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.

BACKGROUND: The 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. METHODS: The 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. RESULTS: During 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). CONCLUSION: Although 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.

Blood pressure measurement and adverse pregnancy outcomes: A cohort study testing blood pressure variability and alternatives to 140/90 mmHg.

OBJECTIVE: To examine the association with adverse pregnancy outcomes of: (1) American College of Cardiology/American Heart Association blood pressure (BP) thresholds, and (2) visit-to-visit BP variability (BPV), adjusted for BP level. DESIGN: An observational study. SETTING: Analysis of data from the population-based UK Southampton Women's Survey (SWS). POPULATION OR SAMPLE: 3003 SWS participants. METHODS: Generalised estimating equations were used to estimate crude and adjusted relative risks (RRs) of adverse pregnancy outcomes by BP thresholds, and by BPV (as standard deviation [SD], average real variability [ARV] and variability independent of the mean [VIM]). Likelihood ratios (LRs) were calculated to evaluate diagnostic test properties, for BP at or above a threshold, compared with those below. MAIN OUTCOME MEASURES: Gestational hypertension, severe hypertension, pre-eclampsia, preterm birth (PTB), small-for-gestational-age (SGA) infants, neonatal intensive care unit (NICU) admission. RESULTS: A median of 11 BP measurements were included per participant. For BP at ≥20 weeks' gestation, higher BP was associated with more adverse pregnancy outcomes; however, only BP <140/90 mmHg was a good rule-out test (negative LR <0.20) for pre-eclampsia and BP ≥140/90 mmHg a good rule-in test (positive LR >8.00) for the condition. BP ≥160/110 mmHg could rule-in PTB, SGA infants and NICU admission (positive LR >5.0). Higher BPV (by SD, ARV, or VIM) was associated with gestational hypertension, severe hypertension, pre-eclampsia, PTB, SGA and NICU admission (adjusted RRs 1.05-1.39). CONCLUSIONS: While our findings do not support lowering the BP threshold for pregnancy hypertension, they suggest BPV could be useful to identify elevated risk of adverse outcomes.

Assessment of visit-to-visit variability in systolic blood pressure over 5 years and phasic left atrial function by two-dimensional speckle-tracking echocardiography.

Visit-to-visit variability in systolic blood pressure (VVV-SBP) has been associated with increased cardiac events. Hence, volume analysis by two-dimensional speckle-tracking echocardiography (2-DSTE) allows physicians to easily measure phasic left atrial (LA) function. However, the relationship of VVV-SBP and functional deformation of the left atrium with patients' clinical outcome is unclear. The aim of the study was to investigate the relationship between phasic LA function and VVV-SBP. The subjects were 70 male participants in whom 2-DSTE was performed to measure blood pressure at health check-ups every year for 5 years. The standard deviation of systolic blood pressure (SBP) was calculated to assess VVV-SBP. The average SBP (Ave-SBP) was also assessed. Total emptying function (EF) (reservoir function), passive EF (conduit function), and active EF (booster pump function) of the left atrium were calculated to evaluate phasic LA function by 2-DSTE. The Pearson correlation, simple regression analysis, and multivariate logistic regression analysis were used in data analysis. Participants' mean age was 50 ± 10 years, and 16 participants had hypertension. VVV-SBP correlated with total EF (r = - 0.30, p = 0.014) and active EF (r = - 0.35, p = 0.003). There was no correlation between the standard deviation of SBP and passive EF (r = - 0.10, p = 0.39). Ave-SBP had no significant relationship with total EF (r = - 0.06, p = 0.62), passive EF (r = - 0.08, p = 0.50), or active EF (r = - 0.03, p = 0.78). Active EF was also associated with VVV-SBP in multiple regression analysis. The active EF was significantly decreased in the highest quartile of VVV-SBP. Despite the small sample size of our study, the VVV-SBP showed a relationship with the phasic LA function. Our findings suggest that high VVV-SBP is noted to be associated with cardiovascular risk including a deterioration of LA function in clinical practice.

Associations of visit-to-visit variabilities and trajectories of serum lipids with the future probability of type 2 diabetes mellitus.

