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Objective: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines., Study Design: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention., Results: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications., Conclusions: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In addition to monoclonal antibodies against proprotein convertase subtilisin-kexin type 9 (PCSK9), vaccines against PCSK9 and smaller molecule inhibitors as well as RNA inhibitors of PCSK9 production have been created. The monoclonal antibodies against PCSK9 and the PCSK9 RNA inhibitors can reduce low-density lipoproteins (LDLs) by over 50%, non-high-density lipoprotein (HDL) cholesterol and triglycerides, and increasing HDL. Although effective in several homozygous familial hypercholesterolemia patient types, PCSK9 inhibitors does not work in all patient types. Outcome trials show no effects on mortality but do show reductions in atherosclerotic events such as myocardial infarctions, strokes, and need for coronary revascularization. PCSK9 inhibitors have a very attractive safety profile with no significant elevations in measures of muscle or liver damage. The current and more advanced experimental agents all require subcutaneous dosing, and injection site reactions are among the most common adverse events. Therapy for the Food and Drug Administration (FDA) approved agents is markedly expensive, and this is the primary barrier to utilization. However, it is possible to identify patients with a number needed to treat to prevent an atherosclerotic event low enough to render it cost-effective and one such factor is whether or not you require a 50% reduction in LDL in order to achieve your LDL goal.

Background: Familial hypercholesterolaemia (FH) in children is under-detected and is difficult to diagnose in clinical practice. The aim of this study was to evaluate clinical, biochemical and vascular imaging variables in order to detect children and adolescents with FH., Methods: A total of 222 children aged 4-18 years old were recruited to participate in a project for the early detection of FH (The DECOPIN Project). They were distributed into 3groups: FH, if genetic study or clinical criteria were positive (n=91); Polygenic hypercholesterolaemia (PH) if LDL-Cholesterol >135mg/dL without FH criteria (n=23), and Control group (CG) if LDL-C <135mg/dL (n=108). Data were collected from family history, anthropometric data, and clinical variables. The usual biochemical parameters, including a complete lipid profile were analysed. The carotid intima-media thickness (cIMT) and thickness of Achilles tendons were determined using ultrasound in all participants., Results: A total of 91 children had a diagnosis of FH, 23 with PH, and 108 with CG. Children with FH had higher concentrations of total cholesterol, LDL-C, ApoB/ApoA1 ratio, and cholesterol-year score, than the other groups. HDL-C was lower in the FH group than in the CG. Thickness of the Achilles tendon and cIMT did not show any differences between groups, although a greater cIMT trend was observed in the FH group. ApoB/ApoA1 ratio >0.82 was the parameter with the highest sensitivity and specificity to predict the presence of mutation in children with FH., Conclusions: Although LDL-C is the main biochemical parameter used to define FH, the ApoB/ApoA1 ratio (>0.82) may be a useful tool to identify children with FH and a positive mutation., (Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Although high serum cholesterol in young adults is known to be a predictor for cardiovascular events, there is not enough evidence for the association of cholesterol level change with cardiovascular disease (CVD). This study aimed to evaluate whether the change in cholesterol is associated with incidence of CVD among young adults., Methods and Results: We examined 2 682 045 young adults (aged 20-39 years) who had undergone 2 consecutive national health check-ups provided by Korean National Health Insurance Service between 2002 and 2005. Cholesterol levels were classified into low (<180 mg/dL), middle (180-240 mg/dL) and high (≥240 mg/dL). CVD events were defined as ≥2 days hospitalization attributable to CVD for 10 years follow-up. Increased cholesterol levels were significantly associated with elevated ischemic heart disease risk (adjusted hazard ration [aHR]=1.21; 95% confidence interval [CI]=1.03-1.42 in low-high group and aHR=1.21; 95% CI=1.15-1.27 in middle-high group) and cerebrovascular disease (CEVD) risk (aHR=1.24; 95% CI=1.05-1.47 in low-high group and aHR=1.09; 95% CI=1.02-1.16 in middle-high group). Decreased cholesterol levels were associated with reduced ischemic heart disease risk (aHR=0.91; 95% CI=0.88-0.95 in middle-low group, aHR=0.65; 95% CI=0.56-0.75 in high-low group and aHR=0.68; 95% CI=0.65-0.73 in high-middle group). Furthermore, lower cerebrovascular disease risk (aHR=0.76; 95% CI=0.62-0.92) was observed in the high-low group compared with patients with sustained high cholesterol., Conclusions: The findings of our study indicate that increased cholesterol levels were associated with high CVD risk in young adults. Furthermore, young adults with decreased cholesterol levels had reduced risk for CVD., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Objective: To investigate clinical, molecular genetic characteristics, and treatment outcomes of 3 children with sitosterolemia. Methods: Three cases of children presented with multiple xanthomas during June 2016 to June 2017 were included. The clinical manifestations, laboratory examinations and follow-up data were retrospectively analyzed. DNA was extracted from peripheral blood and analyzed with whole exome sequencing(WES). All the detected variants were confirmed by Sanger sequencing. Plasma plant sterol concentrations were measured by gas chromatography-mass spectrometry. Results: Three cases of children including 1 boy and 2 girls presented with multiple linear and intertriginous xanthomas around skin of the joint areas at the age from 15 months to 6 years and 2 months. Total cholesterol of the 3 cases was elevated to 14.45, 15.47 and 15.85 mmol/L (3.36-6.46), and low density lipoprotein cholesterol was 9.02, 13.54 and 12.47 mmol/L (< 3.36) respectively. Genetic analysis with WES revealed that 2 cases carried compound heterozygous variants in ABCG5 gene, 1 case carried compound heterozygous variants in ABCG8 gene. Two reported variants (p. N437K, p.R446X) and one novel variant (p.Q251X) of ABCG5 were identified in case 2 and 3. Two novel ABCG8 variants (p.R263Q, c.1528&#95;1530delATC) were found in case 1. All these children had extremely high plasma plant sterol levels, thus the diagnosis of sitosterolemia was confirming. The campesterol level was 111.35, 102.86 and 58.91 μmol/L(0.01-10.00), the stigmasterol was 14.97, 29.43 and 17.79 μmol/L (0.10-8.50) and the sitosterol was 231.20, 177.66 and 114.20 μmol/L (1.00-15.00) respectively. The total serum cholesterol levels of three children decreased to nomal after the patients were placed on the low plant sterol/low cholesterol diet. The xanthomas regressed gradually, and almost disappeared after 8 months of treatment in case 1 and 3. Conclusions: Children with sitosterolemia presented with skin xanthomas around the joint areas. The level of total cholesterol, low density lipoprotein cholesterol and plant sterols increased obviously. One novel variant (p.Q251X) of ABCG5 and 2 novel variants (p.R263Q, c.1528&#95;1530delATC) of ABCG8 were identified. Children with sitosterolemia responded well to a low plant sterols/low cholesterol diet.

