High Variability Group Research Articles

High tacrolimus trough level variability is associated with rejections after heart transplant.

Tacrolimus, the major immunosuppressant after heart transplant (HTx) therapy, is a narrow therapeutic index drug. Hence, achieving stable therapeutic steady state plasma concentrations is essential to ensure efficacy while avoiding toxicity. Whether high variability in steady state concentrations is associated with poor outcomes is unknown. We investigated the association between tacrolimus trough level variability during the first year post-HTx and outcomes during and beyond the first postoperative year. Overall, 72 patients were analyzed for mortality, of whom 65 and 61 were available for rejection analysis during and beyond the first year post-HTx, respectively. Patients were divided into high (median >28.8%) and low tacrolimus level variability (<28.8%) groups. Mean tacrolimus levels did not differ between the groups (12.7 ±3.4 ng/mL vs 12.8 ±2.4 ng/mL, P=.930). Patients in the high variability group exhibited higher long-term rejection rate (median total rejection score: 0.33 vs 0, P=.04) with no difference in rejection scores within the first year post-HTx. Multivariate analysis showed that high tacrolimus trough level variability was associated with >8-fold increased risk for any rejection beyond the first year post-HTx (P=.011). Mortality was associated only with cardiovascular complications (P=.018), with no effect of tacrolimus through level variability.

Variability of serum phosphorus and itsassociation with mortality among hemodialysis patients .

To determine the relationship between the variability of serum phosphorus and mortality among maintenance hemodialysis (MHD) patients. A total of 502 MHD cases were studied from the Shanghai Renal Registry Network. Serum phosphorus variability was indicated by a coefficient of variation (CV). According to the CV median of serum phosphorus, patients were divided into two groups: a high-variability group (CV≥0.226 mmol/L) and a low-variability group (CV<0.226 mmol/L). Average phosphorus ≤1.78 mmol/L was defined as the standard phosphorus group and serum phosphorus >1.78 mmol/L was defined as the non-standard phosphorus group. The relationship between serum phosphorus variability and all-cause and cardiovascular disease (CVD) mortality was assessed. In the 502 MHD cases, the average age of patients was 63.9 ± 14.60 years, and dialysis vintage was 82.0 (43.0 - 139.0) months. 118 patients (23.5%) died, succumbing to all-cause mortality, while 64 patients (14.3%) died from CVD. The high-variability group had increased all-cause mortality (27.7% vs. 19.3%, p=0.028). Death from CVD was increased in the high-variability group, but had no statistical significance (15.4% vs. 10.0%, p=0.082). Cox regression analysis showed that older age, low hemoglobin levels, a higher phosphorus CV, and low serum albumin were independent risk factors for all-cause and CVD mortality. The standard group with low-phosphorus variability had a decreased mortality compared with the non-standard group with high variability (15.3 vs. 29.2%, p=0.047 and 6.0 vs. 15.0%, p=0.033, respectively). The Kaplan-Meier method revealed that patients with low phosphorus variability had a decreased all-cause and CVD mortality (p=0.023 and p=0.047, respectively) compared with high phosphorus variability patients. Higher phosphorus CV was independently correlated with all-cause and CVD mortality. Low phosphorus variability with on-target levels resulted in decreased patient mortality. Thus, stable serum phosphorus levels may improve survival in MHD patients. .

Gait Variability Can Predict the Risk of Cognitive Decline in Cognitively Normal Older People

