Associations between glucocorticoid use and major adverse cardiovascular events in patients with prostate cancer receiving antiandrogen: a retrospective cohort study.

BACKGROUND: Prednisolone/prednisone coadministration with abiraterone may explain abiraterone-related increase in cardiovascular risk. We explored this postulation and glucocorticoid's association with cardiovascular risk. METHODS: Patients with prostate cancer on androgen deprivation therapy and enzalutamide, or abiraterone with 5 mg (ABI + P5) or 10 mg (ABI + P10) daily total prednisolone/prednisone were followed up for major adverse cardiovascular events (MACE). RESULTS: We analyzed 933 patients. ABI + P10, but not enzalutamide, had higher risk of MACE than ABI + P5. Cumulative glucocorticoid dose before enzalutamide/abiraterone initiation was associated with MACE. CONCLUSIONS: Prednisolone/prednisone coadministration with abiraterone likely contributed to abiraterone-related increased cardiovascular risk. Prevalent cumulative glucocorticoid dose was associated with cardiovascular risk.

Comparison of infection risk between enzalutamide and abiraterone in patients with prostate cancer.

BACKGROUND: Enzalutamide and abiraterone may differ in their immunomodulatory effects, and the prednisone coadministered with abiraterone can be immunosuppressive. This study aimed to compare the risk of different types of infection in patients with prostate cancer receiving enzalutamide or abiraterone in combination with androgen deprivation therapy. METHODS: Patients with prostate cancer receiving enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between December 1999 to March 2021 were identified in this retrospective cohort study and followed up until September 2021, death, or crossover. Outcomes, including any sepsis, pneumonia, urinary tract infection, cellulitis or skin abscess, central nervous system infections, and tuberculosis, were analyzed as both time-to-event outcomes (multivariable Fine-Gray regression, with mortality considered a competing event) and recurrent-event outcomes (multivariable negative binomial regression). RESULTS: Altogether, 1582 patients were analyzed (923 abiraterone users; 659 enzalutamide users) with a median follow-up of 10.6 months (interquartile range: 5.3-19.9 months). Compared to abiraterone users, enzalutamide users had lower cumulative incidences of sepsis (adjusted subhazard ratio [SHR] 0.70 [0.53-0.93], p = .014), pneumonia (adjusted SHR 0.76 [0.59-0.99], p = .040), and cellulitis or skin abscess (adjusted SHR 0.55 [0.39-0.79], p = .001), but not urinary tract infection (adjusted SHR 0.91 [0.62-1.35], p = .643). Associations between exposure and central nervous system infections and tuberculosis were not assessed because of low event rates. Analyzing the outcomes as recurrent events gave similar results. Enzalutamide use may be associated with a lower risk of urinary tract infection in patients with diabetes mellitus. CONCLUSIONS: Compared to abiraterone users, enzalutamide users have significantly lower risks of sepsis, pneumonia, cellulitis, or skin abscess.

Associations Between Social Determinants of Health and Cardiovascular Health of U.S. Adult Cancer Survivors.

Background: Relationships between the social determinants of health (SDOH) and cardiovascular health (CVH) of cancer survivors are underexplored. Objectives: This study sought to investigate associations between the SDOH and CVH of adult cancer survivors. Methods: Data from the U.S. National Health Interview Survey (2013-2017) were used. Participants reporting a history of cancer were included, excluding those with only nonmelanotic skin cancer, or with missing data for any domain of SDOH or CVH. SDOH was quantified with a 6-domain, 38-item score, consistent with the Centers for Disease Control and Prevention recommendations (higher score indicated worse deprivation). CVH was quantified based on the American Heart Association's Life's Essential 8, but due to unavailable detailed dietary data, a 7-item CVH score was used, with a higher score indicating worse CVH. Survey-specific multivariable Poisson regression was used to test associations between SDOH quartiles and CVH. Results: Altogether, 8,254 subjects were analyzed, representing a population of 10,887,989 persons. Worse SDOH was associated with worse CVH (highest vs lowest quartile: risk ratio 1.30; 95% CI: 1.25-1.35; P < 0.001), with a grossly linear relationship between SDOH and CVH scores. Subgroup analysis found significantly stronger associations in younger participants (P interaction = 0.026) or women (P interaction = 0.001) but without significant interactions with race (P interaction = 0.051). Higher scores in all domains of SDOH were independently associated with worse CVH (all P < 0.001). Higher SDOH scores were also independently associated with each component of the CVH score (all P < 0.05 for highest SDOH quartile). Conclusions: An unfavorable SDOH profile was independently associated with worse CVH among adult cancer survivors in the United States.

