Median Triglyceride Research Articles

Estimate and prognosis of patients who are candidates for treatment with eicosapentaenoic acid after an acute coronary syndrome

Abstract Background Treatment with eicosapentaenoic acid (EA) has been shown to reduce the incidence of cardiovascular adverse events (MACE) in patients at high cardiovascular risk with mildly to moderately elevated triglyceride values (>135 mg/dl) and non-elevated (<100 mg/dl) low-density lipoprotein cholesterol (LDLc). Methods We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. Patients with LDLc <100 mg/dl and triglycerides >135 mg/dl were analyzed as candidates to EA. Results We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women and 30.4% with an ST-elevation ACS. Mean LDLc was 99.8 (38.5) mg/dl and median triglycerides 120.5 (interquartile range 90-197) mg/dl. A total of 3,028 (20.9%) were classified as candidates for EA, and they had the same mean age (p=0.87) but significantly higher prevalence of diabetes (35.1% vs. 21.9%), dyslipidemia (63.5% vs. 50.1%), previous coronary heart disease (CHD) (25.9% vs. 13.9%), or heart failure (HF) (3.6% vs. 2.5%). Candidates less frequently had an ST-elevation ACS (26.6% vs. 34.1%; p=0.02) and the incidence of Killip >1 was equivalent in candidates vs. non-candidates (16.6% vs. 17.7%; p=0.15). Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE. Candidates for EA had higher mortality (18.4% vs. 14.0%; HR: 1.22 95% CI 1.11-1.35) and MACE (39.0% vs. 33.6%; HR 1.14 95% CI 1.06-1.21) rates. Multivariate analysis (figure), adjusted for age, sex, diabetes (DM), previous coronary heart disease (CHD) or heart failure (HF), and medical treatments at discharge, identified an independently higher risk for all-cause mortality among candidates for EA (HR: 1.15 95% CI 1.04-1.26) [Figure 1] and for MACE (HR: 1.14 95% CI 1.05-1.20). The risk was consistent in all subgroups except for the case of mortality, but not for MACE, and previous ACS (figure 2) were a significant interaction (p=0.01) was observed Conclusions Approximately 20% of patients discharged after an ACS could be candidates for EA, and this subset of patients are at higher risk of death or a first MACE.

Effect of triglycerides on cardiovascular risk in patients with a first vs. recurrent acute coronary syndrome

Abstract Background Triglyceride (TG) levels have gained increasing interest in the prevention of cardiovascular disease although there is divergent evidence that might be explained by confounding factors. Methods We performed a multicenter and retrospective study using the ongoing registries of acute coronary syndrome (ACS) patients of 7 hospitals from Spain. TG were measured during the hospitalization, and mortality and major adverse cardiovascular events (MACE) were analyzed through follow-up. Results We included 14,483 patients discharged after an ACS, mean age 67.5 (13.3), 28.1% women, and 30.4% with an ST-elevation ACS; 2,378 (16.4%) patients had a previous ACS and were classified as recurrent ACS. Median triglyceride level was 120.5 (interquartile range [IQRS] 90-197) mg/dL and was slightly higher in patients with recurrent ACS (135 IQR 98-186 vs. 129 IQR 95-175; p<0.01). Patients with first vs. recurrent ACS received ticagrelor or prasugrel more frequently at discharge (14.8% vs. 7.4%; p<0.01), but no other differences in medical treatments were observed. Median follow-up was 1223 (interquartile range 570-2040) days. All-cause mortality was 15.0% (n= 2,166), and 34.71% (n=5,019) of the patients experienced a first MACE during follow-up. Patients with recurrent ACS had higher mortality (32.9% vs. 11.4%; p<0.01) and MACE (46.5% vs. 32.4%; p<0.01) rates. Multivariate analysis, adjusted for age, sex, diabetes, previous heart failure, and medical treatments at discharge showed that TG levels were not associated with higher risk of mortality (p=0.29) but with higher risk of MACE (p=0.04). A significant interaction (p=0.01) was observed for TG and previous ACS for both endpoints and, therefore, analyses were performed separately (Figure 1). As shown in Figure 2, TG were associated with higher risk of death in patients with first ACS (p=0.02) but not in patients with recurrent ACS (p=0.48); in contrast, TG were associated with higher risk of MACE (p=0.024) in patients with a recurrent ACS but not in patients with a first ACS (p=0.25). Conclusions Previous ACS modifies the risk of TG on mortality and MACE in patients discharged after an ACS. TG might be considered a target for treatment in patients after a first or recurrent ACS, although the exact impact on outcomes might be different.

