Altered Acylcarnitine Metabolism Is Associated With an Increased Risk of Atrial Fibrillation

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, but the pathogenesis is not completely understood. The application of metabolomics could help in discovering new metabolic pathways involved in the development of the disease. Methods and Results We measured 112 baseline fasting metabolites of 3770 participants in the Malmö Diet and Cancer Study; these participants were free of prevalent AF. Incident cases of AF were ascertained through previously validated registers. The associations between baseline levels of metabolites and incident AF were investigated using Cox proportional hazard models. During 23.1 years of follow‐up, 650 cases of AF were identified (incidence rate: 8.6 per 1000 person‐years). In Cox regression models adjusted for AF risk factors, 7 medium‐ and long‐chain acylcarnitines were associated with higher risk of incident AF (hazard ratio [HR] ranging from 1.09; 95% CI, 1.00–1.18 to 1.14, 95% CI, 1.05–1.24 per 1 SD increment of acylcarnitines). Furthermore, caffeine and acisoga were also associated with an increased risk (HR, 1.17; 95% CI, 1.06–1.28 and 1.08; 95% CI, 1.00–1.18, respectively), while beta carotene was associated with a lower risk (HR, 0.90; 95% CI, 0.82–0.99). Conclusions For the first time, we show associations between altered acylcarnitine metabolism and incident AF independent of traditional AF risk factors in a general population. These findings highlight metabolic alterations that precede AF diagnosis by many years and could provide insight into the pathogenesis of AF. Future studies are needed to replicate our finding in an external cohort as well as to test whether the relationship between acylcarnitines and AF is causal.

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Exploration of pathophysiological pathways for incident atrial fibrillation using a multiplex proteomic chip

Open Heart ◽

10.1136/openhrt-2019-001190 ◽

2020 ◽

Vol 7 (1) ◽

pp. e001190 ◽

Cited By ~ 1

Author(s):

John Molvin ◽

Amra Jujic ◽

Olle Melander ◽

Manan Pareek ◽

Lennart Råstam ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Matrix Metalloproteinase ◽

Cox Regression ◽

Matrix Metalloproteinase 2 ◽

First Episode ◽

Risk Markers ◽

Swedish Population ◽

Incident Cases

ObjectiveAtrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk.MethodsPlasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean follow-up time 9.7±3.1 years) were analysed with the Olink proximity extension assay CVD III panel consisting of 92 proteins to identify proteins associated with incident AF or atrial flutter, referred to as incident AF. Incident cases of AF (n=278) were retrieved by linkage to the registers. Participants were followed until the first episode of AF or until censoring by death or emigration. Bonferroni-corrected multivariable Cox regression models adjusted for known risk factors were used to explore possible associations of the 92 proteins and incidence of AF.ResultsMultivariable Cox regression analyses of 11 proteins associated with incident AF (mean follow-up time 9.7±3.1 years) after Bonferroni correction confirmed N-terminal pro-B-type natriuretic peptide (HR per 1 SD increment (95% CI) 1.80 (1.58 to 2.04); p=1.2×10−19) as risk marker of incident AF. Further, matrix metalloproteinase-2 (1.22 (1.07 to 1.39); p=0.002) and osteopontin (1.27 (1.12 to 1.44); p=2.7×10−4) were associated with incident AF at follow-up independently of traditional risk markers and NT-proBNP.ConclusionIn a general Swedish population, we confirmed the well-known association of NT-proBNP with incident AF and also identified matrix metalloproteinase-2 and osteopontin as novel risk markers for incident AF, independently of traditional risk factors and NT-proBNP.

