Risk Of Dyslipidemia Research Articles

Abstract 4138221: Ezetimibe plus statin combination vs. double dose statin for patients with dyslipidemia and ASCVD risk: A Systematic Review and Meta-Analysis

Background: Dyslipidemia is a major risk factor for Atherosclerotic Cardiovascular Disease (ASCVD). Statin is a crucial intervention to fix dyslipidemia and reduce the ASCVD risk. Still, there are several regimens to achieve blood lipid level targets, including increasing the statin dose or adding ezetimibe to the statin used. However, the best option between the two regimens is still a matter of debate. Research Question: We aim to evaluate the efficacy and safety of Ezetimibe plus any type of statin versus a double dose of the same statin in patients with ASCVD risk. Methods: A systematic review and meta-analysis based on randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS till December 2023. We used the random-effects model to report dichotomous outcomes using odds ratio (OR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). Results: Forty-seven studies with a total of 18592 patients were included. Ezetimibe plus statin was associated with a decrease in low-density lipoprotein (LDL) levels [MD: -13.69 with 95% CI (-15.64, -11.74), P <0.01], and more patients achieving their targeted LDL levels [OR: 2.89 with 95% CI (2.40, 3.47), P <0.01]. However, there was no significant difference between the two groups regarding any adverse events [OR: 0.98 with 95% CI (0.89, 1.08), P =0.62], and the composite endpoint of cardiovascular death, major coronary events, or nonfatal stroke [OR: 0.72 with 95% CI (0.39, 1.32), P = 0.29], although there was a trend towards better results for patients with the combination regimen. Conclusion: Ezetimibe plus statin combination led to more reduced LDL levels and more patients achieving their goal levels than double dose statin, without a significant difference in the rate of any adverse events occurrence. More RCTs are mandatory to assess the effect of both regimens on major clinical events such as stroke, coronary events, and death.

Immune-Mediated Inflammatory Diseases, Dyslipidemia, and Cardiovascular Risk: A Complex Interplay.

Individuals with autoimmune inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and psoriasis, are at increased risk for cardiovascular disease. While these diseases share common features of systemic inflammation, the impact of individual autoimmune inflammatory conditions on circulating lipids and lipoproteins varies by specific disease, disease activity, and the immune-suppressing medications used to treat these conditions. A common feature observed in many autoimmune inflammatory diseases is the development of a proatherogenic dyslipidemic state, characterized by dysfunctional HDLs (high-density lipoproteins) and increased oxidation of LDLs (low-density lipoproteins). Various disease-modifying antirheumatic drugs also have complex and variable effects on lipids, and it is critical to take this into consideration when evaluating lipid-related risk in individuals with immune-mediated inflammatory conditions. This review aims to critically evaluate the current understanding of the relationship between immune-mediated inflammatory diseases and dyslipidemia, the underlying mechanisms contributing to atherogenesis, and the impact of various pharmacotherapies on lipid profiles and cardiovascular risk. We also discuss the role of lipid-lowering therapies, particularly statins, in managing residual risk in this high-risk population and explore the potential of emerging therapies with complementary anti-inflammatory and lipid-lowering effects.

Clinical characteristics and outcomes of patients with acute coronary syndrome without standard metabolic cardiovascular risk factors

Abstract Background/Introduction Patients with acute coronary syndrome (ACS) commonly present with hypertension, diabetes mellitus (DM), and dyslipidaemia as standard modifiable metabolic risk factors. However, little is known about patients with ACS who do not have these risk factors. Purpose This study investigated the clinical characteristics and outcomes of patients with ACS without these risk factors who underwent primary percutaneous coronary intervention (PCI). Methods This retrospective, single-centre observational study included 1131 consecutive patients with ACS who were admitted to a hospital between January 2013 and May 2021. After excluding patients who did not undergo revascularization or who underwent emergency coronary artery bypass surgery, 947 patients who underwent primary PCI were included in the analysis. Patients were classified into two groups: those with one or more of the following: hypertension, DM, or dyslipidaemia (risk group) and those without any of these factors (non-risk group). Major adverse cardiovascular events (MACE), including all-cause mortality, myocardial infarction (MI), stroke, and heart failure requiring rehospitalisation, were assessed at the 1-year follow-up. Results This study classified 78 patients (8.2%) in the non-risk group, who exhibited a significantly lower body mass index (BMI) [23.0 (interquartile range: 21.8–24.7) vs. 23.8 (interquartile range: 21.8–26.2) kg/m2, p = 0.016], compared to the risk group. There were no significant differences in smoking history between the two groups (51.2% vs. 48.9%, p = 0.39). Within 1 year after PCI, MACE occurred in 146 (15.4%) patients (88 [9.2%] with all-cause death, 13 [1.3%] with MI, 23 [2.4%] with stroke, and 27 [2.8%] with heart failure requiring rehospitalisation), with a significantly higher incidence in the non-risk group compared to the risk group (24.4% vs. 14.6%, p = 0.027). Multivariate analysis revealed that both being in the non-risk group and having a low BMI (< 21.5) were independent determinants for the incidence of MACE (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.01–2.29; p = 0.042 and HR: 3.08; 95% CI: 1.30–7.27; p = 0.010, respectively). Kaplan–Meier survival analysis showed a higher MACE rate in the non-risk group than in the risk group (p = 0.009). Conclusions Patients with ACS without hypertension, DM, or dyslipidaemia have a poorer prognosis than those with these risk factors, independent of the presence of a lower BMI, and the underlying pathophysiology in this subset of patients needs to be clarified.figure

