Average Successive Variability Research Articles

Impact of visit-to-visit fasting plasma glucose variability on the development of diabetes: The mediation by insulin resistance.

BackgroundLittle is known about the risk of diabetes due to higher glycemic variability and the underlying mechanisms. We aimed to examine the association of visit‐to‐visit variability (VVV) in fasting plasma glucose (FPG) with incident diabetes in Chinese adults and whether the association was mediated by changes in insulin resistance (IR).MethodsWe included 1856 community residents without a history of diabetes and having attended 3 examinations in 2008, 2009, and 2013 respectively. The SD, the average successive variability (ASV), the coefficient of variation (CV), and the variability independent of the mean (VIM) of three recorded FPG measurements were calculated for each participant, and SD, ASV, CV, and VIM were used as a measure of VVV in FPG. Incident diabetes was defined according to the 1999 World Health Organization criteria. IR was evaluated using the homeostatic model assessment (HOMA).ResultsA total of 153 (8.2%) participants developed incident diabetes at the third visit. Compared with the lowest tertile (0–5.83 mg/dl) of FPG‐SD, the highest tertile (9.55–74.17 mg/dl) was associated with a 148% increased risk of diabetes (odds ratio [OR], 2.48; 95% confidence interval [CI], 1.36–4.49), after adjustment for covariates including mean FPG at 3 visits. Mediation analyses suggested that changes in IR (ΔHOMA‐IR) might mediate 17.3% of the association between increased FPG‐SD and elevated diabetes risk. Similar results were found for FPG‐CV, FPG‐ASV, and FPG‐VIM.ConclusionsThe VVV in FPG was significantly associated with risks of diabetes in Chinese adults, which was partially mediated by changes in IR.

The Effect of Total Cholesterol Variability on Clinical Outcomes After Percutaneous Coronary Intervention.

AimExploring the risk factors of prognosis in patients undergoing percutaneous coronary intervention (PCI) is of great importance. Our aim of the study is to investigate the association between variability in total cholesterol (TC) level and major adverse cardiovascular and cerebrovascular events (MACCE) in patients after PCI.MethodsBetween April 2004 and December 2009, 909 patients who underwent primary PCI and with at least three TC values were included in the final study. TC variability was calculated using four indices: standard deviation (SD), coefficient of variation (CV), the average successive variability (ASV), variability independent of the mean (VIM). MACCE comprised all-cause mortality, non-fatal myocardial infarction (MI), unplanned revascularization, hospitalization for heart failure, and non-fatal stroke.ResultsThere were 394 cases of MACCE during the follow-up period. When the subjects were divided into quartile groups by CV of TC, high CV groups were associated with a higher hazard ratio of MACCE than for lower CV groups. In multivariable adjusted models, TC variability and MACCE remained correlated [HR (95% CI): Q2, 1.17 (0.86–1.58); Q3, 1.38 (1.03–1.85); Q4, 1.63 (1.22–2.17)]. Similar patterns of MACCE were noted by quartiles of SD, ASV, and VIM.ConclusionVisit-to-visit TC variability is positively correlated with MACCE in patients after PCI.

Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naïve Korean Population.

Background and AimThere is a growing evidence that fluctuation in lipid profiles is important in cardiovascular outcomes. We aimed to identify single nucleotide polymorphism (SNP) variants associated with low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) variability in statin-naïve Korean subjects and evaluate their associations with coronary atherosclerosis.MethodsIn statin-naïve subjects from Gene-Environment of Interaction and phenotype cohort, we performed genome-wide association studies of lipid variability; the discovery (first) and replication (second) sets included 4,287 and 1,086 subjects, respectively. Coronary artery calcium (CAC) score and degree of coronary artery stenosis were used as outcome measures. Cholesterol variability was determined by standard deviation and average successive variability, and significant coronary atherosclerosis was defined as CAC score ≥400 or coronary stenosis ≥70%.ResultsMean HDL-C and LDL-C level were 54 ± 12 and 123 ± 30 mg/dL in the first set and 53 ± 12 and 126 ± 29 mg/dL in the second set. APOA5 rs662799 and APOA5 rs2266788 were associated with LDL-C variability and PXDNL rs80056520, ALDH2 rs671, HECTD4 rs2074356, and CETP rs2303790 were SNPs associated for HDL-C variability. APOA5 rs662799 passed Bonferroni correction with p-value of 1.789 × 10−9. Among the SNPs associated with cholesterol variability, rs80056520 and rs2266788 variants were associated with CACS ≥400 and coronary stenosis ≥70% and rs662799 variant was associated with coronary stenosis ≥70%.ConclusionTwo SNPs associated with LDL-C variability (APOA5 rs662799 and rs2266788) and one SNP associated with HDL-C variability (PXDNL rs80056520) were significantly associated with advanced coronary artery stenosis. Combining GWAS results with imaging parameters, our study may provide a deeper understanding of underlying pathogenic basis of the link between lipid variability and coronary atherosclerosis.

