Variability Independent Of The Mean Research Articles

Association between visit-to-visit variability of glycated albumin and diabetic retinopathy among patients with type 2 diabetes - A prospective cohort study.

There is a paucity of studies regarding the association between long-term glycemic variability with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes. Therefore, the purpose of this study is to explore the association of glycated albumin (GA) variability and HbA1c variability with the risk of DR in patients with type 2 diabetes. This prospective cohort study included 315 inpatients with type 2 diabetes (191 males and 124 females) with at least 3 measurements of GA and HbA1c within 2years prior to the baseline investigation. Different GA and HbA1c variability markers were calculated, including CV, variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit variability of GA and HbA1c and the risk of DR. After an average follow-up of 3.42years, 81 patients developed incident DR. Multivariable-adjusted (diabetes duration, smoking status, systolic blood pressure, albumin to creatinine ratio, triglycerides, using fibrates, and mean HbA1c) hazard ratios of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit HbA1c variability and the risk of DR. The present study indicated that visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.

The Association Between Variability in Electrolytes and the In-Hospital Mortality in Critically Ill Children in Pediatric Intensive Care Units.

Objective: This study aimed to explore the association between the variability in electrolytes and the in-hospital mortality in critically ill children admitted into intensive care units (ICUs).Design: This is a retrospective case–control study.Setting and Participants: Total of 11,245 children have been admitted to ICUs of Children's Hospital of Zhejiang University from 2010 to 2018.Methods: The coefficient of variation (CV), standard deviation (SD), and variability independent of the mean (VIM) were calculated as variability indices. High variability was defined as having values in the highest quartile for each parameter. Age, sex, diagnoses of disease, and surgical treatment were adjusted in the multivariable-adjusted logistic regression model.Results: A total of 11,245 children were included, and 660 patients died in the hospital. The median (P25, P75) potassium, sodium, and chloride of all patients were 3.8 (3.58, 4.09), 136.83 (135.11, 138.60), and 108.67 (105.71, 111.17), respectively. U-shaped relationships between the mean, lowest, and highest levels of potassium, sodium, and chloride and the in-hospital mortality were observed. The lowest mortality was noted when serum potassium, sodium, and chloride were between ~3.5 and 5.0, 135 and 145, and 105 and 115 mmol/l, respectively. The areas under the curve (AUCs) of three indices of variability in electrolytes were larger than those of the mean and lowest levels of electrolytes in predicting the in-hospital mortality. In the multivariable-adjusted model, the odds ratios and 95% confidence interval (CI) of the in-hospital mortality were 3.14 (2.44–4.04) for one parameter, 5.85 (4.54–7.53) for two parameters, and 10.32 (7.81–13.64) for three parameters compared with subjects having no parameters of high variability measured as the CV. The results were consistent when the variability was determined using the SD and VIM (all P for trend <0.001). Consistent results were noted in various subgroup analyses.Conclusions: This study showed that individuals with higher variability of each parameter were related with higher risk of in-hospital mortality. There was a linear association between the number of high variability parameters and the in-hospital mortality. The variability of electrolytes might be a good predictor for in-hospital mortality of children in ICUs.

Impact of indoor temperature instability on diurnal and day-by-day variability of home blood pressure in winter: a nationwide Smart Wellness Housing survey in Japan

Home blood pressure (HBP) variability is an important factor for cardiovascular events. While several studies have examined the effects of individual attributes and lifestyle factors on reducing HBP variability, the effects of living environment remain unknown. We hypothesized that a stable home thermal environment contributes to reducing HBP variability. We conducted an epidemiological survey on HBP and indoor temperature in 3785 participants (2162 households) planning to have their houses retrofitted with insulation. HBP was measured twice in the morning and evening for 2 weeks in winter. Indoor temperature was recorded with each HBP observation. We calculated the morning-evening (ME) difference as an index of diurnal variability and the standard deviation (SD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM) as indices of day-by-day variability. The association between BP variability and temperature instability was analyzed using multiple linear regression models. The mean ME difference in indoor/outdoor temperature (a decrease in temperature overnight) was 3.2/1.5 °C, and the mean SD of indoor/outdoor temperature was 1.6/2.5 °C. Linear regression analyses showed that the ME difference in indoor temperature was closely correlated with the ME difference in systolic BP (0.85 mmHg/°C, p < 0.001). The SD of indoor temperature was also associated with the SD of systolic BP (0.61 mmHg/°C, p < 0.001). The CV, ARV, and VIM showed similar trends as the SD of BP. In contrast, outdoor temperature instability was not associated with either diurnal or day-by-day HBP variability. Therefore, residents should keep the indoor temperature stable to reduce BP variability.

