Atherogenic Lipid Markers Research Articles

Toxicity and phyto-bioactive constituent of Ficus aurea L. leaf extract: A trado-medicinal herb used in southeastern Nigeria

BackgroundThe intrinsic adroitness of medicinal plants as a therapy for several maladies is well-documented in African Herbal Pharmacopeia. Leaves of Ficus aurea L. ( Moraceae) are commonly used in folkloric medicine in southeastern Nigeria and other areas of the world to treat malaria, dermatitis, circulatory and intestinal parasitic health abnormalities. ObjectiveThe aim of the study was to explore the phytochemical composition and potential toxicity of the ethanolic leaf extract of F. aurea L. (herein afterwards referred to as ELEFA) in albino rats of both sexes. MethodsGas chromatography mass spectrometry (GC–MS) was performed to analyze the chemical constituents of F. aurea. In the acute toxicity study, a single oral dose of up to 5000 mg/kg ELEFA was administered. For the sub-acute toxicity study, rats were randomly assigned to individual cages to eschew copulation. Male groups (A2-A4) and female groups (B2-B4) were administered varying doses of ELEFA (250, 500, 750 mg/kg) for 28 days, while control groups A1 and B1 received 1 mL/kg of distilled water. Standard analytical procedures were utilized to evaluate the biochemical and haematological profiles, as well as liver and kidney histopathology. ResultsThe GC–MS analysis identified 13 phyto-compounds, six of which possess known bioactive and pharmacological properties. These bioactive compounds include gamma-dodecalactone, n-hexadecanoic acid, methyl stearate, 9,12-octadecadienoic acid, oleic acid, octadecanoic acid. In the acute toxicity, no death was recorded within 24 h following oral administration of ELEFA. Remarkably, haematological and renal biomarkers remained unaltered post-ELEFA administration. However, elevated levels of serum aspartate and alanine transaminases were detected in ELEFA-treated groups, indicating potential hepatotoxicity. A reduction in atherogenic lipid markers and a dose-dependent elevation in antioxidant concentrations were observed, suggesting a nuanced impact on oxidative stress. ConclusionThe study emphasized caution regarding higher ELEFA doses, highlighting potential hepatotoxic effects evident in liver histopathology at 500 mg/kg and 750 mg/kg. We recommend the prudent use of lower ELEFA doses for therapeutic purposes to mitigate potential adverse effects.

Association Between Adequate Serum 25(OH)D Levels and Atherogenic Dyslipidemia in Young Adults.

This study aimed to investigate the association between vitamin D deficiency and novel biomarkers of atherogenic dyslipidemia among young adults. A total of 976 young adults were recruited between 2011 and 2019. Their serum 25(OH)D levels were measured, and lipid profile markers, including low-density lipoprotein cholesterol (LDL-C), low-density lipoprotein triglyceride (LDL-TG), and small-dense low-density lipoprotein cholesterol (sdLDL-C), were assessed as novel biomarkers of atherogenic dyslipidemia. Multivariable linear regression was used to analyze the association between vitamin D levels and lipid profile markers. Odds ratios were calculated to assess the risk of atherogenic dyslipidemia in individuals with serum 25(OH)D levels below 30 ng/mL compared to those with levels above 30 ng/mL. Structural equation modeling (SEM) was employed to explore potential mediation pathways. The study found a significant association between vitamin D levels and lower levels of LDL-C, LDL-TG, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides, and total cholesterol. Individuals with serum 25(OH)D levels below 30 ng/mL exhibited significantly higher odds ratios for developing atherogenic dyslipidemia in a dose-response pattern compared to those with vitamin D levels above 30 ng/mL. Notably, structural equation modeling (SEM) analysis revealed that vitamin D did not affect atherogenic lipid markers through the mediation of insulin resistance markers or high-sensitivity C-reactive protein. This study provides evidence of an association between vitamin D deficiency and atherogenic dyslipidemia in young adults. It further highlights that individuals with serum 25(OH)D levels below 30 ng/mL are at a significantly higher risk of developing atherogenic dyslipidemia in a dose-response manner compared to those with higher vitamin D levels. These findings underscore the potential role of vitamin D in dyslipidemia management and emphasize the importance of maintaining sufficient vitamin D levels for cardiovascular health in young adults.

