PURPOSE: Cardiovascular disease (CVD) is a potential adverse effect of endocrine treatment (ET) for prostate cancer (PC). We investigated absolute and relative CVD risk in 76,600 patients with PC undergoing ET, curative treatment, or surveillance. METHODS: PCBaSe Sweden is based on the National Prostate Cancer Register, which covers more than 96% of PC cases. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of ischemic heart disease (IHD), acute myocardial infarction (MI), arrhythmia, heart failure, and stroke were calculated to compare observed and expected (using total Swedish population) numbers of CVD, taking into account age, calendar time, and previous CVD. RESULTS: Between 1997 and 2007, 30,642 patients with PC received primary ET, 26,432 curative treatment, and 19,527 surveillance. SIRs for CVD were elevated in all men with the highest for those undergoing ET, independent of circulatory disease history (SIR MI for men without circulatory disease history: 1.40 [95% CI, 1.31 to 1.49], 1.15 [95% CI, 1.01 to 1.31], and 1.20 [95% CI, 1.11 to 1.30] for men undergoing ET, curative treatment, and surveillance, respectively). Absolute risk differences (ARD) showed that two (arrhythmia) to eight (IHD) extra cases of CVD would occur per 1,000 person-years. SMRs showed similar patterns, with ARD of zero (arrhythmia) to three (IHD) per 1,000 person-years. CONCLUSION: Increased relative risks of nonfatal and fatal CVD were found among all men with PC, especially those treated with ET. Because ET is currently the only effective treatment for metastatic disease and the ARDs were rather small, our findings indicate that CVD risk should be considered when prescribing ET but should not constitute a contraindication when the expected gain is tangible.
Background: Androgen deprivation therapy (ADT) is a non-curative but essential treatment of prostate cancer with severe side effects. Therefore, both over- and underuse should be avoided. We investigated adherence to guidelines for ADT following radical prostatectomy through Swedish population-based data.Material and methods: We used the database Uppsala/Örebro PSA cohort (UPSAC) to study men with localised or locally advanced prostate cancer at diagnosis (clinical stage T1-T3, N0-NX, M0-MX, and prostate-specific antigen (PSA)
Non-therapeutic use of anabolic androgenic steroids (AAS) has been associated with various adverse effects; one of the most serious being direct cardiovascular effects with unknown long-term consequences. Therefore, large studies of the association between AAS and cardiovascular outcomes are warranted. We investigated cardiovascular morbidity and mortality in individuals who tested positive for AAS.
Between 2002 and 2009, a total of 2013 men were enrolled in a cohort on the date of their first AAS test. Mortality and morbidity after cohort entry was retrieved from national registries. Of the 2013 individuals, 409 (20%) tested positive for AAS. These men had twice the cardiovascular morbidity and mortality rate as those with negative tests (adjusted hazard ratio (aHR) 2.0; 95% confidence interval (CI) 1.2-3.3). Compared to the Swedish population, all tested men had an increased risk of premature death from all causes (standardized mortality ratio for AAS-positive: 19.3, 95% CI 12.4-30.0; for AAS-negative: 8.3, 95% CI 6.1-11.0).
Non-therapeutic exposure to AAS appears to be an independent risk factor for cardiovascular morbidity and premature death.
Androgen Deprivation Therapies and Changes in Comorbidity: A Comparison of Gonadotropin-releasing Hormone Agonists and Antiandrogen Monotherapy as Primary Therapy in Men with High-risk Prostate Cancer.
Australian Centre for Precision Health, University of South Australia, Adelaide, Australia; Translational Oncology & Urology Research (TOUR), School of Cancer and Pharmaceutical Sciences, King's College London, London, UK. Electronic address: Kerri.email@example.com.
Some studies suggest that gonadotropin-releasing hormone (GnRH) agonists are associated with higher risk of adverse events than antiandrogens (AAs) monotherapy. However, it has been unclear whether this is due to indication bias.
To investigate rates of change in comorbidity for men on GnRH agonists versus AA monotherapy in a population-based register study.
Men with advanced nonmetastatic prostate cancer (PCa) who received primary AA (n=2078) or GnRH agonists (n=4878) and age- and area-matched PCa-free men were selected from Prostate Cancer Database Sweden 3.0. Increases in comorbidity were measured using the Charlson Comorbidity Index (CCI), from 5yr before through to 5yr after starting androgen deprivation therapy (ADT).
Multivariable linear regression was used to determine differences in excess rate of CCI change before and after ADT initiation. Risk of any incremental change in CCI following ADT was assessed using multivariable Cox regression analyses.
Men on GnRH agonists experienced a greater difference in excess rate of CCI change after starting ADT than men on AA monotherapy (5.6% per yr, p
Lifestyle-related risk factors such as hyperglycemia and dyslipidemia have been associated with several cancers. However, studies exploring their link with prostate cancer (PCa) clinicopathological characteristics are sparse and inconclusive. Here, we investigated the associations between serum metabolic markers and PCa clinicopathological characteristics. The study comprised 14,294 men from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort who were diagnosed with PCa between 1996 and 2011. Univariate and multivariable logistic regression were used to investigate the relation between glucose, triglycerides and total cholesterol and PCa risk categories, PSA, Gleason score, and T-stage. Mean age at time of PCa diagnosis was 69 years. Men with glucose levels >6.9 mmol/L tend to have PSA20 µg/L compared to PSA 4.0-9.9 µg/L. Hypertriglyceridemia was also positively associated with PSA>20 µg/L. Hyperglycemic men had a greater odds of intermediate- and high-grade PCa and advanced stage or metastatic PCa. Similarly, hypertriglyceridemia was positively associated with high-grade PCa. There was also a trend toward an increased odds of intermediate risk localized PCa and advanced stage PCa among men with hypertriglyceridemia. Total cholesterol did not have any statistically significant association with any of the outcomes studied. Our findings suggest that high serum levels of glucose and triglycerides may influence PCa aggressiveness and severity. Further investigation on the role of markers of glucose and lipid metabolism in influencing PCa aggressiveness and severity is needed as this may help define important targets for intervention.