Cardiovascular health of patients with cancer: Challenges abound.

Patients with cancer have elevated cardiovascular risks compared to those without cancer. As cancer incidence increases and cancer-related mortality decreases, cardiovascular diseases in patients with a history of cancer will become increasingly important. This in turn is reflected by the exponentially increasing amount of cardio-oncology research in recent years. This narrative review aims to summarize the key existing literature in several main areas of cardio-oncology, including the epidemiology, natural history, prevention, management, and determinants of the cardiovascular health of patients with cancer, and identify relevant gaps in evidence for further research.

The modified Rajan's heart failure risk score predicts all-cause mortality in patients hospitalized for heart failure with reduced ejection fraction: a retrospective cohort study.

Background: The dimensionless Rajan's heart failure (R-hf) risk score was proposed to predict all-cause mortality in patients hospitalized with chronic heart failure (HF) and reduced ejection fraction (EF) (HFrEF). Purpose: To examine the association between the modified R-hf risk score and all-cause mortality in patients with HFrEF. Methods: Retrospective cohort study included adults hospitalized with HFrEF, as defined by clinical symptoms of HF with biplane EF less than 40% on transthoracic echocardiography, at a tertiary centre in Dalian, China, between 1 November 2015, and 31 October 2019. All patients were followed up until 31 October 2020. A modified R-hf risk score was calculated by substituting brain natriuretic peptide (BNP) for N-terminal prohormone of BNP (NT-proBNP) using EF× estimated glomerular filtration rate (eGFR)× haemoglobin (Hb))/BNP. The patients were stratified into tertiles according to the R-hf risk score. The measured outcome was all-cause mortality. The score performance was assessed using C-statistics. Results: A total of 840 patients were analyzed (70.2% males; mean age, 64±14 years; median (interquartile range) follow-up 37.0 (27.8) months). A lower modified R-hf risk score predicted a higher risk of all-cause mortality, independent of sex and age [1st tertile vs. 3rd tertile: adjusted hazard ratio (aHR), 3.46; 95% CI: 2.11-5.67; P<0.001]. Multivariate Cox regression analysis indicated that a lower modified R-hf risk score was associated with increased cumulative all-cause mortality [univariate: (1st tertile vs. 3rd tertile: aHR, 3.45; 95% CI: 2.11-5.65; P<0.001) and multivariate: (1st tertile vs. 3rd tertile: aHR 2.21, 95% CI: 1.29-3.79; P=0.004)]. The performance of the model, as reported by C-statistic was 0.67 (95% CI: 0.62-0.72). Conclusion: The modified R-hf risk score predicted all-cause mortality in patients hospitalized with HFrEF. Further validation of the modified R-hf risk score in other cohorts of patients with HFrEF is needed before clinical application.

Statin use and mortality risk in Asian patients with prostate cancer receiving androgen deprivation therapy: A population-based cohort study.

