Elevated LDL-C Research Articles

ESTIMATED PREVALENCE OF POSSIBLE AND PROBABLE FAMILIAL HYPERCHOLESTEROLEMIA IN 35,451 STATIN-TREATED PATIENTS IN EUROPE, CANADA, THE MIDDLE EAST, AND SOUTH AFRICA

The EAS consensus paper on familial hypercholesterolemia (FH) indicates a higher prevalence of elevated LDL-C due to genetic reasons than previously estimated. On the basis of the DYSIS registry we aimed to determine the % of patients with possible / probable FH. The cross-sectional, observational

0033: Unexpected high prevalence of possible and probable familial hyper-cholesterolemia in clinical practice – the DYSIS study

The recent EAS consensus paper on familial hypercholesterolæmia (FH) indicates a higher prevalence of elevated LDL-C due to genetic reasons than previously estimated. We aimed to determine the percentage of patients with very high LDL-C levels in the DYSIS study. The cross-sectional, observational study DYSIS examined lipid goal attainment among statin-treated patients in Canada, Europe, the Middle East, Egypt and South Africa. In this analysis we evaluated DYSIS patients to determine very high LDL-C with potential genetic background. We examined the number of patients with LDL-C >190mg/dl despite statin therapy, the number of patients with possible FH (Score 3-5 according to the Dutch Advanced Method) and the number of patients with probable FH (Score 6-8). This score includes several parameters: first degree relative known with premature CHD and/or first degree relative with LDL-C >95 th percentile (1 point); first degree relative with tendon xanthomas or children with LDL-C >95 th percentile (2 points); the patient has premature CAD (2 points), the patient has premature cerebral or peripheral vascular disease (1 point); the patient has tendon xanthomas (6 points), the patient has corneal arcus below the age of 45 years (4 points); LDL-C >330mg/dl (8 points), LDL-C between 250 and 329mg/dl (5 points), LDL-C between 190 and 249mg/dl (3 points) and LDL-C between 155 and 189mg/dl (1 point). The prevalence of patients with LDL-C >190mg/dl despite statin therapy was 3% (UK 0.8%, France 3.5%, Spain 4.2%). The prevalence of patients with possible FH (Score 3-5) was 6% (UK 4.4%, France 5.9%, Spain 5.7%). The prevalence of patients with probable FH (Score 6-8) was 0.3% (UK 0%, France 0.1%, Spain 0.2%). In this multinational study of statin-treated patients, 2.9% showed an elevated LDL-C above 190mg/dl. Genetic causes may explain the very high LDL-C levels despite statin therapy in the DYSIS study.

Nutrigenetics of Japanese Vegetarians with Polymorphism in the Fatty Acid Desaturase

This review investigates how the genotype of vegetarians controls lipid metabolism responses to the dietary intake of n-3 fatty acids. While health indices of Japanese vegetarians are superior to those of omnivores, the effects of genetics have not been studied. The lipid intake of Japanese omnivores and vegans is less than that of Western vegans. Mongolian carnivores and Inuit piscivores have shorter lifespans compared to other Asians who consume a rice diet or taro-fish diet. Our genetic studies on Mongoloids in Asia Pacific regions revealed similar allele frequencies of genes related to diabetes and cardiovascular diseases, which are increasing with recent Westernization because of genetic differences between Mongoloids and Caucasoids. Long-chain n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), play a role in preventing these diseases, yet vegetarians consume nearly 0 g per day. Conversion of plant-derived α-linolenic acid (ALA) to EPA and DHA, and linoleic acid to arachidonic acid (AA) requires the Δ5 desaturase. Thus, plasma concentrations of EPA, DHA and AA in vegetarians are lower than those in omnivores, especially vegans with the C allele of the Δ5 desaturase polymorphism rs174547. The following hypotheses have been proposed to explain the health of C homozygote vegans: 1. They are unable to survive, 2. They cease the vegan diet, 3. They preferentially preserve EPA/DHA by lowered catabolism, 4. Their Δ5 desaturase is activated by specific factors, and 5. Their EPA/AA ratio is elevated and harmful LDL-C and inflammation etc. is reduced. This review does not support hypotheses 1 and 2, but partially accepts 3 and 4 and completely confirms 5. In future, genotype-specific personalized dietary recommendations for optimal health span based on telomere length will be developed. Currently, the pesco-vegetarian diet, which is similar to the traditional Japanese (Washoku) diet, is the healthiest for the majority of subjects.