Frequency of Visit-to-Visit Variability of Resting Heart Rate and the Risk of New-Onset Atrial Fibrillation in the General Population

Resting heart rate (RHR) has been an established predictor for atrial fibrillation (AF). However, the association of visit-to-visit heart rate variability (VVHRV) with new-onset AF risk over long term remains unclear. Our study investigates the relation of VVHRV to new-onset AF in general population in the prospective study of the Kailuan cohort. A total of 46,126 individuals without arrhythmia were included. They underwent 3 health examinations from 2006 to 2010 and performed follow up. VVHRV was measured by coefficient of variation (CV), variability independent of the mean (VIM), and standard deviation (SD). Participants were separately divided into 5 categories by quintiles of visit-to-visit RHR-CV, RHR-VIM and RHR-SD. Multivariate Cox regression and restricted cubic spline models were performed to establish the association between VVHRV and new-onset AF. 241 new-onset AF occurred during a median follow-up of 7.54 years. The incidence of new-onset AF in the group of the lowest (Q1) and highest quintiles (Q5) of RHR-CV were higher than that in other groups. The HRs for the new-onset AF were 2.07 (95% CI, 1.34-3.21, p < 0.01), in the highest quintile group(Q5) compared with group Q2, and 1.89(95% CI, 1.20-2.97, p < 0.01) in the lowest quintile group(Q1) compared with group Q2. The risk for new-onset AF showed a similar trend using RHR-VIM (p < 0.01) and RHR-SD (p < 0.05) parameters. Further sensitivity analyses indicated the consistent results in subjects without prior cardiovascular disease and without taking beta blockers or CCB. To match the covariates, analyses were also performed by propensity score matching, and prominent trends were also found in RHR-SD and RHR-VIM. In conclusion, the study indicated that higher and lower VVHRV were associated with the increasing risk of new-onset AF, which supporting a U-shaped curve existence.

Visit-to-visit office blood pressure variability combined with Framingham risk score to predict all-cause mortality: A post hoc analysis of the systolic blood pressure intervention trial.

We aim to determine if visit‐to‐visit blood pressure variability (BPV) adds prognostic value for all‐cause mortality independently of the Framingham risk score (FRS) in the systolic blood pressure intervention trial (SPRINT). We defined BPV as variability independent of the mean (VIM) and the difference of maximum minus minimum (MMD) of the systolic blood pressure (SBP). Multivariable Cox proportional hazards models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Based on FRS stratification, there were 1035, 2911, and 4050 participants in the low‐, intermediate‐, and high‐risk groups, respectively. During the trial, 230 deaths occurred since the 12th month with an average follow‐up of 2.5 years. In continuous analysis, 1‐SD increase of SBP VIM and MMD were significantly associated with all‐cause mortality (HR 1.18, 95% CI 1.05–1.32, p = .005; and HR 1.21, 95% CI 1.09–1.35, p < .001, respectively). In category analysis, the highest quintile of BPV compared with the lowest quintile had significantly higher risk of all‐cause mortality. Cross‐tabulation analysis showed that the 3rd tertile of SBP VIM in the high‐risk group had the highest HR of all‐cause mortality in total population (HR 4.99; 95% CI 1.57–15.90; p = .007), as well as in intensive‐therapy group (HR 7.48; 95% CI 1.01–55.45; p = .05) analyzed separately. Cross‐tabulation analysis of SBP MMD had the same pattern as VIM showed above. In conclusion, visit‐to‐visit BPV was an independent predictor of all‐cause mortality, when accounting for conventional risk factors or FRS. BPV combined with FRS conferred an increased risk for all‐cause mortality in the SPRINT trial.

Blood pressure variability and night-time dipping assessed by 24-hour ambulatory monitoring: Cross-sectional association with cardiac structure in adolescents.

