Lipid Clinic Research Articles

Jena auf Ziel: get all patients with ST-elevation myocardial infarction on EAS/ESC-LDL-C targets

Abstract Background and aims Low-density lipoprotein cholesterol (LDL-C) reduction is an essential part of the 2019 ESC/EAS dyslipidemia guidelines [1]. Only 18% of patients achieve 2019 ESC/EAS LDL-C target goal in secondary prevention [2]. “Jena auf Ziel – JaZ” (“Jena on target”) is a prospective study that aims at LDL-C target attainment in all patients with ST-elevation myocardial infarction (STEMI) and determination of reasons for failed target attainment. Methods All STEMI patients were started on atorvastatin 80 mg/ezetimibe 10 mg on admission. LDL-C levels were monitored during the hospital stay and a 12 months follow-up period. Patients were educated about cardiovascular risk factor optimization. Individual patient cards to document LDL-C levels over time were used to enforce LDL-C target attainment. Results In the first 50 consecutive patients, LDL-C levels were 3.39±1.23 mmol/L on admission, 1.84±0.86 mmol/L on discharge and 1.30±0.65 mmol/L during the first follow-up visit (6–8 weeks). On atorvastatin 80 mg/ezetimibe 10 mg 14 out of 50 patients (28%) reached the LDL-C goal on discharge, 36 out of 50 patients (72%) after 6–8 weeks. After addition of bempedoic acid or PCSK9-inhibitors all patients which were followed up in our lipid clinic reach the EAS/ESC-LDL-C target. Only two patients reported myalgias of which one patient refused to continue with lipid-lowering drugs. One patient had elevated liver enzymes, which resolved after switching to a lower statin dose. Conclusions One out three STEMI patients reached the EAS/ESC-LDL-C target during the initial hospital stay on atorvastatin 80 mg/ezetimibe 10 mg. Adding bempedoic acid or PCSK9 inhibitors resulted in LDL-C target attainment of all patients during follow-up. EAS/ESC-LDL-C target attainment is feasible and well-tolerated in empowered, well-educated patients. Funding Acknowledgement Type of funding sources: None.

Management of statin intolerance in a pharmacy led cardiology innovative medicines optimisation lipid clinic

Abstract Background Statins are cornerstone in the management of atherosclerotic cardiovascular disease. If a patient has experienced clinically significant adverse drug reactions (ADRs), representing an unacceptable risk or may result in adherence issues, we would consider them intolerant. The prevalence is lower in randomised trials than cohort observational studies, 5% vs. 17%. Purpose To assess how many people we reviewed in clinic were able to be re-challenged and successfully continued on a statin, free from side effects. Methods Over 6 months we reviewed all patients referred to our innovative clinic for lipid optimisation labelled as “statin intolerant”. Initially, as per our protocol, we adopted a person-centred approach and explored this label (actual vs. potential concerns, any previous issues, symptoms experienced and timings, statins tried (if any), and patient's feelings on re-challenge). A statin re-challenge was offered if not contraindicated. If agreed, based on shared-decision making, we offered patients a once weekly statin (usually rosuvastatin 5mg) with a clear self-management plan to up/down-titrate frequency and dose, until they identify a tolerated regimen. We measured LDL-C at baseline and every 3 months thereafter until satisfactory. Results Of 207 patients referred 152 (73%) were labelled as “statin intolerant”. Average age was 62 (±11), 51% females. 78% for secondary prevention and 37% had familial hypercholesterolaemia. The average baseline LDL-C was 4.4mmol/L. 108 (71%) qualified for PCSK9 inhibitors therapy (PCSK9i) as per UK NICE guidance. The top 3 reported ADRs were musculoskeletal side effects (48%), GI upsets (13%) and deranged LFTs (7%). 25 (58%) of those “intolerant” who did not qualify for PCSK9i attempted a re-challenge with statins vs. 44 (41%) among those who qualified. Of the 69 patients, who accepted a re-challenge, 43 (62%) were successfully restarted on a statin. At an average of 14 months post re-challenge, LDL-C (available for >80% of the sample) was reduced by an average of 31% in those not on PCSK9i, compared to a 62% reduction (sustained over an average of 40 months) in those on combination therapy with PCSK9i. The top 3 rosuvastatin regimens established were 5mg OD (29%), 5mg weekly (24%) and 10mg OD (15%). Approximately 80% of patients were on rosuvastatin, and the rest accepted atorvastatin, pravastatin or simvastatin. There was no attempt to re-challenge in 77 (51%) patients, mostly due to choice (45%) or statins re-challenged prior to referral (44%). We stopped statins in 6 cases due to intolerable ADRs. Conclusion(s) By using a person-centred approach, and a variety of strategies to tackle “statin intolerance” we have successfully re-established over 60% of patients with very high CVD risk on statins. While patients who qualified for PCSK9i therapy were less likely to consider re-challenge with statins (41% v 58%), combination lipid-lowering therapies produced better reduction in LDL-C. Funding Acknowledgement Type of funding sources: None.

