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Coronary artery calcium score and cystatin C level combined predict MACCE in chest pain

9th January 2023

Coronary artery calcium scores and cystatin C levels offer prognostic value for risk stratification and adverse cardiac event prediction

Combining a patient’s coronary artery calcium score and their cystatin C level provides an incremental risk assessment of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death, in patients symptomatic with chest pain according to the findings of a study by Chinese researchers.

The World Health Organisation describes how cardiovascular diseases are the leading cause of global deaths, with an estimated 17.9 million lives lost each year. Consequently, risk stratification tools are required to inform on the subsequent management decisions for patients. One such measure to assist in cardiovascular disease risk stratification is the coronary artery calcium (CAC) score, which is a highly specific feature of coronary atherosclerosis. In fact, the extent of CAC has been shown to accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Another potentially useful marker is Cystatin C (Cys-C) which is cysteine protease inhibitor produced at a constant rate by all nucleated cells and used as a sensitive marker of renal function. Moreover, Cys-C has been found to be a strong predictor of the risk of death and cardiovascular events in elderly patients.

Given the potential and independent value of these markers for predicting the risk of a cardiovascular event, the Chinese researchers wondered if there was an association between baseline CAC scores and Cys-C levels and both MACCEs and all-cause death in symptomatic, chest pain patients. They included all individuals presenting with symptomatic chest pain suggestive of CHD and who were referred for cardiac computed tomography (CT) by their cardiologists, which enabled assessment of the coronary artery calcium score. Based on the CT findings, patients were classified into two groups: those with CAC scores < 100 or CAC scores  ≥ 100. Blood samples were taken to measure Cys-C levels and risk stratification of CAC score and Cys-C level were as follows: low risk (CAC score  < 100 or Cys-C < 0.995 mg/L. and high risk (CAC score  ≥ 100 or Cys-C ≥ 0.995 mg/L).

Coronary artery calcium and cysteine C levels and MACCEs

A total of 7140 participants with a median age of 63 years (64.9% male) were included and followed for a median of 1,106 days. During the period of follow-up, 305 MACCEs and 191 all-cause death events were observed.

A higher incidence of MACCEs were independently associated with CAC scores ≥ 100 (hazard ratio, HR = 1.46, 95% CI 1.15 – 1.85, p = 0.002) and where Cys-C levels were ≥ 0.995 mg/L (HR = 1.57, 95% CI 1.24 – 2.00, p < 0.001).

When categorised as high risk (i.e., CAC score  ≥ 100 or Cys-C ≥ 0.995 mg/L), patients also had a significantly increased risk of MACCEs (HR = 2.33, 95% CI 1.64 – 3.29, p < 0.001). In addition, this high risk pattern was also associated with a significantly greater risk of all-cause mortality (HR = 2.85, 95% CI 1.79 – 4.55, p < 0.001). In fact, even in patients with CAC scores of < 100 but a Cys-C ≥ 0.995 mg/L, there was an increased risk of MACCEs (HR = 1.76, p = 0.003) and all-cause mortality (HR = 2.02, p = .007).

The authors concluded that the combined stratification of CAC score and Cys-C showed an incremental risk of MACCEs and all-cause death thus reflecting complementary prognostic value of these measures.

Luo F et al. Coronary artery calcium and cystatin C for risk stratification of MACCEs and all-cause death in symptomatic patients. Clin Cardiol 2022

Adding coronary artery calcium scores to CVD risk assessment provides no clinical benefit

6th May 2022

Addition of coronary artery calcium scores to a patient’s cardiovascular risk assessment does not appear to provide any clinical benefit

Adding coronary artery calcium scores (CACS) to further assess an individual’s cardiovascular risk assessment does not appear to be associated with any clinical benefit. This was the main finding of a systematic review and meta-analysis by a team from the School of Public Health, University of Sydney, Sydney, Australia.

Cardiovascular risk assessment is a critical step in the current approach to primary prevention of heart disease and is calculated using tools such as QRISK. Cardiac computed tomography (CT) imaging is an important tool for cardiovascular risk assessment in observational prospective studies and which provides a measure of subclinical disease such as coronary artery calcium.

Moreover, the use of CACS has been shown to be an independent predictor of incident coronary heart disease among those deemed to be at intermediate-risk based on their Framingham risk score. The use of CACS screening has been found to improve medication adherence and provide superior coronary artery disease risk factor control without increasing downstream medical testing.

By contrast, however, a study in post-menopausal women concluded that there was no independent benefit of coronary CT imaging in a low-to-moderate risk group.

With some uncertainty over whether addition of CACS derived from CT imaging provides an incremental benefit beyond that obtained from traditional risk assessment methods, in the current study, the Australian team undertook a systematic review and meta-analysis of available studies.

They included studies in patients without existing cardiovascular disease, where at least one recognised risk calculator and a CACS had been used. The primary outcome as the change in C statistic for a model which contained the CACS compared to the base model without the CACS.

Coronary artery calcium scores and improvement in CVD risk prediction

A total of 6 studies with 17,961 individuals and 1043 cardiovascular events were included in the analysis. The studies varied in sample size from 470 to 5185 and mean ages ranged from 50 to 75.1 years (38.4 to 59.4% female).

The C statistic for cardiovascular disease (CVD) risk models but without CACS ranged from 0.693 to 0.80. Inclusion of CACS improved the pooled C statistic by 0.036.

When CACS was added, among participants whose risk was reclassified from low to intermediate or high risk, 85.5% to 96.4% did not experience an event during follow-up (ranging from 5.1 to 10 years). Among those who were reclassified from high risk to low risk by CACS, a similarly high proportion, 91.4% to 99.2% did not have a CVD event during follow-up.

The authors suggested that while CACS did appear to provide modest further discriminatory power to traditional risk factor assessments, this additional gain needed to be balanced against the higher costs and radiation risks.

They concluded that while there were gains from inclusion of CACS, which patients might benefit remains to be determined and that there is no evidence to suggest that use of CACS offers a clinical benefit.

Bell KJL et al. Evaluation of the Incremental Value of a Coronary Artery Calcium Score Beyond Traditional Cardiovascular Risk Assessment: A Systematic Review and Meta-analysis JAMA Intern Med 2022