Retinal vessel traits and their association with diabetic retinopathy and cognitive decline in a population with type 2 diabetes

Background People with diabetes are at an increased risk of developing vascular disease, which is the leading cause of morbidity and mortality in this population. The retina is one of the few places in the body that offers noninvasive visualisation of the vascular system and thus provides a rich platform to evaluate local and systemic vascular disease. Recent advancements in retinal image analysis tools allow us to evaluate the retinal microvasculature in a more efficient and unbiased way compared to manual methods. Local retinal changes may provide insight into vascular disease prior to overt pathological changes. Aim The aim of this thesis was to explore and evaluate retinal vessel traits in relation to various manifestations of vascular disease, specifically diabetic retinopathy and cognitive decline, using prospectively collected data. In addition to undertaking this research, this PhD project also aimed to contribute to the collection of primary data from in ongoing longitudinal cohort in order to provide data not only for this project, but for many other future and ongoing projects. Methods Edinburgh Type 2 Diabetes Study is a cohort of 1,066 adults aged 60-75 years with type 2 diabetes living in the Lothian region of Scotland. Data were collected through research clinics as well as record linkage. Diabetic retinopathy status was obtained from the national screening programme and to evaluate cognitive decline, dementia diagnosis was obtained from a combination of medical records, death records and self-report. Cognitive decline was also evaluated using cognitive status derived from a battery of cognitive tests administered at baseline and then again after 10 years. Retinal images were analysed using VAMPIRE software for central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar and venular tortuosity, fractal dimension and density. Results A total of 83 participants (11.6%) developed retinopathy over 10 years. After controlling for a wide number of cardiometabolic, diabetic and vascular risk factors, there was evidence of an association between increased venular tortuosity and incident retinopathy (odds ratio (OR) 1.51, 95% confidence interval (CI) 1.15 to 1.98, p = 0.003), as well as decreased standardised fractal dimension and incident retinopathy (OR 0.75, 0.58 to 0.96, p = 0.025). Of the total 1066, 106 (9.9%) were determined to have a dementia diagnosis after 10 years of follow-up. Cognitive decline, as measured by cognitive testing after 10 years, controlling for baseline cognitive status, was measured in the 581 returning participants. There were no independent associations between the retinal vessel traits and cognitive decline, using either dementia or the general intelligence factor, after controlling for various covariates. There was, however, evidence of age-related decreases in fractal dimension and density over the course of the study. Conclusions This thesis has provided evidence from the ET2DS that venular tortuosity and fractal dimension are independently associated with diabetic retinopathy. The independent associations were modest and need to be contextualised within the heterogeneity that exists within the supporting literature as well as replicated in other studies, but they provide exciting support for the use of the retinal vessel traits in future risk prediction modelling for diabetic retinopathy. There was no evidence of an association between the reported retinal vessel traits and cognitive decline. Novel findings regarding age-related decreases in fractal dimension and density are important as more information is coming to light regarding the vessel traits and their associations with vascular disease

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT.publishedVersio

Cardiovascular outcomes after curative prostate cancer treatment: A population-based cohort study

Objective: To investigate differences in cardiovascular disease (CVD) morbidity and mortality after radical prostatectomy or definitive radiotherapy with or without androgen deprivation therapy (ADT). Materials and methods: We used population-based data from the Cancer Registry of Norway, the Norwegian Patient Registry and the Norwegian Cause of Death Registry including 19 289 men ≤80 years diagnosed with non-metastatic prostate cancer during 2010-2019. Patients were treated with radical prostatectomy or definitive radiotherapy. We used competing risk models to compare morbidity from overall CVD, acute myocardial infarction (AMI), cerebral infarction, thromboembolism, and CVD-specific mortality for the overall cohort and stratified by prognostic risk groups. Results: After a median follow-up time of 5.4 years (IQR 4.6 years), there were no differences in adjusted rates of AMI, cerebral infarction, and CVD-specific death between radical prostatectomy and definitive radiotherapy in any of the prognostic risk groups. Rates of overall CVD (0.82; 95% CI 0.76-0.89) and thromboembolism (0.30; 95% CI 0.20-0.44) were lower for definitive radiotherapy than radical prostatectomy during the first year of follow-up. After this overall CVD rates (1.19; 95% CI 1.11-1.28) were consistently higher across all risk groups in patients treated with definitive radiotherapy, but there were no differences regarding thromboembolism. Conclusions: During the first years after treatment, no differences were found in rates of AMI, cerebral infarction, and CVD-specific death between radiotherapy and radical prostatectomy in any of the prognostic risk groups. This suggests that ADT use in combination with radiotherapy may not increase the risks of these outcomes in a curative setting. The increased overall CVD rate for definitive radiotherapy after the first year indicates a possible relationship between definitive radiotherapy and other CVDs than AMI and cerebral infarction.publishedVersio

