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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]

Background: In cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non-high-density lipoprotein (non-HDL) cholesterol are secondary targets.Objectives: This study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction.Methods: In total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians.Results: High apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction.Conclusions: In statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol. [ABSTRACT FROM AUTHOR]

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]

Non–high-density lipoprotein cholesterol (non-HDL-C) includes atherogenic cholesterol and low-density lipoproteins (LDL) and triglyceride-rich lipoproteins. Patients with diabetes frequently have elevations in non-HDL-C. This study examines temporal trends in the levels of non-HDL-C in free-living subjects with diabetes but a negative history of atherosclerotic cardiovascular disease. National Health and Nutrition Examination Surveys conducted between 1999 and 2016 had data from 3,219 adults (aged 40–75 years) with diabetes. Temporal trends in changes in the distribution of total cholesterol, non-HDL-C, LDL cholesterol (LDL-C), and HDL-C were evaluated. Data were weighted to account for complex survey design. Significant decreases were observed in non-HDL-C (20.1%; P <.0001) and total cholesterol (16.1%; P <.0001) levels between 1999 and 2016. No significant changes were noted in HDL-C levels. LDL-C was reduced by 29.6% in a subset of subjects. The reduction in non-HDL-C and LDL-C occurred simultaneously, with an increase of 4.4% of subjects per year taking cholesterol-lowering drugs and statins. In contrast, the fraction of subjects taking antihypertensives or hypoglycemia agents rose at a rate of 2.2% per year. There was also a significant trend for increases in weight gain (P ≤.013). In subjects with diabetes, non-HDL-C levels have declined over time in parallel with reported increases in cholesterol-lowering drugs. Nonetheless, treatment targets for lipids in subjects with diabetes lag behind current recommendations. Reported intakes for antihypertensive agents and hypoglycemia agents were relatively high throughout the period of study, with little change over time. However, there was a trend for weight increase in diabetic subjects, which may offset some of the benefits of pharmacotherapy. • Non–high-density lipoprotein cholesterol has decreased by 20.1% in diabetes mellitus. • Treatment with hypolipidemia drugs increased since 1999. • Weight has increased significantly (P <.013). • Treatment of lipids lags behind recommendations. [ABSTRACT FROM AUTHOR]

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total – HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20–100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. Image 1 • Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total – HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. • LDL cholesterol is the primary target of lipid-lowering therapies. • Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and lipoprotein(a) should be measured at least once in all patients. • Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). • Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. • Laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. [ABSTRACT FROM AUTHOR]

Background: Extended elevations of non-high-density lipoprotein cholesterol (non-HDL-C) across a lifespan are associated with increased risk of cardiovascular disease (CVD). However, optimal testing intervals to identify individuals with high lipid-related CVD risk are unknown.Objectives: This study determined the extent to which lipid levels in young adulthood predict future lipid trajectories and associated long-term CVD risk.Methods: A sample of 2,516 Framingham Offspring study participants 25 to 40 years of age free of CVD and diabetes had their non-HDL-C progression modeled over 8 study examinations (mean follow-up 32.6 years) using group-based methods. CVD risk based on 25 to 30 years of follow-up was evaluated using Kaplan-Meier analyses for those with mean non-HDL-C ≥160 mg/dl ("high") and <130 mg/dl ("low") at the first 2 examinations. Levels of non-HDL-C for participants on lipid treatment were adjusted by nonparametric algorithm.Results: The trajectories of the lipid levels were generally stable over the 30-year life course; mean non-HDL-C measured in young adulthood were highly predictive of levels later in life. Individuals could be reliably assigned to high and low non-HDL-C groups based on 2 measurements collected between 25 to 40 years of age. Overall, 80% of those with non-HDL-C ≥160 mg/dl at the first 2 exams remained in the high group on subsequent 25-year testing, whereas 88% of those with non-HDL-C <130 mg/dl remained below 160 mg/dl. Those with high non-HDL-C in young adulthood had a 22.6% risk of CVD in the next 25 years as compared with a 6.4% risk in those with low non-HDL-C.Conclusions: Most adults with elevated non-HDL-C early in life continue to have high non-HDL-C over their life course, leading to significantly increased risk of CVD. The results demonstrate that early lipid monitoring before 40 years of age would identify a majority of those with a high likelihood for lifetime elevated lipid levels who also have a high long-term risk for CVD. This information could facilitate informed patient-provider discussion about the potential benefits of preventive lipid-lowering efforts during the early midlife period. [ABSTRACT FROM AUTHOR]

