Higher LDL-C Levels Research Articles

Adiposity and physical activity are among the main determinants of serum vitamin D concentrations in older adults: the EpiFloripa Aging Cohort Study

The identification of factors associated with 25-hydroxycholecalciferol (25(OH)D) concentration can help suggest more specific interventions for older adults. In this cross-sectional study of older adults from southern Brazil, we hypothesized that some sociodemographic, behavioral, and health factors positively or negatively influence the 25(OH)D concentration in this population. This analysis was performed using data from the second wave of the EpiFloripa Aging Cohort Study (2013-2015). Serum 25(OH)D levels were classified according to the guidelines of the Endocrine Society. Multinomial logistic regression was performed to evaluate the relative risks of sociodemographic, behavioral, and health factors in each 25(OH)D category. A total of 574 older adults (aged 63-93 years) participated in this study. The prevalence of insufficiency (21-29 ng/mL) was 43.7% and that of deficiency (≤20 ng/mL) was 23.5%. In the adjusted analysis, female sex, higher levels of low-density lipoprotein cholesterol (LDL-C ≥160 mg/dL), obesity by adiposity (body fat percentage [%fat], male ≥31%; female ≥43%), and body mass index (BMI, >30 kg/m2) presented higher relative risks for insufficiency than for sufficiency. For those with deficiency, the associated factors were female sex, disability in 4 or more activities of daily living (ADLs), LDL-C ≥100 mg/dL, and obesity by %fat and BMI. A protective factor against insufficiency and deficiency was active leisure-time physical activity (PA, ≥150 min/week). Our results demonstrated that being female and having modifiable factors, such as high levels of LDL-C, obesity, and disability on ADLs, were negatively associated with hypovitaminosis D. On the other hand, leisure-time PA was positively associated with adequate serum vitamin D concentration.

Joint effects of paraoxonase 1 rs662 polymorphism and vitamins C/E intake on coronary artery disease severity (Gensini and SYNTAX scores) and lipid profile in patients undergoing coronary angiography.

Considering the emergence of the concept of personalized nutrition in recent years and its importance in the treatment of diseases, the purpose of this study was to investigate the interaction of paraoxonase (PON)1 rs662 polymorphism and vitamin C/E intake on coronary artery disease (CAD) severity and lipid profile in patients undergoing diagnostic angiography. This cross-sectional study was carried out on 428 patients undergoing angiography. The PON-1 genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism technique. Dietary intake was obtained using a valid questionnaire. After adjustment for potential confounders, R allele carriers (RR + RQ) have lower HDL-C levels than non-carriers (QQ) (P ≤ 0.05). On the other hand, higher consumption of vitamin C was associated with a reduced risk of high total cholesterol (OR: 0.42, 95% CI 0.23-0.75, P = 0.003) and low-density lipoprotein cholesterol (OR: 0.49, 95% CI 0.25-0.96, P = 0.038) and an increased risk of low high-density lipoprotein cholesterol (OR: 1.88, 95% CI 1.03-3.42, P = 0.037). Furthermore, a significant interaction was observed between vitamin C intake and genotypes of rs66 polymorphism on LDL-C (P = 0.050). In detail, the R-allele carriers with lower vitamin C intake had higher LDL-C levels than QQ genotype carriers. No significant interaction was found between vitamin E intake and rs662 polymorphism genotypes on the Gensini and SYNTAX scores and lipid profile (P > 0.05). The novel finding of the present study was the existence of a significant interaction between rs662 polymorphism and vitamin C intake on LDL-C. More specifically, R allele carriers with lower vitamin C intake were susceptible to higher LDL-C.

Predictive effect of different blood lipid parameters combined with carotid intima-media thickness on coronary artery disease.

Blood lipids disorder and atherosclerosis are closely related to coronary artery disease (CAD). This study aims to compare different blood lipid parameters combined with carotid intima-media thickness (cIMT) in predicting CAD. This was a retrospective study including patients who underwent coronary angiography for highly suspected CAD. Blood samples were taken for lipid profile analysis and cIMT was evaluated by carotid ultrasound. Logistic analysis was used to establish different models of different lipid parameters in predicting CAD. The area under the receiver operating characteristic curve (AUC) was used to examine the predictive value. The optimal lipid parameter was also used to explore the relationship with multi-vessel CAD. Patients were classified into two groups based on whether CAD existed. Compared with non-CAD patients, the CAD group had higher lipoprotein (a) [Lp (a)], apolipoprotein B/apolipoprotein A, total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C and LDL-C/HDL-C. According to the AUCs, Lp (a) combined with cIMT (AUC: 0.713, P < 0.001) had the best performance in predicting CAD compared to other lipid parameters. High level of Lp (a) was also associated with multi-vessel CAD (odds ratio: 1.41, 95% confidence interval: 1.02-1.95, P = 0.036). For patients with highly suspected CAD, Lp (a) better improved the predictive value of CAD rather than most of blood lipid indices, especially in the absence of high levels of LDL-C. Lp (a) also can be used to predict the multi-vessel CAD.

