Fu Wai Hospital

BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. RESULTS: Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). CONCLUSIONS: In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.)

BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P=0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P=0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P=0.42). CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. (Funded by Bristol-Myers Squibb and Pfizer; ARISTOTLE ClinicalTrials.gov number, NCT00412984.).

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).

BACKGROUND: Although the prevalence of hypertension (HTN) continues to increase in developing countries, including China, recent data are lacking. A nationwide survey was conducted from October 2012 to December 2015 to assess the prevalence of HTN in China. METHODS: A stratified multistage random sampling method was used to obtain a nationally representative sample of 451 755 residents ≥18 years of age from 31 provinces in mainland China from October 2012 to December 2015. Blood pressure (BP) was measured after resting for 5 minutes by trained staff using a validated oscillometric BP monitor. HTN was defined as systolic BP (SBP) ≥140 mm Hg/or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medication within 2 weeks. Pre-HTN was defined as SBP 120 to 139 mm Hg and DBP 80 to 89 mm Hg without antihypertensive medication. HTN control was defined as SBP <140 mm Hg and DBP<90 mm Hg. In addition, the prevalence of HTN (SBP ≥130 or DBP ≥80 mm Hg) and control rate (SBP <130 and DBP <80 mm Hg) of HTN were also estimated according to the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline. RESULTS: =0.819). Among individuals with HTN, 46.9% were aware of their condition, 40.7% were taking prescribed antihypertensive medications, and 15.3% had controlled HTN. Calcium channel blockers were the most commonly used antihypertensive medication (46.5%) as monotherapy, and 31.7% of treated hypertensive patients used ≥2 medications. The prevalence of HTN based on the 2017 American College of Cardiology/American Heart Association guideline was twice as high as that based on 2010 Chinese guideline (46.4%), whereas the control rate fell to 3.0%. CONCLUSIONS: In China, there is a high prevalence of HTN and pre-HTN, and awareness, treatment, and control of HTN were low. Management of medical therapy for HTN needs to improve.

BACKGROUND: Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial. METHODS: We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension. RESULTS: A total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P=0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P<0.001). Worsening of pulmonary arterial hypertension was the most frequent primary end-point event. The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline. Adverse events more frequently associated with macitentan than with placebo were headache, nasopharyngitis, and anemia. CONCLUSIONS: Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study. (Funded by Actelion Pharmaceuticals; SERAPHIN ClinicalTrials.gov number, NCT00660179.).

BACKGROUND: Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension. METHODS: In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg-maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg-maximum group). The 1.5 mg-maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety. RESULTS: By week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg-maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4% and 1%, respectively). CONCLUSIONS: Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.).

The triglyceride-glucose (TyG) index has been identified as a reliable alternative biomarker of insulin resistance (IR). Recently, a considerable number of studies have provided robust statistical evidence suggesting that the TyG index is associated with the development and prognosis of cardiovascular disease (CVD). Nevertheless, the application of the TyG index as a marker of CVD has not systemically been evaluated, and even less information exists regarding the underlying mechanisms associated with CVD. To this end, in this review, we summarize the history of the use of the TyG index as a surrogate marker for IR. We aimed to highlight the application value of the TyG index for a variety of CVD types and to explore the potential limitations of using this index as a predictor for cardiovascular events to improve its application value for CVD and provide more extensive and precise supporting evidence.

BACKGROUND: More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown. METHODS: We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years. RESULTS: The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P=0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001). CONCLUSIONS: Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. (Funded by the Population Health Research Institute and others.).

