Details
Category: Volume 09 Issue 11 November 2021
Hits: 524

Title: A study of correlation of PCSK9 enzyme levels in patients with coronary artery disease and diabetes mellitus

Authors: Balaji Venkateshwaran.M, Ashida T.S., Asmathula

 DOI: https://dx.doi.org/10.18535/jmscr/v9i11.39

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a vital role in lipid metabolism and pathophysiology of atherosclerosis. It is also reported to be associated with diabetes mellitus.

Objective: To determine PCSK9 enzyme levels in patients having coronary artery disease (CAD) with diabetes mellitus and to correlate the enzyme levels with severity of CAD based on angiogram reports.
Material and Methods: The present study was undertaken as a hospital based cross sectional study among 40 patients of either sex in the age group of 30-65 years who were already diagnosed to have CAD with diabetes mellitus. The study was carried out during the period starting from May 2018 to November 2018. Difference in means between two independent groups having non parametric distribution was tested using Mann Whitney U test. A p value <0.05 was considered statistically significant.

Results: Mean PCSK9 levels were found to be considerably high in patients with triple vessel disease as compared to those patients with one or two vessel involvements. For a PCSK9 cut off value of 51.5 ng/dl, the sensitivity and specificity for triple vessel disease was calculated to be 88.24% (65.7% -96.7%) and 95.65% (79%-99.2%), respectively
Conclusion: PCSK9 levels correlated significantly with number of vessels involved in CAD, as evaluated by angiography, among patients with CAD and DM. A PCSK9 cut off level of 51.5 ng/dl had remarkable sensitivity and specificity for triple vessel disease.

Keywords: Diabetes Mellitus, Coronary Artery Disease, Proprotein convertase subtilisin/kexin type 9 (PCSK9), Triple vessel disease.