Lipid profile peculiarities and matrix Gla protein concentration in Ukrainian pediatric patients with heterozygous familial hypercholesterolemia

Atherosclerotic changes in the vascular walls begin early in childhood, especially in association with familial hypercholesterolemia (FH). The process may be subclinical, which nevertheless requires therapeutic and preventive measures. Purpose - to evaluate baseline lipid profiles, the thickness of carotid intima-media complexes, blood pressure indices and the association with concentration changes of dephosphorylated-uncarboxylated matrix Gla protein (dp-uc MGP) as a marker of subclinical arterial lesions in different age groups of pediatric patients with FH. Materials and methods. Children with heterozygous FH (n=15), stratified by age and sex, were included in the study. The control group consisted of healthy peers (n=21). Blood samples were analyzed to determine levels of total (TC), low-density (LDL-C), very-low-density (VLDL-C), high-density (HDL-C), remnant (rC) and non-high-density (non-HDL-C) cholesterol, triglycerides (TG), apolipoproteins A1 (apoA1) and B (apoB), lipoprotein (a), and dp-uc MGP. The intima-media complex thickness of the common carotid artery and blood pressure were measured in all study subjects. The obtained data were processed using the accepted methods of medical statistics and SAS® OnDemand for Academics. Results. Lipid profile changes in pediatric patients with FH were characterized by high levels of LDL-C, non-HDL-C and lipoprotein (a) in the 5-9 years age group; in the 10-14 years age group - high levels of LDL-C, TG, rC, non-HDL-C and lipoprotein (a); in the 15-18 years age group - high levels of LDL-C, TG, non-HDL-C and lipoprotein (a). At the same time, the most marked dyslipidemia changes were evident in children aged 10-14 years in the FH group. apoA1 levels were significantly decreased in all FH children. Elevated levels of lipoprotein (a) (&gt;30 mg/dL) in FH children were found in all age groups, suggesting that elevated lipoprotein (a) levels can be used as a factor for cardiovascular risk stratification. Dp-uc MGP levels were significantly elevated in all age groups of FH children compared to healthy peers. Conclusions. A lipid profile examination is necessary to diagnose FH in children, along with family health history and cascade screening. As atherosclerotic changes at 5-18 years of age remain subclinical, and the instrumental tests available in routine medical practice are not sensitive enough to detect them, therefore, preventive or therapeutic measures cannot be initiated promptly. The evaluation of circulating matrix Gla protein in pediatric patients with FH can be used as a marker of vascular wall calcification, which may allow early preventive measures against microcalcification to be developed. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Analysis of Clinical and Biochemical Characteristics of Patients With Genetically Confirmed Familial Hypercholesterolemia in Russian North Western District Residents.

Aim To compare results of clinical, laboratory, and genetic examination of patients with familial hypercholesterolemia (FHC).Material and methods 112 patients aged 40.2±17.9 years (49 men) were examined. The gene of low-density lipoprotein receptor (LDLR) was analyzed and evaluated using the Dutch Lipid Clinic Network (DLCN) criterion of lipid score ≥6. The LDLR gene mutation was searched for using the conformational polymorphism analysis followed by sequencing of the DNA of isolated LDLR gene exons.Results Mean variables of the blood lipid profile were total cholesterol (C), 10.12±2.32 mmol/l, LDL-C, 7.72±2.3 mmol/l. Corneal arcus was observed in 15 % of patients, tendon xanthomas in 31.8 %, and xanthelasma palpebrarum in 5.3 %. The types of LDLR gene mutations included missense mutations (42.8 %), mutations causing a premature termination of protein synthesis (41.1 %), and frameshift mutations (16.1 %). In the presence of a mutation in exon 4, patients with IHD compared to patients with no IHD had significantly higher levels of total C (10.88±2.08 mmol/l vs. 8.74±1.57 mmol/l, respectively, р=0.001) and LDL-C (8.60±2.14 mmol/l vs. 6.62±1.79 mmol/l, respectively, р=0.005). Patients with IHD compared to patients with no IHD and a mutation in LDLR gene exon 9 had only a higher LDL-C level (8.96±1.53 mmol/l vs. 6.92±1.59 mmol/l, respectively, р=0.022). A differentiated comparison of IHD patients using a logistic regression depending on the identified type of LDLR gene mutation produced formulas for calculating the odds ratio of IHD and myocardial infarction (MI) with adjustments for the patient's age and baseline LDL.Conclusion The detection rate of the LDLR gene mutations was 42.8 % for missense mutations, 41.1 % for mutations causing a premature termination of protein synthesis, and 16.1 % for frameshift mutations. Blood lipid profiles did not differ between patients from different cities and with different types of LDLR gene mutations. Blood lipid profiles were different in IHD patients depending on the mutation type.

