Meals with Similar Fat Content from Different Dairy Products Induce Different Postprandial Triglyceride Responses in Healthy Adults: A Randomized Controlled Cross-Over Trial.

BACKGROUND: Postprandial lipemia is a risk factor for cardiovascular disease. Dairy products differ in nutrient content and food matrix, and little is known about how different dairy products affect postprandial triglyceride (TG) concentrations. OBJECTIVE: We investigated the effect of meals with similar amounts of fat from different dairy products on postprandial TG concentrations over 6 h in healthy adults. METHODS: A randomized controlled cross-over study was performed on 47 subjects (30% men), with median (25th-75th percentile) age of 32 (25-46) y and body mass index of 23.6 (21.0-25.8) kg/m2. Meals included 1 of butter, cheese, whipped cream, or sour cream, corresponding to 45 g of fat (approximately 60 energy%). Serum concentrations of TGs (primary outcome), and total cholesterol (TC), low density lipoprotein cholesterol (LDL cholesterol), high density lipoprotein cholesterol (HDL cholesterol), insulin, glucose, non-esterified fatty acids, and plasma glucose-dependent insulinotropic polypeptide (secondary outcomes) were measured before the meal and 2, 4, and 6 h postprandially. Incremental AUC (iAUC) was calculated for the responses, and data were analyzed using a linear mixed model. RESULTS: Sour cream induced a 61% larger TG-iAUC0-6 h compared to whipped cream (P < 0.001), a 53% larger TG-iAUC0-6 h compared to butter (P < 0.001), and a 23% larger TG-iAUC0-6 h compared to cheese (P = 0.05). No differences in TG-iAUC0-6 h between the other meals were observed. Intake of sour cream induced a larger HDL cholesterol-iAUC0-6 h compared to cheese (P = 0.01). Intake of cheese induced a 124% larger insulin iAUC0-6 h compared to butter (P = 0.006). No other meal effects were observed. CONCLUSIONS: High-fat meals containing similar amount of fat from different dairy products induce different postprandial effects on serum TGs, HDL cholesterol, and insulin in healthy adults. The potential mechanisms and clinical impact of our findings remain to be further elucidated. The study was registered at www.clinicaltrials.gov as NCT02836106.

Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction ­ ALPS-AMI study.

BACKGROUND: Statins reduce the incidence of cardiovascular events, but no randomized trial has investigated the best statins for secondary prevention. We compared the efficacy of hydrophilic pravastatin with that of lipophilic atorvastatin in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: A prospective, multicenter study enrolled 508 patients (410 men; mean age, 66.0 ± 11.6 years) with AMI who were randomly assigned to atorvastatin (n=255) or pravastatin (n=253). The target control level of low-density lipoprotein cholesterol (LDL-C) was <100 mg/dl, and patients were followed for 2 years. The primary endpoint was the composite of death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina or congestive heart failure requiring hospital admission, or any type of coronary revascularization. The primary endpoint occurred in 77 patients (30.4%) and in 80 patients (31.4%) in the pravastatin and atorvastatin groups, respectively (hazard ratio, 1.181; 95% confidence interval: 0.862-1.619; P=0.299), whereas greater reductions in serum total cholesterol and LDL-C were achieved in the atorvastatin group (P<0.001 for each). Changes in hemoglobin A1c, brain natriuretic peptide, and creatinine were not significant between the 2 regimens, and safety and treatment adherence were similar. CONCLUSIONS: On 2-year comparison of hydrophilic and lipophilic statins there was no significant difference in prevention of secondary cardiovascular outcome.

Results of a randomized,open-label,clinical trial investigating the effects of supplementation with Heracleumpersicum extract as an adjunctive therapy for dyslipidemia.

