Recent Advances in Arterial Stiffness and Wave Reflection in Human Hypertension

Abstract

I n recent years, great emphasis has been placed on the role of arterial stiffness and wave reflection in the development of cardiovascular (CV) diseases.Arterial stiffness and wave reflections, which are now well accepted as the most important determinants of increasing systolic and pulse pressures in aging societies, are increasingly used in the clinical assessment of patients with hypertension and various CV risk factors. 1,2This review addresses recent advances in our understanding of the role played by arterial stiffness and wave reflection in the pathophysiology and treatment of human hypertension.According to the editorial rules for "Hypertension Highlights", and to better focus on recent research, apart from large clinical trials, only articles published during the last 2 years are quoted in this review. Determinants Of Arterial Stiffness: Role of Smooth Muscle Cells and InflammationResearch on the molecular determinants of arterial stiffness has focused for years on the structure and amount of the main load bearing proteins: elastin and collagens. 3Indeed, aging and blood pressure, the two major determinants of arterial stiffness, are associated with a number of molecular changes of the load-bearing media of elastic arteries: the orderly arrangement of elastic fibers and laminae is gradually lost over time, and thinning, splitting, fraying, and fragmentation are observed.The degeneration of elastic fibers is associated with an increase in collagenous material and in ground substance, often accompanied by calcium deposition in ground substance and in degenerate elastic fibers. 4owever, quantitative changes in elastin and collagen may not explain, by themselves, paradoxical observations.For instance, the changes in arterial wall material which accompany arterial hypertrophy in animal models of essential hypertension (SHRs and SHR-SPs) and in middle-age hypertensive patients are not necessarily associated with an increased isobaric stiffness. 5We suggested 5 that adaptive mechanisms may include a rearrangement of the arterial wall material through cell-matrix connections, with a major role of integrins. 6This remodeling may involve qualitative and quantitative changes in arterial wall components leading to redistribution of mechanical load toward elastic materials. 5In this respect, the dedifferentiation of smooth muscle cells (SMCs), leading to arterial wall hypertrophy, and the number of elastin/SMC connections, which influences the extent of elastin network anchorage to SMCs, may play an important role. 5,6he role of contractile proteins of SMCs was 7 illustrated by the discovery of an increased aortic stiffness in a genetic disease combining thoracic aortic aneurysm and/or aortic dissection and patent ductus arteriosus.In patients with MYH11 mutation, altering the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, an increased aortic stiffness was observed, in parallel with medial degeneration and very low SMC content of the aorta. 7This is the first example that direct changes in a contractile protein produced specifically in SMC may alter arterial stiffness.Recent studies underlined the role of inflammation in the stiffening of large arteries.The inflammation process, either acute during Salmonella typhi vaccination, 8 or chronic during rheumatoid arthritis 9,10 or systemic lupus erythematosus, 10 has been reported to stiffen the large arteries.This may occur through various mechanisms including endothelial dysfunction, cell release of a number of inducible matrix metalloproteinases (including matrix metalloproteinase [MMP]-9), medial calcifications, changes in proteoglycan composition and state of hydration, and cellular infiltration around the vasa vasorum leading to vessel ischemia. 8 -10 Whether arterial stiffening was associated with inflammation in essential hypertension was only recently demonstrated through the relationships between arterial stiffness and either tumor necrosis factor-alpha (TNF-␣), interleukin-6 (IL-6), or high sensitive C-reactive protein (hs-CRP). 11,12The primary proinflammatory cytokines TNF-␣ and IL-6 are the main inducers for the hepatic synthesis of hs-CRP.Hs-CRP and IL-6 are independent predictors of increased risk of coronary artery disease.IL-6 and TNF-␣ are also independent risk factors for high BP in apparently healthy subjects.In untreated patients with essential hypertension, aortic stiffness, assessed through carotid-femoral pulse wave velocity, was significantly related with hs-CRP and IL-6. 11Baseline hs-CRP was not only an independent predictor of carotidfemoral pulse wave velocity and central augmentation in-