LDL Cholesterolemia Research Articles

Elevation in white blood cell count and development of hyper LDL cholesterolemia

To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03–1.62) for 3rd quartile group and 1.39 (1.10–1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.

Utilization of Small Dense Low-Density Lipoprotein Cholesterol Testing in Korean Patients Visiting Local Clinics and Hospitals.

Small dense low-density cholesterol (sdLDL) has been the focus of studies due to its potential as an independent risk factor for atherosclerotic cardiovascular diseases. We aimed to investigate the utilization of sdLDL testing by LDL particle size analysis and the prevalence of an sdLDL predominant phenotype in Korean adult patients by visiting local clinics and hospitals. Among 9222 Korean adults (4577 men and 4645 women) with a median age of 62.8 years (interquartile range, IQR 54.5 to 71.8 years) undergoing lipid profile testing using LDL particle size analysis, the prevalence of hypercholesterolemia (total cholesterol ≥ 240 mg/dL), hypo HDL cholesterolemia (<40 mg/dL), and hyper LDL cholesterolemia (≥160 mg/dL) was 7.8%, 12.9%, and 0.5%, respectively. The overall prevalence of the sdLDL predominant non-A phenotype of LDL was 46.8% of study subjects. Approximately 32.8% of the study subjects possessed lipid test results that did not exhibit increased risk except for sdLDL (only the sdLDL predominant non-A phenotype as a risk factor). In Korea, sdLDL testing was utilized in patients whose LDL cholesterol level was not increased. Future studies to clarify the clinical significance of this test in the Korean population are needed.

Gradual increasing dyslipidemia in treatment-naive male patients with human immunodeficiency virus and treated with tenofovir plus lamivudine plus efavirenz for 3\xa0years

IntroductionSince the development of antiretroviral therapy (ART) with TDF plus 3TC plus EFV, this specific regimen has not been studied enough with long-term lipid and uric acid monitoring.MethodsA prospective follow-up cohort study was performed. Sixty-one treatment-naive male patients with human immunodeficiency virus (HIV) were divided into three groups based on their baseline CD4+ cell count (26, 12, and 23 patients in the < 200, 200 to 350, and > 350 groups, respectively). The lipid and purine metabolism parameters of the patients over 144 weeks were analyzed.ResultWithin 144 weeks, TG, LDL-c, TC and HDL-c gradually increased, especially TC and HDL-c (P = 0.001, 0.000, respectively). Moreover, the percentages of hyper-cholesterolemia, hyper LDL cholesterolemia, hyper-triglyceridemia and low HDL cholesterolemia also gradually increased, especially low HDL cholesterolemia significantly increased (P = 0.0007). The lower the baseline CD4+ cell counts were, the higher the TG levels and the lower the TC, LDL-c and HDL-c levels were. But there was significant difference of only baseline LDL-c levels between the three groups (P = 0.0457). No significant difference of the UA level and the percentages of hyperuricemia was found between the different follow-up time point groups or between the three CD4+ cell counts groups (all P > 0.05). The risk factors for dyslipidemia included age, anthropometric parameters and follow-up weeks, and for hyperuricemia was virus load.ConclusionsGradual increasing dyslipidemia was found in male patients with human immunodeficiency virus primarily treated with tenofovir plus lamivudine plus efavirenz for 3 years. There-fore lipid metabolism parameters should be closely monitored during long-term ART with the TDF plus 3TC plus EFV regimen.

Effect of EcoR1 Polymorphism of the Apoprotein B100 Gene (Apo B 4154G&amp;gt;A) on Serum Lipid Profile in ART-Naive PLHIV

