術前の成長分化因子15濃度と非心臓大手術後の術後心血管系イベントとの関連性．

Association of Preoperative Growth Differentiation Factor-15 Concentrations and Postoperative Cardiovascular Events after Major Noncardiac Surgery.

抄録

背景:

成長分化因子-15濃度と心血管疾患との関連はよく知られている。本研究の仮説は、非心臓手術患者において、臨床評価に加えて、成長分化因子-15が心臓リスクの層別化に役立つ可能性があるというものである。

BACKGROUND: The association between growth differentiation factor-15 concentrations and cardiovascular disease has been well described. The study hypothesis was that growth differentiation factor-15 may help cardiac risk stratification in noncardiac surgical patients, in addition to clinical evaluation.

方法論:

本研究の目的は、術前の血清成長分化因子-15が、非心臓手術後の心筋損傷と30日後の血管死の複合主要転帰と関連し、非心臓手術における心臓リスク予測を改善できるかどうかを明らかにすることであった。本試験は、45歳以上の非心臓の大手術を受けた患者を対象とした前向きコホート研究である。術前の成長分化因子15と主要転帰の関連は、Revised Cardiac Risk Indexで調整した後に決定した。また、術前のN-terminal-pro hormone brain natriuretic peptideも追加し、growth differentiation factor-15と予測性能を比較した。

METHODS: The objective of the study was to determine whether preoperative serum growth differentiation factor-15 is associated with the composite primary outcome of myocardial injury after noncardiac surgery and vascular death at 30 days and can improve cardiac risk prediction in noncardiac surgery. This is a prospective cohort study of patients 45 yr or older having major noncardiac surgery. The association between preoperative growth differentiation factor-15 and the primary outcome was determined after adjusting for the Revised Cardiac Risk Index. Preoperative N-terminal-pro hormone brain natriuretic peptide was also added to compare predictive performance with growth differentiation factor-15.

結果:

2008年10月27日から2013年10月30日の間に、術前に成長分化因子-15を測定した計5,238人の患者を対象とした（中央値1,325、四分位範囲880～2,132 pg/ml）。非心臓手術後の心筋損傷および血管死のリスクは、成長分化因子-15が1,000 pg/ml未満では1,705人中99人（5.8%）、1,332人中161人（12.1,000～1,500pg/ml未満は1,332例中161例（12.1%）、1,500～3,000pg/ml未満は1476例中302例（20.5%）、3,000pg/ml以上では725例中247例（34.1%）でした。成長分化因子-15濃度が1,000 pg/ml未満の患者と比較して、各成長分化因子-15のカテゴリーに対応する調整済みハザード比は、それぞれ1.93（95% CI, 1.50～2.48）, 3.04（95% CI, 2.41～3.84）, 4.8（95% CI, 3.76～6.14 ）でした。成長分化因子15を加えることで、Revised Cardiac Risk Index単独と比較して、心臓リスク分類が30.1％（1,000人あたり301人）向上した。また、術前のN-terminal-proホルモン脳性ナトリウム利尿ペプチドとRevised Cardiac Risk Indexの組み合わせ（16.1％；1,000人あたり161人）以上のリスク分類を実現した。

RESULTS: Between October 27, 2008, and October 30, 2013, a total of 5,238 patients were included who had preoperative growth differentiation factor-15 measured (median, 1,325; interquartile range, 880 to 2,132 pg/ml). The risk of myocardial injury after noncardiac surgery and vascular death was 99 of 1,705 (5.8%) for growth differentiation factor-15 less than 1,000 pg/ml, 161 of 1,332 (12.1%) for growth differentiation factor-15 1,000 to less than 1,500 pg/ml, 302 of 1476 (20.5%) for growth differentiation factor-15 1,500 to less than 3,000 pg/ml, and 247 of 725 (34.1%) for growth differentiation factor-15 concentrations 3,000 pg/ml or greater. Compared to patients who had growth differentiation factor-15 concentrations less than 1,000 pg/ml, the corresponding adjusted hazard ratio for each growth differentiation factor-15 category was 1.93 (95% CI, 1.50 to 2.48), 3.04 (95% CI, 2.41 to 3.84), and 4.8 (95% CI, 3.76 to 6.14), respectively. The addition of growth differentiation factor-15 improved cardiac risk classification by 30.1% (301 per 1,000 patients) compared to Revised Cardiac Risk Index alone. It also provided additional risk classification beyond the combination of preoperative N-terminal-pro hormone brain natriuretic peptide and Revised Cardiac Risk Index (16.1%; 161 per 1,000 patients).

結論:

成長分化因子-15は、主要な心血管イベントの30日リスクに強く関連し、非心臓手術を受けた患者の心臓リスク予測を有意に改善する。

CONCLUSIONS: Growth differentiation factor-15 is strongly associated with 30-day risk of major cardiovascular events and significantly improved cardiac risk prediction in patients undergoing noncardiac surgery.