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• Real-world data of a national healthcare service on patients initiating inclisiran. • Significant reduction in LDL-C, relative to both peak and pre-inclisiran levels. • High interindividual variability and good short-term adherence. • Attainment rates of LDL-C treatment goals were sub-optimal. • Reduction in concurrent lipid-lowering therapies following initiation of inclisiran. Inclisiran, a small-interfering RNA enabling long-term inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) synthesis, demonstrates a good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps are lacking. To investigate the implementation of inclisiran in real-world clinical setting. Data from a nationwide healthcare organization on patients initiating inclisiran between 3/2022–11/2023. Patients' characteristics, lipid-lowering therapies, post-treatment reduction in low-density lipoprotein cholesterol (LDL-C), and attainment of treatment goals were evaluated. Inclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Cardiovascular disease was present in 54%, and peak LDL-C levels >190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n = 254), median LDL-C reduction from peak levels was 57% (interquartile range [IQR], 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant lipid-lowering therapies (n = 143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%). LDL-C < 70 mg/dL was attained by 39% and LDL-C < 55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C < 55 mg/dL. Overall, 6.5% discontinued inclisiran therapy after initial injection. In real-world practice, inclisiran showed good efficacy in reducing LDL-C with high interindividual variability. However, attainment rates of lipid goals were suboptimal due to limited use of combination lipid-lowering therapy and high rates of severe hypercholesterolemia in our patient population cohort. Lipid-lowering therapy with Inclisiran in the real-world setting: initial data from a health care service. Percent reduction of LDL-C is presented as median and interquartile range. [Display omitted] [ABSTRACT FROM AUTHOR]

• PCSK9 inhibition dramatically reduces both LDL-C and sdLDL-C to a similar degree. • Plasma 7-ketocholesterol levels were not significantly modulated by PCSK9 inhibition. • Changes in 7-ketocholesterol and VLDL-C after PCKS9 inhibition significantly correlated. • 7-Ketocholesterol may be carried by VLDL and lost during LDL formation. Oxidized forms of cholesterol (oxysterols) are implicated in atherogenesis and can accumulate in the body via direct absorption from food or through oxidative reactions of endogenous cholesterol, inducing the formation of LDL particles loaded with oxidized cholesterol. It remains unknown whether drastic reductions in LDL-cholesterol (LDL-C) are associated with changes in circulating oxysterols and whether small dense LDL (sdLDL) are more likely to carry these oxysterols and susceptible to the effects of PCSK9 inhibition (PCSK9i). We investigate the effect of LDL-C reduction accomplished via PCSK9i on changes in plasma levels of sdLDL-cholesterol (sdLDL-C) and a common, stable oxysterol, 7-ketocholesterol (7-KC), among 134 patients referred to our Preventive Cardiology clinic. Plasma lipid panel, sdLDL-C, and 7-KC measurements were obtained from patients before and after initiation of PCSK9i. The intervention caused a significant lowering of LDL-C (-55.4 %). The changes in sdLDL-C levels (mean reduction 51.4 %) were highly correlated with the reductions in LDL-C levels (R = 0.829, p < 0.001). Interestingly, whereas changes in plasma free 7-KC levels with PCSK9i treatment were much smaller than (-6.6 %) and did not parallel those of LDL-C and sdLDL-C levels, they did significantly correlate with changes in triglycerides and very low-density lipoprotein-cholesterol (VLDL-C) levels (R = 0.219, p = 0.025). Our findings suggest a non-preferential clearance of LDL subparticles as a consequence of LDL receptor upregulation caused by PCSK9 inhibition. Moreover, the lack of significant reduction in 7-KC with PCSK9i suggests that 7-KC may be in part carried by VLDL and lost during lipoprotein processing leading to LDL formation. [ABSTRACT FROM AUTHOR]

