Atherogenic Risk Research Articles

Unveiling the Cardioprotective Power: Liquid Chromatography–Mass Spectrometry (LC–MS)-Analyzed Neolamarckia cadamba (Roxb.) Bosser Leaf Ethanolic Extract against Myocardial Infarction in Rats and In Silico Support Analysis

Neolamarckia cadamba (Roxb.) Bosser, a member of the Rubiaceae family, is a botanical species with recognized therapeutic properties. It is commonly used in traditional medicine to treat cardiac ailments and other disorders. However, the precise active constituents and the potential mechanisms by which they manage cardiovascular disorders remain unclear. Therefore, this study aimed to ascertain the bioactive components and investigate their underlying mechanisms of action. N. cadamba is used to treat cardiovascular disorders using the integrated metabolomic methodology. An HPLC-QTOF-MS/MS analysis determined the potential chemicals in the N. cadamba leaf ethanol extract (NCEE). A thorough investigation of the NCEE samples used in this study led to the identification of 32 phytoconstituents. Of the 32 compounds, 19 obeyed Lipinski’s rule of five (RO5). A molecular docking study directed towards HMG-CoA reductase used 19 molecules. The reference drug atorvastatin indicated a binding energy of −3.9 kcal/mol, while the other substances, Cinchonain Ib and Dukunolide B, revealed binding energies of −5.7 and −5.3 kcal/mol, respectively. Both phytocompounds showed no toxicity and exhibited favorable pharmacokinetic properties. In vivo study results concluded that treatment with NCEE significantly reduced the cardiac myocardial infarction (MI) marker CK-MB and atherogenic risk indices, such as the atherogenic index plasma (AIP), cardiac risk ratio (CRR), and atherogenic coefficient (AC) in isoproterenol-induced MI rats. In MI rats, NCEE therapy significantly improved the antioxidant system of the heart tissue, as evidenced by the increased levels of GSH and SOD, lower levels of the oxidative stress marker MDA, and significantly decreased HMG-CoA activity. Additionally, electrocardiogram (ECG) signals from rats treated with NCEE resembled those treated with traditional atorvastatin to treat myocardial infarction. This study used H&E staining to show that administering NCEE before treatment reduced cardiac myocyte degeneration in rats with myocardial infarction, increased the presence of intact nuclei, and increased myocardial fiber strength. The potential cardioprotective effect observed in myocardial infarction (MI) rats treated with NCEE can be extrapolated from computational data to be caused by Cinchonain Ib.

Advanced Lipoproteins and Lipidomic Profile in Plasma Determined by Nuclear Magnetic Resonance Before and After Bariatric Surgery.

Obesity is related to cardiovascular risk factors (CVRF) such as dyslipidemia, diabetes, and hypertension, which increase mortality. Basic lipid determinations could underestimate the true atherogenic risk of patients and the impact of bariatric surgery. The objective of the study is to demonstrate the change in the advanced molecular profile of lipoproteins determined by nuclear magnetic resonance spectroscopy in plasma after bariatric surgery, thus reducing the risk of cardiovascular disease. Descriptive, observational, and prospective study in obese patients undergoing bariatric surgery. Advanced lipid profile was analyzed in plasma from the immediate preoperative period and at the 18th postoperative month by sending samples and performing plasma magnetic resonance spectroscopy in the BiosferTreslab® laboratory. Fifty-two patients were included. Average age of 46.3years; 63.46% were women, 36.54% men. The average BMI was 43.57; the abdominal perimeter 133.50cm; 32.6% were diabetics under medical treatment, 44.23% hypertensive, and 19.23% smokers; 86.53% of the patients presented alterations in at least one of the analytical parameters in the lipid study. Twenty-nine (55.7%) underwent banded gastric bypass (PGB), 19.23% underwent GBP, and 17.31% vertical gastrectomy. The rest were revision surgeries, two BPG-A and two biliopancreatic diversions after GV. All patients presented some improvement in advanced molecular profile of lipoproteins. Twenty percent of the patients normalized all the parameters. Bariatric surgery improves advanced molecular profile of lipoproteins, decreasing CVRF. Analysis of the characteristics of lipoprotein particles by NMR spectrometry is optimal for studying lipoprotein metabolism in patients undergoing bariatric surgery.

