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Background: The potential preventive effect of fenofibrate on lower extremity amputation (LEA) and peripheral arterial disease (PAD) in patients with type 2 diabetes (T2D) is not fully elucidated., Methods: We selected adult patients ≥ 20 years of age with T2D from the Korean National Health Insurance Service Database (2009-2012). The fenofibrate users were matched in a 1:4 ratio with non-users using propensity scores (PS). The outcome variables were a composite of LEA and PAD and the individual components. The risks of outcomes were implemented as hazard ratio (HR) with 95% confidence intervals (CI). For safety issues, the risks of acute kidney injury, rhabdomyolysis and resulting hospitalization were analyzed., Results: A total of 114,920 patients was included in the analysis with a median follow-up duration of 7.6 years (22,984 and 91,936 patients for the fenofibrate user and non-user groups, respectively). After PS matching, both groups were well balanced. The fenofibrate group was associated with significantly lower risks of composite outcome of LEA and PAD (HR 0.81; 95% CI 0.70-0.94), LEA (HR 0.76; 95% CI 0.60-0.96), and PAD (HR 0.81; 95% CI 0.68-0.96). The risk of acute kidney injury, rhabdomyolysis, or hospitalization for these events showed no significant difference between the two groups. Subgroup analyses revealed consistent benefits across age groups, genders, and baseline lipid profiles., Conclusions: This nationwide population-based retrospective observational study suggests that fenofibrate can prevent LEA and PAD in patients with T2D who are on statin therapy., (© 2024. The Author(s).)

Clinical research has revealed that inflammatory skin diseases are associated with dyslipidaemia. Modulating lipids is also a rising potential treatment option. However, there is heterogeneity in the existing evidence and a lack of large-scale clinical trials. Observational research is prone to bias, making it difficult to determine causality. This study aimed to evaluate the causal association between lipid-lowering drugs and inflammatory skin diseases. A drug target Mendelian randomisation (MR) analysis was conducted. Genetic targets of lipid-lowering drugs, including proprotein convertase subtilis kexin 9 (PCSK9) and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitor, were screened. Common inflammatory skin diseases, including psoriasis, allergic urticaria, rosacea, atopic dermatitis, systemic sclerosis and seborrhoeic dermatitis, were considered as outcomes. Gene-predicted inhibition of PCSK9 was causally associated with a decreased risk of psoriasis (OR IVW [95%CI] = 0.600 [0.474-0.761], p = 2.48 × 10 -5 ) and atopic dermatitis (OR IVW [95%CI] = 0.781 [0.633-0.964], p = 2.17 × 10 -2 ). Gene-predicted inhibition of HMGCR decreased the risk of seborrhoeic dermatitis (OR IVW [95%CI] = 0.407 [0.168-0.984], p = 4.61 × 10 -2 ) but increased the risk of allergic urticaria (OR IVW [95%CI] = 3.421 [1.374-8.520], p = 8.24 × 10 -3 ) and rosacea (OR IVW [95%CI] = 3.132 [1.260-7.786], p = 1.40 × 10 -2 ). Among all causal associations, only PCSK9 inhibition demonstrated a robust causal effect on psoriasis after a more rigorous Bonferroni test (p < 4.17 × 10 -3 , which is 0.05/12). Modulating lipids via PCSK9 inhibition may offer potential therapeutic targets for psoriasis and atopic dermatitis. Given the potential cutaneous side effects associated with HMGCR inhibitors, PCSK9 inhibitors could be considered viable alternatives in lipid-lowering medication., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Dyslipidemia remains the major cause of atherosclerotic cardiovascular disease (ASCVD). Lipid management in patients with increased cardiovascular (CV) risk needs improvement across Europe, and data gaps are noticeable at the country level., Hypothesis: We described the current treatment landscape in Belgium, hypothesizing that lipid management in patients with ASCVD remains inadequate and aiming to understand the reasons., Methods: Using data from an anonymized primary care database in Belgium derived from 494 750 individuals, we identified those with any CV risk factor between November 2019 and October 2022 and described the clinical features of patients with ASCVD. The main outcomes were the proportion of patients (i) receiving lipid-lowering therapies (LLTs), (ii) per low-density lipoprotein cholesterol (LDL-C) threshold, stratified per LLT, (iii) reaching the 2021 ESC recommended LDL-C goals, and (iv) LDL-C reduction per type of LLT was also determined., Results: Among 40 888 patients with very high CV risk, 24 859 had established ASCVD. Most patients with ASCVD were either receiving monotherapy (59.6%) or had no documented LLT (25.1%). Further, 64.2% of those with no documented LLT exhibited LDL-C levels ≥ 100 mg/dL. Among common treatment options, one of the greatest improvements in LDL-C levels was achieved with combination therapy of statin and ezetimibe, reducing LDL-C levels by 41.5% (p < 0.0001). Yet, in this group, 24.8% of patients had still LDL-C levels ≥ 100 mg/dL and only 20.7% were at goal., Conclusion: Our study emphasizes the importance of developing strategies to help patients achieve their LDL-C goals, with a focus on supporting the implementation of combination LLT in routine clinical practice., (© 2024 Novartis Pharma NV/SA. Clinical Cardiology published by Wiley Periodicals LLC.)