Many people living with HIV (PLHIV) have dyslipidemia and influence of genetic predisposing factors are suspected. Some apolipoprotein genes polymorphisms are recognized as susceptibility factors, especially EcoR1 polymorphism of Apo B100 gene, main atherogenic lipid metabolizing apoprotein. The objective was to investigate the link between EcoR1 polymorphism of Apo B100 gene (Apo B 4154G>A) and the occurrence of dyslipidemia in ART-naive PLHIV. We did a cross-sectional study which included 32 HIV-negative controls and 23 PLHIV, above 18 years old, with at least one serum lipid and apoprotein disorder. Polymorphism testing was performed by PCR-RFLP and allele distribution study was performed using Hardy Weinberg equilibrium. As results, we found that the subjects were predominantly young males in both groups. BMI was higher in PLHIV. There were lipid disorders common to both PLHIV and HIV- subjects. However, PLHIV were distinguished by hypoapoproteinemia Apo A1 and HDL hypocholesterolemia. The 3 possible genotypes of EcoR1 polymorphism were found in both groups with a predominance of the mutant genotype in PLHIV (85.7% vs 14.3%). Also, the mutant allele frequency was higher in PLHIV (27.1% vs 6.2%). Regardless of HIV status, the mutant allele was more frequent in people under 40 years old, women and people with high BMI. In PLHIV, Hardy Weinberg equilibrium was deviated in all subgroups with the mutant allele frequency higher than 10%. In the overall population, the mutant allele was more frequent in subjects with increased TG, LDL-C, Apo B100, Lp (a), and CT/HDL atherogenicity index and those with normal total cholesterol, decreased HDL-C and Apo A1. Taking into account HIV status, the mutant allele found was more frequent in PLHIV (14% to 32% versus 2% to 21%). In these PLHIV, the mutant allele was more frequent especially in cases of total hypercholesterolemia (28.1%), normal LDL cholesterolemia (26.7%), HDL hypocholesterolemia (27.3%), hypoapoproteinemia A1 (32.1%), hyperapoproteinemia B100 (28.1%), hyperapoproteinemia Lp (a) (28.1%), high atherogenicity indexes (23.7%). In conclusion, the distribution of EcoR1 polymorphism alleles at position 4154 in exon 29 of ApoB100 gene was not random in PLHIV people. The carrying of mutant allele was more frequent in PLHIV and associated to increased atherogenic apolipoproteins and decreased atherosclerotic protective apolipoproteins (Apo A1 and HDL-C). The link between EcoR1 and ART must be investigates.

Efficacy and Safety of Volanesorsen (ISIS 304801): the Evidence from Phase 2 and 3 Clinical Trials.

To revise the clinical evidence supporting the use of volanesorsen as new lipid-lowering drug and to assess the efficacy and safety of volanesorsen (ISIS 304801) through a systematic review of the literature and a meta-analysis of the available phase 2 and phase 3 clinical studies. The meta-analysis of three clinical studies comprising 11 arms (N= l 156 subjects, with 95 in the active-treated arm and 61 in the control one) shows that volanesorsen significantly affects plasma levels of triglycerides (TG) [MD = - 67.90%, 95%CI = - 85.32, - 50.48, P< 0.001], high-density lipoprotein cholesterol (HDL-C) [MD = 40.06%, 95%CI: 32.79, 47.34, P< 0.001], very-low-density lipoprotein cholesterol (VLDL-C) [MD = - 72.90%, 95%CI = - 82.73, - 63.07, P <0.001], apolipoprotein B (Apo B) [MD = 8%, 95%CI = 2.17, 13.84, P= 0.007], Apo B-48 [MD = - 64.63, 95%CI = - 105.37, - 23.88, P= 0.002], ApoCIII [MD = - 74.83%, 95%CI = - 85.93, - 63.73, P< 0.001], and VLDL ApoCIII [MD = - 83.69%, 95%CI = - 94.08, - 73.29, P< 0.001], without significant impact on LDL-C [MD = 47.01%, 95%CI = - 1.31, 95.33, P= 0.057] levels. Treatment with volanesorsen was associated with an higher risk of injection site reaction (OR = 32.89, 95%CI = 7.97,135,74, P< 0.001) and with an increased risk of upper respiratory tract infections (OR = 10.58, 95%CI = 1.23, 90.93, P< 0.05) when compared to placebo. Volanesorsen has a relevant impact on plasma TG and related parameters without affecting LDL cholesterolemia and is associated with an acceptable safety profile.

The Prevalence of Single and Multiple Thyroid Nodules and Its Association with Metabolic Diseases in Chinese: A Cross-Sectional Study.

