Cholesterol Mass Research Articles

The Co-Existence of Hypovitaminosis D and Diabetes Mellitus Triples the Incidence of Severe Coronary Artery Disease in Women.

Background and Aims: Hypovitaminosis D is involved in the development and progression of atherosclerosis, and it is more prevalent in women. The differential impact of hypovitaminosis D on the severity of coronary artery disease (CAD) between genders remains poorly understood. This study aims to address this literature gap. Methods: A total of 1484 consecutive patients with acute myocardial infarction (AMI) were enrolled in the study. Hypovitaminosis D was defined as vitamin D ≤ 20 ng/mL. CAD was defined as the presence of at least one coronary vessel stenosis > 50%, while severe CAD was defined as left main disease and/or three-vessel disease > 50%. Results: The mean age of the cohort was 66.3 (11.5) years, with a predominance of the male gender (71.8%). Vitamin D values were significantly lower in women than in men (15.7 [8.4-25.4] ng/mL vs. 17.9 [11-24.3] ng/mL, p = 0.01). A higher prevalence of severe CAD was observed in female patients with hypovitaminosis D compared to those without (33% vs. 19%, p < 0.01). This finding was not observed in men. Among women, hypovitaminosis D significantly increased the risk of severe CAD (OR: 1.85, p = 0.01), together with diabetes mellitus (DM) and older age, adjusted for GFR < 60 mL/min/1.73 m2, cholesterol and body mass index. Furthermore, women with both hypovitaminosis D and DM had more than three times the risk of severe CAD compared with women who lacked both (OR: 3.56, p = 0.02). Conclusions: In women, hypovitaminosis D increases the risk of severe CAD, and the co-existence of hypovitaminosis D and DM triples the incidence of severe CAD.

Associations of smoking status with long-term cardiovascular events in different arterial territories: the EPIC Norfolk prospective population cohort

Abstract Background Smoking cessation is associated with a reduced risk of cardiovascular disease (CVD) events, mainly in ischemic heart disease (IHD) and stroke. However, the impact of smoking status (never, former or current smoking) on long-term CVD events across different arterial territories remains understudied. Knowledge of such associations is important, as it may assist in risk communication and smoking cessation motivation. We therefore investigated associations between smoking status and territory-specific CVD events in a large cohort with ≥20 years follow-up. Methods We included participants without baseline CVD from the European Prospective Investigation of Cancer (EPIC) Norfolk prospective population cohort. The strengths of associations between smoking, former smoking and never smoking with the first occurrence of a CVD event were evaluated using a competing risk-adjusted regression model. CVD events were defined as hospitalisation or death due to IHD, ischemic stroke, haemorrhagic stroke, peripheral arterial disease (PAD) or aortic aneurysm (AA). Patients were followed-up until the first event, non-CVD death (competing risk) or end of study (15-03-2018). The model was adjusted for sex, age, systolic blood pressure, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), diabetes, renal function and body mass index. We compared former and current smoking (at baseline) with never smoking. Results We included 23,581 participants (56% women) with a median baseline age of 58 years [interquartile range (IQR) 51-66]. During median follow up of 21.3 years (IQR 19.0-22.8), 26.4% experienced ≥1 CVD event. The first event of occurrence was IHD in 17.3%, ischemic stroke in 3.6%, haemorrhagic stroke in 1.4%, PAD in 3.1% and AA in 1.4%. Current (vs. never) smoking was associated with IHD [adjusted hazard rate (aHR) 1.53, 95% confidence interval (CI) 1.36-1.72], PAD (aHR 1.29, 95%CI 1.07-1.56) and AA (aHR 4.81, 95%CI 3.54-6.54). Current smoking was not significantly associated with ischemic stroke (aHR 1.20, 95% CI 0.95-1.52) and haemorrhagic stroke (aHR 1.18, 95% CI 0.81-1.70). In former (vs. never) smoking individuals, the association with AA remained statistically significant but less pronounced [aHR 1.69, 95%CI 1.29-2.23]. Conversely, former smoking was not associated with IHD (aHR 1.07, 95%CI 0.99-1.16) or PAD (aHR 1.09, 95%CI 0.95-1.26) (Figure 1). Conclusion After 20-years of follow-up, former smokers, compared to never-smokers, remain at considerably higher risk for CVD events, particularly for aortic aneurysm. This knowledge may assist in treatment decisions and risk communication.

