Evaluation of glucose-lowering medications in older people: a comprehensive systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is increasingly being diagnosed in older adults. Our objective is to assess the advantages and potential drawbacks of different glucose-lowering medications in this specific population. METHODS: A network meta-analysis was conducted to identify randomized controlled trials that examined patient-centered outcomes in adults aged ≥65 years with T2DM. We searched PubMed, Cochrane CENTRAL, and Embase up to September 23, 2023. Quality of eligible studies were assessed using the Cochrane RoB 2.0 tool. RESULTS: A total of 22 trials that involved 41 654 participants were included, incorporating sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, sulfonylureas (SU) and acarbose. Our findings reveal that GLP-1RAs reduce the risk of major adverse cardiovascular events (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.97) and body weight (mean difference [MD], -3.87 kg; 95% CI, -5.54 to -2.21). SGLT2 inhibitors prevent hospitalization for heart failure (RR, 0.66; 95% CI, 0.57 to 0.77), renal composite outcome (RR, 0.69; 95% CI, 0.53 to 0.89), and reduce body weights (MD, -1.85 kg; 95% CI, -2.42 to -1.27). SU treatment increases the risk of any hypoglycaemia (RR, 4.19; 95% CI, 3.52 to 4.99) and severe hypoglycaemia (RR, 7.06; 95% CI, 3.03 to 16.43). GLP-1RAs, SGLT2 inhibitors, metformin, SU and DPP-4 inhibitors are effective in reducing glycaemic parameters. Notably, the number of treatments needed decreases in most cases as age increases. CONCLUSIONS: Novel glucose-lowering medications with benefits that outweigh risks should be prioritized for older patients with diabetes.

Dissecting the vascular-cognitive nexus: energetic vs. conventional hemodynamic parameters.

Blood pressure or flow measurements have been associated with vascular health and cognitive function. We proposed that energetic hemodynamic parameters may provide a more nuanced understanding and stronger correlation with cognitive function, in comparisons with conventional aortic and carotid pressure and flow parameters. The study comprised 1858 participants, in whom we assessed cognitive function via MoCA method, and measured central aortic and carotid pressure and flow waveforms. In addition to various pressure and flow parameters, we calculated energetic hemodynamic parameters through integration of pressure multiplying flow with respect to time. Energetic hemodynamic parameters, particularly aortic and carotid mean and pulsatile energy and pulsatility index (PI), were significantly associated with MoCA score more than any aortic and carotid pressure and flow parameters, after adjusting for age, sex, education, depression score, heart rate, BMI, HDL-cholesterol, and glucose levels. MoCA exhibited a strong positive relationship with carotid mean energy (standardized beta = 0.053, P = 0.0253) and a negative relationship with carotid energy PI (standardized beta = -0.093, P = 0.0002), exceeding the association with all traditional pressure- or flow-based parameters. Aortic pressure reflection coefficient at the aorto-carotid junction was positively correlated with mean carotid energy and negatively correlated with PI. Aortic characteristic impedance positively correlated with carotid energy PI but not mean energy. Our research indicates that energetic hemodynamic parameters, particularly carotid mean energy and carotid energy PI, have a stronger association with MoCA scores than traditional pressure- or flow-based metrics. This correlation with cognitive function is notably influenced by the properties of the aorto-carotid interface.

Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

Pulse pressure is associated with decline in physical function in older adults.

OBJECTIVES: This study examined the associations between pulse pressure, hypertension, and the decline in physical function in a prospective framework. STUDY DESIGN: The Healthy Aging Longitudinal Study tracked a group of Taiwanese adults aged 55 or more over an average of 6.19 years to assess pulse pressure and decline in physical function, including in handgrip strength, gait speed, and 6-min walking distance, at baseline (2009-2013) and in the second phase of assessments (2013-2020). MAIN OUTCOME MEASURES: Pulse pressure was calculated as the difference between systolic and diastolic blood pressure values. Weakness, slowness, and low endurance were defined as decreases of ≥0.23 m/s (one standard deviation) in gait speed, ≥5.08 kg in handgrip strength, and ≥ 57.73 m in a 6-min walk, as determined from baseline to the second phase of assessment. Linear and logistic regressions were employed to evaluate the associations between pulse pressure, hypertension, and decline in physical function. RESULTS: Baseline pulse pressure was associated with future handgrip strength (beta = -0.017, p = 0.0362), gait speed (beta = -0.001, p < 0.0001), and 6-min walking distance (beta = -0.470, p < 0001). In multivariable models, only handgrip strength (beta = -0.016, p = 0.0135) and walking speed (beta = -0.001, p = 0.0042) remained significantly associated with future pulse pressure. Older adults with high systolic blood pressure (≥140 mmHg) and elevated pulse pressure (≥60 mmHg) exhibited a significantly increased risk of weakness (odds ratio: 1.30, 95 % confidence interval: 1.08-1.58), slowness (1.29, 1.04-1.59), and diminished endurance (1.25, 1.04-1.50) compared with the reference group, who exhibited systolic blood pressure of <140 mmHg and pulse pressure of <60 mmHg. CONCLUSIONS: Among older adults, pulse pressure is associated with a decline in physical function, especially in terms of strength and locomotion.