Background: The aim of this study was to investigate the association of gait speed and gait variability, an index of how much gait parameters, such as step time, fluctuate step-to-step, with risk of cognitive decline in cognitively normal elderly individuals. While high gait variability is emerging as an early indicator of dementing illnesses, there is little research on whether high gait variability predicts cognitive decline in cognitively normal elderly who have no evidence of cognitive impairment. Methods: In this 4-year prospective cohort study on 91 community-dwelling cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism, we evaluated gait speed and step time variability using a tri-axial accelerometer placed on the center of body mass, and diagnosed mild cognitive impairment (MCI) according to the International Working Group on MCI. We performed Kaplan-Meier analysis with consecutive log-rank testing for MCI-free survival by cohort-specific tertiles of gait speed; hazard ratios (HR) of incident MCI were estimated using Cox proportional hazards regression analysis adjusted for age, sex, education level, Cumulative Illness Rating Scale score, GDS score, and presence of the apolipoprotein E ε4 allele. Results: Out of the 91 participants in the baseline assessment, 87 completed one or more 2-year follow-up assessments, and the median duration of follow-up was 47.1 months. Kaplan-Meier curves of incident MCI show evident differences in risk by gait variability group (χ² = 9.64, p = 0.002, log-rank test). Mean MCI-free survival in the high variability group was 12% shorter than in the mid-to-low tertile group (47.4 ± 1.74 [SD] vs. 54.04 ± 0.52 months), while it was comparable between gait speed groups (51.59 ± 0.70 vs. 50.64 ± 1.77 months; χ² = 1.16, p = 0.281). In multivariate analysis, subjects with high gait variability showed about 12-fold higher risk of MCI (HR = 11.97, 95% CI = 1.29–111.37) than those with mid-to-low variability. However, those with slow gait speed showed comparable MCI risk to those with mid-to-high speed (HR = 5.04, 95% CI = 0.53–48.18). Conclusions: Gait variability may be a better predictor of cognitive decline than gait speed in cognitively normal elderly individuals without cerebral ischemic burden or Parkinsonism.

AMBULATORY BLOOD PRESSURE VARIABILITY- THE HIGHER THE WORST?

Objective: Our goal was to establish a normal range for blood pressure variability (BPV) defined by average real variability (ARV) and to assess whether it can be considered as an additional cardiovascular risk factor. Design and method: In contrast to one of our previously published study, which included 110 patients, we selected 80 inefficiently treated hypertensive patient, admitted to County Clinical Hospital Turgu Mures, Romania to adjust hypertensive treatment. The definition of hypertension was based on 24-hour ambulatory BP monitoring (ABPM), by using a validate device (ABPM 05, Meditech Ltd, Hungary®), defined as mean 24-hour BP > 130 and/or > 80 mmHg. After calculating BP variability defined as average real variability (ARV), the median value was used to divide the study population in low (LV) or high variability (HV) group. We compared ABPM derived BP parameters, assessed if there is any correlation between pressure overload and variability. Results: In both groups awake systolic BP was nearly equal 143.7 ± 10.5 mmHg, versus 142.4 ± 12.2 mmHg, p = 0.89. Nighttime diastolic BP was significantly higher in the in the LV group 74.09 ± 8.33 versus 69.02 ± 10.22 mmHg, p = 0.017. In the LV group pressure overload expressed as percent time elevation (PTE%) of systolic and diastolic values were 75.2 ± 15.6/45.21 ± 29 % vs. 67.51 ± 18.21/36.13 ± 25.61% in the HV group, p < 0.0001. The systolic BP load was 322.2 ± 195.7 mmHgxh vs. 314.6 ± 183.7 mmHgxh in the HV group, p < 0.0001. The diastolic BP load was 126.2 ± 112.9 mmHgxh vs. 93.02 ± 101.9 mmHgxh in the HV group, p < 0.0001. No correlation was found between BP variability and systolic PTE or BP load in any of the groups, p > 0.05. Conclusions: We found that patients with low variability presented higher BP values and greater pressure overload. High variability is not necessary a dangerous phenomenon if it is accompanied by low BP values without pressure overload. To appreciate the real efficacy of the antihypertensive treatment, a comprehensive assessment of BP values, variability and pressure overload parameters should be included.

Exemplar Variability Facilitates Retention of Word Learning by Children With Specific Language Impairment.

Variability in the input plays an important role in language learning. The current study examined the role of object variability for new word learning by preschoolers with specific language impairment (SLI). Eighteen 4- and 5-year-old children with SLI were taught 8 new words in 3 short activities over the course of 3 sessions. Half of the children saw 3 identical objects corresponding to each new word during training (No Variability group); the other half of the children saw 3 different objects corresponding to each new word during training (High Variability group). Children completed vocabulary learning tests for objects seen during training and for new within-category objects that were never seen during training as a test of category generalization. Learning was assessed the day after each training activity, and retention was assessed 3 weeks after the last training session. There were no group differences on trained or generalization items immediately following training sessions. However, children in the High Variability group demonstrated significantly better retention 3 weeks after experimental training. These findings demonstrate that object variability facilitates retention of new word learning by children with SLI. https://doi.org/10.23641/asha.5583979.