Purpose The present study aims to investigate the prevalence of single and multiple thyroid nodules and its association with metabolic diseases in subjects who participated in the heath examination in China. Methods This is a cross-sectional study. The participants who attend the physical examination at the Health Management Center of Southwest Hospital, Army Military Medical University, between January 2014 and December 2018, were included. Thyroid nodules were diagnosed by thyroid ultrasound. Multivariable logistic regression was used to investigate the association between metabolic diseases and nodular thyroid disease. Results A total of 9,146 subjects were included in this study; of them, 2,961 were diagnosed with thyroid nodules, with a prevalence of 32.4%. The prevalence in women was significantly higher than that in men (45.2% vs 26.0%; χ2 = 339.56, P < 0.001), and the prevalence was gradually increased with age (Z = 20.05, P < 0.001), and the prevalence was gradually increased with age (Conclusions The prevalence of thyroid nodules was relatively high. Age, female gender, and diabetes are positively associated with nodular thyroid disease. High LDL cholesterolemia is more likely to be associated with multiple thyroid sarcoidosis.

Nutraceutical approach for the management of cardiovascular risk \u2013 a combination containing the probiotic Bifidobacterium longum BB536 and red yeast rice extract: results from a randomized, double-blind, placebo-controlled study

BackgroundProbiotics incorporated into dairy products have been shown to reduce total (TC) and LDL cholesterolemia (LDL-C) in subjects with moderate hypercholesterolemia. More specifically, probiotics with high biliary salt hydrolase activity, e.g. Bifidobacterium longum BB536, may decrease TC and LDL-C by lowering intestinal cholesterol reabsorption and, combined with other nutraceuticals, may be useful to manage hypercholesterolemia in subjects with low cardiovascular (CV) risk. This study was conducted to evaluate the efficacy and safety of a nutraceutical combination containing Bifidobacterium longum BB536, red yeast rice (RYR) extract (10 mg/day monacolin K), niacin, coenzyme Q10 (Lactoflorene Colesterolo®). The end-points were changes of lipid CV risk markers (LDL-C, TC, non-HDL-cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB), HDL-C, apolipoprotein AI (ApoAI), lipoprotein(a) (Lp(a), proprotein convertase subtilisin/kexin type 9 (PCSK9)), and of markers of cholesterol synthesis/absorption.MethodsA 12-week randomized, parallel, double-blind, placebo-controlled study. Thirty-three subjects (18–70 years) in primary CV prevention and low CV risk (SCORE: 0–1% in 24 and 2–4% in 9 subjects; LDL-C: 130–200 mg/dL) were randomly allocated to either nutraceutical (N = 16) or placebo (N = 17).ResultsTwelve-week treatment with the nutraceutical combination, compared to placebo, significantly reduced TC (− 16.7%), LDL-C (− 25.7%), non-HDL-C (− 24%) (all p < 0.0001), apoB (− 17%, p = 0.003). TG, HDL-C, apoAI, Lp(a), PCSK9 were unchanged. Lathosterol:TC ratio was significantly reduced by the nutraceutical combination, while campesterol:TC ratio and sitosterol:TC ratio did not change, suggesting reduction of synthesis without increased absorption of cholesterol. No adverse effects and a 97% compliance were observed.ConclusionsA 12-week treatment with a nutraceutical combination containing the probiotic Bifidobacterium longum BB536 and RYR extract significantly improved the atherogenic lipid profile and was well tolerated by low CV risk subjects.Trial registrationNCT02689934.

Association between Dietary Pattern and Incidence of Cholesterolemia in Korean Adults: The Korean Genome and Epidemiology Study.

We examined the gender-specific association between dietary pattern and risk of developing cholesterolemia based on the data from the Korean Genome and Epidemiology study. A total of 7515 individuals aged 40–69 years participated in this study between 2005 and 2010. Dietary intake was assessed by a semi-quantitative food frequency questionnaire. Low HDL cholesterolemia was defined as a plasma HDL-C level <1.04 mmol/L (men) or <1.30 mmol/L (women), and high LDL cholesterolemia was defined as a plasma LDL-C level >3.37 mmol/L. Multivariate Cox proportional hazard models were used to examine the risk for incident cholesterolemia according to dietary pattern score. Four dietary patterns were derived by gender using factor analysis: prudent pattern; coffee, fat, and sweet pattern; whole grain (men) or white rice and noodle (women) pattern; and westernized pattern. A prudent pattern was inversely associated with risk of low HDL cholesterolemia in both men (Hazard ratio (HR) = 0.76, p for trend = 0.0098) and women (HR = 0.78, p for trend = 0.0324), whereas the coffee, fat, and sweet pattern was positively associated with risk of high LDL cholesterolemia in men only (HR = 1.26, p for trend = 0.0254) after adjustment for potential confounders. Specific dietary patterns were associated with risk of developing cholesterolemia suggesting gender differences.

