PROJECT SUMMARY/ABSTRACT
Cardiovascular disease (CVD) is the leading cause of death in the US and globally. Physical activity has been
clearly shown to improve CVD risk factors and reduce disease incidence; thus, the US (and other countries)
have guidelines for physical activity. Current guidelines call for both aerobic exercise (AE; e.g., walking) and
resistance exercise (RE; e.g., weight lifting). Research on AE, including its dose-response, and health has
been extensive; consequently, guidelines are clear on what should be done (≥150 min/week of moderate
intensity AE). In contrast, there is only limited research on RE; thus, guidelines lack clarity (2 times/week, but
with unspecified duration). A recent meta-analysis of observational studies reported a J-shaped relation where
more time in RE was associated with lower CVD risk only up to 60 min/week, beyond which CVD risk reduction
attenuated, and indeed appeared to increase at ≥130 min/week. While it remains unclear, postulated
mechanisms that may underlie the higher CVD risk with higher RE doses include increased arterial stiffness
due to increased sympathetic activity during RE and chronic inflammation occurring with higher RE doses,
leading to atherosclerosis and systemic vascular damage.
There are currently no randomized controlled trials that have directly tested and compared multiple doses of
RE on CVD risk factors in general population. Thus, to provide data that are crucial for exercise prescription
and translation to public health practice, this proposal seeks to conduct a randomized controlled trial among
240 adults with overweight or obesity (since adiposity increases CVD risk). In the first 6 months (Phase 1), they
will participate in a supervised, lab-based RE training phase. Participants will be randomly assigned to 4 doses
of RE (n=60 per group): 0 min/session (control), 15 min/session, 30 min/session, or 60 min/session, all for 2
sessions/week per current RE guidelines. All 4 groups also will be asked to do AE for 30 min/session, 2
sessions/week, congruent with the current guidelines that require both RE and AE. A primary aim will be to
assess changes from baseline to 6 months in a composite CVD risk score using 4 well-established CVD risk
factors: systolic blood pressure, low-density lipoprotein cholesterol, fasting glucose, and percent body fat.
There will be sufficient statistical power to detect changes in the risk score, based on prior data. Another
primary aim will be to examine potential mechanisms underlying the J-shaped relation of RE on CVD risk, by
assessing changes from baseline to 6 months in aortic arterial stiffness (purse wave velocity) and inflammatory
markers (e.g., CRP, IL-6, TNF-α). In the second 6 months (Phase 2), there will be an unsupervised, self-
maintenance phase where all will be provided with free health club memberships and asked to continue with
their assigned intervention in Phase 1. Continued adherence to their assigned RE dose will be assessed to
address the secondary aim of: which dose(s) will engender best participation in a free-living situation?
This trial will fill important gaps in knowledge on effective, safe, and practical dose(s) of RE for CVD prevention.