Background: Statins are first-line for cholesterol lowering and prevention of atherosclerotic cardiovascular disease (ASCVD), but their use is complicated by side effects and potential for drug-drug interactions. Provider-patient communication is the basis of the recommended shared decision-making, but relatively little is known about this in the context of statin use., Methods: We surveyed 5014 US adults prescribed a statin for hypercholesterolemia to learn their perspectives on communication with their provider., Results: Ninety-four percent reported currently taking a statin while 6% had stopped. Past users vs current users were more likely to be female, age < 65 years, and to have fewer cardiovascular disease-related comorbidities (hypertension, type 2 diabetes mellitus, and coronary heart disease, respectively). Although 93% of current statin users were taking ≥1 other prescription medications (median of 4), 76% were "not at all"/"not very concerned" about potential drug-drug interactions with their statin, and fewer than one-quarter recalled mention of these from their provider. Ninety-five percent of subjects said it was "extremely"/"somewhat" important that their healthcare provider take "an individualized approach to selecting the right statin," but 73% and 76%, respectively, said their statin choice was made with little or no input from them. Only 25% were told that "some statins might be more likely than others to interact with other medications," and only 18% (and only 20% of past users) were told that "their particular statin might interact with other medications.", Conclusion: Provider-patient communication regarding statin therapy appears inadequate, by patient recall, and efforts to improve it are warranted., (© 2018 Wiley Periodicals, Inc.)

Objective: This study analyzes the relationship between number of paid sick days and reported preventive health care service usage among older US workers., Methods: Using a 2014 cross-section of 3235 US workers age 49 to 57 from the National Longitudinal Survey of Youth, this study is the first to measure paid sick leave as an ordinal variable in an effort to refine our understanding of sick leave, and identify the ideal range of sick days necessary for people to access preventive health care services., Results: We find workers with 10 or more paid sick days have increased odds of reporting five different preventive health care services., Conclusion: To support worker and public health, policy planners may want to consider the number of paid sick days that are needed before changes in preventive service use are observed.

Dyslipidaemia and inflammation are closely interconnected in their contribution to atherosclerosis. In fact, low-density lipoprotein (LDL)-lowering drugs have anti-inflammatory effects. The Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS) has shown that interleukin (IL)-1β blockade reduces the incidence of cardiovascular events in patients with previous myocardial infarction and C-reactive protein levels >2 mg/L. These data confirm the connection between lipids and inflammation, as lipids activate the Nod-like receptor protein 3 inflammasome that leads to IL-1β activation. LDL-lowering drugs are the foundation of cardiovascular prevention. Now, the CANTOS trial demonstrates that combining them with IL-1β blockade further decreases the incidence of cardiovascular events. However, both therapies are not at the same level, given the large evidence showing that LDL-lowering drugs reduce cardiovascular risk as opposed to only one randomized trial of IL-1β blockade. In addition, IL-1β blockade has only been studied in patients with C-reactive protein >2 mg/L, while the benefit of LDL-lowering is not restricted to these patients. Also, lipid-lowering drugs are not harmful even at very low ranges of LDL, while anti-inflammatory therapies may confer a higher risk of developing fatal infections and sepsis. In the future, more clinical trials are needed to explore whether targeting other inflammatory molecules, both related and unrelated to the IL-1β pathway, reduces the cardiovascular risk. In this regard, the ongoing trials with methotrexate and colchicine may clarify whether the cardiovascular benefit of IL-1β blockade extends to other anti-inflammatory mechanisms. A positive result would represent a major change in the future treatment of atherosclerosis.

Individuals with chronic kidney disease are at increased risk of premature cardiovascular disease. Among them, many with elevated low-density lipoprotein cholesterol (LDL-C) are unable to achieve optimal LDL-C on statins and require additional lipid-lowering therapy. To study this, we compared the LDL-C-lowering efficacy and safety of alirocumab in individuals with hypercholesterolemia with impaired renal function, defined as eGFR 30-59 ml/min/1.73 m 2 , to those without impaired renal function eGFR ≥60 ml/min/1.73 m 2 . A total of 4629 hypercholesterolemic individuals without or with impaired renal function, pooled from eight phase 3 ODYSSEY trials (double-blind treatments of 24-104 weeks), were on alirocumab 150 mg or 75/150 mg every two weeks vs. placebo or ezetimibe. Overall, 10.1% had impaired renal function and over 99% were receiving statin treatment. Baseline LDL-C in alirocumab and control groups was comparable in subgroups analyzed. LDL-C reductions at week 24 ranged from 46.1 to 62.2% or 48.3 to 60.1% with alirocumab among individuals with or without impaired renal function, respectively. Similar reductions were observed for lipoprotein (a), non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides. Safety data were similar in both treatment subgroups, regardless of the degree of CKD. Renal function did not change over time in response to alirocumab. This post hoc efficacy analysis is limited by evaluation of alirocumab treatment effects on renal and lipid parameters by serum biochemistry. Thus, alirocumab consistently lowered LDL-C regardless of impaired renal function, with safety comparable to control, among individuals with hypercholesterolemia who nearly all were on statin treatment., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine whether identification of previously undiagnosed high cholesterol, hypertension, and/or diabetes during an in-home assessment impacts care seeking among Medicare beneficiaries., Data Sources/study Setting: Data from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, which recruited African American and white participants across the continental United States from 2003-2007, were linked to Medicare claims., Study Design: We used panel data models to analyze changes in doctor visits for evaluation and management of conditions after participants were assessed, utilizing the study's rolling recruitment to control for secular trends., Data Extraction Methods: We extracted Medicare claims for the 24 months before through 24 months after assessment via REGARDS for 5,884 participants., Principal Findings: Semi-annual doctor visits for previously undiagnosed conditions increased by 22 percentage points (95 percent confidence interval: 16-28) 2 years following assessment. The effect was similar by gender, race, region, and Medicaid, but it may have been lower among participants who lacked a usual health care provider., Conclusions: In-home assessment of cholesterol, blood pressure, and blood glucose can increase doctor visits for individuals with previously undiagnosed conditions. However, biomarker assessment may have more limited impact among individuals with low access to care., (© Health Research and Educational Trust.)

Metabolic syndrome (MetS) being a risk factor for many vascular pathologic processes is associated with cognitive dysfunction with vascular genesis. Objective - to study the relationship between clinical and metabolic indicators and the presence of cognitive dysfunction in persons with MetS. A transverse study was conducted in the Turkestan region of Southern Kazakhstan during which a general clinical, laboratory examination and evaluation of cognitive function was performed in 639 patients. To assess the relationship between the MetS, its individual components and cognitive function with Mini Mental State Examination test (MMSE) multinominal logistic regression analysis was used. According to the MMSE test, signs of cognitive impairment were revealed in 4.1% of the examined. A statistically significant positive association was found between the chances of having cognitive impairment andMetS, systolic hypertension, diastolic hypertension, hypercholesterolemia, hyperglycaemia. Our results showed that the components of MetS correlate with cognitive impairment. Further research should be directed towards determining the impact of early detection and treatment of metabolic syndrome on cognitive ability.