Body weight fluctuation is associated with rapid kidney function decline.

This study aimed to evaluate the effects of body weight fluctuations on kidney function deterioration in a prospective cohort of individuals with normal kidney function. Data were obtained from the Korean Genome and Epidemiology Study. Body weight fluctuations were determined using average successive variability (ASV), which was defined as the average absolute body weight change using repeated measurements for all participants. The decline of the estimated glomerular filtration rate (eGFR) over time was calculated using linear regression analysis of serial eGFR measurements for each patient. Rapid eGFR decline was defined as an average eGFR decline > 3 mL/min/1.73 m2 per year. A total of 6,790 participants were analyzed. During a median follow-up of 11.7 years, rapid eGFR decline was observed in 913 (13.4%) participants. When the participants were categorized into tertiles according to ASV, rapid eGFR decline was more prevalent in the highest ASV tertile group than in the lowest. Analyses using multiple logistic regression models revealed that the risk of rapid eGFR decline was increased in the highest ASV tertile group compared with the lowest (odds ratio: 1.66). Body weight fluctuations were significantly associated with an increased risk of rapid kidney function decline in participants with normal kidney function.

Uric Acid Variability as a Predictive Marker of Newly Developed Cardiovascular Events in Type 2 Diabetes.

Background: Cardiovascular disease (CVD) is associated with morbidity and mortality in patients with type 2 diabetes mellitus (T2D). However, the role of serum uric acid as a risk factor for developing cardiovascular disease is controversial. This study investigated whether uric acid variability was associated with new-onset symptomatic CVD in patients with T2D, requiring percutaneous coronary intervention.Methods: A total of 1,071 patients were enrolled in this retrospective cross-sectional study after propensity score matching. Patients with T2D and new-onset symptomatic CVD who received percutaneous coronary intervention for the first time, and with at least three consecutive 6-monthly measurements of serum uric acid were recruited from Severance Hospital between January 2015 and December 2019. Uric acid variability was measured by average successive variability (ASV) and analyzed to evaluate a possible correlation with the risk of developing CVD.Results: The patients were divided into quartiles based on the uric acid variability. Patients in the highest quartile were older and presented lower renal function and a higher mortality from CVD. There was a linear association between a high uric acid variability and the development of CVD. Compared to the lowest quartile, patients in the higher quartiles had a higher risk of CVD [quartile 3: adjusted odds ratio (aOR) = 1.76; 95% confidence interval (CI), 1.20–2.82; P = 0.019; quartile 4 aOR = 2.89; 95% CI, 1.74–4.80; P < 0.001].Conclusion: High uric acid variability is independently associated with an increased risk of new-onset symptomatic CVD requiring percutaneous coronary intervention in patients with T2D. Thus, maintaining serum uric acid in a narrow range by prescribing effective medications is essential to prevent new-onset CVD in patients with T2D. Nonetheless, the potential use of uric acid variability as a predictive marker of CVD in patients with T2D needs further validation.

Long-Term Glycemic Variability Is Associated With Arterial Stiffness in Chinese Adults.

ObjectiveThe aim of the study was to investigate the association between the visit-to-visit variability (VVV) of fasting plasma glucose (FPG) and arterial stiffness in Chinese adults.MethodsWe performed a cohort study involving 2002 Chinese adults with no history of myocardial infarction or stroke. All the participants attended three visits (the baseline visit in 2008, the 2nd visit in 2009 and the 3rd visit in 2013). We used four measures to define the VVV of FPG across the three visits: the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV) and the variability independent of the mean (VIM). We used brachial-ankle pulse wave velocity (ba-PWV) to measure arterial stiffness at the 2nd and the 3rd visits.ResultsCompared with the lowest tertile of all the four measurements of VVV of FPG, significantly increased levels of ba-PWV change, ratio of ba-PWV change and the occurrence of the elevated ba-PWV were found in the highest tertile. The odds ratio (OR) and 95% confidence interval (CI) comparing participants in the highest tertile vs. the lowest tertile of FPG-SD was 1.37 (1.01-1.86) for risks of having elevated ba-PWV, even after adjustment for covariates including the mean FPG. Similar results were found for FPG-CV and FPG-VIM.ConclusionGreater long-term variability of FPG was associated with an increased risk of arterial stiffness, suggesting that the VVV of FPG could be used for an early detection of subclinical atherosclerosis.

