Rate of change and instability in body mass index, insulin resistance, and lipid metabolism as predictors of atherosclerotic vascular disease

Context: By definition, levels of metabolic risk factors predict atherosclerotic vascular disease, but the effects of long-term adverse change and instability remain underresearched. Objective: Our objective was to quantify long-term rates of change and instability in risk factors and relate these measures to clinical atherosclerotic vascular disease outcomes. Design and Setting: We conducted a prospective cohort study with unmatched and age- and follow-up-matched control analyses at a teaching hospital day ward. Participants: Participants included 465 predominantly healthy white males in an occupational cohort who had undergone repeated metabolic risk factor measurements ( mean observation period 11.6 yr, range 2-28 yr), 62 of whom developed clinical atherosclerotic vascular disease. 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 atherosclerotic vascular disease 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 subclinical inflammation were significant predictors. Predictors independent of baseline and mean follow-up levels, confirmed in matched and unmatched analyses, were 1) for atherosclerotic vascular disease, instability in weight ( cases vs. controls: 2.9 vs. +2.5%); 2) for 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 vs. 14.6%) in the high-density lipoprotein/non-high-density lipoprotein cholesterol ratio, declining erythrocyte sedimentation rate, and increasing uric acid; and 3) for 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 atherosclerotic vascular disease.