Folic acid supplementation for stroke prevention: A systematic review and meta-analysis of 21 randomized clinical trials worldwide.

BACKGROUND & AIMS: The AHA/ASA guidelines for primary stroke prevention are almost a decade old. The current recommendation regarding folic acid supplementation is based on only 8 clinical trials, and an additional 13 folate trials have been published since then. This meta-analysis aims to fill in critical evidence gaps by comprehensively evaluating 21 published trials with particular attention given to identifying the true influences through stratification. METHODS: PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched from inception to April 4, 2023. This study included all randomized controlled trials (RCTs) of folic acid with stroke as one of the reporting endpoints. Relative risks and 95% confidence intervals were used to assess the association between folic acid supplementation and the risk of stroke in a random-effects model. RESULTS: Results from the 21 pooled RCTs totaling 115,559 participants showed that folic acid supplementation significantly reduced the risk of stroke by 10% (RR 0.90, 95%CI 0.83 to 0.98). Subgroup analyses showed that folic acid efficacy was greater in areas without fortified grain or with partially-fortified grain (RR = 0.83, 95% CI 0.75 to 0.93; RR = 1.04 in areas with grain fortification, P-interaction = 0.003). In this group, folic acid supplementation was most efficacious in those without a history of stroke or myocardial infarction (RR = 0.77, 95% CI 0.68 to 0.86; RR = 0.94 for participants with a history of stroke or myocardial infarction, P-interaction = 0.008). The efficacy of folic acid remained consistent regardless of baseline folate levels, folic acid dosage, baseline vitamin B12 levels, vitamin B12 dosage, homocysteine reduction, intervention duration, and whether folic acid was taken alone or in combination (all P-interaction>0.05). All 21 trials were free of attrition bias and reporting bias, and there was no significant publication bias. CONCLUSIONS: This is by far the largest meta-analysis of RCTs regarding folic acid supplementation and stroke, demonstrating the overall benefit of folic acid for stroke prevention. Grain fortification and history of stroke or myocardial infarction may be the most important influences on the efficacy of folic acid for stroke prevention.

Exploring CYP2D6 polymorphisms and angiotensin receptor blocker response in the Bai hypertensive population.

OBJECTIVE: The CYP2D6 enzyme is crucial for the metabolism and disposition of a variety of drugs. This study was conducted to examine the relationship between CYP2D6 gene polymorphisms and the response to angiotensin receptor blocker (ARB)-based treatment in patients of Chinese Bai ethnicity with hypertension. METHODS: Seventy-two hypertensive adults from the Chinese Bai ethnic group, exhibiting systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg, were recruited. Targeted regional sequencing was utilized to genotype single nucleotide polymorphisms in the CYP2D6 gene, aiming to assess their frequency and to evaluate their influence on the therapeutic efficacy of ARB medications. RESULTS: Our research identified nine significant CYP2D6 polymorphisms associated with the efficacy of ARB treatment in the Bai hypertensive cohort. Specifically, patients possessing certain mutant genotype at rs111564371 exhibited substantially greater reductions in SBP and DBP, with P -values of 0.021 and 0.016, respectively, compared to those carrying the wild genotype. Additionally, these mutant genotype at rs111564371 and rs112568578 were linked to approximately 20% higher overall efficacy rates and a 10% increased achievement rate relative to the wild genotype. CONCLUSION: Our research with the Bai hypertensive group shows that certain CYP2D6 polymorphisms significantly influence ARB treatment outcomes. Mutations at rs111564371 led to better blood pressure control ( P -values: 0.021 for SBP, 0.016 for DBP), improving ARB efficacy by appromixately 20% and increasing treatment goal achievement by 10% over the wild-type genotype. STATEMENTS: Our investigation into CYP2D6 polymorphisms within the Bai hypertensive cohort marks a substantial advancement towards personalized healthcare, underscoring the pivotal influence of genetic constitution on the effectiveness of ARB therapy.

Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

Background: Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods: We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings: Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation: The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding: SyMap Medical (Suzhou), LTD, Suzhou, China.

Impact of LDLR polymorphisms on lipid levels and atorvastatin's efficacy in a northern Chinese adult Han cohort with dyslipidemia.

BACKGROUND: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia. METHODS: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview. RESULTS: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy. CONCLUSIONS: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care. TRIAL REGISTRATION: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy).

BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes. METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment. RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering. CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg. GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).

Effects of allisartan-isoproxil-based combination antihypertensive regimen in hypertensive patients with microalbuminuria or hyperuricemia.

Microalbuminuria and hyperuricemia management are crucial for the integrated management of hypertensive patients. This retrospective post hoc analysis aims to evaluate the optimal allisartan-isoproxil-based combination regimen for hypertensive patients with microalbuminuria or hyperuricemia. A total of 460 hypertensive patients with microalbuminuria and 486 hypertensive patients with hyperuricemia were included in this study. All patients were initially treated with allisartan-isoproxil for 4 weeks. Thereafter, patients with blood pressure (BP) < 140/90 mmHg continued the monotherapy for 8 weeks; patients with BP ≥140/90 mmHg were randomly assigned in a 1:1 ratio to receive allisartan-isoproxil + amlodipine (Group A + C) or allisartan-isoproxil + indapamide (Group A + D) for 8 weeks. The changes of BP, urinary albumin and serum uric acid (UA) were measured. In patients with microalbuminuria, the urinary albumin/creatinine ratio (UACR) significantly decreased by 10.4 mg/g in Group A + C (vs. baseline p = .0035) and 24.2 mg/g in Group A + D (vs baseline p < .0001), intergroup p = NS. In patients with hyperuricemia, serum UA level decreased by 44.5 µmol/L in Group A + C (vs. baseline p = .0003), but increased by 27.2 µmol/L in Group A + D (vs. baseline p = .0167), intergroup p < .0001. The results suggest that for hypertensive patients with microalbuminuria, angiotensin receptor blocker (ARB) + calcium channel blocker (CCB) or ARB+ diuretic both are good choices based on their improvement of microalbuminuria and BP. But for patients with hyperuricemia, ARB + diuretic may further increase the level of UA.

Does high-normal blood pressure lead to excess cardiovascular disease events and deaths in Chinese people? A post-hoc analysis of the 30-year follow-up of the Da Qing IGT and Diabetes Study.

AIM: Whether systolic/diastolic blood pressure (SBP/DBP) values of 130-139/80-89 mmHg should be defined as hypertension has been debated for decades. We aimed to characterize the effect of high-normal BP on cardiovascular disease (CVD) events and deaths. METHODS: In total, 1726 individuals from the original Da Qing IGT and Diabetes Study were enrolled, and divided into the normal BP group (SBP <130 mmHg and DBP <80 mmHg), high-normal BP group (SBP 130-139 mmHg and/or DBP 80-89 mmHg) and hypertension group (SBP ≥140 mmHg and/or DBP ≥90 mmHg). CVD events and their components were assessed from 1986 to 2016. RESULTS: During the 30-year follow-up, the high-normal BP group was not at higher risk for CVD events [hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.84-1.30, p = .68], coronary heart disease (HR 1.12, 95% CI 0.77-1.63, p = .57), stroke (HR 1.05, 95% CI 0.82-1.34, p = .71), or CVD deaths (HR 1.15, 95% CI 0.82-1.60, p = .41) compared with the normal BP group, after adjusting for covariates. However, the hypertension group exhibited significantly increased cardiovascular risk (CVD events, HR 1.91, 95% CI 1.48-2.46, p < .0001; coronary heart disease, HR 1.73, 95% CI 1.12-2.67, p = .01; stroke, HR 1.90, 95% CI 1.43-2.52, p < .0001; CVD deaths, HR 2.07, 95% CI 1.43-3.01, p = .0001) than the normal BP group. Subgroup analyses showed that, regardless of the presence of diabetes, high-normal BP did not increase CVD events compared with normal BP. CONCLUSIONS: This post-hoc study provided no evidence that the high-normal BP increased cardiovascular risk in the Da Qing study population, suggesting that it was reasonable to continue to define hypertension at 140/90 mmHg in China.

