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1.
Cells ; 13(9)2024 Apr 23.
Article En | MEDLINE | ID: mdl-38727268

Treatment strategies for steatohepatitis are of special interest given the high prevalence of obesity and fatty liver disease worldwide. This study aimed to investigate the potential therapeutic mechanism of L-carnitine (LC) and Ginkgo biloba leaf extract (GB) supplementation in ameliorating the adverse effects of hyperlipidemia and hepatosteatosis induced by a high-cholesterol diet (HCD) in an animal model. The study involved 50 rats divided into five groups, including a control group, a group receiving only an HCD, and three groups receiving an HCD along with either LC (300 mg LC/kg bw), GB (100 mg GB/kg bw), or both. After eight weeks, various parameters related to lipid and glucose metabolism, antioxidant capacity, histopathology, immune reactivity, and liver ultrastructure were measured. LC + GB supplementation reduced serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, glucose, insulin, HOMA-IR, alanine transaminase, and aspartate transaminase levels and increased high-density lipoprotein cholesterol levels compared with those in the HCD group. Additionally, treatment with both supplements improved antioxidant ability and reduced lipid peroxidation. The histological examination confirmed that the combination therapy reduced liver steatosis and fibrosis while also improving the appearance of cell organelles in the ultrastructural hepatocytes. Finally, the immunohistochemical analysis indicated that cotreatment with LC + GB upregulated the immune expression of GLP-1 and ß-Cat in liver sections that were similar to those of the control animals. Mono-treatment with LC or GB alone substantially but not completely protected the liver tissue, while the combined use of LC and GB may be more effective in treating liver damage caused by high cholesterol than either supplement alone by regulating hepatic oxidative stress and the protein expression of GLP-1 and ß-Cat.


Carnitine , Dietary Supplements , Dyslipidemias , Ginkgo biloba , Liver , Plant Extracts , Animals , Liver/drug effects , Liver/pathology , Liver/metabolism , Carnitine/pharmacology , Male , Rats , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Dyslipidemias/drug therapy , Dyslipidemias/metabolism , Fatty Liver/drug therapy , Fatty Liver/pathology , Fatty Liver/metabolism , Rats, Sprague-Dawley , Lipid Metabolism/drug effects , Antioxidants/pharmacology , Diet, High-Fat/adverse effects , Ginkgo Extract
2.
Medicine (Baltimore) ; 103(19): e38122, 2024 May 10.
Article En | MEDLINE | ID: mdl-38728464

BACKGROUND: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. METHODS: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. RESULTS: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. CONCLUSIONS: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.


Atorvastatin , Bone Remodeling , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Postmenopause , Rosuvastatin Calcium , Humans , Rosuvastatin Calcium/therapeutic use , Rosuvastatin Calcium/administration & dosage , Female , Atorvastatin/therapeutic use , Atorvastatin/pharmacology , Middle Aged , Bone Remodeling/drug effects , Postmenopause/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Biomarkers/blood , Collagen Type I/blood , Osteoporosis, Postmenopausal/drug therapy , Dyslipidemias/drug therapy , Dyslipidemias/blood
3.
BMC Cardiovasc Disord ; 24(1): 245, 2024 May 10.
Article En | MEDLINE | ID: mdl-38730371

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.


Guideline Adherence , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Interrupted Time Series Analysis , Practice Guidelines as Topic , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , United States , Time Factors , Retrospective Studies , Male , Female , Aged , Middle Aged , Treatment Outcome , Guideline Adherence/standards , Biomarkers/blood , Dyslipidemias/drug therapy , Dyslipidemias/blood , Dyslipidemias/diagnosis , Dyslipidemias/mortality , Dyslipidemias/epidemiology , Atorvastatin/therapeutic use , Atorvastatin/adverse effects , Cardiovascular Diseases/mortality , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/blood , Databases, Factual , Practice Patterns, Physicians'/standards , Cholesterol/blood , Medication Adherence , Drugs, Generic/therapeutic use , Drugs, Generic/adverse effects , Risk Assessment
4.
PLoS One ; 19(5): e0300745, 2024.
Article En | MEDLINE | ID: mdl-38696494

