Visit-to-visit Variability Research Articles

The association between index-year, average, and variability of the triglyceride-glucose index with health outcomes: more than a decade of follow-up in Tehran lipid and glucose study

BackgroundThe association between baseline triglyceride glucose index (TyG index) and incident non-communicable diseases, mainly in Asian populations, has been reported. In the current study, we aimed to evaluate the association between index-year, average, and visit-to-visit variability (VVV) of the TyG index with incident type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), and all-cause mortality among the Iranian population.MethodsThe study population included 5220 participants (2195 men) aged ≥ 30 years. TyG index was calculated as Ln (fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2). Average values of the TyG index and also VVV (assessed by the standard deviation (SD) and variability independent of mean) were derived during the exposure period from 2002 to 2011 (index-year). Multivariable Cox proportional hazards regression models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the TyG index for incident different health outcomes.ResultsDuring more than 6 years of follow-up after the index year, 290, 560, 361, and 280 events of T2DM, hypertension, CVD, and all-cause mortality occurred. 1-SD increase in the TyG index values at the index-year was independently associated with the incident T2DM [HR (95% CI) 2.50 (2.13–2.93)]; the corresponding values for the average of TyG index were 2.37 (2.03–2.76), 1.12 (0.99–1.26, pvalue = 0.05), 1.18 (1.01–1.36), and 1.29 (1.08–1.53) for incident T2DM, hypertension, CVD, and all-cause mortality, respectively. Compared to the first tertile, tertile 3 of VVV of the TyG index was independently associated with incident hypertension [1.33 (1.07–1.64), Ptrend <0.01]. Likewise, a 1-SD increase in VVV of the TyG index was associated with an 11% excess risk of incident hypertension [1.11 (1.02–1.21)]. However, no association was found between the VVV of the TyG index and other outcomes. Moreover, the impact of index-year and average values of the TyG index was more prominent among women regarding incident CVD (P for interactions < 0.05).ConclusionAlthough the higher TyG index at index-year and its VVV were only associated with the incident T2DM and hypertension, respectively, its average value was capable of capturing the risk for all of the health outcomes.

MINIMUM NUMBER OF READINGS NEEDED TO DETERMINE LONG-TERM VISIT-TO-VISIT SYSTOLIC BLOOD PRESSURE VARIABILITY FOR PREDICTING CARDIOVASCULAR OUTCOMES IN DIABETIC PATIENTS

Objective: In clinical practice, office blood pressure (BP) measurements are used for assessing long-term, visit-to-visit variability (VVV) of BP and the consistency of BP control in patients treated for hypertension. We aimed to determine the reproducibility of VVV and the minimum number of BP measurements required to estimate VVV for predicting cardiovascular outcomes. Design and method: This multicenter, retrospective study used data from the Korea University Medical Center database built on electronic health records. A total of 10,475 diabetic patients with &gt;9 readings of BP during a minimum of two years were identified. Patients were followed up for 3 years after determining the coefficient of variation (CV), and the primary outcome was major adverse cardiovascular events (MACE), including cardiovascular mortality, myocardial infarction, stroke, and hospitalization for heart failure. Results: In diabetic patients, the average age of the patients was 65.2 years; 53.2% were men; and 87.4% had hypertension. The mean CV of systolic BP (SBP) was 9.0 ± 3.6. The mean CV of multiple readings that best predicted 3-year MACE were 8.4 for the 3 SBP readings (area under the curve [AUC], 0.57), 9.5 for the 5 readings (AUC, 0.61), 9.0 for the 7 readings (AUC, 0.63), 9.0 for the 9 readings (AUC, 0.64), and 9.7 for all readings (AUC, 0.66). In univariable analysis, 3-year MACE was significantly associated with high VVV from all SBP readings (HR 2.44, p&lt;0.001) and 5 SBP readings (HR 2.03, p&lt;0.001). Hence, a minimum of 5 SBP readings (median time 252 days) is needed for determining intraindividual VVV. Conclusions: In clinical practice, long-term VVV is reliably reproducible in diabetic patients. We recommend a minimum of five BP measurements for the estimation of intraindividual VVV. It is important to consider the number and duration of BP measurements used to calculate VVV when predicting cardiovascular outcomes.

