Atherogenic Particles Research Articles

A Comprehensive Review of Hass Avocado Clinical Trials, Observational Studies, and Biological Mechanisms.

This first comprehensive review of fresh Hass avocados includes 19 clinical trials, five observational studies, and biological mechanisms. We identified four primary avocado health effects: (1) reducing cardiovascular disease risk in healthy overweight or obese adults with dyslipidemia by lowering non-HDL-C profiles, triglycerides, LDL oxidation, small atherogenic LDL particles and promoting postprandial vascular endothelial health for better peripheral blood flow; (2) lowering the risk of being overweight or obese, supporting weight loss, and reducing visceral fat tissue in overweight or obese women; (3) improving cognitive function in older normal-weight adults and in young to middle age overweight or obese adults especially in frontal cortex executive function; and (4) stimulating improved colonic microbiota health in overweight or obese adults by promoting healthier microflora and fecal metabolites. We also identified a unique combination of four Hass avocado nutritional features that appear to be primarily responsible for these health effects: (1) a 6 to 1 unsaturated (rich in oleic acid) to saturated fat ratio similar to olive oil; (2) a source of multifunctional prebiotic and viscous fiber; (3) a relatively low energy density of 1.6 kcal/g (79% of edible Hass avocado weight consists of water and fiber with a creamy, smooth texture); and (4) its oleic acid and water emulsion increases carotenoid absorption from low-fat fruits and vegetables (e.g., salsa or salad) when consumed with avocados. They are also a good source of micronutrients and polyphenols, and are very low in sodium and available carbohydrates supporting secondary health and wellness benefits. Hass avocado health effects are best demonstrated when consumed in a healthy dietary plan such as the Mediterranean diet. More extensive and longer clinical trials are needed to further enhance our understanding of the Hass avocado’s health effects.

Abstract 13280: apoB-Containing Lipoproteins and Risk of Myocardial Infarction: Distinguishing Between Particle Concentration, Content, and Type

Background: Lipid management typically focuses on levels of LDL cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). Basic investigation and genetic studies, however, suggest that the atherogenic particle subpopulations (LDL & VLDL) are similarly important and that the number of particles is more important than their lipid content. Methods: We performed a prospective cohort analysis in two populations: 1) 389,529 primary prevention patients w/o lipid-lowering therapy from UK Biobank, and 2) 45,708 statin-treated patients w/ established atherosclerosis from the FOURIER and IMPROVE-IT trials. Incident MI was assessed over a median follow up of 11.1 yrs in UKBB and 3.6 yrs in the trials. Adjusted HRs were calculated to determine whether lipid content (non-HDL-C & TG) or particle type (using LDL-C concentration as a surrogate for LDL, and TG concentration as a surrogate for TG-rich lipoproteins) offer predictive value beyond atherogenic particle concentration (apoB). Results: In the primary prevention cohort, apoB, non-HDL-C, and TG each individually predicted incident MI. However, when assessed together, only apoB remained a significant predictor (adj HR per 1-SD = 1.28 [95%CI: 1.16,1.42], p<0.0001) ( Fig, A/B ). Similarly, only apoB remained a predictor of MI in the secondary prevention cohort ( Fig, C/D ). Adjusting for apoB, there was no relationship between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and the risk of MI (p=0.32, Fig, E ), implying that for a given concentration of apoB-containing lipoproteins, the relative proportion of particle subpopulations is not an independent predictor of risk. Conclusion: Risk for MI is best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). Therefore, therapeutic strategies should take into account lowering the overall concentration of all apoB-containing lipoproteins.

Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis

Lipid management typically focuses on levels of low-density lipoprotein cholesterol (LDL-C) and, to a lesser extent, triglycerides (TG). However, animal models and genetic studies suggest that the atherogenic particle subpopulations (LDL and very-low-density lipoprotein [VLDL]) are both important and that the number of particles is more predictive of cardiac events than their lipid content. To determine whether common measures of cholesterol concentration, TG concentration, or their ratio are associated with cardiovascular risk beyond the number of apolipoprotein B (apoB)-containing lipoproteins. This prospective cohort analysis included individuals from the population-based UK Biobank and from 2 large international clinical trials, FOURIER and IMPROVE-IT. The median (IQR) follow-up was 11.1 (10.4-11.8) years in UK Biobank and 2.5 (2.0-4.7) years in the clinical trials. Two populations were studied in this analysis: 389 529 individuals in the primary prevention group who were not taking lipid-lowering therapy and 40 430 patients with established atherosclerosis who were receiving statin treatment. ApoB, non-high-density lipoprotein cholesterol (HDL-C), LDL-C, and TG. The primary study outcome was incident myocardial infarction (MI). Of the 389 529 individuals in the primary prevention group, 224 097 (58%) were female, and the median (IQR) age was 56.0 (49.5-62.5) years. Of the 40 430 patients with established atherosclerosis, 9647 (24%) were female, and the median (IQR) age was 63 (56.2-69.0) years. In the primary prevention cohort, apoB, non-HDL-C, and TG each individually were associated with incident MI. However, when assessed together, only apoB was associated (adjusted hazard ratio [aHR] per 1 SD, 1.27; 95% CI, 1.15-1.40; P < .001). Similarly, only apoB was associated with MI in the secondary prevention cohort. Adjusting for apoB, there was no association between the ratio of TG to LDL-C (a surrogate for the ratio of TG-rich lipoproteins to LDL) and risk of MI, implying that for a given concentration of apoB-containing lipoproteins, the relative proportions of particle subpopulations may no longer be a predictor of risk. In this cohort study, risk of MI was best captured by the number of apoB-containing lipoproteins, independent from lipid content (cholesterol or TG) or type of lipoprotein (LDL or TG-rich). This suggests that apoB may be the primary driver of atherosclerosis and that lowering the concentration of all apoB-containing lipoproteins should be the focus of therapeutic strategies.

Lipoproteins and Cardiovascular Disease: An Update on the Clinical Significance of Atherogenic Small, Dense LDL and New Therapeutical Options.

Dyslipidemia is a potent risk factor for the genesis and progression of cardiovascular disease (CVD), and both the concentration and type of low-density lipoproteins (LDL) augment this association. The small, dense LDL (sdLDL) subfraction is the subtype which is most strongly predictive of atherosclerosis and cardiovascular events. In addition to the traditionally available lipid-lowering treatment options, certain novel therapies have been shown to favorably impact sdLDL, among them the antidiabetic class of agents known as glucagon-like peptide 1 receptor agonists (GLP1-RAs). These drugs seem to alter the pathophysiologic mechanisms responsible for the formation and accumulation of atherogenic lipoprotein particles, thus potentially reducing cardiovascular outcomes. They represent a uniquely targeted therapeutic approach to reduce cardiometabolic risk and warrant further study for their beneficial nonglycemic actions.

Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target.

Apolipoprotein (apo) B, the critical structural protein of the atherogenic lipoproteins, has two major isoforms: apoB48 and apoB100. ApoB48 is found in chylomicrons and chylomicron remnants with one apoB48 molecule per chylomicron particle. Similarly, a single apoB100 molecule is contained per particle of very-low-density lipoprotein (VLDL), intermediate density lipoprotein, LDL and lipoprotein(a). This unique one apoB per particle ratio makes plasma apoB concentration a direct measure of the number of circulating atherogenic lipoproteins. ApoB levels indicate the atherogenic particle concentration independent of the particle cholesterol content, which is variable. While LDL, the major cholesterol-carrying serum lipoprotein, is the primary therapeutic target for management and prevention of atherosclerotic cardiovascular disease, there is strong evidence that apoB is a more accurate indicator of cardiovascular risk than either total cholesterol or LDL cholesterol. This review examines multiple aspects of apoB structure and function, with a focus on the controversy over use of apoB as a therapeutic target in clinical practice. Ongoing coronary artery disease residual risk, despite lipid-lowering treatment, has left patients and clinicians with unsatisfactory options for monitoring cardiovascular health. At the present time, the substitution of apoB for LDL-C in cardiovascular disease prevention guidelines has been deemed unjustified, but discussions continue.