Examining arterial pulsation to identify and risk-stratify heart failure subjects with deep neural network.

Hemodynamic parameters derived from pulse wave analysis have been shown to predict long-term outcomes in patients with heart failure (HF). Here we aimed to develop a deep-learning based algorithm that incorporates pressure waveforms for the identification and risk stratification of patients with HF. The first study, with a case-control study design to address data imbalance issue, included 431 subjects with HF exhibiting typical symptoms and 1545 control participants with no history of HF (non-HF). Carotid pressure waveforms were obtained from all the participants using applanation tonometry. The HF score, representing the probability of HF, was derived from a one-dimensional deep neural network (DNN) model trained with characteristics of the normalized carotid pressure waveform. In the second study of HF patients, we constructed a Cox regression model with 83 candidate clinical variables along with the HF score to predict the risk of all-cause mortality along with rehospitalization. To identify subjects using the HF score, the sensitivity, specificity, accuracy, F1 score, and area under receiver operating characteristic curve were 0.867, 0.851, 0.874, 0.878, and 0.93, respectively, from the hold-out cross-validation of the DNN, which was better than other machine learning models, including logistic regression, support vector machine, and random forest. With a median follow-up of 5.8 years, the multivariable Cox model using the HF score and other clinical variables outperformed the other HF risk prediction models with concordance index of 0.71, in which only the HF score and five clinical variables were independent significant predictors (p < 0.05), including age, history of percutaneous coronary intervention, concentration of sodium in the emergency room, N-terminal pro-brain natriuretic peptide, and hemoglobin. Our study demonstrated the diagnostic and prognostic utility of arterial waveforms in subjects with HF using a DNN model. Pulse wave contains valuable information that can benefit the clinical care of patients with HF.

Evaluating polygenic risk scores for predicting cardiometabolic traits and disease risks in the Taiwan Biobank.

Type 2 diabetes (T2D) and hypertension are common comorbidities and, along with hyperlipidemia, serve as risk factors for cardiovascular diseases. This study aimed to evaluate the predictive value of polygenic risk scores (PRSs) on cardiometabolic traits related to T2D, hypertension, and hyperlipidemia and the incidence of these three diseases in Taiwan Biobank samples. Using publicly available, large-scale genome-wide association studies summary statistics, we constructed cross-ethnic PRSs for T2D, hypertension, body mass index, and nine quantitative traits typically used to define the three diseases. A composite PRS (cPRS) for each of the nine traits was constructed by aggregating the significant PRSs of its genetically correlated traits. The associations of each of the nine traits at baseline as well as the change of trait values during a 3- to 6-year follow-up period with its cPRS were evaluated. The predictive performances of cPRSs in predicting future incidences of T2D, hypertension, and hyperlipidemia were assessed. The cPRSs had significant associations with baseline and changes of trait values in 3-6 years and explained a higher proportion of variance for all traits than individual PRSs. Furthermore, models incorporating disease-related cPRSs, along with clinical features and relevant trait measurements achieved area under the curve values of 87.8%, 83.7%, and 75.9% for predicting future T2D, hypertension, and hyperlipidemia in 3-6 years, respectively.

Aortic Characteristic Impedance and Suspected Mild Cognitive Impairment in a Community-Based Healthy Population.

