Baseline Triglyceride Levels Research Articles

Pancreatitis polygenic risk score is independently associated with all-cause acute pancreatitis risk in the UK Biobank.

Acute pancreatitis (AP) is a complex disease most commonly caused by gallstones, alcohol intake, or hypertriglyceridemia. Even in subjects with hypertriglyceridemia, the risk of AP is heterogeneous. Identifying individuals with a high genetic susceptibility to AP could contribute to a better risk stratification in the clinic. This study aimed to determine if a weighted polygenic risk score (PRS) of common variants in pancreatitis susceptibility genes can independently predict all-cause AP incidence in the general population. A weighted PRS was calculated for 484932 individuals from the UK Biobank, including 3346 individuals who developed AP during follow-up. The PRS included eight single nucleotide polymorphisms in known pancreatitis susceptibility genes. Individuals with a pancreatitis PRS above the 90th percentile had a 1.21-fold (1.03-1.43; P=0.02) increased risk of AP compared with those with a pancreatitis PRS below the 90th percentile. When comparing individuals in the third tertile versus the first tertile, the risk of AP was 1.13-fold (1.00-1.28; P=0.06) higher. Individuals with both a high triglyceride (TG) level and a high pancreatitis PRS (third tertile) had a 2.31-fold (1.83-2.93; P=3.4×10-12) increased risk of AP compared with those with a low pancreatitis PRS and a low TG level (first tertile). Overall, the association between pancreatitis PRS and incident AP was independent of baseline TG level. Results of this study suggest that the accumulation of common variants in pancreatitis susceptibility genes is associated with all-cause AP incidence. Pancreatitis PRS could help clinicians identify patients who may be at higher risk of AP and who may benefit from more aggressive treatment.

Abstract Tu012: Innate Immune Pathway cGAS-STING in Macrophage Function in Atherosclerosis

Macrophages are key cells in atherosclerotic cardiovascular disease. Macrophages within a single plaque are heterogenous: some are lipid-laden “foam cells” with varying ability to recycle lipoproteins or clear dead cells while others secrete traditional “pro-inflammatory” signals. Determining what signals bias macrophages to one phenotype versus another could identify a therapeutic target. Our lab showed that after acute myocardial infarction, macrophages are skewed to a reparative phenotype by loss of cGAS-STING signaling. cGAS-STING are a pattern recognition receptor-adaptor pair that are activated by double stranded DNA in a sequence-independent manner. Global deletion of Sting and Cgas have been shown to protect against atherosclerosis in mice. We hypothesize that hematopoietic-specific loss of Cgas will reduce plaque burden by biasing macrophages to a less inflammatory phenotype and upregulating pro-resolving functions. To test this, B6.129S7- Ldlr tm1Her /J ( Ldlr -/-) mice (female, age 8-12 weeks, 9 per group) underwent total body irradiation followed by bone marrow transplant from C57BL6/N- Cgas -/- ( Cgas -/-) or wildtype donor mice (female, age 6-8 weeks). After bone marrow reconstitution, recipient mice were started on Western diet. Mice will continue Western diet for 12 weeks (through April 24, 2024). Then, aortas, peripheral blood, spleen, and bone marrow will be collected for further analysis including plaque burden, fibrous cap thickness, and macrophage phenotype. We will also perform in vitro studies using primary macrophages to determine how Cgas -/- affects macrophage effector functions critical for atherosclerosis. To date, mice that received Cgas -/- or wildtype donor bone marrow had similar baseline cell count, triglyceride and total cholesterol levels. Bone marrow derived macrophages (BMDM) from Cgas -/- mice have increased expression of fibronectin. Thus, at baseline Cgas -/- BMDM express high levels of a marker associated with pro-reparative macrophages. More studies are needed to characterize this phenotype and determine the consequence for in vivo atherosclerosis.

Association Between Baseline Serum Lipids and Severity of Dry Eye Symptoms in Acne Patients Treated with Isotretinoin.