Adenosine Triphosphate Citrate Lyase and Fatty Acid Synthesis Inhibition

Adenosine triphosphate citrate lyase (ACLY) is a key regulatory enzyme of glucose metabolism, cholesterol and fatty acid synthesis, and the inflammatory cascade. Bempedoic acid, an ACLY inhibitor, significantly reduces atherogenic lipid markers, including low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and apolipoprotein B. Additional effects of ACLY inhibition include antitumor growth; reduction of triglycerides and proinflammatory molecules such as high-sensitivity C-reactive protein; less insulin resistance; reduction of hepatic lipogenesis; and weight loss. While numerous ACLY inhibitors have been identified, most of the clinical data have focused on bempedoic acid. The Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) program was a series of phase 3 clinical trials that evaluated its effects on lipid parameters and safety, leading to US Food and Drug Administration approval in 2020. CLEAR Outcomes was a phase 3, double-blind, randomized, placebo-controlled trial in individuals with a history of statin intolerance, serum LDL-C level of 100 mg/dL or higher, and a history of, or at high risk for, cardiovascular disease. Bempedoic acid modestly reduced the primary 4-way cardiovascular composite end point as well as the individual components of myocardial infarction and coronary revascularization but did not reduce stroke, cardiovascular death, or all-cause mortality. Rates of gout and cholelithiasis were higher with bempedoic acid, and small increases in serum creatinine, uric acid, and hepatic-enzyme levels were also observed. ACLY inhibition with bempedoic acid has been established as a safe and effective therapy in high-risk patients who require further LDL-C lowering, particularly for those with a history of statin intolerance. The recently published CLEAR Outcomes trial revealed modest reductions in cardiovascular events with bempedoic acid, proportional to its LDL-C lowering, in high-risk individuals with statin intolerance and LDL-C levels of 100 mg/dL or higher. The additional effects of ACLY inhibition have prompted a more thorough search for novel ACLY inhibitors for conditions such as cancer, hypertriglyceridemia, chronic inflammation, type 2 diabetes, fatty liver disease, obesity, and metabolic syndrome. Similarly, therapies that reduce fatty acid synthesis are being explored for their use in cardiometabolic conditions.

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis

BackgroundBempedoic acid is a novel non-statin drug that was developed to treat hyperlipidemia in combination with other lipid-lowering drugs in those patients who need additional lipid lowering. Objectives(1) To investigate the lipid efficacy of bempedoic acid; (2) to analyze the anti-inflammatory effects of bempedoic acid estimated through high sensitivity C-reactive protein (hsCRP). MethodsWe performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and hsCRP with a minimum of 4 weeks of follow-up. The primary endpoint was defined as the percentage change in lipids and hsCRP levels measured from baseline to follow-up, comparing groups of subjects on bempedoic acid versus placebo. ResultsSeven eligible trials of bempedoic acid (3892 patients) were included. The bempedoic acid therapy was associated with a significant reduction in LDL-C levels [−20.3% (CI 95% −23.5 to −17.1)]; I2=43%]. Similarly, a significant percentage reduction in the apolipoprotein B levels [−14.3% (CI 95% −16.4 to −12.1)]; p<0.05; I2=46%], non-HDL-C levels [−15.5% (CI 95% −18.1 to −13.0)]; p<0.05; I2=53%] and hsCRP [−23.4% (CI 95% −32.6 to −14.2)]; p<0.05; I2=69%] was demonstrated with the bempedoic acid use. The sensitivity analysis showed that the results were robust. ConclusionOur data suggests that the use of bempedoic acid significantly reduces the levels of all atherogenic lipid markers, including LDL-C, non-HDL-C and apolipoprotein B. Furthermore, considering hsCRP levels, the drug produces an anti-inflammatory effect.