• Remnant cholesterol (RC) is a potential contributor to residual cardiovascular risk. • Association between calculated RC and myocardial infarction (MI) was investigated. • We analyzed 9451 patients with coronary disease undergoing revascularization. • RC was a risk factor for MI independent of lipid-lowering drugs, LDL-C or non-HDL-C. • When RC and non-HDL-C (or LDL-C) were discordant, RC seemed to better reflect risk. Despite substantial reduction in low-density lipoprotein cholesterol (LDL-C), patients develop recurrent cardiovascular events. Remnant cholesterol (RC), the cholesterol content of triglyceride-rich lipoproteins, is a potential contributor to this residual risk. To investigate the association between RC and risk for myocardial infarction (MI) in patients with coronary artery disease, and examine whether the predictive value of RC is retained beyond non-high-density lipoprotein cholesterol (non-HDL-C). Data on 9451 patients undergoing coronary revascularization in a single center. RC was calculated as total cholesterol minus high-density lipoprotein cholesterol minus LDL-C (estimated using Martin–Hopkins equation). Cox-regression models were used to estimate the association between RC and risk for MI. Discordance analyses were performed to examine the correlation between RC and non-HDL-C (or LDL-C) in relation to MI risk. Mean age was 65±11 years; 67% presented with acute coronary syndrome. During median follow-up of 9.6 years, 1690 patients developed MI. After multivariable adjustment including lipid-lowering therapies and non-HDL-C, RC was associated with higher MI risk: hazard ratio (95% confidence interval): 1.36 (1.20-1.56) and 1.58 (1.35-1.85) in those with RC levels ≥75th (32.6 mg/dL) and ≥90th (41.8 mg/dL) percentile, compared to RC <50th percentile (25.5 mg/dL). When RC and non-HDL-C (or LDL-C) levels were discordant, the level of RC better reflected the risk for MI. Elevated RC is a risk factor for MI independent of lipid-lowering therapies and non-HDL-C, providing further support that RC may serve as a residual cardiovascular risk marker and potential treatment target in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

BackgroundThe presence of small dense low-density lipoprotein (LDL) is associated with obesity, type II diabetes, and an increased risk for cardiovascular disease. Apolipoprotein C-III (apoC-III) is involved in the formation of small dense LDL, but the exact mechanisms are still not well defined. ApoC-III is a glycosylated apolipoprotein, with 3 major glycoforms: apoC-III0, apoC-III1, and apoC-III2 that contain 0, 1, or 2 molecules of sialic acid, respectively. In our previous work, we reported an association among apoC-III0 and apoC-III1, but not apoC-III2 with fasting plasma triglyceride levels in obesity and type II diabetes.ObjectiveThe goal of this study was to determine the relationship between changes in the major apoC-III glycoforms and small dense LDL levels after dietary interventions.MethodsMass spectrometric immunoassay was performed on fasting plasma samples from 61 subjects who underwent either a high-carbohydrate diet (n = 34) or a weight loss intervention (n = 27).ResultsAfter both dietary interventions, changes in total apoC-III concentrations were associated with changes in LDL peak particle diameter (r = -0.58, P

• Camelina sativa oil increased LDL cholesteryl ester species with α-linolenic acid. • Fatty fish increased LDL phosphatidylcholine species containing EPA and DHA. • LDL surface lipids were associated with aggregation of LDL particles. There is little knowledge on the effects of alpha-linolenic acid (ALA) and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) on the LDL lipidome and aggregation of LDL particles. We examined if consumption of Camelina sativa oil (CSO) as a source of ALA, fatty fish (FF) as a source of n-3 LCPUFA and lean fish (LF) as a source of fish protein affect the lipidome of LDL as compared to a control diet. Participants with impaired glucose tolerance (39 women and 40 men) were randomized to 4 study groups (CSO providing 10 g/d ALA, FF and LF [both 4 fish meals/wk] and control limiting their fish and ALA intake) in a 12-week, parallel trial. Diets were instructed and dietary fats were provided to the participants. The lipidome of LDL particles isolated from samples collected at baseline and after intervention was analyzed with electrospray ionization-tandem mass spectrometry. In the CSO group, the relative concentrations of saturated and monounsaturated cholesteryl ester species in LDL decreased and the species with ALA increased. In the FF group, LDL phosphatidylcholine (PC) species containing n-3 LCPUFA increased. There was a significant positive correlation between the change in total sphingomyelin and change in LDL aggregation, while total PC and triunsaturated PC species were inversely associated with LDL aggregation when all the study participants were included in the analysis. Dietary intake of CSO and FF modifies the LDL lipidome to contain more polyunsaturated and less saturated lipid species. The LDL surface lipids are associated with LDL aggregation. [ABSTRACT FROM AUTHOR]