Relationship between blood pressure variability and target organ damage in elderly patients.

To investigate the relationship between 24 h systolic blood pressure variability (SBPV) and target organ damage in elderly patients with essential hypertension. 180 elderly patients (≥ 80 y) with hypertension admitted to our hospital from January 2015 to January 2017 were selected as hypertension group and divided into high blood pressure variability (BPV) group and low BPV group according to the 50th percentile (P50) of 24 h SBPV, while 90 elderly non-hypertension patients admitted during the same period were enrolled as control group. 24 h ambulatory blood pressure values of patients in the three groups were recorded. The total cholesterol (TC), left ventricular mass index (LVMI), carotid artery intima-media thickness (IMT), 24 h microalbuminuria (MA) and complications with cardiovascular disease in patients of the three groups were compared and analyzed. Logistic analysis was conducted with MA, IMT and LVMI as the dependent variables and the remaining risk factors as the independent variables. 24 h SBPV and daytime SBPV (d SBPV) in patients of the hypertension group were significantly higher than those in the control group (p < 0.01); the incidences of coronary heart disease and atherosclerotic plaque as well as IMT, LVMI and MA were higher in the high BPV group than those in the low BPV group (p < 0.05 or p < 0.01). The multivariate results showed that 24 h SBPV was associated with IMT, LVMI and MA. BPV can serve as an important indicator to predict target organ damage in elderly patients with essential hypertension. 24 h SBPV can reflect the degree of target organ damage in elderly hypertensive patients.

The impact of glycaemic variability on wound healing in the diabetic foot – A retrospective study of new ulcers presenting to a specialist multidisciplinary foot clinic

AimsGlycaemic variability – the visit-to-visit variation in HbA1c – plays a possible role in the development of micro and macrovascular disease in patients with diabetes. Whether HbA1c variability is a factor determining wound healing in diabetic foot ulcers remains unknown. We aimed to determine whether HbA1c variability is associated with foot ulcer healing time. MethodsA retrospective analysis of patients presenting to our specialist multidisciplinary foot clinic between July 2013 and March 2015, with at least three HbA1c measurements within five years of presentation and more than two follow-up reviews. HbA1c variation was measured by magnitude of standard deviation. Results629 new referrals were seen between July 2013 and March 2015. Of these, 172 patients had their number of days to healing recorded and sufficient numbers of HbA1c values to determine variability. The overall geometric mean days to heal was 91.1 days (SD 80.8–102.7). In the low HbA1c variability group the geometric mean days to heal was 78.0 days (60.2–101.2) vs 126.9 days (102.0–158.0) in the high Hb1Ac variability group (p = .032). Those with low HbA1c (<58 mmol/mol) and low variability healed faster than those with high HbA1c and high variability (73.5 days [59.5–90.8] vs 111.0 days [92.0–134.0], p = .007). Additionally, our results show that time to healing is more dependent on the mean HbA1c than the variability in HbA1c (p = .007). Conclusions/interpretationOur data suggest that there was a significant association between HbA1c variability and healing time in diabetic foot ulcers.

Characteristics of people with high visit‐to‐visit glycaemic variability in Type 2 diabetes

AimsIncreased visit‐to‐visit glycaemic variability is independently associated with adverse outcomes in Type 2 diabetes. Our aim was to identify the patient characteristics associated with raised visit‐to‐visit glycaemic variability in people with Type 2 diabetes.MethodsA case–control study was conducted to establish associations between HbA1c variability and clinical covariates in 10 130 people with Type 2 diabetes. Variability was calculated by two metrics [sd and coefficient of variation (CV)] from a minimum of four HbA1c readings obtained over a 4‐year period. High and low variability groups were defined as the top and bottom tertile of the sd or CV, and used in logistic regression analyses including a number of clinical and biochemical covariates. The analyses were stratified into low mean (< 53 mmol/mol; 7%) and high mean (≥ 53 mmol/mol; 7%) HbA1c groups.ResultsFindings were consistent across both HbA1c groups and variability metrics. Treatment, independent of other factors, was the most strongly associated covariate for the risk of high HbA1c variability. A six‐fold increased risk was observed in the low HbA1c group, between the most and least intense treatment regimens (P < 0.001). Similar findings were present in the high HbA1c group with a three‐fold increase in risk (P < 0.001). In addition, male gender, younger age, reduced HDL‐cholesterol and increased BMI were all found to be independently associated with raised visit‐to‐visit glycaemic variability.ConclusionsIntensive treatment resulting in low mean HbA1c was associated with marked increase in HbA1c variability. Irrespective of diabetes control, the greatest visit‐to‐visit variability was observed in young, insulin resistant men.

