Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity.

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type 1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type 1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type 1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.

End-organ dysfunction and cardiovascular outcomes: the role of the microcirculation.

Risk factors for cardiovascular disease mediate their effects by altering the structure and function of wall and endothelial components of arterial blood vessels. A pathological change in the microcirculation plays a pivotal role in promoting end-organ dysfunction that not only predisposes to further organ damage, but also increases the risk for future macrovascular events. The microcirculation is recognized as the site where the earliest manifestations of cardiovascular disease, especially inflammatory responses, occur that may play a pivotal role in driving the atherosclerotic process in conduit vessels. Furthermore, the vast surface area of the endothelium compared with conduit vessels means that the vascular effects of endothelial dysfunction or activation will be most apparent in this section of the vasculature. Current techniques providing indices of vascular health focus on large arteries without providing insight into the structure and function of small vessels. Techniques capable of detecting microvascular damage and monitoring the response to therapeutic interventions, especially in vulnerable target organs of interest, may improve risk stratification and represent a valuable surrogate for future cardiovascular outcome.

Arterial stiffness: clinical relevance, measurement and treatment.

Most traditional cardiovascular risk factors alter the structure and/or function of arteries. An assessment of arterial wall integrity could therefore allow accurate prediction of cardiovascular risk in individuals. The term 'arterial stiffness' denotes alterations in the mechanical properties of arteries, and much effort has focused on how best to measure this. Pulse pressure, pulse wave velocity, pulse waveform analysis, localized assessment of blood vessel mechanics and other methods have all been used. We review the methodology underlying each of these measures, and present an evidence-based critique of their relative merits and limitations. An overview is also given of the drug therapies that may prove useful in the treatment of patients with altered arterial mechanics.

Impaired microvascular properties in uncomplicated type 1 diabetes identified by Doppler ultrasound of the ocular circulation.

OBJECTIVE: Quantification of Doppler flow velocity waveforms has been shown to predict adverse cardiovascular outcomes and identify altered downstream haemodynamics and vascular damage in a number of organ beds. We employed novel techniques to quantify Doppler flow velocity waveforms from the retro bulbar circulation. METHODS AND RESULTS: In total, 39 patients with uncomplicated Type 1 diabetes mellitus, and no other significant cardiovascular risk factors were compared with 30 control subjects. Flow velocity waveforms were captured from the ophthalmic artery (OA), central retinal artery (CRA) and the common carotid artery. The flow velocity profiles were analysed in the time domain to calculate the resistive index (RI), and time-frequency domain using novel discrete wavelet transform methods for comparison. Analysis of flow waveforms from the OA and CRA identified specific frequency band differences between groups, occurring independently of potential haemodynamic or metabolic confounding influences. No changes were identified in the calculated RI from any arterial site. CONCLUSION: Novel analysis of the arterial flow velocity waveforms recorded from the retro bulbar circulation identified quantifiable differences in Doppler flow velocity waveform morphology in patients with diabetes prior to the development of overt retinopathy. The technique may be useful as an additional marker of cardiovascular risk.