Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer: Contemporary Meta-Analyses

Hu, Jiun-Ruey; Duncan, Meredith S.; Morgans, Alicia K.; Brown, J.; Meijers, Wouter C.; Freiberg, Matthew S.; Salem, Joe‐Elie; Beckman, Joshua A.; Moslehi, Javid

doi:10.1161/atvbaha.119.313046

Cited by 124 publications

(128 citation statements)

References 69 publications

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“…Despite publications on multiple studies and meta-analyses, the effect of ADT on patients was still controversial. In general, meta-analysis of observational studies supported a positive relationship between increased cardiovascular risk and ADT, while the results from randomized studies were negative 9 . Hu et al proposed that the reason for the conflicting outcomes might be related to the study designs 9 .…”

Section: Discussionmentioning

confidence: 92%

“…While most of the observational studies on Caucasian population indicated that ADT would increase the cardiovascular risk of patients 9,22 , the results for Asians suggested otherwise. In several observational studies based on national insurance databases in different populations, the results did not show an increased cardiovascular risk in Asian patients receiving ADT [13][14][15] .…”

Section: Discussionmentioning

confidence: 98%

“…Despite these controversies, a joint statement was issued by the American Urological Association, the American Society for Radiation Oncology and the American Heart Association to raise physicians’ awareness about the potential association between ADT and cardiovascular disease 8 . Nevertheless, the evidence is still inconclusive even in latest meta-analyses 9 .…”

Section: Introductionmentioning

confidence: 99%

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Effect of androgen deprivation therapy on cardiovascular function in Chinese patients with advanced prostate cancer: a prospective cohort study

Chiu

Yee

et al. 2020

Sci Rep

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Androgen deprivation therapy (ADT) is the standard treatment for advanced prostate cancer, but its effect on cardiovascular and metabolic function in Asian patients is still inconclusive. We prospectively assess the effects of ADT on 36 patients with advanced prostate cancer, with reference to another 24 prostate cancer patients not requiring ADT, for 2 years. Patients’ anthropometric, metabolic and vascular parameters were assessed every six-monthly. The baseline parameters of the two groups were comparable. There was a significant negative effect of the usage of ADT on the changes in BMI (p = 0.020), waist to hip ratio (p = 0.005), body fat percentage (p = 0.012), and high-density-lipoprotein (p = 0.012). ADT-patients were 4.9 times more likely to have metabolic syndrome at 24 months. (CI 0.889–27.193, p = 0.068). The Framingham risk score (p = 0.018) and pulse-wave-velocity (p = 0.024) for ADT-group were also significantly higher than controls, which signified increase in cardiovascular risk. Although there was no statistically significant difference in ischemic cardiovascular events between two groups, a trend for more events in ADT-group was observed. Therefore, Asian patients have increased cardiovascular and metabolic risks after being treated with ADT for two years. Appropriate counselling and monitoring of associated complications with ADT are essential.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Effect of androgen deprivation therapy on cardiovascular function in Chinese patients with advanced prostate cancer: a prospective cohort study

Chiu

Yee

et al. 2020

Sci Rep

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“…However, compared to the surgery-only group, the ADT group had markedly greater risk of IHD and stroke. While many studies have shown that ADT is associated with CVD [5][6][7][8][9][10][11][12][13][14] , other studies [15][16][17] have demonstrated conflicting results, which were attributed to differences in the prior history of CV events or type and duration of ADT. A meta-analysis using randomized controlled trials (RCTs) suggested no increased risk of fatal CVD associated with ADT 17 , but pooled analyses of observational studies showed consistent evidence of increased risk of CVD, regardless of the type of ADT therapy 6 .…”

Section: Discussionmentioning

confidence: 99%

Risk of Ischemic Heart Disease and Stroke in Prostate Cancer Survivors: A Nationwide Study in South Korea