BACKGROUND: Aging of the proximal aorta can lead to increased pressure and flow pulsatility in the cerebral microcirculation, which may cause cognitive impairment. This study investigated the association between aortic characteristic impedance (Zc), an indicator of regional stiffness of the proximal aorta, and suspected mild cognitive impairment (MCI), compared with carotid-femoral pulse wave velocity (CFPWV). METHODS AND RESULTS: A total of 1461 healthy community residents (46.4% men; age range, 35-96 years [mean±SD, 59.9±11.8 years]) without a history of cardiovascular events or stroke were included in the study. Zc was estimated using applanation tonometry and echocardiography. Cognitive function was assessed using the Mini-Mental State Examination. Education-adjusted cut points were used to define suspected MCI. Subjects with suspected MCI (n=493 [33.7%]) had significantly higher Zc and CFPWV than those without. In multivariable analysis, both Zc and CFPWV were inversely associated with Mini-Mental State Examination score. Zc (odds ratio per 1 SD, 1.22 [95% CI, 1.09-1.37] and CFPWV (odds ratio per 1 SD, 1.18 [95% CI, 1.01-1.38]) was also significantly associated with suspected MCI, after adjusting for age, sex, education level, mean arterial pressure, hypertension, diabetes, low-density lipoprotein cholesterol, and smoking status. In joint analysis, Zc was significantly associated with suspected MCI, but CFPWV was not. In the age subgroups of <50 years and 50 to 70 years, only Zc was significantly associated with suspected MCI. CONCLUSIONS: This study found that Zc was significantly associated with Mini-Mental State Examination score and suspected MCI, especially in younger and middle-aged adults. These findings suggest that Zc may be a useful biomarker for identifying individuals at risk for MCI.

Transitions of dialysis status and outcomes after the unplanned first dialysis: a nationwide population-based cohort study.

In Taiwan, most first-time dialysis was started without the creation of an arteriovenous shunt. Here, we aimed to elucidate the transitions of dialysis status in the unplanned first dialysis patients and determine factors associated with their outcomes. A total of 50,315 unplanned first dialysis patients aged more than 18 years were identified from the National Health Insurance Dataset in Taiwan between 2001 and 2012. All patients were followed for 5 years for the transitions in dialysis status, including robust (dialysis-free), sporadic dialysis, continued dialysis, and death. Furthermore, factors associated with the development of continued dialysis and death were examined by the Cox proportional hazard models. After 5 years after the first dialysis occurrence, there were 5.39% with robust status, 1.67% with sporadic dialysis, 8.45% with continued dialysis, and 84.48% with death. Notably, we have identified common risk factors for developing maintenance dialysis and deaths, including male gender, older age, diabetes, coronary heart disease, stroke, heart failure, sepsis, and surgery. There was an extremely high mortality rate among the first unplanned dialysis patients in Taiwan. Less than 10% of these patients underwent continued dialysis during the 5-year follow-up period. This study highlighted the urgent need for interventions to improve patient outcomes.

Neutrophil-Lymphocyte Ratio as a Predictor of Cerebral Small Vessel Disease in a Geriatric Community: The I-Lan Longitudinal Aging Study.

Cerebral Small Vessel Disease (CSVD) frequently affects the elderly, with inflammation playing a crucial role in related health complications, including dementia, stroke, and SVD. Studies, including animal experiments, indicate a strong link between inflammation and SVD progression. The Neutrophil-Lymphocyte Ratio (NLR) serves as a possible biomarker for ongoing inflammatory risks. A total of 720 adults aged 50 years or older from the community-based I-Lan Longitudinal Aging Study were included in this study. General linear regression and ordinally logistic regression analyses were performed to evaluate the association between NLR and CSVD. We further examined the presence of lacune, microbleed, and white matter hyperintensity (WMH) on brain MRI, which were used to construct a combined CSVD score. The NLR was positively associated with WMH (adjusted r = 0.109, p = 0.003), microbleed (adjusted r = 0.102, p = 0.006), and lacune (adjusted r = 0.100, p = 0.008). After adjustments for smoking, drinking, and physical activity in the ordinal logistic regression analysis, age, gender, brachial Systolic Blood Pressure (SBP), fasting glucose, LDL-cholesterol, and Hs-CRP were compared among subjects with low tertile (T1), medium tertile (T2) and high tertile (T3) NLR. The results showed that T2 vs. T1 had an odds ratio of 1.23 (0.86-1.77); and T3 vs. T1 had an odds ratio of 1.87 (1.29-2.71) of CSVD scores in four groups (zero (reference group), one, two, and three or more). NLR could be used to assess the state of inflammation in cerebral vessels. A significant and positive correlation between NLR and CSVD was verified in this study. However, the practical clinical application of NLR in CSVD patients and prognosis prediction should be validated through more scientific attempts.

