Atherogenic Lipid Profile Research Articles

APOE Genotypes Modulate Inflammation Independently of Their Effect on Lipid Metabolism

The association between APOE genotypes and cardiovascular disease (CVD) is partially mediated by LDL-cholesterol concentration but persists after adjusting for lipid levels and other cardiovascular risk factors. Data from the Aragon Workers Health Study (AWHS) (n = 4159) and the Lipid Unit at the Hospital Universitario Miguel Servet (HUMS) (n = 3705) were used to investigate the relationship between C-reactive protein (CRP) levels and APOE genotype. Lipoprotein particle and GlycA concentrations were analyzed in a subsample from AWHS. APOE genotyping was carried out by the Sanger method in both cohorts. APOE4 carriers had significantly lower levels of CRP than APOE3 carriers. Furthermore, APOE4 carriers had cholesterol-enriched LDL particles compared to APOE2 carriers. APOE4 carriers also had higher concentrations of small, medium, and large LDL particles. CRP levels were not associated with lipoprotein particle number, size, or composition. GlycA levels were not associated with APOE genotypes. However, GlycA levels were significantly associated with the size and the amount of cholesterol contained in HDL, VLDL, and LDL particles. APOE genotype influences CRP concentration regardless of lipid profile. APOE2 carriers showed the highest CRP levels, followed by APOE3 and APOE4. A more atherogenic lipid profile, but not inflammatory markers could partly explain the higher CVD risk observed in APOE4 carriers.

Residual inflammatory risk appeared related to weight, atherogenic lipid profile and biomarkers of inflammation, but not to glycaemic control in type 1 diabetes

Abstract Background Mortality associated with atherosclerotic cardiovascular disease reduces average life expectancy by more than a decade in type 1 diabetes. Systemic inflammation drives atherosclerosis, and the concept of residual inflammatory risk (defined by high-sensitivity C-reactive protein (hsCRP) ≥2 mg/l) poses a potential, new therapeutic target for lowering residual cardiovascular risk in type 1 diabetes. However, the characteristics of individuals with residual inflammatory risk in type 1 diabetes are unknown. Purpose Identify differences in relevant demographics, clinical and paraclinical parameters for individuals with residual inflammatory risk as compared to those without in type 1 diabetes. Methods Baseline characteristics as stratified for CRP ≥2 mg/l were analysed in 105 patients with type 1 diabetes participating in a previously published clinical trial. The study population was sampled to represent the broad background population struggling with glycaemic control and with a high cardiovascular risk. Results Residual inflammatory risk was seen in 39.1% of the study population. Compared to individuals without residual inflammatory risk, individuals with residual inflammatory risk were more frequently women, had increased body weight, body mass index and dual-energy X-ray absorptiometry (DXA)-assessed fat mass and exhibited elevated levels of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and total cholesterol as well as triglycerides, interleukin 6 and tumour necrosis factor alpha (Table 1). Glycated haemoglobin, blood pressure and markers of renal function were similar between groups (Table 1). Conclusion In the present cohort of individuals with type 1 diabetes, residual inflammatory risk was seen in 39.1% (similar to what is observed outside of type 1 diabetes) and appeared related to overweight/obesity, an atherogenic lipid profile and circulating biomarkers of inflammation but not to glycaemic control, blood pressure or renal function. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZenecaHerlev Gentofte Hospital

28.2 Atherogenic Lipid Profiles Differ Across Mood States Among Youth With Bipolar Disorder

Dyslipidemia is common and associated with mood symptom severity in adults with bipolar disorder (BD). However, there is a gap in knowledge on this topic in youth with BD. We set out to examine the associations of lipid levels with mood states and symptoms in youth with BD.