Treatment and 30-day mortality after myocardial infarction in prostate cancer patients: A population-based study from Norway

Introduction: There is limited knowledge about the use of invasive treatment and mortality after acute myocardial infarction (AMI) in prostate cancer (PCa) patients. We therefore wanted to compare rates of invasive treatment and 30-day mortality between AMIs in patients with PCa and AMIs in the general Norwegian male population. Methods: Norwegian population-based registry data from 2013 to 2019 were used in this cohort study to identify AMIs in patients with a preceding PCa diagnosis. We compared invasive treatment rates and 30-day mortality in AMI patients with PCa to the same outcomes in all male AMI patients in Norway. Invasive treatment was defined as performed angiography with or without percutaneous coronary intervention or coronary artery bypass graft surgery. Standardized mortality (SMR) and incidence ratios, and logistic regression were used to evaluate the association between PCa risk groups and invasive treatment. Results: In 1,018 patients with PCa of all risk groups, the total rates of invasive treatment for AMIs were similar to the rates in the general AMI population. In patients with ST-segment elevation AMIs, rates were lower in metastatic PCa compared to localized PCa (OR 0.15, 95% CI: 0.04–0.49). For non-ST-segment elevation AMIs, there were no differences between PCa risk groups. The 30-day mortality after AMI was lower in PCa patients than in the total population of similarly aged AMI patients (SMR 0.77, 95% CI: 0.61–0.97). Conclusion: Except for patients with metastatic PCa experiencing an ST-segment elevation AMI, PCa patients were treated as frequent with invasive treatment for their AMI as the general AMI population. 30-day all-cause mortality was lower after AMI in PCa patients compared to the general AMI population.publishedVersio

Hva betyr tidligere hjerte- og karsykdom eller kreft for risiko for død etter påvist SARS-CoV-2?

BAKGRUNN Hjerte- og karsykdommer og kreft har vært beskrevet som mulige risikofaktorer for død av covid-19. Hensikten med studien er å undersøke om tidligere påvist hjerte- og karsykdom eller kreft har påvirket risiko for å dø etter påvist covid-19 i Norge. MATERIALE OG METODE Data fra Meldingssystem for smittsomme sykdommer, Nasjonalt register over hjerte- og karsykdommer og Kreftregisteret ble sammenstilt. Bi- og multivariable regresjonsmodeller ble brukt for å beregne både relativ og absolutt risiko. RESULTATER Første halvår 2020 fikk 8 809 personer påvist SARS-CoV-2 og 260 covid-19-assosierte dødsfall ble registrert. Økende alder, mannlig kjønn (relativ risiko (RR): 1,5; konfidensintervall (KI): 1,2 til 2,0), tidligere hjerneslag (RR: 1,5; KI: 1,0 til 2,1) og kreft med fjernspredning på diagnosetidspunktet (RR: 3,0; KI: 1,1 til 8,2) var uavhengige risikofaktorer for død etter påvist covid-19. Etter justering for alder og kjønn var hjerteinfarkt, atrieflimmer, hjertesvikt, hypertensjon og ikke-metastatisk kreft ikke lengre statistisk signifikante risikofaktorer for død. FORTOLKNING Den største risikofaktoren for død blant SARS-CoV-2-testpositive personer var alder. Mannlig kjønn, tidligere påvist hjerneslag og kreft med fjernspredning var også assosiert med forhøyet risiko for død etter påvist covid-19.publishedVersio

Association between medical androgen deprivation therapy and long-term cardiovascular disease and all-cause mortality in nonmetastatic prostate cancer

Studies have suggested that prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are at increased risk of developing or exacerbating cardiovascular disease (CVD). We aimed to explore the association between ADT for PCa and subsequent CVD and all-cause mortality in this nationwide, longitudinal study. We also evaluated the role of cardiovascular risk and ADT duration to determine effect modification. Norwegian registry data were used to identify patients with PCa from 2008-18 and who received primary ADT in the first year after diagnosis. The associations between ADT and composite cardiovascular events, and the individual components of myocardial infarction, stroke and heart failure, in addition to atrial fibrillation and all-cause mortality, were explored using time-varying Cox regression models. We included 30 923 PCa patients, of whom 8449 (27%) received primary ADT. Mean follow-up was 2.9 and 3.8 years for CVD events and mortality, respectively. We found an association between ADT and composite CVD (adjusted HR 1.13: 95% CI 1.05-1.21), myocardial infarction (1.18: 1.05-1.32), stroke (1.21: 1.06-1.38), heart failure (1.23: 1.13-1.35) and all-cause mortality (1.49: 1.39-1.61). These associations persisted in those with low and moderate CVD risk and ADT longer than 7 months. A relationship between ADT and composite CVD and all-cause mortality was observed, especially in those with moderate CVD risk and longer treatment duration. Future studies with more detailed cancer data are needed to verify the clinical relevance of these results, especially when considering all-cause mortality within the context of treatment guidelines and benefits of ADT

Does a history of cardiovascular disease or cancer affect mortality after SARS-CoV-2 infection?

