Changes In Low-density Lipoprotein Cholesterol Research Articles

BMI modifies the effect of dietary fat on atherogenic lipids: a randomized clinical trial

SFA intake increases LDL cholesterol whereas PUFA intake lowers it. Whether the lipid response to dietary fat differs between normal-weight and obese persons is of relevance to dietary recommendations for obese populations. We compared the effect of substituting unsaturated fat for saturated fat on LDL cholesterol and apoB concentrations in normal-weight (BMI ≤25 kg/m2) and obese (BMI: 30-45) subjects with elevated LDL cholesterol. We randomly assigned 83 men and women (aged 21-70 y) stratified by BMI (normal: n=44; obese: n=39) and elevated LDL cholesterol (mean ± SD, normal weight 4.6 ± 0.9 mmol/L; obese 4.4 ± 0.8 mmol/L) to either a PUFA diet enriched with oil-based margarine ( n=42) or an SFA diet enriched with butter (n=41) for 6 wk. Seven-day dietary records showed differences of ∼9 energy percent (E%) in SFA and ∼4 E% in PUFA between the SFA and PUFA groups. In the total study population, the PUFA diet compared with the SFA diet lowered LDL cholesterol (-0.31 mmol/L; 95% CI: -0.47, -0.15 mmol/L, compared with 0.32 mmol/L; 95% CI: 0.18, 0.47 mmol/L; P<0.001) and apoB (-0.08 g/L; 95% CI: -0.11, -0.05 g/L, compared with 0.07 g/L; 95% CI: 0.03, 0.10 g/L; P<0.001). Tests of the BMI × diet interaction were significant for total cholesterol, LDL cholesterol, and apoB ( P values≤0.009). In normal-weight compared with obese participants post-hoc comparisons found that the respective changes in LDL cholesterol were 9.7% (95% CI: 5.3%, 14.2%) compared with 5.3% (95% CI: -0.7%, 11.2%), P=0.206, in the SFA group, and -10.4% (95% CI: -15.2%, -5.7%) compared with -2.3% (95% CI: -7.4%, 2.8%), P=0.020, in the PUFA group. ApoB changes were 7.5% (95% CI: 3.5%, 11.4%) compared with 3.0% (95% CI: -1.7%, 7.7%), P=0.140, in the SFA group, and -8.9% (95% CI: -12.6%, -5.2%) compared with -3.8% (95% CI: -6.3%, -1.2%), P=0.021, in the PUFA group. Responses to dietary fat were not associated with changes in polyprotein convertase subtisilin/kexin type 9 concentrations. BMI modifies the effect of PUFAs compared with SFAs, with smaller improvements in atherogenic lipid concentrations in obese than in normal-weight individuals, possibly supporting adjustment of dietary recommendations according to BMI. This trial was registered with www.clinicaltrials.gov as NCT02589769.

Randomized Evaluation of Anagliptin vs Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) Trial: A 52-week, open-label, randomized clinical trial

Additional reductions in low-density lipoprotein-cholesterol (LDL-C) via antidiabetic therapies should be considered in statin-using patients with sub-optimal LDL-C levels. We compared the efficacy of anagliptin and sitagliptin, two antidiabetic therapies, in reducing LDL-C in type 2 diabetic patients. A randomized, open-label, parallel-group trial was conducted at 17 centres in Japan between April 2015 and January 2018. Adults (age ≥20 years) with type 2 diabetes, any atherosclerotic vascular lesions, and statin prescriptions were included. Anagliptin or sitagliptin were administered for 52 weeks. Primary and secondary endpoints were changes in LDL-C and haemoglobin A1C (HbA1c) levels, respectively. We assessed the superiority (primary endpoint) and non-inferiority (secondary endpoint) of anagliptin over sitagliptin. This study was registered at Clinicaltrials.gov (NCT02330406). Of 380 participants, 353 were eligible and randomized. Mean participant age was 68 years, and 61% were males. Baseline median LDL-C and HbA1c were 108 mg/dL and 6.9%, respectively. Changes in LDL-C were −3.7 mg/dL with anagliptin and +2.1 mg/dL with sitagliptin at 52 weeks, and the estimated treatment difference was a significant −4.5 mg/dL (P = 0.01 for superiority). Changes in HbA1c were +0.02% with anagliptin and +0.12% with sitagliptin (P < 0.0001 for non-inferiority). Overall, anagliptin was superior to sitagliptin in lowering LDL-C without deteriorating HbA1c.