Management of nocturnal hypertension: An expert consensus document from Chinese Hypertension League.

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all-cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24-h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24-h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long-acting antihypertensive medications are preferred for nocturnal and 24-h BP control. Some newly developed agents, renal denervation, and other device-based therapy on nocturnal BP reduction are evaluated.

2023 Chinese expert consensus on the impact of COVID-19 on the management of cardiovascular diseases.

The primary site of infection in COVID-19 exhibit is the respiratory system, but multiple organ systems could be affected. The virus could directly invade cardiomyocytes. Alternatively, cytokine storm could lead to myocardial injury. More importantly, the management of existing cardiovascular diseases must be re-examined in COVID-19 due to, for example, interaction between antiviral agents and with a wide variety of pharmacological agents. The Branch of Cardiovascular Physicians of Chinese Medical Doctor Association organized a panel of experts in cardiovascular and related fields to discuss this important issue, and formulated the "2023 Chinese Expert Consensus on the Impact of COVID-19 on the Management of Cardiovascular Diseases." The Consensus was drafted on the basis of systematic review of existing evidence and diagnosis and treatment experience, and covers three major aspects: myocardial injury caused by COVID-10 and COVID-19 vaccine, the impact of COVID-19 on patients with cardiovascular disease, and the impact of COVID-19 on the cardiovascular system of healthy people, and rehabilitation guidance recommendations. The Consensus involves 11 core clinical issues, including incidence, pathogenesis, clinical manifestations, treatment strategies, prognosis, and rehabilitation. It is our hope that this Consensus will provide a practical guidance to cardiologists in the management of cardiovascular diseases in the new era of COVID-19 pandemic.

Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial.

BACKGROUND: Impaired glucose regulation (defined as either impaired glucose tolerance or impaired fasting glucose) is an important risk factor for the development of diabetes. We aimed to evaluate the safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing diabetes in Chinese participants with impaired glucose regulation. METHODS: We did a multicentre, open-label, randomised controlled trial at 43 endocrinology departments in general hospitals across China. Eligible participants were individuals with impaired glucose regulation (ie, impaired glucose tolerance or impaired fasting glucose, or both), men or women aged 18-70 years with a BMI of 21-32 kg/m2. Eligible participants were randomly assigned (1:1) via a computer-generated randomisation to receive either standard lifestyle intervention alone or metformin (850 mg orally once per day for the first 2 weeks and titrated to 1700 mg orally per day [850 mg twice per day]) plus lifestyle intervention. Block randomisation was used with a block size of four, stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), hypertension, and use of any anti-hypertensive medication. Lifestyle intervention advice was given by investigators at all participating sites. The primary endpoint was the incidence of newly diagnosed diabetes at the end of the 2-year follow-up. Analysis was done using the full analysis set and per-protocol set. This study is registered with ClinicalTrials.gov, number NCT03441750, and is completed. FINDINGS: Between April, 2017, and June, 2019, 3881 individuals were assessed for eligibility, of which 1678 (43·2%) participants were randomly assigned to either the metformin plus lifestyle intervention group (n=831) or the lifestyle intervention alone group (n=847) and received the allocated intervention at least once. During a median follow-up of 2·03 years, the incidence rate of diabetes was 17·27 (95% CI 15·19-19·56) per 100 person-years in the metformin plus lifestyle intervention group and 19·83 (17·67-22·18) per 100 person-years in the lifestyle intervention alone group. The metformin plus lifestyle intervention group showed a 17% lower risk of developing diabetes than the lifestyle intervention alone group (HR 0·83 [95% CI 0·70-0·99]; log-rank p=0·043). A higher proportion of participants in the metformin plus lifestyle intervention group reported adverse events than in the lifestyle intervention alone group, primarily due to more gastrointestinal adverse events. The percentage of participants reporting a serious adverse event was similar in both groups. INTERPRETATION: Metformin plus lifestyle intervention further reduced the risk of developing diabetes than lifestyle intervention alone in Chinese people with impaired glucose regulation, showing additional benefits of combined intervention in preventing progression to diabetes without new safety concerns. FUNDING: Merck Serono China, an affiliate of Merck KGaA, Darmstadt, Germany. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Efficacy of Allisartan Isoproxil in the Treatment of Mild-to-Moderate Essential Hypertension.