BACKGROUND: Earlier trials have shown that a routine invasive strategy improves outcomes in patients with acute coronary syndromes without ST-segment elevation. However, the optimal timing of such intervention remains uncertain. METHODS: We randomly assigned 3031 patients with acute coronary syndromes to undergo either routine early intervention (coronary angiography < or = 24 hours after randomization) or delayed intervention (coronary angiography > or = 36 hours after randomization). The primary outcome was a composite of death, myocardial infarction, or stroke at 6 months. A prespecified secondary outcome was death, myocardial infarction, or refractory ischemia at 6 months. RESULTS: Coronary angiography was performed in 97.6% of patients in the early-intervention group (median time, 14 hours) and in 95.7% of patients in the delayed-intervention group (median time, 50 hours). At 6 months, the primary outcome occurred in 9.6% of patients in the early-intervention group, as compared with 11.3% in the delayed-intervention group (hazard ratio in the early-intervention group, 0.85; 95% confidence interval [CI], 0.68 to 1.06; P=0.15). There was a relative reduction of 28% in the secondary outcome of death, myocardial infarction, or refractory ischemia in the early-intervention group (9.5%), as compared with the delayed-intervention group (12.9%) (hazard ratio, 0.72; 95% CI, 0.58 to 0.89; P=0.003). Prespecified analyses showed that early intervention improved the primary outcome in the third of patients who were at highest risk (hazard ratio, 0.65; 95% CI, 0.48 to 0.89) but not in the two thirds at low-to-intermediate risk (hazard ratio, 1.12; 95% CI, 0.81 to 1.56; P=0.01 for heterogeneity). CONCLUSIONS: Early intervention did not differ greatly from delayed intervention in preventing the primary outcome, but it did reduce the rate of the composite secondary outcome of death, myocardial infarction, or refractory ischemia and was superior to delayed intervention in high-risk patients. (ClinicalTrials.gov number, NCT00552513.)

BACKGROUND: A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead. METHODS: In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies. RESULTS: The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001). CONCLUSIONS: In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).

BACKGROUND: Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS: We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS: In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS: Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

Pulmonary arterial hypertension (PAH) remains a severe clinical condition despite the availability over the past 15 years of multiple drugs interfering with the endothelin, nitric oxide and prostacyclin pathways. The recent progress observed in medical therapy of PAH is not, therefore, related to the discovery of new pathways, but to the development of new strategies for combination therapy and on escalation of treatments based on systematic assessment of clinical response. The current treatment strategy is based on the severity of the newly diagnosed PAH patient as assessed by a multiparametric risk stratification approach. Clinical, exercise, right ventricular function and haemodynamic parameters are combined to define a low-, intermediate- or high-risk status according to the expected 1-year mortality. The current treatment algorithm provides the most appropriate initial strategy, including monotherapy, or double or triple combination therapy. Further treatment escalation is required in case low-risk status is not achieved in planned follow-up assessments. Lung transplantation may be required in most advanced cases on maximal medical therapy.

BACKGROUND: The appropriate target for systolic blood pressure to reduce cardiovascular risk in older patients with hypertension remains unclear. METHODS: In this multicenter, randomized, controlled trial, we assigned Chinese patients 60 to 80 years of age with hypertension to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. RESULTS: Of the 9624 patients screened for eligibility, 8511 were enrolled in the trial; 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. At 1 year of follow-up, the mean systolic blood pressure was 127.5 mm Hg in the intensive-treatment group and 135.3 mm Hg in the standard-treatment group. During a median follow-up period of 3.34 years, primary-outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.92; P = 0.007). The results for most of the individual components of the primary outcome also favored intensive treatment: the hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. CONCLUSIONS: In older patients with hypertension, intensive treatment with a systolic blood-pressure target of 110 to less than 130 mm Hg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to less than 150 mm Hg. (Funded by the Chinese Academy of Medical Sciences and others; STEP ClinicalTrials.gov number, NCT03015311.).

BACKGROUND: The relative benefits and risks of performing coronary-artery bypass grafting (CABG) with a beating-heart technique (off-pump CABG), as compared with cardiopulmonary bypass (on-pump CABG), are not clearly established. METHODS: At 79 centers in 19 countries, we randomly assigned 4752 patients in whom CABG was planned to undergo the procedure off-pump or on-pump. The first coprimary outcome was a composite of death, nonfatal stroke, nonfatal myocardial infarction, or new renal failure requiring dialysis at 30 days after randomization. RESULTS: There was no significant difference in the rate of the primary composite outcome between off-pump and on-pump CABG (9.8% vs. 10.3%; hazard ratio for the off-pump group, 0.95; 95% confidence interval [CI], 0.79 to 1.14; P=0.59) or in any of its individual components. The use of off-pump CABG, as compared with on-pump CABG, significantly reduced the rates of blood-product transfusion (50.7% vs. 63.3%; relative risk, 0.80; 95% CI, 0.75 to 0.85; P<0.001), reoperation for perioperative bleeding (1.4% vs. 2.4%; relative risk, 0.61; 95% CI, 0.40 to 0.93; P=0.02), acute kidney injury (28.0% vs. 32.1%; relative risk, 0.87; 95% CI, 0.80 to 0.96; P=0.01), and respiratory complications (5.9% vs. 7.5%; relative risk, 0.79; 95% CI, 0.63 to 0.98; P=0.03) but increased the rate of early repeat revascularizations (0.7% vs. 0.2%; hazard ratio, 4.01; 95% CI, 1.34 to 12.0; P=0.01). CONCLUSIONS: There was no significant difference between off-pump and on-pump CABG with respect to the 30-day rate of death, myocardial infarction, stroke, or renal failure requiring dialysis. The use of off-pump CABG resulted in reduced rates of transfusion, reoperation for perioperative bleeding, respiratory complications, and acute kidney injury but also resulted in an increased risk of early revascularization. (Funded by the Canadian Institutes of Health Research; CORONARY ClinicalTrials.gov number, NCT00463294.).

