Detailed description of outcomes of interest and covariates in the analyses
| Mortality | |
| Overall mortality | Mortality related to cardiovascular events, cancer and mortality due to unknown/unspecified causes |
| Cardiovascular events | |
| Coronary insufficiency syndrome | History of ≥15 min chest pain accompanied by transient ischaemic changes in the ECG, but without changes in serum biomarkers of myocardial necrosis |
| Recent/acute myocardial infarction (MI) | ≥2 of 3 findings; (1) typical symptoms, (2) changes in serum biomarkers and/or (3) ECG indicating myocardial infarction. Autopsy showing new/recent MI was also accepted as evidence |
| Congestive heart failure (CHF) | Minimum of two major or one major and two minor criteria present concurrently |
| Major criteria: (1) paroxysmal nocturnal dyspnoea or orthopnoea; (2) distended neck veins (other than supine position); (3) rales; (4) increasing heart size by x-ray; (5) acute pulmonary oedema on x-ray; (6) ventricular S(3) gallop; (7) increased venous pressure>16 cm H2O; (8) hepatojugular reflux; (9) pulmonary oedema, visceral congestion, cardiomegaly shown on autopsy; (10) weight loss on CHF Rx: 10 lbs/5 days | |
| Minor criteria: (1) bilateral ankle oedema; (2) night cough; (3) dyspnoea on ordinary exertion; (4) hepatomegaly; (5) pleural effusion by x-ray; (6) decrease in vital capacity by 1/3 from maximum record; (7) tachycardia (≥120 beats per minute); (8) pulmonary vascular engorgement on x-ray | |
| Atherothrombotic brain infarction | Sudden/rapid onset of focal neurological deficit>24 h without known sources of embolism, intracranial haemorrhage, known hypercoagulable states or other disease processes causing focal neurological deficits |
| Covariates | |
| Body mass index (kg/m2) | Weight (kg) and height (m) measured after standardised procedures |
| Blood glucose | Non-fasting glucose of ≥200 mg/dL (≥11.1 mmol/L) or fasting glucose of ≥126 mg/dL (≥ 7.0 mmol/L) |
| Lipid profile | Total cholesterol:high density lipoprotein ratio (used as continuous scale in the analyses) |
| Hypertension | Elevated blood pressure (systolic ≥160 mmHg and/or diastolic ≥95 mmHg) measured by two physicians |
| Previous cardiovascular events | Previous coronary insufficiency syndrome, MI, CHF and atherothrombotic stroke, as described above (ie, the diagnoses were arrived at by a panel of cardiologists and neurologists) |
| Previous self-reported cancer | Previous cancer reported by the patient in a clinical interview |
| Lipid lowering treatment | Current use of resins, niacin or nicotinic acid, fibrates, statins and/or other anticholesterol drugs assessed in a clinical interview |
| Antihypertensives | Currently receiving medication for the treatment of hypertension assessed in a clinical interview |
| Antidiabetics | Current use of insulin and oral hypoglycaemics assessed in a clinical interview |
| Non-steroidal anti-inflammatory drugs | Current use of non-steroidal anti-inflammatory agents (Motrin, ibuprofen, Indocin, Clinoril) assessed in a clinical interview |
| Aspirin | Daily use of aspirin (≥6 days per week) assessed in a clinical interview |
| Alcohol | Alcohol consumption (yes/no) assessed in a clinical interview |
| Smoking (current and previous) | Regularly smoking of cigarettes the last year and smoking of cigars and pipes assessed in a clinical interview (examination cycles 1–5 for Offspring and examination cycles 17–22 for Original cohort) |