scholarly journals Prediagnostic Plasma Folate and the Risk of Death in Patients With Colorectal Cancer

2008 ◽  
Vol 26 (19) ◽  
pp. 3222-3228 ◽  
Author(s):  
Brian M. Wolpin ◽  
Esther K. Wei ◽  
Kimmie Ng ◽  
Jeffrey A. Meyerhardt ◽  
Jennifer A. Chan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Cox Proportional Hazards ◽  
Folate Intake ◽  
Health Study ◽  
Recent Trial ◽  
Risk Of Death ◽  
Plasma Folate ◽  
Increased Risk ◽  
Overall Mortality

Purpose Although previous studies have demonstrated an inverse relationship between folate intake and colorectal cancer risk, a recent trial suggests that supplemental folic acid may accelerate tumorigenesis among patients with a history of colorectal adenoma. Therefore, high priority has been given to research investigating the influence of folate on cancer progression in patients with colorectal cancer. Patients and Methods To investigate whether prediagnostic levels of plasma folate are associated with colorectal cancer–specific and overall mortality, we performed a prospective, nested observational study within two large US cohorts: the Nurses' Health Study and Health Professionals Follow-Up Study. We measured folate levels among 301 participants who developed colorectal cancer 2 or more years after their plasma was collected and compared participants using Cox proportional hazards models by quintile of plasma folate. Results Higher levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality. Compared with participants in the lowest quintile of plasma folate, those in the highest quintile experienced a multivariable-adjusted hazard ratio for colorectal cancer–specific mortality of 0.42 (95% CI, 0.20 0.88) and overall mortality of 0.46 (95% CI, 0.24 0.88). When the analysis was limited to participants whose plasma was collected within 5 years of cancer diagnosis, no detrimental effect of high plasma folate was noted. In subgroup analyses, no subgroup demonstrated worse survival among participants with higher plasma folate levels. Conclusion In two large prospective cohorts, higher prediagnostic levels of plasma folate were not associated with an increased risk of colorectal cancer–specific or overall mortality.

Circulating 25-Hydroxyvitamin D Levels and Survival in Patients With Colorectal Cancer

2008 ◽  
Vol 26 (18) ◽  
pp. 2984-2991 ◽  
Author(s):  
Kimmie Ng ◽  
Jeffrey A. Meyerhardt ◽  
Kana Wu ◽  
Diane Feskanich ◽  
Bruce W. Hollis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Colorectal Carcinogenesis ◽  
Health Study ◽  
Blood Collection ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Overall Mortality

Purpose Higher plasma 25-hydroxyvitamin D3 (25(OH)D) levels are associated with a decreased incidence of colorectal cancer, but the influence of plasma 25(OH)D on the outcome of patients with established colorectal cancer is unknown. Patients and Methods We prospectively examined the association between prediagnosis 25(OH)D levels and mortality among 304 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS) who were diagnosed with colorectal cancer from 1991 to 2002. Participants diagnosed within 2 years of blood collection were excluded. Patients were observed until death, June 2005 (NHS), or January 2005 (HPFS), whichever came first. The primary end point was overall mortality. Cox proportional hazards models were used to calculate hazard ratios (HR) adjusted for other risk factors for cancer survival. Results Higher plasma 25(OH)D levels were associated with a significant reduction in overall mortality (P for trend = .02). Compared with the lowest quartile, participants in the highest quartile had an adjusted HR of 0.52 (95% CI, 0.29 to 0.94) for overall mortality. A trend toward improved colorectal cancer–specific mortality was also seen (HR = 0.61; 95% CI, 0.31 to 1.19). The results remained unchanged after excluding patients diagnosed within 5 years of blood collection (P for trend = .04); the multivariate HR for overall mortality comparing extreme quartiles was 0.45 (95% CI, 0.19 to 1.09). Conclusion Among patients with colorectal cancer, higher prediagnosis plasma 25(OH)D levels were associated with a significant improvement in overall survival. Further study of the vitamin D pathway and its influence on colorectal carcinogenesis and cancer progression is warranted.