Background The laboratory measurement of “low-density lipoprotein cholesterol (LDL-C)” includes the cholesterol content of lipoprotein(a) (Lp(a)-C). Objective To estimate the “true” LDL-C in relation to changes in apolipoprotein B-100 (apoB-100) and assess changes in proprotein convertase subtilisin/kexin 9 (PCSK9) levels in patients with elevated Lp(a) treated with IONIS-APO(a) Rx. Methods A pooled placebo group (n = 29), and cohort A (n = 24, baseline Lp(a) 50–175 mg/dL) and cohort B (n = 8, baseline Lp(a) > 175 mg/dL) treated with IONIS-APO(a) Rx were studied. Lp(a) particle number, ultracentrifugation-measured “LDL-C”, apoB-100, total PCSK9, and lipoprotein-associated PCSK9 (PCSK9-Lp(a), PCSK9-apoB, PCSK9-apoAI) were measured. Lp(a)-cholesterol (Lp(a)-C) and LDL-C corrected for Lp(a)-C (LDL-C corr ) were calculated. Results Baseline mean (standard deviation) “LDL-C” was 120 (42), 128 (45), and 112 (39) mg/dL in placebo, cohorts A and B, respectively, whereas LDL-C corr was 86 (48), 96 (43), and 57 (37) mg/dL ( P < .001 compared with placebo), representing 28%, 25%, and 50% lower levels than “LDL-C”. Following IONIS-APO(a) Rx treatment at day 85/99, Lp(a) particle number and Lp(a)-C decreased –66.8% and –71.6%, apoB-100 –10.3% and –17.5%, “LDL-C” –11.8% and –22.7%, ( P < .001 for all vs placebo), whereas LDL-C corr increased +10.4% ( P = .66) and +49.9% ( P < .001) in cohorts A and B, respectively. Total PCSK9 did not change but PCSK9-Lp(a) decreased with IONIS-APO(a) Rx vs placebo (–39.0% vs +8.4%, P < .001). Conclusion LDL-C corr is lower than laboratory “LDL-C” in patients with elevated Lp(a). Following apolipoprotein(a) inhibition and decline in Lp(a) and Lp(a)-C, the decline in apoB-100 is consistent with the notion that LDL devoid of apo(a) is cleared faster than Lp(a). These types of analyses may provide insights into the mechanisms of drugs affecting Lp(a) levels in clinical trials. [ABSTRACT FROM AUTHOR]

Background Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided. Objectives Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients. Methods Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 μmol/L) were randomized to receive atorvastatin 10 mg ( n = 59) or 80 mg ( n = 60) daily. Baseline and 1-year follow-up data are reported. Results Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin ( P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein. Conclusions High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality. [ABSTRACT FROM AUTHOR]

Background Clinical trials testing proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) have demonstrated an unanticipated but significant lipoprotein (a) (Lp(a))-lowering effect, on the order of 25% to 30%. Although the 50% to 60% reduction in low-density lipoprotein (LDL)-cholesterol (LDL-C) achieved by PCSK9i is mediated through its effect on LDL receptor (LDLR) preservation, the mechanism for Lp(a) lowering is unknown. Objective We sought to characterize the degree of concordance between LDL-C and Lp(a) lowering because of PCSK9i in a standard of care patient cohort. Methods Participants were selected from our Center for Preventive Cardiology, an outpatient referral center in a tertiary academic medical center. Subjects were included in this study if they had (1) at least 1 measurement of LDL-C and Lp(a) before and after initiation of the PCSK9i; (2) baseline Lp(a) > 10 mg/dL; and (3) continued adherence to PCSK9i therapy. They were excluded if (1) they were undergoing LDL apheresis; (2) pre- or post-PCSK9i LDL-C or Lp(a) laboratory values were censored; or (3) subjects discontinued other lipid-modifying therapies. In total, 103 subjects were identified as taking a PCSK9i and 26 met all inclusion and exclusion criteria. Concordant response to therapy was defined as an LDL-C reduction >35% and an Lp(a) reduction >10%. Results The cohort consisted of 26 subjects (15 females, 11 males, mean age 63 ± 12 years). Baseline mean LDL-C and median Lp(a) levels were 167.4 ± 72 mg/dL and 81 mg/dL (interquartile range 38–136 mg/dL), respectively. The average percent reductions in LDL-C and Lp(a) were 52.8% (47.0–58.6) and 20.2% (12.2–28.1). The correlation between %LDL and %Lp(a) reduction was moderate, with a Spearman's correlation of 0.56 ( P < .01). All subjects except for 1 had a protocol-appropriate LDL-C response to therapy. However, only 16 of the 26 (62%; 95% confidence interval 41%–82%) subjects had a protocol-concordant Lp(a) response. Although some subjects demonstrated negligible Lp(a) reduction associated with PCSK9i, there were some whose Lp(a) decreased as much as 60%. Conclusions In this standard-of-care setting, we demonstrate moderate correlation but large discordance (∼40%) in these 2 lipid fractions in response to PCSK9i. The results suggest that pathways beyond the LDLR are responsible for Lp(a) lowering and indicate that PCSK9i have the potential to significantly lower Lp(a) in select patients, although confirmation in larger multicenter studies is required. [ABSTRACT FROM AUTHOR]

The roundtable discussion in this issue will focus on the problems faced by young women with lipid disorders. This is often the source of confusion for the patient and physician because the myth continues that young women do not have complications of atherosclerosis as a result of elevated blood cholesterol. The essential role of women in bearing children during the early years of adulthood also produces difficult decisions because the mother and fetus are usually experiencing similar exposure to therapeutic regimens. We are joined in this discussion by Drs. Pamela Morris of the Medical University of South Carolina and Robert Wild of the University of Oklahoma Health Sciences Center. Dr Morris is an Internist, and Dr Wild is an Obstetrician and Gynecologist. Both are board certified in clinical lipidology and are actively publishing in this field. We have recorded this roundtable discussion during the National Lipid Association Scientific Sessions held in New Orleans during May 2016. [ABSTRACT FROM AUTHOR]

