Changes in Metabolic Syndrome Status and Breast Cancer Risk: A Nationwide Cohort Study

Objective: To our knowledge, no studies have yet looked at how the risk of developing breast cancer (BC) varies with changes in metabolic syndrome (MetS) status. This study aimed to investigate the association between changes in MetS and subsequent BC occurrence. Research Design and Methods: We enrolled 930,055 postmenopausal women aged 40–74 years who participated in a biennial National Health Screening Program in 2009–2010 and 2011–2012. Participants were categorized into four groups according to change in MetS status during the two-year interval screening: sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. We calculated multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for BC incidence using the Cox proportional hazards models. Results: At baseline, MetS was associated with a significantly increased risk of BC (aHR 1.11, 95% CI 1.06–1.17) and so were all of its components. The risk of BC increased as the number of the components increased (aHR 1.46, 95% CI 1.26–1.61 for women with all five components). Compared to the sustained non-MetS group, the aHR (95% CI) for BC was 1.11 (1.04–1.19) in the transition to MetS group, 1.05 (0.96–1.14) in the transition to non-MetS group, and 1.18 (1.12–1.25) in the sustained MetS group. Conclusions: Significantly increased BC risk was observed in the sustained MetS and transition to MetS groups. These findings are clinically meaningful in that efforts to recover from MetS may lead to reduced risk of BC.

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Distinct eGFR trajectories are associated with risk of myocardial infarction in people with diabetes or pre-diabetes

10.21203/rs.3.rs-25392/v1 ◽

2020 ◽

Author(s):

Yingting Zuo ◽

Anxin Wang ◽

Shuohua Chen ◽

Xue Tian ◽

Shouling Wu ◽

...

Keyword(s):

Myocardial Infarction ◽

Proportional Hazards ◽

Exposure Period ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

And Control ◽

Incident Cases

Abstract Background The relationship between estimated glomerular filtration rate (eGFR) trajectories and myocardial infarction (MI) remains unclear in people with diabetes or prediabetes. We aimed to identify common eGFR trajectories in people with diabetes or prediabetes and to examine their association with MI risk. Methods The data of this analysis was derived from the Kailuan study, which was a prospective community-based cohort study. The eGFR trajectories of 24,723 participants from year 2006 to 2012 were generated by latent mixture modeling. Incident cases of MI occurred during 2012 to 2017, confirmed by review of medical records. Cox proportional hazards models were used to calculate hazard ratios (HR) and their 95% confidence intervals (CIs) for the subsequent risk of MI of different eGFR trajectories. Results We identified 5 distinct eGFR trajectories, and named them as low-stable (9.4%), moderate-stable (31.4%), moderate-increasing (29.5%), high-decreasing (13.9%) and high-stable (15.8%) according to their range and pattern. During a mean follow-up of 4.61 years, there were a total of 235 incident MI. Although, the high-decreasing group had similar eGFR levels with the moderate-stable group at last exposure period, the risk was much higher (adjusted HR, 3.43; 95%CI, 1.56–7.54 versus adjusted HR, 2.82; 95%CI, 1.34–5.95). Notably, the moderate-increasing group had reached to the normal range, still had a significantly increased risk (adjusted HR, 2.55; 95%CI, 1.21–5.39). Conclusions eGFR trajectories were associated with MI risk in people with diabetes or prediabetes. Emphasis should be placed on early and long-term detection and control of eGFR decreases to further reduce MI risk.

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Visual impairment and risk of dementia in two population-based prospective cohorts: UK Biobank and EPIC-Norfolk

The Journals of Gerontology Series A ◽

10.1093/gerona/glab325 ◽

2021 ◽

Author(s):

Thomas J Littlejohns ◽

Shabina Hayat ◽

Robert Luben ◽

Carol Brayne ◽

Megan Conroy ◽

...