Abstract Objective The objective of the study is to examine whether the increased levels of non–high-density lipoprotein cholesterol (non-HDL-c) are associated with skipping breakfast among school children. Study design A cross-sectional survey was conducted among 539 school children aged 8–12 years from the Niagara Region of Canada. Methods Non-fasting finger blood was taken for total cholesterol (total-c) and HDL-c measurements. Non-HDL-c was calculated as the difference between total-c and HDL-c. The information of skipping breakfast in a week was obtained from a questionnaire, which was categorized into three groups, i.e., none, 1–3 times and 4 + times. Demographic information and other related variables were described by the three breakfast-skipping groups. Results Approximately 44% of children (n = 182) reported skipping breakfast. There were significant differences between the three groups in the means of total-c, non-HDL-c, body mass index, waist circumference, proportions of overall health excellent, eating dinner with parent and skipping breakfast that affects learning (P < 0.05). The number of days of skipping breakfast was weakly correlated to the level of non-HDL-c (r = 0.145, P < 0.0001). Multiple regression results indicated that every one more time of skipping breakfast would increase approximately 0.05 mmol/L level of non-HDL-c (P < 0.01), on average, after adjusting for those aforementioned potential confounding variables. The adjusted mean levels of non-HDL-c were 2.77, 2.94 and 3.07 mmol/L for none, skipping 1–3 times and skipping 4 + times of breakfast, respectively; the mean differences between none and the other two groups were statistical significant (P < 0.05). Conclusion Non-HDL-c levels is positively associated with the number of skipping breakfast among school children, and further research is needed to confirm this relationship. Highlights • This is a population-based study. • This was the first study to examine the association between skipping breakfast and the levels of non-HDL cholesterol among children. • Children who skip breakfast have a higher average level of non-HDL cholesterol. [ABSTRACT FROM AUTHOR]

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Abstract Objectives Increased prevalence of pediatric obesity and associated co-morbidities has heightened the concern for cardiovascular disease (CVD) risk later in life. Although the fasting lipid profile is traditionally used to assess CVD risk, the non-fasting lipid profile may simplify lipid testing and better predict CVD risk. Unfortunately, non-fasting lipid reference values are limited, particularly for children. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) has recruited thousands of healthy pediatric subjects to develop a pediatric reference interval database. Here, CALIPER reports pediatric reference intervals for non-fasting calculated low-density lipoprotein cholesterol (LDLc), non-high-density lipoprotein cholesterol (non-HDLc) and remnant cholesterol. Methods Non-fasting serum samples from the CALIPER cohort of community children and adolescents were previously analyzed for HDLc, total cholesterol, and triglycerides. These values were used to calculate LDLc, non-HDLc, and remnant cholesterol and subsequently establish reference intervals with corresponding 90% confidence intervals according to CLSI EP28-A3c guidelines. Reference intervals were also calculated using alternative statistical methods highlighted in recent literature. Results All three lipid parameters required an age partition at 1 year due to wider reference intervals in the first year of life. LDLc and non-HDLc required sex partitioning for subjects 1–<10 years. Non-HDLc upper reference limit was higher than the 2011 National Heart, Lung, and Blood Institute (NHLBII) pediatric recommended cut-offs, suggesting elevated atherogenic lipoproteins in a proportion of apparently healthy pediatric subjects. The LDLc upper reference limit (10–<19 year partition) was the same as the NHLBI cut-off, potentially due to lower calculated LDLc values in the non-fasting state. Conclusions With the increased use of non-fasting lipid profiles, age- and sex-specific reference intervals and appropriate clinical decision limits are necessary for pediatric lipid monitoring. Our data supports the notion that appropriate decision limits, rather than reference intervals, should be used to interpret lipid levels in children as there is a high prevalence of hyperlipidemia in the apparently healthy pediatric population. Highlights • Established pediatric reference intervals for non-fasting lipid parameters. • LDLc, non-HDLc, and remnant cholesterol were variable during the first year of life. • All upper reference limits exceeded currently recommended decision limits. [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 and aims Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported. Methods Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis. Results EZE reduced ( p < 0.05) total sterols (−12.5 ± 4.1%) and LDL-sterol (−22.7 ± 5.7%) and its sterol mass of large VLDL (−24.4 ± 4.5%), VLDL remnants (−21.1 ± 7.9%) and large IDL (−22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (−21.8± 5.0%), total sterols/HDL (−28.2 ± 5.5%) and TG/HDL (−27.4 ± 6.5%, all p < 0.01). Conclusions EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