Elevated triglycerides and treatment eligibility in patients with severe, asymptomatic carotid stenosis: CREST 2 Trials

BackgroundData from the Centers for Disease Control show that approximately one-quarter of adults have elevated triglyceride (TG) levels. Some clinical trials, but not all, have demonstrated that pharmacologic treatment of high TG levels in patients already on statin therapy reduces the rate of major vascular events such as myocardial infarction and stroke. We assessed the prevalence of elevated TG levels in patients with asymptomatic carotid stenosis (CS), and medical conditions associated with high TG. MethodsBaseline lipid profiles from patients enrolled in the Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial (CREST 2) were analyzed. to determine treatment eligibility for high TG levels using the criteria established by the REDUCE-IT trial (triglyceride levels ≥150 mg/dL with LDL managed by a statin to <100 mg/dL). Equally assessed was the percentage of patients who were using pharmacologic treatment for high TG levels at study entry. Demographic factors and baseline medical conditions associated with high (>150 mg/dl) TG values were also analyzed. Chi-square and t=tests were used to assess baseline factors and abnormal TG values. ResultsAs of October 2023, of 2377 randomized CREST-2 patients, 2328 (98 %) (mean age 70.0 years, 63 % men) had baseline lipid profiles suitable for analysis. Among 1961 (84 %) patients who met REDUCE-IT criteria, analysis of lipid profiles revealed that 20.5 % of the patients were eligible for treatment of high triglycerides. Of the 1464 patients with fasting lipid profiles, 17.8 % were eligible for treatment. The median TG value was 205 (IQR 91) mg/dl in the total population. TG levels of 150 mg/dl or higher were strongly associated with hypertension, diabetes, obesity, high hemoglobin A1c, and reduced physical activity (all p<0.0001). ConclusionsElevated TG levels are strongly associated with diabetes, hypertension, obesity, and reduced physical activity. Further research is needed on whether treatment of elevated TG levels in patients with asymptomatic carotid stenosis confers benefit.

A-211 Lipids in the Afternoon: Effect on LDL-C, Triglycerides, and Collection Time When Removing Fasting Requirements for Lipid Panels

Abstract Background Calculated LDL cholesterol (LDL-C) is a standard component of the lipid panel and an important risk factor in managing atherosclerotic cardiovascular disease (ASCVD). Due to the assumptions in the derivation of the Friedwald formula, fasting (≥8 hours) and triglyceride levels ≤400mg/dL have long been recommended. More recent data have shown that in most cases fasting has minimal effect on results, leading to the endorsement of non-fasting lipid panels for routine evaluation of ASCVD risk in clinical practice guidelines. Furthermore, newer equations (e.g. Sampson-NIH) allow for more accurate estimation of LDL-C even in the presence of hypertriglyceridemia. Mayo Clinic has implemented the Sampson-NIH LDL-C calculation and removed fasting/non-fasting designation from lipid panel orders. We hypothesized that the change to fasting designation would allow more afternoon draws for routine lipid panels and that increased non-fasting collections may increase triglyceride levels, but that the Sampson-NIH equation would prevent bias in LDL-C estimation. In order to test these hypotheses, we analyzed patient data from 1 year prior and 1 year post-implementation. Methods Results of lipid panels performed for one year preceding (n=334,719) and one year after (n=381,804) removal of the fasting/non-fasting designation and implementation of Sampson-NIH equation were collected. Median, 10th, and 90th percentile of draw time, triglyceride, and LDL-C calculated by either Sampson-NIH or Friedwald formulas were compared by quantile regression. Results Draw times shifted post-implementation at the 10th percentile (7:06 vs. 7:10, p&amp;lt;0.0001), median (8:49 vs. 9:08, p&amp;lt;0.0001) and 90th (12:02 vs. 13:46, p&amp;lt;0.0001). No difference in median triglyceride measurement was observed between pre-and post-implementation (110mg/dL), but slight differences were observed in the 10th and 90th percentile values (60 vs 59mg/dL and 224 vs 229mg/dL, p&amp;lt;0.0001). No difference was observed in 10th, 50th, or 90th percentile LDL values when calculated by Sampson-NIH equation (56, 99, 153mg/dL); however, if the Friedwald formula is used, a slight shift is observed in the 10th and 50th percentile LDL values (54 vs. 53, 97 vs. 96; p&amp;lt;0.0001) but not the 90th (150mg/dL). Conclusions Changing to the Sampson/NIH formula for LDL-C and removing fasting vs. non-fasting designation from routine lipid panels had minimal effect on reported triglyceride and LDL-C values, while allowing increased flexibility in draw time and reporting of LDL-C on patients with triglycerides ≥400mg/dL. Patients with TG ≥400mg/dL represented 1.7% of the dataset overall, including 5,387 patients before the change in which LDL-C could not be reported and 6,697 patients in the year post-implementation for whom LDL-C was reported based on the Sampson-NIH formula. Using an equation that is robust in patients with elevated triglyceride levels and removing fasting requirements from routine lipid panels allows greater flexibility and convenience for patients while allowing for more even distribution of phlebotomy workload and reporting of LDL-C results for patients with hypertriglyceridemia without evidence of clinically significant bias in reported results.

