Intensified, optimized and standardized management of Chinese patients with hypertension: Comments on “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”

The “2018 Chinese Guidelines for Prevention and Treatment of Hypertension”[1](hereinafter referred to as the 2018 Guidelines) published in this issue was revised by the Guidelines Revision Committee which is initiated and organized by the Chinese Hypertension League.Based on the “2010 Chinese Guidelines for the Management of Hypertension” and recent evidence from domestic and international research in the field of hypertension,considering national conditions and the current situation of hypertension management in China,and reference to the latest European and American hypertension guidelines,the 2018 Guidelines make comprehensive and in-depth elaborations and recommendations of the diagnosis and assessment of hypertension,strategies and goals of prevention and treatment of hypertension and pathway of intervention,etc.The 2018 Guidelines not only provide Chinese medical personnel with guidance and reference for the clinical practice and population management of hypertension,but also serve as the latest textbook on updating concepts and knowledge in the field of hypertension.

Rationale and Design of the Randomized Controlled Trial of Intensive Versus Usual ECG Screening for Atrial Fibrillation in Elderly Chinese by an Automated ECG System in Community Health Centers in Shanghai(AF-CATCH)

Objective:The randomized controlled trial(ClinicalTrials.gov identifier NCT02990741)will investigate whether more frequent electrocardiographic(ECG)recordings and analyses with an automated ECG system would improve detection of atrial fibrillation compared with a single annual ECG screen in elderly Chinese in community health centers.Design:Men and women(≥65 years)will be randomized into intensive(n=3500)and usual(n=3500)screening groups,and within the intensive screening group into intensive screening(n=2625)and more intensive screening(n=875)subgroups.ECG recordings will be performed with an automated ECG analysis system(AliveCor heart monitor)at 1 year in the usual screening group,at 3,6,9,and 12 months in the intensive screening subgroup,and at 1,2,3,and 4 weeks and 3,6,9,and 12 months in the more intensive screening subgroup.The primary outcome is the detection rate of atrial fibrillation between the usual screening group and the intensive screening group.Sample size estimation was based on a projected detection rate of atrial fibrillation of 2.0% by a single ECG recording at 12 months,an improvement of 50% with more frequent ECG recordings,α=0.05,power of 80%,and a one-sided test.Conclusions:The trial will provide evidence on the clinical effectiveness of more frequent ECG recordings by a handheld automated analysis system in the detection of atrial fibrillation.

Outcome Trials in the Therapeutic Management of Hypertension in East Asians

According to the most recent epidemiological data,the prevalence of hypertension ranged from about 25% in Chinese living either in the mainland or in Taiwan and Koreans,to approximately 40% in Mongolians.The control rate of hypertension was about 35% in Koreans and Japanese,24% in Mongolians,and less than 10%in Chinese.Four placebo-controlled trials in China unequivocally proved that antihypertensive therapy may prevent stroke and other cardiovascular complications in hypertension or patients with a history of stroke or transient ischemic attack.Four actively-controlled trials in Japan did not show signifi cant difference between various classes or combinations of antihypertensive drugs.Two trials that compared intensive with less intensive blood pressure control in elderly Japanese hypertensive patients did not show further benefi t of controlling systolic blood pressure to a level below 140 mmHg in comparison with blood pressure control to a level of 140 mmHg or above.These trials that compared various classes of antihypertensive drugs or intensive with less intensive blood pressure control often had small sample size and hence inadequate power to detect modest or moderate benefi t.There is still a need for high quality outcome trial data in East Asians.

Alcohol consumption in relation to the incidence of atrial fibrillation in an elderly Chinese population