Background: The accurate assessment of individual risk can be of great value to guiding and facilitating the prevention of atherosclerotic cardiovascular disease (ASCVD). However, prediction models in common use were formulated primarily in white populations. The China-PAR project (Prediction for ASCVD Risk in China) is aimed at developing and validating 10-year risk prediction equations for ASCVD from 4 contemporary Chinese cohorts. Methods: Two prospective studies followed up together with a unified protocol were used as the derivation cohort to develop 10-year ASCVD risk equations in 21 320 Chinese participants. The external validation was evaluated in 2 independent Chinese cohorts with 14 123 and 70 838 participants. Furthermore, model performance was compared with the Pooled Cohort Equations reported in the American College of Cardiology/American Heart Association guideline. Results: Over 12 years of follow-up in the derivation cohort with 21 320 Chinese participants, 1048 subjects developed a first ASCVD event. Sex-specific equations had C statistics of 0.794 (95% confidence interval, 0.775–0.814) for men and 0.811 (95% confidence interval, 0.787–0.835) for women. The predicted rates were similar to the observed rates, as indicated by a calibration χ 2 of 13.1 for men ( P =0.16) and 12.8 for women ( P =0.17). Good internal and external validations of our equations were achieved in subsequent analyses. Compared with the Chinese equations, the Pooled Cohort Equations had lower C statistics and much higher calibration χ 2 values in men. Conclusions: Our project developed effective tools with good performance for 10-year ASCVD risk prediction among a Chinese population that will help to improve the primary prevention and management of cardiovascular disease.

