Lipid lowering therapy in primary and secondary prevention in Austria: are LDL-C goals achieved?

Summary Background Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed. Methods Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL‑C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL‑C goal while receiving stabilized LLT was assessed. Results A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL‑C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently. Conclusion The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.

A new phenotypic classification system for dyslipidemias based on the standard lipid panel

Background Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing. Objective To develop a new algorithm for classifying lipoprotein disorders that only relies on the standard lipid panel. Methods Lipid thresholds for defining the different lipoprotein phenotypes were derived for Non-High-Density Lipoprotein-Cholesterol (NonHDL-C) and Triglycerides (TG) to be concordant when possible with the current US Multi-Society guidelines for blood cholesterol management. Results The new classification method categorizes patients into all the classical Fredrickson-like phenotypes except for Type III dysbetalipoproteinemia. In addition, a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism is described. The validity of the new algorithm was confirmed by lipid analysis by NMR (N = 11,365) and by concordance with classification by agarose gel electrophoresis/beta-quantification (N = 5504). Furthermore, based on the Atherosclerosis Risk in Communities (ARIC) cohort (N = 14,742), the lipoprotein phenotypes differ in their association with ASCVD (TypeV>IIb > IVb > IIa > IVa > normolipidemic) and can be used prognostically as risk enhancer conditions in the management of patients. Conclusions We describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel. It, therefore, can be easily implemented for increasing compliance with current guidelines and for improving the care of patients at risk for ASCVD.

High-Intensity Statin vs. Low-Density Lipoprotein Cholesterol Target for Patients Undergoing Percutaneous Coronary Intervention: Insights From a Territory-Wide Cohort Study in Hong Kong

Background: Different guidelines recommend different approaches to lipid management in patients with atherosclerotic cardiovascular disease. We aim to determine the best strategy for lipid management in Asian patients undergoing percutaneous coronary intervention (PCI).Method: This was a retrospective cohort study conducted in patients who underwent first-ever PCI from 14 hospitals in Hong Kong. All participants either achieved low-density lipoprotein cholesterol (LDL-C) target of <55 mg/dl with ≥50% reduction from baseline (group 1), or received high-intensity statin (group 2), or both (group 3) within 1 yr after PCI. The primary endpoint was a composite outcome of all-cause mortality, myocardial infarction, stroke, and any unplanned coronary revascularization between 1 and 5 yr after PCI.Results: A total of 8,650 patients were analyzed with a median follow-up period of 4.2 yr. After the adjustment of baseline characteristics, complexity of PCI and medications prescribed and the risks of the primary outcome were significantly lower in group 2 (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.74–0.93, P = 0.003) and group 3 (HR, 0.75; 95% CI, 0.62–0.90; P = 0.002). The primary outcome occurred at similar rates between group 2 and group 3.Conclusions: Use of high intensity statin, with or without the attainment of guidelines recommended LDL-C target, was associated with a lower adjusted risk of MACE at 5 yr, compared with patients who attained LDL-C target without high intensity statin.

Non-invasive skin cholesterol testing: a potential proxy for LDL-C and apoB serum measurements