Impact of Diabetes Mellitus and Insulin Use on Survival After Colorectal Cancer Diagnosis: The Cancer Prevention Study-II Nutrition Cohort

2012 ◽  
Vol 30 (1) ◽  
pp. 53-59 ◽  
Author(s):  
Ahmed N. Dehal ◽  
Christina C. Newton ◽  
Eric J. Jacobs ◽  
Alpa V. Patel ◽  
Susan M. Gapstur ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Cancer Prevention ◽  
Cox Proportional Hazards ◽  
Prevention Study ◽  
Men And Women ◽  
Risk Of Death ◽  
Increased Risk ◽  
Specific Mortality ◽  
Insulin Use

Purpose To examine the association between type 2 diabetes mellitus (T2DM) and survival among patients with colorectal cancer (CRC) and to evaluate whether this association varies by sex, insulin treatment, and durations of T2DM and insulin use. Patients and Methods This study was conducted among 2,278 men and women diagnosed with nonmetastatic colon or rectal cancer between 1992 and 2007 in the Cancer Prevention Study-II Nutrition Cohort, a prospective study of cancer incidence. In 1992 to 1993, participants completed a detailed, self-administrated questionnaire. Vital status and cause of death were ascertained through the end of 2008. Multivariable-adjusted relative risks (RRs) and 95% CIs were estimated using Cox proportional hazards regression. Results Among the 2,278 men and women with nonmetastatic CRC, there were 842 deaths by the end of follow-up (including 377 deaths from CRC and 152 deaths from cardiovascular disease [CVD]). Among men and women combined, compared with patients without T2DM, patients with CRC and T2DM were at higher risk of all-cause mortality (RR, 1.53; 95% CI, 1.28 to 1.83), CRC-specific mortality (RR, 1.29; 95% CI, 0.98 to 1.70), and CVD-specific mortality (RR, 2.16; 95% CI, 1.44 to 3.24), with no apparent differences by sex or durations of T2DM or insulin use. Insulin use, compared with no T2DM, was associated with increased risk of death from all causes (RR, 1.68; 95% CI, 1.22 to 2.31) and CVD (RR, 3.87; 95% CI, 2.12 to 7.08) but not from CRC (RR, 0.58; 95% CI, 0.28 to 1.19). Conclusion Patients with CRC and T2DM have a higher risk of mortality than patients with CRC who do not have T2DM, especially a higher risk of death from CVD.

scholarly journals Sedentary Behaviors, TV Viewing Time, and Risk of Young-Onset Colorectal Cancer

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Long H Nguyen ◽  
Po-Hong Liu ◽  
Xiaobin Zheng ◽  
NaNa Keum ◽  
Xiaoyu Zong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Proportional Hazards ◽  
Statistical Tests ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
Viewing Time ◽  
Sedentary Behaviors ◽  
Tv Viewing ◽  
Young Onset ◽  
Increased Risk

Abstract Background Colorectal cancer (CRC) diagnosed before age 50 years, or young-onset CRC, is increasing globally with undefined etiology. A sedentary lifestyle is an emerging risk factor for CRC after age 50 years, but its role in young-onset CRC is unknown. Methods We prospectively evaluated sedentary behaviors, primarily time watching television (TV), and risk of young-onset CRC among 89 278 women in the Nurses’ Health Study II ages 25–42 years at recruitment (1991–2011). We used Cox proportional hazards modelling to estimate relative risks (RR) and 95% confidence intervals (CIs). Statistical tests were two-sided. Results We documented 118 young-onset CRCs over 1 262 540 person-years. Sedentary TV viewing time was statistically significantly associated with increased risk of young-onset CRC, after adjusting for putative risk factors, including obesity and physical activity. Compared to no more than 7 hours per week, women with 7.1–14 hours per week of TV time had a multivariable relative risk (RR) of 1.12 (95% confidence interval [CI] = 0.72 to 1.75), further increased for greater than 14 hours per week (RR = 1.69, 95% CI = 1.07 to 2.67, Ptrend = .03). This association was observed among participants without a CRC family history and was more pronounced for rectal cancer (RR for >14 vs ≤7 hours per week 2.44, 95% CI = 1.03 to 5.78, Ptrend = .04). Overweight or obese participants may be more susceptible. Conclusion Independent of exercise and obesity, prolonged sedentary TV viewing time, a surrogate for a more inactive lifestyle, was associated with increased risk of young-onset CRC, particularly of the rectum. These findings provide further evidence on the importance of maintaining an active lifestyle.

