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Epidemiological studies have reported positive associations between serum perfluorooctanoic acid (PFOA) and total and non-high-density lipoprotein cholesterol (non-HDL-C) although the magnitude of effect of PFOA on cholesterol lacks consistency. The objectives of this study were to evaluate the effect of PFOA on plasma cholesterol and triglyceride metabolism at various plasma PFOA concentrations relevant to humans, and to elucidate the mechanisms using APOE*3-Leiden.CETP mice, a model with a human-like lipoprotein metabolism. APOE*3-Leiden.CETP mice were fed a Western-type diet with PFOA (10, 300, 30 000 ng/g/d) for 4-6 weeks. PFOA exposure did not alter plasma lipids in the 10 and 300 ng/g/d dietary PFOA dose groups. At 30 000 ng/g/d, PFOA decreased plasma triglycerides (TG), total cholesterol (TC), and non-HDL-C, whereas HDL-C was increased. The plasma lipid alterations could be explained by decreased very low-density lipoprotein (VLDL) production and increased VLDL clearance by the liver through increased lipoprotein lipase activity. The concomitant increase in HDL-C was mediated by decreased cholesteryl ester transfer activity and changes in gene expression of proteins involved in HDL metabolism. Hepatic gene expression and pathway analysis confirmed the changes in lipoprotein metabolism that were mediated for a major part through activation of the peroxisome proliferator-activated receptor (PPAR)α. Our data confirmed the findings from a phase 1 clinical trial in humans that demonstrated high serum or plasma PFOA levels resulted in lower cholesterol levels. The study findings do not show an increase in cholesterol at environmental or occupational levels of PFOA exposure, thereby indicating these findings are associative rather than causal., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society of Toxicology.)

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels., (© 2018 Wiley Periodicals, Inc.)

Background: Atherogenic dyslipidemia is highly prevalent in the Arabian Gulf. Non-high-density lipoprotein cholesterol (non-HDL-C) reduction has been proposed as an additional goal to low-density lipoprotein cholesterol (LDL-C) lowering to prevent atherosclerotic cardiovascular disease (ASCVD). Data on non-HDL-C goal attainment in patients with high triglycerides (TGs) on lipid-lowering drugs (LLDs) in the region is scarce., Objective: Evaluate non-HDL-C target attainment according to the National Lipid Association in patients on LLDs stratified by TG (<150 [1.69], 150-200 [1.69-2.26], >200 [2.26] mg/dL [mmol/L]) levels in the Arabian Gulf., Methods: Overall, 4383 patients on LLD treatment from 6 Middle Eastern countries participating in the Centralized Pan-Middle East Survey on the Undertreatment of Hypercholesterolemia study were evaluated. Patients were classified according to TG levels and ASCVD risk., Results: The overall non-HDL-C goal attainment was 41% of the subjects. Non-HDL-C goal was less likely attained in patients with high TGs (12% vs 27% vs 55%; P < .001). Very high ASCVD risk patients with high TGs attained less their non-HDL-C targets compared with those with lower TG levels (8% vs 23% vs 51%; P < .001). Similarly, high ASCVD risk patients with high TGs also failed more in attaining non-HDL-C targets compared with those with lower TGs (26% vs 42% vs 69%; P < .001). In addition, those with high TG also succeeded less in attaining LDL-C and apolipoprotein B goals (P < .001)., Conclusions: A large proportion of very high and high ASCVD patients on LLDs in the Arabian Gulf are not at recommended non-HDL-C targets and hence remain at a substantial residual risk., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Aims: Non-HDL cholesterol represents the pro-atherogenic, apo-B-containing lipoprotein fraction of circulating lipids, and represents a secondary target for CVD prevention in people with diabetes. We therefore assessed the proportion of individuals with diabetes and CVD who attain a non-HDL-C goal of <2.6 mmol/L, the extent to which triglycerides influence this goal attainment, and their relationship with HDL-C and triglyceride-rich lipoproteins (TRL)., Methods and Results: Of 2674 diabetic subjects with baseline CVD in the Hungarian MULTI-GAP programme (mean age 64.8 years, mean HbA1c 7.2%), an LDL-C goal <1.8 and non-HDL-C goal <2.6 mmol/L was attained in 13.5% and 17.7% individuals, respectively. Non-HDL-C goal attainment declined at higher triglyceride concentrations; and graphically this relationship appeared to be continuously and inversely associated with triglyceride concentrations. In contrast, the relationship between LDL-C goal attainment was inversely and continuously associated with triglyceride levels up to about 2.5 mmol/L, after which the graphical appearance plateaued such that no further difference in LDL-C were observed beyond triglyceride levels of 2.5 mmol/L. With increasing triglyceride concentrations, non-HDL-C increased continuously, HDL-C decreased initially but later plateaued (at 1.5-2.0 [men] or 2.0-2.5 mmol/L [women]), LDL-C levels plateaued at about 2.0-2.5 mmol/L, and TRL-cholesterol (non-HDL-C minus LDL-C) rose continuously. In multivariable-adjusted models, elevated triglyceride concentrations, non-specialist care and uncontrolled blood pressure were inversely associated with non-HDL-C goal attainment. Triglyceride levels were more strongly associated with non-HDL-C than with LDL-C goal attainment (ORs per 1-SD increase in log-triglycerides was 0.74, 95% CI 0.61-0.89, for LDL-C goal attainment, and 0.49, 95% CI 0.38-0.61, for non-HDL-C goal attainment)., Conclusion: Non-HDL-C goal attainment was suboptimal in people with diabetes and co-existing CVD. This was most marked at higher triglyceride levels, possibly due to higher levels of TRL., (Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.)