Lipoprotein (a) and new-onset type-2 diabetes in patients with familial combined hyperlipidemia: a 9 years follow-up study

Abstract Background Elevated lipoprotein(a) [Lp(a)] levels have been related with increased cardiovascular (CV) risk in the general population. However, its relationship with type-2 diabetes and CV risk in patients with Familial Combined Hyperlipidemia (FCH) is rather unclear. Thus, the aim of our study was to investigate the prognostic role of Lp(a) regarding new-onset type-2 diabetes and major adverse cardiovascular outcomes in patients with FCH. Methods 485 patients from the outpatient lipid clinic of our hospital (301 males,mean age 49.8±10.8 years, 35%smokers, 16% with diabetes mellitus), without history of CV disease, who fulfilled the FCH criteria participated in the study. Participants were evaluated for a mean follow-up period of 8.9±7.5 years with at least one annual visit. Venous blood samples were obtained at baseline in all patients for the determination of plasma glucose, lipid profile, and levels of Lp(a). All subjects were on lipid-lowering medication (statin and ezetimibe or fibrate) during the follow-up period. The endpoints of our study was new-onset diabetes and the composite of major CV events (coronary artery disease events and stroke). Results The incidence of new-onset diabetes during the follow-up period was 10% (n=42). The group of patients with new-onset diabetes (n=42) had lower levels of Lp(a) at baseline compared to those without new-onset diabetes (n=376) (23.8±19.2 vs 32.9±39.5 mg/dl, p=0.01). Also, those with new-onset diabetes had a lower percentage of increased Lp(a) levels (≥30 mg/dl) at baseline compared to those without new-onset diabetes (21% vs 34%). Multiple Cox regression analysis revealed that increased Lp(a) (≥30 mg/dl) is an independent predictor of lower diabetes incidence during the follow-up period (HR 0.39, 95% CI 0.17–0.90), after adjustment for confounding factors. Moreover, the incidence of new-onset CV events in the total population was 6.4% (n=31).In the group of patients with increased Lp(a) levels at baseline (≥30 mg/dl, n=159, 33%) there was a trend towards a greater incidence of CV events during the follow-up period, compared to the group of patients with lower Lp(a) levels (<30 mg/dl, n=326, 67%), although the difference between the two groups was not statistically significant (8.8% vs 5.1%, p=0.1). Conclusions In patients with FCH, increased baseline Lp(a) is an independent predictor of lower incidence of new-onset type-2 diabetes after an almost 9 years follow-up period. Moreover, increased Lp(a) seems to convey an increased CV risk also in patients with FCH. Funding Acknowledgement Type of funding sources: None.

An outreaching lipid clinic model supporting PCSK9i uptake and lipid optimisation in secondary prevention across primary/secondary care interface

An outreaching lipid clinic model supporting PCSK9i uptake and lipid optimisation in secondary prevention across primary/secondary care interface

Familial Hypercholesterolemia Identification by Machine Learning Using Lipid Profile Data Performs as Well as Clinical Diagnostic Criteria.