Known colorectal cancer susceptibility loci and survival after colorectal cancer diagnosis.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 394-394 ◽  
Author(s):  
Amanda Phipps ◽  
Xabier Garcia-Albeniz ◽  
Carolyn Hutter ◽  
Emily White ◽  
Charles S. Fuchs ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Fixed Effects ◽  
Cancer Susceptibility ◽  
Association Studies ◽  
Cox Proportional Hazards ◽  
Health Study ◽  
Genome Wide Association Studies ◽  
Increased Risk

394 Background: Beyond clinicopathologic stage, there are few established markers of prognosis in colorectal cancer (CRC). Recent genome-wide association studies have identified 17 germline single nucleotide polymorphisms (SNPs) significantly associated with incident CRC. However, it is unclear if these CRC susceptibility SNPs influence survival after CRC diagnosis. Although the functionality of many of these SNPs remains unknown, a few, including rs4939827 in SMAD7, map to genes with plausible biological mechanisms associated with both cancer risk and prognosis. We examined 17 CRC susceptibility SNPs in relation to survival after CRC diagnosis. Methods: We genotyped 2,611 men and women enrolled in five prospective cohort studies who were diagnosed with invasive CRC during study follow-up: the Physicians’ Health Study (N=281), Health Professionals Follow-up Study (N=268), Nurses’ Health Study (N=367), Vitamins and Lifestyle Study (N=281), and the Women’s Health Initiative (N=1414). Analyses were limited to Caucasians with known vital status, cause of death, and survival time. We used Cox proportional hazards regression to assess associations between each SNP and CRC-specific and overall survival in study-specific models adjusted for age, sex, and stage; SNPs were modeled additively to reflect associations per copy of the minor allele. Study-specific results were combined via fixed-effects meta-analysis. Results: The G allele in rs4939827 was associated with poorer CRC-specific survival [hazard ratio (HR)=1.16, p=0.02] and overall survival (HR=1.13, p=0.03) in CRC patients. The A alleles in rs10795668 and in rs4925386 were associated with a 1.14-fold increased risk of overall mortality (both p-values=0.03) but not CRC-specific mortality. Other evaluated SNPs were not associated with survival. Conclusions: Genetic variation in rs4939827 (SMAD7) is associated with CRC-specific and overall survival. These results suggest that SMAD7 may have a role in CRC progression, and provide proof-of-principle that common germline variation may provide prognostic information beyond traditional considerations such as stage.

A phase III study of xilonix in refractory colorectal cancer patients with weight loss.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 685-685 ◽  
Author(s):  
George A. Fisher
Keyword(s):  
Colorectal Cancer ◽  
Cancer Progression ◽  
Human Monoclonal Antibody ◽  
Well Being ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Risk Of Death ◽  
Increased Risk ◽  
Median Change