Intravascular levels of low-density lipoprotein cholesterol (LDL-C) at approximately ≤ 0.6 mmol/L are likely to minimize, and perhaps eliminate, LDL-C-related vascular toxicity while having no effect on essential, intracellular cholesterol homeostatic pathways, according to accumulated knowledge from basic science. Randomized clinical trials, observational reports, and Mendelian randomization trials are also forcing a reconsideration of what "normal" LDL-C means. Recent trials of secondary prevention have substantiated that such levels are safe and associated with a decreased risk of cardiovascular events (CVEs) compared with patients with higher levels of LDL-C. Similarly, treatment to this low range is associated with regression and stabilization of established atherosclerosis. Primary prevention trials also show that low levels of LDL-C are safe and associated with decreased risk of CVEs through cholesterol-lowering in adults with LDL-C ≥ 3.5 mmol/L or when levels are < 3.5 mmol/L in association with other cardiovascular risks. Although there are no randomized clinical outcome trials of familial hypercholesterolemia patients, such patients have very high, lifetime risk of CVE, and registry studies show that LDL-C reduction has nearly normalized their CVE rates. The possibility of familial hypercholesterolemia should be considered if LDL-C is > 4.5 and > 4.0 mmol/L at ages 18-39 years and younger than 18 years, respectively. On the basis of these convergent and internally consistent lines of evidence, in this article we speculate on a translational paradigm aimed at eliminating LDL-C-related CVEs through aggressive primary prevention strategies that are already proven and well accepted in principle., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) plays a key role in atherosclerosis development. It is considered a marker of increased risk of cardiovascular disease (CVD) and plaque vulnerability. Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol and a higher prevalence of early CVD. Our aim was to evaluate the differences in Lp-PLA 2 activity in a population of hypercholesterolemic patients with and without definite FH., Methods and Results: Hypercholesterolemic patients were consecutively recruited. Definite FH was defined according to Dutch Lipid Clinic Network criteria ≥8. All patients underwent routine clinical examination and biological assessments and Lp-PLA 2 activity was measured in blood samples. Among 469 patients, 118 had a definite diagnosis of FH. Lp-PLA 2 activity was significantly higher in definite FH patients compared to non-definite FH patients (206.5 ± 54.5 vs. 180.8 ± 48.4 nmol/min/mL, p < 0.0001). Lp-PLA 2 positively correlated with total cholesterol, LDL-C and apolipoprotein B and negatively with HDL-C and apolipoprotein A-1. In multivariate analysis, definite FH diagnosis, LDL-C, HDL-C and statin treatment remained correlates of Lp-PLA 2 independently of systolic blood pressure., Conclusions: Lp-PLA 2 activity was higher in definite FH than in non-definite FH patients independently of LDL-C levels and statin treatment. These results highlight the particular phenotype of FH subjects among hypercholesterolemic patients. As increased Lp-PLA 2 activity suggests, FH patients exhibit higher arterial inflammation that may contribute to their high cardiovascular risk. Our results reinforce the potential beneficial role of statins pleiotropic effects and the need for proper identification and treatment of FH patients., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Statins are the first-line therapy prescribed to lower plasma cholesterol levels. Although being safe and showing several beneficial cholesterol-independent pleiotropic effects, a significant variability regarding statin's therapeutic goals has been abundantly documented, but less understood. We aimed to investigate the influence of the ABCC2 -24C>T single nucleotide polymorphism on Chilean hypercholesterolaemic individuals treated for 4 weeks with 10 mg/day atorvastatin. A total of 127 individuals medicated with atorvastatin 10 mg/day/4 weeks were included. Lipid profiles were determined before and after drug administration by conventional assays. Genotyping of the ABCC2 rs717620 SNP (-24C>T) was performed with TaqMan ® Drug Metabolism Genotyping Assays. As expected, atorvastatin reduced TC, LDL-C and TG concentrations (p < 0.05). Also, HDL-C levels were increased (p < 0.05). Minor allele frequency for the rs717620 was 0.232. Overall, atorvastatin response was not associated with the ABCC2 rs717620 SNP (p > 0.05). Nonetheless, in male individuals carrying the -24T allele, we observed an attenuated reduction in both TG values and the TG/HDL-C ratio after 10 mg/day atorvastatin. This study indicates that TG levels and the TG/HDL-C ratio are affected by the rs717620 SNP in Chilean males but not female individuals after atorvastatin treatment., (© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Introduction and Objectives: Approximately 20% to 40% of clinically defined familial hypercholesterolemia cases do not show a causative mutation in candidate genes, and some of them may have a polygenic origin. A cholesterol gene risk score for the diagnosis of polygenic hypercholesterolemia has been demonstrated to be valuable to differentiate polygenic and monogenic hypercholesterolemia. The aim of this study was to determine the contribution to low-density lipoprotein cholesterol (LDL-C) of the single nucleotide variants associated with polygenic hypercholesterolemia in probands with genetic hypercholesterolemia without mutations in candidate genes (nonfamilial hypercholesterolemia genetic hypercholesterolemia) and the genetic score in cascade screening in their family members., Methods: We recruited 49 nonfamilial hypercholesterolemia genetic hypercholesterolemia families (294 participants) and calculated cholesterol gene scores, derived from single nucleotide variants in SORT1, APOB, ABCG8, APOE and LDLR and lipoprotein(a) plasma concentration., Results: Risk alleles in SORT1, ABCG8, APOE, and LDLR showed a statistically significantly higher frequency in blood relatives than in the 1000 Genomes Project. However, there were no differences between affected and nonaffected members. The contribution of the cholesterol gene score to LDL-C was significantly higher in affected than in nonaffected participants (P = .048). The percentage of the LDL-C variation explained by the score was 3.1%, and this percentage increased to 6.9% in those families with the highest genetic score in the proband., Conclusions: Nonfamilial hypercholesterolemia genetic hypercholesterolemia families concentrate risk alleles for high LDL-C. Their contribution varies greatly among families, indicating the complexity and heterogeneity of these forms of hypercholesterolemias. The gene score explains a small percentage of LDL-C, which limits its use in diagnosis., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Competing Interests: There are no conflicts of interest

Purpose: Clinical trials of statins and other lipid-lowering therapies (LLTs) often report large inter-individual variations in their effects on low-density lipoprotein cholesterol (LDL-C). We evaluated apparent hyporesponsiveness to the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab (defined as < 15% LDL-C reduction from baseline at all timepoints) using data from 10 Phase 3 trials (3120 hypercholesterolemic patients)., Methods: This report assessed the LDL-C percent reduction from baseline at weeks 4-104 (depending on study), and alirocumab serum levels and antidrug antibodies, in patients with apparent hyporesponsiveness., Results: Among the 3120 patients evaluated, 98.9% responded to alirocumab, and 33 (1.1%) had < 15% LDL C reduction at all measured timepoints. Pharmacokinetics data indicated that 13/33 apparent hyporesponders had not received alirocumab; no pharmacokinetics data were available for 14/33, and 6/33 had detectable alirocumab. For the six patients with confirmed alirocumab receipt, the degree of adherence to pre-study concurrent LLTs could not be determined after study start; one of these patients had persistent antidrug antibodies., Conclusions: Apparent hyporesponsiveness to alirocumab appeared to be due to lack of receipt of alirocumab determined by serum alirocumab levels, possible lack of adherence to concurrent LLTs, a theoretical and rare possibility of biological non-responsiveness due to persistent antidrug antibodies, or other causes, as yet unidentified.

Objectives: To estimate the prevalence, awareness, treatment and control of hypertension, diabetes and hypercholesterolaemia in an Angolan population aged 15 to 64 years and to determine relationships with sociodemographic, behavioural and anthropometric characteristics., Methods: A total of 2 354 individuals were assessed for behavioural, sociodemographic and physical characteristics in a cross-sectional, community-based survey. Post-stratification survey weights were applied to obtain prevalence levels. Adjusted odds ratios for each variable related to the conditions were calculated using logistic regression models., Results: Overall, the prevalence of hypertension was 18.0%, diabetes 9.2% and hypercholesterolaemia 4.0%. Among hypertensive individuals, the awareness rate was 48.5%; 15.8% were on treatment and 9.1% had their blood pressure controlled. Only 10.8% were aware they had diabetes, 4.5% were on treatment and 2.7% were controlled. The awareness level for hypercholesterolaemia was 4.2%, with 1.4% individuals on treatment and 1.4% controlled., Conclusion: The prevalence levels of hypertension and diabetes, which were higher than previous findings for the region, together with the observed low rates of awareness, treatment and control of all conditions studied, constitute an additional challenge to the regional health structures, which must rapidly adapt to the epidemiological shift occurring in this population.

