Risk of Ischemic Stroke Increases Over the Spectrum of Metabolic Syndrome Severity

Background and Purpose: Ischemic stroke is associated with the metabolic syndrome (MetS) as diagnosed using dichotomous criteria; however, these criteria exhibit racial/ethnic discrepancies. Our goal was to assess whether ischemic stroke risk extended over the spectrum of worsening MetS severity using a sex- and race/ethnicity-specific MetS-severity Z score. Methods: We used Cox-proportional hazards models to assess the relationship between baseline MetS- Z score and incident ischemic stroke among participants of the Atherosclerosis Risk in Communities study and Jackson Heart Study who were free from diabetes, coronary heart disease or stroke at baseline, evaluating 13 141 white and black individuals with mean follow-up of 18.6 years. Results: We found that risk of ischemic stroke increased consistently with MetS severity, with a hazard ratio of 1.75 (95% CI, 1.35–2.27) for those >75th percentile compared to those <25th percentile. This risk was highest for white females (hazard ratio, 2.63 [CI, 1.70–4.07]) though without significant interaction by sex and race. Relationships between stroke and all the individual components of MetS were only noted for white females, though again without sex-race interactions. Hazard ratio’s for systolic blood pressure and stroke were significant among all sex/racial subgroups. Conclusions: Ischemic stroke risk increased over the spectrum of MetS severity in the absence of baseline diabetes mellitus, further implicating potential etiologic risks from processes underlying MetS. Individuals with elevated MetS severity should be counselled toward lifestyle modification to lower ischemic stroke risk.

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Metabolic Syndrome and Risk of Ischemic Stroke in Atrial Fibrillation

Stroke ◽

10.1161/strokeaha.119.025376 ◽

2019 ◽

Vol 50 (11) ◽

pp. 3045-3050 ◽

Cited By ~ 2

Author(s):

Joseph J. Decker ◽

Faye L. Norby ◽

Mary R. Rooney ◽

Elsayed Z. Soliman ◽

Pamela L. Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Metabolic Syndrome ◽

Ischemic Stroke ◽

Stroke Risk ◽

Proportional Hazards ◽

International Diabetes Federation ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Increased Risk ◽

Low Hdl

Background and Purpose— Metabolic syndrome (MetS), a prothrombotic state, is associated with an increased risk of atrial fibrillation (AF) and stroke. The CHA 2 DS 2 -VASc score does not account for the MetS components of prehypertension, prediabetes mellitus, abdominal obesity, elevated triglycerides, and low HDL (high-density lipoprotein). Data are limited on the association of MetS with stroke in AF, independent of CHA 2 DS 2 -VASc variables. Our aim was to identify MetS components associated with ischemic stroke in participants with AF in the ARIC study (Atherosclerosis Risk in Communities). Methods— We included 1172 participants with incident AF within 5 years of measurement of MetS components. MetS was defined by ATP criteria and International Diabetes Federation criteria. Incident ischemic stroke was physician adjudicated. Multivariable Cox proportional hazards regression was used to assess the association of MetS components with stroke. Results— After a median follow-up of 14.8 years, there were 113 ischemic stroke cases. Of the individual MetS components, low HDL was borderline associated with increased stroke risk (hazard ratio, 1.48 [95% CI, 0.99–2.21]) after adjustment for CHA 2 DS 2 -VASc variables while the remaining MetS variables were not associated with stroke risk. The presence of ≥3 components of MetS was not significantly associated with ischemic stroke after adjustment for CHA 2 DS 2 -VASc variables (hazard ratio, 1.38 [95% CI, 0.91–2.11]). The risk of stroke increased by 13% for each additional component of MetS; however, this association was borderline significant (hazard ratio, 1.13 [95% CI, 0.99–1.28]). Conclusions— The presence of MetS was not significantly associated with ischemic stroke after adjustment for CHA 2 DS 2 -VASc variables. Consideration of MetS is unlikely to improve stroke prediction in AF.

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Electrocardiographic ST-T Abnormities Are Associated With Stroke Risk in the REGARDS Study

Stroke ◽

10.1161/strokeaha.119.028069 ◽

2020 ◽

Vol 51 (4) ◽

pp. 1100-1106

Author(s):

Mitsuaki Sawano ◽

Ya Yuan ◽

Shun Kohsaka ◽

Taku Inohara ◽

Takeki Suzuki ◽

...