BAKGRUNN Hjerte- og karsykdommer og kreft har vært beskrevet som mulige risikofaktorer for død av covid-19. Hensikten med studien er å undersøke om tidligere påvist hjerte- og karsykdom eller kreft har påvirket risiko for å dø etter påvist covid-19 i Norge. MATERIALE OG METODE Data fra Meldingssystem for smittsomme sykdommer, Nasjonalt register over hjerte- og karsykdommer og Kreftregisteret ble sammenstilt. Bi- og multivariable regresjonsmodeller ble brukt for å beregne både relativ og absolutt risiko. RESULTATER Første halvår 2020 fikk 8 809 personer påvist SARS-CoV-2 og 260 covid-19-assosierte dødsfall ble registrert. Økende alder, mannlig kjønn (relativ risiko (RR): 1,5; konfidensintervall (KI): 1,2 til 2,0), tidligere hjerneslag (RR: 1,5; KI: 1,0 til 2,1) og kreft med fjernspredning på diagnosetidspunktet (RR: 3,0; KI: 1,1 til 8,2) var uavhengige risikofaktorer for død etter påvist covid-19. Etter justering for alder og kjønn var hjerteinfarkt, atrieflimmer, hjertesvikt, hypertensjon og ikke-metastatisk kreft ikke lengre statistisk signifikante risikofaktorer for død. FORTOLKNING Den største risikofaktoren for død blant SARS-CoV-2-testpositive personer var alder. Mannlig kjønn, tidligere påvist hjerneslag og kreft med fjernspredning var også assosiert med forhøyet risiko for død etter påvist covid-19

Hva betyr tidligere hjerte- og karsykdom eller kreft for risiko for død etter påvist SARS-CoV-2?

BAKGRUNN Hjerte- og karsykdommer og kreft har vært beskrevet som mulige risikofaktorer for død av covid-19. Hensikten med studien er å undersøke om tidligere påvist hjerte- og karsykdom eller kreft har påvirket risiko for å dø etter påvist covid-19 i Norge. MATERIALE OG METODE Data fra Meldingssystem for smittsomme sykdommer, Nasjonalt register over hjerte- og karsykdommer og Kreftregisteret ble sammenstilt. Bi- og multivariable regresjonsmodeller ble brukt for å beregne både relativ og absolutt risiko. RESULTATER Første halvår 2020 fikk 8 809 personer påvist SARS-CoV-2 og 260 covid-19-assosierte dødsfall ble registrert. Økende alder, mannlig kjønn (relativ risiko (RR): 1,5; konfidensintervall (KI): 1,2 til 2,0), tidligere hjerneslag (RR: 1,5; KI: 1,0 til 2,1) og kreft med fjernspredning på diagnosetidspunktet (RR: 3,0; KI: 1,1 til 8,2) var uavhengige risikofaktorer for død etter påvist covid-19. Etter justering for alder og kjønn var hjerteinfarkt, atrieflimmer, hjertesvikt, hypertensjon og ikke-metastatisk kreft ikke lengre statistisk signifikante risikofaktorer for død. FORTOLKNING Den største risikofaktoren for død blant SARS-CoV-2-testpositive personer var alder. Mannlig kjønn, tidligere påvist hjerneslag og kreft med fjernspredning var også assosiert med forhøyet risiko for død etter påvist covid-19. Hjerte- og karsykdommer og kreft har tidligere vært beskrevet som mulige risikofaktorer for alvorlig sykdom og død grunnet covid-19 (1, 2). I tillegg til komorbiditet har tidligere publiserte studier også vist at økende alder og mannlig kjønn er assosiert med høyere risiko for død (3–6). I mange studier har man undersøkt hvordan risiko for død påvirkes av komorbiditet hos innlagte pasienter på sykehus eller etter oppfølging av pasienter identifisert i allmennpraksis. Disse studiene inneholder selekterte pasientgrupper og er utført i land med helseregistre av varierende kvalitet. Bortsett fra en nylig publisert studie fra Danmark (6), er det få studier der man har undersøkt risikofaktorer for død basert på populasjonsbaserte data. En oversikt over letalitet i ulike aldersgrupper og risikotilstander blant personer som døde etter påvist SARS-CoV-2 i Norge, er nylig publisert i Tidsskriftet (7). I denne studien har man ikke undersøkt betydningen av tidligere påviste sykdommer for risiko for død. Vi ønsket derfor å bruke nasjonale helseregisterdata for å undersøke om tidligere påvist hjerte- og karsykdom eller kreft påvirket risiko for å dø etter positiv test for SARS-CoV-2 første halvår 2020