Background: Studies have reported associations between neck pain and degenerative changes in the cervical spine in women, and between neck pain and obesity or metabolic syndrome. The present study investigated associations between neck pain or stiffness and lipid profiles in subjects recruited from the general population of a Japanese community., Methods: The 1122 volunteers who participated in this study included 426 men (age 52.6 ± 15.5 years; body mass index 23.6 ± 3.2) and 696 women (age 55.3 ± 15.3 years; body mass index 22.2 ± 3.4). Each subject filled out a questionnaire about any neck pain or neck-shoulder stiffness experienced in the previous 3 months. We recorded the following laboratory results related to metabolic factors, including lipid profiles: total cholesterol, LDL and HDL cholesterol, triglycerides, free fatty acids, glucose, and hemoglobin A1c. We conducted logistic and linear regression analyses using the prevalence of neck pain or neck-shoulder stiffness as the dependent variable and age, sex, body mass index, and laboratory data as independent variables., Results: There was no significant difference in the prevalence of neck pain between men (20.5%) and women (21.5%). However, the prevalence of neck and shoulder stiffness was significantly higher in women (60.3%) than in men (38.0%; P < 0.05). Logistic and linear regression analyses showed a significant negative correlation between the prevalence of neck pain and LDL cholesterol (odds ratio [OR], 0.958; 95% CI, 0.921-0.997), and between the prevalence of neck-shoulder stiffness and age (OR, 1.025; 95% CI, 1.013-1.038) and gender (OR, 0.362; 95% CI, 0.25-0.494)., Conclusion: LDL cholesterol was correlated with neck pain in this cross-sectional population-based study., (Copyright © 2017. Published by Elsevier B.V.)

Background: Vitamin D preparations reduce titers of thyroid antibodies in women with autoimmune thyroiditis. The same effect was induced by high-dose, but not moderate-dose-, statin therapy. No previous study has investigated the impact of concomitant treatment with a statin and vitamin D on thyroid autoimmunity., Methods: The study included three matched groups of women with Hashimoto's thyroiditis and low vitamin D status. Groups B (n=19) and C (n=20) were treated with vitamin D (2000 IU daily). Because of coexistent hypercholesterolemia, groups A (n=18) and B received simvastatin (40mg daily). Plasma lipids, serum levels of thyrotropin, free thyroid hormones and 25-hydroxyvitamin D, as well as titers of thyroid peroxidase and thyroglobulin antibodies were measured at the beginning of the study and 6 months later., Results: At baseline, 25-hydroxyvitamin D levels inversely correlated with titers of thyroid antibodies. In groups A and B, simvastatin reduced plasma levels of total and LDL cholesterol. Simvastatin produced no effect on thyroid antibody titers. Vitamin D decreased titers of thyroid peroxidase antibodies, as well as tended to decrease titers of thyroglobulin antibodies. Simvastatin-vitamin D combination therapy reduced serum titers of thyroid peroxidase and thyroglobulin antibodies and this effect was stronger than the effect of simvastatin and vitamin D administered alone. Treatment-induced changes in thyroid antibody titers correlated with baseline antibody titers, baseline levels of 25-hydroxyvitamin and treatment-induced changes in 25-hydroxyvitamin., Conclusions: The obtained results indicate that simvastatin may potentiate the impact of vitamin D on thyroid autoimmunity in vitamin D-deficient women with Hashimoto's thyroiditis., (Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate and compare the efficacy and safety of rosuvastatin versus atorvastatin in a high-risk Chinese population with hypercholesterolemia., Research Design and Methods: This 6 week, prospective, multicenter, double-blind, three-arm, parallel-group, active-controlled study randomized adult Chinese patients (low-density lipoprotein cholesterol [LDL-C] ≥ 130-<250 mg/dL statin-naive and ≥100-<160 mg/dL in statin treated) to receive rosuvastatin (5 mg or 10 mg) or atorvastatin 10 mg. Patients not achieving National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III LDL-C targets in the randomized phase were administered rosuvastatin 10 mg and 20 mg in the open-label phase., Results: In total 414 patients (mean age: 59.5 ± 9.51 years, 59.4% females, mean LDL-C: 4.242 ± 0.676 mmol/L (rosuvastatin 5 mg), 4.13 ± 0.682 mmol/L (rosuvastatin 10 mg) and 4.213 ± 0.662 mmol/L (atorvastatin 10 mg) were analyzed. Compared with atorvastatin 10 mg, rosuvastatin 5 mg (-41.70% vs. -38.67%, p = .132) and rosuvastatin 10 mg showed greater LDL-C reduction (-46.28% vs. -38.67%, p = .0002). LDL-C target achievement rates with rosuvastatin 5 mg, rosuvastatin 10 mg and atorvastatin 10 mg were 61.0%, 79.1% and 58.3% in the randomized phase. In the open-label phase, LDL-C target achievement occurred in >40% with both doses of rosuvastatin. The rate of ≥1 adverse event was similar with rosuvastatin 5 mg (12.4%), 10 mg (11.7%) and atorvastatin 10 mg (8.9%)., Conclusion: Rosuvastatin 5 mg demonstrated non-inferiority and rosuvastatin 10 mg demonstrated superiority to atorvastatin 10 mg for lowering LDL-C in high-risk Chinese patients with dyslipidemia, which was maintained through the open-label phase., Clinical Trial Registration: NCT00683618.

Background and Purpose: The most common neurological manifestation of antiphospholipid syndrome (APS) is ischaemic stroke. Identifying patients with APS at high risk for developing any thrombotic event remains a major challenge. In this study, the aim was to identify predictive factors of ischaemic stroke in a cohort of primary APS (PAPS) patients who presented with new onset symptoms suggestive of acute stroke., Methods: This prospective multicentre study included 36 consecutive PAPS patients who presented with new onset symptoms suggestive of an acute stroke. Patients were prospectively followed up for 12 months., Results: In 10 (28%) out of 36 PAPS patients [mean age 41 years (SD 13.4), 70% female], the suspicion of an acute stroke was confirmed by brain magnetic resonance imaging. Sixty per cent of these patients were <50 years old. Eight of the 10 patients had a history of previous venous thrombosis and were receiving vitamin K antagonist (VKA), with international normalized ratio target 2-3; one patient had a history of a previous arterial event receiving treatment with VKA target international normalized ratio 2-3 plus low dose aspirin; and one patient had a history of previous pregnancy morbidity receiving only low dose aspirin. Time in the therapeutic range for patients receiving VKA was 77.7% (SD 6.6%). Hypercholesterolaemia was significantly higher in patients with confirmed stroke compared to those without (P < 0.05). Similarly, a significantly higher rate of anti-β2 glycoprotein-I (β2GPI) antibodies (immunoglobulin G/immunoglobulin M; P < 0.05) and higher adjusted global APS score (aGAPSS) values were found in patients with a confirmed stroke [mean aGAPSS 8.9 (SD 4.7) vs. mean aGAPSS 6.4 (SD 2.5); P < 0.05]., Conclusions: Patients with PAPS, including young patients, have a high risk of recurrent thrombosis despite anticoagulation treatment. A careful risk assessment is mandatory to identify patients at risk for recurrence., (© 2017 EAN.)

