Vascular calcification: a left-handed compliment for aging

Editorial FocusVascular calcification: a left-handed compliment for agingLuke P. BrewsterLuke P. BrewsterDepartment of Surgery, Emory University, Atlanta, GeorgiaDepartment of Biomedical Engineering, Emory University, Atlanta, GeorgiaAtlanta Veterans Affairs Medical Center, Surgery and Research Service Lines, Decatur, GeorgiaDepartment of Bioengineering, Georgia Institute of Technology, Atlanta, GeorgiaDepartment of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GeorgiaPublished Online:05 Aug 2021https://doi.org/10.1152/ajpheart.00300.2021This is the final version - click for previous versionMoreSectionsPDF (189 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat “You look good for your age,” “bless your heart,” and other left-handed compliments become more noticeable as we age. But is aging destiny or can something different occur over time? Certainly, it is true that arteries are designed for compliance. The Windkessel effect enables energy-efficient pulsation of blood from the left ventricle to provide perfusion for the end users of arterial flow (the tissues and organs of the entire body). The less energy expended with each heartbeat, the better the left ventricle ages and the better perfused these tissues and organs are. Aging stiffens arteries, but exercise can make our arteries relatively younger (than they are) (1), supporting modifiable pathways in aging. However, calcification is an endgame, and calcification of these energy-efficient machines (arteries) abrogates the Windkessel effect and changes everything (2, 3). In fact, arterial calcification is likely a major driver of mortality in aged persons and those with cardiovascular comorbidities (4).Thus, arterial calcification is a very important topic, and this editorial is written to acknowledge an exciting addition to the literature by the exceptionally productive MacTaggart-Kamenskiy laboratory (5), published in a recent issue of the American Journal of Physiology-Heart and Circulatory Physiology. Using a large clinical imaging database, the authors describe changes in arterial walls and calcification of these walls as they relate to age in patients from the general area around Omaha, Nebraska. This is an important addition to the literature and a building block to our understanding of one of the most puzzling of all arterial pathologies, arterial calcification (6).Major findings include the outward remodeling of the aorta, iliac, and femoral arteries over certain decades of life. Most interesting as it relates to the increased longevity of patients with cardiovascular disease facing high-income and middle-income countries (7), aortic tortuosity doubled by the age of 80 yr and the iliofemoral segment increased sixfold, suggesting that gains in cardiovascular survival have other arterial complications.Calcification of the entire aorta increased with age and ∼80% of this population had calcification by 40 yr of age. Since calcification is a consequence of aging and aging has no evolutionary stress, this is a clinically relevant example of how aging impacts vascular health. The authors also found the already established link between renal disease and calcification, although here the authors found that clinically mild/moderate renal insufficiency had three times more calcification.Finally, by using machine learning, the authors found that age, creatinine, body mass index, coronary arterial disease, and hypertension were the strongest predictors of calcification. Together, these predictors are biologically impactful determinants of aging. Interestingly, the authors found that both diabetes and gender did not have a correlation to these findings. Although our understanding of what role gender has on calcification will continue to develop as we better use clinical imaging with artificial intelligence approaches, the lack of effect of diabetes may be explained by patients with diabetes preferentially calcifying infrapopliteal arteries (8), which is a different part of the arterial tree than the one studied here.Together, the data from this important paper teaches us that calcification is a part of aging, that multiple medical