Analyses of Increased Mortality in New and Known Diabetes in Patients with Coronary Disease Enrolled in the NORSTENT Randomized Study

Background: NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention with drug-eluting stents (DES) or bare-metal stents (BMS) with a 5-year follow-up. Among the patients, 5,512 had measured either fasting glucose level or percent glycated hemoglobin (HbA1c) at the index procedure. That cohort constitutes the present study population analyzing mortality and evaluating treatment heterogeneity of randomized stent in diabetic versus nondiabetic subgroups. Results: The cohort consisted of 4,174 (75.7%) patients without diabetes, 716 (13.0%) with known diabetes, and 622 (11.3%) with no diabetes in history but elevated fasting glucose level >7.0 mmol/L or HbA1c >6.5% and therefore defined as new diabetes. Patients with known diabetes had a significantly increased all-cause (hazard ratio [HR] 1.99, 95% CI 1.51–2.62, p < 0.001), cardiac (subhazard ratio [SHR] 2.47, 95% CI 1.55–3.93, p < 0.001), and noncardiac (SHR 1.74, 95% CI 1.23–2.44, p = 0.002) mortality after adjustment for baseline variables. In the follow-up of 5 years, patients with new diabetes, however, had a marginally increased all-cause (HR 1.40, 95% CI 1.01–1.93, p = 0.043) and significantly increased noncardiac mortality (SHR 1.52, 95% CI 1.06–2.20, p = 0.025), but no increase in cardiac mortality (SHR 1.06, 95% CI 0.53–2.12, p = 0.86) after the same adjustment. The majority of the mortality was cardiac in the first 1–2 years after intervention; thereafter, noncardiac mortality dominated. However, the time period for when noncardiac mortality became the dominating cause varied considerably and significantly between the groups. There was no heterogeneity in mortality in response to randomized stent between diabetics and nondiabetics. Conclusion: Known diabetes has increased cardiac and noncardiac mortality in contrast to new diabetes which is only associated with increased noncardiac mortality during the 5-year follow-up. Diabetic and nondiabetic patients have the same response to the treatment with BMS or DES.acceptedVersio

The effect of drug-eluting stents on target lesion revascularization in native coronary arteries: Results from the NORSTENT randomized study

This is the accepted manuscript version of an article published by S. Karger AG in Cardiology, 2020;145(6):333-341, available at https://doi.org/10.1159/000506042. Background: The NORSTENT trial randomized 9,013 patients to percutaneous coronary intervention (PCI) with a drug-eluting stent (DES) or bare-metal stent (BMS) with 5-year follow-up. No difference was found in the composite primary outcome of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularizations, which were reduced by DES. We report the occurrence of target lesion revascularization (TLR) in time and across demographic and clinical subgroups in patients with lesions in native coronary arteries (n = 8,782). Results: Clinically driven TLR was performed on 488 (5.6%) of the 8,782 patients during 5 years of follow-up. Male gender, older age, visible thrombus in the lesion, and larger stent diameter were associated with less TLR; multivessel disease and longer stents were associated with a higher risk of TLR. There was a substantial and highly significant reduction of the risk of any TLR after 5 years in the DES group (hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.36–0.52], p Conclusion: DES have a time-limited effect on the rate of TLR, but with a substantial and highly significant reduction in the first 2 years after the procedure. This effect was found to be consistent across all important clinical subgroups

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

Is the ongoing obesity epidemic partly explained by concurrent decline in cigarette smoking? Insights from a longitudinal population study. The Tromsø Study 1994–2016

The increase of obesity coincides with a substantial decrease in cigarette smoking. We assessed post-cessation weight change and its contribution to the obesity epidemic in a general population in Norway. A total of 14,453 participants (52.6% women), aged 25–54 years in 1994, who attended at least two of four surveys in the Tromsø Study between 1994 and 2016, were included in the analysis. Hereof 77% participated in both the first and the last survey. Temporal trends in mean body mass index (BMI), prevalence of obesity (BMI ≥ 30 kg/m2) and daily smoking were estimated with generalized estimation equations. We assessed BMI change by smoking status (ex-smoker, quitter, never smoker, daily smoker), and also under a scenario where none quit smoking. In total, the prevalence of daily smoking was reduced over the 21 years between Tromsø 4 (1994–1995) and Tromsø 7 (2015–2016) by 22 percentage points. Prevalence of obesity increased from 5 – 12% in 1994–1995 to 21–26% in 2015–2016, where obesity in the youngest (age 25–44 in 1994) increased more than in the oldest (p < 0.0001). Those who quit smoking had a larger BMI gain compared to the other three smoking subgroups over the 21 years (p < 0.0001). The scenario where none quit smoking would imply a 13% reduction in BMI gain in the population, though substantial age-related differences were noted. We conclude that smoking cessation contributed to the increase in obesity in the population, but was probably not the most important factor. Public health interventions should continue to target smoking cessation, and also target obesity prevention

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

Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50 000 individuals

Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about cancer risks. We aimed to assess the effects of folic acid supplementation on site-specific cancer rates in the randomised trials

Validation of self-reported and hospital-diagnosed atrial fibrillation: The HUNT study

Background: Self-reported atrial fibrillation (AF) and diagnoses from hospital registers are often used to identify persons with AF. The objective of this study was to validate self-reported AF and hospital discharge diagnoses of AF among participants in a population-based study. Materials and methods: Among 50,805 persons who participated in the third survey of the HUNT Study (HUNT3), 16,247 participants from three municipalities were included. Individuals who reported cardiovascular disease, renal disease, or hypertension in the main questionnaire received a cardiovascular-specific questionnaire. An affirmative answer to a question on physician-diagnosed AF in this second questionnaire defined self-reported AF diagnoses in the study. In addition, AF diagnoses were retrieved from hospital and primary care (PC) registers. All AF diagnoses were verified by review of hospital and PC medical records. Results: A total of 502 HUNT3 participants had a diagnosis of AF verified in hospital or PC records. Of these, 249 reported their AF diagnosis in the HUNT3 questionnaires and 370 had an AF diagnosis in hospital discharge registers before participation in HUNT3. The sensitivity of self-reported AF in HUNT3 was 49.6%, specificity 99.2%, positive predictive value (PPV) 66.2%, and negative predictive value (NPV) 98.4%. The sensitivity of a hospital discharge diagnosis of AF was 73.7%, specificity 99.7%, PPV 88.5%, and NPV 99.2%. Conclusion: Use of questionnaires alone to identify cases of AF has low sensitivity. Extraction of diagnoses from health care registers enhances the sensitivity substantially and should be applied when estimates of incidence and prevalence of AF are studied