Abstract TP196: New Zealand Workforce Stroke Incidence: Urban and Rural Risk Factor Evaluation

This analysis aims to assess the impact of urban and rural risk factors on a model of stroke incidence in a New Zealand workforce population. The New Zealand study consisted of 4,926 subjects prospectively enrolled at 46 worksites. The subjects were aged 40-78 years at baseline and had no prior history of stroke. This prospective study defines stroke events experienced by the study subjects during follow-up between 1988 and 2012 based on hospital admission coding. Proportional hazards regression models were fit using baseline characteristics. The difference in stroke outcomes for urban and rural worksites was also evaluated. Results demonstrate that baseline demographic, physical exam, and behavioural measures impact stroke outcomes. While the baseline distribution of stroke risk factors such as Pacific Island ethnicity, smoking status, and increased blood pressure indicates a potentially higher risk of stroke in the rural population, the proportional hazards model does not identify increased stroke risk for rural workers. Additional analysis of the diet, exercise and Quality of Life measures for these subjects may provide further information into the stroke risk profiles of individuals working in different locales.

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Abstract 183: Depressive Symptoms and Incident Stroke in Black and White Participants in the REGARDS Study

Stroke ◽

10.1161/str.43.suppl_1.a183 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Audrey L Austin ◽

Michael G Crowe ◽

Martha R Crowther ◽

Virginia J Howard ◽

Abraham J Letter ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Depressive Symptoms ◽

Racial Differences ◽

Stroke Risk ◽

Depression Scale ◽

Stroke Incidence ◽

Blacks And Whites ◽

The Impact

Background and Purpose: Research suggests that depression may contribute to stroke risk independent of other known risk factors. Most studies examining the impact of depression on stroke have been conducted with predominantly white cohorts, though blacks are known to have higher stroke incidence than whites. The purpose of this study was to examine depressive symptoms as a risk factor for incident stroke in blacks and whites, and determine whether depressive symptomatology was differentially predictive of stroke among blacks and whites. Methods: The REasons for Geographic and Racial Differences in Stroke (REGARDS), is a national, population-based longitudinal study designed to examine risk factors associated with black-white and regional disparities in stroke incidence. Among 30,239 participants (42% black) accrued from 2003-2007, excluding those lacking follow-up or data on depressive symptoms, 27,557 were stroke-free at baseline. As of the January 2011 data closure, over an average follow-up of 4.6 years, 548 incident stroke cases were verified by study physicians based on medical records review. The association between baseline depressive symptoms (assessed via the Center for Epidemiological Studies Depression scale, 4-item version) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographic factors (age, race, and sex), stroke risk factors (hypertension, diabetes, smoking, atrial fibrillation, and history of heart disease), and social factors (education, income, and social network). Results: For the total sample, depressive symptoms were predictive of incident stroke. The association between depressive symptoms and stroke did not differ significantly based on race (Wald X 2 = 2.38, p = .1229). However, race-stratified analyses indicated that the association between depressive symptoms and stroke was stronger among whites and non-significant among blacks. Conclusions: Depressive symptoms were an independent risk factor for incident stroke among a national sample of blacks and whites. These findings suggest that assessment of depressive symptoms may warrant inclusion in stroke risk scales. The potential for a stronger association in whites than blacks requires further study.

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Abstract 153: Novel Machine Learning Proves Stroke Risk is Not Linear

Stroke ◽

10.1161/str.51.suppl_1.153 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Agni Orfanoudaki ◽

Amre M Nouh ◽

Emma Chesley ◽

Christian Cadisch ◽

Barry Stein ◽

...

