Impacts of ABCG2 loss of function variant (p. Gln141Lys, c.421 C > A, rs2231142) on lipid levels and statin efficiency: a systematic review and meta-analysis.

BACKGROUND: The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency. METHODS: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023. RESULTS: Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals. CONCLUSIONS: The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia.

Impact of LDLR polymorphisms on lipid levels and atorvastatin's efficacy in a northern Chinese adult Han cohort with dyslipidemia.

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

Role of statins in the management of dyslipidaemia.

Blood cholesterol has firmly been established as a crucial risk factor for the development of atherosclerotic cardiovascular disease (ASCVD) by elegant epidemiological studies. Naturally, means to reduce blood cholesterol level took the centerstage of research in this field. After initial lukewarm results with nicotinic acid, fibrates and some other agents, statins emerged as the most effective class of medicine to reduce blood cholesterol; in particular, the most atherogenic low density lipoprotein cholesterol (LDL-C). Also, they are very safe and well tolerated. As ASCVD comes in various stages, statins have also been tried in different settings, e.g., primary prevention, secondary prevention, as part of coronary intervention strategy, familial hypercholesterolemia, etc. Almost in all clinical scenarios, statins proved themselves to impart clinical benefit. Though side effects of statins are outweighed by their benefits, nonetheless clinicians should detect the side effects early to avoid major problems.

Dyslipidemia and heart failure: current evidence and perspectives of use of statins.

Heart failure (HF) is a condition with growing morbidity and mortality. Dyslipidemia in HF is not concentrated around hypercholesterolemia as in coronary artery disease. As a corollary, the robust benefits seen with statins across the spectrum of CAD have not been replicated in HF. Multiple potential pleiotropic effects of statins include anti-inflammatory, antioxidant, endothelial stabilization, antiapoptotic, anti-thrombotic, and modulation of the autonomic system apart from lipid lowering. These benevolent actions need to be counterbalanced with the potential derangement of ubiquinone, selenoprotein and endotoxin pathways. While small randomized and non-randomized studies demonstrated a multitude of benefits in clinical and surrogate endpoints, two large RCTs failed to demonstrate unequivocal benefits. However, multiple large meta-analyses do demonstrate definite improvement in clinical endpoints including death and heart failure hospitalization. The clinical likelihood of benefit was higher in younger patients with less advanced HF and use of lipophilic statins.

Effects of statins beyond lipid-lowering agents in ART-treated HIV infection.

Antiretroviral therapies (ART) have reduced human immunodeficiency virus (HIV) infection-associated morbidity and mortality improving the life of people with HIV (PWH). However, ART lead to residual HIV production, which in conjunction with microbial translocation and immune dysfunction contributes to chronic inflammation and immune activation. PWH on ART remain at an increased risk for cardiovascular diseases (CVDs) including myocardial infarction and stroke; which in part is explained by chronic inflammation and immune activation. Lifestyle factors and certain ART are associated with dyslipidemia characterized by an increase of low-density lipoprotein (LDL), which further contributes in the increased risk for CVDs. Lipid-lowering agents like statins are emerging as immune modulators in decreasing inflammation in a variety of conditions including HIV. The international randomized clinical trial REPRIEVE has shed light on the reduction of CVDs with statin therapy among PWH. Such reports indicate a more than expected benefit of statins beyond their lipid-lowering effects. Bempedoic acid, a first-in-class non-statin LDL-lowering drug with immune modulatory effects, may further aid PWH in combination with statins. Herein, we critically reviewed studies aimed at lipid-lowering and immune-modulating roles of statins that may benefit aging PWH.

Prevalence and management of dyslipidemia in primary care practices in Canada.

