Prospective study of restless legs syndrome and total and cardiovascular mortality among women

ObjectiveWe prospectively examined whether women with physician-diagnosed restless legs syndrome (RLS) had a higher risk of total and cardiovascular disease (CVD) mortality relative to those without RLS.MethodsThe current study included 57,417 women (mean age 67 years) from the Nurses' Health Study without cancer, renal failure, and CVD at baseline (2002). Main outcomes were total and CVD mortality. We used the Cox proportional hazards model to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and CVD-specific mortality based on RLS status, adjusting for age, presence of major chronic diseases, and other potential confounders.ResultsWe documented 6,448 deaths during 10 years of follow-up. We did not observe a significant association between presence of physician-diagnosed RLS and high risk of total mortality (adjusted HR 1.15, 95% CI 0.98–1.34). When cause-specific mortality was studied, participants with RLS had a significantly higher risk of CVD mortality (adjusted HR 1.43, 95% CI 1.02–2.00) relative to those without RLS after adjustment for potential confounders. Longer duration of RLS diagnosis was significantly associated with a higher risk of CVD mortality (p for trend = 0.04). Excluding participants with common RLS comorbidities strengthened the association between RLS and total (adjusted HR 1.43, 95% CI 1.03–1.97) and CVD mortality (adjusted HR 2.27, 95% CI 1.21–4.28). However, we did not find a significant association between RLS and mortality due to cancer and other causes.ConclusionsWomen with RLS had a higher CVD mortality rate, which may not be fully explained by common co-occurring disorders of RLS.

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Changes in Plant-Based Diet Quality and Total and Cause-Specific Mortality

Circulation ◽

10.1161/circulationaha.119.041014 ◽

2019 ◽

Vol 140 (12) ◽

pp. 979-991 ◽

Cited By ~ 11

Author(s):

Megu Y. Baden ◽

Gang Liu ◽

Ambika Satija ◽

Yanping Li ◽

Qi Sun ◽

...

Keyword(s):

Diet Quality ◽

Lower Risk ◽

Proportional Hazards ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Environmental Benefits ◽

Health Study ◽

Specific Mortality ◽

Cvd Mortality

Background: Plant-based diets have been associated with lower risk of type 2 diabetes mellitus and cardiovascular disease (CVD) and are recommended for both health and environmental benefits. However, the association between changes in plant-based diet quality and mortality remains unclear. Methods: We investigated the associations between 12-year changes (from 1986 to 1998) in plant-based diet quality assessed by 3 plant-based diet indices (score range, 18–90)—an overall plant-based diet index (PDI), a healthful PDI, and an unhealthful PDI—and subsequent total and cause-specific mortality (1998–2014). Participants were 49 407 women in the Nurses’ Health Study (NHS) and 25 907 men in the Health Professionals Follow-Up Study (HPFS) who were free from CVD and cancer in 1998. Multivariable-adjusted Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Results: We documented 10 686 deaths including 2046 CVD deaths and 3091 cancer deaths in the NHS over 725 316 person-years of follow-up and 6490 deaths including 1872 CVD deaths and 1772 cancer deaths in the HPFS over 371 322 person-years of follow-up. Compared with participants whose indices remained stable, among those with the greatest increases in diet scores (highest quintile), the pooled multivariable-adjusted HRs for total mortality were 0.95 (95% CI, 0.90–1.00) for PDI, 0.90 (95% CI, 0.85–0.95) for healthful PDI, and 1.12 (95% CI, 1.07–1.18) for unhealthful PDI. Among participants with the greatest decrease (lowest quintile), the multivariable-adjusted HRs were 1.09 (95% CI, 1.04–1.15) for PDI, 1.10 (95% CI, 1.05–1.15) for healthful PDI, and 0.93 (95% CI, 0.88–0.98) for unhealthful PDI. For CVD mortality, the risk associated with a 10-point increase in each PDI was 7% lower (95% CI, 1–12%) for PDI, 9% lower (95% CI, 4–14%) for healthful PDI, and 8% higher (95% CI, 2–14%) for unhealthful PDI. There were no consistent associations between changes in plant-based diet indices and cancer mortality. Conclusions: Improving plant-based diet quality over a 12-year period was associated with a lower risk of total and CVD mortality, whereas increased consumption of an unhealthful plant-based diet was associated with a higher risk of total and CVD mortality.