Impact of glycemic variability on the occurrence of periprocedural myocardial infarction and major adverse cardiovascular events (MACE) after coronary intervention in patients with stable angina pectoris at 6 months follow-up

BackgroundWe explored the impact of glycemic variability on the occurrence of periprocedural myocardial infarction and major adverse cardiovascular events (MACE) after coronary intervention in patients with stable angina pectoris (SAP) at 6months follow-up. MethodsFrom May 2015 to April 2016, a total of 746 patients with SAP were divided to high glycemic variability group (H group) (n=261) and low glycemic variability group (L group) (n=485). The primary end point was incidence of periprocedural myocardial infarction and MACE at 6months follow-up. ResultsThe occurrence of periprocedural myocardial infarction occurred in 18.8% of patients in H group and in 12.4% in L group (P=0.03). The incidence of MACE at 6months follow-up was 9.6% in H group and 4.5% in L group (P=0.01). Multivariable analysis suggested that high glycemic variability conferred a 53% risk increment of 6months follow-up MACE (odds ratio 2.13, 95% confidence interval 1.85–5.38; P=0.01). ConclusionsThe trial shows that higher blood glucose variability was correlated with higher incidence of periprocedural myocardial infarction and MACE at 6months follow-up.

A topology-based method to mitigate the dosimetric uncertainty caused by the positional variation of the boost volume in breast conservative radiotherapy

BackgroundTo improve local control rate in patients with breast cancer receiving adjuvant radiotherapy after breast conservative surgery, additional boost dose to the tumor bed could be delivered simultaneously via the simultaneous integrated boost (SIB) modulated technique. However, the position of tumor bed kept changing during the treatment course as the treatment position was aligned to bony anatomy. This study aimed to analyze the positional uncertainties between bony anatomy and tumor bed, and a topology-based approach was derived to stratify patients with high variation in tumor bed localization.MethodsSixty patients with early-stage breast cancer or ductal carcinoma in situ were enrolled. All received adjuvant whole breast radiotherapy with or without local boost via SIB technique. The delineation of tumor bed was defined by incorporating the anatomy of seroma, adjacent surgical clips, and any architectural distortion on computed tomography simulation. A total of 1740 on-board images were retrospectively analyzed. Positional uncertainty of tumor bed was assessed by four components: namely systematic error (SE), and random error (RE), through anterior-posterior (AP), cranial-caudal (CC), left-right (LR) directions and couch rotation (CR). Age, tumor location, and body-mass factors including volume of breast, volume of tumor bed, breast thickness, and body mass index (BMI) were analyzed for their predictive role. The appropriate margin to accommodate the positional uncertainty of the boost volume was assessed, and the new plans with this margin for the tumor bed was designed as the high risk planning target volume (PTV-H) were created retrospectively to evaluate the impact on organs at risk.ResultsIn univariate analysis, a larger breast thickness, larger breast volume, higher BMI, and different tumor locations correlated with a greater positional uncertainty of tumor bed. However, BMI was the only factor associated with displacements of surgical clips in the multivariate analysis and patients with higher BMI were stratified as high variation group. When image guidance was aligned to bony structures, the SE and RE of clip displacement were consistently larger in the high variation group. The corresponding PTV-H margins for the high- and low-variation groups were 7, 10, 10 mm and 4, 9, 6 mm in AP, CC, LR directions, respectively. The heart dose between the two plans was not significantly different, whereas the dosimetric parameters for the ipsilateral lung were generally higher in the new plans.ConclusionsIn patients with breast cancer receiving adjuvant radiotherapy, a higher BMI is associated with a greater positional uncertainty of the boost tumor volume. More generous margin should be considered and it can be safely applied through proper design of beam arrangement with advanced treatment techniques.

