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Investigation of the interplay of PCSK9, cardiac dynamics, oxidative stress in coronary artery disease: case-control
Anmar Hussein Lafta1, Hamidreza Shiri2, Mahsa Iraji2
1Department of Clinical Laboratory Sciences, Faculty of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Insights
This study reveals that oxidized LDL (ox-LDL) and ejection fraction (EF%) are better indicators of significant coronary artery blockage than PCSK9 or LDL-C, even in myocardial infarction patients with normal LDL-C levels.
Area of Science:
- Cardiology
- Biochemistry
- Pathophysiology
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is crucial for elevating low-density lipoprotein cholesterol (LDL-C), a risk factor for myocardial infarction (MI).
- However, approximately half of MI patients present with normal LDL-C levels, suggesting other contributing factors.
- This study investigates the relationship between PCSK9, cardiac function, and oxidative stress markers in MI patients.
Purpose of the Study:
- To explore the association between PCSK9, heart function (ejection fraction - EF%), and oxidative stress markers in patients with myocardial infarction (MI).
- To identify potential biomarkers for diagnosing significant coronary artery blockage (CAB > 50%) in MI patients, particularly those with normal LDL-C.
Main Methods:
- The study included 63 healthy individuals and 63 MI patients with CAB > 50% at Tehran Heart Centre Hospital.
- Assessed parameters included oxidative stress markers (TAC, MDA, MPO, SOD, CAT, GPx), PCSK9, oxidized LDL (ox-LDL), high-sensitivity cardiac troponin I (hs-cTnI), hs-CRP, and ejection fraction (EF%).
- Biochemical parameters and EF% were measured for all participants.
Main Results:
- Higher ejection fraction (EF%) and antioxidant markers (TAC, GPx, CAT, SOD) were linked to a lower risk of significant coronary artery blockage (CAB > 50%).
- Conversely, elevated oxidative stress markers (MDA, MPO), hs-CRP, and ox-LDL were associated with a higher risk of CAB > 50%.
- Oxidized LDL (ox-LDL) and EF% demonstrated superior diagnostic performance for CAB > 50% compared to hs-cTnI, with PCSK9 and LDL-C levels not significantly differing between groups.
Conclusions:
- PCSK9's role in MI may extend beyond LDL-C, potentially involving inflammation and oxidative stress, even with normal PCSK9 and LDL-C levels.
- Oxidized LDL (ox-LDL) and ejection fraction (EF%) are more effective diagnostic indicators for significant coronary artery blockage (CAB > 50%) than hs-cTnI.
- These findings highlight the importance of assessing oxidative stress and cardiac function in MI patients, irrespective of their LDL-C levels.
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.
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