Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study

Arnold, Markus; Schweizer, Juliane; Nakas, Christos T.; Schütz, Valerie; Westphal, Laura P; Inauen, Corinne; Pokorny, Thomas; Luft, Andreas R.; Leichtle, Alexander Benedikt; Arnold, Marcel; Bicvic, Antonela; Fischer, Urs; Marchis, Gian Marco De; Bonati, Leo H.; Müller, Mandy D.; Kahles, Timo; Nedeltchev, Krassen; Cereda, Carlo; Kägi, Georg; Bustamante, Alejandro; Montaner, Joan; Ntaios, George; Foerch, Christian; Spanaus, Katharina; Eckardstein, Arnold von; Katan, Mira

doi:10.1093/eurheartj/ehab081

Cited by 57 publications

(52 citation statements)

References 48 publications

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“…The associations between the Lp(a) level and an increased risk of atherosclerosis in different vascular beds, large artery atherosclerotic stroke, and calcification of the aortic valve have been well-demonstrated in large-scale studies [166][167][168][169][170][171][172]. These associations apply to different ethnicities and may be independent of LDL-C.…”

Section: Lipoprotein(a)mentioning

confidence: 89%

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis

et al. 2021

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Despite advances in pharmacotherapy, intervention devices and techniques, residual cardiovascular risks still cause a large burden on public health. Whilst most guidelines encourage achieving target levels of specific lipids and lipoproteins to reduce these risks, increasing evidence has shown that molecular modification of these lipoproteins also has a critical impact on their atherogenicity. Modification of low-density lipoprotein (LDL) by oxidation, glycation, peroxidation, apolipoprotein C-III adhesion, and the small dense subtype largely augment its atherogenicity. Post-translational modification by oxidation, carbamylation, glycation, and imbalance of molecular components can reduce the capacity of high-density lipoprotein (HDL) for reverse cholesterol transport. Elevated levels of triglycerides (TGs), apolipoprotein C-III and lipoprotein(a), and a decreased level of apolipoprotein A-I are closely associated with atherosclerotic cardiovascular disease. Pharmacotherapies aimed at reducing TGs, lipoprotein(a), and apolipoprotein C-III, and enhancing apolipoprotein A-1 are undergoing trials, and promising preliminary results have been reported. In this review, we aim to update the evidence on modifications of major lipid and lipoprotein components, including LDL, HDL, TG, apolipoprotein, and lipoprotein(a). We also discuss examples of translating findings from basic research to potential therapeutic targets for drug development.

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Section: Lipoprotein(a)mentioning

confidence: 89%

Lipids and Lipoproteins in Health and Disease: Focus on Targeting Atherosclerosis

et al. 2021

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“…Perioperative stroke is a severe complication after cardiac surgery, and has the greatest influence of all potential adverse events [ 14 , 22 ]. It has been shown that elevated Lp(a) on admission is an independent risk factor for subsequent adverse cardiovascular events in patients with coronary artery disease [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the BIOSIGNAL study, Arnold et al reported on the association between elevated Lp(a) levels and large-artery atherosclerosis stroke. The group concluded that elevated Lp(a) levels were independently associated with stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals with evident arteriosclerotic disease [ 14 ]. We found no association between different Lp(a) levels and perioperative stroke; however, the incidence of stroke after the perioperative period was not assessed in the current study period.…”

Section: Discussionmentioning

confidence: 99%

“…Originally, a cutoff concentration of 30 mg/dLwas defined, above which the risk of myocardial infarction increases [ 12 , 13 ]. Elevated Lp(a) may also lead to acute destabilisation of pre-existing but quiescent atherosclerotic plaques, which may induce acute myocardial infarction and stroke [ 9 , 14 , 15 ]. Lp(a) has been proven to be associated with coronary severity and clinical outcomes in patients with various types of coronary artery disease (CAD), such as stable CAD or acute myocardial infarction (AMI) [ 5 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Impact of Lipoprotein(a) Levels on Perioperative Outcomes in Cardiac Surgery

Heinisch

Mihalj

Huber

et al. 2021

Cells

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Altered lipid metabolism has been shown to be of major importance in a range of metabolic diseases, with particular importance in cardiovascular disease (CVD). As a key metabolic product, altered lipoprotein(a) (Lp(a)) levels may be associated with adverse clinical outcomes in high-risk cardiovascular patients undergoing cardiac surgery. We aimed to investigate the impact of the important metabolite Lp(a) on complications and clinical outcomes in high-risk patients. A prospective observational cohort study was performed. Data were derived from the Bern Perioperative Biobank (ClinicalTrials.gov NCT04767685), and included 192 adult patients undergoing elective cardiac surgery. Blood samples were collected at 24 h preoperatively, before induction of general anaesthesia, upon weaning from cardiopulmonary bypass (CPB), and the first morning after surgery. Clinical endpoints included stroke, myocardial infarction, and mortality within 30 days after surgery or within 1 year. Patients were grouped according to their preoperative Lp(a) levels: < 30 mg/dL (n = 121; 63%) or > 30 mg/dL (n = 71, 37%). The groups with increased vs. normal Lp(a) levels were comparable with regard to preoperative demographics and comorbidities. Median age was 67 years (interquartile range (IQR) 60.0, 73.0), with median body mass index (BMI) of 23.1 kg/m2 (23.7, 30.4), and the majority of patients being males (75.5%). Over the observational interval, Lp(a) levels decreased in all types of cardiac surgery after CPB (mean decline of approximately −5 mg/dL). While Lp(a) levels decreased in all patients following CPB, this observation was considerably pronounced in patients undergoing deep hypothermic circulatory arrest (DHCA) (decrease to preoperative Lp(a) levels by −35% (95% CI −68, −1.7), p = 0.039). Increased Lp(a) levels were neither associated with increased rates of perioperative stroke or major adverse events in patients undergoing cardiac surgery, nor with overall mortality in the perioperative period, or at one year after surgery. Other than for cohorts in neurology and cardiology, elevated Lp(a) might not be a risk factor for perioperative events in cardiac surgery.

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“…Las partículas remanentes cargadas de apolipoproteína B aumentan el riesgo de mortalidad y de infarto agudo de miocardio cuando el colesterol unido a lipoproteínas de baja densidad está bajo 16 , y cada vez es mayor la implicación de lipoproteína a en el riesgo de ictus 17 y eventos cardiovasculares.…”

Section: Lípidosunclassified