Background Clinical guidelines suggest preventive interventions such as statin therapy for individuals with a high
estimated 10-year risk of major cardiovascular events. For those with a low or intermediate estimated risk, risk-factor
screenings are recommended at 5-year intervals; this interval is based on expert opinion rather than on direct research
evidence. Using longitudinal data on the progression of cardiovascular disease risk over time, we compared different
screening intervals in terms of timely detection of high-risk individuals, cardiovascular events prevented, and healthcare costs.
Methods We used data from participants in the British Whitehall II study (aged 40–64 years at baseline) who had
repeated biomedical screenings at 5-year intervals and linked these data to electronic health records between baseline
(Aug 7, 1991, to May 10, 1993) and June 30, 2015. We estimated participants’ 10-year risk of a major cardiovascular
event (myocardial infarction, cardiac death, and fatal or non-fatal stroke) using the revised Atherosclerotic
Cardiovascular Disease (ASCVD) calculator. We used multistate Markov modelling to estimate optimum screening
intervals on the basis of progression rates from low-risk and intermediate-risk categories to the high-risk category
(ie, ≥7·5% 10-year risk of a major cardiovascular event). Our assessment criteria included person-years spent in a
high-risk category before detection, the number of major cardiovascular events prevented and quality-adjusted lifeyears (QALYs) gained, and screening costs.
Findings Of 6964 participants (mean age 50·0 years [SD 6·0] at baseline) with 152700 person-years of follow-up (mean
follow-up 22·0 years [SD 5·0]), 1686 participants progressed to the high-risk category and 617 had a major
cardiovascular event. With the 5-year screening intervals, participants spent 7866 (95% CI 7130–8658) person-years
unrecognised in the high-risk group. For individuals in the low, intermediate-low, and intermediate-high risk
categories, 21 alternative risk category-based screening intervals outperformed the 5-yearly screening protocol.
Screening intervals at 7 years, 4 years, and 1 year for those in the low, intermediate-low, and intermediate-high-risk
category would reduce the number of person-years spent unrecognised in the high-risk group by 62% (95% CI 57–66;
4894 person-years), reduce the number of major cardiovascular events by 8% (7–9; 49 events), and raise 44 QALYs
(40–49) for the study population.
Interpretation In terms of timely preventive interventions, the 5-year screening intervals were unnecessarily frequent
for low-risk individuals and insufficiently frequent for intermediate-risk individuals. Screening intervals based on
risk-category-specific progression rates would perform better in terms of preventing major cardiovascular disease
events and improving cost-effectiveness.
Funding Medical Research Council, British Heart Association, National Institutes on Aging, NordForsk, Academy of
Finland.