Lipidic profiles of patients starting peritoneal dialysis suggest an increased cardiovascular risk beyond classical dyslipidemia biomarkers

Patients on peritoneal dialysis (PD) have an increased risk of cardiovascular disease (CVD) and an atherogenic lipid profile generated by exposure to high glucose dialysis solutions. In the general population, the reduction of classic lipids biomarkers is associated with improved clinical outcomes; however, the same results have not been seen in PD population, a lack of data this study aims to fulfill. Single-center prospective observational study of a cohort of CKD patients who started renal replacement therapy with continuous ambulatory peritoneal dialysis. The differences in the lipid profile and analytical variables before and 6 months after the start of peritoneal dialysis were analyzed. Samples were analyzed on an Ultra-Performance Liquid Chromatography system. Thirty-nine patients were enrolled in this study. Their mean age was 57.9 ± 16.3 years. A total of 157 endogenous lipid species of 11 lipid subclasses were identified. There were significant increases in total free fatty acids (p < 0.05), diacylglycerides (p < 0.01), triacylglycerides, (p < 0.01), phosphatidylcholines (p < 0.01), phosphatidylethanolamines (p < 0.01), ceramides (p < 0.01), sphingomyelins (p < 0.01), and cholesterol esters (p < 0.01) from baseline to 6 months. However, there were no differences in the classical lipid markers, neither lysophosphatidylcholines, monoacylglycerides, and sphingosine levels. 6 months after the start of the technique, PD patients present changes in the lipidomic profile beyond the classic markers of dyslipidemia.

Therapie des metabolischen Syndroms

Metabolic syndrome is defined by the simultaneous presence of abdominal obesity, atherogenic dyslipoproteinemia, high blood pressure and increased fasting blood glucose. It is an important precursor of cardiovascular disease sequelae and shows epidemic proportions, not only in western countries. Modifications of lifestyle are central for treatment: negative energy balance with increased physical activity, a prudent balance of nutrients with carbohydrates, proteins and fats, considering atherogenic lipid profiles, blood pressure and the glycemic index of nutrients. Decisive for the implementation is the incorporation of long-term programs with continuous guidance, preferably in group therapy and targeting all individual risk factors. The introduction of sodium-glucose linked transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1) receptor agonists and modern mineralocorticoid receptor blockers has resulted in new options for the effective prevention of sequelae.

Impact of diet on 10-year absolute cardiovascular risk: A prospective population-based cohort study

Background and Aims : The burden of diet on cardiovascular risk is substantial. Current dietary guidelines are not sufficiently implemented and effective strategies to encourage people to change and maintain healthy diets are lacking. The impact of incorporating dietary assessment into 10-year absolute risk charts for cardiovascular disease is unknown.Methods: Using a prospective cohort design including 94,321 individuals from the general population, we generated 10-year absolute risk scores for fatal and non-fatal cardiovascular disease and for ischemic vascular disease according to groups based on adherence to dietary guidelines.Results: Non-adherence to dietary guidelines was associated with an atherogenic lipid and inflammatory profile. In both sexes, 10-year absolute risk of ischemic vascular disease increased with increasing age, increasing systolic blood pressure, and decreasing adherence to dietary guidelines. The highest 10-year absolute risk of ischemic vascular disease of 38% was observed in smoking men aged 65-69 with very low adherence to dietary guidelines and systolic blood pressure between 160-179. The corresponding value for women was 26%. Risk charts using non-HDL cholesterol instead of dietary assessment yielded similar estimates.Conclusions: Incorporation of dietary assessment into 10-year absolute risk charts may contribute to a more effective prevention strategy as it may improve individual motivation to change dietary habits and therefore advance personalized prevention. These risk charts may also be useful in regions of the world where access to laboratory facilities is limited. Improved implementation of national dietary guidelines must be a cornerstone for future prevention of cardiovascular disease in both younger and older individuals. Background and Aims : The burden of diet on cardiovascular risk is substantial. Current dietary guidelines are not sufficiently implemented and effective strategies to encourage people to change and maintain healthy diets are lacking. The impact of incorporating dietary assessment into 10-year absolute risk charts for cardiovascular disease is unknown. Methods: Using a prospective cohort design including 94,321 individuals from the general population, we generated 10-year absolute risk scores for fatal and non-fatal cardiovascular disease and for ischemic vascular disease according to groups based on adherence to dietary guidelines. Results: Non-adherence to dietary guidelines was associated with an atherogenic lipid and inflammatory profile. In both sexes, 10-year absolute risk of ischemic vascular disease increased with increasing age, increasing systolic blood pressure, and decreasing adherence to dietary guidelines. The highest 10-year absolute risk of ischemic vascular disease of 38% was observed in smoking men aged 65-69 with very low adherence to dietary guidelines and systolic blood pressure between 160-179. The corresponding value for women was 26%. Risk charts using non-HDL cholesterol instead of dietary assessment yielded similar estimates. Conclusions: Incorporation of dietary assessment into 10-year absolute risk charts may contribute to a more effective prevention strategy as it may improve individual motivation to change dietary habits and therefore advance personalized prevention. These risk charts may also be useful in regions of the world where access to laboratory facilities is limited. Improved implementation of national dietary guidelines must be a cornerstone for future prevention of cardiovascular disease in both younger and older individuals.