BACKGROUND: Serum lipid abnormalities are generally considered as a major risk factor for type 2 diabetes mellitus (T2DM). However, evidence for the effect of long-term serum lipid fluctuations on future T2DM probability remains limited. METHODS: A total of 4475 nondiabetic participants who underwent annual health examinations between 2010 and 2013 were followed for the subsequent 5-year risk of T2DM. The Cox proportional hazards model was performed to evaluate the associations of visit-to-visit variabilities and trajectories of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) with T2DM probability. RESULTS: During the five-year follow-up, 223 newly developed T2DM cases were identified. Compared with the "Low" TG trajectory, "Moderate" and "Moderate-High" TG trajectories were significantly associated with T2DM incidence, with adjusted hazard ratios (HRs) and 95 % confidence intervals (CIs) of 1.51 (1.12-2.03) and 2.55 (1.62-4.03), respectively. Additionally, participants in the third and fourth quartiles of TG/standard deviation (SD) were associated with increased T2DM probability when compared with those in the lowest quartile. After excluding individuals with prediabetes, participants with "Moderate-High" TG trajectory still had a 2.43-fold greater risk of T2DM compared with those with "Low" TG trajectory (95 % CI: 1.28-4.63). In addition, compared with participants in "Low" HDL-c trajectory, the future T2DM probability was significantly reduced in those with "Moderate" and "High" HDL-c trajectories, with HR (95 % CI) of 0.52 (0.37-0.72) and 0.38 (0.18-0.80), respectively. After excluding individuals with prediabetes, the "Moderate" HDL-c trajectory remained associated with decreased T2DM probability when compared with "Low" HDL-c trajectory (HR: 0.55, 95 % CI: 0.35-0.88). However, the incidence of T2DM was not associated with the long-term fluctuations of TC and LDL-c. CONCLUSIONS: Long-term visit-to-visit variability of TG, and the change trajectories of TG and HDL-c were significantly associated with future T2DM probability. Moreover, these associations were not affected after excluding individuals with prediabetes.

Visit-to-visit variability in blood pressure and the development of chronic kidney disease in treated general hypertensive patients.

BACKGROUND: Data on the association between visit-to-visit variability (VVV) in blood pressure (BP) and the risk of chronic kidney disease (CKD) in general treated hypertensive patients were limited. We aimed to evaluate the relation of VVV in BP with the development of CKD, and examine any possible effect modifiers in hypertensive patients without prior cardiovascular diseases (CVDs) or CKD. METHODS: This is a post hoc analysis of the Renal Sub-study of the China Stroke Primary Prevention Trial (CSPPT). A total of 10 051 hypertensives without CVD and CKD and with at least six visits of BP measurements from randomization to the 24-month visit were included. The main VVV in BP was expressed as standard deviation (SD). The primary outcome was the development of CKD, defined as a decrease in estimated glomerular filtration rate ≥30% and to a level of <60 mL/min/1.73 m2, or end-stage renal disease. RESULTS: The median treatment duration was 4.4 years. After multivariable adjustment, including baseline systolic blood pressure (SBP) and mean SBP during the first 2-year treatment period, there was a significantly positive relationship of SD of SBP with the risk of CKD development (per SD increment; odds ratio, 1.27; 95% confidence interval: 1.10-1.46). The results were similar for coefficient of variation (CV) of SBP. Results across various subgroups, including age, sex, SBP at baseline, treatment compliance, concomitant antihypertensive medications and mean SBP during the first 24-month treatment period, were consistent. CONCLUSIONS: SBP variability, irrespective of mean BP level, was significantly associated with the development of CKD in general treated hypertensive patients.

Impact of visit-to-visit variability in blood pressure on coronary plaque as assessed by integrated backscatter intravascular ultrasound.

INTRODUCTION: Visit-to-visit variability (VVV) in blood pressure (BP) has been reported to be a strong predictor of cardiovascular disease. However, the association between VVV in BP and coronary plaque composition has not been fully elucidated. METHODS: One hundred-two consecutive patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) using integrated backscatter (IB) intravascular ultrasound (IVUS), and who had at least six clinic visits a year before PCI were included. We measured systolic and diastolic BP (SBP and DBP) at each visit and determined VVV in BP expressed as the standard deviation of the average BP. Grayscale and IB IVUS examinations were performed for the culprit lesion of a coronary artery just before PCI. RESULTS: There were no significant associations between the average SBP or DBP and various IVUS parameters. However, VVV in SBP was positively correlated with both the percentage (%) of atheroma volume (ß = 0.23, p = .02) and % lipid volume (ß = 0.53, p < .0001). VVV in DBP was positively correlated with % lipid volume (ß = 0.24, p = .01), while there was no significant correlation between VVV in DBP and % atheroma volume. A  multivariable linear regression analysis showed that VVV in SBP was independently associated with % atheroma volume (p = .04) and % lipid volume (p < .001). CONCLUSIONS: Larger VVV in SBP was significantly associated with an increased plaque burden and lipid composition at the culprit lesion of a coronary artery in CAD patients. The improvement of VVV in SBP may contribute to the regression and stabilization of coronary plaques.