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Abstract P004: Association Between The Liver Fibrosis-4 Score And Incident Atrial Fibrillation In A General Japanese Population Of Middle-aged To Older Adults

Circulation ◽

10.1161/circ.143.suppl_1.p004 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Yoshihiro Tanaka ◽

Sarah Chuzi ◽

Nagisa Morikawa ◽

Hayato Tada ◽

Kenshi Hayashi ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Liver Fibrosis ◽

Cumulative Incidence ◽

Japanese Population ◽

General Japanese Population ◽

Increased Risk ◽

Longitudinal Association ◽

Cox Proportional Hazard Models

Background: There is increasing evidence that end-organ liver dysfunction is an important risk factor for atrial fibrillation (AF). Whether a non-invasive, laboratory-based marker of liver fibrosis, the fibrosis-4 score (FIB-4), is associated with incident AF is not known. Aim: To examine the longitudinal association of FIB-4 with incident AF in a general Japanese population with public health insurance. Methods: We used data from the National Japanese Health Check-Up performed in Kanazawa City, which included unemployed or retired participants aged ≥ 40 years. The baseline examination occurred in 2013 and participants were invited for annual routine examinations with follow-up data available through 2018. We excluded participants with pre-existing AF or missing data at baseline or follow-up. Incident AF was based on 12-lead electrocardiogram. We calculated the FIB-4 score (composed of age [years], aspartate and alanine aminotransferase, and platelet levels) for each participant and estimated the cumulative incidence of AF stratified by FIB-4 score quartiles. We also examined the association between quartiles of FIB-4 and incident AF using Cox proportional hazard models adjusted for risk factors with the lowest FIB-4 quartile as referent. Results: Of 37,892 participants, 37% were male and mean age was 72.4±9.6 years. Median (interquartile range [IQR]) of the FIB-4 score was 1.75 (IQR 1.38, 2.27). During a median (IQR) follow-up period of 5.0 years (4.0, 5.0), 707 cases of incident AF were identified. Cumulative incidence in the highest quartile of FIB-4 was 3.9% compared with 1.0% in the lowest quartile (log-rank p<0.001, Figure A ). Higher quartiles of the FIB-4 score had a dose-dependent increased risk of AF with adjusted HR of 1.70 (1.29, 2.23) in the highest quartile compared with the lowest quartile ( Figure B ). Conclusion: FIB-4 was independently associated with incident AF in a general, older Japanese population and may reflect risk of AF, in addition to traditional cardiovascular risk factors.

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Abstract 69: Increased Risk of Venous Thromboembolism Associated with use of Non Steroidal Anti-Inflammatory Drugs among Patients with Prior Myocardial Infarction - A Nationwide Cohort Study

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.5.suppl_1.a69 ◽

2012 ◽

Vol 5 (suppl_1) ◽

Author(s):

Anne-Marie Schjerning Olsen ◽

Emil L Fosbøl ◽

Jesper Lindhardsen ◽

Charlotte Andersson ◽

Fredrik Folke ◽

...

Keyword(s):

Myocardial Infarction ◽

Individual Level ◽

Cox Proportional Hazard ◽

Increased Risk ◽

History Of ◽

Cox Proportional Hazard Models ◽

Inflammatory Drugs ◽

Cox 2 Inhibitors ◽

First Time

Background: Use of NSAID has shown to be associated with a substantially increased risk of athero-thrombotic adverse events in patients with a history of myocardial infarction. Whether a similar increase in risk is found for VTE is unknown. Methods: Patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. The risk of VTE associated with NSAID use was analyzed by time-dependent Cox proportional hazard models adjusted for age, gender, calendar year, concomitant drug use, and comorbidity. Results A total of 98,901 patients were included (mean age 68 years (SD 13.0), 64.0% men), 44.0% received NSAIDs during follow-up. There were 1847 VTEs. Relative to no NSAID use, the Cox-analyses showed increased risk of VTE with use of any NSAIDs. Overall NSAID use was associated with increased risk of VTE (Hazard ratio [HR] 1.75 95% confidence interval [CI] 1.52-2.02). In particular use of the selective cyclooxygenase-2 (COX-2) inhibitors rofecoxib and the nonselective NSAID diclofenac was associated with significantly increased risk of VTE (HR 2.56 (CI 1.60-4.08) and HR 2.03(CI.1.50-2.74), respectively). Conclusion: Use of most NSAIDs was associated with an increased risk of VTE. The use of rofecoxib and diclofenac was associated with highest risk. Further studies, preferably randomized clinical studies, are warranted to establish the cardiovascular safety of NSAIDs, however this study suggests that risk of VTE should be considered when prescribing NSAIDs patients with MI.

