Discontinuous Deformation Monitoring of Smart Aerospace Structures Based on Hybrid Reconstruction Strategy and Fiber Bragg Grating.

A hybrid enhanced inverse finite element method (E-iFEM) is proposed for real-time intelligent sensing of discontinuous aerospace structures. The method can improve the flight performance of intelligent aircrafts by feeding back the structural shape information to the control system. Initially, the presented algorithm combines rigid kinematics with the classical iFEM to discretize the aerospace structures into elastic parts and rigid parts, which will effectively overcome structural complexity due to fluctuating bending stiffness and a special aerodynamic section. Subsequently, the rigid parts provide geometric constraints for the iFEM in the shape reconstruction method. Meanwhile, utilizing the Fiber Bragg grating (FBG) strain sensor to obtain real-time strain information ensures lightweight and anti-interference of the monitoring system. Next, the strain data and the geometric constraints are processed by the iFEM for monitoring the full-field elastic deformation of the aerospace structures. The whole procedure can be interpreted as a piecewise sensing technology. Overall, the effectiveness and reliability of the proposed method are validated by employing a comprehensive numerical simulation and experiment.

A Large-Scale Sensor Layout Optimization Algorithm for Improving the Accuracy of Inverse Finite Element Method.

The inverse finite element method (iFEM) based on fiber grating sensors has been demonstrated as a shape sensing method for health monitoring of large and complex engineering structures. However, the existing optimization algorithms cause the local optima and low computational efficiency for high-dimensional strain sensor layout optimization problems of complex antenna truss models. This paper proposes the improved adaptive large-scale cooperative coevolution (IALSCC) algorithm to obtain the strain sensors deployment on iFEM, and the method includes the initialization strategy, adaptive region partitioning strategy, and gbest selection and particle updating strategies, enhancing the reconstruction accuracy of iFEM for antenna truss structure and algorithm efficiency. The strain sensors optimization deployment on the antenna truss model for different postures is achieved, and the numerical results show that the optimization algorithm IALSCC proposed in this paper can well handle the high-dimensional sensor layout optimization problem.

Clinical benefit of systolic blood pressure within the target range among patients with or without diabetes mellitus: a propensity score-matched analysis of two randomized clinical trials.

BACKGROUND: Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as "reference." For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression. RESULTS: A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110-120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120-130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60-70 mmHg but were less distinct. CONCLUSIONS: The treatment benefit persists at as low as SBP 110-120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.

Applicability and cost-effectiveness of the Systolic Blood Pressure Intervention Trial (SPRINT) in the Chinese population: A cost-effectiveness modeling study.