Shin

Han

Park

et al. 2020

Sci Rep

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In this study using national health insurance data, we investigated the risk of ischemic heart disease (IHD) and stroke among prostate cancer (PC) survivors compared with the general population, as well as the risk of cardiovascular disease (CVD) according to primary treatment. A total of 48,298 PC patients diagnosed from 2007 to 2013 were included and matched to non-cancer controls. Compared to the general population, PC survivors had a slightly lower risk of IHD (adjusted hazard ratio [aHR] = 0.89, 95% confidence interval [CI] 0.83-0.96) or stroke (aHR 0.90, 95% CI 0.87-0.95). Especially, survivors who underwent surgery had lower risks of IHD (aHR 0.70, 95% CI 0.61-0.80) or stroke (aHR 0.73, 95% CI 0.67-0.81). Compared to survivors in the active surveillance/watchful waiting group, the androgen deprivation therapy (ADT) group had a significantly greater risk of stroke (aHR 1.16, 95% CI 1.02-1.32), but the IHD risk was not significantly elevated (aHR 1.06, 95% CI 0.88-1.29). In conclusion, PC survivors had a slightly lower risk of CVD compared to the general population, which was attributable to self-selection for PSA screening, specifically in the surgery-only group. CVD risk was dependent on treatment received, and attention should be given to patients who receive ADT. Cancer survivor is defined as any person diagnosed with cancer, from the time of diagnosis until his or her death. With improved survival and the increased number of prostate cancer (PC) survivors 1 , management of comorbidities has become increasingly important for this population 2. Cardiovascular disease (CVD) is reported to be the main cause of mortality in PC survivors in the US, comprising 20% of overall mortality, and surpassing mortality from PC and second primary malignancies 3. In a Korean cohort study, CVD was responsible for 29.1% of non-PC mortality in long-term PC survivors 4. Many studies have analyzed the risk of CVD in PC patients treated with androgen deprivation therapy (ADT) 5-17 , but it is not certain whether PC survivors have a greater risk of CVD compared to the general population. To date, only a few studies have compared the CVD risk between PC survivors and the general population 18-20 , but the results were inconsistent: a Swedish study suggested elevated risk 18 , a UK study reported similar risk 19 , and a US study demonstrated lower risk 20. Among these studies, only the Swedish study analyzed the CVD risk according to treatment modality (i.e., surveillance, curative treatment, endocrine therapy) 18. Thus, the risk of CVD among PC survivors who underwent different types of treatment has not been assessed definitively. In addition, there are no reports from Asian countries, where practice patterns may differ from Western countries 21. To address these limitations, we used a Korean national healthcare database to investigate the CVD risk among PC survivors compared with general population controls, as well as the risk of CVD according to primary treatment. Methods Data Source: Korean national Health insurance Service...

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“…Low serum testosterone levels are associated with increased atherosclerosis and risk of cardiovascular mortality, both in men with spontaneous age-associated serum testosterone decline [1], and in patients receiving androgen deprivation therapy (ADT) to control prostate cancer [2]. Meta-analysis of randomized clinical trials of ADT, on the other hand, has failed to replicate the finding from observational studies and causality of the association between castration and cardiovascular disease thus remains unresolved [3].…”

Section: Introductionmentioning

confidence: 99%

Effects of castration on atherosclerosis in Yucatan minipigs with genetic hypercholesterolemia

et al. 2020

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Background Low plasma testosterone, either spontaneous or as a result of androgen deprivation therapy for prostate cancer, is associated with an increased risk of cardiovascular events. The underlying mechanism in humans is not understood. Experimental studies in mice have shown that castration facilitates atherogenesis and may increase signs of plaque vulnerability. Pigs used for translational atherosclerosis research have frequently been castrated for practical or commercial reasons, but the effect of castration on atherosclerosis has never been systematically evaluated in pigs. Objective To study the effect of castration on atherosclerotic plaque burden and type in genetically modified minipigs with hypercholesterolemia. Methods Newborn male Yucatan minipigs with transgenic overexpression of a human gain-of-function mutant of proprotein convertase subtilisin/kexin type 9 were randomized to undergo orchiectomy (n = 8) or serve as controls (n = 6). Minipigs were started on high-fat diet at 3 months of age and the amount and composition of atherosclerotic lesions were analyzed at 12 months of age. Plasma lipid profiles and behavioral parameters were also assessed. Results Plasma lipids were slightly affected to a more atherogenic profile by orchiectomy, but atherosclerotic lesion size was unaltered in the LAD, thoracic aorta, abdominal aorta, and iliac arteries. The distribution of lesion types (xanthomas, pathological intimal thickening and fibroatheromas) were also not statistically different between groups in any of the examined vascular territories. The abdominal aorta developed the most advanced stages of disease with reproducible fibroatheroma formation, and here it was found that the area of necrotic

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Cardiovascular Effects of Androgen Deprivation Therapy in Prostate Cancer: Contemporary Meta-Analyses

Cited by 124 publications

References 69 publications

Effect of androgen deprivation therapy on cardiovascular function in Chinese patients with advanced prostate cancer: a prospective cohort study

Effect of androgen deprivation therapy on cardiovascular function in Chinese patients with advanced prostate cancer: a prospective cohort study

Risk of Ischemic Heart Disease and Stroke in Prostate Cancer Survivors: A Nationwide Study in South Korea

Effects of castration on atherosclerosis in Yucatan minipigs with genetic hypercholesterolemia

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