Consumption of Added Sugars and Lipid Profiles in Korean Population from a Cohort Study

Objectives: The purpose of the study was to examine the relationship between added sugar consumption and dyslipidemia. Methods: Final study subjects consisted of 18,713 participants after the exclusion of participants with dyslipidemia or under lipid lowering medications at baseline. Added sugar levels were categorized into tertiles [men: Low <8.0 g, Middle: 8.0-21.9 g, High ≥22.0 g; women: Low <6.0 g, Middle 6.0-14.9 g, High ≥15.0 g]. Dyslipidemia was analyzed based on two of the most recent guidelines identified from the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and the 2009 Korean Society of Lipidology and Atherosclerosis (KSLA). We used Kaplan-Meier and Cox proportional hazard models to estimate the hazard ratio (HR) with 95% confidence interval (CI) of dyslipidemia. Results: High added sugar was associated with hypercholesteremia (HR, 1.22; 95% CI, 1.06-1.40), high LDL cholesterolemia (1.29; 1.13-1.48), and low HDL cholesterolemia (1.26; 1.10-1.44) based on the KSLA Standard in men. In women, the high added sugar was only related to the risk for hypercholesteremia (1.26; 1.07-1.49) based on the KSLA Standard. A similar trend was shown in both men and women with application of NCEP-ATP III standard. Conclusion: In this study, an increase in added sugar consumption was associated with an increased risk of dyslipidemia in men. Additional studies assessing the association between cardiovascular and other diseases should be conducted in the future.

MTP inhibitor for treating severe LDL cholesterolemia

“mtp inhibitors have prominent effects in lowering LDL cholesterol levels in patients with homozygous familial hypercholesterolemia.”

LDL Cholesterolemia as a Novel Risk Factor for Radiographic Progression of Rheumatoid Arthritis: A Single-Center Prospective Study

Dyslipidemia has been implicated in various musculoskeletal diseases, including rheumatoid arthritis (RA). Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. We prospectively investigated the association of cumulative lipid levels with radiographic progression of RA. RA patients (n = 242) underwent plasma cholesterol assessment at four visits. Disease activity parameters and X-rays of the hands and feet were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by time-integrated values. Serum leptin and adiponectin concentrations were determined by ELISA. When patients were divided into three groups according to time-integrated lipid levels, as expected, patients with LDL cholesterol and/or triglyceride levels in the third tertile had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over two years was observed in patients with higher LDL cholesterol and/or triglyceride levels. In multivariate analysis, time-integrated LDL cholesterol was independently associated with radiographic progression. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both LDL cholesterol and triglyceride levels in the third tertile. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels but not in those without. These results demonstrate that LDL cholesterolemia is a novel serum marker that can be used to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients.

SAT0042 Low-Density Lipoprotein Cholesterolemia as a Novel Risk Factor for Radiographic Progression of Rheumatoid Arthritis: A Single Centered Prospective Study

BackgroundDyslipidemia has been implicated in a variety of musculoskeletal disease including rheumatoid arthritis (RA). Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines.ObjectivesWe prospectively...

