Statins in cardiometabolic disease: what makes pitavastatin different?

The term cardiometabolic disease encompasses a range of lifestyle-related conditions, including Metabolic syndrome (MetS) and type 2 diabetes (T2D), that are characterized by different combinations of cardiovascular (CV) risk factors, including dyslipidemia, abdominal obesity, hypertension, hyperglycemia/insulin resistance, and vascular inflammation. These risk factors individually and interdependently increase the risk of CV and cerebrovascular events, and represent one of the biggest health challenges worldwide today. CV diseases account for almost 50% of all deaths in Europe and around 30% of all deaths worldwide. Furthermore, the risk of CV death is increased twofold to fourfold in people with T2D. Whilst the clinical management of CV disease has improved in Western Europe, the pandemic of obesity and T2D reduces the impact of these gains. This, together with the growing, aging population, means the number of CV deaths is predicted to increase from 17.1 million worldwide in 2004 to 23.6 million in 2030. The recommended treatment for MetS is lifestyle change followed by treatment for the individual risk factors. Numerous studies have shown that lowering low-density lipoprotein-cholesterol (LDL-C) levels using statins can significantly reduce CV risk in people with and without T2D or MetS. However, the risk of major vascular events in those attaining the maximum levels of LDL-C-reduction is only reduced by around one-third, which leaves substantial residual risk. Recent studies suggest that low high-density lipoprotein-cholesterol (HDL-C) (<1 .0 mmol/l; 40 mg/dl) and high triglyceride levels (≥1.7 mmol/l; 150 mg/dl) are independent risk factors for CV disease and that the relationship between HDL-C and CV risk persists even when on-treatment LDL-C levels are low (<1.7 mmol/l; 70 mg/dl). European guidelines highlight the importance of reducing residual risk by targeting these risk factors in addition to LDL-C. This is particularly important in patients with T2D and MetS because obesity and high levels of glycated hemoglobin are directly related to low levels of HDL-C and high triglyceride. Although most statins have a similar low-density lipoprotein-lowering efficacy, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects (for example, high-density lipoprotein-elevating efficacy), adverse event profiles, and drug-drug interactions. The choice of statin should therefore depend on the needs of the individual patient. The following reviews will discuss the potential benefits of pitavastatin versus other statins in the treatment of patients with dyslipidemia and MetS or T2D, focusing on its effects on HDL-C quantity and quality, its potential impact on atherosclerosis and CV risk, and its metabolic characteristics that reduce the risk of drug interactions. Recent controversies surrounding the potentially diabetogenic effects of statins will also be discussed.     

Statin diabetogenicity: guidance for clinicians

Type 2 diabetes (T2D) is a strong, independent risk factor for cardiovascular (CV) and cerebrovascular outcomes. Meta-analysis of five randomised clinical trials (n = 33,040) showed that, although intensive versus standard glycaemic control significantly reduced CV events in people with T2D, the reduction was less than that achieved with lipid-lowering or antihypertensive treatment. Furthermore, fasting plasma glucose (FPG) concentrations were a modest predictor for CV risk in people without T2D. Thus, although effective glycaemic control is important for the prevention/management of T2D, other risk factors must be addressed to effectively reduce CV risk. Reducing low-density lipoprotein-cholesterol levels using statins significantly reduces CV risk in people with and without T2D. Although statins are generally safe and well tolerated, conflicting data exist regarding the diabetogenic effects of some statins. Based on recent clinical trial data, the US Food and Drug Administration have changed the labelling of all statins to include ‘an effect of statins on incident diabetes and increases in haemoglobin A1c and/or FPG’. However, the literature suggests that the beneficial effects of most statins on CV risk continue to outweigh their diabetogenic risks and that statins should remain as first-line therapy for the majority of people with dyslipidaemia and metabolic syndrome or T2D. Mechanisms explaining the potentially higher incidence of T2D with statin therapy have not been confirmed. However, independent predictors for statin-associated T2D appear to include elevated levels of baseline FPG, BMI, blood pressure and fasting triglycerides. Moreover, although some statins (for example, atorvastatin) are associated with increased haemoglobin A1c levels in patients receiving intensive but not moderate therapy, other statins (for example, pitavastatin) have demonstrated neutral or favourable effects on glucose control in patients with and without T2D or metabolic syndrome. The potential diabetogenic effects of statins may therefore differ between drugs. In conclusion, conflicting data exist regarding the diabetogenic effects of statins. Further studies are required to understand whether all statins have the same effect and whether some patient groups are at higher risk than others. Meanwhile, results suggest that the net CV benefit favours the use of statin therapy in patients with dyslipidaemia, irrespective of T2D risk.     