Quantifying Blood Pressure Visit-to-Visit Variability in the Real-World Setting: A Retrospective Cohort Study.

Visit-to-visit variability (VVV) in blood pressure values has been reported in clinical studies. However, little is known about VVV in clinical practice and whether it is associated with patient characteristics in real-world setting. We conducted a retrospective cohort study to quantify VVV in systolic blood pressure (SBP) values in a real-world setting. We included adults (age ≥18 years) with at least 2 outpatient visits between January 1, 2014 and October 31, 2018 from Yale New Haven Health System. Patient-level measures of VVV included SD and coefficient of variation of a given patient's SBP across visits. We calculated patient-level VVV overall and by patient subgroups. We further developed a multilevel regression model to assess the extent to which VVV in SBP was explained by patient characteristics. The study population included 537 218 adults, with a total of 7 721 864 SBP measurements. The mean age was 53.4 (SD 19.0) years, 60.4% were women, 69.4% were non-Hispanic White, and 18.1% were on antihypertensive medications. Patients had a mean body mass index of 28.4 (5.9) kg/m2 and 22.6%, 8.0%, 9.7%, and 5.6% had a history of hypertension, diabetes, hyperlipidemia, and coronary artery disease, respectively. The mean number of visits per patient was 13.3, over an average period of 2.4 years. The mean (SD) intraindividual SD and coefficient of variation of SBP across visits were 10.6 (5.1) mm Hg and 0.08 (0.04). These measures of blood pressure variation were consistent across patient subgroups defined by demographic characteristics and medical history. In the multivariable linear regression model, only 4% of the variance in absolute standardized difference was attributable to patient characteristics. The VVV in real-world practice poses challenges for management of patients with hypertension based on blood pressure readings in outpatient settings and suggest the need to go beyond episodic clinic evaluation.

PS-C12-2: VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND CLINICAL EVENTS IN OLDER PATIENTS RECEIVING HOME MEDICAL CARE: THE OHCARE STUDY

Aim: We investigated the associations of visit-to-visit variability(VVV) of blood pressure (BP) with clinical events (death, hospitalization, falling) in older patient around 85 years old receiving home medical care. Methods: This study was performed in OHCARE (Osaka Home CAre REgistry), which is a prospective cohort study targeted old patients receiving home-based medical care in Japan. There were 103 eligible patients fulfilling the inclusion criteria: aged 65 years or older; BP measurements at least three occasions before the baseline date (median 4.78 occasions); BP measurement interval in 16 ± 13 days (median ± 1SD). We used the standard deviation (SD), Coefficient of variation (CV) of SBP measured at baseline as the VVV of BP. Main outcomes were clinical events including hospitalizations, falling and death during follow-up period. Results: It was clarified that VVV of BP was exists in older patients receiving home medical care (10.7 / 7.2 mmHg). Regarding the relationship between VVV and clinical events during follow-up, the rate of hospitalization was significantly higher in the group with the largest SBP-SD than in the group with the smallest. Furthermore, multivariate analysis adjusted by age, sex, ADL and current diseases showed that SD and CV of SBP were independent positive association of hospitalization events. Conclusion: In older patients with frailty requiring home medical care, a higher VVV in SBP may be related to the occurrence of events leading hospitalizations. Furthermore, higher VVV in SBP could be a predictive marker of clinical events leading to hospitalization.

Baseline risk markers and visit-to-visit variability in relation to kidney outcomes – A post-hoc analysis of the PERL study

BackgroundBaseline risk variables and visit-to-visit variability (VV) of systolic blood pressure (SBP), HbA1c, serum creatinine, and uric acid (UA) are potential risk markers of kidney function decline in type 1 diabetes. MethodsPost-hoc analysis of a double-blind randomized placebo-controlled clinical trial investigating allopurinol’s effect on iohexol-derived glomerular filtration rate (iGFR) in type 1 diabetes with elevated UA. Primary outcome was iGFR change over three years. Linear regression with backwards selection of baseline clinical variables was performed to identify an optimized model forecasting iGFR change. Furthermore, VVs of SBP, HbA1c, serum creatinine, and UA were calculated using measurements from the run-in period; thereafter assessed by linear regression, with iGFR change as the dependent variable. Results404 participants were included in the primary analyses. In the optimized baseline variable model, higher HbA1c, SBP, iGFR, albuminuria, and heart rate, and mineralocorticoid receptor antagonist prescription were associated with greater iGFR decline. Higher VV of SBP was associated with greater iGFR decline (adjusted β (ml/min/1.73 m2/50 % increase): −0.79, p = 0.01). ConclusionsWe identified several risk markers for faster iGFR decline in a high-risk population with type 1 diabetes. While further research is needed, our results indicate possible new and clinically feasible measures to risk stratify for DKD in type 1 diabetes.