Background Childhood cancer survivors have increased risk of dyslipidemia and atherosclerotic cardiovascular disease (CVD). The aim of this study was to evaluate the prevalence and associated cardiovascular risks of specific lipid abnormalities among childhood cancer survivors. Methods Comprehensive lipid panel measurements were obtained from 4115 5-year survivors, with 3406 (mean age at evaluation = 35.2 years, SD = 10.4 years) not having previous dyslipidemia diagnosis, as well as 624 age, sex, and race and ethnicity matched community controls. Results Previously undiagnosed dyslipidemia with abnormal low-density lipoprotein (LDL) cholesterol (>160 mg/dL), non–high density lipoprotein (HDL) cholesterol (>190 mg/dL), HDL cholesterol (<40 mg/dL for men, <50 mg/dL for women), and triglycerides (>150 mg/dL) were identified in 4%, 6%, 30%, and 17%, respectively. Survivors without previous dyslipidemia diagnosis had higher LDL cholesterol and non-HDL cholesterol and lower HDL cholesterol than community controls. Cranial radiotherapy (relative risk [RR] = 2.2, 95% confidence interval [CI] = 1.6 to 3.0 for non-HDL cholesterol) and total body irradiation for hematopoietic cell transplantation (RR = 6.7, 95% CI = 3.5 to 13.0 for non-HDL cholesterol; RR = 9.9, 95% CI = 6.0 to 16.3 for triglycerides) were associated with greater risk of dyslipidemia. Diagnoses of low HDL cholesterol (hazard ratio [HR] = 2.9, 95% CI = 1.8 to 4.7) and elevated triglycerides (HR = 3.1, 95% CI = 1.9 to 5.1) were associated with increased risk for myocardial infarction, and diagnoses of high LDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), high non-HDL cholesterol (HR = 2.2, 95% CI = 1.3 to 3.7), low HDL cholesterol (HR = 3.9, 95% CI = 2.8 to 5.4), and elevated triglycerides (HR = 3.8, 95% CI = 2.7 to 5.5) were associated with increased risk for cardiomyopathy. Conclusions Previously undiagnosed dyslipidemia among childhood cancer survivors was associated with increased risk for myocardial infarction and cardiomyopathy. Comprehensive dyslipidemia evaluation and treatment are needed to reduce cardiovascular morbidity in this population. [ABSTRACT FROM AUTHOR]

Background: Growing evidence shows the undisputable role of non-HDL-C and remnant cholesterol (remnant-C) in cardiovascular disease (CVD) risk assessment and treatment. However, the reference interval (RI) for these lipid parameters is not readily available. The aim of the present investigation was to determine the age and sex-specific RIs for non-HDL-C and remnant-C as well as other lipid parameters among a healthy population in southern Iran. We also report the RI of lipid parameters in rural and urban residents, smokers and post-menopausal women. Methods: Among 14 063 participants of Bandare Kong and Fasa cohort studies, 792 healthy subjects (205 men and 578 women) aged 35-70 years were selected. Fasting blood samples were used for determination of total cholesterol (TC), triglycerides (TG) and HDL-C using colorimetric methods. Non-HDL-C and remnant-C were calculated using the valid formula. The 2.5th and 97.5th percentiles were calculated and considered as RI. Results: In the total population (n = 792, age 35-70), RIs for non-HDL-C and remnant-C was 74.0-206.8 and 8.0-52.7 mg/dL, respectively. Age (35-44 and ≥ 45 years) and gender-specific RIs for serum non-HDL-C and remnant-C were determined. Remnant-C and non-HDL-C level were different between sex and age categories. The mean value of all lipid parameters except HDL-C was higher in men, urban residents, subject with age ≥ 45 years and smokers. Conclusion: This is the first study in which the RIs for non-HDL-C and remnant-C in southern Iran are reported. This may help physicians to conveniently use these lipid parameters for patient care and better cardiovascular risk assessment. [ABSTRACT FROM AUTHOR]

Background: Recent research has demonstrated the possible relevance of bilirubin in metabolic and cardiovascular disorders. Lipid abnormalities are a major problem that is related with an increased risk of cardiovascular disease in diabetics. This study examined the relationship between serum bilirubin and direct bilirubin concentrations and atherogenic lipids in patients with type 2 diabetes (T2DM). Methods: This cross-sectional included 67 patients with type 2 diabetes and 39 matched healthy control. The lipid profile, including total cholesterol, HDL-C, and TG levels, fasting blood glucose, total bilirubin, direct bilirubin, ALT, AST, and ALP were measured using a dimension EXL clinical chemistry analyzer (Siemens Healthcare Diagnostics). Cholesterol in VLDL, LDL, and sdLDL were calculated from standard lipid assay results by the equations of Sampson et al. Results: Serum bilirubin was lower in non T2DM subjects nearly significant (p=0.0.51) whereas direct bilirubin concentrations were lower in T2DM (p=0.008). ALT, AST, and ALP levels were higher in T2DM groups. The mean values of LDL-C, sdLDL-C, non HDL-C and VLDL-C were significantly increased in T2DM group and lower HDL-C. An inverse relationship could be observed with increase in serum total bilirubin and serum levels of LDL-C (r2=0.139, p<0.005), sdLDL-C (r2=0.137, p<0.005), VLDL-C (r2=0.074, p<0.044), and non HDL-C (r2=0.166, p<0.002) in T2DM group. The same inverse relationship was observed with serum direct bilirubin and serum levels of LDL-C (r2=0.133, p<0.006), sdLDL-C (r2=0.172, p<0.001), VLDL-C (r2=0.118, p<0.01), and non HDL-C (r2=0.182, p<0.001) in T2DM group. Conclusions: A significant negative association was found between serum bilirubin levels and direct serum bilirubin with atherogenic lipids, suggesting that serum bilirubin may protect T2DM patients from development of cardiovascular disease. These findings indicate the need for additional research in a large cohort. [ABSTRACT FROM AUTHOR]

