Combined Hyperlipidemia Research Articles

1370-P: Pregnant Dyslipidemia Affects Postpartum Metabolism in Gestational Diabetes Mellitus Patients

Women with gestational diabetes mellitus (GDM) have higher rate of dyslipidemia during pregnancy than those without GDM. However, whether this higher level of blood lipid during pregnancy in GDM women has effects on postpartum metabolism is rarely reported. The purpose of this study is to assess the influence of dyslipidemia during pregnancy on postpartum metabolism in women with history of GDM . A total of 443 women with history of GDM were enrolled in this retrospective cohort study. All of them have completed revisit at 4-12 week postpartum. The demographic and pregnant medical records were collected. In the postpartum revisit, 75g-OGTT test and physical examination were performed. The serum lipid level and insulin concentration were measured. Pregnant dyslipidemia were categorized according to the criteria of Williams obstetrics in pregnancy. The relationship between pregnant dyslipidemia and postpartum metabolism was statistically analyzed. On the whole, postpartum blood lipid levels showed a downward trend comparing with those during pregnancy. However, 39.4% of those GDM women presented dyslipidemia at 4-12 week postpartum, including 61.2% of mixed hyperlipidemia, and 38.8% of single component dyslipidemia. Women with pregnant dyslipidemia had higher postpartum total cholesterol level, TG level as well as LDL-c level. The triglyceride (TG) level during pregnancy were positively correlated with postpartum fasting blood glucose level, fasting insulin level and insulin resistance index (HOMA-IR). On the other hand, the HDL-c level during pregnancy were negatively correlated with postpartum fasting blood glucose and HOMA-IR. In conclusion, the abnormally increased blood lipid levels during pregnancy in GDM women are relative to the postpartum hyperglycemia and hyperlipidemia. Management of pregnant dyslipidemia may be beneficial to the postpartum metabolism in GDM women. Disclosure H. Xiao: None. L. Pei: None. Z. Li: None. X. Huang: None. S. Yue: None. X. Cao: None. Funding Sun Yat-sen University (2017001); Science and Technology Planning Project of Guangzhou (201803010101)

Hypertriglyceridemic Waist and Associated Factors: A Cross-Sectional Study of Bank Employees

Abstract Objectives This paper investigates the prevalence of hypertriglyceridemic waist in bank workers and its association with socioeconomic, labor, behavioral, anthropometric and health condition factors. Methods This is a cross-sectional study based on information from 525 bank workers. Hypertriglyceridemic waist was defined by the simultaneous presence of abdominal obesity, verified by the waist circumference, and elevated serum triglycerides. Associations were verified with sociodemographic, labor, behavioral, anthropometric and health condition variables. Results The investigation resulted in a phenotype prevalence of 19.4%, being higher in men, elderly, married and working in the bank for more than 5 years. The phenotype was also associated with overweight, low HDL-c (high-density lipoprotein), mixed hyperlipidemia, high triglyceride/HDL-c ratio and arterial hypertension. Being over 50 years of age and being overweight increased the chances of the bankers presenting the phenotype. Being female and having adequate levels of HDL-c were shown to be protective factors against the phenotype. Conclusions It was concluded that the prevalence of hypertriglyceridemic waist is high and is associated mainly with the excess weight and unfavorable lipid profile of this population. Funding Sources This research received no external funding.

The brave new world of genetic testing in the management of the dyslipidaemias.

With the exception of familial hypercholesterolaemia, the value of genetic testing for managing dyslipidaemias is not established. We review the genetics of major dyslipidaemias in context of clinical practice. Genetic testing for familial hypercholesterolaemia is valuable to enhance diagnostic precision, cascade testing, risk prediction and the use of new medications. Hypertriglyceridaemia may be caused by rare recessive monogenic, or by polygenic, gene variants; genetic testing may be useful in the former, for which antisense therapy targeting apoC-III has been approved. Familial high-density lipoprotein deficiency is caused by specific genetic mutations, but there is no effective therapy. Familial combined hyperlipidaemia (FCHL) is caused by polygenic variants for which there is no specific gene testing panel. Familial dysbetalipoproteinaemia is less frequent and commonly caused by APOE ε2ε2 homozygosity; as with FCHL, it is responsive to lifestyle modifications and statins or/and fibrates. Elevated lipoprotein(a) is a quantitative genetic trait whose value in risk prediction over-rides genetic testing; treatment relies on RNA therapeutics. Genetic testing is not at present commonly available for managing dyslipidaemias. Rapidly advancing technology may presage wider use, but its worth will require demonstration of cost-effectiveness and a healthcare workforce trained in genomic medicine.