OBJECTIVE: This study aimed to investigate the impacts of continuity of care (COC) between patients and multiple providers, i.e., doctors and community pharmacists, on clinical and economic outcomes. METHODS: This is a retrospective cohort study and analyzed Korean national claims data for ambulatory care setting between 2007 and 2018. Patients with dyslipidemia newly diagnosed in 2008 were identified. COC between providers and patients was computed using the continuity of care index (COCI). Based on COCIs, the study patients were allocated to four groups: HM/HP, HM/LP, LM/HP, and LM/LP. Each symbol represents H for high, L for low, M for doctor, and P for pharmacist. The primary study outcome was the incidence of atherosclerotic cardiovascular disease (ASCVD). RESULTS: 126,710 patients were included. Percentages of patients in the four study groups were as follows: HM/HP 35%, HM/LP 19%, LM/HP 12%, and LM/LP 34%. During the seven-year outcome period, 8,337 patients (6.6%) developed an ASCVD, and percentages in the study groups were as follows; HM/HP 6.2%, HM/LP 6.3%, LM/HP 6.8%, and LM/LP 7.1%. After adjusting for confounding covariates, only the LM/LP group had a significantly higher risk of ASCVD than the reference group, HM/HP (aHR = 1.16 [95% confidence interval = 1.10~1.22]). The risk of inappropriate medication adherence gradually increased 1.03-fold in the HM/LP group, 1.67-fold in the LM/HP, and 2.26-fold in the LM/LP group versus the HM/HP group after adjusting for covariates. Disease-related costs were lower in the HM/HP and LM/HP groups. CONCLUSIONS: The study shows that patients with high relational care continuity with doctors and pharmacists achieved better clinical results and utilized health care less, resulting in reduced expenses. Further exploration for the group that exhibits an ongoing relationship solely with pharmacists is warranted.


Continuity of Patient Care , Dyslipidemias , Humans , Male , Female , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Middle Aged , Retrospective Studies , Republic of Korea/epidemiology , Pharmacists , Aged , Adult , Physicians , Atherosclerosis/epidemiology , Atherosclerosis/therapy , Cohort Studies
5.
BMJ Open ; 14(5): e083046, 2024 May 22.
Article En | MEDLINE | ID: mdl-38777590

INTRODUCTION: Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia. METHODS AND ANALYSIS: MaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications. TRIAL REGISTRATION NUMBERS: Australian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.


Dyslipidemias , Osteoarthritis, Knee , Pentosan Sulfuric Polyester , Humans , Osteoarthritis, Knee/drug therapy , Pentosan Sulfuric Polyester/therapeutic use , Pentosan Sulfuric Polyester/administration & dosage , Dyslipidemias/drug therapy , Dyslipidemias/complications , Quality of Life , Male , Treatment Outcome , Female , Middle Aged , Clinical Trials, Phase II as Topic , Australia , Pain Measurement , Adult
6.
Nutrients ; 16(10)2024 May 18.
Article En | MEDLINE | ID: mdl-38794764

Long-term exposure to even slightly elevated plasma cholesterol levels significantly increases the risk of developing cardiovascular disease. The latest evidence recommends an improvement in plasma lipid levels, even in children who are not affected by severe hypercholesterolemia. The risk-benefit profile of pharmacological treatments in pediatric patients with moderate dyslipidemia is uncertain, and several cholesterol-lowering nutraceuticals have been recently tested. In this context, the available randomized clinical trials are small, short-term and mainly tested different types of fibers, plant sterols/stanols, standardized extracts of red yeast rice, polyunsaturated fatty acids, soy derivatives, and some probiotics. In children with dyslipidemia, nutraceuticals can improve lipid profile in the context of an adequate, well-balanced diet combined with regular physical activity. Of course, they should not be considered an alternative to conventional lipid-lowering drugs when necessary.


Dietary Supplements , Humans , Child , Hypercholesterolemia/blood , Hypercholesterolemia/diet therapy , Hypercholesterolemia/drug therapy , Cholesterol/blood , Anticholesteremic Agents/therapeutic use , Dyslipidemias/drug therapy , Dyslipidemias/blood , Phytosterols , Randomized Controlled Trials as Topic , Pediatrics/methods , Cardiovascular Diseases/prevention & control
7.
Front Immunol ; 15: 1339338, 2024.
Article En | MEDLINE | ID: mdl-38655259

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.