Ministernotomy for aortic valve replacement. Results in the diabetic patient

Introduction: aortic valve stenosis (AS), emerges as a new epidemic due to the aging population.Published data relate diabetes mellitus to risk factors involved in the pathogenesis of atherosclerosis. Objectives: to describe the results of aortic valve replacement by ministernotomy in diabetic patients. Methods: an analytical prospective cohort study was carried out on patients with aortic stenosis and diabetes mellitus treated at the Abel Santamaría Hospital and the Hermanos Ameijeiras Hospital from August 2016 to December 2021, the sample included 16 patients. Clinical and postoperative variables were used. Results: 66,7 % of the patients with aortic stenosis had a history of diabetes mellitus. Of these diabetics, 68,8 % were type 2 and only 31,2 % were type 1. Several post-surgical complications were listed and respiratory infections predominated with 12,5 %. Conclusions: Dyslipidemias and diabetes constitute atherogenic risk factors associated with aortic stenosis. Type 1 diabetes is the most frequently associated with aortic stenosis. The predominant symptoms independent of the type of diabetes were dyspnea and angina, and the predominant post-surgical complication was respiratory infections.

High Atherogenic Risk in Ketosis-Prone Type 2 Diabetic Individuals with Ketosis Episodes: A Cross-Sectional Study.

Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS. A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters. The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (β = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (β = -0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients. Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.

Sex Differences in the Atherogenic Risk Index in Healthy Mexican Population and Its Relationship with Anthropometric and Psychological Factors.

Dyslipidemia is a risk factor for cardiovascular disease and mortality; however, the association of this variable with a wide range of personal and psychological variables has not been researched. Therefore, the aim of this study was to compare lipid levels and anthropometric measures between sexes and to determine the association between personal and psychological variables with the atherogenic risk index (ARI). An adult population which auto-reported as healthy was invited to participate via social media and in person. They filled out a questionnaire with personal and psychological variables; in addition, the body mass index (BMI) and waist-to-hip ratio (WHR) were measured, and a blood sample was obtained to determine serum lipids. A total of 172 participants were included, from which 92 (53.49%) were women; both sexes were comparable in age and most sociodemographic values. Men showed significantly higher levels of total cholesterol, LDL cholesterol, triglycerides, ARI, and lower levels of HDL cholesterol. The men also showed higher values of WHR than the women. In the bivariate analysis, ARI showed the highest correlation with WHR (r = 0.664) in the men and with BMI (r = 0.619) in the women. In the multivariate analysis, the quality of food intake was negatively correlated with ARI in the global and women's samples, and the psychological variables of assertiveness and positive relations with others were negatively correlated with ARI in women, while purpose in life was negatively correlated with ARI in men. In conclusion, the higher levels of serum lipids and ARI in men can be explained by the higher values of WHR in this sex. Behavioral and psychological variables could be protective factors for high ARI.

Maternal Supraphysiological Hypercholesterolemia Is Accompanied by Shifts in the Composition and Anti-Atherogenic Functions of Maternal HDL along with Maternal Cardiovascular Risk Markers at Term of Pregnancy.

Maternal physiological hypercholesterolemia (MPH) occurs in pregnancy for a proper fetal development. When cholesterol increases over the physiological range, maternal supraphysiological hypercholesterolemia (MSPH) is described, a condition underdiagnosed by a lack of evidence showing its biological and clinical relevance. To determine if MSPH associates with maternal vascular dysfunction, along with changes in the composition and function of maternal HDL leading to increased cardiovascular risk. This study included 57 women at term of pregnancy in which a lipid profile was determined. Maternal total cholesterol (TC) and LDL but not HDL were increased in MSPH women. The isolated HDL from a subgroup of MSPH women had a lower protein abundance and a reduced activity of the antioxidant enzyme PON1; however, an increased antioxidant capacity compared to MPH was observed, along with higher serum levels of α-tocopherol. Moreover, HDL from a subgroup of MSPH women had a lower capacity to induce NO synthesis in endothelial cells compared to MPH. In the circulation, we observed a reduced total antioxidant capacity and augmented levels of soluble VCAM, ApoB, ApoCII, ApoCIII, IL-10, and IL-12p70, as well as the cardiovascular risk ratio ApoB/ApoAI, compared to MPH women. MSPH women present dysfunctional HDL and increased atherogenic cardiovascular risk factors.

