Associations between immune-suppressive and stimulating drugs and novel COVID-19—a systematic review of current evidence Beth Russell1,*, Charlotte

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.

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. To perform a meta-analysis using observational data on ADT and risk of CVD events in men with PCa. 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). 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. 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. 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.

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.

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.