Abetalipoproteinemia (ABL) is a rare recessive genetic disease caused by mutations of the MTTP gene. This disease is characterised by a defect in the lipidation of APO B and the absence of VLDL and chylomicron production. Patients affected by ABL present neurological, hemalogical and gastro-intestinal symptoms due to deficiency in lipophilic vitamins and fat malabsorption. We herein report the case of two cousins, one presenting classical symptoms of abetalipoproteinemia and one presenting a much attenuated phenotype. The proband carried a novel combination of MTTP mutations, the 1867+1G>A and the R540C mutations. This patient never received any vitamin supplements and was relatively free of symptoms despite an undetectable APO B concentration. Her cousin was homozygous for 1867+1G>A MTTP mutation and presented most of the classical symptoms of ABL. In conclusion we report a very unusual kindred where on affected member is strongly symptomatic of ABL whereas the other presents very mostly asymptomatic disease suggesting that ABL can present itself with a very incomplete clinical penetrance. [ABSTRACT FROM AUTHOR]

Background There is limited research detailing low-density lipoprotein cholesterol (LDL-C) trends over the long term in children on various lipid-lowering medications. Objectives This study sought to assess factors associated with stability of LDL-C levels in children on long-term pharmacotherapy and their ability to reach the LDL-C goal of ≤130 mg/dL while on pharmacotherapy. Methods Medical records of children seen in a university pediatric cholesterol clinic between 1998 and 2012 treated with a statin, ezetimibe, or both were reviewed. Aggregate data were obtained to determine the number of children able to reach an LDL-C level of ≤130 mg/dL while on pharmacotherapy. Kaplan–Meier curve and proportional hazard regression analysis were used to examine the propensity for LDL-C levels to stabilize over time while on pharmacotherapy as well as factors affecting this propensity. Results Overall, 76 patients who contributed 864 total visits were included. Of the 76 patients, 56 developed a stable LDL-C with median time to stability of 28 months on pharmacotherapy. Younger age at first visit and higher medication potencies/doses were associated with an increased propensity to stabilize. Only 36 patients were able to reach an LDL-C of ≤130 mg/dL, with only 11 of 38 patients with probable familial hypercholesterolemia reaching this goal. Conclusions Most children reached LDL-C stability on pharmacotherapy after a median 28-month interval. However, most children had difficulty in reaching the LDL-C goal of ≤130 mg/dL even with aggressive medication titration. This was specifically true for those with probable familial hypercholesterolemia. [ABSTRACT FROM AUTHOR]

Background Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets, and replacement with poly- and monounsaturated fatty acids is encouraged. Objective To compare the effects of polyunsaturated fatty acid–rich corn oil (CO) and monounsaturated fatty acid–rich extra-virgin olive oil (EVOO) on plasma lipids in men and women (N = 54) with fasting low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and <200 mg/dL and triglycerides (TG) ≤350 mg/dL. Methods In a double-blind, randomized, crossover design (21-day treatments, 21-day washout between), 4 tablespoons/day CO or EVOO were provided in 3 servings study product/day (muffin, roll, yogurt) as part of a weight-maintenance diet (∼35% fat, <10% saturated fat, <300 mg cholesterol). Subjects ate breakfast at the clinic every weekday throughout the study. Lunches, dinners, and snacks (and breakfasts on weekends) were provided for consumption away from the clinic. Results Baseline mean (standard error) lipids in mg/dL were: LDL-C 153.3 (3.5), total cholesterol (total-C) 225.7 (3.9), non–high-density lipoprotein (non–HDL)-C 178.3 (3.7), HDL-C 47.4 (1.7), total-C/HDL-C 5.0 (0.2), and TG 124.8 (7.2). CO resulted in significantly larger least-squares mean % changes (all P < .001 vs EVOO) from baseline in LDL-C −10.9 vs −3.5, total-C −8.2 vs −1.8, non–HDL-C −9.3 vs −1.6, and total-C/HDL-C −4.4 vs 0.5. TG rose a smaller amount with CO, 3.5 vs 13.0% with EVOO ( P = .007). HDL-C responses were not significantly different between conditions (−3.4 vs −1.7%). Conclusion Consumption of CO in a weight-maintenance, low saturated fat and cholesterol diet resulted in more favorable changes in LDL-C and other atherogenic lipids vs EVOO. [ABSTRACT FROM AUTHOR]

