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JACC. Advances Apr 2024Statins reduce low-density lipoprotein cholesterol (LDL-C) and are efficacious in the prevention of atherosclerotic cardiovascular disease (ASCVD). Dose-response to...
BACKGROUND
Statins reduce low-density lipoprotein cholesterol (LDL-C) and are efficacious in the prevention of atherosclerotic cardiovascular disease (ASCVD). Dose-response to statins varies among patients and can be modeled using three distinct pharmacological properties: (1) E (baseline LDL-C), (2) ED (potency: median dose achieving 50% reduction in LDL-C); and (3) E (efficacy: maximum LDL-C reduction). However, individualized dose-response and its association with ASCVD events remains unknown.
OBJECTIVE
We analyze the relationship between ED and E with real-world cardiovascular disease outcomes.
METHOD
We leveraged de-identified electronic health record data to identify individuals exposed to multiple doses of the three most commonly prescribed statins (atorvastatin, simvastatin, or rosuvastatin) within the context of their longitudinal healthcare. We derived ED and E to quantify the relationship with a composite outcome of ASCVD events and all-cause mortality.
RESULTS
We estimated ED and E for 3,033 unique individuals (atorvastatin: 1,632, simvastatin: 1,089, and rosuvastatin: 312) using a nonlinear, mixed effects dose-response model. Time-to-event analyses revealed that ED and E are independently associated with the primary endpoint. Hazard ratios were 0.85 (p < 0.01), 0.83 (p < 0.01), and 0.87 (p = 0.10) for ED and 1.13 (p < 0.001), 1.06 (p < 0.001), and 1.15 (p = 0.009) for E in the atorvastatin, simvastatin, and rosuvastatin cohorts, respectively.
CONCLUSION
The class-wide association of ED and E with clinical outcomes indicates that these measures influence the risk for ASCVD events in patients on statins.
PubMed: 38737008
DOI: 10.1016/j.jacadv.2024.100894 -
BMC Cardiovascular Disorders May 2024The 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,...
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.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; United States; Interrupted Time Series Analysis; Time Factors; Practice Guidelines as Topic; Retrospective Studies; Male; Female; Aged; Middle Aged; Treatment Outcome; Guideline Adherence; Biomarkers; Dyslipidemias; Atorvastatin; Cardiovascular Diseases; Databases, Factual; Practice Patterns, Physicians'; Cholesterol; Medication Adherence; Drugs, Generic; Risk Assessment
PubMed: 38730371
DOI: 10.1186/s12872-024-03921-z -
Medicine May 2024Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
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.
Topics: Humans; Rosuvastatin Calcium; Female; Atorvastatin; Middle Aged; Bone Remodeling; Postmenopause; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Biomarkers; Collagen Type I; Osteoporosis, Postmenopausal; Dyslipidemias
PubMed: 38728464
DOI: 10.1097/MD.0000000000038122 -
Frontiers in Endocrinology 2024A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded...
BACKGROUND
A serious consequence of diabetes is diabetic nephropathy (DN), which is commonly treated by statins. Studies evaluating the effects of statin medication have yielded inconsistent results regarding the potential association with diabetic nephropathy. To manage diabetic nephropathy's onset and improve the quality of life of patients, it is imperative to gain a comprehensive understanding of its contributing factors.
DATA AND METHODS
Our study was conducted using the National Health and Nutrition Examination Survey (NHANES) as well as weighted multivariate logistic regression models to determine the odds ratio (OR) and 95% confidence intervals (95%CI) for diabetic nephropathy. We conducted stratified analyses to examine the impact of statins and the duration of their usage on diabetic nephropathy in different subgroups. A nomogram model and the receiver operating characteristic (ROC) curve were also developed to predict DN risk.
RESULTS
Statin use significantly increased the incidence of DN (OR=1.405, 95%CI (1.199,1.647), p<0.001). Individuals who used statins for 5 to 7 years were more likely to develop diabetic nephropathy (OR=1.472, 95%CI (1.057,2.048), p=0.022) compared to those who used statins for 1-3 years (OR=1.334, 95%CI (1.058,1.682), p=0.015) or <1 year (OR=1.266, 95%CI (1.054,1.522), p = 0.012). Simvastatin has a greater incidence of diabetic nephropathy (OR=1.448, 95%CI(1.177, 1.78), P < 0.001).
CONCLUSION
Taking statins long-term increases the risk of DN. Statin use is associated with an increased risk of DN. Caution should be exercised when prescribing atorvastatin and simvastatin for long-term statin therapy.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Diabetic Nephropathies; Male; Female; Nutrition Surveys; Middle Aged; United States; Adult; Aged; Incidence; Risk Factors
PubMed: 38726340
DOI: 10.3389/fendo.2024.1381746 -
Journal of Yeungnam Medical Science May 2024Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin...
BACKGROUND
Statins reduce the risk of cardiovascular events in patients with chronic kidney disease (CKD). Although diabetes mellitus (DM) is a reported side effect of statin treatment, some studies have indicated that pitavastatin does not cause DM. The present study investigated the effect of pitavastatin on the fatty acid (FA) content of erythrocyte membranes, which affects the occurrence of DM and cardiovascular diseases. In addition, changes in adiponectin and glycated hemoglobin (HbA1c) levels were evaluated after pitavastatin treatment.
