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Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.

ABSTRACT: Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to increased NET burden in STEMI and influences long-term outcomes. We enrolled 711 STEMI patients undergoing primary percutaneous coronary intervention (pPCI), and 1422 controls. Genotyping was performed for DNase 1 Q222R SNP. DNase activity, double-stranded (ds)DNA and citrullinated histone H3 were determined in culprit site and peripheral plasma during pPCI. The association of the Q222R variant on cardiovascular and all-cause mortality was assessed by multivariable Cox regression adjusted for cardiovascular risk factors. Homozygous Q222R DNase 1 variant was present in 64 (9.0%) STEMI patients, at the same frequency as in controls. Patients homozygous for Q222R displayed less DNase activity and increased circulating DNA burden. In overall patients, median survival was 60 months. Homozygous Q222R variant was independently associated with cardiovascular and all-cause mortality after STEMI. dsDNA/DNase ratio independently predicted cardiovascular and all-cause mortality. These findings highlight that the Q222R DNase 1 SNP is associated with increased NET burden and decreased compensatory DNase activity, and may serve as an independent risk factor for poor outcome after STEMI.

SUBMITTER: Hofbauer TM

PROVIDER: S-EPMC8064981 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.

Hofbauer Thomas M TM Mangold Andreas A Ondracek Anna S AS Panzenböck Adelheid A Scherz Thomas T Müller Julian J Distelmaier Klaus K Seidl Veronika V Kastl Stefan S Müller-Nurasyid Martina M Peters Annette A Strauch Konstantin K Winker Robert R Wohlschläger-Krenn Evelyne E Nistler Sonja S Lang Irene M IM

Basic research in cardiology 20210423 1

Upon activation, neutrophils release neutrophil extracellular traps (NETs), which contribute to circulating DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Deoxyribonuclease (DNase) 1 degrades circulating DNA and NETs. Lower DNase activity correlates with NET burden and infarct size. The DNase 1 Q222R single nucleotide polymorphism (SNP), impairing DNase 1 function, is linked with myocardial infarction. We assessed whether the Q222R SNP is connected to in ...[more]

PMID: 33891165

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Project description:BackgroundThere is limited information about the long-term survival of older patients after myocardial infarction (MI).Methods and resultsCRUSADE (Can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines) was a registry of MI patients treated at 568 US hospitals from 2001 to 2006. We linked MI patients aged ≥65 years in CRUSADE to their Medicare data to ascertain long-term mortality (defined as 8 years post index event). Long-term unadjusted Kaplan-Meier mortality curves were examined among patients stratified by revascularization status. A landmark analysis conditioned on surviving the first year post-MI was conducted. We used multivariable Cox regression to compare mortality risks between ST-segment-elevation myocardial infarction and non-ST-segment-elevation myocardial infarction patients. Among 22 295 MI patients ≥ age 65 years (median age 77 years), we observed high rates of evidence-based medication use at discharge: aspirin 95%, β-blockers 94%, and statins 81%. Despite this, mortality rates were high: 24% at 1 year, 51% at 5 years, and 65% at 8 years. Eight-year mortality remained high among patients who underwent percutaneous coronary intervention (49%), coronary artery bypass graft (46%), and among patients who survived the first year post-MI (59%). Median survival was 4.8 years (25th, 75th percentiles 1.1, 8.5); among patients aged 65-74 years it was 8.2 years (3.3, 8.9) while for patients aged ≥75 years it was 3.1 years (0.6, 7.6). Eight-year mortality was lower among ST-segment-elevation myocardial infarction than non-ST-segment-elevation myocardial infarction patients (53% versus 67%); this difference was not significant after adjustment (hazard ratio 0.94, 95% confidence interval, 0.88-1.00).ConclusionsLong-term mortality remains high among patients with MI in routine clinical practice, even among revascularized patients and those who survived the first year.

Dataset Information

Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.

Publications

Deoxyribonuclease 1 Q222R single nucleotide polymorphism and long-term mortality after acute myocardial infarction.

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