Isotretinoin is a commonly prescribed medication for moderate-to-severe acne. Elevated triglycerides and total cholesterol, as well as eye dryness, are frequent side effects of isotretinoin. Objective:This study aims to examine the association between serum baseline levels of triglycerides and total cholesterol with regards to the severity of dry eye symptoms in acne patients treated with isotretinoin. The study was a retrospective review of acne patients treated with isotretinoin for at least four months at the dermatology clinics of Qassim University Medical City, Saudi Arabia. Thirty patients were included in the study as they met the inclusion criteria. Baseline levels of triglycerides and total cholesterol were reviewed for these patients. The Ocular Surface Disease Index (OSDI) questionnaire was sent and filled out by the study participants to assess the severity of eye dryness. 30 patients were included in the study, with 16 (53.3%) females and 14 (46.7%) males. The average age of participants was 22.1 years. The duration of treatment was between 120 and 140 days in 13 (43.3%) participants and 140 and 180 days in 17 (56.7%) participants. The mean ± 1 standard deviation (SD) was reported for each of the three variables, with an Ocular Surface Disease Index (OSDI) score of 27.6 ± 19.2, a baseline total cholesterol of 4.4 ± 0.9 mmol/L, and a baseline triglyceride level of 0.83 ± 0.4 mmol/L. Using a multiple linear regression model, baseline triglycerides and total cholesterol were used as predictors of the OSDI score. There was a significant dependent interaction between baseline total cholesterol and triglycerides and their effect on the OSDI score, with a higher OSDI score at higher levels of both triglycerides and cholesterol and a lower OSDI score at lower levels of both triglycerides and cholesterol. The study result showed that, in acne patients treated with isotretinoin for at least four months, a higher baseline level of both triglycerides and total cholesterol is associated with worse dry eye symptoms compared to those with lower baseline levels. The study concluded that baseline levels of triglycerides and total cholesterol arebothsignificant predictors of the severity of dry eye symptoms in acne patients treated with isotretinoin. Despite study limitations due to the small sample size, we hope that, based on our findings, this will open the door to future studies with a larger sample sizeto further confirmour findingsgeneralizethe result, andapply it to clinical practice so that clinicians may identify those at higher risk of severe eye dryness before starting isotretinoin and subsequently be able to recommend specific measures to minimize symptoms of eye dryness.

Ketonuria as an Indicator of Improvement of Renal Function in Patients with Type 2 Diabetes Receiving SGLT2 Inhibitor Treatment.

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria.

Cardiometabolic and immune response to exercise training in patients with metabolic syndrome: retrospective analysis of two randomized clinical trials.

Metabolic syndrome (MetS) is defined by the presence of central obesity plus ≥two metabolic/cardiovascular risk factors (RF), with inflammation being a major disease-driving mechanism. Structured endurance exercise training (ET) may positively affect these traits, as well as cardiorespiratory fitness (V̇O2peak). We explore individual ET-mediated improvements of MetS-associated RF in relation to improvements in V̇O2peak and inflammatory profile. MetS patients from two randomized controlled trials, ExMET (n = 24) and OptimEx (n = 34), had performed 4- or 3-months supervised ET programs according to the respective trial protocol. V̇O2peak, MetS-defining RFs (both RCTs), broad blood leukocyte profile, cytokines and plasma proteins (ExMET only) were assessed at baseline and follow-up. Intra-individual changes in RFs were analysed for both trials separately using non-parametric approaches. Associations between changes in each RF over the exercise period (n-fold of baseline values) were correlated using a non-parametrical approach (Spearman). RF clustering was explored by uniform manifold approximation and projection (UMAP) and changes in RF depending on other RF or exercise parameters were explored by recursive partitioning. Four months of ET reduced circulating leukocyte counts (63.5% of baseline, P = 8.0e-6), especially effector subtypes. ET response of MetS-associated RFs differed depending on patients' individual RF constellation, but was not associated with individual change in V̇O2peak. Blood pressure lowering depended on cumulative exercise duration (ExMET: ≥102 min per week; OptimEx-MetS: ≥38 min per session) and baseline triglyceride levels (ExMET: <150 mg/dl; OptimEx-MetS: <174.8 mg/dl). Neuropilin-1 plasma levels were inversely associated with fasting plasma triglycerides (R: -0.4, P = 0.004) and changes of both parameters during the ET phase were inversely correlated (R: -0.7, P = 0.0001). ET significantly lowered effector leukocyte blood counts. The improvement of MetS-associated cardiovascular RFs depended on individual basal RF profile and exercise duration but was not associated with exercise-mediated increase in V̇O2peak. Neuropilin-1 may be linked to exercise-mediated triglyceride lowering.

Genetic and biomarker modulation of arterial stiffness change in the SardiNIA population cohort.