Association between apolipoprotein B and dietary fibers

Introduction Global awareness to the importance of natural fibers in vegetables and fruits are still generally very low. Indonesian people consume less fibers, which has been associated with the development of heart disease. Heart disease has been known as the leading cause of morbidity and mortality. Apolipoprotein B (ApoB) is a component of atherogenic particles that can be used as a marker for an increased risk of cardiovascular disease. Researches on apoB profile and its relationship with fiber intake has provided inconsistent results. This is an article review of the current literatures on the relationship between dietary fiber and serum apoB levels.&#x0D; Methods: This is an article review of the current literatures on the relationship between dietary fiber and apoB. We searched PubMed and Google Scholar using keyword “dietary fibers” and “ApoB” to capture meta-analyses, observational and experimental studies. A total of 97 publication and abstracts were screened for this review. After careful screening, nine studies were finally included.&#x0D; Results: Two studies did not find associations between dietary fiber and serum apoB, while other seven found the association. Dietary fiber has been reported to be involved in the metabolism of serum cholesterol and blood pressure; hence, the deficiency of dietary fiber intake is believed to contribute to the epidemic of cardiovascular diseases. Several factors including nutritional status, dietary diet pattern, age, gender, physical activity, and smoking habits might influence the relationship between dietary fiber and serum apoB.&#x0D; Conclusion: More studies are required in the future for better understanding on the effect of dietary fiber on the apoB; hence, the risk of cardiovascular diseases.

OxLDL-Induced Trained Immunity Is Dependent on Mitochondrial Metabolic Reprogramming.

Following brief exposure to endogenous atherogenic particles, such as oxidized low-density lipoprotein (oxLDL), monocytes/macrophages can adopt a long-term pro-inflammatory phenotype, which is called trained immunity. This mechanism might contribute to the chronic low-grade inflammation that characterizes atherosclerosis. In this study, we aim to elucidate immunometabolic pathways that drive oxLDL-induced trained immunity. Primary isolated human monocytes were exposed to oxLDL for 24 h, and after five days stimulated with LPS to measure the cytokine production capacity. RNA-sequencing revealed broad increases in genes enriched in mitochondrial pathways after 24 h of oxLDL exposure. Further omics profiling of oxLDL-trained macrophages via intracellular metabolomics showed an enrichment for tricarboxylic acid (TCA) cycle metabolites. Single cell analysis revealed that oxLDL-trained macrophages contain larger mitochondria, potentially likely linked to increased oxidative phosphorylation (OXPHOS) activity. Co-incubation with pharmacological blockers of OXPHOS inhibited oxLDL-induced trained immunity. The relevance of OXPHOS was confirmed in a cohort of 243 healthy subjects showing that genetic variation in genes coding for enzymes relevant to OXPHOS correlated with the capacity of monocytes to be trained with oxLDL. Interestingly, OXPHOS appears to play an important role in the increased cytokine hyperresponsiveness by oxLDL-trained macrophages. The TCA-cycle can also be fuelled by glutamine and free fatty acids, and pharmacological blockade of these pathways could prevent oxLDL-induced trained immunity. This study demonstrates that the mitochondria of oxLDL-trained macrophages undergo changes to their function and form with OXPHOS being an important mechanism for trained immunity, which could unveil novel pharmacological targets to prevent atherogenesis.

From the Editor’s Desk...

From the Editor’s Desk...

Abstract #1037562: Effect of Glucose Level in the Frequency of Discordance Apo B-Low Density Lipoproteins (LDL)

Background: Apo B determination lets to know the number of atherogenic particles and is a risk factor, probably as crucial as LDL determination. However, the effect of glucose level in the frequency of discordant results, low or average LDL with high Apo B, is still unknown in our city

A lipid lover's guide to novel therapeutics for lipid and cardiovascular risk reduction.

Lipids and lipoproteins are the target of many novel therapeutics and are an area with great potential for the prevention and treatment of cardiovascular disease (CVD). Reduction of low-density lipoprotein cholesterol has been the mainstay of reducing the burden of CVD, however, several other atherogenic particles have more recently come into the spotlight as potential avenues for primary and/or secondary prevention of CVD. These include triglycerides, high sensitivity C-reactive protein, apolipoprotein A, apolipoprotein C3 and lipoprotein(a). In this review, we showcase novel therapeutics to target lipid and cardiovascular risk reduction that are either in development or that have recently been approved for use. We discuss the mechanisms of action, data from clinical trials and expected effects of each therapy based on the current body of literature.

Apolipoprotein B: the Rosetta Stone of lipidology.