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Dietary Intake of Tomato and Lycopene and Risk of All-Cause and Cause-Specific Mortality: Results From a Prospective Study

Frontiers in Nutrition ◽

10.3389/fnut.2021.684859 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xin Xu ◽

Shiqi Li ◽

Yi Zhu

Keyword(s):

Dietary Intake ◽

Cancer Mortality ◽

Dietary Intervention ◽

Proportional Hazards Model ◽

Adult Population ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Specific Mortality ◽

Cvd Mortality

Evidence on the relationship between consumption of tomato or lycopene and mortality is limited. We investigated the associations of raw tomato, tomato catsup or lycopene intake with all-cause and cause-specific mortality using data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) screening trial. A multivariate Cox proportional hazards model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During a total of 1,672,715 follow-up years, 24,141 all-cause deaths, 7,534 cardiovascular disease (CVD) deaths and 7,161 cancer deaths occurred. Total mortality was statistically significantly inversely associated with intake of raw tomato (Q5 vs. Q1; HR, 0.95 [95% CI, 0.91–0.99]), tomato catsup (Q5 vs. Q1; HR, 0.93 [95% CI, 0.89–0.97]), and moderate lycopene (Q4 vs. Q1; HR, 0.88 [95% CI, 0.85–0.93]). CVD mortality was significantly inversely related with intake of moderate raw tomato (Q4 vs. Q1; HR, 0.90 [95% CI, 0.83–0.97]), tomato catsup (Q5 vs. Q1; HR, 0.92 [95% CI, 0.85–0.99]), and moderate lycopene (Q4 vs. Q1; HR, 0.90 [95% CI, 0.83–0.98]). Dietary intake of raw tomato (Q5 vs. Q1; HR, 1.04 [95% CI, 0.96–1.14]) and tomato catsup (Q5 vs. Q1; HR, 1.00 [95% CI, 0.93–1.08]) were not related with cancer mortality. Moderate dietary intake of lycopene was significantly associated with a lower cancer mortality (Q4 vs. Q1; HR, 0.89 [95% CI, 0.82–0.96]). There was a non-linear J-shaped association between consumption of raw tomato, tomato catsup or lycopene and total mortality (P for non-linearity <0.001). In conclusion, in this large nationally representative sample of US adult population, tomato products, and lycopene intake were associated with lower risks of total and CVD mortality. Moderate consumption of lycopene was also related with a reduced cancer mortality. Further clinical studies and dietary intervention studies are warranted to confirm our premilitary findings.

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Association between milk and yogurt intake and mortality: a community-based cohort study (Yamagata study)

BMC Nutrition ◽

10.1186/s40795-021-00435-1 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Akiko Nakanishi ◽

Erika Homma ◽

Tsukasa Osaki ◽

Ri Sho ◽

Masayoshi Souri ◽

...

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Hazard Analysis ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Milk Intake ◽

Community Based ◽

Hazards Model ◽

Kaplan Meier

Abstract Background Dairy products are known as health-promoting foods. This study prospectively examined the association between milk and yogurt intake and mortality in a community-based population. Methods The study population comprised of 14,264 subjects aged 40–74 years who participated in an annual health checkup. The frequency of yogurt and milk intake was categorized as none (< 1/month), low (< 1/week), moderate (1–6/week), and high (> 1/day) intake. The association between yogurt and milk intake and total, cardiovascular, and cancer-related mortalities was determined using the Cox proportional hazards model. Results During the follow-up period, there were 265 total deaths, 40 cardiovascular deaths and 90 cancer-related deaths. Kaplan–Meier analysis showed that the total mortality in high/moderate/low yogurt intake and moderate/low milk intake groups was lower than that in none group (log-rank, P < 0.01). In the multivariate Cox proportional hazard analysis adjusted for possible confounders, the hazard ratio (HR) for total mortality significantly decreased in high/moderate yogurt intake group (HR: 0.62, 95% confidence interval [CI]: 0.42–0.91 for high intake, HR: 0.70, 95%CI: 0.49–0.99 for moderate intake) and moderate milk intake group (HR: 0.67, 95% CI: 0.46–0.97) compared with the none yogurt and milk intake groups. A similar association was observed for cancer-related mortality, but not for cardiovascular mortality. Conclusions Our study showed that yogurt and milk intake was independently associated with a decrease in total and cancer-related mortalities in the Japanese population.

