Diagnosis of CVD in Asymptomatic Patients
Endothelial cell function and its role in maintaining vascular health:
Blood vessels play a vital role in maintaining cardiovascular health and atherosclerosis. A single layer of cells called the endothelium lines the walls of every blood vessel and capillary in the body. Along with a layer of elastic tissue, the endothelium comprises what is called the intima. Endothelial cells are also referred to as the “brain" of the vascular system. Healthy endothelial cells play an important role in maintaining blood vessel flexibility, (or compliance} and influences a number of important aspects of vascular health.
Endothelial cells provide a dynamically-controlled structural barrier between the circulating blood and surrounding tissues and organs, they also produce signaling molecules that influence vasodilation and vasoconstriction. Vasodilation causes blood vessels to relax allowing for greater blood flow. This reduces blood pressure. Vasoconstriction causes blood vessels to tighten reducing blood flow and causing blood pressure to increase.
Independent research suggests that endothelial cells are the controlling factor in the regulation of blood pressure. They produce both nitric oxide which is the most potent vasodilator and endothelin-1 the most potent vasoconstrictor.
The proper production of nitric oxide is fundamental to maintaining normal blood pressures because it maintains basal tone by relaxing the vascular smooth muscle cells.
Consequences of damage to endothelial cells:
However, the effects of excess alcohol, over eating (or eating the wrong foods), tobacco smoke and stress provide a toxic milieu that injures the endothelium. This damage can start when people are in their 20’s or 30”s and causes an inflammatory response intended to heal the artery wall, but that in the face of continuous injury (over years) endothelial cells become damaged and stop releasing the nitric oxide required to help dilate blood vessels.
The progressive result is an accumulation of fatty deposits called plaque that can rupture or have their caps shear off, causing clots that lead to heart attacks. In addition, artery walls can stiffen, transforming compliant arteries into conduits like "Styrofoam tubes," that increase both blood pressure and the workload on the heart.
Independently conducted clinical studies have repeatedly demonstrated that the endothelium plays an important role controlling the vascular inflammatory process, the maintenance of vascular tone, balancing blood fluidity and thrombosis:
Endothelial cell function and the diagnosis of early-stage cardiovascular disease in asymptomatic patients:
Independent clinical studies have demonstrated that endothelial cell dysfunction is a key biomarker of atherosclerosis and CVD; it is also the earliest detectable sign of atherosclerosis.1
- “Studies have shown that the severity of endothelial dysfunction relates to the risk for an initial or recurrent cardiovascular event.”
- “Clinical syndromes such as stable and unstable angina, acute myocardial infarction, claudication, and stroke relate, in part, to a loss of endothelial control of vascular tone, thrombosis, and the composition of the vascular wall.”
- “Finally, a growing number of interventions known to reduce cardiovascular risk also improve endothelial function.”
- Endothelial function serves as a “barometer” for cardiovascular health that can be used for patient care and evaluation of new therapeutic strategies”
Studies have also demonstrated that endothelial dysfunction precedes and predicts the development of atherosclerosis and CVD.2
- “10 studies examining the prognostic value of endothelial vasomotor function involved 1,920 patients with atherosclerosis or hypertension and 333 patients with CVD related events.”
- “These studies strongly and consistently demonstrate that endothelial dysfunction identifies patients who have increased risk for CVD events in the short and long term.”
- “Importantly, endothelial vasomotor dysfunction appears to be a systemic process that can be identified in vascular beds remote from the coronary and cerebral circulations where events occur.”
The value of assessing endothelial function as an early predictor of cardiovascular disease has also been demonstrated in the most important international markets. For example, leading Indian Cardiologists have also published compelling research3 demonstrating the importance of endothelial cell dysfunction as a predictor of atherosclerosis and CVD:
- “These results indicate that raised values of average and maximum carotid intima-media thickness (i.e. the endothelial dysfunction) are significantly associated with the presence of CVD and this association is independent of other conventional cardiovascular risk factors.”
- “Carotid intima-media thickness (IMT) measurement is a promising tool for detecting atherosclerosis in its pre-occlusive phase.”
Leading Indian Cardiologists have also demonstrated that assessing endothelial function can be used as an early marker of future atherosclerotic disease4:
- “Endothelial dysfunction is a key early event in atherogenesis and is known to appear long before the formation of structural atherosclerotic changes.”
- “Assessment of endothelial function, thus, can provide valuable insight into the pre-intrusive phase of atherosclerosis and can be used as an early marker of future atherosclerotic disease.”
- “Endothelial function as assessed by flow mediated dilation (‘FMD’) is significantly impaired in diabetics compared to non-diabetics in the absence of CVD. In addition, a similar degree of impairment in endothelial function is seen diabetics without CVD and non-diabetic patients having CVD, implying CVD risk equivalence of diabetes.”
In summary, the role of endothelial dysfunction in the pathogenesis of atherosclerosis and CVD events has been well defined in the body of medical literature:
- Sources: Journal of the American College of Cardiology Vol. 42, No. 7, 2003; The Clinical Implications of Endothelial Dysfunction; Michael E. Widlansky, MD, Noyan Gokce, MD, FACC, John F. Keaney, JR, MD, FACC, Joseph A. Vita, MD, FACC; Boston, Massachusetts; Journal of the American College of Cardiology Vol. 42, No. 7, 2003; The Clinical Implications of Endothelial Dysfunction; Michael E. Widlansky, MD, Noyan Gokce, MD, FACC, John F. Keaney, JR, MD, FACC, Joseph A. Vita, MD, FACC; Boston, Massachusetts; Carotid Intima-Media Thickness (i.e. the endothelial cells) and Coronary Artery Disease: an Indian Perspective, published in Noninvasive Cardiology, Escorts Heart Institute and Research Center, New Delhi, India; Gupta Hansa MD, Kartikeya Bhargava MD, Manish Bansal MD, Sharad Tandon MD, Ravi Kasliwal DM, 2003, Vol 11, No. 3
- Sources: Journal of the American College of Cardiology Vol. 42, No. 7, 2003; The Clinical Implications of Endothelial Dysfunction; Michael E. Widlansky, MD, Noyan Gokce, MD, FACC, John F. Keaney, JR, MD, FACC, Joseph A. Vita, MD, FACC; Boston, Massachusetts
- Carotid Intima-Media Thickness (i.e. the endothelial cells) and Coronary Artery Disease: an Indian Perspective, published in Noninvasive Cardiology, Escorts Heart Institute and Research Center, New Delhi, India; Gupta Hansa MD, Kartikeya Bhargava MD, Manish Bansal MD, Sharad Tandon MD, Ravi Kasliwal DM, 2003, Vol 11, No. 3
- Endothelium Dependent Brachial Artery Flow Mediated Vasodilation in Patients with Diabetes Melitus With and Without CVD; K Bhargava MD, G Hansa MD, M Bansal MD, S Tandon MD, R Kasliwal DM, JAPI Vol. 51, page 355 to 358, 2003