Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction

PLoS One. 2015 Jun 3;10(6):e0128526. doi: 10.1371/journal.pone.0128526. eCollection 2015.

Abstract

Objectives: There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.

Methods: We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight-6:00 A.M., 6:00 A.M.-noon, noon-6:00 P.M. and 6:00 P.M.-midnight. We used peak creatine kinase as a surrogate marker of infarct size.

Results: Midnight-6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight-6:00 A.M. patients and lowest among 6:00 A.M.-noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight-6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.-noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).

Conclusion: We observed a circadian peak and nadir in infarct size during STEMI onset from midnight-6:00A.M and 6:00A.M.-noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Circadian Rhythm*
  • Creatine Kinase, MB Form / blood
  • Diabetes Complications
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / mortality
  • Female
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / diagnosis*
  • Heart Failure / mortality
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / complications
  • Myocardial Infarction / diagnosis*
  • Myocardial Infarction / mortality
  • Percutaneous Coronary Intervention
  • Photoperiod
  • Retrospective Studies
  • Severity of Illness Index
  • Survival Analysis
  • Time Factors
  • Tropical Climate

Substances

  • Biomarkers
  • Creatine Kinase, MB Form

Grants and funding

This study was accomplished with funding support from the Ministry of Health (MOH), Singapore. MYC is supported by a clinician scientist award (NMRC/CSA 2010/028) and AS receives support from a tier 1 Translational Clinical Research grant (NMRC/TCR11dec007), both from the National Medical Research Council (NMRC), Singapore. The funders had no role in study design and analysis, decision to publish, or preparation of the manuscript.