Familial hypercholesterolemia (FH) is a common genetic disorder and, if not diagnosed and treated early, results in premature cardiovascular disease. Most individuals with FH are undiagnosed and machine learning offers a new prospect to improve FH identification. Our objective was to create a machine learning model from basic lipid profile data with better screening performance than LDL-C (low-density lipoprotein cholesterol) cutoff levels and diagnostic performance comparable to the Dutch Lipid Clinic Network criteria. The model was developed combining logistic regression, deep learning, and random forest classification and trained on a 70% split of a data set of individuals clinically suspected of having FH. Model performance, as well as that of the LDL-C cutoff and Dutch Lipid Clinic Network criteria, were assessed on the internal 30% testing data set and an external data set by comparing the area under the receiver operator characteristic (AUROC) curves. All methodologies were measured against the gold standard of FH diagnosis by mutation identification. Furthermore, the model was also tested on 2 lower prevalence data sets. The machine learning model achieved an AUROC curve of 0.711 on the external data set (n=1376; FH prevalence=64%), which was superior to the LDL-C cutoff (AUROC=0.642) and comparable to the Dutch Lipid Clinic Network criteria (AUROC=0.705). The model performed even better when tested on the medium-prevalence (n=2655; FH prevalence=20%) and low-prevalence (n=1616; FH prevalence=1%) data sets, with AUROC curve values of 0.801 and 0.856, respectively. Despite absence of clinical information, the model better identified genetically confirmed FH in a cohort of individuals suspected of having FH than LDL-C cutoff values and was comparable to the Dutch Lipid Clinic Network criteria. The model achieved higher accuracy when tested on 2 cohorts with lower FH prevalence. The application of machine learning is, therefore, a promising tool in both the screening for, and diagnosis of, individuals with FH.

The burden of severe hypercholesterolemia and familial hypercholesterolemia in a population-based setting in the US

BackgroundContemporary prevalence, awareness, and control of severe hypercholesterolemia (SH) and familial hypercholesterolemia (FH) and the associated atherosclerotic cardiovascular disease risk in the US are unknown. MethodUsing electronic health records, we assessed the burden of SH and FH in Olmsted County, Minnesota, US, between 2004 and 2015. We defined SH as low-density lipoprotein cholesterol (LDL-C) level ≥190 mg/dl without secondary causes of hypercholesterolemia and FH as a Dutch Lipid Clinic Network score ≥6. Controls were age- and sex-matched individuals with LDL-C level <190 mg/dl. ResultsThe age- and sex-adjusted point and period prevalence (age-recursive method) of SH was 4.44% and 8.95%, respectively; 1 in 21 had FH (∼1:233 adults), and 46.2% had a recorded diagnosis. Guideline recommended targets (LDL-C <100 mg/dl and <70 mg/dl in the primary and secondary prevention settings, respectively) were achieved in 33.1% and 21.2% of SH cases, with less women overall achieving the target than men (18.6% vs. 23.7%, p=0.022). After adjustment for conventional risk factors, the hazard ratio for incident coronary heart disease (CHD) in those with SH was 1.21 (1.05-1.39; p=0.010), in those with SH and a family history of CHD was 2.16 (1.57-2.96; p<0.001) and in those with FH was 4.61 (2.66-7.97; p<0.001). The association of SH with CHD was modified by age (p-interaction = 0.015), such that the risk was greater at younger ages. ConclusionsSH was prevalent and an independent risk factor for incident CHD. Awareness and control were low, highlighting a treatment gap (more prominent in women) that needs to be addressed.

The First Report of a Real-world Experience With a PCSK9 Inhibitor in a Large Familial Hyperlipidemia and Very-high-risk Middle Eastern Population

