Variability Independent Of The Mean Research Articles

Age-specific association between visit-to-visit blood pressure variability and hearing loss: A population-based cohort study

Abstract Background and Objectives Hearing loss is common and undertreated, and the impact of blood pressure variability (BPV) on the development of hearing loss remains unclear. We aimed to examine the age-specific association between visit-to-visit BPV and hearing loss. Research Design and Methods This nationally representative cohort study included 3939 adults over 50 years from the Health and Retirement Study in the US. Variabilities of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were assessed by standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM), using SBP and DBP from three visits. Hearing loss was assessed by self-rated questions. Cox proportional risk models were used to evaluate age-specific associations (50-64, 65-79 and ≥80 years) between BPV and hearing loss. The generalized additive Cox models were further used to visualize the combined effect of age and BPV. Results During the follow-up up to 7.0 years, 700 participants developed hearing loss. Among people aged under 65 years, we observed a 36% increased risk of hearing loss with per SD increment in VIM of SBP (HR per SD 1.36, 95% CI 1.13-1.63) and a slightly significant association between VIM of DBP (HR per SD 1.21, 95% CI 1.01-1.45) and hearing loss. We did not observe significant associations among groups aged over 65 years (P>0.05). The generalized additive Cox models also showed younger participants had stronger associations between BPV and hearing loss. Discussion and Implications Higher visit-to-visit variabilities of SBP were associated with an increased risk of hearing loss in middle-aged adults (50-65 years). Intervention in early BPV may help decrease hearing loss in adults aged over 50 years.

Body Weight Variability and Risk of Suicide Mortality: A Nationwide Population-Based Study

Background. Suicide is a pressing global health concern, and identifying its risk factors is crucial for prevention. Body weight variability (BWV) has been increasingly recognized as a potential factor impacting physical and mental health outcomes. We aimed to explore the relationship between BWV and the risk of suicide mortality using a nationally representative database. Methods. This population-based cohort study used data from the Korean National Health Insurance Database and included a total of 1,983,701 subjects. BWV was assessed using at least three health examination datasets and validated variability indices (variability independent of the mean (VIM), average successive variability, and coefficient of variation), and patients were divided into BWV quartiles (Q1–Q4). The primary endpoint was suicide-related death. Results. During a median of 11.3 years of follow-up, 5,883 suicide deaths occurred. A higher baseline body weight was associated with a lower risk of suicide. However, greater BWV (VIM) was associated with a significantly greater risk of suicide (adjusted hazard ratio [95% confidence interval], 1.35 [1.26–1.45] in the Q4 group), even after adjusting for baseline body mass index (BMI). Similar results were observed regardless of obesity or BMI category. Consistent findings were observed when using different variability indices. Subgroup analyses according to sex, age, diabetes, and depression also supported these findings. Conclusion. Our study highlights the importance of considering BWV as a potential risk factor for suicide.

Association of midlife body-weight variability and cycles with earlier dementia onset: a nationwide cohort study

BackgroundGiven the rising awareness of health-related lifestyle modifications, the impact of changes in body weight (BW) on cognitive function and dementia generates significant concern. This study aimed to investigate the association between BW changes and dementia in a middle-aged Korean population.MethodsA retrospective, population-based longitudinal study was conducted utilizing data from the National Health Insurance Service (NHIS) database. Participants aged 40 years or older in 2011 who underwent at least five health checkups between 2002 and 2011 were followed-up for dementia until 2020. A total of 3,635,988 dementia-free Korean aged < 65 at baseline were examined. We analyzed the association between BW variability independent of the mean (VIM) with BW cycle, defined as either an upward or a downward direction of BW, and the risk of incident dementia.ResultsThe results showed an increased risk of dementia in the highest quartile of VIM quartile (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.47–1.58) compared to the lowest quartile of VIM. Additionally, the results showed an even higher increased risk of dementia in the highest BW cycle (≥ 2 cycles of 10% BW = HR 2.00, 95% CI 1.74–1.29). Notably, the combined concept of VIM with BW cycle showed an even higher dementia risk (highest quartile of VIM with ≥ 2 cycles of 10% BW = HR 2.37, 95% CI 2.05–2.74) compared to the baseline group (lowest quartile of VIM with < 3% BW cycle).ConclusionsThe present study highlights the importance of considering BW changes with BW variability along with the BW cycle to assess dementia risk in detail, providing valuable insights for preventive strategies.