Metabolic syndrome (MetS) is associated with non-alcoholic fatty liver disease, which may progress to cirrhosis, a significant risk factor of hepatocellular carcinoma (HCC), the commonest malignant primary liver cancer (PLC). We investigated the association between the individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity), PLC and cirrhosis. A total of 509,436 participants from the Swedish AMORIS cohort, recruited between January 1985 and December 1996 (end-date December 2011), aged =20 with baseline triglycerides (TG), total cholesterol (TC), glucose and liver enzymes were included. Those with baseline benign liver tumours, PLC or cirrhosis were excluded. Multivariate Cox regression, adjusted for age, gender, socio-economic status, liver disease (excluding cirrhosis) and MetS factors were used to estimate the association with PLC and cirrhosis. There were 766 PLC and 2,775 cirrhosis cases over 13 years. Raised TG, low TC, raised glucose, diabetes and low HDL were associated with an increased risk of developing PLC and cirrhosis. ApoB/ApoA-I ratio were also associated with PLC, whilst low LDL, raised TG/HDL, low ApoA-I and low ApoB were associated with cirrhosis. Obesity was significantly associated with PLC but not cirrhosis. Raised TG, low TC, raised glucose and diabetes showed stronger associations with PLC in participants with cirrhosis but many participants developed PLC without cirrhosis. Individual components of MetS (lipids, apolipoproteins, raised glucose, diabetes and obesity) were associated with an increased risk of developing PLC or cirrhosis. MetS components were more strongly associated with PLC with preceding cirrhosis history but many participants developed PLC without cirrhosis.
Cancer Epidemiology Group, Division of Cancer Studies, School of Medicine, King's College London, 3rd Floor, Bermondsey Wing, Guy's Hospital, London SE1 9RT, United Kingdom. firstname.lastname@example.org
Cancer Epidemiol Biomarkers Prev. 2011 Mar;20(3):428-37
To study levels of C-reactive protein (CRP) and leukocytes, as inflammatory markers, in the context of cancer risk.
From the Apolipoprotein MOrtality RISk (AMORIS) study, we selected 102,749 persons with one measurement and 9,273 persons with three repeated measurements of CRP and leukocytes. Multivariate Cox proportional hazards regression was applied to categories of CRP (50 g/L) and quartiles of leukocytes. An inflammation-based predictive score (IPS) indicated whether someone had CRP levels of more than 10 mg/L combined with leukocytes of more than 10×10(9)/L. Reverse causality was assessed by excluding those with less than 3, 5, or 7 years of follow-up. To analyze repeated measurements of CRP and leukocytes, the repeated IPS (IPSr) was calculated by adding the IPS of each measurement.
In the cohort with one measurement, there was a positive trend between CRP and risk of developing cancer, with the lowest category being the 0.99 (0.92-1.06), 1.28 (1.11-1.47), 1.27 (1.09-1.49), and 1.22 (1.01-1.48) for the second to fifth categories, respectively. This association disappeared when excluding those with follow-up of less than 3, 5, or 7 years. The association between leukocytes and cancer was slightly stronger. In the cohort with repeated measurements, the IPSr was strongly associated with cancer risk: 1.87 (1.33-2.63), 1.51 (0.56-4.06), and 4.46 (1.43-13.87) for IPSr=1, 2, and 3 compared with IPSr=0. The association remained after excluding those with follow-up of less than 1 year.
Our large, prospective cohort study adds evidence for a link between inflammatory markers and cancer risk by using repeated measurements and ascertaining reverse causality.
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Previous epidemiological studies have shown positive associations between serum calcium concentration and risk of cardiovascular disease (CVD), but results differ by definition of CVD. We examined the association of circulating calcium with incident and fatal CVD, myocardial infarction (MI), and stroke in the Swedish AMORIS cohort.
We included 441,738 participants of the AMORIS database linked for follow-up information on morbidity and mortality. Concentrations of total calcium were fully automated measured using a colorimetric method; concentrations of albumin were measured with a bromocresol green method between 1985 and 1995. The association of albumin-corrected calcium concentration and risk of incident and fatal CVD, MI, and stroke, respectively, was assessed with multivariable adjusted Cox proportional hazards models.
Until December 31, 2011, during a median follow-up time of 21 years, 90,866 incident cases of CVD, 21,271 of MI, and 25,810 of stroke were identified. High serum calcium concentrations were associated with increased risk of non-fatal CVD (Hazard ratio [HR] = 1.12, 95% CI 1.10-1.14, top [=2.40 nmol/L] vs. bottom [=2-25 nmol/L] quintile), MI (1.19, 1.14-1.25), and stroke (1.11, 1.06-1.15) and fatal disease (CVD: 1.41, 1.35-1.47; MI: 1.41, 1.31-1.51; stroke: 1.30, 1.20-1.41). Effect modification by sex was observed for incident disease such that associations were stronger among women than men. Serum calcium was positively associated with both incident and fatal ischemic stroke and with fatal hemorrhagic stroke, but not with incident hemorrhagic stroke. In a sub-groups analysis, the results remained significant after adjustment for smoking.
The results support a modest positive association between serum calcium and risk of CVD, but the underlying mineral metabolism and the exact mechanisms are currently unclear.
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden; Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University Hospital, Umeå, Sweden. Electronic address: email@example.com.