Background and Aims: Hepatic dysfunction, due to parenteral nutrition, may become severe and lead to cirrhosis and hepatic failure, especially in newborns and infants. This study aimed to evaluate the association between the exclusive use of total parenteral nutrition (TPN) and changes in the hepatic profile, and to investigate the relationship between age, hypertriglyceridemia, and hypercholesterolemia, and the occurrence of laboratory liver dysfunction., Methods: A descriptive and historical cohort study was conducted, evaluating 195 pediatric patients (age: 1 month to 19 years) who received TPN. The following hepatic and lipid profiles were assessed: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma-glutamyl transferase (GGT), bilirubin, triglycerides (TGs), cholesterol, high-density lipoprotein (HDL), albumin, and transthyretin. High C-reactive protein and/or low HDL were considered indicative of inflammatory process., Results: The majority of patients presented normal values of AST (79.2%), ALT (74.9%), GGT (56.4%), and alkaline phosphatase (68.1%). Total bilirubin changed in 68.5% of patients, and transthyretin and albumin were low in 87.3% and 65.1% of the patients, respectively. Incidences of high GGT values were related to age (odds ratio [OR], 2.46; confidence interval [CI] 1.28-4.76; p = 0.007), hypercholesterolemia (OR, 3.00; 95% CI, 1.24-7.25; p = 0.015), and hypertriglyceridemia (OR, 2.39; 95% CI, 1.02-5.60; p = 0.046). Incidences of elevated ALT values were associated with hypercholesterolemia (OR, 4.57; 95% CI, 2.03-10.30; p < 0.001)., Conclusion: Monitoring the hepatic profile from the early stage of TPN is necessary. Changes in the plasma lipid and hepatic profiles were frequently observed during the infusion of TPN, in patients with inflammation. Patients >2 years old and those with high TG and HDL levels were more likely to have elevated GGT levels. Hypercholesterolemia was associated with ALT alterations. Strategies to attenuate these issues should be considered in the early stages, in patients with TPN., (Copyright © 2017 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background and Objective: Statins are commonly used medications. Whereas some observational studies suggested an association of statin use with Barrett's esophagus and some upper gastrointestinal symptoms, there is a dearth of data on the association of statins and common esophageal conditions such as gastroesophageal reflux disease and esophagitis. The aim of this study is to examine the association of statins with esophageal conditions., Methods: This is a retrospective cohort study using regional military healthcare data (1 October, 2003 to 1 March, 2012). The primary analyses evaluated the odds of: esophagitis; symptoms of esophagitis; gastroesophageal reflux disease/dyspepsia; and esophageal complications of gastroesophageal reflux disease in four propensity score-matched cohorts of statin users and non-users (propensity score-overall, propensity score-healthy, propensity score-women, and propensity score-men cohorts). Secondary and sensitivity analyses were performed., Results: In the propensity score-overall cohort (n = 12,684), statin users were more likely to be diagnosed with esophagitis (odds ratio 1.11, 95% confidence interval 1.01-1.22) and gastroesophageal reflux disease/dyspepsia (odds ratio 1.18, 95% confidence interval 1.10-1.27) compared with non-users. Similar findings were seen in the propensity score-healthy cohort and in the propensity score-men cohort. In the propensity score-women cohort, the odds of esophagitis was higher among statin users compared with non-users (odds ratio 1.16, 95% confidence interval 1.02-1.32) but other outcomes were not different. In sensitivity analyses, which excluded patients with obesity, statin use was not associated with an increased odds ratio of gastroesophageal reflux disease/dyspepsia., Conclusion: Statin therapy was associated with higher odds of being diagnosed with esophagitis and gastroesophageal reflux disease/dyspepsia. Further study is warranted to elucidate the potential role of statins in these commonly diagnosed esophageal conditions.

Background: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH., Objectives: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH., Methods: Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol., Results: We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years of age; baseline LDL-C: 571.9 ± 171.7 mg/dl). During a mean follow-up of 14.1 ± 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 ± 85.1 mg/dl (-69.6% from baseline), with a better response in patients taking lomitapide (-88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl. During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%, respectively). No incident stroke was observed. Age (≥30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD., Conclusions: Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We examined the gender-specific association between dietary pattern and risk of developing cholesterolemia based on the data from the Korean Genome and Epidemiology study. A total of 7515 individuals aged 40-69 years participated in this study between 2005 and 2010. Dietary intake was assessed by a semi-quantitative food frequency questionnaire. Low HDL cholesterolemia was defined as a plasma HDL-C level <1.04 mmol/L (men) or <1.30 mmol/L (women), and high LDL cholesterolemia was defined as a plasma LDL-C level >3.37 mmol/L. Multivariate Cox proportional hazard models were used to examine the risk for incident cholesterolemia according to dietary pattern score. Four dietary patterns were derived by gender using factor analysis: prudent pattern; coffee, fat, and sweet pattern; whole grain (men) or white rice and noodle (women) pattern; and westernized pattern. A prudent pattern was inversely associated with risk of low HDL cholesterolemia in both men (Hazard ratio (HR) = 0.76, p for trend = 0.0098) and women (HR = 0.78, p for trend = 0.0324), whereas the coffee, fat, and sweet pattern was positively associated with risk of high LDL cholesterolemia in men only (HR = 1.26, p for trend = 0.0254) after adjustment for potential confounders. Specific dietary patterns were associated with risk of developing cholesterolemia suggesting gender differences., Competing Interests: The authors declare no conflict of interest.