Keyword(s):

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Proportional Hazards ◽

The United States ◽

Incidence Rates ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Common Finding ◽

Increased Risk

Background and Purpose— In previous studies, isolated nonspecific ST-segment and T-wave abnormalities (NSSTTAs), a common finding on ECGs, were associated with greater risk for incident coronary artery disease. Their association with incident stroke remains unclear. Methods— The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a population-based, longitudinal study of 30 239 white and black adults enrolled from 2003 to 2007 in the United States. NSSTTAs were defined from baseline ECG using the standards of Minnesota ECG Classification (Minnesota codes 4-3, 4-4, 5-3, or 5-4). Participants with prior stroke, coronary heart disease, and major and minor ECG abnormalities other than NSSTTAs were excluded from analysis. Multivariable Cox proportional hazards regression was used to examine calculate hazard ratios of incident ischemic stroke by presence of baseline NSSTTAs. Results— Among 14 077 participants, 3111 (22.1%) had NSSTTAs at baseline. With a median of 9.6 years follow-up, 106 (3.4%) with NSSTTAs had ischemic stroke compared with 258 (2.4%) without NSSTTAs. The age-adjusted incidence rates (per 1000 person-years) of stroke were 2.93 in those with NSSTTAs and 2.19 in those without them. Adjusting for baseline age, sex, race, geographic location, and education level, isolated NSSTTAs were associated with a 32% higher risk of ischemic stroke (hazard ratio, 1.32 [95% CI, 1.05–1.67]). With additional adjustment for stroke risk factors, the risk of stroke was increased 27% (hazard ratio, 1.27 [95% CI, 1.00–1.62]) and did not differ by age, race, or sex. Conclusions— Presence of NSSTTAs in persons with an otherwise normal ECG was associated with a 27% increased risk of future ischemic stroke.

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Abstract 19554: Lipoprotein(a) and Risk of Ischemic Stroke in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.132.suppl_3.19554 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Kristine S Alexander ◽

Neil A Zakai ◽

Fred Unverzagt ◽

Virginia Wadley ◽

Brett M Kissela ◽

...

Keyword(s):

Ischemic Stroke ◽

Racial Differences ◽

Stroke Risk ◽

Proportional Hazards ◽

Continuous Variable ◽

Cox Proportional Hazards ◽

Stroke Incidence ◽

Lipoprotein A ◽

Cox Proportional Hazards Models ◽

Regards Study

Background: Increased lipoprotein (a) (Lp(a)) is associated with coronary risk, but links with stroke have been less consistent. Blacks have 2-4-fold higher Lp(a) levels than whites, and have higher stroke incidence than whites, but have been under-represented in studies of Lp(a) and stroke to date. Hypothesis: Lp(a) is a risk factor for ischemic stroke, and this risk differs by race. Methods: REGARDS recruited 30,239 black and white U.S. men and women in 2003-7 to study regional and racial differences in stroke mortality. We measured Lp(a) by immunonepholometric assay in 572 cases of incident ischemic stroke and a 1,104-person cohort random sample. The hazard ratio of stroke by baseline Lp(a) was calculated using Cox proportional hazards models, stratified by race. Lp(a) was modeled both as a continuous variable (per sex- and race-specific SD) and in sex- and race-specific quartiles, given known differences in distributions by race and sex. Results: As shown in the Figure, being in the 4 th vs 1 st Lp(a) quartile was associated with ischemic stroke in black but not white participants, adjusted for age and sex (Model 1). The HRs were essentially unchanged with added adjustment for stroke risk factors (Model 2). There was no significant association between Lp(a) as a continuous variable and stroke, though race-specific patterns were similar. There remained no association between Lp(a) and stroke in whites when we used the sex- and race-specific 90 th percentile as a cut-off (HR: 0.91 95% CI: 0.52, 1.60). Discussion: Lp(a) was associated with ischemic stroke risk in black but not white REGARDS participants, this might partly explain the black/white disparity in stroke. Further studies in racially diverse groups are necessary to confirm these findings. Figure 1. Hazard ratios for Lp(a) and stroke in blacks and whites, per quartile (compared with first quartile) and SD.

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

Cancers ◽

10.3390/cancers13051177 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1177

Author(s):

In Young Choi ◽

Sohyun Chun ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Keun Hye Jeon ◽

...

Keyword(s):

Breast Cancer ◽

Metabolic Syndrome ◽

Proportional Hazards ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Models ◽

Hazard Ratios ◽

Increased Risk ◽

Health Screening Program ◽

Design And Methods

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

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Abstract P030: Variations in Cardiovascular Risk Among Different Clinical Presentations of Metabolic Syndrome in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.125.suppl_10.ap030 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Todd M Brown ◽

Joshua Richman ◽

Vera Bittner ◽

Cora E Lewis ◽

Jenifer Voeks ◽

...