BACKGROUND: This study aimed to examine the associations between the use of statins concurrent with androgen deprivation therapy (ADT) and the risks of mortality in Asian patients diagnosed with prostate cancer (PCa). METHODS: Adult patients (≥18 years old) diagnosed with PCa who were receiving any form of ADT and were being treated at public hospitals in Hong Kong from December 1999 to March 2021 were retrospectively identified, with follow-up conducted until September 2021. Patients who had received medical castration for <180 days without subsequent bilateral orchidectomy, those who had used statins concurrently with ADT for <180 days, and those with missing baseline total cholesterol levels were excluded. Statin users were defined as individuals who had used statins for ≥180 days concurrent with ADT, while non-users were those who had not used any statins. PCa-related mortality was the primary outcome, while all-cause mortality served as the secondary outcome. Inverse probability treatment weighting was employed to balance the covariates. RESULTS: A total of 4920 patients were included, consisting of 2578 statin users and 2342 non-users (mean age 76.1 ± 8.2 years). Over a mean follow-up period of 4.2 ± 3.3 years, it was observed that statin users had significantly lower risks of both PCa-related mortality (weighted hazard ratio [wHR] 0.56 [95% confidence interval (CI) 0.48, 0.65], p < 0.001) and all-cause mortality (wHR 0.57 [95% CI 0.51, 0.63], p < 0.001), regardless of the type of ADT used. Notably, these associations were more pronounced among patients with less advanced PCa, as indicated by the absence of androgen receptor antagonist or chemotherapy usage (p value for interaction <0.001 for both outcomes). CONCLUSION(S): The use of statins concurrent with ADT was associated with reduced mortality risks among Asian patients with PCa. These findings suggest the need for additional research to explore the potential role of statins in the treatment of PCa patients.

Major adverse cardiovascular events of enzalutamide versus abiraterone in prostate cancer: a retrospective cohort study.

BACKGROUND: While the cardiovascular risks of androgen receptor pathway inhibitors have been studied, they were seldom compared directly. This study compares the risks of major adverse cardiovascular events (MACE) between enzalutamide and abiraterone among prostate cancer (PCa) patients. METHODS: Adult PCa patients receiving either enzalutamide or abiraterone in addition to androgen deprivation therapy in Hong Kong between 1 December 1999 and 31 March 2021 were identified in this retrospective cohort study. Patients who switched between enzalutamide and abiraterone, initiated abiraterone used without steroids, or experienced prior cardiac events were excluded. Patients were followed-up until 30 September 2021. The primary outcomes were MACE, a composite of stroke, myocardial infarction (MI), Heart failure (HF), or all-cause mortality and a composite of adverse cardiovascular events (CACE) not including all-cause mortality. The secondary outcomes were individual components of MACE. Inverse probability treatment weighting was used to balance covariates between treatment groups. RESULTS: In total, 1015 patients were analyzed (456 enzalutamide users and 559 abiraterone users; mean age 70.6 ± 8.8 years old) over a median follow-up duration of 11.3 (IQR: 5.3-21.3) months. Enzalutamide users had significantly lower risks of 4P-MACE (weighted hazard ratio (wHR) 0.71 [95% confidence interval (CI) 0.59-0.86], p < 0.001) and CACE (wHR 0.63 [95% CI: 0.42-0.96], p = 0.031), which remained consistent in multivariable analysis. Such an association may be stronger in patients aged ≥65 years or without diabetes mellitus and was independent of bilateral orchidectomy. Enzalutamide users also had significantly lower risks of MI (wHR 0.57 [95% CI: 0.33-0.97], p = 0.040) and all-cause mortality (wHR 0.71 [95% CI: 0.59-0.85], p < 0.001). CONCLUSION: Enzalutamide was associated with lower cardiovascular risks than abiraterone in PCa patients.

Association between serum uric acid and prostate cancer mortality in androgen deprivation therapy: A population-based cohort study.

OBJECTIVE: This population-based study examined the association between baseline uric acid (UA) and prostate cancer (PCa)-related mortality amongst PCa patients receiving androgen deprivation therapy (ADT). METHODS: Adults with PCa who received ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with missing baseline UA were excluded. Patients were followed up until September 2021. The outcome was PCa-related mortality. RESULTS: Altogether, 4126 patients (median follow-up 3.1[interquartile range 1.4-6.0] years) were included. A J-shaped association was observed between baseline UA level and PCa-related mortality risk, with a direct association in those with mean(0.401 mmol/L) or above-mean baseline UA levels (hazard ratio (HR) per standard deviation-increase 1.35 [95% confidence interval 1.21,1.51], p < 0.001), and an inverse association in those with below-mean baseline UA levels (HR 0.78[0.67,0.92], p = 0.003). The former remained significant on competing risk regression, but not the latter. CONCLUSIONS: A J-shaped relationship between baseline UA level and PCa-related mortality risk was identified. This study was mainly limited by potential unmeasured and residual confounders. Further validation studies are warranted.