Background and Objectives: Dyslipidemia is a modifiable major risk factor for coronary heart disease. The objective of this study was to determine the prevalence of dyslipidemia among Turkish adults and its associations with other cardiovascular risk factors. Methods: This study included 4309 people ages 20 to 83 years old from 7 provinces of Turkey. People from the city centers, districts, and villages were selected by a stratified sampling method. Weight, height, and waist and hip circumferences were measured. Blood samples were obtained to determine glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG); these parameters were measured with an autoanalyzer. Dyslipidemia was defined according to National Cholesterol Education Program Adult Treatment Panel III diagnostic criteria. Results: Of 4309 subjects, 43% had high TC, 41.5% had low HDL-C, 36.2% had high LDL-C, and 35.7% had high TG. Of these measures, at least 1 lipid abnormality was diagnosed in 78.7% of men and 80.4% of women. The prevalence of high TC, LDL-C, and TG increased with age, with the highest prevalence in the 46-to-65-year-old age group. The mean values (mg/dL) of TC, LDL-C, HDL-C, and TG were 194.2 ± 47.7, 117.7 ± 41.1, 50.3 ± 16.3, and 145.4 ± 96.3, respectively. Dyslipidemia was positively associated with age, body mass index, waist circumference, fasting blood glucose, and blood pressure, and negatively associated with altitude. Conclusions: The high prevalence of dyslipidemia in Turkey is an important public health problem. Enhanced public health preventive measures should be implemented to better diagnose and comprehensively treat dyslipidemia in Turkey. [Copyright &y& Elsevier]

Abstract: The term “fat” may refer to lipids as well as the cells and tissue that store lipid (ie, adipocytes and adipose tissue). “Lipid” is derived from “lipos,” which refers to animal fat or vegetable oil. Adiposity refers to body fat and is derived from “adipo,” referring to fat. Adipocytes and adipose tissue store the greatest amount of body lipids, including triglycerides and free cholesterol. Adipocytes and adipose tissue are active from an endocrine and immune standpoint. Adipocyte hypertrophy and excessive adipose tissue accumulation can promote pathogenic adipocyte and adipose tissue effects (adiposopathy), resulting in abnormal levels of circulating lipids, with dyslipidemia being a major atherosclerotic coronary heart disease risk factor. It is therefore incumbent upon lipidologists to be among the most knowledgeable in the understanding of the relationship between excessive body fat and dyslipidemia. On September 16, 2012, the National Lipid Association held a Consensus Conference with the goal of better defining the effect of adiposity on lipoproteins, how the pathos of excessive body fat (adiposopathy) contributes to dyslipidemia, and how therapies such as appropriate nutrition, increased physical activity, weight-management drugs, and bariatric surgery might be expected to impact dyslipidemia. It is hoped that the information derived from these proceedings will promote a greater appreciation among clinicians of the impact of excess adiposity and its treatment on dyslipidemia and prompt more research on the effects of interventions for improving dyslipidemia and reducing cardiovascular disease risk in overweight and obese patients. [Copyright &y& Elsevier]

Background: One in every six adults (16.3% of the U.S. adult population) has high total cholesterol levels, and they are at double the risk of heart disease compared with people with optimal levels. Objective: To evaluate compliance of internal medicine residents with the latest National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) guidelines in treating patients with hyperlipidemia. Design: Retrospective observational study. Setting: Ambulatory Clinic, Saint Vincent Hospital, Worcester, Massachusetts. Patients: Patients with a diagnosis of hyperlipidemia who attended the clinic during a 1-ear period, from December 2009 to November 2010. Measurements: A review of medical records was conducted to evaluate residents’ compliance with the NCEP-ATP III guidelines for LDL cholesterol and non-HDL cholesterol management. Results: Seven hundred seventy charts were reviewed. Only 212 (27.5%) met the inclusion criteria. Analysis of data revealed better compliance with drug therapy (44%−77%) and therapeutic lifestyle changes (44%−83%) when compared with follow-up recommendations (22%−31%). An increase in compliance also was noted in all areas of intervention when patients had an abnormal lipid profile. Limitations: Compliance was assessed on the basis of electronic medical record documentation alone and hence we may be underestimating compliance with therapeutic lifestyle changes and follow-up recommendations. Conclusion: Compliance among internal medicine residents in the diagnosis, treatment and follow-up of patients with hyperlipidemia according to NCEP-ATP III guidelines was suboptimal and needs improvement. [ABSTRACT FROM AUTHOR]