Plozasiran for Managing Persistent Chylomicronemia and Pancreatitis Risk.

Persistent chylomicronemia is a genetic recessive disorder that is classically caused by familial chylomicronemia syndrome (FCS), but it also has multifactorial causes. The disorder is associated with the risk of recurrent acute pancreatitis. Plozasiran is a small interfering RNA that reduces hepatic production of apolipoprotein C-III and circulating triglycerides. In a phase 3 trial, we randomly assigned 75 patients with persistent chylomicronemia (with or without a genetic diagnosis) to receive subcutaneous plozasiran (25 mg or 50 mg) or placebo every 3 months for 12 months. The primary end point was the median percent change from baseline in the fasting triglyceride level at 10 months. Key secondary end points were the percent change in the fasting triglyceride level from baseline to the mean of values at 10 months and 12 months, changes in the fasting apolipoprotein C-III level from baseline to 10 months and 12 months, and the incidence of acute pancreatitis. At baseline, the median triglyceride level was 2044 mg per deciliter. At 10 months, the median change from baseline in the fasting triglyceride level (the primary end point) was -80% in the 25-mg plozasiran group, -78% in the 50-mg plozasiran group, and -17% in the placebo group (P<0.001). The key secondary end points showed better results in the plozasiran groups than in the placebo group, including the incidence of acute pancreatitis (odds ratio, 0.17; 95% confidence interval, 0.03 to 0.94; P = 0.03). The risk of adverse events was similar across groups; the most common adverse events were abdominal pain, nasopharyngitis, headache, and nausea. Severe and serious adverse events were less common with plozasiran than with placebo. Hyperglycemia with plozasiran occurred in some patients with prediabetes or diabetes at baseline. Patients with persistent chylomicronemia who received plozasiran had significantly lower triglyceride levels and a lower incidence of pancreatitis than those who received placebo. (Funded by Arrowhead Pharmaceuticals; PALISADE ClinicalTrials.gov number, NCT05089084.).

Clinical characterization and mutation spectrum of patients with hypertriglyceridemia in a German outpatient clinic

Severe hypertriglyceridemia has predominantly multifactorial causes (MCS). Yet, a small subset of patients have the monogenetic form (FCS). It remains a challenge to distinguish patients clinically, since decompensated MCS might mimic FCS's severity. Aim of the current study was to determine clinical criteria that could sufficiently distinguish both forms as well as to apply the FCS score proposed by Moulin et al. We retrospectively studied 72 patients who presented with severe hypertriglyceridemia in our clinic during a time span of seven years and received genetic testing. We classified genetic variants (ACMG-criteria), followed by genetic categorization into MCS or FCS. Clinical data were gathered from the medical records, and the FCS score was calculated for each patient. Molecular genetic screening revealed eight FCS patients and 64 MCS patients. Altogether, we found 13 pathogenic variants of which four have not been described before. The FCS patients showed a significantly higher median triglyceride level than the MCS patients. The FCS score yielded a sensitivity of 75% and a specificity of 93.7% in our cohort and significantly differentiated between the FCS and MCS group (P < 0.001). In our cohort, we identified several variables that significantly differentiated FCS from MCS. The FCS score performed similar to the original study by Moulin, thereby further validating the discriminatory power of the FCS score in an independent cohort.

The Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Coronary Artery Calcium Progression in Subjects With Diabetes and Coronary Artery Disease: A Secondary Analysis of a Randomized Trial

