Aortic Stiffness, Pulse Pressure, and Cerebral Pulsatility Progress Despite Best Medical Management: The OXVASC Cohort

Abstract

Background and Purpose: Increased cerebral arterial pulsatility is associated with cerebral small vessel disease, recurrent stroke, and dementia despite the best medical treatment. However, no study has identified the rates and determinants of progression of arterial stiffness and pulsatility. Methods: In consecutive patients within 6 weeks of transient ischemic attack or nondisabling stroke (OXVASC [Oxford Vascular Study]), arterial stiffness (pulse wave velocity [PWV]) and aortic systolic, aortic diastolic, and aortic pulse pressures (aoPP) were measured by applanation tonometry (Sphygmocor), while middle cerebral artery (MCA) peak (MCA-PSV) and trough (MCA-EDV) flow velocity and Gosling pulsatility index (PI; MCA-PI) were measured by transcranial ultrasound (transcranial Doppler, DWL Doppler Box). Repeat assessments were performed at the 5-year follow-up visit after intensive medical treatment and agreement determined by intraclass correlation coefficients. Rates of progression and their determinants, stratified by age and sex, were determined by mixed-effects linear models, adjusted for age, sex, and cardiovascular risk factors. Results: In 188 surviving, eligible patients with repeat assessments after a median of 5.8 years. PWV, aoPP, and MCA-PI were highly reproducible (intraclass correlation coefficients, 0.71, 0.59, and 0.65, respectively), with progression of PWV (2.4%; P <0.0001) and aoPP (3.5%; P <0.0001) but not significantly for MCA-PI overall (0.93; P =0.22). However, PWV increased at a faster rate with increasing age (0.009 m/s per y/y; P <0.0001), while aoPP and MCA-PI increased significantly above the age of 55 years (aoPP, P <0.0001; MCA-PI, P =0.009). Higher aortic systolic blood pressure and diastolic blood pressure predicted a greater rate of progression of PWV and aoPP, but not MCA-PI, although current MCA-PI was particularly strongly associated with concurrent aoPP ( P <0.001). Conclusions: Arterial pulsatility and aortic stiffness progressed significantly after 55 years of age despite the best medical treatment. Progression of stiffness and aoPP was determined by high blood pressure, but MCA-PI predominantly reflected current aoPP. Treatments targetting cerebral pulsatility may need to principally target aortic stiffness and pulse pressure to have the potential to prevent cerebral small vessel disease.

Arterial Stiffness Is Associated With Small Vessel Disease Irrespective of Blood Pressure in Stroke-Free Individuals

“…In individuals aged >60 years, DBP is believed to decrease with increasing arterial stiffness. In accordance with previous studies, 25,27,29 DBP was associated with CSVD in this study. Since the participants were relatively younger, they were in the process of experiencing increased peripheral vascular resistance and arterial stiffness, which we think was reflected more in DBP than in SBP.…”

New Insights Into Cerebrovascular Pathophysiology and Hypertension

“…This marker of vascular aging has a hazard ratio of 1.54 per SD increase for stroke and 1.42 for all vascular events, [48][49][50] and its progression is hypertension dependent, with a 20 mm Hg elevation of SBP associated with a 1.14 m/s progression in pulse wave velocity per decade. 51 Furthermore, there are strong associations between aortic pulse wave velocity and specific cerebrovascular phenotypes, including acute lacunar stroke, 52 deep intracerebral hemorrhage (by contrast with lobar), 53 cSVD, and cognitive impairment, 54,55 with a similar odds ratio of 1.25 to 1.3 per SD increase in pulse wave velocity associated with an increase in severity of WMHs on the Fazekas scale.…”

“…Figure 3. Rate of progression of aortic pulse wave velocity (PWV) and middle cerebral pulsatility (PI) over 5 y in 188 patients after transient ischemic attack (TIA) or minor stroke, stratified by quartiles of age.Individual changes are show, with summary results derived from a mixed effect linear model, stratified by quartiles of age and subdivided into men (red) and women (blue) 55. …”

Low Heart Rate Is Associated with Cerebral Pulsatility after TIA or Minor Stroke

“… 30 However, SVD is also strongly associated with arterial stiffness and cerebral arterial pulsatility, 11 , 31 reflecting transmission of pulsatile blood flow from the aorta through stiff vessels to the brain. Pulsatility progresses above 55 years, 14 , 32 in parallel with progression of SVD, is highly reproducible over 5 years within‐individuals, and is a biologically plausible mechanism for inducing cSVD, both through increased sheer stress due to excessive systolic pressures and hypoperfusion during diastole. Vasodilating drugs with beneficial effects on stroke 33 risk also reduced cerebral pulsatility, 34 such as cilostazol in the ECLIPSE trial, 35 but vasodilators, and PDE3 inhibitors in particular, also increase HR rather than just lowering BP, suggesting a potential alternative mechanism of action.…”

“… 13 Cerebral pulsatility reflects enhanced transmission of the pulsatile aortic waveform to the brain through increasingly stiff vessels. 14 Following the transition to the late‐life hypertensive phenotype of increased aortic stiffness above 55 years of age, 15 it progresses in parallel with aortic pulsatility, aortic stiffness , 16 and SVD, 17 , 18 , 19 and may play a key role in pathogenesis of SVD and its consequences, through either excessive shear stress during systole or hypoperfusion during diastole.…”