The effect of iatrogenic hypothyroidism on lipoprotein subfractions and serum paraoxonase activity in patients with differentiated thyroid cancer

Background and Aims : The development of atherogenic lipid profile has a major role in hypothyroidism induced accelerated atherosclerosis. In a group of patients with differentiated thyroid cancer (DTC) subclinical hyperthyroidism is maintained after thyroidectomy, interrupted annually with short-term overt hypothyroidism for diagnostic purposes. The effects of short-term overt hypothyroidism on lipid parameters, lipoprotein subfractions and paraoxonase-1 (PON1) activity were studied in these patients.

Characterization of fetuin-A levels in patients with autoimmune thyroid disease

Background and Aims : Hypothyroidism leads to atherogenic lipid profile and might increase the cardiovascular risk of patients. Fetuin-A is a hepatokine with a regulatory role on mineralization, metabolism and the cardiovascular system. Fetuin-A is increased in obesity-linked diseases

Impact of small dense low-density lipoprotein cholesterol and triglyceride-rich lipoproteins on plaque rupture with ST-segment elevation myocardial infarction

Plaque rupture (PR), characterized by a disruption of the fibrous cap of lipid-rich plaques, is the major etiology of ST-segment elevation myocardial infarction (STEMI). Dyslipidemia is a well-known risk factor for PR. Nonetheless, the impact of detailed atherogenic lipid profiles, including small dense low-density lipoprotein cholesterol (sd-LDL-C) and triglyceride-rich lipoproteins (TRLs), on PR has not yet been investigated. To elucidate the impact of sd-LDL-C and TRL levels on PR in patients with STEMI using optical coherence tomography (OCT). A total of 106 consecutive statin-naive patients with STEMI were enrolled. The PR in culprit lesions was assessed on pre-intervention OCT images, and serum samples were collected immediately before coronary angiography. Sd-LDL-C was directly measured using a homogeneous assay. TRL-cholesterol (TRL-C) was estimated by subtracting the LDL-C level from the non-high-density lipoprotein cholesterol level. Clinical characteristics and lipid profiles were compared between the PR and intact fibrous cap (IFC). No difference in LDL-C levels was observed between the PR (n=64) and IFC (n=42) groups (120.0 mg/dL vs. 129.5 mg/dL, p=0.97); however, sd-LDL-C levels were significantly higher in the PR group (38.9 mg/dL vs. 32.4 mg/dL, p=0.04). Similarly, the PR group had higher TRL-C (24.0 mg/dL vs. 18.0 mg/dL, p=0.01) and triglyceride (130.0 mg/dL vs. 100.3 mg/dL, p=0.03) levels than the IFC group.Multivariate logistic regression analysis showed that sd-LDL-C was an independent factor determining PR (odds ratio, 1.53 per 10 mg/dL; p=0.04). Only sd-LDL-C levels were significantly associated with PR in culprit lesions in patients with STEMI.