The present study evaluated the potential benefit of supplementation with Heracleumpersicum as an adjunctive therapy to atorvastatin in dyslipidemic subjects. In a randomized, open-label, clinical trial, 100 dyslipidemic subjects were randomly assigned to: (1) H. persicum group (n=50, completers=18), receiving H. persicum extract (500 mg/day) + atorvastatin (10 mg/day) for 8 weeks, or (2) atorvastatin group (n=50, completers=34), receiving only atorvastatin (20 mg/day) for 8 weeks. Weight, body mass index (BMI), lipid profile, and biomarkers of hepatic and renal injury were determined at baseline and at the end of the trial. There were significant reductions in serum total cholesterol and LDL-C in both the H. persicum (p=0.001) and atorvastatin (p< 0.001) groups. Serum HDL-C was elevated in the atorvastatin group (p< 0.05), while no significant change was observed in the H. persicum group (p> 0.05). Serum triglyceride levels remained statistically unchanged by the end of the trial in both groups (p> 0.05). Serum alanine (p=0.049) and aspartate aminotransferase (p=0.013) levels rose in the atorvastatin, but not the H. persicum(p> 0.05) group. In comparison with baseline values, no significant change was observed in weight and BMI, as well as serum levels of creatinine, blood urea nitrogen, and fasting blood sugar in either of the groups (p> 0.05). Apart from HDL-C, the effects of atorvastatin (20 mg/day) on other lipid profile parameters do not appear to be significantly superior to those achieved by combination therapy with H. persicum+ atorvastatin (10 mg/day).

[Research on the blood components detecting by multi-optical path length spectroscopy technique].

To discuss the feasibility of using the serum's multi-optical path length spectroscopy information for measuring the concentration of the human blood components, the automatic micro-displacement measuring device was designed, which can obtain the near-infrared multi-optical path length from 0 to 4.0 mm (interval is 0.2 mm) spectra of 200 serum samples with multioptical path length spectrum of serum participated in building the quantitative analysis model of four components of the human blood: glucose (GLU), total cholesterol (TC), total protein (TP) and albumin (ALB), by mean of the significant non-linear spectral characteristic of blood. Partial least square (PLS) was used to set up the calibration models of the multi-optical path length near-infrared absorption spectrum of 160 experimental samples against the biochemical analysis results of them. The blood components of another 40 samples were predicted according to the model. The prediction effect of four blood components was favorable, and the correlation coefficient (r) of predictive value and biochemical analysis value were 0.9320, 0.9712, 0.9462 and 0.9483, respectively. All of the results proved the feasibility of the multi-optical path length spectroscopy technique for blood components analysis. And this technique established the foundation of detecting the components of blood and other liquid conveniently and rapidly.

Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia.

AIM: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. METHODS: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent-to-treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and >or=200 mg/dl (2.6 mmol/l) (n = 413). RESULTS: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL(1)-C, LDL(2)-C and LDL(3)-C; real LDL-C (LDL-C(r)); intermediate-density lipoprotein cholesterol (IDL-C), IDL(1)-C, IDL(2)-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL(3)-C; and remnant-like lipoprotein cholesterol (RLP-C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high-density lipoprotein cholesterol (HDL-C) subclass HDL(3)-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL(1 + 2)-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL(4)-C and LDL-C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and >or=200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL(2)-C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL-C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. CONCLUSIONS: Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.

Lipid composition in rats with nonischemic chronic heart failure.

The initial stages of nonischemic chronic heart failure in rats (model of oleothorax) were accompanied by the development of dyslipidemia. This state was characterized by an increase in total cholesterol concentration (due to the fraction of low-density lipoproteins) and atherogenicity index. The concentrations of plasma total cholesterol and low-density lipoproteins were shown to decrease in animals with severe course of nonischemic chronic heart failure. These changes were accompanied by a decrease in the atherogenicity index. Intragastric administration of cholesterol had little effect on the lipid composition of blood plasma in rats, irrespective of the severity of heart failure.

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs.

Substituting abacavir for hyperlipidemia-associated protease inhibitors in HAART regimens improves fasting lipid profiles, maintains virologic suppression, and simplifies treatment.