Relationship between Serum Ferritin Levels and Dyslipidemia in Korean Adolescents

BackgroundFerritin is associated with various cardiometabolic risk factors such as dyslipidemia, hypertension, obesity, and insulin resistance in adults. We aimed to study the association between serum ferritin levels and dyslipidemia in adolescents, because dyslipidemia is considered an important modifiable cardiovascular risk factor in the young.MethodsWe analyzed 1,879 subjects (1,026 boys and 853 girls) from the 2009–2010 Korean National Health and Nutrition Examination Survey IV. Subjects were categorized into quartiles according to their lipid parameters, which were classified according to age and gender. Those in the highest quartile groups for total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglyceride concentrations were diagnosed as having dyslipidemia. Those in the lowest quartile for high-density lipoprotein cholesterol (HDL-C) values were diagnosed with abnormal levels.ResultsIn boys, total cholesterol, LDL-C, and triglyceride concentrations were significantly correlated with serum ferritin levels. In both boys and girls, serum ferritin levels were negatively associated with HDL-C values, even after adjusting for all covariates. Furthermore, there was no significant correlation between serum ferritin levels and total cholesterol, LDL, and triglyceride concentrations in girls.ConclusionSerum ferritin levels were significantly associated with major dyslipidemia parameters, more prominently in boys than in girls, and this association represents a cardiometabolic risk factor.     

Aggressive lipid management for cardiovascular prevention: evidence from clinical trials

Epidemiologic evidence shows that elevated serum cholesterol, specifically low-density lipoprotein cholesterol (LDL-C), increases the risk of coronary heart disease (CHD). Moreover, large-scale intervention trials demonstrate that treatment with HMG-CoA reductase inhibitors (statins), the most effective drug class for lowering LDL-C, significantly reduces the risk of CHD events. Unfortunately, only a moderate percentage of hypercholesterolemic patients are achieving LDL-C targets specified by the National Cholesterol Education Program (NCEP), in part because clinicians are not effectively titrating medications as needed to achieve LDL-C goals. Recent evidence suggests that more aggressive LDL-C lowering may provide greater clinical benefit, even in individuals with moderately elevated serum cholesterol levels. Furthermore, recent studies suggest that statins have cardioprotective effects in many high-risk individuals, including those with baseline LDL-C <100 mg/dl. High-density lipoprotein cholesterol (HDL-C) was recognized by the NCEP-Adult Treatment Panel II (ATP II) as a negative risk factor for CHD. The NCEP-ATP III guidelines have also reaffirmed the importance of HDL-C by increasing the low HDL-C designation from <35 to <40 mg/dl as a major risk factor for CHD. Similarly, triglyceride control will play a larger role in dyslipidemia management. As more clinicians effectively treat adverse lipid and lipoprotein cardiovascular risk factors, patients will likely benefit from reductions in cardiovascular events.     

Effects of Three Strong Statins (Atorvastatin,Pitavastatin, and Rosuvastatin) on Serum Uric Acid Levels in Dyslipidemic Patients

We have retrospectively investigated the effects of three strong statins, atorvastatin, pitavastatin, and rosuvastatin, on serum uric acid (SUA) levels. SUA levels after a few months of statin treatment were compared with those before treatment in 150 outpatients with dyslipidemia. In the atorvastatin (n = 62) and rosuvastatin (n = 45) groups, the SUA levels were reduced by 6.5% (p < 0.0001) and 3.6% (p = 0.03) respectively, but in the pitavastatin group (n = 43), the SUA level increased by 3.7% (p = 0.38). Because uric acid is considered a risk factor for cardiovascular disorders, atorvastatin or rosuvastatin treatment may be recommended when statins are used in patients at high risk for cardiovascular disorders complicated with hyperuricemia.     

