ObjectiveWe studied the association between the coronavirus disease 2019 (COVID-19) pandemic, including the restrictive measures, and metabolic risk factors for cardiovascular disease (CVD) in women and men. Next, we analysed whether changes in these metabolic risk factors were mediated by psychological and behavioural mechanisms.DesignIn this natural experiment, we assessed changes from baseline in metabolic CVD risk factors in the exposed group (whose follow-up measurements were taken during the pandemic), and compared these to the changes in the control group (whose follow-up measurements were taken before the pandemic).ParticipantsThis study used data from 6962 participants from six different ethnic groups (Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan) of the HELIUS study, based in Amsterdam, the Netherlands. We included women and men without prior CVD, who participated in both the baseline (2011-2015) and follow-up measurements (2019-2021).Outcome measuresChanges between baseline and follow-up measurements in six metabolic CVD risk factors were calculated for systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), and estimated glomerular filtration rate (eGFR).ResultsThe exposed group experienced somewhat less favourable changes over time in SBP, DBP and FPG (the latter only in women) than the control group, while temporal changes in HbA1c and eGFR were more favourable among the control group. For instance, SBP was 1.119 mmHg [0.046, 2.193] higher in exposed than non-exposed women, and 1.380 [0.288, 2471] in men. Changes in SBP and DBP were partially mediated by changes in behavioural factors, most notably BMI and alcohol consumption.ConclusionsThe COVID-19 pandemic, including the restrictive lockdown measures, is associated with a deterioration of several CVD risk factors in women and men. These findings may aid in decision making concerning the management of and the recovery following the pandemic.Article SummaryStrengths and limitations of this studyThe COVID19 pandemic lockdown measures led to a pause in the data collection for the prospective, population-based HELIUS study, which shaped a natural experiment.Natural experiments, as quasi-experimental designs, are generally considered stronger than cross-sectional studies.Through inverse-probability weighting, this study aimed to account for baseline differences between the control and exposed group.We could not adjust for differences in follow-up time that occurred as a result of the restrictive measures, which may have affected estimates of variables that change with age.The effects of certain mediators may be underestimated, as the data available for defining these variables were largely based on self-reports.