Lipid-lowering property of Clausena anisum-olens in hypercholesterolemic rats

Context: Clausena anisum-olens (Blanco) Merr. (Rutaceae) is a medicinal shrub which has been reported to have various pharmacological uses. No study regarding the effects of C. anisum-olens on cholesterol-lowering has been reported.

Objective: The effects of the ethanol extract of C. anisum-olens leaves on the cholesterol level of hypercholesterolemic rats were evaluated.

Materials and methods: Acute oral toxicity of the extract (175, 550 and 2000?mg/kg) was determined using female Sprague-Dawley rats, as described in OECD 425 Main test guidelines. The lipid-lowering assay utilized 30 male Sprague-Dawley rats divided into five groups (A–E). Triton X-100 was administered to induce hypercholesterolemia. After hypercholesterolemia induction, oral treatment of Atorvastatin and crude ethanol extract was given daily to the treatment groups for 14 days. The total cholesterol, triglycerides, HDL and LDL were determined before induction, after induction, after first week of treatment and after second week of treatment.

Results: Acute oral toxicity showed the crude extract is nontoxic up to 2000?mg/kg. The lipid-lowering assay indicated reduction of serum cholesterol (87.21?±?5.10?mg/dL), triglycerides (58.09?±?4.10?mg/dL) and LDL (27.82?±?4.11?mg/dL) for 200?mg/kw extract. Reduction in serum cholesterol (74.72?±?3.64?mg/dL), triglycerides (52.79?±?2.98?mg/dL) and LDL (12.06?±?5.51?mg/dL) were observed for 400?mg/kg group. The result is comparable to Atorvastatin, which showed serum cholesterol (80.90?±?9.72?mg/dL), triglycerides (55.94?±?7.19?mg/dL) and LDL (22.09?±?7.60?mg/dL) reduction.

Discussion and conclusion: The crude extract of C. anisum-olens proved to be useful in lowering of cholesterol.     

Myrtenal alleviates hyperglycaemia,hyperlipidaemia and improves pancreatic insulin level in STZ-induced diabetic rats

Context: Myrtenal is monoterpene a constituent of essential oils found mainly in herbs such as mint, pepper, cumin, etc. It exerts admirable pharmacological activities against many diseases including diabetes. Hyperlipidaemia is a secondary complication of diabetes and also a major risk factor for cardiovascular diseases.

Objective: The present study investigated the possible antihyperlipidaemic efficacy of myrtenal on plasma glucose, pancreatic insulin, plasma and tissue lipid levels in streptozotocin (STZ) induced diabetic rats.

Materials and methods: Diabetes was induced in male Wistar rats by a single intraperitoneal injection of STZ (40?mg/kg b.w.). Myrtenal (80?mg/kg) was administered orally to diabetic rats for a period of 28 d. Plasma glucose, pancreatic insulin, TC, TGs, FFAs, PLs, LDL-C, HDL-C, VLDL, atherogenic index, (HMG-CoA) reductase, LPL, LCAT and liver histology were analyzed.

Results: Diabetic rats showed significantly (p?<?0.05) increased plasma glucose (273.18?mg/dL), total cholesterol (142?mg/dL), triglycerides (126?mg/dL), free fatty acids (118?mg/dL), phospholipids (153?mg/dL), low-density lipoprotein (88.07?mg/dL), very low-density lipoprotein (25.2?mg/dL), atherogenic index, whereas a decrease in the levels of pancreatic insulin (97.48?ng/mg) and high-density lipoprotein (29.12?mg/dL). In addition, the activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase (0.94 HMG-CoA ratio/(mevalonate) increased significantly in contrast to the activities of lipoprotein lipase (4.87 μmoles of glycerol liberated/h/L) and lecithin cholesterol acyltransferase (54.61 μmoles of cholesterol esterified/h/L) in diabetic rats. Treatment with myrtenal significantly (p?<?0.05) improved the levels of plasma glucose, pancreatic insulin and lipid profiles. Moreover, the histopathological analysis of liver was also in agreement with the biochemical findings.

Discussion and conclusions: The present study indicates that myrtenal possess antihyperglycaemic and antihyperlipidemic properties, and could potentially be a useful phytochemical in treating diabetes.     

Effects of ezetimibe,simvastatin, atorvastatin,and ezetimibe–statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia

ABSTRACT

Background: Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and ratios of these sterols to total cholesterol (TC) are reported to correlate with efficiency of intestinal cholesterol absorption, whereas levels of certain cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios to TC correlate with cholesterol biosynthesis. However, there is a paucity of published data concerning the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) on these parameters.