Higher coronary artery calcium (CAC) scores and progression of CAC are associated with higher mortality. We previously reported that subjects with coronary artery disease randomly allocated to eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation or none had similar significant increases in CAC score over 30 months. Whether these findings are influenced by diabetes status is unknown. A total of 242 subjects with coronary artery disease who were on statin therapy were randomly allocated to to 1.86 g EPA and 1.5 g DHA daily or none (control). The CAC score was measured at baseline and 30-month follow-up using noncontrast, cardiac computed tomography. A significant interaction term between diabetes status and treatment arm was noted in the prediction of the CAC score (p <0.001). A total of 176 subjects (85.8% men) had no diabetes and 66 subjects (80.3% men) had diabetes. The mean age was 62.9 ± 7.9 versus 63.2 ± 7.1 years, respectively. The mean low-density lipoprotein cholesterol and median triglyceride levels were not significantly different between those without and with diabetes: 77.7 ± 25.9 versus 77.1 ± 30.2 mg/100 ml, respectively, and 117.0 (78.0 to 158.0) versus 119.0 (84.5 to 201.5) mg/100 ml, respectively. Subjects with diabetes on EPA+DHA had a greater increase in CAC score than subjects with diabetes in the control group (median 380.7 vs 183.5, respectively, p = 0.021). In contrast, no difference occurred between the EPA+DHA and control groups in subjects without diabetes (175.7 vs 201.1, respectively, p = 0.41). In conclusion, EPA+DHA supplementation was associated with greater CAC progression in subjects with diabetes than subjects with diabetes in the control group over a 30-month period; whether this indicates progression of the disease burden or plaque stabilization requires further study.

Comprehensive analysis of morbidity and mortality patterns in familial partial lipodystrophy patients: insights from a population study.

There is a lack of information on the clinical and molecular presentation of familial partial lipodystrophy (FPLD), a rare genetic disorder characterized by partial subcutaneous fat loss. This study aimed to provide a comprehensive assessment of the clinical, metabolic, and genetic features of FPLD in the Brazilian population. In a multicenter cross-sectional investigation we evaluated patients with FPLD across five Brazilian reference centers for lipodystrophies. Diagnosis of FPLD was made by clinical evaluation and genetic confirmation. Data on genetic, clinical, and metabolic characteristics were captured. Statistical analysis involved the utilization of the Kruskal-Wallis test to identify differences. The study included 106 patients with genetic confirmation of FPLD. The mean age was 44 ± 15 years, and they were predominantly female (78.3%). LMNA pathogenic variants were identified in 85.8% of patients, PPARG in 10.4%, PLIN1 in 2.8%, and MFN2 in 0.9%. Diabetes mellitus (DM) was highly prevalent (57.5%), affecting 54 females (50.9%). Median triglycerides levels were 199 mg/dL (54-2724 mg/dL), severe hypertriglyceridemia (≥ 500 mg/dL) was found in 34.9% and pancreatitis in 8.5%. Metabolic-associated fatty liver disease (MAFLD) was observed in 56.6%, and cardiovascular disease in 10.4%. The overall mortality rate was 3.8%, due to cardiovascular events. This study presents an extensive cohort of Brazilian patients with FPLD, predominantly DM with several multisystem complications. A comprehensive characterization of lipodystrophy syndromes is crucial for effective patient management and care.

Metabolic abnormalities in patients with non-alcoholic fatty liver disease with immune response to SARS-CoV-2

Background. It is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly infect hepatocytes. At the same time, overweight and obesity are surrogate markers of the adverse effects of coronavirus disease 2019 (COVID-19). The purpose of the study: to evaluate changes in lipid and carbohydrate metabolism and their indices in the serum of patients with non-alcoholic fatty liver disease (NAFLD) with an immune response to SARS-CoV-2. Materials and methods. We studied 37 patients with NAFLD who had IgG to SARS-CoV-2. All patients were divided into two groups: group I consisted of 19 participants who were PCR-negative for SARS-CoV-2, group II included 18 patients who had COVID-19, as confirmed by PCR testing. The content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), glucose, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol (VLDL-C), atherogenicity coefficient, insulin resistance indices (HOMA-IR), TG to glucose (TG/Gly) and TG to HDL-C (TG/HDL-C) ratio were assessed in all patients. Results. Among patients with NAFLD with an immune response to SARS-CoV-2, dyslipidemia manifested by a probable increase in the median TG content in groups I and II by 2.5 and 3.4 times (р = 0.0001), respectively; TC — by 1.2 times (р = 0.0425) in both groups, with a tendency to increase; VLDL-C — by 1.8 (р = 0.010) and 2.5 times (р = 0.0022), respectively, and a decrease in the median content of HDL-C by 1.7 (р = 0.0016) and 1.9 times (р = 0.0008), respectively, in blood serum. The identified changes led to a statistically significant increase in the median atherogenicity coefficient in groups I and II — by 2.2 (р = 0.0036) and 2.5 times (р = 0.007). An increase in the HOMA-IR did not have a statistically significant difference between the groups: in group I, this index increased by 3.1 times (p &lt; 0.05) compared with the controls, in group II — by 3 times (p &lt; 0.05). In addition, patients in both groups had a statistically significant increase in TG/Gly and TG/HDL-C ratio compared to controls. However, the detected changes were more pronounced in group II, where TG/Gly and TG/HDL-C levels were 1.5 (р = 0.038) and 1.9 times (р = 0.035), respectively, higher than in group I. Conclusions. Patients with an immune response to SARS-CoV-2 with NAFLD have disorders of lipid and carbohydrate metabolism. At the same time, the signs of dyslipidemia were more pronounced in participants with a history of SARS-CoV-2. TG/Gly and TG/HDL-C ratio should be included in the diagnostic algorithm for assessing insulin resistance in patients with COVID-19 who are overweight or obese.