BACKGROUND: Allisartan isoproxil is a selective nonpeptide angiotensin II (AT1) receptor blocker developed by China, this study aimed to assess its clinical efficacy for essential hypertension (EH). METHODS: Patients with mild-to-moderate EH, selected at 44 sites in China from September 9, 2016, to December 7, 2018, were administered 240 mg allisartan isoproxil daily for 4 weeks. Patients with controlled blood pressure (BP) continued monotherapy for 8 weeks, others were randomly assigned (1:1) to A + D group (allisartan isoproxil 240 mg + indapamide 1.5 mg) or A + C group (allisartan isoproxil + amlodipine besylate 5 mg) for 8 weeks. BP were measured at week 4, 8 and 12. RESULTS: 2,126 patients were included in the analysis. After 12 weeks of treatment, systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased by 19.24 ± 12.02 and 10.63 ± 8.89 mm Hg, respectively, and the overall BP control rate was 78.56%. The sitting blood pressures (SBP/DBP) decreased by 19.12 ± 11.71/10.84 ± 8.73 mm Hg in patients with 12 weeks allisartan isoproxil monotherapy (both P < 0.0001). The BP reductions and control rates were comparable between A + D and A + C groups. 48 patients with monotherapy-controlled BP underwent ambulatory BP monitoring, with a mean decrease in ambulatory BP of 10.04 ± 10.87/5.50 ± 8.07 mm Hg after 12 weeks of treatment, and consistent reductions between day and night. SBP and DBP had trough-to-peak ratios of 64.64% and 62.63% and smoothness indices of 3.82 and 2.92, respectively. CONCLUSIONS: An allisartan isoproxil-based antihypertensive regimen can effectively control BP in patients with mild-to-moderate EH. PROJECT REGISTRATION NO: CTR20160138 (Registration and Information Disclosure Platform for China Drug Clinical Studies, http://www.chinadrugtrials.org.cn/index.html).

Hyperuricemia is associated with more cardiometabolic risk factors in hypertensive younger Chinese adults than in elderly.

Background: Numerous studies have shown that hyperuricemia (HUA) is associated with cardiovascular and renal outcomes, but few studies specifically explored the effect of age on this relationship. Therefore, our study aimed to explore the relationship between HUA and other cardiometabolic risk factors in different age groups. Methods: This cross-section study used the data from Survey on uric acid in Chinese subjects with essential hypertension (SUCCESS). We performed multivariate logistic regressions in different age groups. Results: After adjusting for potential confounders, among young and middle-aged adults less than 60, HUA was associated with higher body mass index (BMI, adjusted OR = 1.114, 95% CI: 1.057-1.174), higher fasting blood glucose (FBG, adjusted OR = 1.099, 95% CI: 1.003-1.205), triglycerides (TG, adjusted OR = 1.425, 95% CI: 1.247-1.629), higher low-density lipoprotein cholesterol (LDL-C, adjusted OR = 1.171, 95% CI: 1.025-1.337), and lower estimated glomerular filtration rate (eGFR, adjusted OR = 0.992, 95% CI: 0.988-0.996). Among elderly adults 60 years or older, HUA was associated with higher SBP (adjusted OR = 1.024, 95% CI: 1.005-1.042), higher TG (adjusted OR = 1.716, 95% CI: 1.466-2.009), and higher LDL-C (adjusted OR = 1.595, 95% CI: 1.366-1.863). Conclusion: HUA is associated with more cardiometabolic risk factors in younger adults with hypertension (HT). Comprehensive management of HT with HUA is needed in clinical settings.