Double-sided effect of selenium on blood lipids: A dose-response meta-analysis

Abstract Background Selenium, a trace element with both nutritional and toxicological properties, has been suggested to increase cardiovascular risk, particularly concerning diabetes and blood pressure levels. However, the impact of selenium exposure on the risk of dyslipidemia remains uncertain. This meta-analysis explored the shape of the relation between selenium exposure and its effects on lipid profiles in the most relevant experimental human studies, randomized controlled trials (RCTs). Materials and methods The review was registered in PROSPERO (ID: CRD42022380432). Through a bibliographic search conducted on PubMed, Web of Science, Embase, and the Cochrane Library, we identified RCTs investigating the impact of selenium supplementation on lipid profile. We then compared the results between intervention and control groups and, whenever possible, evaluated the non-linear relationship using a dose-response approach. Results We could include 26 RCTs involving different populations, i.e. healthy individuals, pregnant women, and subjects with health conditions such as cardiovascular diseases and Alzheimer’s dementia. Study endpoints were levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. Our dose-response analysis indicated that selenium supplementation exceeding 200 µg/day adversely affected total cholesterol, HDL, and triglyceride levels. Hence, a threshold for such a detrimental effect of selenium was observed on total and HDL cholesterol and triglycerides, while opposite and inconsistent results emerged for levels below 200 µg/day and for LDL-cholesterol. Blood selenium levels at the end of the studies were positively associated with adverse effects on all endpoints. Conclusions This first dose-response meta-analysis of the effects of selenium on blood lipids highlights the potentially adverse effects of this trace element, in the amount and the chemical forms used in the trials. Key messages • Elevated selenium levels correlated with adverse effects on lipid profile. • Selenium doses exceeding 200 µg/day showed adverse effects on total and HDL cholesterol and triglycerides levels.

PCSK9 inhibitors in HIV patients with dyslipidemia

Abstract Introduction Cardiovascular disease has become increasingly prevalent in the HIV (human immunodeficiency virus) population. Antiretroviral therapy and HIV itself independently increase the risk of dyslipidemia. While statins are currently the predominant therapy to treat dyslipidemia in HIV patients, drug-drug interactions and adverse drug events can limit their use. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a naturally occurring inhibitor of the LDL-receptor pathway. PCSK9 inhibitors offer an alternative in patients who cannot tolerate or need additional therapy in addition to statin for optimal dyslipidemia management. Purpose The purpose of this study is to compare major adverse cardiovascular events in HIV patients on a PCSK9 inhibitor (evolucumab, alirocumab, inclisiran) vs patients not on a PCSK9 inhibitor. Methods A retrospective cohort study was conducted using electronic medical records from a global federated health research network. The TriNetX network was searched on February 10, 2024, including records from 2020 to 2024. Patients were included based on a diagnosis of HIV status and concomitant dyslipidemia. Patients with HIV and dyslipidemia on a PCSK9 inhibitor were propensity-score matched for age, sex, race, and comorbidities with patients who were not on a PCSK9 inhibitor. The outcomes were mortality, myocardial infarction, heart failure and stroke. Results A total of 485 patients were included in the study. PCSK9 inhibitor use associated with 9% lower odds of all-cause mortality (odds radio, .29; 95% CI, 0.18-0.48; p<.0001). PCSK9 inhibitor use was also associated with 8% lower odds of heart failure (odds radio, .63; 95% CI, 0.47-0.85; p<.0023). No significant associations were noted for myocardial infarction (odds radio, .87; 95% CI, 0.63-1.21; p=0.406) or stroke (odds radio, .67; 95% CI, 0.45-1.01; p=0.052). Conclusion The role of dyslipidemia in HIV is challenging due the complex pathophysiology of HIV. There is an apparent increased risk of cardiovascular disease from the infection itself as well current antiretroviral therapies. While current guidelines recommend the use of statins as first line therapy for dyslipidemia in this population, the drug-drug interaction of statins with ARTs, as well as their side effects, limit their use at times. PCSK9 inhibitors are associated with lower odds of all-cause mortality and heart failure. No significant association was seen for myocardial infarction or stroke. They should be considered as an early intervention alongside statins in HIV patients with dyslipidemia. Further research should be done for the long term safety and tolerance of this therapy as well as cost-effectiveness and access to PCSK9 inhibitors in this population.