Greater blood pressure (BP) is associated with greater left ventricular mass indexed to height2.7 (LVMi2.7) in adolescents. This study examined whether greater BP variability and reduced night-time dipping are associated with cardiac remodeling in a general population of adolescents. A cross-sectional analysis was undertaken in 587 UK adolescents (mean age 17.7 years; 43.1% male). BP was measured in a research clinic and using 24-hour ambulatory monitoring. We examined associations (for both systolic and diastolic BP) of: 1) clinic and 24-hour mean BP; 2) measures of 24-hour BP variability: standard deviation weighted for day/night (SDdn), variability independent of the mean (VIM) and average real variability (ARV); and 3) night-time dipping with cardiac structures. Cardiac structures were assessed by echocardiography: 1) LVMi2.7; 2) relative wall thickness (RWT); 3) left atrial diameter indexed to height (LADi) and 4) left ventricular internal diameter in diastole (LVIDD). Higher systolic BP was associated with greater LVMi2.7. Systolic and diastolic BP were associated with greater RWT. Associations were inconsistent for LADi and LVIDD. There was evidence for associations between both greater SDdn and ARV and higher RWT (per 1 SD higher diastolic ARV, mean difference in RWT was 0.13 SDs, 95% CI 0.045 to 0.21); these associations with RWT remained after adjustment for mean BP. There was no consistent evidence of associations between night-time dipping and cardiac structure. Measurement of BP variability, even in adolescents with blood pressure in the physiologic range, might benefit risk of cardiovascular remodeling assessment.

Long-Term Visit-to-Visit Mean Arterial Pressure Variability and the Risk of Heart Failure and All-Cause Mortality.

Background: Systolic or diastolic blood pressure (BP) variability is associated with an increased risk of cardiovascular events. We assessed whether BP variability measured by mean arterial pressure (MAP) was associated with increased risk of heart failure (HF) and death in individuals with or without hypertension.Methods: We evaluated 9,305 Atherosclerosis Risk in Communities (ARIC) study participants with or without hypertension and calculated BP variability based on MAP values from visit 1 to 4 [expressed as standard deviation (SD), average real variability (ARV), coefficient of variation (CV), and variability independent of the mean (VIM)]. Multivariate-adjusted Cox regression model and restricted cubic spline curve were used to evaluate the associations of MAP variability with all-cause mortality and HF.Results: During a median follow-up of 16.8 years, 1,511 had an HF event and 2,903 died. Individuals in the highest quartile of VIM were both associated with a 21% higher risk of all-cause mortality [hazard ratio (HR), 1.21; 95% CI, 1.09–1.35] and HF (HR, 1.21; 95% CI, 1.04–1.39) compared with the lowest quartile of VIM. Cubic spline curves reveal that the risk of deaths and HF increased with MAP variability when it reached a higher level. Results were similar in individuals with normotension (all-cause mortality: HR, 1.30; 95% CI, 1.09–1.55; HF, HR, 1.49; 95% CI, 1.12–1.98).Conclusions: In individuals with or without hypertension, greater visit-to-visit MAP variability was associated with a higher risk of all-cause mortality and HF, indicating that the BP variability assessed by MAP might be a potential risk factor for HF and death.

91-OR: Visit-to-Visit Variability of Glycated Albumin Was Associated with the Risk of Diabetic Retinopathy in Patients with Type 2 Diabetes

Background: The association between long-term glycemic variability and diabetic retinopathy (DR) among patients with type 2 diabetes has not been clarified yet. Objective: The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of DR in patients with type 2 diabetes. Design: A prospective cohort study of 315 patients (191 males and 124 females) with at least 3 measurements of HbA1c and GA prior to baseline was performed. Different GA and HbA1c variability markers were calculated, including coefficient of variation (CV), variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit HbA1c and GA variability and the risk of DR. Results: During a mean follow-up period of 3.42 years, 81 participants developed incident DR. Multivariate-adjusted hazard ratios (HRs) of DR across tertiles of GA-CV values were 1.00, 1.42, and 2.12 (P for trend=0.027), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of DR were found. Multivariable-adjusted HRs of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of DR after multivariate adjustment. Conclusion: The visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels. Disclosure J. Zhou: None. D. Dai: None. Y. Shen: None. J. Lu: None. Y. Wang: None. W. Zhu: None. Y. Bao: None. G. Hu: None. Funding National Key Research and Development Project of China (2018YFC2000802); Shanghai Municipal Education Commission (20161430); Shanghai Municipal Key Clinical Specialty

Abstract P102: Variability In Lipid Levels And Risk For Cardiovascular Disease: An Electronic Health Record-based Population Cohort Study