Keyword(s):

Machine Learning ◽

Risk Factors ◽

Risk Score ◽

Stroke Risk ◽

Assessment Tools ◽

Risk Calculator ◽

Stroke Incidence ◽

Non Linear ◽

User Friendly ◽

The Impact

Background: Current stroke risk assessment tools presume the impact of risk factors is linear and cumulative. However, both novel risk factors and their interplay influencing stroke incidence are difficult to reveal using traditional linear models. Objective: To improve upon the Revised-Framingham Stroke Risk Score and design an interactive non-linear Stroke Risk Score (NSRS). Our work aimed at increasing the accuracy of event prediction and uncovering new relationships in an interpretable user-friendly fashion. Methods: A two phase approach was used to develop our stroke risk score predictor. First, clinical examinations of the Framingham offspring cohort were utilized as the training dataset for the predictive model consisting of 14,196 samples where each clinical examination was considered an independent observation. Optimal Classification Trees (OCT) were used to train a model to predict 10-year stroke risk. Second, this model was validated with 17,527 observations from the Boston Medical Center. The NSRS was developed into an online user friendly application in the form of a questionnaire (http://www.mit.edu/~agniorf/files/questionnaire_Cohort2.html). Results: The algorithm suggests a key dichotomy between patients with or without history of cardiovascular disease. While the model agrees with known findings, it also identified 23 unique stroke risk profiles and introduced new non-linear relationships; such as the role of T-wave abnormality on electrocardiography and hematocrit levels in a patient’s risk profile. Our results in both the training and validation populations suggested that the non-linear approach significantly improves upon the existing revised Framingham stroke risk calculator in the c-statistic (training 87.43% (CI 0.85-0.90) vs. 73.74% (CI 0.70-0.76); validation 75.29% (CI 0.74-0.76) vs 65.93% (CI 0.64-0.67), even in multi-ethnicity populations. Conclusions: We constructed a highly predictive, interpretable and user-friendly stroke risk calculator using novel machine-learning uncovering new risk factors, interactions and unique profiles. The clinical implications include prioritization of risk factor modification and personalized care improving targeted intervention for stroke prevention.

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Abstract 44: Cardiorespiratory Fitness Decreases Stroke Incidence in Hypertensive Veterans

Circulation ◽

10.1161/circ.135.suppl_1.44 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Peter Kokkinos ◽

Charles Faselis ◽

Puneet Narayan ◽

Jonathan Myers ◽

Pamela Karasik ◽

...

Keyword(s):

Cardiorespiratory Fitness ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Reference Group ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Prior History ◽

Stroke Incidence ◽

Hypertensive Patients ◽

Metabolic Equivalents

Introduction: Stroke incidence is significantly higher in hypertensive patients compared to normotensive subjects. Cardiorespiratory fitness (CRF) is associated with a more favorable cardiovascular health. The CRF-stroke incidence association in hypertensive patients has not been fully explored. Hypothesis: We assessed the hypothesis that CRF is inversely and independently associated with stroke incidence in hypertensive patients. Methods: From 1985 to 2014, we identified 12,933 hypertensive patients (mean age: 60±11 years) with a normal response to an exercise tolerance test and no prior history of stroke. We established five fitness categories based on age-stratified quintiles of peak metabolic equivalents (MET) achieved: Least-Fit (4.1±1.0 METs; n=2,516); Low-Fit (5.6±1.0; n=2,772); Moderate-Fit (7.0±1.0 METs; n=2,803); Fit (8.4±1.3 METs; n=3,282); and High-Fit (11.4±2.0 METs; n=1,560). A multivariable Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals [CI] for incidence of stroke across fitness categories. The model was adjusted for age, resting blood pressure, BMI, atrial fibrillation, gender, race, other cardiac risk factors, alcohol dependence and medications. The Least-fit category was used as the reference group. Results: During follow-up (median=11.4 years; 152,408 person-years), 694 individuals (4.5 events per 1,000 person-years) developed stroke. The risk for stroke was 5% lower for each 1-MET increase in exercise capacity (HR=0.95, CI: 0.92-0.98; p<0.001). When considering fitness categories, stroke risk was lower by 28% (HR=0.72; CI: 0.57-0.90) for the Moderate-Fit and Fit individuals (HR=0.72; CI: 0.58-0.89) and 33% for High-Fit individuals (HR= 0.67; CI: 0.50-0.88). Conclusions: Increased CRF was inversely related to stroke incidence in hypertensive patients. The association was independent and graded.