Obstructive sleep apnea in relation to beat-to-beat, reading-to-reading, and day-to-day blood pressure variability.

We investigated blood pressure (BP) variability as assessed by beat-to-beat, reading-to-reading and day-to-day BP variability indices in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). In 786 hospitalized hypertensives (mean age, 53.2 years; 42.2% women), we performed 10-min beat-to-beat (n = 705), 24-h ambulatory (n = 779), and 7-day home BP (n = 445) measurements and the full overnight polysomnography. Mild, moderate and severe OSAHS were defined as an apnea-hypopnea index of 5-14, 15-29, and ≥ 30 events per hour, respectively. BP variability indices including variability independent of the mean (VIM), average real variability (ARV), and maximum-minimum difference (MMD), were compared across the OSAHS severity groups. In univariate analysis, beat-to-beat systolic VIM and MMD, reading-to-reading asleep systolic and diastolic ARV and MMD increased from patients without OSAHS, to patients with mild, moderate and severe OSAHS. This increasing trend for beat-to-beat systolic VIM and MMD remained statistically significant after adjustment for confounders (P ≤ 0.047). There was significant (P ≤ 0.039) interaction of the presence and severity of OSAHS with age and body mass index in relation to the beat-to-beat systolic VIM and MMD and with the presence of diabetes mellitus in relation to asleep systolic ARV. The association was stronger in younger (age < 50 years) and obese (body mass index ≥ 28 kg/m²) and diabetic patients. None of the day-to-day BP variability indices reached statistical significance (P ≥ 0.16). BP variability, in terms of beat-to-beat systolic VIM and MMD and asleep reading-to-reading asleep systolic ARV, were higher with the more severe OSAHS, especially in younger and obese and diabetic patients.

Visit-to-visit variability in blood pressure and the risk of open-angle glaucoma in individuals without systemic hypertension: a nationwide population-based cohort study.

We aimed to evaluate the effect of visit-to-visit variability in blood pressure (BP) on the risk of open-angle glaucoma (OAG) in individuals without systemic hypertension using a population-based retrospective cohort study design. The Korean National Health Insurance Service-National Health Screening Cohort database, which collected data of 209,226 individuals between 2002 and 2015, was used to analyze the data of 140,910 eligible participants. The mean follow-up duration was 8.3 years. Visit-to-visit BP variability was assessed using standard deviation (SD), coefficient of variation (CV), and variability independent of the mean (VIM). Participants were categorized into four groups according to BP variability quartiles. We verified the effect of BP variability by comparing participants of the first to third quartiles of BP variability groups with those belonging to the fourth quartile group. A Cox proportional hazards model was used to determine the hazard ratio (HR) of BP variability in cases of newly diagnosed OAG. Moreover, we conducted subgroup analyses using baseline characteristics. In the multivariable analyses, BP variability did not significantly increase the risk of OAG development. However, subgroup analyses revealed significant interactions between age and systolic BP variability in the development of OAG (CV: p = 0.008; SD: p = 0.007). For participants aged <60 years, the risk of OAG development significantly increased with high systolic BP variability (CV: HR, 1.18; 95% confidence interval [CI], 1.00-1.39; p = 0.049). We observed a similar trend using the SD and VIM as the parameters for systolic BP variability. Higher visit-to-visit systolic BP variability was associated with an increased risk of OAG development in participants younger than 60 years of age without systemic hypertension. These results suggest that BP variability can be the considerable factor when assessing the risk of OAG, especially in relatively young people without systemic hypertension.

Association between visit-to-visit lipid variability and risk of ischemic heart disease: a cohort study in China.