Effect of incremental exercise training interventions in a Cardiac Rehabilitation Program following myocardial infarction

Abstract Background Exercise-based cardiac rehabilitation is recommended after myocardial infarction (MI) to improve prognosis, quality of life and control of cardiovascular risk factors. However, the specific impact of different exercise training interventions remains incompletely understood. Purpose To study the health outcomes of three incremental exercise training interventions during a Cardiac Rehabilitation Program (CRP) following MI. Methods We implemented a post-MI Phase 2 CRP in 2022. After initial exercise testing, a 3-month, individualized aerobic and strength ambulatory training program was provided by Cardiologists and Physical Medicine and Rehabilitation physicians (Group 1, n=58). Additionally, a subset of patients received one session of supervised teaching of aerobic and strength training by physiotherapists (Group 2, n=19), and another subset received 8-20 sessions of in-hospital supervised training (Group 3, n=13). Exercise testing was repeated at the end of Phase 2 and peak oxygen consumption (peak VO2) was measured. We analysed quality of life (SF-36), depression (PHQ2), anxiety (GAD2), adherence to Mediterranean diet (PREDIMED) and pharmacological treatment (Morisky-Green), and weekly physical activity (IPAQ). Health outcomes were compared at the beginning and after Phase 2 CRP. Results The cohort comprised 90 patients who completed Phase 2 CRP (mean age 61.2±10.8 years, 84.4% male and 47.8% smokers). Reductions in systolic blood pressure (-10.3±13.8mmHg), LDL cholesterol (-60.7±35.4mg/dL), weight (-2.8±6.6kg, -3±7.8%) and body mass index (-1±2.2) were attained (p&amp;lt;0.05). Smoking abstinence was accomplished in 88.4% of smokers and most patients achieved an LDL&amp;lt;55mg/dL (81.1%). Improvements in quality of life (SF-36 +10.4±19.4 points, p&amp;lt;0.001) and anxiety and depression symptoms (PHQ2 -0.5±1.6 points and GAD2 -0.6±1.6 points, p&amp;lt;0.01) were noted. An increase in peak VO2 (+5.12±5.44ml/kg/min, +23.5±27.4% from baseline, p&amp;lt;0.001) and predicted functional capacity (+13.4±23.8%, p&amp;lt;0.001) was achieved. Patients increased their reported weekly physical activity by 2520.3±2935.4 METS/week (+132% from baseline, p&amp;lt;0.001) and most of them were adherent to Mediterranean diet (91.1%) and pharmacological treatment (95.6%). Patients achieved similar health outcomes regardless of their exercise training group, except for patients in Group 3, who experienced a more pronounced improvement in peak VO2 (+8.1±6.4ml/kg/min, +37.8±34.7% from baseline; p&amp;lt;0.05) and a trend towards higher increase in predicted functional capacity (+21.7±19.2%, p&amp;lt;0.25) and greater weight loss (-5.5±9.4kg, -5.9±9.6%; p&amp;lt;0.2). Conclusions Supervised in-hospital training during a Phase 2 CRP provides superior physical fitness improvements and more pronounced weight loss in MI patients. However, a Phase 2 CRP based on ambulatory training provides similar benefits regarding other health outcomes, such as control of cardiovascular risk factors and quality of life amelioration.Exercise training interventions in a CRP

Genetic evidence supporting the causal role of 25-hydroxyvitamin D levels in the prognosis of ER- breast cancer: A Mendelian randomization study.

This study aims to investigate the connection between 25-hydroxyvitamin D (25(OH)D) levels and the prognosis of breast cancer with various estrogen receptor (ER) statuses. The summary statistics of 25(OH)D levels was obtained from a GWAS of 441,291 individuals and the information of breast cancer was collected from the Breast Cancer Association Consortium. We analyzed the causal association between 25(OH)D levels and breast cancer prognosis using a number of approaches, including inverse variance weighting (IVW). The heterogeneity test was performed using Cochran Q test. IVW, Mendelian randomization (MR)-Egger, and MR Pleiotropy RESidual Sum and Outlier methods were used for sensitivity analysis. In addition, a multivariate MR adjusted for total triglycerides, total cholesterol, and body mass index was used for further analysis. Two-sample MR results showed that 25(OH)D levels were not associated with prognosis in overall breast cancer (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.73-1.19, IVW exam) and estrogen receptor positive (ER+) breast cancers (OR = 1.12, 95% CI = 0.77-1.63, IVW exam) and were protective associated with prognosis in estrogen receptor negative (ER-) breast cancers (OR = 0.55, 95% CI = 0.34-0.87, IVW exam). Sensitivity analysis did not observe the presence of heterogeneity and horizontal pleiotropy. In multivariate MR analysis, after adjusting for total triglycerides, total cholesterol, and body mass index, the correlation between the protective relationship between 25(OH)D levels and the prognosis for ER- breast cancer remained and became increasingly significant (OR = 0.51, 95% CI = 0.31-0.83, P = .007). This study demonstrated a protective relationship between 25(OH)D levels and the prognosis of ER- breast cancer, but there was no connection between 25(OH)D levels and the prognosis of ER+ breast cancer.