Arterial stiffness (AS), quantified by pulse wave velocity (PWV), arises due to impaired arterial elastic tissue and smooth muscle dysfunction. We aimed to examine the longitudinal association of genetic, lipid and inflammation biomarkers with PWV and how these associations may change with aging. We utilized genotype and four time-point biomarker data from the SardiNIA cohort [n = 6,301; mean baseline age 43.3 (SD 17.3); 58% females]. To investigate the association of PWV with genetic variants, lipid, and inflammation biomarkers, we employed linear mixed modeling, using age as the time scale. Biomarkers exhibiting significant longitudinal associations were categorized into tertiles and individuals within the second tertile or those with heterozygous alleles were excluded, leaving a cohort of 2,000 individuals. This cohort was further divided into four risk groups: low genetic and low biomarker (L-L), low genetic and high biomarker (L-H), high genetic and low biomarker (H-L), and high genetic and high biomarker risk (H-H). Subsequent analyses focused on these risk groups to assess their association to PWV with time. Using the complete dataset, we found a significant longitudinal association of total cholesterol (TC), triglycerides (TG), fibrinogen (FGN), and total white blood cell count (TWBC) with PWV, all with p < 3.33 × 10-3. After grouping, individuals with homogeneous risk alleles of SNP rs3742207 and high baseline TG levels (H-H group) exhibited a 1.39-fold higher PWV (m/s) (95% CI, 1.17-1.64, p = 1.21 × 10-4) compared to the L-L group. Similarly, individuals in the H-H group of rs3742207-TWBC combination showed 1.75 times higher PWV (95% CI, 1.48-0.2.07, p = 1.01 × 10-10) compared to the L-L group. Similar patterns were observed for groups based on SNP rs7152623-TWBC risk. Furthermore, these associations became more pronounced with increasing age (p < 3.33 × 10-3). The longitudinal association of TG and TWBC biomarkers with PWV varied by SNPs rs3742207 and rs7152623 genotype. Further studies are warranted to investigate the function of genetics, lipids, and inflammation biomarkers on PWV change.

Traditional Chinese medicine lowering lipid levels and cardiovascular events across baseline lipid levels among coronary heart disease: a meta-analysis of randomized controlled trials.

Dyslipidemia is a critical driver in the development of coronary heart disease (CHD), which further exacerbates the risk of major adverse cardiovascular events (MACEs). Chinese herbal medicine (CHM) plays an important role in the regulation of lipid levels and improvement of prognosis. However, few systematic reviews report whether the efficacy of CHM therapy for regulating lipid levels and lowering cardiovascular events is associated with baseline lipid levels. Randomized controlled trials assessing efficacy of CHM for lipid profiles and MACEs among patients with CHD were searched in six databases. Two authors independently extracted studies according to a predesigned form. Cochrane risk of bias tool and Grading of Recommendations Assessment, Development, and Evaluation system were used to assess the methodological quality of the included studies. The primary outcomes were blood lipid levels and MACEs including cardiovascular mortality, non-fatal myocardial infarction, revascularization, angina pectoris, heart failure, and non-fatal stroke across baseline lipid levels. The secondary outcomes were individual components of the primary outcomes. A total of 23 trials with 7,316 participants were included in this study. Altogether 377 cardiovascular events occurred in 3,670 patients in the CHM group, while 717 events occurred in 3,646 patients in the Western medicine-alone group. Compared with the Western medicine alone, additional CHM significantly lowered low-density lipoprotein cholesterol (LDL-C) [MD = -0.46, 95% CI (-0.60 to -0.32), P < 0.00001, I 2 = 96%]. The risk reduction in MACEs associated with CHM vs. Western medicine therapy was 0.52 [95% CI (0.47-0.58), P < 0.00001, I 2 = 0%], but varied by baseline LDL-C level (P = 0.03 for interaction). Triglycerides (TG) level was also significantly lowered by additional CHM vs. Western medicine alone [MD = -0.27, 95% CI (-0.34 to -0.20), P < 0.00001, I 2 = 81%], and risk reduction for MACEs also varied with baseline TG, with greater risk reduction in higher baseline TG subgroups (P = 0.03 for interaction). Similar results were observed with total cholesterol and high-density lipoprotein cholesterol. Compared with Western medicine alone, additional CHM was associated with lower risk of cardiovascular events and improvement of lipid profiles. Risk reduction for cardiovascular events was associated with baseline LDL-C and TG levels. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023425791.

