Search

This 2023 statement updates clinical guidance for homozygous familial hypercholesterolaemia (HoFH), explains the genetic complexity, and provides pragmatic recommendations to address inequities in HoFH care worldwide. Key strengths include updated criteria for the clinical diagnosis of HoFH and the recommendation to prioritize phenotypic features over genotype. Thus, a low-density lipoprotein cholesterol (LDL-C) >10 mmol/L (>400 mg/dL) is suggestive of HoFH and warrants further evaluation. The statement also provides state-of-the art discussion and guidance to clinicians for interpreting the results of genetic testing and for family planning and pregnancy. Therapeutic decisions are based on the LDL-C level. Combination LDL-C-lowering therapy—both pharmacologic intervention and lipoprotein apheresis (LA)—is foundational. Addition of novel, efficacious therapies (i.e. inhibitors of proprotein convertase subtilisin/kexin type 9, followed by evinacumab and/or lomitapide) offers potential to attain LDL-C goal or reduce the need for LA. To improve HoFH care around the world, the statement recommends the creation of national screening programmes, education to improve awareness, and management guidelines that account for the local realities of care, including access to specialist centres, treatments, and cost. This updated statement provides guidance that is crucial to early diagnosis, better care, and improved cardiovascular health for patients with HoFH worldwide.

Background 2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking. Purpose Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD. Methods The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT). Results Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L. Conclusions European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

AIMS: The first aim was to critically evaluate the extent to which familial hypercholesterolaemia (FH) is underdiagnosed and undertreated. The second aim was to provide guidance for screening and treatment of FH, in order to prevent coronary heart disease (CHD).METHODS AND RESULTS: Of the theoretical estimated prevalence of 1/500 for heterozygous FH, CONCLUSION: Owing to severe underdiagnosis and undertreatment of FH, there is an urgent worldwide need for diagnostic screening together with early and aggressive treatment of this extremely high-risk condition.

AIMS: The aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies.METHODS AND RESULTS: The robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) CONCLUSION: We recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level

Purpose: AMG 145, a fully human monoclonal antibody to PCSK9, significantly reduced LDL-C levels in statin-intolerant patients in the GAUSS trial ([NCT01375764][1]). We report the relationship between pre-trial history of intolerance to statins and on-treatment therapeutic response, tolerability, and safety with AMG 145. Methods: This post-hoc intention-to-treat analysis included 157 patients aged 34-75 years who received 4 weekly subcutaneous administrations of AMG 145 or placebo. Participants, who had all failed standard statin therapy due to muscle-related side effects, were grouped according to their history of intolerance of one, two, or three or more statins prior to the study. Results: See Table 1. View this table: Table 1 Conclusion: Attempts at statin treatment increased with CVD risk but were not related to tolerability of AMG 145. LDL-C reductions appeared to diminish with the number of failed statins but were still comparable with reductions reported with the highest doses of the most effective statins. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01375764&atom=%2Fehj%2F34%2Fsuppl_1%2FP682.atom