Differences In Cardiovascular Mortality Research Articles

Bioprosthetic versus mechanical prostheses in patients aged 50 to 70 years undergoing aortic valve replacement surgery: outcomes analysis from propensity score matching

Abstract Introduction Despite increasing use of bioprosthetic surgical aortic valve replacement (bAVR) in patients ≤70 years [1, 2], the relative benefits compared to mechanical valve replacement (mAVR) remain uncertain [3, 4]. Purpose The current study aims to compare mortality and other important clinical endpoints by prosthesis type for patients aged 50-70 years who received an AVR in a well-characterised Australian cohort. Methods A retrospective cohort study was designed utilising the WAVES Patient Registry and incorporating linked administrative outcome data including all patients who had an AVR in Western Australian public hospitals between 2010-2020. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular (CV) mortality, separately and combined with non-fatal myocardial infarction and non-fatal stroke (MACE), major bleeding, and days alive and out of hospital (DAOH). Outcomes were compared based on a propensity-matched analysis (including demographics, biometrics, and clinical characteristics). Results Within the initial cohort of 727 patients undergoing surgical AVR (mean age = 63 ± SD 6), a propensity-matched cohort identified 151 patients each with bAVR (mean age = 61 ± 4) and mAVR (mean age = 60 ± 5). Patients who received mAVR versus bAVR had improved all-cause survival (Hazard Ratio [HR] 0.50; 95% CI 0.25-0.99) but increased risk of major bleeding (HR 4.85; 95% CI 1.57-14.98). There were no significant differences in CV mortality (HR 0.58; 95% CI 0.19-1.74), MACE (HR 0.59; 95 % CI 0.32-1.07), or DAOH by prosthesis type (P = 0.452). Conclusions Patients aged 50-70 years who underwent mAVR had lower risk of all-cause mortality compared with bAVR, despite higher bleeding risk. Although risks of CV mortality and MACE were lower in mAVR, statistical significance was not reached, likely due to the small sample size. Larger studies are necessary to confirm these findings, which have important clinical implications.

Legacy benefits of blood pressure treatment on cardiovascular events are primarily mediated by improved blood pressure variability: the ASCOT trial.

Visit-to-visit systolic blood pressure variability (BPV) is an important predictor of cardiovascular (CV) outcomes. The long-term effect of a period of blood pressure (BP) control, but with differential BPV, is uncertain. Morbidity and mortality follow-up of UK participants in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure-Lowering Arm has been extended for up to 21 years to determine the CV impact of mean systolic blood pressure (SBP) control and BPV during the trial, and amongst those allocated to amlodipine- and atenolol-based treatment. Eight thousand five hundred and eighty hypertensive participants (4305 assigned to amlodipine ± perindopril-based and 4275 to atenolol ± diuretic-based treatment during the in-trial period (median 5.5 years) were followed for up to 21 years (median 17.4 years), using linked hospital and mortality records. A subgroup of participants (n = 2156) was followed up 6 years after the trial closure with a self-administered questionnaire and a clinic visit. In-trial mean SBP and standard deviation of visit-to-visit SBP as a measure of BPV, were measured using >100 000 BP measurements. Cox proportional hazard models were used to estimate the risk [hazard ratios (HRs)], associated with (i) mean with SBP and BPV during the in-trial period, for the CV endpoints occurring after the end of the trial and (ii) randomly assigned treatment to events following randomization, for the first occurrence of pre-specified CV outcomes. Using BP data from the in-trial period, in the post-trial period, although mean SBP was a predictor of CV outcomes {HR per 10 mmHg, 1.14 [95% confidence interval (CI) 1.10-1.17], P < .001}, systolic BPV independent of mean SBP was a strong predictor of CV events [HR per 5 mmHg 1.22 (95% CI 1.18-1.26), P < .001] and predicted events even in participants with well-controlled BP. During 21-year follow-up, those on amlodipine-based compared with atenolol-based in-trial treatment had significantly reduced risk of stroke [HR 0.82 (95% CI 0.72-0.93), P = .003], total CV events [HR 0.93 (95% CI 0.88-0.98), P = .008], total coronary events [HR 0.92 (95% CI 0.86-0.99), P = .024], and atrial fibrillation [HR 0.91 (95% CI 0.83-0.99), P = .030], with weaker evidence of a difference in CV mortality [HR 0.91 (95% CI 0.82-1.01), P = .073]. There was no significant difference in the incidence of non-fatal myocardial infarction and fatal coronary heart disease, heart failure, and all-cause mortality. Systolic BPV is a strong predictor of CV outcome, even in those with controlled SBP. The long-term benefits of amlodipine-based treatment compared with atenolol-based treatment in reducing CV events appear to be primarily mediated by an effect on systolic BPV during the trial period.

