Metabolic syndrome and cardiovascular disease in cancer survivors.

BACKGROUND: The risk of subsequent cardiovascular disease (CVD) is high in cancer survivors. Although metabolic syndrome is an established risk factor for CVD, its association with cancer survivors has not yet been established. This study aimed to clarify whether metabolic syndrome is associated with subsequent CVD risk in patients with cancer using a nationwide epidemiological dataset. METHODS: We retrospectively analysed 53 510 patients with a history of breast, colorectal, or stomach cancer, which is reportedly a major site for developing cancer in Japan. Study participants were categorized into two groups based on the presence of metabolic syndrome, defined using the Japanese criteria (high waist circumference and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). The clinical outcomes were collected between 2005 and 2021. The primary endpoint was defined as the composite CVD outcome, including myocardial infarction, angina pectoris, stroke, and heart failure. RESULTS: The median patient age was 54 years, and 37.5% of the patients were men. Metabolic syndrome was observed in 5558 (10.4%) patients. Over a mean follow-up period of 973 ± 791 days, 3085 composite CVD outcomes were recorded. Multivariable Cox regression analyses showed that metabolic syndrome was associated with a greater risk of developing CVD events (HR = 1.29, 95% CI = 1.15-1.45). Metabolic syndrome was also associated with an increased risk of CVD in patients with a follow-up period ≥1 year (HR = 1.33, 95% CI = 1.15-1.53). This relationship was also observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.34, 95% CI = 1.21-1.49) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.32, 95% CI = 1.19-1.46). Subgroup analyses showed that the relationship between metabolic syndrome and incident CVD was more pronounced in the non-obese participants than in the obese participants. CONCLUSIONS: Metabolic syndrome is associated with a greater risk of developing CVD, even among cancer survivors.

Association of Cancer and Its Interaction with Conventional Risk Factors on Cardiovascular Disease Risk.

Introduction We sought to examine the association of cancer history with the incidence of individual cardiovascular disease events and to clarify whether the history of cancer modifies the relationship between conventional cardiovascular risk factors and incident cardiovascular disease. Methods This retrospective cohort study used the JMDC Claims Database, including 3,531,683 individuals. The primary endpoint was the composite cardiovascular disease outcome, which included myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Results During a follow-up, 144,162 composite endpoints were recorded. Individuals with a history of cancer had a higher risk of developing composite cardiovascular disease events (HR 1.26, 95% CI 1.22-1.29). The HRs for myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation were 1.11 (95% CI 0.98-1.27), 1.15 (95% CI 1.10-1.20), 1.11 (95% CI 1.05-1.18), 1.39 (95% CI 1.34-1.44), and 1.22 (95% CI 1.13-1.32), respectively. Individuals who required chemotherapy for cancer had a higher risk of developing cardiovascular disease. Although conventional risk factors (e.g., overweight/obesity, hypertension, and diabetes) were associated with incident composite cardiovascular disease even in individuals with a history of cancer, the total population-attributable fractions of conventional risk factors were less in individuals with a history of cancer. Conclusion Individuals with a history of cancer (particularly those requiring chemotherapy) have a higher risk of cardiovascular disease. Traditional risk factors are important in the development of cardiovascular disease in individuals with and without a history of cancer. In individuals with a history of cancer, however, the total population-attributable fractions of conventional risk factors decreased.

Control of Polar/Antipolar Layered Organic Semiconductors by the Odd-Even Effect of Alkyl Chain.

Some rodlike organic molecules exhibit exceptionally high layered crystallinity when composed of a link between π-conjugated backbone (head) and alkyl chain (tail). These molecules are aligned side-by-side unidirectionally to form self-organized polar monomolecular layers, providing promising 2D materials and devices. However, their interlayer stacking arrangements have never been tunable, preventing the unidirectional arrangements of molecules in whole crystals. Here, it is demonstrated that polar/antipolar interlayer stacking can be systematically controlled by the alkyl carbon number n, when the molecules are designed to involve effectively weakened head-to-head affinity. They exhibit remarkable odd-even effect in the interlayer stacking: alternating head-to-head and tail-to-tail (antipolar) arrangement in odd-n crystals, and uniform head-to-tail (polar) arrangement in even-n crystals. The films show excellent field-effect transistor characteristics presenting unique polar/antipolar dependence and considerably improved subthreshold swing in the polar films. Additionally, the polar films present enhanced second-order nonlinear optical response along normal to the film plane. These findings are key for creating polarity-controlled optoelectronic materials and devices.