Visit-to-Visit B-Type Natriuretic Peptide Variability during the Previous Year Has Independent Prognostic Value in Patients with Stable Chronic Heart Failure.

BACKGROUND: There is wide variability of visit-to-visit (V2V) B-type natriuretic peptide (BNP) in patients with chronic heart failure (CHF), even when they are stable. The prognostic significance of V2V-BNP variability has not been investigated. We aimed to test whether V2V-BNP variability during the stable period of CHF has prognostic value regardless of BNP level. METHODS: In 278 stable outpatients (75 ± 10 years, 65% male) with CHF, we studied V2V-BNP variability, which was defined as the coefficient of variance of BNP values measured during 1 year before enrollment. All-cause death and rehospitalization due to HF were considered the primary endpoint. RESULTS: The median V2V-BNP variability was 25.7% (IQR: 19.2-34.4%). During the follow-up period (median 3.2 years), 100 patients reached the endpoint and those with high V2V-BNP variability (≥25.7%) had a significantly higher rate of events (p = 0.001). CHF severity in terms of BNP level and MAGGIC risk score was not significantly different between those with high and low V2V-BNP variability. Multivariable analysis showed that high V2V-BNP variability was independently associated with increased event rates even after adjustment for other known prognostic predictors, including BNP (hazard ratio 1.90, p = 0.003), or for MAGGIC risk score and BNP (hazard ratio 1.72, p = 0.010). The hazard for the outcome consistently increased as V2V-BNP variability increased, with a marked increase up to about 30%. CONCLUSIONS: Even in the stable phase of CHF, V2V-BNP variability was associated with worse long-term outcomes, independent of BNP level.

Visit-to-visit blood pressure variability in children and adolescents with renal disease.

BACKGROUND: Increase in blood pressure (BP) variability (BPV) is associated with cardiovascular events, target organ damage, and arterial stiffness in adults. We previously reported that 24-h BPV may be associated with arterial stiffness and underlie white-coat hypertension (WCH). In this study, we examined whether visit-to-visit variability (VVV) could predict WCH and whether VVV correlated with eGFR, eGFR slope, and albuminuria/proteinuria in children and adolescents with renal diseases. METHODS: VVV was determined as average real variability of office BP measurements between visits, and 24-h BPV as the standard deviation of 24-h ambulatory BP. In 35 renal patients (25 boys and 10 girls, 7-18 years of age), divided into normotension (NT), WCH, and hypertension (HTN), the relationships between VVV and 24-h BPV and VVV in each BP category were studied. In separate 48 renal patients (24 boys and 24 girls, 2-18 years of age), the correlation between VVV and eGFR, eGFR slope, urine albumin or protein excretion was examined. RESULTS: Systolic VVV was significantly correlated with systolic office BP index. There was no correlation between VVV and 24-h BPV or 24-h pulse pressure. In addition, VVV was not different among NT, WCH, and HTN. Systolic VVV was significantly negatively correlated with eGFR but not with eGFR slope, albuminuria, or proteinuria. A cut-off value of systolic VVV for detecting eGFR < 60 ml/min per 1.73 m2 was 8.5. CONCLUSION: VVV could not predict WCH. Systolic VVV correlated with eGFR but not with eGFR slope, albuminuria/proteinuria. Increased VVV could be a marker of decreased eGFR.

Visit-to-visit variability of blood pressure and cardiovascular outcomes in patients with stable coronary heart disease. Insights from the STABILITY trial.

AIMS: To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease. METHODS AND RESULTS: In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0) mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events. CONCLUSION: In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP.

Association between visit-to-visit clinic blood pressure variability and home blood pressure variability in patients with chronic kidney disease.