Background: Larger within-patient variability of lipid levels has been associated with an increased risk of cardiovascular disease (CVD). However, measures of lipid variability are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record (EHR)-based population cohort and assessed associations with incident CVD. Methods: We identified all individuals ≥40 years of age who resided in Olmsted County, MN on 1/1/2006 (index date) without prior CVD. CVD was defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention or stroke. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides during the 5 years before the index date were retained in the analyses. Lipid variability was calculated using variability independent of the mean (VIM). Patients were followed through 9/30/2017 for incident CVD (including CVD death). Cox regression was used to investigate the association between quintiles of lipid VIMs and incident CVD. Results: We identified 18,642 individuals (mean age 60; 55% female) who were free of CVD at baseline and VIM calculated for at least one lipid measurement. After adjustment, those in the highest VIM quintiles of total cholesterol had a 25% increased risk of CVD (Q5 vs. Q1 HR: 1.25, 95% CI: 1.08-1.45; Table). We observed similar results for LDL-C (Q5 vs. Q1 HR: 1.20, 95% CI: 1.04-1.39) and HDL-C (Q5 vs. Q1 HR: 1.25, 95% CI: 1.09-1.43). There was no association between triglyceride variability quintiles and CVD risk. Conclusion: In a large EHR-based population cohort, high variability in total cholesterol, HDL-C and LDL-C was associated with an increased risk of CVD, independently of traditional risk factors, suggesting it may be a target for intervention. Lipid variability can be calculated in the EHR environment but more research is needed to determine its clinical utility.

Abstract MP64: Higher Visit-to-Visit Blood Pressure Variability In Early And Middle Childhood Is Associated With Higher Blood Pressure In Adolescence

Background: In young adults, higher blood pressure (BP) and visit-to-visit BP variability are independent risk factors for incident cardiovascular disease. No studies have examined if BP and visit-to-visit BP variability during early and middle childhood are independently associated with elevated BP during adolescence. Addressing this question can provide targets for primordial prevention of high BP. Hypotheses: Higher BP and BP variability in early and middle childhood are independently associated with higher BP in adolescence. Methods: We studied 476 children in the Boston Birth Cohort (enrolled 1998-2016) who had BP measured in early (1 to &lt;6 y) or middle childhood (6 to &lt;13y) and in adolescence (13 to &lt;18 y). We modelled visit-to-visit BP variability using variability independent of the mean (VIM). We used linear regression models to examine the associations of mean BP and BP VIM in early and middle childhood (exposures) with mean BP in adolescence (outcome) and adjusted for potential confounders (see Table footnote). Results: After multivariable adjustment, a 1-SD higher level of systolic BP (SBP) in early and middle childhood was associated with a 1.89 (95% CI: 1.03, 2.75) and a 4.31 (95% CI: 3.58, 5.03) mmHg higher SBP in adolescence, respectively. A 1-SD higher level of SBP VIM in early and middle childhood was associated with a 1.46 (95% CI: 0.54, 2.38) and a 0.89 (95% CI: 0.05, 1.73) mmHg higher SBP in adolescence, respectively. Higher diastolic BP (DBP) in early and middle childhood was also associated with higher adolescence DBP, but the magnitude was smaller in comparison with SBP results ( Table ). Childhood DBP VIM was not associated with DBP in adolescence. Conclusion: In this prospective US predominantly minority birth cohort, both BP levels and variability during early and middle childhood are associated with higher BP in adolescence. Our findings underscore the need for health professionals to collect early-life BP data to facilitate opportunities for the primordial prevention of high BP in adolescence and beyond.

Abstract P103: Association Of Lipid Variability With Incident Alzheimers Disease And Alzheimers Disease Related Dementias

Background: Prevention strategies for Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRDs) are urgently needed for reducing incidence. Intra-patient variability in lipid levels is a potentially modifiable risk factor for incident AD/ADRD. Although regular lipid measurements are a part of common clinical practice and longitudinal data routinely available in electronic health records (EHR), research examining this association between AD/ADRD and lipid variability across multiple lipid types remains scarce. Methods: All residents living in Olmsted County, MN on 1/1/2006 age ≥60 years without an AD/ADRD diagnosis were identified using Centers for Medicare &amp; Medicaid Services diagnostic codes. Persons with ≥3 lipid measurements (total cholesterol or triglycerides) in the 5 years prior to index date were retained. Lipid variability was quantified using variability independent of the mean (VIM). Models were adjusted for traditional risk factors. Associations between lipid variability quintiles and incident AD/ADRD were assessed using Cox proportional hazards regression. Multiple imputation was used for missing covariates. Participants were followed through 2018 for incident AD/ADRD. Results: The final analysis included data on 11,551 participants with total cholesterol and 11,502 participants with triglycerides. Participants had a mean age of 71 (range 60-99) years, and were primarily white (96%). Females (54%) were also slightly more frequent than males. Median follow up was 12.9 years (range: 0-13). Participants in the highest quintile of variability for total cholesterol and triglycerides had a 20% increased risk of incident AD/ADRD. Similar results were found in the subset with complete covariate data. Conclusion: In a large EHR derived cohort, persons in the highest quintile of lipid variation had an increased risk of incident AD/ADRD. Further studies to identify the mechanisms behind this risk factor and replication of these results across a more diverse population are needed.

