Abstract-Arterial stiffness is a growing epidemic associated with increased risk of cardiovascular events, dementia, and death. Decreased compliance of the central vasculature alters arterial pressure and flow dynamics and impacts cardiac performance and coronary perfusion. This article reviews the structural, cellular, and genetic contributors to arterial stiffness, including the roles of the scaffolding proteins, extracellular matrix, inflammatory molecules, endothelial cell function, and reactive oxidant species. Additional influences of atherosclerosis, glucose regulation, chronic renal disease, salt, and changes in neurohormonal regulation are discussed. A review of the hemodynamic impact of arterial stiffness follows. A number of lifestyle changes and therapies that reduce arterial stiffness are presented, including weight loss, exercise, salt reduction, alcohol consumption, and neuroendocrine-directed therapies, such as those targeting the renin-angiotensin aldosterone system, natriuretic peptides, insulin modulators, as well as novel therapies that target advanced glycation end products. Key Words: arterial stiffness Ⅲ isolated systolic hypertension Ⅲ mechanisms Ⅲ therapeutics Ⅲ pathophysiology I ncreased central arterial stiffening is a hallmark of the aging process and the consequence of many disease states such as diabetes, atherosclerosis, and chronic renal compromise. Accordingly, there is a marked increase in the incidence and prevalence of clinical surrogate markers of vascular stiffness, such as pulse pressure and isolated systolic hypertension, with age and these associated conditions. [1][2][3][4][5][6] Arterial stiffening is also a marker for increased cardiovascular disease risk, including myocardial infarction, heart failure, and total mortality, as well as stroke, dementia, and renal disease. [7][8][9][10][11][12][13][14] This has been recently reviewed by Safar et al. 15 By altering the resting and stress-induced hemodynamics and energy expenditure, vascular stiffness not only contributes to these clinical repercussions and lowers the threshold for their symptoms but also likely contributes to more dyspnea with exertion and orthostatic hypotension in older adults. Although the structural and cellular changes that underlie arterial stiffness may predispose the vasculature to further insult by atherosclerotic disease, the mechanisms explaining this link are still undergoing investigation. Wang and Fitch provide a recent summary of the putative relationship between arterial stiffness and atherosclerosis. 16 Earlier work on arterial properties focused on fluid mechanics and the impact of hemodynamic and reflective wave properties on the development of arterial stiffness and the arterial waveforms. 17,18 The development of methods to measure and assess specific aspects of arterial stiffness, as recently reviewed by Oliver and Webb,19 greatly facilitated understanding of its role in cardiovascular disease. Here, we build on this earlier review to discuss more recent theories on the mechanisms co...

No abstract

No abstract

No abstract

Multimorbidity occurs in adults of all ages, but the number and complexity of comorbid conditions commonly increase with advancing age such that cardiovascular disease (CVD) in older adults typically occurs in a context of multimorbidity. Current clinical practice and research mainly target single disease-specific care that does not embrace the complexities imposed by concurrent conditions. In this paper, emerging concepts regarding CVD in combination with multimorbidity are reviewed, including recommendations for incorporating multimorbidity into clinical decision making, critical knowledge gaps, and research priorities to optimize care of complex older patients.