Association between CT-Detected Coronary Artery Calcification and Serum Homocysteine Level in Asymptomatic Adults: CT-Detected Coronary Artery Calcification and Serum Homocysteine Level in Asymptomatic Adults

Mishal Safdar; Sumaira Aslam; Wajeeha Anwar; Syed Liaquat Ali; Khawar Anwar; Shabzain Ishrat

doi:10.54393/pjhs.v7i8.4072

Authors

Mishal Safdar Department of Biochemistry, Shahida Islam Medical and Dental College, Lodhran, Pakistan
Sumaira Aslam Department of Radiology, Central Park Medical College, Lahore, Pakistan
Wajeeha Anwar Department of Radiology, Shahida Islam Medical and Dental College, Lodhran, Pakistan
Syed Liaquat Ali Department of Biochemistry, Shahida Islam Medical and Dental College, Lodhran, Pakistan
Khawar Anwar Department of Biochemistry, Shahida Islam Medical and Dental College, Lodhran, Pakistan
Shabzain Ishrat Department of Pharmacology, Shahida Islam Medical and Dental College, Lodhran, Pakistan

DOI:

https://doi.org/10.54393/pjhs.v7i8.4072

Keywords:

Computed Tomography, Coronary Artery Calcification, Serum Homocysteine, Asymptomatic

Abstract

The association between CT-detected CAC and serum homocysteine levels in asymptomatic adults may provide valuable insights into the pathophysiological mechanisms underlying subclinical atherosclerosis. Objectives: To determine the association between CT-detected coronary artery calcification and serum homocysteine levels in the asymptomatic Pakistani population. Methods: A cross-sectional analytical study was conducted on 384 asymptomatic Pakistani adults aged 30–65 years. Coronary artery calcification was assessed using non-contrast CT (Agatston score), and serum homocysteine levels were measured. Associations were analyzed using descriptive statistics and Pearson correlation using SPSS. Results: Among 384 asymptomatic adults, coronary artery calcification (CAC) was detected in 41.7% of participants. Individuals with CAC had significantly higher serum homocysteine levels compared to those without calcification (p < 0.001). Serum homocysteine increased progressively with CAC severity and showed a significant positive correlation with CAC score. Statistical testing demonstrated that serum homocysteine was significantly associated with coronary artery calcification after adjusting for traditional cardiovascular risk factors. Conclusions: Elevated serum homocysteine was independently associated with the presence and severity of CT-detected coronary artery calcification in asymptomatic adults. These findings suggest that homocysteine may serve as a useful biomarker for identifying individuals at increased risk of subclinical coronary atherosclerosis.

References

Onnis C, Virmani R, Kawai K. Coronary Artery Calcification: Current Concepts and Clinical Implications. Circulation. 2024 Jan; 149(3): 251-266. doi: 10.1161/CIRCULATIONAHA.123.065657.

Garg PK, Bhatia HS, Allen TS, Grainger T, Pouncey AL, Dichek D et al. Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies. Arteriosclerosis, Thrombosis, and Vascular Biology. 2024 Jan; 44(1): 24-47. doi: 10.1161/ATVBAHA.123.320138.

Savo MT, De Amicis M, Cozac DA, Cordoni G, Corradin S, Cozza E et al. Comparative Prognostic Value of Coronary Calcium Score and Perivascular Fat Attenuation Index in Coronary Artery Disease. Journal of Clinical Medicine. 2024 Sep; 13(17): 5205. doi: 10.3390/jcm13175205.

Razavi AC, Agatston AS, Shaw LJ, De Cecco CN, van Assen M, Sperling LS et al. Evolving Role of Calcium Density in Coronary Artery Calcium Scoring and Atherosclerotic Cardiovascular Disease Risk. Cardiovascular Imaging. 2022 Sep; 15(9): 1648-1662. doi: 10.1016/j.jcmg.2022.02.026.

Feuchtner GM, Lacaita PG, Bax JJ. AI-Quantitative CT Coronary Plaque Features Associate with a Higher Relative Risk in Women: CONFIRM2 Registry. Circulation: Cardiovascular Imaging. 2025 Jun; 18(6): 18235. doi: 10.1161/CIRCIMAGING.125.018235.

Foraker R, Sperling L, Bratzke L, Budoff M, Leppert M, Razavi AC et al. Opportunistic Detection of Coronary Artery Calcium on Noncardiac Chest Computed Tomography: An Emerging Tool for Cardiovascular Disease Prevention: A Scientific Statement from the American Heart Association. Circulation. 2025 Nov; 152(19): 391-401. doi: 10.1161/CIR.0000000000001382.

Mátyás BB, Benedek I, Rat N, Blîndu E, Rodean IP, Haja I et al. Assessment of the association between coronary artery calcification, plaque vulnerability, and perivascular inflammation via coronary CT angiography. Life. 2025 Aug; 15(8): 1288. doi: 10.3390/life15081288.

Mokhtar J, Albaree M, Battistin V, Asbaita M, Akbarpoor F, Lakshmanan J et al. Inadequacy of Coronary Calcium Scoring in Evaluating Coronary Artery Disease: A Call to Shifting to High-Resolution CT Coronary Imaging. International Journal of Cardiology Cardiovascular Risk and Prevention. 2025 Jul: 200476. doi: 10.1016/j.ijcrp.2025.200476.

Huang Z, Zou J, Li Z, Li M, He R, Zeng J et al. Intervention at Circulating Homocysteine Levels> 10 µmol/L for Primary Prevention of Cardiovascular Diseases: A Systematic Review and Dose–Response Meta‐Analysis. Journal of Evidence‐Based Medicine. 2025 Dec; 18(4): 70080. doi: 10.1111/jebm.70080.