匹伐他汀临床应用的最新进展

匹伐他汀(pitavastatin)是新一代人工合成的降血脂类药物。该药是新一代HMG-COA还原酶抑制剂,用于治疗原发型高脂血症和混合型血脂障碍,能够显著降低LDL、TC、TG、及升高HDL-C。药物动力学性质优良,具有肝细胞选择性,并且毒性低,安全性好,具有抗动脉粥样硬化、促进血管生成和抗炎作用。本文就匹伐他汀的临床研究进展进行综述。     

Cholesteryl Ester Transfer Protein (CETP) Deficiency and CETP Inhibitors

Epidemiologic studies have shown that low-density lipoprotein cholesterol (LDL-C) is a strong risk factor, whilst high-density lipoprotein cholesterol (HDL-C) reduces the risk of coronary heart disease (CHD). Therefore, strategies to manage dyslipidemia in an effort to prevent or treat CHD have primarily attempted at decreasing LDL-C and raising HDL-C levels. Cholesteryl ester transfer protein (CETP) mediates the exchange of cholesteryl ester for triglycerides between HDL and VLDL and LDL. We have published the first report indicating that a group of Japanese patients who were lacking CETP had extremely high HDL-C levels, low LDL-C levels and a low incidence of CHD. Animal studies, as well as clinical and epidemiologic evidences, have suggested that inhibition of CETP provides an effective strategy to raise HDL-C and reduce LDL-C levels. Four CETP inhibitors have substantially increased HDL-C levels in dyslipidemic patients. This review will discuss the current status and future prospects of CETP inhibitors in the treatment of CHD. At present anacetrapib by Merck and evacetrapib by Eli Lilly are under development. By 100mg of anacetrapib HDL-C increased by 138%, and LDL-C decreased by 40%. Evacetrapib 500 mg also showed dramatic 132% increase of HDL-C, while LDL-C decreased by 40%. If larger, long-term, randomized, clinical end point trials could corroborate other findings in reducing atherosclerosis, CETP inhibitors could have a significant impact in the management of dyslipidemic CHD patients. Inhibition of CETP synthesis by antisense oligonucleotide or small molecules will produce more similar conditions to human CETP deficiency and may be effective in reducing atherosclerosis and cardiovascular events. We are expecting the final data of prospective clinical trials by CETP inhibitors in 2015.     

Results of the Dyslipidemia International Study (DYSIS)-Middle East: Clinical Perspective on the Prevalence and Characteristics of Lipid Abnormalities in the Setting of Chronic Statin Treatment

Background

Therapeutic intervention with low-density lipoprotein cholesterol-lowering agents known as statins has been demonstrated to reduce cardiovascular risk. However, many patients on statin treatment have persistent dyslipidemia and remain at a high risk of cardiovascular disease. Therefore, the objective of this study was to assess the frequency of lipid abnormalities in patients receiving chronic statin treatment.

Methods

As part of an international, cross-sectional, observational study, DYSIS-Middle East enrolled 2,182 patients in the United Arab Emirates (UAE), Saudi Arabia, Lebanon and Jordan. All patients were over 45 years of age and had been on statin treatment for at least three months. Data on demographics, lipid parameters and cardiovascular risk profile were recorded. Cardiovascular risk was defined according the guidelines of the European Society of Cardiology.

Results

The majority of patients (82.6%) were classified as being at very high risk of cardiovascular events, and 61.8% of all patients did not attain LDL-C target levels. Low high-density lipoprotein cholesterol levels and elevated triglyceride levels were noted in 55.5% and 48.5% of patients, respectively. Multivariate logistical regression modeling indicated that factors independently associated with LDL-C levels not being at goal were lifestyle choices, diabetes mellitus, ischemic heart disease, and blood pressure ≥ 140/90 mmHg.

Conclusions

Almost two-thirds of statin-treated patients in the United Arab Emirates, Saudi Arabia, Lebanon and Jordan had inadequately controlled lipid levels. More comprehensive surveillance, awareness and treatment regimens, as well as modification of lifestyle choices, is necessary to halt the rise in cardiovascular disease-related mortality.     

Interaction of the pitavastatin with model membranes

Pitavastatin is a statin drug that, by competitively inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can lower serum cholesterol levels of low-density lipoprotein (LDL) accompanied by side effects due to pleiotropic effects leading to statin intolerance. These effects can be explained by the lipophilicity of statins, which creates membrane affinity and causes statin localization in cellular membranes. In the current report, the interaction of pitavastatin with POPC model membranes and its influence on the membrane structure were investigated using ¹H, ²H and ³¹P solid-state NMR spectroscopy. Our experiments show the average localization of pitavastatin at the lipid/water interface of the membrane, which is biased towards the hydrocarbon core in comparison to other statin molecules. The membrane binding of pitavastatin also introduced an isotropic component into the ³¹P NMR powder spectra, suggesting that some of the lamellar POPC molecules are converted into highly curved structures.     