Lipoprotein(a) reductions from PCSK9 inhibition and major adverse cardiovascular events: Pooled analysis of alirocumab phase 3 trials

Background and aimsElevated lipoprotein(a) [Lp(a)] levels are considered a causal factor for cardiovascular disease. In phase 3 ODYSSEY trials, alirocumab reduced levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a), with concomitant reductions in the risk of major adverse cardiovascular events (MACE). We assessed whether lower on-study and greater percentage reductions in Lp(a) are associated with a lower risk of MACE. MethodsPost-hoc analysis of data pooled from 10 phase 3 ODYSSEY trials comparing alirocumab with control (placebo or ezetimibe) in patients (n = 4983) with cardiovascular disease and/or risk factors, and hypercholesterolemia despite statin/other lipid-lowering therapies. ResultsMedian (Q1, Q3) baseline Lp(a) levels were 23.5 (8.0, 67.0) mg/dL. Median Lp(a) changes from baseline with alirocumab were −25.6% vs. −2.5% with placebo (absolute reductions 6.8 vs. 0.5 mg/dL) in placebo-controlled trials, and −21.4% vs. 0.0% with ezetimibe (4.5 vs. 0.0 mg/dL) in ezetimibe-controlled trials. During follow-up (6699 patient-years), 104 patients experienced MACE. A 12% relative risk reduction in MACE per 25% reduction in Lp(a) (p=0.0254) was no longer significant after adjustment for LDL-C changes: hazard ratio per 25% reduction: 0.89 (95% confidence interval, 0.79–1.01; p=0.0780). In subgroup analysis, the association between Lp(a) reduction and MACE remained significant in a fully adjusted model among participants with baseline Lp(a) ≥50 mg/dL (p-interaction vs. Lp(a) < 50 mg/dL: 0.0549). ConclusionsIn this population, Lp(a) reductions were not significantly associated with MACE independently of LDL-C reductions. Reducing the risk of MACE by targeting Lp(a) may require greater reductions in Lp(a) with more potent therapies and/or higher initial Lp(a) levels.

Differences in Response to Egg Intake Result in Distinct Lipoprotein Profiles While Plasma Concentrations of Carotenoids and Choline Are Not Affected (P08-102-19)

ObjectivesIt has been demonstrated that some individuals (approximately 1/3 of the population) can be classified as hyper-responders to dietary cholesterol. The objective of this study was to evaluate whether the response to dietary cholesterol (provided by eggs) would affect lipoprotein metabolism and the bioavailability of lutein, zeaxanthin and choline, nutritional components present in eggs. MethodsWe recruited 36 healthy subjects who underwent a two-week washout period in which they consumed zero eggs. Participants were then fed 3 eggs (540 additional mg of dietary cholesterol) for 4 weeks. Plasma lipids were measured by use of an automated chemical clinical analyzer; the number of large and small LDL and HDL particles were measured by Nuclear Magnetic Resonance. Plasma lutein and zeaxanthin were determined by use of HPLC and plasma choline by use of LSM spectroscopy. We classified the normal response to dietary cholesterol as 2.2 mg/dL for each additional 100 mg of dietary cholesterol. Therefore, those individuals who had >12 mg/dL increase in plasma cholesterol after the intervention (n = 12) were considered hyper-responders while the other 24 subjects who presented changes in plasma cholesterol ranging from −16 to 9 mg/dL were considered hypo-responders. ResultsCompared to zero eggs, hyper-responders had significant increases in plasma total, LDL and HDL cholesterol (P < 0.001) with no changes in the LDL/HDL ratio. They also had higher concentrations of large LDL (P < 0.01) with no changes in small LDL. In contrast no changes in plasma total LDL or HDL cholesterol or large LDL were observed in hypo-responders after the consumption of 3 eggs/day. Interestingly, both hypo and hyper-responders had significant increases in large HDL particles (12%), plasma lutein (17%), zeaxanthin (30%) and choline (12%) (P < 0.001) compared to zero egg intake. ConclusionsThese results suggest that egg intake increases the bioavailability of carotenoids and choline present in eggs independently of plasma cholesterol response to dietary cholesterol. Further, the observed increases in large HDL in all individuals could be associated with HDL being a major transporter of lutein and zeaxanthin in plasma. Funding SourcesThe Esperance Family and the Egg Nutrition Center.

