The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin–ramipril study

Abstract

There are several non-invasive methods to study endothelial function, but their interrelation and association to cardiovascular risk have not been well evaluated. We studied macrovascular and microvascular endothelial function simultaneously in different vascular beds in relation to cardiovascular mortality risk (Systematic Coronary Risk Evaluation, SCORE) and hypertension induced cardiac organ damage, and their interrelationship. The study investigated 71 hypertensive patients by forearm post-ischemic flow-mediated vasodilation, pulse wave analysis (applanation tonometry) and beta 2-adrenoceptor agonist stimulation for changes in reflection index, skin microvascular reactivity by laser Doppler fluxmetry with iontophoresis and heat-induced hyperaemia, and coronary microvascular function by subendocardial viability ratio (derived from pulse wave analysis). Flow mediated vasodilation related inversely to SCORE ( r = 0.34, P = 0.011). Adding microalbuminuria and pulse wave velocity strengthened the associations. Pulse wave reflection changes did not relate to SCORE. Skin microvascular reactivity related inversely to SCORE (peak flux change to sodium nitroprusside r = 0.29, P = 0.033, and to heating r = 0.31, P = 0.018). Subendocardial viability ratio did not relate to SCORE. Endothelial function indices showed no consistent relation to cardiac target organ damage. The agreement between the different methods for evaluating indices of macrovascular and microvascular endothelial function was weak. In conclusion, indices of macrovascular and microvascular endothelial function relate to cardiovascular mortality risk. Their use may improve cardiovascular risk prediction in hypertension. However, methods representing different vascular beds show little interrelationship and are not interchangeable, which may depend on different pathogenetic mechanisms representing different aspects of future cardiovascular risk. Trial registry : NCT02901977

Ischemic Stroke and Heart Failure: Facts and Numbers. An Update

“…The presence of a hypercoagulable state has also been reported in patients with HFpEF [ 31 ]. The endothelial dysfunction observed in patients with chronic HF results in decreased endothelium-derived nitric oxide generation and reduced microvascular reactivity of the myocardium, leading to subendocardial damage that finally promotes the development of thromboembolic complications [ 5 , 32 , 33 ]. Furthermore, pathological ventricular remodeling, including dilatation of LV and/or left atrium (LA), LV akinesia, dyskinesia, or aneurysm may also contribute to the stasis of blood flow and thus, promote thrombus formation [ 34 , 35 ].…”

Effects of exenatide on microvascular reactivity in patients with type 2 diabetes and coronary artery disease: A randomized controlled study

“…However, there was an adequate power calculation performed prior to the study. Third, macrovascular and microvascular endothelial function indices relate to cardiovascular risk, but different vascular beds show little interrelationship and are not interchangeable 43 . We cannot from the present study evaluate possible beneficial effects by exenatide in other vascular beds related to future outcome.…”

“…There were no significant differences between the groups. 43 We cannot from the present study evaluate possible beneficial effects by exenatide in other vascular beds related to future outcome. Fourth, the treatment period was only 12 weeks and not all patients managed to receive 10 µg twice daily after the initial starting dose of 5 µg twice daily during the first 4 weeks.…”

The effect of heat therapy on blood pressure and peripheral vascular function: A systematic review and meta‐analysis

“…With ageing there is a deterioration of cardiovascular function and health, associated with the decline in vascular elasticity, endothelial function and nitric oxide (NO) bioavailability (Mitchell et al., 2004; Taddei et al., 2000). Indices of macrovascular and cutaneous microvascular function are associated with cardiovascular mortality risk (Jekell et al., 2019). For example, brachial artery flow‐mediated dilatation (FMD) and pulse wave velocity (PWV) represent early markers of macrovascular dysfunction and arterial stiffness, respectively, with both being independently associated with the development of CVD risk (Green et al., 2011; Hadi et al., 2005; Mattace‐Raso et al., 2006; Mitchell, 2014).…”