• Potential 'Biomarker of the 21st Century' for CVD

    Inflammatory cytokine may help identify patients with poor prognosis

    Known to be upregulated in atherosclerotic disease and heart failure, the inflammatory chemokine CCL21 has the potential to be of prognostic value in acute coronary syndrome (ACS), a study suggested.

    Among frozen serum samples of more than 1,100 ACS patients, those in the top quartile by CCL21 level belonged to people who were more likely to experience more major adverse cardiovascular events both in the short- (adjusted HR 1.66, 95% CI 1.09-2.54) and long-term (adjusted HR 1.41, 95% CI 1.07-1.87).

    Patients had been followed for a median of 98 months as part of the PRACSIS study, according to Thor Ueland, PhD, of Oslo University Hospital Rikshospitalet in Norway, and colleagues. Their study was published in the Aug. 13 issue of the Journal of the American College of Cardiology.

    Importantly, the results remained significant after full adjustment for conventional risk factors and other test results often used for risk stratification, such as high-sensitivity C-reactive protein, troponin I, pro–B-type natriuretic peptide, and left ventricular ejection fraction, the authors noted.

    "Our findings suggest that CCL21 level may be clinically useful for risk stratification when determining both the short- and long-term prognosis of ACS patients," the team concluded.

    Ueland had tried the same analyses on another homeostatic chemokine, CCL19, which turned out only to be associated with the development of heart failure in the long run.

    CCL21 itself was associated in particular with short-term cardiovascular mortality and long-term myocardial infarction at the highest serum levels. There were no ties to long-term all-cause mortality, cardiovascular mortality, heart failure, or stroke.

    "Both CCL19 and CCL21 may enhance the matrix degrading and the prothrombotic potential of macrophages by increasing matrix metalloproteinase and tissue factor levels, and could accordingly contribute to plaque destabilization with subsequent thrombus formation and development of acute ischemic events," the authors said. "Thus, CCL19 and CCL21 could be involved in plaque destabilization, and high levels could, therefore, reflect events both preceding and following ACS."

    PRACSIS included patients who were admitted to a Scandinavian teaching hospital for an ACS during 1995-2001. Serum samples were taken the first morning after hospital admission.

    Lab data was not always complete for every patient, Ueland's group acknowledged.

    They cautioned that the correlations they found between CCL21 and poor outcomes do not mean a causal relationship, either, and the study design does not answer the question of whether CCL21 plays a pathophysiological role or is merely a marker of severity of atherosclerosis.

    "Although one can always argue that these findings need to be translated into clinical benefits and integrated into practical and management strategies, [the study authors] have taken up the challenge to develop inflammatory biomarkers in ACS," commented Jean-Sébastien Silvestre, PhD, of the Paris Cardiovascular Research Center, in an accompanying editorial.

    "Intensive experimental and clinical research have shed the light on the instrumental role of innate and adaptive immunity in atherosclerotic plaque development, rupture, and erosion. It was, therefore, not surprising that specific compounds of the inflammatory reaction would enter the race for the quest of inflammatory biomarkers predictive for ACS and its sequelae," Silvestre added.

    Nevertheless, he said, it will take further research to confirm whether CCL21 and other chemokines pan out to be the "biomarker of the 21st century in cardiovascular diseases."

     

    The research was supported by grants from the Swedish Research Council, the Swedish Heart-Lung Foundation, the Västra Götaland Region, the Swedish state, and the ALF agreement (Agreement on Medical Education and Research).

    Ueland and Silvestre disclosed no conflicts of interest.

    Source:

    Journal of the American College of Cardiology

    Source Reference: Caidahl K, et al "Homeostatic chemokines and prognosis in patients with acute coronary syndromes" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2019.06.030.

    Journal of the American College of Cardiology

    Source Reference: Silvestre J "CCL21 in acute coronary syndromes: biomarker of the 21st century?" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2019.06.029.

     

    Read the original article on Medpage Today: Potential 'Biomarker of the 21st Century' for CVD

     

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