Changes in Serum Lipids from Egg Consumption Are Associated with Clinical Erythrocyte Indices (P08-093-19)

ObjectivesSerum lipids may influence the lifespan of erythrocytes, and have been associated with clinical erythrocyte indices at the population level. Consumption of whole eggs vs. egg whites exerts varying effects on serum lipids and lipoprotein profiles; therefore, we investigated whether egg-induced changes in serum lipids correspond to changes in clinical erythrocyte markers. MethodsYoung, healthy men and women (18–35y, BMI < 30 kg/m2, n = 11) were recruited to participate in an ongoing intervention trial. All subjects followed an egg-free diet for 4 weeks, then were randomized to consume either 3 whole eggs or 3 egg whites per day for 4 weeks. Fasting serum lipids, complete blood cell counts, and dietary intake analysis was performed at the end of each study period. ResultsAverage serum lipids and erythrocyte indices were within normal ranges at the end of each diet period. Changes in total cholesterol following the whole egg (+4.8%) and egg white (0.4%) diet period were not significant as compared to the egg-free diet period. Similarly, clinical erythrocyte markers were not significantly altered by daily consumption of whole eggs or egg whites. However, changes in total cholesterol and LDL-cholesterol between diet periods were positively correlated with changes in total red blood cell counts and hemoglobin. Total cholesterol was additionally correlated with hematocrit levels, and negatively associated with red cell distribution width. Total red blood cell counts and hemoglobin were further correlated with changes in the total cholesterol to HDL-cholesterol ratios, but not HDL-cholesterol alone. ConclusionsOur findings indicate that egg-induced changes in serum lipids are associated with clinical erythrocyte indices, and that total cholesterol levels and dyslipidemia may be more significant determinants of erythrocyte profiles. Funding SourcesThis study was funded by an Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture.

Egg-induced Changes in Serum Lipids Are Associated with Clinical Immune Cell Counts (OR12-04-19)

ObjectivesWe have previously demonstrated that serum lipids can predict clinical immune cell counts at the population level; however, it is unknown whether diet-induced changes in serum lipids correspond to similar shifts in clinical blood cell counts. We hypothesized that whole egg vs. egg white consumption, which is known to differentially affect lipoprotein profiles and inflammatory markers, would induce shifts in clinical immune cells counts that are associated with changes in serum lipids. MethodsIn this ongoing study, healthy men and women (18–35y, BMI < 30 kg/m2, n = 11) consumed an egg-free diet for 4 weeks, followed by a 4-week diet containing either 3 whole eggs or 3 egg whites per day. Fasting serum lipids and complete blood cell counts were measured at the end of each diet period. ResultsFollowing the egg-free diet period, individuals with higher total cholesterol levels had greater absolute lymphocyte counts, and a trend toward greater absolute eosinophils counts. While no significant changes in total cholesterol or LDL-cholesterol were observed between diet periods, HDL-cholesterol was increased in subjects consuming whole eggs only. Similarly, serum triglycerides, alanine aminotransferase, and platelet counts were only decreased by whole egg intake. Interestingly, while egg intake did not alter total white blood counts, there was a trend toward decreased absolute lymphocyte counts in all subjects following consumption of both whole eggs and egg whites, as compared to the egg-free diet period. Across all subjects, a strong positive correlation was observed between changes in HDL-cholesterol vs. changes in absolute monocytes, as well as the percentage of monocytes in total white blood cell counts. Changes in triglycerides were negatively associated with changes in eosinophil levels. ConclusionsThese findings suggest that egg-induced changes in serum lipids are associated with differential shifts in clinical immune cell counts. Funding SourcesThis study was funded by an Agriculture and Food Research Initiative Grant from the USDA National Institute of Food and Agriculture.

636-P: Effect of Obesity and Weight Variations on the Decline of Ankle-Brachial Index in Type 2 Diabetes Subjects without Peripheral Artery Disease

Object: There are very few studies that evaluate the influence of obesity and weight variations on change in ankle-brachial index (ABI) in subjects with type 2 diabetes (T2D) but without peripheral artery disease (PAD). Methods: In this case-control study, T2D subjects who were without baseline PAD (0.9 ≤ ABI &amp;lt; 1.4), and received minimum 2-year interval ABI exams were included. Subjects with prior diagnosed or treated PAD were excluded. Baseline body mass index (BMI) of all subjects was categorized as normal weight (&amp;lt; 23 kg/m2), overweight (23∼25 kg/m2), and obesity (≥ 25 kg/m2). Weight changes during follow-up were categorized by the percentage of weight change; weight loss (&amp;lt; -3%), stable (-3∼3%), gain (&amp;gt; 3%). Subjects with ABI decline were defined as one or both legs worsened to the abnormal (ABI &amp;lt; 0.9) at follow-up exam. Results: A total of 575 subjects were analyzed (188 normal, 140 overweight, and 245 obesity). During the median 2.9 years of follow-up period, 122 (21.2%) subjects showed ABI decline. When split by category of BMI and weight change, the incidence rate of ABI decline showed stepwise increasing pattern according to the obesity and weight gain. Multivariable logistic regression analysis showed that baseline obesity (vs. normal) was significantly associated with the risk of developing ABI decline after adjusting for age, sex, smoking, diabetes duration, mean HbA1c, GFR, LDL cholesterol, blood pressure, hypertensive medication, insulin use, statin use, antiplatelet use, and weight change (OR = 2.06, 95% CI = 1.22 - 3.49). On the contrary, weight loss was significantly associated with reduction in risk of developing ABI decline (OR = 0.52, 95% CI = 0.31 - 0.86). Conclusion: Obesity is an independent risk factor for developing ABI decline in T2D subjects without PAD, whereas weight loss is an independent protective factor. Weight loss should be emphasized especially in obese subjects with T2D. Disclosure Y. Yang: None. J. Lim: None. E. Lee: None. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. B. Cha: None. S. Lee: None. Y. Cho: None.

