Effects of soy isoflavones on serum lipids and lipoprotein (a) in peritoneal dialysis patients.

BACKGROUND AND AIM: Lipid abnormalities are common in peritoneal dialysis (PD) patients and no effective treatment to decrease serum lipoprotein (a) [Lp(a)] in dialysis patients is known so far. Therefore, this research was designed to investigate the effects of soy isoflavone supplement on serum lipids and Lp(a) in PD patients. METHODS & RESULTS: In this randomized, double-blind, placebo-controlled trial, 40 PD patients were randomly assigned to either the isoflavone or the placebo group. The patients in the isoflavone group received 100 mg soy isoflavone daily for 8 weeks, whereas the placebo group received corresponding placebos. At baseline and the end of the 8th week, 7 mL of blood was obtained from each patient and serum triglycerides, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and Lp(a) were measured. Serum Lp(a) reduced significantly up to 10% in the isoflavone group at the end of week 8 compared to baseline (P < 0.05), and the reduction was significant in comparison with the placebo group (P < 0.05). Serum HDL-C increased significantly up to 11.5% in the isoflavone group at the end of week 8 compared to baseline (P = 0.05), and the increment was significant in comparison with the placebo group (P < 0.05). There were no significant differences between the two groups in mean changes of serum triglycerides, total cholesterol, and LDL-C. CONCLUSIONS: This study indicates that daily administration of 100 mg soy isoflavones reduces serum Lp(a) and increases HDL-C concentration which are two determinants of cardiovascular disease in PD patients. CLINICALTRIALS.GOV: NCT03773029. REGISTRATION NUMBER AND DATE: NCT03773029 - 2018.

The dedicated "Lp(a) clinic": A concept whose time has arrived?

The emergence of pathophysiological, epidemiologic, and genetic data strongly supports the causality for lipoprotein(a) [Lp(a)] in cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). In parallel, novel Lp(a) lowering approaches have been developed that have re-invigorated clinical interest in Lp(a). Because Lp(a) is the most prevalent monogenetic lipid disorder globally, with prevalence of Lp(a) > 50 mg/dL estimated at >1.4 billion people, the rationale for diagnosing and managing Lp(a)-mediated risk is now stronger than ever. Patients with elevated Lp(a) are significantly under-diagnosed and the diagnosis is frequently made ad hoc rather than systematically. Elevated Lp(a) levels are associated with atherothrombotic risk and patients present with varied clinical phenotypes, ranging from stroke in pediatric age groups, to ST-segment elevation myocardial infarction in young males, to CAVD in elderly individuals. A new clinical care paradigm of a dedicated "Lp(a) Clinic" would serve to evaluate and manage such patients who have elevated Lp(a) as the pathophysiological etiology. Such a clinic would include multidisciplinary expertise in lipid metabolism, clinical cardiology, vascular medicine, valvular disease, thrombosis, and pediatric aspects of clinical care. This viewpoint argues for the rationale of an Lp(a) outpatient clinic where patients with elevated Lp(a) and their affected relatives can be referred, evaluated, managed and followed, to ultimately reduce Lp(a)-mediated CVD and CAVD risk.

Assessment of traditional and non-traditional risk factors for premature atherosclerosis in children with juvenile dermatomyositis and pediatric controls.

BACKGROUND: Children with juvenile dermatomyositis (JDM), the most common inflammatory myopathy of childhood, may be at increased risk of premature atherosclerosis given a host of traditional and non-traditional risk factors. The primary aim of this study was to determine the underlying frequency of premature atherosclerosis in children with JDM compared to pediatric controls using flow-mediated dilation as a measure of endothelial function. METHODS: Children and adolescents with and without JDM were evaluated for traditional atherosclerotic risk factors and assessment of endothelial function, using Endothelial Pulse Amplitude Testing (Endo-PAT). RESULTS: In this study, 75% of pediatric controls were of Black or Hispanic descent (compared to 55% in the JDM group) and 70% were found to live in a household with a medium income less than $50,000/year (compared to 45% in the JDM group). Among traditional atherogenic risk factors, lipoprotein A appeared to be different between controls and JDM patients (66 nmol/L and 16.5 nmol/L, respectively). Using a reactive hyperemia index (RHI) < 1.67 as evidence of endothelial dysfunction, 75% of controls were defined as having endothelial dysfunction compared to 50% in JDM group. When controlled for lipoprotein A as an atherogenic confounder, JDM patients were found to have a 41% increase in RHI, thus indicating less endothelial dysfunction compared to controls. CONCLUSIONS: In this study, we have shown that atherogenic risk factors are present in the pediatric population and may be associated with endothelial dysfunction, even at very young ages. Despite increasing concerns that children with rheumatologic disorders may be at increased risk of developing premature atherosclerosis, traditional and sociodemographic features may play a greater role in the ultimate development of cardiovascular disease.