Prevalence and predictive modeling of undiagnosed diabetes and impaired fasting glucose in Taiwan: a Taiwan Biobank study.

INTRODUCTION: We investigated the prevalence of undiagnosed diabetes and impaired fasting glucose (IFG) in individuals without known diabetes in Taiwan and developed a risk prediction model for identifying undiagnosed diabetes and IFG. RESEARCH DESIGN AND METHODS: Using data from a large population-based Taiwan Biobank study linked with the National Health Insurance Research Database, we estimated the standardized prevalence of undiagnosed diabetes and IFG between 2012 and 2020. We used the forward continuation ratio model with the Lasso penalty, modeling undiagnosed diabetes, IFG, and healthy reference group (individuals without diabetes or IFG) as three ordinal outcomes, to identify the risk factors and construct the prediction model. Two models were created: Model 1 predicts undiagnosed diabetes, IFG_110 (ie, fasting glucose between 110 mg/dL and 125 mg/dL), and the healthy reference group, while Model 2 predicts undiagnosed diabetes, IFG_100 (ie, fasting glucose between 100 mg/dL and 125 mg/dL), and the healthy reference group. RESULTS: The standardized prevalence of undiagnosed diabetes for 2012-2014, 2015-2016, 2017-2018, and 2019-2020 was 1.11%, 0.99%, 1.16%, and 0.99%, respectively. For these periods, the standardized prevalence of IFG_110 and IFG_100 was 4.49%, 3.73%, 4.30%, and 4.66% and 21.0%, 18.26%, 20.16%, and 21.08%, respectively. Significant risk prediction factors were age, body mass index, waist to hip ratio, education level, personal monthly income, betel nut chewing, self-reported hypertension, and family history of diabetes. The area under the curve (AUC) for predicting undiagnosed diabetes in Models 1 and 2 was 80.39% and 77.87%, respectively. The AUC for predicting undiagnosed diabetes or IFG in Models 1 and 2 was 78.25% and 74.39%, respectively. CONCLUSIONS: Our results showed the changes in the prevalence of undiagnosed diabetes and IFG. The identified risk factors and the prediction models could be helpful in identifying individuals with undiagnosed diabetes or individuals with a high risk of developing diabetes in Taiwan.

Risks and outcomes of critical limb ischemia in hemodialysis patients: a prospective cohort study.

Background: Peripheral arterial disease (PAD) is more common in patients receiving maintenance hemodialysis than in the general population. Critical limb ischemia (CLI), the most severe form of PAD, is associated with high amputation and mortality risk. However, few prospective studies are available evaluating this disease's presentation, risk factors and outcomes for patients receiving hemodialysis. Methods: The Hsinchu VA study, a prospective multicentre study, investigated the impact of clinical factors on cardiovascular outcomes of patients receiving maintenance hemodialysis from January 2008 until December 2021. We evaluated the presentations and outcomes of patients with newly diagnosed PAD and the correlations of clinical variables with newly diagnosed CLI. Results: Of 1136 study participants, 1038 had no PAD on enrolment. After a median follow-up period of 3.3 years, 128 had newly diagnosed PAD. Of these, 65 presented with CLI, and 25 underwent amputation or died from PAD. Patients presenting with CLI had more below-the-knee (52%) and multi-level (41%) disease, and completely occluded segments (41%), and higher risk for amputation or PAD-related death compared with patients without CLI (27.7% vs 9.5%, P = .01). After multivariate adjustment, disability, diabetes mellitus, current smoking and atrial fibrillation were significantly associated with newly diagnosed CLI. Conclusions: Patients undergoing hemodialysis had higher rates of newly diagnosed CLI than the general population. Those with disabilities, diabetes mellitus, smoking and atrial fibrillation may require careful examination for PAD. Trial registration: Hsinchu VA study, ClinicalTrials.gov identifier: NCT04692636.

130/80 mmHg as a unifying hypertension threshold for office brachial, office central, and ambulatory daytime brachial blood pressure.

