the first 3 weeks of treatment. CONCLUSION: Dietary DHA, in the absence of EPA, can affect lipoprotein cholesterol and triglyceride levels in patients with combined hyperlipidemia. The desirable triglyceride and HDL-C changes were present at a dose which did not significantly increased non-HDL-C or LDL-C. These preliminary findings suggest that dietary supplementation with 1.25 g DHA/day, provided in a triglyceride form, may be an effective tool to aid in the management of hypertriglyceridemia.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.