Research Paper Title

History of Cardiovascular Disease, Intensive Lifestyle Intervention, and Cardiovascular Outcomes in the Look AHEAD Trial.

Background

To examine the effects of an intensive lifestyle intervention (ILI) on cardiovascular disease (CVD), the Action for Health in Diabetes (Look AHEAD) trial randomised 5,145 participants with type 2 diabetes and overweight/obesity to a ILI or diabetes support and education.

Although the primary outcome did not differ between the groups, there was suggestive evidence of heterogeneity for pre-specified baseline CVD history subgroups (interaction P = 0.063).

Event rates were higher in the ILI group among those with a CVD history (hazard ratio 1.13 [95% CI: 0.90-1.41]) and lower among those without CVD (hazard ratio 0.86 [95% CI: 0.72-1.02]).

Methods

This study conducted post hoc analyses of the rates of the primary composite outcome and components, adjudicated cardiovascular death, nonfatal myocardial infarction (MI), stroke, and hospitalisation for angina, as well as three secondary composite cardiovascular outcomes.

Results

Interaction P values for the primary and two secondary composites were similar (0.060-0.064). Of components, the interaction was significant for nonfatal MI (P = 0.035).

This interaction was not due to confounding by baseline variables, different intervention responses for weight loss and physical fitness, or hypoglycemic events.

In those with a CVD history, statin use was high and similar by group.

In those without a CVD history, low-density lipoprotein cholesterol levels were higher (P = 0.003) and statin use was lower (P ≤ 0.001) in the ILI group.

Conclusions

Intervention response heterogeneity was significant for nonfatal MI.

Response heterogeneity may need consideration in a CVD-outcome trial design.

Reference

Look AHEAD Research Group., Lewis, C.E., Bantle, J.P., Bertoni, A.G., Blackburn, G., Brancati, F.L., Bray, G.A., Cheskin, L.J., Curtis, J.M., Egan, C., Evans, M., Foreyt, J.P., Ghazarian, S., Barone Gibbs, B., Glasser, S.P., W Gregg, E., Hazuda, H.P., Hesson, L., Hill, J.O., Horton, E.S., Hubbard, V.S., Jakicic, J.M., Jeffery, R.W., Johnson, K.C., Kahn, S.E., Kitabchi, A.E., Kitzman, D., Knowler, W.C., Lipkin, E., Michaels, S., Montez, M.G., Nathan, D.M., Nyenwe, E., Patricio, J., Peters, A., Pi-Sunyer, X., Pownall, H., Reboussin, D.M., Ryan, D.H., Wadden, T.A., Wagenknecht, L.E., Wyatt, H., Wing, R.R. & Yanovski, S.Z. (2020) History of Cardiovascular Disease, Intensive Lifestyle Intervention, and Cardiovascular Outcomes in the Look AHEAD Trial. Obesity (Silver Spring). 28(2), pp.247-258. doi: 10.1002/oby.22676. Epub 2020 Jan 3.