Short- and Medium-Term Outcomes Comparison of Native- and Valve-in-Valve TAVI Procedures.

In high-risk patients with degenerated aortic bioprostheses, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a less invasive alternative to surgical valve replacement. To compare outcomes of ViV and native valve (NV) TAVI procedures. 34 aortic ViV-TAVI performed between 2012 and 2022 using self-expanding valves, were included in this retrospective analysis. Propensity score matching (1:2 ratio, 19 criteria) was used to select a comparison NV-TAVI group from a database of 1206 TAVI procedures. Clinical and echocardiographic endpoints, short- and long-term all-cause mortality (ACM) and cardiovascular mortality (CVM) data were obtained. Subgroup analyses were completed according to the true internal diameter, dividing patients into a small ( 19 mm) valve group (SVG) and a large ( 19 mm) valve group (LVG). Clinical outcomes of ViV- and NV-TAVI were comparable, including device success [88.2% vs. 91.1%, p = 0.727], major adverse cardiovascular and cerebrovascular events [5.8% vs. 5.8%, p = 1.000], hemodialysis need [5.8% vs. 2.9%, p = 0.599], pacemaker need [2.9% vs. 11.7%, p = 0.265], major vascular complications [2.9% vs. 1.4%, p = 1.000], life-threatening or major bleeding [2.9% vs. 1.4%, p = 1.000] and in-hospital mortality [8.8% vs. 5.9%, p = 0.556]. There was a significant difference in the immediate post-intervention mean residual aortic valve gradient (MAVG) [14.6 8.5 mm Hg vs. 6.4 4.5 mm Hg, p 0.0001], which persisted at 1 year [p = 0.0002]. There were no differences in 12- or 30-month ACM [11.8% vs. 8.8%, p = 0.588; 23.5% vs. 27.9%, p = 0.948], and CVM [11.8% vs. 7.3%, p = 0.441; 23.5% vs. 16.2%, p = 0.239]. Lastly, there was no difference in CVM at 1 year and 30 months [11.1% vs. 12.5%, p = 0.889; 22.2% vs. 25.0%, p = 0.742]. Analyzing a limited group (n = 34) of ViV-TAVI procedures out of 1206 TAVIs done at a single institution, ViV-TAVI appeared to be an acceptable approach in patients not deemed appropriate candidates for redo valve replacement surgery. Clinical outcomes of ViV-TAVI were comparable to TAVI for native valve stenosis.

Delta Increment in Pacing QRS Duration Predicts Cardiovascular Mortality in Patients with Pre-Existing Bundle Branch Block Receiving Permanent Pacemakers.

The clinical implication of pre-existing intraventricular conduction disturbance (IVCD) in permanent pacemaker (PPM) recipients is unknown. To explore the clinical outcomes in patients with pre-existing IVCD after implantation of PPMs. A total of 1424 patients who received PPMs were categorized into three groups by pre-procedural electrocardiography: patients without IVCD (n = 1045), patients with right bundle branch block (RBBB) (n = 309), and patients with left bundle branch block (LBBB) (n = 70). The primary outcome was cardiovascular (CV) mortality. Receiver operating characteristic curve analysis was performed to determine the optimal cut-off values of variable in predicting CV mortality. During follow-up, there was no significant difference in CV mortality between patients with and without IVCD. In multivariate analysis, independent predictors of CV mortality were age [hazard ratio (HR): 1.03; 95% confidence interval (95% CI): 1.00-1.05; p = 0.026], history of heart failure [HR: 1.98; 95% CI: 1.19-3.29; p = 0.009], chronic kidney disease [HR: 1.75; 95% CI: 1.11-2.74; p = 0.015] and increment in pacing QRS duration [HR: 1.01; 95% CI: 1.00-1.04; p = 0.038]. Delta increments in pacing QRS duration ≥ 43 msec [HR: 2.91; 95% CI: 1.23-6.83; p = 0.014] in patients with pre-existing RBBB, and ≥ 33 msec [HR: 11.44; 95% CI: 2.03-64.30; p = 0.006] in patients with pre-existing LBBB were independent determinants of CV mortality. There was no difference in CV mortality between patients with or without IVCD. However, wider pacing QRS duration increased the risk of CV mortality in PPM recipients, and delta increment in pacing QRS duration increased the risk of CV mortality in patients with pre-existing IVCD.

