Vascular Risk Factors and Biomarkers of Endothelial Dysfunction in Chronic Migraine patients- A Cross-sectional Study

Abstract

Introduction: The available literature on vascular risk and endothelial dysfunction in patients with Chronic Migraine (CM) is limited. CM patients are known to have a higher risk of cardiovascular and cerebrovascular events. The present study aims to characterise the vascular risk and endothelial dysfunctions in CM patients and compare them with Healthy Controls (HC). Aim: To assess the vascular risk factors and biomarkers of endothelial dysfunction in CM patients and compare them with healthy non-headache controls. Materials and Methods: This cross-sectional study was conducted from October 2021 to January 2023 at the headache clinic of GB Pant Institute of Postgraduate Medical Education and Research in Delhi, India. The patients were diagnosed with CM using the International Classification of Headache Disorders-3 (ICHD-3) criteria. The patients were drug-naïve for preventive medications and did not have medication overuse headache. Clinical vascular risk factors such as Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Ankle Brachial Index (ABI), Body Mass Index (BMI), and Waist Hip Ratio (WHR) were measured. A battery of biochemical vascular risk factors, including serum C-reactive protein, leptin, insulin, fasting and post-prandial glucose, Glycosylated Haemoglobin (HbA1c), lipid profile, lipoprotein-A, pro-Brain Natriuretic Peptide (proBNP), and serum biomarkers of endothelial dysfunction like Intercellular Adhesion Molecules-1 (ICAM-1), Myeloperoxidase (MPO), Interleukin-6 (IL-6), Tumour Necrosis Factor-Alpha (TNFalpha), Asymmetric Dimethyl Arginine (ADMA), fibrinogen, and von Willebrand’s factor were measured in all patients during the interictal period. Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 25.0, and the Mann-Whitney U test, student’s t-test, and Chi-square tests were applied. Results: Thirty-two patients with CM and thirty-two nonheadache healthy subjects were included in the study (age 30.6±8.8 years; 29 females and 3 males) vs. (31.7±7.9 years; 19 females and 13 males, respectively). Compared to HC, CM patients had significantly higher DBP (81.0±8.0 mmHg vs. 66.2±6.2 mmHg; p<0.001). Among the biochemical parameters, CM patients had higher post-prandial blood sugar (mg/dL) (140.2±10.7 vs. 136.6±7.0; p=0.021), HbA1c (%) (5.8±0.8 vs. 5.6±0.4; p=0.034), serum cholesterol (mg/dL) (146.9±36.2 vs. 131±20.8), and Triglyceride (TG) levels (mg/dL) (93.2±10.8 vs. 88.5±13.0; p=0.001) compared to HCs. Among the biomarkers of endothelial dysfunction studied, levels of ICAM-1 (pg/mL) (4.5±3.8 vs. 1.3±0.62; p<0.001), MPO (pg/mL) (415.4±266.0 vs. 108.9±141.4; p=0.001), IL-6 (pg/mL) (10.8±4.9 vs. 4.2±1.5; p<0.001), and ADMA (ng/mL) (32.6±28.3 vs. 23.5±22.1; p=0.008) were higher in the CM group compared to non-headache controls. Conclusion: This study found that patients with CM have significantly higher vascular risk and evidence of endothelial dysfunction compared to healthy non-headache controls. The significantly elevated biomarkers of endothelial dysfunction may possibly be related to persistent neurogenic inflammation in CM and require further exploration through larger studies.