Increased mortality risk in patients with primary and secondary adrenal insufficiency

Abstract Context Mortality data in patients with adrenal insufficiency are inconsistent, possibly due to temporal and geographical differences between patients and their reference populations. Objective To compare mortality risk and causes of death in adrenal insufficiency with an individually-matched reference population. Design Retrospective cohort study. Setting UK general practitioner database (CPRD). Participants 6821 patients with adrenal insufficiency (primary, 2052; secondary, 3948) and 67564 individually-matched controls (primary, 20366; secondary, 39134). Main outcome measures All-cause and cause-specific mortality; hospital admission from adrenal crisis. Results With follow-up of 40799 and 406899 person-years for patients and controls respectively, the hazard ratio (HR; [95%CI]) for all-cause mortality was 1.68 [1.58 - 1.77]. HRs were greater in primary (1.83 [1.66 - 2.02]) than in secondary (1.52 [1.40 - 1.64]) disease; (HR; primary versus secondary disease, 1.16 [1.03 - 1.30]). The leading cause of death was cardiovascular disease (HR 1.54 [1.32-1.80]), along with malignant neoplasms and respiratory disease. Deaths from infection were also relatively high (HR 4.00 [2.15 - 7.46]). Adrenal crisis contributed to 10% of all deaths. In the first two years following diagnosis, the patients’ mortality rate and hospitalisation from adrenal crisis were higher than in later years. Conclusion Mortality was increased in adrenal insufficiency, especially primary, even with individual matching and was observed early in the disease course. Cardiovascular disease was the major cause but mortality from infection was also high. Adrenal crisis was a common contributor. Early education for prompt treatment of infections and avoidance of adrenal crisis hold potential to reduce mortality.

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1445Physical activity and long-term mortality risk in Israeli older adults with and without cardiovascular disease

European Heart Journal ◽

10.1093/eurheartj/ehz748.0080 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

Y Gerber ◽

O Shaked ◽

G Cohen ◽

A Goshen ◽

T Shimony ◽

...

Keyword(s):

Physical Activity ◽

Cardiovascular Disease ◽

Older Adults ◽

Older Adult ◽

Mortality Risk ◽

Protective Factor ◽

Adult Population ◽

Mortality Data ◽

Nutrition Survey

Abstract Background Physical activity (PA) is a known protective factor among both general population and cardiovascular disease (CVD) patients. Yet, only a few cohort studies assessed the role of PA among older adult populations, characterized by high CVD prevalence rates. Objectives To evaluate the association between PA levels and all-cause mortality among Israeli older adults, and to assess whether it differs by baseline CVD status. Methods Participants were drawn from the National Health and Nutrition Survey of Older Adults Aged 65+ (“Mabat-Zahav”), conducted by the Israel Center for Disease Control between July 2005 and December 2006. Clinical, behavioral, and psychosocial data were collected via interview at study entry; a detailed PA questionnaire was also administered, through which participants were classified as sufficiently-active, insufficiently-active, and inactive, according to the American College of Sports Medicine classification. Mortality data (last follow-up, December 2016) were obtained from the Israeli Ministry of Health. Inverse probability weighted Cox proportional hazards models, based on propensity score, were constructed to assess the adjusted association between PA categories and mortality. Results Of the 1799 participants (mean [SD] age, 74.6 [6.2] years; 647 [36%] with a history of CVD), 559 (31%) were sufficiently-active, 506 (28%) were insufficiently-active and 734 (41%) were inactive. During a mean follow-up period of 9.0 years, 684 participants (38%) died. PA and mortality demonstrated an inverse dose-response relationship in both CVD and non-CVD groups, with no CVD-by-PA interaction detected on multiplicative-scale (P=0.70) or additive-scale (P=0.58). Notably, inactive non-CVD subjects had comparable risk to CVD patients who were sufficiently active (Figure). Physical activity and mortality Conclusions In a nationally-based cohort of subjects aged 65 years and over, PA was inversely associated with mortality risk. CVD patients who preformed sufficient PA had a comparable mortality risk to inactive subjects free of CVD. These findings illustrate the importance of PA in the older adult population.