Statin Intensity and Clinical Outcome in Patients with Stable Coronary Artery Disease and Very Low LDL-Cholesterol

BackgroundAlthough intensive statin therapy is recommended for high risk patients, evidence of its benefit in patients with stable coronary artery disease (CAD) and very low low-density lipoprotein-cholesterol (LDL-C) has been very rare. In this study, we investigated whether higher statin intensity reduces cardiovascular risks in this population.MethodsIn this retrospective study, a total of 5234 patients with stable CAD were screened at three tertiary hospitals in Korea; 449 patients (mean age: 65 years, male: 69%) with LDL-C <80 mg/dL were finally analyzed. The statin intensities were classified according to the 2013 American College of Cardiology/American Heart Association guidelines. Patients who received statins equivalent to or weaker than atorvastatin 10 mg (group 1) were compared with those who took statins equivalent to or stronger than atorvastatin 20 mg (group 2). The impact of statin intensity on major adverse cardiac events (MACE) was evaluated during follow-up.ResultsGroup 1 and group 2 consisted of 181 patients (40.3%) and 268 patients (59.7%), respectively. The mean LDL-C level decreased to 52 and 57 mg/dL in group 1 and group 2, respectively, during follow-up. In a median follow-up of 4.5 years, patients of group 2 had a lower incidence of MACE (30 [16.6%] vs. 12 [4.5%], p <0.001), which were mostly related to a lower incidence of coronary revascularization. Cox proportional hazard analyses identified the statin intensity of group 2 (adjusted hazard ratio: 0.25, confidence interval: 0.11–0.55, p <0.001) and the baseline high-density lipoprotein-cholesterol level as independent determinants of MACE.ConclusionThis study provides evidence that higher intensity statins are beneficial for cardiovascular outcomes in patients with stable CAD and very low LDL-C. Statins equivalent to or stronger than atorvastatin 20 mg are more effective than lower intensity statins.     

Advances in Lipid Testing and Management in Patients with Diabetes Mellitus

ObjectiveTo review the pathophysiologic basis for the classic phenotype associated with diabetic dyslipidemia, discuss recent advances in lipid and lipoprotein testing for risk assessment and lipid therapy monitoring, and summarize a systematic approach to the clinical management of diabetic dyslipidemia.MethodsWe review the pertinent literature, including treatment guidelines and results of major clinical trials, and discuss the effectiveness of various pharmacologic interventions for management of lipid levels in patients with diabetes.ResultsThe incidence and prevalence of type 2 diabetes mellitus continue to escalate globally at alarming rates. Diabetes predisposes to multiple microvascular and macrovascular complications, including cardiovascular disease, the number 1 cause of mortality in the United States. The third report of the National Cholesterol Education Program Adult Treatment Panel in 2001 identified diabetes as a coronary heart disease (CHD) risk equivalent, in light of the evidence that CHD risk in persons with diabetes is similar to that of nondiabetic persons with established CHD. Diabetic dyslipidemia is characterized by a constellation of lipid derangements—hypertriglyceridemia, a low concentration of high-density lipoprotein cholesterol (HDL-C), and a high concentration of small, dense low-density lipoprotein (LDL) particles—that accelerate the progression of atherosclerotic disease and the development of atherothrombotic events.ConclusionStatin trials have demonstrated significant reductions in morbidity and mortality from cardiovascular diseases, including in patients with diabetes. Nevertheless, many patients who achieve their LDL cholesterol (LDL-C) goal still have residual CHD risk. Diabetic dyslipidemia contributes to this residual risk because of the increased concentration of atherogenic apolipoprotein B-containing lipoproteins that can persist despite normalized LDL-C levels and low HDL-C levels. Recent clinical trials emphasize the importance of intensive lipid lowering to achieve recommended goals for LDL-C, non-HDL-C, and apolipoprotein B. (Endocr Pract. 2009;15:641-652)     

Statin action favors normalization of the plasma lipidome in the atherogenic mixed dyslipidemia of MetS: potential relevance to statin-associated dysglycemia

The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (−41%), remnant cholesterol (−55%), and LDL-cholesterol (−39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D.     

Subchronic Arsenic Exposure Through Drinking Water Alters Lipid Profile and Electrolyte Status in Rats

Arsenic is a groundwater pollutant and can cause various cardiovascular disorders in the exposed population. The aim of the present study was to assess whether subchronic arsenic exposure through drinking water can induce vascular dysfunction associated with alteration in plasma electrolytes and lipid profile. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. On the 91st day, rats were sacrificed and blood was collected. Lipid profile and the levels of electrolytes (sodium, potassium, and chloride) were assessed in plasma. Arsenic reduced high-density lipoprotein cholesterol (HDL-C) and HDL-C/LDL-C ratio, but increased the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and electrolytes. The results suggest that the arsenic-mediated dyslipidemia and electrolyte retention could be important mechanisms in the arsenic-induced vascular disorder.     