Cardiometabolic index and the risk of new-onset chronic diseases: results of a national prospective longitudinal study.

The cardiometabolic index (CMI) has emerged as a novel marker for evaluating the distribution and dysfunction of visceral adipose tissue, yet its correlation with numerous diseases, particularly new-onset chronic conditions, remains underexplored. Therefore, we aim to explore the association of cardiometabolic index (CMI) and new-onset chronic diseases. The analysis utilized data from the China Health and Retirement Longitudinal Study, with a baseline in 2011 and follow-ups biennially until 2020. Fourteen new-onset chronic diseases were diagnosed based on self-report, and separate cohorts were created for each disease. CMI was calculated as triglycerides/high-density lipoprotein cholesterol multiplied by the waist-to-height ratio. Cox proportional hazards models were used to assess the association between CMI and new-onset chronic diseases, while restricted cubic spline (RCS) models were employed to explore potential nonlinear effects. Additional and sensitivity analyses included Kaplan-Meier survival curves, subgroup analyses, multiple imputations, and exclude outcome events at the first follow-up. Higher levels of CMI were associated with an increased risk of new-onset hypertension (HR=1.05, 95% CI=1.04-1.06, P<0.001), diabetes (HR=1.08, 95% CI=1.06-1.09, P<0.001), dyslipidemia (HR=1.07, 95% CI=1.06-1.09, P<0.001), liver disease (HR=1.05, 95% CI=1.03-1.07, P<0.003), and stroke (HR=1.04, 95% CI=1.02-1.06, P<0.001), although the association with stroke was not significant after adjusting for confounders (HR=1.02, 95% CI=1.00-1.05, P=0.054). Participants in the highest quartile of CMI had a significantly higher risk of these diseases compared to those in the lowest quartile. RCS analyses showed a significant nonlinear relationship between CMI and the risk of these diseases above. CMI showed a significant positive association with the risk of new-onset chronic diseases such as hypertension, diabetes, dyslipidemia, and liver disease. Future applications of CMI hold promise as an effective marker for early identification of chronic disease risk.

Advanced lipid testing in children: a call for pediatric reference intervals

Abstract Introduction Abnormal serum lipid levels in childhood are associated with dyslipidemia and increased risk of cardiovascular disease in adulthood. High prevalence of childhood obesity in the US has increased concerns about the adverse effects of abnormal lipids in children, prompting recommendations for universal lipid screening in adolescents. While specialized analysis of lipoproteins by nuclear magnetic resonance (NMR) has been predominately used in adults with risk factors for CVD, our laboratory also receives pediatric samples for NMR testing, most commonly associated with diagnostic codes for hyperlipidemia and/or abnormal weight gain. Currently adult-based reference ranges for the NMR lipoprotein measurements are used in children. The objective of this pilot study was to compare lipoprotein profiles of healthy adults and children and to assess the impact of reference intervals for children on clinical interpretation of pediatric results. Methods Serum samples were collected from 60 healthy children, ages 1 – 17 years, and 148 healthy adults, ages 19 – 64 years old. NMR lipoprotein analysis was performed using the Axinon lipoFIT by NMR assay on a 600 MHz NMR (Bruker). Statistical analysis was conducted in Excel and GraphPad Prism. Reference intervals (RIs) were determined in EP Evaluator as the central 95% interval. Results The levels of atherogenic low-density lipoprotein particle number (LDL-P) and small LDL-P (sLDL-P) were significantly lower in children compared to adults: 783±222 vs 1212±412 nmol/L and 302±142 vs 498±306 nmol/L, respectively (p&amp;lt;0.00001). Additionally, LDL size (LDL-s) was significantly larger in children than adults (21.23±0.29 vs 21.06±0.44 nm, p=0.006), reflecting prevalence of less dense LDL-P in the former group. Pediatric samples also had lower number of anti-atherogenic high-density lipoprotein particles (HDL-P) compared to adults: 29.4±4.6 vs 33.5±4.6 µmol/L, p&amp;lt;0.00001. The significant differences in the number and size of lipoprotein particles between adults and children implies that currently used adult reference intervals might not be appropriate for evaluating pediatric NMR samples. Therefore, we estimated RIs for our heathy pediatric and adult cohorts and applied these RIs to our retrospective data of 618 samples from children 1-17 years old, which were submitted for NMR lipoprotein testing in recent years. The analysis showed that using the adult RIs, 37% and 27% of pediatric samples would not flag for abnormally elevated LDL-P and sLDL-P, respectively; but they would be flagged based on the RI derived from our pediatric cohort. Moreover, 12% pediatric samples flagged for low HDL-P would have normal HDL-P levels if pediatric RIs are used instead of adult RIs. Conclusions Use of adult reference intervals in children may result in misclassification of lipid status and underestimation or overestimation of dyslipidemia and CVD risk in children. This pilot study highlights the need for pediatric reference intervals to guide interpretation of advanced lipid testing in children.