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Height in Adolescence as a Risk Factor for Glioma Subtypes: a Nationwide Retrospective Cohort Study of 2.2 Million Subjects

Neuro-Oncology ◽

10.1093/neuonc/noab049 ◽

2021 ◽

Author(s):

Roi Tschernichovsky ◽

Lior H Katz ◽

Estela Derazne ◽

Matan Ben-Zion Berliner ◽

Maya Simchoni ◽

...

Keyword(s):

Risk Factor ◽

Statistical Significance ◽

Positive Association ◽

High Grade Glioma ◽

Low Grade ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Models ◽

Glioma Risk ◽

Incident Cases

Abstract Background Gliomas manifest in a variety of histological phenotypes with varying aggressiveness. The etiology of glioma remains largely unknown. Taller stature in adulthood has been linked with glioma risk. The aim of this study was to discern whether this association can be detected in adolescence. Methods The cohort included 2,223,168 adolescents between the ages of 16-19. Anthropometric measurements were collected at baseline. Incident cases of glioma were extracted from the Israel National Cancer Registry over a follow-up period spanning 47,635,745 person-years. Cox proportional hazard models were used to estimate the hazard ratio for glioma and glioma subtypes according to height, body mass index (BMI) and sex. Results 1,195 patients were diagnosed with glioma during the study period. Mean(SD) age at diagnosis was 38.1 (11.7) years. Taller adolescent height (per 10cm increase) was positively associated with the risk for glioma of any type (HR 1.15; p=0.002). The association was retained in subgroup analyses for low-grade glioma (HR 1.17; p=0.031), high-grade glioma (HR 1.15; p=0.025), oligodendroglioma (HR 1.31; p=0.015), astrocytoma (HR 1.12; p=0.049), and a category of presumed IDH-mutated glioma (HR 1.17; p=0.013). There was a trend towards a positive association between height and glioblastoma, however this had borderline statistical significance (HR: 1.15; p=0.07). After stratification of the cohort by sex, height remained a risk factor for men, but not for women. Conclusions The previously - established association between taller stature in adulthood and glioma risk can be traced back to adolescence. The magnitude of association differs by glioma subtype.

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Pregnancy, pregnancy loss and the risk of diabetes in Chinese women: findings from the China Kadoorie Biobank

European Journal of Epidemiology ◽

10.1007/s10654-019-00582-7 ◽

2019 ◽

Vol 35 (3) ◽

pp. 295-303

Author(s):

Sanne A. E. Peters ◽

◽

Ling Yang ◽

Yu Guo ◽

Yiping Chen ◽

...

Keyword(s):