Effect of Bempedoic Acid on atherogenic lipids and inflammation: A meta-analysis

BackgroundBempedoic acid is a novel non-statin drug that was developed to treat hyperlipidemia in combination with other lipid-lowering drugs in those patients who need additional lipid lowering. Objectives(1) To investigate the lipid efficacy of bempedoic acid; (2) to analyze the anti-inflammatory effects of bempedoic acid estimated through high sensitivity C-reactive protein (hsCRP). MethodsWe performed a meta-analysis including randomized trials of bempedoic acid therapy, reporting low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and hsCRP with a minimum of 4 weeks of follow-up. The primary endpoint was defined as the percentage change in lipids and hsCRP levels measured from baseline to follow-up, comparing groups of subjects on bempedoic acid versus placebo. ResultsSeven eligible trials of bempedoic acid (3892 patients) were included. The bempedoic acid therapy was associated with a significant reduction in LDL-C levels [−20.3% (CI 95% −23.5 to −17.1)]; I2=43%]. Similarly, a significant percentage reduction in the apolipoprotein B levels [−14.3% (CI 95% −16.4 to −12.1)]; p<0.05; I2=46%], non-HDL-C levels [−15.5% (CI 95% −18.1 to −13.0)]; p<0.05; I2=53%] and hsCRP [−23.4% (CI 95% −32.6 to −14.2)]; p<0.05; I2=69%] was demonstrated with the bempedoic acid use. The sensitivity analysis showed that the results were robust. ConclusionOur data suggests that the use of bempedoic acid significantly reduces the levels of all atherogenic lipid markers, including LDL-C, non-HDL-C and apolipoprotein B. Furthermore, considering hsCRP levels, the drug produces an anti-inflammatory effect.

Tolerance of Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) Inhibitors in Patients With Self-Reported Statin Intolerance

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to lower atherogenic lipid markers in patients with statin intolerance; however, external validity of these findings is unclear in patients with self-reported statin intolerance. Objective: The objective of this study was to describe the tolerability of evolocumab and alirocumab in patients with self-reported statin intolerance. Secondary objectives were to describe their efficacy and obtainability. Methods: A retrospective chart review was completed and included adult patients with self-reported statin intolerance who were prescribed a PCSK9 inhibitor. Patient-reported side effects, laboratory values, and insurance information were collected for assessment of study objectives. Results: During the study period, 55 patients were prescribed PCSK9 inhibitor, 42 started therapy, and 34 had at least 1 follow-up visit. While myalgias occurred in 14.7% (n = 5) of patients, flu-like symptoms in 11.8% (n = 4), and fatigue in 2.9% (n = 1), only 5.9% (n = 2) of prescriptions for PCSK9 inhibitors were discontinued. Low-density lipoprotein cholesterol (LDL-C) was reduced 48.7% (95% confidence interval [CI]: -1.7%-99.1%), and 20 (58.8%) patients achieved a ≥50% reduction in LDL-C. Regarding obtainability, of the 57 prescriptions written, 77.2% (n = 44) required prior authorization and 5.3% (n = 3) were denied by insurance. Conclusion: PCSK9 inhibitors were well tolerated in patients with self-reported statin intolerance.

Effect of soy on metabolic syndrome and cardiovascular risk factors: a randomized controlled trial.

Cardiovascular diseases are currently the commonest cause of death worldwide. Different strategies for their primary prevention have been planned, taking into account the main known risk factors, which include an atherogenic lipid profile and visceral fat excess. The study was designed as a randomized, parallel, single-center study with a nutritional intervention duration of 12weeks. Whole soy foods corresponding to 30g/day soy protein were given in substitution of animal foods containing the same protein amount. Soy nutritional intervention resulted in a reduction in the number of MetS features in 13/26 subjects. Moreover, in the soy group we observed a significant improvement of median percentage changes for body weight (-1.5%) and BMI (-1.5%), as well as for atherogenic lipid markers, namely TC (-4.85%), LDL-C (-5.25%), non-HDL-C (-7.14%) and apoB (-14.8%). Since the majority of the studied variables were strongly correlated, three factors were identified which explained the majority (52%) of the total variance in the whole data set. Among them, factor 1, which loaded lipid and adipose variables, explained the 22% of total variance, showing a statistically significant difference between treatment arms (p=0.002). The inclusion of whole soy foods (corresponding to 30g/day protein) in a lipid-lowering diet significantly improved a relevant set of biomarkers associated with cardiovascular risk.