Factors Associated with Diabetic Complication Index among Type 2 Diabetes Patients: Focusing on Regular Outpatient Follow-up and HbA1c Variability

Preventing diabetic complications involves regular outpatient follow-up and maintaining low variability in hemoglobin A1c (HbA1c) levels. This study investigated the factors associated with diabetic complications, with a specific focus on the impact of regular outpatient follow-up and HbA1c variability, among patients with type 2 diabetes. The study design was secondary data analysis of electronic medical records from a university hospital in Korea. It included patients aged 40-79 with type 2 diabetes who were prescribed diabetes medication within three months of their first HbA1c test by an endocrinologist and were followed up for at least five years. Follow-up regularity, adjusted standard deviation of HbA1c levels, and diabetic complication indices were collected. Data were analyzed using the Chi-square test, independent t-test, repeated measures analysis of variance, and multiple regression analysis. The study included 1566 patients. Lower follow-up regularity was observed in patients of older age, with comorbidities, diabetic complications, insulin treatment, a history of hospitalization, lower baseline estimated glomerular filtration rate (eGFR) and total cholesterol (TC), and higher HbA1c variability. Higher HbA1c variability was observed in younger patients without comorbidity but with insulin treatment, a history of hospitalization, higher baseline blood glucose (BG), HbA1c, TC, and triglyceride levels. HbA1c variability had the strongest influence on BG and HbA1c levels at the five-year follow-up. Baseline eGFR and TC were the most influential factors for their respective levels at the five-year follow-up. Follow-up regularity significantly affected BG, HbA1c, eGFR, and TC at five-year follow-up. It has been shown that several variables besides regular follow-up and HbA1c variability have an influence. However, these are the two that can be corrected through nursing intervention and are important, so intervention on these is important.

Elevated triglyceride levels are associated with increased risk for major adverse cardiovascular events in statin-naïve rheumatoid arthritis patients: A nationwide cohort study

ObjectivesTo investigate the association between the four components of the lipid profile (total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)) at baseline and composite major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events. MethodsThis nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. ResultsDuring follow-up (median 4.70 years), the incidence of MACE per 1000 person-years was 7.27. Among the four lipid components, only higher baseline TG levels were significantly associated with increased risk for composite MACE in RA subjects. The risk for composite MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.35 [95% confidence interval (CI), 1.03–1.78]) and highest quartiles (adjusted HR, 1.74 [95%CI, 1.33–2.28]) of baseline TG level versus the lowest quartile. ConclusionsIn statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population.

Vitamin D level regulates serum lipids discrepantly in adults with and without dyslipidemia.

Vitamin D deficiency is associated with hyperlipidemia, but it remains unclear whether vitamin D supplementation reduces serum lipid levels. The aims of this study were to investigate the associations between increased serum 25-hydroxyvitamin D (25(OH)D) concentrations and lipid levels, and identify the characteristics of people with or without lipid reduction associated with increased 25(OH)D levels. The medical records of 118 individuals (53 men; mean age, 54.4 ± 10.6 years) whose serum 25(OH)D levels increased between two consecutive measurements were retrospectively reviewed. People with increased 25(OH)D levels (from 22.7 (17.6-29.2) to 32.1 (25.6-36.8) mg/dL; P < 0.01) had a significant reduction in serum levels of triglycerides (TG) (from 111.0 (80-164) to 104.5 (73-142) mg/dL; P < 0.01) and total cholesterol (TC) (from 187.5 (155-213) to 181.0 (150-210) mg/dL; P < 0.05). The individuals who responded to vitamin D (≥10% reduction in TG or TC levels) exhibited significantly higher baseline TG and TC levels than did those who did not. Only patients with hyperlipidemia (not those without hyperlipidemia) at baseline exhibited significantly reduced TG and TC levels at follow-up. However, increasing serum 25(OH)D concentrations were significantly correlated with decreasing lipid levels in individuals with baseline 25(OH)D levels less than 30 ng/mL, and in individuals aged 50-65 years (not in patients younger than 50 years or older than 65 years). In conclusion, increasing serum 25(OH)D concentrations may be potentially helpful for the treatment of hyperlipidemia in people with vitamin D deficiency.

Low Cholesterol Levels in Younger Heart Failure Patients May Predict Unfavorable Outcomes.

