The association between peripheral medial and intimal arterial calcification patterns with central arterial stiffness in individuals with type 2 diabetes mellitus: The cross-sectional Early-HFpEF study

Background: Animal studies suggest that medial arterial calcification (MAC) increases arterial stiffness, which in turn could lead to cardiovascular disease (CVD), but human studies are lacking. We evaluated the associations of peripheral arterial calcification pattern and quantity with arterial stiffness in individuals with type 2 diabetes mellitus (T2DM). Methods: Cross-sectional data was used of 774 individuals (64 ​% men, 67 [63–71] years) with T2DM who underwent carotid-femoral pulse wave velocity measurements (cfPWV) and CT-scans of the lower-extremities. Femoral and crural dominant arterial calcification patterns (MAC, intimal (IAC), absent/indistinguishable) were determined via a histologically-validated scoring algorithm. Calcification Agatston scores were categorized into zero (reference category) and tertiles>0. Multivariable-adjusted linear regression was used. Results: MAC and IAC were dominant in 38% and 24% of femoral arteries versus 29% and 15% of crural arteries, respectively. Femoral and crural MAC were associated with higher cfPWV (0.64 ​m/s [0.26–1.03]; 0.76 [0.37–1.14], respectively). Crural but not femoral IAC was associated with higher cfPWV (0.58 [0.10–1.06]; 0.25 [-0.20–0.69], respectively). Adjusted for calcification quantity, only crural MAC remained significantly associated with higher cfPWV. cfPWV was higher in individuals with MAC versus IAC, but not statistically significant (femoral p ​= ​0.066; crural p ​= ​0.490). Femoral and crural calcification scores in the highest tertile were associated with higher cfPWV (0.86 [0.34–1.39]; 0.78 [0.29–1.27], respectively). Conclusion: Crural MAC was independently associated with increased arterial stiffness. Arterial stiffness was higher in MAC versus IAC. Crural and femoral arterial calcification quantity were associated with increased arterial stiffness. Peripheral arterial calcification, specifically MAC, may lead to CVD via increased arterial stiffness in T2DM.