Eugenia caryophyllus Extract Exerts Hypocholesterolemic and Antioxidant Effects in High-Cholesterol-Fed Rats

Background: Eugenia caryophyllus (clove) is an important aromatic household spice. The plant is believed to possess medicinal properties and is commonly used in herbal preparations by traditional healers in the treatment of different ailments and diseases. Objectives: We investigated the lipid-lowering and antioxidant effects of aqueous extract of Eugenia caryophyllus on high-cholesterol-fed rats. Materials and Methods: Cholesterol (40 mg/0.3 mL) was administered to induce hypercholesterolemia in rats by oral gavage, and Eugenia caryophyllus (100 or 200 mg/kg) and Questran (0.26 g/kg) were administered five times a week for eight consecutive weeks. Serum lipid-profiles, lipid peroxidation (LPO), and antioxidant parameters were examined in liver and heart post mitochondrial fraction (PMF). Aspartate and alanine aminotransferase (ALT and AST) activities and liver tissue histology were used to evaluate tissue toxicity. Results: Hypercholesterolemia produced a noticeable decrease in serum HDL-c, whereas a concurrent elevation in serum LDL-c, total cholesterol, and triglycerides as well as serum ALT and AST was observed. Furthermore, hypercholesterolemia remarkably decreased antioxidant status, but LPO content was increased. These indices were significantly attenuated in hypercholesterolemic rats treated with E. caryophyllus extract (100 or 200 mg/kg of body weight). Specifically, reduced glutathione (GSH) concentration was increased in a dose dependent manner in liver and heart PMF. Conclusions: These results demonstrate that the hypolipidemic and antioxidative effects of aqueous extract of E. caryophyllus might be due to its ability to ameliorate lipid profiles, enhance antioxidant activities, and delay the lipid peroxidation process. This confirms the previously identified protective roles of E. caryophyllus in human health.

Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

Lysosomal Acid Lipase (LAL) is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD), unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis.

Abstract 17499: ETC-1002 Incrementally Lowers Low Density Lipoprotein-cholesterol in Patients With Hypercholesterolemia Receiving Stable Statin Therapy

Background: ETC-1002 is an oral investigational drug that modulates hepatic adenosine triphosphate-citrate lyase to reduce cholesterol biosynthesis and may be beneficial in treating patients with elevated LDL-C despite using stable statin therapy. Methods: A double-blind, parallel group, placebo-controlled multicenter trial evaluated patients (n=134) with baseline LDL-C of 115-220 mg/dL while taking atorvastatin ≤20 mg, simvastatin ≤20 mg, rosuvastatin ≤10mg or pravastatin ≤40 mg randomized to ETC-1002 120 mg, ETC-1002 180 mg, or placebo once daily for 12 weeks. Results: ETC-1002 120 mg (p=0.0055) and 180 mg (p<0.0001) lowered LDL-C significantly more than placebo (primary endpoint) as an add-on to statin therapy. ETC-1002 also lowered (p<0.05) apolipoprotein B, non-high density lipoprotein-cholesterol, total cholesterol and LDL particle number more than placebo. C-reactive protein was also reduced with ETC-1002 120 mg (22%, p=0.26) and 180 mg (30%, p=0.08) versus 0% with placebo. Adverse events (AEs), muscle-related AEs, discontinuations due to AEs and levels of clinical safety labs were generally similar compared with placebo. Conclusion: In patients with elevated LDL-C despite stable statin therapy, ETC-1002 produces incremental LDL-C lowering and is well-tolerated.

Abstract 17279: Have the 2013 AHA/ACC Cholesterol Guidelines Affected Clinicians’ Lipid Management Strategies?