Significant advances in atherosclerotic cardiovascular (ASCVD) risk stratification and treatment have occurred over the past 10 years. While the lipid panel continues to be the basis of risk estimation, imaging for coronary artery calcium is now widely used in estimating risk at the individual level. Statins remain first-line agents for ASCVD risk reduction but in high-risk patients, ezetimibe, proprotein convertase subtilisin kexin-9 inhibitors, and bempedoic acid can be added to further reduce individual cardiovascular risk based on results of cardiovascular outcomes trials. Results of randomized control trials do not support use of medications targeted at triglyceride lowering for ASCVD risk reduction, but icosapent ethyl can be considered., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: We estimated overall refill adherence to all antihypertensive [AHT] and/or lipid-lowering drugs in the treatment regimen and its association with cardiovascular disease (CVD) in adults with type 1 diabetes, taking kidney disease into account., Methods: This Finnish Diabetic Nephropathy Study involved 1,558 adults with type 1 diabetes who had purchased AHT and/or lipid-lowering drugs within ± 0.5 year from baseline and were followed until their first CVD event, death, or end of 2015. Proportion of days covered (PDC) method was used to calculate adherence. The adherence was classified as good (≥80 %), intermediate (≥50 and <80%) or poor (<50%)., Results: Median adherence rate was 74% (IQR 63-84 %). Both good (OR 0.55 [95% CI 0.33, 0.92], P=0.02) and intermediate (0.47 [0.29, 0.77], P=0.003) adherence were associated with lower odds of CVD, compared to poor adherence. Moreover, the higher the adherence percentage point in those with moderate albuminuria, the lower was the odds for CVD (0.81 [0.67, 0.98], P=0.03, per 10 unit increase in adherence)., Conclusions: In adults with type 1 diabetes, refill adherence of 50% or more to cardio-protective medications is associated with lower odds of incident CVD. Our findings highlight the relevance of going beyond prescribing protective CVD drugs, ensuring, and improving medication adherence matters., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: P-H.G. has received lecture honoraria from Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, EloWater, Genzyme, Medscape, MSD, Mundipharma, Novartis, Novo Nordisk, Peer Voice, Sanofi and Sciarc. PHG is an advisory board member for AbbVie, Astellas, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Medscape, MSD, Mundipharma, Nestlé, Novartis, Novo Nordisk, and Sanofi. PHG has received investigator-initiated grants from Eli Lilly and Roche. EBPreports receiving lecture honorariums from Eli Lilly, Abbott, Astra Zeneca, Sanofi, and Boehringer Ingelheim. She was an advisory board member of Sanofi, and since February 2024 she has been a Boehringer-Ingelhiememployee. No other potential conflicts of interest relevant to this article were reported. The funding sources were not involved in the design or conduct of the study. All other authors declare that there is no duality of interest associated with this manuscript., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Elevated levels of lipoprotein(a) [Lp(a)] represent a risk factor for cardiovascular disease including aortic valve stenosis, myocardial infarction and stroke. While the patho-physiological mechanisms linking Lp(a) with atherosclerosis are not fully understood, from genetic studies that lower Lp(a) levels protect from CVD independently of other risk factors including lipids and lipoproteins. Hereby, Lp(a) has been considered an appealing pharmacological target., Results: However, approved lipid lowering therapies such as statins, ezetimibe or PCSK9 inhibitors have a neutral to modest effect on Lp(a) levels, thus prompting the development of new strategies selectively targeting Lp(a). These include antisense oligonucleotides and small interfering RNAs (siRNAs) directed towards apolipoprotein(a) [Apo(a)], which are in advanced phase of clinical development. More recently, additional approaches including inhibitors of Apo(a) and gene editing approaches via CRISPR-Cas9 technology entered early clinical development., Conclusion: If the results from the cardiovascular outcome trials, designed to demonstrate whether the reduction of Lp(a) of more than 80% as observed with pelacarsen, olpasiran or lepodisiran translates into the decrease of cardiovascular mortality and major adverse cardiovascular events, will be positive, lowering Lp(a) will become a new additional target in the management of patients with elevated cardiovascular risk., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients., Objectives: To investigate the patterns in the use of blood pressure-lowering, glucose-lowering, and lipid-lowering medications following BS in Korean patients with morbid obesity., Setting: This study is a retrospective cohort study using the Health Insurance Review and Assignment claims database of South Korea (from 2019 to 2021)., Methods: We included patients who underwent BS between 2019 and 2020 in South Korea. We evaluated the treatment patterns of blood pressure-lowering, glucose-lowering, and lipid-lowering medications at 3-month intervals for 1-year following BS, including medication use, individual medication classes, and the number of medications prescribed. Furthermore, we estimated remission rates for each disorder based on patient characteristics by defining patients who discontinued their medications for at least 2 consecutive quarters as remission., Results: A total of 3810 patients were included in this study. For 1-year following BS, a marked decrease in the number of patients using blood pressure-lowering, glucose-lowering, and lipid-lowering medications was observed. The most remarkable decrease occurred in glucose-lowering medications, which decreased by approximately -75.1% compared with that at baseline. This tendency was consistently observed when analyzing both the number of medications prescribed and the specific medication classes. Regarding remission rates, patients who were female, younger, and received the biliopancreatic diversion-duodenal switch as their BS showed a relatively higher incidence of remission than other groups., Conclusions: BS was associated with a decrease in the use of medications for hypertension, diabetes mellitus (DM), and dyslipidemia., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Numerous epidemiological studies have shown that hypertriglyceridemia is a significant risk factor for cardiovascular diseases (CVD). However, large clinical studies on triglyceride-lowering therapy have yielded inconsistent results. In the current review, we reassess the importance of triglyceride-lowering therapy in preventing CVD based on previous literature and the recently published findings of the PROMINENT trial., Methods: This narrative review is based on literature and public documents published up to November 2023., Results: Meta-analyses of trials on peroxisome proliferator-activated receptor α agonists and triglyceride-lowering therapy, including the PROMINENT trial, have indicated that triglyceride-lowering therapy can reduce CVD events. Mendelian randomization studies have also indicated that triglyceride is indeed a true risk factor for coronary artery disease, leaving no doubt about its relationship to CVD. Meanwhile, the negative results from the PROMINENT trial were likely due to the insufficient triglyceride-lowering effect, slight increases in low-density lipoprotein cholesterol and apolipoprotein B, and the inclusion of mostly high-intensity statin users as target patients. It is unlikely that adverse events counteracted the effectiveness of pemafibrate on outcomes. Additionally, pemafibrate has shown positive effects on non-alcoholic fatty liver disease and peripheral artery disease., Conclusion: Although the PROMINENT trial did not demonstrate the significance of pemafibrate as a triglyceride-lowering therapy in a specific population, it does not necessarily negate the potential benefits of treating hypertriglyceridemia in reducing CVD events. It is necessary to explore appropriate populations that could benefit from this therapy, utilize data from the PROMINENT trial and other databases, and validate findings in real-world settings., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Lipid metabolism plays an essential role in nervous system development. Cholesterol deficiency leads to a variety of neurodevelopmental disorders, such as autism spectrum disorder and fragile X syndrome. There have been a lot of efforts to search for biological markers associated with and causal to ADHD, among which lipid is one possible etiological factor that is quite widely studied. We aimed to evaluate the causal relationship between lipids traits, lipid-lowering drugs, and attention deficit hyperactivity disorder (ADHD) outcomes using Mendelian randomization (MR) studies., Methods: We used summary data from genome-wide association studies to explore the causal relationships between circulating lipid-related traits and ADHD. Then, quantitative trait loci for the expression of lipid-lowering drug target genes and genetic variants associated with lipid traits were extracted. Summary-data-based MR and inverse-variance-weighted MR (IVW-MR) were used to investigate the correlation between the expression of these drug-target genes and ADHD., Results: After rigorous screening, 939 instrumental variables were finally included for univariable mendelian randomization analysis. However, there is no correlation between lipid profile and ADHD risk. Drug target analysis by IVW-MR method observed that APOB -mediated low-density lipoprotein cholesterol was associated with lower ADHD risk (odds ratio [ OR ] = 0.90, 95% confidence interval [CI] [0.84, 0.97]; p  = .007), whereas LPL -mediated triglycerides levels were associated with a higher risk of ADHD ( OR  = 1.13, 95% CI [1.06, 1.21]; p  < .001)., Conclusion: Our results suggest that APOB gene and LPL gene may be candidate drug target genes for the treatment of ADHD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Cardiovascular risk is increased in patients with diabetes. Little is known about glycemic and lipid control in patients with diabetes. We aimed to assess glycemic and lipid controls in patients with diabetes at time of their myocardial infarction., Method: All known patients with type 2 diabetes consecutively admitted for a myocardial infarction in our coronary care unit between March 1 st and December 31 st , 2021 were included in this retrospective study. Glycemic and lipid control was assessed through individualized target of glycated haemoglobin (HbA 1c ) and low-density lipoprotein cholesterol (LDL-c), respectively. At admission, the comprehensive list of chronic medications was obtained through medication reconciliation., Results: This study included 112 patients with a median age of 72 years. Most of patients had an individualized target of HbA 1c and LDL-c of 7.0% (67%) and 0.55g/L (96%), respectively. The rate of uncontrolled patients for HbA 1c and LDL-c and both was 46%, 90%, and 42% respectively. The rate of patients with non-optimal glucose- and lipid-lowering medications in uncontrolled patients was 63% and 87%, respectively. The rate of inappropriate glucose- and lipid-lowering medications was 73% and 91%, respectively., Conclusion: We highlighted the poor glycemic and lipid control in high-risk CV patients. There is an urgent need to develop multidisciplinary approaches to optimize CV risk factors control to reduce myocardial infarction and strokes., (Copyright © 2024. Published by Elsevier Masson SAS.)