Effects of Serum Lipids on the Long-Term Prognosis of Ampullary Adenocarcinoma Patients after Curative Pancreatoduodenectomy.

Serum lipids (SLs), the prominent indicators of lipid metabolism, produce an intricate impact on proliferation, invasion, and metastasis of cancer cells. However, the effects of serum lipids on the prognosis of ampullary adenocarcinoma (AC) have not been investigated. Patients with AC in the National Cancer Center of China between January 1998 and December 2020 were retrospectively reviewed. Survival analysis for overall survival (OS, Time from operation to death) and recurrence-free survival (RFS, Time from operation to first-time recurrence) was performed using Kaplan-Meier analysis and Cox proportional hazards models. A total of 232 AC patients were enrolled into the study. SLs levels were significantly lower in patients with vascular invasion compared to those without (all p &lt; 0.05). The 1-year, 3-year, and 5-year OS rates for AC patients were 86.1%, 64.1%, and 47.6% and 75.8%, 54.8%, and 46.5% for RFS. Biliary/pancreatic fistula (31.9%) and chemotherapy (81.4%) were the majority of postoperative complications and adjuvant therapy, respectively. According to Cox analysis, preoperative LDL-C was an independent prognostic factor for RFS (HR = 0.43, 95% CI: 0.21-0.85, p = 0.015), whereas no statistical significance existed in the analysis of HDL-C, TC, and TG. High levels of preoperative LDL-C is a significant predictor of prolonged prognosis in AC patients, which was also observed to be a protective factor to reduce vascular invasion.

Dyslipidemia among patients with type 2 diabetes in Jordan: Prevalence, pattern, and associated factors.

To determine the prevalence and patterns of dyslipidemia and its associated risk factors among patients with type 2 diabetes attending the National Center for Diabetes, Endocrinology, and Genetics (NCDEG). A cross-sectional study was conducted at the NCDEG in Amman, Jordan. A total of 971 patients with type 2 diabetes were included during the period September- December 2021. The socio-demographic data were collected through face-to-face interview questionnaire and anthropometric and clinical data were abstracted from medical records. The last three readings of lipid profile and HbA1C were abstracted from the medical records. The overall prevalence of dyslipidemia among type 2 diabetic patients was 95.4%. The most common type of dyslipidemia was combined dyslipidemia (37.1%), with high triglycerides and low HDL-c (19.0%) being the most frequent type. Factors associated with hypercholesterolemia were diabetes duration ≤ 10 years, poor compliance to a statin, and HbA1c level (7-8%) (P-values: 0.008, 0.001, 0.021, respectively). Moreover, smoking and poor compliance with statin therapy were associated with high LDL-c level (P-values: 0.046 and 0.001, respectively). The presence of hypertension, high waist circumference, HbA1c level >8%, and diabetes duration ≤ 10 years were all associated with high triglyceride level (P-values: 0.008, 0.016, 0.011, and 0.018, respectively). Hypertension and HbA1c level >8% were associated with low HDL-c level (P-values: 0.010 and 0.011, respectively). The combination of high triglyceride and low HDL-c is the commonest lipid abnormality detected in patients with type 2 diabetes. An educational program that emphasizes the importance of adherence to a healthy lifestyle is strongly recommended. Further studies are needed to capture a wide range of factors that might influence dyslipidemia and glycemic control.

Abstract 13515: LDL-Cholesterol, Coronary Plaque, and Resilience to Coronary Atherosclerosis in a Middle-Aged Asymptomatic US Population: The Miami Heart Study at Baptist Health South Florida