Although both clinic blood pressure (BP) variability and home BP variability are associated with the risk of cardiovascular disease, the relationship between both BP variabilities remain unclear. We evaluated the association between visit-to-visit variability of clinic BP (VVV) and day-by-day home BP variability (HBPV) in patients with chronic kidney disease (CKD). We recruited 143 CKD patients in whom we performed HBP measurements every morning and evening over seven consecutive days. We obtained clinic BP data during 9.6 ± 1.0 consecutive visits within 24 months. The associations between the variables of VVV and HPBV were examined. The CV values of clinic systolic BP (CSBP) was significantly correlated with the mean values of morning systolic BP (MSBP) and those of evening systolic BP (ESBP) (r = 0.23, 0.20; p = 0.007, 0.02, respectively). The CV values of CSBP was significantly correlated with the CV values of MSBP and those of ESBP (r = 0.19, 0.31; p = 0.02, <0.001, respectively). On the multivariate regression analysis, the CV values of CSBP was significantly correlated with the CV values of MSBP and those of ESBP [standardized regression coefficient (ß) = 0.19, 0.34; p = 0.03, <0.001, respectively]. In conclusion, VVV showed a weak but significant association with HBPV, especially the CV values of ESBP in CKD patients. Further studies are necessary to clarify whether these different BPV elements will be alternative marker of BPV.

Visit-to-visit variability in blood pressure and kidney and cardiovascular outcomes in patients with type 2 diabetes and nephropathy: a post hoc analysis from the RENAAL study and the Irbesartan Diabetic Nephropathy Trial.

BACKGROUND: Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy. STUDY DESIGN: Observational analysis of IDNT (Irbesartan Diabetic Nephropathy Trial) and the RENAAL (Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study. SETTING & PARTICIPANTS: 2,739 participants with type 2 diabetes and nephropathy with at least 1 year of blood pressure measurements available. PREDICTORS: Systolic blood pressure visit-to-visit variability was calculated from the SD of the systolic blood pressure from 4 visits occurring 3-12 months postrandomization. OUTCOMES: The kidney disease outcome was defined as time to confirmed doubling of serum creatinine level, end-stage renal disease, or death; the cardiovascular outcome was defined as time to cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization. RESULTS: Mean visit-to-visit variability in systolic blood pressure from 3 to 12 months postrandomization was 12.0±6.8(SD)mmHg. Following this ascertainment period, there were 954 kidney disease and 542 cardiovascular events. Greater systolic blood pressure visit-to-visit variability was associated independently with increased risk of the composite kidney disease end point (HR per 1-SD increment, 1.08 [95%CI, 1.01-1.16]; P=0.02) and end-stage renal disease, but not with the cardiovascular outcome. LIMITATIONS: Observational study with the potential for confounding. CONCLUSIONS: In diabetic individuals with nephropathy, systolic blood pressure visit-to-visit variability is associated independently with hard kidney disease outcomes.

Visit-to-visit variability in multiple biological measurements and cognitive performance and risk of cardiovascular disease: A cohort study.

Background: Visit-to-visit variability in single biological measurements has been associated with cognitive decline and an elevated risk of cardiovascular diseases (CVD). However, the effect of visit-to-visit variability in multiple biological measures is underexplored. We investigated the effect of visit-to-visit variability in blood pressure (BP), heart rate (HR), weight, fasting plasma glucose, cholesterol, and triglycerides on cognitive performance and CVD. Methods: Data on BP, HR, weight, glucose, cholesterol, and triglycerides from study visits in the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were used to estimate the association between visit-to-visit variability, cognitive performance (Mini Mental State Examination (MMSE) score) and CVD (non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death). Visit-to-visit variation for each measurement was estimated by calculating each individuals visit-to-visit standard deviation for that measurement. Participants whose standard deviation was in the highest quarter were classified as having high variation. Participants were grouped into those having 0, 1, 2, 3, or ≥ 4 high variation measurements. Regression and survival models were used to estimate the association between biological measures with MMSE and CVD with adjustment for confounders and mean measurement value. Results: After adjustment for covariates, higher visit-to-visit variability in BP, HR, weight, and FPG were associated with poorer MMSE and a higher risk of CVD. Effect sizes did not vary greatly by measurement. The effects of high visit-to-visit variability were additive; compared to participants who had no measurements with high visit-to-visit variability, those who had high visit-to-visit variability in ≥4 measurements had poorer MMSE scores (-0.63 (95 % CI -0.96 to -0·31). Participants with ≥4 measurements with high visit-to-visit variability compared to participants with none had higher risk of CVD (hazard ratio 2.46 (95 % CI 1.63 to 3.70). Conclusion: Visit-to-visit variability in several measurements were associated with cumulatively poorer cognitive performance and a greater risk of CVD.