BACKGROUND Alcohol consumption is a known modifiable risk factor for atrial fibrillation.The association,however,might differ according to gender.We investigated gender-specific associations between alcohol consumption and incident atrial fibrillation in an elderly Chinese population.METHODS Our study participants were elderly residents(≥65 years)recruited from five community health centers in the urban area of Shanghai(n=6,618).Alcohol intake was classified as never drinkers and current light-to-moderate(<40 g/day)and heavy drinkers(≥40 g/day).Atrial fibrillation was detected by a 30-s single-lead electrocardiography(ECG,AliveCor®Heart Monitor)and further evaluated with a regular 12-lead ECG.RESULTS During a median of 2.1 years(interquartile range:2.0−2.2)follow-up,the incidence rate of atrial fibrillation was 1.10%in all study participants.It was slightly but non-significantly higher in men(n=2849)than women(n=3769,1.30%vs.0.96%,P=0.19)and in current drinkers(n=793)than never drinkers(n=5825,1.64%vs.1.03%,P=0.12).In both unadjusted and adjusted analyses,there was interaction between sex and current alcohol intake in relation to the incidence of atrial fibrillation(P<0.0001).After adjustment for confounding factors,current drinkers had a significantly higher incidence rate of atrial fibrillation than never drinkers in women(12.96%[7/54]vs.0.78%[29/3715],adjusted odds ratio[OR]=10.25,95%confidence interval[CI]:3.54−29.67,P<0.0001),but not in men(0.81%[6/739]vs.1.47%[31/2110],OR=0.62,95%CI:0.25−1.51,P=0.29).CONCLUSIONS Our study showed a significant association between alcohol intake and the incidence of atrial fibrillation in elderly Chinese women,but not men.

RESERCH ON“ANTI-AGING”EFFECT OF QIGONG

Evaluation of Anti-aging Effect of QigongBased on the Theory That the Qigong Exer-cises Correct both Yin and Yang DeficienciesThe TCM theory holds that mainte-nance of a good health depends on the bal-ance of body yin and yang which are con-stantly in motion and change.Premature ag-ing is mainly due to imbalance of yin andyang in the body.Years’ experimental

Why is the Chinese hypertension guideline necessary?

The new Chinese hypertension guideline was eventually published.[1] It has been more than seven years since the previous Chinese hypertension guideline was published in 2011.[2] The guideline committee should also be congratulated that this new Chinese hypertension guideline was for the first time published in full length in the English language in this issue of the Journal of Geriatric Cardiology.[3] This is the fourth Chinese hypertension guideline,[3] after the first,second[4] and third[2] in 1999,2005 and 2011,respectively.The first Chinese hypertension guideline was printed in a booklet.The document was not so sophisticated,but nevertheless played a role in improving management of hypertension at that time in China.The treatment rate of hypertension increased substantially from 45.5% in 1991[5] to 81.8% in 2002[6] in patients who were aware of the disease (Table 1).

PLATELET FREE CALCIUM AND SERUM FREE CALCIUM IN ESSENTIAL HYPERTENSION

Intracellular free calcium of platelets and serum free calcium were studied in human essential hypertension. Intracellular free calcium of platelets was significantly higher in hypertensive patients than that in normotensive subjects, and this was correlated with blood pressure. There was no difference of serum free calcium between hypertensives and normotensive controls. Antihypertensive treatment with nifedipine resulted in a reduction of platelet free calcium, and this was correlated with the fall of blood pressure. In patients treated with clonidine, although there was no difference of platelet free calcium between hypertensives and normotensive controls, serum free clacium was significantly reduced. These results indicated that intracellular free calcium may be regulated by same hormonal or pharmacological factors which determined the height of blood pressure, calcium channel blockers may be more effective in prevention of cardiovascular and cerebrovascular complications caused by platelet hyperfunction in essential hypertension.

ANTI-OXIDATIVE MECHANISMS OF PRAVASTATIN PREVENTING AORTIC ATHEROSCLEROSIS IN apoE KNOCKOUT MICE:ROLE OF p38 MAPK PATHWAY

Objective To determine whether pravastatin exerts anti-oxidative effects on preventing aortic atherosclerosis via modulating p38 MAPK pathway. Methods Male 8-week-old apoE-/- mice fed a diet containing 1.25% cholesterol (wt/wt) were divided into pravastatin group administered with pravastatin (80 mg·kg-1·d-1) and atherosclerosis group administered with PBS; and male 8-week-old C57BL/6J mice fed a normal diet were as control group (n=12). In thoracoabdominal aortas of mice, levels of Malondialdehyde (MDA) and activities of superoxide dismutase (SOD) were measured and expression of phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated signal transducer and activator of transcription 1 (pSTAT1) were examined by Western blotting. Results After eight weeks, atherosclerosis in aortic root was significantly prevented by pravastatin. In aortic atherosclerosis lesion, the level of MDA was significantly reduced; adversely the activity of SOD was increased. Expressions of p-p38 MAPK and pSTAT1 were significantly decreased in aortic atherosclerosis lesion.Conclusion Our results suggests that anti-oxidative mechanisms of pravastatin preventing aortic atherosclerosis may partially depend on modulating p38 MAPK signal pathway.