Assessment of the risk of subclinical atherosclerosis in women with polycystic ovary syndrome

Polycystic ovarian syndrome (PCOS) is one of the most prevalent endocrinal disorders affecting women of reproductive age, which has been linked to an enlarged risk of cardiovascular disease and premature atherosclerosis. Atherosclerosis is a persistent inflammatory and lipid-depositing disease that starts from endothelial response to injury, ultimately leading to critical cardiovascular events. Podocalyxin, a cell surface sialomucin, is found on endothelial cells covering blood vessels. Objectives: Measuring serum podocalyxin to predict early atherosclerosis in PCOS women, also measuring lipid panel including the Atherogenic Index of Plasma (AIP), which is a powerful marker that can accurately predict the likelihood of developing the℮ risk of atherosclerosis even when other atherogenic risk factors appear within normal limits. Materials and Method: This case-control study included 124 age-matched women divided into 63 women diagnosed with PCOS (patients) and 61 healthy women (controls). Lipid panel and serum podocalyxin were measured. Results: There is a significant elevation in the mean value of serum podocalyxin (P=0.000), TG (P=0.39), TC (P=0.002), VLDL-C (P=0.039), LDL-C (P=0.001), a Risk ratio of TC/HDL-C (P=0.000), Risk ratio of LDL/HDL-C (P=0.000), and AIP (P=0.013) with significant decrease in mean value of HDL-C (P=0.000) in PCOS women as compared to healthy control. Conclusion: Higher levels of serum podocalyxin and atherogenic index of plasma were found in PCOS women; a positive correlation was also found between serum podocalyxin and atherogenic index of plasma. Therefore, serum podocalyxin appears to be a predictive marker to detect early atherosclerosis in women with PCOS. Keywords: polycystic ovary syndrome, atherosclerosis, podocalyxin, lipid profile, AIP.

Impaired HDL-associated enzymes and proteins in children and adolescents with weight disorders and their association with novel cardiometabolic indexes

Background and aimsOverweight/obesity (OW/OB) is associated with modifications in lipoprotein (Lp)-associated enzymes and proteins, such as cholesteryl ester transfer protein (CETP), Lp-associated phospholipase A2 (LpPLA2) and paraoxonase (PON)1. No evidence is available regarding underweight (UW). The following indexes have been proposed to better assess atherogenic risk related to weight alterations: triglycerides-glucose index (TyG), visceral adiposity index (VAI) and height-corrected lipid accumulation product (HLAP). Aim: To analyze the presence of alterations in Lp-associated enzymes and proteins in children and adolescents with UW and OW/OB and their relation to novel cardiometabolic indexes. Methods and resultsThirty male children and adolescents with UW, 66 with normal weight (NW) and 30 with OW/OB were included. Anthropometric parameters, glucose, Lp profile and the activities of CETP, LpPLA2 and PON1 were evaluated. Body mass index (BMI)-z, TyG, VAI and HLAP were calculated. UW and NW showed lower CETP activity than OW/OB (Mean ± SD) (218 ± 38vs.224 ± 26vs.237 ± 26%/mL.h; p < 0.05). UW and OW/OB showed lower PON1 activity than NW (318 ± 170vs.409 ± 200vs.310 ± 184 nmol/mL.min; p < 0.05). TyG was higher in OW/OB than UW (p < 0.01), whilst both HLAP (p < 0.05) and VAI (p < 0.01) followed a linear trend across weight categories. After adjusting for age and BMI-z, TyG was an independent predictor of CETP (r2 = 0.25, β = −0.22, p < 0.01) and LpPLA2 (r2 = 0.21,β = −0.21,p < 0.05), while VAI (r2 = 0.21,β = −0.32,p < 0.01) and HLAP (r2 = 0.20,β = −0.31,p < 0.01) of CETP. ConclusionsBoth UW and OW/OB showed impaired antioxidant PON1 activity. Moreover, TyG, VAI and HLAP were all capable of predicting alterations in crucial modulators of Lp metabolism and vascular inflammation in children and adolescents with varying degrees of alterations in body weight.