Age and Cardiovascular Risk Attributable to Apolipoprotein B, Low-Density Lipoprotein Cholesterol or Non-High-Density Lipoprotein Cholesterol.

BackgroundHigher concentrations of the apolipoprotein B (apoB) lipoproteins increase the risk of cardiovascular disease. However, whether the risk associated with apoB lipoproteins varies with age has not been well examined.Methods and ResultsWe determined the associations for total cholesterol, low‐density lipoprotein (LDL)‐cholesterol (LDL‐C), non‐high‐density lipoprotein‐cholesterol (non‐HDL‐C), apoB, apolipoprotein A‐I (apoA‐I), and HDL‐cholesterol (HDL‐C) with myocardial infarction at different ages in 11 760 controls and 8998 myocardial infarction cases of the INTERHEART Study. Logistic regression was used to compute the odds ratio of myocardial infarction for 1 SD change in each lipid marker by decade from <40 to >70 years of age. Except for those >70, plasma levels of total cholesterol, LDL‐C, and non‐HDL‐C and apoB were greater in cases than controls. However, the average levels of these markers decreased significantly as age increased. By contrast, levels of apoA‐I and HDL‐C were significantly greater in controls than cases but increased significantly as age increased. The cardiovascular risk associated with the atherogenic lipid markers differed at different ages. Most notably, there was a significant decline in the odds ratio for total cholesterol, LDL‐C, and non‐HDL‐C, and apoB with increases in age whereas the odds ratios associated with apoA‐I and HDL‐C were consistent across the age groups.ConclusionsThese data indicate that the risk of cardiovascular events associated with apoB particles is greater in younger compared to older individuals. This finding is consistent with greater relative benefit from LDL‐lowering therapy in younger compared to older individuals and so argues for therapy in younger individuals with elevated lipids.

Impact of lipid markers and high-sensitivity C-reactive protein on the value of the 99th percentile upper reference limit for high-sensitivity cardiac troponin I

Objectivesi) To assess the relationship between lipid markers and high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin I (hs-cTnI) in the reference population, and ii) to evaluate the impact of lipid markers and hs-CRP on the 99th percentile upper reference limit (URL) for hs-cTnI. Methods531 questionnaire-identified presumably healthy individuals were enrolled in a single-center, cross-sectional study. Surrogate biomarkers for diabetes, myocardial and renal dysfunction were used to refine the healthy cohort (n=408). Lipid profile, total cholesterol:high-density lipoprotein cholesterol (HDL-C) ratio, non-HDL-C, apolipoprotein AI (apoAI), apolipoprotein B (apoB), apoB:apoAI ratio, lipoprotein(a), small dense low-density lipoprotein cholesterol (LDL-C) and hs-CRP were determined. ResultsIndividuals with detectable vs. non-detectable hs-cTnI concentrations more often showed elevated LDL-C (60% vs. 46%; p=0.002), apoB (73% vs. 61%; p=0.008), apoB:apoAI ratio (53% vs. 40%; p=0.005) and lipoprotein(a) (15% vs. 7%; p=0.015). The apoB:apoAI ratio and to a lesser extent other lipid markers, but not hs-CRP, were positively associated with hs-cTnI concentration in univariate and multivariate analyses. Exclusion of individuals with elevated apoB:apoAI ratio or apoB, but not hs-CRP, lowered the 99th percentile URL in the healthy cohort respectively by 12.9% (6.2 vs. 5.4ng/L) and 14.5% (6.2 vs. 5.3ng/L). The corresponding reduction for both lipid biomarkers in the presumably healthy population was 24.0% (7.5 vs. 5.7ng/L). ConclusionOur study demonstrates that atherogenic lipid markers, particularly apoB:apoAI ratio or apoB, influence the 99th percentile URL for hs-cTnI.

