Abstract P075: Genetic European Ancestry And Incident Diabetes Mellitus In Black Individuals-Insights From The SPRINT Trial

Background: A metabolic paradox of lower triglyceride (TG) and higher high-density lipoprotein cholesterol (HDL-C) levels but a higher incidence of diabetes has been described in Blacks. We evaluated the association of genetic ancestry-related variants with the risk of incident diabetes in self-identified Black individuals in the Systolic Blood Pressure (BP) Intervention Trial (SPRINT). Methods: The genetic European ancestry proportions were estimated using 106 biallelic genotype markers in non-diabetic Black participants. Participants were stratified into tertiles (T1-T3) of European ancestry proportions. Multivariable-adjusted association of baseline metabolic syndrome indices (fasting plasma glucose [FPG], TG, HDL-C, body mass index [BMI], and BP) with the ancestry proportion was assessed. Multivariable-adjusted Cox regression was used to assess the risk of incident diabetes (FPG ≥126 mg/dL or self-reported diabetes treatment) across tertiles. Results: In 2,466 participants with median European ancestry 19% (13 - 27%), those in T1 were relatively younger, with lower Framingham risk score, and worse renal function (p<0.05 for all). At baseline, higher European ancestry proportion was associated with higher TG and lower HDL-C levels after controlling for clinical and demographic factors (p<0.05 for both). FPG, BMI, and BP were not significantly associated with ancestry proportion. Compared with T1, those in second (HR: 0.64 [95% CI: 0.45-0.90]) and third tertiles (HR: 0.61 [0.44-0.89]) had a lower risk of incident diabetes after controlling for covariates. Specifically, a 5% increment in European ancestry was associated with a 29% lower risk of incident diabetes (HR: 0.71 [0.55-0.93]). No interaction was observed between intensive BP control strategy and European ancestry proportion tertiles on incident diabetes. Conclusions: Genetic factors may account for racial differences in TG and HDL-C levels. The higher risk of incident diabetes in Blacks may similarly be genetically determined.

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P1650HIGH-DENSITY LIPOPROTEIN PARTICLES AND THEIR RELATIONSHIP TO POSTTRANSPLANTATION DIABETES IN RENAL TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1650 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Sara Sokooti Oskooei ◽

Tamas Szili-Torok ◽

Jose L Flores-Guerrero ◽

Maryse C.J. Osté ◽

António W Gomes-Neto ◽

...

Keyword(s):

Renal Transplant ◽

Lower Risk ◽

Cox Regression ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Cox Proportional Hazards ◽

Relative Mass ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Cox Regression Analysis