Impact of flaxseed supplementation on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of randomized controlled trials.

The aim of the study was to investigate the impact of supplementation with flaxseed on plasma lipoprotein(a) [Lp(a)] levels through a systematic review and meta-analysis of eligible randomized placebo-controlled trials. PubMed, Scopus, Cochrane Library, and ISI Web of Science were searched for randomized controlled trials (RCTs) which have been published up to November 2019. RCTs that investigated the effect of flaxseed supplementation on plasma Lp(a) levels in adults were included for final analysis. The random effects model was used for calculating the overall effects. Meta-analysis of 7 selected RCTs with 629 individuals showed significant lowering effect of flaxseed supplementation on Lp(a) (MD -2.06 mg/dl; 95% CI: -3.846, -0.274, p = .024), without considerable heterogeneity between studies (p = .986, I2 = 0%). Subgroup analysis also revealed that longer duration only showed significant lowering effect of flaxseed supplementation on Lp(a). This meta-analysis has shown that flaxseed supplementation might significantly decrease plasma Lp(a) levels. Future well-designed and long-term clinical trials are required to confirm these results.

Increased cardiovascular risk associated with hyperlipoproteinemia (a) and the challenges of current and future therapeutic possibilities.

Population, genetic, and clinical studies demonstrated a causative and continuous, from other plasma lipoproteins independent relationship between elevated plasma lipoprotein (a) [Lp(a)] concentration and the development of cardiovascular disease (CVD), mainly those related to athe-rosclerotic CVD, and calcific aortic stenosis. Currently, a strong international consensus is still lacking regarding the single value which would be commonly used to define hyperlipoproteinemia (a). Its prevalence in the general population is estimated to be in the range of 10%-35% in accordance with the most commonly used threshold levels (>30 or >50 mg/dL). Since elevated Lp(a) can be of special importance in patients with some genetic disorders, as well as in individuals with otherwise controlled major risk factors, the identification and establishment of the proper therapeutic interventions that would lower Lp(a) levels and lead to CVD risk reduction could be very important. The majority of the classical lipid-lowering agents (statins, ezetimibe, and fibrates), as well as nutraceuticals (CoQ10 and garlic), appear to have no significant effect on its plasma levels, whereas for the drugs with the demonstrated Lp(a)-lowering effects (aspirin, niacin, and estrogens), their clinical efficacy in reducing cardiovascular (CV) events has not been unequivocally proven yet. Both Lp(a) apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors can reduce the plasma Lp(a) by approximately 20%-30% on average, in parallel with much larger reduction of low-density lipoprotein cholesterol (up to 70%), what puts us in a difficulty to conclude about the true contribution of lowered Lp(a) to the reduction of CV events. The most recent advancement in the field is the introduction of the novel apolipoprotein (a) [apo(a)] antisense oligonucleotide therapy targeting apo(a), which has already proven itself as being very effective in decreasing plasma Lp(a) (by even >90%), but should be further tested in clinical trials. The aim of this review was to present some of the most important accessible scientific data, as well as dilemmas related to the currently and potentially in the near future more widely available therapeutic options for the management of hyperlipoproteinemia (a).

Replacing Saturated Fats with Unsaturated Fats from Walnuts or Vegetable Oils Lowers Atherogenic Lipoprotein Classes Without Increasing Lipoprotein(a).