Longitudinal Changes in Circulating Metabolites and Lipoproteins After Breast Cancer Treatment.

The multimodal treatment of breast cancer may induce long term effects on the metabolic profile and increase the risk of future cardiovascular disease. In this study, we characterized longitudinal changes in serum lipoprotein subfractions and metabolites after breast cancer treatment, aiming to determine the long-term effect of different treatment modalities. Further, we investigated the prognostic value of treatment-induced changes in breast cancer-specific and overall 10-year survival. In this study, serum samples from breast cancer patients (n = 250) were collected repeatedly before and after radiotherapy, and serum metabolites and lipoprotein subfractions were quantified by NMR spectroscopy. Longitudinal changes were assessed by univariate and multivariate data analysis methods applicable for repeated measures. Distinct changes were detectable in levels of lipoprotein subfractions and circulating metabolites during the first year, with similar changes despite large differences in treatment regimens. We detect increased free cholesterol and decreased esterified cholesterol levels of HDL subfractions, a switch towards larger LDL particles and higher total LDL-cholesterol, in addition to a switch in the glutamine-glutamate ratio. Non-survivors had different lipid profiles from survivors already at baseline. To conclude, our results show development towards an atherogenic lipid profile in breast cancer patients with different treatment regimens.

Plasma Homocysteine Level Is Independently Associated With Conventional Atherogenic Lipid Profile and Remnant Cholesterol in Adults.

BackgroundHomocysteine (Hcy) is an independent risk factor for cardiovascular disease, while mechanisms are unclear. Despite inconsistent and limited, epidemiological and experimental studies indicated that hyperhomocysteinemia (HHcy) affected lipid metabolism. This study aims to investigate the association of plasma Hcy with traditional lipid profiles and remnant cholesterol (RC) in Chinese adults.MethodsIn total, 7,898 subjects aged 20–79 years who underwent a physical examination at Beijing Chao-Yang Hospital in Beijing were included in this study. Fasting plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), lipoprotein (a) [Lp(a)], Hcy, and other metabolic risk factors were measured by routine automated laboratory methods. RC was calculated as TC minus HDL-C and LDL-C. The linear regression model and logistic regression model were used to assess the relationship between Hcy and lipids after adjusting potential confounders.ResultsOf the subjects, the median level of plasma Hcy was 13.0 μmol/L and 32.3% had HHcy. Plasma Hcy was negatively associated with HDL-C, ApoA1, and Lp(a) and positively associated with TG levels after adjusting age, sex, body mass index, blood pressure, alanine transaminase, aspartate transaminase, creatinine, uric acid, and glucose. HHcy significantly increased the risk of low HDL-C [odds ratio (OR) 1.26; 95%CI (1.11–1.44); p < 0.001]. The net mediation effects of ApoA1 on the relationship between Hcy and HDL-C before and after adjusting confounders were 46.9 and 30.6%, respectively. More interestingly, the RC level was significantly elevated in subjects with HHcy after adjusting other influencing factors (p = 0.025). Hcy presented a positive correlation with RC levels after adjusting the above confounding factors (β = 0.073, p = 0.004), and the correlation was still significant even after controlling other lipids, including TG, LDL-C, HDL-C, ApoA1, ApoB, and Lp(a).ConclusionOur study showed that plasma Hcy was not only significantly associated with conventional atherogenic lipids but also independently correlated with RC levels beyond other lipids after controlling potential confounders. This finding proposes that identifying Hcy-related dyslipidemia risk, both traditional lipids and RC residual risk, is clinically relevant as we usher in a new era of targeting Hcy-lowering therapies to fight against dyslipidemia or even cardiovascular disease.

Impact of diet on ten-year absolute cardiovascular risk in a prospective cohort of 94 321 individuals: A tool for implementation of healthy diets.