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Traditional Risk Factors as the Underlying Cause of Racial Disparities in Stroke

Stroke ◽

10.1161/strokeaha.111.625277 ◽

2011 ◽

Vol 42 (12) ◽

pp. 3369-3375 ◽

Cited By ~ 98

Author(s):

George Howard ◽

Mary Cushman ◽

Brett M. Kissela ◽

Dawn O. Kleindorfer ◽

Leslie A. McClure ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Systolic Blood Pressure ◽

Socioeconomic Factors ◽

Racial Disparities ◽

Stroke Risk ◽

Proportional Hazards ◽

Stroke Incidence ◽

Relative Risks ◽

Traditional Risk Factors

Background and Purpose— Black/white disparities in stroke incidence are well documented, but few studies have assessed the contributions to the disparity. Here we assess the contribution of “traditional” risk factors. Methods— A total of 25 714 black and white men and women, aged ≥45 years and stroke-free at baseline, were followed for an average of 4.4 years to detect stroke. Mediation analysis using proportional hazards analysis assessed the contribution of traditional risk factors to racial disparities. Results— At age 45 years, incident stroke risk was 2.90 (95% CI: 1.72–4.89) times more likely in blacks than in whites and 1.66 (95% CI: 1.34–2.07) times at age 65 years. Adjustment for risk factors attenuated these excesses by 40% and 45%, respectively, resulting in relative risks of 2.14 (95% CI: 1.25–3.67) and 1.35 (95% CI: 1.08–1.71). Approximately one half of this mediation is attributable to systolic blood pressure. Further adjustment for socioeconomic factors resulted in total mediation of 47% and 53% to relative risks of 2.01 (95% CI: 1.16–3.47) and 1.30 (1.03–1.65), respectively. Conclusions— Between ages 45 to 65 years, approximately half of the racial disparity in stroke risk is attributable to traditional risk factors (primarily systolic blood pressure) and socioeconomic factors, suggesting a critical need to understand the disparity in the development of these traditional risk factors. Because half of the excess stroke risk in blacks is not attributable to traditional risk factors and socioeconomic factors, differential impact of risk factors, residual confounding, or nontraditional risk factors may also play a role.

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Abstract 52: Contributors to the Rural Excess in Stroke Mortality: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Stroke ◽

10.1161/str.48.suppl_1.52 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

George Howard ◽

Dawn O Kleindorfer ◽

D. L Long ◽

Mary Cushman ◽

Virginia J Howard ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Racial Differences ◽

Proportional Hazards ◽

Case Fatality ◽

Stroke Mortality ◽

Rural Regions ◽

Stroke Incidence ◽

Regards Study ◽

The Impact

Introduction: One NIH goal is to investigate the US nationwide rural-urban health disparities; however, few studies provide data to help understand the 30% higher rural stroke mortality. It is unknown if the higher stroke mortality is attributable to a higher incidence of stroke, or to a higher case fatality, in rural regions. Further, the role of risk factors or SES status in higher incidence or case-fatality is unknown. Methods: REGARDS participants stroke-free at baseline (n = 25,090) were stratified by Rural-Urban Commuting Area strata: urban, large rural city/town, or small rural town or isolated region. Participants were followed for incident stroke, and case fatality was defined as death within 30-days of a stroke. Difference in incident stroke was assessed using proportional hazards analysis, and case-fatality by logistic regression, each considered after adjustment for demographic factors, further adjustment for risk factors, and further adjustment for SES. Results: Over an average follow-up of 8.2 years, 1,060 incident strokes occurred, of which 160 died within 30 days. Risk of incident stroke increased with rurality (p = 0.016), with a hazard 1.21-times (95% CI: 1.00 - 1.46) higher in large rural cities/towns, and 1.24-times (95% CI: 1.00 - 1.54) higher in small rural towns or isolated regions (see table). Adjustment for risk factors and SES attenuated the estimated risk by 50%, and the association became non-significant. There was no evidence of a higher case-fatality from stroke in rural regions (p > 0.46). Discussion: The higher stroke mortality in rural regions appears to be attributable to higher stroke incidence, and not to higher case-fatality. Higher stroke incidence in rural regions is partially attributable to a worse risk factor profile and lower SES. Efforts to reduce rural disparity in stroke mortality should focus on preventive strategies, especially those relevant to risk factor development and control, and/or mitigating the impact of lower SES.