HbA1c variability in type 2 diabetes is associated with the occurrence of new-onset albuminuria within three years.

To evaluate the association between HbA1c coefficient of variation (HbA1c-CV) and 3-year new-onset albuminuria risk. A retrospective cohort study involving 716 normoalbuminuric type 2 diabetes patients was conducted between 2010 and 2014. HbA1c-CV was used to categorize patients into low, moderate or high variability groups. Multivariate logistic models were constructed and validated. Integrated discrimination (IDI) and net reclassification (NRI) improvement indices were used to quantify the added predictive value of HbA1c-CV. The mean age of our cohort was 56.1±12.9years with a baseline HbA1c of 8.3±1.3%. Over 3-years of follow-up, 35.2% (n=252) developed albuminuria. An incremental risk of albuminuria was observed with moderate (6.68-13.43%) and high (above 13.44%) HbA1c-CV categories demonstrating adjusted odds ratios of 1.63 (1.12-2.38) and 3.80 (2.10-6.97) for 3-year new-onset albuminuria, respectively. Including HbA1c-CV for 3-year new-onset albuminuria prediction improved model discrimination (IDI: 0.023, NRI: 0.293, p<0.05). The final model had a C-statistic of 0.760±0.018 on validation. HbA1c-CV improves 3-year prediction of new-onset albuminuria. Together with mean HbA1c, baseline urine albumin-to-creatinine ratio and presence of hypertension, accurate 3-year new-onset albuminuria prediction may be possible.

High Intrapatient Tacrolimus Variability Is Associated With Worse Outcomes in Renal Transplantation Using a Low-Dose Tacrolimus Immunosuppressive Regime.

High intrapatient tacrolimus variability has been associated with worse clinical outcomes postrenal transplantation. Theoretically, tacrolimus levels consistently outside the target therapeutic window may result in allograft dysfunction as subtherapeutic tacrolimus levels predispose to episodes of acute rejection, whereas supratherapeutic levels may cause nephrotoxicity. We investigated the effect of tacrolimus variability in a "Symphony" style low-dose tacrolimus based regime, by collecting data from 432 patients over a 4-year period.Three hundred seventy-six patients were included, with a mean follow-up of 1495 days. Tacrolimus variability 6 to 12 months after renal transplantation was calculated, and outcomes were compared in low (n = 186) and high variability (n = 190) groups. High variability patients were found to be at increased risk of rejection during the first posttransplant year (P = 0.0054) and to have reduced rejection-free survival (hazard ratio, 1.953; 95% confidence interval, 1.234-3.093; P = 0.0054). High variability patients had significantly worse (P < 0.0001) glomerular filtration rates at 1, 2, 3, and 4 years posttransplant. High variability patients were at increased risk of allograft loss (hazard ratio, 4.928; 95% confidence interval, 2.050-11.85; P = 0.0004). This suggests that highly variable tacrolimus levels predict worse outcomes postrenal transplantation, although the causal nature of this relationship remains unclear. High tacrolimus variability may identify a subset of patients who warrant increased surveillance and patient education regarding dietary and medication compliance.

Association between glycemic variability and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome during 30-day follow-up

BackgroundWe explored the association between glycemic variability and major adverse cardiovascular and cerebrovascular events (MACCE) in patients with acute coronary syndrome (ACS) during 30-day follow-up. MethodsFrom May 2013 to April 2015, a total of 864 patients with ACS were divided to high glycemic variability group (H group) (n=285) and low glycemic variability group (L group) (n=579). The primary end point was a 30-day incidence of MACCE. Secondary end points were the incidence of atrial fibrillation (AF) during hospitalization and length of hospital stay. ResultsThe primary end point occurred in 15.2% of patients in H group and in 9.7% in L group (p=0.03). The incidence of AF during hospitalization was 14.5% in H group and 8.9% in L group (p=0.02). Compared with the L group, the H group extended the length of hospital stay. Multivariable analysis suggested that high glycemic variability conferred a 57% risk increment of 30-day MACCE (odds ratio 1.97, 95% confidence interval 1.32–6.86; p=0.02). ConclusionThe trial shows that higher blood glucose variability was correlated with higher incidence of MACCE, AF and longer length of stay.

