Essential Hypertension

Hypertension is the largest single contributor to global mortality, with approximately 25% of the population suffering from increased blood pressure. Hypertension is also a great economical burden with around 10% economic spent on therapies. However, though there are currently a myriad of potential therapeutics available around only half of current patients respond to the traditionally available treatment. This can be attributed to the complex presentation of the illness, with a combination of epigentics and environments resulting in a non-specific cause of hypertension in over 90% patients.
Though the risk factors arising from hypertension are widely known, such as stroke, kidney failure and hear disease, the underlying mechanism of the pathophysiology is still not fully understood.

Increased sympathetic nerve activity is widely recognised as a contributor to the increased blood pressure, however the precise cause of this is not known. In animal models of hypertension and in post-mortem human studies, cerebral blood flow has shown to be a key initiator of sympathetic tone.

Dickinson and Thomson initially hypothesised the role of reduced cerebral blood flow due to vertebral artery narrowing as a cause of essential hypertension, known as Cushing's mechanism, though did not provide any evidence of causality. Cates et al., were able to establish this in animal models, showing hypertension followed vertebral artery clamping. In a 2016 study by Warnet et al., was carried out in order to elucidate is Cushing's mechanism could indeed be attributed as a cause of essential hypertension in humans. With wide reaching consequences including the ability to prevent early onset vascular dementia in hypertensive individuals.

The study included a retrospective analysis as well as mechanistic case-control study of participants with a range of varied BP, from borderline hypertension to individuals with uncontrolled  high BP.

The outcome of this study showed a significantly increased vascular resistance in hypertensive individual in comparison to the case-matched group. Uniquely, this study also showed that cerebral vascular remodelling preceded increased sympathetic nerve activation and increased BP. In particular vertebral artery hyperplasia (VAH) and incomplete posterior Circle of Willis (CoW). Though normotensive patients with these variants showed normal cerebral perfusion perhaps indication sufficient compensation to have taken place with for example collateral circulations. Unusually in hypertensive or borderline hypertensive patients with these anatomical variants, has increased BP developed with age, which is perplexing due to the congenital cause of the altered cerebral vasculature. However over all this study puts forward a potentially new diagnostic tool for monitoring individuals who could potentially develop hypertension, with increased cerebral arterial resistance as a biomarker. Though further longitudinal studies must be carried in particular in patients with borderline hypertension and anatomical variants in order to see if hypertension occurs and whether it coincides with other factors such as increased age and weight. Though with hypertension proving to be a great health burden, this area is key in order to develop therapies that can alleviate the long-term stress this disease places at a societal and individual level.