Objectives: To characterize the effects of ezetimibe co-administered with statins, compared with each treatment alone, on cholesterol precursor sterols and plasma phytosterol levels.

Methods: A post-hoc analysis was performed to determine the effects of treatment with ezetimibe 10?mg, simvastatin (10–80?mg), and atorvastatin (10–80?mg), alone or in combination, on these non-cholesterol sterols using plasma samples from two randomized controlled trials involving patients with primary hypercholesterolemia (low-density lipoprotein [LDL-C]?=?145–250?mg/dL; triglycerides ≤350?mg/dL; N?=?975) but without a recent (≤6-month) history of coronary heart disease (CHD) or either uncontrolled or newly diagnosed diabetes mellitus.

Results: Ezetimibe monotherapy significantly reduced plasma sitosterol and campesterol concentrations from baseline compared with placebo (both p?<?0.001), whereas statins significantly lowered desmosterol and lathosterol levels (p?<?0.001 vs. placebo). Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these sterols (p?<?0.001).

Conclusions: The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe–statin) doses and circulating non-cholesterol levels.     

Comparison of self-reported survey (SHIELD) versus NHANES data in estimating prevalence of dyslipidemia

ABSTRACT

Objectives: The study purpose was to compare the prevalence of dyslipidemia between a self-reported survey, Study to Help Improve Early evaluation and management of risk factors Leading to Diabetes (SHIELD), and survey and laboratory data from National Health and Nutrition Examination Survey (NHANES 1999–2002).

Methods: A SHIELD questionnaire was mailed to 200?000 households representative of US adult population (64% response, n = 211?097 individuals) and included if ever diagnosed with diabetes, high blood pressure or cholesterol problems, high total cholesterol (TC), high bad cholesterol (LDL-C), low good cholesterol (HDL-C), or high triglycerides (TG). In NHANES using a combination of interviewer-administered survey and clinical and laboratory data, dyslipidemia was defined as any one of: TC ≥?240?mg/dL or diagnosis of high cholesterol; TG >?200?mg/dL;LDL-C ≥?160?mg/dL; or HDL-C <?40?mg/dL. NHANES diabetes mellitus definition was doctor diagnosis or fasting glucose >?125?mg/dL and hypertension was elevated blood pressure or taking anti-hypertensive medication. Prevalence of dyslipidemia was determined for SHIELD in 2004 and compared to NHANES 1999–2002. Prevalence of diabetes and hypertension was estimated for broader contextual comparison within cardiometabolic diseases.

Results: In contrast to the prevalence of diabetes (8% in SHIELD and 9% in NHANES, p < 0.01) and hypertension (23% in SHIELD and 29% in NHANES, p < 0.01), dyslipidemia was reported only half as frequently in SHIELD (26%) as in NHANES (53%), p < 0.01. Com­ponents of dyslipidemia were uniformly less in SHIELD than NHANES: high TC = 17 vs. 35%, high LDL-C = 10 vs. 14%, high TG = 7 vs. 17% and low HDL-C = 5 vs. 24%; all comparisons p < 0.01.

Limitations: Differences in survey methodology, non-response and timing may have impacted the comparison of SHIELD to NHANES.

Conclusions: Dyslipidemia prevalence was lower in self-reported SHIELD than the objectively assessed NHANES, with especially low self-report of high TG and low HDL-C. Self-reported prevalence of dyslipidemia may under-report the prevalence based on laboratory data.     

Galangin,a dietary flavonoid,ameliorates hyperglycaemia and lipid abnormalities in rats with streptozotocin-induced hyperglycaemia

Context: Galangin, a natural flavonoid, is found in honey and Alpinia officinarum Hance (Zingiberaceae). Galangin has antiviral, antimicrobial, antidiabetic and anticancer properties, without side effects. The effects of galangin on hyperglycaemia and lipid abnormalities are not known.

Objective: To elucidate the effectiveness of galangin on hyperglycaemia-associated complications and lipid changes in rats with streptozotocin (STZ)-induced hyperglycaemia.

Materials and methods: Diabetes was induced in adult Wistar rats by administering 40?mg/kg of STZ. In our previous study, galangin had no toxicity at concentrations up to 320?mg/kg. Therefore three doses of galangin (4, 8 or 16?mg/kg BW) or glibenclamide (600 µg/kg BW) were administered daily to diabetic rats orally for 45 days.

Results: Diabetic rats showed a significant (p?p?p?Discussion and conclusions: Administration of galangin reduced hyperlipidaemia related to the risk of diabetic complications and could be beneficial for diabetic hyperlipidaemic patients. Further work detailing its mechanism-of-action for improving hyperglycaemic-associated lipid abnormalities is needed.     