Lipoprotein Particle Predictors of Arterial Stiffness after 17 Years of Follow Up: The Malmö Diet and Cancer Study.

Background Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malmö Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods Lipoprotein particle analysis was performed on 2,505 men and women from Malmö, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.

Design and rationale of a randomized control trial testing the effectiveness of combined therapy with STAtin plus FENOfibrate and statin alone in non-diabetic, combined dyslipidemia patients with non-intervened intermediate coronary artery disease - STAFENO study

BackgroundDespite the chronicled success of low-density lipoprotein cholesterol (LDLc)-lowering statin therapy, substantial residual cardiovascular (CV) disease risk remains a problem worldwide, highlighting the need to for combination therapies targeting non-LDLc factors, such as with fenofibrate.Methods/designThe STAFENO trial is a prospective, randomized, open-label, multi-center trial to compare the effect of statin plus fenofibrate with statin alone on the reduction and stabilization of plaque in non-diabetic, combined dyslipidemia patients with non-intervened, intermediate coronary artery disease (CAD) using virtual histology-intravascular ultrasound at 12 months. A total of 106 eligible patients are planned to be randomized to receive either a combination therapy (rosuvastatin 10 mg plus fenofibrate 160 mg/day) or monotherapy (rosuvastatin 10 mg/day) for 12 months. The primary endpoint of this study is the percentage change in the necrotic core volume. Secondary endpoints include changes in tissue characteristics and 1-year major CV events, including all-cause mortality, CV mortality, nonfatal myocardial infarction, stroke, and revascularization of the intervened and non-intervened lesions.DiscussionThe STAFENO trial will address whether combination treatment of statin and fenofibrate has an additive beneficial effect compared to statin alone on the reduction and stabilization of plaque and CV events in non-diabetic, combined dyslipidemia patients with non-intervened intermediate CAD.Trial registrationClinicalTrials.gov, NCT02232360. Registered 9 February 2014.https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0004ULE&selectaction=Edit&uid=U00023SZ&ts=2&cx=juppd2

Incidence of type 2 diabetes in familial combined hyperlipidemia

ObjectiveFamilial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees.Research design and methodsFCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998–2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002–2005 (n=275; ‘ultrasound subcohort’).ResultsFollow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox’s proportional hazard regression analyses showed that baseline HOMA2-IR and FLI≥60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D.ConclusionThis study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.

Eruptive Xanthomas as Cutaneous Manifestation of Familial Combined Dyslipidaemia in an Eleven-year-old: A Case Report

Xanthomas are subcutaneous lipid deposits containing macrophages loaded with cholesterol and cholesterol esters. Although quite common in adults, xanthomas in pediatric population are infrequent and when present, may represent a cutaneous manifestation of underlying lipoprotein disorders which most often are familial. We report a case of an eleven-year-old female child, with multiple eruptive xanthomas of skin since two years of age, a positive family history and deranged lipid profile consistent with possible familial hypercholesterolemia.

Lipid lessening drugs overview

Lipid lessening drugs are groups of drugs used to treat the conditions or diseases that associated with elevated blood levels of lipids (cholesterol, triglyceride) and low-density lipoprotein (LDL). These conditions known as dyslipidemias, which is hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia. Many studies found that dyslipidemias inclined and increase the risk of other diseases such as atherosclerosis, diabetes mellitus, and coronary arteries disease.

Familial Combined Hyperlipidemia (FCH) Patients with High Triglyceride Levels Present with Worse Lipoprotein Function Than FCH Patients with Isolated Hypercholesterolemia.