Contribution of single-pill combinations in the management of hypertension: perspectives from China, Europe and the USA.

Uncontrolled hypertension is associated with an increased risk of adverse clinical vascular outcomes and death. Hypertension management guidelines from China and the USA recommend initiation of antihypertensive pharmacotherapy with a single drug for patients without severe hypertension at presentation. Current European hypertension guidelines take a different approach and recommend the use of combination therapy from the time of diagnosis of hypertension for most patients. This article reviews the burden of hypertension in these countries and summarises the evidence base for the use of antihypertensive combination therapy contained within a single tablet (single-pill combinations, SPC). Typically, half or less of populations from China, Europe and the USA who were found to have hypertension were aware of their condition, less than half of those receiving treatment, and fewer still achieved adequate blood pressure (BP) control. The reasons for the unaddressed burden of hypertension are complex and multifactorial, with contributions from factors related to patients, healthcare providers and healthcare systems. The use of SPCs of antihypertensive therapies helps to optimise adherence with therapy and is likely to result in superior BP control. There is a strong evidence base to support current European guideline recommendations on the initiation of antihypertensive therapy with SPCs for the majority of people with hypertension.

Rationale and Design of Sympathetic Mapping/Ablation of Renal Nerves Trial (SMART) for the Treatment of Hypertension: a Prospective, Multicenter, Single-Blind, Randomized and Sham Procedure-Controlled Study.

Renal denervation (RDN) is proposed as a durable and patient compliance independent treatment for hypertension. However, 20-30% non-responder after RDN treatment weakened the therapeutic effect, which may be due to blind ablation. The renal nerve mapping/selective ablation system developed by SyMap Medical Ltd (Suzhou), China, has the function of mapping renal sympathetic/parasympathetic nerve sites and selectively removing renal sympathetic nerves and is expected to meet the urgent unmet clinical need of targeted RDN. The "Sympathetic Mapping/Ablation of Renal Nerves Trial" (SMART) is a prospective, multicenter, randomized, single-blinded, sham procedure-controlled trial, to evaluate the safety and efficacy of targeted renal sympathetic denervation in patients with essential and uncontrolled hypertension. The study is the first clinical registry trial using a targeted RDN for the treatment of uncontrolled hypertension; the dual-endpoint design can answer the question of how many antihypertensive drugs can be reduced in patients after RDN. The trial is registered on clinicaltrials.gov NCT02761811.

Machine learning outperforms traditional logistic regression and offers new possibilities for cardiovascular risk prediction: A study involving 143,043 Chinese patients with hypertension.

Introduction: Identifying people at risk of cardiovascular diseases (CVD) is a cornerstone of preventive cardiology. We developed machine learning (ML) algorithms and investigated their performance in predicting patients' current CVD risk (coronary heart disease and stroke in this study). Materials and methods: We compared traditional logistic regression (LR) with five ML algorithms LR with Elastic-Net, Random Forest (RF), XGBoost (XGB), Support Vector Machine, Deep Learning, and an Ensemble model averaging predictions from RF, XGB, and Deep Learning for CVD risk prediction using pre-existing patient-level data from a multi-center, cross-sectional study (the Microalbuminuria Screening in Hypertensive Patients Project initiated by the China International Exchange and Promotive Association for Medical and Healthcare) that enrolled 143,043 patients with hypertension from 600 tertiary, secondary, or community hospitals. Each of the five ML algorithms incorporated 18 variables, such as demographics, examinations, comorbidities, and treatment regimens, and were trained and evaluated using 5-fold cross-validation. Predictive accuracy was assessed by the area under the receiver operating curve (AUROC). Results: Patients' mean age was 62 ± 12 years and 57% were men. Advanced ML algorithms outperformed the traditional LR model. Particularly, the Ensemble model had superior discrimination with an AUROC of 0.760 than LR (AUC = 0.737) and other tested models. Conclusion: We establishes an Ensemble model that shows better performance in predicting patients' current CVD risk using routine information compared to the traditional LR model. ML can help physicians design follow-up plans with more accurate results, offering new possibilities for short-term risk prediction and early detection. Further, ML models can be trained with longitudinal data and used to predict long-term CVD risks, thereby informing CVD prevention.