BACKGROUND: Walnuts have established lipid-/lipoprotein-lowering properties; however, their effect on lipoprotein subclasses has not been investigated. Furthermore, the mechanisms by which walnuts improve lipid/lipoprotein concentrations are incompletely understood. OBJECTIVES: We aimed to examine, as exploratory outcomes of this trial, the effect of replacing SFAs with unsaturated fats from walnuts or vegetable oils on lipoprotein subclasses, cholesterol efflux, and proprotein convertase subtilisin/kexin type 9 (PCSK9). METHODS: A randomized, crossover, controlled-feeding study was conducted in individuals at risk of cardiovascular disease (CVD) (n = 34; 62% men; mean ± SD age 44 ± 10 y; BMI: 30.1 ± 4.9 kg/m2). After a 2-wk run-in diet (12% SFAs, 7% PUFAs, 12% MUFAs), subjects consumed the following diets, in randomized order, for 6 wk: 1) walnut diet (WD) [57-99 g/d walnuts, 7% SFAs, 16% PUFAs [2.7% α-linolenic acid (ALA)], 9% MUFAs]; 2) walnut fatty acid-matched diet [7% SFAs, 16% PUFAs (2.6% ALA), 9% MUFAs]; and 3) oleic acid replaces ALA diet (ORAD) [7% SFAs, 14% PUFAs (0.4% ALA); 12% MUFAs] (all percentages listed are of total kilocalories ). Serum collected after the run-in (baseline) and each diet period was analyzed for lipoprotein classes and subclasses (vertical auto profile), cholesterol efflux, and PCSK9. Linear mixed models were used for data analysis. RESULTS: Compared with the ORAD, total cholesterol (mean ± SEM -8.9± 2.3 mg/dL; -5.1%; P < 0.001), non-HDL cholesterol (-7.4 ± 2.0 mg/dL; -5.4%; P = 0.001), and LDL cholesterol (-6.9 ± 1.9 mg/dL; -6.5%; P = 0.001) were lower after the WD; no other pairwise differences existed. There were no between-diet differences for HDL-cholesterol or LDL-cholesterol subclasses. Lipoprotein(a) [Lp(a)], cholesterol efflux, and PCSK9 were unchanged after the diets. CONCLUSIONS: In individuals at risk of CVD, replacement of SFAs with unsaturated fats from walnuts or vegetable oils improved lipid/lipoprotein classes, including LDL-cholesterol, non-HDL cholesterol, and total cholesterol, without an increase in Lp(a). These improvements were not explained by changes in cholesterol efflux capacity or PCSK9. This trial was registered at clinicaltrials.gov as NCT01235832.

Impact of phytosterol supplementation on plasma lipoprotein(a) and free fatty acid (FFA) concentrations: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Although some earlier studies have indicated the effect of phytosterol (PS) supplementation on serum lipoprotein(a) (Lp(a)) and free fatty acid (FFA) concentration, findings are still conflicting. We aimed to assess the impact of PS supplementation on serum Lp(a) and FFA concentration through a systematic review and meta-analysis of available RCTs. METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to 21 February 2019 in the following databases: PubMed, Scopus, and Cochrane. The choice of fixed- or random-effect model for analysis was determined according to the I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Pooling of 12 effect sizes from seven articles revealed a significant reduction of Lp(a) levels following PS supplementation (MD: -0.025 mg/dl, 95% CI: -0.045, -0.004, p = 0.017) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.599). Also, PS supplementation significantly lowered FFA (MD: -0.138 mg/dl, 95% CI: -0.195, -0.081, p = 0.000) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.911). The results for meta-regression and sensitivity analysis were not significant. CONCLUSION: The meta-analysis suggests that oral PS supplementation could cause a significant reduction in serum Lp(a) and FFA.

Lipoprotein(a) plasma levels, bone mineral density and risk of hip fracture: a post hoc analysis of the Women's Health Initiative, USA.