SummaryBackgroundAn unhealthy diet is a major risk factor for cardiovascular disease attributing to the burden of non-communicable diseases. Current dietary guidelines are not sufficiently implemented and effective strategies to encourage people to change and maintain healthy diets are lacking. We aimed to evaluate the impact of incorporating dietary assessment into ten-year absolute risk charts for atherosclerotic cardiovascular disease (ASCVD).MethodsIn the prospective Copenhagen General Population Study including 94 321 individuals, we generated sex-specific ten-year absolute risk scores for ASCVD according to adherence to dietary guidelines, using a short and valid food frequency questionnaire. To account for competing risk, we used the method of Fine-Gray.FindingsNon-adherence to dietary guidelines was associated with an atherogenic lipid and inflammatory profile. Ten-year absolute risk of ASCVD increased with increasing age, increasing systolic blood pressure, and decreasing adherence to dietary guidelines for both sexes. The highest ten-year absolute risk of ASCVD of 38% was observed in men aged 65–69 years who smoked, had very low adherence to dietary guidelines, and a systolic blood pressure between 160 and 179 mmHg. The corresponding value for women was 26%. Risk charts replacing dietary assessment with non-HDL cholesterol yielded similar estimates.InterpretationIncorporation of a short dietary assessment into ten-year absolute risk charts has the potential to motivate patients to adhere to dietary guideline recommendations. Improved implementation of national dietary guidelines must be a cornerstone for future prevention of cardiovascular disease in both younger and older individuals.FundingThe Lundbeck Foundation (R278-2018-804) and the Danish Heart Foundation.

Phenotypes of prediabetes and metabolic risk in Caucasian youths with overweight or obesity

PurposeTo assess the prevalence of pre-diabetes phenotypes, i.e., impaired fasting glucose (IFG), impaired glucose tolerance (IGT), increased HbA1c (IA1c), and their association with metabolic profile and atherogenic lipid profile in youths with overweight/obesity (OW/OB).MethodsThis cross-sectional study analyzed data of 1549 youths (5–18 years) with OW/OB followed in nine Italian centers between 2016 and 2020. Fasting and post-load measurements of glucose, insulin, and HbA1c were available. Insulin resistance (IR) was estimated by HOMA-IR and insulin sensitivity (IS) by reciprocal of fasting insulin. The atherogenic lipid profile was assessed by triglycerides-to-HDL ratio or cholesterol-to-HDL ratio. Insulinogenic index was available in 939 youths, in whom the disposition index was calculated.ResultsThe prevalence of overall pre-diabetes, IFG, IGT and IA1c was 27.6%, 10.2%, 8% and 16.3%, respectively. Analyzing each isolated phenotype, IGT exhibited two- to three-fold higher odds ratio of family history of diabetes, and worse metabolic and atherogenic lipid profile vs normoglycemic youths; IFG was associated only with IR, while IA1c showed a metabolic and atherogenic lipid profile intermediate between IGT and IFG.ConclusionPrevalence of pre-diabetes was high and IA1c was the most prevalent phenotype in Italian youths with OW/OB. The IGT phenotype showed the worst metabolic and atherogenic lipid profile, followed by IA1c. More studies are needed to assess whether HbA1c may help improving the prediction of diabetes.

The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents.

Disorders of lipoprotein metabolism are among the major risk factors for cardiovascular disease (CVD) development. Single nucleotide polymorphisms (SNPs) have been associated with the individual variability in blood lipid profile and response to lipid-lowering treatments. Here, we genotyped 34 selected SNPs located in coding genes related to lipid metabolism, inflammation, coagulation, and a polymorphism in the MIR499 gene—a microRNA previously linked to CVD—to evaluate the association with lipid trait in subjects with moderate dyslipidemia not on lipid-lowering treatment (Treatment-naïve (TN) cohort, n = 125) and in patients treated with statins (STAT cohort, n = 302). We also explored the association between SNPs and the effect of a novel phytochemical lipid-lowering treatment in the TN cohort. We found that 6 SNPs (in the MIR499, TNFA, CETP, SOD2, and VEGFA genes) were associated with lipid traits in the TN cohort, while no association was found with the response to twelve-week phytochemical treatment. In the STAT cohort, nine SNPs (in the MIR499, CETP, CYP2C9, IL6, ABCC2, PON1, IL10, and VEGFA genes) were associated with lipid traits, three of which were in common with the TN cohort. Interestingly, in both cohorts, the presence of the rs3746444 MIR499 SNP was associated with a more favorable blood lipid profile. Our findings could add information to better understand the individual genetic variability in maintaining a low atherogenic lipid profile and the response to different lipid-lowering therapies.