Joint effect of visit-to-visit variability in LDL-cholesterol, HDL-cholesterol and HbA1c on cardiovascular and total mortality in patients with diabetes

BackgroundWe aimed to investigate the joint effect of visit-to-visit variability (VVV) in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides and glycosylated hemoglobin (HbA1c) on cardiovascular mortality and total mortality in patients with diabetes.MethodsAmong 5194 participants with type 2 diabetes enrolled in the ACCORD lipid trial, VVVs of LDL-C, triglycerides, HDL-C, and HbA1c were assessed from baseline to 2 years of follow-up and expressed as coefficient of variation (CV). The study outcomes included cardiovascular mortality and all-cause mortality.ResultsOver a median follow-up of 3.0 years from the end of variability measurements at years 2, there were 305 (5.9%) cases of all-cause mortality, of which, 144 were cardiovascular causes. The positive relations between LDL-C CV and cardiovascular mortality were significantly stronger among participants with higher HDL-C CV (P for interaction = 0.023), and higher HbA1c CV (P for interaction = 0.015). However, there were no significant interactions between LDL-C CV and triglycerides CV (P for interaction = 0.591). Similar trends were found for all-cause mortality. Consistently, there were graded trends in the risk of mortality with the increasing numbers of higher CV of the three variables: LDL-C, HbA1c, and HDL-C (P for trend = 0.008 for cardiovascular mortality, and P for trend < 0.001 for all-cause mortality).ConclusionVVVs in LDL-C, HDL-C, and HbA1c may jointly affect the risks of cardiovascular and all-cause mortality in diabetes patients. Those with higher CVs of all three variables had the highest risks of cardiovascular and all-cause mortality.

Visit-to-visit variability in blood pressure and kidney disease progression in IgA nephropathy.

The visit-to-visit variability (VVV) in blood pressure (BP) is an important risk factor for stroke and coronary heart disease and may also be associated with kidney damage and the development of chronic kidney disease (CKD). Data on the association between VVV in BP and the risk of CKD progression among patients with immunoglobulin A nephropathy (IgAN) are limited. We aimed to evaluate the relationships of VVV in BP with the progression of IgAN. We assessed 1376 patients with IgAN at Peking University First Hospital. The main VVV in BP was expressed as the standard deviation (SD), coefficient of variation (CV) and average real variability (ARV). The associations of variability in BP with composite kidney disease progression events, defined as a 50% decline in estimated glomerular filtration rate (eGFR) and kidney failure, were examined using Cox models. During a median follow-up of 44.1months (interquartile range 23.0-76.7), 247 (18.0%) patients experienced composite kidney disease progression events. With a higher SD in systolic BP (SBP) values, the risk of kidney disease progression events increased {hazard ratio [HR] 1.07 [95% confidence interval (CI) 1.03-1.11]; P<.001} after maximal adjustment, including baseline SBP and mean SBP during the first 12-month period. Using the first quartile of SD SBP values as the reference, the risk of composite kidney disease progression events was higher among patients with higher SD SBP values; the HR was 2.12 (95% CI 1.31-3.44) in the highest quartile (P for trend<.001). A similar trend could be observed when analysing the SD of diastolic BP, but the risk was not significantly increased. The associations were similar when analysed with the CV and ARV. SBP variability was significantly associated with kidney disease progression in IgAN.

Age and sex-specific associations of visit-to-visit variability of glycated hemoglobin A1c with all-cause mortality in patients with diabetes.