Hypolipidemic effects of different angiocarp parts of Alpinia zerumbet

Context: In utilization of Alpinia zerumbet (Pers.) Burtt and Smith (Zingiberaceae) (AZ), usually the angiocarps are discarded without further use.

Objective: We speculate whether the angiocarps could show hypolipidemic effect.

Methods and methods: Several diets were prepared: Alpinia seed powder (ASP); Alpinia seed powder/husk (ASH): 40/60; and Alpinia seed essential oil (ASO): 0.01–0.10%. Sprague-Dawley rats divided into 11 groups were fed these diets for 8 weeks and tested for the hypolipidemic bioactivity.

Results: The fecal neutral cholesterol excretion was increased, and the serum total triglyceride (TG) was significantly reduced from 153.7?mg/dL in the high-fat group (H) to 114.3–119.8?mg/dL by ASO; to 116.3–147.9?mg/dL by ASP; and to 116.2–145.3?mg/dL by ASH. Activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were almost unaffected. The high-density lipoprotein (HDL) levels were mostly raised by ASO to 180.3–200.8?mg/dL. The low-density lipoprotein (LDL) levels were mostly reduced to 66.8–82.6?mg/dL by ASH. The level of arachidonic acid was mostly raised to 0.50–0.60% by ASO, compared with 0.37% of group H. More importantly, the significant reduction in hepatic TG and total cholesterol (TC) implicated a crucial liver protective effect.

Discussion and conclusion: ASP and ASH consisted of high crude-fiber content, while ASO consisted of seed essential oil. Both the seed essential oil and the whole powder of AZ previously had been reported to possess potent hypolipidemic bioactivity. Conclusively, the hypolipidemic effect can be attributed to the combined effect of the essential oil and the crude fiber.     

Preventive effects of royal jelly against anaphylactic response in a murine model of cow’s milk allergy

Context: Royal jelly (RJ) has long been used to promote human health.

Objective: The current study investigated the preventive effects of RJ against the development of a systemic and intestinal immune response in mice allergic to cow’s milk proteins.

Materials and methods: Balb/c mice treated orally for seven days with RJ at doses of 0.5, 1 and 1.5?g/kg were sensitized intraperitoneally with β-lactoglobulin (β-Lg). Serum IgG and IgE anti-β-Lg were determined by an enzyme-linked immunosorbent assay (ELISA). Plasma histamine levels, symptom scores and body temperature were determined after in vivo challenge to β-Lg. Jejunums were used for assessment of local anaphylactic responses by an ex vivo study in Ussing chambers and morphologic changes by histological analysis.

Results: RJ significantly decreased serum IgG (31.15–43.78%) and IgE (64.28–66.6%) anti-β-Lg and effectively reduced plasma histamine level (66.62–67.36%) (p?p?p?Discussion and conclusions: We speculate that using RJ may help prevent systemic and anaphylactic response in allergic mice. These effects may be related to its inhibitory effects on the degranulation of mast cells.     

Regulatory/modulatory effect of prune essence concentrate on intestinal function and blood lipids

Context: Prunus domestica Linn (Rosaceae) has been considered a functional food, owing to its various pharmacological activities, including antioxidant, anti-inflammatory, antidiabetic and anticancer.

Objective: This placebo-controlled, randomized study was framed to check the beneficial activity of prune essence concentrates (PEC) in corroboration with intestinal function and lipid profile in mildly hypercholesterolemic subjects.

Materials and methods: Sixty healthy mild hypercholesterolemic subjects were randomly chosen and segregated into three groups as placebo (consume 50?mL of simulated prune drink), PEC I (consume 50?mL of PEC/day) and PEC II (consume 100?mL of PEC/day) for 4 weeks with 2 weeks of follow-up without PEC consumption.

Results: Intake of PEC (I and II) for 4 weeks substantially ameliorated (p?Bifidobacterium spp. (1.18- and 1.19-fold) and Lactobacillus spp. (1.07- and 1.16-fold), but markedly lowered (p?Clostridium perfringens (5.97 and 8.35%) and Escherichia coli (6.25 and 9.38%). Meanwhile, the total cholesterol (TC; 5.90 and 6.99%) levels and LDL-c (6.68 and 6.53%) were significantly reduced (p?p?Discussion and conclusion: Overall, the results suggest that the use of PEC may positively regulate the intestinal microflora and thereby effectively lower the TC levels and thus act as a hypocholesterolemic agent.     