OBJECTIVE: To estimate the prevalence of dyslipidemia and to describe its management in Canadian primary care. DESIGN: Retrospective cohort study using primary care electronic medical record data. SETTING: Canada. PARTICIPANTS: Adults aged 40 years or older who saw a Canadian Primary Care Sentinel Surveillance Network contributor between January 1, 2018, and December 31, 2019. MAIN OUTCOME MEASURES: Presence or absence of dyslipidemia as identified by a validated case definition and the treatment status of patients identified as having dyslipidemia based on having been prescribed a lipid-lowering agent (LLA). RESULTS: In total, 50.0% of the 773,081 patients 40 years of age or older who had had a primary care visit in 2018 or 2019 were identified as having dyslipidemia. Dyslipidemia was more prevalent in patients 65 or older (61.5%), in males (56.7%) versus females (44.7%), and in those living in urban areas (50.0%) versus rural areas (45.2%). In patients with documented dyslipidemia, 42.8% had evidence of treatment with an LLA. Stratifying patients by Framingham risk score revealed that those in the high-risk category were more likely to have been prescribed an LLA (65.0%) compared with those in the intermediate-risk group (48.7%) or the low-risk group (22.8%). The strongest determinants of receiving LLA treatment for dyslipidemia include sex, with males being 1.95 times more likely to have been treated compared with females (95% CI 1.91 to 1.98; P<.0001); and body mass index, with those with obesity having a significantly increased likelihood of being treated with an LLA (adjusted odds ratio of 1.36, 95% CI 1.32 to 1.41; P<.0001). CONCLUSION: This study provides an updated look at the prevalence and treatment of dyslipidemia among Canadians. Half of patients aged 40 years or older have dyslipidemia, with an even higher prevalence observed among adults aged 65 years or older, males, and those with obesity or other chronic conditions. There are still gaps in treatment among those with documented dyslipidemia, principally among those calculated to have high or intermediate Framingham risk scores. Particular attention should also be paid to those at higher risk for not receiving treatment, including female patients and those within normal body mass index ranges.

The Significance of Lipoproteins in the Development of Obesity.

Disruption of lipoprotein metabolism plays an important role in the development of several cardiovascular, inflammatory, and metabolic diseases. This review examines the importance of different types of lipoproteins and the role they play in the development of dyslipidemia in obesity. The causes and consequences associated with the disruption of lipid metabolism and its significance in the pathogenesis of obesity are considered. The relationship between such pathological processes, which occur alongside obesity as dyslipidemia and inflammation, is determined. In view of the current efficacy and toxicity limitations of currently approved drugs, natural compounds as potential therapeutic agents in the treatment of obesity are considered in the review. The complex mechanisms of lipid metabolism normalization in obesity found for these compounds can serve as one of the confirmations of their potential efficacy in treating obesity. Nanoparticles can serve as carriers for the considered drugs, which can improve their pharmacokinetic properties.

The impact of the 2019 ESC/EAS dyslipidaemia guidelines on real-world initial lipid-lowering therapy in patients with acute myocardial infarction.

This study aimed to investigate the impact of the latest guidelines on the real-world clinical practice of initial lipid-lowering therapy, especially on the use of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in China. All adult patients diagnosed with acute myocardial infarction in our hospital between August 31, 2018, and August 31, 2020, were divided into the following 2 groups: those patients treated before the latest guideline release, and those patients treated after the release. A propensity score-matched method was used, and logistic regression was used to assess the association with intensive statin, ezetimibe and PCSK9 inhibitor usage together with treatment results between the 2 groups. A total of 325 patients were enrolled in this study, including 141 patients who were admitted before the release of the latest guideline and 184 patients who were admitted after the release. After a median follow-up time of 8.20 months, the mean low-density lipoprotein cholesterol was 1.87 ±â€…0.59 mmol/L (1.87 ±â€…0.55 in the before group vs 1.88 ±â€…0.62 in the after group, P = .829). After propensity score matching, the initial usage of intensive statin therapy was decreased after guideline release without statistical significance (17.00% vs 28.00%, P = .090), whereas the usage of ezetimibe and PCSK9 inhibitors was increased (19.00% vs 8.00%, P = .039; and 10.00% vs 3.00%, P = .085, respectively). In logistic regression models, the release of the guideline was associated with a statistically significantly increased use of ezetimibe (odds ratio [OR]: 1.91; 95% confidence interval [CI]: 1.21, 3.02; P = .005), a marginally decreased use of intensive statins (OR: 0.68; 95% CI: 0.45, 1.03; P = .069) and a marginally increased use of PCSK9 inhibitors (OR: 1.31; 95% CI: 0.98, 1.76; P = .068). In this single-center, real-world data analysis, after the release of the 2019 European Society of Cardiology/European Atherosclerosis Society guidelines, an increasing number of patients with a recent acute myocardial infarction were initially receiving ezetimibe and PCSK9 inhibitors.

