Potential impact of blood cholesterol guidelines on statin treatment in the U.S. population using interrupted time series analysis.

BACKGROUND: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011. METHODS: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact. RESULTS: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release. CONCLUSIONS: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline.

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.

Assessment of subclinical left ventricular systolic and diastolic dysfunction in patients with type 2 diabetes mellitus under follow-up at Tikur Anbessa specialized hospital, Ethiopia: a case-control study.

BACKGROUND: Individuals with diabetes mellitus are at increased risk of cardiovascular diseases, which in turn are the most common cause of morbidity and mortality in the diabetic population. A peculiar feature of cardiovascular diseases in this population is that they can have significant cardiac disease while remaining asymptomatic. There is a paucity of data regarding subclinical cardiac imaging features among diabetic adults in Africa, particularly in Ethiopia. This study was conducted to compare the magnitude and spectrum of left ventricular systolic and diastolic dysfunction among asymptomatic type 2 diabetic adults versus a normotensive, non-diabetic control group and to evaluate the determinants of left ventricular diastolic and systolic dysfunction. METHODS: This was a case-control study conducted at Tikur Anbessa specialized hospital, Addis Ababa, Ethiopia. A standard transthoracic echocardiography was done for all study participants with type 2 diabetes mellitus and their normotensive and non-diabetic controls. Structured questionnaires were used to collect demographic and clinical characteristics and laboratory test results. Statistical analysis was done using the SPSS 25.0 software. The data was summarized using descriptive statistics. Bivariate and multivariate analysis was performed to determine the association between variables and echocardiographic parameters. The strength of statistical association was measured by adjusted odds ratios and 95% confidence intervals, with significant differences taken at p < 0.05. RESULTS: We analyzed age- and sex-matched 100 participants in the study (diabetic) group and 200 individuals in the control group. Left ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic adults than their sex and age matched controls. Among diabetic individuals, ages of 60 years and above, dyslipidemia, use of Metformin and Glibenclamide, high serum triglyceride level, presence of neuropathy and use of statins correlated significantly with the presence of left ventricular diastolic dysfunction. Chronic kidney disease and neuropathy were determinants of left ventricular systolic dysfunction. CONCLUSION: Left ventricular systolic and diastolic dysfunction were significantly more prevalent among diabetic patients than their sex- and age-matched controls in our study. We recommend early screening for subclinical left ventricular dysfunction, especially in the elderly and in those with chronic kidney disease, dyslipidemia, and microvascular complications such as neuropathy.

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.

Clinical impact of genetic testing for lipid disorders.

PURPOSE OF REVIEW: Genetic testing is increasingly becoming a common consideration in the clinical approach of dyslipidemia patients. Advances in research in last decade and increased recognition of genetics in biological pathways modulating blood lipid levels created a gap between theoretical knowledge and its applicability in clinical practice. Therefore, it is very important to define the clinical justification of genetic testing in dyslipidemia patients. RECENT FINDINGS: Clinical indications for genetic testing for most dyslipidemias are not precisely defined and there are no clearly established guideline recommendations. In patients with severe low-density lipoprotein cholesterol (LDL-C) levels, the genetic analysis can be used to guide diagnostic and therapeutic approach, while in severe hypertriglyceridemia (HTG), clinicians can rely on triglyceride level rather than a genotype along the treatment pathway. Genetic testing increases diagnostic accuracy and risk stratification, access and adherence to specialty therapies, and cost-effectiveness of cascade testing. A shared decision-making model between the provider and the patient is essential as patient values, preferences and clinical characteristics play a very strong role. SUMMARY: Genetic testing for lipid disorders is currently underutilized in clinical practice. However, it should be selectively used, according to the type of dyslipidemia and when the benefits overcome costs.

Dyslipidemia is associated with sarcopenia of the elderly: a meta-analysis.