Background:Visit-to-visit variability (VVV) of glycated hemoglobin (HbA1c) levels have been found to be associated with prognosis of diabetes. However, little is known about whether or to what extent sex and age may modify the effects of VVV.Methods:To investigate age- and sex-specific rates of mortality from all causes and relative hazards of mortality in association with VVV of HbA1c levels, 47,145 patients with diabetes and prescription of any antidiabetic agents >6 months were identified from outpatient visits of a tertiary medical center in northern Taiwan during 2003–2018. VVV of HbA1c was measured by quartiles of standard deviation (SD), coefficient of variation (CV), and average real variability (ARV), respectively. The study subjects were linked to Taiwan’s National Death Registry to identify all-cause mortality. The person-year approach with the Poisson assumption was used to assess the all-cause mortality rates, and Cox proportional hazard regression model was used to evaluate the relative hazards of all-cause mortality concerning various levels of VVV of HbA1c.Results:The lowest all-cause mortality rate was found in either the first or second quartile of various measures for VVV of HbA1c, but the highest mortality rate was consistently observed in the fourth quartile of VVV, regardless of SD, CV, or ARV across ages and sexes. Increased hazards of overall all-cause mortality were noticed from the second to fourth quartile of VVV of HbA1c. In detailed age- and sex-stratified analyses, elevated risk of mortality was seen in the fourth quartile of those aged <50 years while in those aged >69 years, increased risk of mortality was noticed in the third and fourth quartiles of any VVV of HbA1c irrespective of sex. In those aged 50–69 years, incremental increased hazards of mortality were consistently observed in the second to fourth quartiles of VVV of HbA1c.Conclusion:HbA1c variability whether it was SD, CV, or ARV could strongly predict the risks of all-cause mortality. The extent of the relationship between VVV of HbA1c and all-cause mortality in different age groups was comparable between both sexes. Given the importance of long-term glucose fluctuation, the inclusion of HbA1c variability calculated from the standardized method should be considered by clinical guideline policymakers as part of the biochemical panel in daily diabetes management.

Factors, associated with major adverse events in rural males with arterial hypertension at long-term follow-up

Background and Aims : To study the factors, associated with major adverse events (MAEs) in rural males with uncomplicated arterial hypertension (HTN) at long-term follow-up.Methods: The prospective study enrolled 160 rural males with uncomplicated primary HTN (mean age 50 ± 6 years). We analyzed clinical and instrumental data. High-to-very high SCORE cardiovascular risk was identified in 102 (63,7%) patients. Blood pressure visit-to-visit variability (VVV) was assessed by standard deviation and coefficient of variation (CV) (derived from the four consecutive visits). Left ventricular (LV) hypertrophy (by echo) was detected in 129 (80,6%) patients. The median of follow-up was 27 months (interquartile range 24-30 months). During the follow-up period, 14 (8,8%) patients presented with MAEs (totally, 17 events): acute cerebrovascular event (n=9); myocardial infarction (n=2); first-onset atrial fibrillation (AF) (n=2); AF transition in permanent pattern (n=2); and relative LV ejection fraction decline >10% (n=2).Results: At multivariable analysis, the factors, associated with MAEs at long-term follow-up, were as follows: SCORE cardiovascular risk (per 1 % increase: HR 1,09 (95% CI 1,01-1,17); р=0,034); mean arterial pressure (MAP) (per 1 mm Hg increase: HR 1,23 (95% CI 1,07-1,41); р=0,003); CV (MAP) (per 1% increase: HR 1,41 (95% CI 1,08-1,83); р=0,012); and LV myocardial mass, indexed by height2,7 (per 1 g/m2,7 increase: HR 1,07 (95% CI 1,03-1,11); р=0,001).Conclusions: Long-term MAEs in rural HTN males were associated with SCORE cardiovascular risk, MAP, MAP VVV (by CV) and LV myocardial mass index (by height2,7). These factors should be taken into account while MAEs risk stratification in rural males with uncomplicated HTN. Background and Aims : To study the factors, associated with major adverse events (MAEs) in rural males with uncomplicated arterial hypertension (HTN) at long-term follow-up. Methods: The prospective study enrolled 160 rural males with uncomplicated primary HTN (mean age 50 ± 6 years). We analyzed clinical and instrumental data. High-to-very high SCORE cardiovascular risk was identified in 102 (63,7%) patients. Blood pressure visit-to-visit variability (VVV) was assessed by standard deviation and coefficient of variation (CV) (derived from the four consecutive visits). Left ventricular (LV) hypertrophy (by echo) was detected in 129 (80,6%) patients. The median of follow-up was 27 months (interquartile range 24-30 months). During the follow-up period, 14 (8,8%) patients presented with MAEs (totally, 17 events): acute cerebrovascular event (n=9); myocardial infarction (n=2); first-onset atrial fibrillation (AF) (n=2); AF transition in permanent pattern (n=2); and relative LV ejection fraction decline >10% (n=2). Results: At multivariable analysis, the factors, associated with MAEs at long-term follow-up, were as follows: SCORE cardiovascular risk (per 1 % increase: HR 1,09 (95% CI 1,01-1,17); р=0,034); mean arterial pressure (MAP) (per 1 mm Hg increase: HR 1,23 (95% CI 1,07-1,41); р=0,003); CV (MAP) (per 1% increase: HR 1,41 (95% CI 1,08-1,83); р=0,012); and LV myocardial mass, indexed by height2,7 (per 1 g/m2,7 increase: HR 1,07 (95% CI 1,03-1,11); р=0,001). Conclusions: Long-term MAEs in rural HTN males were associated with SCORE cardiovascular risk, MAP, MAP VVV (by CV) and LV myocardial mass index (by height2,7). These factors should be taken into account while MAEs risk stratification in rural males with uncomplicated HTN.