BACKGROUND: The Systolic Blood Pressure Intervention Trial (SPRINT) showed significant reductions in death and cardiovascular disease (CVD) risk with a systolic blood pressure (SBP) goal of <120 mm Hg compared with a SBP goal of <140 mm Hg. Our study aimed to assess the applicability of SPRINT to Chinese adults. Additionally, we sought to predict the medical and economic implications of this intensive SBP treatment among those meeting SPRINT eligibility. METHODS AND FINDINGS: We used nationally representative baseline data from the China Health and Retirement Longitudinal Study (CHARLS) (2011-2012) to estimate the prevalence and number of Chinese adults aged 45 years and older who meet SPRINT criteria. A validated microsimulation model was employed to project costs, clinical outcomes, and quality-adjusted life-years (QALYs) among SPRINT-eligible adults, under 2 alternative treatment strategies (SBP goal of <120 mm Hg [intensive treatment] and SBP goal of <140 mm Hg [standard treatment]). Overall, 22.2% met the SPRINT criteria, representing 116.2 (95% CI 107.5 to 124.8) million people in China. Of these, 66.4%, representing 77.2 (95% CI 69.3 to 85.0) million, were not being treated for hypertension, and 22.9%, representing 26.6 (95% CI 22.4 to 30.7) million, had a SBP between 130 and 139 mm Hg, yet were not taking antihypertensive medication. We estimated that over 5 years, compared to standard treatment, intensive treatment would reduce heart failure incidence by 0.84 (95% CI 0.42 to 1.25) million cases, reduce CVD deaths by 2.03 (95% CI 1.44 to 2.63) million cases, and save 3.84 (95% CI 1.53 to 6.34) million life-years. Estimated reductions of 0.069 (95% CI -0.28, 0.42) million myocardial infarction cases and 0.36 (95% CI -0.10, 0.82) million stroke cases were not statistically significant. Furthermore, over a lifetime, moving from standard to intensive treatment increased the mean QALYs from 9.51 to 9.87 (an increment of 0.38 [95% CI 0.13 to 0.71]), at a cost of Int$10,997 per QALY gained. Of all 1-way sensitivity analyses, high antihypertensive drug cost and lower treatment efficacy for CVD death resulted in the 2 most unfavorable results (Int$25,291 and Int$18,995 per QALY were gained, respectively). Simulation results indicated that intensive treatment could be cost-effective (82.8% probability of being below the willingness-to-pay threshold of Int$16,782 [1× GDP per capita in China in 2017]), with a lower probability in people with SBP 130-139 mm Hg (72.9%) but a higher probability among females (91.2%). Main limitations include lack of specific SPRINT eligibility information in the CHARLS survey, uncertainty about the implications of different blood pressure measurement techniques, the use of several sources of data with large reliance on findings from SPPRINT, limited information about the serious adverse event rate, and lack of information and evidence for medication effectiveness on renal disease. CONCLUSIONS: Although adoption of the SPRINT treatment strategy would increase the number of Chinese adults requiring SBP treatment intensification, this approach has the potential to prevent CVD events, to produce gains in life-years, and to be cost-effective under common thresholds.

FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt.

Heart failure (HF) is the end stage of many cardiovascular diseases and seriously threatens people's health. This article aimed to explore the biological role of fat-mass and obesity-associated gene (FTO) in HF. We constructed HF mouse model by transverse aortic constriction or intraperitoneal injection of doxorubicin. Mouse myocardial cells were exposed to hypoxia/reoxygenation (H/R). FTO and Mhrt were downregulated in heart tissues of HF mice. HF mice exhibited an increase in the total levels of N6 methyladenosine (m6A) and the m6A levels of Mhrt. Moreover, FTO overexpression caused an upregulation of Mhrt and reduced m6A modification of Mhrt in the H/R-treated myocardial cells. FTO upregulation repressed apoptosis of H/R-treated myocardial cells. FTO knockdown had the opposite results. Mhrt overexpression reduced apoptosis of H/R-treated myocardial cells. Moreover, the influence conferred by FTO upregulation was abolished by Mhrt knockdown. In conclusion, our data demonstrate that FTO overexpression inhibits apoptosis of hypoxia/reoxygenation-treated myocardial cells by regulating m6A modification of Mhrt. Thus, FTO may be a target gene for HF treatment.

Atrial Dyssynchrony: A New Predictor for Atrial High-Rate Episodes in Patients with Cardiac Resynchronization Therapy.

BACKGROUND: Heart failure may induce atrial dyssynchrony. We aim to investigate whether preimplantation left atrial (LA) dyssynchrony could predict newly detected atrial high-rate episodes (AHRE) after receiving cardiac resynchronization therapy defibrillator (CRT-D). METHODS: We conducted a retrospective analysis of consecutive patients who received CRT-D for standard indications and without a history of atrial fibrillation. The standard deviation of the time-to-peak strain in each LA segment during ventricular systole (SDs) and late diastole (SDa) were calculated to quantify LA dyssynchrony using two-dimensional speckle tracking echocardiography before device implantation. Patients were divided into the AHRE group and the AHRE-free group, depending on the presence of AHRE during device interrogation. RESULTS: Thirty-one patients (28%) had newly detected AHRE during a mean follow-up of 21 ± 9 months. Patients in the AHRE group had higher SDs (8.2 ± 2.6% vs. 6.3 ± 2.3%, p < 0.001) and SDa (5.4 ± 1.8% vs. 4.1 ± 1.4%, p < 0.001) values before implantation than patients in the AHRE-free group. In the multivariate logistic analysis, both SDs (OR 1.325, 95% CI: 1.074-1.636, p =0.009) and SDa (OR: 1.499, 95% CI: 1.071-2.098, p= 0.018) were independent predictors of newly detected AHRE. At a cutoff value of 7.4% for SDs and 5.3% for SDa, the Kaplan-Meier survival analysis showed that patients with higher SDs and SDa had significantly increased risks of newly detected AHRE after receiving CRT-D. CONCLUSIONS: Dyssynchronous LA lengthening and contraction could assist in the prediction of newly detected AHRE in patients with CRT-D.