Age-Specific Association Between Visit-to-Visit Blood Pressure Variability and Hearing Loss: A Population-Based Cohort Study.

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 3,939 adults over 50 years from the Health and Retirement Study in the United States. Variabilities of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were assessed by standard deviation (SD), coefficient of variation, and variability independent of the mean (VIM), using SBP and DBP from 3 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 (hazard ratio [HR] per SD 1.36, 95% confidence interval [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 > .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.

Systolic blood pressure visit-to-visit variability and outcomes in Asian patients with atrial fibrillation.

We aimed to assess the association between SBP-VVV and outcomes in Asian patients with atrial fibrillation (AF). AF patients in the COOL-AF registry with SBP measured at baseline, and at least two other visits were studied. We defined SBP-VVV using the standard deviation (SD) of average SBP. Patients were categorized according to the quartiles of SBP SD. The associations between SBP-VVV and outcomes were assessed in the adjusted Cox model. We studied 3172 patients (mean age 67.7 years; 41.8% female), with the prevalence of hypertension being 69%. Warfarin was used in 69% of patients, whereas 7% received non-vitamin K antagonist oral anticoagulants. The minimum and maximum SD of average SBP in the study population was 0.58 and 56.38 mmHg respectively. The cutoff of SD of average SBP for each quartile in our study were 9.09, 12.15, and 16.21 mmHg. The rates of all-cause mortality, ischemic stroke or systemic embolization (SSE), major bleeding, and intracranial hemorrhage (ICH) were 3.10, 1.42, 2.09, and 0.64 per 100 person-years, respectively. Compared with the first quartile, patients in the fourth quartile had a significantly higher risk of mortality (adjusted HR 1.60, 95%CI 1.13-2.25), bleeding (aHR 1.92, 95%CI 1.25-2.96) and ICH (aHR 3.51, 95%CI 1.40-8.76). The risk of SSE was not significantly different among the quartiles. SBP-VVV had a significant impact on the long-term outcomes of Asian patients with AF, particularly mortality and bleeding. Adequate SBP control and maintaining SBP stability over time may improve outcomes for AF patients.

LDL Cholesterol Variability Impacts the Prognosis of Patients with Chronic Ischemic Heart Disease: A Real-World Italian Experience.

Epidemiologic, genetic, and clinical intervention studies have indisputably shown that low-density lipoprotein cholesterol (LDL-C) is causal in the development of atherosclerotic cardiovascular disease (ASCVD). However, LDL-C variability could be related to increased ASCVD risk in patients already treated with statins. The aim of the present retrospective real-life study was to assess the prognostic impact of LDL-C variability on all-cause mortality and cardiovascular hospitalizations in patients with stable cardiovascular artery disease. A total of 3398 patients were enrolled and followed up for a median of 56 months. Considering LDL-C < 70 mg/dL as the therapeutical target, during follow-up, the percentage of patients who achieved this goal raised from 20.7% to 31.9%. In total, 1988 events were recorded, of which 428 were all-cause deaths and 1560 were cardiovascular hospitalizations. At the last medical examination, each increase in LDL-C levels of 20 mg/dL corresponded to a 6% raise in the risk of any event (HR 1.06; 95%CI, 1.03 to 1.09). In conclusion, our real-world study supports the hypothesis that a continuous and progressive downward trend in LDL-C levels is needed to achieve and maintain a cardiovascular benefit, at least in secondary prevention.

Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study.