Keyword(s):

Visual Impairment ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Uk Biobank ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Promising Target ◽

Increased Risk

Abstract Visual impairment has emerged as a potential modifiable risk factor for dementia. However, there are a lack of large studies with objective measures of vison and with more than ten years of follow-up. We investigated whether visual impairment is associated with an increased risk of incident dementia in UK Biobank and EPIC-Norfolk. In both cohorts, visual acuity was measured using a “logarithm of the minimum angle of resolution” (LogMAR) chart and categorised as no (≤0.30 LogMAR), mild (>0.3 - ≤0.50 LogMAR), and moderate to severe (>0.50 LogMAR) impairment. Dementia was ascertained through linkage to electronic medical records. After restricting to those aged ≥60 years, without prevalent dementia and with eye measures available, the analytic samples consisted of 62,206 UK Biobank and 7,337 EPIC-Norfolk participants, respectively. In UK Biobank and EPIC-Norfolk. respectively, 1,113 and 517 participants developed dementia over 11 and 15 years of follow-up. Using multivariable cox proportional-hazards models, the hazard ratios for mild and moderate to severe visual impairment were 1.26 (95% Confidence Interval [CI] 0.92-1.72) and 2.16 (95% CI 1.37-3.40), in UK Biobank, and 1.05 (95% CI 0.72-1.53) and 1.93 (95% CI 1.05-3.56) in EPIC-Norfolk, compared to no visual impairment. When excluding participants censored within 5 years of follow-up or with prevalent poor or fair self-reported health, the direction of the associations remained similar for moderate impairment but were not statistically significant. Our findings suggest visual impairment might be a promising target for dementia prevention, however the possibility of reverse causation cannot be excluded.

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Racial Disparities in Delivery Gestational Age among Twin Pregnancies

American Journal of Perinatology ◽

10.1055/s-0037-1603764 ◽

2017 ◽

Vol 34 (11) ◽

pp. 1065-1071

Author(s):

Catherine Vladutiu ◽

Tracy Manuck ◽

Jacqueline Grant

Keyword(s):

Gestational Age ◽

Proportional Hazards ◽

Secondary Analysis ◽

Neonatal Morbidity ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Hydroxyprogesterone Caproate

Objective This study aims to estimate the association between maternal race and delivery gestational age among women with twin gestations. Study Design Secondary analysis of a prospective, randomized control trial of 17-α hydroxyprogesterone caproate versus placebo for preterm birth (PTB) prevention in twin gestations. Non-Hispanic (NH) black and whites were included. Demographic and antenatal characteristics were compared. The primary outcome was delivery gestational age. Secondary outcomes included a composite of major neonatal morbidity. Kaplan–Meier curves estimated survival probabilities for delivery gestational age by race. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 535 women with twin gestations were included; 150 were NH black. NH blacks delivered earlier than NH whites (33.6 ± 4.8 weeks vs. 35.1 ± 3.5 weeks, p < 0.001). Differences in delivery gestational age between NH blacks and whites were consistent across gestation. In adjusted analyses, NH black race (HR: 1.24, 95% CI: 1.02–1.51), prior PTB (HR: 1.59, 95% CI: 1.15–2.19), and cerclage (HR: 3.90, 95% CI: 2.00–7.60) were associated with an increased risk of earlier delivery. Major neonatal morbidity was higher for NH blacks compared with NH whites (12.7 vs. 7.0%, p = 0.036). Conclusion NH blacks with twin gestations have an increased risk of early delivery and neonatal morbidity compared with NH whites.

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The fraction of lung cancer attributable to smoking in the Norwegian Women and Cancer (NOWAC) Study

British Journal of Cancer ◽

10.1038/s41416-020-01131-w ◽

2020 ◽

Author(s):

Merethe S. Hansen ◽

Idlir Licaj ◽

Tonje Braaten ◽

Eiliv Lund ◽

Inger Torhild Gram

Keyword(s):

Lung Cancer ◽

Passive Smoking ◽

Proportional Hazards ◽

Population Attributable Fraction ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Nationally Representative ◽

Never Smokers

Abstract Background We examined the association between active and passive smoking and lung cancer risk and the population attributable fraction (PAF) of lung cancer due to active smoking, in the Norwegian Women and Cancer Study, a nationally representative prospective cohort study. Methods We followed 142,508 women, aged 31–70 years, who completed a baseline questionnaire between 1991 and 2007, through linkages to national registries through December 2015. We used Cox proportional hazards models, to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We calculated PAF to indicate what proportion of lung cancer cases could have been prevented in the absence of smoking. Results During the more than 2.3 million person-years of observation, we ascertained 1507 lung cancer cases. Compared with never smokers, current (HR 13.88, 95% CI 10.18–18.91) smokers had significantly increased risk of lung cancer. Female never smokers exposed to passive smoking had a 1.3-fold (HR 1.34, 95% CI 0.89–2.01) non- significantly increased risk of lung cancer, compared with never smokers. The PAF of lung cancer was 85.3% (95% CI 80.0–89.2). Conclusion More than 8 in 10 lung cancer cases could have been avoided in Norway, if the women did not smoke.