Long-term prognostic impact of cardiovascular comorbidities in patients with prostate cancer receiving androgen deprivation therapy: A population-based competing risk analysis.

Our study investigated how adverse cardiovascular outcomes are impacted by cardiovascular comorbidities in patients with prostate cancer treated by androgen deprivation therapy (ADT). Using prospective, population-based data, all Hong Kong patients with prostate cancer who received ADT during 1 January 1993 to 3 March 2021 were identified and followed up for the endpoint of cardiovascular hospitalization/mortality until 31 September 2021, whichever earlier. Multivariable competing risk regression was used to compare the endpoint's cumulative incidence between different combinations of major cardiovascular comorbidities (heart failure [HF], myocardial infarction [MI], stroke and/or arrhythmia), with noncardiovascular death as competing event. Altogether, 13 537 patients were included (median age 75.9 [interquartile range 70.0-81.5] years old; median follow-up 3.3 [1.5-6.7] years). Compared to those with none of prior HF/MI/stroke/arrhythmia, the incidence of the endpoint was not different in those with only stroke (subhazard ratio [SHR] 1.06 [95% confidence interval (CI): 0.92-1.23], P = .391), but was higher in those with only HF (SHR 1.67 [1.37-2.02], P < .001), arrhythmia (SHR 1.63 [1.35-1.98], P < .001) or MI (SHR 1.43 [1.14-1.79], P = .002). Those with ≥2 of HF/MI/stroke/arrhythmia had the highest incidence of the endpoint (SHR 1.94 [1.62-2.33], P < .001), among whom different major cardiovascular comorbidities had similar prognostic impacts, with the number of comorbidities present being significantly prognostic instead. In conclusion, in patients with prostate cancer receiving ADT, the sole presence of HF, MI or arrhythmia, but not stroke, may be associated with elevated cardiovascular risks. In those with ≥2 of HF/MI/stroke/arrhythmia, the number of major cardiovascular comorbidities may be prognostically more important than the type of comorbidities.

Temporal trends in cardiovascular burden among patients with prostate cancer receiving androgen deprivation therapy: a population-based cohort study.

BACKGROUND: Although androgen deprivation therapy (ADT) is associated with cardiovascular risks, the extent and temporal trends of cardiovascular burden amongst patients with prostate cancer receiving ADT are unclear. METHODS: This retrospective cohort study analyzed adults with PCa receiving ADT between 1993-2021 in Hong Kong, with follow-up until 31/9/2021 for the primary outcome of major adverse cardiovascular events (MACE; composite of cardiovascular mortality, myocardial infarction, stroke, and heart failure), and the secondary outcome of mortality. Patients were stratified into four groups by the year of ADT initiation for comparisons. RESULTS: Altogether, 13,537 patients were included (mean age 75.5 ± 8.5 years old; mean follow-up 4.7 ± 4.3 years). More recent recipients of ADT had more cardiovascular risk factors and used more cardiovascular or antidiabetic medications. More recent recipients of ADT had higher risk of MACE (most recent (2015-2021) vs least recent (1993-2000) group: hazard ratio 1.33 [1.11, 1.59], P = 0.002; Ptrend < 0.001), but lower risk of mortality (hazard ratio 0.76 [0.70, 0.83], P < 0.001; Ptrend < 0.001). The 5-year risk of MACE and mortality for the most recent group were 22.5% [20.9%, 24.2%] and 52.9% [51.3%, 54.6%], respectively. CONCLUSIONS: Cardiovascular risk factors were increasingly prevalent amongst patients with prostate cancer receiving ADT, with increasing risk of MACE despite decreasing mortality.