This review summarizes the evidence that apolipoprotein B (apoB) integrates the conventional lipid markers - total cholesterol, triglycerides, LDL-cholesterol, and non-HDL-cholesterol - into a single index that accurately and simply quantitates the atherogenic risk due to the apoB lipoprotein particles. Marked hypertriglyceridemia remains the essential signal for hyperchylomicronemia and potential pancreatitis. However, with the exception of Lp(a) and the abnormal cholesterol-enriched remnant particles that are the hallmark of type III hyperlipoproteinemia, recent evidence from discordance analyses and Mendelian randomization indicate that apoB integrates the risk due to the atherogenic lipoprotein particles because all LDL particles are, within the limits of our ability to measure any differences, equally atherogenic and all, except the largest VLDL particles are, within the limits of our ability to measure any differences, equally atherogenic. Measuring apoB as well as the conventional lipids is essential for accurate diagnosis. For almost all follow-up, however, apoB is all that need be measured. ApoB is the Rosetta Stone of lipidology because dyslipoproteinemia cannot be understood unless apoB is measured.

Postprandial Apolipoprotein B48 is Associated with Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis.

Objective: To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). Methods: We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (>p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. Results: Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8–12.1) vs. 12.1 (2.3–9,8); p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0–1.3)) and total ApoB (OR [95% CI], 1.12 [1.1–1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). Conclusion: Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.

The Impact of Dietary Glycemic Index and Glycemic Load on Postprandial Lipid Kinetics, Dyslipidemia and Cardiovascular Risk.

Many recent studies have acknowledged postprandial hypetriglyceridemia as a distinct risk factor for cardiovascular disease. This dysmetabolic state is the result of the hepatic overproduction of very low-density lipoproteins (VLDLs) and intestinal secretion of chylomicrons (CMs), which leads to highly atherogenic particles and endothelial inflammation. Postprandial lipid metabolism does not only depend on consumed fat but also on the other classes of nutrients that a meal contains. Various mechanisms through which carbohydrates exacerbate lipidemia have been identified, especially for fructose, which stimulates de novo lipogenesis. Glycemic index and glycemic load, despite their intrinsic limitations, have been used as markers of the postprandial glucose and insulin response, and their association with metabolic health and cardiovascular events has been extensively studied with contradictory results. This review aims to discuss the importance and pathogenesis of postprandial hypertriglyceridemia and its association with cardiovascular disease. Then, we describe the mechanisms through which carbohydrates influence lipidemia and, through a brief presentation of the available clinical studies on glycemic index/glycemic load, we discuss the association of these indices with atherogenic dyslipidemia and address possible concerns and implications for everyday practice.

Prevalence of Elevated Non-HDL Cholesterol among Patients with Diabetes in An Iranian Population

Background and Aims: Non-high density lipoprotein cholesterol (non- HDL-C), which reflects all cholesterol present in potentially atherogenic lipoprotein particles, might be a useful marker of atherosclerosis in diabetic subjects. In the present study, we evaluated the prevalence of high non-HDL-C in patients with dyslipidemia in diabetic and non-diabetic subjects following LDL-C assessment as the first goal of therapy. Materials and Methods: A data set of 2142 individuals was included in the study. All values of lipid profile were compared between non-diabetic and diabetic groups and the prevalence of dyslipidemia was evaluated in two groups. Results and Conclusions: According to the results, 48% of patients with diabetes achieved combined LDL-C ≤2.5 mmol/L and non-HDL ≤3.3 mmol/L targets, and 58.2% of diabetic patients achieved LDL-C goal while only 50.2% attained non-HDL-C goal. Also, the results indicated that non-HDL-C significantly heightened in patients with diabetes. Therefore, non-HDL-C needs to be calculated as a routine assessment in patients with diabetes.

LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a) <10 mg/dl] received pitavastatin calcium (4 mg/day) for 180 days in a single-phase unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids {LPC, lysophosphatidylinositol (LPI), lysoalkylphosphatidylcholine [LPC(O)]; 9, 0.2, and 0.14 mol per mole of apoB, respectively; all P < 0.001 vs. LDL1-4}, suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI, and LPC(O) contents (up to -52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5-3 mol per mole of apoB; 3-7 mmol per mole of PC) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.

Remnant lipoproteins: are they equal to or more atherogenic than LDL?

