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Introduction Current primary prevention strategies in cardiovascular (CV) disease focus on initiating preventive interventions in people at high 10-year risk of CV mortality. However, initiating such strategies should be beneficial not only in the first 10 years, but throughout life. Established risk algorithms estimate the risk of 10-year CV mortality, but limited evidence is available about the relationship between 10-year and longer-term CV mortality. Purpose To compare cumulative incidence of CV mortality in a population cohort at 10- and 20-years follow-up, stratified by sex. Methods We analysed CV mortality at 10-years and 20-years follow-up using Kaplan-Meier estimates among men and women aged 39–70 years without baseline CV disease or diabetes mellitus in the large, prospective population-based EPIC-Norfolk cohort. CV mortality included death with as underlying or contributing cause ischaemic heart disease, heart failure, cerebrovascular disease or peripheral artery disease. Results We analysed data from 20,453 participants (56% women), with a mean age of 56±8 years, and median (IQR) follow-up of 22 (21–23) years. At baseline, there were no clinically relevant differences in CV risk factors between men and women. Overall cumulative CV mortality rate was 1.9% (384 deaths) in the first 10 years, and 7.3% (995 deaths) at 20 years follow-up (ratio 3.8). Among men, 10-year CV mortality was 2.9% (249 deaths), and 9.6% (785 deaths) at 20 years follow-up (ratio 3.3). Among women, CV mortality was 1.2% (135 deaths) at 10 year and 5.5% (594 deaths) at 20 years follow-up (ratio 4.6). Conclusion We observed an incremental increase in CV mortality beyond the 10-year scope of current established CV risk algorithms. At 20 years follow-up, CV mortality rates were 3–5 times higher compared with the first decade, indicating that 20-year CV mortality risk for both men and women cannot simply be estimated based on extrapolation of 10-year risk. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC-Norfolk is supported by programme grants from the Medical Research Council UK (MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (CRUK 8257).

Introduction Interventions to reduce lifestyle-related risk factors (LRFs) such as overweight, physical inactivity and smoking are effective in the secondary prevention of cardiovascular events. However, evidence of the effects of lifestyle-related secondary prevention programmes in older patients with coronary artery disease (CAD) is less conclusive than in younger patients. Purpose To compare the treatment effect on lifestyle-related risk factors (LRFs) in older (≥65 years) versus younger ( Methods The RESPONSE-2 trial was a community-based lifestyle intervention trial (N=824) comparing nurse-coordinated referral to a comprehensive set of three lifestyle interventions (physical activity, weight reduction and/or smoking cessation) to care as usual. The primary outcome was the proportion of patients with improvement at 12 months follow-up (N=711) in at least 1 LRF (without deterioration in the other LRFs). In the current analysis, we assessed if the overall beneficial treatment effect of the RESPONSE-2 intervention varied by age. Results At baseline, older patients (n=245, 69.2±3.9) had significantly more serious cardiovascular risk profiles and comorbidities (hypertension, diabetes mellitus and peripheral artery disease) than younger patients (n=579, 53.7±3.9). The overall treatment effect did not vary by age (OR overall 1.67, 95% CI 1.22 - 2.31). However, older patients were more likely to achieve ≥5% weight loss (OR old 5.58, 95% CI 2.77–11.26 vs. OR young 1.57, 95% CI 0.98 - 2.49, P interaction=0.003) and younger patients were more likely to show non-improved individual LRFs (OR old 0.38, 95% CI 0.22–0.67 vs. OR young 0.88, 95% CI 0.61–1.26, P interaction=0.01). Conclusion Despite more serious cardiovascular risk profiles and comorbidities among older patients, nurse-coordinated referral to community-based lifestyle interventions was at least as successful in improving LRFs in older as in younger patients. Higher age alone should not be a reason to withhold lifestyle interventions in patients with CAD. LRFs at 12 months follow-up Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The RESPONSE-2 trial was sponsored by Weight Watchers International, Inc. (New York, New York) and Philips Consumer Lifestyle (the Netherlands). This work was also supported by the Netherlands Organisation for Scientific Research (NWO) to PJ.