Lipoprotein characteristics were analyzed in familial combined hyperlipidemia (FCH) patients before and after statin treatment. Twenty-six FCH patients were classified according to the presence (HTG group, n = 13) or absence (normotriglyceridemic (NTG) group, n = 13) of hypertriglyceridemia. Fifteen healthy subjects comprised the control group. Lipid profile, inflammation markers, and qualitative characteristics of lipoproteins were assessed. Both groups of FCH subjects showed high levels of plasma C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and apolipoprotein J. Statins reverted the increased levels of Lp-PLA2 and CRP. Lipoprotein composition alterations detected in FCH subjects were much more frequent in the HTG group, leading to dysfunctional low-density lipoproteins (LDL) and high-density lipoproteins (HDL). In the HTG group, LDL was smaller, more susceptible to oxidation, and contained more electronegative LDL (LDL(-)) compared to the NTG and control groups. Regarding HDL, the HTG group had less Lp-PLA2 activity than the NTG and control groups. HDL from both FCH groups was less anti-inflammatory than HDL from the control group. Statins increased LDL size, decreased LDL(-), and lowered Lp-PLA2 in HDL from HTG. In summary, pro-atherogenic alterations were more frequent and severe in the HTG group. Statins improved some alterations, but many remained unchanged in HTG.

The association between serum anti-HSP27 levels with hypertriglyceridemia

BackgroundThere are little data on isolated hypertriglyceridemia and CVD risk. Heat shock protein 27 (Hsp27) is one of the heat shock proteins (Hsps) with low molecular weight. It has been shown that the atherosclerosis patients have higher concentrations of anti-Hsp auto-antibodies. The aim of the current study was to assess the relationship between hypertriglyceridemia with serum anti-Hsp27 titres. MethodsIn this cross-sectional study, fasting serum lipid profile and anthropometric parameters of 1688 subjects (1113 subjects with and 575 without hypertriglyceridemia) aged 35–65 years were analyzed as part of the data derived from the Mashhad stroke and heart atherosclerotic disorders (MASHAD: 2010–2020). A validated questionnaire was used to collect the demographic data. Combined dyslipidemia was defined according to the NCEP ATPIII criteria. ResultsThere were significant differences in waist and hip circumferences, level of fasting blood glucose, hs-CRP, systolic and diastolic blood pressure (p < 0.001 for all variables), between individuals with isolated hypertriglyceridemia (IHTG), those with combined dyslipidemia and control groups. After adjusting for confounding factors, logistic regression analysis showed that high levels of serum anti-Hsp 27 were associated with a lower odds of HTG risk (OR:0.62, 95% CI (0.39–0.97), p: 0.03). ConclusionWe found that serum anti-HSP27 antibody titers were significantly lower in the HTG group compared with individuals without HTG. However, levels of serum anti-HSP27 antibody can be affected by drug treatment. Therefore, the evaluation of drug treatment on the serum anti-HSP27 antibody in a larger population can help to confirm these findings.

Prevalence and Factors Associated with Dyslipidemia in Adults with Sickle Cell Disease in Parakou (Benin)

Objective: Determine the prevalence and factors associated with dyslipidemia in adult subjects with sickle cell disease in Parakou in 2017. Methods: This research work was a descriptive, analytical, cross-sectional and observational study carried out from January 6 to June 6, 2017. It involved 100 adult subjects with sickle cell disease (mean age: 28.77 ± 8.73 years) in the city of Parakou (Benin). Serum lipid parameters were measured through enzymatic colorimetric methods on Mindray ® BS-120 automaton (Guangdong, China). The different types of dyslipidemia were classified according to criteria defined in the National Cholesterol Education Program Adult Treatment Panel III. Results: The overall prevalence of the different types of dyslipidemia was estimated at 82% (95% CI [75.27; 88.34]). The different types of dyslipidemia were distributed as followed: HDL hypocholesterolemia (79%; 95%IC [69.71; 86.51]), LDL hypercholesterolemia (13.0%; 95%CI [7.11; 21.20]), total hypercholesterolemia (7.0%; 95%CI [02.86; 13.89]), hypertriglyceridemia (4.0%; 95%CI [1.10; 9.93]) and mixed hyperlipidemia (1.0%; 95%CI [0.03; 5.45]). Atherogenic dyslipidemia was not found out. HDL hypocholesterolemia was significantly associated with personal history of hypertension (P = 0.029), emaciation (P = 0.023) and age above or equal to 50 years (P = 0,016). Tobacco consumption (P = 0.01) and age below 50 years (P = 0.02) were significantly associated with hypertriglyceridemia. Conclusion: The prevalence of the different types of dyslipidemia is high among adults with sickle cell disease in Parakou.