BACKGROUND: Hyperlipidemia secondary to protease inhibitors (PI) may abate by switching to anti-HIV medications without lipid effects. METHOD: An open-label, randomized pilot study compared changes in fasting lipids and HIV-1 RNA in 104 HIV-infected adults with PI-associated hyperlipidemia (fasting serum total cholesterol >200 mg/dL) who were randomized either to a regimen in which their PI was replaced by abacavir 300 mg twice daily (n = 52) or a regimen in which their PI was continued (n = 52) for 28 weeks. All patients had undetectable viral loads (HIV-1 RNA <50 copies/mL) at baseline and were naive to abacavir and non-nucleoside reverse transcriptase inhibitors. RESULTS: At baseline, the mean total cholesterol was 243 mg/dL, low density lipoprotein (LDL)-cholesterol 149 mg/dL, high density lipoprotein (HDL)-cholesterol 41 mg/dL, and triglycerides 310 mg/dL. Mean CD4+ cell counts were 551 and 531 cells/mm3 in the abacavir-switch and PI-continuation arms, respectively. At week 28, the abacavir-switch arm had significantly greater least square mean reduction from baseline in total cholesterol (-42 vs -10 mg/dL, P < 0.001), LDL-cholesterol (-14 vs +5 mg/dL, P = 0.016), and triglycerides (-134 vs -36 mg/dL, P = 0.019) than the PI-continuation arm, with no differences in HDL-cholesterol (+0.2 vs +1.3 mg/dL, P = 0.583). A higher proportion of patients in the abacavir-switch arm had decreases in protocol-defined total cholesterol and triglyceride toxicity grades, whereas a smaller proportion had increases in these toxicity grades. At week 28, an intent-to treat: missing = failure analysis showed that the abacavir-switch and PI-continuation arms did not differ significantly with respect to proportion of patients maintaining HIV-1 RNA <400 or <50 copies/mL or adjusted mean change from baseline in CD4+ cell count. Two possible abacavir-related hypersensitivity reactions were reported. No significant changes in glucose, insulin, insulin resistance, C-peptide, or waist-to-hip ratios were observed in either treatment arm, nor were differences in these parameters noted between treatments. CONCLUSION: In hyperlipidemic, antiretroviral-experienced patients with HIV-1 RNA levels <50 copies/mL and CD4+ cell counts >500 cells/mm3, substituting abacavir for hyperlipidemia-associated PIs in combination antiretroviral regimens improves lipid profiles and maintains virologic suppression over a 28-week period, and it simplifies treatment.

Serum non-high-density lipoprotein cholesterol levels and the incidence of ischemic stroke in a Japanese population: the Jichi Medical School cohort study.

The predictive value of serum non-high-density lipoprotein cholesterol (non-HDL-C) levels for the incidence of ischemic stroke and its subtypes has not yet been established. The present cohort study investigated their relationships in a Japanese population. The first incidence of ischemic stroke and its subtypes was documented as the primary outcome. A total of 249 ischemic stroke patients (men/women = 145/104) were identified during a follow-up period of 10.7 years among 10 760 community-dwelling subjects (men/women = 4212/6548). Cox proportional hazard model analyses revealed that when compared with the lowest tertile of non-HDL-C, multivariate-adjusted hazard ratios for the highest tertile were 0.55 (95% confidence interval = 0.32-0.95, P = .03) on ischemic stroke and 0.29 (95% confidence interval = 0.08-1.05, P = .06) on cardioembolic infarction in women. Men did not show such significant relationships. Low serum non-HDL-C levels may be a predictive marker associated with an increase in the incidence of ischemic stroke and possibly of cardioembolic infarction in Japanese women.

A single daily dose of soybean phytosterols in ground beef decreases serum total cholesterol and LDL cholesterol in young, mildly hypercholesterolemic men.

BACKGROUND: Consumption of phytosterol-supplemented margarine lowers total plasma cholesterol (TC) and LDL-cholesterol concentrations in older middle-aged hypercholesterolemic individuals. The effects of incorporating phytosterols into lower-fat foods on the plasma lipids of young men at increased risk of developing cardiovascular disease have not been studied. OBJECTIVE: We tested the hypothesis that a single daily dose of soybean phytosterols added to ground beef will lower plasma TC and LDL-cholesterol concentrations in mildly hypercholesterolemic young men. DESIGN: In a triple-blind, 4-wk study, 34 male college students with elevated plasma TC (5.85 +/- 0.70 mmol/L), LDL cholesterol (4.02 +/- 0.60 mmol/L), and TC:HDL cholesterol (5.5 +/- 1.2) were randomly assigned to the control (ground beef alone) or treatment (ground beef with 2.7 g of phytosterols) group. The phytosterol mixture was two-thirds esterified and one-third nonesterified and consisted of beta-sitosterol (48%), campesterol (27%), and stigmasterol (21%). RESULTS: Consumption of phytosterol-supplemented ground beef lowered plasma TC and LDL-cholesterol concentrations and TC:HDL cholesterol from baseline by 9.3%, 14.6%, and 9.1%, respectively (P < 0.001). The LDL particle size did not change, suggesting that the decrease was primarily of particle number. The decreases were similar in subjects with (n = 8) and without (n = 9) a family history of premature cardiovascular disease. No significant changes were found in the control group. CONCLUSION: Phytosterol-supplemented ground beef effectively lowers plasma TC and LDL cholesterol and has the potential to become a functional food to help reduce the risk of cardiovascular disease.