Daily consumption of caper fruit along with atorvastatin has synergistic effects in hyperlipidemic patients: Randomized clinical trial

Background: Dyslipidemia leads to micro- and macro-vascular complications. Atorvastatin is the main therapeutic drug used for dyslipidemia, but it causes side effects such as new type 2 diabetes mellitus onset and elevation of liver enzymes. Herbs may be useful in reducing atorvastatin doses. Caper fruit, an herbal drug in Iranian traditional medicine, has hypolipidemic effects. Hence, the effect of atorvastatin therapy with and without daily caper fruit pickle (CFP) consumption was assessed on hyperlipidemia. Materials and Methods: In this single-blinded, randomized, controlled trial, 60 hyperlipidemic patients were allocated in two groups and treated with 10 mg atorvastatin plus 40-50 g CFP (A10+CFP) or atorvastatin alone (A10) for eight weeks. Biochemical parameters were measured at baseline, 4, and eight weeks of the intervention. One-way repeated measure ANOVA and mixed ANOVA were used to measure the effect of the two treatments and the interaction between the type of treatment and time on lipid profile. Results: Serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the A10+CFP group compared with the A10 group (P&lt;0.001 and P&lt;0.001, respectively) from baseline up to the week 8. At week 4, mean changes of LDL-C was significantly higher in the A10+CFP compared with the A10 (P=.01). Adjusting for the baseline variables, the mean difference of alanine aminotransferase (P&lt;0.01) and triglyceride (P=.003) were significantly higher in the A10+CFP group at the end. Conclusion: This study reports that the intake of CFP along with atorvastatin daily may have synergistic effects which improve the lipid profile in hyperlipidemic patients. [GMJ.2019;8:e1345]

Daily Consumption of Caper Fruit Along With Atorvastatin Has Synergistic Effects in Hyperlipidemic Patients: Randomized Clinical Trial.

Background: Dyslipidemia leads to micro- and macro-vascular complications. Atorvastatin is the main therapeutic drug used for dyslipidemia, but it causes side effects such as new type 2 diabetes mellitus onset and elevation of liver enzymes. Herbs may be useful in reducing atorvastatin doses. Caper fruit, an herbal drug in Persian Medicine, has hypolipidemic effects. Hence, the effect of atorvastatin therapy with and without daily caper fruit pickle (CFP) consumption was assessed on hyperlipidemia. Materials and Methods: In this single-blinded, randomized, controlled trial, 60 hyperlipidemic patients were allocated in two groups and treated with 10 mg atorvastatin plus 40-50 g CFP (A10+CFP) or atorvastatin alone (A10) for eight weeks. Biochemical parameters were measured at baseline, 4, and eight weeks of the intervention. One-way repeated measure ANOVA and mixed ANOVA were used to measure the effect of the two treatments and the interaction between the type of treatment and time on lipid profile. Results: Serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the A10+CFP group compared with the A10 group (P<0.001 and P<0.001, respectively) from baseline up to the week 8. At week 4, mean changes of LDL-C was significantly higher in the A10+CFP compared with the A10 (P=0.01). Adjusting for the baseline variables, the mean difference of alanine aminotransferase (P<0.01) and triglyceride (P=0.003) were significantly higher in the A10+CFP group at the end. Conclusion: This study reports that the intake of CFP along with atorvastatin daily may have synergistic effects which improve the lipid profile in hyperlipidemic patients.