Ahmad A, Corban MT, Toya T, Sara JD, Lerman B, Park JY et al. Coronary Microvascular Endothelial Dysfunction in Patients with Angina and Nonobstructive Coronary Artery Disease is Associated with Elevated Serum Homocysteine Levels. Journal of the American Heart Association. 2020 Oct; 9(19): 17746. doi: 10.1161/JAHA.120.017746.

Jakubowski H and Witucki Ł. Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease. International Journal of Molecular Sciences. 2025 Jan; 26(2): 746. doi: 10.3390/ijms26020746.

Zhang S, Lv Y, Luo X, Weng X, Qi J, Bai X et al. Homocysteine Promotes Atherosclerosis Through Macrophage Pyroptosis Via Endoplasmic Reticulum Stress and Calcium Disorder. Molecular Medicine. 2023 Jun; 29(1): 73. doi: 10.1186/s10020-023-00656-z.

Loubane G, Robert G, Firdaus SB, Venne P, Comeau C, Boudreault PL et al. Conundrum of Dehydroascorbic Acid and Homocysteine Thiolactone Reaction Products: Structural Characterization and Effect on Peptide and Protein N-Homocysteinylation. Free Radical Biology and Medicine. 2023 Sep; 206: 111-124. doi: 10.1016/j.freeradbiomed.2023.06.031.

Wu Z, Zhang H, Li Z, Li H, Miao X, Pan H et al. Mutual Effect of Homocysteine and Uric Acid on Arterial Stiffness and Cardiovascular Risk in The Context of Predictive, Preventive, and Personalized Medicine. European Association for Predictive, Preventive and Personalised Medicine Journal. 2022 Dec; 13(4): 581-595. doi: 10.1007/s13167-022-00298-x.

Karger AB, Steffen BT, Nomura SO, Guan W, Garg PK, Szklo M et al. Association Between Homocysteine and Vascular Calcification Incidence, Prevalence, and Progression in the MESA Cohort. Journal of the American Heart Association. 2020 Feb; 9(3): 13934. doi: 10.1161/JAHA.119.013934.

Kullo IJ, Li G, Bielak LF, Bailey KR, Sheedy PF II, Peyser PA et al. Association of Plasma Homocysteine with Coronary Artery Calcification in Different Categories of Coronary Heart Disease Risk. Mayo Clin Proc. 2006; 81(2): 177–182. doi: 10.4065/81.2.177.

Joseph P, Kutty VR, Mohan V, Kumar R, Mony P, Vijayakumar K et al. Cardiovascular Disease, Mortality, and Their Associations with Modifiable Risk Factors in A Multi-National South Asia Cohort: a PURE substudy. European Heart Journal. 2022 Aug; 43(30): 2831-2840. doi: 10.4065/81.2.177.

Khan UI, Shah S, Qureshi A, Viswanathan S, Merchant AT, Virani SS et al. Burden of Cardiometabolic Diseases and Depression in a Low-Income, Urban Community in Pakistan: A Cross-Sectional Survey. Biomed Central Public Health. 2025 Feb; 25(1): 757. doi: 10.1186/s12889-025-21939-6.

Rasouli ML, Nasir K, Blumenthal RS, Park R, Aziz DC, Budoff MJ. Plasma Homocysteine Predicts Progression of Atherosclerosis. Atherosclerosis. 2005 Jul; 181(1): 159-165. doi: 10.1016/j.atherosclerosis.2005.01.001.

Zubair F, Nawaz SK, Nawaz A, Nangyal H, Amjad N, Khan MS. Prevalence of Cardiovascular Diseases in Punjab, Pakistan: A Cross-Sectional Study. Journal of Public Health. 2018 Oct; 26(5): 523-529. doi: 10.1007/s10389-018-0898-4.

Khan MS, Saeedullah A, Andrews SC, Iqbal K, Qadir SA, Shahzad B et al. Adolescent Afghan Refugees Display a High Prevalence of Hyperhomocysteinemia and Associated Micronutrient Deficiencies Indicating an Enhanced Risk of Cardiovascular Disease in Later Life. Nutrients. 2022 Apr; 14(9): 1751. doi: 10.3390/nu14091751.

Liaquat A, Khan A, Shah SU, Iqbal H, Iqbal S, Rana AI et al. Evaluating the Use of Coronary Artery Calcium Scoring as a Tool for Coronary Artery Disease (CAD) Risk Stratification and Its Association with Coronary Stenosis and CAD Risk Factors: A Single-Centre, Retrospective, Cross-Sectional Study at a Tertiary Centre in Pakistan. BioMedical Journal open. 2022 Jul; 12(7): 57703. doi: 10.1136/bmjopen-2021-057703

van Rosendael AR, van den Hoogen IJ, Bax AM, Al’Aref SJ, Alawamlh OA, Larine D et al. CT and Calcification: Understanding Its Role in Risk Prediction. In: Coronary Calcium. Academic Press. 2019; 83–123. doi: 10.1016/B978-0-12-816389-4.00004-9.

Jung S, Choi BH, Joo NS. Serum Homocysteine and Vascular Calcification: Advances in Mechanisms, Related Diseases, and Nutrition. Korean Journal of Family Medicine. 2022 Sep; 43(5): 277. doi: 10.4082/kjfm.21.0227.

Jung S, Kim YN, Choi BH, Joo NS. Cut-off Value of Serum Homocysteine in Relation to Increase of Coronary Artery Calcification. Journal of Investigative Medicine. 2021 Feb; 69(2): 345-350. doi: 10.1136/jim-2020-001478.