References

  1. Bodkhe S, Jajoo SU, Jajoo UN, Ingle S, Gupta SS, Taksande BA. Epidemiology of confirmed coronary heart disease among population older than 60 years in rural central India-A community-based cross-sectional study. Indian heart journal 2019;71(1):39-44.
  2. Prabhakaran D, Jeemon P, Roy A. Cardiovascular Diseases in India: Current Epidemiology and Future Directions. Circulation 2016;133(16):1605-20.
  3. Roth GA, Johnson CO, Abate KH, Abd-Allah F, Ahmed M, Alam K, et al. The Burden of Cardiovascular Diseases Among US States, 1990-2016. JAMA cardiology 2018;3(5):375-89.
  4. Prasad RV, Bazroy J, Singh Z. Prevalence of overweight and obesity among adolescent students in Pondicherry, South India. International Journal of Nutrition, Pharmacology, Neurological Diseases 2016;6(2):72.
  5. Gupta R, Mohan I, Narula J. Trends in Coronary Heart Disease Epidemiology in India. Annals of global health 2016;82(2):307-15.
  6. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proceedings of the National Academy of Sciences of the United States of America 2003;100(3):928-33.
  7. Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield M, Devlin JJ, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet 2015;385(9984):2264-71.
  8. Seidah NG, Benjannet S, Wickham L, Marcinkiewicz J, Jasmin SB, Stifani S, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation. Proceedings of the National Academy of Sciences of the United States of America 2003;100(3):928-33.
  9. Ding Z, Liu S, Wang X, Mathur P, Dai Y, Theus S, et al. Cross-Talk Between PCSK9 and Damaged mtDNA in Vascular Smooth Muscle Cells: Role in Apoptosis. Antioxidants & redox signaling 2016;25(18):997-1008.
  10. Ding Z, Liu S, Wang X, Theus S, Deng X, Fan Y, et al. PCSK9 regulates expression of scavenger receptors and ox-LDL uptake in macrophages. Cardiovascular research 2018;114(8):1145-53.
  11. Ding Z, Wang X, Liu S, Zhou S, Kore RA, Mu S, et al. NLRP3 inflammasome via IL-1β regulates PCSK9 secretion. Theranostics 2020;10(16):7100-10.
  12. Liu S, Deng X, Zhang P, Wang X, Fan Y, Zhou S, et al. Blood flow patterns regulate PCSK9 secretion via MyD88-mediated pro-inflammatory cytokines. Cardiovascular research 2020;116(10):1721-32.
  13. Zhang Y, Liu J, Li S, Xu R-X, Sun J, Tang Y, et al. Proprotein convertase subtilisin/kexin type 9 expression is transiently up-regulated in the acute period of myocardial infarction in rat. 2014;14(1):1-7.
  14. Hamamura H, Adachi H, Enomoto M, Fukami A, Nakamura S, Nohara Y, et al. Serum Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) is Independently Associated with Insulin Resistance, Triglycerides, Lipoprotein(a) Levels but not Low-Density Lipoprotein Cholesterol Levels in a General Population. J Atheroscler Thromb 2021;28(4):329-37.
  15. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. The New England journal of medicine 2017;376(18):1713-22.
  16. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. 2015;372(16):1489-99.
  17. Werner C, Hoffmann MM, Winkler K, Böhm M, Laufs U. Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vascular pharmacology 2014;62(2):94-102.
  18. Tang ZH, Li TH, Peng J, Zheng J, Li TT, Liu LS, et al. PCSK9: A novel inflammation modulator in atherosclerosis? Journal of cellular physiology 2019;234(3):2345-55.
  19. Kuo WC, Stevens JM, Ersig AL, Johnson HM, Tung TH, Bratzke LC. Does 24-h Activity Cycle Influence Plasma PCSK9 Concentration? A Systematic Review and Meta-Analysis. Current atherosclerosis reports 2020;22(7):30.
  20. Tindall AM, Kris-Etherton PM, Petersen KS. Replacing Saturated Fats with Unsaturated Fats from Walnuts or Vegetable Oils Lowers Atherogenic Lipoprotein Classes Without Increasing Lipoprotein(a). The Journal of nutrition 2020;150(4):818-25.
  21. Peng J, Liu M-M, Jin J-L, Cao Y-X, Guo Y-L, Wu N-Q, et al. Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study. 2020;19(1):1-12.
  22. Arsenault BJ, Pelletier-Beaumont E, Alméras N, Tremblay A, Poirier P, Bergeron J, et al. PCSK9 levels in abdominally obese men: association with cardiometabolic risk profile and effects of a one-year lifestyle modification program. Atherosclerosis 2014;236(2):321-6.
  23. Costet P, Cariou B, Lambert G, Lalanne F, Lardeux B, Jarnoux AL, et al. Hepatic PCSK9 expression is regulated by nutritional status via insulin and sterol regulatory element-binding protein 1c. The Journal of biological chemistry 2006;281(10):6211-8.
  24. Seidah NG, Awan Z, Chrétien M, Mbikay M. PCSK9: a key modulator of cardiovascular health. Circulation research 2014;114(6):1022-36.
  25. Ding Z, Liu S, Wang X, Deng X, Fan Y, Sun C, et al. Hemodynamic shear stress via ROS modulates PCSK9 expression in human vascular endothelial and smooth muscle cells and along the mouse aorta. Antioxidants & redox signaling 2015;22(9):760-71.
  26. Li J, Liang X, Wang Y, Xu Z, Li G. Investigation of highly expressed PCSK9 in atherosclerotic plaques and ox-LDL-induced endothelial cell apoptosis. Mol Med Rep 2017;16(2):1817-25.
  27. Adorni MP, Ruscica M, Ferri N, Bernini F, Zimetti F. Proprotein Convertase Subtilisin/Kexin Type 9, Brain Cholesterol Homeostasis and Potential Implication for Alzheimer's Disease. Frontiers in aging neuroscience 2019;11(120.
  28. Schlüter KD, Wolf A, Weber M, Schreckenberg R, Schulz R. Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way. Basic research in cardiology 2017;112(6):63.
  29. Ding Z, Wang X, Liu S, Shahanawaz J, Theus S, Fan Y, et al. PCSK9 expression in the ischaemic heart and its relationship to infarct size, cardiac function, and development of autophagy. Cardiovascular research 2018;114(13):1738-51.
  30. Yang CL, Zeng YD, Hu ZX, Liang H. PCSK9 promotes the secretion of pro-inflammatory cytokines by macrophages to aggravate H/R-induced cardiomyocyte injury via activating NF-κB signalling. General physiology and biophysics 2020;39(2): 123-34.
  31. Monami M, Sesti G, Mannucci E. PCSK9 inhibitor therapy: A systematic review and meta-analysis of metabolic and cardiovascular outcomes in patients with diabetes. 2019;21(4):903-8.
  32. Cui C-J, Li S, Li J-JJCca. PCSK9 and its modulation. 2015;440(79-86.
  33. Memon R, Malek R, Munir KMJTAjom. Doubling of Hemoglobin A1c on PCSK9 Inhibitor Therapy. 2019;132(1):e17-e8.

Corresponding Author

Balaji Venkateshwaran.M

Postgraduate Department of Medicine