Current trends in non–HDL cholesterol and LDL cholesterol levels in adults with atherosclerotic cardiovascular disease

Low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are targets for prevention of atherosclerotic cardiovascular disease (ASCVD). The American Heart Association and American College of Cardiology recently modified recommendations for clinical management of cholesterol in secondary and primary prevention. Accordingly, the present article examines the need for cholesterol-lowering drugs in the U.S. population with ASCVD. This study examines trends in non-HDL-C and LDL-C levels in a free living population of ASCVD subjects between 1999 and2016. National Health and Nutrition Examination Surveys database included 4920 adults with ASCVD aged 40 to 85years. Complete data were available for 4226. Trend analysis of changes in lipids is shown in box plots. Mean age was 67years with 57% males. Over 17 years, LDL-C decreased significantly by 24% and non-HDL-C by 21%. Over the period of study, reported intake of cholesterol-lowering drugs rose from 37% in 1999-2000 to 69% in 2015 to 2016. Over this same period, serum triglycerides decreased by 29% (P<.001) and HDL-C rose by 6%. The changes in LDL-C and non-HDL-C in patients with ASCVD over a 17-year period probably are related to increased treatment with statins. However, the changes are too small to be explained by widespread use of high-intensity statins, which is the current recommendation for patients with ASCVD. These findings pose a challenge for professional education to support implementation of current guidelines for cholesterol-lowering therapies.

Daily consumption of caper fruit along with atorvastatin has synergistic effects in hyperlipidemic patients: Randomized clinical trial

Background: Dyslipidemia leads to micro- and macro-vascular complications. Atorvastatin is the main therapeutic drug used for dyslipidemia, but it causes side effects such as new type 2 diabetes mellitus onset and elevation of liver enzymes. Herbs may be useful in reducing atorvastatin doses. Caper fruit, an herbal drug in Iranian traditional medicine, has hypolipidemic effects. Hence, the effect of atorvastatin therapy with and without daily caper fruit pickle (CFP) consumption was assessed on hyperlipidemia. Materials and Methods: In this single-blinded, randomized, controlled trial, 60 hyperlipidemic patients were allocated in two groups and treated with 10 mg atorvastatin plus 40-50 g CFP (A10+CFP) or atorvastatin alone (A10) for eight weeks. Biochemical parameters were measured at baseline, 4, and eight weeks of the intervention. One-way repeated measure ANOVA and mixed ANOVA were used to measure the effect of the two treatments and the interaction between the type of treatment and time on lipid profile. Results: Serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the A10+CFP group compared with the A10 group (P&lt;0.001 and P&lt;0.001, respectively) from baseline up to the week 8. At week 4, mean changes of LDL-C was significantly higher in the A10+CFP compared with the A10 (P=.01). Adjusting for the baseline variables, the mean difference of alanine aminotransferase (P&lt;0.01) and triglyceride (P=.003) were significantly higher in the A10+CFP group at the end. Conclusion: This study reports that the intake of CFP along with atorvastatin daily may have synergistic effects which improve the lipid profile in hyperlipidemic patients. [GMJ.2019;8:e1345]

Physical Activity Improves Lipid and Weight-Loss Outcomes After Metabolic Bariatric Surgery in Adolescents with Severe Obesity.

Objective:To test the hypothesis that Physical Activity (PA) improves cardiovascular disease (CVD)-related lipids beyond that associated with weight loss in adolescents with severe obesity, post-metabolic bariatric surgery (MBS).Methods:We used objective StepWatch™ PA data from 108 participants of the Teen Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study from baseline to 3 years post-MBS. Primary outcomes included absolute change in low density lipoprotein (LDL-C) and non-high density lipoprotein (non-HDL-C) from baseline. We adjusted for baseline measurement, visit, surgical procedure, and percent change in iliac waist circumference (IWC) or body mass index (BMI) from baseline in linear regression models using generalized estimating equations. PROC TRAJ in SAS generated optimal activity trajectories based on individual step count.Results:Despite low step counts and slow cadence, differences by activity trajectory were found. Greater absolute decreases in LDL-C and non-HDL-C (−15 mg/dL [95% CI: (−28, −2)], p =0.026 and −15 mg/dL [95% CI: (−28, −1)], p = 0.035), respectively, were associated with more activity (MA). MA was associated with greater resolution of triglycerides, LDL-C and non-HDL-C dyslipidemia and with greater weight loss 3 years post-MBS.Conclusion:More activity in adolescents was associated with improvements in CVD-related lipid measures and weight loss, post-MBS.

Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat—a randomized controlled dietary intervention study

ABSTRACTBackgroundReplacing dietary saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFA) reduces the plasma low-density lipoprotein (LDL) cholesterol and subsequently the risk of cardiovascular disease. However, beyond changes in LDL cholesterol, we lack a complete understanding of the physiologic alterations that occur when improving dietary fat quality.ObjectivesThe aim of this study was to gain knowledge of metabolic alterations paralleling improvements in the fat quality of the diet.MethodsWe recently conducted an 8-wk, double-blind, randomized controlled trial replacing SFAs with PUFAs in healthy subjects with moderate hypercholesterolemia (n = 99). In the present substudy, we performed comprehensive metabolic profiling with multiple platforms (both nuclear magnetic resonance- and mass spectrometry-based technology) (n = 99), and analyzed peripheral blood mononuclear cell gene expression (n = 95) by quantitative real-time polymerase chain reaction.ResultsA large number of lipoprotein subclasses, myristoylcarnitine and palmitoylcarnitine, and kynurenine were reduced when SFAs were replaced with PUFAs. In contrast, bile acids, proprotein convertase subtilisin/kexin type 9, acetate, and acetoacetate were increased by the intervention. Some amino acids were also altered by the intervention. The mRNA levels of LXRA and LDLR were increased, in addition to several liver X receptor α target genes and genes involved in inflammation, whereas the mRNA levels of UCP2 and PPARD were decreased in peripheral blood mononuclear cells after replacing SFAs with PUFAs. Partial least squares-discriminant analysis showed that the 30 most important variables that contributed to class separation spanned all classes of biomarkers, and was in accordance with the univariate analysis.ConclusionsApplying metabolomics in randomized controlled dietary intervention trials has the potential to extend our knowledge of the biological and molecular effects of dietary fat quality. This study was registered at clinicaltrials.gov as NCT 01679496.

A lost decade: No Meaningful Changes in LDL Cholesterol in the United States, 2008-2017: Insights from a National Reference Laboratory

A lost decade: No Meaningful Changes in LDL Cholesterol in the United States, 2008-2017: Insights from a National Reference Laboratory

Long-Term Treatment With Evolocumab Among Japanese Patients - Final Report of the OSLER Open-Label Extension Studies.

Treatment with evolocumab reduces mean low-density lipoprotein cholesterol (LDL-C) up to 75% and cardiovascular events by 16% in the first year and 25% thereafter. Methods and Results: Japanese patients with hypercholesterolemia enrolled in the parent YUKAWA-1-2 studies could enroll, once eligible, in the OSLER studies (n=556). OSLER re-randomized patients 2:1 to evolocumab plus standard of care (SOC; evolocumab+SOC) or SOC alone for 1 year; after year 1, patients could enter the all-evolocumab+SOC open-label extension of OSLER. Patients received evolocumab+SOC from the 2nd year through up to 5 years. Long-term efficacy and safety, including antidrug antibodies, were evaluated. Of 556 patients, 532 continued to the all-evolocumab+SOC extension: mean (standard deviation [SD]) age 61 (10) years, 39% female. A total of 91% of 532 patients completed the studies. Mean (SD) LDL-C change from parent-study baseline with evolocumab from a mean (SD) baseline of 142.3 (21.3) and 105.0 (31.1) mg/dL in OSLER-1 and OSLER-2, respectively, was maintained through the end of the study: -58.0% (19.1%) at year 5 in OSLER-1, -62.7% (25.6%) at year 3 in OSLER-2. The overall safety profile of the evolocumab+SOC periods was similar to that of the year-1 controlled period. Antidrug antibodies were detected transiently in 3 patients. No neutralizing antibodies were detected. Japanese patients who continued evolocumab+SOC for up to 5 years experienced sustained high LDL-C level reduction. Long-term evolocumab+SOC exposure showed no new safety signals.

MON-196 Gender-Affirming Hormonal Therapy and Incidence of Metabolic Syndrome and Cardiovascular Events in Patients with Gender Dysphoria