Habitual physical activity modulates cardiometabolic health in long-term testicular cancer survivors

PurposesPhysical activity (PA) may mitigate late cardiometabolic toxicity of cisplatin-based chemotherapy in testicular germ cell tumor (TGCT) long-term survivors. In this cross-sectional study, we evaluated the effects of habitual PA on metabolic syndrome (MetS) prevalence, and on the markers of cardiometabolic health and chronic inflammation in a population of long-term TGCT survivors.MethodsMetS prevalence was evaluated, and habitual PA was assessed using Baecke’s habitual PA questionnaire in TGCT survivors (n=195, age=41.1±8.1years, 11.7±5.2years post-therapy) and healthy male controls (n=41, age=38.2±8.8years). Participants were stratified into low- and high-PA groups based on median values. Differences were examined between low- and high-PA groups (in the entire sample, TGCT survivor sub-samples differing in disease stage, and healthy controls), and between TGCT survivors and controls. Next, TGCT survivors were stratified into age- and BMI-matched sub-groups based on post-treatment time (5–15/15/30years) and number of chemotherapy cycles (≤3/>3), allowing us to detect age- and BMI-independent effects of habitual PA on cardiometabolic health in the given TGCT survivor sub-populations. A correlation matrix of habitual PA and sport activity with cardiometabolic and pro-inflammatory markers was generated.ResultsTGCT survivors had higher MetS prevalence than controls. Patients with high habitual PA had lower waist circumference and Systemic Inflammation Index. Habitual PA scores correlated positively with HDL-cholesterol and negatively with waist circumference and atherogenic risk. Furthermore, cardiometabolic benefits of habitual PA were more pronounced in patients with disease stages 1 and 2. Effects of habitual PA on patients sub-populations stratified by chemotherapy dose and post-treatment time clearly showed that higher levels of habitual PA were associated with lower numbers of MetS components, except for patients who received more than 3 chemotherapy cycles and were examined more than15 years post-therapy.ConclusionsHigher levels of habitual PA effectively mitigated cardiometabolic toxicity in TGCT survivors. Patients with higher cumulative doses of chemotherapy may need structured exercise interventions involving higher-intensity physical activity to achieve significant improvements in cardiometabolic health.

Targeted Expression to Liver of an antimiR-33 Sponge as a Gene Therapy Strategy against Hypercholesterolemia: In Vitro Study.

Atherosclerosis is the leading cause of cardiovascular diseases in Mexico and worldwide. The membrane transporters ABCA1 and ABCG1 are involved in the reverse transport of cholesterol and stimulate the HDL synthesis in hepatocytes, therefore the deficiency of these transporters promotes the acceleration of atherosclerosis. MicroRNA-33 (miR-33) plays an important role in lipid metabolism and exerts a negative regulation on the transporters ABCA1 and ABCG1. It is known that by inhibiting the function of miR-33 with antisense RNA, HDL levels increase and atherogenic risk decreases. Therefore, in this work, a genetic construct, pPEPCK-antimiR-33-IRES2-EGFP, containing a specific antimiR-33 sponge with two binding sites for miR-33 governed under the PEPCK promoter was designed, constructed, and characterized, the identity of which was confirmed by enzymatic restriction, PCR, and sequencing. Hep G2 and Hek 293 FT cell lines, as well as a mouse hepatocyte primary cell culture were transfected with this plasmid construction showing expression specificity of the PEPCK promoter in hepatic cells. An analysis of the relative expression of miR-33 target messengers showed that the antimiR-33 sponge indirectly induces the expression of its target messengers (ABCA1 and ABCG1). This strategy could open new specific therapeutic options for hypercholesterolemia and atherosclerosis, by blocking the miR-33 specifically in hepatocytes.

The Role of the Low-Density Lipoprotein/High-Density Lipoprotein Cholesterol Ratio as an Atherogenic Risk Factor in Young Adults with Ischemic Stroke: A Case-Control Study.