Background Dyslipidemia has been linked to vascular complications of Type 1 diabetes (T1DM). We investigated the prospective associations of nuclear magnetic resonance-determined lipoprotein subclass profiles (NMR-LSP) and conventional lipid profiles with carotid intima-media thickness (IMT) in T1DM. Methods NMR-LSP and conventional lipids were measured in a subset of Diabetes Control and Complications Trial (DCCT) participants (n = 455) at study entry (‘baseline’, 1983–89), and were related to carotid IMT determined by ultrasonography during the observational follow-up of the DCCT, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, at EDIC Year 12 (2004–2006). Associations were defined using multiple linear regression stratified by gender, and following adjustment for HbA1c, diabetes duration, body mass index, albuminuria, DCCT randomization group, smoking status, statin use, and ultrasound devices. Results In men, significant positive associations were observed between some baseline NMR-subclasses of LDL (total IDL/LDL and large LDL) and common and/or internal carotid IMT, and between conventional total- and LDL-cholesterol and non-HDL-cholesterol and common carotid IMT, at EDIC Year 12; these persisted in adjusted analyses (p < 0.05). Large LDL particles and conventional triglycerides were positively associated with common carotid IMT changes over 12 years (p < 0.05). Inverse associations of mean HDL diameter and large HDL concentrations, and positive associations of small LDL with common and/or internal carotid IMT (all p < 0.05) were found, but did not persist in adjusted analyses. No significant associations were observed in women. Conclusion NMR-LSP-derived LDL particles, in addition to conventional lipid profiles, may help in identifying men with T1DM at highest risk for vascular disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in people at risk for cardiovascular diseases. Mipomersen inhibits apolipoprotein B-100 (apoB) synthesis and causes reduction in LDL-C by reducing apoB. Objective We aimed to perform a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia. Methods We searched PUBMED, CENTRAL, and EMBASE from inception through March 2014 and used random-effects model to compute the effect size. Results We identified 8 randomized controlled trials (n = 462). Mipomersen compared with placebo significantly reduced LDL-C by 32.37% (95% confidence interval, 25.55–39.18; P < .00001), total cholesterol by 24.18% (18.54–29.83; P < .00001), very low–density lipoprotein cholesterol by 21.59% (9.16–34.02; P = .0007), non–high-density lipoprotein cholesterol (HDL-C) by 30.83% (23.92–37.74; P < .00001), and triglycerides by 36.26% (22–50.54; P < .00001). It also significantly reduced apoB, lipoprotein(a), and apolipoprotein A1. However, mipomersen did not significantly change HDL-C levels. In safety analysis, mipomersen compared with placebo increased the risks of injection-site reaction (risk ratio, 2.05; 95% confidence interval, 1.39–3.04; P = .0003), flu-like symptoms (1.63; 1.22–2.17; P = .0008), alanine aminotransferase ≥3X upper limit of normal (4.44; 1.67–11.86; P = .003), and hepatic steatosis (3.85, 1.39–10.67; P = .01). The risks of alanine aminotransferase ≥10X upper limit of normal did not reach statistical significance (1.57; 0.32–7.6, P = .58). Conclusion Mipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo. [ABSTRACT FROM AUTHOR]

Background Non–high-density lipoprotein cholesterol (non–HDL-C) has been identified as a significant predictor of various cardiovascular events in adults. Limited studies have been conducted in the pediatric population with diverse results, depending on ethnic origin. None has been conducted in the Arabic adolescent population so far; this study aims to fill this gap. Methods In this cross-sectional study, 1690 Saudi school adolescents (968 boys [mean age 14.8 ± 1.7] and 722 girls [mean age 14.6 ± 1.7]) were recruited. Anthropometrics were obtained. Fasting blood glucose and lipid profiles were quantified routinely. Non–HDL-C was calculated and screening was done for dyslipidemia using cutoffs obtained from the cohort and elevated fasting glucose. Results Using the 90th percentile cutoff obtained, the overall prevalence of high non–HDL-C (≥4.26 mmol/L) was 10.1%. Prevalence was slightly higher in girls (10.5%) than boys (9.9%). Non–HDL-C was similar to other lipids in terms of significant associations with anthropometric measures and glucose in both boys and girls. Elevated triglycerides was most predictive of elevated glucose in both girls (odds ratio 2.41; confidence interval 1.43–4.08; P = .001) and boys (odds ratio 2.61; confidence interval 1.70–4.0); P < .001). Conclusion Non–HDL-C appears to be gender-specific and is cardiometabolically more associated with Saudi boys, despite higher levels in girls. It is inferior compared with triglycerides in assessing elevated glucose risk. Further investigations may provide a more definite value for non–HDL-C use as a biomarker in assessing cardiometabolic risk in the Arab adolescent population. [ABSTRACT FROM AUTHOR]