RELATIONSHIP AMONG MYOCARDIAL INFARCTION, INSERTION/DELETION POLYMORPHISM OF FVII GENE PROMOTER REGION AND FVII ACTIVITY

Objective To explore the relationship among myocardial infarction ( MI) , promoter region polymorphism of FVII gene and FVII activity in a Chinese population. Methods Denaturing gradient gel electrophoresis technique was used to study promoter region polymorphism of FVll gene, and plasma FVII activity (FVIIC) was examined by one stage clotting assay in 74 cases with M1 as well as 123 normal controls. Results An insertion/deletion polymorphism of 10bp was found in the promoter region. Plasma FVII activity was significantly higher in the myocardial infarction (P<0.05). Conclusion Elevated FVI1 activity may be a risk factor for myocardial infarction. There is no correlation found between the insertion/deletion polymorphism of FVII gene promoter region and myocardial infarction in a Chinese population (74M1 cases and 123 normal controls).

Current and recent cigarette smoking in relation to cardiovascular and non-cardiovascular mortality in an elderly male Chinese population

OBJECTIVE To investigate the association between current and former smoking and the risk of mortality in elderly Chinese men.METHODS Our study participants were elderly(≥60 years)men recruited in a suburban town of Shanghai.Cigarette smoking status was categorized as never smoking,remote(cessation>5 years)and recent former smoking(cessation≤5 years),and light-to-moderate(≤20 cigarettes/day)and heavy current smoking(>20 cigarettes/day).Cox proportional hazards models and restricted cubic splines were used to examine the associations of interest.RESULTS The 1568 participants had a mean age of 68.6±7.1 years.Of all participants,311 were never smokers,201 were remote former smokers,133 were recent former smokers,783 were light-to-moderate current smokers and 140 were heavy current smokers.During a median follow-up of 7.9 years,all-cause,cardiovascular and non-cardiovascular deaths occurred in 267,106 and 161 participants,respectively.Heavy current smokers had the highest risk of all-cause and non-cardiovascular mortality,with an adjusted hazard ratio(HR)of 2.30(95%CI:1.34-4.07)and 3.98(95%CI:2.03-7.83)versus never smokers,respectively.Recent former smokers also had a higher risk of all-cause(HR=1.62,95%CI:1.04-2.52)and non-cardiovascular mortality(HR=2.40,95%CI:1.32-4.37)than never smokers.Cox regression restricted cubic spline models showed the highest risk of all-cause and non-cardiovascular mortality within 5 years of smoking cessation and decline thereafter.Further subgroup analyses showed interaction between smoking status and pulse rate(≥70 beats/min vs.<70 beats/min)in relation to the risk of all-cause and non-cardiovascular mortality,with a higher risk in current versus never smokers in those participants with a pulse rate below 70 beats/min.CONCLUSIONS Cigarette smoking in elderly Chinese confers significant risks of mortality,especially when recent former smoking is considered together with current smoking.

Study on Insulin Resistance and Genetic Polymorphisms in Essential Hypertension Patients of Two Different Kinds of TCM Constitution

Objective： To investigate the relationship of insulin resistance and the polymorphisms of insulin receptor-related genes in essential hypertension patients of two different kinds of TCM constitution. Methods： Oral glucose tolerance test （OGTT） and insulin release test （InRT） were conducted in 217 essential hypertensive patients of either sluggish meticulous （SM） constitution （139 cases） or prosperous impetuous （PI） constitution （78 cases）, and the polymorphism of three genes, including insulin-like growth factor-1 receptor （IGF-1R）, insulin receptor substrate-1 （IRS-1） and 2 （IRS-2） genes were detected. Results： （1） OGTT, InRT and insulin resistance index （Homa-IR） were higher and insulin sensitive index （ISI） was lower in the patients of SM constitution than those in patients of PI constitution. （2） Significant difference of ISI and Homa-IR was shown in patients of both constitutions with genotype G of the 3 genes. Conclusion： Decrease of insulin sensitivity and increase of insulin resistance are more obvious in hypertensive patients with genotype G of the 3 genes of SM constitution than in those of PI constitution. Therefore, the difference in constitution might be one of the genetic characteristics for insulin resistance in hypertensive patients.