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality, necessitating continuous refinement in the management of dyslipidemia, one of its major risk factors, to mitigate cardiovascular risks. Previous studies have proven the critical role of immediate and robust low-density lipoprotein cholesterol (LDL-C) reduction in the aftermath of acute coronary syndrome (ACS). Emphasizing the evidence supporting this approach, we delve into the impact of early intervention on cardiovascular outcomes and propose optimal strategies for achieving rapid LDL-C lowering, while also providing the rationale for early proprotein convertase subtilisin/kexin 9 inhibitor use after an ACS. Given the importance of the residual lipidemic risk, we present an overview of emerging therapeutic avenues poised to reshape dyslipidemia management, such as bempedoic acid, lipoprotein(a) inhibition, ApoC3 modulation, and angiopoietin-like protein 3 targeting. This comprehensive review amalgamates current evidence with future prospects, offering a holistic perspective on the management of dyslipidemia in CAD. By exploring both the urgency for immediate post-ACS LDL-C reduction and the exciting advancements on the horizon, this article provides a roadmap for clinicians navigating the intricate landscape of lipid-lowering therapies in CAD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiovascular diseases (CVD) are currently the most important disease threatening human health, which may be due to the high incidence of risk factors including hyperlipidemia. With the deepening of research on lipoprotein, lipoprotein (a) [Lp(a)] has been shown to be an independent risk factor for atherosclerotic cardiovascular diseases and calcified aortic valve stenosis and is now an unaddressed "residual risk" in current CVD management. Accurate measurement of Lp(a) concentration is the basis for diagnosis and treatment of high Lp(a). This review summarized the Lp(a) structure, discussed the current problems in clinical measurement of plasma Lp(a) concentration and the effects of existing lipid-lowering therapies on Lp(a)., Competing Interests: Declaration of competing interest The authors have declared that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Background: Findings from cardiovascular outcome trials suggest that treatment with fenofibrate may reduce the progression of diabetic retinopathy. However, no dedicated large-scale randomised trials have yet investigated this hypothesis., Methods: LENS is a streamlined randomised double-masked placebo-controlled trial, based in Scotland, assessing whether treatment with fenofibrate (145 mg tablet daily or, in the context of impaired renal function, on alternate days) in people with early retinopathy reduces progression to referable diabetic retinopathy (defined in NHS Scotland's Diabetic Eye Screening grading scheme as referable background or proliferative retinopathy, or referable maculopathy in either eye) or treatment with retinal laser, intravitreal injections or vitrectomy. Adults with diabetes mellitus and non-referable retinopathy (mild background retinopathy in both eyes or observable background retinopathy in one/both eyes at the most recent NHS retinal screening assessment; or observable maculopathy in one/both eyes in the previous 3 years) were eligible. Potential participants were identified from routinely collected healthcare data and followed up using regular contact from the research team and linkage to national electronic morbidity, mortality, biochemistry and retinal screening records. Study treatment was mailed to participants., Results: Between 18 September 2018 and 27 July 2021, 1151 participants were randomised. Their mean age was 61 (SD 12) years, 312 (27%) were female and 305 (26%) had type 1 diabetes. 96% had bilateral mild background retinopathy and 10% had observable maculopathy., Conclusions: LENS will provide a robust evaluation of the efficacy of treating people at risk of progression of diabetic retinopathy with fenofibrate. Results are anticipated in mid-2024., Trial Registrations: NCT03439345; ISRCTN15073006; EuDRACT 2016-002656-24., (© 2024 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Timely carotid endarterectomy (CEA) reduces the risk of future stroke. This benefit is maximized with lifelong drug therapy aimed at reducing further major adverse cardiovascular events (MACEs), including stroke. Studies suggest that around half discontinue these drugs within 12 months. To assess if this is the case following CEA, we considered the MACE-reducing drugs prescribed several years later and compared this with the drugs they were prescribed at CEA., Methods: The electronic primary care records of 347 post-CEA patients a mean of 108 (range 43-185) months after surgery were interrogated. The prescriptions of generic MACE-reducing drugs (antithrombotic, lipid-lowering, antihypertension and diabetes) of the 187 alive were compared with their prescriptions at CEA and with the last prescription of the 160 who had died before the late review. The post-CEA incidence of further MACE in survivors was determined., Results: At late review, fewer of the post-CEA patients alive were taking antiplatelet drugs (143, 76% vs. 170, 91% P < 0.01), but more were fully anticoagulated (37v4 P < 0.01) when compared with prescriptions at CEA. Overall, there was no change in antithrombotic drug prescription rates (167, 89% vs. 172, 92%). Lipid-regulating drugs were well prescribed both at late review and at CEA (173, 93% vs. 169, 90%). The number prescribed antihypertension drugs was significantly higher at late review than at CEA (166, 89% vs. 67, 35% P < 0.01). The number treated for diabetes was similar (64, 34% vs. 42, 23%). There was no difference in the numbers of any of the MACE-reducing drugs prescribed between those who had survived to late review and those who had not. At late review, of those alive, there were 22 (12%) new strokes, and 24 (14%) had developed new or worsening ischemic cardiac symptoms., Conclusions: We found a higher than expected prescription rate of MACE-reducing drugs many years after CEA. This finding may be due, in part, to the nationalized health service in the United Kingdom., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

Background: Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lipid-lowering interventions on this disease., Methods and Results: Data on genetic instruments of lipids/apolipoproteins, as well as characteristic cerebral small vessel disease manifestations, including small vessel stroke (SVS) and white matter hyperintensity (WMH), were obtained from publicly genome-wide association studies. Through 2-sample Mendelian randomization analyses, it was found that decreased levels of high-density lipoprotein cholesterol (odds ratio [OR], 0.85, P =0.007) and apolipoprotein A-I (OR, 0.83, P =0.005), as well as increased level of triglycerides (OR, 1.16, P =0.025) were associated with a higher risk of SVS. A low level of high-density lipoprotein cholesterol (OR, 0.93, P =0.032) was associated with larger WMH volume. Specifically, the genetically determined expressions of lipid fractions in various size-defined lipoprotein particles were more closely related to the risk of SVS than WMH. Moreover, it was found that the hypertension trait ranked at the top in mediating the causal effect of hyperlipidemia on SVS and WMH by using Mendelian randomization-based mediation analysis. For drug-target Mendelian randomization, the low-density lipoprotein cholesterol-reducing genetic variation alleles at HMGCR and NL1CL1 genes and the high-density lipoprotein cholesterol-raising genetic variation alleles at the CETP gene were predicted to decrease the risk of SVS., Conclusions: The present Mendelian randomization study indicates that genetically determined hyperlipidemia is closely associated with a higher risk of cerebral small vessel disease, especially SVS. Lipid-lowering drugs could be potentially considered for the therapies and preventions of SVS rather than WMH.

Competing Interests: Competing interests: None declared.