Pregnancy Loss ◽

Cox Regression ◽

Chinese Women ◽

Later Life ◽

Induced Abortion ◽

Hazard Ratios ◽

Increased Risk ◽

History Of ◽

Incident Cases

AbstractPregnancy and pregnancy loss may be associated with increased risk of diabetes in later life. However, the evidence is inconsistent and sparse, especially among East Asians where reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy and pregnancy loss (miscarriage, induced abortion, and still birth) with the risk of incident diabetes in later life among Chinese women. In 2004–2008, the nationwide China Kadoorie Biobank recruited 302 669 women aged 30–79 years from 10 (5 urban, 5 rural) diverse localities. During 9.2 years of follow-up, 7780 incident cases of diabetes were recorded among 273,383 women without prior diabetes and cardiovascular disease at baseline. Cox regression yielded multiple-adjusted hazard ratios (HRs) for the risk of diabetes associated with pregnancy and pregnancy loss. Overall, 99% of women had been pregnant, of whom 10%, 53%, and 6% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Among ever pregnant women, each additional pregnancy was associated with an adjusted HR of 1.04 (95% CI 1.03; 1.06) for diabetes. Compared with those without pregnancy loss, women with a history of pregnancy loss had an adjusted HR of 1.07 (1.02; 1.13) and the HRs increased with increasing number of pregnancy losses, irrespective of the number of livebirths; the adjusted HR was 1.03 (1.00; 1.05) for each additional pregnancy loss. The strength of the relationships differed marginally by type of pregnancy loss. Among Chinese women, a higher number of pregnancies and pregnancy losses were associated with a greater risk of diabetes.

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P4745Concomitant oral anticoagulant and antidepressant therapy in patients with atrial fibrillation and risk of stroke and bleeding: a population based cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz745.1121 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

J J Komen ◽

P Hjemdahl ◽

A K Mantel - Teeuwisse ◽

O H Klungel ◽

B Wettermark ◽

...

Keyword(s):

Atrial Fibrillation ◽

Propensity Score ◽

Oral Anticoagulant ◽

Cox Regression ◽

Oral Anticoagulants ◽

Anticoagulant Treatment ◽

Oral Anticoagulant Treatment ◽

Increased Risk ◽

Antidepressant Use

Abstract Background Anticoagulation treatment reduces the risk of stroke but increases the risk of bleeding in atrial fibrillation (AF) patients. Antidepressants use is associated with increased risk for stroke and bleeds. Objective To assess the association between antidepressant use in AF patients with oral anticoagulants and bleeding and stroke risk. Methods All AF patients newly prescribed with an oral anticoagulant in the Stockholm Healthcare database (n=2.3 million inhabitants) from July 2011 until 2016 were included and followed for one year or shorter if they stopped claiming oral anticoagulant treatment or had an outcome of interest. Outcomes were severe bleeds and strokes, requiring acute hospital care. During follow-up, patients were considered exposed to antidepressant after claiming a prescription for the duration of the prescription. With a time-varying Cox regression, we assessed the association between antidepressant use and strokes and bleeds, adjusting for confounders (i.e., age, sex, comorbidities, comedication, and year of inclusion). In addition, we performed a propensity score matched analysis to test the robustness of our findings. Results Of the 30,595 patients included after claiming a prescription for a NOAC (n=13,506) or warfarin (n=17,089), 4 303 claimed a prescription for an antidepressant during follow-up. A total of 712 severe bleeds and 551 strokes were recorded in the cohort. Concomitant oral anticoagulant and antidepressant use was associated with increased rates of severe bleeds (4.7 vs 2.7 per 100 person-years) compared to oral anticoagulant treatment without antidepressant use (aHR 1.42, 95% CI: 1.12–1.80), but not significantly associated with increased stroke rates (3.5 vs 2.1 per 100 person-years, aHR 1.23, 95% CI: 0.93–1.62). No significant differences were observed between different oral anticoagulant classes (i.e., warfarin or NOAC) or different antidepressant classes (i.e., SSRI, TCA, or other antidepressant). Additional propensity-score matched analyses yielded similar results but showed a significantly increased risk for stroke (HR: 1.47, 95% CI: 1.08–2.02). Incidence rates of strokes and bleeds Conclusion Concomitant use of an oral anticoagulant and an antidepressant, irrespective of type, is associated with an increased bleeding risk. Increased awareness and a critical consideration for the need of an antidepressant is recommended in this population. Acknowledgement/Funding Swedish Heart Lung Foundation

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P1441 Predictors of systemic embolisms in a large cohort of left ventricular noncompaction patients

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez319.869 ◽

2020 ◽

Vol 21 (Supplement_1) ◽

Author(s):

G Casas ◽

G Oristrell ◽

J Limeres ◽

R Barriales ◽

J R Gimeno ◽

...