P213 HLA-DRB1 haplotypes predict cardiovascular mortality in inflammatory arthritis

Abstract Background/Aims Haplotypes defined by amino acids at HLA-DRB1 positions 11, 71 and 74 associated with susceptibility to rheumatoid arthritis (RA), are associated with radiological outcome, anti-TNF response and all cause-mortality. RA is associated with cardiovascular (CV) morbidity and mortality, but increased prevalence of risk factors of CV disease in RA only partially explains this association. The aim was to investigate whether haplotypes associated with RA disease susceptibility and disease severity are associated with CV mortality. Methods The Norfolk Arthritis register (NOAR) is a primary care-based inception cohort of patients with inflammatory polyarthritis (IP). NOAR patients with at least 2 years of follow-up and available mortality and genetic data were included. Mortality data was provided by the Office for National Statistics. Univariate Cox proportional hazard models were applied using STATA/IC 14.0. Models for CV mortality were adjusted for CV risk factors selected using stepwise regression: namely obesity, gender and hypertension. Hazard models were applied to the entire cohort of patients with inflammatory polyarthritis (IP). When calculating differences between highest and lowest risk genetic factors, bivariate analysis was used. Results HLA-DRB1 amino acids, haplotypes or haplotype groups associated with RA susceptibility are also associated with CV mortality as shown in the table. HLA-DRB1 polymorphisms encoding amino-acid haplotypes associated with an increased or decreased susceptibility to RA consistently show the same magnitude and direction of association for overall and CV mortality in IP. For example, the SEA-haplotype, associated with the lowest susceptibility to RA, and the best radiographic outcome, was found to be associated with decreased CV mortality (HR 0.67, 95% CI 0.47, 0.91, p = 0.023). The relative difference in CV mortality between carriers of the high susceptibility VKA haplotype and carriers of the SEA haplotype was significant (HR 1.67, 95% CI 1.13, 2.48, p = 0.01). Associations were independent of anti-CCP status. Conclusion HLA-DRB1 haplotypes associated with susceptibility to RA also predispose to increased risk of CV mortality in IP, independent of known CV risk factors and anti-CCP status, which suggests that, in the future, genetic factors will add to prediction of risk of cardiovascular mortality beyond serological markers. Disclosure S.D. Sharma: None. D. Plant: None. J. Bowes: Grants/research support; British Heart Foundation. A. Macgregor: None. A. Barton: Grants/research support; BMS. Other; Speaker Fees from Roche Chugai. S. Viatte: None.

Association of early initiation of dialysis with all-cause and cardiovascular mortality: A propensity score weighted analysis of the United States Renal Data System.

Early initiation of maintenance hemodialysis has been associated with excess mortality in some studies, but the effects on cardiovascular (CV) mortality has not been studied. Moreover, whether the increased mortality is due to co-morbidities or early initiation of dialysis is unclear. We used a propensity score weighted analysis of the United States Renal Data System (USRDS) to examine how the estimated glomerular filtration rate (eGFR) at initiation of dialysis affects total and CV mortality. Association between tertiles of eGFR at initiation of hemodialysis and all-cause and CV mortality were assessed in 676,196 adult patients who initiated hemodialysis between 2006 and 2014, using inverse probability of treatment weighting (IPTW) weighted multivariable regression models. The intermediate (eGFR 8.7 to <13.0 mL/min) and early start groups (eGFR ≥13.0 mL/min) had a 42% and 93% increased all-cause mortality, respectively compared to late (eGFR < 8.7), start group (unadjusted hazard ratio (HR) = 1.42; 95% CI, 1.41-1.43 and HR = 1.93; 95%CI, 1.91-1.94, respectively). This association was attenuated but remained significant in propensity weighted multivariable analysis (adjusted HR = 1.13; 95%CI, 1.12-1.14 for intermediate and HR = 1.37; 95%CI, 1.36-1.39, for early start, respectively). The CV mortality was similarly increased (adjusted HR = 1.08; 95%CI, 1.07-1.10 and HR = 1.23; 95%CI, 1.21-1.24, for intermediate and early start, respectively). In patients with cystic kidney disease, all-cause mortality was increased with early start, but there were no differences in CV mortality between groups. Early initiation of dialysis is associated with increased all-cause and CV mortality. Our observations support delaying hemodialysis according to the eGFR values.