MO668: An Increase of Free Fatty Acids on Patients Starting Peritoneal Dialysis Suggests an Increased Cardiovascular Risk Beyond Classical Dyslipidemia Biomarkers

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) produces profound changes in lipid metabolism, and these associated lipid disorders, in turn, contribute to the progression of CKD and its cardiovascular complications. Patients on peritoneal dialysis have a more atherogenic lipid profile than non-dialysis-dependent CKD patients or on HD. In the general population, the reduction of total cholesterol and LDL levels is associated with improved clinical outcomes in terms of morbidity and mortality; however, several studies have failed to obtain these same results in patients on dialysis. The use of lipidomics to detect a broader panel of lipid species can improve the prediction of the different alterations that influence cardiovascular mortality. METHOD This is a single-center prospective observational study of a cohort of CKD patients who start renal replacement therapy with continuous ambulatory peritoneal dialysis (CAPD). Data from 39 patients were examined. All samples for routine laboratories and lipidomics studies were obtained the day before starting CAPD (T0) and 6 months after (T1). Samples were analysed on an Ultra-Performance Liquid Chromatography system. The differences in the lipid profile analytical variables between baseline and 6 months after the start of CAPD were analysed. For the lipidomic analysis, each compound was grouped with its possible adducts and compound class based on the International Lipid Classification. RESULTS Thirty-nine patients were enrolled the study. Their mean age was 57.9 ± 16.3 years. The underlying renal diseases were glomerular disease (15 patients), diabetic kidney disease (10), congenital kidney disease (4), hypertensive kidney disease (2), interstitial nephropathy (2) and others (6). Hypertension was present in 96.3% of the patients, diabetes mellitus in 30.8% and 30 of the 39 patients had dyslipidemia (76.9%). Of the group of patients with dyslipidemia, only one of them was not on statin treatment. Table 1 shows the results of the analytical variables of lipid profile, serum glucose and renal function before and 6 months after initiating CAPD. The levels of CT and LDL were lower 6 months after CAPD initiation, but these were not statistically significant. Using the plasma lipid profile, with a mass spectrometry approach, a significant increase (P &amp;lt; 0.05) in total free fatty acids (FFA) was observed from T0 to T1. FFA (16:1) and FFA (18:0) were the FFAs with the highest peak response (Fig. 1). CONCLUSION Our LC-QTOF/MS-based lipidomics approach to study the effect of starting renal replacement therapy with CAPD in patients with CKD shows that total FFAs increased after 6 months on this technique. Within this group of lipids, FA 16:1 (palmitoleic acid) and FA 18:0 (stearic acid) were the ones that increased the most. An earlier study demonstrated that FFA levels are increased in the plasma of CKD patients; moreover, they have reported that higher levels of saturated fatty acids in serum correlate with sudden cardiac death in patients starting HD. Likewise, monounsaturated fatty acids are the products of stearoyl-CoA desaturase (SCD) catalyzed reactions and act as substrates to synthesize phospholipids and triglycerides. The activity of SCD is very high in patients with cardiovascular disease, hypertension and diabetes.