‘ Since the information which the pulse affords is of so great importance, and so often consulted, surely it must be to our advantage to appreciate fully all it tells us, and to draw from it every detail that it is capable of imparting’ F.A. Mahomed 1872 [1] It is now possible to generate the ascending aortic pressure wave from the arterial pressure pulse, recorded noninvasively by applanation tonometry in the radial or carotid artery. This represents a blend of nineteenth century sphygmography with cuff sphygmomanometry, and is made possible by introduction of high fidelity tonometers, by characterization of arterial hydraulic properties in the upper limb and neck, and through application of mathematical engineering techniques in modern computer systems. This review will consider historical development, theoretic background, present status and future potential, as well as comparing this technique with radial and carotid tonometry alone, and with analysis of flow pulse and volume pulse waveforms as determined by Doppler or photoplethysmographic techniques. The arterial pulse is the most fundamental sign in clinical medicine, and has since antiquity been identified with the physician and the art of medicine. Palpation of the pulse forms the crest of the Royal College of Physicians of London, which was established to improve the scientific basis and practice of medicine and in an era when William Harvey, as anatomist to that college, wrote his classic text ‘de Motu Cordis…’[2]. William Bright [3] based his diagnosis of high blood pressure on ‘hardness’ of the pulse, and on the pressure required to extinguish the pulse. A scientific basis only arose after Marey [4], and then Mahomed [1] developed graphic methods to record the arterial pulse. By the beginning of the twentieth century, sphygmography was well established in medical journals and in medical textbooks and had been used to describe heart block and effects of antianginal medication as well as hypertension and other conditions [5–9]. In life insurance examinations sphygmocardiography was widely used for detecting persons with ‘arterial senility’ and increased risk of premature death [10]. Unfortunately sphygmography lapsed with introduction of the cuff sphygmomanometer, which provided numbers for the extremes of the pulse, and a veneer of scientific accuracy. Frederick Akbar Mohamed established the foundation of pulse wave analysis in a short medical lifetime from 1872 to 1884. He described the normal radial pressure waveform and showed the difference between this and the carotid wave [1]. He showed the effect of high blood pressure on the radial waveform, and used the waveform to describe the natural history of essential hypertension, and the difference between this and chronic nephritis [7, 8]. He also described the effects of arterial degeneration with ageing on the arterial pulse [7]. These features were identified and utilized in the life insurance studies of the late nineteenth century [10]. Mahomed's sphygmogram, and the popular Dudgeon sphygmogram which followed, and which was used by Sir James MacKenzie [9] were mechanical devices, awkward to use and prone to artifact. Modern tonometer systems are piezo-electric and are far more accurate, reliable, and easy to use. While originally introduced clinically to measure intraocular pressure, they have been adapted for vascular use by Drzwiecki [11], Millar and others [5, 6]. While Mahomed was the first to recognize the difference between pressure waves in central and peripheral arteries, McDonald [12] was responsible for explaining this phenomenon on the basis of wave reflection, and for introducing transfer functions to characterize properties of vascular beds in the frequency domain, and (with his colleague J.R. Womersley) for establishing the validity of assuming linearity in the arterial tree [13]. The work of McDonald, Womersley, Taylor and others, originally from Harvey's own hospital (St Bartholomew's, London) has led on to the techniques described here for pulse wave analysis. The technique of noninvasive aortic pulse wave analysis, as described here, depends on accurate recording of the radial pressure wave, its calibration against brachial pressure, then generation of the ascending aortic pressure waveform through use of a generalized transfer function in a computerized process. Ascending aortic waveforms are ensemble averaged into a single calibrated wave whose different features can be identified automatically with clinically important measures of pressure and time intervals measured and printed out in an interpretive report (Figure 1). Steps in the process are described below. The Sphygmocardiograph: computerized report on analysis of radial artery and synthesized aortic pressure waves. A series of radial artery pressure waves, recorded over an 8 s period (upper continuous tracing) are used to synthesize a series of ascending aortic pressure waves (lower continuous trace) using a convolutional algorithm and a generalized transfer function which characterizes hydraulic properties of the upper limb vasculature. The radial waves are ensemble-averaged into a single wave (centre left), and the aortic waves into a single synthesized aortic wave (centre right), with the radial wave calibrated to brachial systolic and diastolic pressure, and integrated mean pressure taken to be identical at radial and aortic sites. Features of the waves (foot, shoulder, peak, incisura) are identified automatically using differentials, and flagged. The detailed report gives information relevant to ventricular/vascular interaction from both pressure and time values, as calculated from the synthesized aortic waveform. Accurate applanation tonometry requires that the artery be applanated (flattened) underneath the sensor. This requires pressure from the operator with the vessel supported behind by the radius bone at the wrist or vertebral column and ligaments in the neck [14, 15, 16]. Complete confidence is gained when the device is applied to the eyeball to measure ocular pressure, or to an exposed artery, and where applanation can be confirmed visually. Reasonable confidence is gained if the pressure waves are completely consistent, beat to beat, if amplitude is the greatest that can be achieved, and if the pulse wave measured has the same character as one would expect in the artery i.e. sharp upstroke, straight rise to the first systolic peak, a definite sharp incisura, and near-exponential pressure decay in late diastole (Figure 1). Requirements for accurate quantitive tonometry cannot be achieved in practice because of the soft tissue which intervenes between the skin and anterior wall of the artery, but they can be approximated. Though others have been more fortunate, we have never been confident about relying on the instrument's internal calibration even for of wave and to systolic and diastolic pressure in the radial artery from cuff in the brachial artery. carotid we on through use of transfer functions from the radial artery to ascending and then from the ascending to carotid artery or through assuming that the mean and diastolic pressure are the same in the carotid artery as in the brachial and radial artery and systolic pressure high or systolic and pulse be recorded in the carotid artery when the internal calibration is high systolic carotid pressure be a of so that the vessel is the it is most often when the carotid are of the aortic from the radial or carotid pressure wave a generalized transfer function to describe arterial properties between the ascending and peripheral recording of a generalized transfer function that properties of the arterial between the are the same in all persons and all this is the since vascular on and vascular properties with arterial pressure, with and with it were it would be to the transfer function to from using a generalized transfer function are and to in features of the ascending aortic pressure wave be to the that upper is different between different that upper limb pulse wave with [5, or with of arterial pressure [5, or with the of used in clinical practice [5, in upper limb properties to have a effect on the frequency of where of the pressure wave are with far effect at the whose are The transfer functions that we have established in a of at are to that we had originally