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Physical Activity and Long-Term Mortality Risk in Older Adults with and without Cardiovascular Disease: A Nationwide Cohort Study

Gerontology ◽

10.1159/000518169 ◽

2021 ◽

pp. 1-9

Author(s):

Or Shaked ◽

Gali Cohen ◽

Abigail Goshen ◽

Tal Shimony ◽

Tamar Shohat ◽

...

Keyword(s):

Physical Activity ◽

Cardiovascular Disease ◽

Older Adults ◽

Propensity Score ◽

Mortality Risk ◽

Mortality Data ◽

Cox Models ◽

Long Term Mortality

Aims: To evaluate the association between physical activity (PA) levels and mortality among older adults, to determine whether it differs according to cardiovascular disease (CVD) status, and to assess the optimal weekly duration of PA associated with subsequent survival. Methods: Participants (n = 1,799) were drawn from a national survey conducted from 2005 to 2006, constituting Israeli adults aged ≥65 years. Sociodemographic, clinical, behavioral, and psychosocial data were collected via interview at study entry. Based on a detailed PA questionnaire and according to published guidelines, participants were classified as sufficiently active, insufficiently active, and inactive. CVD status was self-reported. Mortality data (last follow-up, December 2016) were obtained from the Israeli Ministry of Health. Using Cox models, inverse probability weighted hazard ratios (HRs) for mortality, based on propensity score, were estimated for PA categories. Results: Among the participants at baseline (mean age, 74.6 years), 559 (31.1%) were sufficiently active, 506 (28.1%) were insufficiently active, and 734 (40.8%) were inactive. During follow-up (mean, 9.0 years), 684 participants (38.0%) died. PA was inversely associated with mortality, with propensity score-adjusted HRs (95% confidence intervals) of 0.84 (0.71–1.01) in insufficiently and 0.73 (0.61–0.88) in sufficiently active participants (ptrend < 0.001). No PA-by-CVD interaction was detected on multiplicative scale (p = 0.36) or additive scale (p = 0.58). A monotonic survival benefit was observed until ∼150 min of PA per week, beyond which no further gain was apparent. Conclusions: In a nationwide cohort of older adults, nearly 70% did not meet the guideline for PA. PA engagement was inversely associated with long-term mortality risk, similarly in individuals with and without CVD. A maximum survival advantage was achieved at around 150 min of exercise per week.

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Association of disability with mortality in the Spanish adult non-institutionalised population

Journal of Epidemiology & Community Health ◽

10.1136/jech-2021-217421 ◽

2021 ◽

pp. jech-2021-217421

Author(s):

Javier Damián ◽

Alicia Padron-Monedero ◽

Javier Almazán-Isla ◽

Fernando J García López ◽

Jesús de Pedro-Cuesta ◽

...

Keyword(s):

Mortality Risk ◽

Adult Population ◽

Community Dwelling ◽

Mortality Data ◽

Standard Population ◽

All Cause Mortality ◽

Specific Mortality ◽

Nationally Representative ◽

Rate Ratios

BackgroundThere are scant studies focused on measuring the association between disability and all-cause mortality based on large representative national samples of the community-dwelling adult population; moreover, the number of such studies which also include cause-specific mortality is yet lower.MethodsLongitudinal cohort study that used baseline data from 162 381 adults who participated in a countrywide disability survey (2008). A nationally representative sample was selected and interviewed in their homes. We present data on people ≥18 years. Disability was considered as any substantial limitation found on a list of 44 life activities that have lasted or are expected to last more than 1 year and originate from an impairment. Cause-specific mortality data were obtained from the Spanish Statistical Office. Subjects contributed follow-up time from baseline interview until death or the censoring date (31 December 2017). We computed standardised rate ratios (SRRs), with age, sex, living with a partner and education level distribution of the total group as standard population.ResultsAdults with disability (11%) had an adjusted mortality rate more than twice as high as adults without disability (SRR 2.37, 95% CI 2.24 to 2.50). The increased mortality risk remained over the 10-year follow-up period. Mortality due to diseases of the nervous system (SRR 4.86, 95% CI 3.93 to 6.01), diseases of the musculoskeletal system (SRR 3.45, 95% CI 2.18 to 5.47), infectious diseases (SRR 3.38, 95% CI 2.27 to 5.01) and diabetes mellitus (SRR 3.56, 95% CI 2.71 to 4.68) was particularly high in those with disability.ConclusionsAll-cause mortality rates are markedly higher among adults with disability. Preventive measures and health promotion initiatives are needed to reduce mortality risk in this population. Special attention should be paid to disabled people with certain specific diseases.

