History of distal gastrectomy prevents metabolic syndrome and chronic kidney disease

AimsChronic kidney disease (CKD) due to metabolic syndrome has recently become a social problem in Japan. In this report, the associations between the history of distal gastrectomy (DG) and the incidence of metabolic syndrome or CKD were evaluated.MethodsArteriosclerosis-related factors were compared among patients with a history of DG who were <70 years old (n = 41) and controls selected at random (n = 410) after matching for age and sex.ResultsThe patients with a history of DG were less obese than controls and had lower low-density lipoprotein cholesterol and higher high-density lipoprotein cholesterol serum levels. Furthermore, they had an excellent estimated glomerular filtration rate, which was used as an index of CKD.ConclusionsThese findings suggest that a history of DG prevents metabolic syndrome and reduces the risk of CKD.     

Statins do not meet expectations for lowering low-density lipoprotein cholesterol levels when used in clinical practice

BACKGROUND: Statins have become a mainstay in the treatment of hyperlipidemia, based on their potency and favorable side-effect profile. Drug choice is presumed to be guided by the estimated degree of low-density lipoprotein (LDL) cholesterol lowering required in a particular patient and the projected efficacy of any drug-dose combination, as contained in the package inserts for each medication. We investigated whether these expectations were met in a clinical practice. METHODS: Data were analyzed for 367 hyperlipidemic patients in a preventive cardiology practice who were not taking statins at entry, who were given a standard statin dose at their first visit, and who had at least one follow-up visit on the same drug/dose. Expected LDL cholesterol reductions were calculated for each patient based on guidelines in the package inserts for each drug. RESULTS: The mean (+/-SD) observed LDL cholesterol reduction of 26% +/- 20% was significantly less than expected (34% +/- 7%, P < 0.001). The ratio of observed to expected reduction was not different for the three statins used (atorvastatin, 0.79 +/- 0.48; simvastatin, 0.88 +/- 0.61; pravastatin, 0.75 +/- 0.69; P = 0.39). CONCLUSIONS: The use of statins in a clinical practice led to observed reductions in LDL cholesterol level that were significantly less than those projected by package insert guidelines. We believe this gap reflects the reduced patient compliance frequently observed in clinical practice settings, rather than any inherent difference in statin responsiveness of a practice versus a trial population. Physicians should be aware of this disparity when using statins in the clinical setting.     

Effects of pravastatin on coronary events in 2073 patients with low levels of both low-density lipoprotein cholesterol and high-density lipoprotein cholesterol: results from the LIPID study.

AIMS: Fibrates or nicotinic acid are usually recommended for secondary prevention of coronary heart disease in patients with low plasma levels of both low-density lipoprotein cholesterol (LDL-C) < or =140 mg/dL (< or =3.6 mmol/L) and high-density lipoprotein cholesterol (HDL-C) < or =40 mg/dL (< or =1.03 mmol/L). The LIPID trial, a randomised, placebo-controlled trial in 9014 patients at 87 centres in Australia and New Zealand, provided an opportunity to investigate the effects of an HMG-CoA reductase inhibitor in patients with low LDL-C and low HDL-C. METHODS AND RESULTS: Participants in this post hoc substudy were 2073 patients aged 31-75 years with baseline LDL-C < or =140 mg/dL (< or =3.6 mmol/L), HDL-C < or =40 mg/dL (< or =1.03 mmol/L), and triglyceride < or =300 mg/dL (< or =3.4 mmol/L). The relative risk reduction with pravastatin treatment was 27% for major coronary events (95% CI 8-42%), 27% for coronary heart disease mortality (95% CI 0-47%), 21% for all-cause mortality (95% CI 0-38%), and 51% for stroke (95% CI 24-69%). The number needed to treat to prevent a major coronary event over 6 years was 22. CONCLUSIONS: Treatment with pravastatin in patients with both low LDL-C and low HDL-C significantly reduced major coronary events, stroke, and all-cause mortality. The level of HDL-C is crucial to the risk of recurrent CHD events and, consequently, the benefit of lowering LDL-C.     