Background: No routinely recommended cardiovascular disease (CVD) risk prediction equations have adjusted for CVD preventive medications initiated during follow-up (treatment drop-in) in their derivation cohorts. This will lead to underestimation of risk when equations are applied in clinical practice if treatment drop-in is common. We aimed to quantify the treatment drop-in in a large contemporary national cohort to determine whether equations are likely to require adjustment., Methods: Eight de-identified individual-level national health administrative datasets in Aotearoa New Zealand were linked to establish a cohort of almost all New Zealanders without CVD and aged 30-74 years in 2006. Individuals dispensing blood-pressure-lowering and/or lipid-lowering medications between 1 July 2006 and 31 December 2006 (baseline dispensing), and in each 6-month period during 12 years' follow-up to 31 December 2018 (follow-up dispensing), were identified. Person-years of treatment drop-in were determined., Results: A total of 1 399 348 (80%) out of the 1 746 695 individuals in the cohort were not dispensed CVD medications at baseline. Blood-pressure-lowering and/or lipid-lowering treatment drop-in accounted for 14% of follow-up time in the group untreated at baseline and increased significantly with increasing predicted baseline 5-year CVD risk (12%, 31%, 34% and 37% in <5%, 5-9%, 10-14% and ≥15% risk groups, respectively) and with increasing age (8% in 30-44 year-olds to 30% in 60-74 year-olds)., Conclusions: CVD preventive treatment drop-in accounted for approximately one-third of follow-up time among participants typically eligible for preventive treatment (≥5% 5-year predicted risk). Equations derived from cohorts with long-term follow-up that do not adjust for treatment drop-in effect will underestimate CVD risk in higher risk individuals and lead to undertreatment. Future CVD risk prediction studies need to address this potential flaw., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Conflict of interest: G.F.W. has received honoraria for lectures, advisory boards or research grants from Amgen Inc., Arrowhead, AstraZeneca, Esperion, Kowa, Novartis, Regeneron, and Sanofi. D.C.C. does not declare any conflict of interest.

Competing Interests: Conflict of interest: none declared.

Background: The impact on cardiovascular health is lost when a patient does not obtain a newly prescribed lipid-lowering medication, a situation termed "initial medication nonadherence" (IMN). This research summarizes the published evidence on the prevalence, associated factors, consequences, and solutions for IMN to prescribed lipid-lowering medication in the United States., Methods: A systematic literature search using PubMed and Google Scholar, along with screening citations of systematic reviews, identified articles published from 2010 to 2021. Studies reporting results of IMN to lipid-lowering medications were included. Studies that evaluated non-adult or non-US populations, used weaker study designs (e.g., case series), or were not written in English were excluded., Results: There were 19 articles/18 studies that met inclusion and exclusion criteria. Estimates of the prevalence of IMN to newly prescribed lipid-lowering medications ranged from 10 to 18.2% of patients and 1.4-43.8% of prescriptions (n = 9 studies). Three studies reported prescriber and patient characteristics associated with IMN. Hispanic ethnicity, Black race, lower Charlson Comorbidity Index score and no ED visits or hospitalization were associated with IMN. Lipid lowering prescriptions from primary care providers were also associated with IMN. Four studies described patient-reported reasons for IMN, including preference for lifestyle modifications, lack of perceived need, and side effect concerns. Four intervention studies reported mixed results with automated calls, live calls, or letters. One study reported worse clinical outcomes in patients with IMN: higher levels of low-density lipoprotein and greater risk of emergency department visits., Conclusions: Up to one-fifth of patients fail to obtain a newly prescribed lipid-lowering medication but there is limited information about the clinical consequences. Future research should assess outcomes and determine cost-effective approaches to address IMN to lipid-lowering therapy., (© 2024. The Author(s).)

Observational studies suggest dyslipidemia as an atopic dermatitis (AD) risk factor and posit that lipid-lowering drugs may influence AD risk, but the causal link remains elusive. Mendelian randomization was applied to elucidate the causal role of serum lipids in AD and assess the therapeutic potential of lipid-lowering drug targets. Genetic variants related to serum lipid traits and lipid-lowering drug targets were sourced from the Global Lipid Genetics Consortium GWAS data. Comprehensive AD data were collated from the UK Biobank, FinnGen, and Biobank Japan. Colocalization, Summary-data-based Mendelian Randomization (SMR), and mediation analyses were utilized to validate the results and pinpoint potential mediators. Among assessed targets, only Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) was significantly linked to a reduced AD risk, corroborated across three separate AD cohorts. No association between serum lipid concentrations or other lipid-lowering drug targets and diminished AD risk was observed. Mediation analysis revealed that beta nerve growth factor (b-NGF) might mediate approximately 12.8% of PCSK9's influence on AD susceptibility. Our findings refute dyslipidemia's role in AD pathogenesis. Among explored lipid-lowering drug targets, PCSK9 stands out as a promising therapeutic agent for AD., (© 2024. The Author(s).)

This article examines the care gaps in lipid-lowering therapy for atherosclerotic cardiovascular disease (ASCVD), primarily focusing on discrepancies between recommended practices and actual clinical implementation. It provides an overview of the different challenges in lipid management following percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS). Studies reveal gaps in lipid testing and treatment adequacy post-PCI and ACS, as well as knowledge and practice gaps among primary care practitioners, particularly in adhering to the latest lipid guidelines. Initiatives such as the Guidelines Oriented Approach to Lipid-Lowering (GOAL) Canada program and the North American ACS Reflective III Pilot demonstrate improvements in the uptake of nonstatin therapies and achievement of low-density lipoprotein cholesterol targets through targeted educational and feedback interventions. Nonetheless, systemic challenges in the drug approval and reimbursement process persist and affect the accessibility of newer lipid-lowering agents. The most notable contribution of the reviewed studies is the demonstration of improved lipid management outcomes in high-risk ASCVD populations through targeted educational interventions, highlighting their potential value to change clinical practice., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