Olezarsen for Hypertriglyceridemia in Patients at High Cardiovascular Risk.

Reducing the levels of triglycerides and triglyceride-rich lipoproteins remains an unmet clinical need. Olezarsen is an antisense oligonucleotide targeting messenger RNA for apolipoprotein C-III (APOC3), a genetically validated target for triglyceride lowering. In this phase 2b, randomized, controlled trial, we assigned adults either with moderate hypertriglyceridemia (triglyceride level, 150 to 499 mg per deciliter) and elevated cardiovascular risk or with severe hypertriglyceridemia (triglyceride level, ≥500 mg per deciliter) in a 1:1 ratio to either a 50-mg or 80-mg cohort. Patients were then assigned in a 3:1 ratio to receive monthly subcutaneous olezarsen or matching placebo within each cohort. The primary outcome was the percent change in the triglyceride level from baseline to 6 months, reported as the difference between each olezarsen group and placebo. Key secondary outcomes were changes in levels of APOC3, apolipoprotein B, non-high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol. A total of 154 patients underwent randomization at 24 sites in North America. The median age of the patients was 62 years, and the median triglyceride level was 241.5 mg per deciliter. The 50-mg and 80-mg doses of olezarsen reduced triglyceride levels by 49.3 percentage points and 53.1 percentage points, respectively, as compared with placebo (P<0.001 for both comparisons). As compared with placebo, each dose of olezarsen also significantly reduced the levels of APOC3, apolipoprotein B, and non-HDL cholesterol, with no significant change in the LDL cholesterol level. The risks of adverse events and serious adverse events were similar in the three groups. Clinically meaningful hepatic, renal, or platelet abnormalities were uncommon, with similar risks in the three groups. In patients with predominantly moderate hypertriglyceridemia at elevated cardiovascular risk, olezarsen significantly reduced levels of triglycerides, apolipoprotein B, and non-HDL cholesterol, with no major safety concerns identified. (Funded by Ionis Pharmaceuticals; Bridge-TIMI 73a ClinicalTrials.gov number, NCT05355402.).

Influence of triglyceride concentration in lipoprotein(a) as a function of dyslipidemia

BackgroundRecently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the Lipid Units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methodsFive thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. ResultsThe mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values ​​exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. ConclusionsOur results show an inverse Lp(a)-TG relationship in TG concentrations >300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Incidence of Hypertriglyceridemia in Patients on Propofol, Clevidipine, or Both.

Propofol and clevidipine (PC) are commonly used in the treatment of critically ill patients. While both medications are lipid emulsions, there is limited evidence concerning the incidence of hypertriglyceridemia (HTG) when these agents are used individually or concurrently. The objective of this study is to determine the effects of propofol, clevidipine, or concurrent PC on triglycerides (TGs) and related outcomes in critically ill adults. This was a retrospective cohort study conducted at an academic medical center. Patients were included if they received ≥24 hours of continuous propofol and/or clevidipine. Excluded were those without TG levels after ≥24 hours of infusion, baseline HTG, acute pancreatitis at admission, or receiving total parenteral nutrition with lipids. The primary outcome was incidence of HTG (defined as a TG level >400 mg/dL). Secondary outcomes included median and peak TG levels, hospital length of stay, intensive care unit length of stay, total lipid infused, time to peak TG level, peak lipase level, and development of pancreatitis. In total, 190 patients were studied: 109 in the propofol group, 50 in the clevidipine group, and 31 in the PC group. Incidence of HTG was similar (19 [17.4%] vs 6 [12%] vs 4 [12.9%] patients, P = 0.6246). Peak and median TG levels were similar for propofol, clevidipine, and PC groups (216 mg/dL vs 189.5 mg/dL vs 205 mg/dL, P = 0.7069; 177 mg/dL vs 185.5 mg/dL vs 177 mg/dL, P = 0.6791). There was a similar incidence of HTG in all groups. The results of this study suggest that the concurrent use of PC should not modify the frequency of TG level monitoring.

Long-term clinical outcomes and management of hypertriglyceridemia in children with Apo-CII deficiency

Background and aimAPO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. Methods and resultsThe data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277–14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). ConclusionsApo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.