Prognostic Implications of QRS Duration in Third-Degree Atrioventricular Block Patients with Heart Failure Treated with Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) improves heart function and prognosis in third-degree atrioventricular block (AVB) patients with heart failure (HF). However, it is still unclear how to screen for appropriate patients before implantation. This study aimed to evaluate the value of using QRS duration to predict CRT efficacy.This study enrolled a total of 72 third-degree AVB patients with HF who received CRT implantation. The patients were divided into Groups A (QRS duration < 120 ms, 33 cases), B (120 ms ≤ QRS duration < 150 ms, 22 cases), and C (QRS duration ≥ 150 ms, 17 cases) according to their baseline QRS duration. The effects of different QRS durations on CRT efficacy were analyzed.The CRT response rate were 30.3%, 50.0%, and 76.5% in Groups A, B, and C, respectively (P = 0.008). The patients in the 3 groups showed significant changes in left ventricular (LV) end-diastolic volume, LV end-systolic volume, and LV ejection fraction over the baseline values at 12 months after the implantation (P < 0.05), with the greatest change observed in Group C. Survival analysis indicated statistically significant differences among Groups A, B, and C (P = 0.024). Multivariate logistic regression analysis suggested that QRS duration was an independent prognostic factor for CRT efficacy. Baseline QRS duration was associated with improved myocardial remodeling and reductions in the incidence rates of primary endpoint events.QRS ≥ 150 ms is an effective predictor of postoperative outcome in patients with third-degree AVB and HF treated with CRT.

[Influence of diastolic filling pattern on the efficacy of cardiac resynchronization therapy in patients with non-ischemic cardiomyopathy].

OBJECTIVE: To investigate the influence of diastolic filling pattern on the efficacy of cardiac resynchronization therapy (CRT) in patients with non-ischemic cardiomyopathy. METHODS: Between January 2012 and September 2013, 100 patients with non-ischemic cardiomyopathy undergoing CRT were enrolled in the study, and all patients were grouped by the pre-CRT diastolic filling pattern as impaired relaxation, pseudonormalized and restrictive filling. After follow up for 12 months, the New York Heart Association (NYHA) Class and echocardiography were used to assess the efficacy of CRT.The endpoint was rehospitalization for heart failure or cardiac death. Kaplan-Meier survival curves were plotted to assess prognosis. RESULTS: All patients had varying degrees of diastolic dysfunction.Logistic regression analysis indicated that diastolic filling pattern was the independent factor for the response of CRT.(1)The response rate (78.7%) of impaired relaxation group (n=61) was significantly higher than that of the other two groups (P<0.01); postoperative NYHA class, left ventricular ejection fraction (LVEF), fraction shortening (FS), left ventricular end-systolic volume (LVESV) and left ventricular end-diastolic volume (LVEDV) were significantly improved (all P<0.01). (2)For pseudonormalized group (n=18), at the 3(rd) month, NYHA class decreased from 3.3±0.5 to 2.3±0.5, LVEF increased from 27%±7% to 31%±6% (both P<0.01), and FS improved significantly (P<0.05); no significant decrease of LVEDV and LVESV was found. At the 6(th) month, LVEF improved significantly (P<0.01); LVESV was reduced (P<0.05). (3)In restrictive filling group (n=21), CRT brought short-term improvement in NYHA class but did not induce any significant improvement in LVEF, FS, LVESV and LVEDV.At the 6(th) month, there were significant differences in efficacy among the three groups (P<0.05). At the end of follow-up, 5 patients died, and the cumulative endpoint incidence was significantly higher in restrictive filling group (81%) than the other two groups (P<0.05). CONCLUSIONS: In patients with moderate-to-severe heart failure, left ventricular diastolic dysfunction affects the efficacy of CRT, patients with impaired relaxation benefit significantly, pseudonormalized patients take longer to benefit, but patients with restrictive filling do not benefit from CRT.