Carotid intima-media thickness in low-risk individuals with asymptomatic atherosclerosis: baseline data from the METEOR study*

ABSTRACT

Objective: Carotid intima-media thickness (CIMT) is an index for changes in atherosclerosis burden and changes in CIMT may relate to clinical events. We present baseline data from the METEOR study, a randomized, placebo-controlled trial evaluating the efficacy of rosuvastatin 40?mg on changes in CIMT. We set out to compare differ­ences in CIMT between several subgroups of individuals.

Design and methods: A total of 984 individuals aged 45–70 years (men) or 55–70 (women) were randomized. Participants were required to have: maximum CIMT ≥?1.2–<?3.5?mm; 2+ risk factors and 10-year coronary heart disease (CHD) risk <?10%, or <?2 CHD risk factors. Demo­graphic characteristics were compared in two groups: USA versus Europe, and individuals with maximum CIMT <?2?mm versus those with CIMT ≥?2?mm.

Baseline data: Overall, mean age was 57 years and mean low-density lipoprotein cholesterol was 152?mg/dL (3.9?mmol/L). Body mass index (BMI), triglyceride and high-sensitivity C-reactive protein levels were all higher in US individuals, whereas smoking, hypertension and high-density lipoprotein cholesterol levels were higher in Europeans. Mean CIMT levels were the same in both populations, and the percentage of individuals with ≥?2 CHD risk factors was similar. Increased baseline CIMT (>?2?mm) was related to increasing age, male gender, smoking, hypertension and lipid levels.

Conclusions: In this global trial, differences in baseline characteristics between participants from the USA and Europe are apparent. However, a strong association between CIMT and several cardiovascular risk factors was observed across the two continents.

Trial registration: ClinicalTrials.gov identifier: NCT00225589.     

Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter,double-blind,double-mimic,randomized clinical trial

Abstract

Background: We investigated the lipid-lowering efficacy and safety of coenzyme A (CoA) versus fenofibrate in Chinese patients with moderate dyslipidemia.

Methods: A total of 417 subjects (aged 18–75?years) diagnosed with moderate dyslipidemia (triglyceride 2.3–6.5?mmol/L) from 13 large cardiovascular centers in China were recruited and randomly divided into a fenofibrate group (n?=?207), which received 200?mg of fenofibrate orally once daily, and a CoA group (n?=?210), which received 400?mg of CoA orally once a day. Blood lipoproteins, liver and renal function, creatine kinase, and blood glucose were measured at baseline, and after 4 and 8?weeks of treatment.

Results: The baseline triglyceride (TG) level in the fenofibrate group and the CoA group was 3.39?±?0.99?mmol/L and 3.60?±?1.11?mmol/L, respectively. After treatment for 4 and 8?weeks with fenofibrate, TG was reduced by 31.62% and 33.13%. In the CoA group, TG was reduced by 17.29% and 23.80%. Compared with baseline, total cholesterol (TC) was significantly decreased in both groups after either 4 or 8?weeks of treatment (p?<?.05). CoA increased high-density lipoprotein cholesterol (HDL-C) after 4?weeks of treatment, whereas it had no significant effect on HDL-C after 8?weeks of treatment. Low-density lipoprotein cholesterol (LDL-C) was not modified in either group. The incidence of side effects was significantly lower in the CoA group compared with the fenofibrate group (p?<?.05).

Conclusions: Compared with fenofibrate, CoA has less effect on reducing plasma TG levels in subjects with moderate dyslipidemia. However, it has fewer adverse effects.     

Effect of ezetimibe in patients who cannot tolerate statins or cannot get to the low density lipoprotein cholesterol target despite taking a statin

ABSTRACT

Background: Recent guidelines underline the need for high-risk patients to reach strict low density lipoprotein cholesterol (LDL?C) targets (1.8–2.6?mmol/L; 70–100?mg/dL), and specifically mention the possible use of combination therapy (e.g. statin + ezetimibe) to achieve these goals.

Methods: A retrospective case-note audit was carried out to assess the response to administering ezetimibe in patients unable to tolerate statins (Group 1), or high dose of statins (Group 2) and patients who cannot achieve the LDL?C target (2.6?mmol/L; 100?mg/dL) despite taking a statin (Group 3).

Results: Ezetimibe lowered LDL?C levels by 20–29% across the 3 patient groups after 2–3 months of treatment. High density lipoprotein cholesterol (HDL?C) levels tended to remain unchanged, although there was a consistent trend for a fall if baseline values were ‘high’. However, the LDL-C/HDL-C ratio changed significantly and favourably in all groups. The fall in fasting triglyceride levels in all groups was greater (reaching 19–25%) when baseline levels were ≥ 1.5 or 1.7?mmol/L (136–150?mg/dL). There were no marked abnormalities in liver function tests or creatine kinase activity. In Group 3 there was a significant trend for a fall in serum creatinine levels across the tertiles of baseline creatinine values.