Background and Objectives: Hypercholesterolemia is a main risk-factor leading to ischemic heart disease (IHD). However, among patients with heart failure, the use of lipid lowering drugs in the presence of low cholesterol might be dangerous. This 18-year longitudinal study of patients ≤51 years old investigated the relationship between baseline total cholesterol, low-density lipoprotein cholesterol (LDL-c) and triglyceride levels, and survival among patients with severe HF. Materials and Methods: The average NYHA score of 82 patients ≤51 years old with heart failure was 2.61. They were followed for a mean of 11.3 years (15 months-20 years). Total mortality was 22%. Patients were divided into three groups. Group 1 had plasma LDL-c levels ≤ 80 mg/dl, Group 2, 80-115 mg/dl and Group 3 > 115 mg/dl. Results: Patients with the highest baseline total cholesterol, triglyceride and LDL-c levels > 115 mg/dl had a better survival rate (83%) compared to those with LDL-c < 80 mg/dl (50% survival, p = 0.043). The association between higher LDL-c levels and lower mortality was most noticeable among patients with heart failure. Conclusion: Longitudinal follow-up found that low LDL-c levels may indicate poorer prognosis among patient with heart failure who are ≤51 years old, similar to elderly heart failure patients. Cholesterol lowering drugs in younger patients with heart failure may increase mortality.

1247-P: Mildly Elevated Triglyceride Levels Are Associated with Increased Risk for Major Adverse Cardiovascular Events in Statin-Naïve Rheumatoid Arthritis Patients—A Nationwide Cohort Study

Objectives: To investigate the association between the four components of the lipid profile at baseline and major adverse cardiovascular events (MACEs) in statin-naïve rheumatoid arthritis (RA) patients with no previous history of cardiovascular events compared to non-RA controls. Methods: This nationwide population-based cohort study was performed on a total of 15,216 statin-naïve RA patients and 60,864 non-RA controls. The end point was a composite of clinical events, including myocardial infarction (MI), stroke, coronary revascularization, and cardiovascular death. We compared the incidence of and risk for clinical events according to each lipid variable. Results: During follow-up (median 4.70 years in RA group and 5.05 years in non-RA group), the incidence of MACE per 1000 person-years was 7.27 in the RA group and 7.16 in the non-RA group. Among the four lipid components, only higher baseline triglyceride (TG) levels were significantly associated with increased risk for MACE in the RA group. The risk for MACE was significantly higher in the third (adjusted hazard ratio (HR), 1.31 [95% confidence interval (CI), 1.00-1.71]) and highest quartiles (adjusted HR, 1.71 [95%CI, 1.30-2.23]) of baseline TG level versus the lowest quartile. In contrast, higher baseline total cholesterol, TG, and low-density lipoprotein cholesterol, and lower high-density lipoprotein cholesterol levels were significantly associated with increased MACE risk in the propensity score-matched non-RA group. Conclusions: In statin-naïve RA patients, increased TG level is associated with increased risk for MACE. Therefore, screening and intervention for increased TG level may be clinically beneficial in this population. Disclosure W.Choi: None. J.Kang: None. J.Park: None. A.Hong: None. J.Yoon: None. H.Kim: None. H.Kang: None. Funding National Research Foundation of Korea (2022R1C1C1006021)

Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in moderate to severe plaque psoriasis: evaluation of lipid parameters in the phase 3 POETYK PSO-1 and PSO-2 trials

Introduction: Tyrosine kinase 2 (TYK2), an intracellular kinase, mediates signaling of cytokines (IL-23 and Type I interferons) involved in psoriasis pathogenesis. Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved by the US Food and Drug Administration for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. Deucravacitinib was significantly more efficacious than placebo or apremilast and was well tolerated in the phase 3 POETYK PSO-1 and PSO-2 trials. We evaluated changes in lipid parameters in these trials.&#x0D; Methods: PSO-1 (NCT03624127) and PSO-2 (NCT03611751) were 52-week, double-blind trials conducted globally. Patients with moderate to severe plaque psoriasis (PASI ≥12, sPGA ≥3, BSA involvement ≥10%) were randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. This analysis evaluated serum lipids in patients taking placebo, deucravacitinib, or apremilast during Weeks 0-16 and those taking deucravacitinib continuously during Weeks 0-52 in PSO-1 and PSO-2. Mean changes in total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels are reported, as are shifts from baseline in CTCAE v5 severity grade of hypercholesterolemia and hypertriglyceridemia.&#x0D; Results: 666 and 1020 patients were randomized in PSO-1 and PSO-2, respectively. Mean baseline levels of total cholesterol, HDL cholesterol, and LDL cholesterol were comparable between treatment groups. Mean changes from baseline to Week 16 were small; none was clinically meaningful. Worsening of hypercholesterolemia grade from baseline was observed with similar frequencies among patients receiving placebo, deucravacitinib, and apremilast (10.6%, 11.7%, and 8.4%, respectively); nearly all shifts were 1 grade, and there was no grade ≥3 event. Baseline triglyceride levels were near the upper limit of normal (150 mg/dL) across treatment groups. A 10.3 mg/dL increase in mean triglycerides from baseline to Week 16 was observed with deucravacitinib, but worsening in hypertriglyceridemia &gt;1 grade from baseline was rare (1.2%) and comparable to placebo (1.4%). Most deucravacitinib-treated patients maintained the same or shifted to a lower grade of hypertriglyceridemia from baseline to Week 16. Among patients treated with deucravacitinib continuously for 52 weeks, mean changes in total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were small. Shifts in &gt;1 grade from baseline for hypercholesterolemia and hypertriglyceridemia were uncommon (0.2% and 1.9%, respectively). No patient discontinued deucravacitinib due to a lipid-related adverse event.&#x0D; Conclusion: There were no meaningful changes in total cholesterol, HDL cholesterol, and LDL cholesterol levels with deucravacitinib treatment. Minimal increases in mean triglyceride levels from baseline to Weeks 16 and 52 were accompanied by very few worsening shifts &gt;1 grade.