Accuracy Evaluation of Carotid-Femoral Pulse Wave Velocity Estimated by Smart Terminal Watch.

To evaluate the accuracy of the smartwatch in estimating carotid-femoral pulse wave velocity (cfPWV). A cohort of gender-matched volunteers aged 18-80 years were recruited. At the sitting and supine positions, cfPWV was measured alternately by smartwatch and CompliorAnalyse, for each participant, and nine sets of data were collected from each participant with a 60 s interval between measurements. The accuracy of cfPWV measurement for smartwatches was assessed using mean error (ME) and mean absolute error (MAE), while the consistency of the two methods was assessed using the Bland-Altman analysis and concordance class correlation. A total of 347 participants were enrolled. The mean cfPWV was 9.01 ± 2.29 m/s measured by CompliorAnalyse and 9.06 ± 1.94 m/s by smartwatch. The consistency correlation coefficient (CCC) was 0.9045 (95% CI 0.8853-0.9206), the ME was 0.046 ± 0.92, and the MAE was 0.66 (95% CI 0.59-0.73). Bland-Altman analysis showed that the error of 95% samples was in the range between -1.77 m/s and 1.86 m/s. The Kappa value of cfPWV greater than 10 m/s was 0.79, the area under the ROC curve was 0.97 (P < 0.001), sensitivity was 0.90, specificity was 0.93, positive predictive value was 0.83 and negative predictive value was 0.96. Smartwatch can accurately estimate cfPWV to evaluate arterial stiffness. This method is simple and feasible and is suitable for people to actively and early monitor vascular elasticity.

Application of Angiotensin Receptor-Neprilysin Inhibitor in Chronic Kidney Disease Patients: Chinese Expert Consensus.

Chronic kidney disease (CKD) is a global public health problem, and cardiovascular disease is the most common cause of death in patients with CKD. The incidence and prevalence of cardiovascular events during the early stages of CKD increases significantly with a decline in renal function. More than 50% of dialysis patients die from cardiovascular disease, including coronary heart disease, heart failure, arrhythmia, and sudden cardiac death. Therefore, developing effective methods to control risk factors and improve prognosis is the primary focus during the diagnosis and treatment of CKD. For example, the SPRINT study demonstrated that CKD drugs are effective in reducing cardiovascular and cerebrovascular events by controlling blood pressure. Uncontrolled blood pressure not only increases the risk of these events but also accelerates the progression of CKD. A co-crystal complex of sacubitril, which is a neprilysin inhibitor, and valsartan, which is an angiotensin receptor blockade, has the potential to be widely used against CKD. Sacubitril inhibits neprilysin, which further reduces the degradation of natriuretic peptides and enhances the beneficial effects of the natriuretic peptide system. In contrast, valsartan alone can block the angiotensin II-1 (AT1) receptor and therefore inhibit the renin-angiotensin-aldosterone system. These two components can act synergistically to relax blood vessels, prevent and reverse cardiovascular remodeling, and promote natriuresis. Recent studies have repeatedly confirmed that the first and so far the only angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril/valsartan can reduce blood pressure more effectively than renin-angiotensin system inhibitors and improve the prognosis of heart failure in patients with CKD. Here, we propose clinical recommendations based on an expert consensus to guide ARNI-based therapeutics and reduce the occurrence of cardiovascular events in patients with CKD.