Stepwise high-throughput virtual screening of Rho kinase inhibitors from natural product library and potential therapeutics for pulmonary hypertension.

CONTEXT: Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary arterial pressure and vascular resistance due to pulmonary vasoconstriction and vessel remodeling. The activation of RhoA/Rho-kinase (ROCK) pathway plays a central role in the pathologic progression of PH and thus the Rho kinase, an essential effector of the ROCK pathway, is considered as a potential therapeutic target to attenuate PH. OBJECTIVE: In the current study, a synthetic pipeline is used to discover new potent Rho inhibitors from various natural products. MATERIALS AND METHODS: In the pipeline, the stepwise high-throughput virtual screening, quantitative structure-activity relationship (QSAR)-based rescoring, and kinase assay were integrated. The screening was performed against a structurally diverse, drug-like natural product library, from which six identified compounds were tested to determine their inhibitory potencies agonist Rho by using a standard kinase assay protocol. RESULTS: With this scheme, we successfully identified two potent Rho inhibitors, namely phloretin and baicalein, with activity values of IC50 = 0.22 and 0.95 µM, respectively. DISCUSSION AND CONCLUSION: Structural examination suggested that complicated networks of non-bonded interactions such as hydrogen bonding, hydrophobic forces, and van der Waals contacts across the complex interfaces of Rho kinase are formed with the screened compounds.

Nomogram Model to Predict Acute Kidney Injury in Hospitalized Patients with Heart Failure.

Background: Acute kidney injury (AKI) is a common complication of acute heart failure (HF) that can prolong hospitalization time and worsen the prognosis. The objectives of this research were to ascertain independent risk factors of AKI in hospitalized HF patients and validate a nomogram risk prediction model established using those factors. Methods: Finally, 967 patients hospitalized for HF were included. Patients were randomly assigned to the training set (n = 677) or test set (n = 290). Least absolute shrinkage and selection operator (LASSO) regression was performed for variable selection, and multivariate logistic regression analysis was used to search for independent predictors of AKI in hospitalized HF patients. A nomogram prediction model was then developed based on the final identified predictors. The performance of the nomogram was assessed in terms of discriminability, as determined by the area under the receiver operating characteristic (ROC) curve (AUC), and predictive accuracy, as determined by calibration plots. Results: The incidence of AKI in our cohort was 19%. After initial LASSO variable selection, multivariate logistic regression revealed that age, pneumonia, D-dimer, and albumin were independently associated with AKI in hospitalized HF patients. The nomogram prediction model based on these independent predictors had AUCs of 0.760 and 0.744 in the training and test sets, respectively. The calibration plots indicate a strong concordance between the estimated AKI probabilities and the observed probabilities. Conclusions: A nomogram prediction model based on pneumonia, age, D-dimer, and albumin can help clinicians predict the risk of AKI in HF patients with moderate discriminability.

Association between intensive blood pressure lowering and stroke-free survival among patients with and without Diabetes.

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.

Fabry disease caused by the GLA p.Gly183Asp (p.G183D) variant: Clinical profile of a serious phenotype.