Serum uric acid: an independent risk factor for cardiovascular disease in Pakistani Punjabi patients

BackgroundIt is well-known that serum uric acid (SUA) can increase the risk of hypertension, diabetes, obesity and dyslipidemia. However, its independent association with the risk of cardiovascular diseases (CVD) is controversial particularly in different populations. Hence, this study was aimed to assess an independent association of SUA with CVD risk in a Punjabi Pakistani cohort.MethodsThis is a retrospective observational study in which 502 human subjects having CVD, hypertension and/or diabetes were grouped based on SUA levels as normouricemia (n = 266) and hyperuricemia (n = 236). Role of SUA was assessed in increasing the risk of CVD independent of other key confounding factors (i.e. age, gender, dyslipidemia, hypertension, diabetes, dietary and life-style habits). All clinical and biochemical data were analyzed in SPSS (ver. 20).ResultsSubjects aged 55 ± 13 years were of both genders (males: 52%). SUA levels were significantly different among clinical subtypes of CVD [i.e. acute coronary syndrome (ACS), myocardial infarction (MI) and heart failure (HF)]. Spearman correlation showed a significantly positive association between CVD and SUA (rho = 0.149, p < 0.001). Multivariate logistic regression of SUA quartiles showed that hyperuricemia is associated with CVD [3rd quartile: OR: 1.78 (CI: 1.28–2.48), p = 0.001 and 4th quartile: OR: 2.37 (CI: 1.72–3.27), p < 0.001]. Moreover, this association remained significant even after adjusting for confounding factors.ConclusionThis study showed that SUA is positively associated with CVD, thus it can act as an independent risk factor for CVD.

Maternal Lipids in Pregnancy and Later Life Dyslipidemia: The POUCHmoms Longitudinal Cohort Study.

Maternal lipid levels increase in normal pregnancies. Here, we examine whether pregnancies with the highest total cholesterol, low-density lipoprotein (LDL) or triglyceride levels or the lowest high-density lipoprotein (HDL) levels predict future dyslipidemia post-pregnancy. Longitudinal cohort study. Five communities in Michigan, USA. Pregnant women (n = 649) with blood lipid levels measured at mid-pregnancy in the Pregnancy Outcomes and Community Health (POUCH) Study and at the POUCHmoms Study follow-up, 7-15 years later. Maternal mid-pregnancy lipid levels were defined as 'high' (upper quartile of triglycerides ≥ 216 mg/dL, LDL ≥ 145 mg/dL and total cholesterol ≥ 256 mg/dL) or 'low' (lower quartile, HDL < 58 mg/dL) using whole sample lipid distributions. At follow-up, dyslipidemia was classified by the clinical cutoffs of triglycerides and total cholesterol ≥ 200 mg/dL, LDL ≥ 130 mg/dL and HDL < 50 mg/dL. Weighted regression models estimated the risk of dyslipidemia at follow-up in relation to pregnancy lipid levels, adjusted for baseline confounders. Dyslipidemia later in life. Mid-pregnancy triglycerides, LDL, and total cholesterol levels at the upper quartile were associated with at least threefold increase in the risk of abnormal triglycerides, LDL and total cholesterol levels later in life. Women with low mid-pregnancy HDL levels had just over a twofold increased risk of abnormally low HDL levels at follow-up. These associations persisted following adjustment for covariates, i.e. demographics, lifestyle, and years of follow-up. Higher mid-pregnancy LDL, total cholesterol and triglycerides and lower levels of HDL may signal future dyslipidemia risk and the need for closer lipid monitoring to ensure timely interventions that can attenuate cardiovascular disease risk.

Cardiometabolic factors and vitamin D deficiency in pediatric patients with chronic kidney disease.

Patients with chronic kidney disease (CKD) are at increased risk for cardiovascular disease. Up to 80% of patients with CKD may exhibit inadequate vitamin D (VD) levels, which have been linked to the presence of cardiometabolic factors (CFs) in the adult population. However, research on this association in the pediatric population is limited. To analyze the effects of 25-hydroxyvitamin D3 (25-[OH]D) levels and status on the presence of CFs in children receiving kidney replacement therapy (KRT). This cross-sectional study included pediatric patients receiving KRT, aged 8-17 years, who were receiving hemodialysis or peritoneal dialysis from January 2021 to March 2024. We conducted anthropometric measurements, blood pressure assessments, and glucose, 25-(OH)D, and lipid profiling for all participants. The daily dose of cholecalciferol supplementation, as well as other medications affecting bone and lipid metabolism and antihypertensive drugs, were documented. Statistical analyses were performed using Student's t-tests and chi-square tests to compare the CFs between groups with and without VD deficiency. The study involved 156 patients with an average age of 12.9 years and a mean serum VD level of 22.5 ng/dL. Patients with VD deficiency presented higher levels of total cholesterol and diastolic blood pressure (p < 0.05). No statistically significant differences were found in other biochemical profile variables or in the frequency of cardiometabolic factors. Vitamin D deficiency seems to increase the risk of dyslipidemia and uncontrolled hypertension in children and adolescents with end-stage CKD.