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POS0141 ACTIVE SCREENING FOR GOUT IDENTIFIES A LARGER CARDIOVASCULAR POPULATION AT HIGH MORTALITY RISK

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1872 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 282.2-282

Author(s):

S. Ruiz-Simón ◽

I. Calabuig ◽

M. Gomez-Garberi ◽

M. Andrés

Keyword(s):

High Mortality ◽

Mortality Risk ◽

Cardiovascular Events ◽

Cox Regression ◽

Field Studies ◽

High Mortality Risk ◽

Active Screening ◽

Tertiary Centre ◽

All Cause Mortality

Background:We have recently revealed by active screening that about a third of gout cases in the cardiovascular population is not registered in records [1], highlighting the value of field studies.Objectives:To assess whether gout screening in patients hospitalized for cardiovascular events may also help identify patients at higher risk of mortality after discharge.Methods:A retrospective cohort field study, carried out in 266 patients admitted for cardiovascular events in the Cardiology, Neurology and Vascular Surgery units of a tertiary centre in Spain. The presence of gout was established by records review and face-to-face interview, according to the 2015 ACR/EULAR criteria. The occurrence of mortality during follow-up and its causes were obtained from electronic medical records. The association between gout and subsequent mortality was tested using Cox regression models. Whether covariates affect the gout-associated mortality was also studied.Results:Of 266 patients recruited at baseline, 17 were excluded due to loss to follow-up (>6mo), leaving a final sample of 249 patients (93.6%). Thirty-six cases (14.5% of the sample) were classified as having gout: twenty-three (63.9%) had a previously registered diagnosis, while 13 (36.1%) had not and was established by the interview.After discharge, the mean follow-up was 19.9 months (SD ±8.6), with a mortality incidence of 21.6 deaths per 100 patient-years, 34.2% by cardiovascular causes.Gout significantly increased the risk of subsequent all-cause mortality, with a hazard ratio (HR) of 2.01 (95%CI 1.13 to 3.58). When the analysis was restricted to gout patients with registered diagnosis, the association remained significant (HR 2.89; 95%CI 1.54 to 5.41).The adjusted HR for all-cause mortality associated with gout was 1.86 (95% CI 1.01-3.40). Regarding the causes of death, both cardiovascular and non-cardiovascular were numerically increased.Secondary variables rising the mortality risk in those with gout were age (HR 1.07; 1.01 to 1.13) and coexistent renal disease (HR 4.70; 1.31 to 16.84), while gender, gout characteristics and traditional risk factors showed no impact.Conclusion:Gout was confirmed an independent predictor of subsequent all-cause mortality in patients admitted for cardiovascular events. Active screening for gout allowed identifying a larger population at high mortality risk, which may help tailor optimal management to minimize the cardiovascular impact.References:[1]Calabuig I, et al. Front Med (Lausanne). 2020 Sep 29;7:560.Disclosure of Interests:Silvia Ruiz-Simón: None declared, Irene Calabuig: None declared, Miguel Gomez-Garberi: None declared, Mariano Andrés Speakers bureau: Grunenthal, Menarini, Consultant of: Grunenthal, Grant/research support from: Grunenthal

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Association with Longevity of Phosphatidylinositol 3-Kinase Regulatory Subunit 1 Gene Variants Stems from Protection against Mortality Risk in Men with Cardiovascular Disease

Gerontology ◽

10.1159/000515390 ◽

2021 ◽

pp. 1-9

Author(s):

Timothy A. Donlon ◽

Randi Chen ◽

Kamal H. Masaki ◽

Bradley J. Willcox ◽

Brian J. Morris

Keyword(s):

