Guideline-directed low-density lipoprotein management in high-risk ischemic stroke or transient ischemic attack admissions in China from 2015 to 2019

Objective: To evaluate the association of serum malondialdehyde low-density lipoprotein (MDA-LDL), an oxidatively modified LDL, with the prevalence of high-risk plaques (HRP) determined with coronary computed tomography angiography (CTA) in statin-treated patients. Methods: This study was a single-center retrospective cohort comprising 268 patients (mean age 67 years, 58% men) with statin therapy and who underwent coronary CTA for suspected stable coronary artery disease. Patients were classified into two groups according to median MDA-LDL level or median LDL-C level. Coronary CTA-verified HRP was defined when two or more characteristics, including positive remodeling, low-density plaques, and spotty calcification, were present. Results: Patients with HRP had higher MDA-LDL (p = 0.011), but not LDL-C (p = 0.867) than those without HRP. High MDA-LDL was independently associated with HRP (odds ratio 1.883, 95% confidential interval 1.082–3.279) after adjustment for traditional risk factors. Regarding incremental value of MDA-LDL for predicting CTA-verified HRP, addition of serum MDA-LDL levels to the baseline model significantly increased global chi-square score from 26.1 to 32.8 (p = 0.010). Conclusions: A high serum MDA-LDL level is an independent predictor of CTA-verified HRP, which can lead to cardiovascular events in statin-treated patients.

Download Full-text

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

European Journal of Preventive Cardiology ◽

10.1177/2047487320940102 ◽

2020 ◽

pp. 204748732094010

Author(s):

Konstantinos C Koskinas ◽

Baris Gencer ◽

David Nanchen ◽

Mattia Branca ◽

David Carballo ◽

...

Keyword(s):

Cardiovascular Disease ◽

High Risk ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Atherosclerotic Cardiovascular Disease ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Coronary Syndrome ◽

Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

Download Full-text

Monoclonal Antibodies in the Management of Familial Hypercholesterolemia: Focus on PCSK9 and ANGPTL3 Inhibitors

Current Atherosclerosis Reports ◽

10.1007/s11883-021-00972-x ◽

2021 ◽

Vol 23 (12) ◽

Author(s):

Angela Pirillo ◽

Alberico L. Catapano ◽

Giuseppe D. Norata

Keyword(s):

Monoclonal Antibodies ◽

High Risk ◽

Familial Hypercholesterolemia ◽

Plasma Levels ◽

Low Density Lipoprotein ◽

Genetic Defect ◽

Density Lipoprotein ◽

Lipid Lowering ◽

Low Density ◽

Premature Cardiovascular Disease

Abstract Purpose of Review Familial hypercholesterolemia (FH) is a monogenic disorder characterized by high plasma levels of low-density lipoprotein cholesterol (LDL-C) since birth and a high risk of premature cardiovascular disease. The genetic defect is carried in only one allele in heterozygous FH (HeFH) or in both in the most severe homozygous FH (HoFH). Current guidelines recommend to reduce substantially LDL-C levels in these high-risk patients, with the need to use association therapy combining agents with different mechanisms of action. As most cases of FH are attributable to mutations in the gene encoding the low-density lipoprotein receptor (LDLR), statins, even in combination with ezetimibe, are less effective in reducing LDL-C plasma levels in FH patients, who require a more intensive approach with additional lipid-lowering agents. Additional targets playing key roles in regulating LDL-C levels are represented by PCSK9 and ANGPTL3. Recent Findings Two monoclonal antibodies (mAbs) targeting PCSK9, evolocumab and alirocumab, significantly reduce LDL-C levels in HeFH patients. In patients with HoFH, the efficacy of mAbs to PCSK9 is strictly related to the presence of a residual LDLR activity; thus, patients carrying null mutations do not respond to the therapy with these mAbs, whereas some effects can be appreciated in HoFH bearing defective mutations. Conversely, evinacumab, the mAb targeting ANGPTL3, is highly effective in reducing LDL-C levels even in HoFH patients carrying null LDLR mutations, thanks to its LDLR-independent mechanism of action. Summary Monoclonal antibodies inhibiting PCSK9 have shown a robust effect in FH patients presenting a residual LDLR activity, while ANGPTL3 inhibitors appear to be promising even in patients carrying null LDLR mutations.

Download Full-text

Dilative Arteriopathy and Leucencephalopathy as Manifestations of a Neurometabolic Disease

The Open Neurology Journal ◽

10.2174/1874205x01509010028 ◽

2015 ◽

Vol 9 (1) ◽

pp. 28-31 ◽

Cited By ~ 4

Author(s):

Josef Finsterer ◽

Adam Bastovansky

Keyword(s):

Ischemic Stroke ◽

Recurrent Stroke ◽

Low Density Lipoprotein ◽

Cerebral Arteries ◽

Mitochondrial Disorder ◽

Density Lipoprotein ◽

Internal Capsule ◽

Low Density ◽

Megadolichobasilar Artery ◽

Caucasian Female

Background: Dilative arteriopathy plus leucencephalopathy as a manifestation of a mitochondrial disorder (MID) is rare. Case report: In a 70yo Caucasian female, height 160cm, weight 62kg, with mild right-sided hemiparesis due to subacute ischemic stroke in the posterior leg of the left internal capsule, a megadolichobasilar artery and marked leucencephalopathy and gliosis of the pons were detected. In addition, microbleeds in a peripheral distribution at the cortical/subcortical border were noted. After the exclusion of various differentials, which could have explained her abnormalities, a MID was suspected. Conclusions: Dilative arteriopathy of the intra-cerebral arteries, in association with recurrent stroke and supra- and infratentorial leucencephalopathy, but the absence of neurofibromatosis or increased low-density lipoprotein values, is most likely attributable to a non-syndromic MID.

Download Full-text