Calciprotein crystallization time (T50) and its association with surrogate cardiovascular disease risk markers in individuals with type 2 diabetes mellitus: the cross-sectional EARLY-HFpEF study

BACKGROUND: Heart failure and peripheral artery disease (PAD) are the two most common cardiovascular diseases (CVD) in individuals with type 2 diabetes mellitus (T2DM). The T50 calciprotein crystallization test measures the transformation of calciprotein particles type 1 (CPP1) into CPP2 in vitro and has been introduced as a low-cost biomarker for arterial calcification and CVD risk. We aimed to investigate the association between T50 and (1) heart failure with preserved ejection fraction (HFpEF), (2) ankle-brachial index (ABI) as measure of PAD, (3) pulse wave velocity (PWV) as measure of central arterial stiffness and (4) arterial calcification in individuals with T2DM.

METHODS: Cross-sectional data was used of 771 individuals with T2DM (64% men, 67 [63-71] years). T50 was measured using nephelometry on non-fasting serum samples. Presence of HFpEF was assessed with echocardiography based on current guidelines. ABI was categorized as ≤ 0.9 (PAD), 0.9-1.4 (normal) and ≥ 1.4 (high). Central arterial stiffness was measured using carotid-femoral PWV. Lower-extremity and coronary calcification were measured using computed tomography and quantified using Agatston scores categorized into zero (reference category) and tertiles > 0. Multivariable-adjusted Poisson, multinomial and linear regression analyses were used to study the associations with aforementioned surrogate CVD risk markers.

RESULTS: Mean T50 was 355 ± 55 min. HFpEF and PAD were present in 36.6% and 5.8% of the cohort, respectively. Mean cfPWV was 12.9 ± 2.5 m/s. Median calcification scores in the coronary arteries and lower-extremities were 315 [40-1246] and 791 [64-3820] Agatston units, respectively. Every 60-min decrease in T50, indicating higher calcification risk, was associated with increased coronary arterial calcification (e.g. highest tertile OR = 1.63 [1.15-2.30], p = 0.006), but not with lower-extremity arterial calcification (e.g. highest tertile OR = 1.28 [0.96-1.69], p = 0.088). Moreover, T50 ≤ 330 min versus T50 ≥ 390 min was associated with PAD (OR = 3.04 [1.03-8.94], p = 0.044). Finally, every 60-min decrease in T50 was not associated with neither HFpEF (RR = 1.02 [0.90-1.17], p = 0.736) nor cfPWV (β =  - 0.08 [ - 0.26-0.10], p = 0.398).

CONCLUSION: Low T50 was associated with increased risks of coronary arterial calcification and PAD (measured by ABI ≤ 0.9) in individuals with T2DM, but not with HFpEF, central arterial stiffness and lower-extremity arterial calcification. Further research is warranted to evaluate the additive value of T50 in CVD risk stratification in clinical care.