Optimal Medical Therapy for Stable Ischemic Heart Disease in 2024: Focus on Blood Pressure and Lipids.

Hypertension and dyslipidemia are 2 highly prevalent and modifiable risk factors in patients with stable ischemic heart disease. Multiple lines of evidence demonstrate that lowering blood pressure and low-density lipoprotein cholesterol improves clinical outcomes in patients with ischemic heart disease. Accordingly, clinical guidelines recommend intensive treatment targets for these high-risk patients. This article summarizes the pathophysiology, supporting evidence, and treatment recommendations for management of hypertension and dyslipidemia among patients with manifest ischemic heart disease and points to future research and unmet clinical needs.

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon-like peptide 1.

Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat-regulating peptides such as GLP-1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP-1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP-IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton-induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co-administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and ß-hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high-fat diet (HFD)-fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP-1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.

Intensity of statin therapy and primary prevention of cardiovascular in Korean patients with dyslipidemia.

This study aimed to investigate the association between the intensity of statin therapy and the development of cardiovascular disease (CVD) and diabetes in individuals without prior diabetes who were being treated for dyslipidemia with statins for the primary prevention of CVD, using the National Health Insurance Service-Health Screening database. The database is a longitudinal cohort study of Korean men and women 40 years of age or older who underwent comprehensive biannual screening health examinations by Korean National Health Insurance Service from January 1, 2002, to December 31, 2015. We included patients in the health screening checkup cohort who underwent health checkups in 2009 and 2010.The primary outcome was the occurrence of a first major cardiovascular or cerebrovascular event, new-onset diabetes. A total of 20,322 participants without prior diabetes at baseline from 2009 to 2015 were followed up for a mean duration of 81.2 ±â€…6.6 months. The mean age of all participants at baseline was 59.2 ±â€…8.4 years and 43.0% of them were male. Their index low lipoprotein cholesterol level was 130.4 ±â€…mg/dL, the mean duration of taking statins was 337.4 ±â€…52.3 days, and 93.9% of them had been taking moderate-intensity statins. At that time, a total of 641 diabetes cases occurred, 41 from using low-intensity statins, 588 from moderate-intensity statins, and 11 from high-intensity statins. The results indicated no significant differences in the incidence of death, CVD death, or CVD among those in the strong statin group compared with the reference groups. While statin treatment for the primary prevention of CVD in patients with dyslipidemia showed a subtle difference in the incidence of diabetes, there was no difference in the occurrence of CVD or CVD death according to statin intensity.

Contrast-specific propensity scores for causal inference with multiple interventions.

Existing methods that use propensity scores for heterogeneous treatment effect estimation on non-experimental data do not readily extend to the case of more than two treatment options. In this work, we develop a new propensity score-based method for heterogeneous treatment effect estimation when there are three or more treatment options, and prove that it generates unbiased estimates. We demonstrate our method on a real patient registry of patients in Singapore with diabetic dyslipidemia. On this dataset, our method generates heterogeneous treatment recommendations for patients among three options: Statins, fibrates, and non-pharmacological treatment to control patients' lipid ratios (total cholesterol divided by high-density lipoprotein level). In our numerical study, our proposed method generated more stable estimates compared to a benchmark method based on a multi-dimensional propensity score.

Dyslipidemia in American Indian Adolescents and Young Adults: Strong Heart Family Study.