Background: The bile acid sequestrant colesevelam has been shown to significantly reduce low-density lipoprotein particle concentration (LDL-P) in adults with primary hyperlipidemia or type 2 diabetes mellitus (T2DM). Objective: To assess the effect of initial combination therapy with metformin plus colesevelam on lipoprotein particles in patients with T2DM (secondary efficacy variables). Methods: This 16-week, randomized, double-blind, placebo-controlled study enrolled drug-naïve adults with T2DM, glycated hemoglobin 6.5%–10.0%, low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL, and triglycerides <500 mg/dL. Patients were randomized 1:1 to either open-label metformin (titrated to 1700 mg/day) plus double-blind colesevelam 3.75 g/day or open-label metformin plus double-blind placebo. Results: In total, 286 patients were randomized (metformin plus colesevelam [n = 145]; metformin plus placebo [n = 141]). Compared with metformin plus placebo, the combination of metformin plus colesevelam significantly reduced LDL-C (mean treatment difference: −16.3%), total cholesterol (−6.1%), non–high-density lipoprotein cholesterol (−8.3%), and apolipoprotein (apo) B (−8.0%) and significantly increased triglycerides (median treatment difference: 18.6%) and apoA-I (mean treatment difference: 4.4%; all P < .001). Metformin plus colesevelam significantly reduced total LDL-P (mean treatment difference: absolute change –186 nmol/L [percent change −11.7%]; both P < .0001), largely attributable to a reduction in small LDL-P, and increased total very-low-density lipoprotein particle concentration (mean treatment difference: absolute change 6 nmol/L; P = .03 [percent change 8.3%; P = .06]) and total high-density lipoprotein particle concentration (1.0 μmol/L; P = .03 [4.5%; P = .01]) versus metformin plus placebo. Conclusion: Initial combination therapy with metformin plus colesevelam improved the atherogenic lipoprotein profile of patients with early T2DM by significantly reducing LDL-P. ClinicalTrials.gov identifier: NCT00570739. [Copyright &y& Elsevier]

Background: Prescription omega-3-acid ethyl esters (P-OM3) often are used for hypertriglyceridemic patients receiving statin therapy who have residual increases in atherogenic lipoprotein lipid levels. To date, limited information has been published regarding the effects of omega-3 fatty acid consumption on lipoprotein particle concentrations. Objective: We evaluated the effects of adding P-OM3 4g/d to an ongoing regimen of simvastatin 40mg/d on lipoprotein particles (P) in subjects with hypertriglyceridemia. Methods: Data were analyzed from the multicenter, randomized, double-blind, placebo-controlled Combination of Prescription Omega-3s with Simvastatin (COMBOS) study. After an 8-week simvastatin lead-in, 254 subjects received P-OM3 (n=122) or placebo (n=132) for an additional 8 weeks. Nuclear magnetic resonance spectroscopy was used to assess lipoprotein concentrations and sizes. Remnant-like particle cholesterol, apolipoprotein (Apo) CIII, Apo AI, and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels also were measured. Results: Compared with placebo, P-OM3 reduced mean very-low-density lipoprotein (VLDL-P) size and increased low-density lipoprotein particle (LDL-P) size (P < .006 for both) without altering high-density lipoprotein particle (HDL-P) size. P-OM3 did not significantly change total VLDL-P or LDL-P concentrations relative to placebo, but large VLDL-P and intermediate-density lipoprotein particle (IDL-P) concentrations were lowered (P < .01 for both), and the large LDL-P concentration was increased (P < .0001). HDL-P concentration was reduced (P < .0001) as the result of a decrease in medium HDL-P. Remnant-like particle cholesterol, Apo CIII, and Lp-PLA2 concentrations were reduced compared with placebo (all P < .003). Conclusions: P-OM3 induces changes in sizes, concentrations, and compositions of lipoproteins that may have relevance for the atherothrombotic process. [Copyright &y& Elsevier]

Background: The Adult Treatment Panel III guideline recommends a low-density lipoprotein-cholesterol (LDL-C) goal of <100mg/dl for patients with coronary heart disease or risk equivalence (ie, other forms of atherosclerotic vascular disease [peripheral vascular disease, abdominal aortic aneurysm, cerebrovascular disease], diabetes). An optional LDL-C goal of <70mg/dl is recommended for patients considered “very high risk.” This category is not well defined, and clinical interpretation of this category varies. Methods: To define this category and to determine eligibility for an LDL-C goal of <70mg/dl, 5 definitions of “very high risk” were developed. Patients with coronary heart disease or risk equivalence within the University of Colorado Family Medicine system over the course of 2 years were identified using International Classification of Diseases, 9th Revision codes (n=445). Their medical records were evaluated retrospectively. Patients characterized as “very high risk” according to the 5 definitions were assessed for LDL-C <70mg/dl goal attainment. Results: Twenty-seven patients did not have LDL-C measurements and were excluded. Using the 5 definitions, we discovered that prevalence as “very high risk” was 10.8% (atherosclerotic vascular disease [AVD] plus smoking), 19.1% (AVD plus diabetes), 21.5% (AVD plus metabolic syndrome plus uncontrolled hypertension or smoking), 47.1% (AVD plus metabolic syndrome), and 67.2% (All AVD), P < .0001. LDL-C <70mg/dl was attained in 26.7%, 46.3%, 31.1%, 39.1%, and 35.2%, respectively (P =.13). Conclusion: Classifying patients as “very high risk” is highly variable depending on individual definitions, but this does not appear to alter the rates of attaining an LDL-C goal of <70mg/dl. When the Adult Treatment Panel IV guidelines are developed and issued, simplicity and clarity will be important in assisting clinicians in defining patient risk and developing LDL-C goals. [Copyright &y& Elsevier]

