Short-term treatment with low-dose aspirin improved metabolic status and attenuated atherothrombotic risk factors in female rats exposed to combined oral contraceptives

 

Abstract

Background: Atherothrombosis is a chronic and progressive disease responsible for a significant number of deaths globally, and it has become essential to understand how this consequence contributes to enhanced cardiovascular disease in women on combined oral contraceptives (COC).

Objectives: To assess the impact of COC administration on metabolic status and the risk of atherothrombotic disorder in female rats, beyond evaluating the therapeutic effects of short-term treatment with low-dose aspirin (LDA).

Methods: Thirty (n=30) five-week-old female Sprague Dawley rats were given low-dose COC (LCOC) or a high-dose COC (HCOC) for six weeks before treatment with LDA for another four weeks. These rats were compared to those that were only given LCOC or HCOC without treatment with LDA. Whereas rats that received distilled water (as a vehicle) and LDA only served as controls. Body weights and metabolic status were measured weekly. Whereas parameters related to glucose regulation, lipid profiles, inflammatory cytokines, hematological indices, coagulation, and endothelial dysfunction were recorded at the terminal end of the experiment.

Results: Rats exposed to HCOC presented with abnormal metabolic status and lipid profiles, as seen with impaired glucose tolerance (p < 0.001), which was accompanied by significantly higher levels of insulin, triglycerides, and very low-density lipoprotein when compared to the controls (p < 0.05). The HCOC treatment was also consistent with enhanced platelet count (p = 0.02), and elevated markers of inflammation and endothelial dysfunction, including interleukin 6 (p < 0.05); tumour necrosis factor-alpha (p < 0.05); monocyte chemoattractant protein-1 (p < 0.001), as well as tissue factor (p < 0.001), D-dimer (p < 0.001), Von Willebrand factor (p < 0.05), and low nitric oxide (p < 0.001). Notably, systolic blood pressure and mean arterial pressure were also significantly higher (p = 0.02) in these animals, suggesting an increased cardiovascular disease risk in response to HCOC. Surprisingly, short-term LDA attenuates cardiovascular risk by improving metabolic status, reducing inflammation levels, and mitigating endothelial dysfunction in rats exposed to HCOC.

Conclusion: A high dose of COC is associated with an increased risk of cardiovascular disease (CVD) in female rats, whereas short-term LDA attenuates the various factors associated with CVD risk by improving metabolic status, reducing inflammatory responses, and enhancing endothelial function. However, additional studies are essential to unravel the plausible mechanistic interaction between LDA and COC.

Keywords: combined oral contraceptive; cardiovascular disease; low-dose aspirin; inflammation; coagulation; endothelial dysfunction.