Keyword(s):

Risk Factors ◽

Metabolic Syndrome ◽

Racial Differences ◽

Central Obesity ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Next Of Kin ◽

Cox Proportional Hazards Models ◽

Chd Risk ◽

The Individual

Background: Some individuals classified as having metabolic syndrome (MetSyn) are centrally obese while others are not with unclear implications for cardiovascular (CV) risk. Methods: REGARDS is following 30,239 individuals ≥45 years of age living in 48 states recruited from 2003-7. MetSyn risk factors were defined using the AHA/NHLBI/IDF harmonized criteria with central obesity being defined as ≥88 cm in women and ≥102 cm in men. Participants with and without central obesity were stratified by whether they met >2 or ≤2 of the other 4 MetSyn criteria, resulting in the creation of 4 groups. To ascertain CV events, participants are telephoned every 6 months with expert adjudication of potential events following national consensus recommendations and based on medical records, death certificates, and interviews with next-of-kin or proxies. Acute coronary heart disease (CHD) was defined as definite or probable myocardial infarction or acute CHD death. To determine the association between these 4 groups and incident acute CHD, we constructed Cox proportional hazards models in those free of CHD at baseline by race/gender group, adjusting for sociodemographic variables. Results: A total of 20,018 individuals with complete data on MetSyn components were free of baseline CHD. Mean age was 64+/−9 years, 58% were women, and 42% were African American. Over a mean follow-up of 3.4 (maximum 5.9) years, there were 442 acute CHD events. In the non-centrally obese with>2 other risk factors, risk for CHD was higher for all but AA men, though significant only for white men. In contrast, in the centrally obese with >2 other risk factors, risk was doubled for women, but only non-significantly and modestly increased for men. Only AA women with central obesity and ≤2 other risk factors had increased CHD risk (Table). Conclusion: The CHD risk associated with the MetSyn varies by the presence of central obesity as well as the race and gender of the individual.

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Markers of Iron Metabolism and Stroke Risk: Cross-Sectional and Longitudinal Findings from the China Health and Nutrition Survey (CHNS)

Iranian Journal of Public Health ◽

10.18502/ijph.v51i1.8302 ◽

2022 ◽

Author(s):

Dong Liu ◽

Ya Zhang ◽

Cui-Cui Wang ◽

Xiao-Hong E ◽

Hui Zuo

Keyword(s):

Iron Metabolism ◽

Stroke Risk ◽

Proportional Hazards ◽

High Sensitivity ◽

Cox Proportional Hazards ◽

Contributing Factors ◽

Nutrition Survey ◽

Cross Sectional ◽

Health And Nutrition ◽

Cox Proportional Hazards Models

Background: The association of iron metabolism or status with the stroke risk remains unclear. We aimed to examine the associations between markers of iron metabolism or status and stroke risk using data from the China Health and Nutrition Survey (CHNS). Methods: Overall, 8589 in the CHNS in 2009, and 7290 participants between 2009 and 2015 were included in the cross-sectional and longitudinal analyses, respectively. Markers included hemoglobin, ferritin (FET), transferrin (TRF), soluble transferrin receptor (sTRF-R), and ratio of sTRF-R/log FET (sTfR-F index). Multivariable logistic regression and Cox proportional hazards models were used to analyze the associations between those markers and risk of stroke. Age, gender, high-sensitivity CRP (hsCRP), body mass index (BMI), current smoking, drinking status, diabetes and hypertension were included as potential confounding factors. Results: We observed longitudinal associations of hemoglobin (HR: 1.54, 95% CI: 1.15 – 2.06, P = 0.004), and sTfR-F index (HR: 0.68, 95% CI: 0.46 – 0.99, P = 0.044) with stroke risk among the participants whose BMI ≤ 23 kg/m2. In addition, FET levels were significantly associated with stroke risk among female (HR: 1.45, 95% CI: 1.00 – 2.09, P = 0.049) after a median of 6.1 years follow-up. Hemoglobin, FET, TRF, sTRF-R, and sTfR-F index were not associated with the risk of stroke in overall analyses. Conclusion: FET among female, hemoglobin and sTfR-F index among those BMI ≤ 23 kg/m2 may be contributing factors for stroke.

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Abstract P005: Comparative Effectiveness of Rivaroxaban versus Warfarin for the Treatment of Patients with Non-valvular Atrial Fibrillation

Circulation ◽

10.1161/circ.133.suppl_1.p005 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Faye L Norby ◽

Lindsay G Bengtson ◽

Lin Y Chen ◽

Richard F MacLehose ◽

Pamela L Lutsey ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Real World ◽