Background We performed an extended follow-up of the RESPONSE-2 trial, which evaluated a new secondary prevention strategy for patients with coronary artery disease (CAD). Selective loss to follow-up (LTFU) however, may induce biased results. Objectives To assess LTFU and its implications on the internal validity of the trial at extended follow-up. Methods RESPONSE-2 (N=824) was a randomised trial of nurse-coordinated referral of CAD patients to ≤3 commercial lifestyle interventions, on top of usual-care, or to usual-care alone. The primary outcome was assessed at 1-year follow-up, after which the interventions were discontinued. An extended follow-up was performed two years later. We evaluated overall selective LTFU, between-group selective LTFU and within-group selective LTFU, by comparing baseline characteristics, compliance with the lifestyle interventions (intervention group only) and achievement of lifestyle-related risk factor (LRF) targets at 1-year follow-up for attendees and non-attendees of the extended follow-up. In all variables a standardized mean difference (SMD) of ≥0.2 with a p-value Results In total, 520 patients attended the extended follow-up: 266/411 in the intervention and 254/413 in the control group. Patients LTFU were generally younger (56.5 vs. 59.3 years; SMD=0.299), more often baseline smokers (37% vs. 22%; SMD=0.334) and had less often quit smoking directly after hospitalization (17% vs. 25%; SMD=0.203). We found no evidence of between-group selective LTFU and several indications of within-group selective LTFU (table). Intervention group attendees were more compliant with the lifestyle interventions compared with non-attendees (weight loss: SMD=0.450; p≤0.05 and physical activity: SMD=0.516; p≤0.01) Conclusion Baseline LRF control, compliance with the lifestyle interventions and achievement of LRF targets were less favourable for non-attendees of the extended follow-up. Effective handling of missing data is recommended to minimize loss of contrast due to within-group selective LTFU and to ensure generalizability of results. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The RESPONSE-2 trial was sponsored by Weight Watchers International, Inc. (New York, New York) and Philips Consumer Lifestyle (the Netherlands). The sponsors had no role in the design, data collection, data analysis, data interpretation, and writing of the manuscript.

Oblectives The purpose of this study was to determine the variability of quantitative measurements from intracoronary ultrasound images, and the influence of the cardiac cycle on this variability, as a basis for in vivo applications. Methods Methods Two observers analysed 30 MHz cross-sectional images from 96 in-vivo coronary arterial sites. By computer-assisted contour tracing we determined lumen area, vessel area, lesion area (vessel area minus lumen area) and percent obstruction (l00% × lesion area/vessel area). Intra- and inter-observer and beat-to-beat variability, and systolic to diastolic differences were calculated by paired analysis. Results Consistent intra- and inter-observer differences (bias) were small (≤0·9%). Random variations in the two direct parameters were ≤21·l%, but for the two derived parameters they were up to 40%. For all four parameters, random inter-observer variability was significantly greater (up to 119% for vessel area: 19·3 vs 8·8%) than intraobserver variability, but consistent variability was similar. Consistent beat-to-beat differences were small (≤1·4%), random variations were 8·9% to l7·5%. Random beat-to-beat variability for all four parameters was greater in diastolic than in systolic frames (up to 47·0% difference (11·9 vs 17·5%) for lesion area). Vascular dimensions were significantly greater in systole (2%). We found an error of 0·24 mm (2SD) for intra-observer variability of calculated mean arterial diameters, which is similar to the error described in angiographic studies (0·22 mm). Conclusions Quantitative measurements from intracoronary ultrasound images generally reproduce well. It is preferable to use directly measured parameters as opposed to derived parameters, as they are less subject to variability. Variability can be reduced by selecting systolic images. (Eur Heart J 1996; 17: 1593–1599)