Objective To objectively evaluate lipid-lowering therapy and low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment in metabolic syndrome (MetS) patients in China. Methods Data regarding patient demographics, lipid-lowering agents, lipid parameters, and cardiovascular risk profiles were analyzed for 25,317 patients of the Dyslipidemia International Study-China. MetS was defined according to criteria of the NCEP-ATP III and the 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. Results The prevalence of MetS was 39.9% and 37.4% according to the NCEP-ATP III and 2007 Chinese Guidelines, respectively. LDL-C goal attainment occurred less frequently among MetS patients than in those without MetS (NCEP-ATP III: 46.9% vs 68.6%; 2007 Chinese Guidelines: 52.2% vs 67.1%; p < 0.001). Similar results were obtained for non-HDL-C goal attainment (2007 Chinese Guidelines: 51.0% vs 72.0%; p < 0.001). As the risk class increased, LDL-C and non-HDL-C goal attainment decreased. In multivariate logistic regression analysis, DM, CHD, ischemic cerebrovascular disease, and higher SBP were independently associated with failure to achieve LDL-C and non-HDL-C goal attainment. The type of lipid-lowering agent was not significantly correlated with LDL-C not at goal attainment but was correlated with non-HDL-C not at goal attainment. Conclusion Goal attainment for both LDL-C and non-HDL-C occurs less frequently in MetS patients than in those without MetS. The residual risk due to elevated non-HDL-C levels should be considered in MetS patients. Strategies for controlling multiple risk factors in order to decrease the residual risk related to dyslipidemia in MetS patients should be recommended in future guidelines. [ABSTRACT FROM AUTHOR]

Background Despite clear guideline recommendations, there is a paucity of data regarding the prevalence and type of persistent lipid profile abnormalities in patients on stable lipid-lowering therapy in China. Methods This cross-sectional trial included 25,697 patients treated with lipid-lowering agents from 122 centres between April 2012 and October 2012; all underwent clinical examination and had their latest fasting lipid profiles while on lipid-lowering therapy recorded. Logistic regression was performed to assess predictors for lipid abnormalities classified according to current Chinese guidelines. Findings Overall, 29.1% of patients had no lipid abnormalities, and 38.5% of patients did not achieve the therapeutic goal for low-density lipoprotein cholesterol (LDL-C), either as a single lipid anomaly or associated with low high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, or both. Subjects with low risk were more likely than those with very high and high risk to be at target LDL-C levels. Furthermore, 10.4% of very high-risk patients and 11.1% of high-risk patients who attained the LDL-C goal failed to attain non-HDL-C goals. Diabetes was shown to be a strong predictor of failure in attaining non-HDL-C and both goals (OR 3.03; 3.22, 95% CI 2.58-3.55; 2.73-3.79, respectively). Conclusion Although great improvements have been made over the past decade, the large majority of very high-risk and high-risk patients treated with lipid-lowing agents still had one or more manifestations of dyslipidaemia. Further clinical evidence is needed to clarify whether adding other lipid-lowering agents to a statin will be associated with additional cardiovascular risk reduction. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We evaluated the prevalence of aspirin resistance and predictive factors for aspirin resistance in Korean type 2 diabetes patients. Approach and results: A total of 1045 type 2 diabetes patients from 11 hospitals who were taking aspirin (100 mg/day for ≥2 weeks) and no other antiplatelet agents were studied to evaluate aspirin resistance. Aspirin resistance was measured in aspirin reaction units using VerifyNow®. Aspirin resistance was defined as ≥550 aspirin reaction units. Aspirin resistance was detected in 102 of the 1045 subjects (prevalence 9.8%). Aspirin resistance was associated with total cholesterol (P = 0.013), LDL-cholesterol (P = 0.028), and non-HDL cholesterol (P = 0.008) concentrations in univariate analysis. In multivariate logistic regression analysis, only non-HDL cholesterol was associated with aspirin resistance in obese (BMI >25 kg/m2) type 2 diabetes patients (adjusted odds ratio 3.55, 95% CI: 1.25–10.05, P = 0.017). Conclusions: The prevalence of aspirin resistance in Korean type 2 diabetes patients is 9.8%. Non-HDL cholesterol is an independent risk factor for aspirin resistance, especially in obese type 2 diabetes patients. [Copyright &y& Elsevier]

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: Background: The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has been reported to be associated with metabolic syndrome (MetS) and insulin resistance (IR). Non-HDL-C is regarded as a surrogate marker for apoB in routine clinical practice. However, it is unclear whether the ratio of non-HDL-C to HDL-C is an equal or a better predictor than the apoB/apoA1 ratio for the identification of MetS and IR. Methods: We performed a retrospective study of 41,821 Korean adults who participated in a routine health screening examination. Anthropometry, fasting glucose, fasting insulin, HOMA-IR, CRP, lipid profiles, apoB, and apoA1 were measured. Results: To compare the predictive value for MetS between different lipid ratios, we analyzed the ROC curves of apoB/apoA1 and non-HDL-C/HDL-C ratios. ROC analysis showed that the AUCs of non-HDL-C/HDL-C (0.75 [95% CI=0.74–0.76] in men and 0.84 [95% CI=0.83–0.85] in women) were significantly higher than those of apoB/apoA1 (0.66 [95% CI=0.65–0.67] in men and 0.77 [95% CI=0.76–0.78] in women). The non-HDL-C/HDL-C ratio also showed a significantly stronger association with HOMA-IR than the apoB/apoA1 ratio. The optimal cutoff value of the non-HDL-C/HDL-C ratio for detection of MetS in men was 3.39, with a sensitivity of 66.7% and a specificity of 71.8%, whereas the optimal ratio cutoff value in women was 2.89, with a sensitivity of 75.7% and a specificity of 78.1%. Conclusions: Our findings indicate that the non-HDL-C/HDL-C ratio is a better marker than the apoB/apoA1 ratio for identifying IR and MetS in Koreans. [Copyright &y& Elsevier]

