Current Hypertension Reviews - Volume 5, Issue 2, 2009

Hypertension is the major modifiable risk factor for fatal, nonfatal strokes and other vascular diseases. In a pooled analysis of 61 prospective studies including about one million individuals, the reported risk of stroke increased progressively with blood pressure from values as low as 115/75 mm/Hg. Each increment of 20/10 mm/Hg doubles the risk of cardiovascular disease and such a correlation is consistent at all ages. Blood pressure lowering strongly reduces the risk of either first stroke or recurrent stroke but the possibility that specific drugs may prevail over others for protection from stroke remains unclear. There is some evidence that specific classes of antihypertensive drugs have different effects and/or their pharmacological actions differ in patient subgroups. Currently, there are five classes of first-line blood pressure lowering drugs: diuretics, beta-blockers, calcium channel blockers, angiotensin-converting inhibitors and angiotensin II receptor blockers. This review evaluates the development of antihypertensive therapies and the latest studies of arterial hypertension and stroke prevention.

Renal artery stenosis (RAS) causing either renovascular hypertension (RVH) or ischemic nephropathy (IN) is a complicated pathophysiologic entity. The diagnosis may remain uncertain in many cases and is frequently obscured by other overlapping sources of hypertension. Improved sensitivities of non-invasive diagnostic imaging modalities has led to an increase in the detection of RAS without necessarily guiding treatment recommendations. Simultaneously, widespread, multidisciplinary competence with minimally-invasive, catheter-based therapies has led to frequent treatment of RAS without clearcut benefit. Establishing a causal relationship between the renal artery lesion and hypertension, when feasible, is of paramount importance in recommending therapy and achieving expected results. Broad lesion classification and location is also helpful in guiding therapies when indicated. Developmental lesions of the renal arteries typical of RVH affecting children behave differently than typical fibromuscular dysplastic (FMD) lesions or atherosclerotic renal artery disease (ASO-RAS). Unilaterality versus bilaterality, ostial versus branch vessel, focal versus diffuse and renal functional status are equally important in recommending therapy. Renovascular surgery and results of renal artery angioplasty /stenting (RAA) are discussed in the context of outcomes and durability. Ongoing investigations examining results of catheter-based treatments of RAS utilizing embolic protection devices (EPD) are presently in the forefront of the current literature and discussed in this review.

Atherosclerosis is an inflammatory disease which begins in the first decade of life. As clinically apparent atherosclerosis occurs in adulthood, there is a very long time-interval in which arterial wall abnormalities constitute asymptomatic or “preclinical” atherosclerosis. High-resolution B-mode ultrasound constitutes a valid, reliable and inexpensive method for detecting early both structural and functional atherosclerotic changes in the arterial wall. Impaired flowmediated dilation of brachial artery and increased thickness of the intima-media complex of the carotid artery have been found in healthy subjects with risk factors for cardiovascular disease. In this review we evaluated the influence in healthy young subjects of a positive family history of (premature) coronary artery disease, hypertension or type 2 diabetes mellitus on preclinical atherosclerosis.

Although many studies have addressed the relevance of assessing blood pressure (BP) control over a 24-hour period, it is still an area of dispute among clinicians. There is no clear agreement as to which 24-hour parameters are most important and no standardized definitions. Different types of 24-hour measurement have different implications for outcomes and, differ in their impact on the health economics of hypertension. For example, several groups have reported a connection between the systolic BP surge on rising and the incidence of cardiovascular complications in hypertensives. As BP surge on rising occurs toward the end of the dosing period, the use of an antihypertensive with extended duration of action and proven forgiveness to missed dose is more likely to attenuate the adverse outcomes associated with an early morning BP surge. Studies in this area provide quantitative estimates of the relationship between suboptimal 24-hour BP control and morbidity and mortality outcomes. Growing evidence demonstrates that there are improved outcomes in those patients whose BP values are lowered throughout a 24-hour period. However, 24-hour control is even more difficult to achieve than clinic BP control, and not all antihypertensive drugs are equally capable of reducing BP over the full 24-hour period. Some drugs claim beneficial effects on certain aspects of 24-hour control but may not control other aspects adequately; plus not all drugs have the same effects on target organ damage (over and above effects due to BP control). Whilst 24-hour measurements are not needed for routine clinical practice, choosing an antihypertensive that is proven to provide complete 24-hour coverage is likely to translate into improved outcomes. Mathematical modeling can be a useful tool in linking various measures of 24-hour BP control to longer-term outcomes and when evaluating antihypertensive strategies for reimbursement purposes. However, it is important to develop standardized and agreed modeling approaches that look at effects over the whole 24-hour period, including when doses are missed.