EEF1A2 identified as a hub gene associated with the severity of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disease that ranges from metabolic dysfunction-associated steatotic liver (MASL) to metabolic dysfunction-associated steatohepatitis (MASH), and may eventually progress to cirrhosis and hepatocellular carcinoma (HCC). The underlying mechanism of MASLD remains incompletely understood. This study aimed to identify key gene implicated in MASLD pathogenesis and validate its correlation with disease severity through an integration of bioinformatics and experimental approaches. Liver transcriptome data from MASLD patients were obtained from the Gene Expression Omnibus (GEO) database. A diet-induced MASLD mouse model was developed, and liver RNA-sequencing was performed. Liver specimens and clinical data from patients were collected for further analysis. A total of 120 differentially expressed genes (DEGs) were shared between datasets GSE89632 and GSE213621, with functional enrichment in inflammatory, metabolic, and cell cycle-related pathways. Protein-protein interaction (PPI) network analysis identified three modules associated with MASLD, with the cell cycle-related module being the most notable. EEF1A2 was identified as a novel hub gene and revealed to be elevated with MASLD progression through dataset analysis. EEF1A2 was confirmed to be highly expressed in the livers of both MASLD mouse models and patients. Moreover, the increased expression of EEF1A2 in MASH was positively correlated with higher serum alanine aminotransferase (ALT), alanine aminotransferase (AST), total cholesterol (TC), and body mass index (BMI). In conclusion, EEF1A2 is a novel hub gene significantly associated with MASLD severity and is a promising biomarker and therapeutic target for MASLD.

The dyslipidemic effect of cytostatics in the treatment of early breast cancer as a serious risk factor of cardiovascular diseases.

The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.

Cardiovascular Risk Factors as Independent Predictors of Diabetic Retinopathy in Type II Diabetes Mellitus: The Development of a Predictive Model.

Background: Diabetic retinopathy (DR) is a leading cause of blindness in patients with type 2 diabetes mellitus (T2DM). Cardiovascular risk factors, such as hypertension, obesity, and dyslipidemia, may play a crucial role in the development and progression of DR, though the evidence remains mixed. This study aimed to assess cardiovascular risk factors as independent predictors of DR and to develop a predictive model for DR progression in T2DM patients. Methods: A retrospective cross-sectional study was conducted on 377 patients with T2DM who underwent a comprehensive eye exam. Clinical data, including blood pressure, lipid profile, BMI, and smoking status, were collected. DR staging was determined through fundus photography and classified as No DR, Non-Proliferative DR (NPDR), and Mild, Moderate, Severe, or Proliferative DR (PDR). A Multivariate Logistic Regression was used to evaluate the association between cardiovascular risk factors and DR presence. Several machine learning models, including Random Forest, XGBoost, and Support Vector Machines, were applied to assess the predictive value of cardiovascular risk factors and identify key predictors. Model performance was evaluated using accuracy, precision, recall, and ROC-AUC. Results: The prevalence of DR in the cohort was 41.6%, with 34.5% having NPDR and 7.1% having PDR. A multivariate analysis identified systolic blood pressure (SBP), LDL cholesterol, and body mass index (BMI) as independent predictors of DR progression (p < 0.05). The Random Forest model showed a moderate predictive ability, with an AUC of 0.62 for distinguishing between the presence and absence of DR XGBoost showing a better performance, featuring a ROC-AUC of 0.68, while SBP, HDL cholesterol, and BMI were consistently identified as the most important predictors across models. After tuning, the XGBoost model showed a notable improvement, with an ROC-AUC of 0.72. Conclusions: Cardiovascular risk factors, particularly BP and BMI, play a significant role in the progression of DR in patients with T2DM. The predictive models, especially XGBoost, showed moderate accuracy in identifying DR stages, suggesting that integrating these risk factors into clinical practice may improve early detection and intervention strategies for DR.