血压、血脂、血糖、同型半胱氨酸及超敏C反应蛋白水平与脑梗死发病危险性的关系

目的:探讨血压、血脂、血糖、糖化血红蛋白、同型半胱氨酸(HCY)和超敏C反应蛋白(hs-CRP)与脑梗死发病危险性的相关性,为及时防止脑梗死的发病及早期诊断脑梗死提供理论依据。方法:采用回顾性病例对照研究,用全自动生化分析仪器检测各项生化指标,并运用SPSS 20.0软件包对256例脑梗死患者和216例健康对照者的血生化指标进行统计分析。同时,将脑梗死组分为三组:单纯脑梗死组、合并高血压组、合并糖尿病组,分别与正常对照组进行血脂水平的分析比较。结果:血压、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇酯(HDL-C)、同型半胱氨酸(HCY)、血糖、hs-CRP水平和总胆固醇/高密度脂蛋白胆固醇(TC/HDL-C)比值在病例组和对照组间有显著性差异(P0.05)。同时,在三组不同的病例组中血脂(TC、TG、LDL-C、TC/HDL-C)水平和HCY水平明显高于正常对照组,而HDL-C水平则明显低于对照组。(P0.05)。结论:高血压、高血糖、HCY、hs-CRP水平增高及血脂异常均与脑梗死发病危险性相关,联合检测上述指标对预防及治疗脑梗死均有重要意义。     

9758 例健康体检者血糖与血脂的关系分析

目的:探讨健康体检人群血糖与血脂现况及两者之间的相关性。方法:采集我院9758例健康体检者的空腹静脉血,检测其空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)水平,比较不同FPG水平组间各血脂水平,分析FPG水平与血脂的相关性。结果:各年龄组FPG、TC、TG、HDL-C和LDL-C水平差异均具有统计学意义(P0.05);FPG均与TC、TG和LDL-C水平呈现正相关(r=0.127,0.189,0.141,P0.005),而与HDL-C呈现负相关(r=-0.112,P0.005);根据FPG水平由高到低分为糖尿病(DM)组,血糖调节受损(IFG)组及血糖正常组,其中对TC和LDL-C水平异常率而言,IFG组DM组血糖正常组;对TG、HDL-C水平异常率而言,DM组IFG组血糖正常组。结论:健康人群中血糖和血脂水平呈现一定的相关性,两者的水平异常会增加慢性疾病的发生风险。     

Plasma triglyceride/HDL-cholesterol ratio,insulin resistance,and cardiometabolic risk in young adults

Studies in mature adults suggest that the plasma concentration ratio of triglyceride (TG)/HDL-cholesterol (HDL-C) provides a simple way to identify apparently healthy individuals who are insulin resistant (IR) and at increased cardiometabolic risk. This study extends these observations by examining the clinical utility of the TG/HDL-C ratio and the metabolic syndrome (MetS) in 2,244 healthy college students (17–24 years old) of Mexican Mestizo ancestry. The TG/HDL-C ratio separating the 25% with the highest value was used to identify IR and increased cardiometabolic risk. Cardiometabolic risk factors were more adverse in men and women whose TG/HDL-C ratios exceeded 3.5 and 2.5, respectively, and approximately one third were identified as being IR. The MetS identified fewer individuals as being IR, but their risk profile was accentuated. In conclusion, both a higher TG/HDL-C ratio and a diagnosis of the MetS identify young IR individuals with an increased cardiometabolic risk profile. The TG/HDL-C ratio identified a somewhat greater number of “high risk” subjects, whereas the MetS found a group whose risk profile was somewhat magnified. These findings suggest that the TG/HDL-C ratio may serve as a simple and clinically useful approach to identify apparently healthy, young individuals who are IR and at increased cardiometabolic risk.     