Introduction: The interplay between LDL-C and coronary plaque has not been described in contemporary, asymptomatic US cohorts undergoing CCTA assessment. Also, the prevalence of resilience to coronary atherosclerosis despite high LDL-C in the general primary prevention population is poorly understood. Methods: Cross-sectional analysis using data from the ongoing, prospective Miami Heart Study. Descriptive statistics were computed among statin-naïve participants by LDL-C levels (&lt;70, 70-100, 100-130, 130-160, 160-190, ≥190 mg/dL) and a combined group of statin-naïve with LDL-C≥190 and statin users with LDL-C≥130 (“high LDL-C”). Study outcomes included CAC=0 vs &gt;0, any plaque on CCTA, maximal stenosis ≥50%, and ≥1 and ≥2 high-risk plaque features. Logistic regression models evaluated associations between LDL-C and the outcomes, adjusting for other risk factors. Results: The demographics and outcomes of 1,808 participants not on statin are summarized in the Table by LDL-C levels. Higher LDL-C levels were strongly and independently associated with CAC&gt;0 (fully adjusted OR for LDL≥190 vs &lt;70 mg/dL: 2.62, 95%CI 1.04, 6.60) and had a marginally significant association with any plaque (fully adjusted OR: 2.26, 95%CI 0.95, 5.37). However, among participants with LDL-C≥190, 54% had CAC=0, and 40% no plaque. Similar numbers were observed among participants with “high LDL-C” (N=159), in which 45% had CAC=0 and 35% no plaque. Among those with high LDL-C and CAC=0, approximately 28% had non-calcified plaque on CCTA, although the prevalence of high-risk plaque findings was very low. Conclusions: LDL-C is strongly associated with coronary atherosclerosis. However, in this cohort (mean age 53 years; 54% women), CAC=0 and the absence of coronary plaque were frequent findings among individuals with high LDL-C. These observations may be used to inform more personalized paradigms in ASCVD risk assessment and in the allocation of novel LDL-C-lowering therapies in this group.

Abstract 11538: The Impacts of the Patient Voice in Continuing Medical Education (CME) to Enhance Homozygous Hypercholesterolemia (HoFH) Diagnosis and Management

Introduction: Early diagnosis and management of HoFH are key to achieving CV risk reduction. However, barriers to identifying probable cases, low awareness of current guidelines, and a lack of knowledge of treatment options continue to present challenges to HCPs. Hypothesis: CME with the patient voice can enhance HCP's competence in diagnosing and managing HoFH and adopting newest treatment options. Methods: A 60-minute CME activity that incorporated the patient voice was launched live-online 7/20/21 and was available on-demand for 1 year. Test questions were administered before and immediately after the activity. A follow-up survey on HCP behavior was sent to post-test respondents 2 months after activity completion. Responses were analyzed for engagement, lessons learned, and continuing gaps. Chi-square tests compared paired responses (P less than 0.05; pre/post). Results: As of 6/6/22, 1,806 HCPs had engaged (14% cardiologists and 57% PCPs managing an average of 50.2 patients per year with very high lipid levels). At entry, 68% of HCPs were at least “somewhat confident” in managing HoFH, while 48% did not know about newly approved agents for HoFH. Outcomes showed significant increases (pre vs post) in ability to recognize manifestations of HoFH (47% vs 87%), apply guidelines to reduce high LDL-C levels despite statin therapy (38% vs 92%), and recognize mechanism of action of evinacumab (43% vs 88%). On follow up, HCPs reported positive impacts on practice related to diagnosing HoFH, applying guideline-driven care to lower LDL-C, identifying high-risk patients, and referring appropriately. Conclusions: Live and on-demand CME including the voice of the patient successfully highlighted HoFH patient’s expectations of care and enhanced HCPs’ ability to adapt to the changing HoFH landscape. Additional education on this evolving landscape and associated guidelines can further enhance quality of care for HoFH patients.

Safety and efficacy of very low LDL-cholesterol intensive lowering: a meta-analysis and meta-regression of randomized trials.

We performed a study-level meta-analysis to provide more robust evidence on safety of very low LDL-cholesterol (LDL-C) levels. Concerns on the safety of LDL-C values achieved with potent lipid-lowering therapies have been raised. We searched randomized trials reporting clinical outcomes with intensive lipid-lowering treatments leading to very low (<40mg/dL) LDL-C levels vs. a control group with higher LDL-C levels. Only studies with follow-up duration≥3 months were considered. Primary endpoint was the incidence of various safety measures. A total of 10 randomized trials were overall included, with 38427 patients being in the very low LDL-C group vs. 70668 in the control group. Median follow-up duration was 28.8 months. The incidence of all safety outcomes was similar in the two groups: non-cardiovascular death: OR 1.13, 95% CI 0.87-1.45; P=0.36; any adverse events: OR 1.00, 0.90-1.11, P=0.94; adverse events leading to drug discontinuation: OR 1.00, 0.87-1.15, P=0.99; cancer: OR 1.02, 0.95-1.10, P=0.57; haemorrhagic stroke OR 0.89, 0.66-1.20, P=0.44; new-onset diabetes: OR 1.16, 0.91-1.47, P=0.23; neurocognitive disorders: OR 0.97, 0.91-1.04, P=0.41; haepatobiliary disorders: OR 0.99, 0.83-1.18, P=0.93; muscle disorders: OR 0.94, 0.77-1.13, P=0.49; cataract: OR 1.28, 0.78-2.10, P=0.34. The rates of major adverse cardiovascular events were significantly lower in the very low LDL-C group: OR 0.82, 0.72-0.94, P=0.005. This meta-analysis indicates that very low LDL-C levels on intensive lipid-lowering treatments are not associated with any adverse event and maintain a persistent reduction of cardiovascular events.

