Vascular Calcification

Abstract

M ost individuals aged Ͼ60 years have progressively enlarging deposits of calcium mineral in their major arteries. 1 This vascular calcification reduces aortic and arterial elastance, which impairs cardiovascular hemodynamics, resulting in substantial morbidity and mortality [2][3][4] in the form of hypertension, aortic stenosis, cardiac hypertrophy, myocardial and lower-limb ischemia, congestive heart failure, and compromised structural integrity. [5][6][7] The severity and extent of mineralization reflect atherosclerotic plaque burden 8 and strongly and independently predict cardiovascular morbidity and mortality. 9 Previously considered passive and degenerative, vascular calcification is now recognized as a pathobiological process sharing many features with embryonic bone formation. As evidence of this change in paradigm, research on vascular calcification has accelerated dramatically in the past decade. A search of PubMed (www.ncbi.nlm.nih.gov; US National Library of Medicine) under the key words vascular calcification returned Ϸ16 articles in 1982, 100 in 1994, and 250 in 2004. This year, 400 new publications are expected, for a total Ͼ3500.A breakthrough in this field was the recognition of its similarity to bone development and metabolism, in which endothelial, mesenchymal, and hematopoietic cells interact and respond to mechanical, inflammatory, metabolic, and morphogenetic signals governing skeletal mineralization; their counterparts in the artery wall govern arterial mineralization. With increasing age and dysmetabolic conditions in our population, the clinical burden of vascular calcification will continue to increase. Clinical Impact of Arterial CalcificationAortic calcification promotes congestive heart failure by eroding compliance and elastance. The hemodynamic demands of the cardiovascular system require that the aorta store energy in its elastance during systole and release it during diastole, which minimizes cardiac work and is the basis for balloon counterpulsation. This function, known as Windkessel physiology, is reflected in the high density of elastin in the arch, where mechanical energy is highest. Its loss is detectable as increased arterial pulse wave velocity in calcified arteries, resulting in thoracic summation of reflected and orthograde pressure waves, thereby increasing systolic and pulse pressures. It also increases cardiac work, promoting heart failure, left ventricular hypertrophy, and diastolic dysfunction, independently of atherosclerosis, aging, or diabetes. The link between aortic rigidity and heart failure is most evident in the hypertensive cardiomyopathy observed in patients with idiopathic infantile arterial calcification and in animal models with aortic banding.In the aortic valve, calcification produces life-threatening aortic stenosis. Although previously considered a passive, degenerative, untreatable disorder of "wear and tear" unrelated to atherosclerosis, recent findings now show that valvular calcification is regulated in a manner similar to that of atheroscler...

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

“…Aortic and cardiac valve calcification as well as the abnormal pressure caused by calcification increase cardiac afterload and therefore may promote the development of systolic and diastolic cardiac dysfunction, LV hypertrophy, aortic stenosis, and subsequently congestive heart failure 21. In the present study, these findings were substantiated by demonstrating an aggravation of cardiac dysfunction in VKA patients compared with the reference group without VKA.…”

Ankle Brachial Index and Subsequent Cardiovascular Disease Risk in Patients With Chronic Kidney Disease

“…Vascular calcification is highly prevalent in CKD patients 18, 19. Medial arterial calcification is common in CKD patients and causes arterial stiffness, a decrease in perfusion, and impairment of collateral circulation formation,20, 21, 22, 23 which may contribute to PAD. Our study suggests that ABI ≥1.4 is not significantly associated with MI, HF, composite CVD, and all‐cause mortality in patients with CKD.…”

Atherosclerotic Calcification: Wnt Is the Hint

“…VC is a marker for atherosclerosis and is associated with several cardiovascular pathological features, including hypertension, congestive heart failure, cardiac hypertrophy, and ischemia, and increased risk of MI and stroke 38, 39. VC is a significant risk factor for morbidity and mortality in cardiovascular disease 7, 19, 37, 40, 41, 42, 43, 44.…”

“…Once thought to be a passive degenerative process, it is now evident that biomineralization of the arterial wall is a complex regulated process 5, 45, 46. There are 4 histoanatomic variants of VC, which include medial artery calcification, atherosclerotic intimal calcification, cardiac valve calcification, and soft tissue calciphylaxis or calcific uremic arteriolopathy 38, 47. A major breakthrough in the study of VC was the realization that the ectopic deposition of calcium in vascular structures is similar to intramembranous and endochondral ossification in bone development 48.…”