Relation of electrocardiographic abnormalities to levels of serum C-reactive protein

T link between electrocardiographic abnormalities and cardiovascular disease are explained partly by the presence of cardiovascular risk factors. The relation between C-reactive protein (CRP), a sensitive marker of inflammation, and electrocardiographic abnormalities is unknown. In this study, we hypothesized that electrocardiographic abnormalities are related to elevated levels of CRP. • • • The population analyzed in this study was obtained from the Prevention of REnal and Vascular ENdstage Disease (PREVEND) study. The PREVEND study is designed to investigate the natural course of microalbuminuria and its relation to renal and cardiovascular disease in the general population, as previously described.1 The study cohort comprised men and women, aged 28 to 75 years, from the city of Groningen, The Netherlands. All participants gave written informed consent. The PREVEND study was approved by the local medical ethics committee and conducted in accordance with the guidelines of the Declaration of Helsinki. To study the association between electrocardiographic abnormalities and CRP, CRP was dichotomized (low: 3 lowest quartiles, CRP 2.97 mg/L vs high: highest quartile, CRP 2.97 mg/L) as previously reported in several studies.2,3 Systolic and diastolic blood pressures were calculated as the mean of the last 2 of 10 measurements taken at 2 visits. Body mass index was calculated as the ratio between weight and the square of height (kilograms per square meters). We defined traditional cardiovascular risk factors as male gender and age 60 years. Diabetes mellitus was defined as a fasting plasma glucose level of 7.0 mmol/L or a nonfasting plasma glucose level of 11.1 mmol/L, or the use of antidiabetic medication. Obesity was defined as a body mass index of 30 kg/m. Hypertension was defined as systolic blood pressure 140 mm Hg or diastolic blood pressure 90 mm Hg or the use of antihypertensive medication. Hypercholesterolemia was defined as a total serum cholesterol level of 6.5 mmol/L (251 mg/dl) or the use of lipid-lowering therapy. Smoking was categorized as no smoking, current smoking, or discontinued 1 year before the study. A family history of cardiovascular disease was defined as first-degree relatives who experienced a cardiovascular event at 55 years of age. High-sensitivity CRP was determined by nephelometry with a threshold of 0.175 mg/L and intraand interassay coefficients of 4.4% and 5.7%, respectively (BNII N, Dade Behring, Marburg, Germany). Plasma glucose and serum cholesterol was measured by Kodak Ektachem dry chemistry (Eastman Kodak, Rochester, New York). Standard 12-lead electrocardiograms were recorded with Cardio Perfect equipment (Cardio Control, Delft, The Netherlands), stored digitally, and classified according to the Minnesota code4 using the Modular ECG Analysis System (MEANS) computer program.5,6 Signal analysis and classification of MEANS have been extensively evaluated in clinical and general population samples.7,8 Infarct patterns, suggestive of myocardial infarction, were defined by Minnesota codes 1.1 and 1.2. Major ischemia was defined by codes 4.1, 4.2, 5.1, or 5.2, after exclusion of infarct patterns. Minor ischemia was defined by codes 1.3, 4.3, or 5.3, after exclusion of infarct patterns and major ischemia. Finally, we measured the T-axis, which is a strong independent predictor for fatal and nonfatal cardiac events.9,10 T-axes were computed from vectorcardiographic X, Y, and Z, which can be reconstructed from standard electrocardiographic leads. The mean spatial axis was obtained by vectorially adding the instantaneous heart vectors during the T wave. The mean frontal axis was then taken to be the angle between the X-axis and the projection of the mean spatial axis on the frontal plane. Based on previously published reports,9 an abnormal T-axis was defined as 180° to 15° and 105° to 180° after exclusion of subjects with an infarct pattern or major ischemia on the electrocardiogram. Subjects with complete bundle branch block (QRS duration 120 ms) were also excluded because these conditions cause secondary T-wave changes. The exclusion of subjects with right or left ventricular hypertrophy, which can also cause secondary T-wave changes, had no effect on the results and were therefore not excluded from the analysis. From the Department of Clinical Pharmacology, University of Groningen, Groningen; Departments of Cardiology, Internal Medicine, Nephrology and Trial Coordination Center, University Hospital Groningen, Groningen; and Department of Medical Informatics, Erasmus University, Rotterdam, The Netherlands. This study was financially supported by grant E.013 from the Dutch Kidney Foundation, Bussum, The Netherlands; by grant 99.103 from the Netherlands Heart Foundation, Den Haag, The Netherlands; and by a grant from Bristol-Myers Squibb, Woerden, The Netherlands. Dr. Asselbergs’ address is: Department of Clinical Pharmacology, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands. E-mail: f.w.asselbergs@thorax.azg.nl. Manuscript received October 22, 2002; revised manuscript received and accepted February 14, 2003.