Plasma PCSK9 Levels Are Elevated with Acute Myocardial Infarction in Two Independent Retrospective Angiographic Studies

Abstract

ObjectiveProprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein (LDL) receptor. Mutations that block PCSK9 secretion reduce LDL-cholesterol and the incidence of myocardial infarction (MI). However, it remains unclear whether elevated plasma PCSK9 associates with coronary atherosclerosis (CAD) or more directly with rupture of the plaque causing MI.Methods and ResultsPlasma PCSK9 was measured by ELISA in 645 angiographically defined controls (<30% coronary stenosis) and 3,273 cases of CAD (>50% stenosis in a major coronary artery) from the Ottawa Heart Genomics Study. Because lipid lowering medications elevated plasma PCSK9, confounding association with disease, only individuals not taking a lipid lowering medication were considered (279 controls and 492 with CAD). Replication was sought in 357 controls and 465 with CAD from the Emory Cardiology Biobank study. PCSK9 levels were not associated with CAD in Ottawa, but were elevated with CAD in Emory. Plasma PCSK9 levels were elevated in 45 cases with acute MI (363.5±140.0 ng/ml) compared to 398 CAD cases without MI (302.0±91.3 ng/ml, p = 0.004) in Ottawa. This finding was replicated in the Emory study in 74 cases of acute MI (445.0±171.7 ng/ml) compared to 273 CAD cases without MI (369.9±139.1 ng/ml, p = 3.7×10−4). Since PCSK9 levels were similar in CAD patients with or without a prior (non-acute) MI, our finding suggests that plasma PCSK9 is elevated either immediately prior to or at the time of MI.ConclusionPlasma PCSK9 levels are increased with acute MI.

Increased Plasma PCSK9 Levels Are Associated with Reduced Endotoxin Clearance and the Development of Acute Organ Failures during Sepsis

“…Le Bras et al [40] found that plasma PCSK9 doubled from an admission level of 231 to 480 ng/ml in severe trauma, and the peak levels were correlated with poor outcome, including length of stay in the intensive care unit and duration of mechanical ventilation. PCSK9 levels were more modestly increased by 20-30% during angiography for acute myocardial infarction in a two-cohort, case-control retrospective review [10]. Similar to values reported in the literature [41] for later sepsis, lipids in our cohort were dramatically decreased in very early sepsis.…”

“…We understand that a new consensus definition will collapse to sepsis and septic shock. Prior reports of plasma PCSK9 in acute conditions are limited to trauma [40] and acute myocardial infarction [10]. Le Bras et al [40] found that plasma PCSK9 doubled from an admission level of 231 to 480 ng/ml in severe trauma, and the peak levels were correlated with poor outcome, including length of stay in the intensive care unit and duration of mechanical ventilation.…”

“…In our initial search, 26 studies were found and we limited the analysis to those with subjects aged at least 18 years and acute medical process or intervention without a ‘baseline' plasma draw. This eliminated 11 studies, leaving 15 for analysis [10,11,12,13,14,15,16,17,18,19,20,21,22]. Pooled medians were reported with 95% confidence intervals.…”

Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

“…There are several reasons for restricting our analysis to a cohort of this type. Differences in PCSK9 levels during acute and stable periods have been reported [16], but few studies have focused on patients with AMI and the predictive value of the acute-phase plasma PCSK9 level for risk of recurrent CV events. One study assessed the association between PCSK9 and recurrent CV events in patients with ACS who presented within 5 days of pain onset [9].…”

“…This finding is interesting and requires further investigation because there is currently little evidence that PCSK9 circulates in association with LDL-C during the acute phase. A prior study suggested that plasma PCSK9 was elevated either immediately prior to or at the time of AMI and was uncoupled from LDL-C, at least at the time of AMI [16]. Several other investigations have reported that LDL-C decreases rapidly after AMI [28, 29].…”