Hemodynamic differences between women and men with elevated blood pressure in China: A non-invasive assessment of 45,082 adults using impedance cardiography.

BACKGROUND: Whether there are sex differences in hemodynamic profiles among people with elevated blood pressure is not well understood and could guide personalization of treatment. METHODS AND RESULTS: We described the clinical and hemodynamic characteristics of adults with elevated blood pressure in China using impedance cardiography. We included 45,082 individuals with elevated blood pressure (defined as systolic blood pressure of ≥130 mmHg or a diastolic blood pressure of ≥80 mmHg), of which 35.2% were women. Overall, women had a higher mean systolic blood pressure than men (139.0 [±15.7] mmHg vs 136.8 [±13.8] mmHg, P<0.001), but a lower mean diastolic blood pressure (82.6 [±9.0] mmHg vs 85.6 [±8.9] mmHg, P<0.001). After adjusting for age, region, and body mass index, women <50 years old had lower systemic vascular resistance index (beta-coefficient [ß] -31.7; 95% CI: -51.2, -12.2) and higher cardiac index (ß 0.07; 95% CI: 0.04, 0.09) than men of their same age group, whereas among those ≥50 years old women had higher systemic vascular resistance index (ß 120.4; 95% CI: 102.4, 138.5) but lower cardiac index (ß -0.15; 95% CI: -0.16, -0.13). Results were consistent with a propensity score matching sensitivity analysis, although the magnitude of the SVRI difference was lower and non-significant. However, there was substantial overlap between women and men in the distribution plots of these variables, with overlapping areas ranging from 78% to 88%. CONCLUSIONS: Our findings indicate that there are sex differences in hypertension phenotype, but that sex alone is insufficient to infer an individual's profile.

Association Between Heart Rate and Major Adverse Cardiovascular Events Among 9,991 Hypertentive Patients: A Multicenter Retrospective Follow-Up Study.

Objective: To assess the effect of heart rate at baseline on major adverse cardiovascular events (MACEs) among hypertensive patients in China. Methods: A multicenter retrospective study was conducted with a 24 month follow-up period. A total of 10,031 hypertensive patients treated with standard antihypertensive drugs were grouped according to their heart rate before treatment: <65 beats per min (bpm), 65-69 bpm, 70-74 bpm, 75-79 bpm, and ≥80 bpm. The occurrence of any of MACEs was as the endpoint event during the 24 month follow-up period. The effect of heart rate at baseline on MACEs was analyzed using univate and multivariable Cox proportional regression analyses, with hazard ratios (HRs) and 95% confidence intervals (CIs). The restricted cubic spline (RCS) model was used to fit the Cox proportional harzard model with 5 knots at the 5th, 25th, 50th, 75th, and 95th percentiles of heart rate. Results: Totally 9,991 patients were finally enrolled with the mean systolic pressure (SBP)/diastolic pressure (DBP) of 130.59 ± 7.13/77.66 ± 5.99 mmHg at 24 month follow-up. The incidence of MACEs was 4.80% (n = 480). After adjustment for age, gender, baseline blood pressure, alcohol drinking, smoking, hyperlipidemia, diabetes, coronary heart disease, cerebrovascular disease and antihypertensive drug use, patients with heart rate <65 bpm (HR = 1.450, 95% CI: 1.098-1.915) and ≥80 bpm (HR = 1.391, 95% CI: 1.056-11.832) showed 0.45 fold and 0.391 fold increases of MACE risks, compared with patients with heart rate of 70-74 bpm. Furthermore, MACE risks were increased by 86.0% and 65.4% in men, and 59.3% and 69.0% in elderly patients aged ≥65 years at heart rate <65 bpm or ≥80 bpm, respectively. We also found a non-liner U-shaped correlation between heart rate and the occurrence of MACEs. Conclusions: Heart rate might be an independent risk factor for MACEs in hypertensive patients. An appropriate range of heart rate control may offer guidance to hypertension treatment.