Dyslipidemia is a major atherogenic risk factor for ischemic stroke. Stroke patients tend to have high levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and low levels of high-density lipoprotein cholesterol (HDL-C). Therefore, it is noteworthy that there has been an increase in ischemic stroke cases in young and elderly individuals in recent years. This study investigated the TC/HDL-C ratio and the LDL-C/HDL-C ratio, which may be more specific and common lipid parameters in young patients with ischemic stroke. This study aimed to demonstrate the sensitivity and specificity of TC/HDL-C and LDL-C/HDL-C ratios as atherogenic markers for young adult ischemic strokes. This trial was conducted as a retrospective case-control study. A total of 123 patients (patient group) and 86 healthy individuals (control group) aged 18-50 years were randomly selected from four different hospitals. Lipid parameters and TC/HDL-C and LDL-C/HDL-C ratios were compared between these two groups. The mean age was 38.8 ± 7.3 years in patients and 37.7 ± 9 years in controls (p > 005). The HDL-C levels were 39.1 ± 10.8 mg/dL in patients and 48.4 ± 13.8 mg/dL in controls (p < 0.001). LDL-C/HDL-C ratios were 3.23 ± 1.74 and 2.38 ± 0.87, and TC/HDL-C ratios were 5.24 ± 2.31 and 4.10 ± 1.25 in the patient and control groups, respectively (p < 0.001). The LDL-C/HDL-C and TC/HDL-C cutoff values in ROC analyses were 2.61 and 4.40 respectively; the AUCs (95% CI) were determined to be 0.680 (0.608-0.753) and 0.683 (0.610-0.755) (p < 0.001), respectively. An increased risk of stroke was observed in those with a high LDL-C/HDL-C ratio (OR = 1.827; 95% CI = 1.341-2.488; p < 0.001). Our study obtained similar results when we compared the mean TC and LDL-C levels between the two groups. However, considering the TC/HDL-C and LDL-C/HDL-C ratios, it is noteworthy that there was a significant difference between the patient and control groups.

Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

Association of Atherogenic Index of Plasma with Cardiometabolic Risk Factors and Markers in Lean 14-to-20-Year-Old Individuals: A Cross-Sectional Study.

Cardiometabolic risk factors at a young age pose a significant risk for developing atherosclerotic cardiovascular disease in adulthood. Atherogenic dyslipidemia is highly associated with obesity and metabolic syndrome already in young age. It remains unclear whether cardiometabolic risk factors associate with the atherogenic index of plasma (AIP = log (TAG/HDL-C) in lean subjects with low atherogenic risk. As both the AIP and markers of cardiometabolic risk are continuous variables, we expected their association to be linear before the manifestation of obesity and atherogenic dyslipidemia. We analyzed the prevalence of increased atherogenic risk (AIP ≥ 0.11) in 2012 lean 14-to-20-year-old subjects (55% females) and the trends of cardiometabolic risk factors across the quartiles (Q) of AIP in a subgroup of 1947 (56% females) subjects with low atherogenic risk (AIP < 0.11). The prevalence of AIP ≥ 0.11 reached 3.6% in females and 8.5% in males. HDL-C, non-HDL-C, triglycerides, and the continuous metabolic syndrome score showed a stepwise worsening across the AIP quartiles in both sexes. Measures of obesity and insulin resistance were worse in Q4 vs. Q1 groups, and leukocyte counts were higher in Q4 and Q3 vs. Q1. Females in Q4 presented with a higher C-reactive protein and lower adiponectin, estradiol, and testosterone levels. The multivariate regression model selected non-HDL-C, QUICKI, and erythrocyte counts as significant predictors of AIP in males; and non-HDL-C and C-reactive protein in females. A question arises whether the lean individuals on the upper edge of low atherogenic risk are prone to earlier manifestation of metabolic syndrome and shift to the higher AIP risk group.

Association of sex and cardiovascular risk factors with atherosclerosis distribution pattern in lower extremity peripheral artery disease.