OBJECTIVES: Elevated Lipoprotein(a) (Lp[a]) is a well-known risk factor for cardiovascular disease. However, its roles in bone metabolism and fracture risk are unclear. We therefore investigated whether plasma Lp(a) levels were associated with bone mineral density (BMD) and incident hip fractures in a large cohort of postmenopausal women. DESIGN: Post hoc analysis of data from the Women's Health Initiative (WHI), USA. SETTING: 40 clinical centres in the USA. PARTICIPANTS: The current analytical cohort consisted of 9698 white, postmenopausal women enrolled in the WHI, a national prospective study investigating determinants of chronic diseases including heart disease, breast and colorectal cancers and osteoporotic fractures among postmenopausal women. Recruitment for WHI took place from 1 October 1993 to 31 December 1998. EXPOSURES: Plasma Lp(a) levels were measured at baseline. OUTCOME MEASURES: Incident hip fractures were ascertained annually and confirmed by medical records with follow-up through 29 August 2014. BMD at the femoral neck was measured by dual X-ray absorptiometry in a subset of participants at baseline. STATISTICAL ANALYSES: Cox proportional hazards and logistic regression models were used to evaluate associations of quartiles of plasma Lp(a) levels with hip fracture events and hip BMD T-score, respectively. RESULTS: During a mean follow-up of 13.8 years, 454 incident cases of hip fracture were observed. In analyses adjusting for confounding variables including age, body mass index, history of hysterectomy, smoking, physical activity, diabetes mellitus, general health status, cardiovascular disease, use of menopausal hormone therapy, use of bisphosphonates, calcitonin or selective-oestrogen receptor modulators, baseline dietary and supplemental calcium and vitamin D intake and history of fracture, no significant association of plasma Lp(a) levels with low hip BMD T-score or hip fracture risk was detected. CONCLUSIONS: These findings suggest that plasma Lp(a) levels are not related to hip BMD T-score or hip fracture events in postmenopausal women. TRIAL REGISTRATION NUMBER: NCT00000611; Post-results.

The effects of coenzyme Q10 supplementation on lipid profiles among patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic inflammation and increased oxidative stress significantly contribute in developing coronary artery disease (CAD). Hence, antioxidant supplementation might be an appropriate approach to decrease the incidence of CAD. This systematic review and meta-analysis was aimed to determine the effects of coenzyme Q10 (CoQ10) supplementation on lipid profile, as one of the major triggers for CAD, among patients diagnosed with coronary artery disease. METHODS: EMBASE, Scopus, PubMed, Cochrane Library, and Web of Science were searched for studies prior to May 20th, 2018. Cochrane Collaboration risk of bias tool was applied to assess the methodological quality of included trials. I-square and Q-tests were used to measure the existing heterogeneity across included studies. Considering heterogeneity among studies, fixed- or random-effect models were applied to pool standardized mean differences (SMD) as overall effect size. RESULTS: A total of eight trials (267 participants in the intervention group and 259 in placebo group) were included in the current meta-analysis. The findings showed that taking CoQ10 by patients with CAD significantly decreased total-cholesterol (SMD -1.07; 95% CI, - 1.94, - 0.21, P = 0.01) and increased HDL-cholesterol levels (SMD 1.30; 95% CI, 0.20, 2.41, P = 0.02). We found no significant effects of CoQ10 supplementation on LDL-cholesterol (SMD -0.37; 95% CI, - 0.87, 0.13, P = 0.14), lipoprotein (a) [Lp(a)] levels (SMD -1.12; 95% CI, - 2.84, 0.61, P = 0.20) and triglycerides levels (SMD 0.01; 95% CI, - 0.22, 0.24, P = 0.94). CONCLUSIONS: This meta-analysis demonstrated the promising effects of CoQ10 supplementation on lowering lipid levels among patients with CAD, though it did not affect triglycerides, LDL-cholesterol and Lp(a) levels.

Does coffee consumption alter plasma lipoprotein(a) concentrations? A systematic review.

Coffee consumption alters plasma lipid and cholesterol concentrations, however, its effects on lipoprotein(a) (Lp(a)) have received little study. The aim of this PRISMA compliant systematic review was to examine the role of coffee on serum Lp(a). This study was prospectively registered (PROSPERO 2015:CRD42015032335). PubMed, Scopus, Web of Science and Cochrane Central were searched from inception until 9th January 2016 to detect trials and epidemiological studies investigating the impact of coffee on serum Lp(a) concentrations in humans. We identified six relevant publications describing nine experimental trials of various designs. There were a total of 640 participants across all studies and experimental groups. In short-term controlled studies, consumption of coffee, or coffee diterpenes was associated with either a reduction in serum Lp(a) of ≤11 mg/dL (6 trials, 275 participants), or no effect (2 trials, 56 participants). Conversely, one cross-sectional study with 309 participants showed serum Lp(a) was elevated in chronic consumers of boiled coffee who had a median Lp(a) of 13.0 mg/dL (range 0-130) compared with consumers of filtered coffee who had median Lp(a) 7.9 mg/dL (range 0-144). The effect of coffee on Lp(a) is complex and may follow a biphasic time-course. The type of coffee and the method of preparation appear to be important to determining the effect on Lp(a).

Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis.

BACKGROUND: Soy supplementation has been shown to reduce total and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol. However, contradictory effects of soy isoflavone supplementation on lipoprotein(a) [Lp(a)] have been reported suggesting the need for a meta-analysis to be undertaken. OBJECTIVE: The aim of the study was to investigate the impact of supplementation with soy isoflavones on plasma Lp(a) levels through a systematic review and meta-analysis of eligible randomized placebo-controlled trials. METHODS: The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases (by March 26, 2017), and quality of studies was evaluated according to Cochrane criteria. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. RESULTS: Ten eligible studies comprising 11 treatment arms with 973 subjects were selected for the meta-analysis. Meta-analysis did not suggest any significant alteration of plasma Lp(a) levels after supplementation with soy isoflavones (standardized mean difference: 0.08, 95% confidence interval: -0.05, 0.20, P = .228). The effect size was robust in the leave-one-out sensitivity analysis. In meta-regression analysis, neither dose nor duration of supplementation with soy isoflavones was significantly associated with the effect size. CONCLUSION: This meta-analysis of the 10 available randomized placebo-controlled trials revealed no significant effect of soy isoflavones treatment on plasma Lp(a) concentrations.

Curcuminoids modify lipid profile in type 2 diabetes mellitus: A randomized controlled trial.

BACKGROUND: Type 2 diabetes (T2D) is an established risk factor for cardiovascular disease (CVD) and is associated with disturbed metabolism of lipids and lipoproteins. Curcuminoids are natural products with anti-diabetic and lipid-modifying actions but their efficacy in improving dyslipidemia in diabetic individuals has not been sufficiently studied. OBJECTIVE: To investigate the efficacy of supplementation with curcuminoids, plus piperine as an absorption enhancer, in improving serum lipids in patients with T2D. METHODS: In this 12-week randomized double-blind placebo-controlled trial, subjects with T2D (n=118) were assigned to curcuminoids (1000mg/day plus piperine 10mg/day) or placebo plus standard of care for T2D. Serum concentrations of lipids including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), lipoprotein(a) [Lp(a)], and non-HDL-C were determined at baseline and at the end of trial. RESULTS: Between-group comparison of change in the study parameters revealed significant reductions in serum levels of TC (-21.86±25.78 versus -17.06±41.51, respectively; p=0.023), non-HDL-C (-23.42±25.13 versus -16.84±41.42, respectively; p=0.014) and Lp(a) (-1.50±1.61 versus -0.34±1.73, respectively; p=0.001) and elevations in serum HDL-C levels (1.56±4.25 versus -0.22±4.62, respectively; p=0.048) in the curcuminoids group as compared with the placebo group (p<0.05). Serum TG and LDL-C changes did not show any significant difference between the study groups (p>0.05). CONCLUSION: Curcuminoids supplementation can reduce serum levels of atherogenic lipid indices including non-HDL-C and Lp(a). Therefore, curcuminoids supplementation could contribute to a reduced risk of cardiovascular events in dyslipidemic patients with T2D.

Association of polyunsaturated/saturated fatty acids to metabolic syndrome cardiovascular risk factors and lipoprotein (a) in hypertensive type 2 diabetic patients.