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Abstract MP49: Sugar Sweetened and Artificially Sweetened Beverages and risk of Mortality in US adults

Circulation ◽

10.1161/circ.129.suppl_1.mp49 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Vasanti S Malik ◽

An Pan ◽

Lawrence de Koning ◽

Eva Schernhammer ◽

Walter C Willett ◽

...

Keyword(s):

Proportional Hazards ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Health Study ◽

Sweetened Beverages ◽

Risk Of Mortality ◽

Regular Consumption ◽

Increased Risk ◽

Artificially Sweetened Beverages ◽

Cvd Mortality

Background: Sugar sweetened beverages (SSBs) are the single largest source of calories and added sugars in the US diet and regular consumption has been associated with weight gain and risk of chronic diseases. Artificially sweetened beverages (ASBs) are often suggested as alternatives to SSB but little is known about their long-term health effects. Whether consumption of SSBs or ASBs is associated with risk of mortality is unknown. Methods: We prospectively followed 38,602 men from the Health Professional’s Follow-up study (1986-2010) and 82,592 women from the Nurses’ Health study (1980-2010) who were free from cardiovascular disease (CVD) and cancer at baseline. Diet was assessed using validated food frequency questionnaires every 4 years and Cox Proportional Hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: We documented 27,691 deaths (6,631 CVD and 10,447 cancer deaths) during 3.14 million person-years. After adjusting for major dietary and lifestyle risk factors, and BMI, baseline diabetes, hypertension and hypercholesterolemia, consumption of SSBs was associated with an increased risk of total mortality, which was mainly driven by CVD mortality among individuals consuming at least 2 servings per day; pooled HRs (95% CIs) across categories (<1/month, 1-4/month, 2-6/week, 1-<2/day and ≥2/day) were 1.00, 0.95 (0.91, 0.98), 0.96 (0.93, 0.99), 1.02 (0.96, 1.08), and 1.18 (1.04, 1.33), respectively (P-trend= 0.0001) for total mortality, and 1.00, 0.97 (0.90, 1.02), 0.96 (0.90, 1.02), 1.04 (0.93, 1.16) and 1.28 (1.09, 1.51), respectively (P-trend=0.007) for CVD mortality. In contrast, ASBs were not associated with mortality; pooled HR’s (95% CIs) across categories (<1/month, 1-4/month, 2-6/week, 1-<2/day and ≥2/day) were 1.00, 0.92 (0.89, 0.95), 0.91 (0.86, 0.97), 0.91 (0.86, 0.95) and 0.99 (0.85, 1.15), respectively (P-trend=0.50) for total mortality and 1.00, 0.86 (0.80, 0.92), 0.87 (0.81, 0.94), 0.96 (0.88, 1.06) and 0.96 (0.74, 1.25), respectively (P-trend=0.99) for CVD mortality. No associations were observed with cancer mortality for either SSBs or ASBs in multi-variable adjusted models. Conclusion: Regular consumption of SSBs is associated with an increased risk of total and CVD mortality, providing additional support for recommendations and policies to limit intake of these beverages.

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Prediagnosis plasma concentrations of enterolactone and survival after colorectal cancer: the Danish Diet, Cancer and Health cohort

British Journal Of Nutrition ◽

10.1017/s0007114518002143 ◽

2018 ◽

Vol 122 (5) ◽

pp. 552-563 ◽

Cited By ~ 4

Author(s):

Cecilie Kyrø ◽

Kirsten Frederiksen ◽

Marianne Holm ◽

Natalja P. Nørskov ◽

Knud E. B. Knudsen ◽

...