Background: Autosomal recessive hypercholesterolemia (ARH) is a rare inherited lipid disorder. In Sardinia, differently from other world regions, the mutated allele frequency is high. It is caused by mutations in the low-density lipoprotein receptor adaptor protein 1 gene. Fourteen different mutations have been reported so far; in Sardinia, 2 alleles (ARH1 and ARH2) explain most of the cases. Four ARH patients, all carriers of the ARH1 mutation, have been identified in mainland Italy and 2 in Sicily., Objective: The objectives of the study were to improve the molecular diagnosis of familial hypercholesterolemia (FH) and to estimate the frequency of the ARH1 allele in 2 free-living Sicilian populations., Methods: We sequenced by targeted next-generation sequencing 20 genes related to low-density lipoprotein metabolism in 50 hypercholesterolemic subjects. Subjects from 2 free-living populations from Northern (Ventimiglia Heart Study, 848 individuals) and Southern Sicily (Zabut Zabùt Aging Project, 1717 individuals) were genotyped for ARH1 allele., Results: We identified 1 homozygous carrier of the ARH1 mutation among the 50 hypercholesterolemic outpatients. Population-based genotyping of ARH1 in 2565 subjects allowed the identification of 1 heterozygous carrier. The overall estimated allele frequency of ARH1 in Sicily was 0.0002 (0.02%)., Conclusions: The identification of a new case of ARH in Sicily among 50 clinically diagnosed FH highlights the importance of next-generation sequencing analysis as tool to improve the FH diagnosis. Our results also indicate that ARH1 carrier status is present in ∼1:2500 of Sicilian inhabitants, confirming that ARH is extremely rare outside Sardinia., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Objective: Evidence suggests that individuals with Alzheimer's disease (AD) are often diagnosed in the later stages of their disease with a poor prognosis. This study is aimed to identify patterns in signs and symptoms preceding the clinical diagnosis of AD to suggest a predictive model for earlier diagnosis of the disease in the primary care., Design: A retrospective medical record review; nested case control design., Participants: Participants included one hundred and nine patients from three general practice (GP) surgeries in Milton Keynes and Luton Clinical Commissioning Groups (CCG) (37 cases with AD and 72 controls without AD)., Main Outcome Measure: A retrospective analysis using the logistic regression of the presence of signs and symptoms before the diagnosis of AD was attained. Identification of the timing and sequence of appearance of these presentations as first reported before the clinical diagnosis was measured., Result: Episodic memory with an odds ratio of 1.85 was the most frequent presentation, documented in 1.38% of the controls and 75.6% in cases. Auditory disturbance with an odds ratio of 3.03, which has not previously been noted except in the form of auditory hallucination, could have a diagnostic value., Conclusion: Auditory disturbance, which occurred mostly in the Caucasian females, could discriminate individuals with AD from those without the disease. The symptom, which presented up to 14.5 (mean time) years prior to clinical diagnosis, was identified in Caucasians and mixed race individuals only., Strengths: The study demonstrates that auditory disturbance could allow an earlier diagnosis of AD in Caucasian females. Episodic memory was confirmed as being frequently noted in AD patients prior to a clinical diagnosis as per previous publications. This study supports the development of a scoring system for the earlier diagnosis of AD. The data used was free from the confounding effects of misinformation, as this was written at the point of collection, thereby benefitting from the use of GP data that is diversified, reliable and valid., Limitations: Limited sample size that will not allow for generalization of less frequent observations due to their low prevalence in case notes. Randomisation was not achieved; however, the best available nonrandomisation which is consecutive sampling was used. Patterns identified were in LOAD, the baseline could vary with other geographical areas., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Sitosterolemia is associated with increases in intestinal sterol absorption, low-density lipoprotein cholesterol (LDL-C), and cardiovascular disease risk., Objective: We examined the relationship between hypercholesterolemia and sitosterolemia in a large population and report a new sitosterolemia case., Methods: Plasma sterol concentrations were measured by gas chromatography/mass spectrometry, and LDL-C by direct assay., Results: Of 207,926 subjects tested, 4.3% had LDL-C ≥190 mg/dL. Plasma β-sitosterol concentrations ≥8.0 mg/L (99th percentile) were found in 4.3% of these subjects vs 0.72% with LDL-C <130 mg/dL. Among all subjects, 0.050% had β-sitosterol levels ≥15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C ≥190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a β-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 ABCG8 mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low-cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (-29%) and β-sitosterol to 44.6 mg/L (-27%). On atorvastatin 20 mg/d, his LDL-C decreased to 299 mg/dL (-38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60 mg/dL (-80% further decrease); and his β-sitosterol decreased to 14.1 mg/L (-68% further decrease)., Conclusions: Our data indicate that about 4% of subjects with LDL-C concentrations ≥190 mg/dL have plasma β-sitosterol concentrations above the 99th percentile and about 0.3% have concentrations consistent with sitosterolemia. Therefore, this diagnosis should be considered in such patients., (Copyright © 2017. Published by Elsevier Inc.)

Familial hypercholesterolemia (FH) is a common inherited disease that exhibits significantly increased levels of low-density lipoprotein cholesterol (LDL-C), skin or tendon xanthomas, corneal arcus and premature coronary heart disease (CHD). The prevalence of heterozygous FH is nearly 1/300 worldwide, and the prevalence of homozygous FH (HoFH) is 1/160,000 - 1/300,000. The Dutch Lipid Clinic Network diagnostic (DLCN) criteria is the most commonly recommended criteria for diagnosing FH patients. However, another disease with a similar clinical phenotype to FH must be differentiated from FH. This disease is a rare autosomal recessive disorder, sitosterolemia, and its incidence rate is approximately 1/5 million. We report a 16-month-old child with suspected HoFH and LDL-C levels that were reduced from 14.69 mmol/L to 3.24 mmol/L after dietary control without statin therapy. Gas chromatography detection of plant sterol levels and targeted exon sequencing chips for genetic testing were used to reach confirmed the diagnosis of sitosterolemia., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Cardiovascular diseases have been the major cause of mortality and morbidity all over the world accounting for more than 80% of the deaths from heart attacks and strokes. Hypercholesterolemia, an autosomal disorder of lipoprotein metabolism is one of the foremost causes of CVDs. An increased level of low-density lipoprotein cholesterol (LDL-C) in the plasma results in the rise of incidence rates in disease patients. Several conventional and combinational therapies have been proposed for lowering the LDL-C levels in the blood. These therapeutic agents are designed to target some crucial molecules that participates in the lipid metabolism such as apolipoprotein B, HMGCoA reductase, proprotein convertase subtilisin/kexin 9, etc. Although these therapies are effective but are associated with certain side effects. This article presents an overview on different conventional and nanotechnology-based approaches for the treatment and diagnosis of hypercholesterolemia. Numerous nanomaterial-based therapies including polymeric nanoparticles, cationic lipids, liposomes, dendrimers and inorganic nanoparticles have been discussed in lowering the cholesterol level along with recent advancement in diagnosis and imaging.

Background: Familial hypercholesterolaemia (FH) is the most common genetic disease leading to premature atherosclerosis., Aim: The aim of the study was to evaluate the prevalence, diagnosis, and treatment of FH in outpatient practices in Poland., Methods: The study included a representative sample of 147 primary care physicians, cardiologists, and diabetologists caring for 2812 adult patients with hypercholesterolaemia and low-density lipoprotein cholesterol (LDL-C) level > 1.8 mmol/L, who were treated with statins or did not receive statins due to intolerance or contraindications. The physicians declared whether they diagnosed FH in the study group. In addition, we evaluated the Dutch Lipid Clinic Network (DLCN) diagnostic criteria for FH in all patients. The results were weighted and extrapolated to the general outpatient population in Poland. Treatment and its effectiveness were also evaluated., Results: FH6+ score by the DLCN criteria was found in 3.6% of the study group, which translates by extrapolation to 136,300 adult patients with FH in Poland. Among patients with FH6+, this diagnosis was correctly made by physicians in 25% of cases and was not established in 75% of cases. Only 32.8% of patients received high statin doses. High LDL-C levels were found in a large proportion of patients, including levels ≥ 5.0 mmol/L in 42.7% of patients and ≥ 4.1 mmol/L in 59.7% of patients., Conclusions: Familial hypercholesterolaemia is inadequately diagnosed and treated in Poland, which calls for a radical im-provement of pre- and postgraduate education in this regard.