Association between causative mutations and response to PCSK9 inhibitor therapy in subjects with familial hypercholesterolemia: A single center real-world study

Background and aimsFamilial hypercholesterolemia (FH) is an autosomal dominant disease that leads to cardiovascular (CV) disease. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9-I) demonstrated efficacy in low-density lipoprotein cholesterol (LDL-C) reduction and in prevention of CV events. The aim of our study is to evaluate the relationship between LDL receptor (LDLR) mutations and response to PCSK9-I therapy.Methods and resultsWe evaluated total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in consecutive patients with FH before PCSK9-I treatment and after 12 (T12w) and 36 (T36w) weeks of treatment. We evaluated LDL-C target achievement according to different mutations in LDLR. Eighty FH subjects (mean age:54 ± 13.3 years), 39 heterozygous (He) with defective LDLR gene mutations, 30 He with null mutations and 11 compound-He or homozygous (Ho) were recruited. At baseline, 69 subjects were under maximal lipid lowering therapy (MLLT) and 11 subjects had statin-intolerance. From baseline to T36w we observed an overall 51% reduction in LDL-C. We found no difference in LDL-C changes between subjects with He-defective mutation and He-null mutations both at T12w (p = 1.00) and T36w (p = 0.538). At T36w, LDL-C target was achieved in 59% of He-defective mutations subjects and in 36% of He-null mutations subgroup (p = 0.069), whereas none of compound-He/Ho-FH achieved LDL-C target.ConclusionsAfter 36 weeks there were no differences in response to PCSK9-I therapy between different groups of He-FH subjects. Response to PCSK9-I was significantly lower in carriers of compound-He/Ho mutations.Registration number for clinical trials: NCT04313270 extension.     

Effect of atorvastatin on lipogenic,inflammatory and thrombogenic markers in women with the metabolic syndrome

Background and aimSpecific drug therapy to target the underlying proinflammatory and prothrombotic state in patients with metabolic syndrome (MS) is lacking. We sought to study the effect of high-intensity atorvastatin on markers of lipogenesis, inflammation and thrombogenesis, in women with MS in the absence of cardiovascular disease or diabetes.Methods and resultsThis randomized double-blinded controlled trial included 88 women with MS (according to National Cholesterol Education Panel Adult Treatment Panel III criteria) and low atherosclerotic cardiovascular risk. Participants were randomized to receive atorvastatin 80 mg or matching placebo. Thrombogenic, lipogenic and inflammatory markers were collected at the time of enrollment, after a 6-week dietary run-in phase (time of randomization), and at 6- and 12-weeks after randomization. At 6 weeks post-randomization, there was significant reduction in total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein-B (Apo-B) and Apo-B/Apo-A1 ratio in the atorvastatin arm compared to placebo. This difference persisted at 12-weeks post randomization. There was no significant difference in fasting blood glucose, high-density lipoprotein cholesterol, high sensitivity C-reactive protein, serum leptin, Apo-A1, intercellular adhesion molecule 1 and platelet activity. A significant increase in vascular adhesion molecule 1 at 6 and 12 weeks was seen within the atorvastatin arm. No difference was observed in blood pressure and waist circumference.ConclusionsIn conclusion, high-intensity atorvastatin has an early and significant impact on lipoproteins and apolipoproteins but did not lower inflammatory, thrombogenic or biomarkers of platelet activity and aggregation in women with MS. The use of statins for primary prevention in these patients should be further explored.     

Simvastatin treatment upregulates intestinal lipid secretion pathways in a rodent model of the metabolic syndrome

Objective

Statins are widely used for the treatment of hyperlipidemia to reduce cardiovascular disease (CVD) risk. Intriguingly, recent reports suggest that whilst statins are effective in reducing hepatic cholesterol synthesis, they in turn may up-regulate intestinal cholesterol absorption. The direct effects and/or mechanisms of this phenomenon remain largely unknown. The aim of this study was to investigate the potential for statins to increase intestinal lipid absorption and/or secretion in a rodent model of the metabolic syndrome (MetS).