Body weight variability and the risk of cardiovascular outcomes in patients with nonalcoholic fatty liver disease

We investigated the association between body weight variability and the risks of cardiovascular disease and mortality in patients with nonalcoholic fatty liver disease (NAFLD) using large-scale, nationwide cohort data. We included 726,736 individuals with NAFLD who underwent a health examination between 2009 and 2010. NAFLD was defined as a fatty liver index ≥ 60, after excluding significant alcohol intake, viral hepatitis, and liver cirrhosis. Body weight variability was assessed using four indices, including variability independent of the mean (VIM). During a median 8.1-year follow-up, we documented 11,358, 14,714, and 22,164 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively. Body weight variability was associated with an increased risk of MI, stroke, and mortality after adjusting for confounding variables. The hazard ratios (HRs) (95% confidence intervals) for the highest quartile, compared with the lowest quartile, of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.56 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively. Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in NAFLD patients. Appropriate interventions to maintain a stable weight could positively affect health outcomes in NAFLD patients.

Visit-to-visit variability of lipid and cardiovascular events in patients with familial hypercholesterolemia.

Visit-to-visit variability in lipid has been suggested as a predictor of major adverse cardiovascular events (MACEs). However, no evidence exists on the prognostic value of lipid variability in patients with familial hypercholesterolemia (FH). This prospective cohort study aimed to investigate whether lipid variability affects future MACEs in patients with FH receiving standard lipid-lowering therapy. A total of 254 patients with FH were consecutively enrolled and followed for MACEs. Variability in the triglyceride, total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] were evaluated from 3 months after discharge using the standard deviation (SD), coefficient of variation (CV) and variability independent of the mean (VIM). During a mean follow-up of 49 months, 22 (8.7%) events occurred. Visit-to-visit variability in Lp(a) was significantly higher in the MACE group compared to the non-MACE group. In the multivariate Cox analysis, only Lp(a)-related parameters were independent predictors for MACEs. The hazard ratios and 95% confidence intervals of each 1-SD increase of SD, CV, and VIM of Lp(a) were 1.42 (1.12-1.80), 1.50 (1.11-2.02) and 1.60 (1.16-2.22), respectively. Kaplan-Meier analysis revealed that patients with higher Lp(a) variability presented lower event-free survival. The results were consistent in various subgroups. Our study firstly suggested that Lp(a) variability was associated with MACEs in real-world patients with FH, which emphasized the importance of regular lipid monitoring in the patients with high risk.

The association of blood lipid parameters variability with ischemic stroke in hypertensive patients

Background and aimsThe relationship between lipid variability and stroke among patients with hypertension were inconclusive. We aimed to investigate the association of lipid variability with ischemic stroke in hypertensive patients. Methods and resultsThis retrospective cohort study included 4995 individuals with hypertension between 2013 and 2015, and recorded their status of ischemic stroke until the end of 2018. The variability in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using the standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM) and average absolute difference between successive values (ASV). Multivariate Cox proportional hazards models with hazard ratios (HRs) and 95% confidence interval (CI) were performed. There were 110 cases of ischemic stroke during a median follow up of 4.2 years. The multivariable adjusted HRs and 95% CIs comparing the highest versus the lowest quartiles of SD of TC, LDL-C, HDL-C and TG were 4.429 (95% CI: 2.292, 8.560), 2.140 (95% CI: 1.264, 3.621), 1.368 (95% CI: 0.793, 2.359) and 1.421 (95% CI: 0.800, 2.525), respectively. High variability in TC and LDL-C were associated with a higher risk for ischemic stroke. Similarly, the results were consistent when calculating variability of TC and LDL-C using CV, ASV and VIM, and in various subgroup analyses. ConclusionHigher variability of TC and LDL-C associated with the risk of ischemic stroke among hypertensive patients. These findings suggest reducing variability of lipid parameters may decrease adverse outcomes.

