Individual Variability of Coronary Heart Disease Risk Markers and Sleep Responses to Exercise

A Replicated Crossover Study Exploring Individual Variability of Postprandial Coronary Heart Disease Risk Markers and Sleep Quality in Response to Acute Exercise in Healthy Young Men

The aim of this study is to examine the reproducibility of postprandial coronary heart disease (CHD) risk marker and sleep responses to acute exercise bouts and to quantify the magnitude of individual variability in responses using a replicated crossover design. Healthy, recreationally active men will complete two identical rest control and two identical exercise (60 min at 60% maximum oxygen uptake) conditions in randomised sequences. Fasting and postprandial venous blood samples, arterial blood pressure and arterial stiffness measurements will be taken at pre-determined intervals, and sleep duration and quality will be assessed. Reproducibility and individual variability will be examined using bivariate correlations and linear mixed modelling.

Single bouts of exercise reduce circulating concentrations of postprandial triacylglycerol - an established independent risk marker for coronary heart disease (CHD). The exercise-induced reduction in postprandial triacylglycerol concentrations has been shown to coincide with transient changes in other CHD risk markers, including reductions in postprandial insulin, interleukin-6, arterial stiffness and resting arterial blood pressure, and exercise may also promote sleep duration and quality. Individual variability in these responses is suspected but has not been examined using robust designs and appropriate statistical models. A recent approach to quantify individual variability in the intervention response involves quantifying the participant-by-condition interaction from replicated intervention and comparator arms. Using this approach (the replicated crossover design), the present study will (i) examine whether the postprandial CHD risk marker and sleep responses to acute exercise are reproducible on repeated occasions; and (ii) determine whether there is true individual variability in postprandial CHD risk marker and sleep responses to acute exercise. A total of 20 healthy, recreationally active men will be recruited. Participants will undertake a preliminary measures visit (visit 1) to confirm eligibility, to undergo anthropometric measurements and to determine maximum oxygen uptake. Participants will complete four, 2-day experimental conditions in randomised sequences separated by at least one week: two identical control and two identical exercise conditions. On day 1 (visits 2, 4, 6 and 8), participants will arrive fasted at 08:00 and a baseline blood sample, blood pressure and arterial stiffness measurement will be taken. Participants will consume a standardised high fat breakfast at 08:45 (0 h) and lunch at 12:45 (4 h). A second arterial stiffness measurement will be taken at 16:45 (8 h). The two control and two exercise conditions will be identical, except that participants will be asked to exercise on the treadmill for 60 minutes at 60% of their maximum oxygen uptake at 15:15 (6.5 h) in both exercise conditions. On day 2 (visits 3, 5, 7 and 9), participants will arrive fasted at 08:00 and will rest in the laboratory throughout the day in the two control and two exercise conditions. Participants will consume a standardised breakfast at 08:45 (0 h) and a standardised lunch at 12:45 (4 h). Venous blood samples will be collected at 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h. Resting arterial blood pressure will be measured at hourly intervals. Arterial stiffness will be measured at 0, 2.5 and 5 h. Sleep duration and quality will be assessed for three nights before and two nights after visits 3, 5, 7 and 9 using a triaxial actigraphy watch. Reproducibility and individual variability will be explored by correlating the two sets of response differences between exercise and control conditions. Within-participant covariate-adjusted linear mixed models will be used to quantify participant-by-condition interactions. It is hypothesised that (i) control-adjusted postprandial CHD risk marker and sleep responses to acute exercise will be reproducible; and (ii) true interindividual variability will exist in postprandial CHD risk marker and sleep responses to acute exercise beyond any random within-subject variation.

Participants will rest in the laboratory on day 1 and day 2 (08:00-17:00). A high fat breakfast and lunch will be consumed on both days at pre-determined intervals.

Participants will rest in the laboratory on day 1 and day 2 (08:00-17:00). A high fat breakfast and lunch will be consumed on both days at pre-determined intervals.

Participants will complete 60 min of treadmill exercise on day 1 (15:15-16:15). Participants will rest in the laboratory for the remainder of day 1 and throughout day 2 (08:00-17:00). A high fat breakfast and lunch will be consumed on both days at pre-determined intervals.

Participants will complete 60 min of treadmill exercise on day 1 (15:15-16:15). Participants will rest in the laboratory for the remainder of day 1 and throughout day 2 (08:00-17:00). A high fat breakfast and lunch will be consumed on both days at pre-determined intervals.

Fasted plasma triacylglycerol concentration on day 1 and day 2. Time-averaged total area under the curve for triacylglycerol on day 2 in response to exercise and/or feeding.

Day 1: fasted; Day 2: fasted (0 hours), 0.5 hours, 1 hours, 2 hours, 3 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours and 8 hours

Fasted plasma glucose concentration on day 1 and day 2. Time-averaged total area under the curve for glucose on day 2 in response to exercise and/or feeding.

Day 1: fasted; Day 2: fasted (0 hours), 0.5 hours, 1 hours, 2 hours, 3 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours and 8 hours

Fasted plasma insulin concentration on day 1 and day 2. Time-averaged total area under the curve for insulin on day 2 in response to exercise and/or feeding.

Day 1: fasted; Day 2: fasted (0 hours), 0.5 hours, 1 hours, 2 hours, 3 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours and 8 hours

Fasted resting systolic and diastolic blood pressure on day 1 and day 2. Time-averaged total area under the curve for systolic and diastolic blood pressure on day 2 in response to exercise and/or feeding.

Day 1: fasted; Day 2: fasted (0 hours), 1 hours, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours and 8 hours

Time-course of resting pulse wave analysis in response to exercise and/or feeding on day 1 and day 2.

Time-course of resting pulse wave velocity in response to exercise and/or feeding on day 1 and day 2.

Number of times that sleep is terminated after one minute expressed as a percentage of the total sleep time.

Inclusion Criteria: 18 to 45-year-old men; Be able to run continuously for 1 hour; Body mass index between 18.5 and 29.9 kg/m2; No known contradictions to maximal exertion exercise (e.g., recent musculoskeletal injury, congenital heart disease). Exclusion Criteria: Musculoskeletal injury that has affected normal ambulation within the last month; Uncontrolled exercise-induced asthma; Coagulation or bleeding disorders; Heart conditions; Diabetes (metabolism will be different to non-diabetics potentially skewing the data); Taking any medication that might influence fat metabolism, blood glucose or appetite; Smoking (including vaping); Dieting or restrained eating behaviours; Weight fluctuation greater than 3 kg in the previous 3 months to study enrolment; Presence of any diagnosed sleeping disorder; A food allergy.

Anonymised individual participant data for all primary and secondary outcome measures will be made available upon request.

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