Associations of physical activity, sedentary time, and fitness with cardiovascular risk and atherosclerosis over 3 years in women with systemic lupus erythematosus

IntroductionCardiovascular (CV) diseases are among the main causes of death in systemic lupus erythematosus (SLE). Physical activity (PA) and fitness are potential protective factors against the progression of CV risk factors and atherosclerosis. AimTo analyze trends over time in PA, sedentary time (ST) and physical fitness and their associations of with traditional and novel markers of CV risk and subclinical atherosclerosis in women with SLE over a 3-year follow-up period. MethodsIn this exploratory study, 77 White Hispanic women with SLE (43.3±13.8 years) with mild disease activity were followed after 3 years (n=44). HDL and LDL cholesterol (blood samples), BMI and muscle mass (stadiometer and bioimpedance device), blood pressure (BP), pulse wave velocity (PWV, Mobil-O-Graph® monitor), carotid plaques and intima–media thickness (General Electric Medical Systems, LOGQ-6 model) were assessed. PA and ST were measured using triaxial accelerometers. Physical fitness was assessed with the back-scratch, handgrip strength, 30-s chair stand, and 6-min walk, tests. ResultsAfter 3 years, LDL-c (estimated mean change [est]=13.77mg/dL) and PWV (0.13m/s) increased while diastolic BP (−2.80mmHG) decreased (all, p<0.05). In mixed models, 6-min walk test was positively associated with HDL-c (est=0.07); back scratch (est=0.33) and chair-stand (est=1.19) tests were positively associated with systolic BP (all, p<0.05). No other trends or associations over time were identified (all, p>0.05). ConclusionsPA, ST, fitness, and most studied CV risk factors remained stable over time, with only marginal changes in LDL-c, PWV, and diastolic BP. Overall, PA and ST were not longitudinally associated with CV risk factors and subclinical atherosclerosis and contradictory weak associations were found for physical fitness.

Associations of disordered eating and unhealthy weight control behaviors with cardiovascular health: The coronary artery risk development in young adults study.

Few studies have investigated disordered eating and unhealthy weight control behaviors and cardiovascular health (CVH) outside of adolescence and early adulthood. We examined the cross-sectional and prospective associations of these behaviors and CVH in middle adulthood. A total of 2,095 Coronary Artery Risk Development in Young Adults participants were assessed at Year 10 (Y10, 1995-1996) and Year 30 (Y30, 2015-2016). The Y10-administered Questionnaire on Eating and Weight Patterns-Revised was used to create the problematic relationship to eating and food (PREF) score (range 0-8). Higher scores indicated greater disordered eating and/or unhealthy weight control behaviors across eight components. PREF was modeled categorically: 0-1 (reference), 2-3, and 4-8. Diet, physical activity, smoking, blood pressure, cholesterol, glucose, and body mass index (BMI) were measured at Y10 and Y30 (diet at Y7 and Y20) and used to define CVH. CVH was modeled categorically: poor-to-intermediate (0-9) and ideal (10-14; reference). Logistic regression was used to evaluate associations between PREF and CVH categories and components. PREF 4-8 was associated with Y10 poor-to-intermediate CVH (OR = 2.35, 95% confidence interval (CI) [1.78, 3.10]) but not Y30 (OR = 1.34, 95% CI [0.96, 1.87]) compared to PREF 0-1. PREF 2-3 was not associated with Y10 or Y30 CVH. Individual PREF components were not uniformly associated with individual CVH components, although all PREF components were associated with Y10 poor-to-intermediate BMI. Disordered eating and unhealthy weight control behaviors are cross-sectionally but not prospectively associated with poorer CVH during middle age. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effect of Substitution of Beef and Broiler Meat with Tuna Meat on Chemical and Sensory Quality of Meatballs.