determined from aortic to brachial artery and in determined by a of others at and from noninvasive studies These are also to calculated for our of the upper limb of our own methods have been described by in and the studies that the radial and brachial artery pressure are different to in the ascending with and as the the calculated for diastolic and pulse pressure the for the and at for recorded radial for of this technique for noninvasively recorded waveforms to be of systolic and diastolic for the wave with a cuff on the of this for one the of the cuff and for pressure then use of this technique is a in central pressure from of applanation tonometry is but it of theoretic of normal waveforms and use. It is possible to record and even waveforms when the tonometer is applied and we have been of waveforms in from with use. (Figure information on of pulse pressure and diastolic pressure and recorded waveforms as a have it to from ascending aortic pressure waves from the carotid waveform to against that from the radial waveform when the is or studies and for tonometry and These with our own in using techniques are to own studies of and as well as comparing from both radial and from the would be to with use of they and to in In the arterial pulse has the same in central and peripheral arteries, and is to that in amplitude is of but it wave in and the of the wave is in late [5, to late the peripheral pulse with the central pulse, the of the wave into and the diastolic wave in These pressure wave for the in peripheral pulse pressure and systolic pressure between and late which is so in studies The pressure pulse waveform in and to the is on the basis of of wave from peripheral to central In this is to short the and pulse wave In the the is and its high pulse wave for of wave normal have and heart [5, of and heart have so that waves are in diastole The generalized transfer function used by and others to generate ascending aortic pressure waves have been established in fully and are to whose wave and in the upper limb as well as in the and most wave first out by Mahomed ageing has effects on the arterial pulse at different The most studies on normal have been by and in the late systolic pressure in both radial and carotid arteries, with of the diastolic pressure are at both but at the late systolic pressure wave is in the radial artery in the have been in the ascending from taken at but late systolic is in the carotid and far in the radial artery. in and amplitude of pressure waves recorded in the radial artery and carotid in normal between the first and of are ensemble averaged into from different with of the is the to late systolic pressure after the systolic shoulder, and can be in or in as pulse pressure by the pressure to the first systolic shoulder, or as by pulse the aortic wave in is measured as or as as of pulse In late amplitude of the ascending aortic systolic pressure wave the with This to life with of in In radial pressure wave is to with a pressure wave of amplitude to the from in late in life is to of wave from the and at the of arterial the where high of is by arterial which pulse wave aortic is as in pulse wave which has also been by our in normal and in normal have of [5, wave more between and [5, This is a normal ageing and is responsible for the in pulse pressure and in systolic pressure which is with The phenomenon is by hypertension and by arterial and is by as well as by arterial as below. to the effects of ageing on the arterial pulse and to be with systolic of the pulse in different This is one expect if had a effect on function the of and to both of wave and of pulse wave have the effect of of the carotid and aortic pulse, but the has been is that persons with of aortic ageing more with and so are more to and in While of function in is between and pulse wave The of upper limb function with in different is with definite in pulse wave or other of arterial in the upper limb [5, of even a can wave from the and so the of the arterial pressure wave, the of late systolic [5, this be to It that of of or of effect be in the the and the of This to in of the arterial pressure wave, the of waves with the wave by with of heart in period to of and and with in heart of This has been by and and for in aortic in heart in heart also of the pulse wave between and peripheral arteries, on of the of at to the of of the transfer function for this in generation of the ascending aortic from the peripheral pressure wave at different heart The effects of heart are most with pulse pressure be more as great in the radial artery as in the ascending and when radial systolic pressure be pressure waves that in the arterial pulse It that in a of be achieved, with heart and and with the greatest a phenomenon have a if were and systolic pressure were and diastolic pressure and for artery, is on in in persons in in between and is to be a risk for wave with increased aortic systolic pressure and with increased and be the While have effects on arterial in pulse between and and after the can be on the basis of in has the most and effect on the arterial pulse. This is from the with in aortic pulse wave and of wave reflection, that the wave in diastole into with of pressure in late This has been as a phenomenon since it is in all with The aortic is by and of the is by from to in the and is with aortic this process in and of the and arteries, where the of This ageing into a process which must be as a and is It in in pulse pressure and systolic pressure, which is described as systolic systolic pressure by wave for a to systolic pressure in central [5, hypertension be a of aortic hypertension can also aortic and by the same pressure wave as with ageing but at an The here is and and is to increased and pulse wave in the more in the arterial pulse, with increased amplitude of the systolic pressure wave in the radial artery, was by Mahomed [7, as the of arterial pressure, and was so used by in clinical studies over the cuff was It that the upper limb generalized transfer function for generation of central from peripheral pressure in the of hypertension, since of the brachial artery and its and transfer function with of arterial pressure [5, are studies in arterial in with artery or with other of and our every we have been to the of on the basis of the arterial pressure wave, and we are that others have been to this in have been to definite difference in aortic pulse wave in with generalized and can this as a for can others have this own for aortic pulse wave were identical in with and high of [5, must the and must to wave are that it has so effect on measured of arterial or on the of the arterial pulse, which is so to in with has been described as arterial of aortic or of pulse wave have been to in the diagnosis of to in of its studies have but definite of aortic in with and with in aortic this in it can only be that the effects of ageing and of hypertension to over the effects on aortic and on pulse wave of as and In clinical one persons with aortic for or for of arterial from one are in In our persons are often and in but with an history of vascular of the we have have had vascular the of of persons is to be and These well the of persons with premature by Mahomed his pulse will and the of medical for life insurance [10]. In to with and pulse wave analysis is as a in heart In diastolic is on of often in with have utilized this to a diagnosis of diastolic in with and to in the of this from systolic (Figure and heart effects of wave on from on brachial and aortic pressure waves and on ascending aortic flow trace) with of systolic pressure in life from left), then with of and heart and from and heart of with from chronic in is the normal pressure is of and in 1). in with increased pressure most of diastole of systolic pressure is and is and pressure is are the systolic of the aortic pressure waves taken from and on an for and (with of systolic as by In systolic is on of wave a effect on flow on pressure This phenomenon for the of a pulse in systolic heart with with central pressure or and with of wave in diastole [5, have used this phenomenon to systolic and diastolic and to the of systolic [5, as well as to systolic from diastolic as the of is through use of through in wave reflection, and and to is to the of wave analysis the effects of which are or