Influencia de la concentración de triglicéridos en la lipoproteína(a) en función de la dislipidemia

BackgroundRecently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)–TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias. Patients and methodsFive thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included. ResultsThe mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0–210) and Lp(a) 55.0 nmol/L (IQR 17.9–156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)–TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300–399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL. ConclusionsOur results show an inverse Lp(a)–TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Severe hypertriglyceridemia and its correlation with clinical atherosclerosis and pancreatitis investigated in beta-quantification

Abstract Background Severe hypertriglyceridemia is commonly associated with pancreatitis and questionably atherosclerotic cardiovascular disease (ASCVD). However, while some patients develop those sequelae at relatively low levels, others with extreme levels remain spared from it. Purpose This study serves to validate, whether the distribution of triglycerides (TG), either in very-low-density lipoprotein (VLDL) particles or chylomicrons (CM) can be decisive for the development of clinical disease. Methods Patients with TG levels above 500 mg/dL, who routinely visited our lipid outpatient clinic between 2016 and 2021 with their lipid panel done via beta-quantification were retrospectively investigated for the presence of clinical pancreatitis and ASCVD via electronic chart-review. Results In total, 221 patients met eligibility criteria, with a mean age of 48 years, BMI of 29.7, with 72.4% males. Median TG and low-density lipoprotein cholesterol levels were 827 mg/dL and 62 mg/dL, respectively. A history of pancreatitis was present in 13.7% of patients, while ASCVD was present in 20.7%. TG distribution, described as the ratio of TG in VLDL per TG in CM showed no significant differences with regards to pancreatitis incidence (p=0.393). For ASCVD, the ratio was significantly higher in those with ASCVD vs those without (3.54 vs 2.25) (p=0.008). CM-dominant TG distribution was present in 19.5% of patients and was associated with higher total TG levels (2122 mg/dL vs 825 mg/dL), compared to VLDL-dominant TG distribution. Conclusion A higher relative amount of TGs in VLDL compared to CM, as most prevalent pattern, was associated with ASCVD, while very high levels of TG frequently relate to hyperchylomicronemia.

Increased triglyceride independently associates with premature structural and functional cardiac damage progression in asymptomatic adolescents: a 7-year longitudinal study

Abstract Background High levels of triglyceride have been associated with poor cardiovascular health in adults. The relationships between triglyceride and early signs of vascular organ damage among adolescents and young adults are inconsistent. There is a scarcity of longitudinal evidence regarding the potentially deleterious effects of increased triglyceride on cardiac structure and function in apparently healthy youth. Purpose To investigate the longitudinal association of changes in triglyceride with structural and functional cardiac damage progression during growth from adolescence through young adulthood. Methods From the Avon Longitudinal Study of Parents and Children (ALSPAC), UK birth cohort, 1595 adolescents aged 17 years who had fasting plasma triglyceride measured at 17- and 24-year clinic visits were included. Repeated echocardiography measured LVM indexed for height2.7 (LVMI2.7), relative wall thickness (RWT), LV diastolic function from mitral E/A ratio (LVDF), and LV filling pressure from E/e´ ratio (LVFP) were available at baseline and follow-up. LVMI2.7 ≥51g/m2.7, RWT ≥0.44, LVDF&amp;lt;1.5, and LVFP ≥8 were categorised as LV hypertrophy, high RWT, LVD dysfunction, and high LVFP, respectively. Multivariable adjusted associations were examined using generalized linear mixed-effect models and generalized logit mixed-effect models and adjusted for sex, and time-varying covariates measured at both baseline and follow-up such as age, insulin, high-sensitivity C-reactive protein, heart rate, systolic blood pressure, glucose, fat mass, lean mass, smoking status, family history of hypertension/diabetes/high cholesterol/vascular disease, socioeconomic status, sedentary time, light physical activity, moderate to vigorous physical activity, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Results Among 1595 adolescents (mean [SD] age at baseline, 17.74 [0.38] years; 955 [59.8%] females]) median triglyceride values increased in males from 0.72 mmol/L to 0.86 mmol/L and in females from 0.74 mmol/L to 0.80 mmol/L, over 7 years. The prevalence of LV hypertrophy increased in males from 3.6% to 11.9% and in females from 1.6% to 4% over 7 years. The prevalence of LVD dysfunction increased in males from 7.8% to 16.6% and in females from 10.3% to 15.4%. In a fully adjusted model, each 1 mmol increase in triglyceride was significantly associated with higher odds of LV hypertrophy progression (odds ratio 2.89; [95% CI, 1.54 – 5.43], p&amp;lt;0.001), LVD dysfunction (1.98 [1.86 – 3.71], p=0.032), and high LVFP (2.19; [1.29 – 3.70], p=0.004) but not high RWT (1.45; [0.77 – 2.73], p=0.245), over 7 years. Conclusion Increased triglyceride during growth from adolescence through young adulthood was independently associated with progressive structural and functional cardiac damage in asymptomatic youth.