Keyword(s):

Colorectal Cancer ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Plasma Concentrations ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Limited Attention ◽

Hazards Model ◽

Specific Mortality ◽

Cancer Specific Mortality

AbstractThe association between lifestyle and survival after colorectal cancer has received limited attention. The female sex hormone, oestrogen, has been associated with lower colorectal cancer risk and mortality after colorectal cancer. Phyto-oestrogens are plant compounds with structure similar to oestrogen, and the main sources in Western populations are plant lignans. We investigated the association between the main lignan metabolite, enterolactone and survival after colorectal cancer among participants in the Danish Diet, Cancer and Health cohort. Prediagnosis plasma samples and lifestyle data, and clinical data from time of diagnosis from 416 women and 537 men diagnosed with colorectal cancer were used. Enterolactone was measured in plasma using a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. Participants were followed from date of diagnosis until death or end of follow-up. During this time, 210 women and 325 men died (170 women and 215 men died due to colorectal cancer). The Cox proportional hazards model was used to estimate hazard ratios (HR) and 95 % CI. Enterolactone concentrations were associated with lower colorectal cancer-specific mortality among women (HRper doubling: 0·88, 95 % CI 0·80, 0·97, P=0·0123). For men, on the contrary, enterolactone concentrations were associated with higher colorectal cancer-specific mortality (HRper doubling: 1·10, 95 % CI 1·01, 1·21, P=0·0379). The use of antibiotics affects enterolactone production, and the associations between higher enterolactone and lower colorectal cancer-specific mortality were more pronounced among women who did not use antibiotics (analysis on a subset). Our results suggest that enterolactone is associated with lower risk of mortality among women, but the opposite association was found among men.

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Physical activity attenuates the associations of systemic immune-inflammation index with total and cause-specific mortality among middle-aged and older populations

Scientific Reports ◽

10.1038/s41598-021-91324-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hang Li ◽

Xiulong Wu ◽

Yansen Bai ◽

Wei Wei ◽

Guyanan Li ◽

...

Keyword(s):

Physical Activity ◽

Proportional Hazards ◽

Total Mortality ◽

Cox Proportional Hazards ◽

Related Factors ◽

Specific Mortality ◽

Immune Inflammation ◽

General Populations ◽

High Level ◽

Cvd Mortality

AbstractSystemic immune-inflammation index (SII) emerged as a biomarker of chronic inflammation and an independent prognostic factor for many cancers. We aimed to investigate the associations of SII level with total and cause-specific mortality risks in the general populations, and the potential modification effects of lifestyle-related factors on the above associations. In this study, we included 30,521 subjects from the Dongfeng-Tongji (DFTJ) cohort and 25,761 subjects from the National Health and Nutrition Examination Survey (NHANES) 1999–2014. Cox proportional hazards regression models were used to estimate the associations of SII with mortality from all-cause, cardiovascular diseases (CVD), cancer and other causes. In the DFTJ cohort, compared to subjects in the low SII subgroup, those within the middle and high SII subgroups had increased risks of total mortality [hazard ratio, HR (95% confidence interval, CI) = 1.12 (1.03–1.22) and 1.26 (1.16–1.36), respectively) and CVD mortality [HR (95%CI) = 1.36 (1.19–1.55) and 1.50 (1.32–1.71), respectively]; those within the high SII subgroup had a higher risk of other causes mortality [HR (95%CI) = 1.28 (1.09–1.49)]. In the NHANES 1999–2014, subjects in the high SII subgroup had higher risks of total, CVD, cancer and other causes mortality [HR (95%CI) = 1.38 (1.27–1.49), 1.33 (1.11–1.59), 1.22 (1.04–1.45) and 1.47 (1.32–1.63), respectively]. For subjects with a high level of SII, physical activity could attenuate a separate 30% and 32% risk of total and CVD mortality in the DFTJ cohort, and a separate 41% and 59% risk of total and CVD mortality in the NHANES 1999–2014. Our study suggested high SII level may increase total and CVD mortality in the general populations and physical activity exerted a beneficial effect on the above associations.

