The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death

The Multi-Ethnic Study of Atherosclerosis (MESA)

Miguel Cainzos-Achirica, Cristina Enjuanes, Philip Greenland, John W. McEvoy, Mary Cushman, Zeina Dardari, Khurram Nasir, Matthew J. Budoff, Mouaz H. Al-Mallah, Joseph Yeboah, Michael D. Miedema, Roger S Blumenthal, Josep Comin-Colet, Michael Blaha

Research output: Contribution to journalArticle

Abstract

Background and aims: We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population. Methods: We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer. Results: Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23–10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017). Conclusions: IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.

Original languageEnglish (US)
Pages (from-to)217-225
Number of pages9
JournalAtherosclerosis
Volume278
DOIs
StatePublished - Nov 1 2018

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Cause of Death
Interleukin-6
Atherosclerosis
Heart Failure
Cardiovascular Diseases
Stroke
Mortality
Venous Thromboembolism
Multiple Chronic Conditions
Atrial Fibrillation
Chronic Disease
Biomarkers
Regression Analysis
Outcome Assessment (Health Care)
Inflammation
Population
Neoplasms

Keywords

  • Cardiovascular disease
  • Heart failure
  • Inflammation
  • Interleukin 6
  • Prediction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death : The Multi-Ethnic Study of Atherosclerosis (MESA). / Cainzos-Achirica, Miguel; Enjuanes, Cristina; Greenland, Philip; McEvoy, John W.; Cushman, Mary; Dardari, Zeina; Nasir, Khurram; Budoff, Matthew J.; Al-Mallah, Mouaz H.; Yeboah, Joseph; Miedema, Michael D.; Blumenthal, Roger S; Comin-Colet, Josep; Blaha, Michael.

In: Atherosclerosis, Vol. 278, 01.11.2018, p. 217-225.

Research output: Contribution to journalArticle

Cainzos-Achirica, M, Enjuanes, C, Greenland, P, McEvoy, JW, Cushman, M, Dardari, Z, Nasir, K, Budoff, MJ, Al-Mallah, MH, Yeboah, J, Miedema, MD, Blumenthal, RS, Comin-Colet, J & Blaha, M 2018, 'The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death: The Multi-Ethnic Study of Atherosclerosis (MESA)', Atherosclerosis, vol. 278, pp. 217-225. https://doi.org/10.1016/j.atherosclerosis.2018.09.034
Cainzos-Achirica, Miguel ; Enjuanes, Cristina ; Greenland, Philip ; McEvoy, John W. ; Cushman, Mary ; Dardari, Zeina ; Nasir, Khurram ; Budoff, Matthew J. ; Al-Mallah, Mouaz H. ; Yeboah, Joseph ; Miedema, Michael D. ; Blumenthal, Roger S ; Comin-Colet, Josep ; Blaha, Michael. / The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death : The Multi-Ethnic Study of Atherosclerosis (MESA). In: Atherosclerosis. 2018 ; Vol. 278. pp. 217-225.
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abstract = "Background and aims: We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population. Methods: We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer. Results: Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95{\%} CI 1.23–10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017). Conclusions: IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.",
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T1 - The prognostic value of interleukin 6 in multiple chronic diseases and all-cause death

T2 - The Multi-Ethnic Study of Atherosclerosis (MESA)

AU - Cainzos-Achirica, Miguel

AU - Enjuanes, Cristina

AU - Greenland, Philip

AU - McEvoy, John W.

AU - Cushman, Mary

AU - Dardari, Zeina

AU - Nasir, Khurram

AU - Budoff, Matthew J.

AU - Al-Mallah, Mouaz H.

AU - Yeboah, Joseph

AU - Miedema, Michael D.

AU - Blumenthal, Roger S

AU - Comin-Colet, Josep

AU - Blaha, Michael

PY - 2018/11/1

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N2 - Background and aims: We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population. Methods: We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer. Results: Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23–10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017). Conclusions: IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.

AB - Background and aims: We aimed to evaluate the associations and prognostic value of interleukin-6 (IL6) for the prediction of atherosclerotic cardiovascular disease (ASCVD) events, heart failure (HF), and other chronic diseases in a large, multi-ethnic, contemporary population. Methods: We included 6617 participants from the Multi-Ethnic Study of Atherosclerosis (5640 non-users, 977 users of statins at baseline). Main outcomes were hard ASCVD events and HF; secondary outcomes included all-cause death, atrial fibrillation, venous thromboembolism and cancer. Results: Median follow-up was 13.2 years. Strong associations were observed in Cox regression analyses between higher IL6 levels and ASCVD events, HF, and mortality, particularly among statins users. In the latter, associations remained strong after adjusting for traditional risk factors and other inflammation biomarkers (e.g., risk factor, hsCRP-adjusted hazard ratio for incident HF comparing 3rd vs. 1st IL6 tertiles: 3.55, 95% CI 1.23–10.27). Although IL6 did not improve CHD prediction beyond traditional risk factors, among statin users it improved the prediction of stroke (improvement in the C statistic +0.018), incident HF (+0.028, the largest C statistic increase across all study outcomes), and all-cause death (+0.017). Conclusions: IL6 is strongly and independently associated with ASCVD events, HF, and all-cause mortality, particularly among statin users. Although the prognostic value of IL6 is limited for the prediction of CHD events, it may have a role for the prediction of stroke, HF and all-cause death in asymptomatic statin users. Larger studies are needed to replicate these findings.

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KW - Inflammation

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