7822 Mild Autonomous Cortisol Secretion In High Suspicious Adrenal Incidentaloma

Abstract Disclosure: N. Zavrashvili: None. N. Margvelashvili: None. K. Chanturishvili: None. Mild Autonomous Cortisol Secretion in High Suspicious Adrenal IncidentalomaIntroduction: Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. 55-year-old women with 5-year history of hypertension and hyperlipidemia. She was treated with a three-drug program: verapamil 250 mg daily, combined B-blocker, atenolol 100 mg and chlorthalidone 25 mg daily. Blood pressure control remained suboptimal. Her body mass index was 29,5 kg/m2. She had no signs or symptoms of overt Cushing syndrome.She was referred to CT coronary angiogram by her cardiologist, which revealed adrenal incidentaloma.Adrenal dedicated CT showed left-sided 3,4 cm high density node (41HU), with absolute washout &amp;lt;60. She was consulted by oncologist to exclude adrenal metastasis. The baseline laboratory test results excluded PA and Pheochromocytoma. The diagnosis of glucocorticoid secretory autonomy was based on positive low-dose dexamethasone suppression test (DST), low serum ACTH concentration, low-normal DHEA-S and lack of complete suppression of serum cortisol with an overnight 8-mg DST. Patient was referred to left-sided laparoscopic adrenalectomy with perioperative glucocorticoid coverage (100 mg hydrocortisone administered IV and again 8 hours later). Conclusion: Mild autonomous cortisol secretion is a term used to describe biochemical evidence of abnormal cortisol secretion in patients with adrenal incidentaloma, but without the classical external manifestations of overt CS, such as central muscle weakness, adipose tissue redistribution, and skin fragility. The management of patients with an incidentally discovered adrenal adenoma who do not have overt Cushing’s syndrome but who have MACS is more controversial as the available studies comparing outcomes of adrenalectomy vs conservative management have been generally small. It is associated with an increased risk of Type 2 diabetes mellitus, HBP, obesity, dyslipidemia, and global cardiovascular risk. Therefore, it is of great importance to correctly identify these patients. There are different tests for the screening of hypercortisolism. However, in the absence of a single test considered as the gold standard, it is necessary to combine the different tests to reach an adequate diagnostic capacity. The indication of surgery in ACS patients should be based mainly on the hormonal evaluation and the comorbidities potentially mediated by cortisol. Presentation: 6/1/2024

6707 Preconception Lipids, Birthweight, And Pregnancy Outcomes In Pre-existing Diabetes

Abstract Disclosure: J. Chang: None. S. Hsu: None. T. Thaweethai: None. K.E. James: None. L.L. Shook: None. J. Maya: None. C.E. Powe: Consulting Fee; Self; Mediflix Inc. Other; Self; Wolters Kluwer, Up to Date Author. Objective Prior studies suggest that higher preconception triglycerides are associated with higher infant birthweight in people without pre-existing diabetes. People with pre-existing diabetes have high risk for dyslipidemia and large for gestational age (LGA) neonates; however, data is scarce on the association between preconception lipids and pregnancy outcomes in this population. Methods: We retrospectively analyzed pregnancies with pre-existing diabetes who had triglyceride levels available prior to conception. We used generalized estimating equations (GEE) for linear regression to examine the association of preconception log-transformed triglycerides with birthweight percentile (primary outcome) while accounting for pregnancies that occurred in the same person. We used logistic regression via GEE for other pregnancy outcomes, including LGA. We built unadjusted models and models adjusted for maternal age, race/ethnicity, parity, insurance status, marital status, first trimester blood pressure, and BMI and hemoglobin A1C at 12 weeks’ gestation. We assessed for effect modification by diabetes type via stratification and interaction models. Results: Among 217 pregnancies in 189 people, 27% had preconception triglycerides ≥150 mg/dL and 32% resulted in LGA infants. Log-transformed triglycerides were not significantly associated with birthweight percentile in the full cohort in either adjusted (P = 0.62) or unadjusted models (P = 0.35). However, in unadjusted analyses stratified by diabetes type, a one unit increase in log-transformed triglycerides was associated with a 10.4 percentile increase in birthweight in pregnancies with type 2 diabetes (T2D; N=137) (95% confidence interval [CI] [1.12, 19.63], P = 0.03) and a 16.0 percentile decrease in birthweight in those with type 1 diabetes (T1D; N=76) (95% CI [-30.03, -1.95], P = 0.03). These associations were significantly different from each other (P for interaction = 0.002). Associations were attenuated after multivariate adjustment (T2D: β = 6.62, 95% CI [-3.42, 16.66], P= 0.20; T1D: β = -11.12, 95% CI [-23.61, 1.37], P= 0.08). Analyses of LGA incidence were consistent with primary findings, as those with T2D and higher log-transformed triglyceride levels were more likely to have LGA infants (odds ratio [OR] = 3.84, 95% CI [1.71, 8.62], P= 0.001) while an inverse association was seen in T1D (OR = 0.35, 95% CI [0.13, 0.94], P= 0.04). After multivariate adjustment, the association with LGA persisted in T2D (OR = 4.03, 95% CI [1.42, 11.44], P= 0.01) but was attenuated in T1D (OR = 0.34, 95% CI [0.09, 1.27], P= 0.11). Conclusion: Higher preconception triglycerides are associated with higher infant birthweight in people with T2D, while the inverse may be seen in those with T1D. Mechanisms linking preconception triglycerides and birthweight in people with diabetes should be examined in future studies. Presentation: 6/2/2024