A STUDY ON THE RELATIONS BETWEEN DIETARY PARAMETERS AND BLOOD PRESSURE IN 8 CHINESE COMMUNITIES

Relations between 67 dietary parameters and blood pressure in 8 Chinese communities （745 men aged 40～59 years） were studied. Results showed. UNa, Na/K, Ca, Ca/Mg, parameters reflecting the protein-intake, serum levels of Sr, valine, cysteine,threonine, Vit A, Vit E, cholesterol, C16:0, C18:0, （saturated fatty acid）/（polyunsaturated fatty acid）,（C20:5+C22:6 （ω3））/（C18:2+C20:3+C20:4 （ω6））, γ-glutamyl transferase （an index of alcohol consumption） and plasma glucose correlated positively with BP, while serum levels of K, Mg, glycine, phenylalanine, leucine, VitC, C18:2, Ni, V, Co, Cr and Cd, inversely. And also, a metabolic imbalance among BP, blood glucose and lipids was exhibited.

Ambulatory blood pressure monitoring for the management of hypertension

Ambulatory blood pressure monitoring(ABPM)has become indispensable in the current management of hypertension.ABPM is particularly useful in the accurate diagnosis of hypertension.Its diagnostic thresholds had been recently established based on hard clinical outcomes.Cross-classification of patients according to office and ambulatory blood pressure identifies white-coat,masked,and sustained hypertension.ABPM is also useful in cardiovascular(CV)risk assessment.It provides information on daytime and nighttime blood pressure and circadian rhythm,particularly nighttime blood pressure dipping.Nighttime blood pressure is predictive of CV risk independent of office and daytime blood pressure.Isolated nocturnal hypertension is a special form of masked hypertension,with normal daytime but elevated nocturnal blood pressure.It also helps in the evaluation of blood pressure fluctuation and variation,such as morning blood pressure surge and reading-to-reading blood pressure variability.ABPM may derive several other indexes,such as ambulatory blood pressure index and salt sensitivity index,which may be useful in CV evaluations.

Consensus of Chinese Specialists on Diagnosis and Treatment of Resistant Hypertension

INTRODUCTION Resistant hypertension has become a challenge in the treatment of hypertension.As the population continues to age and obesity,sleep apnea hypopnea syndrome,and chronic kidney disease increase in incidence,resistant hypertension has become an increasingly common issue in clinical practice.Failure to control blood pressure can impair target organs such as the heart,brain,and kidney,facilitating the occurrence of clinical cardiovascular events.

MEDICAL AND HEALTH CARE QIGONG(Qu Bing Yang Sheng Gong)(Continued)

Qigong is one of the Chinese traditionalexercises for medical and health care.Qigong exercisers achieve self-regulationand self-control through mental inductionand respiratory adjustment.Since 1958,wehave focused our study on the effect ofQigong on prevention and treatment ofcardiovascular diseases and anti-aging.Sub-stantial data suggest that Qigong can regu-late the body function in various ways,andis an effective measure for keeping a goodhealth.

Serum triglycerides concentration in relation to total and cardiovascular mortality in an elderly Chinese population