Abstract 17070: Dyslipidemia Prevalence Among a Diverse Cohort of Childhood, Adolescent and Young Adult Cancer Survivors

Background: In the general population, dyslipidemia impacts 36% of adults between the ages of 20 and 29 years. Among survivors of childhood, adolescent, and young adult-onset cancer (C-AYAs), the prevalence of dyslipidemia in racially diverse cohorts as well as our understanding of which measured fats are most commonly abnormal are limited. Question: Among a diverse group of C-AYAs, what is the prevalence of dyslipidemia and which fats are most contributory? Methods: Individuals diagnosed with cancer at age ≤39 years and treated with anthracycline based chemotherapy between 2010-2022 were identified. Depending on age at time of collection, post-treatment lipid panels were analyzed according to AAP (&lt;20 years) or ACC/AHA (≥20 years) guidelines. Non-fasting panels were included, in accordance with ACC/AHA guidelines. The prevalence of dyslipidemia and median values for measured fats were determined. Non-parametric testing was used to examine associations between dyslipidemia, age, and race. Results: Among a diverse (40% Black, 52% White) cohort of C-AYAs (227 total) with a median current age of 25 years (interquartile range (IQR) 20-36 years) and median total doxorubicin isotoxic equivalents of 200mg/m 2 (IQR 120-300 mg/m 2 ), the prevalence of dyslipidemia was 55%. Prevalence of dyslipidemia was not associated with race (Black 55%, White 64%, Other 44%, p=0.281) or age (&lt;20 years 51%, ≥20 years 64%, p = 0.055). Among Black and White subjects, HDL was most commonly abnormal (Black 42%, White 38%), followed by triglycerides (TG) (Black 29%, White 41%). Median TG levels were significantly lower among Black individuals ≥20 years compared with White individuals (117 mg/dL vs 143 mg/dL, p = 0.030). Conclusions: Among a diverse group of C-AYAs, dyslipidemia was highly prevalent even at a younger age (&lt;20 years). Race was not associated with prevalence of dyslipidemia. Dyslipidemia was primarily driven by HDL and TG abnormalities, fats associated with metabolic syndrome.

Outcomes of Dolutegravir-Based Antiretroviral Therapy in Thai Youth Aged 18 to 24 Years Living with HIV in Bangkok: A Retrospective Cohort Study

Objective: Dolutegravir (DTG) is recommended globally for people living with HIV. The present study aimed to describe the efficacy and safety of DTG-based regimens among youth aged 18 to 24 years. Materials and Methods: A retrospective cohort study was conducted among youth aged 18 to 24 years living with HIV at Chulalongkorn Hospital. Participants were divided into antiretroviral naïve (AN), antiretroviral experienced with treatment failure (AETF), and antiretroviral experienced and virally suppressed (AEVS). DTG was prescribed as a daily individual tablet or as part of a fixed-dose combination. The primary outcome was virological suppression defined as VL of less than 200 copies/mL within 12 months after DTG initiation. Secondary outcomes included body weight and lipid profile changes. Results: Between 2017 and 2022, 87 youth with a median age of 20.6 (IQR 19.6 to 21.9) years were initiated on DTG. Fifty-six (64.3%) were male. Twelve participants were AN, 18 were AETF, and 57 were AEVS. HIV viral suppression was 100% and 96.2% among those AN and AEVS, but only 54.5% amongst the AETF group (p&lt;0.001). CD4 lymphocyte counts increased in all groups at follow-up. Median body weight change was +0.4 (IQR –1.8 to 3.6) kg in males and +0.5 (IQR –2.8 to 1.7) kg in females. Median total cholesterol declined from 167 (IQR 142 to 186) to 152 (IQR 135 to 170) mg/dL, p=0.003. Median triglycerides declined from 83 (IQR 60 to 129) to 66 (IQR 46 to 78), p&lt;0.001. No hospitalizations or mortalities were observed in the study. Conclusion: DTG was effective and well-tolerated in youth living with HIV, with no significant weight gain and improved lipid profiles. DTG implementation among youth living with HIV should be continued. Keywords: Dolutegravir; Antiretroviral therapy; Adolescents living with HIV

FRI058 Treatment With Mibavademab, A Novel Leptin Receptor Agonist, Is Associated With Improvement In Metabolic Parameters In Individuals With Generalized Lipodystrophy

