Clinical trial NCT03830138: Oxidized LDL With Oxygen Therapy in Acute Coronary Syndrome.
Official title: Oxidized LDL, Oxidized LDL Receptor 1 (OLR1) Gene Polymorphism With Oxygen Therapy in Acute Myocardial Infarction.
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Coronary Syndrome
Keywords: Oxidized-LDL
OLR1 gene
Single nucleotide polymorphism
Oxygen therapy
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2019-02-05
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Acute coronary syndrome patients

Brief summary: Coronary artery disease (CAD) is increasing rapidly in Egyptian people and manifesting a younger age. Higher plasma low-density lipoprotein cholesterol (LDL-C), is a major predictor for the development of CAD. However, whether oxidized-LDL (ox-LDL) can be used as a risk factor for myocardial infarction (MI) has not been fully investigated. Therefore, the aim of the present study was to examine the role of ox-LDL as a risk factor for the presence and clinical outcomes in patients with MI.

Detailed description: Cardiovascular disease, which is multifactorial and caused by complex interactions of genetic and environmental factors, represents the main cause of death all over the world. Traditional risk factors for coronary atherosclerosis include age, smoking, male gender, hypertension and diabetes. Newly defined risk factors such as hyper-homocysteine, elevated plasma levels of OxLDL and oxidative stress are also emerging.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is the major receptor of oxidized low-density lipoproteins which regulates the growth of a variety of cells and is important in inflammation, atherosclerosis, oxidative stress, and tissue remodeling. LOX-1 is expressed in various cells, including endothelial cells, macrophages, and chondrocytes, and its expression is enhanced by proinflammatory cytokines. The LOX1 gene, also known as OLR1, is located on the chromosome 12p13.1-p12.3. The LOX1 protein is synthesized as a 40-kDa precursor protein and is composed of four domains: an extracellular lectin-like domain at the C-terminal, a connecting neck domain, a transmembrane domain, and an N-terminal cytoplasmic domain. Three single nucleotide polymorphism (SNPs), namely, intron 4 (G→A), intron 5(T→G), and 3' UTR (T→C) in the LOX1 gene, have been previously reported. These polymorphisms have also been associated with CAD.

Oxygen is a lifesaving drug. Giving oxygen to a patient with an impending clinical emergency has become knee-jerk reflex reaction of the clinician. Patient with AMI has compromised myocardial perfusion and event arises due to myocardial hypoxia. It appears quite logical and biologically plausible to give oxygen in such situations to improve the oxygenation of the ischemic myocardial tissue and decrease ischemic pain. On the other side, oxygen may be harmful with a mechanism such as the paradoxical effect of oxygen in decreasing coronary artery blood flow and increasing coronary vascular resistance due to increased oxygen free radicals. The investigators aimed to examine the association of the OLR1 gene with AMI or CAD in a novel, well-phenotyped, and homogenous, population and its correlation with oxygen therapy in these patients.

Eligibility criteria: Inclusion Criteria:

* Patients were included irrespective of concomitant risk factors for atherosclerosis such as smoking, arterial hypertension and diabetes mellitus.
* Participants were both sexes.

Exclusion Criteria:

* Congenital heart disease.
* Dilated, hypertrophic or restrictive cardiomyopathy.
* acute and chronic liver disorders.

Primary outcomes:
measure: The mean difference of oxidized-LDL gene polymorphism between patients and controls
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References:
citation: Ehara S, Ueda M, Naruko T, Haze K, Itoh A, Otsuka M, Komatsu R, Matsuo T, Itabe H, Takano T, Tsukamoto Y, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes. Circulation. 2001 Apr 17;103(15):1955-60. doi: 10.1161/01.cir.103.15.1955.
citation: Trabetti E, Biscuola M, Cavallari U, Malerba G, Girelli D, Olivieri O, Martinelli N, Corrocher R, Pignatti PF. On the association of the oxidised LDL receptor 1 (OLR1) gene in patients with acute myocardial infarction or coronary artery disease. Eur J Hum Genet. 2006 Jan;14(1):127-30. doi: 10.1038/sj.ejhg.5201513.
citation: Zhao X, Zhang HW, Xu RX, Guo YL, Zhu CG, Wu NQ, Gao Y, Li JJ. Oxidized-LDL is a useful marker for predicting the very early coronary artery disease and cardiovascular outcomes. Per Med. 2018 Nov;15(6):521-529. doi: 10.2217/pme-2018-0046. Epub 2018 Oct 26.
citation: Raut MS, Maheshwari A. Oxygen supplementation in acute myocardial infarction: To be or not to be? Ann Card Anaesth. 2016 Apr-Jun;19(2):342-4. doi: 10.4103/0971-9784.179594. No abstract available.