High Triglyceride Variability Increases the Risk of First Attack of Acute Pancreatitis.

Hypertriglyceridemia is the third most common etiology of acute pancreatitis. Whether triglyceride variability, independent of absolute triglyceride levels, is a predictor of acute pancreatitis is unknown. We identified 98,819 patients who were diagnosed with hyperlipidemia between January 1, 2007, and December 31, 2013, and had at least 1 triglyceride measurement annually for 4 consecutive years from the Chang Gung Research Database in Taiwan. Triglyceride variability, defined as variability independent of the mean, was calculated in the 4-year run-in period. The patients were stratified according to the quartiles of triglyceride variability and were followed until December 31, 2019, for first attack of acute pancreatitis. During a mean follow-up of 5.9 years, 825 (0.83%) patients were newly diagnosed with acute pancreatitis (14.1 events per 10,000 person-years; 95% confidence interval 13.2-15.1). Triglyceride variability was significantly associated with an increased risk of acute pancreatitis, independent of baseline triglyceride and mean triglyceride levels (hazard ratio, 1.28 [95% confidence interval 1.05-1.57] for the highest vs the lowest quartiles of triglyceride variability; P for trend = 0.006 over the quartiles of triglyceride variability). Subgroup analysis showed that this association was more pronounced among the patients with a higher neutrophil-to-lymphocyte ratio ( P for trend = 0.022). In this multi-institutional cohort study, high triglyceride variability was associated with an increased risk of first attack of acute pancreatitis, independent of baseline and mean triglyceride levels. The association between triglyceride variability and acute pancreatitis may be partly mediated by subclinical inflammation.

U-shaped association between triglyceride and risk of incident diabetes in normoglycemic males with NAFLD: A population-base cohort study.

Background: Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. Methods: A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. Results: During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). Conclusions: A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.

Increased residual cardiovascular risk in U.S. veterans with moderately-elevated baseline triglycerides and well-controlled LDL-C levels on statins

Recent studies have demonstrated a causal role for elevated triglycerides (TG) in incident cardiovascular (CV) events in patients with established coronary heart disease (CHD) and those with CV risk factors alone, particularly diabetes. Using a large cohort of U.S. veterans with statin-controlled LDL-C levels (40-100 mg/dL), we explored residual CV risk among patients with elevated baseline TG levels (150-499 mg/dL) vs. those with normal TG levels (<150 mg/dL). We identified veterans receiving a statin but not a TG-lowering agent from the VA electronic health records database, from 2010 to 2015. We compared composite CV event rates (MI, stroke, unstable angina, coronary revascularization, and CV death) between the elevated TG and normal TG groups. We stratified the study cohort according to 3 CV risk groups: (1) no diabetes and no prior CV event, (2) diabetes and no prior CV event, and (3) prior CV event. We calculated crude event rates, rate ratios, and event rate ratios adjusted for age, sex, systolic blood pressure, estimated glomerular filtration rate, and weight. The cohort included 396,189 veterans (predominantly male and white) of whom 109,195 (28%) had elevated TG levels. Those with elevated TG were younger (age 73 vs. 77 years) and had a higher body mass index (31.3 vs. 28.3 Kg/M2). The overall composite crude and adjusted rate ratios comparing the elevated and normal TG groups were 1.10 (1.09, 1.12) and 1.05 (1.03, 1.06), respectively. For CV risk groups 1, 2 and 3, the adjusted rate ratios comparing the elevated and normal TG groups were 0.99 (0.96, 1.02), 1.05 (1.02, 1.08), and 1.07 (1.04, 1.10), respectively. An association of increased rate ratios did not hold for fatal events. Those with elevated TG levels and well-controlled LDL-C on statins showed a modest increase in CV events compared to those with normal TG. Elevated TG levels were associated with increased CV events in patients with established CV disease and with diabetes only, suggesting that elevated TG levels are associated with a similar degree of residual risk in high-risk primary prevention and secondary prevention settings.

