Early Detection of Microvascular Dysfunction in Asymptomatic Individuals with Different Cardiovascular Diseases Risk Factors

Abstract

In health, the endothelium maintains the balance between opposing dilator and constrictor influences, while in disease, it is the common ground on which cardiovascular risk factors act and a site at which cardiovascular disease begins. Consequently, as such, the endothelial acts as a barometer of an individual’s likely future cardiovascular health; however, the currently used cardiovascular diseases risk assessments scores tend to overlook the importance of endothelial dysfunction in the progress of cardiovascular diseases. Moreover, the presence and severity of endothelial dysfunction in apparently healthy individuals suggest considerable variability in pre-clinical risk that could be identified well before the onset of the disease. The earlier detection of cardiovascular diseases can improve the effectiveness of treatments and avoid long-term complications and may lead to longer survival.
This possibility has led to public health programs to recommend periodic screening examinations for detecting specific chronic diseases, for example, cancer, diabetes, and cardiovascular disease.
Therefore, this thesis aimed to investigate microvascular dysfunction as an early culprit in the pathophysiology of cardiovascular diseases in clinically healthy individuals with different cardiovascular risk factors. As cardiovascular diseases are clearly multifactorial with risk factors that tend to cluster and interact, in an individual to determine the level of future disease risk and to increase the clinical accuracy of the conducted investigations, influences of systemic circulatory oxidative stress biomarkers on retinal microvascular function were also evaluated.

The principal sections and findings of this work are:
1. Microvascular Function and Oxidative Stress in Adult individuals with Early Onset of Cardiovascular Disease
• Prehypertension patients showed abnormal retinal vascular response to flicker light stimuli throughout the entire functional response curve for arteries. Systemic blood pressure and impairments in microvascular function at the retinal level correlated with established plasma markers for oxidative stress.

2. European Society of Cardiology/European Society of Hypertension versus the American College of Cardiology/American Heart Association guidelines on the cut-off values for early hypertension: A Microvascular Perspective
• Microvascular dysfunction was present in ESC/ESH grade 1 hypertension patients and not in stage 1 hypertension in the form of altered peripheral and retinal responses to systemic stimuli (blood occlusion, flickering light).

3. Dry Eye Disease is Associated with Retinal Microvascular Dysfunction and Possible Risk for Cardiovascular Disease
• Individuals with a positive diagnosis of Dry Eye Disease exhibit a higher risk for cardiovascular disease than age, sex-matched normal individuals. These alterations were correlated to circulatory blood cholesterols.

4. Novel Composite Early Risk Markers for Vascular Ageing and Risk for Cardiovascular Disease
• Study findings confirmed the systemic association between plasma oxysterol levels and gradual microvascular endothelial dysfunction at the retinal arterial level after the age of 30. This association was also correlated to decreased systemic antioxidant capacity without any significant change in NO concentrations.

5. Prediction of Cardiovascular Risk in Asymptomatic Individuals: A Symbolic Regression-Based Analysis of Single and Composite Vascular-Omics
• Study findings confirmed the predictive power of the telomere and retinal arteries function as a composite biomarker for predicting cardiovascular risk factors such as blood pressure, while the assessment of retinal vascular function is better predictor of chronological ageing than relative telomere length.

Date of Award	Sept 2021
Original language	English
Supervisor	Doina Gherghel (Supervisor) & Nicola Logan (Supervisor)