Methods and results

Mets JCR:LA-cp rats received a 1% cholesterol diet containing Simvastatin (0.01% w/w), for 8 weeks. Fasting and postprandial plasma biochemical profile was assessed using enzymatic assays and a modified apoB48 (chylomicron; CM) western blotting protocol. Statin treatment reduced fasting plasma TG (−49%), cholesterol (−24%) and postprandial plasma apoB48 (−58%). The intestinal secretion of lipids into mesenteric lymph was assessed using lymph fistulae procedures. Interestingly, MetS rats treated with statin secreted greater cholesterol (1.9-fold) and TG (1.5-fold) per apoB48 particle, into mesenteric lymph. This was shown to be as a result of simvastatin-induced increase in intestinal cholesterol absorption (31.5%). Experiments using in vivo inhibition of lipoprotein lipase (LPL; poloxamer-407) demonstrated statin treatment reduced hepatic cholesterol secretion (−49%), but significantly increased hepatic (73%) TG secretion in MetS rats. Statin treatment also increased the expression of genes involved in lipid synthesis (Hmgcr, Srebp1, Fas, Acc; 33–67%) and reduced those involved in efflux (Abca1, Abcg8; −36 to 73%) in enterocytes and liver of MetS rats versus untreated control.

Conclusions

In a rodent model of MetS, statin treatment adversely up-regulates intestinal lipid secretion as a result of increased intestinal cholesterol absorption, and increases the intestinal expression of genes involved in lipid synthesis; effects which may confound clinical benefits to remnant dyslipidemia.     

Associations of vitamin D status with markers of metabolic health: A community-based study in Shanghai,China

Aims

This study investigated the associations of vitamin D status (i.e., serum 25(OH)D concentration) with markers of metabolic health and metabolic syndrome (MS), as well as possible gender differences in these associations, with metabolic syndrome (MS) for a sample from Shanghai, China.

The role of HDL cholesterol in metabolic syndrome predicting cardiovascular events. The Gubbio population study

Background and aims

Metabolic syndrome (MS) has recently been claimed to be an important new risk factor for the occurrence of coronary heart disease (CHD) and cardiovascular disease (CVD) events, although it is simply a combination of known risk factors used in a dichotomized fashion. The aims of this analysis were to explore the predictive role of MS for CHD and CVD events in a population study, in comparison with using the same factors in a continuous fashion, with special emphasis on HDL cholesterol.

Methods and results

In the second examination of the Gubbio population study from central Italy, 2650 cardiovascular disease-free men and women, aged 35-74 years around 1990, were examined and followed-up for 12 years. The classic risk factors (sex, age, systolic blood pressure, serum cholesterol and smoking habits) were studied as predictors of CHD and CVD events, alone and with the contribution of other factors (HDL cholesterol, blood glucose, serum triglycerides and waist circumference) included in the so-called MS, based on several multivariate models. MS was also tested after adjustment for other risk factors.MS produced a predictive significant relative risk of 1.67 for CHD events and 1.82 for CVD events, but considering its single risk factors, the only ones contributing to prediction were HDL cholesterol and systolic blood pressure. Dedicated analyses showed that MS does not add anything to the power of prediction beyond the role of the single risk factors treated in a continuous fashion, while the best predictive power is obtained using classic risk factors (sex, age, smoking habits, total cholesterol, systolic blood pressure) with the addition of HDL cholesterol.

Conclusions

The predictive power of MS is bound only to the presence of HDL cholesterol and blood pressure and does not add anything to using the same risk factor treated in a continuous fashion.     