In the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), statins are the primary pharmacologic intervention for ASCVD risk reduction. Statins have proven efficacy and safety in reducing cardiovascular events and total mortality in patients with and without clinically evident ASCVD. The purpose of this brief review is to provide a stepwise approach to lipid management, including lifestyle recommendations and medical therapy. We first review the main available approaches to lipid lowering and their mechanisms of action. We then summarise the findings of large randomised controlled trials investigating the benefit of statin therapy from 1994 to the present. The available statins are then reviewed, along with their main pharmacologic properties and potential adverse effects. Although statins are generally well tolerated, certain patients may require dose adjustments or alternative treatments because of side-effects. In patients not achieving adequate lipid control on a maximally tolerated statin, nonstatin medications, including ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, provide enhanced low-density lipoprotein cholesterol reduction and cardiovascular benefits, especially in high-risk patients inadequately managed with statins alone. We review the role of triglyceride-lowering agents, including fibric acid derivatives and icosapent ethyl. We then deal with special populations, including those with hepatic steatosis, chronic kidney disease, pregnancy, and heart failure. This field continues to progress, and novel therapies are under active investigation, including an oral PCSK9 inhibitor and molecular therapies targeting lipoprotein(a), angiopoietin-like protein 3, and apolipoprotein CIII. We can look forward to exciting developments that will have major impacts on patient health and management., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ischemic heart disease and stroke are the leading causes of death worldwide. Herein we review the burden, epidemiology, and risk factors for atherosclerotic cardiovascular disease (ASCVD). The focus of this review is on the current state of ASCVD in Canada, however, the findings regarding epidemiological trends are likely to be reflective of global trends, particularly in high-income countries, and the discussion regarding risk factors and lipid lowering is universally applicable. In Canada, the burden of death from ASCVD is second only to cancer deaths. There are major differences in disease burden related to sex, geography, and socioeconomic status. The major risk factors for ASCVD have been identified, although new and emerging risk factors are an active area of research. Recent developments such as polygenic risk scores provide potential to identify individuals at risk for ASCVD earlier in life and institute preventative measures. Dyslipidemia, and in particular elevated concentrations of low-density lipoprotein cholesterol and apolipoprotein B are a major cause of ASCVD. Therapies to lower low-density lipoprotein/apolipoprotein B levels are key components to treating and preventing ASCVD. Addressing the causal risk factors for ASCVD in a manner that comprehensively considers the clinical, social, and economic implications of prevention strategies will be essential to reduce the burden of ASCVD and improve outcomes for patients., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Atherosclerotic cardiovascular disease (ASCVD) is a significant health challenge, and apolipoprotein B (ApoB)-containing lipoproteins are increasingly recognized as central to its progression. Initially labelled as the "low-density lipoprotein hypothesis," our understanding of the etiology of ASCVD has evolved into the "ApoB principle," which highlights the causal and consistent role of all ApoB lipoproteins in ASCVD development. We review the large body of data from genetic studies, to epidemiologic studies, to clinical trials that support this foundational principle. We also provide an overview of the recommendations from guideline committees across the globe on dyslipidemia management and compare these with recent Canadian guidelines. With a few key differences, recent guidelines worldwide provide largely concordant recommendations for diagnosing and managing dyslipidemia with general consensus regarding the need for optimal control of low-density lipoprotein cholesterol and ApoB-containing lipoproteins to prevent cardiovascular events and improve patient care., (Copyright © 2024. Published by Elsevier Inc.)

Background: Idiopathic pulmonary fibrosis (IPF) is a respiratory disorder of obscure etiology and limited treatment options, possibly linked to dysregulation in lipid metabolism. While several observational studies suggest that lipid-lowering agents may decrease the risk of IPF, the evidence is inconsistent. The present Mendelian randomization (MR) study aims to determine the association between circulating lipid traits and IPF and to assess the potential influence of lipid-modifying medications for IPF., Methods: Summary statistics of 5 lipid traits (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, apolipoprotein A, and apolipoprotein B) and IPF were sourced from the UK Biobank and FinnGen Project Round 10. The study's focus on lipid-regulatory genes encompassed PCSK9, NPC1L1, ABCG5, ABCG8, HMGCR, APOB, LDLR, CETP, ANGPTL3, APOC3, LPL, and PPARA. The primary effect estimates were determined using the inverse-variance-weighted method, with additional analyses employing the contamination mixture method, robust adjusted profile score, the weighted median, weighted mode methods, and MR-Egger. Summary-data-based Mendelian randomization (SMR) was used to confirm significant lipid-modifying drug targets, leveraging data on expressed quantitative trait loci in relevant tissues. Sensitivity analyses included assessments of heterogeneity, horizontal pleiotropy, and leave-one-out methods., Results: There was no significant effect of blood lipid traits on IPF risk (all P＞0.05). Drug-target MR analysis indicated that genetic mimicry for inhibitor of NPC1L1, PCSK9, ABCG5, ABCG8, and APOC3 were associated with increased IPF risks, with odds ratios (ORs) and 95% confidence intervals (CIs) as follows: 2.74 (1.05-7.12, P = 0.039), 1.36 (1.02-1.82, P = 0.037), 1.66 (1.12-2.45, P = 0.011), 1.68 (1.14-2.48, P = 0.009), and 1.42 (1.20-1.67, P = 3.17×10 -5 ), respectively. The SMR method identified a significant association between PCSK9 gene expression in whole blood and reduced IPF risk (OR = 0.71, 95% CI: 0.50-0.99, P = 0.043). Sensitivity analyses showed no evidence of bias., Conclusions: Serum lipid traits did not significantly affect the risk of idiopathic pulmonary fibrosis. Drug targets MR studies examining 12 lipid-modifying drugs indicated that PCSK9 inhibitors could dramatically increase IPF risk, a mechanism that may differ from their lipid-lowering actions and thus warrants further investigation., (© 2024. The Author(s).)

Aim: We aimed to evaluate the impact of a multicomponent healthcare intervention, primarily designed to improve glycemic control, on blood pressure and lipids in individuals with poorly controlled type 2 diabetes mellitus (T2DM) in the Catalonian primary care setting METHODS: A cluster, non-randomized, controlled pragmatic trial was conducted across 11 primary care centers. The intervention group (N=225) received a comprehensive, patient-centered approach, including a dedicated monographic consultation to address therapeutic inertia. The control group (N=181) mirrored the intervention group but lacked the monographic consultation. Secondary endpoints included lipid and blood pressure control assessed at baseline and after a 12-month follow-up., Results: 245 participants completed the study over 12 months. We found no differences in the reduction of lipid laboratory parameters between the groups at the final visit. However, no significant differences were found between the groups for other lipids or the proportion of participants achieving lipid target values. Likewise, no differences were noted between the groups for blood pressure, its target control, and treatment at the final visit. Various clinical factors such as age, sex, diabetes duration, HbA1c levels, BMI, and macrovascular complications among the participants were associated with achieving lipid and blood pressure targets at the final visit., Conclusion: The pragmatic multicomponent intervention proposed in the INTEGRA study, showed that including a component designed to reduce clinical inertia in the management of glycemia did not demonstrate benefits in improving lipids and blood pressure in patients with poorly controlled T2DM., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The funders had no role in the design of the study, in the collection, analysis, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. M.M.-C. has received advisory and or speaking fees from Astra-Zeneca, Bayer, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the institution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi. J. F.-N. has received advisory and or speaking fees from Astra-Zeneca, Ascensia, Boehringer Ingelheim, GSK, Lilly, MSD, Novartis, Novo Nordisk, and Sanofi; he has received research grants to the in-stitution from Astra-Zeneca, GSK, Lilly, MSD, Novartis, Novo Nordisk, Sanofi, and Boehringer. D.M. has received advisory and/or speaking fees from AB Biotics, Amgen, Almirall, Ferrer, Gilead, Menarini, MSD, Novo Nordisk and Sanofi. A.M has received advisory and or speaking fees from Astra-Zeneca, Boehringer Ingelheim, Lilly, MSD, Novo Nordisk, and Sanofi; he has received research grants to the institution from Sanofi. M.G, A.B., E.R. and B.V. have no conflict of interest to declare., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Purpose: Neuroendocrine neoplasms (NENs) are a heterogeneous group of malignancies originating from cells with a neuroendocrine phenotype. The complex relationship between lipid metabolism and cancer is gaining interest and a potential anti-cancer effect of lipid lowering agents is being considered. This review aims to discuss the current understanding and treatment of dyslipidaemia in NENs, focusing on the role of lipid lowering agents, including new therapeutic approaches, and future perspectives as possible tool in cancer prevention and tumor-growth control., Methods: We performed an electronic-based search using PubMed updated until December 2023, summarizing the available evidence both in basic and clinical research about lipid lowering agents in NENs., Results: Dyslipidemia is an important aspect to be considered in NENs management, although randomized studies specifically addressing this topic are lacking, unlike other cancer types. Available data mainly regard statins, and in vitro studies have demonstrated direct antitumor effects, including antiproliferative effects in some cancers, supporting possible pleiotropic effects also in NENs, but data remain conflicting. Ezetimibe, omega 3-fatty acids, fibrates and inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) may enhance the regulation of lipid homeostasis, as demonstrated in other cancers., Conclusions: Targeting dyslipidemia in NENs should be part of the multidisciplinary management and an integrated approach may be the best option for both metabolic and tumor control. Whether lipid lowering agents may directly contribute to tumor control remains to be confirmed with specific studies, focusing on association with other metabolic risk, disease stage and primary site., (© 2024. The Author(s).)