Abstract Background and Aims It is established that high concentrations of High-Density Lipoprotein (HDL) are associated with low risk of type 2 diabetes and posttransplantation diabetes mellitus (PTDM). However, HDL particles vary by size, density, and biological action. The aim of our study was to determine the association between different HDL particles with the development of PTDM in renal transplant recipients (RTRs). Method We included 351 stable outpatient adult RTR with a functioning graft ≥1 year from the Tranplantlines Food and Nutrition Study(NCT02811835). HDL particle concentration and size were measured by 1H-NMR spectroscopy using a Vantera® NMR Clinical Analyzer (LabCorp, Raleigh, NC). HDL size was weighted averages derived from the sum of the diameter of each subclass multiplied by its relative mass percentage. Estimated ranges of HDL diameter for the HDL subclasses were as follows: large HDL particles, 9.6–13 nm; medium HDL particles, 8.1–9.5 nm; and small HDL particles, 7.4–8.0 nm. PTDM was defined according the American Diabetes Association’s diagnostic criteria for diabetes. Multivariable-adjusted Cox proportional-hazards regression analyses were performed to assess the prospective association of HDL particles with PTDM. Results During 5.2 (IQR, 4.1–5.8) years of follow-up, 39 (11%) RTR developed PTDM. In a multivariable Cox regression analysis, higher HDL cholesterol was associated with a lower risk of PTDM development, after adjustment for age, sex and BMI (hazard ratio[HR] 0.55, 95% CI 0.36-0.83 per 1SD mg/dL; P=0.005). Moreover, among different HDL indices; HDL size, and large HDL were inversely associated with PTDM, after adjustment for age, sex, and BMI ([ HR 0.48, 95% CI 0.31-0.76 per 1SD nm; P=0.002], and [HR 0.63, 95% CI 0.47-0.84 per 1SD µmol/L; P=0.002], respectively ). However medium HDL and small HDL were not associated with risk of developing PTDM ([ HR 0.88, 95% CI 0.64-1.23 per 1SD µmol/L; P=0.48], and [HR 1.14, 95% CI 0.85-1.52 per µmol/L; P=0.37], respectively ). In additional models, the association remained significant for HDL cholesterol, HDL size, and large HDL after adjustment for other confounders including, the lifestyle, use of medication, kidney function and transplantation-specific parameters. In the last model after adjustment for age, sex, BMI, triglycerides, systolic blood pressure, and fasting plasma glucose, association were similar for HDL cholesterol, HDL size, and large HDL ([ HR 0.61, 95% CI 0.40-0.94 per 1SD mg/dL; P=0.024], [HR 0.58, 95% CI 0.36-0.93 per 1SD nm; P=0.025], and [HR 0.68, 95% CI 0.50-0.93 per 1SD µmol/L; P=0.017]. Conclusion In this study, we found that higher concentrations of HDL cholesterol, large HDL, and higher HDL size were associated with a lower risk of developing PTDM in RTRs, independent of established risk factors for PTDM development.

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Abstract P278: Life's Simple 7 and Risk of Incident Stroke in Black and White Americans: REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.125.suppl_10.ap278 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Ambar Kulshreshtha ◽

Suzanne Judd ◽

Viola Vaccarino ◽

Virginia Howard ◽

William McClellan ◽

...

Keyword(s):

Racial Differences ◽

Lower Risk ◽

Cardiovascular Health ◽

Cox Regression ◽

Disease Incidence ◽

Heart Association ◽

P Value ◽

Life’S Simple 7 ◽

Blacks And Whites ◽

Life's Simple 7

Background: The American Heart Association has developed Life’s Simple 7 (LS-7) as a measure of cardiovascular health. In a recent study, LS-7 showed a graded relationship with cardiovascular disease incidence. The association of LS-7 with incident stroke has not been reported previously. Methods: We analyzed data from REGARDS, a national population-based cohort of 30,239 blacks and whites, aged ≥ 45 years of age, sampled from US population between 2003 and 2007. Data for LS-7 was collected by telephone, mail questionnaires, and an in-home exam. Participants were contacted every 6 months for possible stroke, which was validated by physicians using medical record review. LS-7 components (blood pressure, cholesterol, glucose, BMI, smoking, physical activity, diet) were each coded as: poor (1 point), intermediate (2 points) and ideal (3 points). An overall LS-7 score, created by summing the 7 component scores (possible range: 7 to 21), was categorized as: highest (17–21), medium (12–16) and lowest (7–11) cardiovascular health. Cox regression was used to model LS-7 score categories with stroke events. Results: There were 22,914 participants with data on LS-7 and no previous CVD. Mean age was 65 years, 40% were black, and 55% female. Over 4.9 years of follow-up, there were 432 incident strokes. Mean (SD) LS-7 score was 13.5 (2.5). After adjustment for age and sex, mean LS-7 scores were lower for blacks (12.9 ± 0.02) than whites (14.3 ± 0.02). LS-7 categories were associated with incident stroke in a graded fashion (figure). After adjusting for age, race, sex, income, and education, each better health category was associated with a 25% lower risk of incident stroke (HR=0.75, 95% CI = 0.63, 0.90). In stratified analyses, HR was similar for blacks and whites (p-value = 0.55). Conclusion: Blacks had lower levels of cardiovascular health factors than whites. Better cardiovascular health based on LS-7 score was associated with a lower risk of stroke. Results suggest that efforts to improve the LS-7 score may be useful for stroke prevention.