PS 02-68 THE RELATIONSHIP BETWEEN VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND CLIMATE IN JEJU

Objective: In Korea, Jeju Island is a region where monthly mean temperature does not drop below 0 degrees Celsius. The purpose of this study is to find out the relationship between visit-to-visit blood pressure variability (BPV) and the warm climate. Design and Method: From Jan. 2013 to Dec. 2015, 596 patients who take antihypertensive medication were analyzed in our hospital. 70 patients were excluded: 24 paid no visit more than 3 times, 31 had no blood pressure records, and 15 had atrial fibrillation. The measurement of the BPV is standard deviation. The high variability group was defined as the increased medication or the more than 15mmHg of standard deviation (more than 75 percentile) without decreased medication. Results: An inverse correlations were observed between the monthly mean BP, monthly mean temperature (r = −0.847, p < 0.001; Figure1). In high variability group, which were significantly different compared to the normal variability group (130.7 ± 8.5 mmHg vs. 136.1 ± 11.8 mmHg, p < 0.001; 16.5 ± 1.4oC vs.16.2 ± 1.4oC, p = 0.008). In multivariable analysis, higher monthly mean systolic blood pressure (B = 0.058, odds ratio [OR] = 1.06, p < 0.001, 95% CI = 1.04 – 1.08) and lower monthly mean temperature (B = -0.214, odds ratio [OR] = 0.81, p = 0.003, 95% CI = 0.70 – 0.93) were associated with the high variability group. Conclusions: Even in Jeju, a relatively warm region, blood pressure changed according to the temperature. Blood pressure variability in patients who are taking antihypertensive medication had an association with monthly high mean systolic blood pressure and monthly mean temperature.

PS 02-70 ASSOCIATION BETWEEN AMBULATORY BLOOD PRESSURE VARIABILITY AND ARTERIAL STIFFNESS IN HYPERTENSIVE PATIENTS

Objective: The cardio-ankle vascular index (CAVI) is a recently developed index used to assess arterial stiffness that is independent of blood pressure components. The purpose of this study is to evaluate the association between ambulatory blood pressure (BP) variability and arterial stiffness. Design and Method: Study subjects were 114 subjects with hypertension (75 were female, aged 66.1 ± 11.1 years) who underwent ambulatory BP monitoring and cardio-ankle vascular index (CAVI) measurement. The CAVI was measured using the VaSera VS-1000 vascular screening system employing oscillometric technology (Fukuda Denshi Co. Ltd., Tokyo, Japan). We compared the CAVI between the highest (high variability) and lowest (low variability) tertiles of the standard deviation (SD) of systolic BP. Results: Lowest tertile of SD was less than 17.62 mmHg and highest tertile of SD was more than 21.63 mmHg. Mean systolic and diastolic BP were higher in high variability group (systolic BP 139.7 ± 20.5 versus 126.2 ± 15.9 mmHg, p = 0.002; diastolic BP 79.8 ± 9.0 versus 75.1 ± 8.5 mmHg, p = 0.021). CAVI was not significant different between both groups (high variability group versus low variability group 8.97 ± 2.43 versus 8.70 ± 2.39, p = 0.629). Conclusions: These results indicate that ambulatory BP variability is not associated with arterial stiffness.

OS 18-03 GREATER VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY WAS ASSOCIATED WITH COGNITIVE FUNCTION IMPAIRMENT IN AN ELDERLY POPULATION