Abstract: Objective: LDL-receptor deficiency may provide a mechanism which contributes to atherogenic lipoprotein abnormalities in experimental nephrosis and in humans with glomerular proteinuria. The proprotein convertase subtilisin–kexin type 9 (PCSK9) pathway plays a key role in lipoprotein metabolism by promoting LDL-receptor degradation. We tested whether plasma PCSK9 is elevated in proteinuric states, and determined relationships of PCSK9 with lipoprotein responses to proteinuria reduction. Methods: Thirty-nine kidney patients (e-GFR 61 ± 29 mL/min/1.73 m2, proteinuria 1.9 [0.9–3.3] g/day; 19 on statin treatment) were studied during 2 randomized double-blind 6-week periods on either lisinopril (40 mg/day) and a regular sodium diet (194 ± 49 mmol Na+/day; baseline treatment) or lisinopril plus valsartan (320 mg/day) and a low sodium diet (102 ± 52 mmol Na+/day; maximal treatment), and compared to age- and sex-matched controls. Maximal treatment decreased proteinuria to 0.5 [0.3–1.1] g/day (P < 0.001). Results: Plasma PCSK9 was increased at baseline in proteinuric subjects (213 [161–314] vs. 143 [113–190] ug/L in controls, P ≤ 0.001), irrespective of statin use, e-GFR and BMI. PCSK9 correlated with proteinuria at baseline (R = 0.399, P = 0.018) and at maximal antiproteinuric treatment (R = 0.525, P = 0.001), but did not decrease during proteinuria reduction (P = 0.84). Individual changes in total cholesterol (R = 0.365, P = 0.024), non-HDL cholesterol (R = 0.333, P = 0.041), and LDL cholesterol (R = 0.346, P = 0.033) were correlated positively with individual PCSK9 responses. PCSK9 at baseline independently predicted the total/HDL cholesterol ratio response to treatment (P = 0.04). Conclusion: Plasma PCSK9 was elevated in proteinuria, predicted lipoprotein responses to proteinuria reduction but remained unchanged after proteinuria reduction. Inhibition of the PCSK9 pathway may provide a novel treatment strategy in proteinuric subjects. [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 preference of the apolipoprotein (apo) B/apoA-I ratio over the total cholesterol/HDL cholesterol (TC/HDL-C) ratio in cardiovascular risk prediction is disputed. Cholesteryl ester transfer protein (CETP) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins. We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event (MACE) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio. Methods: A prospective case-cohort study was performed (PREVEND cohort; no previous cardiovascular disease and no use of lipid-lowering drugs initially). Fasting serum TC/HDL-C, apoB/apoA-I, triglycerides, and common CETP variations (TaqIB [rs708272] and -629C>A [rs1800775] polymorphisms) were measured at baseline. The composite end point was incident MACE. Results: A total of 532 of 6780 subjects experienced a first MACE during 10.8 years follow-up. The age- and sex-adjusted hazard ratio was 1.31 (95 % confidence interval 1.23–1.41) for the apoB/apoA-I ratio and 1.22 (95% confidence interval 1.26–1.39) for the TC/HDL-C ratio (both P < .001). These relationships were essentially similar within each TaqIB and -629C>A CETP genotype group. No interactions of the apoB/apoA-I ratio and the TC/HDL-C ratio with the TaqIB and the -629C>A CETP variations on incident MACE were observed (P > .20 for all). Conclusion: The relationship of first MACE with the TC/HDL-C and the apoB/apoA-I ratio is not to an important extent dependent on common CETP variations. CETP variations are unlikely to affect the strength of the relationship of first MACE with the apoB/apoA-I ratio compared with the TC/HDL-C ratio. [ABSTRACT FROM AUTHOR]

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]

Abstract: Objective: This study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study. Methods: 9955 patients ≥20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries. Results: Success 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. Conclusions: Non-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients. [Copyright &y& Elsevier]