The interactions between fatty acids (FA) classes: polyunsaturated (PUFA-ω6, PUFA-ω3), saturated (SFA), EPA (eicosapentaenoic acid-ω3), DHA (docosahexaenoic-ω3) and cardiometabolic syndrome (CMS) clusters, thrombosis development and vascular inflammation are subtle. This relationship is mediated by insulin resistance (IR), endothelial dysfunction, platelet aggregation disorder and atherosclerosis. OBJECTIVES: We investigated whether PUFA/SFA - PUFA-ω6/PUFA-ω3 ratios and EPA + DHA can be associated with predictive atherothrombogenic biomarkers status in type 2 diabetes (T2D) patients with or without hypertension (HT). The study was conducted on 507 adult subjects (men and women) cohort (36-54 years), divided into 3 groups: T2D, diabetic-hypertensive (DH) and healthy group. Patients were phenotyped regarding their CMS profile using the NCEP/ATPIII criteria. Hypertension was defined as systolic (SBP) and diastolic (DBP) blood pressure ≥140/90 mmHg, respectively. Insulin resistance was assessed by Homa-IR model. Metabolic, atherothrombogenic and inflammatory parameters (CRP) were analyzed by various automata; Non-esterified fatty acids (NEFA) by microfluorimetry; PUFA-ω6 and PUFA-ω3 by gas phase chromatography. CMS clusters and IR were found in T2D and DH groups. Dyslipidemia was correlated with accretion NEFA levels. The PUFA/SFA ratio and PUFA-ω3 level are decreased, concomitant with an increase ApoB100/ApoA1 ratio and very high lipoprotein (a) concentrations. Raising the PUFA-ω6/PUFA-ω3 ratio and PUFA-ω6 levels were associated with the drop HDL-c/LDL-c ratio and EPA+DHA drastic depletion. In conclusion, fatty acids nutritional quality may be associated with atherothrombogenic biomarkers, mainly Lp (a), to prevent the thrombosis and an accident vascular risk in diabetic-hypertensive subjects.

Lipoprotein(a) concentrations in rheumatoid arthritis on biologic therapy: Results from the CARdiovascular in rheuMAtology study project.

BACKGROUND: Plasma concentrations of lipoprotein (a) (Lp(a)), a lipoprotein with atherogenic and thrombogenic properties, have a strong genetic basis, although high concentrations of Lp(a) have also been reported in the context of inflammation, as in rheumatoid arthritis (RA). Few studies evaluate the impact of biologic therapies (BT) on Lp(a) in RA, taking into account that with these new therapies a better control of inflammation is achieved. OBJECTIVE: The aim of the study was to evaluate the plasma concentrations of Lp(a) in Spanish RA patients on BT attending rheumatology outpatient clinics. METHODS: Baseline analysis of the CARdiovascular in rheuMAtology project, a 10-year prospective study, evaluating the risk of cardiovascular events in RA and other forms of inflammatory arthritis. RA patients were classified according to treatment: no biologic, anti-tumor necrosis factor, anti-interleukin-6 receptor tocilizumab (TCZ), and other biologic (rituximab or abatacept). A model of linear multivariate regression was built in which the dependent variable was Lp(a) concentration and the explanatory variable was BT. The model was adjusted for confounding factors. RESULTS: Seven hundred and seventy-five RA patients were analyzed. Plasma concentrations of total cholesterol and triglyceride were significantly higher in TCZ-treated patients. Nevertheless, no significant difference in the atherogenic index between TCZ-treated patients and patients without BT was found. After adjusting for confounding factors, patients with BT had lower concentrations of Lp(a) than those without BT; however, only TCZ-treated patients achieved statistically significant differences (ß: -0.303, 95% confidence interval: -0.558 to -0.047; P = .02). CONCLUSIONS: RA patients treated with TCZ show lower plasma concentrations of Lp(a) compared with patients without BT.

Lipid Biomarkers for Risk Assessment in Acute Coronary Syndromes.

PURPOSE OF REVIEW: The objective of this review was to summarize evidence gathered for the prognostic value of routine and novel blood lipids and lipoproteins measured in patients with acute coronary syndromes (ACS). RECENT FINDINGS: Data supports clear association with risk and actionable value for non-high-density lipoprotein (Non-HDL) cholesterol and plasma ceramides in a setting of ACS. The prognostic value and clinical actionability of apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] in ACS have not been thoroughly tested, while the data for omega-3 fatty acids and oxidized low-density lipoprotein (Ox-LDL) are either untested or more varied. Measuring basic lipids, which should include Non-HDL cholesterol, at the time of presentation for ACS is guideline mandated. Plasma ceramides also provide useful information to guide both treatment decisions and follow-up. Additional studies targeting ACS patients are necessary for apoB, Lp(a), omega-3 fatty acids, and Ox-LDL.

