Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study

Abstract

Background

There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS.

Methods and findings

We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin.

Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L ( n = 38,390), 2 to 4.9 mg/L ( n = 27,397), 5 to 9.9 mg/L ( n = 26,957), and 10 to 15 mg/L ( n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.

Conclusions

These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation.

Trial registration

ClinicalTrials.gov - NCT03507309

Abstract

Amit Kaura and colleagues investigate whether mildly elevated high sensitivity C-reactive protein is associated with mortality risk in patients with suspected acute coronary syndromes.

Author summary

Why was this study done?

• C-reactive protein (CRP) is a protein produced by the liver and released into the bloodstream in response to inflammation. A blood test called a high-sensitivity C-reactive protein (hsCRP) accurately measures low levels of CRP.

• In patients presenting with a suspected heart attack, low levels of hsCRP on admission may prove useful in predicting death beyond using troponin, a marker of heart muscle damage.

What did the researchers do and find?

• In this study of 102,337 patients with suspected heart attack, a higher hsCRP level was associated with a higher risk of death.

• This relationship was independent of the troponin level in all patients with suspected heart attack and was further verified in those who were confirmed to have a heart attack.

What do these findings mean?

• These findings suggest that hsCRP is a clinically meaningful marker of risk of death in addition to troponin in patients with suspected heart attack.

• hsCRP has potential utility in selecting patients with heart attack for new treatments that target reducing inflammation.