Increased Risk of Nonalcoholic Fatty Liver Disease in Individuals with High Weight Variability.

BackgroundWeight loss through lifestyle modification is recommended for patients with nonalcoholic fatty liver disease (NAFLD). Recent studies have suggested that repeated loss and gain of weight is associated with worse health outcomes. This study aimed to examine the association between weight variability and the risk of NAFLD in patients without diabetes.MethodsWe examined the health-checkup data of 30,708 participants who had undergone serial examinations between 2010 and 2014. Weight variability was assessed using coefficient of variation and the average successive variability of weight (ASVW), which was defined as the sum of absolute weight changes between successive years over the 5-year period divided by 4. The participants were classified according to the baseline body mass index and weight difference over 4 years.ResultsOn dividing the participants into four groups according to ASVW quartile groups, those in the highest quartile showed a significantly increased risk of NAFLD compared to those in the lowest quartile (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.63 to 2.19). Among participants without obesity at baseline, individuals with high ASVW showed increased risk of NAFLD (OR, 1.80; 95% CI, 1.61 to 2.01). Participants with increased weight over 4 years and high ASVW demonstrated higher risk of NAFLD compared to those with stable weight and low ASVW (OR, 4.87; 95% CI, 4.29 to 5.53).ConclusionRegardless of participant baseline obesity status, high weight variability was associated with an increased risk of developing NAFLD. Our results suggest that further effort is required to minimize weight fluctuations after achieving a desirable body weight.

Glycemic variability and the risk of nonalcoholic fatty liver disease : A nationwide population-based cohort study

AimAlthough few recent studies have reported the association between the glycemic variability and the development of type 2 diabetes mellitus and cardiovascular disease in individuals without diabetes mellitus, the impact of the long-term variability in fasting plasma glucose (FPG) levels on the incident nonalcoholic fatty liver disease (NAFLD) has not been evaluated. MethodsThe study included 57,636 Korean men and women without NAFLD and diabetes mellitus from the Korean National Health Insurance System cohort. FPG variability was calculated using the coefficient of variation (FPG-CV), standard deviation (FPG-SD), variability independent of the mean (FPG-VIM), and average successive variability (FPG-ASV). ResultsThe cumulative incidence of NAFLD demonstrated progressively increasing trends according to the higher quartiles of FPG variability in Kaplan-Meier curves. A multivariable Cox proportional hazard analysis revealed that the hazard ratio for incident NAFLD was 1.15 (95% confidence interval, 1.06–1.24) in the highest quartile of FPG-CV compared with the lowest quartile of FPG-CV after adjusting for various confounding factors, including mean FPG levels. When using FPG-SD, FPG-VIM, and FPG-ASV, the results were similar. The 10-unit increase in FPG variability was associated with a 14% increased risk of NAFLD in the fully adjusted model. Moreover, this effect remained consistent in the subgroup and sensitivity analyses. ConclusionIncreased long-term FPG variability is associated with the development of NAFLD, independent of confounding risk variables including mean FPG levels.

Association of Body-Weight Fluctuation With Outcomes in Heart Failure With Preserved Ejection Fraction.