Arrhythmias Beyond Atrial Fibrillation Detection Using Smartwatches: A Systematic Review.

BACKGROUND: Over the past few years, smartwatches have become increasingly popular in the monitoring of arrhythmias. Although the detection of atrial fibrillation with smartwatches has been the subject of various articles, there is no comprehensive research on the detection of arrhythmias other than atrial fibrillation. In this study, we included individual cases from the literature to identify the characteristics of patients with smartwatch-detected arrhythmias other than atrial fibrillation. METHODS: PubMed, Embase, and SCOPUS were searched for case reports, case series, or cohort studies that reported individual participant-level data, until January 6, 2022. The following search string was used for each databases: ('Smart Watch' OR 'Apple Watch' OR 'Samsung Gear') AND ('Supraventricular Tachycardia' OR 'Cardiac Arrhythmia' OR 'Ventricular Tachycardia' OR 'Atrioventricular Nodal Reentry Tachycardia' OR 'Atrioventricular Reentrant Tachycardia' OR 'Heart Block' OR 'Atrial Flutter' OR 'Ectopic Atrial Tachycardia' OR 'Bradyarrhythmia'). RESULTS: A total of 52 studies from PubMed, 20 studies from Embase, and 200 studies from SCOPUS were identified. After screening, 18 articles were included. A total of 22 patients were obtained from 14 case reports or case series. Four cohort studies evaluating various arrhythmias were included. Arrhythmias, including ventricular tachycardia, atrial fibrillation, atrial flutter, atrioventricular nodal reentry tachycardia, atrioventricular reentrant tachycardia, second- or third-degree atrioventricular block, and sinus bradycardia, were detected with smartwatches. CONCLUSIONS: Cardiac arrhythmias other than atrial fibrillation are also commonly detected with smartwatches. Smartwatches have an important potential besides traditional methods in the detection of arrhythmias and clinical practice.

Metformin use and hospital attendance-related resources utilization among diabetic patients with prostate cancer on androgen deprivation therapy: A population-based cohort study.

BACKGROUND: Androgen deprivation therapy (ADT), used increasingly in the treatment of prostate cancer (PCa), negatively influences glycemic control in diabetes and is associated with an increased risk of diabetes complications where hospitalization commonly ensues. Metformin could decrease the metabolic consequences of ADT and enhance its effect. This study examined the association of metformin use with healthcare resources utilization among diabetic, PCa patients receiving ADT. METHODS: Diabetic adults with PCa on ADT in Hong Kong between December 1999 and March 2021 were identified. Patients with <6 months of concurrent metformin and ADT use were excluded. All included patients were followed up until September 2021. The outcomes were hospital attendances and related costs. RESULTS: In total, 1,284 metformin users and 687 non-users were studied. Over 8,045 person-years, 9,049 accident and emergency (A&E), and 21,262 inpatient attendances, with 11,2781 days of hospitalization were observed. Metformin users had significantly fewer A&E attendances (incidence rate ratio (IRR): 0.61 [95% confidence interval 0.54-0.69], p < 0.001), inpatient attendances (IRR: 0.57 [0.48-0.67], p < 0.001), and days of hospitalization (IRR: 0.55 [0.42-0.72], p < 0.001). Annual attendance costs were lower for metformin users than non-users (cost ratio: 0.28 [0.10-0.80], p = 0.017). CONCLUSIONS: Metformin use was associated with decreased hospital attendances, days of hospitalization, and associated costs, which could help reduce healthcare resource utilization following ADT in the treatment of PCa.

Association between immune checkpoint inhibitors and myocardial infarction in Asians: A population-based self-controlled case series.

