Endothelium is the monolayer of endothelilal cells lining the lumen of blood vessels . It maintains a balance between vasoactive and vasodilator susbstances and the loss of this function leads to endothelial dysfunction. Insight into the function of endothelium has led to the development of tests for its assessment. All of these tests are based on the vasomotor response of endothelium to vasoactive stimuli. Intracoronary doppler techniques have disadvantages like invasive nature, expensive, relatively inaccessibility, risks inherent with coronary artery, difficulty in extending to larger studies and understanding microvascular pathophysiology and failure to represent true changes in conduit arteries predisposed to atherosclerosis [15, 16]. The drawbacks associated with plethysmography are reproducibility, invasive nature, risk of median nerve injury, infection and vascular injury . Vascular tonometry and measurement of vascular stiffness are limited by influence of structural aspects of the vasculature beyond the endothelium.
Non-invasive ultrasound test is based on the measurement of changes in brachial artery diameter in response to reactive hyperemia and is considered as a gold standard for clinical studies on conduit artery endothelial biology . It is repeatable and reproducible, reflects important biology, has some data to support its predictability and is useful in serial studies of disease reversibility . Brachial artery endothelium-dependent dilatation was found to be correlated with coronary circulation in the same patient [12, 19]. A single measurement of endothelial function in both the coronary and peripheral circulation can be of prognostic value in both normal and coronary heart disease patients [16, 20, 21].
Several studies have observed lower flow mediated dilation in CSX patients when compared to healthy controls [22–26] but few studies [24–26] observed no difference in endothelium independent vasodilatation. In the present study also, we have observed lower endothelium dependent flow mediated dilation in CSX patients when compared to the healthy control (p < 0.01). In case of glyceryl nitrite dependent dilation, no such difference was observed in our observation. It appears that endothelium dependent vascular dysfunction in CSX group of patients, is probably a generalized phenomenon as observed earlier .
Elevated levels of total cholesterol, LDL cholesterol, apolipoprotein B100, Lp(a), aortic and fractional pulse, platelet volume, nocturnal melatonin levels, CRP, reactive oxygen species and hydroperoxides and decreased oestrogen were observed in CSX patients [2, 24, 28–32]. In the present study, higher mean levels of body mass index, systolic and diastolic blood pressure was observed in CSX patients when compared to the control group.
An area under curve for cut-off value of 11.1 showed a value of 0.874 indicating that ultrasound is useful tool for identifying endothelial impairment in Csx patients and able to predict the impairment in 86% of subjects as shown by specificity of the cut-off value. This cut-off value is observed in a cross-sectional study and has to be established in longitudinal study involving larger sample size. To the best of our knowledge, no study in India reported cutt-off value for flow mediated dilation in Csx patients and this study attempts to propose the cut-off value for flow-mediated dilatation in Indian population. We have assessed the endothelial function manually using hand held probe and this is the limitation of the study.
In the present study, higher mean body mass index, systolic and diastolic blood pressure in FMD < 11.11 than FMD > 11.11 group (p < 0.01) was observed. Systolic blood pressure and body mass index significantly associated with impairment of endothelial function. A 5.77 fold increase in the incidence of hypertension in the lowest than highest FMD quartile was observed over a follow up of 3.5 years in risk factor free post menopausal women . A specific endothelial NO abnormality in microcirculation and conductance vessels of hypertensive subjects has been confirmed in multiple well controlled clinical investiagations . Increase in systemic blood pressure in normotenisve subjects after intravenous infusion of nitric oxide synthase antagonists was observed . Higher blood pressure in endothelial nitric oxide synthase knock out when compared to normal mice, more nitric oxide synthase 3 gene mutations in hypertnsive subjects also established impaired endothelial function .
Lower FMD was observed with increase in BMI [36, 37]. Nuclear Factor κB Activation contributes to vascular endothelial dysfunction via oxidative stress in overweight/obese middle-aged and older humans . Modest weight loss can improve endothelial function and affect the entire cluster of coronary heart disease risk factors simultaneously .
The results of the present study showed higher prevalence of microvascular dysfunction (78%) in the CSx patients when compared to the control subjects and suggest that early detection and management of systolic blood pressure and encouraging weight loss may be helpful in the management of CSX.