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The predictive role of sickness absence spell durations in associations with inpatient- and specialized outpatient care among a population-based Swedish twin sample

BMC Health Services Research ◽

10.1186/s12913-021-06310-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Annina Ropponen ◽

Mo Wang ◽

Jurgita Narusyte ◽

Sanna Kärkkäinen ◽

Victoria Blom ◽

...

Keyword(s):

Patient Care ◽

Sickness Absence ◽

Outpatient Care ◽

Proportional Hazards ◽

Population Based ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Predictive Role

Abstract Background The associations between a sickness absence spell duration and patient care have been rarely studied. An assumption is that associations would differ by spell duration and by the patient care type, inpatient- or specialized outpatient, due to severity of diseases and/or conditions. We aimed to investigate sickness absence spells in various spell durations as a predictor for subsequent inpatient- and specialized outpatient care separately, and to study if familial confounding plays a role in these associations. Methods We followed a population-based sample of Swedish twins born 1925–90 with national registers from 2001 for first incident sickness absence spell (days to calculate spell duration categorized into ≤30 days, 31–90 days, 91–180 days and ≥ 181 days), or no sickness absence, and for inpatient- and specialized outpatient care until 2013 (n = 24,975). Cox proportional hazards models were applied for hazard ratios (HR) with 95% confidence intervals (CI) while accounting for covariates and familial confounding. Results First incident sickness absence spell across all duration categories was associated with an increased risk of inpatient- (age- and sex adjusted HR 1.28 to 6.05) or specialized outpatient care (HR 1.17–2.50), both in comparison to those without any sickness absence or the shortest sickness absence spell category (1–30 days). The associations remained statistically significant while controlling for covariates or familial confounding. Conclusions First incident sickness absence spell increases the risk of inpatient care or specialized outpatient care regardless of the duration of the sickness absence spell. Hence, incident sickness absence spells should be noted and targeted to actions at workplaces as well as in primary and occupational health care.

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Probable REM sleep behavior disorder and risk of stroke

Neurology ◽

10.1212/wnl.0000000000003902 ◽

2017 ◽

Vol 88 (19) ◽

pp. 1849-1855 ◽

Cited By ~ 24

Author(s):

Chaoran Ma ◽

Milena Pavlova ◽

Yesong Liu ◽

Ying Liu ◽

Chunmei Huangfu ◽

...

Keyword(s):

Rem Sleep ◽

Proportional Hazards ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Cox Proportional Hazards ◽

Sleep Behavior ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk

Objective:To examine whether probable REM sleep behavior disorder (pRBD) was associated with increased risk of developing stroke in a community-based cohort.Methods:The study included 12,003 participants (mean age 54.0 years) of the Kailuan Study, free of stroke, cancer, Parkinson disease, dementia, and head injury at baseline (2012). We determined pRBD using a validated REM sleep behavior disorder (RBD) questionnaire in 2012. Incident stroke cases were confirmed by review of medical records. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of stroke according to pRBD status, adjusting for several sleep measures (i.e., insomnia, daytime sleepiness, sleep duration, snoring, and use of hypnotics) and other potential confounders.Results:During 3 years of follow-up, we documented 159 incident stroke cases. Relative to participants without pRBD at the baseline, those with pRBD had a 157% higher risk (95% CI 59%–313%) of developing stroke. Presence of pRBD was associated with increased risk of both stroke types—the adjusted HR was 1.93 (95% CI 1.07–3.46) for ischemic stroke and 6.61 (95% CI 2.27–19.27) for hemorrhagic stroke.Conclusions:Presence of pRBD was associated with a higher risk of developing stroke, including both ischemic and hemorrhagic types. Future studies with clinically confirmed RBD and a longer follow-up would be appropriate to further investigate this association.