Background: The 2013 ACC/AHA Cholesterol Guidelines departed from prior ATPIII guidelines, recommending statin treatment based on patients’ predicted 10-year ASCVD risk and de-emphasizing LDL-C targets. However, the degree to which these new guidelines have been adopted by clinicians in community practice is unknown. Methods: We surveyed 522 clinicians in 133 cardiology, primary care, and endocrinology practices participating in the Patient and Provider Assessment of Lipid Management (PALM) Registry. Clinicians were asked about their likelihood of prescribing statins in 4 hypothetical patient scenarios. Results: Among responders, 79% were physicians (60% cardiologists, 38% primary care or general practice, 2% endocrinology), 18% were advanced practice providers, and 3% trainees. When queried, 73% of providers reported primarily using the 2013 ACC/AHA Guidelines to guide lipid management. However, only half reported “often” or “always” calculating 10-year ASCVD risk to aid lipid management decisions for primary prevention. When presented with a high 10-year ASCVD risk patient (>15%) with a high LDL-C (150 mg/dL), 92% of providers recommended statins. Similarly, 83% of providers would use statins in a diabetic patient with a LDL-C of 140 mg/dL. Yet, only 37% reported they would prescribe a statin to an older adult (age 70) for whom guidelines recommend statin based on high 10-year ASCVD risk alone (10.1%). And up to 40% would prescribe a statin to a younger (age 40) with a low 10-year risk, but a high LDL (165 mg/dL) who would not otherwise meet criteria for statin therapy under the new guidelines. Cardiologists and non-cardiologists were similarly likely prescribe statins in most scenarios with the exception of to the younger patient with elevated LDL-C were cardiologists used statins more commonly (32% vs. 42%. OR 1.5, 95% CI 1.1-2.2, p=0.02). Conclusion: Initial survey results show that while most clinicians claim adoption of the 2013 ACC/AHA Guidelines, reported practices are not always adherent to these guidelines. Providers do not always calculate 10-year ASCVD risk to guide lipid management and many do not prescribe statins to patients eligible based on 10-year ASCVD risk.

Abstract 17990: Common PCSK9 Gain-of-function E32K Variant Carriers Reveal Milder LDL-C but Higher TG Elevation Compared With LDLR Mutations

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) gene is the third causal gene of familial hypercholesterolemia (FH), and is now an emerging therapeutic target. We have found Gain-of-function mutation E32K in PCSK9 gene is common in Japanese FH. We investigated clinical characteristics of gain-of-function PCSK9 variant carriers. Methods: A total of 940 Clinically diagnosed FH heterozygotes were investigated for LDLR, PCSK9, and APOB gene. High-resolution melting (HRM) method followed by Sanger sequence were used for point mutation, and multiplex ligation-dependent probe amplification methods were applied for large rearrangements in LDLR. Fasting lipid levels without lipid-lowering drugs were analyzed. Results: LDLR mutations were identified in 732 patients (78%) and 10% of them were large rearrangements. PCSK9 E32K mutation was identified in 56 patients (6%). No APOB mutations causing FH were identified, and 143 patients showed no known FH-gene mutations. LDLR mutation carriers showed significantly higher LDL-C (LDLR 268±73, PCSK9 198±82, No mutation 198±65 mg/dL, p <0.001) and higher apoB (183±51, 130±49, 148±42 mg/dL, p <0.001) compared with other two groups. On the other hand, PCSK9 and No mutation group had higher TG compared with LDLR mutations (126±94, 150±84, 145±74 mg/dL, p <0.05 in log-transformed TG). Hypertriglyceridemia was common in PCSK9 mutation (25%, 41%, 36%, p <0.01). HDL-C was higher in No mutation group (47±15, 51±51, 55±27 mg/dL, p <0.01). Achilles tendon xanthoma was more frequent in LDLR mutations. Lp(a) levels did not significantly different with PCSK9 mutation. Results: PCSK9 gain-of-function mutation E32K showed mild LDL-C elevation, but with frequent hypertriglyceridemia. This result will support basic reports that PCSK9 regulates not only LDL-R degradation but also VLDL metabolism.

Abstract 19544: The Familial Hypercholesterolemia Phenotype in the United States is Associated With an Age-dependent Increase in Long-term Coronary Heart Disease Risk

