Progression of Coronary Artery Calcification and Risk of Clinical Events in CKD: The Chronic Renal Insufficiency Cohort Study.

Rationale & objective: Coronary artery calcification (CAC) progresses rapidly in people with chronic kidney disease (CKD) compared with the general population. We studied the association between CAC progression and higher risks of atherosclerotic cardiovascular disease (CVD), congestive heart failure, and all-cause mortality among adults with CKD.

Study design: Prospective cohort study.

Setting & participants: 1,310 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had at least 1 CAC scan with no prior history of CVD and with observed or imputed data on changes in CAC over time.

Exposure: Observed or imputed CAC progression, categorized as incident CAC among participants with 0 CAC on the baseline scan or progressive CAC when the baseline scan demonstrated CAC and there was an increase in CAC≥50 Agatston units per year.

Outcome: Atherosclerotic CVD (myocardial infarction or stroke), congestive heart failure, and all-cause mortality.

Analytical approach: Cause-specific Cox proportional hazards regression, stratified by presence of CAC at baseline.

Results: A total of 545 participants without and 765 with prevalent CAC at baseline were included. During a mean 3.3 years between CAC assessments, 177 participants (32.5%) without baseline CAC developed incident CAC while 270 participants (35.3%) with baseline CAC developed a≥50 Agatston units per year increase in CAC. After multivariable adjustment, incident CAC was associated with 2.42-fold higher rate of atherosclerotic CVD (95% CI, 1.23-4.79) and 1.82-fold higher rate of all-cause mortality (95% CI, 1.03-3.22). Progressive CAC (≥50 units per year) was not associated with atherosclerotic CVD (HR, 1.42 [95% CI, 0.85-2.35]) but was associated with a 1.73-fold higher rate of all-cause mortality (95% CI, 1.31-2.28). Progressive CAC was not associated with incident heart failure.

Limitations: Residual confounding and limited statistical power for some outcomes.

Conclusions: Among adults with CKD stages 2-4, CAC progression over a mean 3.3 years was associated with higher risk of atherosclerotic CVD and all-cause mortality. The associations were strongest among participants without CAC at baseline.

Plain-language summary: Prior research has shown that coronary artery calcification (CAC) is a marker of higher risk of heart disease and death. Less is known about how changes in CAC over time might affect risk, particularly among patients with kidney disease. In this study, participants with chronic kidney disease who developed CAC or had worsening CAC over time showed higher rates of heart attack, stroke, and death than those who did not develop CAC. These findings support the need for further research on longitudinal changes in CAC as a possible aid to establishing prognosis among patients with kidney disease and to inform treatment.