Association of Extracoronary Calcification and Incident Heart Failure in the Multiethnic Study of Atherosclerosis (MESA)

Background: Extracoronary calcification (ECC) is a prevalent cardiovascular risk factor. Objectives: The aim of this study was to examine the association between ECC and heart failure (HF), including heart failure with preserved ejection fraction (HFpEF). Methods: MESA (Multi-Ethnic Study of Atherosclerosis) participants with computed tomographic imaging at baseline for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta were included. ECC score was calculated by rescaling Agatston scores from 0 to 1 for each ECC site and summing the rescaled scores. Multivariable Cox proportional hazards regression was performed to examine the association between ECC quartiles and incident HF. Results: Of all MESA participants, 3,617 (53.1%) and 3,192 (46.9%) had ECC scores of 0 and >0, respectively. During a mean follow-up period of 12.9 ± 4.2 years, 358 HF events were observed, 179 HF with reduced ejection fraction and 135 HFpEF. After controlling for demographics and risk factors, the highest ECC quartile (compared with the lowest quartile) had 1.7-fold greater hazard of incident HF (adjusted HR: 1.72 [95% CI: 1.16-2.55]; P = 0.007), though this was attenuated to borderline significance after additional adjustment for coronary artery calcification. In contrast for HFpEF, the highest ECC quartile (compared with the lowest quartile) remained independently and statistically significantly associated with 3-fold greater hazard of incident HFpEF (adjusted HR: 3.09 [95% CI: 1.45-6.60]; P = 0.003) after full adjustment, including for coronary artery calcification. Conclusions: ECC is associated with increased risk for HF, in particular HFpEF. If this finding is confirmed in other studies, ECC could help improve traditional risk factor estimation and clinical risk assessments for HF and HFpEF.