Physicians' Academy for Cardiovascular Education

First study to evaluate circulating PCSK9 in ACS patients during angiography

Gencer B. et al, Heart J 2015

Prognostic value of PCSK9 levels in patients with acute coronary syndromes


Gencer B, Montecucco F, Nanchen D, et al.
Heart J 2015; published online ahead of print
 

Background

LDL cholesterol levels are poorly controlled 1 year after ACS in patients with clinical familial hypercholesterolaemia [1,2]. Studies have shown that in this patient population, approximately two-third of patients on maximal recommended statin therapy do not reach the LDL target of ≤1.8 mmol/L [1-3]. A possible explanation for this observation could be that PCSK9 levels are up-regulated at the beginning of statin therapy, leading to statin resistance [4].
PCSK9 levels have been correlated to physical activity in healthy volunteers [5], and have been used to predict acute cardiovascular events in patients with stable coronary heart disease on statin treatment [6]. Whether PCSK9 levels can be used as an independent marker for clinical outcomes that provides additional information beyond available risk stratification is not known.
It has not been evaluated whether PCSK9 levels in the early phase of acute coronary syndromes have a prognostic value. This study evaluated the association between PCSK9 plasma levels during coronary angiography with 1-year all-cause death or cardiac death, in a large Swiss cohort of patients with acute coronary syndromes. The association between PCSK9 plasma levels and LDL cholesterol targets 1 year after the qualifying event was also assessed.
 

Main results

• Patients with higher PCSK9 levels at angiography were more likely to
  - have clinical familial hypercholesterolaemia (RR: 1.21, 95% CI: 1.09–1.53)
  - be treated with lipid-lowering therapy (RR: 1.46, 95% CI: 1.30–1.63)
  - present with longer time interval of chest pain (RR: 1.29, 95% CI: 1.09–1.53)
  - present with higher C-reactive protein levels (RR: 1.22, 95% CI: 1.16–1.30)
• PCSK9 increased 12–24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001)
• At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI: 0.69–1.85) for all-cause death and remained similar after adjustment for the GRACE score.  
• Patients with higher PCSK9 levels were less likely to have reached the recommended LDL cholesterol targets at 1 year (RR: 0.81, 95% CI: 0.66–0.99), independently of baseline LDL levels
• Patients with ACS who underwent coronary angiography 72 h after chest pain onset presented with higher PCSK9 levels
 

Conclusion

High plasma levels of circulating PCSK9, taken during angiography, did not predict mortality at 1 year in ACS patients. However, these data suggest that PCSK9 levels are predictive of future target LDL cholesterol levels, independently of the use of lipid-lowering therapy. Moreover, PCSK9 levels might be useful for the identification of patients with familial hypercholesterolaemia.


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References

1. Nanchen D, Gencer B, auer R, et al. Prevalence and management of familial hypercholesterolemia in patients with acute coronary syndromes. Eur Heart J 2015;36:2438–2445.
2. Gencer B, Rodondi N, Auer R, et al. Reasons for discontinuation of recommended therapies according to the patients after acute coronary syndromes. Eur J Intern Med 2015;26:56–62.
3. Mayne J, Dewpura T, Raymond A, et al. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans. Lipids Health Dis 2008;7:22.
4. Wattanasuwan N, Khan IA, Gowda RM, et al. Effect of acute myocardial infarction on cholesterol ratios. Chest 2001;120:1196–1199.
5. Hlatky MA, Greenland P, Arnett DK, et al.  Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation 2009;119:2408–2416.
6. Klingenberg R, Heg D, Raber L, et al. Safety profile of prasugrel and clopidogrel in patients with acute coronary syndromes in Switzerland. Heart 2015;101:854–863.