Tuna meat is rich in protein and polyunsaturated fatty acids (PUFA), but low in cholesterol and fat, which makes it an excellent candidate for replacing beef and broiler chicken to produce higher quality meatballs. The aim of this study is to determine how substituting beef and broiler meat with tuna meat affects the chemical and sensory characteristics of meatballs. In this study, 1000 g of meatballs were prepared from 60 % of beef or broiler chicken. Each meat was replaced with tuna meat at mass fractions of 0, 20 and 40 %. The meat was finely ground and mixed with mass fractions (in %) of: tapioca flour 20, garlic 1.2, salt 2, ground pepper 0.5, egg white 0.3 and ice cubes 16. The tested variables included the chemical quality (moisture, protein, fat, ash, cholesterol and fatty acids) and sensory quality (colour, aroma, elasticity, texture and taste) of the meatballs. The data obtained were statistically analysed using a completely randomised factorial design analysis of variance. The results show that increasing the mass fraction of tuna as a substitute for beef and broiler meat significantly increased (p<0.01) the moisture, protein and PUFA mass fractions and colour, but decreased (p<0.01) the cholesterol and fat mass fraction of the meatballs. A significant interaction (p<0.01) was observed between the tuna mass fraction and the type of meat, which affected the mass fractions of moisture, protein, cholesterol and fat as well as colour of the meatballs. In particular, increasing the tuna mass fraction to 40 % significantly increased (p<0.01) the moisture mass fraction of the beef meatballs, as well as the protein mass fraction and colour of the beef and chicken meatballs. However, the moisture mass fraction of chicken meatballs and the fat and cholesterol mass fraction of beef and chicken meatballs decreased significantly (p<0.01). In conclusion, replacing 40 % of beef and chicken meatballs with tuna can improve protein content and colour, and reduce fat and cholesterol content. These results suggest that tuna can be used as a substitute for beef and chicken to produce higher quality meatballs that are rich in protein but low in cholesterol and fat. This approach can also be applied to other processed meat products such as sausages and nuggets to improve their nutritional quality.

The Impact of Clinical Pharmacists on Cardiovascular Disease Management in Spain: A Community Pharmacy-Based Intervention Study

Background: Cardiovascular Disease (CVD) is a significant global health concern, causing 17.3 million deaths annually. In Spain, CVD accounts for 14.6% of mortality, necessitating effective management strategies. Clinical Pharmacists (CPs) have emerged as crucial players in early CVD identification and management, particularly through community pharmacies. Methods: This study enrolled 900 individuals across 55 pharmacies, with 820 meeting inclusion criteria based on existing CVD risk factors. Participants were randomly assigned to either a control group receiving standard treatment (n = 353) or an intervention group receiving enhanced guidance from CPs (n = 375). Outcomes measured included changes in CVD risk factors, blood pressure, lipid profiles, and smoking cessation over a three-month period. Results: The intervention group exhibited a statistically significant reduction in projected CVD risk, with a mean decrease of 6.42% (p &lt; 0.001). Improvements were noted in LDL cholesterol, blood pressure, and body mass index in both groups, underscoring the effectiveness of CP-led interventions. No adverse events were reported. Conclusion: CPs play a vital role in managing CVD risk factors through education, counseling, and medication management. This study highlights the effectiveness of CP interventions in community pharmacy settings, emphasizing the need for further research to evaluate long-term clinical and humanistic outcomes. Expanding the role of CPs in the healthcare system could significantly alleviate the burden of CVD in Spain.

Comprehensive Genetic Analysis of Associations between Obesity-Related Parameters and Physical Activity: A Scoping Review.

Genetic epidemiological studies have shown that numerous genetic variants cumulatively increase obesity risk. Although genetically predisposed individuals are more prone to developing obesity, it has been shown that physical activity can modify the genetic predisposition to obesity. Therefore, genetic data obtained from earlier studies, including 30 polymorphisms located in 18 genes, were analyzed using novel methods such as the total genetic score and Biofilter 2.4 software to combine genotypic and phenotypic information for nine obesity-related traits measured before and after the realization of the 12-week training program. The results revealed six genes whose genotypes were most important for post-training changes-LEP, LEPR, ADIPOQ, ADRA2A, ADRB3, and DRD2. Five noteworthy pairwise interactions, LEP × LEPR, ADRB2 × ADRB3, ADRA2A × ADRB3, ADRA2A × ADRB2, ADRA2A × DRD2, and three specific interactions demonstrating significant associations with key parameters crucial for health, total cholesterol (TC), high-density lipoprotein (HDL), and fat-free mass (FFM), were also identified. The molecular basis of training adaptation described in this study would have an enormous impact on the individualization of training programs, which, designed according to a given person's genetic profile, will be effective and safe intervention strategies for preventing obesity and improving health.