Background/objective: Obstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.Methods: We retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects' lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.Results: Out of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57-66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.Conclusions: Atherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients. [ABSTRACT FROM AUTHOR]

• It is acceptable to screen with nonfasting lipids. • It is recommended to follow up abnormal results with fasting levels. • Non-HDL cholesterol levels can effectively guide ASCVD prevention. • Advanced lipoprotein tests may guide therapeutic decisions in select patients. • Better harmonization of advanced lipid measurement methods is needed. • Recommendations for lipids in clinical care. Lipoprotein measurements are pivotal in the management of patients at risk for atherosclerotic coronary heart disease (CHD) with myocardial infarction and coronary death as the main outcomes, and for atherosclerotic cardiovascular disease (ASCVD), which includes CHD and stroke. Recent developments and changes in guidelines affect optimization of using lipid measures as cardiovascular biomarkers. This scientific statement reviews the pre-analytical, analytical, post-analytical, and clinical aspects of lipoprotein measurements. Highlights include the following: i) It is acceptable to screen with nonfasting lipids. ii) non-high-density lipoprotein HDL-cholesterol (non-HDL-C) is measured reliably in either the fasting or the nonfasting state and can effectively guide ASCVD prevention. iii) low density lipoprotein cholesterol (LDL-C) can be estimated from total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) measurements. For patients with LDL-C>100 mg/dL and TG ≤150 mg/dL it is reasonable to use the Friedewald formula. However, for those with TG 150-400 mg/dL the Friedewald formula for LDL-C estimation is less accurate. The Martin/Hopkins method is recommended for LDL-C estimation throughout the range of LDL-C levels and up to TG levels of 399 mg/dL. For TG levels ≥400 mg/dL LDL-C estimating equations are currently not recommended and newer methods are being evaluated. iv) When LDL-C or TG screening results are abnormal the clinician should consider obtaining fasting lipids. v) Advanced lipoprotein tests using apolipoprotein B (apoB), LDL Particle Number (LDL-P) or remnant cholesterol may help to guide therapeutic decisions in select patients, but data are limited for patients already on lipid lowering therapy with low LDL-C levels. Better harmonization of advanced lipid measurement methods is needed. Lipid measurements are recommended 4-12 weeks after a change in lipid treatment. Lipid laboratory reports should denote desirable values and specifically identify extremely elevated LDL-C levels (≥190 mg/dL at any age or ≥160 mg/dL in children) as severe hypercholesterolemia. Potentially actionable abnormal lipid test results, including fasting triglycerides (TG) ≥500 mg/dL, should be reported as hypertriglyceridemia. Appropriate use and reporting of lipid tests should improve their utility in the management of persons at high risk for ASCVD events. [ABSTRACT FROM AUTHOR]

The increasing burden of diabetes mellitus is one of the major public health challenges in African countries, including Ethiopia. This is the first study aimed to identify factors associated with prediabetes and diabetes defined by both fasting blood glucose and glycated hemoglobin in Ethiopians. We analyzed data of a cross-sectional survey (1372 adults aged 25-64 years) conducted between October 2015 and February 2016; multinomial logistic regression models were applied. Abdominal obesity, total cholesterol, and non–high-density lipoprotein cholesterol were independently associated with prediabetes and diabetes in both sexes. Increased triglycerides and religious fasting practices were independently associated with prediabetes and diabetes only in men; hypertension was associated with prediabetes and diabetes only in women, while high-density lipoprotein cholesterol was not associated with prediabetes and diabetes in either sex. Sex differences in the association of triglycerides, hypertension, and dietary habit suggest that different approaches of lifestyle modification may be required for men and women. [ABSTRACT FROM AUTHOR]

ObjectiveThis study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study.Methods9955 patients ≥20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries.ResultsSuccess rates for non-HDL-C goals were 86% in low, 70% in moderate, and 52% in high-risk patients (63% overall). In patients with triglycerides of >200 mg/dL success rates for non-HDL-C goals were 35% vs. 69% in those with ≤200 mg/dL (p < 0.0001). Among patients attaining their LDL-C goal, 18% did not attain their non-HDL-C goal. In those with coronary disease and at least two risk factors, only 34% and 30% attained respectively their non-HDL-C and LDL-C goals. Rates of failure in attaining both LDL-C and non-HDL-C goals were highest in Latin America.ConclusionsNon-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients.