Aims: To investigate the relationship between body-weight fluctuation and risks of clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF).Methods and Results:We measured intra-individual variations in body weight from baseline and follow-up visits in 1,691 participants with HFpEF from the Americas from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. The primary endpoint was any cardiovascular events (a composite of death from cardiovascular disease, non-fatal myocardial infarction, aborted cardiac arrest, or hospitalization for HF). The body-weight fluctuation was measured according to average successive variability and high variability was defined as greater than or equal to the median. After adjustment for risk factors, mean body weight and weight change, each increase of 1 standard deviation in body-weight variability was significantly associated with increased risks of any cardiovascular events (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.15–1.33, P < 0.001). Patients with high variability had a 47% increased risk of any cardiovascular events and 27% increased risk of all-cause death compared with those with low variability. Such association was similar among patients with New York Heart Association functional class I/II vs. III/IV, obesity vs. non-obesity, and weight loss, gain vs. stability (the P-values for interaction were all insignificant).Conclusion: Among patients with HFpEF, body-weight fluctuation was associated with increased risks of cardiovascular events independent of traditional cardiovascular risk factors, and regardless of HF severity, baseline weight or weight change direction.Clinical Trial Registration: Aldosterone antagonist therapy for adults with heart failure and preserved systolic function (TOPCAT), https://clinicaltrials.gov, identifier [NCT00094302].

Increased Visit-to-Visit Liver Enzyme Variability Is Associated with Incident Diabetes: A Community-Based 12-Year Prospective Cohort Study.

BackgroundFatty liver and/or increased liver enzyme values have been reported to be associated with incident diabetes. We sought to determine whether increased visit-to-visit liver enzyme variability is associated with incident diabetes.MethodsStudy participants were recruited from the Korean Genome and Epidemiologic Study (KoGES). A total of 4,151 people aged 40 to 69 years was recruited and tested every 2 years for up to 12 years. Visit-to-visit aspartate aminotransferase (AST) and alanine aminotransferase (ALT) variability was evaluated in first the 6-year period through the use of various variability measurements: standard deviation (SD), average successive variability, coefficient of variation (CV), and variation independent of mean (VIM). Oral glucose tolerance test was performed at every visit.ResultsDuring the 6-year follow-up appointments, 13.0% (538/4,151) of people developed incident diabetes. Visit-to-visit AST variability was associated with an increased risk of diabetes independent of conventional risk factors for diabetes (hazard ratio per 1-SD increment [95% confidence interval]: 1.06 [1.00 to 1.11], 1.12 [1.04 to 1.21], and 1.13 [1.04 to 1.22] for SD, CV, and VIM, respectively; all P<0.05); however, no such associations were observed in the visit-to-visit ALT variability. According to alcohol consumption status, both AST and ALT variability were independent predictors for incident diabetes in subjects with heavy alcohol consumption; however, neither AST nor ALT variability was associated with diabetes risk in subjects who did not drink alcohol heavily.ConclusionVisit-to-visit liver enzyme variability is an independent predictor of incident diabetes. Such association was more evident in those who consumed significant amounts of alcohol.

Body mass index trajectories and the risk for Alzheimer\u2019s disease among older adults

The effect of body mass index (BMI) changes and variability on the risk for Alzheimer’s disease (AD) remains unclear. We analyzed 45,076 participants, whose BMI were measured on phase 1 (2002–2003), phase 2 (2004–2005), and phase 3 (2006–2007), of the Korean National Health Insurance Service-Health Screening Cohort. We evaluated the effect of 2- and 4-year BMI changes and BMI variability on the risk of AD using Cox regression models. In men, association between 2-year BMI changes, BMI variability, and the risk of AD was not significant. Risk of AD was higher in men whose BMI had decreased 10.1–15.0% over 4 years. In women, aHRs and 95% CIs for AD were 1.14 (1.02–1.29), 1.44 (1.17–1.79), and 1.51 (1.09–2.09) when 2-year BMI loss was 5.1–10.0%, 10.1–15.0%, and > 15.0%. The HRs for AD in women significantly increased when 4-year BMI loss was > 5.0%. The aHR and 95% CI for AD was 1.31 (1.17–1.46) in the 4th quartile of average successive variability (ASV) compared with the 1st quartile of ASV in women. BMI loss over 2- and 4-year period was associated with increased risk for AD, and risk increased in women with higher BMI variability. Appropriate body weight management is recommended to prevent AD.

Visit-to-visit blood pressure variability is associated with arterial stiffness in Chinese adults: A prospective analysis.