BACKGROUND: Although many studies on the association between dyslipidemia and cardiovascular disease (CVD) exist in older adults, data on the association among adolescents and young adults living with disproportionate burden of cardiometabolic disorders are scarce. METHODS AND RESULTS: The SHFS (Strong Heart Family Study) is a multicenter, family-based, prospective cohort study of CVD in an American Indian populations, including 12 communities in central Arizona, southwestern Oklahoma, and the Dakotas. We evaluated SHFS participants, who were 15 to 39 years old at the baseline examination in 2001 to 2003 (n=1440). Lipids were measured after a 12-hour fast. We used carotid ultrasounds to detect plaque at baseline and follow-up in 2006 to 2009 (median follow-up=5.5 years). We identified incident CVD events through 2020 with a median follow-up of 18.5 years. We used shared frailty proportional hazards models to assess the association between dyslipidemia and subclinical or clinical CVD, while controlling for covariates. Baseline dyslipidemia prevalence was 55.2%, 73.6%, and 78.0% for participants 15 to 19, 20 to 29, and 30 to 39 years old, respectively. Approximately 2.8% had low-density lipoprotein cholesterol ≥160 mg/dL, which is higher than the recommended threshold for lifestyle or medical interventions in young adults of 20 to 39 years old. During follow-up, 9.9% had incident plaque (109/1104 plaque-free participants with baseline and follow-up ultrasounds), 11.0% had plaque progression (128/1165 with both baseline and follow-up ultrasounds), and 9% had incident CVD (127/1416 CVD-free participants at baseline). Plaque incidence and progression were higher in participants with total cholesterol ≥200 mg/dL, low-density lipoprotein cholesterol ≥160 mg/dL, or non-high-density lipoprotein cholesterol ≥130 mg/dL, while controlling for covariates. CVD risk was independently associated with low-density lipoprotein cholesterol ≥160 mg/dL. CONCLUSIONS: Dyslipidemia is a modifiable risk factor that is associated with both subclinical and clinical CVD, even among the younger American Indian population who have unexpectedly high rates of significant CVD events. Therefore, this population is likely to benefit from a variety of evidence-based interventions including screening, educational, lifestyle, and guideline-directed medical therapy at an early age.

Monoclonal antibodies for dyslipidemia in adults: a focus on vulnerable patients groups.

INTRODUCTION: Dyslipidemia significantly contributes to atherosclerotic cardiovascular disease (ASCVD). Patients with lipid-rich vulnerable plaques are particularly susceptible to cardiovascular complications. Despite available lipid-lowering therapies (LLTs), challenges in effective lipid management remain. AREAS COVERED: This article reviews monoclonal antibody (mAb) therapy in dyslipidemia, particularly focusing on vulnerable plaques and patients. We have reviewed the definitions of vulnerable plaques and patients, outlined the efficacy of traditional LLTs, and discussed in-depth the mAbs targeting PCSK9. We extensively discuss the potential mechanisms, intracoronary imaging, and clinical evidence of PCSK9mAbs in vulnerable plaques and patients. A brief overview of promising mAbs targeting other targets such as ANGPTL3 is also provided. EXPERT OPINION: Research consistently supports the potential of mAb therapies in treating adult dyslipidemia, particularly in vulnerable patients. PCSK9mAbs are effective in regulating lipid parameters, such as LDL-C and Lp(a), and exhibit anti-inflammatory and anti-thrombotic properties. These antibodies also maintain endothelial and smooth muscle health, contributing to the stabilization of vulnerable plaques and reduction in adverse cardiovascular events. Future research aims to further understand PCSK9 and other targets like ANGPTL3, focusing on vulnerable groups. Overall, mAbs are emerging as a promising and superior approach in dyslipidemia management and cardiovascular disease prevention.

The Current and Emerging Role of Statins in the Treatment of PCOS: The Evidence to Date.