To explore the associations between visit-to-visit lipid variability and risk of ischemic heart disease (IHD) in a population-based cohort in China. We evaluated lipid variability in 30,217 individuals from the Yinzhou Health Information System who had ≥3 recorded lipid measurements during 2010-2014. We used various indicators including standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV) to quantify the variability in triglycerides, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, a total of 1305 participants with IHD were identified during the follow-up of 194,421 person-years. Subjects in Q4 had a 21% elevated risk of IHD (HR = 1.21, 95% CI: 1.03-1.41) for LDL-C variability (CV) compared with the reference (Q1). The HRs for Q4 vs Q1 were 1.21 (95% CI: 1.04-1.42) for HDL-C variability, and 1.28 (95% CI: 1.10-1.50) for TC variability. However, no association was observed between triglycerides variability and risk of IHD. Higher variability in LDL-C, HDL-C, and TC levels was associated with an elevated risk of IHD, suggesting that lipid variability could be considered as an independent risk factor of IHD.

Cognitive Decline Associated with Longitudinal Changes in 24‐h Ambulatory Blood Pressure Variability

AbstractBackgroundCognitive decline has been associated with variability in blood pressure (BP). However, whether the increment of the BP variability during follow‐up precedes cognitive decline remains undocumented. We aimed this study to investigate cognitive decline in relation to longitudinal changes in 24‐h reading‐to‐reading BP variability.MethodsWe conducted an observational longitudinal study that included 717 dementia‐free participants from the Maracaibo Aging Study who underwent follow‐up assessment in both 24‐h ambulatory BP monitoring and cognitive tests between 1998 and 2015. Cognitive domains consisted of selective reminding tests (total, long‐term, short‐term, and recognition memory) and the Mini‐Mental State Examination (MMSE). Cognitive decline was a longitudinal decrease in cognitive scores. Participants underwent 24‐h ambulatory BP monitoring between 2‐4 times – with at least one‐year interval. Systolic and diastolic BP variability was studied during 24‐h and divided into daytime (from 06h00 to 23h00), and nighttime (23h00 to 06h00) periods. To account for BP level, we used variability independent of the mean (VIM) to compute systolic and diastolic BP variability. Other measures of BP variability included the nocturnal BP drop in comparison to the daytime BP level, which was estimated as the night‐to‐day ratio. Statistics included multivariate linear regression mixed models.ResultsOverall, the mean age was 65.6±7.36 years old and 66.5% (n = 447) of the participants were women. In mixed models, a decline in all memory domains was associated with greater variability in the 24‐h, daytime, and nighttime systolic BP during follow‐up, with an estimated decline in cognitive scores ranging from ‐0.2 to ‐0.04 points per unit increase in VIM systolic BP during follow‐up (P values ranged from 0.022 to 0.003). Decline in total, short‐term, and MMSE memory domains was associated with greater 24‐h and daytime diastolic BP variability (P≤0.015). A lower night‐to‐day dipping ratio during follow‐up increased the risk of cognitive decline, with a ‐5.8 to ‐1.6 decline in long‐term memory and MMSE scores; respectively (P≤0.037).ConclusionsCognitive decline associates with greater reading‐to‐reading 24‐h BP variability and lower falls in nocturnal BP over time. These findings might be indicative of deteriorated regulatory mechanisms to maintain steady BP levels as individuals age.

The association between HbA1c variability and strokes in patients receiving anticoagulants