Non-high density lipoprotein cholesterol (non-HDLC) represents the cholesterol in triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL). Apolipoprotein B (apoB) reflects the number of TRL and LDL particles. In hypertriglyceridemia (HTG), there is triglyceride (TG) enrichment of TRLs, and also a substantial increase of cholesterol in larger TRLs that considerably augments the non-HDLC value. Therefore, in HTG, non-HDLC could increase disproportionately with respect to apoB. We aimed to compare the relative effect of the full range of mild, moderate, and severe HTG on the status of non-HDLC and apoB as cardiovascular disease (CVD) risk markers. Analysis of lipid profile data from 4347 patients in a Lipid Clinic cohort with baseline fasting lipid profiles documented prior to starting lipid-lowering medications. The correlation between non-HDLC and apoB was assessed in intervals of increasing TG. Non-HDLC and apoB were analyzed at each TG level using comparative CVD risk equivalent categories and assessed for divergence and discordance. With increasing TG levels: (1) the correlation between non-HDLC and apoB diminished progressively, (2) non-HDLC levels increased continuously, whereas apoB levels plateaued after an initial increase up to TG of ~ 4.0-5.0 mmol/L (~354-443 mg/dL), (3) there was divergence in the stratification of non-HDLC and apoB into CVD risk equivalent categories. Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in the presence of severe HTG. This has never been tested. With increasing HTG severity, discordance between non-HDLC and apoB can cause clinically important divergence in CVD risk categorization. • As TG increases, the correlation between non-HDLC and apoB decreases progressively. • In HTG, discordant non-HDLC and apoB causes divergence in CVD risk categorization. • Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in HTG. [ABSTRACT FROM AUTHOR]

Aims The 2019 vs. 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) dyslipidaemia guidelines contains new recommendations for primary prevention with statins; however, the potential impact of these changes is unclear. We compared the 2019 and 2016 guidelines regarding statin eligibility and potential impact on prevention of atherosclerotic cardiovascular disease (ASCVD) in the general population. Methods and results We examined 45 750 individuals aged 40–75 from the Copenhagen General Population Study, all free of ASCVD and statin use at baseline. During the 9.2-year follow-up, 3337 experienced ASCVD (myocardial infarction, stroke, and cardiovascular death). For Class I/A recommendations, 32.3% (95% confidence interval: 31.8–32.7) and 15.4% (15.1–15.7) of individuals were statin eligible according to the 2019 and 2016 guidelines. The increased statin eligibility by the 2019 guidelines was explained by lower low-density lipoprotein cholesterol (LDL-C) thresholds alone (explaining 33.2%), older age range alone (49.4%), older age range in combination with lower LDL-C thresholds (14.7%), and updated SCORE risk algorithm (2.8%). If fully implemented, the estimated percentage of ASCVD events that can be prevented by using high-intensity statins for 10 years were 25% and 11% with the 2019 and 2016 guidelines. Mainly because of older age range in the 2019 guidelines, the corresponding estimated numbers needed to treat (NNT) to prevent one ASCVD event were 19 and 20. Conclusion Due to lower LDL-C threshold and older age range, the 2019 vs. 2016 ESC/EAS guidelines doubles the number of individuals eligible for primary prevention with statins. This considerably improves the potential for ASCVD prevention in the general population, with similar NNT to prevent one event. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Abstract: Background: Premature myocardial infarction (≤40 years) represents a rare disease with a distinct risk factor profile and a lipid phenotype that is characterized by a predominance of elevated triglyceride‐rich lipoproteins. So far high‐density and low‐density lipoproteins remain the primary targets for risk stratification and treatment evaluation in coronary artery disease, but this strategy might be insensitive in patients with premature myocardial infarction. Aim: Aim of this study was to investigate the predictive value of different lipid fractions on long‐term cardiovascular outcome in patients with premature myocardial infarction. Methods: We prospectively enrolled 102 consecutive AMI survivors (≤40 years) in this prospective multicentre study and investigated the influence of the familial combined hypercholesterolaemia phenotype and a corresponding multimarker panel of different lipid fractions on cardiovascular outcome. Results: Total cholesterol, non‐HDL cholesterol, remnant cholesterol and Apo B lipoprotein were significantly higher in patients experiencing MACE as compared to those who did not. The familial combined hypercholesterolaemia phenotype was associated with an unfavourable cardiovascular outcome even after adjustment for potential cofounders (adjusted HR 3.04,95% CI, 1.26‐7.34, P = 0.013). Remnant cholesterol revealed the strongest association with MACE (adj.HR 1.94, 95%CI. 1.30‐2.99, P = 0.001). Interestingly LDL and HDL revealed no significant impact on cardiovascular outcome in this study cohort. Conclusion: Non‐HDL and remnant cholesterol are strongly associated with an unfavourable outcome in patients with premature myocardial infarction and might be the preferred treatment target for lipid‐lowering therapy. [ABSTRACT FROM AUTHOR]

Background and aims Non–high-density lipoprotein cholesterol (non-HDL-C) goals are defined as 30 mg/dL (0.78 mmol/L) higher than the respective low-density lipoprotein cholesterol (LDL-C) goals. This definition, however, do not consider the population distribution of non-HDL-C, which could represent a more appropriate individual goal when both markers are discordant. The aim of this study is to establish non-HDL-C goals at the same population percentiles of LDL-C. Methods Non-HDL-C values were assigned at the same percentiles correspondent to the LDL-C treatment goals for 14,837 participants from the Longitudinal Study of Adult Health (ELSA-Brasil) with triglycerides levels ≤ 400 mg/dL (4.52 mmol/L). We also assessed the frequency of reclassification, defined as the number of subjects with LDL-C levels in the recommended therapeutic category, but with non-HDL-C levels above or below the category. Results The non-HDL-C values, based on correspondent LDL-C population percentiles, were 92 (2.38), 122 (3.16), 156 (4.04), 191 (4.95), and 223 mg/dL (5.78 mmol/L). Among participants with LDL-C <70 mg/dL (1.81 mmol/L), 22.8% were reclassified in a higher category according to the guidelines-based non-HDL-C cut-off and 30.1% according to the population percentile-based cut-off; 25.6% and 64.1%, respectively, if triglycerides concurrently 150–199 mg/dL (1.69–2.25 mmol/L). Conclusions Our results demonstrated that non-HDL-C percentiles-based goals were up to 8 mg/dL (0.21 mmol/L) lower than the guidelines recommended goal and had a profound impact on the reclassification of participants, notably when LDL-C was <100 mg/dL (2.56 mmol/L), the treatment goal for high risk patients. Therefore, non-HDL-C goals should be changed for reduction of residual risk. [ABSTRACT FROM AUTHOR]