Correlation of serum vitamin D with lipid profiles in middle-aged and elderly Chinese individuals.

Deficiency of vitamin D has been associated with various health conditions. The purpose of this study was to evaluate the associations between the serum 25OHD concentration and lipid profiles in Chinese individuals. Serum 25OHD and lipid profiles were obtained for a cross sectional sample of 10100 individuals aged 40-75 years from Lanzhou city, which is located in western China. Linear-by-linear association, partial correlation analysis and multiple logistic regression analysis were used to evaluate associations between serum 25OHD concentration and lipid profiles. 10038 subjects aged 40- 75 years were included in the study. The 25OHD deficient and insufficient groups had higher TC, LDL-C and TG when compared to the optimal group. The dyslipidemia rates of vitamin D deficiency, insufficiency, and sufficiency groups were 45.4%, 41.6%, 38.8%, respectively. The prevalence rates of dyslipidemia, high cholesterol, high LDL-C, hypertriglyceridemia and mixed type hyperlipidemia exhibited decline trend in vitamin D deficiency, insufficiency and sufficiency groups. The correlation coefficients in between TC and 25OHD, LDL-C and 25OHD, TG and 25OHD were -0.033, -0.022, -0.044, respectively. Low 25OHD levels were associated with the risk of onset of dyslipidemia [OR 1.225 (95% CI 1.075-1.397), p=0.002] in the logistical regression analyses. Deficient serum 25OHD is associated with higher TC, LDL-C, and TG in middle-aged and elderly Chinese individuals. These findings suggest that low 25OHD levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.

Lipid/Lipoprotein Abnormalities Among Adult Type 1 Diabetics in Nigeria

Background: Dyslipidemia abounds among diabetics. However, these are poorly characterized among patients with type 1 diabetes (T1DM). The current study determined the pattern of dyslipidemia and their relationship with glycemic status among adult T1DM subjects. Methods: This survey was conducted retrospectively among 346 newly-diagnosed/treatment-naïve T1DM adults attending outpatient units of a third-level hospital in Nigeria. Patients’ fasting plasma glucose and lipid parameters at the time of T1DM diagnosis were abstracted from their medical files. Lipid parameters included triglyceride (Tg), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Abstracted parameters were analyzed using descriptive and comparative statistics. Results: Of the 346 studied, 46.8% (n=162) were dyslipidemic (aged: 32.69±6.29) with female predominance (59.3%; p=0.018). Categorically, females predominated among isolated dyslipidemics while males predominated among the combined/mixed dyslipidemics. High plasma Tg concentration (n=142;87.7%) was the most common isolated dyslipidemia without male/female difference (p>0.05); seconded by low HDL-C (n=80;49.4%) with the females predominating (p<0.05). The most combined and mixed dyslipidemia was high plasma Tg/low HDL-C (total n=28, 17.3%; males n=16, 24.2% vs. females n=12, 12.5%; p=0.011) and high plasma Tg/high LDL-C/low-HDL-C (total n=30, 18.5%; males n=18, 27.3% vs. females n=12, 12.5%; p=0.001) concentrations, respectively with male predominance. The female dyslipidemics were younger with lower BMI, higher systolic blood pressure, glycemia, and mean plasma Tg levels (p<0.05). The overall dyslipidemics had poor glycemic status and their risk of dyslipidemia increases with worsening glycemia. Conclusion: Dyslipidemia was common and associated with poor glycemic status among the studied cohorts. This finding informs the need for more rigorous monitoring of dyslipidemia among T1DM subjects to reduce the risk of its complications.