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The impact of age on genetic risk for common diseases

PLoS Genetics ◽

10.1371/journal.pgen.1009723 ◽

2021 ◽

Vol 17 (8) ◽

pp. e1009723 ◽

Cited By ~ 1

Author(s):

Xilin Jiang ◽

Chris Holmes ◽

Gil McVean

Keyword(s):

Risk Factors ◽

Relative Risk ◽

Genetic Risk ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Explanatory Power ◽

Genetic Risk Factors ◽

Individual Risk ◽

Common Diseases ◽

The Impact

Inherited genetic variation contributes to individual risk for many complex diseases and is increasingly being used for predictive patient stratification. Previous work has shown that genetic factors are not equally relevant to human traits across age and other contexts, though the reasons for such variation are not clear. Here, we introduce methods to infer the form of the longitudinal relationship between genetic relative risk for disease and age and to test whether all genetic risk factors behave similarly. We use a proportional hazards model within an interval-based censoring methodology to estimate age-varying individual variant contributions to genetic relative risk for 24 common diseases within the British ancestry subset of UK Biobank, applying a Bayesian clustering approach to group variants by their relative risk profile over age and permutation tests for age dependency and multiplicity of profiles. We find evidence for age-varying relative risk profiles in nine diseases, including hypertension, skin cancer, atherosclerotic heart disease, hypothyroidism and calculus of gallbladder, several of which show evidence, albeit weak, for multiple distinct profiles of genetic relative risk. The predominant pattern shows genetic risk factors having the greatest relative impact on risk of early disease, with a monotonic decrease over time, at least for the majority of variants, although the magnitude and form of the decrease varies among diseases. As a consequence, for diseases where genetic relative risk decreases over age, genetic risk factors have stronger explanatory power among younger populations, compared to older ones. We show that these patterns cannot be explained by a simple model involving the presence of unobserved covariates such as environmental factors. We discuss possible models that can explain our observations and the implications for genetic risk prediction.

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Abstract TP159: Risk of Ischemic Stroke in Patients with Atrial Flutter

Stroke ◽

10.1161/str.48.suppl_1.tp159 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Mais Al-Kawaz ◽

Setareh Salehi Omran ◽

Neal S Parikh ◽

Mitchell S Elkind ◽

Elsayed Z Soliman ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Lower Risk ◽

Stroke Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Administrative Claims ◽

Primary Analysis ◽

Stroke Incidence ◽

The Difference

Introduction: Guidelines advise anticoagulation for patients with both atrial fibrillation (AF) and flutter (AFL). However, the risk of stroke associated with these two conditions has not been robustly compared. Methods: Using inpatient and outpatient Medicare administrative claims data from 2008-2014 for a 5% sample of all beneficiaries ≥66 years of age, we identified all patients diagnosed with AFL or AF. Patients with prior stroke were excluded. The primary outcome was ischemic stroke. Predictors and the outcome were ascertained by validated ICD-9-CM diagnosis codes. Patients were censored at the time of ischemic stroke, death, or last available follow-up. In the primary analysis, patients with AFL were censored upon diagnosis of AF. Survival statistics were used to compare stroke incidence in patients with AF versus AFL. We used Cox proportional hazards analysis to compare the associations of AFL and AF with ischemic stroke after adjustment for demographics and risk factors. In a secondary analysis, patients with AFL were not censored upon diagnosis of AF because the natural history of AFL frequently features the development of AF. Results: We identified 16,441 patients with AFL and 338,726 with AF. Patients with AFL were less often female (42.4% versus 53.0%), but other baseline characteristics, including mean CHA 2 DS 2 -VASc scores (3.9), were similar between groups. Over 2.4 (±2.0) years, 16,451 ischemic strokes were identified. The annual incidence of ischemic stroke in patients with AFL was 0.60% (95% confidence interval [CI], 0.48-0.75%), whereas it was 2.00% (95% CI, 1.96-2.02%) in patients with AF. After adjustment for demographics and vascular risk factors, AFL was associated with a lower risk of ischemic stroke than AF (hazard ratio [HR], 0.30; 95% CI, 0.24-0.37). Within 1 year, 64.9% (95% CI, 64.1-65.6%) of patients with AFL received a diagnosis of AF. The difference between stroke risk in AFL compared to AF was attenuated (HR, 0.85; 95% CI, 0.79-0.92) when patients with AFL were not censored upon diagnosis of AF. Conclusions: Patients with AFL may face a lower risk of ischemic stroke than patients with AF. However, AF often develops in those with AFL, and taking this into account, the difference in stroke risk between the two conditions grows smaller.