The association of visit-to-visit blood pressure variability with score2 cardiovascular risk in Ukrainian rural males with arterial hypertension

Background and Aims : To study the association of blood pressure (BP) visit-to-visit variability (VVV) with cardiovascular risk, assessed by SCORE2 model, in Ukrainian rural males with arterial hypertension (HTN).

394-P: Baseline Risk Markers and Visit-to-Visit Variability in Relation to Kidney Outcomes: A Post Hoc Analysis of the PERL Study

Background: Baseline risk variables and visit-to-visit variability (VV) of systolic blood pressure (SBP) , HbA1c, serum creatinine, and uric acid (UA) are potential risk markers of kidney function decline in type 1 diabetes. Methods: Post-hoc analysis of the PERL study (NCT02017171) - a double-blind randomized placebo-controlled clinical trial investigating allopurinol’s effect on iohexol-derived glomerular filtration rate (iGFR) in type 1 diabetes with elevated UA. Primary outcome was iGFR change over three years. Linear regression with backwards selection of baseline clinical variables was performed to identify an optimized model forecasting iGFR change. VV of SBP, HbA1c, serum creatinine, and UA were calculated as standard deviations of the residuals in individual linear regression models (LV) and coefficients of variation (CV) using all available measurements in the run-in period; thereafter assessed by linear regression, with iGFR change as the dependent variable. Adjustment included sex, baseline age, diabetes duration, BMI, HbA1c, SBP, kidney function (iGFR or eGFR, as appropriate) , urine albumin excretion rate (UAER) , smoking, and renin-angiotensin system inhibitor use. Results: 422 participants completed the trial, 4were included in this analysis. In the optimized baseline risk marker model, race other (including but not limited to Hawaiian/Pacific Islander) than White, Black, or Asian, higher HbA1c, UAER, and heart rate, and lower iGFR were associated with faster iGFR decline; Hispanic/Latino ethnicity was not. Assessing VV, higher LV and CV of SBP was associated with faster iGFR decline (adjusted LV β: -0.79, p=0.01; CV β: -0.79, p=0.04) ; VVs of HbA1c, creatinine, and UA were not. Conclusions: We identified several risk markers of faster iGFR decline in a high-risk population of individuals with type 1 diabetes. In addition to previously described associations, higher SBP VV was a risk marker for faster kidney function decline. Disclosure V.Rotbain curovic: None. S.Polsky: Advisory Panel; Medtronic, Other Relationship; diaTribe, Research Support; Dexcom, Inc., Eli Lilly and Company, Leona M. and Harry B. Helmsley Charitable Trust, Medtronic, National Institute of Diabetes and Digestive and Kidney Diseases, Sanofi-Aventis U.S. R.Pop-busui: Advisory Panel; Averitas Pharma, Inc., Boehringer Ingelheim International GmbH, Nevro Corp., Novo Nordisk, Reata Pharmaceuticals, Inc., Regenacy Pharmaceuticals, Inc. R.J.Sigal: Advisory Panel; Novo Nordisk Canada Inc., Research Support; Novo Nordisk Canada Inc. K.R.Tuttle: Advisory Panel; Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Consultant; AstraZeneca, Eli Lilly and Company, Research Support; Bayer AG, Goldfinch Bio, Inc., Novo Nordisk, Travere. G.E.Umpierrez: Research Support; AstraZeneca, Dexcom, Inc., Novo Nordisk. A.Wallia: Advisory Panel; Eli Lilly and Company, Research Support; Novo Nordisk, UnitedHealth Group. S.Rosas: Advisory Panel; AstraZeneca, Teladoc Health, Other Relationship; Bayer AG, Research Support; AstraZeneca, Bayer AG. P.Rossing: Consultant; Astellas Pharma Inc., AstraZeneca, Bayer AG, Gilead Sciences, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi, Speaker's Bureau; Eli Lilly and Company. The perl study group: n/a. N.Roy: None. T.W.Hansen: Stock/Shareholder; Novo Nordisk A/S. L.Caramori: Advisory Panel; Bayer AG, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk, Research Support; Bayer AG, Novartis AG. D.Cherney: Other Relationship; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Research &amp; Development, LLC, Lilly, Maze, BMS, CSL-Behring, Merck, Otsuka, Novartis and Novo-Nordisk , Mitsubishi Tanabe Pharma Corporation, Sanofi, Research Support; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. I.De boer: Advisory Panel; AstraZeneca, Bayer AG, Cyclerion Therapeutics, Inc., George Clinical, Goldfinch Bio, Inc., Other Relationship; American Society of Nephrology, Research Support; Dexcom, Inc. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. I.Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S, Consultant; Novo Nordisk, Research Support; NovoNordisk; Mylan; Merck, Sanofi. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. Funding Supported by grants from the NIDDK (R03-DK-094484, R34-DK-097808, UC4-DK-101108, P30-DK-036836, and P30-DK-020572) , the JDRF (17-2012-377) , the National Center for Advancing Translational Sciences (UL1-TR-002494, UL1-TR- 001422, UL1-TR-002556, UL1-TR-002319, and UL1-TR- 001105) , and the National Institute on Aging (Claude Pepper Center grant number, P30-AG-024824)

Novel Strategies for Assessing Associations Between Selenium Biomarkers and Cardiometabolic Risk Factors: Concentration, Visit-to-Visit Variability, or Individual Mean? Evidence From a Repeated-Measures Study of Older Adults With High Selenium.

Background and AimsPrevious studies have focused only on the cardiometabolic effects of selenium concentrations. We explored whether selenium levels and their visit-to-visit variability (VVV) and individual mean (IM) are independently associated with cardiometabolic risk factors.MethodsA three-wave repeated-measures study of older adults with high selenium (n = 201) was conducted in Beijing from 2016 to 2018. Whole blood selenium and urinary selenium concentrations were measured. VVV and IM were used to profile the homeostasis of the selenium biomarkers. Four indicators, namely standard deviation, coefficient of variation, average real variability, and variability independent of the mean, were employed to characterize VVV. We considered 13 cardiometabolic factors: four lipid profile indicators, three blood pressure indices, glucose, uric acid, waistline, hipline, waist-hip ratio, and sex-specific metabolic syndrome score. Linear mixed-effects regression models with random intercepts for the participants were employed to explore the associations of the selenium concentrations, VVV, and IM with the cardiometabolic factors.ResultsThe geometric mean whole blood and urinary selenium levels were 134.30 and 18.00 μg/L, respectively. Selenium concentrations were significantly associated with numerous cardiometabolic factors. Specifically, whole blood selenium was positively associated with total cholesterol [0.22, 95% confidence interval (CI): 0.12, 0.33], low-density lipoprotein cholesterol (LDL-C; 0.28, 95% CI: 0.13, 0.42), glucose (0.22, 95% CI: 0.10, 0.34), and uric acid (0.16, 95% CI: 0.04, 0.28). After adjustment for VVV, the IM of whole blood selenium was positively correlated with total cholesterol (0.002, 95% CI: 0.001, 0.004), triglycerides (0.007, 95% CI: 0.004, 0.011), and LDL-C (0.002, 95% CI: 0.000, 0.004). However, we did not observe any robust associations between the VVV of the selenium biomarkers and cardiometabolic risk factors after adjustment for IM.ConclusionOur findings suggest that selenium concentrations and their IMs are significantly associated with cardiometabolic risk factors among older adults with high selenium. Longer repeated-measures studies among the general population are required to validate our findings and elucidate the relevant underlying mechanisms.