Keyword(s):

Risk Factors ◽

Atrial Fibrillation ◽

Oral Anticoagulation ◽

Systolic Dysfunction ◽

Left Ventricular ◽

Left Ventricular Noncompaction ◽

Severe Phenotype ◽

Ventricular Noncompaction ◽

Increased Risk

Abstract BACKGROUND Left ventricular noncompaction (LVNC) is associated with an increased risk of systemic embolisms (SE). However, incidence and risk factors are not well established. PURPOSE To evaluate the rate of SE in LVNC and describe risk factors. METHODS LNVC patients were included in a multicentric registry. Those with SE were considered for the analysis. RESULTS 514 patients with LVNC from 10 Spanish centres were recruited from 2000 to 2018. During a median follow-up of 4.2 years (IQR 1.9-7.1), 23 patients (4.5%) had a SE. Patients with SE (Table 1) were older at diagnosis, with no differences in gender and had similar cardiovascular risk factors. They were more frequently under oral anticoagulation (OAC). Besides, they had a more reduced LVEF, and more dilated LV and left atrium (LA). Late gadolinium enhancement (LGE) was more frequent, altogether suggesting a more severe phenotype. Patients with SE had non-significantly higher rates of hospitalization for heart failure (33% Vs 24%, p = 0.31) and atrial fibrillation (35% Vs 19%, p = 0.10). In multivariate analysis, only LA diameter was an independent predictor of SE (OR 1.04, p = 0.04). A LA diameter > 45 mm had an independent 3 fold increased risk of SE (OR 3.04, p = 0.02) (Image 1). CONCLUSIONS LVNC carries a moderate mid-term risk of SE, which appears to be irrespective of atrial fibrillation and associated with age, LV dilatation and systolic dysfunction and mainly LA dilatation. This subgroup of patients should be considered for oral anticoagulation in primary prevention. Table 1 Systemic embolisms (n = 23) No systemic embolisms (n = 491) p Men, n (%) 15 (65) 289 (56) 0.52 Median age at diagnosis (IQR) - yr 60 (48-76) 48 (30-64) 0.02 Median follow up (IQR) - yr 5.9 (3.1-7.8) 4.2 (1.8-7.1) 0.18 OAC, n (%) 19 (83) 118 (24) 0.01 LVEF (SD) - % 37 (15) 48 (17) 0.01 LVEDD (SD) - mm 58 (11) 54 (10) 0.04 LA diameter (SD) - mm 46 (9) 39 (9) 0.01 Characteristics of patients with and without systemic embolisms Abstract P1441 Figure. Image 1

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Prenatal and childhood antecedents of suicide: 50-year follow-up of the 1958 British Birth Cohort Study

Psychological Medicine ◽

10.1017/s003329171300189x ◽

2013 ◽

Vol 44 (6) ◽

pp. 1245-1256 ◽

Cited By ~ 24

Author(s):

M.-C. Geoffroy ◽

D. Gunnell ◽

C. Power

Keyword(s):

