What is the most appropriate follow-up time for detecting the epidemiological relationship between coronary artery disease and its main risk factors: novel findings from a 35-year follow-up study.

Abstract

The aim was to investigate the most appropriate follow-up time to detect the associations of coronary artery disease (CAD) with its traditional risk factors in a long-term prospective cohort study. The Kuopio Ischaemic Heart Disease Risk Factors Study provided the study material of 1958 middle-aged men free from CAD at baseline and followed up for 35 years. We performed Cox models adjusted for age, family history, diabetes, obesity, hypercholesterolemia, hypertension, smoking, and physical activity, investigated covariate interactions, and tested Schoenfeld residuals to detect time-dependent covariates. Moreover, we applied a sliding window procedure with a subarray of 5 years to better differentiate between risk factors manifested within years and those manifested within decades. The investigated manifestations were CAD and fatal acute myocardial infarction (AMI). Seven hundred seventeen (36.6%) men had CAD, and 109 (5.6%) men died from AMI. After 10 years of follow-up, diabetes became the strongest predictor of CAD with a fully adjusted hazard ratio (HR) of 2.5-2.8. During the first 5 years, smoking was the strongest predictor (HR 3.0-3.8). When the follow-up time was 8-19 years, hypercholesterolemia predicted CAD with a HR of >2. The associations of CAD with age and diabetes depended on time. Age hypertension was the only statistically significant covariate interaction. The sliding window procedure highlighted the significance of diabetes over the first 20 years and hypertension after that. Regarding AMI, smoking was associated with the highest fully adjusted HR (2.9-10.1) during the first 13 years. The associations of extreme and low physical activity with AMI peaked when the follow-up time was 3-8 years. Diabetes showed its highest HR (2.7-3.7) when the follow-up time was 10-20 years. During the last 16 years, hypertension was the strongest predictor of AMI (HR 3.1-6.4). The most appropriate follow-up time for most CAD risk factors was 10-20 years. Concerning smoking and hypertension shorter and longer follow-up times could be considered, respectively, particularly when studying fatal AMI. In general, prospective cohort studies of CAD would provide more comprehensive results by reporting point estimates in relation to more than one timepoint and concerning sliding windows.