Remnant cholesterol, LDL cholesterol, and APOB absolute mass changes explain results of prominent and other fibrate trials

Remnant cholesterol, LDL cholesterol, and APOB absolute mass changes explain results of prominent and other fibrate trials

The diabetic parkinsonian – the association of diabetes mellitus comorbidity and symptoms of Parkinson’s disease

Introduction and objective: Many studies have investigated the interplay between Parkinson’s disease and diabetes mellitus, suggesting that glucose metabolism impairment may worsen the clinical course of Parkinson’s disease. This study aimed to explore the association between diabetes mellitus and the course of Parkinson’s disease. Materials and methods: A retrospective study was performed by analysing the clinical data of patients diagnosed with Parkinson’s disease who were hospitalised in University Clinical Centre of the Medical University of Silesia from 2019 to 2021. The study group comprised 241 patients selected according to the study’s inclusion and exclusion criteria. Their clinical conditions were assessed using body mass index, the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Hoehn–Yahr scale, Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT) and Beck Depression Inventory (BDI). Data were collected on current anti-parkinsonian treatment, fasting glycaemia, lipid panel, and thyroid stimulating hormone, homocysteine and vitamin D3 levels. Results: The study group included 31 patients diagnosed with diabetes mellitus and 240 patients without glucose metabolism impairment. Both groups were matched by considering age, disease duration, and gender distribution. Diabetic patients displayed a higher MDS-UPDRS part III OFF rating (42 [31–55] vs. 48 [39–59]; p = 0.0043), higher MDS-UPDRS part III ON rating (17 [11–26] vs. 26.5 [19–32]; p = 0.0009) and higher BDI score (7 [4–11] vs. 11 [9–16]; p = 0.0013). As expected, patients with diabetes mellitus had a higher fasting glycaemia, total cholesterol, lower high-density lipoprotein cholesterol and higher body mass index. Conclusions: Our study confirms the relationship between diabetes mellitus and a worse clinical course for Parkinson’s disease.

Cardiometabolic Profile in Young Adults With Diverse Cigarette Smoking Histories: A Longitudinal Study From Adolescence.

For the first time, the present study investigated smoking trajectory and cardiometabolic profile from adolescence to young adulthood in a middle-income developing country facing a high prevalence of smoking and cardiovascular disease-related outcomes. Data on 1082 adolescents (12-18 years of age) who participated in the TLGS (Tehran Lipid and Glucose Study) were gathered,and participants were followed for a median of 12.5 years (baseline: 1999-2002, last follow-up: 2014-2017). Participants were categorized as non/rare smokers, experimenters, and escalators using group-based trajectory models. Statistical analysis was used to compare the trajectory groups' cardiometabolic components, clinical characteristics, and cardiometabolic changes due to the individuals' placement in experimenter and escalator groups compared with non/rare smokers. The smoking trajectory groups in young adulthood differ significantly in blood pressure, triglycerides, high-density lipoprotein cholesterol, waist circumference, and body mass index, with the escalator group having the highest risk values for each component. Significant differences were observed in blood pressure (P=0.014), triglycerides (P<0.001), and waist circumference (P<0.001) status after using clinical cut points. The adjusted linear regression revealed that the escalator group had 3.16 mm Hg-lower systolic blood pressure SBP (P=0.016), 2.69 mm Hg-lower diastolic blood pressure (P=0.011), and 4.42 mg/dL-lower high-density lipoprotein cholesterol (P=0.002), compared with the non/rare smoker group. Despite elevated risks in unadjusted analyses for all cardiometabolic components among smokers, our study identified a modest protective link between early smoking and blood pressure in addition to a remarkable harmful association with high-density lipoprotein cholesterol levels exclusively in the escalator group during the developmental stage to young adulthood, using adjusted analyses.

Life’s Essential 8 is inversely associated with high-sensitivity C-reactive protein

Life’s Essential 8 (LE8) is a score that includes modifiable risk factors for cardiovascular disease. Four health behaviors (diet, physical activity, nicotine exposure and sleep health) and four health factors (non-HDL cholesterol, blood glucose, blood pressure and body mass index) are included. These modifiable risk factors promote inflammation, and inflammation is one of the biological mechanisms of cardiovascular disease development. Thus, we examined the relationship between cardiovascular health measured by LE8 and low-grade inflammation measured by high-sensitivity C-reactive protein (hs-CRP) in the cross-sectional population-based Swedish CArdioPulmonary bioImage Study (SCAPIS). The study consisted of 28,010 participants between 50 and 64 years (51.5% women, mean age 57.5 years). All individual LE8 components were assigned a score between 0 (unhealthy) and 100 (healthy) points, and a global score was calculated. The association between LE8 scores and high-risk hs-CRP (defined as > 3.0 mg/L) was analyzed using adjusted logistic regression with spline analyses. There was a strong, dose response and inverse association between LE8 scores and levels of hs-CRP. Thus, those with a low LE8 score (= 50.0 points) had 5.8 higher (95% confidence interval [CI] 5.2–6.4) odds ratio (OR) of having high hs-CRP as compared to those with a high LE8 score (= 80.0 points). In conclusion, our findings show strong inverse associations between LE8 scores and levels of hs-CRP.