Effects of alirocumab on cardiovascular events and all-cause mortality: a systematic review and meta-analysis

Evaluation of the effects of alirocumab on cardiovascular (CV) events, CV mortality and all-cause mortality. Data search was carried out using the Cochrane Library, PubMed, Web of Science and Embase. The search time is up to November 18, 2020. All randomized clinical trials (AEs) comparing alirocumab with placebo were searched. Meta-analysis was performed by Review Manager version 5.3 (The Cochrane Collaboration, Copenhagen, Denmark), and the heterogeneity between studies was tested by Cochrane's Q test and measured with I2 statistics. A total of 13 randomized controlled trials with 24,815 participants were included. Alirocumab usage can considerably lower the incidence of CV events when compared to the control group (risk ratio(RR) 0.89, 95% confidence interval(CI) 0.83-0.95). No significant difference in CV mortality between the two groups was observed (RR 0.87, 95% CI 0.74-1.04). Treatment with alirocumab has been associated with a major decrease in all-cause mortality compared to placebo (RR 0.80, 95% CI 0.66-0.96). The incidence of serious adverse events (AEs) was similar in the two groups (RR 0.94, 95% CI 0.90-0.99). Alirocumab can reduce CV events and all-cause mortality. The AEs were mild and tolerable.

P1666Do beta-blockers increase the risk for hospitalizations in heart failure with preserved ejection fraction? A secondary analysis of beta-blocker use in the TOPCAT trial

Abstract Background The use of beta-blockers for treatment of heart failure (HF) with a reduced ejection fraction (EF) is unequivocally beneficial, but their role in the treatment of preserved EF (HFpEF) remains unclear. Purpose In a contemporary HFpEF cohort, we sought to assess the association of HF hospitalizations and the use of beta-blockers in patients with an EF above and below 50%. Methods The TOPCAT trial tested spironolactone vs. placebo among patients with HFpEF, including some with mild reductions in EF between 45–50%. The primary outcome was a composite of cardiovascular (CV) mortality, aborted cardiac arrest, or HF hospitalizations. Medication use, including beta-blockers, was reported at each visit and hospitalization. In the 1,761 participants from the Americas, we compared the association of beta-blocker use (vs. no use) and HF hospitalization or CV mortality using Cox proportional hazards models adjusted for baseline demographics, history of myocardial infarction, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and hypertension. The analyses were repeated in the EF strata ≥50% and &lt;50%. Results Among patients included in the current analysis (mean age 72 years, 50% female, 78% white), 1,496/1,761 (85%) received beta-blockers and 1,566/1,761 (89%) had an EF ≥50%. HF hospitalizations and CV mortality occurred in 399/1,761 (23%) and 223/1,761 (13%) of participants, respectively. Beta-blocker use was associated with an increase in risk of HF hospitalization among patients with preserved EF ≥50% [HR 1.56, (95% CI 1.09–2.24), p=0.01] and was associated with a reduction in risk of hospitalization in patients with an EF &lt;50% [HR 0.42, (95% CI 0.18- 0.99), p&lt;0.05]. We found a significant interaction for EF threshold and beta-blocker use on incident HF hospitalizations (p=0.01). There were no differences in CV mortality. Figure 1. Kaplan Meier incidence plots Conclusions Beta-blocker use was associated with an increase in HF hospitalizations in patients with HFpEF (EF≥50%) but did not affect CV mortality. Further research is needed to confirm these findings and elucidate causality.

OBESITY AND MORTALITY - RESULTS FROM THE EPIDEMIOLOGY OF HYPERTENSION IN CROATIA (EHUH STUDY) - MORTALITY DATA AFTER 17 YEARS OF FOLLOW-UP