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Metabolic Syndrome, Its Components and Risk of Cardiometabolic Multimorbidity: Findings From the UK Biobank Cohort

10.21203/rs.3.rs-189744/v1 ◽

2021 ◽

Author(s):

Yanan Qiao ◽

Siyuan Liu ◽

Guochen Li ◽

Yanqiang Lu ◽

Ying Wu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Cardiometabolic Disease ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Previous Diagnosis ◽

The Uk

Abstract Background: Metabolic syndrome (MetS) and its components have been acknowledged as risk factors for a single cardiometabolic disease, but their relationship with the risk of cardiometabolic multimorbidity is unclear. The present study aimed to prospectively investigate the association of MetS and its components with the risk of cardiometabolic multimorbidity.Methods: In this prospective cohort study, we analyzed data of 353,427 participants from the UK Biobank. Participants with a previous diagnosis of cardiometabolic disease or those with missing data on the items of MetS were not eligible. Cardiometabolic multimorbidity was defined as the co-existence of two and more conditions of type 2 diabetes, coronary heart disease (CHD), and stroke. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the relationship between MetS, components of MetS and cardiometabolic multimorbidity. Results: During a median of 8.9 years of follow-up, 3389 participants developed the cardiometabolic multimorbidity. Compared with individuals without MetS, individuals with MetS had a three times higher risk of developing cardiometabolic multimorbidity (adjusted HR: 3.02, 95% CI: 2.82-3.24). The accumulation of MetS components was associated, in a dose-response manner, with the risk of cardiometabolic multimorbidity (P for trend <0.0001). For the temporal sequences in the development of cardiometabolic diseases, the corresponding HRs (95% CIs) for individuals with ≥4 metabolic abnormalities were 1.57 (1.47-1.68) for cardiovascular disease only, 10.27 (7.62-13.84) for cardiovascular disease with subsequent diabetes, 25.34 (21.95-29.24) for diabetes only, and 42.97 (21.19-87.13) for diabetes with subsequent cardiovascular disease.Conclusions: MetS was independently associated with the risk of cardiometabolic multimorbidity, and the risk substantially increased with a greater number of MetS components. Our findings highlight the importance of screening and treatment of MetS in the prevention of cardiometabolic multimorbidity.

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Antipsychotics, Prolactin and Breast Cancer

10.1101/2021.06.06.21258408 ◽

2021 ◽

Author(s):

Tahir Rahman ◽

John Sahrmann ◽

Margaret A. Olsen ◽

Katelin B. Nickel ◽

j Philip Miller ◽

...

Keyword(s):

Breast Cancer ◽

Antipsychotic Drug ◽

Invasive Breast Cancer ◽

Antipsychotic Drugs ◽

Drug Exposure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Serum Prolactin ◽

Cox Proportional Hazards Models ◽

Increased Risk

Objective: Antipsychotic drugs are well established to alter circulating prolactin levels by blocking dopamine D-2 receptors in the pituitary. Prolactin activates many genes important in the development of breast cancer. The aim of this study was to evaluate the risk of breast cancer in women exposed to antipsychotic drugs, stratified by prolactin elevating potential (high, mid, and low), compared to women taking anticonvulsants and/or lithium. Methods: The IBM MarketScan Commercial and Medicaid Databases were used to establish a large, observational cohort of women taking antipsychotics drugs compared to control drugs. Invasive breast cancer was identified using diagnostic codes. Bivariable and multivariable Cox proportional hazards models were used to evaluate the risk of breast cancer by antipsychotic drug exposure, both as pooled antipsychotics and by prolactin specific categories. Results: A total of 2,708 (0.2%) cases of invasive breast cancer were identified among 1,562,839 women. Exposure to antipsychotics with high prolactin elevating potential was associated with a 23% increased risk of breast cancer (aHR 1.23; 95% CI, 1.11-1.35), whereas mid and low prolactin categories of antipsychotics were not significant. Conclusion: In the largest study of antipsychotics taken by women, a modest risk between antipsychotic drug use and the risk for breast cancer was observed, with a differential higher association with high prolactin elevating drugs. Residual confounding factors included incomplete information on parity, race and socioeconomic status, and differential outpatient visits. Clinicians should consider monitoring serum prolactin levels and adopting vigilant mammography screening practices, especially in older women taking category one antipsychotics.