Successful correction of hyperglycemia is critical for weight loss and a decrease in cardiovascular risk in obese patients

Weight loss is recommended for obese patients with cardiovascular risk; however, it remains questionable how hyperglycemia affects this process. To address this problem, we aimed to determine the association between weight loss, lipid profile, and body mass parameters in obese normoglycemic and hyperglycemic patients. Obese (body mass index30 kg/m2) normoglycemic and hyperglycemic volunteers were placed on a weight reduction program that included a balanced, low-calorie diet and moderate exercise for 6 months. Participants were assessed for serum glucose, β-cell functions, insulin resistance, lipid metabolism, lipoprotein profile, and body mass parameters. This weight reduction program fully normalized serum glucose levels only in a subpopulation of patients. These individuals also exhibited a significant reduction in body weight, and significant improvement in serum lipid profile and insulin resistance. In contrast, the patients that remained hyperglycemic were characterized by persistent insulin resistance, increased levels of atherogenic fractions of LDL and HDL lipoproteins, and elevated values of a modified Atherogenic Index of Plasma. Correlation analysis indicated a strong positive association between the modified Atherogenic Index of Plasma with atherogenic lipid profile, insulin resistance, and body mass parameters, indicating its usefulness in clinical studies in obese patients. Overall, our data indicate that successful treatment of hyperglycemia facilitates weight loss and improves the composition of blood lipids, while persisting hyperglycemia negatively affects the weight loss process and maintains an atherogenic lipid profile. Because hyperglycemia predisposes to cardiovascular disorders, its correction should be the primary goal during weight reduction therapy.

Serum Lipidome Signatures of Dogs with Different Endocrinopathies Associated with Hyperlipidemia.

Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia) is a common finding in human and veterinary patients with endocrinopathies (e.g., hypothyroidism and hypercortisolism (Cushing’s syndrome; CS)). Despite emerging use of lipidomics technology in medicine, the lipid profiles of these endocrinopathies have not been evaluated and characterized in dogs. The aim of this study was to compare the serum lipidomes of dogs with naturally occurring CS or hypothyroidism with those of healthy dogs. Serum samples from 39 dogs with CS, 45 dogs with hypothyroidism, and 10 healthy beagle dogs were analyzed using a targeted lipidomics approach with liquid chromatography-mass spectrometry. There were significant differences between the lipidomes of dogs with CS, hypothyroidism, and the healthy dogs. The most significant changes were found in the lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylinositols, phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, ceramides, and sphingosine 1-phosphates. Lipid alterations were especially pronounced in dogs with hypothyroidism. Several changes suggested a more atherogenic lipid profile in dogs with HT than in dogs with CS. In this study, we found so far unknown effects of naturally occurring hypothyroidism and CS on lipid metabolism in dogs. Our findings provide starting points to further examine differences in occurrence of atherosclerotic lesion formation between the two diseases.

The Effects of Exercise on Plaque Volume and Composition in a Mouse Model of Early and Late Life Atherosclerosis.

BackgroundExercise is associated with a less atherogenic lipid profile; however, there is limited research on the effect of exercise on atherosclerotic plaque composition and markers of plaque stability.MethodsA total of 110 apolipoprotein (apo)E−/− mice were placed on a chow diet and randomly assigned to control or exercise for a period of 10 weeks, commencing either at 12 weeks of age (the early-stage atherosclerosis, EA group) or at 40 weeks of age (the late-stage atherosclerosis, LA group). At the end of the exercise period, blood was assayed for lipids. Histologic analysis of the aortic sinus was undertaken to assess plaque size and composition that includes macrophage content, monocyte chemoattractant protein (MCP)-1, matrix metalloproteinase-2 (MMP-2), and tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and 2).ResultsA total of 103 mice (38 EA, 65 LA) completed the protocol. In the EA group, exercise reduced plasma total cholesterol (TC) (−16%), free cholesterol (−13%), triglyceride (TG) (−35%), and phospholipid (−27%) levels, when compared to sedentary control mice (p < 0.01). In the EA group, exercise also significantly reduced plaque stenosis (−25%, p < 0.01), and there were higher levels of elastin (3-fold increase, p < 0.0001) and collagen (11-fold increase, p < 0.0001) in plaques, compared to control mice. There was an increase in plaque MMP-2 content in the exercise group (13% increase, p < 0.05) but no significant difference in macrophage or MCP-1 content. In the LA group, exercise reduced plaque stenosis (−18%, p < 0.05), but there was no significant difference in plaque composition. There was no difference in macrophage, MCP-1, or MMP-2 content in the LA groups. TIMP-1 was lower with exercise in both the EA and LA groups (−59%, p < 0.01 and −51%, p < 0.01 respectively); however, there was no difference in TIMP-2 levels.ConclusionA 10-week exercise period reduces atherosclerotic plaque stenosis when commenced at both early- and late-stage atherosclerosis. Intervening earlier with exercise had a greater beneficial effect on lipids and plaque composition than when starting exercise at a later disease stage.