The effect of aerobic exercise intensity on attenuation of postprandial lipemia is dependent on apolipoprotein E genotype

ObjectiveTo investigate the effect of aerobic exercise intensity on postprandial lipemia according to allelic variants of the apolipoprotein E gene. MethodsThree groups of 10 healthy men each were formed based genotyping of the APOE gene, rested or performed 500 Kcal tests in a random sequence separated by a minimum 48 h interval, as follows: (a) no exercise (control), (b) intense intermittent exercise, (c) moderate continuous exercise. Each test series was completed 30-min before ingestion of a high-fat meal (1 g fat/kg). Venous blood was collected before and at 1, 2, 3 and 4 h after the high-fat meal. Postprandial lipemia was assessed using the area under the curve approach as well as the kinetic profile of mean lipid variables. Statistical significance was adopted at P ≤ 0.05 level. ResultsThe main results show that, in the moderate continuous exercise, total postprandial cholesterolemia was higher in ɛ4 than in ɛ2 carriers, whereas under intense intermittent exercise, total and LDL cholesterolemia were higher in ɛ4 than in ɛ2 and ɛ3 carriers. There was no difference in the lipemic profile of the subjects across APOE genotypes at baseline. ConclusionModerate and intense exercise were effective in attenuating PPL in both ɛ2 and ɛ3 subjects, with ɛ2 subjects being more susceptible to the lipid lowering effect of moderate training than ɛ3 subjects. Carriers of the ɛ4 allele, however, showed no attenuation of postprandial lipemia.

Pathogenetic role of hypercholesterolemia in a novel preclinical model of vascular injury in pigs

Objective Most strategies against intimal hyperplasia developed in several preclinical models failed in terms of clinical application, often due to a discrepancy between animal and human disease. The aim of this study was to setup for the first time a porcine vascular injury model with mild hypercholesterolemia able to significantly increase the degree of stenosis resembling human settings and investigate the pathogenetic role of hypercholesterolemia on protective genes and inflammatory response affecting matrix deposition and cell proliferation. Methods Pigs were fed with standard (SD, n = 7) or high-cholesterol diet (HCD, n = 7) for 120 days. A balloon angioplasty injury was induced in carotid arteries. Results Hypercholesterolemia induced a mild significant increase of total and LDL cholesterolemia. HCD significantly increased the degree of stenosis (48 ± 3% vs. 13 ± 4%, p = 0.001), with induction of cell proliferation, matrix deposition, TGF-β1/TGFβRII and MMP2 expression and reduction of collagen. The reduced expression of the protective gene heme oxygenase-1 and inducible-nitric oxide synthase in HCD was associated to a systemic inflammation with a significant increase in circulating leukocytes, serum IFN-γ and TNF-α and a local inflammatory response with an increase of CD3-positive cell infiltrates. There was a significant correlation between CD3 infiltrates and the degree of stenosis. Conclusion We developed for the first time a porcine vascular injury model with mild hypercholesterolemia able to significantly increase the degree of stenosis and showed the pathogenetic role of hypercholesterolemia on intimal hyperplasia. New therapeutical strategies to prevent restenosis can be tested in this preclinical hypercholesterolemic model resembling human disease.

EVIDENCE-BASED MEDICINE CRITERIA APPLIED TO HYPOLIPIDEMIC AND ANTIHYPERTENSIVE DRUG TRIALS: IS DRUG EFFICACY ALWAYS THE SAME?

Changes in cardiovascular risk after lipid lowering medications are generally expressed as relative risk reduction (RRR). Comparison of the eight major studies published in this last decade indicates that the RRRs ranged from a minimum (19%) for the LRC Study with cholestyramine, to maximal values of 34–37% for studies such as the HHS, 4S and AFCAPS/TexCAPS. These RRRs were barely related to the drugs’ effects on major lipid parameters, e.g. LDL cholesterol. Instead, by using the absolute risk reduction (ARRs), easily calculated by subtracting the percentage end points for the drug treated from these values of the placebo group in all studies, a wide range of values was found, also adding to the series a non pharmacological study such as the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial. Calculated ARRs were directly correlated to the baseline cardiovascular (CV) risk in all studies, thus allowing an easy prediction of a drug's effect in the selected population. Drugs with different mechanisms (statins, fibrates and resins) all fitted into this correlation nomogram. These findings clearly indicate that the CV effects of lipid changes, such as LDL cholesterol and triglyceride reduction or HDL rises, are in the same direction, and can be well predicted. The similar, almost identical behavior of drugs affecting LDL cholesterolemia to a different degree or not at all, indicates that novel approaches should be sought to improve risk reduction and that individual therapy should be ideally pursued, rather than a ‘one drug’ approach.