The present study investigated the prognostic values for office brachial (OB), office central (OC), and ambulatory daytime brachial (AmDB) hypertension, as defined by a unifying threshold of 130/80 mmHg, and the incremental value of either OC or AmDB hypertension to OB hypertension. A total of 1219 community residents without receiving anti-hypertensive treatment (671 men and 548 women, aged ≥ 30 years old) from central Taiwan and Kinmen islands had OB, OC, and AmDB blood pressure measurements during a cardiovascular survey conducted in 1992-1993. OB hypertension, OC hypertension, and AmDB hypertension were all defined in retrospect at the threshold of 130/80 mmHg. They were followed up for nonfatal and fatal cardiovascular events until December 31, 2017, by linking the baseline database to the National Health Insurance Research dataset and the National Death Registry. During a follow-up of 25 612.5 person-years (Average event-free time: 21.0 years), there were 368 fatal and nonfatal cardiovascular events. In multivariable analyses, OB hypertension, OC hypertension, and AmDB hypertension had similar hazard ratios for cardiovascular events [2.03, 95% confidence interval: 1.47-2.80]; 1.92 (1.47-2.51); and 1.79 (1.41-2.29), respectively. Using OB normotension as the reference, either the concordant OB and OC hypertension [2.24 (1.61-3.12)], or the concordant OB and AmDB hypertension [2.52 (1.80-3.54)] was significantly associated with cardiovascular events. Moreover, OB hypertension plus AmDB normotension was also significantly associated with increased risk for cardiovascular events. We concluded that OB hypertension, OC hypertension, and AmDB hypertension defined by a unifying threshold of 130/80 mmHg may provide similar estimates of long-term risk for cardiovascular events. Cross-classification analyses suggest that addition of OC hypertension or AmDB hypertension may improve the prognostic value of OB hypertension.

Central obesity and elevated blood pressure in middle life are associated with physical and cognitive impairment in later life: A retrospective design with repeated measures.

BACKGROUND AND AIMS: Physical and cognitive function decline indicates the prestage of disability and is associated with mortality among older adults. We investigated the association of metabolic disorders in midlife with physical and cognitive function decline in later life in a retrospective cohort. MATERIAL AND METHODS: A total of 618 older adults aged ≥60 years in wave-6 (2014-2017) were enrolled in the Cardiovascular Disease Risk Factor Two-Township Study to evaluate physical (hand grip strength and 4-m walking speed) and cognitive function (Mine-Mental State Examination [MMSE] score). Repeated metabolic disorder measures in wave-2, wave-3, and wave-5 were obtained to identify three trajectory pattern groups according to each metabolic disorder through group-based trajectory modeling. Linear and logistic regressions were conducted to investigate the association of metabolic disorders in middle life with physical and cognitive function decline in later life. RESULTS: The prevalence rates of a weak hand grip (<28 kg for men and <18 kg for women), slow walking speed (<0.8 m/s), and poor cognitive function (MMSE <25) were 24.43 %, 16.83 % and 10.5 %, respectively, among the older adults. In the retrospective cohort with 15-year follow-up, those with a waist circumference of ≥95 cm for men and ≥85 cm for women in middle life exhibited a significantly weak hand grip (odds ratio: 2.78 [95 % confidence interval: 1.26, 6.11]) and slow walking speed (2.26 [1.15, 4.43]) in later life compared with those with a smaller waist circumference (<85 cm for men and <75 cm for women). Elevated blood pressure (systolic blood pressure [BP] ≥130 mmHg or diastolic BP ≥80 mmHg) was significantly associated with a higher risk of cognitive function decline in later life. Furthermore, the high-trajectory and middle-trajectory groups' body mass index (3.17 [1.25, 8.04] and 2.27 [1.28, 4.00], respectively) and waist circumference (4.39 [2.07, 9.31] and 2.54 [1.39, 4.67], respectively) were significantly associated with a weak hand grip and slow walking speed, respectively, compared with those of the low-trajectory group. The high-trajectory diastolic BP group was significantly associated with a higher risk of cognitive function decline compared with the low-trajectory diastolic BP group. CONCLUSION: Waist circumference and BP in middle life were associated with physical function decline and poor cognitive function in later life. The management of central obesity and BP in midlife may slow the decline of physical and cognitive function in later life.

Education level may modify the association between cardiac index and cognitive function among elders with normal ejection function.