Cardiovascular Disease ◽

Life Span ◽

Mortality Risk ◽

Regulatory Subunit ◽

Phosphatidylinositol 3 Kinase ◽

Survival Curves ◽

Genotypic Effect ◽

Hazard Ratios ◽

Phosphatidylinositol 3

Introduction: Genetic variation in the phosphatidylinositol 3-kinase reregulatory subunit 1 gene (PIK3R1) is associated with longevity. Objective: The aim of the study was to determine whether cardiovascular disease (CVD) affects this association. Methods: We performed a longitudinal study of longevity-associated PIK3R1 single-nucleotide polymorphism rs7709243 genotype by CVD status in 3,584 elderly American men of Japanese ancestry. Results: At baseline (1991–1993), 2,254 subjects had CVD and 1,314 did not. The follow-up until Dec 31, 2019 found that overall, men with a CVD had higher mortality than men without a CVD (p = 1.7 × 10−5). However, survival curves of CVD subjects differed according to PIK3R1 genotype. Those with longevity-associated PIK3R1 TT/CC had survival curves similar to those of subjects without a CVD (p = 0.11 for TT/CC, and p = 0.054 for TC), whereas survival curves for CVD subjects with the CT genotype were significantly attenuated compared with survival curves of subjects without a CVD (p = 0.0000012 compared with TT/CC, and p = 0.0000028 compared with TC). Men without CVD showed no association of longevity-associated genotype with life span (p = 0.58). Compared to subjects without any CVD, hazard ratios for mortality risk were 1.26 (95% CI, 1.14–1.39; p = 0.0000043) for CT subject with CVD and 1.07 (95% CI 0.99–1.17; p = 0.097) for CC/TT subjects with CVD. There was no genotypic effect on life span for 1,007 subjects with diabetes and 486 with cancer. Conclusion: Our study provides novel insights into the basis for PIK3R1 as a longevity gene. We suggest that the PIK3R1 longevity genotype attenuates mortality risk in at-risk individuals by protection against cellular stress caused by CVD.

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Multi-trajectories of lipid indices with incident cardiovascular disease, heart failure, and all-cause mortality: 23 years follow-up of two US cohort studies

Journal of Translational Medicine ◽

10.1186/s12967-021-02966-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Fatemeh Koohi ◽

Davood Khalili ◽

Mohammad Ali Mansournia ◽

Farzad Hadaegh ◽

Hamid Soori

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Cohort Studies ◽

Significant Risk ◽

Density Lipoprotein ◽

Lipid Levels ◽

Cvd Risk ◽

All Cause Mortality ◽

Over Time

Abstract Background Understanding the distinct patterns (trajectories) of variation in blood lipid levels before diagnosing cardiovascular disease (CVD) might carry important implications for improving disease prevention or treatment. Methods We investigated 14,373 participants (45.5% men) aged 45–84 from two large US prospective cohort studies with a median of 23 years follow-up. First, we jointly estimated developmental trajectories of lipid indices, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) concentrations using group-based multi-trajectory modeling. Then, the association of identified multi-trajectories with incident CVD, heart failure, and all-cause mortality were examined using Cox proportional hazard model. Results Seven distinct multi-trajectories were identified. The majority of participants (approximately 80%) exhibited decreasing LDL-C but rising TG levels and relatively stable HDL-C levels. Compared to the individuals with healthy and stable LDL-C, HDL-C, and TG levels, those in other groups were at significant risk of incident CVD after adjusting for other conventional risk factors. Individuals with the highest but decreasing LDL-C and borderline high and rising TG levels over time were at the highest risk than those in other groups with a 2.22-fold risk of CVD. Also, those with the highest and increased triglyceride levels over time, over optimal and decreasing LDL-C levels, and the lowest HDL-C profile had a nearly 1.84 times CVD risk. Even individuals in the multi-trajectory group with the highest HDL-C, optimal LDL-C, and optimal TG levels had a significant risk (HR, 1.45; 95% CI 1.02–2.08). Furthermore, only those with the highest HDL-C profile increased the risk of heart failure by 1.5-fold (95% CI 1.07–2.06). Conclusions The trajectories and risk of CVD identified in this study demonstrated that despite a decline in LDL-C over time, a significant amount of residual risk for CVD remains. These findings suggest the impact of the increasing trend of TG on CVD risk and emphasize the importance of assessing the lipid levels at each visit and undertaking potential interventions that lower triglyceride concentrations to reduce the residual risk of CVD, even among those with the optimal LDL-C level.