PURPOSE: Sarcopenia is a pathological change characterized by muscle loss in older people. According to the reports, there is controversy on the relationship between dyslipidemia and sarcopenia. Therefore, this meta-analysis aimed to explore the association between sarcopenia and dyslipidemia. METHODS: We searched the Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Wan Fang, China Science and Technology Journal Database (VIP Database) for case‒control studies to extract data on the odds ratio (OR) between sarcopenia and dyslipidemia and the MD(mean difference) of TC, LDL-C, HDL-C, TG, and TG/HDL-C between sarcopenia and nonsarcopenia. The JBI(Joanna Briggs) guidelines were used to evaluate the quality. Excel 2021, Review Manager 5.3 and Stata 16.0 were used for the statistical analysis. RESULTS: Twenty studies were included in the meta-analysis, 19 of which were evaluated as good quality. The overall OR of the relationship between sarcopenia and dyslipidemia was 1.47, and the MD values of TC, LDL-C, HDL-C, TG, and TG/HDL-C were 1.10, 1.95, 1.27, 30.13, and 0.16 respectively. In female, compared with the non-sarcopnia, the MD of TC, LDL-C, HDL-C, TG of sarcopenia were - 1.67,2.21,1.02,-3.18 respectively. In male, the MD of TC, LDL-C, HDL-C, TG between sarcopenia and non-sarcopenia were - 0.51, 1.41, 5.77, -0.67. The OR between sarcopenia and dyslipidemia of the non-China region was 4.38, and it was 0.9 in China. In the group(> 60), MD of TC between sarcopenia and non-sarcopenia was 2.63, while it was 1.54 in the group(20-60). CONCLUSION: Dyslipidemia was associated with sarcopenia in the elderly, which was affected by sex, region and age.

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.

Temporal relationship between elevated serum uric acid levels and dyslipidemia: A 5-year cohort study using cross-lagged panel analysis.

BACKGROUND AND AIM: Previous studies have demonstrated an association between SUA and dyslipidemia. This study aims to explore the temporal relationship between SUA and dyslipidemia. METHODS AND RESULTS: Based on the Beijing Health Management Cohort conducted from 2013 to 2018, the data of a physical examination population was collected, including a total of 6630 study subjects. Cross-lagged panel analysis was employed to examine the temporal relationship between elevated SUA levels and dyslipidemia, indicated by either elevated TG or decreased HDL-C. The path coefficient and the 95 % CI from baseline TG to follow-up SUA were as follows: in the general population, men, women, and people with BMI ≥25 kg/m2were 0.027 (0.008-0.045), 0.024 (0.001-0.048), 0.032 (0.001-0.063) and 0.033 (0.006-0.059) (P < 0.05); however, the path coefficient from baseline SUA to follow-up TG and the 95 % CI were not statistically significant. Furthermore, the path coefficients and 95 % CIs between elevated SUA and decreased HDL-C were not statistically significant, both in the general population and in populations stratified by gender and BMI. CONCLUSIONS: We found a temporal relationship from elevated TG to elevated SUA in the general population and the populations stratified by gender and BMI (≥25 kg/m2). However, we did not observe a reverse relationship from elevated SUA to elevated TG. Additionally, we did not find a temporal relationship between decreased HDL-C and elevated SUA in both the general population and the stratified populations.

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People.

BACKGROUND: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. METHODS AND RESULTS: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. CONCLUSIONS: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

Dyslipidemia and Efficacy of Remote Ischemic Conditioning in Acute Moderate Ischemic Stroke: A Post Hoc Analysis of the RICAMIS Study.

BACKGROUND: Ischemic conditioning-induced cardioprotection was attenuated by dyslipidemia in some animal and clinical studies, which is not investigated in patients with stroke. We conducted a post hoc analysis of the RICAMIS (Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke) trial to investigate the association of dyslipidemia on admission with the efficacy of remote ischemic conditioning (RIC). METHODS AND RESULTS: In this analysis, eligible patients were divided into dyslipidemia and normal-lipid groups according to the levels of 4 blood lipid profiles (total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), which were further subdivided into RIC and control subgroups. We analyzed the differences in functional outcome between RIC and control subgroups in dyslipidemia and normal-lipid patients, respectively, and the interaction effects of RIC treatment with blood lipid levels were evaluated. Among 1776 patients from intention-to-treat analysis, 1419 patients with data of blood lipid profiles were included in the final analysis. A significantly higher proportion of modified Rankin Scale score 0 to 1 was identified in the RIC versus control subgroup across the normal-total cholesterol group (69.9% versus 63.5%; P=0.04), normal-triglycerides group (68.1% versus 60.5%; P=0.016), high-low-density lipoprotein cholesterol group (65.7% versus 57.7%; P=0.025), and normal-high-density lipoprotein cholesterol group (68.3% versus 60.5%; P=0.005). Similar statistical trends were found in the high-total cholesterol group (62.8% versus 55.5%; P=0.059), high-triglycerides group (67.8% versus 60.1%; P=0.099), normal-low-density lipoprotein cholesterol group (69.8% versus 63.7%; P=0.105), but no statistical significance was found in the low-high-density lipoprotein cholesterol group (63.4% versus 61%; P=0.705). Furthermore, no significant interaction effect of RIC intervention by blood lipid profiles was found. Similar results were obtained for lipids as continuous variables. CONCLUSIONS: Blood lipids on admission was not associated with the neuroprotective effect of RIC.