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.

PROGNOSTIC SIGNIFICANCE AND LIMITATION OF VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY IN PATIENTS WITH REDUCED EJECTION FRACTION: A MINI-REVIEW

Visit-to-visit variability (VVV) of blood pressure (BP) can facilitate in predicting future reduced ejection fractions cases. In the recent past, the prognostic significance of visitto-visit variability of BP has been examined widely in patients with a high risk of cardiovascular disease. The findings of numerous investigations have indicated that increased visit-to-visit variability of blood pressure can lead to better estimation or proper treatments that can minimize blood pressure variability and associated risks while enhancing clinical outcomes. However, inconsistent data of the visit-to-visit hypothesis in the post-hoc analysis have also been explored. Therefore, this review discusses recent analysis, background, and reports of the limitations of visit-to-visit blood pressure variability (VVV-BP) and the prognostic significance of visit-to-visit blood pressure variability in populations at high risk of reduced ejection fractions in predictions of future vascular diseases. The role of the antihypertensive drugs is highlighted while describing the clinical implications and future research directions.

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.

Blood pressure visit-to-visit variability and outcomes in patients with heart failure with preserved ejection fraction.

AimsPrevious studies report that blood pressure (BP) variability is associated with increased risk of adverse outcomes in patients diagnosed with cardiovascular disease. However, studies have not fully explored this association in patients with heart failure with preserved ejection fraction (HFpEF). This study sought to explore the association between visit‐to‐visit variability (VVV) of BP and clinical outcomes in patients with HFpEF.Methods and resultsA total of 1988 patients (mean age of 67.73 ± 9.22, 51.7% female) from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included in this study. BP‐VVV was determined by standard deviation (SD) of mean systolic BP (SBP‐SD) from six measurements (baseline and months 1, 2, 4, 8, and 12) during the first 12 months after randomization. Mean on‐treatment SBP during the first 12 months was 127.77 ± 10.42 mmHg, and the median of SBP‐SD was 8.15 mmHg. A total of 192 (9.7%) patients met the primary outcome during the subsequent median follow‐up of 35.16 months, including a composite of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Multiple Cox regression analysis showed that SBP‐SD was independently associated with the increased risk of the primary outcome after adjusting for age, gender, method of BP measurement, treatment, renal function and common co‐morbidities, and the mean SBP during the first 12 months [hazard ratio (HR) for fourth vs. first quartile, 1.63; 95% confidence interval (CI), 1.07–2.49; P = 0.024]. Analysis showed that SBP‐SD as continuous variable was associated with a 23% increase in the risk of primary outcome (HR 1.23, 95% CI 1.06–1.43; P = 0.006).ConclusionsThe findings of the current study show that high SBP‐VVV in patients with HFpEF is associated with an increased risk of adverse outcomes independent of the mean on‐treatment SBP.

Visit-to-visit blood pressure variability in rural males with arterial hypertension: the association with the score cardiovascular risk and risk age

Background and Aims: To study the association of blood pressure (BP) visit-to-visit variability (VVV) with cardiovascular risk and risk age, assessed by the SCORE model, in rural males with arterial hypertension (HTN).