Background: Apolipoprotein B (apoB) is known to be a more powerful predictor of cardiovascular disease than conventional lipids. We aimed to determine the clinical relevance of a newly developed equation to estimate serum apoB levels based on total cholesterol, HDL cholesterol and triglycerides in patients with high cardiovascular risk. Methods: The occurrence of a major cardiovascular event (MCVE) was assessed using the data from the Treating to New Targets (TNT) and Incremental Decrease in End points through Aggressive Lipid lowering (IDEAL) trials. Results: Pooled analysis of these two data sets showed that both directly-measured apoB (HR per 1-SD (95% CI): 1.16 (1.11--1.21), P < 0.001) and apoB estimated from the eq. (HR per 1-SD (95% CI): 1.14 (1.09--1.19), P < 0.001) were significantly associated with the development of a future MCVE. Prediction of MCVEs by the apoB eq. (C statistic 0.650) was nearly identical to that of directly-measured apoB (0.651). In addition, the net reclassification indices indicated no difference in the prediction of MCVEs between models including the apoB equation and directlymeasured apoB (1% (--1.3--4.0), P = 0.31). Conclusions: Our equation to predict apoB levels showed MCVE risk prediction comparable to directly-measured apoB in high risk patients with previous coronary heart disease. [ABSTRACT FROM AUTHOR]

Objetivos: verificar el nivel de cumplimiento de las metas en colesterol LDL, colesterol no-HDL, triglicéridos y colesterol HDL, de acuerdo con lo indicado por la guía del NCEP-ATPIII y las recomendaciones actuales, en una población de pacientes hospitalizados por causa no cardiovascular pero con antecedente de enfermedad coronaria. Analizar, además, los hipolipemiantes que utiliza esta población, así como la prevalencia de síndrome metabólico, glucemia anormal en ayunas y diabetes mellitus tipo 2. Metodología: el porcentaje de cumplimiento de estas metas se evaluó mediante el programa de análisis estadístico STATA. Se compararon los hallazgos del perfil lipídico con la propuesta de la guía del NCEP-ATPIII y las recomendaciones actuales (punto final primario). Igualmente, se analizaron los hipolipemiantes utilizados, así como la prevalencia de glucemia anormal en ayunas, diabetes mellitus tipo 2 y síndrome metabólico (punto final secundario). Resultados: se identificaron 281 pacientes que cumplían con los criterios de inclusión. En la tabla 2 se resumen los resultados del punto final primario. De acuerdo con el NCEP-ATPIII, en el riesgo alto, el porcentaje de pacientes que cumplían con las metas en el cLDL (objetivo principal en el tratamiento de las dislipidemias), era de 57,2 y en el riesgo muy alto de 23,5%. En la actualidad, a los pacientes con enfermedad coronaria, independiente de la presencia de síndrome metabólico o diabetes mellitus, se les recomienda una meta para el cLDL menor de 70 mg/dL (Recomendación IIa), la cual se observó en 21,7% de los pacientes estudiados. La prevalencia de glucemia anormal en ayunas fue de 25,6%, la de diabetes mellitus tipo 2 de 20% y la de síndrome metabólico de 45,2%. Con respecto a los hipolipemiantes utilizados, se observó que 56% usaba lovastatina, 14% no utilizaba hipolipemiantes y ninguno tenía asociación de estos fármacos. Conclusiones: después de nueve años de la publicación de las guías del NCEP-ATPIII y de las recomendaciones posteriores sobre las metas del perfil lipídico en pacientes con enfermedad coronaria y a pesar de la divulgación de las mismas a través de conferencias, congresos y publicaciones, estas metas las cumple un porcentaje bajo de pacientes, tal como lo demuestra este estudio observacional en sujetos hospitalizados por causas diferentes a la enfermedad coronaria pero con este antecedente. Una de las explicaciones para este pobre resultado es el uso de lovastatina, estatina de baja efectividad para reducir el cLDL. Se analizan otras posibles causas y se hacen propuestas para lograr los objetivos.Objectives: to verify the level of compliance with the targets in LDL cholesterol, non-HDL cholesterol, triglycerides, HDL cholesterol, in accordance with the recommendations of the NCEP-ATPIII guide and current recommendations in a population of patients hospitalized for non-cardiovascular causes but with a history of coronary disease. Analyze also lipid-lowering drugs used by this population as well as the prevalence of metabolic syndrome, abnormal fasting glucose and type 2 diabetes mellitus. Methodology: the percentage of fulfillment of these goals was assessed using the STATA statistical analysis program. Findings of the lipid profile were compared with the proposal from the NCEP-ATPIII guide and current recommendations (primary endpoint). Similarly, lipid-lowering drugs used were analyzed as well as the prevalence of abnormal fasting glucose, diabetes mellitus type 2 and metabolic syndrome (secondary endpoint). Results: we identified 281 patients who met the inclusion criteria. Table 2 summarizes the results of the primary endpoint. According to the NCEP-ATPIII, in high risk, the percentage of patients who met the LDL cholesterol goals (main goal in the treatment of dyslipidemias), was 57,2% and in the very high risk, 23,5%. Currently, patients with coronary heart disease independent of the presence of metabolic syndrome or diabetes mellitus, a goal for LDL cholesterol below 70 mg/dL is recommended (Recommendation IIa); this was observed in 21.7% of patients studied. The prevalence of abnormal fasting glucose was 25.6%, that of type 2 diabetes mellitus was 20% and that of metabolic syndrome 45.2%. With respect to lipid-lowering drugs used, we observed that 56% used lovastatin, 14% did not use lipid-lowering drugs and none had any association of these drugs. Conclusions: after nine years of the publication of NCEP-ATPIII guidelines and subsequent recommendations on the goals of the lipid profile in patients with coronary disease and despite the dissemination of these through lectures, conferences and publications, these goals are met by a low percentage of patients, as evidenced by this observational study in patients hospitalized for causes other than coronary heart disease but with this history. One explanation for this poor performance is the use of lovastatin, that is a low efficacy statin to reduce LDL cholesterol. Other possible causes are analyzed and proposals to achieve the objectives are made.