The role of mitochondrial DNA copy number in cardiometabolic disease: a bidirectional two-sample mendelian randomization study.

BACKGROUND: This study used a bidirectional 2-sample Mendelian randomization study to investigate the potential causal links between mtDNA copy number and cardiometabolic disease (obesity, hypertension, hyperlipidaemia, type 2 diabetes [T2DM], coronary artery disease [CAD], stroke, ischemic stroke, and heart failure). METHODS: Genetic associations with mtDNA copy number were obtained from a genome-wide association study (GWAS) summary statistics from the UK biobank (n = 395,718) and cardio-metabolic disease were from largest available GWAS summary statistics. Inverse variance weighting (IVW) was conducted, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses. We repeated this in the opposite direction using instruments for cardio-metabolic disease. RESULTS: Genetically predicted mtDNA copy number was not associated with risk of obesity (P = 0.148), hypertension (P = 0.515), dyslipidemia (P = 0.684), T2DM (P = 0.631), CAD (P = 0.199), stroke (P = 0.314), ischemic stroke (P = 0.633), and heart failure (P = 0.708). Regarding the reverse directions, we only found that genetically predicted dyslipidemia was associated with decreased levels of mtDNA copy number in the IVW analysis (ß= - 0.060, 95% CI - 0.044 to - 0.076; P = 2.416e-14) and there was suggestive of evidence for a potential causal association between CAD and mtDNA copy number (ß= - 0.021, 95% CI - 0.003 to - 0.039; P = 0.025). Sensitivity and replication analyses showed the stable findings. CONCLUSIONS: Findings of this Mendelian randomization study did not support a causal effect of mtDNA copy number in the development of cardiometabolic disease, but found dyslipidemia and CAD can lead to reduced mtDNA copy number. These findings have implications for mtDNA copy number as a biomarker of dyslipidemia and CAD in clinical practice.

Effectiveness of peer-led intervention in control of non-communicable diseases in rural areas of Khordha district: study protocol for a cluster randomized controlled trial.

BACKGROUND: The main contributors to death and disability from chronic illnesses in developing nations are elevated blood pressure (hypertension), blood sugar (diabetes mellitus), and blood cholesterol (dyslipidaemia). Even though there are affordable treatments, the treatment gap for these conditions is still significant. Few pilot studies from industrialized nations discuss the value of peer-led interventions for achieving community-level management of blood pressure and blood sugar. This study aims to evaluate the effectiveness of peer-led intervention compared to standard care in achieving control of selected non-communicable diseases (NCDs) in Indian context at 1 year of intervention among people of 30-60 years with hypertension and/or diabetes mellitus and/or dyslipidaemia. METHODS: A cluster-randomized controlled trial will be conducted in villages of two rural blocks of the Khordha district of Odisha from August 2023 to December 2024. A total of 720 eligible participants (360 in the intervention group and 360 in the control group) will be recruited and randomized into two study arms. The participants in the intervention arm will receive a peer-led intervention model for 6 months in addition to standard care. The sessions will be based on the six domains of NCDs - self-care, follow-up care, medication, physical activity, diet, limiting substance use, mental health and co-morbidities. The mean reduction in blood pressure, HbA1C, and blood cholesterol in the intervention arm compared to the standard care arm will be the main outcome. DISCUSSION: The increasing burden of NCDs demands for newer strategies for management. Peer-led interventions have proven to be useful at the international level. Incorporating it in India will have remarkable results in controlling NCDs. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI) CTRI/2023/02/050022. Registered on 23 February 2023.