Abstract: Objectives: Coronary artery disease (CAD) has emerged as the major cause of morbidity and mortality among Asian Indians in the recent past. The following study was undertaken to assess the predictive value of novel biomarkers of dyslipidemia for risk assessment for CAD in the Indian population. Design and methods: The study group comprised of 100 clinically assessed patients of myocardial infarction and 100 age and sex matched healthy controls. Apolipoprotein-A (Apo-AI) and Apolipoprotein-B (Apo-B) were estimated and small dense LDL was derived mathematically. Results: The cases showed significantly high levels of total serum cholesterol, triglycerides, LDL cholesterol, Apo-B, sdLDL, and non-HDL cholesterol. On carrying out multivariate regression analysis, Lp(a)/HDL ratio emerged as the best determinant of CAD risk Conclusion: The above data clearly underlines the role of these novel biomarkers in the risk assessment for CAD in the Indian context. [Copyright &y& Elsevier]

Abstract: There is little understanding of the reliability of laboratory measurements among clinicians. Low-density lipoprotein cholesterol (LDL-C) measurement is the cornerstone of cardiovascular risk assessment and prevention, but it is fraught with error. Therefore, we have reviewed issues related to accuracy and precision for the measurement of LDL-C and the related markers non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B. Despite the widespread belief that LDL-C is standardized and reproducible, available data suggest that results can vary significantly as the result of methods from different manufacturers. Similar problems with direct HDL-C assays raise concerns about the reliability of non-HDL-C measurement. The root cause of method-specific bias relates to the ambiguity in the definition of both LDL and HDL, and the heterogeneity of LDL and HDL particle size and composition. Apolipoprotein B appears to provide a more reliable alternative, but assays for it have not been as rigorously tested as direct LDL-C and HDL-C assays. [Copyright &y& Elsevier]

Background: Dysbetalipoproteinemia, also known as type III hyperlipoproteinemia (type III HL), is characterized by the accumulation of β-very low density lipoprotein (β-VLDL). However, demonstration of the presence of β-VLDL is not easy because it requires preparative ultracentrifugation of lipoproteins. The primary genetic defect in type III HL is the presence of apolipoprotein (apo) E2, a mutant form of apoE. However, another metabolic defect, such as overproduction of VLDL, is also required for the full phenotype. Patients with only E2 homozygosity usually do not have HL. Because apoE genotyping is expensive, the selection of patients for this analysis by effective use of common clinical measures would be very helpful. Objective: We examined the non-HDL-C/apoB ratio as an index for type III HL screening. Methods: We studied nine patients with type III HL. Most patients with type III HL show mixed hyperlipidemia. We compared the plasma of patients with combined hyperlipidemia and the dyslipidemia of hypothyroidism with those with type III HL. The serum levels of total cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C), as well as the serum apoB and apoE levels, were measured by routine laboratory methods. Results: Individual values of serum lipids and apolipoproteins did not distinguish type III HL from the two other types of HL. The non-HDL-C/apoB ratio in type III HL was significantly greater than that in the two comparison groups, with no overlap. Conclusion: The non-HDL-C/apoB ratio is a novel index that appears to be reliable for screening of patients for type III HL, and the index can be determined at regular clinical laboratories without the need for any complicated lipoprotein analysis. Thus, we propose the clinical usefulness of this index. [Copyright &y& Elsevier]

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]

Abstract: Background: Serum non-HDL cholesterol is a strong predictor of cardiovascular diseases. We studied the relationship between habitual alcohol drinking and non-HDL cholesterol. Methods: Healthy male subjects (n =27,005) and female subjects (n =16,805) were divided into 5 groups by average daily ethanol intake. Serum non-HDL cholesterol level and prevalence of serum high non-HDL cholesterol (≥170 mg/dl) were compared among the groups. Results: Non-HDL cholesterol level and prevalence of high non-HDL cholesterol became lower as alcohol intake increased. The threshold alcohol intake in the drinker groups showing significantly lower non-HDL cholesterol level and significantly lower prevalence of high non-HDL cholesterol, compared with those in non-drinkers, was lower in women (<10 g/d) than in men (≥10 and <20 g/d). Odds ratios of each drinker group vs. the non-drinker group for high non-HDL cholesterol became lower as alcohol intake increased. The odds ratio of each drinker group vs. the non-drinker group for high non-HDL cholesterol tended to be lower in women than in men. Conclusions: The results suggest that even light drinking is sufficient to significantly lower serum non-HDL cholesterol and that this effect of alcohol drinking on non-HDL cholesterol is more pronounced in women than in men. [Copyright &y& Elsevier]