Aims: To determine whether specific lipid parameters are better predictors of cardiovascular disease (CVD) in Japanese mild-to-moderate hypercholesterolemic patients with and without diabetes.Methods: Mildly or moderately hypercholesterolemic patients with no history of CVD received diet therapy or diet therapy plus pravastatin. In this post-hoc subanalysis, 5-year data from 3170 patients (668 diabetes, 2502 non-diabetes) on diet therapy alone were used to compare lipid parameters as predictors of CVD. We examined the data by tertiles, using hazard ratio (HR) per one-standard deviation (SD) increment (decrease for high-density lipoprotein cholesterol, HDL-C), χ(2) value, receiver operating characteristic curve analysis, and spline analysis.Results: In mild-to-moderate hypercholesterolemic patients with diabetes, increased total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C and decreased HDL-C were strongly associated with increased incidence of CVD (tertile analysis). In non-diabetes, increased non-HDL-C, and LDL-C/HDL-C were significantly associated with increased incidence of CVD. A one-SD decrease in HDL-C and a one-SD increment in non-HDL-C, TC/HDL-C, and LDL-C/HDL-C were significantly associated with increased HRs for CVD in both diabetes and non-diabetes. Linear CVD risk increases were found for non-HDL-C in diabetes and for non-HDL-C and HDL-C in non-diabetes (spline analysis).Conclusions: In mild-to-moderate hypercholesterolemia, CVD risk prediction by stratifications of single or combination of traditional lipid parameter values illustrates various patterns. Parameters including HDL-C are better predictors of cardiovascular risk than only using TC or LDL-C alone. Non-HDL-C could be the most useful lipid parameter to assess CVD risk, considering it is easy to calculate and less affected by food intake. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to examine patient-level discordance between population percentiles of non–high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Background: Non–HDL-C is an alternative to LDL-C for risk stratification and lipid-lowering therapy. The justification for the present guideline-based non–HDL-C cutpoints of 30 mg/dl higher than the LDL-C cutpoints remains largely untested. Methods: We assigned population percentiles to non–HDL-C and Friedewald-estimated LDL-C values of 1,310,440 U.S. adults with triglyceride levels <400 mg/dl who underwent lipid testing by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Results: LDL-C cutpoints of 70, 100, 130, 160, and 190 mg/dl were in the same population percentiles as non–HDL-C values of 93, 125, 157, 190, and 223 mg/dl, respectively. Non–HDL-C values reclassified a significant proportion of patients within or to a higher treatment category compared with Friedewald LDL-C values, especially at LDL-C levels in the treatment range of high-risk patients and at triglyceride levels ≥150 mg/dl. Of patients with LDL-C levels <70 mg/dl, 15% had a non–HDL-C level ≥100 mg/dl (guideline-based cutpoint) and 25% had a non–HDL-C level ≥93 mg/dl (percentile-based cutpoint); if triglyceride levels were 150 to 199 mg/dl concurrently, these values were 22% and 50%, respectively. Conclusions: There is significant patient-level discordance between non–HDL-C and LDL-C percentiles at lower LDL-C and higher triglyceride levels, which has implications for the treatment of high-risk patients. Current non–HDL-C cutpoints for high-risk patients may need to be lowered to match percentiles of LDL-C cutpoints. Relatively small absolute reductions in non–HDL-C cutpoints result in substantial reclassification of patients to higher treatment categories with potential implications for risk assessment and treatment. (The Very Large Database of Lipids [VLDL-2]; NCT01698489) [Copyright &y& Elsevier]