Frequency of occurrence of the PPAR family gene polymorphisms and their relationship with lipid levels in healthy young individuals

Objective . To determine the frequency of occurrence of the genotypes of the PPARG (Pro12Ala), PPARD (294T/C), and PPARA (G2528C) gene polymorphic variants, and to establish their relationship with blood lipid levels in healthy young individuals. Materials and methods . The study included healthy young individuals (n=90) aged 20.1 ± 0.6 years. The parameters of the lipidogram were evaluated: total cholesterol (TC), low-density lipoprotein cholesterol (LDL cholesterol), highdensity lipoprotein cholesterol (HDL cholesterol), triglycerides (TGs), atherogenicity coefficient (CA). The polymorphic variants of the PPAR genes were determined. The results of the study were processed using the STATISTICA 10.0 application package. Results . The genotype distribution of the Pro12Ala polymorphic variant of the PPARG gene (χ 2 =0.0079; p=0.73), 294T/C of the PPARD gene (χ 2 =0.26; p=0.65), and G2528C of the PPARA gene (χ 2 =4.72; p=0.8) in the healthy young individuals corresponded to the expected Hardy-Weinberg equilibrium. No significant differences between the lipid levels in carriers of different variants of the polymorphic PPARG gene (Pro12A1a) were obtained. Conclusion . Individuals with the C/C polymorphic variant had significantly higher TG levels, lower HDL cholesterol levels in the blood, and the highest CA compared with carriers of the T/T and T/C variants of the PPARD (294T/C) polymorphic gene. Carriers of the C/C polymorphic variant had significantly (p=0.049) higher LDL-C levels than carriers of the G/C variant of the PPARA (G2528C) polymorphic gene. The risk of hypertriglyceridemia is 9.6 times, of low HDL-C is 6.9 times, and of having an elevated CA rate is 5.2 times as high in individuals with the C/C polymorphic variant as in individuals with the T variants /T and T/C of the PPARD gene (294T/C).

The pattern of dyslipidaemia and factors associated with elevated levels of non-HDL-cholesterol among patients with type 2 diabetes mellitus in the Ho municipality: A cross sectional study

BackgroundDyslipidaemia is a key comorbid condition of type 2 diabetes mellitus that increases the risk of cardiovascular disease. This study describes the pattern of dyslipidaemia and factors associated with elevated levels of non-high density lipoprotein cholesterol (HDL-C) among patients with type 2 diabetes mellitus in Ho. MethodsThis hospital-based cross-sectional study enrolled 210 patients with type 2 diabetes mellitus from Ho municipality. A semi-structured questionnaire was used to obtain demographic and other relevant parameters. Anthropometric, haemodynamic, and biochemical variables were obtained using standard methods. Dyslipidaemia was defined according to the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria while elevated levels of non-HDL-C was defined as non-HDL-C level ≥3.37 mmol/L. A Chi-square test and multivariate logistic regression analyses were performed to determine factors associated with elevated non-HDL-C levels. ResultsOverall, dyslipidaemia and elevated levels of non-HDL-C prevalence was 67.1% and 64.3%, respectively. The frequency of atherogenic, isolated, and mixed dyslipidaemias were 10.5%, 58.09% and 53.33 %, respectively. Females were four times more likely to develop elevated levels of non-HDL-C after adjustment for age (AOR: 4.07; CI: 2.20–7.51; p < 0.0001). Likewise, overweight (AOR: 3.1; CI: 1.45–6.61; p = 0.0035), grade 1 obesity (AOR: 2.8; CI: 1.20–6.49; p = 0.0168), and truncal obesity (AOR: 3.09; CI: 1.54–6.19; p < 0.0001) were three times each more likely to develop elevated levels of non HDL-C after adjustment for age and gender. However, alcohol intake was 66% unlikely to develop elevated levels of non-HDL-C (COR: 0.34; CI: 0.16–0.73; p = 0.006). ConclusionDyslipidaemia and elevated levels of non-HDL-C were common in our study participants. Hypercholesterolaemia and co-occurrence of high TG and high LDL-C levels were the most prevalent isolated and mixed dyslipidaemias, respectively. The female gender, overweight, grade 1 obesity and truncal obesity, as well as alcohol intake were significant predictors of elevated levels of non-HDL-C.