Substantially elevated TSH, not traditional clinical subclinical thyroid disorder groupings, are associated with smaller LDL-P mean size: ELSA-Brasil

LDL appears to drive atherogenesis in overt hypothyroidism, but in subclinical dysfunction, its role is not completely elucidated. The aim of this study was to evaluate subfractions of LDL in subclinical (SC) thyroid disorders. Individuals were divided into three groups by baseline thyroid function (SC hypothyroidism, euthyroidism, and SC hyperthyroidism). LDL particle (LDL-P) subfractions were analyzed by Nuclear Magnetic Resonance (NMR) spectroscopy. The association between LDL-P subfractions and thyroid groups and quintiles was evaluated by linear regression models. We evaluated 3304 participants (54.1% women, 51.2% white, mean age 50.6±8.7 years). In the univariate analysis, small LDL particle concentrations (SLDL-P) were not different between SC hypo- and hyperthyroidism compared to euthyroid individuals (p=0.485 and p=0.314, respectively). Large LDL-P (LDL-P) levels also did not differ in SC hyperthyroidism and SC hypothyroidism compared to euthyroidism (p=0.698 and 0.788 respectively). Intermediate LDL-P levels were not different across the groups. These numbers did not materially change in multivariate analysis. However, we also analyzed LDL subfractions according to quintiles of TSH. We showed that in the higher TSH quintile LDL subfractions presented a significantly smaller mean size of LDL subfractions compared to the first quintile. SC thyroid disorders are not associated with significant changes in LDL-P subfractions measured by NMR spectroscopy. However, it seems that the LDL mean size decreases as TSH levels increase, which may represent a more atherogenic lipid profile.

Elevated atherogenic lipid profile in youth with bipolar disorder during euthymia and hypomanic/mixed but not depressive states

ObjectiveAbnormal blood lipid levels are common in individuals with bipolar disorder (BD). Previous studies have revealed lipid-mood associations in adults with BD, but no data on this relationship is available in youth populations. This cross-sectional study examined the associations of lipid levels with mood states and symptoms in a cohort of youth with BD. MethodsParticipants were youth with BD and healthy controls (HCs) between the ages of 13–20 years. We compared the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and TG/HDL-C ratio between 4 participant episode groups: BD-euthymic (n = 28), BD-depressed (n = 29) BD-hypomanic/mixed (n = 31), and HCs (n = 89). We also examined for dimensional associations of lipids with mania and depression scores in the overall BD group and within BD episode subgroups. ResultsTG levels were significantly higher in the BD-euthymic group (p = 0.008, d = 0.59) and in the BD-mixed/hypomanic group (p = 0.03, d = 0.44) compared to the HC group. TG/HDL-C ratio was also higher in the BD-euthymic group compared to the HC group (p = 0.01, d = 0.51). No dimensional associations were found between lipids and mood symptom scores in the overall BD group. However, within the BD-mixed/hypomanic subgroup, higher mania scores were associated with higher TG (β = 0.42, p = 0.04), TG/HDL-C ratio (β = 0.59, p = 0.002), and lower HDL-C (β = 0.56 p = 0.002). ConclusionsYouth with BD demonstrate atherogenic lipid profiles. Higher atherogenic lipids were associated with hypomanic but, contrasting adult BD studies, not depressive symptoms. Future prospective studies are warranted to evaluate the temporal association between lipids and mood among youth with BD.