Zinc absorption, mineral balance, and blood lipids in women consuming controlled lactoovovegetarian and omnivorous diets for 8 wk.

Zinc absorption, mineral balance, and blood lipid concentrations were measured in 21 women aged 33 +/- 7 y (range: 20-42 y) consuming controlled lactoovovegetarian and nonvegetarian diets for 8 wk each in a crossover design. The lactoovovegetarian and nonvegetarian diets, respectively, provided (by analysis) 973 and 995 mg Ca, 1.8 and 1.3 mg Cu, 367 and 260 mg Mg, 5.9 and 2.5 mg Mn, 1457 and 1667 mg P, 9.1 and 11.1 mg Zn, and (by calculation) 40 and 16 g dietary fiber, 2.5 and 0.8 mmol phytic acid, molar ratios of phytate to Zn of 14 and 5, and millimolar ratios of (phytate x Ca) to Zn of 344 and 111. Dietary zinc absorption was measured by extrinsic isotopic labeling and whole-body counting. Plasma cholesterol, cholesterol fractions, and lipoproteins were reduced 7-12% with the lactoovovegetarian diet, consistent with predictions based on dietary cholesterol and fat. Blood pressure was unaffected. Calcium, copper, magnesium, and phosphorus balances were not different between diets; manganese balance tended to be greater with the lactoovovegetarian diet (P < 0.07). The lactoovovegetarian diet was associated with a 21% reduction in absorptive efficiency that, together with a 14% reduction in dietary zinc, reduced the amount of zinc absorbed by 35% (2.4 compared with 3.7 mg/d) and reduced plasma zinc by 5% within the normal range. Zinc balance was maintained with both diets. Although there is a greater risk of zinc deficiency in persons consuming lactoovovegetarian compared with omnivorous diets, with inclusion of whole grains and legumes zinc requirements can be met and zinc balance maintained.

Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type I.

Glycogen storage disease type I (GSD-I) is frequently complicated by severe hyperlipoproteinemia and the increased potential risk of premature atherosclerosis. The effects of fish-oil supplementation [MaxEPA, 10 g.(1.73 m2)-1 for 3 mo] were investigated prospectively in seven hyperlipoproteinemic patients with GSD-I. Hypertriglyceridemia and hypercholesterolemia improved after 3 mo of fish-oil treatment, decreasing 49% (P < 0.005) and 23%, respectively. This was accompanied by a reduction in both low-density-lipoprotein (LDL) cholesterol (25%, P < 0.03) and apolipoprotein B (40%) and by increased high-density-lipoprotein increased (HDL) cholesterol (30%, P < 0.002) and apolipoprotein A-I (31%, P < 0.05). Low pretreatment ratios of HDL to total cholesterol and HDL to LDL, indicators of elevated atherosclerosis risk, increased significantly (P < 0.05). Plasma lipoprotein profile as well as lipoprotein composition [triglyceride (TG) enrichment and cholesteryl depletion] improved. Reduced TG concentrations were due to enhanced fat catabolism, as evidenced by the significantly increased hepatic and extrahepatic lipoprotein lipase activity (P < 0.05). Withdrawal of fish oil for 3 mo was associated with a return to pretreatment abnormalities in plasma lipids and lipoproteins. Fish-oil supplementation thus improves the hyperlipoproteinemia in GSD-I and may significantly reduce the risk of premature atherosclerotic cardiovascular disease.

Effects of graded amounts (0-50 g) of dietary fat on postprandial lipemia and lipoproteins in normolipidemic adults.

Eight normolipidemic males ingested on separate days and in a random order five mixed meals containing 0, 15, 30, 40, or 50 g fat. Fasting and postprandial blood samples were obtained for 7 h and chylomicrons and lipoproteins were isolated. The nonfat and 15-g fat meals did not generate noticeable postprandial variations except for HDL phospholipids (P < 0.05). The serum and chylomicron triacylglycerol responses obtained after the meals correlated positively with the amount of fat ingested and peaked after 2-3 h. Serum free cholesterol and phospholipids increased and esterified cholesterol decreased postprandially in a dose-response manner. At the same time, triacylglycerol-rich-lipoprotein triacylglycerols, esterified cholesterol, LDL free cholesterol, HDL triacylglycerols, phospholipids, and free cholesterol increased whereas LDL and HDL esterified cholesterol decreased when the amount of ingested fat increased. The data showed that increasing the amount of fat in the usual range of ingestion (0-50 g) led to stepwise increases in the postprandial rise of chylomicron and serum triacylglycerols and induced marked changes in serum lipoproteins postprandially. The existence of a no-effect level of dietary fat (15 g) on postprandial lipemia and lipoproteins in healthy adults was shown.