HIV Infections , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , HIV Infections/drug therapy , HIV Infections/immunology , HIV Infections/complications , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , Dyslipidemias/drug therapy , Dyslipidemias/immunology , Cardiovascular Diseases/etiology , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/adverse effects
8.
Biomed Pharmacother ; 174: 116582, 2024 May.
Article En | MEDLINE | ID: mdl-38642504

The aim of this study was to investigate whether the therapeutic effect of theabrownin extracted from Qingzhuan tea (QTB) on metabolic dysfunction-associated steatosis liver disease (MASLD) is related to the regulation of intestinal microbiota and its metabolite short-chain fatty acids (SCFAs). Mice were divided into four groups and received normal diet (ND), high-fat diet (HFD) and HFD+QTB (180, 360 mg/kg) for 8 weeks. The results showed that QTB significantly reduced the body weight of HFD mice, ameliorated liver lipid and dyslipidemia, and increased the level of intestinal SCFAs in HFD mice. The results of 16 S rRNA showed that the relative abundance of Bacteroides, Blautia and Lachnoclostridium and their main metabolites acetate and propionate were significantly increased after QTB intervention. The relative abundance of Colidextribacter, Faecalibaculum and Lactobacillus was significantly reduced. QTB can also significantly up-regulate the expression of ATGL, PPARα, FFAR2 and FFAR3, and inhibit the expression of LXRα, SREBP-1c, FAS and HMGCR genes. This makes it possible to act as a prebiotic to prevent MASLD.


Catechin/analogs & derivatives , Diet, High-Fat , Gastrointestinal Microbiome , Mice, Inbred C57BL , Tea , Animals , Gastrointestinal Microbiome/drug effects , Diet, High-Fat/adverse effects , Male , Tea/chemistry , Mice , Fatty Acids, Volatile/metabolism , Liver/drug effects , Liver/metabolism , Lipid Metabolism/drug effects , Dyslipidemias/drug therapy , Dyslipidemias/prevention & control , Fatty Liver/prevention & control , Fatty Liver/drug therapy
10.
Diabetes Metab Res Rev ; 40(4): e3793, 2024 May.
Article En | MEDLINE | ID: mdl-38661109

AIMS: The aims of the present study were to assess the effects of lipid-lowering drugs [HMG-CoA reductase inhibitors, proprotein convertase subtilisin/kexin type 9 inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors] on novel subtypes of adult-onset diabetes through a Mendelian randomisation study. MATERIALS AND METHODS: We first inferred causal associations between lipid-related traits [including high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoproteins A-I, and apolipoproteins B] and novel subtypes of adult-onset diabetes. The expression quantitative trait loci of drug target genes for three classes of lipid-lowering drugs, as well as genetic variants within or nearby drug target genes associated with LDL-C, were then utilised as proxies for the exposure of lipid-lowering drugs. Mendelian randomisation analysis was performed using summary data from genome-wide association studies of LDL-C, severe autoimmune diabetes, severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD), and mild age-related diabetes. RESULTS: There was an association between HMGCR-mediated LDL-C and the risk of SIRD [odds ratio (OR) = 0.305, 95% confidence interval (CI) = 0.129-0.723; p = 0.007], and there was an association of PCSK9-mediated LDL-C with the risk of SIDD (OR = 0.253, 95% CI = 0.120-0.532; p < 0.001) and MOD (OR = 0.345, 95% CI = 0.171-0.696; p = 0.003). Moreover, NPC1L1-mediated LDL-C (OR = 0.109, 95% CI = 0.019-0.613; p = 0.012) and the increased expression of NPC1L1 gene in blood (OR = 0.727, 95% CI = 0.541-0.977; p = 0.034) both showed a significant association with SIRD. These results were further confirmed by sensitivity analyses. CONCLUSIONS: In summary, the different lipid-lowering medications have a specific effect on the increased risk of different novel subtypes of adult-onset diabetes.