A-227 One Step Toward Implementation of Advanced Lipoprotien Testing in Children: A Pilot Study on Pediatric Reference Ranges

Abstract Background Abnormal serum lipid levels in childhood are associated with dyslipidemia and increased risk of cardiovascular disease in adulthood. High prevalence of childhood obesity in the US has increased concerns about the adverse effects of abnormal lipids in children, prompting recommendations for universal lipid screening in adolescents. While specialized analysis of lipoproteins by nuclear magnetic resonance (NMR) has been predominately used in adults with risk factors for CVD, our laboratory also receives pediatric samples for NMR testing, most commonly associated with diagnostic codes for hyperlipidemia and/or abnormal weight gain. Currently adult-based reference ranges for the NMR lipoprotein measurements are used in children. The objective of this pilot study was to compare lipoprotein profiles of healthy adults and children and to assess the impact of reference intervals for children on clinical interpretation of pediatric results. Methods Serum samples were collected from 60 healthy children, ages 1 - 17 years, and 148 self-identified healthy adults, ages 19 - 64 years old. NMR lipoprotein analysis was performed using the Axinon lipoFIT by NMR assay on a 600 MHz NMR (Bruker). Statistical analysis was conducted in Excel and Graph Pad Prism. Reference intervals (RIs) were determined in EP Evaluator as the central 95% interval. Results The levels of atherogenic low-density lipoprotein particle number (LDL-P) and small LDL-P (sLDL-P) were significantly lower in children compared to adults: 783±222 vs 1212±412 nmol/L and 302±142 vs 498±306 nmol/L, respectively (p&amp;lt;0.00001). Additionally, LDL size (LDL-s) was significantly larger in children than adults (21.23±0.29 vs 21.06±0.44 nm, p=0.006), reflecting prevalence of less dense LDL-P in the former group. Pediatric samples also had lower number of anti-atherogenic high-density lipoprotein particles (HDL-P) compared to adults: 29.4±4.6 vs 33.5±4.6 µmol/L, p&amp;lt;0.00001. The significant differences in the number and size of lipoprotein particles between adults and children implies that currently used adult reference intervals might not be appropriate for evaluating pediatric NMR samples. Therefore, we estimated RIs for our heathy pediatric and adult cohorts and applied these RIs to our retrospective data of 618 samples from children 1-17 years old, which were submitted for NMR lipoprotein testing in recent years. The analysis showed that using the adult RIs, 37% and 27% of pediatric samples would not flag for abnormally elevated LDL-P and sLDL-P, respectively; but they would be flagged based on the RI derived from our pediatric cohort. Moreover, 12% pediatric samples flagged for low HDL-P would have normal HDL-P levels if pediatric RIs are used instead of adult RIs. Conclusions Use of adult reference intervals in children may result in misclassification of lipid status and underestimation or overestimation of dyslipidemia and CVD risk in children. This pilot study highlights the need for pediatric reference intervals to guide interpretation of advanced lipid testing in children.