A machine-learning-based prediction of non-home discharge among acute heart failure patients.

BACKGROUND: Scarce data on factors related to discharge disposition in patients hospitalized for acute heart failure (AHF) were available, and we sought to develop a parsimonious and simple predictive model for non-home discharge via machine learning. METHODS: This observational cohort study using a Japanese national database included 128,068 patients admitted from home for AHF between April 2014 and March 2018. The candidate predictors for non-home discharge were patient demographics, comorbidities, and treatment performed within 2 days after hospital admission. We used 80% of the population to develop a model using all 26 candidate variables and using the variable selected by 1 standard-error rule of Lasso regression, which enhances interpretability, and 20% to validate the predictive ability. RESULTS: We analyzed 128,068 patients, and 22,330 patients were not discharged to home; 7,879 underwent in-hospital death and 14,451 were transferred to other facilities. The machine-learning-based model consisted of 11 predictors, showing a discrimination ability comparable to that using all the 26 variables (c-statistic: 0.760 [95% confidence interval, 0.752-0.767] vs. 0.761 [95% confidence interval, 0.753-0.769]). The common 1SE-selected variables identified throughout all analyses were low scores in activities of daily living, advanced age, absence of hypertension, impaired consciousness, failure to initiate enteral alimentation within 2 days and low body weight. CONCLUSIONS: The developed machine learning model using 11 predictors had a good predictive ability to identify patients at high risk for non-home discharge. Our findings would contribute to the effective care coordination in this era when HF is rapidly increasing in prevalence.

Association of Metabolic Dysfunction-Associated Fatty Liver Disease With Risk of HF and AF.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel concept of hepatic disease. Although the prevalences of heart failure (HF) and atrial fibrillation (AF) are increasing worldwide, limited data have assessed the extent to which MAFLD is associated with incident HF and AF. Objectives: The authors sought to examine the association of MAFLD with incident HF and AF. Methods: Analyses were conducted using a nationwide epidemiologic database including 3,279,918 individuals (median age 45 years; 57.6% men). Metabolic dysfunction was defined as 1 or more of the following: overweight (body mass index ≥23 kg/m2), metabolic syndrome, or diabetes mellitus. FLD was defined as fatty liver index of >30. MAFLD was defined as the coexistence of metabolic dysfunction and FLD. We categorized study participants into 4 groups: non-FLD/nonmetabolic dysfunction (n = 1,709,116), metabolic dysfunction (n = 584,483), FLD (n = 89,497), and MAFLD (n = 896,822). The primary outcomes were HF and AF. Results: Over a mean follow-up period of 1,160 ± 905 days, 62,746 incident HF events and 15,408 incident AF events were recorded. Compared with the non-FLD/non-metabolic dysfunction group, HRs for HF and AF, respectively, were 1.20 (95% CI: 1.18-1.23) and 1.13 (95% CI: 1.08-1.19) for metabolic dysfunction, 1.24 (95% CI: 1.19-1.30) and 1.13 (95% CI: 1.04-1.23) for FLD, and 1.73 (95% CI: 1.69-1.76) and 1.51 (95% CI: 1.46-1.57) for MAFLD. MAFLD was also associated with a higher risk of developing myocardial infarction, angina pectoris, and stroke. A risk of developing cardiovascular events differed between MAFLD subtypes (Wald test P < 0.001). Conclusions: MAFLD was associated with a greater risk of developing HF and AF, suggesting the clinical importance of this novel hepatic disease concept.

Association Between Early Initiation of Cardiac Rehabilitation and Short-Term Outcomes of Patients With Acute Heart Failure Admitted to the Intensive Care Unit.