Limitations of the present study include the small sample size (especially in Groups 1 and 2), its short-term duration and the absence of event-based end-points. Therefore, the results are hypothesis-generating rather than conclusive.

Conclusions: When used alone or added to a statin, ezetimibe favourably altered the LDL?C/HDL?C ratio and lowered triglyceride levels. Ezetimibe was well tolerated in patients with statin intolerance and was associated with a 26% fall in LDL?C. An additional action may be some degree of improved renal function. Further studies are needed to confirm these findings.     

Uric acid and incident chronic kidney disease in dyslipidemic individuals

Background: Elevated uric acid (UA) is a recognized risk factor for chronic kidney disease (CKD). This study aimed to investigate whether this association exists in dyslipidemic patients receiving multifactorial treatment.

Methods: An observational study conducted in Greece including 1,269 dyslipidemic individuals followed-up in a lipid clinic for ≥3 years. Estimated glomerular filtration rate (eGFR) was calculated by CKD-EPI equation and CKD was defined as ≤60?mL/min/1.73 m². The correlation was assessed between UA levels and the CKD risk after adjusting for potential confounding factors, after defining the following UA quartiles: Q1: ?6?mg/dL.

Results: After excluding patients with baseline eGFR <60?mL/min/1.73 m², gout and those taking UA-lowering drugs, 1,095 individuals were eligible; of those, 91% and 69% were treated with statins and anti-hypertensive drugs, respectively. During their follow-up (6 years; IQR?=?4–10), 11.9% of the subjects developed CKD, whereas the median annual eGFR decline was 0.69?mL/min/1.73 m² (IQR?=?0.45–2.33). Multivariate analysis showed that baseline UA levels (HR?=?1.26; 95% CI?=?1.09–1.45, p?=?.001), female gender (HR?=?1.74; 95% CI?=?1.14–2.65, p?=?.01), age (HR?=?1.10; 95% CI?=?1.07–1.12, p?p?=?.03), cardiovascular disease (HR?=?1.62; 95% CI?=?1.02–2.58, p?=?.04), decreased baseline renal function (eGFR <90?mL/min/1.73 m²) (HR?=?2.38; 95% CI?=?1.14–4.81, p?=?.02), and low-density lipoprotein cholesterol reduction (HR?=?0.995; 95% CI?=?0.991–0.998, p?=?.01) were associated with incident CKD. Additionally, patients with UA ≥6?mg/dL exhibited a higher risk of incident CKD compared with those in the lowest UA quartile (HR?=?2.01; 95% CI?=?1.11–3.65, p?=?.02).

Conclusion: Higher UA levels are correlated with a higher risk of incident CKD in dyslipidemic individuals taking multifactorial treatment.     

Beneficial effect of Citrus limon peel aqueous methanol extract on experimentally induced urolithic rats

Context: Citrus limon (L.) Burm.f. (Rutaceace) is a commonly available fruit variety with high medicinal and industrial values.

Objective: Lemon peel (LP) extract was studied as a potent preventive and curative agent for experimentally induced hyperoxaluric rats.

Materials and methods: Gas chromatography–mass spectrometry (GC–MS) analyses and toxicity study were performed for aqueous methanol LP extract. Twenty-four Wistar rats were segregated into four groups. Group 1: Control; Group 2: Urolithic (ethylene glycol (EG) – 0.75%); Group 3: Preventive study (EG?+?LP extract administration from 0th to 7th week); Group 4: Curative study (EG?+?LP extract administration from 4th to 7th week). Animals received LP extract daily by oral administration (100?mg/kg body weight) for 7 weeks.

Results and discussion: GC–MS analyses revealed that compound 6 was abundant in the LP extract (32%) followed by compound 1 (～21%). The LD₅₀ value of LP extract was found to be >5000?mg/kg of body weight. Urolithic rats showed significantly higher urinary calcium and oxalate (4.47?±?0.44 and 18.86?±?0.55?mg/24 h, respectively) excretion compared with control and experimental rats. Renal function parameters like urea (84?±?8.5 and 96.1?±?3.6?mg/dL), creatinine (1.92?±?0.27 and 1.52?±?0.22?mg/dL), and urinary protein (2.03?±?0.02 and 2.13?±?0.16?mg/24 h) were also reduced by LP extract (p?<?0.001) and corroborated with tissue analyses (SOD, catalase, and MDA levels) and histological studies in normal and experimental animals. Immunohistochemical staining of THP and NF-κB in urolithic animals showed elevated expression than the control, while LP extract suppressed the expression of these proteins.

