BACKGROUND: The need for conversional metabolic and bariatric surgery (CMBS) is still growing. No large-scale prospective cohort studies have assessed changes in lipid-lowering treatment (LLT) after CMBS.
OBJECTIVE: This study assesses and compares the effectiveness of the 4 main CMBS sequences after sleeve gastrectomy (SG) and adjustable gastric banding (AGB) on reimbursement and cost of LLT.
METHODS: France.
METHODS: This nationwide observational population-based cohort study analyzed data from the French National Health Insurance database. It included all patients who had undergone primary SG and AGB in France between January 1, 2012, and December 31, 2014, and followed until December 31, 2020. The study assessed LLT reimbursement evolution and costs across 4 different CMBS sequences.
RESULTS: During follow-up, 6396 patients underwent the 4 CMBS sequences: SG-RYGB (Roux-en-Y gastric bypass) (n = 2400), AGB-SG (n = 2277), AGB-RYGB (n = 1173), and SG-SG (n = 546), with a rate of LLT reimbursement of 9.8%, 3.6%, 6.6%, and 7.9%, respectively, in the year before CMBS. The rates of discontinuation of treatment at 2 and 4 years were 41.9%, 35.4%, 45.6%, 20.5% and 45.6%, 31.3%, 64.3%, 31.6%, respectively. At 4 years, the median [interquartile range] annual costs (euros) per patient were significantly lower (P < .01) than the costs in the year before CMBS for each sequence: 86.8 [57.3; 136.1] versus 38.0 [.0; 64.6], 79.1 [50.5; 120.1] versus 50.4 [15.6; 64.1], 89.0 [66.5; 139.6] versus .0 [.0; 58.8], and 89.8 [66.1; 121.4] versus 63.1 [.0; 93.4].
CONCLUSIONS: Our study underlines the effectiveness of CMBS in significantly reducing the need and associated costs of LLT for patients with dyslipidemia over a 4-year period.

Nowdays a small proportion of patients with high/very high/extreme atherosclerotic cardiovascular disease risk achieves the optimal target of LDL-cholesterol, because of drug intolerance, poor adherence to the therapy, or inapplicability of the stepwise strategy in lipid lowering therapy, recommended by the current guidelines. The new oral agent bempedoic acid lowers plasma LDL-cholesterol by inhibiting adenosine triphosphate-citrate lyase, an enzyme involved in the synthesis of cholesterol, and, ultimately, by up-regulating the LDL receptors. Several clinical trials in patients with atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia demonstrated that bempedoic acid alone or combined with statins and/or ezetimibe significantly reduced LDL-cholesterol and high-sensitivity C-reactive protein. Bempedoic acid is well tolerated with no significant increase in muscle-related symptoms, since it can be activated only in the liver but not in the skeletal muscles. Bempedoic acid provides an effective tool to further reduce LDL-cholesterol as add on therapy in patients unable to reach the target despite maximally tolerated lipid lowering therapy.

OBJECTIVE: Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297).
METHODS: MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH.
RESULTS: Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality.
CONCLUSIONS: Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

OBJECTIVE: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). Since the first functional and morphologic changes of the arterial wall occur in childhood, treatment should start early in childhood to mitigate the elevated risk of ASCVD. Pediatricians play an important role in the detection and care of children with FH. In this study, we aim to explore potential gaps in FH care amongst Dutch pediatricians, in order to enhance their knowledge and awareness of detecting and treating children with FH.
METHODS: An anonymous online survey, deployed using Google Forms, including 26 closed and semi-closed questions on FH care in children was distributed by the Dutch Association of Pediatrics via a newsletter to which the majority of the practicing Dutch pediatricians subscribe. In addition, we requested that the pediatric departments of all Dutch hospitals in the Netherlands distribute this survey personally among their employed pediatricians. Respondents were instructed to answer the questions without any help or use of online resources.
RESULTS: Between September 1st, 2023 and November 1st, 2023, 158 (an estimated 11% response rate) Dutch pediatricians completed the survey. They reported a median (IQR) of 15.0 (6.0-22.0) years of experience as a pediatrician, and 34 (21.5%) were working in academic hospitals. The majority (76.6%) of pediatricians correctly identified a typical FH lipid profile but 68 (43.0%) underestimated the true prevalence of FH (1:300). Underestimation and unawareness of the increased risk of FH patients for ASCVD were reported by 37.3% and 25.9% of pediatricians, respectively. Although 70.9% of the pediatricians correctly defined FH, only 67 (42.4%) selected statins and ezetimibe to treat severe hypercholesterolemia.
CONCLUSIONS: The results of this study suggest significant gaps in knowledge and awareness of FH in children among Dutch pediatricians. FH care in children needs improvement through educational and training initiatives to mitigate the life-long risk of ASCVD from early life.
BACKGROUND: • Familial hypercholesterolemia (FH) leads to elevated LDL-cholesterol levels, which increases the risk of premature atherosclerotic cardiovascular disease (ASCVD). • The process of atherosclerosis starts in childhood • Pediatricians play an important role in the detection and treatment of children with FH.
BACKGROUND: • Our results highlight significant gaps in care for children with FH amongst pediatricians and this may lead to suboptimal detection and treatment. • FH care in children needs improvement by educational initiatives to ultimately prevent ASCVD in adulthood.