METHODS
A total of 45 patients were enrolled, 28 of whom completed the study. Over 24 weeks, 16 patients received 2 mg pitavastatin and 12 patients received 10 mg atorvastatin. Dosages were adjusted after 12 weeks if additional lipid control was required. There were 10 and nine patients with DM in the pitavastatin and atorvastatin groups, respectively. Erythrocyte membrane FAs and adiponectin levels were measured using gas chromatography and enzyme-linked immunosorbent assay, respectively.
RESULTS
In both groups, saturated FAs, palmitic acid, trans-oleic acid, total cholesterol, and low-density lipoprotein cholesterol levels were significantly lower than those at baseline. The arachidonic acid (AA) content in the erythrocyte membrane increased significantly in the pitavastatin group, but adiponectin levels were unaffected. HbA1c levels decreased in patients treated with pitavastatin. No adverse effects were associated with statin treatment.
CONCLUSION
Pitavastatin treatment in patients with CKD may improve glucose metabolism by altering erythrocyte membrane AA levels. In addition, pitavastatin did not adversely affect glucose control in patients with CKD and DM.
PubMed: 38715530
DOI: 10.12701/jyms.2024.00094 -
American Heart Journal Aug 2024The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of...
BACKGROUND
The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.
METHODS
This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations.
RESULTS
Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance.
CONCLUSION
Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Female; Male; Cholesterol, LDL; Comorbidity; Denmark; Middle Aged; Aged; Atorvastatin; Registries; Simvastatin; Hypoglycemic Agents; Metformin; Cohort Studies
PubMed: 38710378
DOI: 10.1016/j.ahj.2024.04.018 -
Clinical Medicine (London, England) May 2024Statin-induced immune-mediated necrotising myopathy (IMNM) is an inflammatory myopathy that can present as proximal muscle weakness and, in some cases, as dysphagia and...
Statin-induced immune-mediated necrotising myopathy (IMNM) is an inflammatory myopathy that can present as proximal muscle weakness and, in some cases, as dysphagia and respiratory distress. In this report, we present a case of statin-induced IMNM in a 78-year-old male. The patient had significantly high levels of creatinine kinase and myoglobinuria and experienced gradual weakness in the proximal muscles for 1 month after initiating a 20 mg dose of Atorvastatin 10 months before admission. Rapid clinical improvement was observed with the use of high-dose glucocorticoids in conjunction with methotrexate.
Topics: Humans; Male; Aged; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myositis; Atorvastatin; Methotrexate; Pyrroles; Immunosuppressive Agents; Heptanoic Acids; Necrosis; Glucocorticoids; Muscular Diseases
PubMed: 38710328
DOI: 10.1016/j.clinme.2024.100217 -
Clinical, Cosmetic and Investigational... 2024Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare...
Xanthomas are well-circumscribed skin lesions that are commonly seen in patients with familial hypercholesterolemia (FH). The aim of this report is to present a rare case of multiple large tuberous and tendinous xanthomas. A 17-year-old female patient in this report presented with multiple asymptomatic and papulo-nodular masses in both sides of palms, elbows, buttocks, knees, and Achilles tendons. Surgical removal of the masses was carried out in combination with lipid-lowering therapy. A following up of 3 months showed all wounds were healing well, and no recurrence of masses was observed. Therefore, for patients with xanthomas related with familial hypercholesterolaemia, lipid-lowering therapy has reportedly reduced the size of masses, but surgical treatment may be essential for large xanthomas caused pain or limitation of daily activities.
PubMed: 38707607
DOI: 10.2147/CCID.S445163 -
Free Radical Biology & Medicine Aug 2024Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity...
Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.
Topics: Animals; Atorvastatin; Extracellular Traps; Sepsis; Mice; Imipenem; NADPH Oxidase 2; Disease Models, Animal; Lung Injury; Male; MAP Kinase Signaling System; Neutrophils; Signal Transduction; Humans; Mice, Inbred C57BL; Drug Therapy, Combination
PubMed: 38704053
DOI: 10.1016/j.freeradbiomed.2024.05.006 -
Annals of Medicine and Surgery (2012) May 2024Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are...
BACKGROUND AND PURPOSE
Nonalcoholic fatty liver disease (NAFLD) is a growing problem with a significant burden. Lifestyle modification is the recommended treatment, but researchers are exploring other options. This study focused on the effects of (FP) extracts on NAFLD induced by a high-fat diet in rats.
EXPERIMENTAL APPROACH
Thirty-five 10-week-old male Wister-Albino rats were divided into seven groups: normal diet control, high fat diet control, high fat diet with oral normal saline gavage, high fat diet with oral Atorvastatin gavage, and three groups receiving high fat diet with FP extract in 200 mg/kg, 400 mg/kg, and 700 mg/kg.Blood samples of rats were used for the measurement of total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP).1×1 cm Liver biopsies were taken, stained with Trichrome Stain (Masson) and Hematoxylin and eosin (H&E) stain for evaluation by a pathologist.
FINDINGS/RESULTS
Lab results showed that FP extract inhibits weight gain, has positive effects on triglyceride and alkaline phosphatase levels, and reduces hepatocyte ballooning and inflammation in rats.
CONCLUSION
FP extract may lower liver enzymes and have a positive impact on triglyceride, LDL, and HDL levels in rats with NAFLD.
PubMed: 38694306
DOI: 10.1097/MS9.0000000000001890