Blood pressure (BP) variability may have its effect on the development of vascular disease. The authors aimed to examine the association between the visit‐to‐visit variability (VVV) of BP and arterial stiffness in Chinese adults. The authors included 1407 participants from a prospective cohort study of community residents who were ≥40 years, without a history of myocardial infarction or stroke, and with data at the baseline, the second and the third visits in 2008, 2009, and 2013. The VVV of BP was defined as the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV), and the variability independent of the mean (VIM) in BP levels at the 3 visits. Arterial stiffness was measured by brachial‐ankle pulse wave velocity (ba‐PWV) at the 2nd and the 3rd visits. Levels of ba‐PWV change and the occurrence of an elevated ba‐PWV increased significantly in the highest tertile of VVV measures of systolic BP (SBP) and pulse pressure (PP) compared with the lowest tertile, respectively. The multivariable regression analysis revealed that VVV measures of SBP and PP were significantly associated with levels of ba‐PWV change and the risks of developing an elevated ba‐PWV. The odds ratios (ORs) and 95% confidence intervals (CIs) for the risk were 2.12 (1.57–3.12) and 1.92 (1.38–2.68) in participants with the highest versus the lowest tertile of SBP‐SD and PP‐SD, respectively. No significant association was found for diastolic BP variability measures. The increased long‐term variabilities of SBP and PP were associated with an increased risk of arterial stiffness.

Association of Visit-to-Visit Variability in Kidney Function and Serum Electrolyte Indexes With Risk of Adverse Clinical Outcomes Among Patients With Heart Failure With Preserved Ejection Fraction

Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear. To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF. This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020. Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models. Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44). In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.

Abstract 13571: Association Between Pre-kidney Transplantation Medial Arterial Calcification Andpost-transplant Visit-to-visit Blood Pressure Variability: A Propensity Score Matching Analysis

Introduction: Arterial calcification is associated with vascular stiffness, which manifests with visit-to-visit blood pressure variability (VVBPV). Although media arterial calcification (MAC) is significantly associated with poor cardiovascular outcomes in kidney patients, the association in kidney transplant (KT) patients is unknown. Hypothesis: We hypothesize that MAC is associated with VVBPV in long-tern post-KT. Methods: Since MAC, which is detected from mammogram (MG) and determined by linear calcified breast arteries, is exclusively medial, female KT patients with ≥1 MG during pre-KT period were included in this study. VVBPV was examined by average successive variability (ASV), which is the average absolute difference between successive BP measured at 4, 12, 24, 36, and 48 weeks post-KT. After balancing patients with and without MAC by using propensity score matching based on age, diabetes, and obesity status, the association between MAC and systolic and diastolic VVBPV (VVSBPV and VVDBPV) at 48 weeks post-KT was tested by multiple linear regression (Figure1A&amp;1B). Results: Of 51 patients, mean age±SD is 54±12 years, 21 had diabetes, and 21 were obese. Mean duration of follow-up was 47±9 years. Among 20 patients with MAC, mean VVSBPV was 20±14 mmHg; whereas, VVSBPV in non-MG group was 14±8 mmHg (mean difference -6± 3.0, p 0.06, 95%CI -12.03, 0.15). Mean VVDBPV in MG and non-MG groups were 12±5 and 11±5.6 mmHg, respectively (mean difference -1±1.6, p 0.41, 95%CI -4.44, 1.86). Laboratory-related bone and mineral metabolism were not different between both groups. On average, MG group had 8 mmHg higher VVSBPV compared to non-MG group (Coef. 3.62, p 0.02, 95%CI 1.16, 15.34). The MG group remained having higher VVDBPV but the magnitude of the association decreased and no statistical significance (Coef. 0.58, p 0.83, 95%CI -4.58, 5.73). Conclusions: Similar to non-transplant patients, KT recipients with pre-KT MAC had significant higher VVSBPV at the late post-KT.

Prognostic impact of renal function trajectories and temporal variability amongst anticoagulated atrial fibrillation patients: a subgroup analysis of the SPORTIF III and V trials