Proportional Hazards ◽

Large Population ◽

Population Based ◽

Cox Proportional Hazards ◽

Gi Bleeding ◽

Cox Proportional Hazards Models ◽

The Us

Background: Rivaroxaban is a novel oral anticoagulant approved in the US in 2011 for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF). Information on risks and benefits among rivaroxaban users in real-world populations is limited. Methods: We used data from the US MarketScan Commercial and Medicare Supplemental databases between 2010 and 2013. We selected patients with a history of NVAF and initiating rivaroxaban or warfarin. Rivaroxaban users were matched with up to 5 warfarin users by age, sex, database enrollment date and drug initiation date. Ischemic stroke, intracranial bleeding (ICB), myocardial infarction (MI), and gastrointestinal (GI) bleeding outcomes were defined by ICD-9-CM codes in an inpatient claim after drug initiation date. Cox proportional hazards models were used to assess the association between rivaroxaban vs. warfarin use and outcomes adjusting for age, sex, and CHA2DS2-VASc score. Separate models were used to compare a) new rivaroxaban users with new warfarin users, and b) switchers from warfarin to rivaroxaban to continuous warfarin users. Results: Our analysis included 34,998 rivaroxaban users matched to 102,480 warfarin users with NVAF (39% female, mean age 71), in which 487 ischemic strokes, 179 ICB, 647 MI, and 1353 GI bleeds were identified during a mean follow-up of 9 months. Associations of rivaroxaban vs warfarin were similar in new users and switchers; therefore we pooled both analyses. Rivaroxaban users had lower rates of ICB (hazard ratio (HR) (95% confidence interval (CI)) = 0.72 (0.46, 1.12))) and ischemic stroke (HR (95% CI) = 0.88 (0.68, 1.13)), but higher rates of GI bleeding (HR (95% CI) = 1.15 (1.01, 1.33)) when compared to warfarin users (table). Conclusion: In this large population-based study of NVAF patients, rivaroxaban users had a non-significant lower risk of ICB and ischemic stroke than warfarin users, but a higher risk of GI bleeding. These real-world findings are comparable to results reported in published clinical trials.

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Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Neurology ◽

10.1212/wnl.0000000000004586 ◽

2017 ◽

Vol 89 (18) ◽

pp. 1877-1885 ◽

Cited By ~ 41

Author(s):

Ariela R. Orkaby ◽

Kelly Cho ◽

Jean Cormack ◽

David R. Gagnon ◽

Jane A. Driver

Keyword(s):

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Confounding By Indication ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Us Veterans

Objective:To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.Methods:This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.Results:We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61–0.73) and 0.78 (95% CI 0.72–0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79–0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87–1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99).Conclusions:After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

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Metabolic Syndrome and Ischemic Stroke Risk

Stroke ◽

10.1161/strokeaha.107.496588 ◽

2008 ◽

Vol 39 (1) ◽

pp. 30-35 ◽

Cited By ~ 159

Author(s):

Bernadette Boden-Albala ◽

Ralph L. Sacco ◽

Hye-Sueng Lee ◽

Cairistine Grahame-Clarke ◽

Tanja Rundek ◽

...

Keyword(s):

Metabolic Syndrome ◽

Ischemic Stroke ◽

Stroke Risk ◽

Ischemic Stroke Risk

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Phospholipid Levels at Seroconversion are Associated with Resolution of Persistent Islet Autoimmunity: The Diabetes Autoimmunity Study in the Young

10.2337/figshare.14414342 ◽

2021 ◽

Author(s):

Patrick M. Carry ◽

Lauren A. Vanderlinden ◽

Randi K. Johnson ◽

Teresa Buckner ◽

Oliver Fiehn ◽

...

Keyword(s):

Proportional Hazards ◽

Principal Component ◽

Enrichment Analysis ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Islet Autoimmunity ◽

Potential Influence ◽

Serum Samples ◽

Sugar Intake ◽

Cox Proportional Hazards Models

Reversion of islet autoimmunity (IA) may point to mechanisms that prevent IA progression. We followed 199 individuals who developed IA during the Diabetes Autoimmunity Study in the Young. Untargeted metabolomics was performed in serum samples following IA. Cox-proportional hazards models were used to test if the metabolites (2,487) predicted IA reversion, two or more consecutive visits negative for all autoantibodies. We conducted a principal component analysis (PCA) of the top metabolites, |hazard ratio (HR) >1.25| and nominal p<0.01. Phosphatidylcholine (16:0_18:1(9Z) was the strongest individual metabolite (hazard ratio (HR) per 1 standard deviation: 2.16, FDR adjusted p=0.0037). Enrichment analysis identified four clusters (FDR p<0.10) characterized by an overabundance of sphingomyelin (d40:0), phosphatidylcholine (16:0_18:1(9Z)), phosphatidylcholine (30:0), and L-decanoylcarnitine. Overall, 63 metabolites met the criteria for inclusion in the PCA. PC1 (HR: 1.4, p<0.0001), PC2 (HR: 0.85, p=0.0185), and PC4 (HR: 1.28, p=0.0103) were associated with IA reversion. Given the potential influence of diet on the metabolome, we investigated whether nutrients were correlated with PCs. We identified 20 nutrients that were correlated with the PCs (p<0.05). Total sugar intake was the top nutrient. Overall, we identified an association between phosphatidylcholine, sphingomyelin, and carnitine levels and reversion of IA.

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