Effect of sleeve gastrectomy on lipid parameters and cardiometabolic risk in young women.

to analyze the effect of vertical gastrectomy on lipid profile and cardiometabolic risk in young women, preoperatively and 6 months after the operation. retrospective study, encompassing medical record reviews of women's charts, preoperatively and in six months after the operation. Data collection was performed in the second half of 2015, using a review protocol with questions on the clinical-laboratory profile, anthropometric and laboratory classification of dyslipidemias. Descriptive and inferential analysis were used to treat the variables, using measures of variance, association and linear regression. we analyzed medical records of 114 women undergoing vertical gastrectomy, with a mean age of 33.82±10.92, and with complete high school education. There was a significant reduction of anthropometric data, as well as serum lipid values, six months after the surgical procedure. The coefficients of determination and the results of linear regression, showed that the reduction in serum triglyceride values and increase in high-density lipoprotein have a direct impact on the reduction of the cardiometabolic risk. Regarding the laboratory classification of dyslipidemias, it was observed that the majority presented a significant reduction at the six-month follow-up. Mixed hyperlipidemia showed no significant reduction. The categorized cardiometabolic risk showed a significant reduction in women at risk before vertical gastrectomy. at the six-month follow-up, vertical gastrectomy was effective in reducing the serum lipid profile and the cardiometabolic risk of young women when compared to the preoperative data. There was also a different improvement in the laboratory classification of dyslipidemias at the six-month follow-up after the surgical procedure.

Association between qat chewing and dyslipidaemia among young males.

ObjectivesThis study investigated the association between qat chewing and prevalence and patterns of dyslipidaemia among young Yemeni males.MethodsIn this cross-sectional study, we used a multistage random cluster sampling method. Data were obtained using a questionnaire. Additionally, anthropometric measurements and fasting blood samples were collected. We used Program-Adult Treatment Panel III. The blood samples were analysed for lipid profile measurements including levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C).ResultsA total of 440 Yemeni male with mean age of 21.4 ± 3.6 years were enrolled. The students were divided into the following two groups—qat chewers (n = 283) and non-qat chewers (n = 77). The overall occurrence of dyslipidaemia was significantly higher in qat chewers than that in non-qat chewers (89.8% versus 80.5%) (P < 0.05). Hypercholesterolaemia, hypertriglyceridaemia, high LDL-C level, and mixed hyperlipidaemia were lower in qat chewers than in non-qat chewers (16.6%, 58.3%, 16.3%, and 10.6%, respectively, versus 20.8%, 64.9%, 18.2%, and 20.8%, respectively). Isolated hypertriglyceridaemia was slightly higher in qat chewers than in non-qat chewers (47.7% versus 44.2%). However, the incidence of low HDL-C level, isolated low HDL-C level, and isolated hypercholesterolaemia were generally higher in qat chewers than in non-qat chewers (83%, 25.1%, and 6%, respectively, versus 75.3%, 15.6%, and 0%, respectively).ConclusionThis study showed high prevalence of dyslipidaemia among Yemeni male qat chewers. Low HDL-C level was the main lipid variable, followed by hypertriglyceridaemia. Genetic factors, war conditions, physical inactivity, and low-fat traditional Yemeni diet were considered the determinants of the study findings.

A novel mutation in USF1 gene is associated with familial combined hyperlipidemia.