Abstract Background Diabetes, higher glycaemic level, is associated with an increased risk of stroke in patients with atrial fibrillation (AF) and is integrated into the CHA2DS2-VASc score for stroke risk prediction. However, the association between glycaemic variability and stroke risk in AF patients remains unclear. Objective To evaluate the association between glycaemic variability and stroke among diabetic and non-diabetic patients with nonvalvular AF receiving anticoagulants. Methods Newly diagnosed AF from 2013-2018 (n=8,790) were divided by their diabetes status. Variability in glycaemic, represented by coefficient of variation (CV) on HbA1c (haemoglobin A1c), was assessed by at least three HbA1c measurements following enrollment to the end of the follow-up period. Participants with ischaemic stroke (IS)/systemic embolism (SE), haemorrhagic stroke (HS) or all-cause mortality at baseline or within 1 year of enrollment were excluded. Multivariate Cox regression was performed to evaluate the association between variability in HbA1c and subsequent incident IS/SE, HS and all-cause mortality. Sensitivity analyses included defining HbA1c variability using average successive variability (ASV) and variability independent of the mean (VIM). Results Diabetes status significantly modified the relationship between HbA1c variability and risk of IS/SE (Pinteraction = 0.36)and all-mortality (Pinteraction &amp;lt;0.01). Greater incidence rates were observed among individuals with diabetes, compared to those without diabetes (3.74 vs. 2.41 for IS/SE, 0.54 vs. 0.33 for HS and 4.89 vs. 2.42 for all-cause mortality per 100 person years). Among those with diabetes, greater HbA1c variability was significantly associated with increased risk of IS/SE (hazard ratio [HR] = 1.21, 95% confidence interval [CI]: 1.11-1.31), all-cause mortality (HR = 1.13, 95%CI: 1.05-1.20) and HS (HR = 1.10, 95%CI: 1.02-1.23). Similar patterns were found in individuals without diabetes (IS/SE: HR = 1.28, 95%CI: 1.08-1.52; all-cause mortality: HR = 1.50, 95%CI: 1.29-1.75). However, no significant association was observed between glycemia variability and HS among those without diabetes. Results were consistent with alternative measures of HbA1c variability. Conclusion Variability in HbA1c was independently associated with the risk of IS/SE and all-cause mortality among patients with AF, regardless of diabetes status.

Abstract 14567: Lipid Variability as a Risk Factor of Major Adverse Cardiovascular Outcomes. Meta-Analysis of Observational Studies

Introduction: Serum lipids variability has been described as a risk factor for cardiovascular disease. However, there is no published systematic review in the literature at the moment. The purpose is to evaluate the association between lipid variability and outcomes related to cardiovascular disease. Methods: We made a systematic search in Pubmed, Science Direct, Clinical Key, CINAHL, Lilacs, and Google Scholar using: lipids, variability, death, stroke, myocardial infarction, and cholesterol variability as keywords. Two independent researchers selected and made an extraction of the data. Non-agreement was solved by a third researcher. Non-language limitations were made. Exposure factors were coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) from LDL, HDL, Non-HDL, Total Cholesterol, and Triglycerides. MACE was the outcome of interest. We made a forest plot and heterogeneity analysis using I2. All analyses were made using STATA v. 14.2 Results: Eight papers from the initial 9785 met the inclusion criteria. All papers were cohort studies and a high heterogeneity was identified in the majority of them. The main heterogeneity causes were the difference in the number of participants in the studies, the years following, and the age of the participants included in the studies. In relation to the studies of low heterogeneity (&lt;40%), we found that the high variability of HDL analyzed with CV increases the risk of myocardial infarction (RR=1.39 [95% CI 1.35-1.42, I2 0%]). On the other hand, there were found significative relations between the variability of HDL analyzed with VIM to cardiovascular disease (RR=1.26 [95% CI 1.20-1.33], however, it had a high heterogeneity (I2 68.4%). Conclusions: The comparisons of the studies that analyze lipid variability have a high heterogeneity due to population differences. A relationship was found in the variability of HDL and myocardial infarction.

Risk of depression and anxiety disorders according to long-term glycemic variability

