Investigation of the Interplay of PCSK9, Cardiac Dynamics, Oxidative Stress in Coronary Artery Disease: Case-Control Study

Anmar Hussein Lafta ¹ Hamidreza Shiri ² Mahsa Iraji ² Amin Karimpour ² Mahboobe Sattari ² Monireh Rahimkhani ³ Nahid Einollahi ^1* Ghodratollah Panahi ^2*

• ¹ Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Alborz, Iran
• ² Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
• ³ School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Alborz, Iran

Background: PCSK9 plays a key role in raising LDL-C levels, which contributes to heart attacks (MI). However, studies show that about half of MI patients have normal LDL-C levels. This study aims to explore the link between PCSK9, heart function, and oxidative stress markers in MI patients.Methods: This investigation was carried out at Tehran Heart Centre Hospital on healthy individuals (n=63) and patients (n=63) with MI who had a coronary artery block above 50% (CAB > 50%). Oxidative stress (OS) parameters, such as total antioxidant capacity (TAC), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity, PCSK9, oxidized Low-density lipoprotein (ox-LDL), high-sensitivity cardiac troponin I (hs-cTnI), and hs-CRP are assessed. Indeed, biochemical parameters and EF% were measured.Results: Higher EF% (>37.5%), TAC (>1.05 mmol Fe²⁺/L), GPx (>16.48 mU/mL), CAT (>11.32 nmol/min/mL), and SOD (>297.16 U/mL) were linked to a lower risk of CAB > 50%. In contrast, higher MDA (>32.07 nmol/mL), MPO (>17.77 U/L), hs-CRP (>5.5 mg/L), and ox-LDL (>64.87 μg/L) were associated with a higher risk. There was no significant difference in PCSK9 and LDL-C levels between groups. EF% was positively linked to SOD but negatively related to MDA, MPO, ox-LDL, hs-cTnI, and hs-CRP. Ox-LDL correlated positively with MPO but negatively with TAC, CAT, and GPx. PCSK9 showed a positive relationship with MDA. The best markers for CAB > 50% diagnosis were ox-LDL (AUC = 83.22, cut-off > 63.35 μg/L), EF% (AUC = 82.35, cut-off < 46.25%), and hs-cTnI (AUC = 81.3, cut-off > 0.265 ng/mL).Conclusion: While PCSK9's role in MI through LDL-C is well known, its impact on inflammation and oxidative stress may also be important, even when LDL-C and PCSK9 levels are normal.Additionally, ox-LDL and EF% are better indicators of CAB > 50% than hs-cTnI.