We report the case of acute myocardial infarction in a 25-year-old woman with sitosterolemia. She was treated using statins, but her low-density lipoprotein cholesterol (LDL-C) levels did not decrease appreciably. Genetic analysis revealed mutations in the ABCG8 gene. Ezetimibe treatment was initiated, and her LDL-C levels decreased substantially. Sitosterolemia must be considered in the differential diagnosis of familial hypercholesterolemia in case of early onset cardiovascular disease patient with high LDL-C., (Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Elevated levels of low-density lipoprotein cholesterol (LDL-C) and glycosylated hemoglobin (HbA1c) are risk factors for cardiovascular complications. This study evaluated LDL-C goal attainment in Russian clinical practice among patients with moderate to very high cardiovascular risk. The study also assessed LDL-C goal attainment in patients prescribed lipid-lowering therapy for primary compared with secondary cardiovascular disease (CVD) prevention, predictors of LDL-C goal attainment, and the proportion of individuals with diabetes mellitus who achieved HbA1c < 7%., Methods: The Centralized Pan-Russian Survey on the Undertreatment of Hypercholesterolemia in Russia II (CEPHEUS II) was a multicenter, non-interventional, cross-sectional study conducted in the Russian Federation from September 2014 to November 2015. Participants were aged ≥ 18 years, were receiving a stable dose of lipid-lowering medication and had a moderate to very high cardiovascular risk. The primary variable was the proportion of patients reaching LDL-C goals established by the Fifth Joint European Task Force guidelines. Secondary analyses used McNemar and χ 2 tests., Results: Data from 2703 patients were analyzed; 91.2% had a very high cardiovascular risk and 24.0% had been diagnosed with diabetes mellitus. Overall, 17.4% of patients (95% confidence interval [CI] 15.9-18.8%) achieved LDL-C goals. Investigators estimated this proportion at 21.8% (95% CI 20.3-23.4%). LDL-C goals were achieved by more patients in the primary CVD prevention subgroup than in the secondary CVD prevention subgroup (19.7% vs 16.1%, p = 0.017). Patient-related factors associated with a decreased likelihood of achieving LDL-C goals included having ischemic heart disease or a family history of premature coronary heart disease, forgetting to take hypercholesterolemia treatment or considering it acceptable to miss prescribed doses more than once per week, and dissatisfaction with or concern about lipid-lowering therapy. Overall, 367/593 (61.9%) patients with diabetes mellitus and interpretable HbA1c results achieved HbA1c < 7%., Conclusions: Hypercholesterolemia management is suboptimal in patients with moderate to very high cardiovascular risk in Russian clinical practice. Substantial opportunity remains to improve treatment target attainment and reduce the risk of cardiovascular complications. Lipid-modifying strategies may need to be intensified to reduce CVD risk in this setting. Trial registration ClinicalTrials.gov: NCT02230241 (registered 26 August 2014).

Context: Royal jelly (RJ) has been reported for its health promoting factors such as antioxidant, anti-inflammatory and lipid lowering activities., Objective: The present randomized, placebo-controlled study examines the hypolipidemic beneficial effect of RJ through evaluating anthropometric measurements, lipid profile and various hormone levels in mildly hypercholesterolemic participants., Materials and Methods: Forty subjects with mild hypercholesterolemia (180-200 mg/dL) were randomly selected and divided into two groups as experimental or placebo, who requested to intake nine capsules (350 mg/capsule) of RJ or placebo/day, respectively, for three months with one month of follow-up without any supplementation., Results: No significant changes were noted in any of the anthropometric parameters like body weight, waist and body fat. The serum total cholesterol (TC; 207.05-183.15 mg/dL) and low-density lipoprotein cholesterol (LDL-c; 126.44-120.31 mg/dL) levels were reduced significantly (p < 0.05) after administration of RJ. However, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c) levels were not considerably altered. Moreover, three months of RJ consumption significantly ameliorated (p < 0.05) the concentration of sex hormones like dehydroepiandrosterone sulphate (DHEA-S; 1788.09-1992.31 ng/mL). Also, intake of RJ did not elicit any hepatic or renal damage., Discussion and Conclusion: Intervention with RJ for three months considerably lowered the TC and LDL-c levels through improving the levels of DHEA-S and thus alleviates the risk of cardiovascular disease (CVD).

Objectives: To examine patterns of non-high-density lipoprotein (HDL) cholesterol in early childhood and identify factors associated with persistent high non-HDL cholesterol in healthy urban children., Study Design: We identified all children enrolled in a primary care practice-based research network called TARGet Kids! (The Applied Research Group for Kids) with ≥3 laboratory measurements of non-HDL cholesterol. Latent class growth model analysis was performed to identify distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then categorized into "normal" vs "persistent-high" non-HDL cholesterol based on guideline cut-off values and logistic regression was completed to examine the association between trajectory group and the presence of anthropometric and cardiometabolic risk factors., Results: A total of 608 children met inclusion criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9 months). Four trajectory groups were identified with 2 groups (n = 451) categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI 1.27-3.28) was associated significantly with persistent high non-HDL cholesterol, whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78), longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent high non-HDL cholesterol., Conclusions: Patterns of non-HDL cholesterol are identified during early childhood, and family history of high cholesterol was associated most strongly with persistent high non-HDL cholesterol. Future research should inform the development of a clinical prediction tool for lipids in early childhood to identify children who may benefit from interventions to promote cardiovascular health., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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 < 0.05) the colony number of Bifidobacterium spp. (1.18- and 1.19-fold) and Lactobacillus spp. (1.07- and 1.16-fold), but markedly lowered (p < 0.05) the colony number of 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 < 0.05), but no change in other lipid parameters. Whereas, the antioxidant capacity was also concomitantly elevated (p < 0.05) upon administration with PEC., 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.

Aims Identification and management of the Standard Modifiable Cardiovascular Risk Factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) has substantially improved cardiovascular disease outcomes. However, cardiovascular disease remains the leading cause of death worldwide. Suspecting an evolving pattern of risk factor profiles in the ST elevation myocardial infarction (STEMI) population with the improvements in primary care, we hypothesized that the proportion of 'SMuRFless' STEMI patients may have increased. Methods/results We performed a single centre retrospective study of consecutive STEMI patients presenting from January 2006 to December 2014. Over the study period 132/695 (25%) STEMI patients had 0 SMuRFs, a proportion that did not significantly change with age, gender or family history. The proportion of STEMI patients who were SMuRFless in 2006 was 11%, which increased to 27% by 2014 (odds ratio 1.12 per year, 95% confidence interval: 1.04-1.22). The proportion of patients with hypercholesterolaemia decreased (odds ratio 0.92, 95% confidence interval 0.86-0.98), as did the proportion of current smokers (odds ratio 0.93, 95% confidence interval 0.86-0.99), with no significant change in the proportion of patients with diabetes and hypertension. SMuRF status was not associated with extent of coronary disease; in-hospital outcomes, or discharge prescribing patterns. Conclusion The proportion of STEMI patients with STEMI poorly explained by SMuRFs is high, and is significantly increasing. This highlights the need for bold approaches to discover new mechanisms and markers for early identification of these patients, as well as to understand the outcomes and develop new targeted therapies.

Sitosterolemia is an autosomal recessive metabolic disease caused by mutations in ABCG5 or ABCG8 genes which encode for the (ATP)-binding cassette (ABC) transporters that are responsible for the trafficking of xenosterols. Liver involvement is not a recognized manifestation of this disease, and cirrhosis has been reported only once in the medical literature. We describe a fatal case of a 21-year old South Asian male who presented with decompensated cirrhosis, and biochemical abnormalities consistent with sitosterolemia. Genetic testing showed a homozygous pathogenic mutation in ABCG5, confirming the diagnosis. Sitosterolemia is a rare, but likely under-recognized condition, and a high degree of suspicion is imperative to make the diagnosis. We propose that sitosterolemia should be included in the differential diagnosis for patients with cryptogenic cirrhosis, especially as there are effective oral therapies to treat this condition. Newly diagnosed sitosterolemia patients should undergo a thorough hepatology evaluation and follow-up to evaluate for the presence, development, and progression of any hepatic involvement.