Background: The detailed clinical phenotype of patients carrying the α-galactosidase gene (GLA) c.548 G > A/p.Gly183Asp (p.G183D) variant in Fabry disease (FD) has not been thoroughly documented in the existing literature. Methods: This paper offers a meticulous overview of the clinical phenotype and relevant auxiliary examination results of nine confirmed FD patients with the p.G183D gene variant from two families. Pedigree analysis was conducted on two male patients with the gene variant, followed by biochemical and genetic screening of all high-risk relatives. Subsequently, evaluation of multiple organ systems and comprehensive instrument assessment were performed on heterozygotes of the p.G183D gene variant. Results: The study revealed that all patients exhibited varying degrees of cardiac involvement, with two demonstrating left ventricular wall thickness exceeding 15 mm on echocardiography, and the remaining six exceeding 11 mm. Impaired renal function was evident in all six patients with available blood test data, two of whom underwent kidney transplantation. Eight cases reported neuropathic pain, and five experienced varying degrees of stroke or transient ischemic attack (TIA). Conclusion: This study indicates that the GLA p.G183D gene variant can induce premature organ damage, particularly affecting the heart, kidneys, and nervous system.

Recurrent heart failure hospitalizations in heart failure with preserved ejection fraction: an analysis of TOPCAT trial.

AIMS: Recurrent heart failure hospitalization (HFH) is an important feature of the progression of heart failure (HF). In the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, we analysed risk factors for recurrent HFH events in HF patients with preserved ejection fraction (HFpEF) and developed a risk prediction model for recurrent HFH. METHODS AND RESULTS: This analysis focused on the subset of TOPCAT participants enrolled in the Americas (n = 1767). Recurrent HFH was defined as two or more hospitalizations for HF during the follow-up period. Lasso regression and multivariate logistic regression were used to screen the risk factors, and the risk prediction model of recurrent HFH was established. During a median follow-up period of 3.4 (95% confidence interval: 3.3-3.6) years, 72.2% (542 of 751 total hospitalizations) of HFH events occurred in 9.4% (n = 163) of patients with recurrent HFHs. Patients in the recurrent HFH group had higher cardiovascular mortality rate [6.2 per 100 patient-years (PY) vs. 3.8 per 100 PY, P = 0.016] and all-cause mortality rate (10.0 per 100 PY vs. 6.8 per 100 PY, P = 0.015) than those in the non-recurrent HFH group. The model consisting of nine predictors has moderate predictive power for recurrent HFH events in patients with HFpEF (AUC = 0.75, Brier score = 0.08). Decision curve analysis showed a net clinical benefit from the application of the prediction model. CONCLUSIONS: In patients with HFpEF, the majority of HFHs occur in a small proportion of patients with repeated hospitalizations, who typically have more comorbidities and are at higher risk of death. The predictive model developed in this study helps to identify patients at high risk of recurrent HFH.

Time-weighted blood pressure with cardiovascular risk among patients with or without diabetes.

BACKGROUND: Usual measures of blood pressure (BP) do not account for both the magnitude and duration of exposure to elevated BP over time. We aimed to demonstrate the effect of a novel time-weighted BP on cardiovascular outcomes using a post hoc analysis of two published randomized trials. HYPOTHESIS: Time-weighted blood pressure is associated with cardiovascular risk among patients with or without diabetes. METHODS: The limited-access ACCORD and SPRINT data sets were used for the current study. Time-weighted BP is obtained by dividing cumulative BP by the total follow-up time. Time-weighted BP burden above a threshold is also determined after deriving the time-weighted BP by re-zeroing the interpolated pressure values at two different hypertension thresholds (>140/90 and >130/80 mmHg). RESULTS: Eighteen thousand five hundred forty-one patients from the two clinical trials were enrolled in this study. A J-curve relation was observed between time-weighted BP and major cardiovascular events (MACE). The systolic blood pressure (SBP) burden independently predicted MACE across the two trials at different thresholds (ACCORD: SBP > 130 mmHg, HR = 1.05 [1.03-1.06]; SBP > 140 mmHg, HR = 1.06 [1.04-1.08]; SPRINT: SBP > 130 mmHg, HR = 1.04 [1.03-1.05]; SBP > 140 mmHg, HR = 1.05 [1.04-1.07]). Consistent results were found for diastolic blood pressure (DBP) burden (ACCORD: DBP > 80 mmHg, HR = 1.10 [1.06-1.15]; DBP > 90 mmHg, HR = 1.20 [1.11-1.30]. SPRINT: DBP > 80 mmHg, HR = 1.06 [1.02-1.09]; DBP > 90 mmHg, HR = 1.12 [1.06-1.18]). Significant associations were also observed for stroke, myocardial infarction, cardiovascular death, and all-cause mortality. CONCLUSION: Both time-weighted SBP and DBP independently influenced the risk of adverse cardiovascular events among patients with and without diabetes, regardless of the definition of hypertension (130/80 or <140/90 mmHg).