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Abstract P309: Vulnerabilities to Health Disparities and Statin Use in the REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

Circulation ◽

10.1161/circ.133.suppl_1.p309 ◽

2016 ◽

Vol 133 (suppl_1) ◽

Author(s):

Praful Schroff ◽

Christopher M Gamboa ◽

Raegan W Durant ◽

Asikhame Oikeh ◽

Joshua S Richman ◽

...

Keyword(s):

Health Insurance ◽

Racial Differences ◽

Density Lipoprotein ◽

Poverty Line ◽

Older Age ◽

Small City ◽

Framingham Risk ◽

Federal Poverty Line ◽

Regards Study ◽

Statin Use

Introduction: Statins reduce the incidence of major cardiovascular disease events, but many individuals do not receive them. The AHRQ National Healthcare Disparities Report identifies several vulnerable populations, but few studies have examined statin use from the perspective of the presence of multiple vulnerabilities in the same individual. Hypothesis: A greater number of vulnerabilities is associated with lower statin use. Methods: This study used data from the REGARDS study, which included 30,239 adults of age 45 and older recruited between 2003 and 2007 from the 48 contiguous US states. Baseline data included a 45-minute telephone interview and an in-home visit. Vulnerabilities included older age, black race, being a woman, rural/small city residence, area level poverty, Southeastern residence, and lack of health insurance. Prevalence ratios were estimated from Poisson models and adjusted for factors influencing health services utilization (education, awareness of hyperlipidemia, medication adherence, cigarette smoking, depressive symptoms, obesity, high-density lipoprotein cholesterol, physical functioning and Adult Treatment Panel III Framingham Risk Group). Results: The study sample included 18,047 individuals of mean age 65.8 years with indications for statin therapy; 41.7% were black, 50.8% were women, 8.7% lived in a rural area/small city, 25.2% lived in areas with >25% of residents living below the Federal poverty line, 55.0% lived in the Southeastern states and 6% did not have health insurance. Older age, being black, being a woman, area level poverty, and health insurance were significantly associated with lower statin use. Statin use decreased as the number of vulnerabilities increased. Conclusions: A greater burden of healthcare disparity vulnerabilities was associated with a graded pattern of lower statin use. Individuals with multiple vulnerabilities have the greatest risk of under treatment and should be targeted for intervention.

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Higher thyrotropin leads to unfavorable lipid profile and somewhat higher cardiovascular disease risk: evidence from multi-cohort Mendelian randomization and metabolomic profiling

BMC Medicine ◽

10.1186/s12916-021-02130-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Nicolien A. van Vliet ◽

Maxime M. Bos ◽

Carisha S. Thesing ◽

Layal Chaker ◽

Maik Pietzner ◽

...

Keyword(s):

Cardiovascular Disease ◽

Lipid Profile ◽

Metabolic Profile ◽

Mendelian Randomization ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Density Lipoprotein ◽

European Ancestry ◽

Thyroid Status ◽

Genetically Determined

Abstract Background Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. Methods Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. Results Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99–1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96–1.04; p value 0.59). Conclusions Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk.

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Genetically-determined higher TSH is associated with lower risk of diabetes mellitus in individuals with low BMI

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab277 ◽

2021 ◽

Author(s):

Maxime M Bos ◽

Nicolien A van Vliet ◽

Simon P Mooijaart ◽

Raymond Noordam ◽

Diana van Heemst

Keyword(s):