To critically appraise new insights into the biology of remnant lipoproteins and their putative role in the pathophysiology of atherosclerotic cardiovascular disease, and to compare the atherogenicity of remnant particles with that of low-density lipoproteins (LDL). New in-vivo stable isotope tracer studies of the kinetics of apoB48 and apoB100-containing lipoproteins in postprandial conditions have revealed that apoB48-containing very low-density lipoproteins (VLDL) accumulated markedly in hypertriglyceridemic patients. These intestinally-derived particles were cleared slowly, and represented up to 25% of circulating VLDL; as part of the remnant particle population, they may increase cardiovascular risk. Importantly, the PCSK9 inhibitor, evolocumab, was shown to reduce remnant levels (-29%) during the postprandial period in diabetic patients on statin therapy - an effect which may be additive to that of LDL-cholesterol reduction in conferring cardiovascular benefit. In recent Mendelian randomization studies, the effect of lowering triglyceride-rich lipoproteins or LDL-cholesterol translated to similar clinical benefit per unit of apoB. Finally, in randomized trials involving statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol levels were associated with coronary atheroma progression independently of LDL-cholesterol. Overall, data from observational studies in large cohorts, Mendelian randomization studies, meta-regression analyses, and post-hoc analyses of randomized trials are consistent with the contention that remnants are highly atherogenic particles and contribute to the atherosclerotic burden in an equivalent manner to that of LDL.

OR08-04 Differences in Advanced Lipoprotein Profile Between Rabson-Mendenhall Syndrome and Lipodystrophy

Insulin resistance (IR) is associated with metabolic dyslipidemia (high triglycerides [TG] and low HDL) and increased cardiovascular disease (CVD) risk. In obesity-associated IR, dyslipidemia is thought to be caused by increased insulin-mediated stimulation of hepatic lipogenesis, whereas IR in glucoregulatory pathways leads to hyperglycemia. This dichotomy in insulin signaling pathways is termed selective insulin resistance. Rare human conditions exist in which there is extreme, non-selective, IR impairing all insulin signaling pathways (e.g. mutations of the insulin receptor, INSR) or extreme IR affecting only selected intracellular insulin signaling pathways analogous to obesity (e.g. lipodystrophy). Lipodystrophy leads to very high TG, low HDL, and increased CVD, while INSR mutation leads to low TG and high HDL, with unknown CVD risk. We sought to further characterize the lipid phenotype and atherogenicity in these conditions in order to understand effects of different insulin signaling pathways on CVD risk.We studied 7 patients with INSR mutation (42% female; 5 homozygous; 2 heterozygous) and 21 with lipodystrophy (85% female; 5 generalized; 16 partial). Fasting lipoprotein profiles were assessed by NMR using the LP4 deconvolution algorithm. The major lipoprotein particle categories defined by this method are small, medium, and large HDL and LDL particles (HDLP and LDLP) and very small, small, medium, large, and very large TG rich lipoprotein particles (TRLP).Very small TRLP (median 189.6 [68.7, 315.0] vs 4.5 [0.00, 9.4], p=0.0001), small LDLP (mean 1425.0 ± 636.2 vs 612.8 ± 233.9, p=0.003), small HDLP (mean 14.0 ± 4.7 vs 9.0 ± 3.2, p=0.014) were more elevated in patients with lipodystrophy vs INSR mutation. This lipoprotein profile has been associated with increased atherosclerotic coronary artery disease. GlycA, a marker of inflammation was also more elevated in lipodystrophy vs INSR mutation (435.9 ± 107.2 vs 315.7 ± 74.4, p=0.01). Insulin resistance assessed by HOMA-IR was higher in patients with INSR mutation vs lipodystrophy (mean 93.5 ± 94.4 vs 15.6 ± 14.7, p=0. 00085).) Lipoprotein insulin resistance (LPIR), an index of IR based on lipoprotein particles, was lower in patients with INSR mutation (25.0 ± 19.0 vs 84.0 ± 9.0, p < 0.0001) despite their higher HOMA-IR.In conclusion, severe, selective insulin resistance in patients with lipodystrophy was associated with a more atherogenic lipoprotein particle profile and increased inflammation compared to severe, non-selective insulin resistance caused by INSR mutations. Patients with INSR mutations had a striking discrepancy between a glucose/insulin-based index of insulin resistance (HOMA-IR) and a lipid-based marker of insulin resistance (LPIR). These findings point toward a key role of selective insulin resistance in the development of an atherogenic lipid profile, which should lead to increased CVD risk.