685 Background: Xilonix, an anti-interleukin-1α true human monoclonal antibody is being assessed as cancer therapy to improve overall survival (OS) in advanced colorectal cancer (CRC) patients. Methods: An open label multicenter randomized comparator controlled study to evaluate efficacy and safety of Xilonix in CRC complicated with cachexia. Eligible patients had metastatic CRC, failed oxaliplatin or irinotecan based chemotherapy, and lost ≥5% total body weight in the previous 6 months (m). Patients were 1:1 randomized to Xilonix (3.75 mg/kg intravenously every two weeks) or megestrol acetate (MA, oral 800 mg daily) until progression. Primary endpoint was OS. Secondary endpoints included assessment of patient well-being using the EORTC QLQ-C30 questionnaire. Platelets support tumor growth and metastasis and platelet counts increase during cancer progression. IL-1α on platelets may be a target of Xilonix and thus platelet count was a key pharmacodynamic measure. Results: 40 patients were enrolled between March 2013 and July 2014, at which time the study was halted to revise inclusion criteria to reduce screen failures. An eligibility violation excluded 1 Xilonix patient from analysis (Xilonix n=19, MA n=20). MA treatment arm had a 39% shorter median OS (2.0 versus 2.8 months) and a trend in increased risk of death (hazard ratio 2.17, p=0.17). Physical and role function worsened in patients receiving megesterol (median change of -13.3 (p=0.02), -16.7 (p=0.02) respectively), whereas in Xilonix treated patients these functions did not decline during therapy (median change 0, p=0.88 and 0, p=0.69, respectively). Xilonix patients had treatment-related reduction in platelets compared to the MA group (median -60,000/mm3, vs 10,000/mm3, p=0.03). No infusion reactions, no discontinuations due to adverse events (AEs) and no related SAEs were reported for Xilonix. Conclusions: The trend in OS for Xilonix patients was encouraging and consistent with improved function and intended pharmacodynamic activity. An amended Phase III protocol has been developed to simplify enrollment for an ongoing study of Xilonix in an advanced CRC population. (NCT01767857) Clinical trial information: NCT01767857.

Prediagnostic plasma adiponectin and survival among patients with colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 526-526
Author(s):  
Dawn Q. Chong ◽  
Raaj Mehta ◽  
Mingyang Song ◽  
Dmitriy Kedrin ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Statistical Tests ◽  
Cox Proportional Hazards Model ◽  
Health Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Study Cohort ◽  
Plasma Adiponectin ◽  
Increased Risk ◽  
Overall Mortality

526 Background: Adiponectin is a hormone secreted by adipose tissue and has been demonstrated to possess anticarcinogenic, anti-inflammatory and insulin-sensitizing effects. Circulating adiponectin has been shown to be inversely associated with the risk of colorectal cancer (CRC) in prospective studies. However, the association of prediagnostic adiponectin with survival among patients with established colorectal cancer is unclear. Methods: We conducted a prospective study of 621 incident colorectal cancer cases from the Nurses’ Health Study and Health Professionals Follow-up Study to evaluate the association between prediagnostic plasma adiponectin and mortality. Plasma adiponectin levels were determined by enzyme-linked immunosorbent assay from ALPCO Diagnostics. The interbatch coefficient of variation from quality control samples randomly interspersed among the case samples was 8.6%. We examined the associations between quartiles of plasma adiponectin and mortality using a Cox proportional hazards model adjusted for established and putative risk factors. All statistical tests were two sided. Results: After a median follow-up of 9 years, there were 267 (43%) total deaths and 130 (21%) CRC deaths in the total study cohort. Compared with patients in the lowest quartile of adiponectin, patients in the highest quartile had a multivariate hazard ratio (HR) for CRC-specific mortality of 2.70 [95% confidence interval (CI), 1.54-4.75; Ptrend = 0.001]. The corresponding multivariate HR for overall mortality was 1.64 (95% CI, 1.14-2.36; Ptrend = 0.007). These associations were reasonably consistent in analyses according to subgroups defined by age, gender, body mass index, stage, grade and site of primary cancer. Similar results were yielded after excluding patients diagnosed within 4 years of blood collection (Ptrend = 0.027). Conclusions: Prediagnostic adiponectin is associated with an increased risk of colorectal cancer- specific and overall mortality. Further studies are needed to elucidate the mechanistic basis for these findings and determine the potential role of adiponectin as a prognostic marker in colorectal cancer.

scholarly journals Association of Age With Survival in Patients With Metastatic Colorectal Cancer: Analysis From the ARCAD Clinical Trials Program

2014 ◽  
Vol 32 (27) ◽  
pp. 2975-2982 ◽  
Author(s):  
Christopher H. Lieu ◽  
Lindsay A. Renfro ◽  
Aimery de Gramont ◽  
Jeffrey P. Meyers ◽  
Timothy S. Maughan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Proportional Hazards ◽  
Performance Status ◽  
Cox Proportional Hazards ◽  
Risk Of Death ◽  
Mutational Status ◽  
Increased Risk ◽  
Risk Of Progression

Purpose This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC). Patients and Methods A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age, sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study. Results Of total patients, 3,051 (15%) were age ≤ 50 years. Age was prognostic for both OS (P < .001) and PFS (P < .001), with U-shaped risk (ie, highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted for PS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status. Conclusion Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted.