Effectiveness of Resmetirom in Reducing Cholesterol Levels in Patients With Nonalcoholic Steatohepatitis: A Systematic Review and Meta-Analysis.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) associated with metabolic syndrome and increased cardiovascular risk. Resmetirom, a novel liver-directed selective thyroid hormone receptor-β (THR-β) agonist, has shown promise in addressing both hepatic and systemic lipid metabolism. This systematic review and meta-analysis aimed to evaluate the efficacy of resmetirom in improving cholesterol levels in NASH patients. A systematic literature search was conducted across multiple databases including PubMed, Embase, Cochrane Library, andClinicalTrials.gov, identifying three randomized controlled trials for inclusion. The meta-analysis revealed that resmetirom significantly reduced low-density lipoprotein cholesterol (LDL-C) levels compared to placebo (MD: -23.62; 95% CI: -37.32 to -9.93; p < 0.001). Similarly, triglyceride (TG) levels showed a significant reduction in the resmetirom group (MD: -33.86; 95% CI: -47.79 to -19.92; p < 0.001). Importantly, there was no significant difference in the risk of serious adverse events between resmetirom and placebo groups (RR: 1.09; 95% CI: 0.73 to 1.63; p = 0.67). These findings suggest that resmetirom effectively improves lipid profiles in NASH patients without compromising safety. However, the analysis was limited by the small number of studies, all from the same research group, and high heterogeneity in results. Future research should include more diverse studies, longer follow-up periods, and cost-effectiveness evaluations. Despite these limitations, resmetirom shows promise as a potential treatment for managing dyslipidemia and cardiovascular risk in NASH patients, potentially influencing future treatment guidelines for both liver and cardiovascular health in this population.

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

A potential marker for increased LDL and hypertriglyceridemia risk

Background and objectives. Serum uric acid (SUA), traditionally associated with gout, is increasingly recognized for its potential role in cardiometabolic disorders, including dyslipidemia. Elevated SUA levels may influence lipid metabolism, thus enhancing cardiovascular disease risk. This study aims to explore the association between SUA levels, dyslipidemia, and related risk factors in a cohort of patients, contributing to a better understanding of their interplay and implications for cardiovascular health. Material and methods. We conducted a retrospective case series involving 30 participants selected from the outpatient Department of General Medicine. The study was approved by the Institutional Review Board, and informed consent was waived due to the retrospective design and use of de-identified data. Participants were aged 18 or older with available data on SUA, LDL cholesterol, and triglycerides, excluding those with a history of gout, renal impairment, or current use of urate-lowering medications. Data were analyzed using descriptive statistics, chi-square tests, and Mann-Whitney U tests, with significance set at p &lt;0.05. Results. The study population had a mean age of 54.7 ± 6.3 years and a mean BMI of 28.4 ± 2.4 kg/m². The mean SUA level was 6.9 ± 0.8 mg/dL, LDL cholesterol was 138 ± 13 mg/dL, and triglycerides were 162 ± 25 mg/dL. Dyslipidemia was present in 60% of the participants. Significant associations were found between hyperuricemia and dietary habits, family history of gout, CVD, and dyslipidemia, as well as the duration of hyperuricemia. Conclusion. Elevated SUA levels are significantly associated with dyslipidemia and other cardiovascular risk factors. The findings suggest the importance of managing SUA levels and lipid profiles concurrently to reduce cardiovascular risks. Further research is needed to explore the long-term cardiovascular outcomes of persistent hyperuricemia and dyslipidemia.

The progressive Role of Dyslipidemia and Inflammation in Type 2 Diabetes in Iraqi Patients

Type II diabetes is a complex metabolic disorder that raises the risk of dyslipidemia and obesity. Inflammation is the primary factor in the pathogenesis of this disease and coincides with metabolic dyslipidemia. This work aims to predict the role of dyslipidemia and inflammatory markers in development type II DM by evaluating the levels of lipid profile, TNF-R2, systemic immune inflammatory index (SII) and related biochemical factors in patients with type 2 diabetes. Thirty samples were obtained from diabetic patients and 30 samples from non-diabetic individuals as a control. D10 apparatus (BIO-RAD, USA) used to measure hemoglobin A1c HbA1c, Enzymatic and colorimetric method used to measure biochemical parameter, ELISA technique used to estimate the TNF-R2 levels, and Complete Blood Count determine to calculate SII by the formula (neutrophil *platelet / lymphocyte count) . The results showed significant increase in most of lipid profile levels in patients than control except HDL has the verse results. Also, the results showed that HbA1C was significantly increased in patient compared to healthy group. Furthermore, TNF-R2 and SII appeared higher significant values in patients than control. Furthermore, the results indicated positive correlation between HbA1C and lipid profile (TC, TGs, VLDL and LDL), TNF-R2, SII, and BMI. It can be concluded that dyslipidemia and both TNF-R2 and SII inflammatory parameters have a cardinal role in the development of T2DM and can be served as early diagnostic factors to detect disease progression.