Comparative Analysis of Biochemical Abnormalities in Diabetic Patients with or without Cardiovascular Complications

Aim: To assess the lipid profile and blood glucose concentration association between diabetic patients with and without cardiac disease. Study design: Case-control study Place and Duration: National Institute of Cardiovascular Diseases Karachi from January 2021 to June 2021 Methodology: The study included a total of 180 participants categorized into comparative groups. Diabetic patients were categorized into cardiac and non-cardiac patients. Demographic data were collected using a questionnaire, and clinical data were recorded with the physical examination. Blood was collected from all patients for further glucose and lipid profile testing. Data were evaluated using SPSS version 21. Results: The average age was 49.53 ± 11.24 and 54.38 ± 11.87 years for non-cardiac and cardiac patients. Whereas BMI of 28.16 ± 5.89 and 27.64 ± 4.18 was observed in diabetic patients with non-cardiac and cardiac diseases. A total of 73 (81.2%) were smokers with cardiac diseases, and 58 (64.4%) were smokers without cardiac disease. A total of 80% of cardiac and 57.7% of non-cardiac patients had a family history of diabetes. Significant high levels of Cholesterol, LDL-C, and Glucose were observed. However, significantly lower levels of HDL-C were observed between patients with and without cardiac disease. Conclusion:The results of the current study indicate that patients with diabetes having cardiovascular disease have a significant association with biochemical parameters. Those with diabetes are more likely to acquire hyperlipidemia. Keywords: Biochemical parameter, cardiovascular disease, Diabetes Mellitus, Cholesterol, Dyslipidemia

Docosahexaenoic Acid as the Bidirectional Biomarker of Dietary and Metabolic Risk Patterns in Chinese Children: A Comparison with Plasma and Erythrocyte.

Objective: The present study aims to measure docosahexaenoic acid (DHA) in both the plasma and erythrocyte of a child population and compares them with respect to their associations with dietary and metabolic risk patterns. Methods: A cross-sectional study was conducted, and a total of 435 children ages 5–7 years old were recruited. Diet information was collected using a food frequency questionnaire (FFQ). The physical indicators, blood pressure, and glycolipid metabolic indicators were determined. The plasma and erythrocyte DHA were analyzed using a gas chromatography mass spectrometer. Principal component analysis was used to identify dietary and metabolic risk patterns. Multivariate regression analyses were used to investigate the associations of DHA status with dietary and metabolic risk patterns. Results: A significant correlation between plasma and the erythrocyte DHA concentration was found (r = 0.232, p < 0.001). A diversified dietary pattern characterized that a high intake of diversified foods had a positive association with the plasma DHA level (β = 0.145, 95% CI: 0.045~0.244, p = 0.004). Children of obesity risk patterns with a high weight, pelvis breadth, BMI, upper arm circumference, and chest circumference had lower plasma DHA concentrations (OR = 0.873, 95% CI: 0.786~0.969, p = 0.011). Children with higher plasma and erythrocyte DHA concentrations were adhered to blood lipid risk patterns with high CHOL and LDL-C levels. The plasma DHA (OR = 1.271, 95% CI: 1.142~1.415, p < 0.001) had a stronger association with a blood lipid risk pattern than erythrocyte (OR = 1.043, 95% CI: 1.002~1.086, p = 0.040). Conclusions: The diversified dietary pattern had a higher plasma DHA concentration. Lower levels of plasma DHA were positively associated with obesity in children. DHA in plasma appears to be more strongly associated with blood lipid metabolism than erythrocyte. Plasma DHA may be a more sensitive bidirectional biomarker to evaluate the recently comprehensive diet intake and metabolic risk of children.

Polygenic risk score for hypercholesterolemia in a Brazilian familial hypercholesterolemia cohort