Background: Lower cardiac index (CI) in elders has been associated with incident dementia, and higher CI has protectively effect with brain aging. In the present study, we investigated the modulating effects of education level and arterial stiffness on the association between CI and cognitive function among older adults. Methods: A total of 723 elders (≥60 years, 50.1% women) with normal left ventricular ejection fraction (≥50%) were identified from the Cardiovascular Diseases Risk Factor Two-Township Study. CI was calculated from the Doppler-derived stroke volume. We evaluated arterial stiffness by measuring carotid-femoral pulse wave velocity (CFPWV) and global cognitive function by using the Mini-Mental Short Examination (MMSE). Education level was determined by years of formal education. Results: In linear regression analysis adjusting for age, sex, formal years of education, and CFPWV, CI was significantly positively associated with MMSE (BETA=0.344±0.130, P = 0.0082). In logistic regression analysis adjusting for age, sex, formal years of education, and CFPWV, subjects with a CI≥75 percentile had a significantly lower risk of low MMSE (<26) (OR = 0.495, 95% CI = 0.274-0.896, P = 0.02). In subgroup analysis, higher CI was significantly associated with higher MMSE and lower risk of low MMSE only in elders with ≤ 9 years of formal education. Causal mediation analysis suggests that higher CI maintains higher MMSE in elders with lower education levels whereas higher CFPWV causes lower MMSE in all the elders. Conclusion: In elders with normal ejection fraction, a higher CI was associated with a lower risk of cognitive function impairment, independent of arterial stiffness, mainly in subjects with a lower education level and possibly a smaller cognitive reserve.

The association of long-term blood pressure variability with hemodialysis access thrombosis.

Background: Blood pressure variability (BPV) is an important risk factor for cardiovascular events in hemodialysis patients. We sought to determine the impact of BPV on hemodialysis access thrombosis. Methods: We enrolled 1,011 prevalent hemodialysis patients from 12 hemodialysis centers since January 2018 and followed them until December 2020. Predialysis blood pressure (BP) was assessed at 12-week intervals. The coefficient of variation derived from 36 consecutive BP measurements was used as the metric for variability. The primary outcome was incident hemodialysis access thrombosis. Linear regression models were used to assess factors associated with BPV at baseline. Kaplan-Meier curves of the time until vascular access events were drawn and log-rank tests were calculated. Cox proportional hazards models were performed to assess the association of BPV with incident vascular access events. Results: The average coefficient of variance for systolic BPV was 10.9%. BPV was associated with age, body mass index, mean BP, diabetes, coronary and peripheral artery disease, history of access dysfunction, graft access, intradialytic hypotension, and use of antihypertensive medications. There were 194 access thrombosis events and 451 access stenosis events during a median follow-up period of 30 months. After adjustment of potential confounding factors, BPV was associated with increased risk of access thrombosis [hazard ratio = 1.27, 95% confidence interval (CI), 1.18-1.44, per 1 standard deviation increase in BPV]. The patients in the highest BPV quartile had 2.45 times the risk of thrombosis (CI, 1.62-3.70). The association was independent of average BP, intradialytic hypotension, and comorbidities. Similar trends of association were found in the subgroups analyzed. Comparative analysis using a time-varying variable model and different metrics of BPV showed consistent results. Conclusion: Our findings underscored the impact of BP fluctuation on vascular access thrombosis.

Higher Arm Versus Lower Arm Systolic Blood Pressure and Cardiovascular Outcomes: a Meta-Analysis of Individual Participant Data From the INTERPRESS-IPD Collaboration.

BACKGROUND: Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference-Individual Participant Data Collaboration. METHODS: One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared. RESULTS: We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P<0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P<0.001). Higher arm BP models better predicted cardiovascular events with Framingham and atherosclerotic cardiovascular disease risk scores (both P<0.001) and reclassified 4.6% and 3.5% of participants respectively to higher risk categories compared with lower arm BPs). CONCLUSIONS: Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42015031227.

Evaluating the effectiveness of population-based breast cancer service screening: an analysis of parsimonious patient survival information with the time-varying Cox model.