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Protective Effects of Familial Longevity Decrease with Age and Become Negligible for Centenarians

The Journals of Gerontology Series A ◽

10.1093/gerona/glab380 ◽

2021 ◽

Author(s):

Natalia S Gavrilova ◽

Leonid A Gavrilov

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Lower Mortality ◽

Protective Effects ◽

Hazards Model ◽

Specific Mortality ◽

Theory Of Aging ◽

Familial Longevity

Abstract It is known that biological relatives of long-lived individuals demonstrate lower mortality and longer lifespan compared to relatives of shorter-lived individuals, and at least part of this advantage is likely to be genetic. Less information, however, is available about effects of familial longevity on age-specific mortality trajectories. We compared mortality patterns after age 50 years for 10,045 siblings of U.S. centenarians and 12,308 siblings of shorter-lived individuals (died at age 65 years). Similar comparisons were made for sons and daughters of longer-lived parents (both parents lived 80 years and more) and shorter-lived parents (both parents lived less than 80 years) within each group of siblings. Although relatives of longer-lived individuals have lower mortality at younger ages compared to relatives of shorter lived individuals, this mortality advantage practically disappears by age 100 years. To validate this observation further, we analyzed survival of 3,408 U.S. centenarians born in 1890-97 with known information on maternal and paternal lifespan. We found using the Cox proportional hazards model that both maternal and paternal longevity (lifespan 80+ years) is not significantly associated with survival after age 100 years. The results are compatible with the predictions of reliability theory of aging suggesting higher initial levels of system redundancy (reserves) in individuals with protective familial/genetic background and hence lower initial mortality. Heterogeneity hypothesis is another possible explanation for the observed phenomena.

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Factors influencing prostate cancer specific mortality in patients receiving delayed androgen deprivation therapy for metastasis after biochemical recurrence following radical prostatectomy

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.4571 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 4571-4571 ◽

Cited By ~ 1

Author(s):

D. V. Makarov ◽

B. J. Trock ◽

E. B. Humphreys ◽

L. A. Mangold ◽

M. A. Carducci ◽

...

Keyword(s):

Prostate Cancer ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Failure Times ◽

Factors Influencing ◽

Hazards Model ◽

Psa Failure ◽

Specific Mortality

4571 Background: For men developing PSA failure after radical prostatectomy (RP), administration of immediate androgen deprivation therapy (ADT) has not been shown to improve survival compared to delaying ADT until evidence of metastatic disease. We evaluated factors influencing prostate cancer (PCa) specific mortality (PCSM) in a cohort of PSA era patients developing metastases after RP treated with delayed ADT. Methods: 3,658 men had RP by a single surgeon at Johns Hopkins Hospital from 4/82 until 6/05. 553 had PSA failure. 216 developed radiographically evident distant metastasis. Of these, 91 men formed the study cohort: initially treated during the PSA era (1987–2005), received ADT only after documented metastasis, and having complete data. 41 of these men died. Median failure times were estimated with the Kaplan-Meier method. Prognostic impact was estimated as the hazard ratio (HR) derived from the Cox proportional hazards model. Results: Median followup from RP was 10 yrs (range 2–18). Actuarial median failure times are: 1 yr from RP to PSA failure (range 1–11), 32 mos from PSA failure to metastasis (range 0–129), 79 mos from metastasis to death (range 7–181), and 13 yrs from RP to death (range 2–18). The following variables were significant prognostic factors for PCSM in univariate analyses: Pain at diagnosis of metastases (p < 0.01), time from RP to metastasis (p = 0.02), hematocrit at metastasis (p < 0.01) and PSADT <3 mos during the 2 years prior to metastasis (p < 0.01). A multivariable Cox proportional hazards model demonstrated the following independent predictors of PCSM: pain (HR = 10.5 p < 0.01), PSA at metastasis ≥100 ng/mL (HR = 5.3 p < 0.01) and PSADT < 3 months (HR = 7.1 p < 0.01). PSADT determined in the two years immediately after PSA failure (HR = 1.0 p = 0.37) and time from RP to bone metastasis (HR = 1.0 p = 0.80) were not independent predictors of PCSM. Conclusion: Men receiving delayed ADT for development of metastasis after RP may have a prolonged survival time (13 yrs post RP - range 2–18). Optimizing the time for ADT in these patients requires well-designed, prospective randomized studies. Our data may facilitate the selection of patients and thresholds for implementation of ADT. No significant financial relationships to disclose.