Diabetes Mellitus, Type 2 , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypolipidemic Agents , PCSK9 Inhibitors , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/pathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Niemann-Pick C1 Protein/antagonists & inhibitors , PCSK9 Inhibitors/adverse effects , Hypolipidemic Agents/adverse effects , Genome-Wide Association Study , Mendelian Randomization Analysis , Dyslipidemias/drug therapy , Risk Assessment , Quantitative Trait Loci , Odds Ratio
11.
Curr Atheroscler Rep ; 26(6): 217-230, 2024 06.
Article En | MEDLINE | ID: mdl-38662272

PURPOSE OF REVIEW: Dyslipidemia and type 2 diabetes mellitus are two common conditions that are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In this review, we aimed to provide an in-depth and contemporary review of non-invasive approaches to assess subclinical atherosclerotic burden, predict cardiovascular risk, and guide appropriate treatment strategies. We focused this paper on two main imaging modalities: coronary artery calcium (CAC) score and computed tomography coronary angiography. RECENT FINDINGS: Recent longitudinal studies have provided stronger evidence on the relationship between increased CAC, thoracic aorta calcification, and risk of cardiovascular events among those with primary hypercholesterolemia, highlighting the beneficial role of statin therapy. Interestingly, resilient profiles of individuals not exhibiting atherosclerosis despite dyslipidemia have been described. Non-conventional markers of dyslipidemia have also been associated with increased subclinical atherosclerosis presence and burden, highlighting the contribution of apolipoprotein B-100 (apoB)-rich lipoprotein particles, such as remnant cholesterol and lipoprotein(a), to the residual risk of individuals on-target for low-density lipoprotein cholesterol (LDL-C) goals. Regarding type 2 diabetes mellitus, variability in atherosclerotic burden has also been found, and CAC testing has shown significant predictive value in stratifying cardiovascular risk. Non-invasive assessment of subclinical atherosclerosis can help reveal the continuum of ASCVD risk in those with dyslipidemia and diabetes mellitus and can inform personalized strategies for cardiovascular disease prevention in the primary prevention setting.


Atherosclerosis , Diabetes Mellitus, Type 2 , Dyslipidemias , Humans , Dyslipidemias/complications , Dyslipidemias/drug therapy , Diabetes Mellitus, Type 2/complications , Atherosclerosis/diagnosis , Computed Tomography Angiography , Coronary Angiography/methods
12.
Indian J Pharmacol ; 56(2): 97-104, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38687313

OBJECTIVES: India has taken several initiatives to provide health care to its population while keeping the related expenditure minimum. Since cardiovascular diseases are the most prevalent chronic conditions, in the present study, we aimed to analyze the difference in prices of medicines prescribed for three cardiovascular risk factors, based on (a) listed and not listed in the National List of Essential Medicines (NLEM) and (b) generic and branded drugs. MATERIALS AND METHODS: Outpatient prescriptions for diabetes mellitus, hypertension, and dyslipidemia were retrospectively analyzed from 12 tertiary centers. The prices of medicines prescribed were compared based on presence or absence in NLEM India-2015 and prescribing by generic versus brand name. The price was standardized and presented as average price per medicine per year for a given medicine. The results are presented in Indian rupee (INR) and as median (range). RESULTS: Of the 4,736 prescriptions collected, 843 contained oral antidiabetic, antihypertensive, and/or hypolipidemic medicines. The price per medicine per year for NLEM oral antidiabetics was INR 2849 (2593-3104) and for non-NLEM was INR 5343 (2964-14364). It was INR 806 (243-2132) for generic and INR 3809 (1968-14364) for branded antidiabetics. Antihypertensives and hypolipidemics followed the trend. The price of branded non-NLEM medicines was 5-22 times higher compared to generic NLEM which, for a population of 1.37 billion, would translate to a potential saving of 346.8 billion INR for statins. The variability was significant for sulfonylureas, angiotensin receptor blockers, beta-blockers, diuretics, and statins (P < 0.0001). CONCLUSION: The study highlights an urgent need for intervention to actualize the maximum benefit of government policies and minimize the out-of-pocket expenditure on medicines.


Hypoglycemic Agents , India , Humans , Retrospective Studies , Hypoglycemic Agents/economics , Hypoglycemic Agents/therapeutic use , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/economics , Drugs, Generic/economics , Drugs, Generic/therapeutic use , Hypolipidemic Agents/economics , Hypolipidemic Agents/therapeutic use , Heart Disease Risk Factors , Drug Costs , Hypertension/drug therapy , Hypertension/economics , Diabetes Mellitus/drug therapy , Diabetes Mellitus/economics , Dyslipidemias/drug therapy , Dyslipidemias/economics , Antihypertensive Agents/economics , Antihypertensive Agents/therapeutic use , Costs and Cost Analysis
13.
Circ Cardiovasc Qual Outcomes ; 17(5): e010685, 2024 May.
Article En | MEDLINE | ID: mdl-38682335

BACKGROUND: Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed. METHODS: The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences. RESULTS: Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66-0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80-1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62-0.98]). CONCLUSIONS: In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.