Association of High-Density Lipoprotein Cholesterol Variability and the Risk of Developing Parkinson Disease.

To investigate the longitudinal association among high-density lipoprotein cholesterol (HDL-C) level, HDL-C variability, and the risk of developing Parkinson disease (PD). We conducted a nationwide, population-based cohort study. We included 382,391 patients aged ≥65 years who underwent at least 3 health examinations provided by the Korean National Health Insurance System from 2008 to 2013 and followed up until 2017. Individuals with a history of PD and missing values were excluded (n = 1,987). We assessed HDL-C variability using 3 indices, including variability independent of the mean (VIM). A multivariate-adjusted Cox proportional hazards regression analysis was performed. Among the 380,404 participants, 2,733 individuals were newly diagnosed with PD during a median follow-up period of 5 years. The lowest quartile (Q1) group of baseline HDL-C and mean HDL-C was associated with increased PD incidence as compared with the highest quartile (Q4) group (adjusted hazard ratio [aHR], 1.20; 95% confidence interval [CI], 1.08-1.34; and aHR, 1.16; 95% CI, 1.04-1.30, respectively). The Q4 group of HDL-C variability (VIM) was associated with increased PD incidence compared to the Q1 group (aHR, 1.19; 95% CI, 1.06-1.33). The group with the Q1 of baseline HDL-C and with the Q4 of HDL-C variability had the highest risk of PD incidence (aHR, 1.6; 95% CI, 1.31-1.96). Lower HDL-C level and greater HDL-C variability were associated with a higher incidence of PD.

Lipid Level, Lipid Variability, and Risk of Multiple Myeloma: A Nationwide Population-Based Study of 3,527,776 Subjects.

Simple SummaryThere is preclinical evidence that abnormalities in lipid metabolism promote cancer development, and a few studies show the association between lipid levels and multiple myeloma (MM). However, to our knowledge, the role of lipid variability as a risk factor for MM has not been evaluated. We investigated whether lipid level and its variability are associated with the development of MM at a population level. Lower baseline lipid levels of total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, and high variability in high-density lipoprotein cholesterol were all associated with increased risk of developing MM. These findings support the role of lipid metabolism in MM risk.(1) Background: There is evidence that abnormality in lipid metabolism promotes cancer development. This study investigated whether lipid level and its variability are associated with the development of MM at a population level. (2) Methods: A retrospective cohort study included a total of 3,527,776 subjects aged 40 and above who participated in ≥3 health examinations within the previous five years, including the index year (2012–2013). Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) were measured, and visit-to-visit lipid variability were calculated by variability independent of the mean (VIM) method. The study population was followed from the health examination date in the index year until the diagnosis of MM, death, or the last follow-up date (31 December 2017). (3) Results: During a median (5–95%) 5.1 years of follow-up, 969 subjects developed MM. A lower risk of MM was observed with higher quartiles of baseline lipid levels compared to the lowest quartile group (Q4 vs. Q1: adjusted hazard ratios (aHRs) 0.51, 95% confidence interval (CI) (0.42–0.61) for TC; 0.50 (0.41–0.61) for HDL-C; 0.65 (0.54–0.77) for LDL-C; and 0.72 (0.60–0.87) for TG in model (3). Among all lipid measures, only variability in HDL-C was associated with risk of MM: aHRs (95% CI) were 1.12 (0.91–1.38), 1.19 (0.97–1.46), and 1.34 (1.09–1.65) in the Q2, Q3, and Q4, respectively, compared to the Q1 of VIM of HDL-C. (4) Conclusions: This study shows that patients with lower lipid levels and high HDL-C variability are at increased risk of developing MM.

Potassium variability during hospitalization and outcomes after discharge in patients with acute myocardial infarction.