Long-term glucose variability and incident cardiovascular diseases and all-cause mortality events in subjects with and without diabetes: Tehran Lipid and Glucose Study

AimTo examine whether visit to visit variability (VVV) of fasting plasma glucose (FPG) is associated with incident cardiovascular diseases (CVD) and all-cause mortality in individuals with and without type 2 diabetes (T2D). MethodsA total of 4756 participants aged ≥30 years entered the study in 2002–2005 and underwent two subsequent examinations in 2005–2008 and 2008–2011. FPG variability measures included standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of mean (VIM). Multivariate Cox proportional hazard models were used to assess the risk of incident CVD and all-cause mortality for each unit increase in different FPG variability measures. ResultsDuring a median follow-up of 18.14 years after baseline recruitment, 492 incident cardiovascular diseases and 338 all-cause mortality were recorded. Among individuals without T2D, the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD were 1.02 (1.01–1.04), 1.02 (1.01–1.04), 1.01 (1.00–1.02), and 1.01 (1.00–1.01) for SD, CV, ARV, and VIM, respectively (all P-values <0.05). Among individuals with T2D, the corresponding HRs and 95% CIs for all-cause mortality were 1.01 (1.00–1.02), 1.02 (1.01–1.03), 1.01 (1.00–1.02), and 1.01 (1.00–1.01), respectively (all P-values <0.05). ConclusionLong-term (VVV) of FPG is significantly associated with increased risk of CVD among participants without T2D, and all-cause mortality among participants with T2D.

Impact of visit-to-visit blood pressure variability on hypertensive-mediated target organ damage and future cardiovascular events: the Campania salute network.

Exaggerated variability of blood pressure (BP) poses additional stress on cardiovascular system independent of BP average value, increasing risk of target organ damage (HMOD) and cardiovascular events. We assessed the impact of visit-to-visit variability (VVV) of BP on development of cardiovascular events and HMOD. Standard deviation (SD) and coefficient of variability of mean SBP and DBP were calculated in 3555 patients from the Campania Salute Network registry, with available echocardiogram and more than six visits during follow-up. Values from the first visit were excluded. The impact of VVV of BP on cardiovascular events, and mediation of HMOD were assessed at final visit. Mean number of visits was 11 ± 6 with mean interval between visits of 9.1 ± 3.7 months. Mean visit-to-visit SD during follow-up was 13 ± 5 for systolic and 8 ± 3 mmHg for DBP; coefficients of variability were 9.7 ± 3.5 and of 9.6 ± 3.2, respectively. In multivariable analysis, left ventricular mass at follow-up was correlated with systolic VVV of BP independently of significant effect of age, BMI, mean SBP during follow-up and initial left ventricular mass. Follow-up GFR was inversely associated with systolic and diastolic VVV, independently of significant effect of age, mean glucose and SBP during follow-up, and initial GFR. In Cox regression, high VVV of BP was also associated with increased risk of cardiovascular events (hazard ratio 1.49, 95% confidence interval 1.08-2.06, P = 0.015), independently of significant effect of HMOD. VVV is associated with prevalent HMOD and development of cardiovascular events, independently of mean BP value during follow-up and HMOD.

Visit-to-visit variability of blood pressure and cardiovascular events among the working-age population in Japan: findings from the Japan Epidemiology Collaboration on Occupational Health Study.

Increased visit-to-visit variability (VVV) of blood pressure, which is calculated based on several readings, has been suggested to be a significant predictor of cardiovascular events and mortality, independent of mean blood pressure. This study examined associations between the VVV of systolic blood pressure (SBP) measured annually and cardiovascular disease (CVD) events among 72,617 Japanese subjects. Data were obtained from the Japan Epidemiology Collaboration on Occupational Health Study, which is an ongoing epidemiological survey of workers in Japan. VVV was calculated as the coefficient of variation of SBP readings from 2008 to 2011; information on fatal and nonfatal CVD events was collected from registries of specific outcomes between April 2012 and March 2019. A Cox proportional hazards model was applied to investigate associations after adjusting for mean SBP between 2008 and 2011 and covariates. During the 7-year follow-up period, there were 63 CVD fatalities and 314 CVD events (combining fatal and nonfatal events). The results showed that a one-standard deviation increase in VVV was associated with a significant increase in the risk of CVD mortality (hazard ratio [HR] = 1.42; 95% confidence interval [CI] = 1.32-1.54); those in the highest tertile had a 3.20 times (95% CI = 1.26-8.17) higher risk of CVD mortality than those in the lowest tertile. We found less pronounced associations regarding CVD events (HR = 1.08, 95% CI = 1.02-1.15). In conclusion, VVV was significantly associated with CVD mortality in our Japanese working population.