Omacor in familial combined hyperlipidemia: effects on lipids and low density lipoprotein subclasses.

Elevations of plasma cholesterol and/or triglycerides, and the prevalence of small, dense LDL particles remarkably increase coronary risk in patients with familial combined hyperlipidemia (FCHL). A total of 14 FCHL patients were studied, to investigate the ability of Omacor, a drug containing the n-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA and DHA), to favorably correct plasma lipid/lipoprotein levels and LDL particle distribution. The patients received four capsules daily of Omacor (providing 3.4 g EPA+DHA per day) or placebo for 8 weeks in a randomized, double-blind, cross-over study. Omacor significantly lowered plasma triglycerides and VLDL-cholesterol levels, by 27 and 18%, respectively. Total cholesterol did not change but LDL-cholesterol and apolipoprotein B (apoB) concentrations increased by 21 and 6%. As expected, LDL particles were small (diameter=24.9+/-0.3 nm) and apoB-rich (LDL-cholesterol/apoB ratio=1.27+/-0.26) in the selected subjects. After Omacor treatment LDL became enriched in cholesterol (LDL-cholesterol/apoB ratio=1.40+/-0.17), mainly cholesteryl esters, indicating accumulation in plasma of more buoyant and core enriched LDL particles. Indeed, the separation of LDL subclasses by rate zonal ultracentrifugation showed an increase of the plasma concentration of IDL and of the more buoyant, fast floating LDL-1 and LDL-2 subclasses after Omacor, with a parallel decrease in the concentration of the denser, slow floating LDL-3 subclass. However, the average LDL size did not change after Omacor (25.0+/-0.3 nm). The resistance of the small LDL pattern to drug-induced modifications implies that a maximal lipid-lowering effect must be achieved to reduce coronary risk in FCHL patients.

Coronary angiographic characteristics in Japanese patients with heterozygous familial hypercholesterolemia.

Coronary angiographic findings were analyzed in 51 consecutive patients (36 males and 15 females) with heterozygous familial hypercholesterolemia (FH) and 279 consecutive patients (216 males and 63 females) without FH (non-FH). The coronary stenosis index and over 75% stenosis vessel subset were almost three times as high in the FH group. The incidence of myocardial infarction was almost twice as high in the FH group. Levels of total cholesterol and its lipoprotein fractions, except HDL-cholesterol, were almost twice as high in the FH group. In the FH group aged under 50 years, the two parameters of coronary angiogram and the incidence of myocardial infarction were significantly higher in males than in females. However, in the group aged over 50 years, all three parameters were not significantly different between those in males and females. The level of HDL-cholesterol was significantly lower in males than in females. A significantly higher incidence (18%) of coronary ectasia was observed in the FH group compared with the incidence (2%) in non-FH. All patients with coronary ectasia were males, except one female with FH. On comparison of the males among the FH patients with those among the non-FH patients matched for total cholesterol, age and other risk factors, the FH patients were associated with a significantly higher degree of coronary atherosclerosis and lower level of HDL-cholesterol. Seven FH patients with a normal coronary angiogram were observed. However, any factors as regards age, total cholesterol, HDL-cholesterol and Achilles tendon thickness failed to distinguish between the FH patients with a normal coronary angiogram and those without.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the statin atorvastatin on intracellular signalling by the prostacyclin receptor in vitro and in vivo.

Prostacyclin plays a central role within the vasculature. We have previously established that the prostacyclin receptor (IP) undergoes isoprenylation, a lipid modification obligate for its function. The aim of the current study was to investigate the effect of the hydroxy methyl glutaryl co-enzyme A reductase inhibitor atorvastatin on signalling and function of the IP expressed in mammalian whole cells and in platelets isolated from patients undergoing therapeutic intervention with atorvastatin. Initially, the effect of atorvastatin on signalling by the human (h) and mouse (m) IP overexpressed in human embryonic kidney 293 cells and the hIP endogenously expressed in human erythroleukaemic 92.1.7 cells was investigated. Atorvastatin significantly reduced IP-mediated cAMP generation (IC(50) 6.6-11.1 microm) and [Ca(2+)](i) mobilization (IC(50) 7.2-16.4 microm) in a concentration-dependent manner, but had no effect on signalling by the nonisoprenylated beta(2) adrenergic receptor or the alpha or beta isoforms of the human thromboxane A(2) receptor (TP). Moreover, atorvastatin significantly reduced IP-mediated crossdesensitization of signalling by TP alpha (IC(50) 10.4 microm), but not by TP beta. In contrast to the whole-cell data, atorvastatin therapy did not interfere with IP-mediated cAMP generation or IP-induced inhibition of TP-mediated aggregation of platelets isolated from human volunteers undergoing therapeutic intervention with atorvastatin (10-80 mg per daily dose). In conclusion, while data generated in whole cells indicated that atorvastatin significantly impairs signalling by both the hIP and mP, the in vivo clinical data indicated that, at the administered therapeutic dose, atorvastatin does not significantly compromise IP signalling and function in humans.

