Calcific aortic stenosis: another face of atherosclerosis? (original) (raw)
Progression of aortic valve sclerosis to aortic stenosis
The American Journal of Cardiology, 2003
level or low-density lipoprotein cholesterol and highdensity lipoprotein cholesterol concentrations. It would be interesting to know the effects of these factors on severe calcific AS.
New England Journal of Medicine, 2009
Calcific aortic valve disease is, by far, the most prevalent form of aortic stenosis (AS) worldwide. In the developing world, AS may also be caused by rheumatic heart disease. Calcific aortic valve disease is characterized by fibro-calcific remodelling of the valve leaflets. In the first phase of the disease, termed aortic sclerosis, the valve becomes thickened and mildly calcified but these changes do not cause any obstruction to blood flow. Over the years, the disease evolves to severe valve calcification with impaired leaflet motion and vast blood flow obstruction, which are hallmarks of calcific AS 1 (TABLE 1). In developed countries, AS is the third-most common cardiovascular disease after coronary artery disease and systemic arterial hypertension 2. Over the past five decades, the management of calcific AS has changed dramatically. Doppler echocardiography has replaced cardiac catheterization as the method of choice for the diagnosis and follow-up of AS, and transcatheter valve therapy has emerged as an alternative to surgery for aortic valve replacement (AVR). However, no pharmacotherapy has proved to reduce either the progression of valve stenosis or the resulting adverse effects on left ventricular function and patient outcomes. Hence, surgical or transcatheter AVR are the only effective treatment options for severe AS 3,4. Overall, this disease is directly responsible for approximately 85,000 AVRs and 15,000 deaths per year in North America 2. In this Primer, we discuss the epidemiology, mechanisms, diagnosis and management of calcific AS, and highlight how the introduction of transcatheter-based valve replacement has transformed patient outcomes. Epidemiology Calcific AS is the consequence of progressive fibrocalcific remodelling occurring on an initially normal (tricuspid) aortic valve or a congenitally abnormal (bicuspid) aortic valve. Although the prevalence of bicuspid aortic valve is only 0.5-1.0% in children, it accounts for nearly half of aortic valves that are surgically removed because of calcific AS 5. During their lifetime, most individuals with a bicuspid aortic valve develop some kind of aortic valve pathology, the most common being AS 5-8. Furthermore, patients with bicuspid valve develop calcific AS one or two decades earlier than those with a tricuspid valve. Aortic sclerosis, which is the preclinical phase of calcific aortic valve disease, is defined as focal areas of valve calcification and leaflet thickening without
Epidemiology and cardiovascular risk factors of aortic stenosis
Cardiovascular ultrasound, 2006
The abnormalities of aortic valve morphology and function represent the most common cardiac-valve lesion particularly in elderly. The etiology of aortic stenosis is degenerative-calcific in the majority of patients. Many risk factors seems to be linked to the calcification and the stenosis of the aortic valve but they must be confirmed. In this review the etiology and the possible physiopathology of the aortic valve stenosis is discussed.
2013
Aortic stenosis due to calcific aortic valve disease (CAVD) is currently the main indication for aortic valve replacement in developed countries (Iung et al, 2003). Due to an aging population and a decline in rheumatic heart disease, CAVD has become the most common heart valve disease in the Western countries, affecting approximately 25% of adults over 65 years, of which 2-3% has clinically significant aortic stenosis (Stewart et al, 1997). Even mild CAVD is associated with adverse outcomes, with a 50% increased risk of cardiovascular death (Lloyd-Jones et al, 2009). There are no known therapies that slow disease progression, and surgical valve replacement is the only effective treatment for aortic stenosis. More than 85,000 aortic valve replacement surgeries are done in the United States, and over 275,000 are performed worldwide. This numbers are expected to triple by 2050 (Takkenberg et al, 2008). These statistics emphasize the burden of aortic valve disease and the necessity of understanding its mechanisms, underscored recently by recommendations set out by The National Heart, Lung and Blood Institute Aortic Stenosis Working Group (http://www.nhlbi.nih.gov/meetings/workshops/cas.htm). CAVD is a progressive disease that starts with initial changes in the cell biology of the valve leaflets, which develop into atherosclerotic-like lesions and aortic sclerosis, and eventually lead to calcification of the valve, causing left ventricular outflow tract obstruction (Rajamannan et al, 2007, Otto, 2008). Although CAVD progresses with age, it is not an inevitable consequence of aging. CAVD traditionally has been considered a degenerative phenomenon, in which years of mechanical stress on an otherwise normal valve, cause calcium to deposit on the surface of the aortic valve leaflets. The evolving concept, however, is that CAVD is an actively regulated process that cannot be characterized simply as "senile" or "degenerative". The progressive calcification process involves lipid accumulation, increasing angiotensin-converting enzyme