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of LDL-C leading to premature cardiovascular disease (CAD). Only about 40% of individuals with a clinical diagnosis of FH have a causative genetic variant identified, and a proportion of genetically negative cases may have a polygenic cause rather than a still unidentified monogenic cause. This work aims to evaluate and validate the role of a polygenic risk score (PRS) associated with hypercholesterolemia in a Brazilian FH cohort and its clinical implications. MethodsWe analyzed a previously derived PRS of 12 and 6 SNPs (Single Nucleotide Polymorphism) in 684 FH individuals (491 mutation-negative [FH/M−], 193 mutation-positive [FH/M+]) and in 1605 controls. Coronary artery calcium (CAC) score was also evaluated. ResultsThe PRS was independently associated with LDL-C in control individuals (p < 0.001). Within this group, in individuals in the highest quartile of the 12 SNPs PRS, the odds ratio for CAC score >100 was 1.7 (95% CI: 1.01–2.88, p = 0.04) after adjustment for age and sex. Subjects in the FH/M− group had the highest mean score in both 12 and 6 SNPs PRS (38.25 and 27.82, respectively) when compared to the other two groups (p = 2.2 × 10-16). Both scores were also higher in the FH/M+ group (36.48 and 26.26, respectively) when compared to the control group (p < 0.001 for the two scores) but inferior to the FH/M− group. Within FH individuals, the presence of a higher PRS score was not associated with LDL-C levels or with CAD risk. ConclusionA higher PRS is associated with significantly higher levels of LDL-C and it is independently associated with higher CAC in the Brazilian general population. A polygenic cause can explain a fraction of FH/M− individuals but does not appear to be a modulator of the clinical phenotype among FH individuals, regardless of mutation status.

Residual Risk of Coronary Atherosclerotic Heart Disease and Severity of Coronary Atherosclerosis Assessed by ApoB and LDL-C in Participants With Statin Treatment: A Retrospective Cohort Study.

BackgroundLow-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy on the management of hypercholesterolemia in the United States and European guidelines, while apolipoprotein B (apoB) is the secondary target. The objective was to determine if elevated levels of apoB is superior to LDL-C in assessing residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment.MethodsThis study included 131 participants with statin treatment. The generalized linear model and relative risk regression (generalized linear Poisson model with robust error variance) were used to analyze the association of the levels of apoB and LDL-C with the severity of coronary atherosclerosis and residual risk of coronary atherosclerotic heart disease.ResultsCategorizing apoB and LDL-C based on tertiles, higher levels of apoB were significantly associated with the severity of coronary atherosclerosis (Ptrend = 0.012), whereas no such associations were found for elevated levels of LDL-C (Ptrend = 0.585). After multivariate adjustment, higher levels of apoB were significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level apoB (≤0.66 g/L), the multivariate adjusted RR and 95% CI of intermediate-level apoB (0.67–0.89 g/L) and high-level apoB (≥0.90 g/L) were 1.16 (1.01, 1.33) and 1.31 (1.08, 1.60), respectively (Ptrend = 0.011). There was a 45% increased residual risk of coronary atherosclerotic heart disease per unit increment in natural log-transformed apoB (Ptrend <0.05). However, higher levels of LDL-C were not significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level LDL-C (≤1.56 mmol/L), the multivariate adjusted RR and 95% CI of intermediate-level LDL-C (1.57–2.30 mmol/L) and high-level LDL-C (≥2.31 mmol/L) were 0.99 (0.84, 1.15) and 1.10 (0.86, 1.42), respectively (Ptrend = 0.437). Similar results were observed in the stratified analyses and sensitivity analyses. No significant interactions were detected for both apoB and LDL-C (all Pinteraction >0.05).ConclusionsElevated apoB are superior in assessing the residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment.

Sex Differences in Cardiovascular Prevention in Type 2: Diabetes in a Real-World Practice Database.

Women with type 2 diabetes mellitus (T2DM) have a 40% excess risk of cardiovascular diseases (CVD) compared to men due to the interaction between sex and gender factors in the development, risk, and outcomes of the disease. Our aim was to assess differences between women and men with T2DM in the management and degree of control of cardiovascular risk factors (CVRF). This was a matched cross-sectional study including 140,906 T2DM subjects without previous CVD and 39,186 T2DM subjects with prior CVD obtained from the System for the Development of Research in Primary Care (SIDIAP) database. The absolute and relative differences between means or proportions were calculated to assess sex differences. T2DM women without previous CVD showed higher levels of total cholesterol (12.13 mg/dL (0.31 mmol/L); 95% CI = 11.9–12.4) and low-density lipoprotein cholesterol (LDL-c; 5.50 mg/dL (0.14 mmol/L); 95% CI = 5.3–5.7) than men. The recommended LDL-c target was less frequently achieved by women as it was the simultaneous control of different CVRF. In secondary prevention, women showed higher levels of total cholesterol (16.89 mg/dL (0.44 mmol/L); 95% CI = 16.5–17.3), higher levels of LDL-c (8.42 mg/dL (0.22 mmol/L); 95% CI = 8.1–8.8), and higher levels of triglycerides (11.34 mg/dL (0.13 mmol/L); 95% CI = 10.3–12.4) despite similar rates of statin prescription. Recommended targets were less often achieved by women, especially LDL-c < 100 mg/dL (2.59 mmol/L). The composite control was 22% less frequent in women than men. In conclusion, there were substantial sex differences in CVRF management of people with diabetes, with women less likely than men to be on LDL-c target, mainly those in secondary prevention. This could be related to the treatment gap between genders.