fully from cuff of arterial in amplitude of the systolic wave in the radial artery, even with of the in ascending aortic and systolic pressure (Figure a in radial artery after (Figure the antianginal effect of this is at in to in [5, (Figure this to effects of and other to effects from the synthesized aortic pressure pulse, for and to other of vascular and because it is often possible to the systolic on the radial pressure wave after is to measure in of the in the of on of the ascending aortic and brachial pressure waves recorded in the ascending and brachial artery of an at conditions and represents amplitude of the wave by represents the of the artery the effects of as in the late systolic of the radial artery pressure pulse. from the first in of the of as an antianginal of of peripheral systolic pressure in central aortic and systolic pressure after as has been confirmed and a more effect of on the heart measured by The are on the basis of in wave from the The that brachial transfer function is by and that the ascending aortic pressure wave can be determined from the radial that has a effect on wave in the upper limb in the the synthesized aortic pulse to the effects of in hypertension, and with is to wave reflection, and to aortic and aortic and systolic pressure, and to of ventricular/vascular In systolic to of the aortic pulse waveform is as described through wave reflection, and of can be on the and aortic pulse [5, The of is to of and has been as a measure of this have used aortic flow waveforms to describe the effects of wave on the ascending aortic flow and to describe the effects of in wave with wave analysis is in effects of since this in has effects on or on peripheral effects in wave are on the basis of [5, interaction between and is of great clinical importance, and the by the have been made of pulse wave analysis, and on the basis of of blood pressure in when of were used own studies of based on pulse wave analysis, and that the effect of and this for to 8 wave analysis, with to late systolic a for this and of required after at by the and effects of can be from the arterial pressure pulse. to wave as well as and in in central and in aortic and systolic pressure This is the effects of in and diastolic are to in diastolic with with [5, aortic systolic pressure through and this is they and diastolic even in persons This effect can to by if This effect well of and of with we pulse wave analysis in clinical The cuff information only on the between which pressure through the in the upper limb this is and information on and (with generation of the ascending aortic pulse wave analysis more accurate systolic and pressure, and with the to other of ventricular/vascular of a using a tonometer an this in hypertension in diagnosis and can the diagnosis of hypertension by the of late systolic in the aortic pressure wave, and the diagnosis when brachial systolic pressure is but this is present can a diagnosis of systolic hypertension of other and that would be on a well [5, In with systolic hypertension we would be more about a with one In with in the of systolic a of when and to is by of the arterial pulse. In we can peripheral from in mean pressure, wave from in pressure heart and effect of a from in diastolic period as well as in heart (Figure in a with hypertension and with in aortic systolic pressure of is to of and of mean pressure in we can systolic from diastolic from wave and of of systolic can be from and and from the by In with of of short at or with that be to or [5, a for and for of medical to can be from pulse wave for pulse wave analysis are to be in the are by of high in of premature arterial but have been completely to this from risk have in the pulse waves of with or that in of but recognize that are but have been to have Mahomed and his in persons with for heart arterial and have that persons often have that persons have premature arterial degeneration that has been by other The has a between carotid and and are the of carotid and aortic in the The of pulse wave with in but with review with is at It is that first made a and first clinical described the of late systolic of the radial pulse in an normal his pulse will Mahomed was in the process of a clinical record in with the at the time of his premature death at This is the of modern studies and of the College of is that had it pulse waveform analysis would have been and as now be about the arterial pulse as a as is about blood pressure a which was introduced more after Mahomed's use of pulse wave analysis by life insurance lapsed when work in established the of the technique [10]. While is here to the most of pulse waveform analysis of the ascending aortic pressure to be made on the of other pulse The radial pressure pulse all the information from which the ascending aortic pulse is that is determined from the aortic pulse can be from the of and diastole are measured from the radial pulse, and its with ageing and with can be in the same as the it is more to in late on the radial pulse. and systolic pressure cannot be systolic pressure, the from which is calculated [5, of the radial pulse be for and on of brachial systolic and diastolic pressure and of have developed a for analysis of the diastolic of the peripheral pressure waveform This consider pulse pressure the period of and has and theoretic The diastolic of the pulse is the most when recorded systolic pressure beginning of is in the radial artery in the The requires noninvasive of from arterial pressure and a of the arterial and to the to wave from the pressure A has been developed and is use the carotid pulse waveform to against the radial when this use the carotid pulse as a of the ascending its is to the aortic the it cannot be calibrated with the same of confidence as the and is the and persons the are to be with are also about never in the this is at a theoretic Doppler flow are recorded from the carotid and peripheral to with on arterial is from increased flow The Doppler technique is for ascending aortic flow and for the of late systolic in flow that the of and systolic heart flow also be in the diagnosis of or [5, The is widely used for volume in and is to the waveform. have that this the carotid pressure pulse, and a to the aortic pulse. have to the of the and use this as an of vascular ageing and This developed in more in the The of this technique is from is in is to this at present by our so that others will of confidence is in journals is difference between aortic and brachial pressure This be the conditions in persons as after but it to the to persons with with heart or with The technique described here to a of to between central and peripheral systolic the most a difference of mean has to the that were when the most report is of a mean using the of with confidence intervals of of this are to our own and of In the we have that a be applied to aortic systolic pressure from from over in well with of but we are with the which has confidence which pulse waveform, in of to measured aortic systolic pressure, and with (Figure from in different the between aortic systolic pressure and brachial artery systolic pressure, determined by cuff between aortic systolic pressure and measured radial artery systolic pressure for different conditions in at to of between aortic systolic pressure and measured aortic systolic pressure for in is of is The greatest in accurate noninvasive of aortic pressure to the pressure wave or convolutional process but to calibration from the here that the radial waveform, calibrated from recorded arterial pressure, can be used to generate an accurate ascending aortic pressure waveform a of the same cannot be for calibration against the studies have between and cuff blood pressure to ascending aortic pressure noninvasively will be at the of cuff it be that studies have been based on the cuff on so that the the the this were we that the ascending aortic pressure waveform that we generate and of the of the cuff sphygmomanometer, and so improve on the information that it has provided over the a is of and This review is based on Mahomed's it must be to our advantage to appreciate fully all the pulse tells us, and to draw from the pulse all that it is capable of it is William Harvey's to and his on the of on the one or of on the in of a is a of a for pulse wave analysis.

