Mieke Van Hemelrijck

Absolute and Relative Risk of Cardiovascular Disease in Men With Prostate Cancer: Results From the Population-Based PCBaSe Sweden.

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.

Cohort Profile: The National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

Quantifying Observational Evidence for Risk of Fatal and Nonfatal Cardiovascular Disease Following Androgen Deprivation Therapy for Prostate Cancer: A Meta-analysis

CONTEXT Whether androgen deprivation therapy (ADT) for men with prostate cancer (PCa) increases the risk of cardiovascular disease (CVD) remains controversial. Pooled analyses using data from randomised controlled trials suggest no increased risk of fatal CVD following ADT, but no pooled analyses exist for observational studies. OBJECTIVE To perform a meta-analysis using observational data on ADT and risk of CVD events in men with PCa. EVIDENCE ACQUISITION PubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on associations between types of ADT and nonfatal and fatal CVD outcomes using information from observational studies. Random effects meta-analyses were conducted to estimate relative risks (RRs) and 95% confidence intervals (CIs). EVIDENCE SYNTHESIS A total of eight observational studies were identified studying at least one type of ADT and a nonfatal or fatal CVD outcome. The RR for risk of any type of nonfatal CVD was 1.38 (95% CI, 1.29-1.48) for men with PCa on gonadotropin-releasing hormone (GnRH) agonists, compared with men not treated with ADT. When analysing nonfatal ischemic heart disease only, the RR was 1.39 (95% CI, 1.26-1.54). The associations between GnRH agonists and nonfatal or fatal myocardial infarction or stroke were even stronger: RR: 1.57 (95% CI, 1.26-1.94) and RR: 1.51 (95% CI, 1.24-1.84), respectively. The results for other types of ADT in relation to the risk of any nonfatal CVD were RR: 1.44 (95% CI, 1.28-1.62) for orchiectomy and RR: 1.21 (95% CI, 1.07-1.367) for antiandrogens. CONCLUSIONS Observational data show a consistent positive association between ADT and the risk of CVD. This finding supports the need for future randomised trials of PCa patients that include older patients and men with multiple comorbidities to better reflect the general population. PATIENT SUMMARY We investigated all the available data from observational studies on hormonal treatment for prostate cancer and its possible cardiovascular adverse effects. We found consistent evidence that this treatment may increase the risk of cardiovascular disease.

Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

PURPOSE Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. METHODS By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. RESULTS From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. CONCLUSION Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

Blood Pressure and Risk of Cancer Incidence and Mortality in the Metabolic Syndrome and Cancer Project

Observational studies have shown inconsistent results for the association between blood pressure and cancer risk. We investigated the association in 7 cohorts from Norway, Austria, and Sweden. In total, 577799 adults with a mean age of 44 years were followed for, on average, 12 years. Incident cancers were 22184 in men and 14744 in women, and cancer deaths were 8724 and 4525, respectively. Cox regression was used to calculate hazard ratios of cancer per 10-mmHg increments of midblood pressure, which corresponded with 0.7 SDs and, for example, an increment of systolic/diastolic blood pressure of 130/80 to 142/88 mmHg. All of the models used age as the time scale and were adjusted for possible confounders, including body mass index and smoking status. In men, midblood pressure was positively related to total incident cancer (hazard ratio per 10 mmHg increment: 1.07 [95% CI: 1.04–1.09]) and to cancer of the oropharynx, colon, rectum, lung, bladder, kidney, malignant melanoma, and nonmelanoma skin cancer. In women, midblood pressure was not related to total incident cancer but was positively related to cancer of the liver, pancreas, cervix, uterine corpus, and malignant melanoma. A positive association was also found for cancer mortality, with HRs per 10-mmHg increment of 1.12 (95% CI: 1.08–1.15) for men and 1.06 (95% CI: 1.02–1.11) for women. These results suggest a small increased cancer risk overall in men with elevated blood pressure level and a higher risk for cancer death in men and women.

Risk of thromboembolic diseases in men with prostate cancer: results from the population-based PCBaSe Sweden

Summary Background Cancer is associated with an increased risk of thromboembolic diseases, but data on the association between prostate cancer and thromboembolic diseases are scarce. We investigated the risk of thromboembolic disease in men with prostate cancer who were receiving endocrine treatment, curative treatment, or surveillance. Methods We analysed data from PCBaSe Sweden, a database based on the National Prostate Cancer Register, which covers over 96% of prostate cancer cases in Sweden. Standardised incidence ratios (SIR) of deep-venous thrombosis (DVT), pulmonary embolism, and arterial embolism were calculated by comparing observed and expected (using the total Swedish male population) occurrences of thromboembolic disease, taking into account age, calendar-time, number of thromboembolic diseases, and time since previous thromboembolic disease. Findings Between Jan 1, 1997, and Dec 31, 2007, 30 642 men received primary endocrine therapy, 26 432 curative treatment, and 19 526 surveillance. 1881 developed a thromboembolic disease. For men on endocrine therapy, risks for DVT (SIR 2·48, 95% CI 2·25–2·73) and pulmonary embolism (1·95, 1·81–2·15) were increased, although this was not the case for arterial embolism (1·00, 0·82–1·20). Similar patterns were seen for men who received curative treatment (DVT: 1·73, 1·47–2·01; pulmonary embolism: 2·03, 1·79–2·30; arterial embolism: 0·95, 0·69–1·27) and men who were on surveillance (DVT: 1·27, 1·08–1·47; pulmonary embolism: 1·57, 1·38–1·78; arterial embolism: 1·08, 0·87–1·33). Increased risks for thromboembolic disease were maintained when patients were stratified by age and tumour stage. Interpretation All men with prostate cancer were at higher risk of thromboembolic diseases, with the highest risk for those on endocrine therapy. Our results indicate that prostate cancer itself, prostate cancer treatments, and selection mechanisms all contribute to increased risk of thromboembolic disease. Thromboembolic disease should be a concern when managing patients with prostate cancer. Funding Swedish Research Council, Stockholm Cancer Society, and Cancer Research UK.