青中年冠心病患者代谢综合征危险因素的分布与聚集状况分析

目的分析青中年冠心病患者中代谢综合征(MS)危险因素的分布与聚集状况,为早期防治干预提供依据。方法对103例青中年男性[年龄30～50(43.3±5.7)岁]冠心病患者及64例男性[年龄28～50(42.8±6.3)岁]冠状动脉造影正常的对照组的临床特征和生化特点进行比较。按照中华医学会糖尿病学分会标准诊断MS。结果两组在年龄上无差异。冠心病组的吸烟率显著高于对照组,但在冠心病家族史方面两组无差异。冠心病组的总胆固醇(TC)、餐后2h血糖(2hPBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMAIR)均显著高于对照组,而HDLC显著低于后者。冠心病组MS的发生率显著高于对照组(P<0.01)。Logistic回归分析显示,吸烟、低HDLC、HOMAIR、MS使青中年人冠心病患病的相对危险度增加。结论青中年冠心病患者多种代谢异常更加严重,对于青中年男性应重视MS的预防,以减少心血管事件的发生。     

Comparison of rosuvastatin with atorvastatin, simvastatin and pravastatin in achieving cholesterol goals and improving plasma lipids in hypercholesterolaemic patients with or without the metabolic syndrome in the MERCURY I trial

AIM: The metabolic syndrome (MS) increases the risk of coronary heart disease, yet few data are available on the effects of statin treatment in improving lipid measures in patients with the syndrome. This analysis compares the effects of statin therapy on plasma low-density lipoprotein cholesterol (LDL-C) goal achievement and lipid levels in hypercholesterolaemic patients with or without the MS. METHODS: The Measuring Effective Reductions in Cholesterol Using Rosuvastatin TherapY I (MERCURY I) trial compared rosuvastatin 10 mg with atorvastatin 10 mg and 20 mg, simvastatin 20 mg and pravastatin 40 mg over 8 weeks in patients with coronary or other atherosclerotic diseases or diabetes who had fasting levels of LDL-C of >or=2.99 mmol/l and triglycerides of <4.52 mmol/l. Modified National Cholesterol Education Program Adult Treatment Panel III (ATP III) criteria for the MS were met by 1342 (43%) of 3140 patients. RESULTS: LDL-C goal achievement rates and reductions in LDL-C, total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) were similar in patients with and without the MS within statin treatment groups; triglycerides were reduced more and HDL-C tended to be increased more in patients with the MS, as expected. Treatment with rosuvastatin 10 mg was more effective in allowing patients with and without the MS to reach European and ATP III LDL-C goals, compared to atorvastatin 10 mg, simvastatin 20 mg and pravastatin 40 mg (p < 0.0001 for all comparisons); consistently produced greater reductions in LDL-C, total cholesterol and non-HDL-C, compared to these treatments; and produced similar or greater reductions in triglycerides and increases in HDL-C, compared to the other treatments. CONCLUSIONS: Statin therapy is effective in allowing LDL-C goal achievement and improving the lipid profile in hypercholesterolaemic high-risk patients with the MS. Rosuvastatin 10 mg presents significant advantages in goal achievement and lipid lowering over other statins at commonly used doses in patients both with and without the MS.     

Influence of endothelial dysfunction on telomere length in subjects with metabolic syndrome: LIPGENE study

Previous evidences support that increased oxidative stress (OxS) may play an important role in metabolic syndrome (MetS) and both are closely linked to vascular dysfunction. This study determined whether there is a relationship between endothelial function and relative telomere length (RTL) in MetS subjects. In this cross-sectional study from the LIPGENE cohort, a total of 88 subjects (36 men and 52 women) were divided into four groups by quartiles of telomere length. We measured ischemic reactive hyperemia (IRH), total nitrite (NO) and protein carbonyl (PC) plasma levels, F2-isoprostanes urinary levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) plasma activities. IRH and NO plasma levels were higher in subjects with longer RTL (quartiles 3 and 4), while PC plasma levels, F2-isoprostanes urinary levels, and GPx and SOD plasma activities were lower in quartile 4 subjects (longest RTL). Additionally, MetS subjects with longer RTL had greater homeostatic model assessment-β level and lower triglycerides plasma levels. Our results suggest that endothelial dysfunction, associated with high levels of OxS, could be entailed in an increment of telomere attrition. Thus, further support of the molecular and cellular mechanisms involved in vascular dysfunction may contribute to the development of strategies to decelerate vascular aging or prevent cardiovascular disease.     