Evolocumab, a monoclonal inhibitor of proprotein convertase subtilisin/kexin 9, has been shown to reduce proatherogenic lipoproteins in patients with or without familial hypercholesterolemia (FH), diabetes mellitus, or atherosclerotic cardiovascular disease (ASCVD). We explored the safety profile and clinical effectiveness of evolocumab in an outpatient population of Emirati individuals with FH diagnosed per Dutch Lipid Clinic Network criteria, previous ASCVD, or statin intolerance. This study was a retrospective review of patients initiating evolocumab treatment for any indication at Imperial College London Diabetes Centre between 2017 and 2020. All individuals followed up for at least 90 days or with at least one lipid panel postinitiation were included. Participants were subclassified into primary prevention (no previous ASCVD event, n=81) and secondary prevention (any prior clinical ASCVD event, n=102) groups. Evolocumab was initiated in 183 individuals (mean [SD] age, 51.5 [12.4] years; 51% male); 108 (59%) had a clinical or genetic FH diagnosis, and 70.5% had diabetes mellitus. Statin intolerance was a treatment indication in 60 (32.8%) individuals. At 90 days, substantial reductions in serum LDL-C, triglycerides (TG), and total cholesterol:HDL-C (TC:HDL-C) were observed in both the primary and secondary prevention groups, and both FH and non-FH individuals. In the primary prevention group, median (interquartile range) reduction in LDL-C was 43.7% (10.8%; 63.0%); TG, 15.0% (7.2%; 35.3%); and TC:HDL-C, 31.5% (11.1%; 46.0%). In the secondary prevention group, median (interquartile range) reduction in LDL-C was 48.3% (22%; 70%); TG, 19.6% (1.2%; 32.5%); and TC:HDL-C, 32.6% (14.6%; 46.3%) (all, P < 0.0001). American College of Cardiology/American Heart Association LDL-C targets were consistently achieved in 114 (62.3%) patients during a follow-up of 359 (79-639) days. Nonattainment of the LDL-C target was attributed to nonadherence in 36 (52.2%) patients and discontinuation of treatment in 14 (20.3%) patients. Evolocumab was discontinued in 4 patients because of adverse events. This study is the first from the Middle East and North Africa region that reports the real-world efficacy of evolocumab in a mixed risk population of individuals with FH and other non-FH indications. Clinically meaningful and sustained reductions in LDL-C, TG, and cholesterol ratios were observed after evolocumab initiation. Few adverse events were reported in this predominantly Arabic population, consistent with previous safety reports for evolocumab. Notable strengths of this study include a relatively large cohort, patient heterogeneity and high retention, and a minimum follow-up of 1 year. Despite these strengths, the study has some limitations, including the selection bias due to the retrospective design and absence of comparative group.

Evaluating Statin Tolerability in Historically Intolerant Patients After Correcting for Subclinical Hypothyroidism and Vitamin D Insufficiency.

Atherosclerotic cardiovascular disease (ASCVD) is the major cause of morbidity and mortality worldwide. Statins provide primary and secondary ASCVD prevention. Intolerance due to statin-associated myalgias reduces long-term adherence, thus muting potential benefits. Our analysis sought to determine whether transition from a lipophilic statin to a water-soluble statin, or correction of subclinical hypothyroidism and/or vitamin D insufficiency/deficiency (metabolic abnormalities), improved statin tolerance. We performed a retrospective analysis of the data from patients referred to our lipid clinic because of statin intolerance. Patients intolerant to a lipophilic statin were switched to a water-soluble statin. Patients having vitamin D insufficiency/deficiency or subclinical hypothyroidism were re-challenged with a water-soluble statin (or lipophilic statin with minimal systemic exposure) after correction of the metabolic abnormality. 169 patients were statin intolerant. 86% (n = 145) were white and 48% (n = 81) were male. 82 of these patients had one or both metabolic abnormalities. The remaining patients (n = 87) had no metabolic abnormality, however, were unable to tolerate a lipophilic statin. 72% (n = 73) of eligible patients (n = 101), defined as those with a corrected metabolic abnormality or without a metabolic abnormality on a lipophilic statin, were able to tolerate a water-soluble statin or lipophilic statin with minimal systemic exposure. In addition, 75% (n = 127) of this total cohort met their LDL-C goal. Our findings suggest that either correction of subclinical hypothyroidism and/or vitamin D insufficiency/deficiency or transition from a lipophilic statin to water-soluble statin (or lipophilic statin with minimal systemic exposure) improves statin tolerance.

Familial hypercholesterolaemia and coronary risk factors among patients with angiogram-proven premature coronary artery disease in an Asian cohort.