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Estimates of mortality rates in people with diabetes and cardiovascular disease using administrative pharmaceutical data

International Journal for Population Data Science ◽

10.23889/ijpds.v4i3.1166 ◽

2019 ◽

Vol 4 (3) ◽

Author(s):

Shaun Purkiss ◽

Tessa Keegel ◽

Hassan Vally ◽

Dennis Wollersheim

Keyword(s):

Cardiovascular Disease ◽

Mortality Risk ◽

Age Groups ◽

Mortality Rates ◽

World Health ◽

Data Set ◽

Medication Discontinuation ◽

Disease Mortality ◽

Health Organization

BackgroundQuantifying the mortality risk for people with diabetes is challenging because of associated comorbidities. The recording of cause specific mortality from accompanying cardiovascular disease in death certificate notifications has been considered to underestimate the overall mortality risk in persons with diabetes. Main AimDevelop a technique to quantify mortality risk from pharmaceutical administrative data and apply it to persons diagnosed with diabetes, and associated cardiovascular disease and dyslipidaemia before death. MethodsPersons with diabetes, cardiovascular disease and dyslipidaemia were identified in a publicly available Australian Pharmaceutical data set using World Health Organization anatomic therapeutic codes assigned to medications received. Diabetes associated multi-morbidity cohorts were constructed and a proxy mortality (PM) event determined from medication and service discontinuation. Estimates of mortality rates were calculated from 2004 for 10 years and compared persons with diabetes alone and associated cardiovascular disease and dyslipidemia. ResultsThis study identified 346,201 individuals within the 2004 calendar year as having received treatments for diabetes (n=51,422), dyslipidaemia (n=169,323) and cardiovascular disease including hypertension (n=280,105). Follow up was 3.3 x 106 person-years. Overall crude PM was 26.1 per 1000 person-years. PM rates were highest in persons with cardiovascular disease and diabetes in combination (47.5 per 100 person years). Statin treatments significantly improved the mortality rates in all persons with diabetes and cardiovascular disease alone and in combination over age groups >44 years (p<.001). Age specific diabetes PM rates using pharmaceutical data correlated well with Australian data from the National Diabetes Service Scheme (r=0.82) ConclusionProxy mortality events calculated from medication discontinuation in persons with chronic conditions can provide an alternative method to estimate disease mortality rates. The technique also allows the assessment of mortality risk in persons with chronic disease multi-morbidity.

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Predictors of three-month mortality among hospitalized older adults in Togo

10.21203/rs.3.rs-38973/v2 ◽

2020 ◽

Author(s):

Fifonsi Adjidossi GBEASOR-KOMLANVI ◽

Martin Kouame TCHANKONI ◽

Akila Wimima BAKOUBAYI ◽

Matthieu Yaovi LOKOSSOU ◽

Arnold SADIO ◽

...

Keyword(s):

Older Adults ◽

Hospital Mortality ◽

Cox Regression ◽

Sub Saharan Africa ◽

Mortality Data ◽

Kaplan Meier ◽

All Cause Mortality ◽

Hospitalized Older Adults ◽

Sub Saharan

Abstract Background: Assessing hospital mortality and its predictors is important as some of these can be prevented through appropriate interventions. Few studies have reported hospital mortality data among older adults in sub-Saharan Africa. The objective of this study was to assess the mortality and associated factors among hospitalized older adults in Togo.Methods: We conducted a prospective cohort study from February 2018 to September 2019 among patients ≥50 years admitted in medical and surgical services of six hospitals in Togo. Data were recorded during hospitalization and through telephone follow-up survey within 90 days after admission. The main outcome was all-cause mortality at 3 months. Survival curves were estimated using the Kaplan-Meier method and Cox regression analyses were performed to assess predictors of mortality.Results: The median age of the 650 older adults included in the study period was 61 years, IQR: [55-70] and at least one comorbidity was identified in 59.7% of them. The all-cause mortality rate of 17.2% (95%CI: 14.4-20.4) and the majority of death (93.7%) occurred in hospital. Overall survival rate was 85.5% and 82.8% after 30 and 90 days of follow-up, respectively. Factors associated with 3-month mortality were the hospital level in the health pyramid, hospitalization service, length of stay, functional impairment, depression and malignant diseases.Conclusion: Togolese health system needs to adjust its response to an aging population in order to provide the most effective care.