Tumor necrosis factor super family 15 (TNFSF15) is one of the more recently identified TNF ligands. Emerging studies are beginning to reveal the function of TNFSF15 in physiology and pathology. TNFSF15 has been found to have a prominent role in endothelial cell biology. The abundance of TNFSF15 in the vasculature suggests that the endothelium be the major production site of this cytokine. TNFSF15 has been shown to be a negative regulator of angiogenesis with a unique characteristic of inhibiting proliferation only on endothelial cells. In addition, TNFSF15 is also involved in the modulation of inflammation. It stimulates T cell activation, Th1 cytokine production, and dendritic cell maturation. Thus, similar to other TNF ligands, TNFSF15 is a multifunctional, yet specialized, cytokine. The various functions of TNFSF15 are mostly mediated by death receptor 3 (DR3). We review the experimental evidences on the identification, isoforms, structure and expression of TNFSF15, and its activities in anti-angiogenesis, anti-tumor, inflammation and immune system mobilization.

Acute dissection is the most common life threatening condition of the aorta affecting 5-30 per million people per year [1]. Left untreated, the majority of patients with dissections involving the ascending aorta will die within days of an acute episode [2]. Patients presenting with descending thoracic aortic dissections seem to fare better, with one in ten patients dying before leaving hospital. Ultimately, these patients are at risk of aortic rupture with nearly 20% of these patients requiring some form of surgical or endovascular intervention [3]. Judicious medical, surgical and endovascular management of this condition aims to reduce propagation of the dissection plane and concomitant branch vessel compromise, halt aortic expansion and prevent fatal aortic rupture. Early recognition of these disease entities in conjunction with urgent and pertinent management is the key to a successful outcome in these patients.

Static cerebral blood flow (CBF) autoregulation maintains a constant CBF despite changes in cerebral perfusion pressure (CPP) within certain limits; this is achieved through adaptive responses in the cerebrovascular resistance, i.e. arteriolar vasoconstriction and vasodilation. This system may protect the brain from hyper- and hypoperfusion upon CPP challenges. CBF autoregulation appears to be mediated through myogenic and metabolic feedback systems, which may involve the vasoconstrictor 20-hydroxyeicosatetraenoic acid as well as an oxygen-sensing mechanism that may involve nitric oxide signalling. Static CBF autoregulation is modulated or impaired in various pathological conditions. In chronic arterial hypertension, both the lower and upper limit of CBF autoregulation are shifted towards higher CPPs; however, CBF autoregulation may be readapted to normal by antihypertensive therapy. Furthermore, CBF autoregulation is impaired in a wide range of clinical conditions, including cerebral ischaemia, traumatic brain injury, intracranial space-occupying processes, subarachnoid haemorrhage, acute bacterial meningitis, fulminant hepatic failure and diabetes. In some of these conditions, CBF autoregulation may be restored by means of hyperventilation and/or induced hypothermia. At present, the clinical impact of CBF autoregulation impairment and of treatment strategies that aim to restore CBF autoregulation remains unclear.

Hyperhomocysteinemia (HHcy) is a significant and independent risk factor for cardiovascular diseases. Endothelial dysfunction (ED) is the earliest indicator of atherosclerosis and vascular diseases. We and others have shown that HHcy induced ED in human and in animal models of HHcy induced by either high-methionine load or genetic deficiency. Six mechanisms have been suggested explaining HHcy-induced ED. These include 1) nitric oxide inhibition, 2) prostanoids regulation, 3) endothelium-derived hyperpolarizing factors suppression, 4) angiotensin II receptor-1 activation, 5) endothelin-1 induction, and 6) oxidative stress. The goal of this review is to elaborate these mechanisms and to discuss biological and molecular events related to HHcy-induced ED.