Familial combined hyperlipidemia or FCHL is one of the most common genetic causes of hyperlipidemia and is associated with elevation of cholesterol, triglycerides or both, and increased serum apolipoprotein B (apoB). Linkage analysis and next generation sequencing have been successfully used for identifying rare genetic variants that have moderate-to-large effects. We characterized a large pedigree from a proband identified following recruitment into the MASHAD study, in northeast Iran, with FCHL accompanied by early-onset coronary artery disease. We used linkage analysis for several candidate regions in previous studies such as 1q21-23, 11q23, and 8p, and then whole-exome sequencing to identify the disease-associated gene in this family. We identified a novel variant in the USF1 gene, leading to a substitution of a tryptophan for arginine at position 196. Arg196Trp co-segregated in all the affected family members in this pedigree with clinical syndrome and was not found in any unaffected family members of this pedigree, or in unrelated controls. We speculate that this mutation [Arg196Trp] in the USF1 gene might be associated with FCHL and early-onset coronary heart disease in this family. However, the substantial mechanism requires further investigation. These findings indicate that USF1 plays an important role in the biological pathways associated with lipid metabolism.

A novel variant in LPL gene is associated with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common genetic disorder characterized by increased fasted serum cholesterol, triglycerides, and apolipoprotein B-100. Molecular genetic techniques such as next generation sequencing have been very successful methods for rare variants finding with a moderate-to large effect. In this study, we characterized a large pedigree from MASHAD study in northeast Iran with coinheritance of FCHL and early-onset coronary heart disease. In this family, we used whole-exome sequencing and Sanger sequencing to determine the disease-associated gene. We identified a novel variant in the LPL gene, leading to a substitution of an asparagine for aspartic acid at position 151. The D151N substitution cosegregated with these characters in all affected family members in the pedigree but it was absent in all unaffected members in this family. We speculated that the mutation D151N in LPL gene might be associated with FCHL and early-onset coronary heart disease in this family. However, the substantial mechanism requires further investigation.

P730Decreased adiponectin levels and FDG uptake in visceral adipose tissue in familial combined hyperlipidemia compared to heterozygous familial hypercholesterolemia and normolipidemics

Abstract Background Adipose tissue regulates energy balance and glucose homeostasis via the secretion of circulating molecules, termed adipokines, such as leptin and adiponectin. Excess adiposity and adipose tissue dysfunction have been involved in the pathogenesis of dyslipidemias. Positron emission tomography/computed tomography (PET/CT) with F-18-Fluorodeoxyglycose (FDG) has been used for the assessment of adiposity. Purpose To compare abdominal adipose tissue function assessed by FDG uptake with serum indices, such as plasma adipokines' levels in individuals with different subtypes of dyslipidemia and normolipidemics. Methods Seventy individuals (mean age 44±13 years, range 21–75, 43 men) with a clinical diagnosis of either heterozygous familial hypercholesterolemia (heFH) (n=38) or familial combined hyperlipidemia (FCH) (n=32), not under statins for at least one year, and 20 age and sex matched controls, were enrolled. Visceral (VAT) and subcutaneous adipose tissue metabolic activity (SAT) was assessed with FDG-PET/CT imaging and was quantified by calculating the target-to-background ratios (TBR) in consecutive axial fat images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by dividing the average of the mean standard uptake value (SUV) to the mean SUV of the vena cava. Leptin and adiponectin were measured in all the subjects. Results There was no significant difference of plasma leptin values between FCH, heFH and non dyslipidemics subjects (p=0.204). FCH had reduced adiponectin values compared to heFH patients and controls [median 5.7 IQR (3.9–7.6) vs. 13.1 (9.2–23.3) vs. 10.9 (6.1–19.1) μg/mL, respectively, p&lt;0.001]. There was no difference in FDG uptake in subcutaneous adipocytes (SATTBR) between FCH, heFH and controls (p=0.161). In contrast, patients with FCH had reduced VATTBR values compared to heFH patients and controls (0.63±0.14 versus 0.81±0.17 versus 0.86±0.28, p=0.005). This difference remained significant even after adjustment for age, sex and cardiovascular risk factors (b=-0.428, p=0.001, adjusted R2=0.219). SATTBR was inversely correlated to leptin levels (r=−0.484, p&lt;0.001), while no significant association was observed with adiponectin values (p=0.167). No significant associations were observed between VATTBR and either serum leptin (p=0.066) or adiponectin levels (p=0.254). Conclusions Visceral adipose tissue FDG uptake is reduced in patients with FCH compared to those with heFH and normolipidemics. In addition, serum adiponectin levels are lower in patients with FCH. These findings highlight the different pathophysiological role of visceral fat function in the two most common types of familial dyslipidemia and suggest that visceral fat could be an attractive target for the treatment of FCH.