conditions that spur premature aging are associated with aorto-ilio-femoral calcification, and that calcification of the left (but not right) femoral artery was most predictive of total calcification of these arteries.I will close with words that form a blessing from an older to a younger generation organized by a famous left-handed Nobel Laureate, the voice of a generation (that sadly has gotten old), and a man who just celebrated his 80th birthday, Bob Dylan.May your heart always be joyfulMay your song always be sungAnd may you stayForever young. (9)May the hard work of this readership yield novel and translatable solutions to provide more gentle and youthful aging (of your arteries, body, and soul) to all humanity.GRANTSThis work was supported by National Heart, Lung, and Blood Institute Grant R01HL143348 and Veterans Affairs Grants I21RX003188 and I01BX004707.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author.AUTHOR CONTRIBUTIONSL.P.B. drafted manuscript, edited and revised manuscript, and approved final version of manuscript.REFERENCES1. Sangha GS, Goergen CJ, Prior SJ, Ranadive SM, Clyne AM. Preclinical techniques to investigate exercise training in vascular pathophysiology. Am J Physiol Heart Circ Physiol 320: H1566–H1600, 2021. doi:10.1152/ajpheart.00719.2020. Link | ISI | Google Scholar2. Zettervall SL, Marshall AP, Fleser P, Guzman RJ. Association of arterial calcification with chronic limb ischemia in patients with peripheral artery disease. J Vasc Surg 67: 507–513, 2018. doi:10.1016/j.jvs.2017.06.086. Crossref | PubMed | ISI | Google Scholar3. Ho CY, Shanahan CM. Medial arterial calcification: an overlooked player in peripheral arterial disease. Arterioscler Thromb Vasc Biol 36: 1475–1482, 2016. doi:10.1161/ATVBAHA.116.306717. Crossref | PubMed | ISI | Google Scholar4. Leow K, Szulc P, Schousboe JT, Kiel DP, Teixeira-Pinto A, Shaikh H, Sawang M, Sim M, Bondonno N, Hodgson JM, Sharma A, Thompson PL, Prince RL, Craig JC, Lim WH, Wong G, Lewis JR. Prognostic value of abdominal aortic calcification: a systematic review and meta-analysis of observational studies. J Am Heart Assoc 10: e017205, 2021. doi:10.1161/JAHA.120.017205. Crossref | PubMed | ISI | Google Scholar5. Jadidi MP, Poulson W, Aylward P, MacTaggart J, Sanderfer C, Marmie B, Pipinos M, Kamensky A. Calcification prevalence in different vascular zones and its association with demographics, risk factors, and morphometry. Am J Physiol Heart Circ Physiol 320: H2313–H2323, 2021. doi:10.1152/ajpheart.00040.2021. Link | ISI | Google Scholar6. O'Neill WC, Han KH, Schneider TM, Hennigar RA. Prevalence of nonatheromatous lesions in peripheral arterial disease. Arterioscler Thromb Vasc Biol 35: 439–447, 2015. doi:10.1161/ATVBAHA.114.304764. Crossref | PubMed | ISI | Google Scholar7. Song P, Rudan D, Zhu Y, Fowkes FJI, Rahimi K, Fowkes FGR, Rudan I. Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis. Lancet Glob Health 7: e1020–e1030, 2019. doi:10.1016/S2214-109X(19)30255-4. Crossref | PubMed | ISI | Google Scholar8. Bourron O, Aubert CE, Liabeuf S, Cluzel P, Lajat-Kiss F, Dadon M, Komajda M, Mentaverri R, Brazier M, Pierucci A, Morel F, Jacqueminet S, Massy ZA, Hartemann A. Below-knee arterial calcification in type 2 diabetes: association with receptor activator of nuclear factor kappaB ligand, osteoprotegerin, and neuropathy. J Clin Endocrinol Metab 99: 4250–4258, 2014. doi:10.1210/jc.2014-1047. Crossref | PubMed | ISI | Google Scholar9. Dylan B. Forever Young. Planet Waves. 1974.Google ScholarAUTHOR NOTESCorrespondence: L. P. Brewster ([email protected]edu). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Related ArticlesCalcification prevalence in different vascular zones and its association with demographics, risk factors, and morphometry 26 May 2021American Journal of Physiology-Heart and Circulatory Physiology More from this issue > Volume 321Issue 2August 2021Pages H422-H423 Crossmark Copyright & PermissionsPublished by the American Physiological Society.https://doi.org/10.1152/ajpheart.00300.2021PubMed34296967History Received 1 June 2021 Accepted 19 July 2021 Published online 5 August 2021 Published in print 1 August 2021 Keywordsagingarterial calcification Metrics