BACKGROUND: While immune checkpoint inhibitors (ICIs) are associated with elevated cardiovascular risks, evidence of any association between ICIs and myocardial infarction (MI) was scarce, especially in Asians. METHODS: Using prospectively collected population-based data, this self-controlled case series included patients prescribed an ICI between 1/1/2014 and 31/12/2020 in Hong Kong who had MI within January 1, 2013 to December 31, 2021. Incidence rate ratios (IRRs) for MI during and after ICI exposure were estimated, compared to the year before ICI initiation. RESULTS: Of 3684 identified ICI users, 24 had MI during the study period. MI incidence increased significantly in the first 90 days of exposure (IRR 3.59 [95% confidence interval: 1.31-9.83], p = 0.013), but not days 91-180 (p = 0.148) or ≥181 (p = 0.591) of exposure, nor postexposure (p = 0.923). Sensitivity analyses excluding patients with MI-related death and incorporating extended exposure periods produced consistent results separately. CONCLUSIONS: ICIs were associated with increased MI incidence in Asian Chinese patients during the first 90 days of use, but not later.

HbA1c Variability and Cardiovascular Events in Patients with Prostate Cancer Receiving Androgen Deprivation Therapy.

Background: Androgen deprivation therapy (ADT) worsens glycaemic control and cardiovascular outcomes. The prognostic value of visit-to-visit HbA1c variability (VVHV) has been unexplored in prostate cancer (PCa) patients receiving ADT. Objective: To explore the effect of ADT on VVHV and the cardiovascular prognostic value of VVHV. Design setting and participants: PCa patients receiving ADT in Hong Kong between January 1, 1993 and March 31, 2021 were included in this retrospective cohort study. Those with fewer than three HbA1c results available within 3 yr after ADT initiation, <6 mo of ADT, missing baseline HbA1c, prior diagnosis of any component of major adverse cardiovascular events (MACEs), and MACEs occurring within 3 yr were excluded. Patients were followed up until September 31, 2021. Outcome measurements and statistical analysis: The outcome was MACEs (composite of heart failure, myocardial infarction, stroke, and cardiovascular mortality). VVHV was calculated from HbA1c levels within 3 yr after and, separately where available, before ADT initiation using coefficient of variation (CV; standard deviation [SD] divided by mean) and average real variability (ARV; average difference between consecutive measurements). Results and limitations: Altogether, 1065 patients were analysed (median age 74.4 yr old [interquartile range 68.3-79.5 yr]). In 709 patients with VVHV available before and after ADT initiation, VVHV increased after ADT initiation (p < 0.001), with 473 (66.2%) and 474 (66.9%) having increased CV and ARV, respectively. Over a median follow-up of 4.3 yr (2.8-6.7 yr), higher VVHV was associated with a higher risk of MACEs (adjusted hazard ratio [per SD] for CV 1.21 [95% confidence interval: 1.02, 1.43], p = 0.029; ARV 1.25 [1.06, 1.48], p = 0.008). Limitations included residual confounding and selection bias. Conclusions: In PCa patients receiving ADT, VVHV increased after ADT initiation. Higher VVHV was associated with an increased risk of MACEs. Patient summary: In prostate cancer patients receiving androgen deprivation therapy (ADT), glycaemic control is less stable after initiating ADT, which was associated with an increased cardiovascular risk.

Risk of diabetes mellitus among users of immune checkpoint inhibitors: A population-based cohort study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are increasingly established cancer therapeutics, but they are associated with new-onset diabetes mellitus (DM). Such risks have not been adequately quantified, and between-class and -sex differences remain unexplored. METHODS: This was a prospective cohort study of cancer patients receiving any ICI in Hong Kong between 2013 and 2021. Patients with known DM were excluded. Due to few patients using other ICIs, only programmed cell death 1 inhibitors (PD-1i) and programmed death ligand 1 inhibitors (PD-L1i) were compared, alongside between-sex comparison. When comparing PD-1i against PD-L1i, patients with the use of other ICIs or both PD-1i and PD-L1 were further excluded. Inverse probability treatment weighting (IPTW) was used to minimize between-group covariate imbalances. RESULTS: Altogether, 3375 patients were analyzed (65.2% males, median age 62.2 [interquartile range 53.8-69.5] years old). Over a median follow-up of 1.0 [0.4-2.4] years, new-onset DM occurred in 457 patients (13.5%), with a 3-year risk of 14.5% [95% confidence interval 13.3%, 15.8%]. IPTW achieve acceptable covariate balance between sexes, and between PD-1i (N = 622) and PD-L1i (N = 2426) users. Males had significantly higher risk of new-onset DM (hazard ratio 1.35 [1.09, 1.67], p = 0.006), while PD-1i and PD-L1i users did not have significantly different risks (hazard ratio vs PD-L1i 0.81 [0.59, 1.11], p = 0.182). These were consistent in those with at least 1 year of follow-up, and on competing risk regression. CONCLUSION: Users of ICI may have a substantial risk of new-onset DM, which may be higher in males but did not differ between PD-1i and PD-L1i.