Dyslipidemia in adults with congenital heart disease: A systematic review and meta-analysis.

AIMS: Several particular characteristics of patients with congenital heart disease could affect lipid levels. The objectives of this study were: a) to analyze the prevalence of dyslipidemia in congenital heart disease patients; 2) to compare lipid levels between congenital heart disease patients and a control group. DATA SYNTHESIS: This systematic review and meta-analysis was performed according to PRISMA guidelines (PROSPERO CRD42023432041). A literature search was performed to detect studies that have reported lipid levels or the prevalence of dyslipidemia in congenital heart disease patients. We performed a qualitative analysis (studies that reported dyslipidemia prevalence) and quantitative analysis (studies that compared lipid values between congenital heart disease patients and controls). In total, 29 observational studies involving 22,914 patients with congenital heart disease and 641,086 controls were eligible for this review. The reported presence of "hyperlipidemia" or "dyslipidemia" ranged from 14.3% to 69.9%. When studies analyzed lipid variables dichotomously between congenital heart disease patients and controls, the results were conflicting. The quantitative analysis showed that patients with congenital heart disease have lower levels of total cholesterol (MD: -18.9 [95% CI: -22.2 to -15.7]; I2 = 93%), LDL-C (MD: -10.7 [95% CI: -13.1 to -8.3]; I2 = 90%) and HDL-C (MD: -6.3 [95% CI: -7.7 to -4.9]; I2 = 95%) compared to controls. CONCLUSIONS: The qualitative analysis showed some concerns, but the quantitative analysis indicates that congenital heart disease patients showed lower levels of total cholesterol, LDL-C, and HDL-C compared to controls. New research should be developed to clarify this relevant topic.

Serum apolipoproteins (apoA-1, apoB, and apoB/apoA-1 ratio) for early identification of dyslipidemia in children with CKD.

BACKGROUND: Dyslipidemia in children with chronic kidney disease (CKD) is identified based on lipid profile parameters; however, changes in lipoprotein quality precede quantitative changes. METHODS: A cross-sectional study was done from January to October 2021; overweight, obese children, known cases of diabetes mellitus, hypothyroidism or on steroid therapy, or lipid lowering drugs were excluded. Clinical details were elicited and examinations done. Besides hemogram, kidney function tests, liver function tests, total cholesterol, low density lipoproteins (LDL), triglycerides, high density lipoproteins (HDL), and apolipoproteins A-1 and B were estimated to identify dyslipidemia. Relevant tests of significance were applied, and ROC curves were drawn for apoA-1, apoB, and apoB/apoA-1 ratios. RESULTS: A total of 76 (61 M:15 F) children with median (IQR) age 7 (3.25-11) years were enrolled; cause of CKD was CAKUT in 82.3% patients. Dyslipidemia (alteration of 1 or more lipid parameters) was seen in 78.9% with a prevalence of 71.7% in early and 95.7% in later stages of CKD (P = 0.02); most had elevated serum triglyceride levels. The median (IQR) values of apoB, apoA-1, and apoB/apoA-1 ratio were 78 (58-110) mg/dl, 80 (63-96.75) mg/dl, and 0.88 (0.68-1.41), respectively; apoB, apoA-1, and apoB/apoA-1 ratio had a sensitivity of 26.67%, 86.67%, and 70%, respectively, and specificity of 87.5%, 62.5%, and 62.5%, respectively, for diagnosis of dyslipidemia. The ROC for apoB, apoA-1, and apoB/apoA-1 ratio showed AUC of 0.66, 0.68, and 0.74 (P = 0.4, 0.02, < 0.01), respectively. CONCLUSIONS: The prevalence (78.9%) of dyslipidemia was high in patients with CKD especially in those with later stages. The ratio of apoB/apoA-1 was altered early and appears to be promising for early detection.

Role of Gut Microbiota in Statin-Associated New-Onset Diabetes-A Cross-Sectional and Prospective Analysis of the FINRISK 2002 Cohort.