Polycystic ovary syndrome (PCOS) manifests a multifactorial pathology characterized by polycystic ovaries, menstrual cycle disorders, varying degrees of hyperandrogenism, and an ad-verse metabolic risk profile. The position of hyperandrogenism in this syndrome has been extensively studied. A multitude of mechanisms place it in the position of cause but also of consequence; therefore, ongoing research efforts are focused on identifying medications that can effectively reduce levels of androgens in women with PCOS. Moreover, lipid abnormalities are common in this population, with up to 70% of patients having dyslipidemia. Statins may have potential therapeutic benefits for women with PCOS, as they have been shown to improve insulin resistance and reduce the risk of cardiovascular disease. In addition, their role in accelerated steroidogenesis by limiting one source of cholesterol, influencing enzymatic activity, and providing several other beneficial mechanisms is widely investigated. This review aimed to provide a comprehensive overview of the pathogenesis of androgen excess and dyslipidemia in PCOS, as well as the therapeutic potential of statins.

A pan-PPAR agonist E17241 ameliorates hyperglycemia and diabetic dyslipidemia in KKAy mice via up-regulating ABCA1 in islet, liver, and white adipose tissue.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease. Peroxisome proliferator-activated receptors (PPARs) play crucial roles in regulating glucolipid metabolism. Previous studies showed that E17241 could ameliorate atherosclerosis and lower fasting blood glucose levels in ApoE-/- mice. In this work, we investigated the role of E17241 in glycolipid metabolism in diabetic KKAy mice. APPROACH AND RESULTS: We confirmed that E17241 is a powerful pan-PPAR agonist with a potent agonistic activity on PPARγ, a high activity on PPARα, and a moderate activity on PPARδ. E17241 also significantly increased the protein expression of ATP-binding cassette transporter 1 (ABCA1), a crucial downstream target gene for PPARs. E17241 clearly lowered plasma glucose levels, improved OGTT and ITT, decreased islet cholesterol content, improved ß-cell function, and promoted insulin secretion in KKAy mice. Moreover, E17241 could significantly lower plasma total cholesterol and triglyceride levels, reduce liver lipid deposition, and improve the adipocyte hypertrophy and the inflammatory response in epididymal white adipose tissue. Further mechanistic studies indicated that E17241 boosts cholesterol efflux and insulin secretion in an ABCA1 dependent manner. RNA-seq and qRT-PCR analysis demonstrated that E17241 induced different expression of PPAR target genes in liver and adipose tissue differently from the PPARγ agonist rosiglitazone. In addition, E17241 treatment was also demonstrated to have an exhilarating cardiorenal benefits. CONCLUSIONS: Our results demonstrate that E17241 regulates glucolipid metabolism in KKAy diabetic mice while having cardiorenal benefits without inducing weight gain. It is a promising drug candidate for the treatment of T2DM.

Prescription drug coverage and effective coverage of three chronic conditions of high prevalence in Chile: Hypertension, diabetes and dyslipidemia.

BACKGROUND: Access to medicines is a serious problem globally and in Chile. Despite the creation of coverage policies, part of the population with chronic conditions of high prevalence, still does not have access to the medicines it requires and disease control continues to be low. The objective of the study was to estimate the medication use and effective coverage for diabetes, dyslipidemia and hypertension in Chile, analyzing them according to sociodemographic variables and social determinants of health. METHODS: Cross-sectional analytical study with information from the 2016-2017 National Health Survey (sample = 6,233 people aged 15 years or older, expanded = 14,518,969). Descriptive analyses of medication use and effective coverage for hypertension, diabetes and dyslipidemia were carried out, and multivariate logistic regression models were developed to analyze possible associations with variables of interest. RESULTS: 60% of people with hypertension or diabetes use medications and only 27.7% in dyslipidemia. While 54.2% of those with diabetes have their glycemia controlled, in hypertension and dyslipidemia the effective coverage drops to 33.3% and 6.6%, respectively. There are no differences in use by health system, but there are differences in the control of hypertension and diabetes, favoring beneficiaries of the private subsystem. Effective coverage of dyslipidemia and hypertension also increases in those using medications. The drugs coincide with the established protocols, although beneficiaries of the private sector report greater use of innovative drugs. CONCLUSION: A significant proportion of Chileans with hypertension, diabetes or dyslipidemia still do not use the required medications and do not control their conditions.