Introduction: Heterozygous familial hypercholesterolemia (FH) has an estimated prevalence of 1:200-500, affecting up to 1,500,000 individuals in the US. Available CHD risk prediction equations do not account for lifetime exposure to elevated LDL-C in FH patients, and while relative risks of 7-100 have been reported for CHD in FH, US outcomes of FH are unknown. We aimed to evaluate long-term CHD risk in US adults with an FH phenotype. Methods: Using pooled data from 6 US epidemiologic cohorts, participants were stratified by LDL-C level at index ages 25, 35, 45, 55, 65 and 75 years. LDL-C≥190 and <130 mg/dL defined the FH phenotype and referent groups, respectively. We used Cox regression models to assess covariate-adjusted associations of the FH phenotype with the hazard for fatal/nonfatal MI and CHD death and to generate 30-year event-free survival curves. Results: A total of 42,390 baseline person-exams were available across the index ages. The table shows the 30-year event rates for patients with the FH phenotype (LDL-C≥190 mg/dL) compared with the referent from each index age, as well as covariate-adjusted HRs for CHD death or fatal/nonfatal MI. As expected, the relative increase in 30-year events is highest for the youngest individuals, with rates up to 12 times higher for CHD death, and attenuates at older index ages. After adjustment, HRs for both CHD death and fatal/nonfatal MI are more modest but show a similar age-dependent pattern. The figure shows the adjusted 30-year survival free of fatal/nonfatal MI for the youngest two index ages, by LDL-C stratum. Conclusions: In the US, the FH phenotype is associated with substantial long-term CHD risk in younger adults, with more modest elevations in risk at older ages. The absolute HRs are lower than previously described, possibly due to unique features in the US population, improved management compared to other historical cohorts, or misclassification of some participants who did not have longstanding high LDL-C.

Abstract 16584: Association of Lower Height and Higher LDL-c in a Statewide Schoolchild Cholesterol Screening Program

Introduction: The Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) Project has screened West Virginia 5th graders since 1998 to facilitate primordial prevention of coronary heart disease (CHD) in WV. LDL-c levels above 175 mg/dl in children suggest Familial Hyperlipidemia (FH) in the child’s family and a level above 160 mg/dl with history of CHD in relatives can also establish a diagnosis. Hypothesis: Based on previous adult literature, the association of lower height with higher LDL level observed in adults begins in childhood and is prominent in children with LDL in FH range. Methods: Fifth graders are screened yearly in WV schools with parental consent for Body Mass Index and lipid panel. Lipids were analyzed with respect to either short stature < 2 SD for height or comparing 1st (shortest) and 4th quartiles of the population. Statistical analysis for age- and gender-adjusted height percentiles was performed in SAS. Results: 59,386 children had lipid and height data. Mean LDL-c for 1st vs. 4th quartile of height was 94.08 mg/dl (95% Confidence Interval-CI 93.66-94.51) vs. 90.03 mg/dl (CI 89.65-90.42). First quartile of height students had average 4.05 mg/dl higher LDL-c (95% CI 3.48 -4.62 mg/dl). 4398 children had an LDL level above 130 g/dl, 632 above 160 mg/dl and 247 above 175 mg/dl. The Chi square analysis of short stature (height 130 g/dl was also significant (p=0.013) with increased odds of LDL-c above 130 g/dl compared to non-short stature (OR= 1.37, CL 1.07-1.75). Table 1 shows odds ratio for varying levels of elevated LDL-c for the first (shortest) vs. 4th (tallest) quartile of students. Conclusions: Shorter stature is associated with higher LDL-c level in WV 5th graders generally and in those children with increased risk for genetic dyslipidemia. The trend to increasing odds ratio in strata of higher LDL-c supports a recent report of association of single nucleotide polymorphisms selecting for lower genetic height and higher LDL-c.

Immediate release niacin effect at stratified lipid levels

BackgroundThe Coronary Drug Project demonstrated a significant decrease in non-fatal myocardial infarction, and total mortality using immediate release niacin (IRN). However, AIM-HIGH and HPS-2-THRIVE showed no additional benefit from adding niacin to statin therapy.ObjectiveTo evaluate the efficacy and tolerability of IRN on low-density-lipoprotein-cholesterol (LDL-C), high-density-lipoprotein-cholesterol (HDL-C), triglycerides, and lipoprotein (a) (Lpa) at stratified lipid levels in a monotherapy IRN group (MTG) and a combined therapy group (CTG) statin+IRN. MethodsWe retrospectively studied 185 patients who were prescribed IRN for elevated LDL-C, triglycerides, lipoprotein a (Lpa), or low HDL-C. All patients used the same IRN products. Results157 patients had complete records. (MTG=74 patients, CTG=83 patients with 68 combined with statins). Mean IRN dose=2474mg. Mean duration=3.05years.If initial LDL-C was <130, LDL-C did not decrease significantly with IRN. If initial LDL-C>=130, LDL-C decreased 35% in MTG vs. 32% decrease in CTG. If initial HDL-C<40, there was a 40% increase in MTG vs. 61% increase in CTG. If initial triglycerides>150, there was a 48% decrease in MTG vs. 54% decrease in CTG. Lpa decreased 49% for all patients with initially elevated Lpa. Data except for LDL-C<130 were significant (p<.001). ConclusionLowering LDL-C is the corner stone for decreasing cardiovascular events. IRN reduces LDL-C significantly when initial LDL-C>130, but not significantly when LDL-C<130. Patients in AIM-HIGH and HPS-2-THIRVE received statin therapy causing very low initial LDL-C. Our results may explain why adding niacin to statin therapy failed in AIM-HIGH and HPS-2-THRIVE since niacin did not further lower LDL-C.

Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits.

The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation.

BODY ADIPOSITY AND ITS RELATIONSHIP OF METABOLIC SYNDROME COMPONENTS IN COLOMBIAN ADULTS

recently, Bergman et al. have introduced a new index of adiposity, namely, body adiposity index (BAI), as a marker of obesity excess body fat in clinical practice. We aimed to determine the prevalence of obesity and metabolic syndrome (MetS) and to assess the predicting ability of BAI in various atherogenic indices, MetS and its components among adult from Bogota, Colombia. cross-sectional study in 690 male. MetS components (waist circumference ≥ 90 cm; fasting plasma glucose ≥ 100 mg/dL, blood pressure ≥ 135/85 mm Hg; triglycerides ≥ 150 mg/dL and HDL-c ≤ 40 mg/dL were measured. Atherogenic indices (cholesterol/HDL-c, LDL-c/HDL-c, triglycerides/HDL-c, lipid-metabolic index [LMI] and MetS score) were calculated. the prevalence of obesity by BAI (cut-point > 26.1%) and MetS was 50.1% and 19.1%, respectively. Subjects with MetS and obesity by BAI, show lower HDL-c levels and more frequently components of MetS (waist circumference, cholesterol and serum triglycerides). Predicting ability of BAI with a greater odds for atherogenic indices were 1.78 (95%CI 1.25 to 2.55), 1.46 (95%CI 1.01 to 2.14), 1.97 (95% 1.29 to 3.02), 2.04 (95%CI 1.23 to 3.39) and 1.47 (95%CI 1.03 to 2.11), elevation in LDL-c, LMI, MetS score and cholesterol/ HDL-c, and triglyceride/HDL-c, respectively (p < 0.05). subjects with higher levels of BAI show raised prevalence of obesity and positively associated with components of MetS.

Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20mg/kg/day), or HCD plus atorvastatin (10mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and decreased the elevated I/M ratio. This effect was confirmed by histopathological examination of the aorta. Moreover, flavocoxid effectively suppresses the release of inflammatory markers. In conclusion, these findings demonstrated that flavocoxid would be useful in preventing oxidative stress, inflammation, and vascular dysfunction induced by HCD.

Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation

Sex differences have been previously highlighted in the cardioprotective effects of the Mediterranean diet (MedDiet). The objective of this study was to investigate whether sex differences also exist with regard to LDL particle size distribution and oxidation. Participants were 37 men and 32 premenopausal women (24–53 years) with slightly elevated LDL-C concentrations (3.4–4.9 mmol/L) or total cholesterol/HDL-C ≥5.0. Variables were measured before and after a four-week isoenergetic MedDiet. Sex differences were found in response to the MedDiet for the proportion of medium LDL (255–260 Å) (p for sex-by-time interaction = 0.01) and small, dense LDL (sdLDL; <255 Å) (trend; p for sex-by-time interaction = 0.06), men experiencing an increase in the proportion of medium LDL with a concomitant reduction in the proportion of sdLDL, while an opposite trend was observed in women. A sex difference was also noted for estimated cholesterol concentrations among sdLDL (p for sex-by-time interaction = 0.03), with only men experiencing a reduction in response to the MedDiet. The MedDiet marginally reduced oxidized LDL (oxLDL) concentrations (p = 0.07), with no sex difference. Results suggest that short-termconsumption of the MedDiet leads to a favorable redistribution of LDL subclasses from smaller to larger LDL only in men. These results highlight the importance of considering sex issues in cardiovascular benefits of the MedDiet.