Generalisability and potential deaths averted from intensive blood pressure treatment among the elderly population in the US and China: A nationally representative cross-sectional study.

Background: The Systolic Blood Pressure Intervention Trial (SPRINT) from the US and the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial from China have consistently demonstrated clinical benefits from intensive blood pressure (BP) treatment among elderly adults with hypertension. However, we have little data on the generalisability and potential implications of a scale-up of intensive BP treatment to all eligible elderly in the US and China. Methods: We used two nationally representative data sets from China (Health and Retirement Longitudinal Study (CHALRS), 2011-2012) and the US (National Health and Nutrition Examination Survey (NHANES), 2007-2012) and linked them with CHARLS follow-up data (2013) and the National Death Index (1999-2015), respectively. We estimated the percentage, number, and characteristics of elderly (≥60 years old) meeting the STEP and SPRINT eligibility criteria, and deaths that would be prevented or postponed with the implementation of intensive BP treatment. Results: Among the Chinese adults aged 60 years and over, 38.89% (95% confidence interval (CI) = 36.97-40.84) or 85.39 (95% CI = 81.14-89.64) million subjects met the STEP criteria, and 40.90 million (47.90%) adults were not taking antihypertensive medications. In the US, 23.77% (95% CI = 22.32%-25.28) or 12.46 (95% CI = 11.68-13.24) million elderly were eligible for the SPRINT, and 5.78 million (46.36%) were untreated. Overall, 0.07 (95% CI = 0.06-0.08) million deaths in the US and 0.31 (95% CI = 0.25-0.39) in China would be averted annually if intensive BP treatment was implemented, while 120 000 and 680 000 of hypotension cases would be identified yearly inthe US and China, respectively. Conclusions: A substantial percentage of Chinese and the US elderly meet the eligibility criteria for STEP and SPRINT. If intensive BP treatment was adopted, 70 000 and 310 000 deaths would be prevented or postponed yearly in the US and China, respectively.

Longer time in blood pressure target range improves cardiovascular outcomes among patients with Type 2 diabetes: A secondary analysis of a randomized clinical trial.

AIMS: To examine the prognostic value of time in target range (TIR) with adverse outcomes and validate it with common blood pressure (BP) metrics among patients with Type 2 diabetes mellitus. METHODS: We performed a post hoc analysis of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial. TIR for each subject was calculated using linear interpolation and an SBP target range of 110 to 130 mmHg. Cox models were used to assess the association of TIR and other BP metrics with the rate of clinical outcomes. RESULTS: A higher TIR (61.9-100.0 %) was associated with a 46 % reduction in major adverse cardiovascular events (MACE) (hazard ratio [HR]:0.54; 95 % CI: 0.43, 0.67) compared with TIR 0-22.9 %. Results were similar for stroke (0.19; 0.10, 0.36), myocardial infarction (0.67; 0.51, 0.89), heart failure (0.47; 0.33, 0.66), cardiovascular death (0.63; 0.42, 0.93) and all-cause mortality (0.70; 0.54, 0.91). Further analyses suggested a curvilinear association of TIR with MACE, and this association was independent with baseline, final SBP, mean SBP, or visit-to-visit SBP variability. CONCLUSIONS: Longer TIR is associated with lower cardiovascular risk and may add value as an outcome measure for hypertension control studies among patients with diabetes.