Conclusion: In conclusion, lemon peel is effective in curing kidney stone disease and also can be used to prevent the disease and its recurrence.     

Effect of raloxifene on the incidence of elevated low density lipoprotein (LDL) and achievement of LDL target goals in postmenopausal women

SUMMARY

Objective: To determine the extent to which raloxifene can maintain low density lipoprotein cholesterol (LDL-C) levels below 160?mg/dL or reduce elevated LDL-C levels to below lipidlowering goals in postmenopausal women.

Patients and methods: The Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial randomized 7705 postmenopausal women to placebo or raloxifene (60?mg or 120 mg) daily for a core treatment phase of 3 years. Changes in LDL-C and other serum lipids in a subset of women was a predefined secondary objective. This post-hoc analysis included the 2413 women who did not take lipid-lowering medications at any time during the trial and for whom LDL-C measurements were available. The threshold for high LDL-C (≥ 160?mg/dL) and LDL-C lipid-lowering goals were defined according to National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines.

Results: The percent of women with LDL-C < 160?mg/dL was comparable between treatment groups at baseline (placebo, 57.5%; raloxifene 60?mg, 56.4%; raloxifene 120?mg, 56.8%). At 3 years, the percent of these women whose LDL-C had increased to above 160?mg/dL was significantly less in the raloxifene 60?mg and 120?mg groups compared with placebo by 65% (95% CI, 44%–78%) and 64% (95% CI, 43%–77%), respectively. Among women with elevated (defined for these analyses as ≥ 160?mg/dL) LDL-C at baseline, the proportion having elevated LDL-C at 3 years was significantly less in the raloxifene 60?mg and 120?mg groups compared with placebo by 32% (95% CI, 24%–40%) and 40% (95% CI, 32%–48%), respectively. Fifty percent and 13% of these women achieved LDL-C goals of <160?mg/dL and <130?mg/dL, respectively (P <0.001 vs. placebo for both) in the raloxifene 60?mg group, with similar results for the raloxifene 120?mg group.

Conclusions: In postmenopausal women with osteoporosis not taking concurrent lipid-lowering therapy, raloxifene significantly reduced the incidence of LDL-C ≥ 160?mg/dL and significantly increased the proportion achieving LDL-C goals for lipid-lowering compared with placebo. Whether these and other effects of raloxifene on cardiovascular risk markers will improve cardiovascular outcomes requires further study.     

Impact of noncompliance with urate-lowering drug on serum urate and gout-related healthcare costs: administrative claims analysis

ABSTRACT

Objective: To determine the association between allopurinol compliance and serum urate (sUA) level; and examine the association between sUA and gout-related healthcare costs in a large managed care population.

Research design and methods: This retrospective administrative claims analysis examined subjects with gout (≥2 medical claims with ICD-9-CM diagnosis code 274.xx or ≥1 claim with a gout diagnosis and ≥1 pharmacy claim for allopurinol, probenecid, colchicine, or sulfinpyrazone) between January 1, 2002 and March 31, 2004. Each subject was observed during 1-year pre-index and 1-year post-index periods.

Main outcome measures: Outcomes were allopurinol medication possession ratio (MPR) and compliance (MPR?≥?0.80), sUA (mg/dL), and gout-related healthcare costs. ‘Post-allopurinol’ sUA was measured during three periods after the first observed allopurinol fill: 30–89 days; 90–149 days; ≥150 days. A baseline sUA on or before the start of the post-index period was also identified. Outcomes were stratified by post-allopurinol or baseline sUA and compliance. Generalized linear modeling (GLM) regression measured the impact of baseline sUA on gout-related healthcare costs, controlling for demographic and health status variables.

Results: The study sample comprised 18?243 subjects with mean age of 53.9 years. In all, 55% (n?=?10?073) of subjects used allopurinol. There were 1473 (8.1%) subjects with a post-allopurinol sUA and 2438 (13.4%) subjects with a baseline sUA result. Among all subjects with a post-allopurinol sUA, 45.6% were compliant; between 49.3% and 56.8% of compliant subjects had an sUA?<?6.0?mg/dL compared with 22.5–27.8% of non-compliant subjects, depending on the post-allopurinol time period (all p?<?0.001). GLM results showed gout-related costs associated with baseline sUA?≥?6.0 and?<?9.0?mg/dL were 58% higher (95% confidence interval (CI): 1.012 –2.456; p?=?0.044) than were costs for sUA?<?6.0?mg/dL. There was no significant difference in gout-related costs between baseline sUA?<?6.0?mg/dL and ≥9.0?mg/dL.