Familial hypercholesterolaemia (FH) patients have elevated levels of low-density lipoprotein cholesterol, rendering them at high risk of premature coronary artery disease (PCAD). However, the FH prevalence among angiogram-proven PCAD (AP-PCAD) patients and their status of coronary risk factors (CRFs) have not been reported in the Asian population. This study aimed to (1) determine the prevalence of clinically diagnosed FH among AP-PCAD patients, (2) compare CRFs between AP-PCAD patients with control groups, and (3) identify the independent predictors of PCAD. AP-PCAD patients and FH patients without PCAD were recruited from Cardiology and Specialist Lipid Clinics. Subjects were divided into AP-PCAD with FH (G1), AP-PCAD without FH (G2), FH without PCAD (G3) and normal controls (G4). Medical records were collected from the clinic database and standardised questionnaires. FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria. A total of 572 subjects were recruited (males:86.4%; mean±SD age: 55.6±8.5years). The prevalence of Definite, Potential and All FH among AP-PCAD patients were 6%(19/319), 16% (51/319) and 45.5% (145/319) respectively. G1 had higher central obesity, family history of PCAD and family history of hypercholesterolaemia compared to other groups. Among all subjects, diabetes [OR(95% CI): 4.7(2.9,7.7)], hypertension [OR(95% CI): 14.1(7.8,25.6)], FH [OR(95% CI): 2.9(1.5,5.5)] and Potential (Definite and Probable) FH [OR(95% CI): 4.5(2.1,9.6)] were independent predictors for PCAD. Among FH patients, family history of PCAD [OR(95% CI): 3.0(1.4,6.3)] and Definite FH [OR(95% CI): 7.1(1.9,27.4)] were independent predictors for PCAD. Potential FH is common among AP-PCAD patients and contributes greatly to the AP-PCAD. FH-PCAD subjects have greater proportions of various risk factors compared to other groups. Presence of FH, diabetes, hypertension, obesity and family history of PCAD are independent predictors of PCAD. FH with PCAD is in very-high-risk category, hence, early management of modifiable CRFs in these patients are warranted.

Hypertension and clinical outcomes in patients with familial hypercholesterolemia.

Hypertension is a known risk factor for cardiovascular disease; however, its impact on clinical outcomes in patients with heterozygous familial hypercholesterolemia (HeFH) is unclear. Hence, we aimed to investigate the effects of hypertension on severity of coronary artery atherosclerosis and cardiovascular outcomes in patients with HeFH. A total of 480 patients with clinical or molecular diagnosis of definite or probable familial hypercholesterolemia according to Dutch Lipid Clinic Network criteria (DLCN score ≥6) were included in the study. They were divided into the two groups according to their blood pressure status: hypertension group and normotension group. The severity of coronary stenosis was assessed by a number of diseased vessels, Gensini, Syntax, and Jeopardy scores. All individuals were followed up for cardiovascular events (CVEs) and cox proportion hazard models were used to evaluate the association of hypertension with cardiovascular outcomes. Patients with hypertension had more severe coronary stenosis and a higher incidence of CVEs compared with the ones with normotension (log-rank P < 0.001). After multivariable adjustment, there was a 2.1-fold increased risk of CVEs among patients with hypertension compared with patients with normotension (adjusted hazard ratio 2.06, 95% confidential interval 1.17-3.65, P < 0.01). Hypertension control status was also associated with CVEs even after adjustment of multiple variables. However, no combined effect on increased cardiovascular risks was detected in this HeFH cohort. In patients with HeFH, hypertension is an independent risk factor for cardiovascular events. Moreover, blood pressure control status in patients with hypertension is associated with the worse outcomes.

FindMyLipidClinic.com: A global Directory of lipid clinics and patient organisations to improve dyslipidemia care: FindMyLipidClinic.com

Information available on lipid clinics and patient support and advocacy groups, such as location and services provided, is limited or unknown to patients with dyslipidaemia and their family members who may also be affected, and non-specialist clinicians, hindering accessibility to appropriate healthcare. To overcome this, the European Atherosclerosis Society Familial Hypercholesterolemia Study Collaboration (EAS FHSC) led by Imperial College London has, in collaboration with the European FH Patient Network (FH Europe), developed FindMyLipidClinic.com, a global Directory of lipid clinics and patient support groups in 29 languages. Since its launch in 2020, around 4,000 visitors have conducted 12,000 searches across 1,100 locations, which may have retrieved up to 124 lipid clinics and 29 patient groups currently listed in 39 and 28 countries, respectively. Clinics and patient organisations not currently listed are encouraged to join this directory, and it would also benefit further from collaborations with other existing directories able to contribute.

Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study.

Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units. Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels >250 mg/dl were identified in subjects >18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained. Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels >250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant. Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine.

A Comprehensive Neuropsychological Study of Familial Hypercholesterolemia and Its Relationship with Psychosocial Functioning: A Biopsychosocial Approach.

BACKGROUND: Over the past few years, there has been an increasing interest in viewing the diagnosis of familial hypercholesterolemia (FH) through the lens of the biopsychosocial model. However, other than a few epidemiological surveys, there is a dearth of studies from emerging economies that have examined FH using the biological, psychological, and socio-environmental facets of the aforementioned model. AIM. The three aims of the current study were as follows: (i) to examine the psychosocial status among patients with genetically confirmed FH, (ii) to compare their intellectual capacity and cognitive outcomes with a reference group, and (iii) to examine the relationship between health literacy and cognitive functioning. METHOD: Consecutive FH patients referred to the lipid clinic at a tertiary care center for an expert opinion were recruited into this study conducted from September 2019 to March 2020. Information regarding psychosocial functioning, health literacy, quality of life, and affective ranges was surveyed. Indices of current reasoning ability and cognition (attention and concentration, memory, and executive functioning) were compared with a socio-demographically-matched reference group. The current hypothesis also explored the impact of FH on health literacy and cognition. RESULT: A total of 70 participants out of 106 (response rate: 66.0%) initially agreed to participate. However, 18 out of 70 dropped out of the study, yielding a final total of 52 FH patients. With 27 (51.9%) males and 25 (48.1%) females, the mean participant age stood at 37.2 years (SD = 9.2), ranging from 21 to 52 years of age. In the psychosocial data, thirty-two percent (n = 17) of them had anxiety (HADS ≥ 8), and twenty-five percent (n = 13) had depressive symptoms (HADS ≥ 8). The performance of the FH patients was significantly impaired compared to the control group on the indices of current reasoning ability and all domains of cognitive functioning. In the univariate analysis conducted to compare cognitive functioning with health literacy status, only indices of attention and concentration emerged as being significant. CONCLUSION: The current study indicates that the FH population is marked with impediments in biopsychosocial functioning, including indices tapping into the integrity of health literacy, quality of life, affective ranges, and higher functioning such as cognition and current reasoning ability when compared with a socio-demographically-matched reference group. The present results support the hypothesis that chronic diseases vis-à-vis the sequelae of coronary artery disease can potentially impede biopsychosocial functioning.

Burden of cardiovascular disease in a large contemporary cohort of patients with heterozygous familial hypercholesterolemia

Background and aimsHeterozygous familial hypercholesterolemia (HeFH) is increasingly better diagnosed and treatments can improve the cardiovascular prognosis. We evaluated the long-term cardiovascular risk of HeFH using the French REgistry of Familial hypERCHOLesterolemia (REFERCHOL). MethodsWe studied HeFH patients diagnosed genetically and clinically by the Dutch Lipid Clinic Network (DLCN) criteria in all lipid clinics across the country and their 5-year risk of cardiovascular events (all fatal and non-fatal acute coronary, cerebral and peripheral arterial disease events, aortic valve replacement surgery) using the French national health data system. ResultsThe database comprised 3202 individuals, 2010 (62.8%) with genetically verified HeFH and 1192 (37.2%) a DLCN score ≥6. Of these individuals, 2485 (77.6%) were in primary prevention and 717 (22.4%) in secondary prevention. The incidence of cardiovascular events was 24.58 per 1000 person-years for the overall sample, 19.15 in primary prevention and 43.40 in secondary prevention. The incidence of myocardial infarction, cerebral infarction and death was 16.32 per 1000 person-years for the overall sample, 12.93 in primary prevention and 28.08 in secondary prevention. The incidence of aortic valve replacement was 1.78 per 1000 person-years. In the overall sample, at inclusion, 41% were not treated for LDL cholesterol, 48% of these in primary prevention and 20% in secondary prevention and high-dose statins were used by only 24% of individuals, 15% of these in primary prevention and 45% in secondary prevention. ConclusionsThe incidence of cardiovascular events in HeFH is high and lipid-lowering treatment is far from optimal. The cardiovascular risk of HeFH is underestimated and patients are inadequately treated.