In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD. Most notably, the FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial and SPIRE-1 and -2 (Studies of PCSK9 Inhibition and the Reduction of Vascular Events), assessing evolocumab and bococizumab, respectively, have published final results of cardiovascular outcomes trials in patients with clinical ASCVD and in a smaller number of high-risk primary prevention patients. In addition, further evidence on the types of patients most likely to benefit from the use of ezetimibe in addition to statin therapy after acute coronary syndrome has been published. Based on results from these important analyses, the ECDP writing committee judged that it would be desirable to provide a focused update to help guide clinicians more clearly on decision making regarding the use of ezetimibe and PCSK9 inhibitors in patients with clinical ASCVD with or without comorbidities. In the following summary table, changes from the 2016 ECDP to the 2017 ECDP Focused Update are highlighted, and a brief rationale is provided. The content of the full document has been changed accordingly, with more extensive and detailed guidance regarding decision making provided both in the text and in the updated algorithms. Revised recommendations are provided for patients with clinical ASCVD with or without comorbidities on statin therapy for secondary prevention. The ECDP writing committee judged that these new data did not warrant changes to the decision pathways and algorithms regarding the use of ezetimibe or PCSK9 inhibitors in primary prevention patients with LDL-C <190 mg/dL with or without diabetes mellitus or patients without ASCVD and LDL-C ≥190 mg/dL not due to secondary causes. Based on feedback and further deliberation, the ECDP writing committee down-graded recommendations regarding bile acid sequestrant use, recommending bile acid sequestrants only as optional secondary agents for consideration in patients intolerant to ezetimibe. For clarification, the writing committee has also included new information on diagnostic categories of heterozygous and homozygous familial hypercholesterolemia, based on clinical criteria with and without genetic testing. Other changes to the original document were kept to a minimum to provide consistent guidance to clinicians, unless there was a compelling reason or new evidence, in which case justification is provided., (Copyright © 2017. Published by Elsevier Inc.)

The ACC/AHA 2013 guideline recommends high-intensity statin therapy for a decrease in low-density lipoprotein cholesterol (LDL-C) level by >50% among patients with baseline values of ≥190 mg/dL (approximately 4.872 mmol/L); however, this value should be modified before applying it to Korean populations. We investigated the statin-specific LDL-C-lowering effects in Korean patients with baseline LDL-C value ≥4.872 mmol/L. Data of patients prescribed a statin for the first time from January 2009 to December 2013 were assessed. In patients with baseline LDL-C value ≥4.872 mmol/L, laboratory data for a maximum of 6 months from the date of first statin prescription were collected. Among 33,721 patients who were prescribed a statin for the first time, 655 patients had a baseline LDL-C value ≥4.872 mmol/L (1.9%). Of these, 179 patients were analysed. Patients receiving moderate-intensity statins were divided into two groups based on LDL-C reduction rate (p = 0.0002), defined as moderate-high-intensity (atorvastatin 20 mg, rosuvastatin 10 mg, simvastatin 20 mg) and moderate-low-intensity (atorvastatin 10 mg, pitavastatin 2 mg, pravastatin 40 mg) statin groups. LDL-C reduction rates did not significantly differ between the moderate-high- and high-intensity statin groups (p = 0.4895). We found that some moderate-intensity statins demonstrated a LDL-C-lowering effect of more than 50% in Korean patients with a baseline LDL-C value ≥4.872 mmol/L. Our results reflect the need of a large-scale, randomized, controlled trial on partial reclassification of statins for patients with baseline LDL-C value ≥4.872 mmol/L before adopting ACC/AHC guidelines in Korea., (© 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Background and Aims: Childhood/Adult-onset Lysosomal Acid Lipase Deficiency (LAL-D) is a recessive disorder due to loss of function variants of LAL, the enzyme which hydrolyses cholesteryl esters, derived from internalized apoB containing lipoproteins. The disease is characterized by multi-organ involvement including the liver, spleen, intestine and cardiovascular system. The aim of this study was the clinical and molecular characterization of 14 (13 unrelated) previously unreported patients with childhood-onset LAL-D., Methods: Data collected included clinical and laboratory investigations, liver imaging, liver biopsy and LIPA gene analysis. The response to lipid-lowering medications, liver transplantation and enzyme replacement therapy (ERT) was reported for some patients., Results: LAL-D was suspected at 4.4 ± 3.3 years of age for the presence of hepatomegaly, elevated serum transaminases and hypercholesterolemia, and was confirmed by liver biopsy/imaging and LAL assay. The follow up period ranged from 3 to 40 years (mean 7.8 ± 4.0 years in 13 cases). Patients treated with statins with or without ezetimibe showed 28% reduction of plasma LDL-cholesterol without a tangible effect on liver enzymes; some patients receiving ERT showed normalized lipoprotein profile and transaminase levels. The common c.894G > A variant was observed in homozygosity or compound heterozygosity in 10 patients. We found seven previously reported variants: p.(Trp140*), p.(Arg218*), p.(Gly266*), p.(Thr288Ile), p.(Leu294Ser), p.(His295Tyr) and p.(Gly342Arg) and two novel variants: p.(Asp345Asn), affecting the LAL catalytic triad, and c.229+3A > C, affecting splicing. Homozygosity for p.(Thr288Ile) or c.229+3A > C was associated with a severe phenotype., Conclusions: This study provides additional data on the features of childhood-onset LAL-D and describes two novel pathogenic variants of the LIPA gene., (Copyright © 2017. Published by Elsevier B.V.)

Background and Aims: The clustering of high levels of LDL cholesterol (LDL-C) and other risk factors represents a predisposing condition for atherosclerotic disease development. Cardiovascular prevention is based on effective control of these conditions. In adult subjects with mild hypercholesterolemia we compared in the real life the effects of a new combination of nutraceuticals on lipid and glucose metabolism and blood pressure with those of an established nutraceutical combination., Method and Results: This multicenter, controlled, randomized, single-blind trial was designed to compare the effect of Armolipid Plus ® versus that of LopiGLIK ® on lipid and glucose levels and blood pressure (BP) in subjects with mild hypercholesterolemia not on statin therapy. Primary outcome was the proportion of subjects achieving therapeutic targets of LDL-C (<130 mg/dl); secondary outcomes were the effects on HDL-C, glycated haemoglobin and insulin levels. Data from an overall sample of 359 adult individuals (age 55.2 ± 11.1 years, women 57.7%, LDL-C 157.3 ± 22.6 mg/dl, HDL-C 50.7 ± 13.0 mg/dl) are reported. 72% of subjects treated with LopiGLIK ® and 43% treated with Armolipid Plus ® achieved the primary endpoint (p < 0.0001). Both treatments reduced plasma levels of total and LDL-C and triglycerides (p < 0.001 for all comparisons). The treatments also reduced systolic and diastolic blood pressure, plasma levels of glycated haemoglobin, insulin and HOMA index. The changes induced by LopiGLIK ® in all these metabolic parameters were greater than those obtained with Armolipid Plus ® ., Conclusions: The present analysis shows that LopiGLIK ® may represent a more effective tool for clinical management of CV risk factors in subjects with mild hypercholesterolemia., (Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)