Time to Benefit of Sodium-Glucose Cotransporter-2 Inhibitors Among Patients With Heart Failure.

Importance: Emerging evidence has consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) hospitalization and cardiovascular (CV) death among patients with HF. However, it remains unclear how long a patient needs to live to potentially benefit from SGLT2 inhibitors in this population. Objectives: To estimate the time to benefit from SGLT2 inhibitors among patients with HF. Design, Setting, and Participants: This comparative effectiveness study systematically searched PubMed for completed randomized clinical trials about SGLT2 inhibitors and patients with HF published until September 5, 2022; 5 trials with the year of publication ranging from 2019 to 2022 were eventually included. Statistical analysis was performed from April to October 2022. Intervention: Addition of SGLT2 inhibitors or placebo to guideline-recommended therapy. Main Outcomes and Measures: The primary outcome was the time to first event of CV death or worsening HF, which was broadly comparable across the included trials. Results: Five trials consisting of 21 947 patients with HF (7837 [35.7%] were female; mean or median age older than 65 years within each trial) were included. SGLT2 inhibitors significantly reduced the risk of worsening HF or CV death (hazard ratio [HR], 0.77 [95% CI, 0.73-0.82]). Time to first nominal statistical significance (P < .05) was 26 days (0.86 months), and statistical significance was sustained from day 118 (3.93 months) onwards. A mean of 0.19 (95% CI, 0.12-0.35) months were needed to prevent 1 worsening HF or CV death per 500 patients with SGLT2 inhibitors (absolute risk reduction [ARR], 0.002). Likewise, 0.66 (95% CI, 0.43-1.13) months was estimated to avoid 1 event per 200 patients with SGLT2 inhibitors (ARR, 0.005), 1.74 (95% CI, 1.07-2.61) months to avoid 1 event per 100 patients (ARR, 0.010), and 4.96 (95% CI, 3.18-7.26) months to avoid 1 event per 50 patients (ARR, 0.020). Further analyses indicated a shorter time to benefit for HF hospitalization and among patients with diabetes or HF with reduced ejection fraction. Conclusions and Relevance: In this comparative effectiveness research study of estimating the time to benefit from SGLT2 inhibitors among patients with HF, a rapid clinical benefit in reducing CV death or worsening HF was found, suggesting that their use may be beneficial for most individuals with HF.

Hypertension Subtypes, Mortality Risk, and Differential Effects Between Two Hypertension Guidelines.

Aim: To examine which hypertension subtypes are primarily responsible for the difference in the hypertension prevalence and treatment recommendations, and to assess their mortality risk if 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline were adopted among Chinese adults. Methods: We used the nationally representative data of China Health and Retirement Longitudinal Study (CHARLS) to estimate the differences in the prevalence of isolated systolic hypertension (ISH), systolic diastolic hypertension (SDH) and isolated diastolic hypertension (IDH) between the 2017 ACC/AHA and the 2018 China Hypertension League (CHL) guidelines. We further assessed their mortality risk using follow-up data from the China Health and Nutrition Survey (CHNS) by the Cox model. Results: The increase from the 2017 ACC/AHA guideline on hypertension prevalence was mostly from SDH (8.64% by CHL to 25.59% by ACC/AHA), followed by IDH (2.42 to 6.93%). However, the difference was minuscule in the proportion of people recommended for antihypertensive treatment among people with IDH (2.42 to 3.34%) or ISH (12.00 to 12.73%). Among 22,184 participants with a median follow-up of 6.14 years from CHNS, attenuated but significant associations were observed between all-cause mortality and SDH (hazard ratio 1.56; 95% CI: 1.36,1.79) and ISH (1.29; 1.03,1.61) by ACC/AHA but null association for IDH (1.15; 0.98,1.35). Conclusion: Adoption of the 2017 ACC/AHA may be applicable to improve the unacceptable hypertension control rate among Chinese adults but with cautions for the drug therapy among millions of subjects with IDH.

Prognostic Value of Time in Blood Pressure Target Range Among Patients With Heart Failure.

BACKGROUND: Blood pressure (BP) is a continuous and dynamic measure. However, standard BP control metrics may not reflect the variability in BP over time. OBJECTIVES: This study assessed the prognostic value of time in BP target range among hypertensive patients with heart failure (HF). METHODS: The authors performed a post hoc analysis of data from the TOPCAT (Treatment of Preserved Cardiac Function HF with an Aldosterone Antagonist) trial and the BEST (Beta-Blocker Evaluation of Survival Trial). Time in target range (TTR) for each patient was calculated using linear interpolation across the study period with the target range of systolic BP between 120 and 130 mm Hg. RESULTS: A total of 4,789 hypertensive patients (n = 1,654 from BEST and n = 3,135 from TOPCAT) were included. The cumulative incidences of primary endpoint (ie, cardiovascular death or HF hospitalization) were highest among the top quartile of TTR with a dose-dependent manner across quartiles (Ptrend <0.005). The top quartile of TTR was significantly associated with a lower risk of primary outcome using adjusted Cox regression model (HR: 0.71; 95% CI: 0.60-0.82), cardiovascular mortality (HR: 0.68; 95% CI: 0.55-0.84), HF hospitalization (HR: 0.70; 95% CI: 0.58-0.85), all-cause mortality (HR: 0.69; 95% CI: 0.58-0.83), and any hospitalization (HR: 0.76; 95% CI: 0.67-0.85). Further analyses using restricted cubic spline indicated a linear relationship between TTR and primary outcome. Similar patterns were observed in the individual trial. Sensitivity analyses generated consistent results while redefining target range as 110 to 130 mm Hg for systolic BP or 70 to 80 mm Hg for diastolic BP. CONCLUSIONS: TTR could independently predict major adverse cardiovascular events in hypertensive patients with HF.

Time to Clinical Benefit of Intensive Blood Pressure Lowering in Patients 60 Years and Older With Hypertension: A Secondary Analysis of Randomized Clinical Trials.

Importance: Recent guidelines recommend a systolic blood pressure (BP) goal of less than 150 mm Hg or even 130 mm Hg for adults aged 60 years or older. However, harms from intensive BP treatments occur immediately (eg, syncope, fall), and benefits for cardiovascular event reduction emerge over time. Therefore, harms with low chance of benefit need to be clearer, particularly for those with limited life expectancy. Objective: To estimate the time needed to potentially derive clinical benefit from intensive BP treatment in patients 60 years and older. Design, Setting, and Participants: This secondary analysis included individual patient data from published randomized clinical trials with 27 414 patients 60 years or older with hypertension. Patient-level survival data were reconstructed when the original data were not available. Published trials were identified by searching PubMed until October 15, 2021. Exposures: Intensive BP lowering vs standard BP lowering with the treat-to-target design. Main Outcomes and Measures: Major adverse cardiovascular event (MACE) defined by each trial, which was broadly similar with all trials including myocardial infarction, stroke, and cardiovascular mortality. Results: Six trials (original data from 2 trials and reconstructed data from 4 trials) with 27 414 participants (mean age, 70 years; 56.3% were women) were included in the analysis. Intensive BP treatment with a systolic BP target below 140 mm Hg was significantly associated with a 21% reduction in MACE (hazard ratio, 0.79; 95% CI, 0.71-0.88; P < .001). On average, 9.1 (95% CI, 4.0-20.6) months were needed to prevent 1 MACE per 500 patients with the intensive BP treatment (absolute risk reduction [ARR], 0.002). Likewise, 19.1 (95% CI, 10.9-34.2) and 34.4 (95% CI, 22.7-59.8) months were estimated to avoid 1 MACE per 200 (ARR, 0.005) and 100 (ARR, 0.01) patients, respectively. Conclusions and Relevance: In this analysis, findings suggest that for patients 60 years and older with hypertension, intensive BP treatment may be appropriate for some adults with a life expectancy of greater than 3 years but may not be suitable for those with less than 1 year.