The metabolic syndrome predicts cardiovascular events in subjects with normal fasting glucose: results of a 15 years follow-up in a Mediterranean population

The aim of this study was to evaluate the cardiovascular (CV) risk due to the metabolic syndrome in a 15-year prospective study of a Sicilian population. In the Mediterranean area obesity is highly prevalent, but epidemiological data on the metabolic syndrome are limited. METHODS AND RESULTS: Among the 1351 subjects enrolled in the "Ventimiglia di Sicilia" epidemiological project, we selected 687 subjects between 35 and 75 years of age; baseline parameters were assessed and subjects have been followed for 15 years recording CV events, total and cardiovascular mortality. The metabolic syndrome was defined according to both the Adult Treatment Panel III and the International Diabetes Federation criteria. Metabolic syndrome (ATPIII criteria) was significantly (p<0.00001) more prevalent in women (31.5%) than in men (12.4%). The metabolic syndrome increased the risk of CV events with a hazard ratio of 1.9 (confidence interval CI; 1.46-2.46). Using a Cox proportional hazards estimation model, the survival curve of subjects with metabolic syndrome and normal fasting glucose did not significantly differ from the curve of subjects with metabolic syndrome and impaired fasting glucose (IFG). CONCLUSIONS: In a 15-year follow-up the metabolic syndrome is predictive of CV events regardless of the presence of IFG or diabetes mellitus.     

代谢综合征患者阿司匹林抵抗的临床研究

目的探讨代谢综合征患者阿司匹林抵抗的发生率和临床特征。方法对2005年5月至6月北京首钢社区人群中221例病情稳定的代谢综合征患者,口服阿司匹林200mg/d共10d后,应用血小板聚集仪测定花生四烯酸(AA)诱导的血小板聚集率。以0.5g/LAA诱导的血小板平均聚集率≥20%为阿司匹林抵抗。结果阿司匹林抵抗发生率为17.6%(39/221)。阿司匹林抵抗(AS)组患者的纤维蛋白原水平显著高于阿司匹林敏感(AR)组的患者[(2.6±0.4)g/L对(2.4±0.4)g/L,P=0.017)]。两组患者的血压、年龄、空腹血糖、血脂以及体重指数等差异均无统计学意义;性别、吸烟、既往心梗或脑梗病史的分布也无统计学意义。进一步根据患者性别进行分层分析发现,在男性患者中心梗病史是阿司匹林抵抗的预测因素(50%对14.5%,P=0.020),在女性患者中舒张压高于85mmHg(1mmHg=0.133kPa)是阿司匹林抵抗的预测因素(34.0%对15.5%,P=0.043)。结论研究人群中阿司匹林抵抗的发生率为17.6%,高纤维蛋白原是阿司匹林抵抗的危险因素,心梗病史和较高的舒张压可能分别是男性和女性阿司匹林抵抗的预测因素。     

Impact of statins in microalbuminuric subjects with the metabolic syndrome: a substudy of the PREVEND Intervention Trial.

AIMS: Microalbuminuria frequently clusters with the metabolic syndrome and may identify subjects at increased coronary risk. Statin treatment may reduce the incidence of major adverse cardiac events in subjects with the metabolic syndrome, but evidence is limited. We evaluated the impact of pravastatin treatment on the incidence of major adverse cardiac events in microalbuminuric subjects with the metabolic syndrome. METHODS AND RESULTS: This substudy of the PREVEND Intervention Trial (a randomized, placebo-controlled trial with a 2x2 factorial design) included 864 microalbuminuric subjects, who were randomized to fosinopril 20 mg or matching placebo and pravastatin 40 mg or matching placebo (mean follow-up 46 months). The metabolic syndrome was defined according to the NCEP ATPIII-report. Subjects with or without the metabolic syndrome were characterized by a higher age, male sex, and increased albuminuria. The incidence of major adverse cardiac events in subjects with the metabolic syndrome [9.1%; 95% confidence interval (CI) 6.0-13.0%] was increased vs. those without [3.6%; 95% CI 2.3-5.5%; P=0.007). Pravastatin treatment lowered the incidence of major adverse cardiac events in subjects with the metabolic syndrome after adjustment for age and sex (hazard ratio=0.39; 95% CI 0.17-0.89; P=0.025). CONCLUSION: This study supports the use of statins in microalbuminuric subjects with the metabolic syndrome to reduce the incidence of major adverse cardiac events.     