The risk of dyslipidemia on PLHIV associated with different antiretroviral regimens in Huzhou

Background Dyslipidemia is increasingly common in people living with HIV (PLHIV), thereby increasing the risk of cardiovascular events and diminishing the quality of life for these individuals. The study of blood lipid metabolism of PLHIV has great clinical significance in predicting the risk of cardiovascular disease. Therefore, this study aims to examine the blood lipid metabolism status of HIV-infected patients in Huzhou before and after receiving highly active antiretroviral therapy (HAART) and to explore the impact of different HAART regimens on dyslipidemia. Method PLHIV confirmed in Huzhou from June 2010 to June 2022 was included. The baseline characteristics and clinical data during the follow-up period were collected, including some blood lipid indicators (total cholesterol and triglycerides) and HAART regimens. A multivariate logistic regression model and the generalized estimating equation model were used to analyze the independent effects of treatment regimens on the risk of dyslipidemia. Result The overall prevalence of dyslipidemia among PLHIV after HAART was 70.11%. PLHIV receiving lamivudine (3TC) + efavirenz (EFV) + zidovudine (AZT) had a higher prevalence of dyslipidemia compared to those receiving 3TC+EFV+tenofovir disoproxil fumarate (TDF). In a logistic analysis adjusted for important covariates such as BMI, age, diabetes status, etc., we found that the risks of dyslipidemia were higher with 3TC+EFV+AZT (dyslipidemia: odds ratio [OR] = 2.09, 95% confidence interval [Cl]: 1.28–3.41; TG ≥1.7: OR = 2.40, 95%Cl:1.50–3.84) than with 3TC+EFV+TDF. Furthermore, on PLHIV that was matched 1:1 by the HAART regimens, the results of the generalized estimation equation again showed that 3TC+EFV+AZT (TG ≥1.7: OR = 1.84, 95%Cl: 1.10–3.07) is higher for the risk of marginal elevations of TG than 3TC+EFV+TDF. Conclusion The prevalence of dyslipidemia varies according to different antiretroviral regimens. Using both horizontal and longitudinal data, we have repeatedly demonstrated that AZT has a more adverse effect on blood lipids than TDF from two perspectives. Therefore, we recommend caution in using the 3TC+EFV+AZT regimen for people at clinical risk of co-occurring cardiovascular disease.

The association of organochlorine pesticides and polychlorinated biphenyls exposure with dyslipidemia and blood lipids: The mediating effect of white blood cell counts

Epidemiological evidence regarding the associations of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) with lipid metabolism and its potential biological mechanisms remain largely unknown. We intended to explore the associations of OCPs and PCBs with dyslipidemia and blood lipid levels, and further evaluate the mediating role of total and differential white blood cell (WBC) counts. We measured the blood lipid levels, the concentration of OCPs/PCBs and WBC counts in serum among 2036 adults in Wuhan city, China. In the multiple-pollutant models, the results showed that β-hexachlorocyclohexane (HCH), p,p′-dichlorodiphenyldichloroethylene (DDE), and PCB-153 were positively correlated with increased odds of dyslipidemia. p,p′-DDE and PCB-153 were correlated with elevated triglyceride (TG) and lowered high-density lipoprotein cholesterol (HDL-c). A positive relationship was observed between p,p′-DDE and total cholesterol (TC) as well. Meanwhile, weighted quantile sum (WQS) regression analyses revealed that PCB and OCP mixtures were positively related to dyslipidemia risk and TG and negatively associated with HDL-c, to which p,p′-DDE was the major contributor. BMI, gender and age might modify the associations of OCPs and PCBs with dyslipidemia and TG. Furthermore, we found that WBC counts were significantly associated with dyslipidemia and blood lipid levels, and a positive correlation was also found between p,p′-DDE and lymphocyte count. Mediation analysis further indicated that lymphocyte count might mediate the associations of p,p′-DDE with dyslipidemia, TG, and TC. Accordingly, our results showed that OCPs and PCBs were related to abnormal lipid metabolism, which was partially mediated by WBC counts.

A six-year study in a real-world population reveals an increased incidence of dyslipidemia during COVID-19.

Recent studies conducted in COVID-19 survivors suggest that SARS-CoV-2 infection is associated with an increased risk of dyslipidemia. However, it remains unclear whether this augmented risk is confirmed in the general population and how this phenomenon is impacting the overall burden of cardiometabolic diseases. To address these aspects, we conducted a 6-year longitudinal study to examine the broader effects of COVID-19 on dyslipidemia incidence within a real-world population (228,266 subjects) residing in Naples, Southern Italy. The pre-COVID-19 and the COVID-19 groups were balanced for demographic and clinical factors using propensity score matching. Our analysis spans over a period of three years during the pandemic (2020-2022), comparing dyslipidemia incidence with pre-pandemic data (2017-2019), with a follow-up time of at least 1,095 days corresponding to 21,349,215 person-years. During the COVID-19 period we detected an increased risk of developing any dyslipidemia when compared with the pre-COVID-19 triennium (OR = 1.29, 95% CI 1.19-1.39). Importantly, these estimates were adjusted for comorbidities by a multivariate analysis. Taken together, our data reveal a notable rise in dyslipidemia incidence amid the COVID-19 pandemic, suggesting to establish specialized clinical monitoring protocols for COVID-19 survivors to mitigate the risk of dyslipidemia development.