BACKGROUND AND PURPOSE: Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. METHODS: To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials. RESULTS: There was a highly significant reduction of 7 per 1000 (SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin versus 457 [2. 3%] control, 2P<0.000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in death without further stroke (5.0% versus 5. 4%, 2P=0.05). Against these benefits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or hemorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P=0.07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the overall risk of further stroke or death in hospital (8.2% versus 9.1%, 2P=0.001). For the reduction of one third in recurrent ischemic stroke, subgroup-specific analyses found no significant heterogeneity of the proportional benefit of aspirin (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=24.8, 2P<0.000001) was sufficiently large for such subgroup analyses to be statistically informative. The absolute risk among control patients was similar in all 28 subgroups, so the absolute reduction of approximately 7 per 1000 in recurrent ischemic stroke does not differ substantially with respect to age, sex, level of consciousness, atrial fibrillation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximately 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(2)(18)=16.5, NS). Among the 9000 patients (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroke; moreover, even among the 800 (2%) who had inadvertently been randomized after a hemorrhagic stroke, there was no evidence of net hazard (further stroke or death, 63 aspirin versus 67 control). CONCLUSIONS: Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.

AIMS: To assess the effect of mobile phone intervention on glycaemic control in diabetes self-management. METHODS: We searched three electronic databases (PubMed, EMBASE and Cochrane Library) using the following terms: diabetes or diabetes mellitus and mobile phone or cellular phone, or text message. We also manually searched reference lists of relevant papers to identify additional studies. Clinical studies that used mobile phone intervention and reported changes in glycosylated haemoglobin (HbA(1c) ) values in patients with diabetes were reviewed. The study design, intervention methods, sample size and clinical outcomes were extracted from each trial. The results of the HbA(1c) change in the trials were pooled using meta-analysis methods. RESULTS: A total of 22 trials were selected for the review. Meta-analysis among 1657 participants showed that mobile phone interventions for diabetes self-management reduced HbA(1c) values by a mean of 0.5% [6 mmol/mol; 95% confidence interval, 0.3-0.7% (4-8 mmol/mol)] over a median of 6 months follow-up duration. In subgroup analysis, 11 studies among Type 2 diabetes patients reported significantly greater reduction in HbA(1c) than studies among Type 1 diabetes patients [0.8 (9 mmol/mol) vs. 0.3% (3 mmol/mol); P=0.02]. The effect of mobile phone intervention did not significantly differ by other participant characteristics or intervention strategies. CONCLUSIONS: Results pooled from the included trials provided strong evidence that mobile phone intervention led to statistically significant improvement in glycaemic control and self-management in diabetes care, especially for Type 2 diabetes patients.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.