Diabetes Mellitus ◽

Lower Risk ◽

European Ancestry ◽

Risk Scores ◽

P Value ◽

Protective Effects ◽

Uk Biobank ◽

Thyroid Status ◽

Low Bmi ◽

Genetically Determined

Abstract Context Thyroid status is hypothesized to be causally related with the risk of diabetes mellitus (DM), but previous results were conflicting possibly due to a complex interaction between TSH, body mass index (BMI) and DM. Objective To investigate the causal association between thyroid status with DM and glucose homeostasis and to what extent this association is dependent on BMI Design Mendelian Randomization study. Setting European-ancestry participants from the UK Biobank population. Participants The present study was performed in 408,895 individuals (mean age 57.4 years (standard deviation 8.0), 45.9% men), of which 19,773 DM cases. Interventions Genetic variants for circulatory thyroid stimulating hormone (TSH), free thyroxine (fT4) concentrations and BMI to calculate weighted genetic risk scores. Main Outcome Measures(s) self-reported DM, stratified analyses by BMI. Analyses were repeated for non-fasting glucose and Hb1Ac among individuals without DM. Results Genetically-determined TSH and fT4 levels were not associated with risk of DM in the total UK Biobank population. However, in analyses stratified on genetically-determined BMI, genetically-determined higher TSH, and not fT4, was associated with a lower risk for DM only in the low BMI group (odds ratio 0.91; 95% confidence interval 0.85,0.98 in low BMI; p-value for interaction = 0.06). Similar results were observed for glucose and Hb1Ac among individuals without DM. Conclusions TSH, but not fT4, is a potential causal risk factor for DM in individuals with genetically determined low BMI highlighting potential protective effects of TSH only in low-risk populations.

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Mediating Effects of High-density Lipoprotein for Alcohol Consumption and Myocardial Infarction: The Multi-Ethnic Study of Atherosclerosis (OR19-07-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz046.or19-07-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Shue Huang ◽

Xiang Gao ◽

Shanshan Li ◽

Gregory Shearer

Keyword(s):

Myocardial Infarction ◽

Alcohol Consumption ◽

High Density Lipoprotein ◽

Lower Risk ◽

Alcohol Intake ◽

Cox Regression ◽

Density Lipoprotein ◽

High Density ◽

Mediating Effect ◽

Ethnic Study

Abstract Objectives The aim of this study was to investigate whether and to what extent the association between alcohol intake and incident myocardial infarction (MI) is mediated through high density lipoprotein cholesterol (HDL-C), and HDL particles (HDL-P). Methods A total of 6,704 participants from the Multi-Ethnic Study of Atherosclerosis were included in the analysis. Alcohol consumption information was assessed via a questionnaire at baseline (exam 1). HDL-C concentrations and HDL-P were both measured at exam 1. Cox regression was used to model the association of habitual alcohol intake and risk for MI before and after adjusting HDL-C and HDL-P, in addition to adjustment of all potential covariates. Mediated effects through HDL-C, and HDL-P were estimated using the causal mediation analysis. Results After a median of 8 years follow-up, 171 incident MI cases were documented. Alcohol intake was associated with a lower risk for incident MI (adjusted Hazard Ratio (HR) = 0.69, 95% Confidence Interval (CI): 0.50-0.95), relative to non-drinkers. The relation between alcohol intake and MI became nonsignificant after further adjusting HDL-P. The HRs of the indirect effect of alcohol through HDL-C and HDL-P were 0.97 (95% CI: 0.93, 1.01) (P = 0.16) and 0.94 (95% CI: 0.90, 0.99) (P = 0.02), indicating that on average, alcohol intake reduced the risk of MI by 6% through its effect on HDL-P and not through HDL-C. The proportion of the effect of alcohol on MI mediated by HDL-P was 14.6%. Conclusions This study indicates that the lower risk of MI related to alcohol intake appears to partially work through increasing HDL-P, however, the mechanism for much of alcohol's effect to reduce MI risk remains unexplained. This suggests that HDL-P can be a target for MI prevention, however the mediating effect of HDL-P is very moderate. Funding Sources N/A.

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Fracture Risk in Patients with Myasthenia Gravis: A Population-Based Cohort Study

Journal of Neuromuscular Diseases ◽

10.3233/jnd-200612 ◽

2021 ◽

pp. 1-8

Author(s):

Charles Kassardjian ◽

Jessica Widdifield ◽

J. Michael Paterson ◽

Alexander Kopp ◽

Chenthila Nagamuthu ◽

...