Efficacy and safety of lomitapide in familial chylomicronaemia syndrome

Background and aimsFamilial chylomicronaemia syndrome (FCS) is a rare autosomal recessive disorder, resulting in elevated triglycerides (TGs), abdominal pain and pancreatitis. Treatment options are limited. Lomitapide, a microsomal triglyceride transfer protein inhibitor, is approved for the treatment of homozygous familial hypercholesterolaemia. Whether its therapeutic use may be extended to FCS remains unknown. The aim of this study was to evaluate the efficacy and safety of lomitapide in adult patients with FCS. MethodsThe open-label, single-arm ‘LOCHNES’ study of lomitapide in FCS enrolled patients >18 years with genetically confirmed FCS, elevated fasting TG ≥ 750 mg/dL and history of pancreatitis. Patients were administered lomitapide to the maximum tolerated dose for 26 weeks. The primary endpoint was the percent change in TGs from baseline to Week 26. ResultsEighteen patients were enrolled with median baseline TG levels 1803.5 mg/dL (97.5% CI, 1452–2391 mg/dL). At Week 26, median fasting TGs were reduced to 305 mg/dL (97.5% CI 219–801 mg/dL; 70.5% reduction); median lomitapide dose was 35 mg/day; 13 patients achieved TGs ≤750 mg/dL. Adverse events were mild to moderate and mainly related to gastrointestinal tolerability. Liver imaging at baseline and Week 26 revealed hepatic fat increases from median 12.0%–32.5%, while median hepatic stiffness remained normal. No patient experienced acute pancreatitis or severe abdominal pain during lomitapide treatment. ConclusionsLomitapide is effective and well tolerated in reducing TGs in FCS patients with a history of pancreatitis. Larger studies are warranted to determine lomitapide effectiveness in FCS.

481-P: Eligibility for Icosapent Ethyl in Patients with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease: An Analysis of VERTIS CV

Among patients with type 2 diabetes (T2D) treated with statins, residual cardiovascular (CV) risk remains. Because icosapent ethyl (IPE) has been shown to decrease CV risk in patients on statin therapy, we explored potential eligibility for IPE therapy in VERTIS CV (NCT01986881) , the CV outcomes trial of ertugliflozin in which all patients had T2D and atherosclerotic CV disease (ASCVD) . We analyzed eligibility for IPE based on REDUCE-IT trial inclusion criteria (on statin, fasting triglyceride of 135 to 499 mg/dL and low-density lipoprotein cholesterol of 41 to 100 mg/dL) . Among 8246 patients randomized, the mean age was 64 years and 30% were female. At baseline, 6747 (81.8%) patients used statins, while 293 (3.6%) used ezetimibe, 389 (4.7%) used fish oil, and 8 (0.1%) used IPE. The REDUCE-IT trial inclusion criteria were met by 2444 (29.6%) patients at baseline and an additional 2500 (30.3%) did not fully meet the criteria but had baseline triglyceride level &amp;gt;135 mg/dL (Figure) . In conclusion, this analysis of the VERTIS CV trial population identified important opportunities to reduce residual CV risk: consideration of adding statin therapy in 18% of patients and of adding IPE based on the REDUCE-IT trial inclusion criteria or triglyceride level threshold in 60% of patients. These findings highlight the need to optimize lipid therapies in patients with T2D and ASCVD. Disclosure J.M.Kim: Other Relationship; Pfizer Inc. R.Frederich: Employee; Pfizer Inc., Stock/Shareholder; Bristol-Myers Squibb Company, Pfizer Inc. J.P.Mancuso: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. C.P.Cannon: Advisory Panel; Alnylam Pharmaceuticals, Inc., Amarin Corporation, Amgen Inc., Amryt Pharma Plc, Applied Therapeutics, Ascendis Pharma A/S, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck &amp; Co., Inc., Pfizer Inc., Rhoshan, Sanofi, Research Support; Amgen Inc., Better Therapeutics, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Daiichi Sankyo, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc. D.L.Bhatt: Research Support; Afimmune Limited, Amarin Corporation, Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Chiesi USA, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Novartis AG, Sanofi. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Sanofi. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. F.Cosentino: Advisory Panel; Merck Sharp &amp; Dohme Corp., Pfizer Inc., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Lilly, Merck Sharp &amp; Dohme Corp., Novo Nordisk. D.K.Mcguire: Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, ESPERION Therapeutics, Inc., Lexicon Pharmaceuticals, Inc., Lilly, Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi. R.E.Pratley: Other Relationship; Bayer AG, Corcept Therapeutics, Dexcom, Inc., Hanmi Pharm. Co., Ltd., Merck &amp; Co., Inc., Metavention, Novo Nordisk, Pfizer Inc., Poxel SA, Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. C.Liu: Employee; Merck &amp; Co., Inc., Stock/Shareholder; Merck &amp; Co., Inc. N.B.Cater: Employee; Pfizer Inc., Stock/Shareholder; Pfizer Inc. Funding Merck Sharp &amp; Dohme Corp.