Background Lipid management is the first line of treatment for decreasing the incidence of cardiovascular events in patients with coronary heart disease (CHD), and a variety of indicators are used to evaluate lipid management. This work analyses the differences in LDL-C and apoB for lipid management evaluation, as well as explores the feasibility of skin cholesterol as a marker that can be measured non-invasively for lipid management. Methods The prospective study enrolled 121 patients who had been diagnosed with acute coronary syndrome (ACS) at the department of emergency medicine of the First Affiliated Hospital of the USTC from May 2020 to January 2021, and the patients were grouped into Group I (n=53) and Group II (n=68) according to whether they had comorbid hyperlipidemia and/or diabetes mellitus. All patients were administered 10 mg/day of rosuvastatin and observed for 12 weeks. Lipid management was assessed on the basis of LDL-C and apoB, and linear correlation models were employed to assess the relationship between changes in these well accepted markers to that of changes in skin cholesterol. Results Out of 121 patients with ACS, 53 patients (43.80 %) had combined hyperlipidemia and/or diabetes mellitus (Group I), while 68 patients (56.20 %) did not (Group II). Cardiovascular events occur at earlier ages in patients with CHD who are comorbid for hyperlipidemia and/or diabetes (P<0.05). LDL-C attainment rate is lower than apoB attainment rate with rosuvastatin therapy (P<0.05), which is mainly attributable to patients with low initial LDL-C. Skin cholesterol reduction correlated with LDL-C reduction. (r=0.501, P<0.001) and apoB reduction (r=0.538, P<0.001). Skin cholesterol reduction continued over all time points measured. Conclusions Examination of changes in apoB levels give patients with low initial LDL-C more informative data on lipid management than LDL-C readings. In addition, non-invasive skin cholesterol measurements may have the potential to be used independently for lipid management evaluation.

The Lipocalin Apolipoprotein D Functional Portrait: A Systematic Review

Apolipoprotein D is a chordate gene early originated in the Lipocalin protein family. Among other features, regulation of its expression in a wide variety of disease conditions in humans, as apparently unrelated as neurodegeneration or breast cancer, have called for attention on this gene. Also, its presence in different tissues, from blood to brain, and different subcellular locations, from HDL lipoparticles to the interior of lysosomes or the surface of extracellular vesicles, poses an interesting challenge in deciphering its physiological function: Is ApoD a moonlighting protein, serving different roles in different cellular compartments, tissues, or organisms? Or does it have a unique biochemical mechanism of action that accounts for such apparently diverse roles in different physiological situations? To answer these questions, we have performed a systematic review of all primary publications where ApoD properties have been investigated in chordates. We conclude that ApoD ligand binding in the Lipocalin pocket, combined with an antioxidant activity performed at the rim of the pocket are properties sufficient to explain ApoD association with different lipid-based structures, where its physiological function is better described as lipid-management than by long-range lipid-transport. Controlling the redox state of these lipid structures in particular subcellular locations or extracellular structures, ApoD is able to modulate an enormous array of apparently diverse processes in the organism, both in health and disease. The new picture emerging from these data should help to put the physiological role of ApoD in new contexts and to inspire well-focused future research.

A New Phenotypic Classification System for Dyslipidemias Based on the Standard Lipid Panel

BACKGROUND Dyslipoproteinemias can be classified by their distinct lipoprotein patterns, which helps determine atherosclerotic cardiovascular disease (ASCVD) risk and directs lipid management but this has required advanced laboratory testing. OBJECTIVE To develop a new algorithm for classifying lipoprotein disorders that only relies on the standard lipid panel. METHODS Lipid thresholds for defining the different lipoprotein phenotypes were derived for Non-High-Density Lipoprotein-Cholesterol (NonHDL-C) and Triglycerides (TG) to be concordant when possible with the current US Multi-Society guidelines for blood cholesterol management. RESULTS The new classification method categorizes patients into all the classical Fredrickson-like phenotypes except for Type III dysbetalipoproteinemia. In addition, a new hypolipidemic phenotype (Type VI) due to genetic mutations in apoB-metabolism is described. The validity of the new algorithm was confirmed by lipid analysis by NMR (N = 11,365) and by concordance with classification by agarose gel electrophoresis/beta-quantification (N = 5504). Furthermore, based on the Atherosclerosis Risk in Communities (ARIC) cohort (N = 14742), the lipoprotein phenotypes differ in their association with ASCVD (TypeV > IIb > IVb > IIa > IVa > normolipidemic) and can be used prognostically as risk enhancer conditions in the management of patients. CONCLUSIONS We describe a clinically useful lipoprotein phenotyping system that is only dependent upon the standard lipid panel. It, therefore, can be easily implemented for increasing compliance with current guidelines and for improving the care of patients at risk for ASCVD.