Androgen deprivation therapy for prostate cancer, measures of adiposity and strength, and adverse cardiovascular outcomes: observations from 3000 men in 5 countries in the RADICAL PC study
Key result
Lower handgrip strength linked to ~24% higher cardiovascular risk per quartile reduction.
- HR 1.24
- 95% CI 1.01-1.52
- n=3,080
Why the study?
No prostate cancer study had examined the relationship between physical characteristics, their change with ADT, and cardiovascular outcomes.
Does androgen deprivation therapy alter adiposity and muscle strength, and do these physical measures predict adverse cardiovascular outcomes in men with prostate cancer?
Key Points
- To assess one-year changes in physical measures among men with prostate cancer receiving versus not receiving androgen deprivation therapy and determine their link to adverse cardiovascular outcomes.
- Prospective cohort evaluation of 3,080 men with prostate cancer (mean age 68 years; 41% receiving androgen deprivation therapy) recruited across 37 sites in 5 countries.
- Measured body weight, waist and hip circumference, handgrip strength, and get-up-and-go time at baseline and 1 year, adjusting for demographic and clinical covariates.
- Tracked participants over a median of 3 years for adiposity-related cardiovascular events, evaluating associations with baseline physical measures using multivariable Cox proportional hazards models.
- Androgen deprivation therapy recipients gained 5-fold more weight, experienced a 43% larger decline in muscle strength, and showed a 13% reduction in gait speed compared to non-recipients at 1 year.
- Over follow-up, 144 adverse cardiovascular events occurred, exhibiting a continuous inverse relationship with handgrip strength (adjusted HR 1.24, 95% CI 1.01–1.52 per quartile reduction).
- No statistically detectable associations were observed between other physical measures, including weight and waist-to-hip ratio, and adverse cardiovascular events.
Study Design
Type
Cohort (n=3,080)
Multicenter
Yes
Structured PICO
Does androgen deprivation therapy alter adiposity and muscle strength, and do these physical measures predict adverse cardiovascular outcomes in men with prostate cancer?
P
Population
3,080 men (mean age 68) with newly diagnosed or recently treated prostate cancer, followed for a median of 3 years to evaluate the impact of ADT on physical measures and cardiovascular outcomes.
E
Exposure
Androgen deprivation therapy (ADT)
C
Comparator
Not receiving ADT
O
Outcome
1-year changes in physical measures (weight, waist and hip circumference, handgrip strength, get-up-and-go time) and adverse cardiovascular outcomes (myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism and atrial fibrillation) over median 3 years follow-up.composite
Main Result
Hazard Ratio: 1.24 (95% CI 1.01–1.52)
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
Darryl P. LeongCardiologist and senior scientist, Population Health Research Institute, McMaster University“Future research should seek to determine whether increasing muscle strength in patients with [prostate cancer] can reduce the risk for adverse cardiovascular outcomes.”
Implication
In men with prostate cancer, reduced muscle strength as reflected by low handgrip strength predicts adverse cardiovascular outcomes better than increased adiposity, potentially explaining the cardiovascular risk associated with ADT.
Abstract
Background Androgen deprivation therapy (ADT) is prescribed to nearly half of patients with prostate cancer (PC). ADT is associated with weight gain, reduced muscle strength and increased cardiovascular (CV) risk. However, no PC study has examined the relationship between these physical characteristics, their change with ADT and cardiovascular outcomes. Purpose In men with PC: To compare 1-year changes in physical measures in those receiving versus not receiving ADT To evaluate the relationship between physical measures and adverse CV outcomes Methods We prospectively studied 3080 men with PC from 37 sites in 5 countries (mean age 68 years), 41% on ADT. Inclusion criteria were one of: PC diagnosed in the past 12 months; started ADT within the past 6 months; or plan to start ADT in the next month. Weight, waist and hip circumference, handgrip strength and get-up-and-go time were recorded at baseline and 1 year. Change in measurements were adjusted for age, education, race, tobacco and alcohol use, baseline cardiovascular disease and renal function. Participants were followed for a median 3 years from enrolment to document adverse CV outcomes associated with adiposity: myocardial infarction, angina, stroke, cerebrovascular disease, peripheral arterial disease, arterial revascularization, heart failure, venous thromboembolism and atrial fibrillation. The relationship between baseline physical measures and outcomes was evaluated by Cox proportional hazards models adjusted for age, diabetes, hypertension, total cholesterol, tobacco use and physical activity levels. Results Changes in physical measures are displayed in Table. ADT recipients gained 5x more weight than non-recipients. Weight gain was distributed evenly between waist and hips, resulting in no difference in waist:hip ratio. Muscle strength decreased in both groups but with 43% larger decrease among ADT recipients. The ratio of strength to body weight fell twice as much in ADT recipients as non-recipients. Gait speed slowed by 13% after 12 months’ ADT. We observed 144 adverse CV events. There was a continuous relationship between handgrip strength and CV events. Each quartile reduction in strength was associated with adjusted hazard ratio (95% CI) 1.24 (1.01-1.52). There was no detectable association between other physical measures and CV events. Conclusion ADT use is associated with increased adiposity and reduced muscle strength. Low muscle strength, reflected by low handgrip strength is a better predictor of adverse CV outcomes than increased adiposity. These findings may explain help the association between ADT use and adverse CV outcomes.
Discussion
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Cite This Study
Leong et al. (2023) conducted a cohort in Prostate cancer (n=3,080). Handgrip strength reduction vs. Higher handgrip strength was evaluated on Adverse cardiovascular events (HR 1.24, 95% CI 1.01-1.52). Each quartile reduction in handgrip strength was associated with an increased risk of adverse cardiovascular events (HR 1.24; 95% CI 1.01-1.52).