Atherosclerosis expression varies across not only coronary, cerebrovascular, and peripheral arteries but also within the peripheral vascular tree. The underlying pathomechanisms of distinct atherosclerosis phenotypes in lower extremity peripheral artery disease (PAD) is poorly understood. We investigated the association of cardiovascular risk factors (CVRFs) and atherosclerosis distribution in a targeted approach analyzing symptomatic patients with isolated anatomic phenotypes of PAD. In a cross-sectional analysis of consecutive patients undergoing first-time endovascular recanalization for symptomatic PAD, data of patients with isolated anatomic phenotypes of either proximal (iliac) or distal (infrageniculate) atherosclerosis segregation were extracted. We performed a multivariable logistic regression model with backward elimination to investigate the association of proximal and distal PAD with CVRFs. Of the 637 patients (29% females) with endovascular recanalization, 351 (55%) had proximal and 286 (45%) had distal atherosclerosis. Female sex [odds ratio (OR) 0.33, 95% confidence interval (CI) 0.20-0.54, p = 0.01], active smoking (OR 0.16, 95% CI 0.09-0.28, p < 0.001), and former smoking (OR 0.33, 95% CI 0.20-0.57, p < 0.001) were associated with proximal disease. Diabetes mellitus (DM) (OR 3.25, 95% CI 1.93-5.46, p < 0.001), chronic kidney disease (CKD) (OR 1.18, 95% CI 1.08-1.28, p < 0.001), and older age (OR 1.31, 95% CI 1.06-1.61, p = 0.01) were associated with distal disease. Female sex, particularly in the context of smoking, is associated with clinically relevant, proximal atherosclerosis expression. Our additional findings that distal atherosclerosis expression is associated with DM, CKD, and older age suggest that PAD has at least two distinct atherosclerotic phenotypes with sex-specific and individual susceptibility to atherogenic risk factors.

Atherogenic Index of Plasma and Oxidized-LDL as Strong and Independent Predictor of CHD in Young Smokers

Cigarette smoking is an environmental risk factor for cardiovascular disease and induces changes in lipid profile by the oxidation of lipids, particularly LDL. Hence the need for determine ox-LDL and its association with atherogenic indices in the prediction of cardiovascular risk arises. The study aimed to determine oxidized-LDL and atherogenic indices in relation to smoking habits in cigarette smokers. This case-control study included 240 individuals in which cigarette smokers were (n=120) and were compared with (n=120) non-smokers. The ox-LDL, APO-A1 and APO-B were performed using Enzyme-linked Immune Sorbent Assay (ELISA) and atherogenic risk ratios were calculated. The study shows that ox-LDL was significantly increased in smokers and significant increase in TC, TGL and LDL was also observed. When compared to nonsmokers, smokers had considerably higher atherogenic risk indices. Pearson correlation tests revealed that ox-LDL and AIP were substantially and positively linked with non-HDL, CRI- Castelli's risk index-I, CRII- Castelli's risk index-II, AC-Atherogenic coefficient, CI-Cholindex and APO-B- Apolipoprotein B (p&lt;0.001). The unadjusted odds ratios for ox-LDL and AIP in the univariate logistic regression analysis were 1.861 (95% confidence interval: 1.347-2.375), p&lt;0.001 and 1.782 (95% confidence interval: 1.490-2.131), P.001) respectively. Multivariate logistic regression analysis demonstrated that ox-LDL and AIP were independent risk factors for CHD in young smokers. In smokers, ox-LDL and atherogenic indices appear to be strong predictors of CHD than conventional lipid parameters.

Lipoprotein Lipase Activity Does Not Differ in the Serum Environment of Vegans and Omnivores.

Although vegan diets have been reported to be associated with a reduced risk of cardiovascular disease, it was not known whether this might be partly due to vegan diets' effects on plasma triglyceride metabolism. This study aimed to investigate if there are differences in the activity of lipoprotein lipase (LPL), an enzyme that functions at the vascular endothelium and is responsible for triglyceride breakdown, in sera obtained from vegans and omnivores. LPL activity was assessed using isothermal titration calorimetry, which allows measurements in undiluted serum samples, mimicking physiological conditions. Fasted sera from 31 healthy participants (12F 2M vegans, 11F 6M omnivores) were analyzed. The results indicated no significant differences in average LPL activity between the vegan and omnivore groups. Interestingly, despite similar triglyceride levels, there were considerable variations in LPL activity and total very-low-density lipoprotein triglyceride breakdowns between individuals within both groups. Biomarker analysis showed that vegans had lower total cholesterol and LDL-C levels compared to omnivores. These findings suggest that the lipid-related benefits of a vegan diet, in terms of atherogenic risk, may primarily stem from cholesterol reduction rather than affecting serum as a medium for LPL-mediated triglyceride breakdown. In healthy individuals, lipid-related changes in serum composition in response to a vegan diet are likely overshadowed by genetic or other lifestyle factors.

