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

Paul Philipp Heinisch,Markus Huber,Juerg Schmidli,Frank Stüber,Joerg C Schefold,Alexander Hartmann,Elisabeth Steinhagen-Thiessen,Maks Mihalj,Markus M Luedi,Lorenz Räber,Michael Walter

doi:10.3390/cells10112829

Abstract

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.

Highlights

Elevated lipoprotein(a) (Lp(a)) levels have previously been shown to be an independent cardiovascular (CV) risk factor and an acute-phase reactant involved in the repair of tissue injury—most likely via angiogenesis [1,2,3]
To the best of our knowledge, there are currently no studies reporting the impact of preoperative elevated Lp(a) on perioperative outcomes after coronary artery bypass grafting or valvular and aortic cardiac surgery. In this prospective study using multiple timed blood samples, we examined the role of Lp(a) changes in patients during and after different types of cardiac surgery, and related the data to clinical complications and outcomes
While Lp(a) levels were decreased in all patients following cardiopulmonary bypass (CPB), this decrease was less consistent in patients with lower Lp(a) levels, and was most evident and significant in patients with deep hypothermic circulatory arrest (DHCA) (decrease in preoperative Lp(a) levels of −35%, p = 0.039), followed by operation duration (for each additional hour of surgery, preoperative Lp(a) values decreased by −11%

Summary

Introduction

Elevated lipoprotein(a) (Lp(a)) levels have previously been shown to be an independent cardiovascular (CV) risk factor and an acute-phase reactant involved in the repair of tissue injury—most likely via angiogenesis [1,2,3]. Lp(a) levels are genetically determined, and are associated with elevated risk of CV disease and calcified aortic stenosis [4,5,6]. There are currently limited therapeutic medications that selectively target increased Lp(a); a variety of potential treatments are being investigated [7]. A therapeutic approach with antisense oligonucleotides (APO(a)LRx) was shown to potently and selectively reduce Lp(a) levels [8]. The current evidence suggests that the risk of CV disease is increased by over 40% in patients with Lp(a) levels of 30 mg/dL or greater, compared with patients with levels

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Conclusion