Practical Approaches for Whole-Genome Sequence Analysis of Heart- and Blood-Related Traits.

Whole-genome sequencing (WGS) allows for a comprehensive view of the sequence of the human genome. We present and apply integrated methodologic steps for interrogating WGS data to characterize the genetic architecture of 10 heart- and blood-related traits in a sample of 1,860 African Americans. In order to evaluate the contribution of regulatory and non-protein coding regions of the genome, we conducted aggregate tests of rare variation across the entire genomic landscape using a sliding window, complemented by an annotation-based assessment of the genome using predefined regulatory elements and within the first intron of all genes. These tests were performed treating all variants equally as well as with individual variants weighted by a measure of predicted functional consequence. Significant findings were assessed in 1,705 individuals of European ancestry. After these steps, we identified and replicated components of the genomic landscape significantly associated with heart- and blood-related traits. For two traits, lipoprotein(a) levels and neutrophil count, aggregate tests of low-frequency and rare variation were significantly associated across multiple motifs. For a third trait, cardiac troponin T, investigation of regulatory domains identified a locus on chromosome 9. These practical approaches for WGS analysis led to the identification of informative genomic regions and also showed that defined non-coding regions, such as first introns of genes and regulatory domains, are associated with important risk factor phenotypes. This study illustrates the tractable nature of WGS data and outlines an approach for characterizing the genetic architecture of complex traits.

Effects of Flaxseed Oil on Serum Lipids and Lipoproteins in Hemodialysis Patients: a Randomized Controlled Trial.

INTRODUCTION: One of the major risk factors for cardiovascular disease is lipid abnormalities among hemodialysis patients. The present study was designed to investigate the effects of flaxseed oil consumption on serum lipids and lipoproteins in hemodialysis patients. MATERIALS AND METHODS: In a randomized double-blinded controlled trial, 34 hemodialysis patients were assigned to either the flaxseed oil or the control group. The patients in the flaxseed oil group received 6 g/d of flaxseed oil for 8 weeks, whereas the control group received 6 g/d of medium chain triglycerides oil. At baseline and the end of week 8, blood samples were obtained after a 12- to 14-hour fast and serum concentrations of triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lipoprotein(a) were measured. RESULTS: Serum triglyceride concentration decreased significantly up to 23% in the flaxseed oil group at the end of week 8 compared to baseline, and the reduction was significant in comparison with the medium chain triglycerides oil group (P < .01). There were no significant differences between the two groups in the mean changes of serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and lipoprotein(a). CONCLUSIONS: This study indicates that daily consumption of 6 g of flaxseed oil reduces serum triglyceride concentration, which is a risk factor for cardiovascular disease in hemodialysis patients, whereas it has no effects on other lipid parameters, especially lipoprotein(a).

Effect of extended-release niacin on plasma lipoprotein(a) levels: A systematic review and meta-analysis of randomized placebo-controlled trials.

AIM: Lipoprotein(a) (Lp(a)) is a proatherogenic and prothrombotic lipoprotein. Our aim was to quantify the extended-release nicotinic acid Lp(a) reducing effect with a meta-analysis of the available randomized clinical trials. METHODS: A meta-analysis and random-effects meta-regression were performed on data pooled from 14 randomized placebo-controlled clinical trials published between 1998 and 2015, comprising 17 treatment arms, which included 9013 subjects, with 5362 in the niacin arm. RESULTS: The impact of ER niacin on plasma Lp(a) concentrations was reported in 17 treatment arms. Meta-analysis suggested a significant reduction of Lp(a) levels following ER niacin treatment (weighted mean difference - WMD: -22.90%, 95% CI: -27.32, -18.48, p<0.001). Results also remained similar when the meta-analysis was repeated with standardized mean difference as summary statistic (WMD: -0.66, 95% CI: -0.82, -0.50, p<0.001). When the studies were categorized according to the administered dose, there was a comparable effect between the subsets of studies with administered doses of <2000mg/day (WMD: -21.85%, 95% CI: -30.61, -13.10, p<0.001) and ≥2000mg/day (WMD: -23.21%, 95% CI: -28.41, -18.01, p<0.001). The results of the random-effects meta-regression did not suggest any significant association between the changes in plasma concentrations of Lp(a) with dose (slope: -0.0001; 95% CI: -0.01, 0.01; p=0.983), treatment duration (slope: -0.40; 95% CI: -0.97, 0.17; p=0.166), and percentage change in plasma HDL-C concentrations (slope: 0.44; 95% CI: -0.48, 1.36; p=0.350). CONCLUSION: In this meta-analysis of randomized placebo-controlled clinical trials, treatment with nicotinic acid was associated with a significant reduction in Lp(a) levels.

