Context: By definition, levels of metabolic risk factors predict atherosclerotic vascular disease (AVD), but the effects of long-term adverse change and instability remain under-researched.

Objective: To quantify long-term rates of change and instability in risk factors and relate these measures to clinical AVD outcomes.

Design: Prospective cohort study with unmatched and age- and follow-up-matched control analyses.

Setting: Teaching hospital day ward.

Participants: Four-hundred and sixty-five predominantly healthy white males in an occupational cohort, who had undergone repeated metabolic risk factor measurements (mean observation period 11.6 years, range 2–28), 62 of whom developed clinical AVD.

Main outcome measures: Rate of change and instability in metabolic risk factor levels were quantified in each individual by linear regression with time and evaluated as predictors of AVD and coronary and cerebrovascular disease separately.

Results: As expected, baseline and/or mean follow-up measures of established risk-factors relating to blood pressure, lipid metabolism and sub-clinical inflammation were significant predictors. Predictors independent of baseline and mean follow-up levels, confirmed in matched and unmatched analyses, were: i) AVD: instability in weight (cases vs controls:2.9% vs +2.5%); ii) coronary heart disease: instability in body mass index (3.0% vs +2.3%), a decline (-0.041 vs -0.011 per decade) and instability (19.1% v 14.6%) in the HDL / non-HDL cholesterol ratio, declining ESR and increasing uric acid; iii) cerebrovascular disease: a decline in insulin sensitivity (-0.394 vs 0.324 per decade).

Conclusions: Within an individual, long-term change in metabolic risk factors, as well as their absolute levels, can be important in AVD.