随访肥胖人群中代谢综合征发生的相关因素分析

目的 探讨影响随访肥胖人群代谢综合征(MS)发生的相关因素.方法 研究对象来自2000年筛查出的413例单纯肥胖者(体重指数≥25 kg/m2)及196名正常体重的健康人,7年后对此人群的体脂、血压、血脂、血糖情况进行随访调查.并测定随访前后胰岛素抵抗指数和血管内皮功能.结果 共随访到553例,其中单纯肥胖者381例(单纯肥胖组),正常体重者172名(正常体重组).单纯肥胖组MS累积发生率35.17％,正常体重组MS累积发生率8.14％.单纯肥胖组有MS者与无MS者比较,基线时的腰围、腰臀比、甘油三酯、空腹血糖、空腹胰岛素、稳态模型评估的胰岛素抵抗指数( HOMA-IR)显著升高(均P＜0.05),内皮依赖性舒张功能(EDD)明显降低(P＜0.01).正常体重组发生MS者的腰围、腰臀比、空腹胰岛素也高于未发生MS者(均P＜0.05),而EDD低于未发生者(P＜0.05).Logistic回归分析显示,男性性别、腰围、腰臀比、空腹血糖、HOMA-IR和EDD是发生MS的危险因素.结论 腹型肥胖、胰岛素抵抗和内皮功能障碍是MS发生的基本病因.     

Correlates of metabolic syndrome in patients with depression: A study from north-western India

Background and AimsMetabolic syndrome (MS) is found to be prevalent in patients with mental illness including depression. Data is sparse on the role of lifestyle factors on MS in depression.MethodsThis study was aimed to assess correlates of MS in patients with depression. Methodology: Three hundred eighty-two patients with depressive disorders were assessed for the prevalence of MS by using modified National Cholesterol Education Program- Adult Treatment Panel-III criteria (NCEP ATP-III). Their illness severity, functionality, physical activity and nutritional habits were also assessed.ConclusionsMajority of patients with depression (82.2%) were drug naive. One-fourth of the patients had metabolic syndrome (27.7%). Additionally, other 59% of patients had one or two metabolic abnormalities and one-third of patients were obese. Lower high density lipoprotein cholesterol level was the most common abnormality (65%), while abnormal blood pressure was the least common abnormality (18%). Significant correlates of MS were greater age, and age at onset of depression, greater illness duration, lesser physical activity and lower nutritional score.ConclusionNearly one-fourth of patients with depression had MS; another three-fifth of patients had one or two metabolic abnormalities. MS was more commonly seen with sedentary lifestyle and poor nutritional habits. It calls for comprehensive assessment and timely management of cardiovascular risk factors as well as lifestyle factors in depression.     

Behavior of the total antioxidant status in a group of subjects with metabolic syndrome

AimsOur purpose was to examine the total antioxidant status (TAS) in subjects with metabolic syndrome (MS) subdivided according to the presence or not of diabetes mellitus.MethodsWe enrolled 106 subjects (45 women, 61 men) with MS subsequently subdivided in diabetics (14 women, 29 men) and nondiabetics (31 women, 29 men). TAS was obtained using an Assay kit which relies on the ability of plasma antioxidant substances to inhibit the oxidation of 2,2′-azino-bis(3-ethylbenzthiazoline sulfonic acid) to the radical ABTS+.ResultsIn the group of MS subjects a significant decrease in TAS (p < 0.05) in comparison with normal controls was evident. This difference was present between normal subjects and nondiabetic subjects with MS (p < 0.001) but not between normal and diabetic subjects with MS. Examining the linear regression among TAS, age, anthropometric profile, blood pressure values and glycometabolic pattern, conflicting data were found.ConclusionsAlthough we know that TAS includes several enzymatic and non enzymatic antioxidants, we retain that the difference observed in the two subgroups of subjects with MS must be looked in particular into two pathophysiological aspects regarding bilirubin and uric acid.