OBJECTIVE: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event.
METHODS: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment.
RESULTS: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure.
CONCLUSIONS: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions.

BACKGROUND: Heterozygous familial hypercholesterolemia (HeFH) predisposes to premature cardiovascular diseases. Since 2015, the European Atherosclerosis Society has advocated initiation of statins at 8-10 years of age and a low-density lipoprotein cholesterol (LDL-C) target of <135 mg/dL. Longitudinal data from large databases on pharmacological management of pediatric HeFH are lacking.
OBJECTIVE: Here, we describe treatment patterns and LDL-C goal attainment in pediatric HeFH using longitudinal real-world data.
METHODS: This was a retrospective and prospective multicenter cohort study (2015-2021) of children with HeFH, diagnosed genetically or clinically, aged <18 years, and followed up in the National French Registry of FH (REFERCHOL). Data on the study population as well as treatment patterns and outcomes are summarized as mean±SD.
RESULTS: We analyzed the data of 674 HeFH children (age at last visit: 13.1 ± 3.6 years; 82.0 % ≥10 years; 52.5 % females) who were followed up for a mean of 2.8 ± 3.5 years. Initiation of lipid-lowering therapy was on average at 11.8 ± 3.0 years of age for a duration of 2.5 ± 2.8 years. At the last visit, among patients eligible for treatment (573), 36 % were not treated, 57.1 % received statins alone, 6.4 % statins with ezetimibe, and 0.2 % ezetimibe alone. LDL-C was 266±51 mg/dL before treatment and 147±54 mg/dL at the last visit (-44.7 %) in treated patients. Regarding statins, 3.3 %, 65.1 %, and 31.6 % of patients received high-, moderate-, and low-intensity statins, respectively. Overall, 59 % of children on statin therapy alone and 35.1 % on bitherapy did not achieve the LDL-C goal; fewer patients in the older age group did not reach the treatment goal.
CONCLUSIONS: Pediatric patients with FH followed up in specialist lipid clinics in France receive late treatment, undertreatment, or suboptimal treatment and half of them do not reach the therapeutic LDL-C goal. Finding a more efficient framework for linking scientific evidence to clinical practice is needed.

OBJECTIVE: Lipoprotein (a) [Lp(a)] concentration influences serum low-density lipoprotein cholesterol (LDL-C) levels. How it influences the achievement of LDL-C targets established in the guidelines is not well studied. Our aim was to know the prevalence of elevated Lp(a) levels in patients with coronary artery disease, and to assess its influence on the achievement of LDL-C targets.
METHODS: We conducted a cross-sectional study in a cardiology department in Spain. A total of 870 patients with stable coronary artery disease had their lipid profile determined, including Lp(a). Patients were stratified into 2 groups according to Lp(a)>50mg/dL and Lp(a)≤50mg/dL. The association of Lp(a)>50mg/dL with achievement of LDL-C targets was assessed by logistic regression analysis.
RESULTS: The prevalence of Lp(a)>50mg/dL was 30.8%. Patients with Lp(a)>50mg/dL had higher baseline (142.30±47.54 vs. 130.47±40.75mg/dL; p=0.0001) and current (72.91±26.44 vs. 64.72±25.30mg/dL; p=0.0001), despite the fact that they were treated with more high-potency statins (77.2 vs. 70.9%; p=0.058) and more combination lipid-lowering therapy (37.7 vs. 25.7%; p=0.001). The proportion of patients achieving target LDL-C was lower in those with Lp(a)>50mg/dL. Independent predictors of having elevated Lp(a) levels>50mg/dL were the use of high-potency statins (OR 1.5; 95% CI 1.08-2.14), combination lipid-lowering therapy with ezetimibe (OR 2.0; 95% CI 1.45-2.73) and failure to achieve a LDL-C ≤55mg/dL (OR 2.3; 95% CI 1.63-3.23).
CONCLUSIONS: Elevated Lp(a) levels influence LDL-C levels and hinder the achievement of targets in patients at very high cardiovascular risk. New drugs that act directly on Lp(a) are needed in these patients.

The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence.
Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment.
Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk.
In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of potent lipid-lowering drugs. Oxidized low-density lipoprotein (ox-LDL) is the key pathogenic factor leading to atherosclerosis. However, its effect on ox-LDL levels has not been clinically reported. The clinical data of 290 very high-risk atherosclerotic cardiovascular disease (ASCVD) patients diagnosed in the First Affiliated Hospital of Zhengzhou University from May 2022 to October 2022 were collected retrospectively. According to whether evolocumab (a PCSK9 inhibitor) was used after percutaneous coronary intervention (PCI), they were divided into evolocumab group (153 cases) and statin monotherapy group (137 cases). At hospital admission, ox-LDL, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoproteinA1 (apoA1), apolipoprotein B-100 (apoB), lipoprotein (a) [Lp(a)], and high-sensitivity reactive protein (hs-CRP) levels were collected and used as baseline data. After two weeks of treatment, ox-LDL in the evolocumab group and statin monotherapy group were significantly lower than those before treatment (p<0.05). The decrease of ox-LDL in the evolocumab group was more than in the stain monotherapy group (p<0.05). In conclusion, PCSK9 inhibitors reduce ox-LDL levels in very high-risk ASCVD patients in a short time.

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48-0.92, p = 0.01), CAC score > 100 (1.59; 1.08-2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19-3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.