Management of High-Risk Hypercholesterolemic Patients and PCSK9 Inhibitors Reimbursement Policies: Data from a Cohort of Italian Hypercholesterolemic Outpatients.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are effective and safe lipid-lowering treatments (LLT). The primary endpoint of the study was to assess the prevalence of patients eligible for treatment with PCSK9 inhibitors in a real-life clinical setting in Italy before and after the recent enlargement of reimbursement criteria. For this study, we consecutively considered the clinical record forms of 6231 outpatients consecutively admitted at the Lipid Clinic of the University Hospital of Bologna (Italy). Patients were stratified according to whether they were allowed or not allowed to access to treatment with PCSK9 inhibitors based on national prescription criteria and reimbursement rules issued by the Italian Medicines Agency (AIFA). According to the indications of the European Medicines Agency (EMA), 986 patients were candidates to treatment with PCSK9 inhibitors. However, following the prescription criteria issued by AIFA, only 180 patients were allowed to access to PCSK9 inhibitors before reimbursement criteria enlargement while 322 (+14.4%) with the current ones. Based on our observations, low-cost tailored therapeutic interventions for individual patients can significantly reduce the number of patients potentially needing treatment with PCSK9 inhibitors among those who are not allowed to access to the treatment. The application of enlarged reimbursement criteria for PCSK9 inhibitors could mildly improve possibility to adequately manage high-risk hypercholesterolemic subjects in the setting of an outpatient lipid clinic.

Association between circulating PCSK9 and proteinuria in nephrotic syndrome: A cross-sectional study

BackgroundNephrotic syndrome (NS) is associated with both hypercholesterolemia and hypertriglyceridemia, which could exacerbate disease progression and accelerate atherosclerosis. It has been reported that PCSK9, a proprotein convertase involved in hypercholesterolemia, was increased in patients with NS. ObjectiveTo investigate the association between PCSK9 concentrations and the magnitude of proteinuria. MethodsA total of 168 patients from nephrology and lipid clinics of the Centre Hospitalier de l’Université de Montreal were included in this cross-sectional observational study. Proteinuria level was classified in three groups: nephrotic syndrome (n = 51), proteinuria (n = 66), and control (n = 51) according to proteinuria and albuminemia concentrations. Plasma PCSK9 concentration was measured by an in-house ELISA and the lipid profile was assayed using an automated biochemical analyzer (COBAS INTEGRA 400, Roche Diagnostic). ResultsPlasma PCSK9 concentration was highest in the NS group (170.9 ng/mL), intermediate in the proteinuria group (156.4 ng/mL) and lowest in the control group (136.0 ng/mL), P = 0.005. We observed an association between the protein/creatinine (P/C) ratio and plasma PCSK9 concentrations in the whole cohort (β = 0.205, P = 0.006) after adjustment for age, sex, LDL-C, statin use, other lipid-lowering therapy use, diabetes, and eGFR. ConclusionsPatients with nephrotic syndrome have an increased risk of cardiovascular complications. PCSK9 is significantly elevated in NS and is associated with a detrimental lipid profile that could contribute to a worse prognosis of the disease. Future studies evaluating the efficacy of PCSK9 inhibitors in patients with NS would be justified.