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Abstract 73: Sex Hormone Binding Globulin: A Novel Hormonal Biomarker for Ischemic Stroke Risk?

Stroke ◽

10.1161/str.51.suppl_1.73 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Tracy E Madsen ◽

Xi Luo ◽

Mengna Huang ◽

Ki Park ◽

Marcia L Stefanick ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Stroke Risk ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Inverse Association ◽

Hormone Binding

Introduction: Sex hormone binding globulin (SHBG) is a sex-steroid transporter previously linked to cardiometabolic outcomes such as diabetes (DM) and coronary heart disease and their risk factors. It remains uncertain whether SHBG also affects stroke risk, particularly in women. We investigated whether SHBG affects risk of incident ischemic stroke (IS) among women in the Women’s Health Initiative (WHI). Methods: The WHI includes randomized trials and an observational cohort of 161808 postmenopausal women enrolled at 40 sites across the U.S. from 1993 - 1998. We identified 13,192 participants free of prevalent stroke at baseline who were included in one of eleven ancillary studies with serum SHBG. Incident IS events through 2017 were identified via physician adjudication of medical records. We used Cox proportional hazards regression to assess IS risk across quartiles of SHBG levels (Q1 - Q4), first adjusted for demographics, body mass index (BMI), hypertension, alcohol use, and smoking status (Model 1). History of DM was added to remove indirect effects through DM (Model 2), followed by the addition of reproductive risk factors and physical activity (Model 3). Results: Of 13,192 participants (mean age 62.5 years, 67.4% non-Hispanic white, 18.5% black, 5.0% Asian, 7.6% Hispanic), 877 IS events were confirmed during follow-up. Compared to the highest SHBG quartile (referent), women in the lowest quartile had a higher risk of IS in all three models (Model 1: HR 1.51, 95%CI 1.23 - 1.86, Model 2: HR 1.46, 95%CI 1.18 - 1.80, Model 3: HR: 1.38, 95%CI 1.07 - 1.76, trend tests p <0.05 for all). Women in the middle quartiles (Q2, Q3) also had increased IS risk compared with those in the highest SHBG quartile (Table). Conclusions: In this prospective cohort of post-menopausal women, there was a statistically significant inverse association between SHBG levels and IS risk, which supports the notion that SHBG could be used as a risk stratification tool for predicting IS in women.

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Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial

Journal of the American Society of Nephrology ◽

10.1681/asn.2021070942 ◽

2021 ◽

pp. ASN.2021070942

Author(s):

Rajiv Agarwal ◽

Amer Joseph ◽

Stefan Anker ◽

Gerasimos Filippatos ◽

Peter Rossing ◽

...

Keyword(s):

Risk Factors ◽

Serum Potassium ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Study Drug ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Short Term ◽

The Impact ◽

Reduced Risk

Background: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD. Methods: This post hoc safety analysis defined hyperkalemia as ≥mild or ≥moderate based on serum potassium concentrations of >5.5 or >6.0 mmol/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen-Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced ≥mild hyperkalemia had the study drug withheld until serum potassium was ≤5.0 mmol/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration. Results: Over 2.6 years' median follow-up, 597/2785 (21.4%) and 256/2775 (9.2%) of patients treated with finerenone and placebo, respectively, experienced treatment-emergent ≥mild hyperkalemia; 126/2802 (4.5%) and 38/2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for ≥mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-to-creatinine ratio, younger age, female sex, beta-blocker use, and finerenone assignment. Diuretic or sodium-glucose co-transporter-2 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo Conclusions: Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.

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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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