Background: Long-term effects of gender-affirming hormonal therapy (GAHT) on cardiovascular risk factors and metabolic syndrome (MS) is currently unclear. Particularly, the effect of GAHT on cardiovascular outcomes in older individuals (>60 years) with gender dysphoria (GD) is unknown. The aim of this study was to examine the effect of GAHT on cardiovascular risk factors, MS and the incidence of T2DM in subjects with GD. Methods: We reviewed the records of 75 subjects with GD, 54 transwomen (age 49 ± 2 years) and 21 transmen (age 37 ± 2 years), who had a detailed clinical, biochemical and hormonal profile (lipid profile, HbA1C, FPG, testosterone, estradiol) of which 55 were followed for at least 1 year. MS was defined based on ATP III criteria. As a control group, we reviewed the records of 30 subjects without GD who attended the endocrinology clinic for other hormone-related disorders. Results: The median (IR) follow-up was 22 (11-39) months for transwomen and 15 (11-21) months for transmen. In transwomen plasma testosterone levels decreased (379 ± 31 vs 71 ± 18 ng/dL), estradiol increased (40 ± 7 vs 124 ± 34 pg/mL) while the plasma testosterone levels increased in transmen (57 ± 14 vs 411 ± 79 ng/dL). At baseline, 24% of transwomen had MS and after 1 year, 16% of subjects had MS. In transmen, the prevalence of MS was similar before and 1 year after treatment (25 % vs. 24%). In transwomen, GAHT was associated with mild weight gain, BMI increased (29 ± 1 vs. 30 ± 1 kg/m2, p=0.04). There was no difference in HDL, total cholesterol and triglyceride levels before and after hormone therapy, though LDL cholesterol tended to decrease (101 ± 6 vs. 90 ± 6 mg/dL, p=0.06). There was no change in HbA1C, FPG or SBP in transwomen, though DBP decreased (77 ± 1 vs. 74 ± 1 mmHg, p=0.05). In transmen, no changes were observed in BMI, HDL, total cholesterol, triglycerides, LDL, HbA1C, FPG and blood pressure. There were no new cases of T2DM, however 1 transman developed MS, 1 transman had CABG and 1 transwoman died from laryngeal cancer. There were no new cases of myocardial infarction or stroke in subjects with and without GD. For subjects above 60 years (n=16, 13 transwomen and 3 transmen), BMI in transwomen increased (27 ± 1 vs. 29 ± 2 kg/m2, p=0.03), there was no change in HDL, LDL and total cholesterol, triglycerides, HbA1C, FPG or blood pressure. In 3 transmen older than 60 years old, only the LDL decreased (194 ± 59 vs. 141 ± 55 mg/dL, p=0.006). In the entire group as well as older individuals with GD the incidence of CV events were not different from the control group. Conclusion: GAHT for 1.5 years was not associated with worsening cardiovascular risk factors, metabolic syndrome or incidence of T2DM in both transmen and transwomen regardless of their age. Long-term studies are required to assess the definite effects of GAHT on cardiovascular outcomes.

Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial.

AimThe aim of this study was to evaluate the efficacy and safety of evolocumab with background atorvastatin in Chinese patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia.Materials and methodsThis is a pre‐specified analysis of patients in the BERSON study (ClinicalTrials.gov, NCT02662569) in China. Patients initiated background atorvastatin 20 mg/d, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Co‐primary endpoints were percentage change in LDL cholesterol (LDL‐C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures and adverse events (AEs).ResultsAmong 453 patients randomized in China, 451 received at least one dose of study drug (evolocumab or placebo). Evolocumab significantly reduced LDL‐C compared with placebo at week 12 (Q2W, −85.0%; QM, −74.8%) and at the mean of weeks 10 and 12 (Q2W, −80.4%; QM, −81.0%) (adjusted P < 0.0001 for all) when administered with background atorvastatin. Non‐HDL‐C, ApoB100, total cholesterol, Lp(a), triglycerides, HDL‐C and VLDL‐C significantly improved with evolocumab vs placebo. No new safety findings were observed with evolocumab. The incidence of diabetes AEs was higher with evolocumab compared with placebo. There were no differences over time between evolocumab and placebo in measures of glycaemic control.ConclusionsIn patients in China with T2DM and hyperlipidaemia or mixed dyslipidaemia receiving background atorvastatin, evolocumab significantly reduced LDL‐C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Residential greenness and blood lipids in urban-dwelling adults: The 33 Communities Chinese Health Study

While exposure to places with higher greenness shows health benefits, evidence is scarce on its lipidemic effects. We assessed the associations between residential greenness and blood lipids and effect mediations by air pollution, physical activity, and adiposity in China. Our study included 15,477 adults from the population-based 33 Communities Chinese Health Study, conducted between April and December 2009, in Northeastern China. We measured total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Residential greenness was estimated using two satellite-derived vegetation indices – the Normalized Difference Vegetation Index (NDVI) and the Soil Adjusted Vegetation Index (SAVI). We used both nitrogen dioxide (NO2) and particles ≤2.5 μm in aerodynamic diameter (PM2.5) as proxies of outdoor air pollution. Associations were assessed using linear mixed effects regression models and logistic mixed effects regression models, and mediation analyses were also performed. Living in higher greenness areas was consistently associated with lower TC, TG, and LDL-C levels and higher HDL-C levels (e.g., change in TC, TG, LDL-C, and HDL-C per 0.1-unit increase in NDVI500-m was −1.52%, −3.05%, −1.91%, and 0.52%, respectively). Similar results were obtained for the corresponding dyslipidemias. These associations were generally stronger in women and older adults. While educational levels showed effect modifications, the effect pattern was inconsistent. Both outdoor air pollution and body mass index mediated 9.1–62.3% and 5.6–40.1% of the associations for greenness and blood lipids, respectively, however, physical activity did not. Our results suggest beneficial associations between residing in places with higher greenness and blood lipid levels, especially in women and the elder individuals. The associations were partly mediated by lower air pollution and adiposity.

