World Health Organization (WHO) and International Society of Hypertension (ISH) risk prediction charts: assessment of cardiovascular risk for prevention and control of cardiovascular disease in low and middle-income countries.

Cardiovascular disease (CVD) is the leading cause of the growing global disease burden due to non-communicable diseases. For successful prevention and control of CVD, strategies that focus on individuals need to complement population-wide strategies. Strategies that focus on individuals are cost effective only when targeted at high-risk groups. Risk prediction tools that easily and accurately predict an individual's absolute risk of CVD are key to targeting limited resources at high-risk individuals who are likely to benefit the most. Health systems in low-income countries do not have the basic infrastructure facilities to support resource-intensive risk prediction tools, particularly in primary healthcare. The WHO/ISH charts presented here, enable the prediction of future risk of heart attacks and strokes in people living in low and middle income countries, for the first time. Furthermore, since the charts use simple variables they can be applied even in low resource settings. Thus the WHO/ISH risk predication charts and the accompanying guideline will improve the effectiveness of cardiovascular risk management even in settings which do not have sophisticated technology.

Vascular remodeling: implications for small artery function and target organ damage.

At the level of the small artery, essential hypertension is associated with eutrophic inward remodeling. This involves reduction in lumen diameter by an increase in wall thickness. Previously thought to involve either hypertrophy or hyperplasia of the vascular smooth muscle cells in the media, it is now felt to be mediated by a functional property of the wall: myogenic tone. This is the ability of an artery to contract in response to an increase in intraluminal pressure. This autoregulatory function is also vital to ensure stabilisation of distal capillary pressures and so prevent, or limit, organ damage. Indeed in any animal model studied, when myogenic autoregulation is affected, target organ damage ensues. We have also observed, in two studies, that when myogenic autoregulation is damaged in the context of hypertension, eutrophic remodeling is replaced by an outward growth of the arterial wall with preservation of lumen diameter. This is called hypertrophic remodeling and, independently, has been observed by a number of groups in small arteries from patients with type 2 diabetes. We believe that this is a key reason for the unique propensity to hypertensive injury seen in patients with diabetes. We also discuss the significance of integrins, transmembrane proteins with wide ranging functions; from initiation of cell migration to intracellular signalling. Two particular integrins, alpha5beta1 and alphanubeta3, have been found to be necessary for both normal myogenic autoregulation and eutrophic remodeling and the possibility that damage to these may occur in diabetes is examined.