The Role of Metformin Response in Lipid Metabolism in Patients with Recent-Onset Type 2 Diabetes: HbA1c Level as a Criterion for Designating Patients as Responders or Nonresponders to Metformin.

BackgroundIn this study, we investigated whether response to metformin, the most frequently drug for diabetes treatment, influences the therapeutic effects of antilipidemic medication in newly diagnosed patients with type 2 diabetes mellitus (T2DM).MethodsA total of 150 patients with T2DM were classified into two groups following 3 months of metformin therapy (1000 mg twice daily): responders (patients showing ≥1% reduction in HbA1c from baseline) and nonresponders (patients showing <1% reduction in HbA1c from baseline). The patients received atorvastatin 20 mg, gemfibrozil 300 mg, or atorvastatin 20 mg and gemfibrozil 300 mg daily.Principal FindingsHbA1c and fasting glucose levels were significantly different between baseline and 3 months among responders receiving atorvastatin; however, these differences were not statistically significant in nonresponders. Atherogenic ratios of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LDL-C/HDL-C; p = 0.002), total cholesterol to HDL-C (TC/HDL-C; p<0.001) and AIP (the atherogenic index of plasma; p = 0.004) decreased significantly in responders receiving atorvastatin than in nonresponders. Moreover, responders receiving atorvastatin showed a significant increase in HDL-C levels but nonresponders receiving atorvastatin did not (p = 0.007). The multivariate model identified a significant association between metformin response (as the independent variable) and TG, TC, HDL-C and LDL-C (dependent variables; Wilk's λ = 0.927, p = 0.036).ConclusionsMetformin response affects therapeutic outcomes of atorvastatin on atherogenic lipid markers in patients newly diagnosed with T2DM. Metformin has a greater impact on BMI in responders of metformin compared to nonresponders. Adoption of better therapeutic strategies for reducing atherogenic lipid markers may be necessary for metformin nonresponders.

The association of HDL-apoCIII with coronary heart disease and the effect of statin treatment on it.

BackgroundApolipoprotein CIII (apoCIII) is considered to impair the anti-atherogenic effect of high density lipoprotein (HDL) in coronary heart disease (CHD) patients, and apoCIII content in HDL (HDL-apoCIII) predicts CHD more accurately. However, the relationship between HDL-apoCIII and CHD, and the effect of statin treatment on HDL-apoCIII are still unclear. The aims of the study are to establish the association of HDL-apoCIII with CHD, and investigate the effect of statin treatment on HDL-apoCIII in CHD patients.MethodsWe conducted a hospital-based observational study. Totally 80 non-CHD patients and 120 CHD patients without statin treatment were previously enrolled in this study. All the CHD patients received statin treatment, and 63 of them were followed after 3 months of regular statin treatment. HDL sample of each patient was isolated by density gradient ultracentrifugation from fasting venous plasma, and HDL-apoCIII of each patient was measured by ELISA method.ResultsHDL-apoCIII was significantly higher in CHD patients than non-CHD patients (p < 0.05), and it was still an independent predictor of CHD after adjusting for other factors. Total plasma apoCIII, especially HDL-apoCIII was significantly elevated after statin treatment in CHD patients, whereas total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and apolipoprotein B (apoB) were decreased significantly (p < 0.05). Compared with CHD patients without diabetes mellitus (DM), the effect of statin treatment on apoCIII markers was minor in CHD patients with DM. And HDL-apoCIII correlated with plasma TG significantly in non-CHD and CHD patients (p < 0.05), but the correlation in CHD patients did not exist after statin treatment (p > 0.05).ConclusionsHDL-apoCIII has a significant and positive association with CHD. Although conventional atherogenic lipid markers have a significantly decrease in CHD patients after statin treatment, HDL-apoCIII has a further elevation at the same time.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0129-8) contains supplementary material, which is available to authorized users.