BackgroundPoor glycemic control has been linked to psychiatric symptoms. However, studies investigating the relationship between glycemic variability (GV) and depression and anxiety disorders are limited. We investigated the association of GV with depression and anxiety disorders. In addition, the relationship between trends in fasting plasma glucose (FPG) levels and these disorders were explored. MethodsWe analyzed the National Health Insurance Service-National Sample Cohort database (2002−2013) with 151,814 participants who had at least three health screenings between 2002 and 2010. Visit-to-visit FPG variability was measured as variability independent of the mean (VIM). Depression and anxiety disorders were diagnosed using ICD-10 codes (F41 for anxiety and F32 or F33 for depression) after index date. We analyzed the association between GV and incidences of these disorders using Kaplan-Meier and Cox proportional hazards methods. Trajectory analysis was conducted to explore the relationship between FPG trends and these disorders. ResultsDuring follow-up, 7166 and 14,149 patients were newly diagnosed with depression and anxiety disorders, respectively. The highest quartile group of FPG-VIM had a greater incidence of depression and anxiety than the lowest quartile group, with adjusted hazard ratios of 1.09 (95 % confidence interval [CI]: 1.02–1.17) and 1.08 (95 % CI: 1.03–1.14). Group with persistent hyperglycemia, identified through trajectory clustering of FPG levels, had a 1.43-fold increased risk of depression compared to those with consistently low FPG levels. LimitationsPotential selection bias by including participants with at least three health screenings. ConclusionsHigh GV and persistent hyperglycemia are associated with increased incidence of depression and anxiety disorders.

Effect of 24-h blood pressure dysregulations and reduced ocular perfusion pressure in open-angle glaucoma progression.

Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests (n = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG (P < 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from -2.84 dB [95% confidence interval (CI) -4.12 to -1.57] to -2.16 dB (95% CI -3.46 to -0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP.

Visit-to-Visit Glucose Variability, Cognition, and Global Cognitive Decline: The Multi-Ethnic Study of Atherosclerosis.

Higher visit-to-visit glucose variability (GV) is associated with dysglycemia and type 2 diabetes (T2D), key risk factors for cognitive decline. Evaluate the association of GV with cognitive performance and decline in racially/ethnically diverse older populations with and without T2D. We calculated the standard deviation of glucose (SDG), average real variability (ARV), and variability independent of the mean (VIM) among 4367 Multi-Ethnic Study of Atherosclerosis participants over 6 clinical examinations. Participants completed a cognitive assessment at the fifth examination, and a subset completed a second assessment 6 years later. We used multivariable linear regression to estimate the association of intraindividual GV with cognitive test scores after adjustments for cardiovascular risk factors and mean glucose level over the study period. Two-fold increments in the VIM and SDG were associated with worse Cognitive Abilities Screening Instrument (CASI) performance, while two-fold increments in VIM and ARV were associated with worse Digit Symbol Coding test score. GV measures were not associated with change in CASI performance among 1834 participants with repeat CASI data 6 years later. However, among 229 participants with incident T2D, the SDG and VIM were associated with decline in CASI (-1.7 [95% CI: -3.1, -0.3] and -2.1 [-3.7, -0.5] points, respectively). In contrast, single-timepoint glucose and HbA1c were not associated with CASI decline among participants with or without incident T2D. Higher visit-to-visit GV over 16 to 18 years is associated with worse cognitive performance in the general population, and with modest global cognitive decline in participants with T2D.

Glycemic variability correlates with medial temporal lobe atrophy and decreased cognitive performance in patients with memory deficits.

In the past, researchers have observed a significant link between glycemia and dementia. Medial temporal atrophy (MTA) is regarded as a common marker of dementia. The correlation between glycemic variability and MTA is unclear, and it has not been determined whether glycemic variability can be utilized as a biomarker of MTA and cognitive performance. The patients in a memory clinic who underwent brain MRI scans and cognitive assessments within the first week of their hospital visit, were enrolled. All participants underwent three fasting blood glucose and one HBA1c assessments on three self-selected days within 1 week of their first visit. The variability independent of the mean (VIM) was employed. Validated visual scales were used to rate the MTA results. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were employed to assess the cognitive functions of the participants. Spearman's correlation and regression models were used to examine the relationship between the MMSE and MoCA scales, and also determine the link between the MRI characteristics and cognitive status, where vascular risk factors, educational status, age, gender, and mean glucose parameters served as covariates. Four hundred sixty-one subjects completed the MMSE scale, while 447 participants completed the MoCA scale. Data analysis revealed that 47.72% of the participants were men (220/461), and the median age of the patients was 69.87 ± 5.37 years. The findings of Spearman's correlation analysis exhibited a strong negative relationship between the VIM and MMSE score (r = -0.729, P < 0.01), and the MoCA score (r = -0.710, P < 0.01). The VIM was regarded as an independent risk factor for determining cognitive impairment in both the MMSE and MoCA assessments. The results were unaffected by sensitivity analysis. In addition, a non-linear relationship was observed between the VIM and MTA scores. The variability in the blood glucose levels, which was presented as VIM, was related to the reduced cognitive function, which was reflected by MMSE and MoCA scales. The relationship between the VIM and the MTA score was non-linear. The VIM was positively related to the MTA score when the VIM was less than 2.42.