OBJECTIVE To investigate serum triglycerides in relation to all-cause,cardiovascular,and non-cardiovascular mortality in an elderly Chinese population.METHODS The study participants(n=3565)were elderly(≥60 years)community dwellers living in a suburban town of Shanghai.Hypertriglyceridemia was defined as a serum triglycerides concentration≥2.30 mmol/L(definite)and≥1.70 mmol/L(borderline),respectively.RESULTS The prevalence of definite and borderline hypertriglyceridemia at baseline was 7.5%and 29.5%,respectively.It was higher in women(n=1982,9.0%and 33.8%,respectively)than men(n=1583,6.2%and 27.9%,respectively),in obese and over-weight participants(n=1566,10.5%and 36.4%,respectively)than normal weight participants(n=1999,5.6%and 27.1%,respect-ively),and in diabetic participants(n=177,11.9%and 39.0%,respectively)than non-diabetic participants(n=3388,7.5%and 30.8%,respectively).During a median of 7.9 years follow-up,all-cause,cardiovascular and non-cardiovascular deaths occurred in 529,216 and 313 participants,respectively.In analyses according to the quintile distributions of serum triglycerides concentration,the sex-and age-standardized mortality rate was lowest in the middle quintile for all-cause,cardiovascular and non-cardiovascu-lar mortality(18.6,7.8 and 11.9 per 1000 person-years,respectively,versus 21.5,10.5 and 12.7 per 1000 person-years,respectively,in the two lower quintiles and 21.7,9.5 and 14.0 per 1000 person-years,respectively,in the two higher quintiles).The fully adjus-ted hazard ratios(95%CI)for the middle quintile versus the combined two lower with two higher quintiles were 0.85(95%CI:0.67-1.07,P=0.17),0.81(95%CI:0.54-1.19,P=0.28)and 0.87(95%CI:0.64-1.17,P=0.35)for all-cause,cardiovascular and non-cardiovascular mortality,respectively.CONCLUSIONS Our study showed high prevalence of hypertriglyceridemia,especially when defined as borderline and in obese and overweight participants,and mildly but non-significantly elevated risks of cardiovascular mortality relative to the middle level of serum triglycerides.

Rationale and Design of a Randomized Controlled Trial on Intensive Management of Blood PRESSure and Cholesterol in Elderly Chinese with Hypertension and Atrial FibrillatION (IMPRESSION)

Hypertension significantly increases the risk of embolic stroke and systemic embolism in patients with atrial fibrillation, while statin therapy can improve long-term outcomes in hypertensive patients at high risk. However, it is still unclear whether patients with both hypertension and atrial fibrillation can benefit from intensive management of blood pressure and cholesterol. IMPRESSION is a 3-year prospective, randomized, open-label, blinded-endpoint investigation. A total of 1200 hypertensive patients with atrial fibrillation from about 40 clinical centers nationwide will be included upon confirming the presence of both hypertension and atrial fibrillation and will be randomly assigned to groups for intensive or standard management of blood pressure and cholesterol. Patients in all groups will have office and home blood pressure measured by the end of the first month and every 3 months thereafter. The effects of blood pressure and cholesterol management strategies in patients with hypertension and atrial fibrillation on fatal and non-fatal stroke, acute myocardial infarction, and cardiovascular death at 3 years will be assessed. The IMPRESSION study protocol has received approval from the Ethics Committee of Ruijin Hospital, Shanghai Jiaotong University School of Medicine. The procedures set out in this protocol are in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The results will be published following the CONSORT statement in a peer-reviewed scientific journal (Trial registration number: NCT04111419).

TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostasis.However,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood.Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l infusion.Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload.Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre mice.Echocardiographic and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac remodeling.Mechanistically,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 target.TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression.Furthermore,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 promoter.In conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

Long-term correction of hemorrhagic diathesis in hemophilia A mice by an AAV-delivered hybrid FⅧcomposed of the human heavy chain and the rat light chain

Conventional therapies for hemophilia A(HA)are prophylactic or on-demand intravenous FⅧinfusions.However,they are expensive and inconvenient to perform.Thus,better strategies for HA treatment must be developed.In this study,a recombinant FⅧcDNA encoding a human/rat hybrid FⅧwith an enhanced procoagulant potential for adeno-associated virus(AAV)-delivered gene therapy was developed.Plasmids containing human FⅧheavy chain(hHC),human light chain(hLC),and rat light chain(rLC)were transfected into cells and hydrodynamically injected into HA mice.Purified AAV viruses were intravenously injected into HA mice at two doses.Results showed that the hHC+rLC protein had a higher activity than the hHC+hLC protein at comparable expression levels.The specific activity of hHC+rLC was about 4-to 8-fold higher than that of their counterparts.Hydrodynamic injection experiments obtained consistent results.Notably,the HA mice undergoing the AAV-delivered hHC+rLC treatment exhibited a visibly higher activity than those treated with hHC+hLC,and the therapeutic effects lasted for up to 40 weeks.In conclusion,the application of the hybrid FⅧ(hHC+rLC)via an AAV-delivered gene therapy substantially improved the hemorrhagic diathesis of the HA mice.These data might be of help to the development of optimized FⅧexpression cassette for HA gene therapy.