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Alcohol Consumption and Risk of All-Cause and Cardiovascular Disease Mortality in Men

Journal of Aging Research ◽

10.4061/2011/805062 ◽

2011 ◽

Vol 2011 ◽

pp. 1-10 ◽

Cited By ~ 13

Author(s):

Erin K. Howie ◽

Xuemei Sui ◽

Duck-chul Lee ◽

Steven P. Hooker ◽

James R. Hébert ◽

...

Keyword(s):

Cardiovascular Disease ◽

Alcohol Consumption ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Alcoholic Beverages ◽

Future Research ◽

Psychological Variables ◽

Cvd Mortality

This study examined the association between consumption of alcoholic beverages and all-cause and cardiovascular disease (CVD) mortality in a cohort of men (n=31,367). In the Cox proportional hazards model adjusted for age, year of examination, body mass index (BMI), smoking, family history of CVD, and aerobic fitness, there were no significant differences in risk of all-cause mortality across alcohol intake groups. Risk of CVD mortality was reduced 29% in quartile 1 (HR = 0.71, 95% confidence interval (CI): 0.53, 0.95) and 25% in quartile 2 (HR = 0.75, 95% CI: 0.58, 0.98). The amount of alcohol consumed to achieve this risk reduction was <6 drinks/week; less than the amount currently recommended. The addition of other potential confounders and effect modifiers including blood pressure, insulin sensitivity, lipid levels, and psychological variables did not affect the magnitude of association. Future research is needed to validate the current public health recommendations for alcohol consumption.

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Age at Exposure to Parental Suicide and the Subsequent Risk of Suicide in Young People

Crisis ◽

10.1027/0227-5910/a000468 ◽

2018 ◽

Vol 39 (1) ◽

pp. 27-36 ◽

Cited By ~ 5

Author(s):

Kuan-Ying Lee ◽

Chung-Yi Li ◽

Kun-Chia Chang ◽

Tsung-Hsueh Lu ◽

Ying-Yeh Chen

Keyword(s):

Young People ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Birth Registry ◽

Data Set ◽

Parental Suicide ◽

The Impact ◽

Age At Exposure

Abstract. Background: We investigated the age at exposure to parental suicide and the risk of subsequent suicide completion in young people. The impact of parental and offspring sex was also examined. Method: Using a cohort study design, we linked Taiwan's Birth Registry (1978–1997) with Taiwan's Death Registry (1985–2009) and identified 40,249 children who had experienced maternal suicide (n = 14,431), paternal suicide (n = 26,887), or the suicide of both parents (n = 281). Each exposed child was matched to 10 children of the same sex and birth year whose parents were still alive. This yielded a total of 398,081 children for our non-exposed cohort. A Cox proportional hazards model was used to compare the suicide risk of the exposed and non-exposed groups. Results: Compared with the non-exposed group, offspring who were exposed to parental suicide were 3.91 times (95% confidence interval [CI] = 3.10–4.92 more likely to die by suicide after adjusting for baseline characteristics. The risk of suicide seemed to be lower in older male offspring (HR = 3.94, 95% CI = 2.57–6.06), but higher in older female offspring (HR = 5.30, 95% CI = 3.05–9.22). Stratified analyses based on parental sex revealed similar patterns as the combined analysis. Limitations: As only register-based data were used, we were not able to explore the impact of variables not contained in the data set, such as the role of mental illness. Conclusion: Our findings suggest a prominent elevation in the risk of suicide among offspring who lost their parents to suicide. The risk elevation differed according to the sex of the afflicted offspring as well as to their age at exposure.

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