Cumulative effects of hypertriglyceridemia in HIV-infected patients switching from NNRTIs to PI-based antiretroviral therapy.

The objective of this study was to investigate changes in serum lipids among HIV-infected patients switching from non-nucleoside-reverse transcriptase inhibitors (NNRTI) to protease inhibitor (PI)-based highly active antiretroviral therapy (HAART), and to determine if changes of lipid profiles impacted the monocyte subsets recovery. Fifty-seven subjects who switched from NNRTIs to PI-based HAART (NNRTIs to PI group) and fifty-five subjects who initially started with PI-based HAART (initial PI group) were recruited. According to their baseline triglyceride (TG) levels, the NNRTIs to PI and initial PI groups were further divided into non-hypertriglyceridemia and hypertriglyceridemia subgroups, respectively. The effects of PI-based HAART on lipid profiles and monocyte subsets were analyzed. At 48 weeks, the TG changes in the NNRTIs to PI group was higher than that of the initial PI group. The increases of serum TG levels in the initial PI non-hypertriglyceridemia group was greater than that of the NNRTIs to PI non-hypertriglyceridemia group. For the hypertriglyceridemia group at baseline, significant increment in TG levels were observed in the NNRTIs to PI hypertriglyceridemia group. The percentages of circulating CD14highCD16+ and CD14lowCD16+ subsets were elevated in the two groups. At 48 weeks, the proportion of CD14highCD16+ monocytes declined gradually, and the proportion of CD14lowCD16+ monocytes decreased independently of the TG level. For non-hypertriglyceridemia individuals at baseline, PI-based regimens increased the TG level in the initial PI group. For the NNRTIs to PI hypertriglyceridemia group, PI-based regimens reinforced HAART-related hypertriglyceridemia.

Global assessment improves risk stratification for major adverse cardiac events across a wide range of triglyceride levels: Insights from the KP REACH study

ObjectivePatients with risk factors for or established atherosclerotic cardiovascular disease (ASCVD) remain at high risk for subsequent ischemic events despite statin therapy. Triglyceride (TG) levels may contribute to residual ASCVD risk, and the performance of global risk assessment calculators across a broad range of TG levels is unknown. MethodsWe performed a retrospective cohort study of Kaiser Permanente Northern California members aged ≥45 years with ≥1 ASCVD risk factor (primary prevention cohort) or established ASCVD (secondary prevention cohort) between 2010 and 2017 who were receiving statin therapy and had a low-density lipoprotein cholesterol between 41–100 mg/dL. Global ASCVD risk assessment was performed using both the Kaiser Permanente ASCVD Risk Estimator (KPARE) and the ACC/AHA ASCVD Pooled Cohort Equation (PCE). Outcomes included major adverse cardiovascular events (MACE) defined as myocardial infarction, stroke, or peripheral artery disease, and expanded MACE (MACE + coronary revascularization + hospitalization for unstable angina). ResultsAmong 373,389 patients in the primary prevention cohort, median TG was 122 mg/dL (IQR 88–172 mg/dL) and there were 0.2 MACE events and 0.3 expanded MACE events per 100-person years. Among 97,832 patients in the secondary prevention cohort, median TG level was 116 mg/dL (IQR 84–164 mg/dL) and there were 9.6 MACE events and 22.0 expanded MACE events per 100-person years. KPARE and the ACC/AHA PCE stratified patients for MACE and expanded MACE over the entire range of TGs. ConclusionIn a cohort receiving statin therapy for primary or secondary prevention, we found global assessment further improves risk stratification for initial and/or recurrent ASCVD events irrespective of baseline TG level.