Summary: Objectives: To assess the relationship between non-classical cardiovascular (CV) risk factors including non-HDL cholesterol (non-HDL-C), apolipoprotein B, triglycerides to HDL ratio, LDL size, inflammation or oxidative stress parameters and carotid intima-media thickness (CIMT), in order to better identify prevention or therapeutic targets. In addition, we studied the relationship between metabolic syndrome (MS) and CIMT. Methods: Cross-sectional study including 232 HIV-positive (HIV+) adults (80% treated by combined antiretroviral therapy) extracted from the ANRS CO3 Aquitaine Cohort. Results: There was a significant association of higher non-HDL-C (p <0.01), apolipoprotein B (p <0.01) levels or TG/HDL ratio (p <0.05) with higher CIMT when compared the first vs fourth quartile, while there is no association between CIMT and LDL-C (p =0.09) or LDL size (p =0.55). In multivariate analysis, only the TG/HDL molar ratio > 1.5 tend toward significance (p =0.08). MS was observed in only 7.3% of patients with the NCEP-ATP III definition and 11.2% with the IDF criteria. Whatever the used definition, there was a significant association between MS presence and increased CIMT (p <0.05) in univariate and multivariate model. Conclusions: Non-HDL-C, TG/HDL ratio and apolipoprotein B levels, which are closely linked to lipid disorders associated to the MS, appear as stronger predictive markers than LDL-C for screening subclinical atherosclerosis in HIV+ populations. Achieving non-HDL-C target defined by the NCEP-ATP III guidelines appears of great importance to reduce CV complications in HIV+ patients. [Copyright &y& Elsevier]

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]

Background: The cholesterol content of low-density lipoprotein (LDL) particles is variable, causing frequent discrepancies between concentrations of LDL cholesterol (LDL-C) and LDL particle number (LDL-P). In managing patients at risk for cardiovascular disease (CVD) to LDL target levels, it is unclear whether LDL-C provides the optimum measure of residual risk and adequacy of LDL-lowering treatment. Objective: To compare the ability of alternative measures of LDL to provide CVD risk discrimination at relatively low levels consistent with current therapeutic targets. Methods: Concentrations of LDL-C and non–HDL-C were measured chemically and LDL-P and VLDL-P were measured by nuclear magnetic resonance in 3066 middle-aged white participants (53% women) without CVD in the Framingham Offspring cohort. The main outcome measure was incidence of first CVD event. Results: At baseline, the cholesterol content per LDL particle was negatively associated with triglycerides and positively associated with LDL-C. On follow-up (median 14.8 years), 265 men and 266 women experienced a CVD event. In multivariable models adjusting for nonlipid CVD risk factors, LDL-P was related more strongly to future CVD in both genders than LDL-C or non–HDL-C. Subjects with a low level of LDL-P (<25th percentile) had a lower CVD event rate (59 events per 1000 person-years) than those with an equivalently low level of LDL-C or non–HDL-C (81 and 74 events per 1000 person-years, respectively). Conclusions: In a large community-based sample, LDL-P was a more sensitive indicator of low CVD risk than either LDL-C or non–HDL-C, suggesting a potential clinical role for LDL-P as a goal of LDL management. [Copyright &y& Elsevier]

Summary: Objective: Few studies have compared non-HDL cholesterol (non-HDLc) and Apolipoprotein B (apoB) as markers of atherosclerotic risk. No such study has yet been undertaken in Asian-Indians who have a different lipid–lipoprotein profile than their Western counterparts. Our aim, therefore, was to evaluate the role of non-HDLc and apoB, as markers of all potentially atherogenic species, and to further assess as to which is the better index of the risk of cardiovascular disease (CVD) in type 2 diabetic subjects. Research design and methods: Lipidic parameters, apoB and carotid mean intima–media thickness (IMT) were determined in the 95 diabetic subjects included in the study. Subjects were classified on the basis of apoB and triglyceride as well as non-HDLc and triglyceride levels. Agreement of the resultant phenotypes with IMT was assessed (correlation and concordance (κ) analysis), and the major contributor to the variance of IMT was determined using multistep linear regression. Results: HyperapoB was the most prevalent lipoproteic abnormality. The correlation between apoB and non-HDLc was strong in the whole cohort (r =0.60, p <0.01) and better in the hypertriglyceridemic subgroup (r =0.67, p <0.01). There was significant concordance between IMT and apoB and non-HDLc in the whole cohort (κ =0.490, p <0.0001; κ =0.403, p <0.000); while the concordance between the apoB and non-HDLc dependent phenotypes and IMT was better in the hypertriglyceridemic subgroup (HtgHapob-κ =0.598, p <0.0001; HtgHnonhdl-κ =0.481, p <0.0001) as opposed to the normotriglyceridemic subgroup (NtgHapob-κ =0.387, p <0.0001; NtgHnonhdl-κ =0.043, p =NS). Further apoB was a better predictor of IMT in all the subgroups as well as the whole cohort (R 2 =0.378, β-coefficient=0.002) as compared to non-HDLc (R 2 change=0.030, β-coefficient=0.0017). Conclusions: Non-HDLc and apoB are equivalent atherogenic markers of cardiovascular risk in hypertriglyceridemic diabetic subjects, but apoB is a better index of the risk of cardiovascular disease in normotriglyceridemic subjects. Thus, measurement of apoB might be helpful in identification of a subgroup of apparently normolipidemic subjects who have hyperapoB and thus stand increased cardiovascular risk. [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]