Effects of chlorthalidone plus amiloride compared with amlodipine on short-term blood pressure variability in individuals with hypertension and obstructive sleep apnea: a randomized controlled trial.

To compare the effects of chlortalidone plus amiloride and amlodipine on blood pressure (BP) variability in patients with hypertension and obstructive sleep apnea syndrome (OSA). A randomized, controlled, double-blind trial enrolled men and women aged 40 years or older with a diagnosis of OSA (apnea-hypopnea index 10-40 apneas/h of sleep) confirmed by overnight laboratory polysomnography and systolic BP 140-159 mmHg or diastolic BP 90-99 mmHg. Participants were randomized to receive chlortalidone 25 mg plus amiloride 5 mg daily or amlodipine 10 mg daily for 8 weeks. BP variability was calculated from 24-hour ambulatory BP monitoring at baseline and follow-up using the following indices: SD, coefficient of variation, average real variability (ARV), time-rate index, and variability independent of the mean (VIM). The study included 65 patients, with 33 assigned to the chlortalidone plus amiloride group and 32 to the amlodipine group. Participants in both groups had similar baseline characteristics. Short-term BP variability decreased within groups for SD and ARV indexes for 24-hour systolic BP and daytime systolic BP, but statistically significant time*group interactions were found for sleep systolic SD and VIM, with greater reduction in patients treated with amlodipine. In brief, our study has shown that the use of chlorthalidone in combination with amiloride and amlodipine produces comparable effects on short-term BP variability in patients with hypertension and OSA. Therefore, our findings suggest that BP variability may not be a significant factor when choosing between these medications for the treatment of hypertension and OSA.

A prospective cohort study of long-term fasting blood glucose variability and risk of mortality in patients with type 2 diabetes

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T1 group, the Cox regression model showed that HRs of T3 group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

Visit-to-visit HbA1c variability is associated with aortic stiffness progression in participants with type 2 diabetes

BackgroundGlycemic variability plays an important role in the development of cardiovascular disease (CVD). This study aims to determine whether long-term visit-to-visit glycemic variability is associated with aortic stiffness progression in participants with type 2 diabetes (T2D).MethodsProspective data were obtained from 2115 T2D participants in the National Metabolic Management Center (MMC) from June 2017 to December 2022. Two brachial-ankle pulse wave velocity (ba-PWV) measurements were performed to assess aortic stiffness over a mean follow-up period of 2.6 years. A multivariate latent class growth mixed model was applied to identify trajectories of blood glucose. Logistic regression models were used to determine the odds ratio (OR) for aortic stiffness associated with glycemic variability evaluated by the coefficient of variation (CV), variability independent of the mean (VIM), average real variability (ARV), and successive variation (SV) of blood glucose.ResultsFour distinct trajectories of glycated hemoglobin (HbA1c) or fasting blood glucose (FBG) were identified. In the U-shape class of HbA1c and FBG, the adjusted ORs were 2.17 and 1.21 for having increased/persistently high ba-PWV, respectively. Additionally, HbA1c variability (CV, VIM, SV) was significantly associated with aortic stiffness progression, with ORs ranging from 1.20 to 1.24. Cross-tabulation analysis indicated that the third tertile of the HbA1c mean and VIM conferred a 78% (95% confidence interval [CI] 1.23–2.58) higher odds of aortic stiffness progression. Sensitivity analysis demonstrated that the SD of HbA1c and the highest HbA1c variability score (HVS) were significantly associated with the adverse outcomes independent of the mean of HbA1c during the follow-up.ConclusionsLong-term visit-to-visit HbA1c variability was independently associated with aortic stiffness progression, suggesting that HbA1c variability was a strong predictor of subclinical atherosclerosis in T2D participants.