Keyword(s):

Myasthenia Gravis ◽

Lower Risk ◽

Cox Regression ◽

Large Population ◽

Population Based ◽

Osteoporosis Prevention ◽

Inception Cohort ◽

Hazard Ratios ◽

Multiple Covariates ◽

Region Of Residence

Background: Prednisone is a common treatment for myasthenia gravis (MG), and osteoporosis is a known potential risk of chronic prednisone therapy. Objective: Our aim was to evaluate the risk of serious fractures in a population-based cohort of MG patients. Methods: An inception cohort of patients with MG was identified from administrative health data in Ontario, Canada between April 1, 2002 and December 31, 2015. For each MG patient, we matched 4 general population comparators based on age, sex, and region of residence. Fractures were identified through emergency department and hospitalization data. Crude overall rates and sex-specific rates of fractures were calculated for the MG and comparator groups, as well as rates of specific fractures. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. Results: Among 3,823 incident MG patients (followed for a mean of 5 years), 188 (4.9%) experienced a fracture compared with 741 (4.8%) fractures amongst 15,292 matched comparators. Crude fracture rates were not different between the MG cohort and matched comparators (8.71 vs. 7.98 per 1000 patient years), overall and in men and women separately. After controlling for multiple covariates, MG patients had a significantly lower risk of fracture than comparators (HR 0.74, 95% CI 0.63–0.88). Conclusions: In this large, population-based cohort of incident MG patients, MG patients were at lower risk of a major fracture than comparators. The reasons for this finding are unclear but may highlight the importance osteoporosis prevention.

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Predictive value of small dense low-density lipoprotein cholesterol for cardiovascular events in Chinese elder diabetes mellitus patients

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00667-y ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Li Xu ◽

Xu Chen ◽

Jingfen Lu ◽

Yan Xu ◽

Honglin Yang ◽

...

Keyword(s):

Predictive Value ◽

Cardiovascular Events ◽

Cox Regression ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Type 2 Dm

Abstract Background As a subcomponent of low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C) has been suggested to be a better predictor of cardiovascular diseases (CVD). The aim of this research was to evaluate the predictive value of the sdLDL-C in cardiovascular events (CVs) in Chinese elderly patients with type 2 diabetes mellitus (DM). Methods A total of 386 consecutive type 2 DM patients were included into this study during December 2014 to December 2016. The serum sdLDL-C level of each subject was measured by homogeneous method. During a period of 48-month’s follow-up, the occurrence of CVs and associated clinical information were recorded. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serum sdLDL-C to occurrence of major CVs. Results A total of 92 CVs occurred during the study period. The ROC curve analysis manifested that sdLDL-C in the study population had a matchable discriminatory power (AUC for sdLDL-C was 0.7366, P = 0.003). In addition, Kaplan-Meier event-free survival curves displayed an obvious increase of CVs risk for sdLDL‐C ≧ 26 mg/dL (log-rank = 9.10, P = 0.003). This phenomenon had analogous results in patients who received statins at baseline (log rank = 7.336, P = 0.007). Cox regression analysis revealed that the increase in HbA1c, glucose, LDL-C, sdLDL-C, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) and the decrease in apolipoprotein AI (ApoAI) were obviously interrelated with heightened CVs risk. Multiple Cox regression demonstrated that the increase of sdLDL-C and hemoglobin A1c (HbA1c) was significantly correlated with CVs. The results of the study indicated that high sdLDL-C level (> 10 mg/dL) was a risk factor for CVs in the multivariate model (HR 1.281, 95% CI 1.225–16.032; P < 0.01). Conclusion sdLDL-C level could be an effective predictor in predicting the future CVs for Chinese elderly patients with type 2 DM and dyslipidemia.

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Associations of observational and genetically determined caffeine intake with coronary artery disease and diabetes

European Heart Journal ◽

10.1093/ehjci/ehaa946.1493 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Said ◽