Background We aimed to examine separate and joint associations of remnant cholesterol (RC) accumulation and variability with the risk of carotid atherosclerosis (CAS) in the general population. Methods and Results A total of 6213 participants who underwent 3 sequential health examinations during 2010 to 2015 were enrolled and were followed up until December 31, 2021. Cumulative RC (cumRC) and RC variability among the 3 visits were the exposure of interest in our study. Adjusted Cox models were performed to calculate the hazard ratio (HR) and 95% CI. C-statistics, integrated discrimination improvement, and the net reclassification index were used to estimate the incremental predictive ability. During a median follow-up of 4.00 years, 2613 participants developed CAS. Higher cumRC (HR, 1.33 [95% CI, 1.17-1.52]) and greater RC variability (HR, 1.22 [95% CI, 1.08-1.39]) were significantly associated with elevated risk of CAS, independent of traditional cardiovascular risk factors and low-density lipoprotein cholesterol. Participants were divided into 4 groups according to the median of cumRC and RC variability to assess their joint associations. Compared with "low cumRC and low variability," "high cumRC and high variability" had the highest risk of CAS, followed by "high cumRC and low variability" and "low cumRC and high variability." Finally, joint assessment of RC accumulation and variability had the significantly highest incremental effect on the predictive value of CAS versus single-time-point measures of RC. Conclusions Excessive cumRC levels and greater RC variability were each independently associated with higher incidence of CAS, and their coexistence could further yield significantly higher risks.

Visit-to-visit variability in albuminuria predicts renal function deterioration in patients with type 2 diabetes.

AIMS/INTRODUCTION: We aimed to study the predictive ability of visit-to-visit variability in albuminuria for changes in renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: The cohort study was carried out in a single medical center. In the model development cohort of 1008 subjects, we developed the albuminuria variability score (AVS) to evaluate the visit-to-visit variability in albuminuria, which was the percentage of the number of changes in the urine albumin : creatinine ratio ≥3.39 mg/mmol among all visit-to-visit urine albumin : creatinine ratio differences within an individual. Multivariate logistic regression was applied to predict the influence of AVS levels on the occurrence of study end-points. In another independent validation cohort of 310 participants, survival analysis was carried out to evaluate the ability of AVS in predicting the study end-point. RESULTS: In the model development cohort, a higher AVS was associated with higher adjusted odds of having a declined or rapidly declined estimated glomerular filtration rate (eGFR) trajectory (1.84, 95% confidence interval 1.23-2.76 and 5.70, 95% confidence interval 2.28-14.25, respectively), a resultant eGFR <60 mL/min/1.73 m2 (2.61, 95% confidence interval 1.63-4.16) and a >40% decline in eGFR from baseline (6.44, 95% confidence interval 2.15-19.26). In the validation cohort, a higher AVS independently predicted a 5-year decrease of >40% in eGFR to <60 mL/min/1.73 m2 (adjusted hazard ratio 3.33, 95% confidence interval 1.10-10.05). Integrated discrimination index and concordance statistics showed that AVS significantly improved the predictive ability of the models. CONCLUSIONS: Visit-to-visit variability in albuminuria can independently predict long-term renal function deterioration in patients with type 2 diabetes mellitus. Further investigations are warranted to elucidate the potential clinical applications.

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 Aims: Previous 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. Methods: A 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. Results: The 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. Conclusion: Our 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.

BACKGROUND: Little 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). METHODS: We 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). RESULTS: A 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. CONCLUSIONS: The VVV in FPG was significantly associated with risks of diabetes in Chinese adults, which was partially mediated by changes in IR.

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai.

OBJECTIVE: This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease (CKD) in Shanghai community residents. METHODS: We used data from a cohort study of community residents who participated in three examinations in 2008, 2009, and 2013, respectively. Fasting plasma glucose (FPG) level, blood pressure (BP), and lipid levels were determined in 2,109 participants at all three visits, and CKD was evaluated between the second and the third visits. Visit-to-visit variabilities in metabolic factors were described by coefficients of variation (CV) at three visits. A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV. CKD was defined as the estimated glomerular filtration rate < 60 mL/min per 1.73 m 2 or urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS: A total of 200 (9.5%) participants had CKD at the third visit. Compared with the lowest quartile of CV, the highest quartile was associated with a 70% increased risk of CKD for FPG [odds ratio, OR = 1.70; 95% confidence interval ( CI) 1.06-2.72], 62% for systolic BP ( OR = 1.62, 95% CI 1.04-2.50), and 85% for low-density lipoprotein cholesterol ( OR = 1.85, 95% CI 1.23-2.80). Furthermore, the risk of CKD increased significantly with an increasing variability score. Compared with participants with score 0, participants with scores of 1, 2, and 3 were associated with 58% ( OR = 1.58, 95% CI 1.08-2.32), 121% ( OR = 2.21, 95% CI 1.40-3.49), and 548% ( OR = 6.48, 95% CI 3.18-13.21) higher risks of CKD, respectively. CONCLUSION: The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.