Association Between Fluctuations in Blood Lipid Levels Over Time With Incident Alzheimer Disease and Alzheimer Disease-Related Dementias.

Prevention strategies for Alzheimer disease and Alzheimer disease-related dementias (AD/ADRDs) are urgently needed. Lipid variability, or fluctuations in blood lipid levels at different points in time, has not been examined extensively and may contribute to the risk of AD/ADRD. Lipid panels are a part of routine screening in clinical practice and routinely available in electronic health records (EHR). Thus, in a large geographically defined population-based cohort, we investigated the variation of multiple lipid types and their association to the development of AD/ADRD. All residents living in Olmsted County, Minnesota on the index date January 1, 2006, aged 60 years or older without an AD/ADRD diagnosis were identified. Persons with ≥3 lipid measurements including total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in the 5 years before index date were included. Lipid variation was defined as any change in individual's lipid levels over time regardless of direction and was measured using variability independent of the mean (VIM). Associations between lipid variation quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Participants were followed through 2018 for incident AD/ADRD. The final analysis included 11,571 participants (mean age 71 years; 54% female). Median follow-up was 12.9 years with 2,473 incident AD/ADRD cases. After adjustment for confounding variables including sex, race, baseline lipid measurements, education, BMI, and lipid-lowering treatment, participants in the highest quintile of total cholesterol variability had a 19% increased risk of incident AD/ADRD, and those in highest quintile of triglycerides, variability had a 23% increased risk. In a large EHR derived cohort, those in the highest quintile of variability for total cholesterol and triglyceride levels had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this association are needed.

1432-P: Lipid Profile and Visit-to-Visit Variability of LDL Cholesterol, the Association with Risk of Young-Onset Type 2 Diabetes—Nationwide Retrospective Cohort Study

Background: It is reported that the prevalence of young-onset type 2 diabetes (YOD) is increasing in recent. YOD usually defined that it diagnosis at age &amp;lt;40 year. However, the underlying pathophysiology of YOD is still unknown. Previous studies suggested that lipid level and its variability associated with various health outcome. Aim: We aimed to examine the effect of lipid profile and variability of low-density lipoprotein cholesterol (LDL-C) on the risk of young-onset type 2 diabetes in Participants with 20 to 40 Years Methods: We examined the General Health Check-up sub-dataset of the Korean National Health Insurance Service (NHIS) of 1,376,416 participants with 20 to 40 year who had at least three health check-ups between 2012 and 2017, and were not reported to have diabetes during that time. The visit to visit variability of LDL-C was measured using variability independent of the mean (VIM), standard deviation (SD), average successive variability (ASV), and coefficient of variation (CV),. Results: During a median of 5 years of follow up, 19,706 subjects (1.5%) developed YOD. Risk of incident YOD increased with quartiles 2, 3 and 4 versus quartile 1 in Total cholesterol (TC), LDL-C, triglyceride (TC) whereas, inversely associated with high density lipoprotein cholesterol (HDL-C) in multivariate analysis. Compare with the lowest quartile, the highest quartile of VIM, SD, ASV and CV of LDL-C was associated with 1.22-1.43 fold risk of YOD (VIM HR, 1.292; SD HR 1.428; ASV HR 1.364; CV HR 1.218, P for trend &amp;lt;0.0001) in the multivariable adjusted model. When calculating variability of TC, LDL and HDL-C index, we did not observe that consistent results were obtained. Conclusion: Risk of incident YOD is increased with increasing lipid profile. High visit to visit LDL-C variability and level of LDL-C per se, were independent predictors of YOD. Both lowering and stabilizing LDL-C can be beneficial for reducing diabetes risk in young population. Disclosure M.Seo: None. S.Park: None. E.Rhee: None. W.Lee: None.

