Vascular calcification: a left-handed compliment for aging

“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 joyful

May your song always be sung

And may you stay

Forever 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.

GRANTS

This work was supported by National Heart, Lung, and Blood Institute Grant R01HL143348 and Veterans Affairs Grants I21RX003188 and I01BX004707.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the author.

AUTHOR CONTRIBUTIONS

L.P.B. drafted manuscript, edited and revised manuscript, and approved final version of manuscript.