BACKGROUND: Dyslipidemia is treated effectively with statins, but treatment has the potential to induce new-onset type-2 diabetes. Gut microbiota may contribute to this outcome variability. We assessed the associations of gut microbiota diversity and composition with statins. Bacterial associations with statin-associated new-onset type-2 diabetes (T2D) risk were also prospectively evaluated. METHODS: We examined shallow-shotgun-sequenced fecal samples from 5755 individuals in the FINRISK-2002 population cohort with a 17+-year-long register-based follow-up. Alpha-diversity was quantified using Shannon index and beta-diversity with Aitchison distance. Species-specific differential abundances were analyzed using general multivariate regression. Prospective associations were assessed with Cox regression. Applicable results were validated using gradient boosting. RESULTS: Statin use associated with differing taxonomic composition (R2, 0.02%; q=0.02) and 13 differentially abundant species in fully adjusted models (MaAsLin; q<0.05). The strongest positive association was with Clostridium sartagoforme (ß=0.37; SE=0.13; q=0.02) and the strongest negative association with Bacteroides cellulosilyticus (ß=-0.31; SE=0.11; q=0.02). Twenty-five microbial features had significant associations with incident T2D in statin users, of which only Bacteroides vulgatus (HR, 1.286 [1.136-1.457]; q=0.03) was consistent regardless of model adjustment. Finally, higher statin-associated T2D risk was seen with [Ruminococcus] torques (ΔHRstatins, +0.11; q=0.03), Blautia obeum (ΔHRstatins, +0.06; q=0.01), Blautia sp. KLE 1732 (ΔHRstatins, +0.05; q=0.01), and beta-diversity principal component 1 (ΔHRstatin, +0.07; q=0.03) but only when adjusting for demographic covariates. CONCLUSIONS: Statin users have compositionally differing microbiotas from nonusers. The human gut microbiota is associated with incident T2D risk in statin users and possibly has additive effects on statin-associated new-onset T2D risk.

Characterization and LDL-C management in a cohort of high and very high cardiovascular risk patients: The PORTRAIT-DYS study.

AIM: This study aims to characterize sociodemographic and clinical characteristics, use of lipid-lowering therapies (LLTs), and low-density lipoprotein cholesterol (LDL-C) control in a population with increased cardiovascular (CV) risk. METHODS: A cross-sectional observational study that uses electronic health records of patients from one hospital and across 14 primary care health centers in the North of Portugal, spanning from 2000 to 2020 (index date). Patients presented at least (i) 1 year of clinical data before inclusion, (ii) one primary care appointment 3 years before the index date, and (iii) sufficient data for CV risk classification. Patients were divided into three cohorts: high CV risk; atherosclerotic cardiovascular disease (ASCVD) risk equivalents without established ASCVD; evidence of ASCVD. CV risk and LDL-C control were defined by the 2019 and 2016 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidemia guidelines. RESULTS: A total of 51 609 patients were included, with 23 457 patients classified as high CV risk, 19 864 with ASCVD equivalents, and 8288 with evidence of ASCVD. LDL-C control with 2016 ESC/EAS guidelines was 32%, 10%, and 18% for each group, respectively. Considering the ESC/EAS 2019 guidelines control level was even lower: 7%, 3%, and 7% for the same cohorts, respectively. Patients without any LLT prescribed ranged from 37% in the high CV risk group to 15% in patients with evidence of ASCVD. CONCLUSION: We found that LDL-C control was very low in patients at higher risk of CV events. An alarming gap between guidelines on dyslipidemia management and clinical implementation persists, even in those at very high risk or with established ASCVD.

Effect of atorvastatin on muscle tissues of dermatomyositis and antisynthetase syndrome patients with dyslipidemia.

INTRODUCTION: In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients. METHODS: Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo]. The results were analyzed considering differences in expression fold change before and after treatment. Histological and histochemical analyses were also performed. RESULTS: In both groups, no significant changes were observed in genes related to the mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways. Histological analysis showed a slight variability in the fiber size that was preserved after the intervention. In addition, the mosaic of muscle fibers was preserved in the internal architecture of the fibers and all histological regions. No fiber necrosis or atrophy, focal failures, subsarcolemmal accumulation, lipids, areas of fibrosis, or alterations in mitochondrial activity were observed. All muscle fibers were labeled for MHC I. CONCLUSION: Atorvastatin did not promote significant changes in the expression of genes related to mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways in the muscle tissues of DM and ASS patients with dyslipidemia. Atorvastatin did not also promote histological and histochemical changes in muscle tissues. Our results reinforce the safety of the administration of atorvastatin to treat dyslipidemia in patients with DM and ASS.

