CAC Predicts CVD Risk in Chronic Kidney Disease
NEW ORLEANS, LA — New research supports a strong, independent association between coronary artery calcium (CAC) scores and the risk of cardiovascular disease events and all-cause mortality in dialysis-naïve patients with chronic kidney disease (CKD).
Further, it suggests that calcium scoring provides a significant improvement in risk prediction beyond that established by American College of Cardiology/American Heart Association atherosclerotic CVD predictors and novel CVD risk factors.
“These findings have important clinical and public-health implications because cardiovascular disease is the major cause of premature death in patients with CKD,” lead author Dr Jing Chen (Tulane University, New Orleans, LA) and colleagues write in the study, published online March 22, 2017 in JAMA Cardiology.
Dr Michael Blaha (Johns Hopkins School of Medicine, Baltimore, MD) told heartwire from Medscape that while the prognostic value of CAC in the general population has been known for a decade, a key strength of the present study is that it’s the first dedicated study to do so in CKD.
He added, “In this study, where they looked at a whole bunch of risk factors that you might, if you didn’t know the literature well, presuppose would be strong factors, the calcium score really blows them away.”
Chen and colleagues studied CVD risk factors among 1541 dialysis-naïve participants, aged 21 to 74 years and without a history of CVD, recruited between 2003 and 2008 for the prospective Chronic Renal Insufficiency Cohort (CRIC) study. All underwent CAC testing with electron-beam or multidetector computed tomography (CT) and were divided into CAC score categories: 0 (no CAC), >0–100 (moderate CAC), or >100 (severe CAC).
Compared with those without CAC, participants with CAC had higher levels of BMI, systolic blood pressure, hemoglobin A1c, phosphorus, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), fibroblast growth factor 23, and urinary protein, but lower levels of total cholesterol, HDL and LDL cholesterol, and estimated glomerular filtration rate (eGFR).
During an average follow-up of 5.9 years, there were 188 CVD events, including 60 MIs, 120 heart failures, and 27 strokes, and 137 all-cause deaths.
Compared with no CAC, moderate and severe CAC were associated with a higher cumulative incidence of CVD, MI, heart failure, and all-cause mortality.
Within each ACC/AHA atherosclerotic CVD risk score category, CVD risk also significantly increased at higher CAC levels after adjustment for sex, race/ethnicity, and clinical sites.
CVD by ACC/AHA Risk Score and CAC Score
| ACC/AHA risk score category | Hazard ratio (95%CI) |
| <5.0% | |
| CAC score 0 | 1 [reference] |
| CAC score >0-100 | 1.28 (0.36–4.60) |
| CAC score >100 | 3.16 (1.46–6.84) |
| 5.0%–7.5% | |
| CAC score 0 | 2.45 (1.05–5.71) |
| CAC score >0-100 | 2.41 (0.76–7.64) |
| CAC score >100 | 6.70 (3.18–14.10) |
| >7.5% | |
| CAC score 0 | 2.25 (0.64–7.93) |
| CAC score >0-100 | 6.09 (1.94–19.10) |
| CAC score >100 | 10.00 (4.76–21.00) |
After full adjustment, the hazard ratios per one standard deviation log of CAC were 1.40 for cardiovascular disease (95% CI 1.16–1.69; P <0.001), 1.44 for MI (95% CI 1.02–2.02; P=0.04), 1.39 for heart failure (95% CI 1.10–1.76; P=0.006), and 1.19 for all-cause mortality (95% CI 0.94–1.51; P=0.15). The model included multiple established risk factors, including those from the ACC/AHA as well as novel risk factors in patients with CKD such as phosphorus level, NT-proBNP level, and eGFR.
Finally, inclusion of the CAC score in the prediction model led to a small but significant increase in the C statistic of 0.02 (P<0.001) for predicting CVD over use of all the other CVD risk factors.
Blaha said the C statistic is always hard to move but what matters to clinicians is the CVD risk in the individual patient.
“They clearly show that for patients who had a zero score vs those who had a high score, there’s this marked difference in their risk, and that speaks to the individual patient who might have a score as low or as high as that,” he said.
“That might not change the therapy depending on the individual patient, but it might change our aggressiveness with lipid-lowering therapy, maybe antihypertensive therapy, etc. So it is a really important finding, and it extends to the CKD population, which is a little less where we use this test.”
Calcium testing is more commonly used in patients who are asymptomatic without a major comorbidity. The Society of Cardiovascular Computed Tomography recently published an expert consensus document on the clinical indications for CAC testing in the asymptomatic patient, and it concluded quite firmly that CAC testing should be most strongly considered in patients in the intermediate-risk zone with an ASCVD risk score between 5% and 20%.
The guidelines are directed at the general asymptomatic primary-prevention patient, but it’s reasonable to extend that to patients with CKD as well, said Blaha, a coauthor of that document.
“There’s a fair amount of patients I comanage with nephrologists and I’m the cardiologist, and we’ve already decided on treatment patterns and the calcium score probably wouldn’t add that much. But I think this speaks to the patient who came into the system via CKD and has not really been considered for cardiovascular disease yet. I think it would be a great test in that scenario,” he said.
CRIC is funded by the National Institute of Diabetes and Digestive and Kidney Diseases. This study was also supported by awards from the National Institutes of Health and the National Center for Advancing Translational Sciences. Chen reports no relevant financial relationships. Disclosures for the coauthors are listed in the paper.