Abstract: Aim: Our objective was to assess the number of patients with an indication for lipid-lowering therapy according to their non-HDL cholesterol (N-HDL-C) (>130 mg/dL) concentrations despite on-target LDL (≤100 mg/dL) values determined using ultracentrifugation (UC) or direct enzymatic methods (DM). Methods: In 1590 patients we studied the lipid profile using standard biochemical methods and sequential UC (N = 637) or triglyceride (TG) independent DM (N = 953). The indications for lipid-lowering therapy were compared by evaluating the real LDL concentration or N-HDL-C concentration. Results: The LDL/N-HDL-C correlation significantly decreased with increasing triglyceride concentrations: normal (r = 0.924, p < 0.001), 150–400 mg/dL (r = 0.825, p < 0.001) and higher than 400 mg/dL (r = 0.460, p < 0.001) (p < 0.001). The percentage of patients with an N-HDL-C concentration above the recommended level, despite having an LDL concentration that was on target, also increased significantly across the TG tertiles (3.1%, 15.6% and 57.%, respectively; p < 0.001). Of the patients with a TG level above 400 mg/dL and an LDL concentration that was on target, 86% had an N-HDL-C concentration above 130 mg/dL. Of the patients with a TG level above 400 and an N-HDL-C concentration qualifying for therapy, 40% had an LDL concentration that was on target. The ApoB concentration had a stronger concordance with the LDL concentration than N-HDL-C. Conclusions: Using the N-HDL-C concentration as a therapeutic target in hypertriglyceridemic patients almost doubled the number of patients requiring treatment. The ApoB concentration had a better association with LDL when determining the need for lipid-lowering therapy. [Copyright &y& Elsevier]

Background: The Adult Treatment Panel III guidelines established non–high-density lipoprotein cholesterol (non-HDL-C) as a secondary treatment target. However, non-HDL-C levels are not reported on standard lipid panels by many hospital-based and/or commercial biochemical laboratories. Objective: We determined whether reporting non-HDL-C was associated with improved non-HDL-C goal attainment. Methods: We identified patients with cardiovascular disease (CVD) and/or diabetes receiving care within the Veterans Health Administration. We matched a facility that reported non-HDL-C levels on lipid panels (3994 CVD and 5108 diabetes patients) to a facility with similar size, patient complexity, and academic mission that did not report non-HDL-C (4269 CVD and 6591 diabetes patients). We performed patient-level analysis to assess differences in non-HDL-C from baseline to the most recent lipid panel at these facilities. Results: Baseline non-HDL-C levels for CVD patients were 114 mg/dL and 107 mg/dL at the reporting and nonreporting facilities, respectively. At 2.3-year follow-up, non-HDL-C levels decreased at both facilities but by a greater amount at the reporting facility (−11 mg/dL vs −3 mg/dL at the nonreporting facility, P < .001). Results remained significant (P < .001) after we adjusted for patient''s age, race, gender, illness burden, history of diabetes, hypertension, medication adherence, statin use, number of lipid panels, and number of primary care visits between baseline and follow-up. Reductions were greater among CVD patients with triglycerides ≥200 mg/dL (−25 mg/dL vs −16 mg/dL at the respective facilities, P = .004). Results were similar in diabetes patients. Reporting was also associated with greater proportions of patients meeting non-HDL-C treatment goal of <130 mg/dL. Conclusion: Non-HDL-C reporting could improve non-HDL-C goal attainment. [Copyright &y& Elsevier]

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Abstract: Epidemiological evidence supports the use of non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B-100 (apoB), and low-density lipoprotein particles as markers of atherogenic risk. Treatment guidelines also identify these as additional targets of lipid-modifying intervention in patients with elevated triglycerides (TG). Even when TG are only moderately elevated, many patients on statin monotherapy who have achieved targets for low-density lipoprotein cholesterol (LDL-C) fail to reach non-HDL-C treatment goals, and even fewer reach apoB goals. Combination lipid-modifying therapy is therefore indicated for comprehensive lipid management, particularly in patients with type 2 diabetes and metabolic syndrome in whom LDL-C levels are often considered ‘optimal’. Of the available options, adding either a niacin, fibrate or omega-3 fatty acids provides greater opportunity to achieve non-HDL-C and apoB targets, given complementary profiles of lipid-modifying activity and supported by evidence from clinical studies. Improvement in lipid control and reduction in atherogenic risk could be anticipated to translate to benefits in clinical outcomes. [Copyright &y& Elsevier]

