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.

Citation
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

Colchicine use significantly reduces MACE in patients undergoing percutaneous coronary interventions

25th January 2022

Colchicine use in patients undergoing a percutaneous coronary intervention significantly reduces major adverse cardiovascular events (MACE)

Colchicine use in patients with coronary artery disease undergoing a percutaneous intervention, significantly reduced the incidence of major adverse cardiovascular events (MACE) according to a meta-analysis by a team from the University of Oxford, UK.

Coronary artery disease is characterised by atherosclerotic plaque accumulation in the epicardial arteries and can be managed with various interventions including lifestyle modification, pharmacological therapies and invasive interventions, all of which are designed to achieve disease stabilisation or regression. One particular intervention is percutaneous coronary intervention (PCI) and defined as a non-surgical, invasive procedure which seeks to relieve the narrowing or occlusion of the coronary artery and improve blood supply to the ischaemic tissue.

The importance of inflammation in the pathogenesis of coronary artery disease was established many years ago and during PCI, damage to the endothelial layer after stent implantation can also lead to a further inflammatory response. Moreover, the presence of residual inflammation can increase the risk of subsequent complications such as a myocardial infarction therefore highlighting the importance of minimising inflammation to improve patient outcomes.

Colchicine use represents a low cost anti-inflammatory agent and there is evidence that they drug has beneficial effects as a secondary preventative measure, especially after a myocardial infarction. Nevertheless, the value of colchicine use as an adjunctive intervention to PCI to prevent cardiovascular events remains unclear and was the objective of the current analysis.

The team undertook a systematic review and meta-analysis for studies that compared the efficacy of colchicine use to either no use or placebo in patients undergoing PCI and which reported on MACE. The primary outcome measures were the MACE and which included outcomes including in-stent restenosis (ISR), repeat vessel revascularisation, stent thrombosis, stroke and all cause mortality.

Findings

A total of 7 trials including 6660 participants with a mean age of 60.9 years (3347 assigned to colchicine use) and a follow-up time ranging from 3 days to 22.6 months were analysed.

The incidence of MACE was 7.08% in those assigned to colchicine use and 9.15% in the control arm, leading to a significant reduction in MACE (risk ratio, RR = 0.73, 95% CI 0.61 – 0.87, p = 0.0003) and with little evidence of heterogeneity across the analysis.

Use of colchicine was associated with a significant reduction in stent thrombosis (RR = 0.50), repeat vessel revascularisation (RR = 0.47) and stroke (RR = 0.50). However, there was no significant difference in all-cause mortality (RR = 1.12, 95% CI 0.49 – 2.58, p = 0.79).

The authors calculated the number needed to treat with colchicine to prevent one episode of MACE to be 41. They concluded that colchicine use significantly reduced the risk of MACE in patients with coronary artery disease undergoing PCI and called for future trials to further evaluate the value of colchicine with different types of stents and alternative dosing regimes.

Citation

Aw KL et al. Colchicine for symptomatic coronary artery disease after percutaneous coronary intervention Open Heart 2022