Study design and population

The present study protocol was complied with Declaration of Helsinki and was approved by the hospital ethics review board (Fu Wai Hospital & National Center for Cardiovascular Diseases, Beijing, China). Every patient signed the informed written consent before enrolled in this study.

The flowchart of the current study was presented in supplementary Fig. S1. We consecutively recruited 2583 patients with angina-like chest pain from October 2012 to April 2018 and 2433 patients who completed the determination of PCSK9 and routine coagulation tests including APTT, PT and TT.

Because lipid-lowering medications could increase circulating PCSK9 concentration and anti-coagulation drugs could prolong clotting time, confounding study results, patients taking any lipid-lowering agents within 3 months and taking any anti-coagulation agents within 1 month prior to entering the study were excluded from the present study. In addition, patients with acute or heart failure (left ventricular ejection fraction, left ventricular ejection fraction < 45%), acute coronary syndrome, significant hematologic disorders (white blood cell count ≤3.0 × 10⁹/L or ≥ 20 × 10⁹/L), infectious or systematic inflammatory disease, thyroid dysfunction, severe liver and/or renal insufficiency and malignant disease were excluded from this study. 2348 patients were followed-up for MACEs. During a follow-up with a mean of 38.3 months, 91 patients lost to follow-up. Finally, a total of 2293 patients with angina-like chest pain were included in this study. All patients were divided according to the median of PCSK9 concentration (low/high PCSK9 groups) and further stratified by the mean of PT levels (low/high PT groups).

In the current study, 1447 patients were proven stable CAD according to following diagnostic criteria. Stable CAD was defined as typical angina-like chest pain, a positive treadmill exercise test (> 1 mm ST-segment depression), and stable obstructive lesion > 50% in at least 1 of the 3 major coronary arteries or major branches assessed by at least two independent senior interventional cardiologists who had no knowledge of the patients’ clinical characteristics and biochemical data. 1418 patients were diagnosed with hypertension. The definition of hypertension was repeated systolic and/or diastolic blood pressure ≥ 140 and/or ≥ 90 mmHg on 2 different occasions or if patients were currently taking antihypertensive drugs. 538 patients with diabetes was diagnosed as fasting serum glucose levels ≥6.99 mmol/L in multiple determinations or patients were being treated with oral hypoglycemic agents or insulin.