Y.J Van De Vegte ◽

N Verweij ◽

P Van Der Harst

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Mendelian Randomization ◽

Cox Regression ◽

Caffeine Intake ◽

Uk Biobank ◽

Genome Wide ◽

Artery Disease ◽

Genetically Determined

Abstract Background Caffeine is the most widely consumed psychostimulant and is associated with lower risk of coronary artery disease (CAD) and type 2 diabetes (T2D). However, whether these associations are causal remains unknown. Objectives This study aimed to identify genetic variants associated with caffeine intake, and to investigate possible causal links between genetically determined caffeine intake and CAD or T2D. Additionally, we aimed to replicate previous observational findings between caffeine intake and CAD or T2D. Methods Genome wide associated studies (GWAS) were performed on caffeine intake from coffee, tea or both in 407,072 UK Biobank participants. Identified variants were used in a two-sample Mendelian randomization (MR) approach to investigate evidence for causal links between caffeine intake and CAD in CARDIoGRAMplusC4D (60,801 cases; 123,504 controls) or T2D in DIAGRAM (26,676 cases; 132,532 controls). Observational associations were tested within UK Biobank using Cox regression analyses. Results Moderate observational caffeine intakes from coffee or tea were associated with lower risks of CAD or T2D compared to no or high intake, with the lowest risks at intakes of 120–180 mg/day from coffee for CAD (HR=0.77 [95% CI: 0.73–0.82; P<1e-16]), and 300–360 mg/day for T2D (HR=0.76 [95% CI: 0.67–0.86]; P=1.57e-5). GWAS identified 51 novel genetic loci associated with caffeine intake, enriched for central nervous system genes. In contrast to observational analyses, MR analyses in CARDIoGRAMplusC4D and DIAGRAM yielded no evidence for causal links between caffeine intake and the development of CAD or T2D. Conclusions MR analyses indicate caffeine intake might not protect against CAD or T2D, despite protective associations in observational analyses. Manhattan_plot_CaffeineIntake Funding Acknowledgement Type of funding source: None

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Association of Dyskalemias with Ischemic Stroke in Advanced Chronic Kidney Disease Patients Transitioning to Dialysis

American Journal of Nephrology ◽

10.1159/000516902 ◽

2021 ◽

pp. 1-9

Author(s):

Ankur A. Dashputre ◽

Keiichi Sumida ◽

Fridtjof Thomas ◽

Justin Gatwood ◽

Oguz Akbilgic ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Ischemic Stroke ◽

Kidney Disease ◽

Lower Risk ◽

Chronic Exposure ◽

Cox Regression ◽

Acute Exposure ◽

Continuous Exposure ◽

Advanced Chronic Kidney Disease

Introduction: Hypo- and hyperkalemia are associated with a higher risk of ischemic stroke. However, this association has not been examined in an advanced chronic kidney disease (CKD) population. Methods: From among 102,477 US veterans transitioning to dialysis between 2007 and 2015, 21,357 patients with 2 pre-dialysis outpatient estimated glomerular filtration rates <30 mL/min/1.73 m2 90–365 days apart and at least 1 potassium (K) each in the baseline and follow-up period were identified. We separately examined the association of both baseline time-averaged K (chronic exposure) and time-updated K (acute exposure) treated as categorized (hypokalemia [K <3.5 mEq/L] and hyperkalemia [K >5.5 mEq/L] vs. referent [3.5–5.5 mEq/L]) and continuous exposure with time to the first ischemic stroke event prior to dialysis initiation using multivariable-adjusted Cox regression models. Results: A total of 2,638 (12.4%) ischemic stroke events (crude event rate 41.9 per 1,000 patient years; 95% confidence interval [CI] 40.4–43.6) over a median (Q1–Q3) follow-up time of 2.56 (1.59–3.89) years were observed. The baseline time-averaged K category of hypokalemia (adjusted hazard ratio [aHR], 95% CI: 1.35, 1.01–1.81) was marginally associated with a significantly higher risk of ischemic stroke. However, time-updated hyperkalemia was associated with a significantly lower risk of ischemic stroke (aHR, 95% CI: 0.82, 0.68–0.98). The exposure-outcome relationship remained consistent when using continuous K levels for both the exposures. Discussion/Conclusion: In patients with advanced CKD, hypokalemia (chronic exposure) was associated with a higher risk of ischemic stroke, whereas hyperkalemia (acute exposure) was associated with a lower risk of ischemic stroke. Further studies in this population are needed to explore the mechanisms underlying these associations.

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