Supplementary Material

High-sensitivity cardiac troponin I in the general population –

Defining reference populations for the determination of the 99th percentile in the Gutenberg Health Study

Tanja Zeller1,2, Francisco Ojeda1, Fabian Brunner1, Philipp Peitsmeyer1, Thomas Münzel3,4,Harald Binder5, Norbert Pfeiffer6, Matthias Michal7, Philipp S Wild3,4,8, Stefan Blankenberg1,2, Karl J Lackner9

1 University Heart Center Hamburg, Clinic of general and interventional Cardiology, Hamburg, Germany

2 German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Lübeck/Kiel

3Department of Medicine II, University Medical Center, Johannes Gutenberg University Mainz, Germany

4 German Center for Cardiovascular Research (DZHK), Partner Site Rhein-Main

5Institute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz

6Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany, Mainz, Germany

7Department of Psychosomatic Medicine and Psychotherapy, University Medical Center of the Johannes Gutenberg-University Mainz, Germany

8 Clinical Epidemiology, Center for Thrombosis and Haemostasis, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany

9 Department of Laboratory Medicine, University Medical Center, Johannes Gutenberg University Mainz; Germany

Definition of cardiovascular risk factors

Within the Gutenberg Health Study (GHS) smokers were classified into daily smokers (≥ 1 cigarette/day) and occasional smokers (< 1 cigarette/day). Waist circumference ≥ 102 cm for men or ≥ 88 cm for women identified subjects with body mass index ≥ 30 kg/m²and was used to classify subjects as to be obese. Diabetes mellitus was defined as being diagnosed by a physician, a fasting glucose ≥ 126 mg/dl in the examination after an overnight fast of at least 8 hours or as a blood glucose level of ≥ 200mg/dl in the examination after a fasting period <8 hours. Dyslipidemia was defined as diagnosed by a physician or as an LDL/HDL-ratio of > 3.5. Hypertension was defined as a systolic blood pressure ≥ 140 mmHg or a diastolic blood pressure ≥ 90 mmHg at rest obtained as the mean of the second and third measurement, or by taking any antihypertensive drugs within the last 2 weeks. Any family history of myocardial infarction in first-degree relatives before the age of 65 years for females and before the age of 60 years for males was defined as positive family history. Glomerular filtration rate (GFR) as a marker of renal function was estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation (Levey et al. 2009 Ann Intern Med). History of coronary artery disease, myocardial infarction and medicated heart failure were self-reported in a standardized interview.

Echocardiography

All subjects underwent multimodal echocardiography with an iE33 echocardiography system with an S5–1 sector array transducer (Royal Philips Electronics, Amsterdam, The Netherlands) – a phased array with 80 elements and 5 to 1 MHz operating frequency range. The examinations were performed according to standard operating procedures by trained and certified medical technical assistants at a single center. For the present investigation, echo-cardiograms were obtained from the left parasternal window. As recommended by the American Society of Echocardiography (Devereux RB et al. 1986, Am J Cardiol), left ventricular (LV) internal diameters and wall thicknesses were measured at the level of the LV minor axis, approximately at the mitral valve leaflet tips.

Assessment and definition of LVEF and E/E´

Left ventricular ejection fraction was defined as 100*(end-diastolic volume – end-systolic volume)/( end-diastolic volume), with volumes determined according to the Simpson method in 4- and 2-chamber views.The Doppler-derived Tei index, was calculated as the sum of isovolumic contraction time and isovolumic relaxation time divided by LV ejection time. The E/E′ ratio of diastolic function was calculated by dividing the early filling velocity of transmitral Doppler (E) by the early relaxation velocity on tissue Doppler (E′). (Kasner M et al. 2007, Circulation).