Cardiac rehabilitation (CR) is a promising therapeutic option for chronic heart failure (HF). However, the extent to which early rehabilitation is beneficial for patients receiving critical care remains controversial. This study examined the association between the early initiation of CR and the short-term clinical outcomes of patients admitted to the intensive care unit (ICU) with acute HF. We used the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan, and included patients with acute HF admitted to the ICU within 2 days after hospital admission. We defined the early initiation of CR as its initiation within 2 days of hospital admission. We performed an overlap weighting based on the propensity scores and inverse probability of treatment weighting analysis to compare the clinical outcomes between patients with and without early initiation of CR. Among 25,362 eligible patients, 3,582 (14.1%) received an early initiation of CR. Overlap weighting created well-balanced cohorts, which showed that the early initiation of CR was related to lower in-hospital mortality (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.68 to 0.96) and shorter hospital stay. The inverse probability of treatment weighting analysis also showed that in-hospital mortality was lower in the patients with the early initiation of CR (OR 0.80, 95% CI 0.67 to 0.96). The instrumental variable analysis also demonstrated the association of the early initiation of CR with lower in-hospital mortality (OR 0.64, 95% CI 0.44 to 0.93). In conclusion, early initiation of CR after hospital admission was associated with better short-term outcomes in patients with acute HF admitted to the ICU, suggesting the potential of the early administration of CR for acute HF requiring intensive care.

Impact of Stent Expansion Index on Stent Failure After Left Main Stenting.

Impact of the stent expansion index (EXPI) in percutaneous coronary intervention (PCI) for unprotected left main distal bifurcation lesions (ULMD) has been not completely understood especially in current-generation drug-eluting stent (cDES) era. We evaluated the impact of EXPI on clinical outcomes after PCI with cDES for ULMD. We identified 342 patients treated with cDES for ULMD and postintervention intravascular ultrasound between January 2010 and December 2019. In this study, the ratio of minimum stent area (MSA) to reference vessel area at the MSA site was adopted to assess the stent expansion. We defined the patients with the first and second tertile as low-intermediate EXPI group and those with the third tertile as high EXPI group and compared the clinical outcomes between both groups. The primary end point was target lesion failure (TLF). TLF was defined as a composite of cardiac death, target lesion revascularization (TLR) ,and myocardial infarction. The MSA was located in the ostium of left anterior descending coronary artery in most cases (318 of 342 patients; 93.0%). There were no significant differences between both groups in the baseline clinical, lesion, and procedural characteristics. The high EXPI group had lower TLF rate than the low-intermediate EXPI group (10.2% vs 19.9%, log-rank p = 0.033). In conclusion, this is the first report that the higher ratio of MSA to reference vessel area at the MSA site, which was defined as stent EXPI, was associated with more favorable clinical outcomes after PCI for ULMD.

Malnutrition and inflammation status in nonobese patients with inflammatory bowel disease are associated with nonalcoholic fatty liver disease: a retrospective study.

BACKGROUND/AIMS: The frequency and details of nonalcoholic fatty liver disease (NAFLD) complications in patients with inflammatory bowel disease (IBD) remain unclear. This study aimed to clarify characteristics of NAFLD in patients with IBD. METHODS: We retrospectively identified and enrolled patients with IBD diagnosed with or without NAFLD by undergoing abdominal computed tomography (CT) at our institution between 2005 and 2020. The primary endpoint was the complication rate of NAFLD in patients with IBD. Secondary endpoints were the clinical characteristics of nonobese patients with IBD and comorbid NAFLD and their association with nutritional and inflammatory parameters. RESULTS: Twenty-one (21.9%) of 96 eligible patients with IBD also had NAFLD. In nonobese patients (defined as patients with a body mass index <25 kg/m2), C-reactive protein (CRP; P<0.001) and alanine aminotransferase (P=0.018) levels were higher and the albumin level (P=0.005) and prognostic nutritional index (PNI; P=0.002) values were lower in patients with NAFLD than in those without NAFLD. The PNI value was positively correlated (P<0.001) and the CRP level was negatively correlated (P=0.001) with the hepatosplenic ratio. However, in the NAFLD combined group, PNI (P<0.05) and CRP values (P<0.001) were improved over time after CT imaging by continuing IBD treatment. CONCLUSIONS: Worsening nutritional and inflammatory status in IBD patients is associated with complications of NAFLD. Diagnosis of NAFLD in IBD patients using CT imaging might be useful not only for early detection of NAFLD but also in assessing the need for therapeutic intervention for IBD.

Efficacy of azilsartan on left ventricular diastolic dysfunction compared with candesartan: J-TASTE randomized controlled trial.

Characterized by ventricular and vascular stiffness, heart failure with preserved ejection fraction (HFpEF) has led to high morbidity and mortality. As azilsartan is an angiotensin receptor blocker with the highest myocardial and vascular affinities, azilsartan may improve the left ventricular (LV) diastolic function in patients with hypertension and either HFpEF or HF with mildly reduced ejection fraction (HFmrEF) more than candesartan. In this randomized, open-label trial, we randomly assigned 193 hypertensive patients with HF and LV ejection fraction ≥ 45% to 20 mg of azilsartan (n = 95) or 8 mg of candesartan (n = 98), once daily for 48 weeks. After the initiation of treatment, changes in the doses of the study drugs were permitted based on the patient's conditions, including blood pressure (median dose at 48 weeks: azilsartan 20.0 mg/day, candesartan 8.0 mg/day). The primary endpoint was the baseline-adjusted change in the ratio of peak early diastolic transmitral flow velocity (E) to early diastolic mitral annular velocity (e') (E/e'). Adjusted least-squares mean (LSM) change in E/e' was - 0.8 (95% confidence interval [CI] - 1.49 to - 0.04) in the azilsartan group and 0.2 (95% CI - 0.49 to 0.94) in the candesartan group, providing the LSM differences of - 1.0 (95% CI - 2.01 to 0.03, P = 0.057). The median change in left atrial volume index was - 2.7 mL/m2 with azilsartan vs 1.4 mL/m2 with candesartan (P = 0.091). The frequency of adverse events related to hypotension and hyperkalemia did not differ between the groups. The current study did not provide strong evidence that azilsartan improves LV diastolic dysfunction, and further confirmatory study is required.

Association of four health behaviors in Life's Essential 8 with the incidence of hypertension and diabetes mellitus.

BACKGROUND: The association between health behaviors and the risk of developing hypertension and diabetes is not fully understood. We aimed to examine the association between four health behaviors involved in Life's Essential 8, the American Heart Association's key measures for improving and maintaining cardiovascular health, and the incidence of hypertension and diabetes. METHODS: This observational cohort study used the JMDC Claims Database between 2005 and 2021, which is a health check-up and claims database. We analyzed 2,912,183 participants without a history of hypertension, diabetes, cardiovascular disease, or renal failure. Non-ideal health behaviors included smoking, slow gait speed, eating fast, and poor sleep quality. RESULTS: During 1140 ± 877 days, 201,385 hypertension and 142,156 diabetes events were recorded. In a multivariable Cox regression analysis, the risk of hypertension and diabetes increased with an increasing number of non-ideal health behaviors. The hazard ratios (HRs) (95% confidence interval [CI]) per 1-point increase in non-ideal health behavior components for hypertension and diabetes were 1.11 (1.10-1.11) and 1.08 (1.08-1.09), respectively. Each health behavior was independently associated with the incidence of hypertension and diabetes. A 1-point improvement in health behaviors was associated with a lower risk of developing hypertension (HR 0.94, 95% CI 0.93-0.95) and diabetes (HR 0.95, 95% CI 0.94-0.96). CONCLUSION: Factors that can be substituted for the four health behaviors involved in Life's Essential 8 can stratify the risk of hypertension and diabetes, and improving these health behaviors is useful in preventing hypertension and diabetes in general population.

Subjective Gait Speed and Risk of Developing Cardiovascular Events in 56,589 Cancer Survivors.

Despite having a higher risk of cardiovascular disease (CVD), there are currently limited data for stratifying CVD risk among cancer survivors. The purpose of this study was to uncover the relationship of subjective gait speed with incident CVD among cancer survivors.This retrospective observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2021 including 56,589 patients with a prior history of breast, colorectal, or stomach cancer but no history of CVD. Gait speed was evaluated using information from self-reported questionnaires collected during health checkups. The primary endpoint was composite CVD outcome, which included heart failure, myocardial infarction, angina pectoris, and stroke.The median (interquartile range) age was 54 (48-61) years, and 20,981 (37.1%) were male. Among them, 25,933 patients (45.8%) reported fast gait speed. During a mean follow-up period of 1002 ± 803 days, 3,221 composite CVD outcomes were recorded. In multivariate Cox regression analysis, slow gait speed was associated with a higher risk of developing CVD compared with fast gait speed (hazard ratio, 1.14, 95% confidence interval, 1.06-1.22). This association was consistent across a variety of sensitivity analyses.We demonstrated that subjective slow gait speed was associated with a greater risk of CVD development among cancer survivors. This suggests the potential value of gait speed assessment for the CVD risk stratification of cancer patients as well as the clinical importance of maintaining exercise capacity among patients living with cancer.

The estimation of coronary artery calcium thickness by computed tomography angiography based on optical coherence tomography measurements.

Optical coherence tomography (OCT) is recommended to be the most appropriate modality in assessing calcium thickness, however, it has limitations associated with infrared attenuation. Although coronary computed tomography angiography (CCTA) detects calcification, it has low resolution and hence not recommended to measure the calcium size. The aim of this study was to devise a simple algorithm to estimate calcium thickness based on the CCTA image. A total of 68 patients who had CCTA for suspected coronary artery disease and subsequently went on to have OCT were included in the study. 238 lesions of them divided into derivation and validation dataset at 2:1 ratio (47 patients with 159 lesions and 21 with 79, respectively) were analyzed. A new method was developed to estimate calcium thickness from the maximum CT density within the calcification and compared with calcium thickness measured by OCT. Maximum Calcium density and measured calcium-border CT density had a good correlation with a linear equation of y = 0.58x + 201 (r = 0.892, 95% CI 0.855-0.919, p < 0.001). The estimated calcium thickness derived from this equation showed strong agreement with measured calcium thickness in validation and derivation dataset (r2 = 0.481 and 0.527, 95% CI 0.609-0.842 and 0.497-0.782, p < 0.001 in both, respectively), more accurate than the estimation by full width at half maximum and inflection point method. In conclusion, this novel method provided the estimation of calcium thickness more accurately than conventional methods.

Association of Body Mass Index and Its Change With Incident Diabetes Mellitus.

CONTEXT: There have been insufficient data on the threshold of body mass index (BMI) for developing diabetes mellitus (DM) and the relationship between change in BMI and the subsequent risk of DM. OBJECTIVE: We sought to clarify the association of BMI and its change with incident DM. METHODS: We conducted a retrospective observational cohort study using the JMDC Claims Database between 2005 and 2021. We included 3 400 303 individuals without a prior history of DM or usage of glucose-lowering medications. The median age was 44 years, and 57.5% were men. We categorized the study participants into 4 groups: underweight (BMI < 18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2). According to the change in BMI from the initial health check-up to the health check-up 1 year after that, we divided the study participants into 3 groups: ≤-5.0%, -5.0% to +5.0%, and ≥+5.0%. RESULTS: The risk of developing DM increased steeply after BMI exceeded approximately 20 to 21 kg/m2. Compared with participants with stable BMI (-5.0% to +5.0%), the relative risk for DM among those whose BMI had increased by 5.0% or more was 1.33 (95% CI 1.31-1.36). In contrast, the relative risk for DM among those whose BMI decreased by 5.0% or more was 0.82 (95% CI 0.80-0.84). Moreover, people classified as normal weight, overweight, and obese reduced the risk of developing DM when they reduced their BMI, whereas the risk of developing DM for people classified as underweight increased when they reduced their BMI. CONCLUSION: Our findings offer novel insights into improving an optimal bodyweight management strategy to prevent the development of DM.

Association of early acute-phase rehabilitation initiation on outcomes among patients aged ≥90 years with acute heart failure.

BACKGROUND: Data on the potential benefit of acute-phase rehabilitation initiation in very old (aged ≥90) patients with acute heart failure (AHF) have been scarce. METHODS: We retrospectively analyzed data from the Diagnosis Procedure Combination database, which is a nationwide inpatient database. This study included patients hospitalized for heart failure (HF) from January 2010 to March 2018, those aged ≥90 years, who had a length of stay of ≥3 days, New York Heart Association (NYHA) class of ≥II, and had not undergone major procedures under general anesthesia. Propensity score matching and generalized linear models were used to compare in-hospital mortality, length of stay, 30-day readmission rate due to HF, all-cause 30-day readmission, and improvement in activities of daily living (ADL) between patients with and without an acute-phase rehabilitation initiation, which is defined as the rehabilitation initiation within 2 days after hospital admission. RESULTS: Acute-phase rehabilitation was initiated in 8588 of 41,896 eligible patients. Propensity score matching created 8587 pairs. Patients with acute-phase rehabilitation initiation have lower in-hospital mortality (9.0% vs. 11.2%, p < 0.001). Acute-phase rehabilitation initiation was associated with lower in-hospital mortality (odds ratio, 0.778; 95% confidence interval, 0.704-0.860). Patients with acute-phase rehabilitation initiation have a shorter median length of stay (17 days vs. 18 days, p < 0.001), lower 30-day readmission rate due to HF (5.5% vs. 6.4%, p = 0.011) and all-cause 30-day readmission (10.2% vs. 11.2%, p = 0.036), and better ADL improvement (49.7% vs. 46.9%, p < 0.001). Subgroup analysis revealed consistent results (sex, body mass index, NYHA class, and Barthel Index). CONCLUSIONS: The acute-phase rehabilitation initiation was associated with improved short-term clinical outcomes in patients aged ≥90 years with AHF.

HDL cholesterol and clinical outcomes in diabetes mellitus.

AIMS: HDL cholesterol (HDL-C) has been thought to protect against cardiovascular disease (CVD), whereas a U-shaped association of both low and extremely high HDL-C with a high mortality risk has been increasingly reported in recent years. However, whether this U-shaped association is universal regardless of the individual's clinical background, including lifestyle diseases, remains unclear. We examined whether fasting plasma glucose modifies the U-shaped association between the HDL-C level and clinical outcomes. METHODS AND RESULTS: This retrospective observational cohort study analysed data from the JMDC Claims Database between 2005 and 2021 for 3 282 389 participants without a history of CVD. The median age was 44 years (IQR, 36-51), and 1 878 164 participants (57.2%) were men. The median HDL-C level was 62 (IQR 52-74) mg/dL. The study participants were categorized according to fasting plasma glucose (FPG) levels (<100 mg/dL, 100-125 mg/dL, and ≥126 mg/dL). The primary endpoint was composite CVD outcome, consisting of myocardial infarction, stroke, and all-cause death. During a mean follow-up period of 1181 ± 932 days, 35 233 composite CVD events were recorded. The association between low HDL-C and CVD risk increased with the FPG level, and the relationship of high HDL-C with CV outcome was prominent only in people with diabetes mellitus. A similar relationship was observed in the individual subgroups and in each CV outcome. CONCLUSION: The U-shaped association between HDL-C and clinical outcomes was amplified with worsening glucose tolerance, suggesting a potential interaction between HDL-C levels and glycaemic status on clinical outcomes.

The aim of this study is to clarify whether fasting plasma glucose modifies the U-shaped association between HDL cholesterol and clinical outcomes. Key findings The U-shaped association between HDL cholesterol and clinical outcomes (including myocardial infarction, stroke, and death) was amplified with worsening glucose tolerance, suggesting a potential interaction between HDL cholesterol levels and glycaemic status on clinical outcomes.

Gait Speed and Cardiovascular Disease by Glycemic Status.

INTRODUCTION: The aim of this study was to clarify whether the association of gait speed with the incidence of cardiovascular disease depends on baseline glycemic status. METHODS: This retrospective observational cohort study used the Japan Medical Data Center Claims Database between 2005 and 2021 and analyzed 3,090,048 participants without a cardiovascular disease history. The median (IQR) age was 44 (37-53) years, and 1,755,205 of the participants (56.8%) were men. Information on gait speed was obtained from self-reported questionnaires in health checkups. Study participants were categorized according to HbA1c levels (<5.7%, 5.7-6.4%, and ≥6.5%). The primary endpoint was defined as a composite cardiovascular disease outcome that consists of heart failure, myocardial infarction, angina pectoris, and stroke. RESULTS: During the mean follow-up period of 1,120±857 days, 116,678 composite cardiovascular disease outcomes were documented. Self-reported fast gait speed was related to a lower risk of developing cardiovascular disease; this relationship was more pronounced with increasing HbA1c levels. Compared with slow gait speed, the hazard ratio (95% CI) of self-reported fast gait speed for cardiovascular disease was 0.935 (0.921-0.949) in participants with an HbA1c <5.7%, 0.911 (0.891-0.932) in participants with an HbA1c of 5.7-6.4%, and 0.846 (0.811-0.883) in participants with HbA1c ≥6.5% (p-value for interaction<0.001). CONCLUSIONS: The relationship of subjective gait speed with the risk of cardiovascular disease was amplified in individuals with prediabetes or diabetes mellitus, suggesting that maintaining exercise capacity could be more important in individuals with impaired glucose tolerance for preventing cardiovascular disease.

Sex Differences in the Association Between Hypertension and Incident Atrial Fibrillation.

Background Limited evidence is available on sex differences about the association between hypertension and incident atrial fibrillation (AF). Methods and Results We used a nationwide health checkup and claims database to analyze 3 383 738 adults (median age, 43 (36-51) years, 57.4% men). We investigated the relationship between hypertension and incident AF in men and women using a Cox regression model. We used restricted cubic spline functions to identify the association of blood pressure (BP) as a continuous parameter with incident AF. We categorized the men and women into 4 groups according to the 2017 American College of Cardiology/American Heart Association BP guidelines. During a mean follow-up of 1199±950 days, 13 263 AF diagnoses were recorded. The incidence (95% CI) of AF was 15.8 (15.5-16.1) per 10 000 person-years in men and 6.1 (5.9-6.3) per 10 000 person-years in women. Compared with normal BP, elevated BP, stage 1 hypertension, and stage 2 hypertension were associated with an increased risk AF in both men and women. However, the hazard ratios were greater in women than in men, and the P value for interactions in the multivariable model was 0.0076. The models using restricted cubic spline showed that the risk of AF associated with elevated systolic BP increased steeply above an approximate threshold of systolic BP of 130 mm Hg in men and 100 mm Hg in women. Although our primary findings were consistent across subgroup analyses, this association was most significant in younger individuals. Conclusions Although the incidence of AF was higher in men, the association between hypertension and incident AF was more pronounced in women than in men, suggesting a potential sex difference in the relationship between hypertension and incident AF.

The association of BP with cardiovascular outcomes in patients with dipstick proteinuria and preserved kidney function.

Little is known about the relationship between blood pressure (BP) and incident cardiovascular disease (CVD) in people with proteinuria and a preserved estimated glomerular filtration rate (eGFR). This study sought to investigate the association of BP with CVD risk in adults with proteinuria and preserved eGFR. We studied 188,837 individuals with proteinuria and preserved eGFR ≥60 mL/min/1.73 m2. We categorized individuals who were not taking BP-lowering medications into four groups based on the 2017 American College of Cardiology/American Heart Association BP guideline and categorized those who were taking BP-lowering medications using the same BP ranges. The primary outcome was a composite CVD endpoint that included myocardial infarction, angina pectoris, stroke, and heart failure. Over a mean follow-up of 1,050 days, 7,039 CVD events were identified. Compared with normal BP, stage 1 hypertension (hazard ratio [HR]: 1.30, 95% confidence interval [95% CI]: 1.21-1.40) and stage 2 hypertension (HR: 2.17, 95% CI: 2.01-2.34) were associated with an increased risk for CVD events among medication-naïve individuals. Only stage 2 hypertension range (HR: 1.19, 95% CI: 1.02-1.38) was associated with an increased CVD event risk among people taking BP-lowering medications. Restricted cubic spline analysis showed that the risk of CVD events increased monotonically with BP at an SBP/DBP > 120/80 mmHg among medication-naïve individuals, but risk increased only at an SBP/DBP > 140/90 mmHg among individuals taking BP-lowering medications. In conclusion, among people with proteinuria and preserved eGFR, stage 1 and stage 2 hypertension were associated with a greater risk of CVD among medication-naïve individuals, whereas only stage 2 hypertension was associated with an increased CVD risk among those taking BP-lowering medications.

Interaction of Blood Pressure and Glycemic Status in Developing Cardiovascular Disease: Analysis of a Nationwide Real-World Database.

Background Hypertension and diabetes frequently coexist. However, little is known about the interaction between high blood pressure (BP) and hyperglycemia in the development of cardiovascular disease (CVD). Methods and Results We conducted an observational cohort study that included 3 336 363 patients (median age, 43 years old; men, 57.2%). People taking BP- or glucose-lowering medications or those with prior history of CVD were excluded. We defined stage 1 hypertension as having systolic BP of 130 to 139 mm Hg or diastolic BP of 80 to 89 mm Hg and stage 2 hypertension as having systolic BP of ≥140 mm Hg or diastolic BP of ≥90 mm Hg. We defined prediabetes as having fasting plasma glucose of 100 to 125 mg/dL and diabetes as having fasting plasma glucose of ≥126 mg/dL. Over a mean follow-up period of 1185 ± 942 days, 5665 myocardial infarction, 52 475 angina pectoris, 25 436 stroke, 54 508 heart failure, and 12 932 atrial fibrillation events occurred. The BP and fasting plasma glucose categories additively increased the risk of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. However, the relative risk of stage 1 and stage 2 hypertension developing into CVD was attenuated with deteriorating glycemic status. Similarly, the relative risk of prediabetes and diabetes developing into CVD was attenuated with increasing BP. For example, the relative risk reduction of stage 2 hypertension for heart failure was 53.5% in individuals with normal fasting plasma glucose, 46.4% in those with prediabetes, and 37.2% in those with diabetes. The robustness of our findings was confirmed using a multitude of sensitivity analyses. Conclusions Although hypertension and hyperglycemia additively increase the risk of developing CVD, the relative contribution of hypertension to the development of CVD decreased with deteriorating glycemic status and that of hyperglycemia was attenuated with increasing BP. Our results indicate a potential interaction between hypertension and hyperglycemia in the development of CVD.

Giant bulk piezophotovoltaic effect in 3R-MoS2.

Given its innate coupling with wavefunction geometry in solids and its potential to boost the solar energy conversion efficiency, the bulk photovoltaic effect (BPVE) has been of considerable interest in the past decade1-14. Initially discovered and developed in ferroelectric oxide materials2, the BPVE has now been explored in a wide range of emerging materials, such as Weyl semimetals9,10, van der Waals nanomaterials11,12,14, oxide superlattices15, halide perovskites16, organics17, bulk Rashba semiconductors18 and others. However, a feasible experimental approach to optimize the photovoltaic performance is lacking. Here we show that strain-induced polarization can significantly enhance the BPVE in non-centrosymmetric rhombohedral-type MoS2 multilayer flakes (that is, 3R-MoS2). This polarization-enhanced BPVE, termed the piezophotovoltaic effect, exhibits distinctive crystallographic orientation dependence, in that the enhancement mainly manifests in the armchair direction of the 3R-MoS2 lattice while remaining largely intact in the zigzag direction. Moreover, the photocurrent increases by over two orders of magnitude when an in-plane tensile strain of ~0.2% is applied, rivalling that of state-of-the-art materials. This work unravels the potential of strain engineering in boosting the photovoltaic performance, which could potentially promote the exploration of novel photoelectric processes in strained two-dimensional layered materials and their van der Waals heterostructures.