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SUPPLEMENTAL DATA
METHODS (Supplemental Data)
Study population
Details of the LURIC baseline examination have been described previously (1). In brief, in the
LURIC study clinically relevant CAD was defined as the occurrence of at least 1 stenosis ≥20%
in at least 1 of 15 coronary segments of the 3 major coronary arteries. The angiographic
severity of disease was reported as one-, two-, or three-vessel disease according to the number
of vessels with stenosis ≥50% of the three major coronary arteries. Hypertension was
diagnosed when systolic or diastolic blood pressure exceeded 140 or 90 mmHg, respectively, or
in case of a known history of hypertension, evident through the use of antihypertensive drugs.
Dyslipidemia was defined when one or more of the following criteria were present at baseline:
total cholesterol ≥240 mg/dL (≥6.2 mmol/L), HDL-cholesterol <40 mg/dL (<1.0 mmol/L), LDL
cholesterol >160 mg/dL (>4.1 mmol/L), triglycerides ≥150 mg/dL (≥1.6 mmol/L), and/or use of
lipid-lowering medication. Diabetes mellitus was diagnosed when fasting glucose was ≥126
mg/dL (≥7.0 mmol/L), the 2 hour value from an oral glucose tolerance test was ≥200 mg/dL
(≥11.1 mmol/L), and/or the glycosylated haemoglobin was ≥6.5%. Patients receiving antidiabetic medication were also classed as being diabetic. Current smoking, family history of
cardiovascular disease (either fatal or non-fatal myocardial infarction or stroke) and medications
from medical records and by self-reporting. Cerebrovascular disease was defined clinically by a
documented previous cerebrovascular disease event (transient ischemic attack, prolonged
ischemic neurologic deficit, and cerebral infarction with or without a permanent neurologic
deficit) or by documented carotid stenosis with >50% luminal obstruction. Peripheral vascular
disease was defined by a history of intermittent claudication, angiographic documentation of
atherosclerotic luminal obstruction of the peripheral arteries, or a history of a peripheral arterial
intervention for atherosclerotic disease (angioplasty, vascular surgery, and/or amputation). Left
ventricular ejection fraction (LVEF) was estimated with echocardiography using the Simpson
method and categorized into normal (≥55%), mildly reduced (45–54%), moderately reduced
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(30–44%), and severely reduced (<30%). A clinical diagnosis of heart failure with reduced LVEF
was defined by the combined presence of dyspnea on exertion and the echocardiographic
finding LVEF<45% and the functional capacity for patients with heart failure was estimated
according to New York Heart Association (NYHA) classification.
Biochemical analysis
Routine laboratory parameters were measured as described in detail previously (1). In Brief,
Glucose was measured in serum enzymatically on a Hitachi 717 (Roche Diagnostics). Glycated
hemoglobin was measured in EDTA whole blood with an immunoassay (hemoglobin A1c
UNIMATE 5; Hoffmann-LaRoche) and the coefficients of variation (CVs) were 1.4-3.6% (1).
Total cholesterol and triglycerides were quantified in serum with an enzymatic assay on a
Hitachi 717 (Roche Diagnostics) (1). Lipoproteins (LDL- and HDL-cholesterol) were determined
in plasma by a combined ultracentrifugation and precipitation method and measured with
enzymatic reagents on a WAKO 30 R analyzer (WAKO Chemicals) as described previously (1).
The CVs of all Lipids and Lipoproteins varied between 1-3% (1). Creatinine concentration was
measured in serum by a kinetic colorimetric assay according to the Jaffé method on a Hitachi
717 (Roche Diagnostics) and estimated glomerular filtration rate (eGFR) was calculated
according to the none-IDSMS traceable MDRD equation (2). Cholinesterase was measured in
serum with a colorimetric assay on a Hitachi 717 (Roche Diagnostics) (1). High sensitivity Creactive protein (hs-CRP) was measured in serum by immunonephelometry on a Behring
Nephelometer II (Dade Behring, Marburg) (1). Interleukin-6 was measured in plasma with a high
sensitivity enzyme immunoassay (R&D Systems) (1).
REFERENCES (Supplemental Data)
1. Winkelmann BR, März W, Boehm BO, Zotz R, Hager J, Hellstern P, et al. Rationale and
design of the LURIC study--a resource for functional genomics, pharmacogenomics and
long-term prognosis of cardiovascular disease. Pharmacogenomics. 2001;2:S1-S73.
2. Levey AS, Greene T, Kusek JW, Beck GJ. A simplified equation to predict glomerular
filtration rate from serum creatinine. J Am Soc Nephrol 2000;11:A0828.
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Table 1 (Supplemental Data). Baseline biochemical markers of all patients with stable CAD and
according to all-cause mortality
Total cholesterol, mmol/L
LDL cholesterol, mmol/L
HDL cholesterol, mmol/L
Triglycerides, mmol/L
Glycosylated haemoglobin, mmol/mol
Glucose, mmol/L
Creatinine, µmol/L
eGFR, mL/min/1.73m2
Cholinesterase, µmol/sL
hs-CRP, mg/L
Interleukin-6, ng/L
NT-proBNP, pmol/L
hs-cTnT, ng/L
Galectin-3, ng/mLb
sST2, ng/mL
All
Survivors
Decedents
(n=1345)
(n=868)
(n=477)
5.0 (4.3-4.7)
2.95 (2.40-3.57)
0.98 (0.83-1.14)
1.69 (1.27-2.30)
43 (39-50)
5.2 (4.6-6.1)
80 (71-97)
81 (70-92)
97 (82-111)
2.8 (1.2-6.7)
3.0 (1.7-5.7)
35 (13-103)
10 (6-19)
14.7 (11.6-18.8)
19.4 (15.7-24.6)
5.0 (4.3-5.7)
2.97 (2.40-3.59)
0.98 (0.83-1.14)
1.71 (1.28-2.30)
42 (38-48)
5.1 (4.6-5.8)
80 (71-89)
83 (72-93)
99 (85-113)
2.3 (1.0-5.5)
2.6 (1.7-4.5)
24 (10-57)
8 (5-14)
14.2 (11.3-17.8)
18.5 (15.4-23.2)
4.9 (4.4-5.6)
2.92 (2.40-3.52)
0.96 (0.80-1.14)
1.68 (1.21-2.29)
45 (39-56)
5.4 (4.7-6.9)
89 (71-97)
78 (65-90)
91 (78-106)
4.1 (1.6-9.3)
4.3 (2.3-7.6)
89 (30-215)
17 (9-31)
15.6 (12.3-20.7)
21.4 (16.6-28.3)
P value a
0.488
0.662
0.016
0.497
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
Continuous variables are presented as median (interquartile range).
a
Univariate comparisons between survivors and decedents were performed with the the non-parametric
Mann–Whitney U test for continuous variables.
b
Plasma concentrations for galectin-3 were available in 1025 patients.
Respective P values were not adjusted for multiple comparisons and are therefore descriptive only.