ArticlesAssociation between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis
Introduction
Clinical trials have shown that lifestyle interventions can effectively reduce the risk of developing type 2 diabetes in high-risk individuals with impaired glucose tolerance,1, 2 and detailed modelling analyses have shown them to be highly cost-effective in the prevention of type 2 diabetes.3, 4 Consequently, lifestyle changes form the cornerstone of diabetes prevention initiatives that have been translated into routine clinical practice.5, 6 However, whether changes to lifestyle factors affect the risk of cardiovascular disease in individuals with impaired glucose tolerance is unclear, since previous diabetes prevention trials were not designed, and consequently lack sufficient power, to assess this outcome. This is an important limitation, since cardiovascular disease is the most deleterious consequence of dysglycaemia and the primary cause of death in those with type 2 diabetes.7
Observational studies have consistently shown that higher levels of physical activity or cardiorespiratory fitness are associated with a lower risk of cardiovascular morbidity and mortality.8, 9, 10, 11 However, this evidence has been limited by several factors. Physical activity is usually assessed by self-reported questionnaires, which are known to have poor validity, particularly when assessing habitual or total physical activity levels.12 Alternatively, cardiorespiratory fitness, even when measured objectively, is affected by factors beyond physical activity, including genetic makeup, which also affect survival.13 Along with limitations around measurement, the extent to which change in physical activity can act to ameliorate the risk of cardiovascular disease in individuals already displaying impaired glucose tolerance and other cardiovascular risk factors is also unknown.
The NAVIGATOR trial provides the first detailed opportunity in an international pharmacotherapy trial to investigate whether change in objectively-assessed ambulatory activity is associated with a lower risk of a cardiovascular event independently of randomised therapy allocation, other lifestyle factors, or body-mass index.
Section snippets
Study design and population
We analysed prospective data from NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research),14, 15, 16 a multicentre, randomised, placebo controlled, 2 × 2 factorial trial designed to investigate whether nateglinide (meglitinide analogue) or valsartan (angiotensin II receptor antagonist) reduce the risk of cardiovascular events in individuals with impaired glucose tolerance and either existing cardiovascular disease (if 50 years or older) or with at least one
Results
Follow-up data for cardiovascular events were available for 9018 participants over an average of 5 years after the 12-month landmark; characteristics including those with imputed data, are given in the appendix. Compared to patients with complete pedometer data at baseline and 12 months, those with missing pedometer data across at least one timepoint were more likely to be from Europe (55·0% [2568 of 4673] for missing data vs 50·8% [2209 of 4345] for complete data) or North America (25·4% [1189
Discussion
Both baseline ambulatory activity and change in ambulatory activity over 12 months were associated independently with the risk of a cardiovascular event in the ensuing 5 years. Specifically, every 2000 step per day increment in ambulatory activity at baseline (roughly equivalent to 20 min a day of moderately-paced walking activity18) was associated with a 10% lower risk of a cardiovascular event. Moreover, each 2000 step per day change from baseline to 12 months was associated with an
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