ANTI-DYSLIPIDAEMIA AND CARDIO-PROTECTIVE EFFECTS OF NIGERIAN BITTER HONEY IN STREPTOZOTOCIN INDUCED DIABETIC RATS

Background and Aim: Chronic hyperglycemia, oxidative stress, and dyslipidemia usually predispose to cardiac aberrations. Certain honey samples have been reported to worsen glycemic control or proven to be cardiotoxic. The study sought to elucidate the roles of Nigerian bitter honey in experimental diabetes. Experimental Procedures: Diabetes was induced in adult female Wistar rats (90–110g) by single administration of streptozotocin (65 mg/kg body weight, i.p.). Rats were randomly allocated into six groups (n= 8). Bitter honey (50 mg/kg) and metformin (100 mg/kg) were orally administered daily for 28 days. Animals were sacrificed on day 29 and blood samples were obtained via cardiac puncture. Lipid profile and lipid peroxidation analysis were carried out using standard methods. Atherogenic, coronary, and cardiovascular risk indexes were calculated. Heart, pancreas, and lung tissues were harvested and subjected to histopathological assessment. Data were analyzed using one way ANOVA, and statistical significant level was set at p&lt;0.05. Result and Discussion: Bitter honey treatment in the diabetic animals significantly reduced hyperglycemia, triglyceride, total cholesterol, low-density lipoprotein, malondialdehyde, and cardiovascular risk levels (p&lt;0.05). Correspondingly, HDL and reduced glutathione levels were significantly higher (p&lt;0.05). Bitter honey preserved the histoarchitectural integrity of the cardiomyocytes and lungs tissue. Conclusion: The bitter honey is a highly remarkable repository of naturally occurring bioactive compounds that can potentially modulate downstream biochemical pathways of hyperglycemia, dyslipidemia and lipid peroxidation. The bitter honey may therefore be a promising new source of anti-diabetic and cardio protective nutraceuticals. Peer Review History: Received: 9 February 2023; Revised: 7 March; Accepted: 29 April 2023, Available online: 15 May 2023 Academic Editor: Dr. Amany Mohamed Alboghdadly, Ibn Sina National College for Medical Studies in Jeddah, Saudi Arabia, amanyalboghdadly@gmail.com Received file: Reviewer's Comments: Average Peer review marks at initial stage: 6.0/10 Average Peer review marks at publication stage: 7.0/10 Reviewers: Dr. Sangeetha Arullappan, Universiti Tunku Abdul Rahman, Malaysia, sangeetha@utar.edu.my Dr. Rawaa Souhil Al-Kayali, Aleppo University, Syria, rawah67@hotmail.com

Measurement of Serum Low Density Lipoprotein Cholesterol and Triglyceride-Rich Remnant Cholesterol as Independent Predictors of Atherosclerotic Cardiovascular Disease: Possibilities and Limitations

The serum low density lipoprotein cholesterol (LDL-C) concentration is the dominant clinical parameter to judge a patient’s risk of developing cardiovascular disease (CVD). Recent evidence supports the theory that cholesterol in serum triglyceride-rich lipoproteins (TRLs) contributes significantly to the atherogenic risk, independent of LDL-C. Therefore, combined analysis of both targets and adequate treatment may improve prevention of CVD. The validity of TRL-C calculation is solely dependent on the accuracy of the LDL-C measurement. Direct measurement of serum LDL- C is more accurate than established estimation procedures based upon Friedewald, Martin–Hopkins, or Sampson equations. TRL-C can be easily calculated as total C minus high density lipoprotein C (HDL-C) minus LDL-C. Enhanced serum LDL-C or TRL-C concentrations require different therapeutic approaches to lower the atherogenic lipoprotein C. This review describes the different atherogenic lipoproteins and their possible analytical properties and limitations.