Background: Findings from cardiovascular outcome trials suggest that fenofibrate therapy may reduce the progression of diabetic retinopathy., Methods: We recruited and followed adults with nonreferable diabetic retinopathy or maculopathy using the national Diabetic Eye Screening (DES) program in Scotland. We randomly assigned participants to receive 145-mg fenofibrate tablets or placebo (taken daily or, in those with impaired renal function, on alternate days). The primary outcome was a composite of developing referable diabetic retinopathy or maculopathy (based on Scotland's DES grading scheme) or treatment (intravitreal injection, retinal laser, vitrectomy) for retinopathy or maculopathy., Results: A total of 1151 participants were randomly assigned to treatment. During a median of 4.0 years, progression to referable diabetic retinopathy or maculopathy, or treatment thereof, occurred in 131 (22.7%) of 576 participants in the fenofibrate group and 168 (29.2%) of 575 in the placebo group (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.91; P=0.006). In the fenofibrate group compared with the placebo group, the frequencies for any progression of retinopathy or maculopathy were 185 (32.1%) vs. 231 (40.2%); hazard ratio, 0.74; 95% CI, 0.61 to 0.90 and for the development of macular edema were 22 (3.8%) vs. 43 (7.5%); hazard ratio, 0.50; 95% CI, 0.30 to 0.84. Seventeen (3.0%) participants assigned fenofibrate and 28 (4.9%) assigned placebo were given treatment for retinopathy (hazard ratio, 0.58; 95% CI, 0.31 to 1.06). There was no effect on visual function, quality of life, or visual acuity. Trial-averaged estimated glomerular filtration rate was 7.9 (95% CI, 6.8 to 9.1) ml/min/1.73 m 2 lower in participants in the fenofibrate group compared with the placebo group. Serious adverse events occurred in 208 (36.1%) participants allocated fenofibrate and 204 (35.5%) participants allocated placebo., Conclusions: Fenofibrate reduced progression of diabetic retinopathy compared with placebo among participants with early retinal changes. (Funded by the National Institute for Health and Care Research; ClinicalTrials.gov number, NCT03439345; ISRCTN number, ISRCTN15073006.).

Cardiovascular disease (CVD) remains a significant global health challenge despite advancements in prevention and treatment. Elevated Lipoprotein(a) [Lp(a)] levels have emerged as a crucial risk factor for CVD and aortic stenosis, affecting approximately 20 of the global population. Research over the last decade has established Lp(a) as an independent genetic contributor to CVD and aortic stenosis, beginning with Kare Berg's discovery in 1963. This has led to extensive exploration of its molecular structure and pathogenic roles. Despite the unknown physiological function of Lp(a), studies have shed light on its metabolism, genetics, and involvement in atherosclerosis, inflammation, and thrombosis. Epidemiological evidence highlights the link between high Lp(a) levels and increased cardiovascular morbidity and mortality. Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Previous observational studies have reported a possible association between circulating lipids and lipid-lowering drugs and male infertility (MIF), as well as the mediating role of circulating vitamin D. Then, due to issues such as bias, reverse causality, and residual confounding, inferring causal relationships from these studies may be challenging. Therefore, this study aims to explore the effects of circulating lipids and lipid-lowering drugs on MIF through Mendelian randomization (MR) analysis and evaluate the mediating role of vitamin D., Method: Genetic variations related to lipid traits and the lipid-lowering effect of lipid modification targets are extracted from the Global Alliance for Lipid Genetics Genome-Wide Association Study. The summary statistics for MIF are from the FinnGen 9th edition. Using quantitative expression feature loci data from relevant organizations to obtain genetic variations related to gene expression level, further to explore the relationship between these target gene expression levels and MIF risk. Two-step MR analysis is used to explore the mediating role of vitamin D. Multiple sensitivity analysis methods (co-localization analysis, Egger intercept test, Cochrane's Q test, pleiotropy residuals and outliers (MR-PRESSO), and the leave-one-out method) are used to demonstrate the reliability of our results., Result: In our study, we observed that lipid modification of four lipid-lowering drug targets was associated with MIF risk, the LDLR activator (equivalent to a 1-SD decrease in LDL-C) (OR=1.94, 95% CI 1.14-3.28, FDR=0.040), LPL activator (equivalent to a 1-SD decrease in TG) (OR=1.86, 95% CI 1.25-2.76, FDR=0.022), and CETP inhibitor (equivalent to a 1-SD increase in HDL-C) (OR=1.28, 95% CI 1.07-1.53, FDR=0.035) were associated with a higher risk of MIF. The HMGCR inhibitor (equivalent to a 1-SD decrease in LDL-C) was associated with a lower risk of MIF (OR=0.38, 95% CI 0.17-0.83, FDR=0.39). Lipid-modifying effects of three targets were partially mediated by serum vitamin D levels. Mediation was 0.035 (LDLR activator), 0.012 (LPL activator), and 0.030 (CETP inhibitor), with mediation ratios of 5.34% (LDLR activator), 1.94% (LPL activator), and 12.2% (CETP inhibitor), respectively. In addition, there was no evidence that lipid properties and lipid modification effects of six other lipid-lowering drug targets were associated with MIF risk. Multiple sensitivity analysis methods revealed insignificant evidence of bias arising from pleiotropy or genetic confounding., Conclusion: This study did not support lipid traits (LDL-C, HDL-C, TG, Apo-A1, and Apo-B) as pathogenic risk factors for MIF. It emphasized that LPL, LDLR, CETP, and HMGCR were promising drug targets for improving male fertility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Li, Zha, Che, Yu, Yang and Li.)