Ezetimibe , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Non-ST Elevated Myocardial Infarction , Registries , ST Elevation Myocardial Infarction , Humans , Female , Male , Time Factors , France/epidemiology , Aged, 80 and over , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Treatment Outcome , ST Elevation Myocardial Infarction/mortality , ST Elevation Myocardial Infarction/therapy , ST Elevation Myocardial Infarction/diagnosis , Age Factors , Risk Factors , Non-ST Elevated Myocardial Infarction/mortality , Non-ST Elevated Myocardial Infarction/diagnosis , Non-ST Elevated Myocardial Infarction/therapy , Ezetimibe/therapeutic use , Ezetimibe/adverse effects , Ezetimibe/administration & dosage , Risk Assessment , Dyslipidemias/drug therapy , Dyslipidemias/mortality , Dyslipidemias/diagnosis , Dyslipidemias/blood , Atorvastatin/administration & dosage , Atorvastatin/adverse effects , Drug Therapy, Combination , Percutaneous Coronary Intervention/mortality , Percutaneous Coronary Intervention/adverse effects , Lipids/blood
14.
BMC Cardiovasc Disord ; 24(1): 202, 2024 Apr 08.
Article En | MEDLINE | ID: mdl-38589776

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.


Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Rosuvastatin Calcium , Genetic Predisposition to Disease , Cholesterol, LDL/metabolism , Dyslipidemias/diagnosis , Dyslipidemias/drug therapy , Dyslipidemias/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism , Neoplasm Proteins/genetics , Neoplasm Proteins/metabolism
15.
Eur Rev Med Pharmacol Sci ; 28(7): 2860-2877, 2024 Apr.
Article En | MEDLINE | ID: mdl-38639527

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.


Coronary Artery Disease , Dyslipidemias , Heart Failure , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Dyslipidemias/drug therapy , Heart Failure/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Randomized Controlled Trials as Topic , Meta-Analysis as Topic
16.
Lipids Health Dis ; 23(1): 106, 2024 Apr 14.
Article En | MEDLINE | ID: mdl-38616260

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).


Dyslipidemias , Polymorphism, Genetic , Adult , Humans , Atorvastatin/therapeutic use , 3' Untranslated Regions/genetics , Cholesterol, LDL , Dyslipidemias/drug therapy , Dyslipidemias/genetics , China
17.
Indian Heart J ; 76 Suppl 1: S33-S37, 2024 Mar.
Article En | MEDLINE | ID: mdl-38599727

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.


Anticholesteremic Agents , Atherosclerosis , Cardiovascular Diseases , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hyperlipoproteinemia Type II , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cholesterol, LDL , Dyslipidemias/drug therapy , Atherosclerosis/prevention & control , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/drug therapy , Anticholesteremic Agents/therapeutic use
18.
Can Fam Physician ; 70(3): 187-196, 2024 Mar.
Article En | MEDLINE | ID: mdl-38499368

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.


Dyslipidemias , North American People , Adult , Male , Humans , Female , Retrospective Studies , Prevalence , Canada/epidemiology , Risk Factors , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Obesity/epidemiology , Primary Health Care
19.
Medicine (Baltimore) ; 103(11): e37536, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38489707

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.


Cardiovascular Diseases , Diabetes Mellitus , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Humans , Male , Female , Middle Aged , Aged , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Longitudinal Studies , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/etiology , Dyslipidemias/complications , Dyslipidemias/drug therapy , Dyslipidemias/epidemiology , Primary Prevention/methods , Diabetes Mellitus/epidemiology , Republic of Korea/epidemiology
20.
Front Biosci (Schol Ed) ; 16(1): 8, 2024 Mar 18.
Article En | MEDLINE | ID: mdl-38538342

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.


Cardiovascular System , Dyslipidemias , Humans , Lipoproteins/metabolism , Lipoproteins/therapeutic use , Obesity/drug therapy , Obesity/complications , Dyslipidemias/drug therapy , Dyslipidemias/metabolism , Cardiovascular System/metabolism , Cardiovascular System/pathology , Inflammation/drug therapy
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