Abstract Disclosure: B. Olenchock: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Podgrabinska: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. C. Hou: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. B. Musser: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. J. Mendell: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A. Harman: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. R.J. Sanchez: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. K. Miller: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. P. Parasoglou: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Hectors: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Karnik: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. O.E. Pagovich: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. R. SinhaRoy: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. C.A. Harris: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. B. Akinci: Advisory Board Member; Self; Regeneron Pharmaceuticals, Amryt Pharmaceuticals. Consulting Fee; Self; Amryt Pharmaceuticals, Regeneron Pharmaceuticals, Third Rock Ventures, AstraZeneca, Lilly USA, LLC, Novartis Pharmaceuticals, Novo Nordisk, Boehringer Ingelheim, Servier, Sanofi-Aventis, MSD. I. Yildirim simsir: None. S. Ozen: None. E. Sorkina: Advisory Board Member; Self; Amryt Pharmaceuticals, Regeneron Pharmaceuticals. A. Garg: Consulting Fee; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Grant Recipient; Self; Aegerion Pharmaceuticals, Pfizer, Inc., Regeneron Pharmaceuticals, Amryt Pharmaceuticals, Ionis Pharmaceuticals Inc. R.J. Vargas Gonzalez: None. D.M. Weinreich: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. G. Herman: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. E.A. Oral: Consulting Fee; Self; Regeneron Pharmaceuticals, Third Rock Ventures, Amryt Pharmaceuticals, Rejuvenate Inc, Ionis Pharmaceuticals. Grant Recipient; Self; Gemphire Theraputics, Amryt Pharmaceuticals, Ionis Pharmaceuticals. R.J. Brown: Grant Recipient; Self; Regeneron Pharmaceuticals. Background: Generalized lipodystrophy (GLD) is characterized by the deficiency of adipose tissue and consequently, low levels of the adipose-derived hormone leptin. Leptin deficiency in GLD leads to metabolic abnormalities which are often refractory to treatment with conventional agents. Recombinant human leptin, the only approved therapeutic, improves metabolic abnormalities of GLD, however, daily dosing is required and there is a risk of immunogenicity. There is an unmet need for effective therapies in GLD that are safe, administered less frequently, and can treat patients who have developed neutralizing antibodies to recombinant leptin. Mibavademab is an investigational human leptin receptor agonist monoclonal antibody. We report here the safety, tolerability and pharmacodynamic (PD) responses to mibavademab in a Phase 2 trial (NCT04159415) in patients with GLD. Methods: Patients ≥12 years with acquired or congenital GLD were randomized to mibavademab or placebo. After a single-blind placebo run-in, patients were randomized 1:1 to one of two fixed sequence arms comprising sequential 8-week treatment periods (Arm A: placebo, low-dose mibavademab, high-dose mibavademab; Arm B: low-dose mibavademab, high-dose mibavademab, high-dose mibavademab). Patients in each arm received an IV loading dose of placebo or mibavademab followed by weekly SC administration of study drug tiered by body weight (≥50 kg or &amp;lt;50 kg). Both arms were followed by an open-label high-dose mibavademab treatment period. Safety, pharmacokinetics, and PD of mibavademab were assessed. Primary efficacy endpoints, glycated hemoglobin (HbA1c) and fasting triglycerides (TGs) were measured at Week 8 and at predetermined time points thereafter until study completion. Results: Sixteen patients with GLD and baseline diabetes (mean HbA1c 9.6%, range 6.0%-12.2%) or hypertriglyceridemia (median TGs 669 mg/dL, range 107-2899 mg/dL) were randomized and completed ≥28 weeks of mibavademab treatment. After 8 weeks of low-dose mibavademab, drug levels were significantly lower than predicted in the active arm, and clinically meaningful differences were not observed for any of the primary efficacy endpoints as compared to placebo. In an exploratory pooled analyses after 28 weeks of mibavademab administration, serum drug concentrations were significantly higher than observed at Week 8, and clinically significant reductions from baseline in HbA1c (mean: -1.9%, SD: 2.0) and in TGs (median: -102.1 mg/dL, IQR: 1355.5 mg/dL, -49.3% [57.2%]). Mibavademab was generally well tolerated with no serious adverse events related to administration. Conclusions: Treatment with high-dose mibavademab for up to 28 weeks was associated with clinically meaningful improvements in metabolic parameters, and was generally well-tolerated. Mibavademab represents a potential new therapeutic option for patients with GLD. Presentation: Friday, June 16, 2023

Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency

Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization. To describe the manifestations and management of 19 pediatric patients with LPL-FCS. LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed. Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3 mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed. This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10en% or <20en% depending on different ages. MCTs potentially provide extra energy.