Association of folate intake and colorectal cancer risk in the postfortification era in US women

2021 ◽  
Author(s):  
Fenglei Wang ◽  
Kana Wu ◽  
Yanping Li ◽  
Rui Song ◽  
You Wu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
United States ◽  
Folic Acid ◽  
Lower Risk ◽  
The United States ◽  
Cox Proportional Hazards ◽  
Colorectal Carcinogenesis ◽  
Folate Intake ◽  
Health Study ◽  
Female Population

ABSTRACT Background Folate may play a preventive role in the early stages of colorectal carcinogenesis, but long latencies may be needed to observe a reduction in colorectal cancer (CRC) incidence. In addition, concerns have been raised about the potential for cancer promotion with excessive folate intake, especially after the mandatory folic acid fortification in the United States in 1998. Objective We aimed to examine the association between folate intake in different chemical forms and CRC risk, especially in the postfortification era in the United States. Design We prospectively followed 86,320 women from the Nurses’ Health Study (1980–2016). Folate intake was collected by validated food frequency questionnaires. CRC was self reported and confirmed by review of medical records. The association between the folate intake and CRC risk was assessed using Cox proportional hazards regression. Results We documented 1988 incident CRC cases during follow-up. Analyzing folate intake as a continuous variable, greater total folate intake 12–24 y before diagnosis was associated with lower risk of CRC (per increment of 400 dietary folate equivalents (DFE)/d, HR: 0.93, 95% CI: 0.85, 1.01 for 12–16 y; HR: 0.83, 95% CI: 0.75, 0.92 for 16–20 y; and HR: 0.87, 95% CI: 0.77, 0.99 for 20–24 y); and greater synthetic folic acid intake 16–24 y before diagnosis was also associated with a lower CRC risk (per increment of 400 DFE/d, HR: 0.91, 95% CI: 0.84, 0.99 for 16–20 y and HR: 0.91, 95% CI: 0.83–1.01 for 20–24 y). In the postfortification period (1998–2016), intake of total or specific forms of folate was not associated with CRC risk, even among multivitamin users. Conclusions Folate intake, both total and from synthetic forms, was associated with a lower risk of overall CRC after long latency periods. There was no evidence that high folate intake in the postfortification period was related to increased CRC risk in this US female population.

scholarly journals Association of oral contraceptives and tubal ligation with risk of early natural menopause

2021 ◽  
Author(s):  
C R Langton ◽  
B W Whitcomb ◽  
A C Purdue-Smithe ◽  
L L Sievert ◽  
S E Hankinson ◽  
...  
Keyword(s):  
Oral Contraceptives ◽  
Proportional Hazards ◽  
Reproductive Factors ◽  
Cox Proportional Hazards ◽  
Tubal Ligation ◽  
Health Study ◽  
Early Menopause ◽  
Natural Menopause ◽  
Increased Risk