Estimating Risk Factor Time Paths Among People with Type 2 Diabetes and QALY Gains from Risk Factor Management.

Most type 2 diabetes simulation models utilise equations mapping out lifetime trajectories of risk factors [e.g. glycated haemoglobin (HbA1c)]. Existing equations, using historic data or assuming constant risk factors, frequently underestimate or overestimate complication rates. Updated risk factor time path equations are needed for simulation models to more accurately predict complication rates. (1) Update United Kingdom Prospective Diabetes Study Outcomes Model (UKPDS-OM2) risk factor time path equations; (2) compare quality-adjusted life-years (QALYs) using original and updated equations; and (3) compare QALY gains for reference case simulations using different risk factor equations. Using pooled contemporary data from two randomised trials EXSCEL and TECOS (n = 28,608), we estimated: dynamic panel models of seven continuous risk factors (high-density lipoprotein cholesterol, low density lipoprotein cholesterol, HbA1c, haemoglobin, heart rate, blood pressure and body mass index); two-step models of estimated glomerular filtration rate; and survival analyses of peripheral arterial disease, atrial fibrillation and albuminuria. UKPDS-OM2-derived lifetime QALYs were extrapolated over 70 years using historical and the new risk factor equations. All new risk factor equation predictions were within 95% confidence intervals of observed values, displaying good agreement between observed and estimated values. Historical risk factor time path equations predicted trial participants would accrue 9.84 QALYs, increasing to 10.98 QALYs using contemporary equations. Incorporating updated risk factor time path equations into diabetes simulation models could give more accurate predictions of long-term health, costs, QALYs and cost-effectiveness estimates, as well as a more precise understanding of the impact of diabetes on patients' health, expenditure and quality of life. ClinicalTrials.gov NCT01144338 and NCT00790205.

Cumulative effect of metabolic risk factors on left ventricular geometry in those with versus without early-onset type 2 diabetes or prediabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) study.

To investigate metabolic risk factors (RFs) that accumulated over 20 years related to left ventricular mass index (LVMI), relative wall thickness (RWT) and LV remodelling patterns in participants with versus without early-onset type 2 diabetes (T2D) or prediabetes (pre-D). A total of 287 early-onset T2D/pre-D individuals versus 565 sociodemographic-matched euglycaemic individuals were selected from the Coronary Artery Risk Development in Young Adults (CARDIA) study, years 0-25. We used the area under the growth curve (AUC) derived from quadratic random-effects models of four or more repeated measures of RFs (fasting glucose [FG], insulin, triglycerides [TG], low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-c), total cholesterol (total-c), blood pressure and body mass index) to estimate the cumulative burden, and their associations with LV outcomes. One standard deviation greater AUC of log (TG) (per 0.48) and HDL-c (per 13.5 mg/dL) were associated with RWT (β 0.21 and -0.2) in the early-onset T2D/pre-D group, but not in the euglycaemia group (β 0.01 and 0.05, P interactions .02 and .03). In both the early-onset T2D/pre-D and euglycaemia groups, greater AUCs of log (FG) (per 0.17) and log (insulin) (per 0.43) were associated with higher RWT (β ranges 0.12-0.24). Greater AUCs of systolic blood pressure (per 10 mmHg) and diastolic blood pressure (per 7.3 mmHg) were associated with higher RWT and LVMI, irrespective of glycaemic status (β ranges 0.17-0.28). Cumulative TG (odds ratio 3.4, 95% confidence interval: 1.8-6.3), HDL-c (0.23, 0.09-0.59), total-c (1.9, 1.1-3.1) and FG (2.2, 1.25-3.9) were statistically associated with concentric hypertrophy in the T2D/pre-D group only. Sustained hyperglycaemia and hyperinsulinaemia are associated with RWT, and those individuals with early T2D/pre-D are potentially at greater risk because of their higher levels of glucose and insulin. Dyslipidaemia was associated with LV structural abnormalities in those individuals with early-onset T2D/pre-D.