Abstract: Elevated low-density lipoprotein cholesterol (LDL-C) level in childhood is an increasing problem, mainly due to a rising prevalence secondary to the childhood obesity epidemic and better recognition and screening. Vascular changes and impaired endothelial function associated with elevated LDL-C are apparent even in early childhood. Secondary adiposity-related cases are at higher risk due to the clustering of risk factors besides overweight, such as the atherogenic lipid triad, change in the atherogenic properties of the LDL-C particle itself, and the presence of insulin resistance. Prevention should focus on maintaining a healthy lifestyle, including a restricted fat and cholesterol diet, encouraging physical activity, and decreasing sedentary pursuits to maintain an appropriate weight in children. For children and adolescents found to have elevated LDL-C, management should focus on the pursuit of a healthy lifestyle mirroring that for prevention for at least 6 months. Additional dietary therapy, such as plant stanol and sterol esters, have also been shown to modestly reduce LDL-C levels. If the adoption of a healthy lifestyle is not sufficient to reduce LDL-C, lipid-lowering drugs should be considered in selected patients. Current drugs of choice are statins and potentially ezetimibe. Long-term treatment with statins has been shown to markedly reduce carotid intima-media thickness in children and adolescents, particularly when started early. Current evidence supports early and efficient treatment for affected children. [Copyright &y& Elsevier]

Abstract: Background: Hypertensive African Americans have higher rates of coronary heart disease (CHD) than their non-Hispanic white counterparts, despite having higher high-density lipoprotein cholesterol (HDL-C) levels and lower triglyceride levels. Objective: The goal of the present study was to assess whether low-density lipoprotein (LDL) particle size, a correlate of the above lipid traits and a risk factor for CHD, differs between hypertensive African Americans and whites. Methods: Participants included 1,177 hypertensive African Americans from Jackson, MS (60 ± 7 years, 72.4% women) and 860 hypertensive whites from Rochester, MN (58 ± 7 years, 56.7% women). LDL particle size was measured by polyacrylamide gradient gel electrophoresis. Within each gender, we assessed whether ethnicity was significantly associated with differences in LDL particle size after adjustment for CHD risk factors (age, total cholesterol, HDL-C, triglycerides, systolic blood pressure, diabetes, history of smoking, body mass index), statin use, and estrogen use (in women), and lifestyle variables (physical activity and alcohol intake). Results: Although HDL-C levels were higher and triglyceride levels lower in African Americans, LDL particle size (adjusted for CHD risk factors) was lower (P < 0.0001) in African-American men and women than in their white counterparts (mean ± SD; men, 267.6 ± 5.2 Å vs 270.2 ± 4.8 Å; women 268.7 ± 5.1 Å vs 271.3 ± 5.1 Å). In both genders, African-American ethnicity was associated with lower LDL particle size after adjustment for CHD risk factors, statin use and estrogen use (in women), as well as physical activity and alcohol intake. Conclusion: Hypertensive African-American men and women have lower LDL particle size than their white counterparts, despite having higher HDL-C and lower triglycerides. [Copyright &y& Elsevier]