Effect of Text Messaging on Risk Factor Management in Patients With Coronary Heart Disease: The CHAT Randomized Clinical Trial

Mobile health technologies are low cost, scalable interventions with the potential to promote patient engagement and behavior change. We aimed to test whether a culturally sensitive text messaging intervention supporting secondary prevention improves the control of risk factors in patients with coronary heart disease in China. In this multicenter, single-blinded randomized controlled trial, 822 patients (mean age, 56.4 [SD, 9.5] years; 14.1% women) with coronary heart disease and without diabetes mellitus from 37 hospitals in China were enrolled between August 2016 and March 2017. In addition to usual care, the control group (n=411) received 2 thank you messages/month; the intervention group (n=411) received 6 text messages/week for 6 months delivered by an automated computerized system. The messages provided educational and motivational information related to disease-specific knowledge, risk factor control, physical activity, and medication adherence. The primary end point was change in systolic blood pressure from baseline to 6 months. Secondary end points included the proportion with systolic blood pressure <140 mm Hg, smoking status, and change in body mass index, LDL-C (low-density lipoprotein cholesterol), and physical activity (assessed using the International Physical Activity Questionnaire). The end points were assessed using analyses of covariance. Follow-up was 99.6%. At 6 months, systolic blood pressure was not significantly lower in the intervention group compared with the control group, with a mean change (SD) of 3.2 (14.3) mm Hg and 2.0 (15.0) mm Hg ( P>0.05) from baseline, respectively (mean net change, -1.3 mm Hg [95% CI, -3.3 to 0.8]; P=0.221). There were no significant differences in the change in LDL-C level, physical activity, body mass index, or smoking status between the 2 groups. Nearly all patients in the intervention group reported the text messages to be useful (96.1%), easy to understand (98.8%), appropriate in frequency (93.8%), and reported being willing to receive future text messages (94.8%). Text messages supporting secondary prevention among patients with coronary heart disease did not lead to a greater reduction in blood pressure at 6 months. Mobile phone text messaging for secondary prevention was feasible and highly acceptable to patients. URL: https://clinicaltrials.gov . Unique identifier: NCT02888769.

A subanalysis of Taiwanese patients from ODYSSEY South Korea and Taiwan study evaluating the efficacy and safety of alirocumab.

Alirocumab can provide significant reductions in low-density lipoprotein cholesterol (LDL-C). However, data regarding its efficacy and safety in Asians are limited. A subgroup analysis of Taiwanese patients (n = 116) in a randomized trial evaluating the efficacy and safety of alirocumab in South Korea and Taiwan (ODYSSEY KT, clinicaltrials.gov Identifier: NCT02289963) was performed. Patients with hypercholesterolemia at high cardiovascular risk on maximally tolerated statin were randomized to alirocumab (75 mg every 2 weeks; with dose increased to 150 mg at Week 12 if LDL-C ≥ 70 mg/dL at Week 8) or placebo for 24 weeks. The primary efficacy endpoint was the percent change in LDL-C from baseline to Week 24. Safety was assessed for a total of 32 weeks. At Week 24, the percent change in calculated LDL-C in the alirocumab group (n = 57) was -51%, whereas that in the placebo group (n = 59) was 2.5%. Alirocumab significantly improved other lipid parameters, including non-high-density lipoprotein cholesterol, apolipoprotein B and A1, lipoprotein (a), high-density lipoprotein cholesterol, and total cholesterol. A significantly higher proportion of patients in the alirocumab group reached an LDL-C target below 70 mg/dL than those in the placebo group (81.3% vs 15.4%). The incidence of treatment-emergent adverse events was comparable between both groups. Alirocumab treatment provided a favorable effect on LDL-C levels and other lipid parameters, and was generally well-tolerated in patients from Taiwan. The results of current analysis were consistent with the overall ODYSSEY phase 3 program.