Prostate cancer risk in the Swedish AMORIS study : the interplay among triglycerides, total cholesterol, and glucose

In a cohort including 5112 prostate cancer (pCa) patients, the authors investigated associations among triglycerides (TG), total cholesterol (TC), and pCa while taking into account glucose.

Global incidence and outcome of testicular cancer

Background Testicular cancer is a rare tumor type accounting for 1% of malignancies in men. It is, however, the most common cancer in young men in Western populations. The incidence of testicular cancer is increasing globally, although a decline in mortality rates has been reported in Western countries. It is important to identify whether the variations in trends observed between populations are linked to genetic or environmental factors. Methods Age-standardized incidence rates and age-standardized mortality rates for testicular cancer were obtained for men of all ages in ten countries from the Americas, Asia, Europe, and Oceania using the Cancer Incidence in Five Continents (CI5plus) and World Health Organization (WHO) mortality databases. The annual percent change was calculated using Joinpoint regression to assess temporal changes between geographical regions. Results Testicular cancer age-standardized incidence rates are highest in New Zealand (7.8), UK (6.3), Australia (6.1), Sweden (5.6), USA (5.2), Poland (4.9), and Spain (3.8) per 100,000 men. India, China, and Colombia had the lowest incidence (0.5, 1.3, and 2.2, respectively) per 100,000 men. The annual percent changes for overall testicular cancer incidence significantly increased in the European countries Sweden 2.4%, (2.2; 2.6); UK 2.9%, (2.2; 3.6); and Spain 5.0%, (1.7; 8.4), Australia 3.0%, (2.2; 3.7), and China 3.5%, (1.9; 5.1). India had the lowest overall testicular cancer incidence −1.7%, (−2.5; −0.8). Annual percent changes for overall testicular cancer mortality rates were decreasing in all study populations, with the greatest decline observed in Sweden −4.2%, (−4.8; −3.6) and China −4.9%, (−6.5; −3.3). Conclusion Testicular cancer is increasing in incidence in many countries; however, mortality rates remain low and most men are cured. An understanding of the risks and long-term side effects of treatment are important in managing men with this disease.

Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons : the Swedish AMORIS study

BACKGROUND Apart from using gamma-glutamyltransferase (GGT) as a predictor of diabetes, cardiovascular and chronic kidney disease, some evidence suggests GGT as an indicator of cancer risk. We aimed to study the association between GGT and cancer in a large Swedish cohort with 37,809 primary cancers. METHODS In a cohort of 545,460 persons (aged >20 years) who had a measurement of GGT in the Apolipoprotein Mortality Risk (AMORIS) study, multivariate Cox proportional hazards regression was used to investigate categories of GGT (<18, 18-36,36-72, ≥72 U/L) in relation to cancer risk. Stratified analyses were conducted by gender, levels of alanine aminotransferase (ALT) (</≥ 50 U/L), glucose (</≥ 6.11 mmol/L) and triglycerides (</≥1.71 mmol/L). RESULTS A positive association was found between categories of GGT and overall cancer risk (HR: 1.07 (95%CI: 1.04-1.09,), 1.18 (1.14-1.22), 1.32 (1.26-1.38) for the 2nd, 3rd and 4th categories compared to the 1st). Stratified analyses showed that for those with glucose ≥6.11 mmol/L, the association between GGT and risk of prostate, breast and liver cancer became stronger (e.g. HR for GGT ≥72 U/L and prostate cancer: 1.11 (0.98-1.26) and 1.35 (1.00-1.81) for glucose <6.11 and ≥6.11 mmol/L, respectively). With pancreatic cancer, the association with GGT was weaker for those with elevated glucose levels compared to those with normal levels. No effects of ALT or triglyceride levels on risk were found. CONCLUSION We found evidence of associations between elevated GGT and risk of developing different cancers. The strength of this association may vary by glucose levels because hyperglycaemia can result in oxidative stress initiating damaging pathways of carcinogenesis.

Calcium intake and serum concentration in relation to risk of cardiovascular death in NHANES III

Background Evidence for an association between calcium intake and risk of cardiovascular death remains controversial. By assessing dietary intake, use of supplements, and serum levels of calcium, we aimed to disentangle this link in the third National Health and Nutrition Examination Survey (NHANES III). Methods Mortality linkage of NHANES III to death certificate data for those aged 17 years or older (n = 20,024) was used to estimate risk of overall cardiovascular death as well as death from ischemic heart disease (IHD), acute myocardial infarction (AMI), heart failure (HF), and cerebrovascular disease (CD) with multivariate Cox proportional hazards regression analysis. Results About 10.0% of the population died of cardiovascular disease and the majority (5.4%) died of IHD. There was increased risk of overall CVD death for those in the bottom 5% of serum calcium compared to those in the mid 90% (HR: 1.51 (95% CI: 1.03–2.22)). For women there was a statistically significant increased risk of IHD death for those with serum calcium levels in the top 5% compared to those in the mid 90% (HR: 1.72 (95%CI: 1.13–2.61)), whereas in men, low serum calcium was related to increased IHD mortality (HR: 2.32 (95% CI 1.14–3.01), Pinteraction: 0.306). No clear association with CVD death was observed for dietary or supplemental calcium intake. Conclusions Calcium as assessed by serum concentrations is involved in cardiovascular health, though differential effects by sex may exist. No clear evidence was found for an association between dietary or supplementary intake of calcium and cardiovascular death.