Abstract Background Renal function is a major determinant of major adverse outcomes in patients with atrial fibrillation (AF). Scarce data are available about the impact of renal function trajectories and creatinine clearance (CrCl) temporal variability, on prognosis. Aim To evaluate the progression and impact of renal function impairment and variability on outcomes over a long-term follow-up observation in a cohort of anticoagulated AF patients. Methods We included warfarin-treated AF patients in SPORTIF trials with available creatinine clearance (according to Cockroft-Gault) at baseline and at least 4 evaluations throughout their follow-up. Patients with a BMI ≥45 kg/m2 were excluded from the analysis. Average successive variability (ASV) was used as measure of variability. Results Among 3665 original patients, 3366 (91.8%) were included in this analysis. Median [IQR] CHA2DS2-VASc score was 3 [2–4] and HAS-BLED was 3 [2–4]. At baseline, 876 (26.0%) patients had CKD (CrCl &amp;lt;60 mL/min), with 14 (0.4%) patients having severe CKD (&amp;lt;30 mL/min), with a mean (SD) CrCl of 86.7 (47.4) mL/min. Over a mean (SD) 577.1 (122.1) days of follow-up, a total of 521 new CKD cases were found with an overall incidence of 13.1 per 100 patient-years, with 91 new severe CKD cases (1.71 per 100 patient-years). Across follow-up, prevalence of CKD and severe CKD increased progressively (both p&amp;lt;0.001) [Figure]. Mean (SD) AVS was −0.567 (±2.803) mL/min. According to AVS, patients were divided into quartiles: i) Q1: +34.012/+0.450; ii) Q2: +0.449/−0.443; iii) Q3: −0.443/−1.503; Q4: −1.505/−19.750. While no difference was found in stroke/systemic embolism, rate of major bleeding was higher in Q4 (4.5%) and Q1 (4.0%) than in other quartiles (Q2 2.5%, Q3 2.0%; p=0.009) as well as all-cause death (Q4: 6.7%; p=0.003 compared to other quartiles). A Cox multivariate adjusted model documented that AVS Q1 and Q4 were independently associated with a higher risk of major bleeding, while Q4 was associated with a higher risk of all-cause death (Table). Conclusion In a cohort of AF patients treated with warfarin, characterized by a progressive increase in the proportion with CKD and severe CKD, the largest reduction in CrCl throughout follow-up was associated to an increased risk of major bleeding and all-cause death. Renal Function Trajectories Funding Acknowledgement Type of funding source: None

Prognostic value of long-term gamma-glutamyl transferase variability in individuals with diabetes: a nationwide population-based study

We examined whether long-term gamma-glutamyl transferase (GGT) variability can predict cardiovascular disease (CVD) and mortality in individuals with diabetes. We included 698,937 Koreans diabetes patients older than 40 years without histories of CVD, chronic liver disease, or heavy alcoholics who received health exams supported by the Korean government more than once in 2009–2012 (baseline). We used Cox proportional analyses to estimate the risk of stroke, myocardial infarction (MI), and all-cause mortality until December 31, 2016, according to the quartiles of the average successive variability (ASV) of GGT measured during the five years before the baseline. A total 26,119, 15,103, and 39,982 cases of stroke, MI, and death, respectively, were found. GGT ASV quartile 4 had a significantly higher risk of stroke and all-cause mortality than quartile 1, with adjustment for risk factors, such as baseline glucose and GGT level, and comorbidities. Hazard ratios (95% confidence intervals) for GGT ASV quartile 4 were 1.06 (1.03–1.10) and 1.23 (1.20–1.27) for stroke and mortality, respectively. This significant association was shown consistently across the baseline GGT quartiles. GGT variability was related to the risk of stroke and all-cause mortality. The effect was most pronounced in all-cause mortality, irrespective of baseline GGT level.

Abstract P037: Association Between Early Post-kidney Transplant Visit-to-Visit Systolic Blood Pressure Variability And Late Post-Transplant Systolic Blood Pressure

Background: Visit-to-visit blood pressure variability (VVBPV) results from regional or systemic circulatory factors such as stiffness or neuro-hormonal factors. Association between VVBPV and long-term post-kidney transplant (KT) blood pressure (BP) is unknown. Method: VVBPV was measured by average successive variability (ASV), which is the average absolute difference between successive BP measured at 4, 12, and 24 weeks post-KT. Association between the VVBPV and BP at 48 weeks post-KT was examined by multiple linear regression. Results: Of all 105 KT recipients, mean age±SD was 54±12 years and 64 patients (61%) was female. Mean ASV of SBP and DBP were 16±12 mmHg (range 1-58) and 11±6.3 mmHg (range 1-29.5), respectively. Mean SBP at 24 and 48 weeks post-KT were 135±19 and 133±16 mmHg, respectively. Similar to SBP, mean DBP at 24 weeks post-KT was higher than DBP at 48 weeks (DBP 24 vs 48 weeks 80±12 vs 77±11 mmHg). Every 10-mmHg increase in ASV of SBP predicts 3.4 mmHg increase in SBP at 48 weeks post-KT (p 0.01; 95%CI 0.83, 6.14; Figure 1A). However, an increase in 10 mmHg of ASV of DBP predicts a decrease in DBP of 0.12 mmHg (p 0.12, 95%CI -0.28, 0.04; Figure 1B). After adjusted for age, gender, donor type (deceased vs living), induction immunosuppressive medications, pre-KT weight-spline interaction term at 70 kg, every 10 mmHg increase in ASV of SBP was significantly associated with 2.7 mmHg increase in SBP at 48 weeks post-KT (p 0.04, 95%CI 0.15, 5.29); whereas, 10 mmHg increase in ASV of DBP predicts a decrease in DBP of 2.13 mmHg with no statistical significance (p 0.16, 95% -5.14, 0.88) Conclusion: Higher VVSBPV during early post-KT predicts a higher SBP, but not DBP, at late post-KT period.