Abstract STUDY QUESTION What is the association of oral contraceptives (OCs) and tubal ligation (TL) with early natural menopause? SUMMARY ANSWER We did not observe an association of OC use with risk of early natural menopause; however, TL was associated with a modestly higher risk. WHAT IS KNOWN ALREADY OCs manipulate hormone levels, prevent ovulation, and may modify the rate of follicular atresia, while TL may disrupt the blood supply to the ovaries. These mechanisms may be associated with risk of early menopause, a condition associated with increased risk of cardiovascular disease and other adverse health outcomes. STUDY DESIGN, SIZE, DURATION We examined the association of OC use and TL with natural menopause before the age of 45 years in a population-based study within the prospective Nurses’ Health Study II (NHSII) cohort. Participants were followed from 1989 to 2017 and response rates were 85-90% for each cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included 106 633 NHSII members who were premenopausal and aged 25-42 years at baseline. Use, duration and type of OC, and TL were measured at baseline and every 2 years. Menopause status and age were assessed every 2 years. Follow-up continued until early menopause, age 45 years, hysterectomy, oophorectomy, death, cancer diagnosis, or loss to follow-up. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs adjusted for lifestyle, dietary, and reproductive factors. MAIN RESULTS AND THE ROLE OF CHANCE Over 1.6 million person-years, 2579 members of the analytic cohort experienced early natural menopause. In multivariable models, the duration, timing, and type of OC use were not associated with risk of early menopause. For example, compared with women who never used OCs, those reporting 120+ months of OC use had an HR for early menopause of 1.01 (95% CI, 0.87-1.17; P for trend=0.71). TL was associated with increased risk of early menopause (HR = 1.17, 95% CI, 1.06-1.28). LIMITATIONS, REASONS FOR CAUTION Our study population is homogenous with respect to race and ethnicity. Additional evaluation of these relations in more diverse populations is important. WIDER IMPLICATIONS OF THE FINDINGS To our knowledge, this is the largest study examining the association of OC use and TL with early natural menopause to date. While TL was associated with a modest higher risk of early menopause, our findings do not support any material hazard or benefit for the use of OCs. STUDY FUNDING/COMPETING INTEREST(S) The study was sponsored by UO1CA176726 and R01HD078517 from the National Institutes of Health and Department of Health and Human Services. The work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have no competing interests to report. TRIAL REGISTRATION NUMBER N/A

Cognitive Impairment after Lacunar Stroke and the Risk of Recurrent Stroke and Death

2021 ◽  
pp. 1-7
Author(s):  
Abraham Kwan ◽  
Jingkai Wei ◽  
N. Maritza Dowling ◽  
Melinda C. Power ◽  
Zurab Nadareshvili ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Memory Impairment ◽  
Recurrent Stroke ◽  
Cox Proportional Hazards ◽  
Hazard Ratio ◽  
Cognitive Screening ◽  
Lacunar Stroke ◽  
Domain Specific ◽  
Risk Of Death ◽  
Increased Risk

Introduction: Patients with poststroke cognitive impairment appear to be at higher risk of recurrent stroke and death. However, whether cognitive impairment after lacunar stroke is associated with recurrent stroke and death remains unclear. We assessed whether global or domain-specific cognitive impairment after lacunar stroke is associated with recurrent stroke and death. Methods: We considered patients from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial with a baseline cognitive exam administered in English by certified SPS3 personnel, 14–180 days after qualifying lacunar stroke. We considered a baseline score of ≤86 on the Cognitive Assessment Screening Instrument to indicate global cognitive impairment, <10 on the Clock Drawing on Command test to indicate executive function impairment, and domain-specific summary scores in the lowest quartile to indicate memory and nonmemory impairment. We used Cox proportional hazards models to estimate the association between poststroke cognitive impairment and subsequent risk of recurrent stroke and death. Results: The study included 1,528 participants with a median enrollment time of 62 days after qualifying stroke. During a mean follow-up of 3.9 years, 11.4% of participants had recurrent stroke and 8.2% died. In the fully adjusted models, memory impairment was independently associated with an increased risk of recurrent stroke (hazard ratio, 1.48; 95% confidence interval [95% CI]: 1.04–2.09) and death (hazard ratio, 1.87; 95% CI: 1.25–2.79). Global impairment (hazard ratio, 1.66; 95% CI: 1.06–2.59) and nonmemory impairment (hazard ratio, 1.74; 95% CI: 1.14–2.67) were associated with an increased risk of death. Discussion/Conclusion: After lacunar stroke, memory impairment was an independent predictor of recurrent stroke and death, while global and nonmemory impairment were associated with death. Cognitive screening in lacunar stroke may help identify populations at higher risk of recurrent stroke and death.

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