Small dense low-density lipoprotein cholesterol is strongly associated with NIHSS score and intracranial arterial calcification in acute ischemic stroke subjects

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Small dense low-density lipoprotein cholesterol (sd-LDL-c) was independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether sd-LDL-c is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Serum sd-LDL-c levels and other biochemical parameters were analyzed. Admission NIHSS score and mRS score at discharge were collected. After 60-days 85 patients died during hospitalization and follow-up. Partial correlation analysis showed that serum sd-LDL-c levels were associated with admission NIHSS score and IAC score after adjusted age and gender. Logistic regression analysis showed that serum sd-LDL-c levels independently predicted NIHSS scores (β = 1.537, 95%CI: 0.134-2.878, p = 0.042) and IAC scores (β = 1.355, 95%CI: 0.319-2.446, p = 0.015). The average level of sd-LDL-c in patients who died was also significantly increased compared to survival patients (1.04 ± 0.59 vs 0.88 ± 0.44 mmol/L, p = 0.017). However, multivariate logistic regression analysis showed serum sd-LDL-c levels could not predict all-cause mortality and prognosis in AIS patients. Our study found that sd-LDL-c as a strong atherogenic lipid particle can independently predict admission NIHSS scores and the severity of cerebral artery calcification in AIS patients. However, its prognostic value in AIS patients still needs further study in the future.

Triglyceride-Rich Lipoprotein Cholesterol, Small Dense LDL Cholesterol, and Incident Cardiovascular Disease

BackgroundElevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populations are mostly limited to coronary heart disease. ObjectivesThe purpose of this study was to prospectively evaluate whether triglyceride-rich lipoprotein cholesterol (TRL-C) and small-dense low-density lipoprotein cholesterol (sdLDL-C) concentrations associate with composite and individual incident cardiovascular disease (CVD) outcomes including myocardial infarction (MI), ischemic stroke (IS), and peripheral artery disease (PAD). MethodsIn a prospective case-cohort study within the Women’s Health Study, TRL-C and sdLDL-C (mg/dl) were directly measured in baseline blood specimens of case subjects (n = 480) and the reference subcohort (n = 496). Risk associations were evaluated for total CVD (MI, IS, PAD, and CVD death), coronary and cerebrovascular disease (MI, IS, CVD death), and individual outcomes (MI, IS, and PAD). Models were adjusted for traditional risk factors, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein. ResultsThe risk of both composite outcomes significantly increased across quartiles of TRL-C and sdLDL-C. TRL-C was significantly associated with MI and PAD (MI hazard ratio [HR]Q4: 3.05 [95% confidence interval (CI): 1.46 to 6.39]; ptrend = 0.002; PAD HRQ4: 2.58 [95% CI: 1.18 to 5.63]; ptrend = 0.019), whereas sdLDL-C was significantly associated with MI alone (HRQ4: 3.71 [95% CI: 1.59 to 8.63]; ptrend < 0.001). Both markers weakly associated with IS. Association patterns were similar for continuous exposures and, for TRL-C, among subjects with low atherogenic particle concentrations (apolipoprotein B <100 mg/dl). ConclusionsTRL-C strongly associates with future MI and PAD events, whereas sdLDL-C strongly associates with MI alone. These findings signal that the cholesterol content of TRLs and sdLDL influence atherogenesis independently of low-density lipoprotein cholesterol, and high sensitivity C-reactive protein, with potentially different potency across vascular beds. (Women’s Health Study; NCT00000479)

Regulation of Apolipoprotein B by Natural Products and Nutraceuticals: A Comprehensive Review.

Cardiovascular Disease (CVD) is the most important and the number one cause of mortality in both developing and industrialized nations. The co-morbidities associated with CVD are observed from infancy to old age. Apolipoprotein B100 (Apo B) is the primary apolipoprotein and structural protein of all major atherogenic particles derived from the liver including Very-Low- Density Lipoproteins (VLDL), Intermediate-density Lipoprotein (IDL), and Low-density Lipoprotein (LDL) particles. It has been suggested that measurement of the Apo B concentration is a superior and more reliable index for the prediction of CVD risk than is the measurement of LDL-C. Nutraceuticals and medicinal plants have attracted significant attention as it pertains to the treatment of non-communicable diseases, particularly CVD, diabetes mellitus, hypertension, and Nonalcoholic Fatty Liver Disease (NAFLD). The effect of nutraceuticals and herbal products on CVD, as well as some of its risk factors such as dyslipidemia, have been investigated previously. However, to the best of our knowledge, the effect of these natural products, including herbal supplements and functional foods (e.g. fruits and vegetables as either dry materials, or their extracts) on Apo B has not yet been investigated. Therefore, the primary objective of this paper was to review the effect of bioactive natural compounds on plasma Apo B concentrations. It is concluded that, in general, medicinal plants and nutraceuticals can be used as complementary medicine to reduce plasma Apo B levels in a safe, accessible, and inexpensive manner in an attempt to prevent and treat CVD.