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Sex-Specific Associations between Blood Pressure and Risk of Atrial Fibrillation Subtypes in the Tromsø Study

Journal of Clinical Medicine ◽

10.3390/jcm10071514 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1514

Author(s):

Hilde Espnes ◽

Jocasta Ball ◽

Maja-Lisa Løchen ◽

Tom Wilsgaard ◽

Inger Njølstad ◽

...

Keyword(s):

Atrial Fibrillation ◽

Blood Pressure ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Pressure Management ◽

Reference Models ◽

Proportional Hazards Regression ◽

Hazard Ratios ◽

Increased Risk

The aim of this study was to explore sex-specific associations between systolic blood pressure (SBP), hypertension, and the risk of incident atrial fibrillation (AF) subtypes, including paroxysmal, persistent, and permanent AF, in a general population. A total of 13,137 women and 11,667 men who participated in the fourth survey of the Tromsø Study (1994–1995) were followed up for incident AF until the end of 2016. Cox proportional hazards regression analysis was conducted using fractional polynomials for SBP to provide sex- and AF-subtype-specific hazard ratios (HRs) for SBP. An SBP of 120 mmHg was used as the reference. Models were adjusted for other cardiovascular risk factors. Over a mean follow-up of 17.6 ± 6.6 years, incident AF occurred in 914 (7.0%) women (501 with paroxysmal/persistent AF and 413 with permanent AF) and 1104 (9.5%) men (606 with paroxysmal/persistent AF and 498 with permanent AF). In women, an SBP of 180 mmHg was associated with an HR of 2.10 (95% confidence interval [CI] 1.60–2.76) for paroxysmal/persistent AF and an HR of 1.80 (95% CI 1.33–2.44) for permanent AF. In men, an SBP of 180 mmHg was associated with an HR of 1.90 (95% CI 1.46–2.46) for paroxysmal/persistent AF, while there was no association with the risk of permanent AF. In conclusion, increasing SBP was associated with an increased risk of both paroxysmal/persistent AF and permanent AF in women, but only paroxysmal/persistent AF in men. Our findings highlight the importance of sex-specific risk stratification and optimizing blood pressure management for the prevention of AF subtypes in clinical practice.

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Effects of antiarrhythmic drugs on atrioventricular conduction in patients with preexisting bundle branch block

European Heart Journal ◽

10.1093/ehjci/ehaa946.3358 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Kochav ◽

R.C Chen ◽

J.M.D Dizon ◽

J.A.R Reiffel

Keyword(s):

Proportional Hazards ◽

Cox Proportional Hazards ◽

Class I ◽

Class Iii ◽

Bundle Branch Block ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

History Of ◽

Propensity Score Stratification

Abstract Background Theoretical concern exists regarding AV block (AVB) with class I antiarrhythmics (AADs) when bundle branch block (BBB) is present. Whether this is substantiated in real-world populations is unknown. Purpose To determine the relationship between type of AAD and incidence of AVB in patients with preexisting BBB. Methods We retrospectively studied all patients with BBB who received class I and III AADs between 1997–2019 to compare incidence of AVB. We defined index time as first exposure to either drug class and excluded patients with prior AVB or exposed to both classes. Time-at-risk window ended at first outcome occurrence or when patients were no longer observed in the database. We estimated hazard ratios for incident AVB using Cox proportional hazards models with propensity score stratification, adjusting for over 32,000 covariates from the electronic health record. Kaplan-Meier methods were used to determine treatment effects over time. Results Of 40,120 individuals with BBB, 148 were exposed to a class I AAD and 2401 to a class III AAD. Over nearly 4,200 person-years of follow up, there were 22 and 620 outcome events in the class I and class III cohorts, respectively (Figure). In adjusted analyses, AVB risk was markedly lower in patients exposed to class I AADs compared with class III (HR 0.48 [95% CI 0.30–0.75]). Conclusion Among patients with BBB, exposure to class III AADs was strongly associated with greater risk of incident AVB. This likely reflects differences in natural history of patients receiving class I vs class III AADs rather than adverse class III effects, however, the lack of worse outcomes acutely with class I AADs suggests that they may be safer in BBB than suspected. Funding Acknowledgement Type of funding source: None

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