Triglyceride and coronary heart disease mortality in a 24-year follow-up study in Xi'an, China.

PURPOSE: To study whether serum triglyceride (TG) was associated with coronary heart disease (CHD) mortality. METHODS: A cohort analytic study carried out in a machinery factory in Xi'an, China on 1696 subjects aged 35 years or above (1124 men and 572 women) examined in 1976 and followed up till 2000. RESULTS: At baseline, the mean serum total cholesterol (TC) and triglyceride (TG) was 4.64 and 1.16 mmol/L in men, 4.62 and 1.10 mmol/L in women, respectively. Three hundred six (239 men, 67 women) had died within 37,781 person-years of follow-up, with 49 CHD deaths (36 male, 13 female). The relative risk (95% confidence interval) of CHD mortality per mmol/L increase in TG was 2.13 (1.46-3.17) after adjusting for age, marital status, occupation, education, systolic blood pressure and TC. Dose-response relationship between TG levels by tertiles and CHD risk was found. Stratified analyses showed TG was an independent predictor for CHD mortality in subjects with lower or higher TC. CONCLUSIONS: Chinese had lower levels of TC and TG than Western populations. This study provides new evidence that TG is an independent risk factor of CHD in subjects with lower or higher TC levels, and supports the lowering of cut-off value for elevated triglyceride.

Total cholesterol and mortality in China, Poland, Russia, and the US.

PURPOSE: To examine the relationships of total and cause-specific mortality to serum cholesterol in four diverse populations. METHODS: Chinese, Polish, Russian, and US population-based samples were studied. The relationship between cholesterol levels and mortality was assessed by Cox proportional hazard regression with restricted piecewise cubic splines. RESULTS: The cholesterol and total mortality relationship was statistically significantly J-shaped for all men combined. In country-specific relationships, cholesterol was significantly, linearly, and positively related to total mortality in Russian and US men. For women, the relationship was non-linear, but not statistically significant, and became statistically significant upon adjustment for other risk factors. For Polish women, a statistically significant inverse relationship existed. CHD mortality and cardiovascular disease (CVD) mortality increased linearly with cholesterol in Polish, Russian, and US men and the aggregate of men, but there was no relationship for women. Cancer mortality was not related to cholesterol except for the Polish cohort and Russian women, where there was an inverse relationship. CONCLUSIONS: Serum cholesterol was a strong, consistent predictor of CHD and CVD mortality in Polish, Russian, and US men despite their social diversity. In contrast to CHD mortality, the relation of cholesterol to total mortality and non-CVD mortality varied by country and gender.

Metabolic effects of diuretic and beta-blocker treatment of hypertension in patients with non-insulin-dependent diabetes mellitus.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) and hypertension were studied before and after three months of combined beta-blocker-diuretic treatment. Blood pressure fell significantly (P less than .001) from (mean +/- SEM) 167 +/- 3/99 +/- 1 to 142 +/- 3/88 +/- 1 mm Hg. However, mean (+/- SEM) fasting plasma glucose concentration increased significantly (P less than .001) from 132 +/- 11 to 153 +/- 10 mg/dL. In addition, significant increases (P less than .05) were noted in fasting concentration of plasma total triglyceride, very-low-density lipoprotein (VLDL)-triglyceride and VLDL-cholesterol, whereas fasting plasma high-density lipoprotein (HDL)-cholesterol was significantly lower (P less than .05). Thus, a common treatment program for hypertension exacerbated the abnormalities of carbohydrate and lipid metabolism commonly present in patients with NIDDM. Since the changes noted would increase risk of vascular disease, attention should be focused on selection of treatment programs for lowering blood pressure in patients with NIDDM in order to avoid this outcome.