BACKGROUND: This study is aimed at estimating the unbiased effectiveness of population-based breast cancer service screening based on case survival information alone rather than large-scale individual screening data pursuant to the intention-to-treat principle of a randomized-controlled trial. METHODS: A novel time-dependent switched design with two modalities of cancer detection (screen-detected vs clinically detected) was proposed to evaluate the effectiveness of breast cancer screening. We used data on 767 patients from Kopparberg in the Swedish Two-County trial and on 78 587 patients in the Taiwan population-based service screening. We estimated the relative rate of the screen-detected vs the clinically detected with adjustment for both truncation and lead-time biases. The absolute effectiveness in terms of the number needed to screen (NNS) for averting one death from breast cancer was estimated. RESULTS: The relative rate of effectiveness was estimated as 33%, which was consistent with the 37% reported from the original Swedish randomized-controlled trial. The corresponding estimate for the Taiwan screening programme was 42%, which was also very close to that estimated using individual screening history data (41%). Both relative estimates were further applied to yield 446 and 806 of NNS for averting one death from breast cancer for the corresponding two data sets. CONCLUSION: The proposed time-dependent switched design and analysis with two modalities of case survival information provides a very efficient means for estimating the unbiased estimates of relative and absolute effectiveness of population-based breast cancer service screening dispensing with a large amount of individual screening history data.

Association of Frailty With Thrombosis of Hemodialysis Vascular Access: A Prospective Taiwanese Cohort Study.

RATIONALE & OBJECTIVE: Frailty, a multidimensional construct, has been associated with poor outcomes in patients receiving maintenance dialysis. This study assessed the association of frailty with dialysis vascular access patency. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 761 prevalent patients receiving hemodialysis at 9 centers in Taiwan as of January 2018. EXPOSURE: Performance-based frailty was defined as 3 of the following: unintentional weight loss, weakness, exhaustion, low physical activity, and slow gait speed. Patients were categorized as prefrail if they had 1 or 2 of these characteristics. OUTCOME: Rate of and time to dialysis access thrombosis. Data regarding vascular access events were collected for 30 months after enrollment through December 31, 2020. ANALYTICAL APPROACH: Logistic regression analysis was used to estimate the association of clinical characteristics with frailty. Cox proportional hazards regression analysis was used to estimate the association of frailty with vascular access thrombosis adjusted for known clinical risk factors. RESULTS: The patients' mean age was 66 years, 46% were female, 18% had synthetic graft accesses, and 82% arteriovenous fistulas. Overall, 31% were frail, 35% were prefrail, and 34% were not frail. The frailty phenotype was associated with age, female sex, low body mass index, diabetes mellitus, and prior stroke. During a median follow-up of 731 days, 161 patients (21%) had access thrombosis events (not frail, 14%; prefrail, 20%; frail, 30%; P < 0.001). Frail patients had a higher risk of vascular access thrombosis than nonfrail patients (HR, 2.31 [95% CI, 1.55-3.39], P < 0.001). After multivariable adjustment for age and comorbidities, frailty remained significantly associated with access thrombosis for both fistulas and grafts. LIMITATIONS: Limited generalizability and potential residual confounding. CONCLUSIONS: Frailty is associated with an increased risk of vascular access thrombosis. These findings highlight the risks of access failure experienced by frail patients receiving hemodialysis.

Developing and Validating Risk Scores for Predicting Major Cardiovascular Events Using Population Surveys Linked with Electronic Health Insurance Records.

A risk prediction model for major cardiovascular events was developed using population survey data linked to National Health Insurance (NHI) claim data and the death registry. Another set of population survey data were used to validate the model. The model was built using the Nutrition and Health Survey in Taiwan (NAHSIT) collected from 1993-1996 and linked with 10 years of events from NHI data. Major adverse cardiovascular events (MACEs) were identified based on hospital admission or death from coronary heart disease or stroke. The Taiwanese Survey on Hypertension, Hyperglycemia, and Hyperlipidemia (TwSHHH), conducted in 2002 was used for external validation. The NAHSIT data consisted of 1658 men and 1652 women aged 35-70 years. The incidence rates for MACE per 1000 person-years were 13.77 for men and 7.76 for women. These incidence rates for the TwSHHH were 7.27 for men and 3.58 for women. The model had reasonable discrimination (C-indexes: 0.76 for men; 0.75 for women), thus can be used to predict MACE risks in the general population. NHI data can be used to identify disease statuses if the definition and algorithm are clearly defined. Precise preventive health services in Taiwan can be based on this model.