PSRC1 May Affect Coronary Artery Disease Risk by Altering CELSR2, PSRC1, and SORT1 Gene Expression and Circulating Granulin and Apolipoprotein B Protein Levels.

ObjectiveThe aim of the study was to identify additional factors that contributed to coronary artery disease (CAD).MethodsWe conducted integrative analysis on publicly available data from genome-wide association studies and quantitative trait locus studies by employing Mendelian randomization methods to examine the associations of gene expression in liver cells and circulating protein levels with LDL-C and CAD.ResultsWe found that the mRNA expression levels of CELSR2, PSRC1, SORT1, SYPL2, RHD, RHCE, ANGPTL3, ATXN7L2, DNAH11, FADS3, ST3GAL4, NYNRIN, CETP, EFCAB13, and SPTLC3 were significantly associated with LDL-C. The expression levels of SORT1, PSRC1, and CELSR2 in liver cells were significantly associated with CAD. Higher expression levels of SORT1, PSRC1, and CELSR2 in the liver were significantly associated with lower circulating LDL-C levels and CAD risk. PSRC1 variants were strongly associated with SORT1, PSRC1, and CELSR2 gene expression in liver cells. Higher circulating granulin and apolipoprotein B levels, which were strongly affected by PSRC1 variants, were significantly associated with higher LDL-C levels and CAD risk, with odds ratios of 1.15 (1.10–1.19) and 1.45 (1.21–1.74), respectively.ConclusionThis study showed that regulatory SNPs in PSRC1 may affect CAD risk by altering CELSR2, PSRC1, and SORT1 gene expression in liver cells and circulating granulins and apolipoprotein B proteins.

Left Atrial Appendage Thrombus in Patients with Nonvalvular Atrial Fibrillation before Catheter Ablation and Cardioversion: Risk Factors beyond the CHA2DS2-VASc Score.

Left atrial appendage thrombus (LAAT) is a surrogate of thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We aimed to investigate the risk factors for LAAT formation before catheter ablation and cardioversion beside the CHA2DS2-VASc score. In this case-control study, patients with NVAF who underwent transesophageal echocardiography (TEE) were included. Demographic data, laboratory results, and echocardiographic measurements were retrospectively collected. Logistic regression analysis was performed to determine risk factors predicting LAAT. Of the 543 included patients, LAAT was identified in 50 patients (9.2%). Multivariable logistic regression analysis for the entire cohort showed that NT-proBNP (per 500 ng/L increase, OR (95% CI): 1.09 (1.00–1.19), p = 0.038) and LDL-C (per 1 mmol/L increase, OR (95% CI): 1.70 (1.05–2.77), p = 0.032) were independently correlated with the presence of LAAT after the adjustment for CHA2DS2-VASc score and anticoagulant therapy. The subgroup analysis of patients without anticoagulant therapy also yielded similar results. Regarding patients with CHA2DS2-VASc scores ≤ 1, a higher level of LDL-C (per 1 mmol/L increase, OR (95% CI): 6.31 (2.38–16.74), p < 0.001) independently correlated with the presence of LAAT. The present study suggests that beyond CHA2DS2-VASc score, raised NT-proBNP and LDL-C are additional predictors for LAAT in NVAF patients.

Lack of association between methylation status of CpG in the MCP-1 promoter and type 2 diabetes mellitus and its complications in a Moroccan population

BackgroundMonocyte chemoattractant protein −1 (MCP-1) plays an important role in the development of diseases related to metabolic syndromes, such as type 2 diabetes mellitus (T2DM) and its complications. The present study investigates the relationship between the methylation status of CpG sites in the MCP-1 promoter and T2DM and its complications in Morocco. Material and methodsWe conducted a population-based case-control study of 108 T2DM cases and 101 controls. Methylation Specific Polymerase chain reaction (MSP) was used to analyze the MCP-1 methylation profile in leucocyte's DNA. ResultsThis study did not indicate a significant association between the methylation status of CpG sites in the MCP1 promoter and T2DM and its complications (p ˃ 0.05). The hypomethylation profile is significantly associated with higher LDL-C levels (142.37 ± 58.37; p = 0.041) and treatment with antidepressants (18.8%; p = 0.043) in patients with T2DM. The hypermethylation profile is most frequently observed in type 2 diabetic patients with complications and cigarettes smokers (31.6%; p = 0.052). ConclusionResults of our study showed no association between the methylation status of CpG in the MCP-1 promoter and T2DM and its complications in the Moroccan population. However, the methylation status might be related to LDL-C levels, treatment with antidepressants, and smoking status.