LDL has been widely recognized as the major atherogenic lipoprotein and designated as the primary target for prevention of coronary heart disease (CHD); however, there is growing evidence that other triglyceride-rich lipoproteins, such as very low-density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) carry atherogenic potential as well. This led to the designation of non-HDL cholesterol (HDL-C) (LDL + IDL + VLDL) as a secondary target of treatment for hyperlipidaemia. As each one of LDL, IDL and VLDL particles carries only one apolipoprotein B-100 (ApoB-100) molecule, the total ApoB value represents the total number of potentially atherogenic lipoproteins, whereas non-HDL-C provides the cholesterol content of these same lipoproteins. Recent data from epidemiological, observational and interventional studies suggest that non-HDL-C, apolipoproteins ApoA1 and ApoB may improve CHD risk assessment by identifying more high-risk individuals than the usual lipid profile alone. However, the targets for the optimal treatment of dyslipidaemia remain a subject of considerable debate. Further studies are needed to determine whether ApoB and ApoA1 are superior to conventional lipid parameters as predictors of cardiovascular disease or therapeutic targets of hyperlipidaemias. In this review, we summarize the current opinions on the use of ApoA1 and ApoB values as estimates of cardiovascular risk or as treatment goals in patients undergoing treatment for hyperlipidaemia. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of this study was to investigate the cholesterol-lowering mechanisms of corn fiber oil (CFO), ferulate phytostanyl esters (FPEs) and parent compounds of FPE, including sitostanol and ferulic acid, in hamsters. Method: Seventy male Golden Syrian hamsters were randomly assigned to six experimental diets for 4 weeks: (1) cornstarch–casein–sucrose-based control diet (control); and (2) control diet plus 0.1% (wt/wt) cholesterol (cholesterol–control). The remaining four groups were given cholesterol–control diet with: (3) 10% (wt/wt) CFO; (4) 0.5% (wt/wt) sitostanol; (5) 0.23% (wt/wt) ferulic acid; and (6) 0.73% (wt/wt) FPE. At the end of dietary intervention, total plasma cholesterol, high-density lipoprotein cholesterol and triglyceride concentrations were determined. Parameters of cholesterol kinetics, including cholesterol absorption and synthesis, as well as mRNA expression of sterol transporters such as Niemann–Pick C1 like 1 (NPC1L1), ATP-binding cassette G5 (ABCG5) and ABCG8, were assessed. Results: Supplementation with CFO decreased (P<.0001) plasma total cholesterol levels by 29% as compared with the cholesterol–control group, while FPE and sitostanol reduced (P<.02) cholesterolemia by 15% and 14%, respectively. CFO and sitostanol decreased (P<.05) cholesterol absorption by 24% compared to the cholesterol–control group. Dietary intervention did not alter the intestinal gene expression of ABCG5, ABCG8 and NPC1L1. Conclusion: The present results show that the CFO-induced and sitostanol-induced decrease in cholesterol absorption is independent of intestinal enterocyte sterol transporters such as ABCG5, ABCG8 and NPC1L1 in hamsters. [Copyright &y& Elsevier]

Purpose: Many guidelines advocate measurement of total or low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides (TG) to determine treatment recommendations for preventing coronary heart disease (CHD) and cardiovascular disease (CVD). This analysis is a comparison of lipid variables as predictors of cardiovascular disease. Methods: Hazard ratios for coronary and cardiovascular deaths by fourths of total cholesterol (TC), LDL, HDL, TG, non-HDL, TC/HDL, and TG/HDL values, and for a one standard deviation change in these variables, were derived in an individual participant data meta-analysis of 32 cohort studies conducted in the Asia-Pacific region. The predictive value of each lipid variable was assessed using the likelihood ratio statistic. Results: Adjusting for confounders and regression dilution, each lipid variable had a positive (negative for HDL) log-linear association with fatal CHD and CVD. Individuals in the highest fourth of each lipid variable had approximately twice the risk of CHD compared with those with lowest levels. TG and HDL were each better predictors of CHD and CVD risk compared with TC alone, with test statistics similar to TC/HDL and TG/HDL ratios. Calculated LDL was a relatively poor predictor. Conclusions: While LDL reduction remains the main target of intervention for lipid-lowering, these data support the potential use of TG or lipid ratios for CHD risk prediction. [Copyright &y& Elsevier]

Objetivos: verificar el nivel de cumplimiento de las metas en colesterol LDL, colesterol no-HDL, triglicéridos y colesterol HDL, de acuerdo con lo indicado por la guía del NCEP-ATPIII y las recomendaciones actuales, en una población de pacientes hospitalizados por causa no cardiovascular pero con antecedente de enfermedad coronaria. Analizar, además, los hipolipemiantes que utiliza esta población, así como la prevalencia de síndrome metabólico, glucemia anormal en ayunas y diabetes mellitus tipo 2. Metodología: el porcentaje de cumplimiento de estas metas se evaluó mediante el programa de análisis estadístico STATA. Se compararon los hallazgos del perfil lipídico con la propuesta de la guía del NCEP-ATPIII y las recomendaciones actuales (punto final primario). Igualmente, se analizaron los hipolipemiantes utilizados, así como la prevalencia de glucemia anormal en ayunas, diabetes mellitus tipo 2 y síndrome metabólico (punto final secundario). Resultados: se identificaron 281 pacientes que cumplían con los criterios de inclusión. En la tabla 2 se resumen los resultados del punto final primario. De acuerdo con el NCEP-ATPIII, en el riesgo alto, el porcentaje de pacientes que cumplían con las metas en el cLDL (objetivo principal en el tratamiento de las dislipidemias), era de 57,2 y en el riesgo muy alto de 23,5%. En la actualidad, a los pacientes con enfermedad coronaria, independiente de la presencia de síndrome metabólico o diabetes mellitus, se les recomienda una meta para el cLDL menor de 70 mg/dL (Recomendación IIa), la cual se observó en 21,7% de los pacientes estudiados. La prevalencia de glucemia anormal en ayunas fue de 25,6%, la de diabetes mellitus tipo 2 de 20% y la de síndrome metabólico de 45,2%. Con respecto a los hipolipemiantes utilizados, se observó que 56% usaba lovastatina, 14% no utilizaba hipolipemiantes y ninguno tenía asociación de estos fármacos. Conclusiones: después de nueve años de la publicación de las guías del NCEP-ATPIII y de las recomendaciones posteriores sobre las metas del perfil lipídico en pacientes con enfermedad coronaria y a pesar de la divulgación de las mismas a través de conferencias, congresos y publicaciones, estas metas las cumple un porcentaje bajo de pacientes, tal como lo demuestra este estudio observacional en sujetos hospitalizados por causas diferentes a la enfermedad coronaria pero con este antecedente. Una de las explicaciones para este pobre resultado es el uso de lovastatina, estatina de baja efectividad para reducir el cLDL. Se analizan otras posibles causas y se hacen propuestas para lograr los objetivos.