Age-dependent association of metabolic dyslipidemia with clinical expression of hypertrophic cardiomyopathy.

BACKGROUND: Previous studies have shown that the clinical expression of hypertrophic cardiomyopathy (HCM) can be determined by obesity and metabolic syndrome. The present study aimed to investigate the association between triglyceride and high-density lipoprotein cholesterol (HDLC) level, the two dyslipidemia-related components of metabolic syndrome, and the incidence of HCM. We also explored an age-dependent association between them. METHODS: Individuals without previous HCM diagnosis who underwent a designated national health examination in 2009 were recruited. Individuals who used lipid-lowering medications within 1-year of the baseline were excluded. The outcome of interest was a newly diagnosed HCM. RESULTS: Our cohort consisted of 8,652,709 individuals (mean 46 years, 55.6% men). During the median 9.3 years of follow-up, 5932 (0.07%) individuals were newly diagnosed with HCM. There was a gradual increase in the incidence of HCM towards higher triglyceride and lower HDL-C levels (log-rank p < 0.001). When stratified by age, the incidence of HCM was highest in individuals aged ≥65 years, followed by those aged 40-64 and 20-39 years (0.22% vs. 0.07% vs. 0.03%, log-rank p < 0.001). In individuals aged 20-39 years, a higher triglyceride level was associated with a higher incidence of HCM (i.e., ≥200 vs. <100 mg/dL: adjusted hazard ratio 2.28, 95% confidence interval 1.89-2.75), whereas there was no significant association in older groups (p-for-interaction<0.001). Similarly, a lower HDL-C level was associated with a higher incidence of HCM, particularly in individuals aged 20-39 years (p-for-interaction = 0.001). CONCLUSIONS: High triglyceride and low HDL-C levels are associated with a higher incidence of HCM, particularly in young individuals.

Long-term secondary prevention and outcome following acute coronary syndrome: real-world results from the Swedish Primary Care Cardiovascular Database.

AIMS: Most studies of treatment adherence after acute coronary syndrome (ACS) are based on prescribed drugs and lack long-term follow-up or consecutive data on risk factor control. We studied the long-term treatment adherence, risk factor control, and its association to recurrent ACS and death. METHODS AND RESULTS: We retrospectively included 3765 patients (mean age 75 years, 40% women) with incident ACS from 1 January 2006 until 31 December 2010 from the Swedish Primary Care Cardiovascular Database of Skaraborg. All patients were followed until 31 December 2014 or death. We recorded blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), recurrent ACS, and death. We used data on dispensed drugs to calculate the proportion of days covered for secondary prevention medications. Cox regressions were used to analyse the association of achieved BP and LDL-C to recurrent ACS and death. The median follow-up time was 4.8 years. The proportion of patients that reached BP of <140/90 mm Hg was 58% at Year 1 and 66% at Year 8. 65% of the patients reached LDL-C of <2.5 mmol/L at Year 1 and 56% at Year 8; however, adherence to statins varied from 43% to 60%. Only 62% of the patients had yearly measured BP, and only 28% yearly measured LDL-C. Systolic BP was not associated with a higher risk of recurrent ACS or death. Low-density lipoprotein cholesterol of 3.0 mmol/L was associated with a higher risk of recurrent ACS {hazard ratio [HR] 1.19 [95% confidence interval (CI) 1.00-1.40]} and death HR [1.26 (95% CI 1.08-1.47)] compared with an LDL-C of 1.8 mmol/L. CONCLUSION: This observational long-term real-world study demonstrates low drug adherence and potential for improvement of risk factors after ACS. Furthermore, the study confirms that uncontrolled LDL-C is associated with adverse outcome even in this older population.

In this real-world retrospective observational study, we followed 3765 elderly patients for up to 8 years after incident acute coronary syndrome.Only a low proportion of the studied population had yearly measured blood pressure and cholesterol, a low proportion had satisfied risk factor control (blood pressure and cholesterol), and adherence to secondary prevention medication was low.In this elderly population (mean age 75 years), higher levels of low-density lipoprotein cholesterol were associated with a higher risk of recurrent coronary event and death.