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Abstract WP226: The Association of Green Tea and Coffee Consumption With Mortality From Cardiovascular Disease and All Causes Among Persons With and Without History of Stroke or Myocardial Infarction: The JACC Study

Stroke ◽

10.1161/str.51.suppl_1.wp226 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Masayuki Teramoto ◽

Isao Muraki ◽

Kokoro Shirai ◽

Akiko Tamakoshi ◽

Hiroyasu Iso

Keyword(s):

Myocardial Infarction ◽

Cardiovascular Disease ◽

General Population ◽

Green Tea ◽

Coffee Consumption ◽

Tea Consumption ◽

Food Frequency ◽

All Cause Mortality ◽

History Of

Background: Both green tea and coffee consumption have been associated with lower risks of mortality from cardiovascular disease (CVD) and all causes in general population, but little is known about those impact on persons with history of CVD. We examined the association of those consumption with these mortalities among persons with and without history of stroke or myocardial infarction in general population. Methods: The study subjects were 60,664 participants (896 stroke and 1751 myocardial infarction survivors and 58,017 persons with no history of stroke or myocardial infarction), aged 40-79 years at the baseline (1988-1990), who completed a lifestyle and medical history questionnaire including self-administered food frequency under the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). Results: During the median follow-up of 18.5 years, a total of 12,745 (7,458 men and 5,287 women) deaths including 3,737 CVD deaths were documented. Green tea and coffee consumption were inversely associated with CVD and all-cause mortality among myocardial infarction survivors as well as persons without history of stroke or myocardial infarction. After adjustment for known cardiovascular risk factors, the lower risks of mortality from CVD and all-causes associated with frequent green tea consumption (5-6 and ≥7 cups/day) or coffee consumption (≥2 cups/day) remained statistical. Conclusions: Both green tea and coffee consumption were inversely associated with risks of CVD and all-cause mortality among myocardial infarction survivors and persons without history of stroke or myocardial infarction.

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High Serum Folate Concentrations Are Associated with Decreased Risk of Mortality among Japanese Adults

Journal of Nutrition ◽

10.1093/jn/nxaa382 ◽

2021 ◽

Author(s):

Sanmei Chen ◽

Takanori Honda ◽

Jun Hata ◽

Satoko Sakata ◽

Yoshihiko Furuta ◽

...

Keyword(s):

Mortality Risk ◽

Serum Vitamin ◽

Mthfr C677t ◽

Serum Folate ◽

Vitamin B ◽

Mthfr C677t Polymorphism ◽

Japanese Adults ◽

All Cause Mortality ◽

Vitamin B 12

ABSTRACT Background Folate and vitamin B-12 are essential nutrients for normal cell growth and replication, but the association of serum folate and vitamin B-12 concentrations with mortality risk remains uncertain. Objective This study was performed to investigate the associations of serum folate and vitamin B-12 concentrations with mortality risk and test whether the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism modifies these associations. Methods A total of 3050 Japanese community residents aged ≥40 y were prospectively followed-up for mortality between 2002 and 2012. Cox proportional hazards models and restricted cubic splines were used to estimate HRs and 95% CIs of mortality. Results During a median follow-up period of 10.2 y, 336 participants died. Higher serum folate concentrations were associated with lower risks of all-cause mortality [multivariable-adjusted HR: 0.73; 95% CI: 0.56, 0.96 for the second tertile (8.8–12.2 nmol/L; median 10.4 nmol/L) and HR: 0.61; 95% CI: 0.46, 0.80 for the third tertile (≥12.5 nmol/L; median 15.6 nmol/L) serum folate concentrations compared with the first tertile (≤8.6 nmol/L; median 7.0 nmol/L)]. This association remained significant in all sensitivity analyses. Spline analyses showed a steady decline in all-cause mortality risk with increasing serum folate concentrations up to 20–25 nmol/L. This association persisted regardless of the MTHFR C677T genotypes. For serum vitamin B-12, the multivariable-adjusted HR of 1.32 (95% CI: 0.97, 1.79) of all-cause mortality was marginally significantly greater in the first tertile compared with the second tertile. This association was attenuated and nonsignificant after the exclusion of participants with a history of cardiovascular disease or cancer, or participants aged ≥85 y at baseline, or deaths in the first 3 y of follow-up. Conclusions Serum folate concentrations were inversely associated with the risk of all-cause mortality in Japanese adults. Serum vitamin B-12 concentrations were not consistently associated with all-cause mortality risk after accounting for reverse-causation bias.

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