Objective: Our aim was to analyze the association of obesity with all-cause and cardiovascular (CV) mortality in a random sample of Croatian population, an original cohort from the EH-UH study. Design and method: EH-UH study is a nation-wide survey on prevalence, treatment and control of hypertension in Croatia. In 2001–2003 a random sample of 1267 subjects were enrolled. Mortality data collected from the National Public Health Institute records were analyzed after an average period of 17 years. Subjects were divided in BMI1 (< 25 kg/m2), BMI2 (25–30 kg/m2) and BMI3 (>30 kg/m2). Results: There were significantly more all-cause deaths in BMI2 and BMI3 vs. BMI1(X 2 = 9.478; p = 0.002; X 2 = 9.959; p = 0.001; BMI 2 vs BMI3 p > 0.05). We failed to find differences in CV mortality among BMI groups. Subjects in BMI1 were younger than BMI2 and BMI3 (p < 0.01). There were more women than men in BMI1 and BMI3 (p = 0.007;p = 0.0015; respectively). BP values were significantly lower in BMI 1 vs. BMI2 and BMI3 (p < 0.01). BMI2 subjects had significantly lower BP values than BMI3. There were significantly more subjects with optimal BP in BMI1 group and high normal subjects in BMI3 group (p = 0.0000). Prevalence of hypertension was the highest in BMI3 and lowest in BMI1. There were no differences in achieved BP control. BMI1 was more educated (<8 vs >12years) than BMI 2 and BMI3 (p < 0.0001), and BMI2 than BMI3 (p < 0.005). Significantly more subjects with low income (< 400 Eu/months) were detected in BMI3 vs. BMI1 and BMI2 (X 2 = 10.426; p = 0.001; X 2 = 5.423; p = 0.019, respectively). Significant differences in smoking, alcohol intake, positive history of diabetes and dyslipidemia were observed among BMI groups. No difference in history for stroke or myocardial infarction were found. Conclusions: We failed to find increased CV mortality in obese and overweight subjects despite they were older, had more hypertension and were associated with various unfavourable risk factors and conditions. This could be explained with achieved same BP control and same past medical history. In addition, high cancer mortality observed in all BMI subgroups could attenuate association of BMI and CV deaths.

Long-term cardiovascular mortality after radiotherapy for breast cancer: A systematic review and meta-analysis.

Radiotherapy (RT) is frequently associated with late cardiovascular (CV) complications. The mean cardiac dose from irradiation of a left-sided breast cancer is much higher than that for a right-sided breast cancer. However, data is limited on the long-term risks of RT on CV mortality. RT for breast cancer is associated with long term CV mortality and left sided RT carries a greater mortality than right sided RT. We searched PubMed, Cochrane Central, Embase, EBSCO, Web of Science, and CINAHL databases from inception through December 2015. Studies reporting CV mortality with RT for left- vs right-sided breast cancers were included. The principal outcome of interest was CV mortality. We calculated summary risk ratio (RR) and 95% confidence intervals (CI) with the random-effects model. The analysis included 289 109 patients from 13 observational studies. Women who had received RT for left-sided breast cancer had a higher risk of CV death than those who received RT for a right-sided breast cancer (RR: 1.12, 95% CI: 1.07-1.18, P < 0.001; number needed to harm: 353). Difference in CV mortality between left- vs right-sided breast RT was more apparent after 15 years of follow-up (RR: 1.23, 95% CI: 1.08-1.41, P < 0.001; number needed to harm: 95). CV mortality from left-sided RT was significantly higher compared with right-sided RT for breast cancer and was more apparent after ≥15 years of follow-up.

Abstract 19275: Gender Differences in Cardiovascular- and Cancer Mortality During Long-term Follow-up After Acute Myocardial Infarction

Background: The existence of gender differences in cause-specific mortality after acute myocardial infarction (AMI) is unknown. Aim: To study gender differences in all-cause and cause-specific mortality in women and men with AMI. Methods: Consecutive AMI patients were enrolled in a prospective cohort study during 2005-2011. Cardiovascular (CV) risk factors, treatment and in-hospital complications were registered. Date and cause of death were obtained from the Norwegian cause of death registry, with censoring date set to Dec 31, 2012. Patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were analysed separately. We used Kaplan Meier- and cumulative incidence function-plots to assess gender differences in CV, cancer and all-cause mortality. Cox- and Fine-Gray regression models, adjusted for age, estimated the effect of female gender. Results: We included 5159 NSTEMI (34% women) and 4899 STEMI (25% women) patients. Women were older and had more complications compared to men. After a median follow-up time of 1043 and 1262 days for NSTEMI and STEMI, respectively, 1461 NSTEMI (28%) and 886 STEMI (18%) patients had died. After adjustment for age, NSTEMI women had lower (HR 0.89 [95% CI: 0.80-0.99]) and STEMI women similar (HR 1.05 [95% CI: 0.91-1.22]) risk of all-cause mortality compared to men. There were no gender differences in CV mortality. We observed a non-significant trend toward lower cancer mortality in women than men with NSTEMI (adjusted subhazard ratio 0.76 [95% CI:0.56-1.03]). In both genders, CV death was more prevalent (Figure) and occurred earlier than cancer death. Conclusion: After adjustment for age, there were no excess risks of all-cause or CV mortality in women versus men with AMI during long-term follow-up. Possible gender differences in risk of cancer mortality needs further investigation.