Immediate effect of fluvastatin on lipid levels in acute coronary syndrome

It is widely assumed that acute benefit of statin therapy is mediated especially by non-lipid effects. The immediate influence of statins on lipid levels in patients with acute coronary syndrome (ACS) is, however, not clear. A total of 64 consecutive patients with ACS were randomized at admission to fluvastatin 80 mg (Group 1, N = 32) or standard therapy without statin (Group 2, N = 32). The levels of total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG) were examined at admission and after 24 h. Baseline characteristics were comparable in both groups. In Group 1, fluvastatin significantly decreased the levels of TC by 14.5%, LDL-C by 17.2%, and HDL-C by 10.0% (P < 0.001); TG were not influenced. In Group 2 only marginal reductions in TC (by 4.1%, P = 0.03) and HDL-C (by 7.5%, P < 0.01) were detected; the levels of LDL-C and TG were not changed. As compared with Group 2, in Group 1 the final levels of TC (P = 0.02) and LDL-C (P = 0.01) were significantly lower. Fluvastatin therapy, when started at admission in patients with ACS, significantly reduces TC and LDL-C already after 24 h. We suggest that the lipid-lowering effect of statins in the therapy of ACS is probably as prompt as non-lipid effects.     

Association of circulating selenium concentration with dyslipidemia: Results from the NHANES

BackgroundObservational studies have suggested that selenium levels might associate with the risk of cardio-metabolic diseases, but how circulating selenium is related to dyslipidemia remains inconclusive.ObjectivesTo investigate the association of circulating selenium levels with lipid profiles and dyslipidemia among US adults.MethodsUsing the data collected from the National Health and Nutrition Examination Survey (NHANES 1999–2006), we performed multivariate logistic regression to examine the association of circulating selenium levels (in quartiles) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and atherogenic index (AI).ResultsWe included 2903 adults (49.3 % male) (average age: 61.9) for analysis. Circulating selenium had non-linear association with TC, LDL-C, HDL-C, and AI (all p < 0.05). When comparing with the lowest quartile, subjects with the highest quartile of circulating selenium (>147.00 μg/L) had the higher odds of elevated TG (OR: 1.75, 95% CI = 1.14, 2.68), TC (OR: 2.47, 95% CI = 1.62, 3.76), LDL-C (OR: 2.52, 95% CI = 1.60, 3.96), non-HDL-C (OR: 2.17, 95% CI = 1.41, 3.33), AI (OR: 1.20, 95% CI = 0.73, 1.97) and low-HDL-C (OR: 2.10, 95% CI = 1.19, 3.72). Similar patterns were observed in subgroup analysis.ConclusionsHigher circulating selenium levels had non-linear association with lipid profiles and the increased odds of dyslipidemia.     

Lipid profile in trained subjects undergoing complete food deprivation combined with prolonged intermittent exercise

Sixteen male subjects [18-21 years, maximal oxygen consumption (VO2max) = 59.2 ml.kg-1.min-1 +/- SEM 5.6] participated in a study to evaluate the effect of prolonged, complete food deprivation combined with physical effort, on plasma lipoprotein concentrations. The subjects were deprived of food for 81 h but were supplied with water: they walked for 10 h a day at 40% of VO2max, covering a total of 105 km. During this period the subjects' average mass decreased significantly (P less than 0.05) reflecting a marked catabolic process. Plasma concentration of low density lipoprotein-cholesterol [( LDL-C]) and triglycerides were significantly lower (P less than 0.05) and total cholesterol, high-density lipoprotein-cholesterol [( HDL-C]), and free fatty acid levels were significantly higher (P less than 0.05) at the end of the experimental period compared to the start. The ratio between plasma [HDL-C] to plasma [LDL-C] increased from 0.51 to 0.89 at the end of the exercise period, reflecting a marked anti-atherogenic effect. All changes were transient and reversible within 12 days of recovery.     

Lipidomic analysis of variation in response to simvastatin in the Cholesterol and Pharmacogenetics Study

Statins are commonly used for reducing cardiovascular disease risk but therapeutic benefit and reductions in levels of low-density lipoprotein cholesterol (LDL-C) vary among individuals. Other effects, including reductions in C-reactive protein (CRP), also contribute to treatment response. Metabolomics provides powerful tools to map pathways implicated in variation in response to statin treatment. This could lead to mechanistic hypotheses that provide insight into the underlying basis for individual variation in drug response. Using a targeted lipidomics platform, we defined lipid changes in blood samples from the upper and lower tails of the LDL-C response distribution in the Cholesterol and Pharmacogenetics study. Metabolic changes in responders are more comprehensive than those seen in non-responders. Baseline cholesterol ester and phospholipid metabolites correlated with LDL-C response to treatment. CRP response to therapy correlated with baseline plasmalogens, lipids involved in inflammation. There was no overlap of lipids whose changes correlated with LDL-C or CRP responses to simvastatin suggesting that distinct metabolic pathways govern statin effects on these two biomarkers. Metabolic signatures could provide insights about variability in response and mechanisms of action of statins.