Effects of improved fat meat products consumption on emergent cardiovascular disease markers of male volunteers at cardiovascular risk.

High meat-product consumption has been related to cardiovascular disease (CVD). However, previous results suggest the benefits of consuming improved fat meat products on lipoprotein-cholesterol and anthropometric measurements. Present study aims to assess the effect of consuming different Pâté and Frankfurter formulations on emergent CVD biomarkers in male volunteers at increased CVD risk. Eighteen male volunteers with at least two CVD risk factors were enrolled in a sequentially controlled study where different pork-products were tested: reduced-fat (RF), omega-3-enriched-RF (n-3RF), and normal-fat (NF). Pork-products were consumed during 4-week periods separated by 4-week washout. The cardiometabolic index (CI), oxidized low density lipoproteins (oxLDL), apolipoproteins (Apo) A1 and B, homocysteine (tHcys), arylesterase (AE), C-reactive Protein (CRP), tumor necrotic factor-alpha (TNFα), and lipoprotein (a) (Lp(a)) were tested and some other related ratios calculated. AE, oxLDL and Lp(a), AE/HDLc, LDLc/Apo B, and AE/oxLDL rate of change were differently affected (P<0.01) by pork-products consumption. RF increased (P < 0.05) AE, AE/HDLc and AE/oxLDL ratios and decreased TNFα, tHcys; n-3RF increased (P < 0.001) AE, AE/HDLc and AE/oxLDL ratios and decreased (P < 0.05) Lp(a); while NF increased (P<0.05) oxLDL and Lp(a) levels. In conclusion, RF and n-3RF products affected positively the level of some emergent CVD markers. The high regular consumption of NF-products should be limited as significantly increased Lp(a) and oxLDL values. The high variability in response observed for some markers suggests the need to perform more studies to identify targets for RF- and n-3RF-products. Graphical Abstract Emergent CVD markers.

Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: A systematic review and meta-analysis.

Plasma lipoprotein(a) [Lp(a)] elevations are associated with increased cardiovascular risk. Coenzyme Q10 (CoQ10) is a member of the mitochondrial respiratory chain with a prominent role as a potent gene regulator. The Lp(a)-lowering efficacy of CoQ10 has been investigated in different clinical settings with contrasting results. A systematic literature search in Medline, SCOPUS, Web of Science and Google Scholar databases was conducted to identify controlled trials investigating the efficacy of CoQ10 supplementation on plasma Lp(a) levels. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in Lp(a) levels using a random-effects model. Random-effects meta-regression was performed to assess the effect of putative confounders on plasma Lp(a) levels. Seven randomized controlled trials with a total of 409 subjects (206 in the CoQ10 arm and 203 in the control arm) met the eligibility criteria. Overall, CoQ10 supplementation was paralleled by a slight but significant reduction of plasma Lp(a) levels (WMD: -3.54 mg/dL, 95% CI: -5.50, -1.58; p<0.001), this effect being more robust in those trials with higher baseline Lp(a) levels (slope: -0.44; 95% CI: -0.80, -0.08; p=0.018). Reduction of plasma Lp(a) levels was consistent across different CoQ10 doses, with an inverse association between administered CoQ10 dose and Lp(a) lowering (slope: 0.04; 95% CI: 0.01, 0.07; p=0.004). Neither total cholesterol and cholesterol subfractions, nor triglyceride levels were affected by CoQ10 supplementation. In conclusion, CoQ10 supplementation, in the tested range of doses, reduces plasma Lp(a) concentrations, particularly in patients with Lp(a)≥ 30 mg/dL. Other lipid indices were not altered by CoQ10 supplementation.