Aims: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA., Methods and Results: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, P = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, P = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, P = 1.78 × 10-04). PCSK9 (proprotein convertase subtilisin/kexin type 9) and CETP (cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, P = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, P = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA., Conclusion: This study provides causal evidence for the genetic association between lipid-lowering drugs and AA. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objectives: To compare secondary prevention care for patients with coronary heart disease (CHD) and stroke, exploring particularly the influences due to frequency and regularity of primary care visits., Setting: Secondary prevention for patients (≥18 years) in the National Prescription Service administrative electronic health record database collated from 458 Australian general practice sites across all states and territories., Design: Retrospective cross-sectional and panel study. Patient and care-level characteristics were compared for differing CHD/stroke diagnoses. Associations between the type of cardiovascular diagnosis and medication prescription as well as risk factor assessment were examined using multivariable logistic regression., Participants: Patients with three or more general practice encounters within 2 years of their latest visit during 2016-2020., Outcome Measures: Proportions and odds ratios (ORs) for (1) prescription of antihypertensives, antilipidaemics and antiplatelets and (2) assessment of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) in patients with stroke only compared against those with CHD only and those with both conditions., Results: There were 111 892 patients with CHD only, 27 863 with stroke only and 9791 with both conditions. Relative to patients with CHD, patients with stroke were underprescribed antihypertensives (70.8% vs 82.8%), antilipidaemics (63.1% vs 78.7%) and antiplatelets (42.2% vs 45.7%). With sociodemographic factors, comorbidities and level of care considered as covariates, the odds of non-prescription of any recommended secondary prevention medications were higher in patients with stroke only (adjusted OR 1.37; 95% CI (1.31, 1.44)) compared with patients with CHD only. Patients with stroke only were also more likely to have neither BP nor LDL-C monitored (adjusted OR 1.26; 95% CI (1.18, 1.34)). Frequent and regular general practitioner encounters were independently associated with the prescription of secondary prevention medications (p<0.001)., Conclusions: Secondary prevention management is suboptimal in cardiovascular disease patients and worse post-stroke compared with post-CHD. More frequent and regular primary care encounters were associated with improved secondary prevention., Competing Interests: Competing interests: CC reports grants from the National Health and Medical Research Council and National Heart Foundation of Australia, outside the submitted work; JY reports that this work was submitted towards the requirements of the degree of Doctor of Medicine., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The beneficial effects of fenofibrate on atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes and statin treatment are unclear. We investigated the effects of fenofibrate on all-cause mortality and ASCVD in patients with diabetes, high triglyceride (TG) levels and statin treatment., Methods: We performed a nationwide propensity-score matched (1:1) cohort study using data from the National Health Information Database in the Republic of Korea from 2010 to 2017. The study included 110,723 individuals with diabetes, TG levels ≥ 150 mg/dL, and no prior diagnoses of ASCVD who used statins and fenofibrate, and an equal matched number of similar patients who used statins alone (control group). The study outcomes included newly diagnosed myocardial infarction (MI), stroke, both (MI and/or stroke), and all-cause mortality., Results: Over a mean 4.03-year follow-up period, the hazard ratios (HR) for outcomes in the fenofibrate group in comparison to the control group were 0.878 [95% confidence interval (CI) 0.827-0.933] for MI, 0.901 (95% CI 0.848-0.957) for stroke, 0.897 (95% CI 0.858-0.937) for MI and/or stroke, and 0.716 (95% CI 0.685-0.749) for all-cause death. These beneficial effects of fenofibrate were consistent in the subgroup with TG 150-199 mg/dL but differed according to low-density lipoprotein cholesterol (LDL-C) levels., Conclusion: In this nationwide propensity-score matched cohort study involving individuals with diabetes and TG ≥ 150 mg/dL, the risk of all-cause death and ASCVD was significantly lower with fenofibrate use in conjunction with statin treatment compared to statin treatment alone. However, this finding was significant only in individuals with relatively high LDL-C levels., (© 2024. The Author(s).)

Background: Lipid-lowering drugs are widely used among the elderly, with some studies suggesting links to muscle-related symptoms. However, the causality remains uncertain., Methods: Using the Mendelian randomization (MR) approach, we assessed the causal effects of genetically proxied reduced low-density lipoprotein cholesterol (LDL-C) through inhibitions of hydroxy-methyl-glutaryl-CoA reductase (HMGCR), proprotein convertase subtilisin/kexin type 9 (PCSK9), and Niemann-Pick C1-like 1 (NPC1L1) on sarcopenia-related traits, including low hand grip strength, appendicular lean mass, and usual walking pace. A meta-analysis was conducted to combine the causal estimates from different consortiums., Results: Using LDL-C pooled data predominantly from UK Biobank, genetically proxied inhibition of HMGCR was associated with higher appendicular lean mass (beta = 0.087, P = 7.56 × 10 - 5 ) and slower walking pace (OR = 0.918, P = 6.06 × 10 - 9 ). In contrast, inhibition of PCSK9 may reduce appendicular lean mass (beta = -0.050, P = 1.40 × 10 - 3 ), while inhibition of NPC1L1 showed no causal impact on sarcopenia-related traits. These results were validated using LDL-C data from Global Lipids Genetics Consortium, indicating that HMGCR inhibition may increase appendicular lean mass (beta = 0.066, P = 2.17 × 10 - 3 ) and decelerate walking pace (OR = 0.932, P = 1.43 × 10 - 6 ), whereas PCSK9 inhibition could decrease appendicular lean mass (beta = -0.048, P = 1.69 × 10 - 6 ). Meta-analysis further supported the robustness of these causal associations., Conclusions: Genetically proxied HMGCR inhibition may increase muscle mass but compromise muscle function, PCSK9 inhibition could result in reduced muscle mass, while NPC1L1 inhibition is not associated with sarcopenia-related traits and this class of drugs may serve as viable alternatives to sarcopenia individuals or those at an elevated risk., (© 2024. The Author(s).)

Objective: To explore the correlation between asthma risk and genetic variants affecting the expression or function of lipid-lowering drug targets., Methods: We conducted Mendelian randomization (MR) analyses using variants in several genes associated with lipid-lowering medication targets: HMGCR (statin target), PCSK9 (alirocumab target), NPC1L1 (ezetimibe target), APOB (mipomersen target), ANGPTL3 (evinacumab target), PPARA (fenofibrate target), and APOC3 (volanesorsen target), as well as LDLR and LPL. Our objective was to investigate the relationship between lipid-lowering drugs and asthma through MR. Finally, we assessed the efficacy and stability of the MR analysis using the MR Egger and inverse variance weighted (IVW) methods., Results: The elevated triglyceride (TG) levels associated with the APOC3, and LPL targets were found to increase asthma risk. Conversely, higher LDL-C levels driven by LDLR were found to decrease asthma risk. Additionally, LDL-C levels (driven by APOB, NPC1L1 and HMGCR targets) and TG levels (driven by the LPL target) were associated with improved lung function (FEV1/FVC). LDL-C levels driven by PCSK9 were associated with decreased lung function (FEV1/FVC)., Conclusion: In conclusion, our findings suggest a likely causal relationship between asthma and lipid-lowering drugs. Moreover, there is compelling evidence indicating that lipid-lowering therapies could play a crucial role in the future management of asthma., (© 2024. The Author(s).)

Background: Hyperglycemia in diabetes mellitus (DM) can lead to dyslipidemia, which is a risk factor for macrovascular complications such as heart disease and stroke. Aside from administering antidiabetic medications, DM treatment can also be achieved through the use of natural components, such as Myrmecodia pendans , commonly known as the ant nest plant (ANP)., Aim: This study aimed to investigate the impact of administering the ANP on the lipid profile of Wistar rats., Methods: A group of 20 rats was divided into two categories: 6 rats served as healthy controls (H), while the remaining 14 rats were subjected to a high-lipid diet and streptozotocin to generate a model of type 2 diabetes mellitus (T2DM). The diabetic rats were divided into two groups: the DM group consisted of rats that did not receive any treatment, while the ANP group was administered the herb orally., Results: The results revealed significant variations in triglyceride, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels among the three groups ( p < 0.05). The post hoc test revealed disparities in triglyceride and LDL between those in the DM group and the ANP group ( p < 0.05)., Conclusion: Myrmecodia pendans demonstrated the ability to decrease triglyceride and LDL, while increasing HDL levels in rats with T2DM., Competing Interests: The author of this paper does not have any conflicting interests.