Proprotein convertase subtilisin/kexin type-9 inhibitors (PCSK9i) effectively reduce low-density lipoprotein cholesterol (LDL-C), improving cardiovascular outcomes in clinical trials when added to statin therapy. As real-world evidence is lacking, we aimed to evaluate treatment and adherence patterns using PCSK9i in clinical practice. We investigated 1600 patients initiating PCSK9i between January 2016 and December 2019 in a large health maintenance organization. Treatment discontinuation was defined as a gap ≥60 days between last days' supply of one prescription and the start of the next. Re-initiation rates as well as proportion of days covered (PDC) over 1-year period and attainment of lipid goals under PCSK9i, were analyzed. Evolocumab 140 mg was initiated by 50.7%, alirocumab 75 mg by 29.5% and 150 mg by 19.8%. Cumulative discontinuation rates were 28.1% after 6-months and 49.9% after 3-years. Overall, 58% of the patients that discontinued therapy have re-initiated PCSK9i (31% after 3-months from discontinuation). Mean PDC over 1-year of therapy was 56% ± 29, with PDC ≥80% evident in 29%. Of those with established cardiovascular disease (n = 991), 55% achieved LDL-C<70 mg/dL and 38% LDL-C<55 mg/dL. Attainment rates were lower in patients with PDC<80%, baseline LDL-C>190 mg/dL and in those not treated with concurrent statin therapy. In real-world practice of patients treated by PCSK9i, high proportion of early treatment discontinuation was evident, with non-negligible re-initiation rates but overall low medication coverage over time. This have contributed to sub-optimal attainment of LDL-C treatment goals, particularly observed in patients with severe hypercholesterolemia, inadequate drug adherence, and those using PCSK9i as monotherapy. • We evaluated real-world treatment and adherence patterns with PCSK9 inhibitors. • High proportion of early treatment discontinuation was evident (28% over 6-months). • Non-negligible re-initiation rates, but overall low medication coverage over time. • PCSK9 inhibitors often used as monotherapy, with decline in concurrent statin therapy. • Treatment/adherence patterns led to sub-optimal attainment of lipid treatment goals. [ABSTRACT FROM AUTHOR]

Background Hypercholesterolemia is one of the modifiable risk factors for atherosclerosis and cardiovascular diseases. Prevention and treatment of hypercholesterolemia and other lipid abnormalities require reliable data regarding the current prevalence of these abnormalities in the country. Objective This study aims to determine the current prevalence, awareness, and treatment of lipid abnormalities in Iran. Methods We planned to recruit 31,050 individuals who are 18 years old and above and take blood samples from individuals who are 25 years and above as representative sample at national and provincial levels in 2016. In practice, we recruited 21,293 Iranian adult aged more than 25 years through a systematic random sampling from 30 provinces of Iran. Sociodemographic, anthropometric, and lifestyle data and history of cardiometabolic diseases were gathered. Serum total cholesterol, high-density lipoprotein-cholesterol (HDL-C), triglyceride, low-density lipoprotein-cholesterol (LDL-C), and non–HDL-C were investigated. The prevalence of lipid abnormalities, awareness, treatment, and achievement to non–HDL-C and LDL-C goals were determined based on National Cholesterol Education Program Adult Treatment Panel III criteria. Results In this representative Iranian adult population, 80.0% had at least one lipid abnormality, 69.2% had low HDL-C, 39.5% had high non–HDL-C, 28.0% had hypertriglyceridemia, and 26.7% hypercholesterolemia. Of those with hypercholesterolemia, 74.2% were aware of their lipid abnormality. Only 22.0% and 36.5% of the study population met the desired level of non–HDL-C and LDL-C, respectively. Conclusion Low HDL-C is the main lipid abnormality in adult Iranian population. The majority of the population did not meet the desired level of non–HDL-C and LDL-C. Public health preventive policies should be made and implemented to better manage dyslipidemia. Highlights • Low high-density lipoprotein-cholesterol is the main lipid abnormality in adult Iranian population. • Eighty percent of the Iranian adult population had at least one lipid abnormality. • Of those with hypercholesterolemia, 74.2% were aware of their lipid abnormality. • The majority of the population did not meet the desired level of non–high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol. [ABSTRACT FROM AUTHOR]

Background Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. Objective We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)–containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. Methods Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days. Results Reduction in low-density lipoprotein (LDL) cholesterol, ApoB, and triglycerides (TGs) was essentially complete at 42 days (–38%, –32%, and –35%, respectively); rapid reduction equally occurred in remnant cholesterol, ApoCII, CIII, and E levels (day 6; –35%, –50%, –23%, and –26%, respectively). Small dense LDLs (LDL4 and LDL5 subpopulations) predominated at baseline and were markedly reduced on treatment (–29% vs total LDL mass). Cholesteryl ester (CE) transfer protein activity and mass decreased progressively (–18% and –16%, respectively); concomitantly, TG depletion (up to –49%) and CE enrichment occurred in all high-density lipoprotein (HDL) particle subpopulations with normalization of CE/TG mass ratio at 180 days. ApoAI was redistributed from LpAI to LpAI:AII particles in HDL2a and HDL3a subpopulations; ApoCIII was preferentially depleted from LpAI:AII–rich particles on treatment. Conclusion Overall, statin action exhibits duality in mixed dyslipidemia, as CE transfer protein–mediated normalization of the HDL CE/TG core lags markedly behind subacute reduction in elevated levels of atherogenic ApoB-containing lipoproteins. Normalization of the HDL neutral lipid core is consistent with enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic marker of perturbed HDL metabolism in insulin-resistant states, equally allowing monitoring of statin impact on HDL metabolism, structure, and function. [ABSTRACT FROM AUTHOR]