The significance of PCSK-9's level and polymorphism in premature coronary artery disease: Relation to risk and severity.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a circulating protein that plays an important role in lipid metabolism and is linked to inflammation, which has implications for atherosclerosis and its severe cardiac effects. We studied the potential association of the PCSK-9 gene single nucleotide polymorphism (SNP), Oxidized low-density lipoprotein receptor 1- (OLR-1), and caspase-3 serum levels with the risk and severity of premature coronary artery disease (PCAD). The potential contribution of PCSK-9 serum level to the severity of PCAD patients was also assessed. METHOD: This case-control study included 120 PCAD patients (age < 45), and 60 age matched healthy controls. Serum PCSK-9 and caspase-3 levels and clinical characteristics were recorded. SYNTAX score was calculated to estimate the severity of the coronary artery lesions. The SNP rs2483205 of the PCSK-9 gene and the rs11053646 of the OLR-1gene were genotyped in all participants. RESULTS: Serum PCSK-9 levels were higher in PCAD patients and were significantly different among the three SYNTAX score groups (SS ≤ 12, 12 < SS ≤ 21.5, and SS > 21.5). The diagnostic cutoff values of PCSK-9 and caspase-3 levels for PCAD were > 3.2 ng/mL for both, yielding an area under the curve (AUC) of 0.98 and 0.92, sensitivity of 85 %, 98 %, and specificity of 99.5 %, 93 % for PCSK-9 and caspase-3, respectively. The genotypes TT + CT vs. CC of PCSK-9's rs2483205 SNP presented a higher risk for PCAD and higher SYNTAX scores. Furthermore, the rs11053646 SNP of OLR-1 presented the CG genotype as more risky and having higher SYNTAX scores. CONCLUSION: Circulating PCSK9 and caspase-3 concentrations were higher in PCAD patients and were associated with CAD severity. The SNPs of PCSK-9 (rs2483205) and OLR-1 (rs11053646) were associated with PCAD and its severity.

Copeptin, miRNA-208, and miRNA-499 as New Biomarkers for Early Detection of Acute Coronary Syndrome.

cTn and CK-MB are gold standard biomarkers for acute coronary syndrome (ACS) but are less sensitive in the first 3 h after onset of symptoms. A need thus exists for novel biomarkers for early detection of ACS. We evaluated circulating copeptin, miRNA-208, and miRNA-499 as possible biomarkers for early detection of unstable angina (UA) and non-ST-segment elevation myocardial infarction (NSTEMI). Sixty-five patients with probable ACS that presented within 4 h of the onset of chest pain (23 UA and 42 NSTEMI) and 25 apparently healthy individuals were studied. Two sets of blood samples collected in the first 3 h and at 6 h after onset were analyzed for copeptin levels via ELISA and miRNA-208 and miRNA-499 expression via real-time PCR. Copeptin, miRNA-208, and miRNA-499 expression levels were significantly increased in UA and NSTEMI patients compared with controls (p < 0.001) and in NSTEMT compared with UA patients (p < 0.001). Levels were also significantly elevated in UA and NSTEMI patients with negative cardiac troponin in the first 3 h (p < 0.001). ROC curves displayed AUC for prediction of ACS of 0.96 for copeptin, 0.97 for miRNA-208, and 0.97 for miRNA-499. Their combination improved AUC to 0.98. Copeptin and miRNA-208 and miRNA-499 expression are promising biomarkers for UA and NSTEMI that present in the first 3 h of pain onset. A combination of these markers with cTn may increase the accuracy of diagnosis by avoiding the gray zone of cTn as a biomarker.