Objective: We aimed to investigate the association between visit-to-visit blood pressure variability (BPV) and future cognitive dysfunction in an elderly population. Design and Method: The Cardiovascular Disease Risk Factors two-Township study (CVDFACTS) was a longitudinal cohort study and the first wave survey was established during 1989–1991 and four waves of survey were carried out between 1992 and 2002. The on-going sixth wave survey was started in 2015. A total of 320 seniors aged more than 60 years participated in the sixth wave survey and received the Mini-Mental State Examination (MMSE) to evaluate the global cognitive function in 2015. All seniors had participated in at least three waves of survey during 1989 to 2002. The visit-to-visit BPV was calculated as the standard deviation of measurements of brachial SBP and diastolic blood pressure (DBP) from each wave of survey. The first quartiles of SBP and DBP BPV were defined as the high variability group and others as the normal variability group. The general linear regression and the logistic regression were used to evaluate the associations between visit-to-visit BPV and MMSE and cognitive dysfunction (MMSE < 24), respectively. Results: Both SBP and DBP BPV were significantly negatively associated with cognitive function. The correlation coefficients between BPV and MMSE were -0.132 (p-value = 0.0182) for SBP and -0.158 (p-value = 0.0047) for DBP. However, the association BPV and MMSE remained significant only for DBP (r = 0.39, p-value <0.01) but not for SBP (r = −0.09, p-value = 0.135) when age and sex were accounted for. DBP BPV remained significantly associated with MMSE and cognitive dysfunction in the multivariate models with adjustment for DBP, history of stroke and other confounders in the linear regression (beta = −0.11, p-value = 0.0347) and the logistic regression (odds ratio = 1.17, 95% CI = 1.03–1.32). Subjects with high visit-to-visit DBP BPV had significantly lower MMSE and higher prevalence of cognitive dysfunction. Conclusions: High visit-to-visit DBP BPV was associated with future cognitive dysfunction.

Blood pressure variability and its association with echocardiographic parameters in hypertensive diabetic patients.

BackgroundBlood pressure (BP) variability is associated with target organ damage in hypertension and diabetes. The 24 h ambulatory blood pressure monitoring (24 h-ABPM) has been proposed as an evaluation for BP variability using several indexes [standard deviation (SD) of mean BP, coefficient of variation (CV), BP variation over time (time-rate index)].MethodsWe evaluated the association between BP variability measured by 24 h-ABPM indexes and echocardiographic variables in a cross-sectional study in 305 diabetic-hypertensive patients.ResultsTwo groups were defined by the median (0.55 mmHg/min) of time-rate systolic BP (SBP) index and classified as low or high variability. Age was 57.3 ± 6.2 years, 196 (64.3 %) were female. Diabetes duration was 10.0 (5.0–16.2) years, HbA1c was 8.2 ± 1.9 %. Baseline clinical characteristics were similar between low (n = 148) and high (n = 157) variability groups. Office SBP and systolic 24 h-ABPM were higher in the high variability group (139.9 mmHg vs 146.0 mmHg, P = 0.006; 128.3 mmHg vs 132.9 mmHg, P = 0.019, respectively). Time-rate index, SD and CV of SBP, were higher in high variability group (P < 0.001; P < 0.001 and P = 0.003, respectively). Time-rate index was not independently associated with the echocardiography’s variables in multiple linear model when adjusting for age, 24 h-ABPM, diabetes duration and HbA1c. The multiple linear regression model revealed that the significant and independent determinants for septum thickness, relative wall thickness and posterior wall thickness (parameters of left ventricular hypertrophy) were: age (p = 0.025; p = 0.010; p = 0.032, respectively) and 24 h-SBP (p < 0.001 in the three parameters).ConclusionBP variability estimated by 24 h-ABPM is not independently associated with echocardiographic parameters in diabetic-hypertensive patients.

Can Ambulatory Blood Pressure Variability Contribute to Individual Cardiovascular Risk Stratification?

Objective. The aim of this study is to define the normal range for average real variability (ARV) and to establish whether it can be considered as an additional cardiovascular risk factor. Methods. In this observational study, 110 treated hypertensive patients were included and admitted for antihypertensive treatment adjustment. Circadian blood pressure was recorded with validated devices. Blood pressure variability (BPV) was assessed according to the ARV definition. Based on their variability, patients were classified into low, medium, and high variability groups using the fuzzy c-means algorithm. To assess cardiovascular risk, blood samples were collected. Characteristics of the groups were compared by ANOVA tests. Results. Low variability was defined as ARV below 9.8 mmHg (32 patients), medium as 9.8–12.8 mmHg (48 patients), and high variability above 12.8 mmHg (30 patients). Mean systolic blood pressure was 131.2 ± 16.7, 135.0 ± 12.1, and 141.5 ± 11.4 mmHg in the low, medium, and high variability groups, respectively (p = 0.0113). Glomerular filtration rate was 78.6 ± 29.3, 74.8 ± 26.4, and 62.7 ± 23.2 mL/min/1.73 m2 in the low, medium, and high variability groups, respectively (p = 0.0261). Conclusion. Increased values of average real variability represent an additional cardiovascular risk factor. Therefore, reducing BP variability might be as important as achieving optimal BP levels, but there is need for further studies to define a widely acceptable threshold value.