A Danish nationwide study of individuals suspected of FH referred from general practice to lipid clinics: Clinical characteristics, plasma lipoprotein(a) and final diagnosis

Background and Aims : Familial hypercholesterolemia (FH) is an inherited condition characterized by severely elevated plasma levels of low-density lipoprotein (LDL) cholesterol believed to occur in approximately 1:250 subjects. FH is associated with a very high risk of premature atherosclerotic cardiovascular disease. Unfortunately, less than 20% of the affected are currently diagnosed in Denmark, which represents a health challenge here and in most other (Western) countries. The aims of the study were to describe important clinical characteristics and examine the proportion of verified FH diagnoses among adult subjects referred from General Practice to Danish Lipid Clinics on suspicion of FH. Also we aimed to investigate the importance of plasma lipoprotein(a) levels for a diagnosis of FH.Methods: All subjects referred from General Practice to one of the 15 Danish Lipid Clinics between September 2020 and November 2021 will be included. More than 1.200 individuals are expected to be recruited into the study and informed consent will be obtained from the subjects. Referrals for suspicion of FH were based on pre-specified criteria including LDL cholesterol levels > 5.0 mmol/l (> 4.0 mmol/l in subjects < 40 years) or premature cardiovascular disease. Secondary dyslipidaemias were excluded before admittance. Individuals were interviewed for personal and familial cardiovascular disease, diet, lifestyle, treatment and examined for cholesterol deposits. Individuals were classified according to the Dutch Lipid Clinic Network Score for FH.Results: Main results will be available in April 2022 and will be presented at the Congress.Conclusions: Will be presented when the results are available. Background and Aims : Familial hypercholesterolemia (FH) is an inherited condition characterized by severely elevated plasma levels of low-density lipoprotein (LDL) cholesterol believed to occur in approximately 1:250 subjects. FH is associated with a very high risk of premature atherosclerotic cardiovascular disease. Unfortunately, less than 20% of the affected are currently diagnosed in Denmark, which represents a health challenge here and in most other (Western) countries. The aims of the study were to describe important clinical characteristics and examine the proportion of verified FH diagnoses among adult subjects referred from General Practice to Danish Lipid Clinics on suspicion of FH. Also we aimed to investigate the importance of plasma lipoprotein(a) levels for a diagnosis of FH. Methods: All subjects referred from General Practice to one of the 15 Danish Lipid Clinics between September 2020 and November 2021 will be included. More than 1.200 individuals are expected to be recruited into the study and informed consent will be obtained from the subjects. Referrals for suspicion of FH were based on pre-specified criteria including LDL cholesterol levels > 5.0 mmol/l (> 4.0 mmol/l in subjects < 40 years) or premature cardiovascular disease. Secondary dyslipidaemias were excluded before admittance. Individuals were interviewed for personal and familial cardiovascular disease, diet, lifestyle, treatment and examined for cholesterol deposits. Individuals were classified according to the Dutch Lipid Clinic Network Score for FH. Results: Main results will be available in April 2022 and will be presented at the Congress. Conclusions: Will be presented when the results are available.

Routine use of Fribrosis-4 index in lipid clinic

Background and Aims : Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is a common cause of chronic liver disease and abnormal liver function test (LFT) in UK, yet it remains underdiagnosed. The number of patients presenting to lipid clinic with metabolic syndrome is increasing. Non-invasive biomarkers such as Fribrosis-4 (FIB-4) index is a helpful screening tool to exclude advanced fibrosis in high-risk patients. Therefore, we assessed the clinical utility of FIB-4 in a secondary care lipid clinic.

Bile acid malabsorption – A novel indication for PCSK9 inhibitor therapy: 3 cases from a lipid clinic

Background and Aims: People with bile acid malabsorption/diarrhea and concurrent hypercholesterolaemia struggle to tolerate statins (HMG-CoA reductase inhibitors) and fibrates because these pharmacological agents can worsen their symptoms. Statins increase bile acid production by promoting expression of cholesterol 7α hydroxylase (CYP7A1), the rate-limiting enzyme in synthesis of bile acids from cholesterol. Fibrates increase bile acid transport from hepatocytes by inducing expression of BA efflux transporters and decrease expression of ileal BA transporters reducing uptake.

The patient will see you now: Patient preferences for lipid clinic reviews in a COVID era

Background and Aims : The COVID-19 pandemic disturbed health systems across the world. Telephone reviews became the only method of review for most outpatients. For our Lipid Clinic to operate efficiently, staff contacted the patient pre-clinic to organize updated biochemical tests and check availability. We aimed to seek the opinion of our patients to inform our future service model.