activity, inflammation, neovascularization, and extracellular matrix degradation. Furthermore, the risk factors for CAVD are similar to those for atherosclerosis: age, gender, hypercholesterolemia, diabetes, smoking, renal failure, and hypertension (Stewart et al, 1997). In addition, pathological studies of explanted human stenotic aortic valves have identified lesions similar to those in atherosclerotic plaques, which contain inflammatory cells and calcific deposits (Otto et al, 1994). The involvement of high cholesterol levels is corroborated by studies demonstrating that patients with familial hypercholesterolemia develop aortic valve lesions that calcify with age (Rajamannan et al, 2001). Furthermore, preclinical studies have demonstrated atherosclerotic-like lesions in aortic valve leaflets in www.intechopen.com Aortic Valve 134 atherosclerosis in rabbits and mice. From the notion that CAVD and atherosclerosis might share a similar mechanism, statins (3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors) emerged as a potential therapy for treating CAVD. Indeed, retrospective studies have demonstrated a reduction in disease progression when patients were treated with statins (Aronow et al, 2001, Novaro et al, 2001, Bellamy et al, 2002). In addition, animal studies confirmed that statin treatment inhibits calcificication (Rajamannan et al, 2005, Aikawa et al, 2007). Large prospective clinical trials, however have not shown slowed CAVD progression in patients treated with high doses of statins (Cowell et al, 2005, Rossebo et al, 2008). This may be due to the late implementation of the statins, after aortic valve calcification has progressed to the irreversible stage. The aortic valve consists of endothelial cells and valvular interstitial cells that maintain the health of the valve and are important in valvular disease. Valvular interstitial cells likely mediate the progression of CAVD (Mohler et al, 1999). Signals in aortic valve biology that trigger activation, differentiation, or pathological change are unclear. However, we know that in CAVD, valvular interstitial cells differentiate to myofibroblasts and osteoblast-like cells, which are eventually responsible for calcium deposition (Mohler et al, 2001). Possible pathological triggers include hemodynamic shear stress, solid tissue stresses, reactive oxygen species (ROS), inflammatory cytokines and growth factors, and physiological imbalances such as the metabolic syndrome, diabetes mellitus, end-stage renal disease, and calcium or phosphate imbalance (Schoen, 2008, New & Aikawa, 2011, Miller et al, 2010). The cellular and molecular factors involved in the development of aortic valve stenosis, however, remain largely obscure. The poor prognosis and increased mortality after the onset of symptoms provide a rationale for the pursuit of a better understanding of the disease process, which can lead to effective therapeutic strategies to prevent CAVD. This chapter discusses our current understanding of the pathophysiology, risk factors, cellular mechanisms, diagnosis, and clinical management of CAVD, and describes areas of future research vital for diagnosing, treating, and potentially preventing this disease.
World Journal of Cardiology, 2010
Aortic stenosis (AS) is the most common valvular heart disease in the world. It is a disease of the elderly and as our population is getting older in both the developed and the developing world, there has been an increase in the prevalence of AS. It is impacting the mortality and morbidity of our elderly population. It is also causing a huge burden on the healthcare system. There has been tremendous progress in our understanding of AS in recent years. Lately, studies have shown that AS is not just a disease of the aortic valve but it affects the entire systemic vasculature. There are studies looking at more sophisticated measures of disease severity that might better predict the optimal timing of valve replacement. The improvement in our understanding in etiology and pathophysiology of the disease process has led to a number of trials with possible treatment options for AS. In this review, we talk about our understanding of the disease and latest developments in disease assessment and management. We look forward to a time when there will be medical treatment for AS.
Calcific aortic valve disease and aortic atherosclerosis--two faces of the same disease?
Romanian journal of internal medicine = Revue roumaine de médecine interne
Calcific (degenerative) aortic valve disease is the most common etiology of acquired aortic valve stenosis. Historically, it was seen as a degenerative, "senile-like" process, resulting from aging--"wearing and tearing"--of the aortic valve. However, several lines of evidence suggest that calcific valve disease is not simply due to age-related degeneration but, rather, it is an active disease process with identifiable initiating factors, clinical and genetic risk factors, and cellular and molecular pathways that mediate disease progression. Histopathologically, the early lesions of aortic valve sclerosis resemble arterial atherosclerotic plaques. Furthermore, atherosclerotic risk factors and clinical atherosclerotic cardiovascular disease are independently associated with aortic sclerosis suggesting that it represents an atherosclerosis-like process involving the aortic valve. Until now, the only established treatment for symptomatic aortic valve stenosis has bee...