Late Antibody-Mediated Rejection (AMR) in Heart Transplantation: How “Late” Is It?

Late Antibody-Mediated Rejection (AMR) in Heart Transplantation: How “Late” Is It?

Androgen Deprivation Therapy and Cardiovascular Risk

The potential association between androgen deprivation therapy (ADT) and cardiovascular mortality (CVM) remains controversial. This study assessed mortality outcomes in a large national registry to further elucidate the association between treatment selection and cause of mortality. A total of 7,248 men in the CaPSURE registry were analyzed. Treatment was categorized as local only, primary ADT monotherapy, local treatment plus ADT, and watchful waiting/active surveillance (WW/AS). Competing hazards survival analysis was performed for prostate cancer-specific mortality (PCSM), CVM, and all-cause mortality. A propensity score-adjusted and a propensity-matched analysis were undertaken to adjust for imbalances in covariates among men receiving various treatments. Patients treated with ADT or WW/AS had a higher likelihood of PCSM than those treated with local therapy alone. Patients treated with primary ADT had an almost two-fold greater likelihood of CVM (HR, 1.94; 95% CI, 1.29 to 2.97) than those treated with local therapy alone; however, patients treated with WW/AS had a greater than two-fold increased risk of CVM (HR, 2.46; 95% CI, 1.53 to 3.95). A propensity-matching algorithm in a subset of 1,391 patients was unable to find a significant difference in CVM between those who did or did not receive ADT. Patients matched on propensity to receive ADT did not show an association between ADT and CVM. This suggests that potential unmeasured variables affecting treatment selection may confound the relationship between ADT use and cardiovascular risk. However, an association may yet exist, because the propensity score could not include all known risk factors for CVM.

Long-term survival and competing causes of death in men with stage I seminoma.

226 Background: To better understand the impact of RT on mortality, we analyzed long-term survival and patterns of excess mortality in men with stage I seminoma. Methods: 9,045 men with stage I seminoma were identified in the Surveillance Epidemiology and End Results database. Time to testicular-cancer mortality (TCM), death from second malignancy (SM), cardiovascular mortality (CVM) or suicide (SUIC) and all-cause mortality (ACM) were calculated. Survival estimates were calculated using the Kaplan-Meier method. Gender- and age-adjusted standardized mortality ratios (SMR) were calculated using U.S. population data. Cox and Fine and Gray multivariable analysis were used to evaluate the effect of RT on mortality outcomes. Results: 7,025 men (78%) received RT. After a median follow-up of 11.7 years, 869 men (9.6%) had died: sixty-five from TCM, 279 from SM, 169 from CVM and 37 from SUIC. 10-year rates of ACM and TCM were 4.24% and 0.52% among men who received RT and 7.14% and 1.22% among men who did not. Compared to the adjusted general population, men with seminoma had increased risk of ACM (SMR 1.12; 95% confidence interval [CI] 1.12-1.28), SM (SMR 1.78; 95% CI 1.58-2.00) and SUIC (SMR 1.40; 95% CI 1.02-1.94) and decreased risk of CVM (SMR 0.73; 95% CI 0.62-0.84). Rates of ACM, SM and SUIC (SMR, all p &lt; 0.05) were increased whether RT was used or not. Men who received RT were less likely to die (adjusted hazard ratio [AHR] 0.76; 95% CI 0.65-0.89; p &lt; 0.001) and had a lower risk of TCM (AHR 0.39; 95% CI 0.24-0.65; p &lt; 0.001). There was no difference in CVM between men who did and did not receive RT (AHR 0.89; 95% CI 0.60-1.15; p = 0.230) and a numerical increase in SM in men who received RT as compared to others (AHR 1.25; 95% CI 0.90-1.72; p=0.180). Conclusions: Compared to the general population, men with a history of stage I seminoma had increased risks of all-cause mortality, death from second malignancies, and suicide. Our data suggest that 15 years after diagnosis, men who did receive RT may be more likely to die from a second malignancy than men who did not. Although not receiving RT was associated with higher testicular-cancer mortality, the results may reflect decreased access to care or follow-up as active surveillance protocols were not common during the study era. No significant financial relationships to disclose.