P5302Significant correlation of visceral adiposity and adipocytokines with arterial inflammation in genetic dyslipidaemias

Abstract Background The adipose tissue is now established as a major regulator of cardiovascular status, mediated by the secretion of several bioactive molecules, including adipocytokines. Individuals with genetic dyslipidaemias of either familial combined hyperlipidemia (FCH) or heterozygous familial hypercholesterolemia (heFH) subtype are characterized by accelerated atherosclerosis. Nonetheless, limited data exists on the relationship between adiposity and arterial inflammation, a marker of cardiovascular risk, in this setting. Purpose To investigate the relationship between adiposity indices and arterial inflammation evaluated by 18F fluorodeoxyglycose positron emission tomography (PET/CT) in patients with hereditary lipid metabolism disorders. Methods Consecutive patients with either FCH or heFH, free of statin therapy, and normolipidaemic individuals underwent PET/CT imaging. Arterial FDG uptake was estimated as the average value of target-to-background ratio (TBR) within aortic and carotid wall. Volumes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were measured from CT images between the proximal (cephalic) end of the L1 and distal (caudal) end of the L3 vertebrae by selecting all voxels with attenuation between −190 and −30 Hounsfield Units (HU). Serum adiponectin and leptin levels were measured with ELISA by available commercial kits. For comparisons with arterial TBR, adiponectin and leptin concentrations above and below the 25th percentile, were stratified as high and low, respectively. Results In total, 60 individuals (20 FCH, 20 heFH and 20 controls) were included. A modest but significant correlation between SAT volume and arterial TBR (R=0.386, p=0.004) was detected. This relationship did not remain significant after controlling for VAT volume (p=0.303). A strong correlation between VAT volume and arterial TBR (R=0.621, p=0.001) was observed. This relationship remained significant after controlling for SAT volume (R=0.541, p&lt;0.001). Arterial TBR values were higher in individuals with low plasma adiponectin levels (p=0.010). In addition, patients with higher leptin levels exhibited increased arterial FDG uptake compared to subjects with low serum leptin concentrations (p=0.05) Conclusions Abdominal adipose tissue imaging markers and serum adipocytokines correlate with arterial inflammation as assessed by PET/CT in patients with familial dyslipidaemias highlighting the role of abdominal adipose tissue for atherosclerosis progression in this population.

The relationship of hyperlipidemia with maternal and neonatal outcomes in pregnancy: A cross-sectional study.

BackgroundConcentrations of plasma lipids levels during pregnancy clearly increases. According to some studies, dyslipidemia is effective in the incidence of preeclampsia and insulin resistance. Objective: This study aimed to examine the relationship between hyperlipidemia and maternal and neonatal outcomes in pregnant women.Materials and MethodsThis is a cross-sectional study which was conducted on two groups of pregnant women with hyperlipidemia and normal ones to assess maternal and neonatal outcomes. Maternal data including gestational age, mother's age, body mass index, and maternal weight gain during pregnancy, gestational diabetes mellitus, preeclampsia, cholestasis, and delivery method. Also, birth weight and Apgar score were gathered as the neonatal outcomes.Results The results showed that the prevalence of abnormal lipid parameters increased with increasing gestational age. In pregnant women with dyslipidemia in combination with increased triglyceride, cholesterol and Low-density lipoprotein, and decreased High-density lipoprotein, the incidence rates of gestational diabetes (p 0.001), preeclampsia (p 0.001), cholestasis (p = 0.041), fetal growth retardation (p 0.001), and macrosomia (p 0.001) were statistically higher.ConclusionDyslipidemia was associated with some adverse effects of pregnancy and harmful fetal outcomes. Therefore, it seems that adding laboratory assessment of lipid profiles before and during pregnancy can be effective in early diagnosis of dyslipidemia.