Conclusions: Analysis revealed an important associations between allopurinol compliance, sUA, and gout-related costs: compliance was positively associated with favorable sUA (<6.0?mg/dL) in unadjusted comparisons. GLM showed that baseline sUA?<?6.0 was inversely associated with gout-related costs relative to baseline sUA?≥?6.0 and <9.0?mg/dL. Nevertheless, a substantial portion of subjects, even compliant ones, did not achieve sUA?<?6.0?mg/dL. These results should be interpreted carefully in light of study limitations, including incomplete laboratory data, the potentially incorrect inference that medications were taken as prescribed, and lack of generalizability from Medicare managed care enrollees to the broader Medicare population.     

Hesperidin,a citrus flavonoid,protects against l-methionine-induced hyperhomocysteinemia by abrogation of oxidative stress,endothelial dysfunction and neurotoxicity in Wistar rats

Context: Hesperidin (HSP), a flavanoglycone found in citrus fruits, has antioxidant, anti-inflammatory and neuroprotective properties.

Objective: This study evaluates the protective effect of HSP on l-methionine-induced hyperhomocysteinemia (HHcy) in rats.

Materials and methods: Male Wistar rats were randomly divided into seven groups as DMSO, l-methionine, HSP (25, 50 and 100?mg/kg), HSP-per se (100?mg/kg) and donepezil (0.1?mg/kg). HHcy was induced by oral administration of l-methionine (1.7?g/kg) for 32 days. From the 14^th day of study HSP (25, 50 and 100?mg/kg) and donepezil was administered orally to l-methionine-treated rats. Cognitive impairment induced by HHcy was determined using the Morris water maze (MWM) and Y-maze on video tracking system (28^th–32^nd day). Different biomarkers of HHcy in serum and brain and vascular reactivity were evaluated and histopathology (thoracic aorta and brain) was done.

Results: HSP (100?mg/kg) treatment in l-methionine-treated rats exhibited significant (p?p?l-methionine on acetylcholine-induced endothelial-dependent relaxation and increased serum nitrite and vascular nitric oxide bioavailability along with the restoration of histological aberrations.

Conclusion: HSP exerts a protective effect on HHcy by abrogating oxidative stress, ED and neurotoxicity.     

Curcumin inhibits hyperlipidemia and hepatic fat accumulation in high-fructose-fed male Wistar rats

Context: Curcumin, an active principal of Curcuma longa Linn. (Zingiberaceae), has potent antioxidant and anti-inflammatory properties.

Objectives: This study investigated the effects of curcumin on hyperlipidemia and hepatic steatosis in high-fructose-fed Wistar rats.

Materials and methods: Forty male Wistar rats were divided into four groups with 10 rats in each. Two groups were fed with standard rodent diet and the other two with 60% high-fructose diet for 10 weeks. Curcumin (200?mg/kg body weight) was administered along with the diets simultaneously to each of the aforementioned diet groups. After 10 weeks of experiment, blood samples were collected from tail vein. Liver, adipose and epididymal tissues were collected after sacrifice of the animals and stored for further analyses.

Results: Administration of curcumin reduced body weight (280.6?±?7.4?g), liver weight (2.5?±?0.2?g/100?g BW), adipose weight (1.4?±?0.3?g/100?g BW), plasma levels of TAG (86.1?±?13.5?mg/dL), VLDL-C (17.2?±?2.7?mg/dL), lipid ratios and increased HDL-C (28.4?±?4.5?mg/dL) in fructose-fed rats. Curcumin supplementation significantly lowered TAG content and decreased the protein expression of LXR-α (43%) and SREBP1c (59%) in the liver. Furthermore, curcumin suppressed the expression of lipogenic enzymes, ACLY (95%), ACC (50%) and FAS (77%) in rats fed with high-fructose diet. No significant change was found in the expression of PPAR-α.

Discussion and conclusion: Curcumin prevented the high-fructose induced hyperlipidemia and hepatic steatosis.     

Protective effects of Ficus carica leaves on glucose and lipids levels,carbohydrate metabolism enzymes and β-cells in type 2 diabetic rats

Context: The decoctions of Ficus carica Linn. (Moraceae) leaves are used in the folklore treatment of diabetes.

Objective: To evaluate the effect of F. carica on glucose and lipids levels, carbohydrate metabolism enzymes and β-cells protective effects in type 2 diabetes.

Material and methods: Diabetes was induced in 15 days high-fat diet (HFD)-fed Wistar rats by intraperitoneal injection of streptozotocin (STZ) (40?mg/kg). The ethyl acetate extract (250 and 500?mg/kg) of F. carica leaves was administered for 28 days. Oral glucose tolerance (OGTT) and intraperitoneal insulin tolerance tests (ITT) were evaluated on 15th and 25th days, respectively.