The Prevalence and Epidemiological Features of Ischaemic Heart Disease in Sri Lanka.

There is limited evidence on the prevalence of ischaemic heart disease (IHD) and its association with risk factors and socioeconomic status (SES) in low- and middle-income countries (LMICs). Given the relatively high levels of access to healthcare in Sri Lanka, the association of IHD with SES may be different from that observed in other LMICs. To estimate the prevalence of IHD in Sri Lanka, determine its associated risk factors and its association with SES. We analysed data from 6,513 adults aged ≥18 years examined in the 2018/19 Sri Lanka Health and Ageing Study. We used the Rose angina questionnaire to classify participants as having angina (Angina+) and used self-report or medical records to identify participants with a history of IHD (History+). The association of Angina+ and History+ with age, ethnicity, sector of residence, education level, household SES wealth quintile, area SES wealth quintile, hypertension, diabetes, smoking, total cholesterol, cholesterol-to-HDL ratio, waist-to-hip ratio and body mass index were analysed in unadjusted and adjusted models. Additional analyses were performed to investigate sensitivity to correction for missing data and to benchmark estimates against evidence from other studies. We estimated prevalence of History+ of 3.9% (95% CI 3.3%-4.4%) and Angina+ of 3.0% (95% CI 2.4%-3.5%) in adults aged 18 years and over. The prevalence of Angina+ was higher in women than men (3.9% vs. 1.9%, p < 0.001) whilst prevalence of History+ was lower (3.8% vs. 4.0%, p = 0.8), which may suggest a higher rate of undiagnosed IHD in women. A history of IHD was strongly associated with age, hypertension and diabetes status even after adjusting for sociodemographic factors. Though the prevalence of History+ was higher in the most developed area SES tertile and urban areas, History+ was also associated with less education but not household SES, consistent with patterns emerging from other LMICs.

Abstract 1056: Overexpression Of Lysosomal Acid Lipase

Background: Previous evidence suggests arterial smooth muscle cells (SMCs) comprise the majority of atherosclerotic lesion foam cells in human and mouse atheromas, have reduced expression of ABCA1 and lysosomal acid lipase (LAL) compared to macrophages, and retain cholesteryl esters in lysosomes rather than in the cytoplasm as in macrophage foam cells. Exogenous LAL can increase cholesterol efflux from SMC foam cells despite low ABCA1. Hypothesis: Overexpression of LAL increases cholesterol efflux from SMC foam cells by ABCA1-dependent and -independent mechanisms. Methods: Human vascular SMCs were transfected with 500 MOI AdV- LIPA or AdV- mCherry (adenovirus) control for 6 h and cholesterol loaded using 100 μg/ml aggregated LDL (agLDL) for 24 h. LAL activity was measured by specific enzymatic assay and location of stored cholesteryl esters (CE) was determined using LAMP-1 (lysosome marker) and BODIPY (neutral lipid) staining by confocal microscopy. Cholesterol efflux to 10 μg/ml apoliprotein A-I (ApoA-I) or 100 μg/ml HDL was determined following ABCA1 siRNA treatment or control, with cholesterol mass determined using Amplex Red assay. Student’s t test was used for statistical analysis of LAL activity, and Mann-Whitney U Test for analysis of colocalization of lipid pools. Results: LAL activity increased 1.67-fold 72 h after transfection with AdV- LIPA compared to SMCs transfected with AdV- mCherry (n=5, p = 0.001). Increased LAL expression in the absence of cholesterol acceptor resulted in a shift in CE storage from lysosomes to non-lysosomal compartments (Pearson correlation coefficient for BODIPY/LAMP-1 colocalization 0.27 in AdV- LIPA vs. 0.47 in AdV- mCherry SMCs, n=103, p &lt; 0.00001). Preliminary cholesterol efflux studies indicate SMCs overexpressing LAL release cholesterol by both ABCA1-dependent and -independent mechanisms. Conclusion: Our study provides evidence that despite low ABCA1 and LAL expression, SMC foam cells mobilize lysosomal cholesterol for cellular trafficking and efflux following supplementation with LAL. Further studies will examine changes in gene expression and the mechanism of ABCA1-independent efflux following LAL supplementation in SMC foam cells.