Impact of Glucagon-Like Peptide 1 Receptor Agonists on Biochemical Markers of the Initiation of Atherosclerotic Process.

Atherosclerosis stands out as one of the leading causes of global mortality. The inflammatory response against vascular wall components plays a pivotal role in the atherogenic process. The initiation of this process is notably driven by oxidized low-density lipoprotein (oxLDL) and a range of pro-inflammatory cytokines, with interleukin-1ß (Il-1ß) and tumor necrosis factor α (TNFα) emerging as particularly significant in the early stages of atherosclerotic plaque formation. In recent years, researchers worldwide have been diligently exploring innovative therapeutic approaches for metabolic diseases, recognizing their impact on the atherogenesis process. Our study aimed to investigate the influence of glucagon-like peptide 1 receptor agonists (GLP-1RA) on cytokine concentrations associated with the initiation of atherosclerotic plaque formation in a group of patients with type 2 diabetes and dyslipidemia. The study encompassed 50 subjects aged 41-81 (mean: 60.7), all diagnosed with type 2 diabetes, dyslipidemia and confirmed atherosclerosis based on B-mode ultrasound. Following a 180-day treatment with dulaglutide or semaglutide, we observed a statistically significant reduction in biochemical markers (oxLDL, TNFα and Il-1ß) associated with the initiation of the atherosclerotic process (p < 0.001) within our study group. In addition to the already acknowledged positive effects of GLP-1RA on the metabolic parameters of treated patients, these drugs demonstrated a notable reduction in proinflammatory cytokine concentrations and may constitute an important element of therapy aimed at reducing cardiovascular risk.

Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.

Coronary artery disease incidence, risk factors, awareness, and medication utilization in a 10-year cohort study.

BACKGROUND: There is a substantial disparity in coronary artery disease (CAD) burden between Iran and other nations that place a strong emphasis on the assessment of CAD risk factors and individuals' awareness and ability to control them. METHODS: Two thousand participants of a community-based Iranian population aged 20-74 years were investigated with a mean follow-up of 9.9 years (range: 7.6 to 12.2). An analysis of Cox regression was conducted to determine the association between CAD development and classic risk factors such as age, sex, smoking, physical activity, education, obesity, dyslipidemia, hypertension, and diabetes mellitus. Furthermore, we computed the population attributable fraction for these risk factors. RESULTS: After a follow-up period of nearly 10 years, 225 CAD events were reported, constituting 14.5% of the overall incidence. Nighty three percent of participants had more than one risk factor. Age was the most predictive risk factor, with a hazard ratio (HR) and confidence interval (CI) of 5.56 (3.87-7.97, p < 0.001) in men older than 45 and females older than 55 compared to lower ages. In comparison to females, males had an HR of 1.45 (CI: 1.11-1.90, p value = 0.006) for developing CAD. Nearly 80% of the patients had dyslipidemia, with a hazard ratio of 2.19 (CI: 1.40-3.44, p = 0.01). Among the participants, 28.9% had hypertension, and 52% had prehypertension, which had HRs of 4.1 (2.4-7.2, p < 0.001) and 2.4 (1.4-4.2, p < 0.001), respectively. Diabetes, with a prevalence of 17%, had an HR of 2.63 (CI: 2 -3.47, p < 0.001), but prediabetes was not significantly associated with CAD. Awareness of diabetes, dyslipidemia, and hypertension was 81%, 27.9%, and 48.1%, respectively. Regarding medication usage, the corresponding percentages were 51% for diabetes, 13.2% for dyslipidemia, and 41% for hypertension. CONCLUSIONS: Compared to previous studies in Iran and neighboring countries, the current study found a higher incidence of CAD, more prevalent risk factors, and a lower awareness and ability to control these risk factors. Thus, an effective preventive strategy is needed to reduce the CAD burden in Iran.