Fasting Plasma Glucose Variability and Gastric Cancer Risk in Individuals Without Diabetes Mellitus: A Nationwide Population-Based Cohort Study.

INTRODUCTION:Long-term glycemic variability is associated with various adverse health outcomes in patients with diabetes mellitus (DM). However, the relationship between glycemic variability and gastric cancer remains unclear. We aimed to investigate the association between glycemic variability and gastric cancer incidence in individuals without DM.METHODS:We used the Korean National Health Insurance Service data sets of claims and health checkups and included 202,562 individuals without DM. Fasting plasma glucose (FPG) variability was measured using the variability independent of the mean (VIM), coefficient of variation, SD, and average successive variability. The association between FPG variability and gastric cancer incidence was analyzed using Cox regression adjusting for age, sex, body mass index, smoking status, alcohol consumption, regular exercise, income level, family history of cancer, mean FPG level, and number/mean interval of FPG measurements.RESULTS:In total, 1,920 patients developed gastric cancer (0.95%) within a median follow-up of 5.6 (5.3, 6.4) years. The fully adjusted hazard ratio and 95% confidence interval for gastric cancer were 1.26 and 1.18–1.34, respectively, in the highest quartile of FPG variability assessed by VIM compared with that in the lowest quartile. Similar results were obtained in the normal and impaired fasting glucose groups and when using the variability indexes, including coefficient of variation, SD, and average successive variability. There was a sequential increase in the incidence of gastric cancer according to the increase in the deciles of FPG variability (P for linear trend <0.001). A 1-SD increase in FPG variability assessed by VIM was significantly associated with a 10.0% increase in gastric cancer risk in the fully adjusted model.DISCUSSION:In a DM-free population, high variability in visit-to-visit FPG levels was independently associated with an increased risk of gastric cancer.

Gamma-glutamyl transferase variability can predict the development of end-stage of renal disease: a nationwide population-based study

The aim of this study is to investigate whether GGT variability is able to predict the risk of end-stage renal disease (ESRD). The study subjects were Koreans who conducted health exams supported by the Korean National Health Insurance Corporation during 2009–2012 (baseline). After excluding individuals aged < 40 years, heavy alcoholics, or those with histories of chronic liver disease or ESRD, we followed 6,058,995 individuals. We calculated the average successive variability (ASV) of GGT values during the 5 years before the baseline as a parameter of variability. Using Cox proportional analyses, we evaluated the risk of ESRD according to GGT ASV quartiles, defined as the initiation of renal replacement therapy or kidney transplantation, or December 31, 2016. During 38,663,279.3 person-years of follow-up, 12,057 cases of ESRD were identified. Compared with GGT ASV quartile 1, the risk of ESRD was higher in ASV quartiles 3–4 and increased serially, even after adjustment for several metabolic parameters, baseline renal function, presence of comorbidities, low income, and baseline GGT and hemoglobin level. The fully adjusted hazard ratios (95% confidence intervals) of GGT ASV quartiles 3 and 4 were 1.06 (1.01–1.12) and 1.12 (1.06–1.18), respectively. In conclusion, GGT variability is a putative risk factor for ESRD in Koreans.

Association of Long-term Change and Variability in Glycemia With Risk of Incident Heart Failure Among Patients With Type 2 Diabetes: A Secondary Analysis of the ACCORD Trial.

To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM). Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF. The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08-1.75] and for ≥10% increase 1.55 [1.19-2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17-1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability. Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.