Metformin use and mortality in Asian, diabetic patients with prostate cancer on androgen deprivation therapy: A population-based study.

BACKGROUND: This study aims to examine the associations between metformin use concurrent with androgen deprivation therapy (ADT) and mortality risks in Asian, diabetic patients with prostate cancer (PCa). METHODS: This study identified diabetic adults with PCa receiving any ADT attending public hospitals in Hong Kong between December 1999 and March 2021 retrospectively, with follow-up until September 2021. Patients with <6 months of medical castration without subsequent bilateral orchidectomy, <6 months of concurrent metformin use and ADT, or missing baseline HbA1c were excluded. Metformin users had ≥180 days of concurrent metformin use and ADT, while non-users had no concurrent metformin use and ADT or never used metformin. The primary outcome was PCa-related mortality. The secondary outcome was all-cause mortality. The study used inverse probability treatment weighting to balance covariates. RESULTS: The analyzed cohort consisted of 1971 patients (1284 metformin users and 687 non-users; mean age 76.2 ± 7.8 years). Over a mean follow-up of 4.1 ± 3.2 years, metformin users had significantly lower risks of PCa-related mortality (weighted hazard ratio [wHR]: 0.49 [95% confidence interval, CI:  0.39-0.61], p < 0.001) and all-cause mortality (wHR 0.53 [0.46-0.61], p < 0.001), independent of diabetic control or status of chronic kidney disease. Such effects appeared stronger in patients with less advanced PCa, which is reflected by the absence of androgen receptor antagonist or chemotherapy use (p value for interaction: 0.017 for PCa-related mortality; 0.048 for all-cause mortality). CONCLUSIONS: Metformin use concurrent with ADT was associated with lower risks of mortality in Asian, diabetic patients with PCa.

Association Between Visit-to-Visit Lipid Variability and Incident Cancer: A Population-based Cohort Study.

Dyslipidemia is associated with increased cancer risk. However, the prognostic value of visit-to-visit lipid variability (VVLV) is unexplored in this regard. To investigate the associations between the VVLV and the risk of incident cancer, we conducted a retrospective cohort study on adult patients attending a family medicine clinic in Hong Kong during 2000-2003, excluding those with <3 tests for low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and total cholesterol (TC) each, those with prior cancer diagnosis, and those with <1 year of follow-up. Visit-to-visit LDL-C, HDL-C, TC, and triglycerides variabilities were measured by the coefficient of variation (CV). Patients were followed up until 31st December 2019 for the primary outcome of incident cancer. Altogether, 69,186 patients were included (26,679 males (38.6%); mean age 60 ± 13 years; mean follow-up 16 ± 3 years); 7958 patients (11.5%) had incident cancer. Higher variability of LDL-C, HDL-C, TC, and TG was associated with higher risk of incident cancer. Patients in the third tercile of the CV of LDL-C (adjusted hazard ratio (aHR) against first tercile 1.06 [1.00, 1.12], P = 0.049), HDL-C (aHR 1.37 [1.29, 1.44], P< 0.001), TC (aHR 1.10 [1.04, 1.17], P = 0.001), and TG (aHR 1.11 [1.06, 1.18], P < 0.001) had the highest risks of incident cancer. Among these, only HDL-C variability remained associated with the risk of incident cancer in users of statins/fibrates. To conclude, higher VVLV was associated with significantly higher long-term risks of incident cancer. VVLV may be a clinically useful tool for cancer risk stratification.