Results: The ethyl acetate extract (250 and 500?mg/kg) of n F. carica leaves showed significant effect (p?F. carica (250 and 500?mg/kg) significantly (p?F. carica enhanced the glucose utilization significantly (p?<?0.005) over 30 and 60?min compared to diabetic control. Further, the altered activities of key carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6-bisphosphatase and hexokinase in the liver tissue of diabetic rats were significantly (p?F. carica. Immumohistochemical studies of islets substantiated the cytoprotective effect on pancreatic β-cells.

Discussion and conclusions: F. carica leaves exerted significant effect on carbohydrate metabolism enzymes with promising hypoglycemic and hypolipidemic activities in type 2 diabetic rats.     

A randomised study comparing the efficacy and safety of rosuvastatin with atorvastatin for achieving lipid goals in clinical practice in Asian patients at high risk of cardiovascular disease (DISCOVERY-Asia study)

ABSTRACT

Background: Most studies investigating the benefits of statins have focused on North American and European populations. This study focuses on evaluating the lipid-lowering effects of rosuvastatin and atorvastatin in Asian patients.

Objectives: The DIrect Statin COmparison of LDL‐C Values: an Evaluation of Rosuvastatin therapY (DISCOVERY)-Asia study is one of nine independently powered studies assessing the efficacy of starting doses of statins in achieving target lipid levels in different countries worldwide. DISCOVERY-Asia was a 12-week, randomised, open-label, parallel-group study conducted in China, Hong Kong, Korea, Malaysia, Taiwan, and Thailand.

Results: A total of 1482 adults with primary hypercholesterolaemia and high cardiovascular risk (>?20%/10 years, type 2 diabetes, or a history of coronary heart disease) were randomised in a 2?:?1 ratio to receive rosuvastatin 10?mg once daily (o.d.) or atorvastatin 10?mg o.d. The percentage of patients achieving the 1998 European Joint Task Force low-density lipoprotein cholesterol (LDL‐C) goal of <?3.0?mmol/L at 12 weeks was significantly higher in the rosuvastatin group (n = 950) compared with the atorvastatin group (n = 471) (79.5 vs. 69.4%, respectively; p < 0.0001). Similar results were observed for 1998 European goals for total cholesterol (TC), and the 2003 European goals for LDL‐C and TC. LDL‐C and TC levels were reduced significantly more with rosuvastatin compared with atorvastatin. Both drugs were well-tolerated and the incidence and type of adverse events were similar in each group.

Conclusions: This 12-week study showed that the starting dose of rosuvastatin 10?mg o.d. was significantly more effective than the starting dose of atorvastatin 10?mg o.d. at enabling patients with primary hypercholesterolaemia to achieve European goals for LDL‐C and TC in a largely Asian population in real-life clinical practice. The safety profile of rosuvastatin 10?mg is similar to that of atorvastatin 10?mg in the Asian population studied here, and is consistent with the known safety profile of rosuvastatin in the white population.

Trial registration: ClinicalTrials.gov identifier: NCT00241488.     

Effect of rosuvastatin versus atorvastatin treatment on paraoxonase-1 activity in men with established cardiovascular disease and a low HDL-cholesterol

ABSTRACT

Objective: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity.

Methods: We performed a prespecified prospective study in 68 patients, part of a larger, multicentre randomized study – RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport). Patients aged 40–80 years, all men, with established cardiovascular disease and high-density lipoprotein cholesterol (HDL?C) < 1.0?mmol/L (< 40?mg/dL) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10?mg or atorvastatin 20?mg daily for 6 weeks. Doses were increased after 6 weeks to rosuvastatin 20?mg or atorvastatin 40?mg and after 12 weeks to rosuvastatin 40?mg or atorvastatin 80?mg daily. Serum PON-1 activity and lipid profile were determined at baseline, 6 and 18 weeks.

Results: After 18 weeks, the rosuvastatin arm showed a significant increase of PON-1 activity (6.39?U/L, p = 0.02) whereas this was not observed in the atorvastatin arm (1.84?U/L, p = 0.77). The difference between groups did not reach significance (?p = 0.11). Both rosuvastatin and atorvastatin resulted in significant (?p = 0.0001) and similar increases in HDL?C after 6 weeks [0.06?mmol/L (2.32?mg/dL) vs. 0.05?mmol/L (1.93?mg/dL)] and after 18 weeks [0.10?mmol/L (3.87?mg/dL) vs. 0.10?mmol/L (3.87?mg/dL)].

Conclusions: Rosuvastatin treatment resulted in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin.