BACKGROUND AND AIMS:The Lancet Diabetes and Endocrinology Commission recently proposed the new definition of preclinical and clinical obesity. Our study aimed to investigate the associations of the novel obesity classifications with incident cardiovascular disease (CVD). METHODS:In 459,102 UK Biobank participants enrolled between 2006 and 2010, we applied the new definitions of clinical and preclinical obesity, based on the presence of excess adiposity with or without organ dysfunction, to assess their associations with incident CVD and its subtypes. Participants were further stratified into a seven-category classification integrating the Lancet framework with traditional body mass index (BMI) categories. Multivariable Cox regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for each obesity classification in relation to CVD risk. RESULTS:Over a median follow-up of 11.0 years, a total of 51,640 cases of CVD incidence were recorded. Compared to those with no obesity, individuals with preclinical obesity exhibited modestly elevated risks of CVD (HR 1.11, 95% CI 1.08-1.15), while clinical obesity was associated with substantially higher risks of total CVD (HR 1.77, 95% CI 1.72-1.82) and all subtypes, including coronary heart disease (CHD), stroke, and heart failure. Furthermore, newly diagnosed preclinical and clinical obesity with BMI below the conventional obesity threshold also had elevated incident CVD risk, with strongest association for CHD. CONCLUSIONS:The new framework advances CVD risk stratification beyond BMI alone, emphasizing the importance of incorporating excess body fat and functional health assessments into obesity diagnosis. Stronger associations with clinical obesity highlight its utility as a cumulative disease burden classifier, identifying individuals at higher cardiovascular risk.

Kidney disease is a major public health challenge, affecting millions of people worldwide. Conventional treatments often produce suboptimal outcomes and are associated with various adverse effects. Traditional Chinese Medicine has shown promising therapeutic potential, offering distinct advantages over conventional therapies for preventing and treating kidney diseases. Salvianolic acids, the principal bioactive constituents of Salvia miltiorrhiza, are widely used in the management of renal disorders. However, no dedicated review has systematically synthesized pharmacological evidence across different models of kidney disease. To advance both basic research and clinical applications, this review summarizes current knowledge on the therapeutic effects of salvianolic acids in acute kidney injury, diabetic kidney disease, and nephrotic syndrome. Their renoprotective actions arise from the modulation of multiple pathological processes, including inflammation, oxidative stress, apoptosis, mitochondrial dysfunction, endoplasmic reticulum stress, and autophagy dysregulation. Collectively, salvianolic acids hold promise as potential therapeutic agents for kidney diseases. Further studies are needed to confirm these molecular mechanisms and identify specific targets. Additionally, large-scale, long-term, multicenter clinical trials are crucial to evaluate the efficacy and safety of salvianolic acids in treating kidney diseases.

ETHNOPHARMACOLOGICAL RELEVANCE:Jianpi Qinghua Granule (JPQH) is a hospital-prepared traditional Chinese medicine formula used for insulin resistance and related metabolic disorders. However, its pharmacodynamic basis and epigenetic mechanisms in metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. AIM OF THE STUDY:This study aimed to evaluate the therapeutic effects of JPQH on high-fat diet (HFD)-induced MAFLD and determine whether its action involves regulation of DNMT-mediated DNA methylation and hepatic urea cycle metabolism. MATERIALS AND METHODS:HFD-induced MAFLD mice were treated with JPQH for 4 weeks. Blood-absorbed constituents were identified by UHPLC-Q Exactive Orbitrap MS/MS. Network pharmacology, liver transcriptomics, and targeted metabolomics were integrated to explore mechanisms. Pyrosequencing, RT-qPCR, Western blotting, molecular docking, and molecular dynamics simulations were used for validation. RESULTS:JPQH ameliorated glucose-lipid metabolic disorders and liver injury, as indicated by reduced serum TC, TG, ALT, and AST levels (P < 0.05), decreased hepatic MDA levels (P < 0.01), improved OGTT/ITT responses (P < 0.001), restored GSH/GSSG ratio (P < 0.05), and downregulation of inflammatory- and fibrosis-related gene expression (P < 0.05). A total of 44 blood-absorbed constituents and 87 JPQH-MAFLD overlapping targets were identified. Integrated analyses highlighted nitrogen metabolism and arginine and proline metabolism. JPQH restored urea cycle intermediates, upregulated CPS1, OTC, ASS1, ASL, and ARG1 expression (P < 0.01), and reduced hepatic ammonia accumulation (P < 0.01). Mechanistically, JPQH reduced DNMT1/DNMT3A expression, attenuated promoter hypermethylation of urea cycle enzyme genes, and restored their transcriptional and protein expression. Core flavonoids, including genistein, baicalein, nepetin, hispidulin, and quercetin 3,4'-dimethylether, exhibited stable binding to DNMT1 and DNMT3A in silico. CONCLUSIONS:JPQH exerts protective effects against MAFLD by restoring hepatic nitrogen metabolism and ammonia detoxification via epigenetic regulation of the DNMT-urea cycle axis.

BACKGROUND:To directly compare the predictive ability of carotid-femoral pulse wave velocity (cf-PWV) and brachial-ankle pulse wave velocity (ba-PWV) for cardiovascular events within the same population. METHODS:This is a community-based prospective cohort study that included older adults (>65 years). The primary end point was major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. RESULTS:A total of 3309 participants (median age [quartiles], 70 [67-75] years; 1434 [43.3%] male) were included. The median follow-up time was 6.40 [6.37-6.41] years. Cf-PWV and ba-PWV were moderately correlated (R=0.588; P<0.001). Participants were divided into 4 groups by quartiles or 2 groups using cutoff values. Aalen-Johansen estimators and Cox regression analyses indicated that both cf-PWV and ba-PWV were associated with an increased rate of MACEs. When cf-PWV and ba-PWV were cross-adjusted, only cf-PWV remained significantly associated with MACEs and mortality (hazard ratio, 1.12 [95% CI, 1.00-1.25]; P=0.048 and 1.16 [95% CI, 1.03-1.29]; P=0.032, respectively) in both full-model and stepwise regressions. Stratification based on cf-PWV and ba-PWV cutoff values further revealed that elevated cf-PWV was associated with a higher risk of MACEs, independent of baseline ba-PWV. Concordance index, net reclassification improvement, and integrated discrimination improvement analyses confirmed the additive value of cf-PWV to conventional cardiovascular risk factors. Other stiffness-related parameters, including pulse pressure and its amplification, were not independently associated with MACEs. CONCLUSIONS:Both cf-PWV and ba-PWV are associated with cardiovascular events, and cf-PWV demonstrates a higher predictive value compared with ba-PWV. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02368938.

Based on the regulation of mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway, this study investigated the effect of Jianpi Qinghua Formula on the mitochondrial fatty acid β-oxidation pathway in the livers of mice with metabolic-associated fatty liver disease(MAFLD) induced by a high-fat diet. MAFLD mice were fed a high-fat diet to establish the model, and after successful modeling, the mice were divided into the model group, the Jianpi Qinghua Formula group, and the metformin group, with an additional control group. Each group was treated with the corresponding drug or an equivalent volume of saline via gavage. Body mass and food intake were measured regularly during the experiment. At the end of the experiment, blood lipid levels and liver function-related indices were measured, liver pathological changes were observed, and protein expression levels of PGC1α, PPARα, PPARγ, and CPT1A were detected by Western blot. The results showed that, with no difference in food intake, compared to the model group, the body mass of the Jianpi Qinghua Formula group and the metformin group was reduced, liver weight and liver index decreased, and levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol(LDL-C) were lowered. Additionally, a decrease in alanine aminotransferase(ALT) and aspartate aminotransferase(AST) was observed. Hematoxylin and eosin(HE) staining revealed reduced pathological damage to hepatocytes, while oil red O staining showed improvement in fatty infiltration. The liver disease activity score decreased, and transmission electron microscopy revealed improvement in mitochondrial swelling and restoration of internal cristae. Western blot analysis indicated that Jianpi Qinghua Formula significantly increased the expression of PGC1α, PPARα, and CPT1A proteins in the liver and reduced the expression of PPARγ. These results suggest that the Jianpi Qinghua Formula improves mitochondrial function, promotes fatty acid oxidation, and alleviates the pathological changes of MAFLD. In conclusion, Jianpi Qinghua Formula can improve MAFLD by mediating mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway.

Apolipoprotein B (apoB) can be measured directly and accurately, and better predicts atherogenic risk than conventional lipid profiles. We aimed to investigate whether total and regional (trunk or leg) fat deposits are associated with apoB levels in general US adults. 4585 participants were enrolled from the US National Health and Nutritional Surveys from 2011 to 2016. Overall and regional body fat were measured using dual-energy X-ray absorptiometry. The associations of total and regional fat with apoB levels were evaluated using linear regression models. Following adjustment for demographic, lifestyle, and clinical risk factors, whole-body fat percentage was positively associated with apoB levels. Additionally, percent trunk fat was positively associated (highest vs. lowest tertile beta = 17.73 for men and 14.89 for women, respectively), whereas percent leg fat was inversely associated (highest vs. lowest tertile beta = - 4.84 for men and - 6.55 for women, respectively) with apoB levels in both sexes. The association for trunk fat and leg fat remained significant after further adjustment for body mass index or waist circumference. Higher percent trunk fat combined with lower percent leg fat was associated with particularly higher apoB. In conclusion, among general US adults, both elevated trunk fat and reduced leg fat are associated with higher levels of apoB. Further research is required to elucidate the underlying pathophysiological mechanisms.

Introduction: Fat distribution is a stronger predictor for cardiometabolic morbidity and mortality. We aimed to investigate the association of elevated iron stores, measured as serum ferritin levels, with total and regional body fat. Methods: Data from 2,646 adults from the National Health and Nutrition Examination Survey 2017-2018 were analyzed. Dual-energy X-ray absorptiometry was used to measure overall and regional body fat. The fat mass index (FMI) was calculated by dividing the fat mass (kg) by the square of body height (m(2)). The leg fat mass to trunk fat mass ratio (LTR) was used to assess the relative distribution of leg fat compared to trunk fat. Results: Medians (IQR) of serum ferritin levels were 0.168 mu g/mL (0.104-0.269) for men and 0.053 mu g/mL (0.026-0.102) for women. After adjusting for sociodemographic, lifestyle, and metabolic factors, serum ferritin showed a significant positive association with total FMI (beta = 2.662) and trunk FMI (beta = 0.983), and a negative association with leg FMI (beta = -0.324) and LTR (beta = -0.160) in men. In women, serum ferritin showed a significant positive association with total FMI (beta = 4.658), trunk FMI (beta = 2.085), and negative association with LTR (beta = -0.312). Significant positive trends were observed for serum ferritin with total and trunk FMI in men and women, using the lowest serum ferritin quartile as the reference group. Additionally, significant negative trends were observed for serum ferritin with leg FMI and LTR in men. The mediation analysis revealed that C-reactive protein mediated 16.4% and 22.6% of the potential effects of serum ferritin on trunk FMI in men and women, respectively. Conclusion: Higher ferritin levels were associated with greater total and trunk fat but lower leg fat. Further prospective and mechanistic studies are warranted to confirm the study results.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD + loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD + loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Background Body fat mass (FM) is associated with multiple organ damage. However, data regarding the relationship between various organ damage and FM are rare in the elderly. Therefore, we aim to perform an analysis on the relationship between organ damage and FM in a geriatric cohort. Methods 3331 participants were included in this analysis. Based on age, body height, body weight, waist circumference, and race, we calculated FM with the established formula. Organ damage, including arterial stiffening, lower extremity atherosclerosis, left ventricular hypertrophy (LVH), micro-albuminuria, and chronic kidney disease (CKD), were measured and calculated with standard methods. Results All organ damage parameters were significantly related to FM (all p < 0.001). In univariate logistics regression, the highest quartile of FM was tied to the increased risk of arterial stiffening, lower extremity atherosclerosis, LVH, micro-albuminuria, and CKD (all p < 0.05). After adjustment, participants with higher quantiles of FM had a significantly increased odd ratio (OR) for arterial stiffening [OR = 1.51, 95% confidence interval (CI): 1.15–1.99, p = 0.002] and LVH (OR = 1.99, 95% CI: 1.48–2.67, p < 0.001). Moreover, FM was linearly associated with arterial stiffening and LVH in total population and gender subgroups. Independent of confounders, FM was significantly correlated with arterial stiffening, lower extremity atherosclerosis, LVH and CKD in female, while was only related to LVH in male. Conclusions Among various organ damage, elevated FM is significantly and independently associated with arterial stiffening and LVH in the elderly. Compared with men, women with increased FM are more likely to have multiple organ damage.

Epidemiological studies have suggested a positive association between environmental cadmium (Cd) exposure and type 2 diabetes mellitus (T2DM). Skeletal muscle insulin resistance (IR) plays a critical role in the pathogenesis of T2DM. This study aimed to investigate the effects of chronic low-level Cd exposure on skeletal muscle IR and its potential mechanism. Rats were exposed to drinking water containing 2 or 10 mg/L Cd for 24 weeks. Differentiated L6 myotubes were treated with Cd for 72 h. Immunofluorescence, flow cytometry assay, RNAsequencing, and Seahorse analysis were conducted to determine the effects of Cd and its underlying mechanism on relevant parameters, including insulin sensitivity, glucose uptake, oxidative stress, mitophagy, and mitochondrial function in skeletal muscle and L6 myotubes. N-acetyl-cysteine (NAC), a scavenger of reactive oxygen species (ROS), and mitophagy inhibitor Cyclosporin A (CsA) were used to confirm the role of oxidative stress in mitophagy and mitochondrial dysfunction caused by Cd. We found that rats exposed to 10 mg/L Cd exhibited hyperglycemia and skeletal muscle IR. Cd markedly increased IRS-1 phosphorylation at Ser612, while decreased levels of phosphorylated PI3K, Akt, AS160, inhibited GLUT4 translocation and glucose uptake. Mechanistically, Cd increased the intracellular ROS, hydrogen peroxide, and malondialdehyde levels and decreased antioxidase activity in L6 myotubes. Furthermore, Cd upregulated the mRNA and protein levels of LC3II/I, PINK1, and Parkin. In addition, Cd induced the formation of mitophagosomes, reduced the mitochondrial membrane potential, decreased the adenosine triphosphate content, and impaired the mitochondrial respiratory capacity. Strikingly, NAC ameliorated oxidative stress, excessive mitophagy, and the associated reduction in myotube insulin sensitivity, while inhibition of mitophagy by CsA alleviated skeletal muscle IR. In conclusion, this study reveals a previously unrecognized mechanism that chronic low-level Cd exposure may induce mitophagy by activating the PINK1/Parkin signal pathway by increasing ROS, thus causing skeletal muscle IR and elevated blood glucose.

AbstractObjectiveHeart failure with preserved ejection fraction (HFpEF) is a growing concern among the elderly population, significantly impacting morbidity and mortality rates. This study aimed to screen and investigate the characteristics and prognosis of early‐stage HFpEF in the elderly.MethodsA total of 1789 community‐dwelling individuals aged over 65 from northern Shanghai were enrolled. According to American Heart Association (AHA) guidelines, participants were classified into four groups: HFpEF stage 0, HFpEF stage A, HFpEF stage B and HFpEF stage C. Major endpoints included major adverse cardiovascular events (MACEs), all‐cause death and cardiovascular death.ResultsAfter a mean follow‐up period of 7.10 ± 1.27 years, 1623 elderly subjects were included [HFpEF stage 0 (10.3%), HFpEF stage A (16.3%), HFpEF stage B (60.6%) and HFpEF stage C (12.8%)]. Patients with HFpEF stage A, HFpEF stage B and HFpEF stage C exhibited more MACEs than those in HFpEF stage 0 (P < 0.01). Patients with HFpEF stage C had a significantly higher cardiovascular (P < 0.001) and all‐cause death ratio (P < 0.01). With HFpEF stage 0 as a reference, the increases in MACEs were significantly associated with HFpEF stage A [hazard ratio (HR): 2.97, 95% confidence interval (CI) (1.13, 7.82), P < 0.05], HFpEF stage B [HR: 2.69, 95% CI (1.09, 6.64), P < 0.05] and HFpEF stage C [HR: 4.86, 95% CI (1.88, 12.59), P < 0.01] in the Cox regression analysis. Our finding remains unaltered in the sensitivity analysis, with no interaction for effectiveness.ConclusionsCompared with those with HFpEF stage 0, patients with HFpEF, whether in stage B or C, exhibit significantly higher cardiovascular and all‐cause mortality in the elderly. This study underscores the importance of early‐stage HFpEF screening, particularly in older, asymptomatic stage B individuals.

Abstract. Background:. The serum vitamin D level varies widely by population, and studies have linked vitamin D levels with the risk of type 2 diabetes mellitus (T2DM). However, the relationship is inconsistent and the impact of vitamin D on T2DM among East Chinese adults is unclear. The study aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) levels and the risk of T2DM and evaluated whether the association is modified by genetic predisposition. Methods:. In the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China) cohort, 1862 participants free of T2DM at baseline were included. A weighted genetic risk score was calculated with 28 variants associated with T2DM. Hierarchical logistic models were used to examine the association of serum 25(OH)D and genetic risk with T2DM. Results:. After a 5-year follow-up, 132 cases of T2DM were documented. We observed no significant association between quartiles of serum 25(OH)D and T2DM risk after multivariable adjustment (χ2 = 0.571, Pfor trend = 0.426). Compared to those in the lowest quartile of 25(OH)D, the odds ratios (ORs) (95% confidence interval [CI]) for participants with increased quartiles were 1.29 (0.74–2.25), 1.35 (0.77–2.36), and 1.27 (0.72–2.24), respectively. We observed a positive association of glycated hemoglobin (HbA1c) with 25(OH)D at baseline (β = 1.752, P = 0.001) and after follow-up (β = 1.385, P = 0.003), and a negative association of ln conversion homeostasis model assessment (HOMA)-β with 25(OH)D at baseline (β = -0.982, P = 0.021). There was no significant interaction between 25(OH)D and diabetes genetic predisposition on the risk of T2DM (χ2 = 2.710, Pfor interaction = 0.100). The lowest OR (95% CI) of T2DM was among participants with low genetic risk and the highest quartile of 25(OH)D (0.17 [0.05–0.62]). Conclusion:. Serum 25(OH)D may be irrelevant to the risk of incident T2DM among East Chinese adults regardless of genetic predisposition.

Objective: To investigate the association of major adverse cardiovascular events and mortality with left ventricular geometry in elderly. Design and method: We prospectively recruited 3363 community-dwelling elderly (43.6% male, aged 71.1 ± 5.9 years; 56.4% female, aged 71.1 ± 6.1 years) from local community. Echocardiographic parameters were collected, left ventricular mass index (LVMi) above 115 g/m 2 in male or 95 g/m 2 in female, relative wall thickness (RWT) above 0.42 were considered as abnormal. Participants then were classified into 4 mutually exclusive groups as: normal geometry (normal LVMi and normal RWT), concentric remodeling (normal LVMi and increased RWT), eccentric hypertrophy (increased LVMi and normal RWT), concentric hypertrophy (increased LVMi and increased RWT). Cardiovascular death, non-fatal myocardial infarction including non-fatal ischemic stroke were recorded as incident MACE. Adjusted Cox regression models were used to evaluate the hazard ratios of MACE and all-cause mortality. Results: Mean LVMi and RWT were 87.0 ± 28.4 g/m 2 and 0.39 ± 0.08. During a median follow-up of 5.4 years, we identified 224 incident MACE cases and 233 deaths. All-cause mortality was significantly greater in participants with eccentric hypertrophy (adjusted hazard ratio [HR]: 1.649; 95% confidence interval [CI]: 1.143-2.379) compared with normal geometry in multivariate analyses after adjusting for baseline covariates. Incident MACE was significant both in concentric hypertrophy (HR: 1.982; 95% CI: 1.239-3.170) and eccentric hypertrophy (HR: 1.846; 95% CI: 1.266-2.692) but not in concentric remodeling (HR:1.101; 95% CI: 0.759-1.597). Baseline LVMi was a significant predictor of all-cause mortality (HR: 1.047 per 10g/m 2 increase in LVMi; 95% CI: 1.004-1.093). Similar results were observed with non-fatal myocardial infarction, non-fatal ischemic stroke and cardiovascular death. Conclusions: Increased baseline LVMi and abnormal left ventricular geometry portend an increased risk for incident MACE and all-cause mortality in community dwelling elderly. From the pathophysiology point of view, per 10 g/m 2 increase in LVMi add 5% risk for all-cause mortality.

Background and aims: Inflammation closely correlates with atherosclerosis and cardiovascular disease (CVD). Monocyte to high-density lipoprotein cholesterol ratio (MHR) is a novel inflammation index that can be obtained by routine blood tests. We aimed to investigate the associations between MHR and atherosclerosis and arteriosclerosis. Methods and results: We enrolled 2451 participants from the Northern Shanghai Study. Atherosclerosis (carotid plaque (CP), lower extremity atherosclerotic (LEA) assessed by ankle-brachial index) and arteriosclerosis (arterial stiffness (AS) assessed by carotid-femoral pulse wave velocity) were measured using standard methods. In the univariable logistic regression model, higher MHR was significantly associated with increased AS, CP, and LEA risk. In the multivariable logistic regression model, after adjustment for age, sex, hypertension, diabetes mellitus, body mass index, smoking habit, low-density lipoprotein cholesterol, and family history of premature CVD, quartile 4 (Q4) of MHR was associated with an increased risk of AS (odds ratio (OR) = 1.41; 95% confidence interval (CI):1.05-1.88; P for trend = 0.036), CP (OR = 1.35; 95%CI:1.04-1.77; P for trend = 0.044), and LEA (OR = 2.23; 95%CI:1.49-3.35; P for trend< 0.001). Similar results were observed when MHR was analyzed as a continuous variable. The restricted cubic spline (RCS) curve showed that the association between MHR and AS was nonlinear (P nonlinear = 0.021), but not LEA (P nonlinear = 0.177) or CP (P nonlinear = 0.72). Conclusion: MHR presents a linear association with atherosclerosis and a nonlinear association with arteriosclerosis in the elderly Chinese population. These findings may indicate the need for early assessment and intervention for inflammation. The registration number for clinical trials: NCT02368938. (c) 2022 Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University.

Objective: Several clinical trials showed that intensive blood pressure (BP) control reduced the risk of mortality among hypertensive patients. We aimed to verify whether patients with peritoneal dialysis (PD) and hypertension could benefit from intensive BP control. Design and method: This is a retrospective single-center cohort study. 146 long-term PD hypertensive patients (81 male, mean age 60.2±11.7 years) with official sitting SBP 100 to <160mmHg at baseline were included in the present analysis. Patients were divided into the intensive group (100 to <130 mmHg) and the non-intensive group (130 to <160 mmHg). Kaplan-Meier curves and log-rank tests were performed to compare the survival rates of the two groups. Cox proportional regression was used to calculate the adjusted hazard ratios (HRs) and 95% CIs of all-cause and cardiovascular mortality of the intensive group compared to the non-intensive group. Results: 41 patients were in the intensive group and 105 patients were in the non-intensive group. The median follow-up time was 28 (quartiles 19-56) months. 65 all-cause deaths and 28 cardiovascular deaths were identified in total. Kaplan-Meier curves showed that compared with the non-intensive group, patients in the intensive group were at higher risk of all-cause mortality (HR, 1.91 [95% CI, 1.10-3.31], P = 0.02) and cardiovascular mortality (HR, 2.56 [1.12-5.88], P = 0.03). Cox regressions showed that after adjustment for potential confounders including age, gender, BMI, LDL-C, diabetes, and creatinine clearance rate, intensive BP control was also associated with the increased risk of all-cause mortality (HR, 2.14 [1.18-3.86], P = 0.01) and cardiovascular mortality (HR, 3.35 [1.37-8,17], P = 0.01). Conclusions: Lower systolic BP (<130mmHg) in patients with PD and hypertension was associated with a higher risk of all-cause and cardiovascular mortality. Our results suggested that intensive blood control should be cautious in hypertensive PD patients, and more clinical studies especially random controlled trials focusing on the blood pressure target of PD patients are warranted in the future.

With the epidemic of risk factors such as unhealthy lifestyle, obesity and mental stress, the prevalence of hypertension continues to rise across the world. Although standardized treatment protocols simplify the selection of antihypertensive drugs and ensure therapeutic efficacy, the pathophysiological state of some patients remains, which may also lead to the development of other cardiovascular diseases. Thus, there is an urgent need to consider the pathogenesis and selection of antihypertensive drug for different type of hypertensive patients in the era of precision medicine. We proposed the REASOH classification, based on the etiology of hypertension, including renin-dependent hypertension, elderly-arteriosclerosis-based hypertension, sympathetic-active hypertension, secondary hypertension, salt-sensitive hypertension and hyperhomocysteinemia hypertension. The aim of this paper is to propose a hypothesis and provide a brief reference for the personalized treatment of hypertensive patients.

Little is known about the predictive value of soluble AXL (sAXL) in heart failure (HF). This study aimed to describe the prognostic value of plasma sAXL in patients with symptomatic HF. This is a multicentre observational prospective cohort study (Registration No. NCT03727828). Plasma sAXL were measured on admission. The primary endpoint is a composite of cardiovascular mortality and HF rehospitalization. Associations between plasma sAXL levels and clinical endpoints are described using Cox regression models and Kaplan–Meier methods. A total of 1030 symptomatic HF patients were enrolled in the study; the mean age (65% men) was 71 ± 12 years, with a median follow-up of 32 months (IQR: 26–41 months). The mean baseline sAXL levels were 20.03 ± 6.74 ng/mL. Plasma sAXL positively associated with NYHA classification and negatively associated with left ventricular ejection fraction (both P  < 0.001). Cox regression showed that 1-SD increment of sAXL was associated with primary endpoint [HR (CI): 1.128 (1.024–1.242)], cardiovascular mortality [1.112 (1.032–1.198)], all-cause mortality [1.142 (1.057–1.234)], and HF rehospitalization [1.122 (1.030–1.224)] after adjustment for potential confounders including NT-proBNP. Kaplan–Meier curves revealed that patients with the highest sAXL levels were at the highest risk of primary endpoint events, cardiovascular mortality, and all-cause mortality (all P values < 0.001). Furthermore, both Kaplan–Meier method and Categorical analysis demonstrated that the combined use of sAXL and NT-proBNP were more likely to predict all-cause or cardiovascular mortality (both P  < 0.001). Similar results were observed when separating patients with respect to left ventricular ejection fraction, namely, in HFrEF, HFmrEF, and HFpEF groups. Plasma sAXL concentrations are of great importance in predicting clinical outcomes in HF patients, independent of NT-proBNP, suggesting that sAXL is a promising prognostic marker for further study.