Relationship between Atherogenic Dyslipidaemia and Lipid Triad and Scales That Assess Insulin Resistance

Background: Atherogenic dyslipidaemia (AD) and lipid triad (LT) are characterised by high triglyceride levels together with low HDL and normal or high LDL cholesterol and are favoured by a persistent state of insulin resistance (IR), which increases the release of free fatty acids from abdominal adipose tissue. This alteration in the lipid profile favours the accelerated development of atherosclerosis, which is the most important cause of morbidity and mortality in all countries in the developed and developing world. One of the elements that plays a major role in the genesis of AD is IR. The aim of this study was to determine the relationship between variables that assess atherogenic risk (AD and LT) and scales that assess the risk of presenting insulin resistance. Methods: A descriptive cross-sectional study of 418,343 workers was conducted to evaluate atherogenic dyslipidaemia and lipid triad; a relationship with three insulin resistance risk scales (Triglycerides/HDL, TyG index, METS-IR) was established. The usefulness of IR risk scales for predicting AD and LT was calculated by applying ROC curves, obtaining the area under the curve (AUC) and cut-off points with their sensitivity, specificity, and Youden index. Multivariate analysis was performed by binary logistic regression. Results: The prevalence of high-risk values for insulin resistance with all of the scales is much higher in people with AD and LT compared to those without. The ROC curves present us with an AUC with the three insulin resistance risk scales for the two dyslipidaemias studied with figures ranging between 0.856 and 0.991, which implies that the results are good/very good. Conclusions: A relationship between atherogenic dyslipidaemia and the three insulin resistance risk scales assessed is revealed, with higher IR mean values and prevalence in people with atherogenic dyslipidaemia and lipid triad. The three scales make it possible to adequately classify the presence of AD and LT. The highest AUC is presented by the triglycerides/HDL scale, with a result close to 1. METS-IR is the most recommended formula to estimate insulin resistance.

Central androgen action reverses hypothalamic astrogliosis and atherogenic risk factors induced by orchiectomy and high-fat diet feeding in male mice.

Hypogonadism in males confers elevated cardiovascular disease (CVD) risk by unknown mechanisms. Recent radiological evidence suggests that low testosterone (T) is associated with mediobasal hypothalamic (MBH) gliosis, a central nervous system (CNS) cellular response linked to metabolic dysfunction. To address mechanisms linking CNS androgen action to CVD risk, we generated a hypogonadal, hyperlipidemic mouse model with orchiectomy (ORX) combined with hepatic PCSK9 overexpression. After 4 wk of high-fat, high-sucrose diet (HFHS) consumption, despite equal body weights and glucose tolerance, androgen-deficient ORX mice had a more atherogenic lipid profile and increased liver and leukocyte inflammatory signaling compared with sham-operated control mice. Along with these early CVD risk indicators, ORX markedly amplified HFHS-induced astrogliosis in the MBH. Transcriptomic analysis further revealed that ORX and high-fat diet feeding induced upregulation of inflammatory pathways and downregulation of metabolic pathways in hypothalamic astrocytes. To interrogate the role of sex steroid signaling in the CNS in cardiometabolic risk and MBH inflammation, central infusion of T and dihydrotestosterone (DHT) was performed on ORX mice. Central DHT prevented MBH astrogliosis and reduced the liver inflammatory signaling and monocytosis induced by HFHS and ORX; T had a partial protective effect. Finally, a cross-sectional study in 41 adult men demonstrated a positive correlation between radiological evidence of MBH gliosis and plasma lipids. These findings demonstrate that T deficiency in combination with a Western-style diet promotes hypothalamic gliosis concomitant with increased atherogenic risk factors and provide supportive evidence for regulation of lipid metabolism and cardiometabolic risk determinants by the CNS action of sex steroids.NEW & NOTEWORTHY This study provides evidence that hypothalamic gliosis is a key early event through which androgen deficiency in combination with a Western-style diet might lead to cardiometabolic dysregulation in males. Furthermore, this work provides the first evidence in humans of a positive association between hypothalamic gliosis and LDL-cholesterol, advancing our knowledge of CNS influences on CVD risk progression.