Blood Pressure Variability and Cerebrovascular Reactivity

In the current issue of the American Journal of Hypertension, the study by Dr Sible and colleagues aimed to examine the relationship between blood pressure variability (BPV) and cerebrovascular reactivity (CVR).1 In community-dwelling older adults without a history of dementia or stroke, elevated short-term systolic BPV was related to lower whole brain CVR during hypo- and hypercapnia breathing conditions, independently of average blood pressure levels.1 These findings add to the growing body of literature that links blood pressure variations to organ damage and cerebrovascular disease burden. Blood pressure is one of the key determinants for the evaluation of health status. Chronic hypertension affects the structure and function of cerebral blood vessels. Blood pressure can fluctuate over time due to mutual interactions between external and internal stimuli and regulatory mechanisms.2 Far from being a background noise or a random phenomenon, the fluctuation in blood pressure levels can be reproducible within individuals, where its pathogenic role in organ damage has been increasingly recognized.2,3 Excessive variation in blood pressure levels is particularly detrimental to high-flow organs like the brain.4 This hypothesis concords with the stronger association between BPV and stroke than BPV and heart disease.4 Of note, systolic BPV is increased in cohorts at high risk of stroke and predicts stroke independently of average blood pressure.5–7 In addition, high BPV is significantly associated with the burden of white matter lesions, cerebral microbleeds, and brain atrophy and may increase the risk of cognitive impairment and dementia.2,8,9 Different mechanisms can explain the relationships between BPV and the alterations in brain structure and function. The shear stress on the vessel wall due to high blood pressure and its steep variations can cause endothelial injury, impair the functioning of vascular smooth muscle, and favor microvascular damage and arterial remodeling. In turn, the stiffening of the vascular wall represents an upstream determinant of the imbalance of cerebral blood flow.2,3 Reduction in CVR and the right shift of cerebral autoregulation curve, which are commonly observed in elderly and in hypertensive patients, can further augment the effects of BPV.10 Little is known about the relationships between BPV and markers of cerebrovascular dysfunction. CVR represents the compensatory ability of the cerebral arterioles to dilate in response to a dilatory stimulus to maintain an adequate cerebral blood flow.11 In the absence of major arterial stenosis, diminished cerebral vasomotor reactivity may be a surrogate index of the increased rigidity of the arteriolar walls.11 Arterial stiffening may hamper the dilation and constriction of the vessels and compromise the cerebral vasomotor response in regulating cerebral blood flow. In addition, the BPV may inhibit the synthesis of nitric oxide and affect the function of the neurovascular unit.4 In a vicious cycle, the impairment of endothelium-dependent synthesis of vasodilating and vasoconstricting substances may further impact the maintenance of stable blood pressure.4 The neurovascular uncoupling and depletion of the cerebrovascular reserve, which follow the impairment of CVR, make the brain more vulnerable to vascular insufficiency and are responsible for the brain damage and dysfunction that translate into increased risks of stroke and cognitive impairment as major clinical correlates.12–14 Within this frame, the study by Dr Sible pointed out an intriguing relationship between BPV and CVR and suggested an attractive perspective. However, further research is warranted to explore whether elevated BPV and reduction in CVR are causally related or whether they are both markers of accumulating vascular damage. The long preclinical phase represents an important feature of vascular diseases. During this period, pathological conditions such as endothelial damage, arterial stiffening, inflammation, and atherosclerosis can contribute to vascular injury.15 This scenario of potentially treatable, cumulative mechanisms points out the opportunity to develop preventive and therapeutic interventions. In this regard, a very relevant issue is the possibility that BPV may be considered a therapeutic target modulated by antihypertensive agents. Clinical implications would include: (i) recording and monitoring blood pressure values in routine practice; (ii) providing standardized definitions and measures of BPV to analyze short- and long-term fluctuations of blood pressure and their detrimental effects; (iii) focusing on the effects that different classes of antihypertensive drugs have on individual variations of blood pressure levels.5 In summary, BPV has become a significant vascular risk factor and potentially promising interventional target. Studies are warranted to explore whether stabilizing blood pressure can reduce the risk of cerebrovascular disorders and their global burden. The authors declared no conflict of interest.