BACKGROUND: It has long been known that depression is associated with hypertension but whether depression is a risk factor for hypertension incidence is still inconclusive. OBJECTIVES: To assess whether depression increases the incidence of hypertension. METHOD: Literatures were searched from PubMed, EMBASE, Cochrane and PsycINFO without language restrictions. Any prospective cohort study was included, which reported the correlation between depression and incidence of hypertension in apparently healthy normotensive individuals. At baseline, the studies which had at least one self-report or interview-based assessment on depressive symptoms/disorders were selected. The definition of hypertension was defined as a repeatedly elevated blood pressure exceeding 140 (systolic) and/or over 90 mmHg (diastolic) determined in interview, use of antihypertensive medications, or self-reported or recorded diagnosed hypertension. Studies with cross-sectional or case-control design were excluded. Data abstraction was conducted independently by two authors. RESULTS: Seventy-five full texts were initially searched, but only nine studies met our inclusion criteria, and they were comprised of 22 367 participants with a mean follow-up period of 9.6 years. We found that depression increased the risk of hypertension incidence [adjusted relative risk 1.42, 95% confidence interval (CI) 1.09 to 1.86, P = 0.009] and the risk was significantly correlated with the length of follow-up (P = 0.0002) and the prevalence of depression at baseline (P < 0.0001). CONCLUSIONS: Our meta-analysis supports that depression is probably an independent risk factor of hypertension. It is important to take depression into consideration during the process of prevention and treatment of hypertension. Further studies are needed to exclude the effects of other confounding factors.