Association of gamma-glutamyl transferase variability with risk of osteoporotic fractures: A nationwide cohort study.

Gamma-glutamyl transferase (GGT) is related to inflammation, osteoporosis, and vascular diseases. Recently, changes in metabolic parameters have been proposed as osteoporosis biomarkers. We aimed to assess longitudinally the association of GGT variability with osteoporotic fractures. From the National Health Insurance Service-Health Screening Cohort database, participants who underwent three or more health examinations between 2003 and 2008 were included (n = 1,072,432). Variability indexes were as follows: (1) coefficient of variation (CV), (2) standard deviation (SD), and (3) variability independent of the mean (VIM). The primary outcome was occurrence of osteoporotic fracture, defined as identification of one of the following international classification of diseases-10 codes: vertebral fractures (S22.0, S22.1, S32.0, S32.7, T08, M48.4, M48.5, M49.5), hip fractures (S72.0, S72.1), distal radius fractures (S52.5, S52.6), or humerus fractures (S42.2, S42.3). During a median of 12.3 years (interquartile range 12.1-12.6), osteoporotic fractures occurred in 49,677 (4.6%) participants. In multivariable analysis, GGT variability based on CV positively correlated with the occurrence of osteoporotic fracture (adjusted hazard ratio [HR] of the highest quartile compared with the lowest quartile 1.15, 95% confidence interval [CI] 1.12-1.18, P < 0.001). These results were consistent even when GGT variability was defined by SD (adjusted HR 1.22, 95% CI 1.19-1.25, P < 0.001) and VIM (adjusted HR 1.12, 95% CI 1.09-1.15, P < 0.001). Increased GGT variability is associated with an increased risk of osteoporotic fractures in the Korean population. Maintaining constant and stable GGT level may help reduce the risk of osteoporotic fractures.

Association of HbA1c trajectory and variability with cognitive function

AbstractBackgroundType 2 diabetes (T2D) is an important modifiable risk factor for cognitive decline, and increasing evidence suggests that worse glucose control, in addition to a diagnosis of T2D, may play a role in cognitive function in later life. Despite this increasing concern, evidence regarding the relative contributions of poor glucose control and higher glucose variability to cognitive dysfunction among individuals with overweight or obesity is limited, mostly due to lack of repeated measures in many studies.MethodLook AHEAD MIND Study participants, aged 45‐76 years at baseline (2001‐04) with T2D and overweight or obesity, were randomized to an intensive lifestyle intervention focused on weight loss or a diabetes support and education condition, which were discontinued after ∼10 years. HbA1c levels were evaluated at years 1‐4, 6, 8, and 10. Cognitive function was evaluated up to four times between years 8‐18 with a cognitive battery that assessed memory, attention, and executive function domains. Cognitive scores were binned into four groups based on relative timing of cognitive assessments (8‐9; 10‐11; 12‐14; and 15‐18 years). We classified HbA1c variability according to: Variability Independent of the Mean (VIM), Average Real Variability (ARV), and data‐driven latent trajectories. Mixed linear regression models for standardized composite cognitive scores were adjusted for: repeated measures, order of cognitive test, years from randomization, randomization arm, age, sex, race/ethnicity, years of education, CVD history, and APOE ε4.ResultFour HbA1c trajectories were identified: increasing, decreasing, stable‐high, and stable‐low. Composite cognitive scores were significantly lower for increasing, decreasing, and stable‐high HbA1c trajectories ‐compared to stable‐low HbA1c (Table). In multivariable analysis, higher baseline HbA1c, ARV, and VIM were associated with lower composite cognitive scores, and differences between groups were similar by years since randomization. Estimates for ARV and VIM were attenuated when adjusted for baseline HbA1c (not shown). Estimates were similar for tests from all cognitive domains, with little heterogeneity by randomization arm.ConclusionAmong individuals with T2D, higher HbA1c at baseline and greater HbA1c variability over 10 years were significantly associated with lower cognitive scores, suggesting that maintaining glucose control may be useful for the prevention of cognitive decline.