Association of Human Adenovirus-36 With Dyslipidemia in Tehranian Children and Adolescent; TLGS

Background: The human adenovirus-36 (Adv36) has been associated with obesity and lipid disorders in some countries. The primary dyslipidemia related to obesity is characterized by increased TG, decreased HDL levels and abnormal LDL composition. Childhood obesity is a major public health problem in most developing countries. Objectives: The aim of this study was to investigate the association between Adv36 and lipid disorders in Tehranian youth. Patients and Methods: In a cross-section/observational study, anthropometric, blood pressure and biochemical measurements were examined in 54 youth, aged below 19 years, selected randomly from participants of Tehran Lipid and Glucose Study (TLGS) of Iran. Human Adv36 antibody of serum was determined using ELISA method. Results: Of 54 youth, with a mean age of 14.78 ± 2.62 years, 85.2% were Adv36 seropositive (N = 46) and 14.8% were seronegative (N = 8). Subjects with Adv36 seropositive had higher mean of age, weight, TC, LDL-C, TG and SBP and lower level of HDL-C, waist, FBS and DBP. The unadjusted OR for elevated TG increased in participants who were Adv36 seropositive (OR 3.062, 95% CI: 0.344-27.293). Although the unadjusted OR for other lipid variables, such as elevated TC and LDL-C or decreased HDL-C, tended to increase in participants who were Adv36 seropositive (OR 1.028, 95% CI: 0.996 - 1.060; OR 1.057, 95% CI: 0.107 - 10.481; OR 1.125, 95% CI: 0.238 - 5.325, respectively), the results were not significant. Conclusions: It seems that seropositive Adv36 has a strong association with lipid disorders, especially elevated TG level in Tehranian children and adolescent.

Dyslipidemia in type 1 diabetes mellitus: Relation to diabetes duration, glycemic control, body habitus, dietary intake and other epidemiological risk factors

BackgroundDiabetes is associated with a high risk of cardiovascular disease (CVD). The classic “diabetic dyslipidemia” is mostly described as hypertriglyceridemia and low levels of HDL-C. Elevated LDL-C is an established risk factor for CVD. ObjectiveIdentify the pattern of dyslipidemia in children and adolescents with type 1 diabetes mellitus regularly following at Diabetes Endocrine and Metabolism Pediatric Unit (DEMPU) at Children’s Hospital of Cairo University; and to detect its relation to different risk factors. MethodsSixty children and adolescents with T1DM, (34 males and 26 females, mean age 12.5±2.4years and mean duration of diabetes 4.3±2.7years) were evaluated by full history and clinical examination including 3day dietetic history for analysis, BMI and waist circumference. Records were revised for mean blood glucose and HbA1c. Fasting lipid profile (total cholesterol, triglycerides, HDL-C and LDL-C) was performed. Thirty-nine healthy age and sex matched children were included as control for lipid profile. ResultsDyslipidemia significantly more frequent among T1DM children and adolescents compared to control subjects (39/60, 65% vs. 11/39, 28.2%, p<0.001); and the dyslipidemic (39/60) compared to normoalbuminuric (21/60) children had significantly higher mean waist circumference. Both groups were comparable regarding age, age at onset and duration of diabetes, family history of diabetes and CVD, degree of glycemic control and dietary analysis. ConclusionDyslipidemia is significantly more frequent in children and adolescents with T1DM compared to non-diabetic peers. The most frequent type of dyslipidemia was high LDL-C and low HDL-C in the dyslipidemic group.

Dietary high oleic canola oil supplemented with DHA oil attenuates plasma PCSK9 levels in humans

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel circulating protein, which plays an important role in regulation of cholesterol metabolism by promoting hepatic LDL receptor degradation. However, the action of dietary fat composition on PCSK9 levels remains unknown. A double‐blinded RCT, consisting of five 30‐d intervention periods, was conducted to investigate varying dietary oils on circulating PCSK9 levels in healthy humans. Treatments included 60 g/d of conventional canola oil (Canola), high oleic canola oil (CanoalOleic), high oleic canola/DHA oil blend (CanolaDHA), corn/safflower oil blend (CornSaff) and flax/safflower oil blend (FlaxSaff). PCSK9 levels using ELISA were assessed at the end of each phase. Lipid profiles (n=54) showed that CanolaDHA feeding resulted in the highest (p&lt;0.05) serum total cholesterol (TC) and LDL‐C levels among all five treatments. CanolaDHA feeding also produced the lowest (p&lt;0.05) plasma PCSK9 concentrations (204.5±9.6 ng/ml) compared to Canola (231.6±9.6 ng/ml) and CanolaOleic (230.2±9.6 ng/ml) diets. In CanolaDHA diet, PCSK9 levels correlated (r=0.35, p&lt;0.01) with TC levels but not with LDL‐C levels. Results indicate that post‐diet response in PCSK9 may be altered with CanolaDHA diet. In conclusion, the elevated LDL‐C levels from a DHA oil treatment may not be deleterious as they are accompanied by a decline in PCSK9 levels. (Supported by the Canola Council of Canada and Growing Forward II program)