Atherogenic lipid markers and testosterone levels in Nigerian men with prostate disorders

Atherogenic lipid markers and testosterone levels in Nigerian men with prostate disorders

Association of triglyceride-rich lipoproteins-related markers and low-density lipoprotein heterogeneity with cardiovascular risk: Effectiveness of polyacrylamide-gel electrophoresis as a method of determining low-density lipoprotein particle size

BackgroundDespite well-controlled low-density lipoprotein cholesterol (LDL-C), hypertriglyceridemia is an independent predictor of coronary events. We investigated the risk of atherosclerotic cardiovascular disease through examining the relation between triglyceride (TG) metabolism and LDL-heterogeneity as assessed by polyacrylamide-gel electrophoresis (PAGE). Methods and resultsEstimated LDL-particle size [relative LDL migration (LDL-Rm value)] measured by PAGE with the LipoPhor system (Joko, Tokyo, Japan) was evaluated in 645 consecutive patients with one additional risk factor for atherosclerotic cardiovascular disease.Multivariate regression analysis after adjustments for traditional risk factors revealed an elevated triglyceride-rich lipoproteins (TRLs)-related markers [TG, remnant-like particle cholesterol (RLP-C), very LDL (VLDL) fraction, apolipoprotein (apo) C-II, and apo C-III] level to be an independent predictor of smaller-size LDL-particle size, both in the overall population, and in a subset of patients with serum LDL-C <100mg/dL. Even among the patients with LDL-C levels <100mg/dL, the serum levels of atherogenic lipid markers in those with a LDL-Rm value ≥0.40, suggesting the presence of large amounts of small-dense LDL and upper limit (mean+2 standard deviation) in this population, were significantly higher than in those with a LDL-Rm value <0.40. Moreover, the serum levels of TRLs-related markers showed high accurate area under the receiver-operating characteristic curve (TG, 0.896; RLP-C, 0.875; VLDL fraction, 0.803; apo C-II, 0.778; and apo C-III, 0.804, respectively) in terms of evaluation of the indicators of LDL-Rm value ≥0.40. ConclusionTo further reduce the risk of atherosclerotic cardiovascular disease, it may be of particular importance to pay attention not only to the quantitative change in the serum LDL-C, but also TG-metabolism associated with LDL-heterogeneity. Combined evaluation of TRLs-related markers and LDL-Rm value may be useful for assessing the risk of atherosclerotic cardiovascular disease.

Impact of diet, physical activity, lipid status and glycoregulation in estimation of score (systematic coronary risk evaluation) for ten years in postmenopausal women.

The incidence of cardiovascular diseases (CVD) in women, although lower than in men, increases dramatically after the menopause. Diabetes mellitus is a more powerful predictor of CHD risk and prognosis in women than in men. The aim of this study was to promote diet and physical activity (PA) regimen in order to decrease coronary risk in next years in postmenopausal women with impaired glucose tolerance. Methodological approach of this research is to compare data gathered trough prospective and retrospective analysis of anamnestic data, clinical research, diagnostic tests and biochemical parameters of 100 examinees, regarding the glycoregulation, lipid status, body mass indexes, incidence of hypertension, uric acid and fibrinogen level. The SCORE (Systematic Coronary Risk Evaluation) assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal CVD events over a ten-year period. It was documented that the then year risk of fatal CVD exerted a shift toward the lower percent value in postmenopausal women after proposed diet/PA regimen. In pre-menopausal women the estimated ten year risk of fatal CVD by SCORE was shifted toward the level below 1%. The risk of 15% and above was not documented after diet/physical activity regimen. The prevalence of the atherogenic lipid markers at the beginning and the end of the assay decreased for all investigated lipid parameters in the group of pre-menopausal women what was more than in postmenopausal ones. Presented data indicate that dietary regimen and physical activity are crucial factors in CVD prevention throughout menopause and beyond. Behavioral changes aimed at decreasing food intake and increasing energy expenditure, should be implemented in pre-menopausal period of life.