BACKGROUNDThe variability of metabolic biomarkers has been determined to provide incremental prognosis information, but the implications of electrolyte variability remained unclear.METHODSWe investigate the relationships between electrolyte fluctuation and outcomes in survivors of acute myocardial infarction (n = 4386). Ion variability was calculated as the coefficient of variation, standard deviation, variability independent of the mean (VIM) and range. Hazard ratios (HR) were estimated using the multivariable-adjusted Cox proportional regression method. RESULTSDuring a median follow-up of 12 months, 161 (3.7%) patients died, and heart failure occurred in 550 (12.5%) participants after discharge, respectively. Compared with the bottom quartile, the highest quartile potassium VIM was associated with increased risks of all-cause mortality (HR = 2.35, 95% CI: 1.36–4.06) and heart failure (HR = 1.32, 95% CI: 1.01–1.72) independent of cardiac troponin I (cTnI), N terminal pro B type natriuretic peptide (NT-proBNP), infarction site, mean potassium and other traditional factors, while those associations across sodium VIM quartiles were insignificant. Similar trend remains across the strata of variability by other three indices. These associations were consistent after excluding patients with any extreme electrolyte value and diuretic use.CONCLUSIONSHigher potassium variability but not sodium variability was associated with adverse outcomes post-infarction. Our findings highlight that potassium variability remains a robust risk factor for mortality regardless of clinical dysnatraemia and dyskalaemia.

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.

Variabilities in Weight and Waist Circumference and Risk of Myocardial Infarction, Stroke, and Mortality: A Nationwide Cohort Study.

BackgroundEvidence regarding the association between variabilities in obesity measures and health outcomes is limited. We aimed to examine the association between variabilities in obesity measures and cardiovascular outcomes and all-cause mortality.MethodsWe identified 4,244,460 individuals who underwent health examination conducted by the Korean National Health Insurance Service during 2012, with ≥3 anthropometric measurements between 2009 and 2012. Variabilities in body weight (BW) and waist circumference (WC) were assessed using four indices including variability independent of the mean (VIM). We performed multivariable Cox proportional hazards regression analyses.ResultsDuring follow-up of 4.4 years, 16,095, 18,957, and 30,200 cases of myocardial infarction (MI), stroke, and all-cause mortality were recorded. Compared to individuals with the lowest quartiles, incrementally higher risks of study outcomes and those of stroke and all-cause mortality were observed among individuals in higher quartiles of VIM for BW and VIM for WC, respectively. The multivariable adjusted hazard ratios and 95% confidence intervals comparing the highest versus lowest quartile groups of VIM for BW were 1.17 (1.12 to 1.22) for MI, 1.20 (1.16 to 1.25) for stroke, and 1.66 (1.60 to 1.71) for all-cause mortality; 1.07 (1.03 to 1.12) for stroke and 1.29 (1.25 to 1.33) for all-cause mortality regarding VIM for WC. These associations were similar with respect to the other indices for variability.ConclusionThis study revealed positive associations between variabilities in BW and WC and cardiovascular outcomes and all-cause mortality. Our findings suggest that variabilities in obesity measures are associated with adverse health outcomes in the general population.

Impact of variability in estimated glomerular filtration rate on major clinical outcomes: A nationwide population-based study.

BackgroundThe estimated glomerular filtration rate (eGFR), commonly estimated using the serum creatinine value, often fluctuates throughout the serial measurement. The clinical significance of GFR variation among the general population with normal renal function has not yet been demonstrated. Thus, we explored the impact of GFR variability on adverse clinical outcomes.MethodsA nationwide retrospective cohort study using the Korean National Health Insurance System database was performed. National health screening examinees who underwent creatinine measurement ≥3 times between 2012 and 2016 were considered. Those with eGFR under 60 mL/min/m2 were excluded. The fluctuation of eGFR was represented with variability independent of the mean (VIM) index; which was calculated by the standard deviation divided by the exponent of the regression coefficient of the mean. Then, the risks of myocardial infarction (MI), stroke and death were assessed according to the quartiles of the VIMResultsOf total 3,538,500 participants, 0.29% of myocardial infarction (MI), 0.14% of stroke, 0.36% of deaths were observed during the median follow up of 3.27 years. Participants with the highest VIM index, which represents the highest eGFR variability, were significantly associated with an increased risk of MI (hazard ratio [HR]; 1.10, 95% confidence interval [95% CI]; 1.04–1.16), stroke (HR: 1.16; 95% CI 1.09–1.23), and death (HR: 1.18; 95% CI 1.12–1.24). The elevated risk of adverse events was consistent after the multivariate adjustment with potential confounding factors, except the risk of MI (HR 1.06; 95% 1.00–1.06).ConclusionsIncreased eGFR variability exhibited an association with major clinical outcomes, indicating that monitoring eGFR variability might be a useful parameter for predicting the adverse outcomes.