Hypolipidemic and anti-atherogenic effect of aqueous extract leaves of Ficus glumosa (Moraceae) in rats

Leaves of Ficus glumosa are used in northern Cameroon and southern Chad for the treatment of cardiovascular diseases, as food and as a stimulant for milk production in both women and animals. Atherosclerosis is a disease in which frequency increases with age. The first lesions appear at the young subject during adolescence. Atherosclerosis lesions appear very precociously and worsen with age. They interest the levels chronologically aortic, coronary then carotid. Age is a risk factor in that it reflects the exposure time of individual to the other risk factors. The frequency of the atherosclerosis increases with age because of the aging of the cells. This study was undertaken to evaluate the hypolipidemic and anti-atherosclerotic properties of aqueous extract of the leaves of F. glumosa in rats with hypercholesterolemia (HC). 60 male rats were fed for 4weeks with a high-cholesterol diet (1%) and 3 doses (225, 300 and 375mg/kg) of extract of F. glumosa were used in these experiments. The experiments were conducted under the same conditions with atorvastatin (1mg/kg), as pharmacological reference substance. The effects of F. glumosa on weight gain, water and food consumption, levels of serum lipids and lipoprotein lipid oxidation and stress markers in the blood and liver were examined. The administration of F. glumosa extract prevented significant (P<0.05) elevation in TC, LDL-c, VLDL-c, hepatic and aortic TG and TC. The atherogenic, triglyceride, and lipid peroxidation (TBARS) indexes were also decreased in the rats treated with the extract. F. glumosa favored the performance of fecal cholesterol. It also significantly inhibited the changes and the formation of aortic atherosclerotic plaques. These results revealed the hypolipidemic and antiatherosclerotic effects of F. glumosa extract and support the traditional use of the extract of this plant in the treatment of hypertension and diabetes.

0015: High LDL cholesterol decreases life expectancy in primary prevention

The 2012 ESC guidelines recommend a LDL-cholesterol (LDL-C) lower than 3 mmol/L for subjects at low or moderate risk with a class I/A and a strong grade. According to ESC, statins should be used as the drugs of first choice. The aim of this study was to assess the association between elevated LDL-C with total and cardiovascular (CV) mortality in primary prevention. Our study population consisted in patients who had been admitted from 1995 to 2011 in a preventive cardiology unit of a large French university hospital. We excluded patients whose age was less than 30 and all patients with previous ischemic heart disease. Vital status in 2011 was checked through the death national database. 4885 patients were included (59% men; 53±10 yrs). After a mean follow-up of 8.6 years, 129 deaths, including 31 CV deaths, were recorded. The mean LDL-C was 3.98±1.18 mmol/L (3.90 in men and 4.11 in women). Among these 4885 patients, 2648 (54.2%) had LDL-C lower than 4 mmol/L, 1890 (38.7%) had LDL-C between 4 and 6 mmol/L, 347 (7.1%) had LDL-C higher than 6 mmol/L, and 1833 (37.5%) were on current lipid-lowering treatment. After adjustment for age, gender, smoking, hypertension and diabetes, an increased LDL-C > 4 mmol/L was significantly associated with all cause mortality (hazard ratio (HR) 2.06; 95% confidence interval (CI) [1.42-3.00], p=0.001) and with CV mortality (HR 2.18; 95% CI [1.04-4.57], p=0.04). After adjustment for these classical risk factors and for lipid-lowering treatment, LDL-C remained significantly associated with an increasing risk of all cause mortality; with LDL-C < 4 mmol/L as a reference class, LDL-C levels between 4 and 6 mmol/L were associated with an increased all cause mortality (HR 1.72; 95% CI [1.17-2.54], p=0.006) as well as LDL-C > 6 mmol/L (HR 2.60; 95% CI [1.49-4.85], p=0.001). LDL-C levels higher than 4 mmol/L were significantly associated with all-cause and cardiovascular mortality in primary prevention.