Multidisciplinary Treatment of the Metabolic Syndrome Lowers Blood Pressure Variability Independent of Blood Pressure Control.

Blood pressure (BP) variability (BPV) contributes to target organ damage independent of BP. The authors examined the effect of a 1-year multidisciplinary intervention on BPV in patients with the metabolic syndrome (MetS) as defined by criteria from the Third Report of the Adult Treatment Panel. Forty-four nondiabetic patients underwent clinical and biochemical profiling, 24-hour ambulatory BP monitoring (ABPM), body composition, carotid intima-media thickness, and carotid-femoral pulse wave velocity (PWV). The intervention targeted all MetS components. BPV was assessed by the standard deviation of daytime systolic BP derived from ABPM. Patients with low and high BPV (lower or higher than the median daytime standard deviation of 11.6 mm Hg) did not differ in regards to systolic and diastolic BP, age, fasting glucose, glycated hemoglobin, and body mass index, but the high-variability group had higher values of low-density lipoprotein and leg fat. The 1-year intervention resulted in weight reduction but not BP-lowering. BPV declined in the high-variability group in association with lowering of PWV, C-reactive protein, glycated hemoglobin, alanine aminotransferase, asymmetric dimethylarginine, and increased high-density lipoprotein cholesterol. A multidisciplinary intervention independent of BP-lowering normalized BPV, lowered PWV, and enhanced metabolic control.

PP.17.26

Objective: Average real variability (ARV), as a reliable index has been proposed to define blood pressure oscillations occurring trough 24-hour, but a normal range or cut off point has not been established. Therefore, the aim of the present study is to define low, medium and high variability range and to assess the relationship between these groups of variability and blood pressure values. Design and method: This observational study was conducted between 2012–2014 in County Clinical Hospital- Department for Internal Medicine IV, Targu-Mures, Romania and included 102 patients with treated hypertension. Circadian blood pressure was recorded with a validated 24-hour ambulatory monitoring device (Meditech 05 ABPM). Blood pressure variability was calculated according to the formula of average real variability, using a computerized soft. Based on variability, patients were divided in to low, medium or high variability group. Blood samples were collected regarding cardiovascular risk factors (total cholesterol, triglycerides, blood glucose, creatinine). Characteristics of the groups were compared by one way-ANOVA test, correlations were analysed with Pearson's test, categorical variables were compared with chi2 test, using Graph Pad Prism 5 statistical program. Results: Low variability was defined as ARV between 4.32–9.85 mmHg (34 patients), medium 9.86–12.87 mmHg (45 patients), high variability between 12.88–16.87 mmHg (23 patients). Mean age was statistically significant among the groups, 57.02 ± 13.52, versus 62.42 ± 11.01 versus 65.69 ± 13.1 years, p = 0.02. The 24-hour systolic blood pressure differed significantly between the groups, 131,38 ± 16.31 versus 136,13 ± 12.04 versus140.9 ± 12.21, p = 0.037. Although, glomerular filtration rate was lowest in the high variability group 71,12 ± 28,91 the difference was statistically not significant (p = 0.88). In the high variability group positive correlation was found between blood pressure variability and 24-hour systolic blood pressure (p = 0.02, r2 = 0.2196, CI:0.06984 to 0.7383). Conclusions: High blood pressure variability could be defined as ARV greater than 12.88 mmHg. Elderly patients show greater blood pressure values, higher blood pressure variability and impaired kidney function. To prevent end organ damage, evaluation and reduction of blood pressure variability could be at least as important as blood pressure lowering.