Lipid abnormalities associated with urinary albumin excretion rate in Taiwanese type 2 diabetic patients.Background.The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients.Methods.A total of 275 (122 men and 153 women; aged 60.6± 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria (N= 152) and albuminuria (N= 123) were defined as urinary albumin-to-creatinine ratio (ACR) of<30 and≥30μg/mg, respectively. Total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1 (ApoA1) and B (ApoB) were measured and non-HDL cholesterol calculated. The subjects were divided into four phenotypes based on triglycerides (<1.5 or≥1.5 mmol/L) and ApoB (<1.2 or≥1.2 g/L).Results.Total cholesterol, ApoB, and non-HDL cholesterol were significantly (P<0.05) higher in patients with albuminuria. For quartiles of the lipid parameters, prevalences of albuminuria showed significant association with ApoB and non-HDL cholesterol (Ptrend<0.05). After adjusting for age, systolic blood pressure and hemoglobin A1c (HbA1c) correlation coefficients between the natural logarithm (ln) ACR and lipid parameters, odds ratios for albuminuria, and standardized regression coefficients for ln ACR, were significant for total cholesterol, ApoB and non-HDL cholesterol in all subjects and in men, but only ApoB was significant in women. For patients with normoalbuminuria, frequencies of normotriglycerides/normo-ApoB, hypertriglycerides/normo-ApoB, normotriglycerides/hyper-ApoB, and hypertriglycerides/hyper-ApoB were 44.7%, 28.9%, 10.5%, and 15.8%, respectively; and were 30.1%, 19.5%, 15.4%, and 35.0% for patients with albuminuria (P<0.001). The respective adjusted odds ratio for albuminuria for the four phenotypes was 1.00, 1.04 (0.54 to 2.00), 2.25 (1.02 to 5.00), and 3.38 (1.75 to 6.53).Conclusion.Increased UAER is associated with ApoB-containing lipoproteins and the phenotype of hypertriglycerides/hyper-ApoB is associated with the highest risk of albuminuria. The surrogate marker of non-HDL cholesterol for ApoB is more applicable to the diabetic men. [ABSTRACT FROM AUTHOR]

Abstract: Atherosclerosis is a chronic inflammatory vascular disease, and an association between elevated blood lipids and atherosclerosis has previously been recognized. Low-density lipoprotein cholesterol (LDLc) levels have also been recognized as indicators of cardiovascular complications, but two people who have exactly the same LDLc concentrations may have different risk factors, and the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines recommend patching non-high-density lipoprotein cholesterol (non-HDLc) as another indicator. The present study investigated diabetic dyslipidemia to determine if there is a correlation between dyslipidemia and C-reactive protein (CRP). The data shows that non-HDLc was an independent risk factor for cardiovascular events in patients with diabetes and that CRP could indicate the risk of future cardiovascular events in both high-risk and healthy individuals. [Copyright &y& Elsevier]

Abstract: Objectives: To reconcile observing a positive correlation of betaine excretion with homocysteine in lipid disorder patients but not other study groups. Design and methods: Correlations were estimated in subgroups of a control group and the lipid disorder patients. Results: Plasma non high-density lipoprotein (non-HDL) cholesterol differed (p<0.0001) between the groups. The correlation increased with the median plasma non-HDL cholesterol in subgroups. Conclusions: This correlation is associated with patients with elevated plasma lipids. [Copyright &y& Elsevier]

Secondary dyslipidemia with predominant hypertriglyceridemia may occur as a consequence of both common and rare causes. After accounting for obesity and associated insulin resistance, clinicians should carefully consider other contributing factors and conditions. Genetic background and causative factors prevail during gestation, infancy, and childhood and continue in adults. Elevations in triglyceride (TG) are associated with transfer of TG to high-density lipoprotein (HDL) and low-density lipoprotein (LDL) resulting in lipolysis, HDL degradation, and formation of atherogenic LDL particles. Defining and treating the underlying cause is the first step toward restoring the lipids and lipoproteins to normal, especially in cases with severe hypertriglyceridemia, who are at risk for acute pancreatitis. Disorders involving the liver, kidney, endocrine, and immune systems and medications need to be considered. Rare diseases such as lipodystrophy and glycogen storage disease are particularly challenging, and there have been promising new developments. Treatment depends on the severity; prevention of acute pancreatitis being a priority in severe cases and lifestyle modification being a foundation for general management followed by targeting TG and predictors of coronary artery disease such as LDL cholesterol and non–HDL cholesterol, when they exceed cutpoints. [ABSTRACT FROM AUTHOR]