Aim: To investigate the impact of triglyceride on hypertriglyceridemic acute pancreatitis (HTG-AP) and different lipid-lowering methods on triglyceride-lowering efficiency and HTG-AP., Methods: The patients with HTG-AP from January 2012 to December 2023 in Civil Aviation General Hospital were analyzed, retrospectively. Patients were divided and compared according to whether their triglycerides were below 5.56 mmol/L at 48 and 72 h of admission. The patients were divided into control group, insulin group, and low molecular weight heparin (LMWH)+bezafibrate group based on the different methods of lipid-lowering. Propensity score matching (PSM) was employed to balance the baseline characteristics., Results: There was no correlation between the severity of HTG-AP and the triglyceride at admission. The incidence of severity, local complications, and persistent organ failure (POF) were significantly decreased in patients with 48-h and 72-h triglyceride attainment. Following PSM, the incidence of infectious pancreatic necrosis (IPN) (3.3% vs. 13.3%) was significantly reduced in insulin group compared with control group ( p  < .05). Compared with control group, LMWH + bezafibrate group had higher lipid reduction efficiency, and the incidence of IPN (0.9% vs. 10.1%) and POF (8.3% vs. 19.3%) was significantly decreased ( p  < .05). There was no significant difference in the efficiency of lipid-lowering, complications, and POF between LMWH + bezafibrate group and insulin group ( p  > .05)., Conclusion: The severity of HTG-AP is not associated with the triglyceride levels at admission. However, rapid reduction of triglyceride levels can lower the incidence of local complications and respiratory failure. Compared with conservative treatment, insulin and LMWH + bezafibrate can both reduce the incidence of IPN in patients with HTG-AP.

Purpose: The objective of this investigation is to examine the benefits and potential risks of these drugs in individuals by varying baseline low-density lipoprotein cholesterol (LDL-C) values, utilizing the concept of the number needed to treat (NNT)., Methods: We extensively searched electronic databases, such as PubMed, EMBASE, Cochrane, and Web of Science, up to 6 August 2023. Baseline LDL-C values were stratified into four categories: < 100, 100-129, 130-159, and ≥ 160 mg/dL. Risk ratios (RRs) and NNT values were computed., Results: This analysis incorporated data from 46 randomized controlled trials (RCTs), encompassing a total of 237,870 participants. The meta-regression analysis demonstrated an incremental diminishing risk of major adverse cardiovascular events (MACE) with increasing baseline LDL-C values. Statins exhibited a significant reduction in MACE [number needed to treat to benefit (NNTB) 31, 95% confidence interval (CI) 25-37], but this effect was observed only in individuals with baseline LDL-C values of 100 mg/dL or higher. Ezetimibe and PCSK9 inhibitors also were effective in reducing MACE (NNTB 18, 95% CI 11-41, and NNTB 18, 95% CI 16-24). Notably, the safety outcomes of statins and ezetimibe did not reach statistical significance, while the incidence of injection-site reactions with PCSK9 inhibitors was statistically significant [number needed to treat to harm (NNTH) 41, 95% CI 80-26]., Conclusion: Statins, ezetimibe, and PCSK9 inhibitors demonstrated a substantial capacity to reduce MACE, particularly among individuals whose baseline LDL-C values were relatively higher. The NNT visually demonstrates the gradient between baseline LDL-C and cardiovascular disease (CVD) risk., Systematic Review Registration: Registration: PROSPERO identifier number: CRD42023458630., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Research Question: Does the observed correlation between dyslipidaemia and endometriosis indicate a bidirectional causal association?, Design: Bidirectional Mendelian randomization was used to investigate the causal association between lipid traits and endometriosis. Drug-target Mendelian randomization was used to explore potential drug-target genes for managing endometriosis. In cases where lipid-mediated effects via specific drug targets were significant, aggregate analyses, such as summary-data-based Mendelian randomization and colocalization methods, were introduced to validate the outcomes. Mediation analyses supplemented these evaluations., Results: The bidirectional Mendelian randomization results suggested that genetically predicted triglyceride (OR 1.15, 95% CI 1.08-1.23), high-density lipoprotein cholesterol (OR 0.87, 95% CI 0.81-0.94), low-density lipoprotein cholesterol (OR 1.20, 95% CI 1.06-1.34) and apolipoprotein A (OR 0.90, 95% CI 0.83-0.96) concentrations were causally associated with endometriosis. Reverse Mendelian randomization results revealed that genetically proxied endometriosis was causally associated with triglyceride concentration (OR 1.02, 95% CI 1.01-1.02). In drug-target Mendelian randomization, genetic mimicry in proprotein convertase subtilisin/kexin type 9 (PCSK9) (OR 1.40, 95% CI 1.13-1.72), apolipoprotein B (APOB) (OR 1.49, 95% CI 1.21-1.86) and angiopoietin-related protein 3 (ANGPTL3) (OR 1.57, 95% CI 1.14-2.16) was significantly associated with the risk of endometriosis stages 1-2., Conclusion: There is a potential bidirectional causal association between endometriosis and dyslipidaemia. Genetic mimicry of PCSK9, APOB and ANGPTL3 is associated with the risk of early-stage endometriosis. The development of lipid-lowering drugs to treat endometriosis is of potential clinical interest., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Aim: To evaluate the association between frailty and initiating, continuing, or discontinuing secondary prevention medications following myocardial infarction (MI)., Methods: We conducted a cohort study using linked health data, including all adults aged ≥65 years who discharged from hospital following MI from January 2013 to April 2018 in Victoria, Australia (N = 29,771). The Hospital Frailty Risk Score (HFRS) was used to assess frailty. Logistic regression was used to investigate associations of frailty with initiation, continuation, and discontinuation of secondary prevention medications (P2Y12 inhibitor antiplatelets, beta-blockers, renin-angiotensin-aldosterone system (RAAS) inhibitors, and lipid-lowering therapies) in the 90 days from discharge post-MI, by HFRS, adjusted for age, sex, and Charlson Comorbidity Index., Results: Increasing frailty was associated with lower probability of initiating and continuing P2Y12 inhibitors, RAAS inhibitors, and lipid-lowering therapies, but not beta-blockers. At at an HFRS of 0, the predicted probabiliy of having all four medications initiated or continued was 0.59 (95 %CI 0.57-0.62) for STEMI and 0.35 (0.34-0.36) for non-STEMI, compared to 0.38 (0.33-0.42) and 0.16 (0.14-0.18) at an HFRS of 15. Increasing frailty was associated with higher probability of discontinuing these medications post-MI. The predicted probability of discontinuing at least one secondary prevention medication post-MI at an HFRS of 0 was 0.10 (0.08-0.11) for STEMI and 0.14 (0.13-0.15) for non-STEMI, compared to 0.27 (0.22-0.32) and 0.34 (0.32-0.36) at an HFRS of 15., Conclusion: People with higher levels of frailty were managed more conservatively following MI than people with lower levels of frailty. Whether this conservative treatment is justified warrants further study., Competing Interests: Declaration of competing interest JSB was supported by a National Health and Medical Research Council (NHMRC) Boosting Dementia Research Leadership Fellowship and has received grant or consulting funds from the NHMRC, Medical Research Future Fund, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Program, Amgen, and several aged care provider organizations unrelated to this work. All grants and consulting funds were paid to the employing institution. All other authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)