Introduction: Metabolic syndrome (MetSyn) reportedly confers higher risk of cardiovascular disease (CVD) than its individual components. Although typically defined as a binary exposure, each of its component factors can vary over time. Little is known about whether CVD risk differs according to MetSyn stability.
Methods: We defined longitudinal states of obesity and metabolic health among 2,952 Framingham Offspring Study participants for whom we had sufficient data to define MetSyn at ≥4 exams between Exams 2 (1979-1983) and 9 (2011-2014). Obesity was defined as BMI ≥30 kg/m2, high triglycerides as ≥150 mg/dL/taking lipid-lowering medication, low HDL as <40 mg/dL for males/ <50 mg/dL for females; high blood pressure as systolic blood pressure ≥130 mm Hg/diastolic blood pressure ≥85 mm Hg/taking antihypertensive medication, and high blood glucose as ≥100 mg/dL/taking antidiabetic medication. Metabolic health was defined as having <2 metabolic conditions. Obesity and metabolic health were classified as unstable if there was a change from one state to the other in ≥33% of observations occurring before a CVD event or end of follow-up, stable obese/metabolically unhealthy if not unstable and >50% of observations were classified as stable obese/metabolically unhealthy, or stable non-obese/metabolically healthy otherwise. CVD was defined as any of the following coronary death, myocardial infarction, coronary insufficiency, angina pectoris, stroke, transient ischemic attack, intermittent claudication, or congestive heart failure. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) using Cox proportional hazards regression with age as the time scale.
Results: We classified 332 participants (11.3%) as having unstable metabolic health, and 130 (4.4%) as having unstable obesity. We observed 1,206 events in 75,673 person-years of follow-up (median 30 years). Participants classified as stable metabolically unhealthy had the highest CVD risk (HR 1.77, 95% CI 1.47, 2.13, compared to stable metabolically healthy). Stable obesity was associated with a 48% (95% CI 24, 80) increase in CVD risk relative to stable non-obese. Unstable metabolic health and obesity were associated with moderate increases in risk compared to stable metabolically healthy and stable non-obese (HRs: 1.32, 95% CI 1.03, 1.71 and 1.25, 95% CI 0.88, 1.77, respectively). There was no interaction between obesity- and metabolic health stability (pinteraction=0.23).
Conclusions: In our sample, stability of obesity and of metabolic health influenced CVD risk, with the highest risk of CVD observed among stable metabolically unhealthy participants. Instability of both obesity and metabolic health convey a risk intermediate between the stable obese/metabolically healthy and stable non-obese/metabolically unhealthy conditions.