Risk Factors ◽

Birth Cohort ◽

Social Services ◽

Institutional Care ◽

Birth Cohort Study ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Models ◽

Childhood Antecedents

BackgroundWe aimed to elucidate early antecedents of suicide including possible mediation by early child development.MethodUsing the 1958 birth cohort, based on British births in March 1958, individuals were followed up to adulthood. We used data collected at birth and at age 7 years from various informants. Suicides occurring up to 31 May 2009 were identified from linked national death certificates. Multivariable Cox proportional hazard models were used to investigate risk factors.ResultsAltogether 12399 participants (n = 44 suicides) had complete data. The strongest prenatal risk factors for suicide were: birth order, with risk increasing in later-born children [ptrend = 0.063, adjusted hazard ratio (HR)], e.g. for fourth- or later-born children [HR = 2.27, 95% confidence interval (CI) 0.90–5.75]; young maternal age (HR = 1.18, 95% CI 0.34–4.13 for ⩽19 years and HR = 0.41, 95% CI 0.19–0.91 for >29 years, ptrend = 0.034); and low (<2.5 kg) birth weight (HR = 2.48, 95% CI 1.03–5.95). The strongest risk factors at 7 years were externalizing problems in males (HR = 2.96, 95% CI 1.03–8.47, ptrend = 0.050) and number of emotional adversities (i.e. parental death, neglected appearance, domestic tension, institutional care, contact with social services, parental divorce/separation and bullying) for which there was a graded association with risk of suicide (ptrend = 0.033); the highest (HR = 3.12, 95% CI 1.01–9.62) was for persons with three or more adversities.ConclusionsRisk factors recorded at birth and at 7 years may influence an individual's long-term risk of suicide, suggesting that trajectories leading to suicide have roots in early life. Some factors are amenable to intervention, but for others a better understanding of causal mechanisms may provide new insights for intervention to reduce suicide risk.

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Long-Term All-Cause Mortality and Its Association with Cardiovascular Risk Factors in Thyroid Cancer Survivors: An Israeli Population-Based Study

10.21203/rs.3.rs-39122/v3 ◽

2020 ◽

Author(s):

Elena Izkhakov ◽

Lital Keinan-Boker ◽

Micha Barchana ◽

Yacov Shacham ◽

Iris Yaish ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Thyroid Cancer ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Cox Regression ◽

Increased Risk ◽

All Cause Mortality

Abstract Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the long-term all-cause mortality in TC survivors compared to the general population, and its association with cardiovascular risk factors. Methods: Individuals diagnosed with TC during 2001-2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. Results: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5,677 (10.2%) TC patients and 1,235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR=1.89, 95%CI 1.71-2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR=1.49, 95%CI 1.33-1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P < 0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group. Conclusions: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.

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Association between Cardiovascular Risk Factors and Long-Term All-Cause Mortality in Thyroid Cancer Survivors: An Israeli Population-Based Study

10.21203/rs.3.rs-39122/v1 ◽

2020 ◽

Author(s):

Elena Izkhakov ◽

Lital Keinan-Boker ◽

Micha Barchana ◽

Yacov Shacham ◽

Iris Yaish ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Thyroid Cancer ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Cox Regression ◽

Increased Risk ◽

All Cause Mortality

Abstract Background: The global incidence of thyroid cancer (TC) has risen considerably during the last three decades, while prognosis is generally favorable. We assessed the association between long-term all-cause mortality and cardiovascular risk factors in TC survivors compared to the general population. Methods: Individuals diagnosed with TC during 2001-2014 (TC group) and age- and sex-matched individuals from the same Israeli healthcare system without thyroid disease or a cancer history (non-TC group) were compared. Cox regression hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality were calculated by exposure status. Results: During a 15-year follow-up (median 8 years), 577 TC survivors out of 5,677 (10.2%) TC patients and 1,235 individuals out of 23,962 (5.2%) non-TC patients died. The TC survivors had an increased risk of all-cause mortality (HR=1.89, 95%CI 1.71-2.10), after adjusting for cardiovascular risk factors already present at follow-up initiation. This increased risk was most pronounced in the 55- to 64-year-old age group (HR=1.49, 95%CI 1.33-1.67). The TC survivors who died by study closure had more hypertension (14.6% vs. 10.3%, P = 0.002), more dyslipidemia (11.4% vs. 7.2%, P < 0.001), and more cardiovascular disease (33.6% vs. 22.3%, P = 0.05) compared to those who died in the non-TC group. Conclusions: This large cohort study showed higher all-cause mortality with a higher prevalence of hypertension, dyslipidemia, and cardiovascular disease among TC survivors compared to matched non-TC individuals. Primary and secondary prevention of cardiovascular risk factors in TC survivors is mandatory.

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