Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Impact of long-term fertilization on phosphorus fractions and manganese oxide with their interactions in paddy soil aggregates.

One under-studied microelement, manganese (Mn), due to its potential to considerably interact, and limit labile, and moderately-labile soil phosphorus (P) pools, was studied in Nanchang (NC), and Qiyang (QY) under paddy conditions. The Hedley's P sequential fractionation procedure was utilized to extract, and quantify various P fractions at both surface (0-20 cm) and subsurface (20-40 cm) layers. Unfertilized control (CK), nitrogen, phosphorus, and potassium (NPK), and NPK amended with animal manure (NPKM) were used as treatments. From both sites, the manure amended fertilizer (NPKM) compared to chemical NPK formed higher proportions of macro-aggregates (>2 and 2-0.25 mm) in both layers. Total P (TP) values of 842.1 (>2 mm), and 744.4 mg kg-1 (2-0.25 mm) from NC, and QY, respectively were accumulated by NPKM compared to NPK, and CK. Total P values of 806.4, and 350.4 mg kg-1 in the >2 mm aggregate size, respectively for NC, and QY were observed in the subsurface layer. Inorganic moderately labile P (NaOH-Pi) was the dominant fraction under all fertilizer treatments. Concentrations of 232.3 (<0.053 mm), and 202.1 mg kg-1 (0.25-0.053 mm) of NaOH-Pi were accumulated by NPKM, respectively for NC, and QY in the surface layer. In the subsurface layer, concentrations of NaOH-Pi (217.5 mg kg-1; <0.053 mm) from NC, and residual-P (57.3 mg kg-1; >2 mm) from QY were accumulated by NPKM. Similarly, NPKM in contrast to NPK contributed higher Mehlich-3 manganese (M3-Mn) oxide in all aggregate sizes from both sites. Generally, macro-aggregates contributed higher TP, fractions of P, and M3-Mn oxide than micro-aggregates. There was a positive relationship between P pools and M3-Mn oxide at both sites. Additions of animal manure were associated with increased P fractions, and Mn oxides in the paddy soil aggregates, which raises environmental concern.

Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE).

BACKGROUND AND PURPOSE: The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. METHODS: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). RESULTS: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). CONCLUSIONS: The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.

Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE): A Case-Control Study.

BACKGROUND: Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke. METHODS: We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS: Compared with an estimated urinary sodium excretion of 2.8-3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65-2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26-1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93-2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50-1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8-3.5 g/day) was associated with the lowest risk of stroke. CONCLUSIONS: The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake-rather than low sodium intake-combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.

Variations in knowledge, awareness and treatment of hypertension and stroke risk by country income level.

OBJECTIVE: Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. METHODS: We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. RESULTS: Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (p-heterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lower-income regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime non-measurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46). CONCLUSIONS: Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.

A Peridynamic Computational Scheme for Thermoelectric Fields.

Thermoelectric materials are materials that involve the coexistence of heat flux and electric current in the absence of magnetic field. In such materials, there is a coupling among electric potential and temperature gradients, causing the thermoelectric effects of Seebeck and Peltier. Those coupling effects make the design and analysis of thermoelectric materials complicated and sophisticated. The main aim of this work is dealing with thermoelectric materials with discontinuities. Since heat and electric fluxes are undefined at the crack tip and the temperature and electric fields across the crack surface are discontinuous, it is better to apply peridynamic (PD) theory to capture such details at the crack tips. Hence, we propose in this paper a PD theory which is suitable in tackling such discontinuities in thermal and electric fields. In this study, the continuum-based electrical potentials and temperature fields are written in the form of nonlocal integrals of the electrical potentials and temperature that are effective whether we have discontinuities or not. To illustrate the consistency of the peridynamic technique, a number of examples were presented and witnessed that PD results were in good agreement with those results from the literature, finite element solutions and analytical solutions.

Intensive glucose-lowering and the risk of vascular events and premature death in patients with decreased kidney function: The ADVANCE trial.

To assess the effects of intensive glucose control on the risk of major clinical outcomes according to estimated glomerular filtration rate (eGFR) levels in people with type 2 diabetes. Of 11 140 ADVANCE trial participants, 11 096 with baseline eGFR measurements were included, and classified into three eGFR groups: ≥90 mL/min/1.73 m2 ; 60 to 89 mL/min/1.73 m2 ; and < 60 mL/min/1.73 m2 . Relative risk reduction of randomized intensive glucose control with regard to the composite outcome of major macro- and microvascular events, all-cause death and cardiovascular death did not significantly vary by eGFR level (P for heterogeneity ≥0.49). The risk of severe hypoglycaemia increased with intensive glucose control; however, this risk did not vary across eGFR groups (P for heterogeneity = 0.83). The risk-benefit profile of intensive glucose control in patients with type 2 diabetes and impaired kidney function appears similar to that observed in those with preserved kidney function.

Preliminary clinical analysis of direct renin inhibitor aliskiren in the treatment of severe coronavirus disease 2019 patients with hypertension / 中华内科杂志

Objective:To explore the feasibility of direct renin inhibitor aliskiren for the treatment of severe or critical coronavirus disease 2019 (COVID-19) patients with hypertension.Methods:The antihypertensive effects and safety of aliskiren was retrospectively analyzed in three severe and one critical COVID-19 patients with hypertension.Results:Four patients, two males and two females, with an average age of 78 years (66-87 years), were referred to hospital mainly because of respiratory symptoms. Three were diagnosed by positive novel coronavirus 2019 (2019-nCoV) nucleic acid or antibody, and the critical patient with cardiac insufficiency was clinically determined. Two patients were treated with calcium channel antagonist (CCB), one with angiotensin converting enzyme inhibitor (ACEI), and one with angiotensin Ⅱ receptor antagonist (ARB). After admission, ACEI and ARB were discontinued, one patient with heart failure was treated by aliskiren combined with diuretic.Three patients were treated with aliskiren combined with CCB among whom two withdrew CCB due to low blood pressure after 1 to 2 weeks. Based on comprehensive treatment including antiviral and oxygenation treatment, blood pressure was satisfactorily controlled by aliskiren after three to four weeks without serious adverse events. All patients were finally discharged.Conclusion:Our preliminary clinical data shows that antihypertensive effect of aliskiren is satisfactory and safe for severe COVID-19 patients complicated with hypertension.

StudyoncognitiveimpairmentandriskfactorsinpatientswithWilsondisease / 中国神经精神疾病杂志

Objective To explore cognitive impairment and related factors in patients with Wilson disease (WD) and to screen the risk factors of cognitive impairment in order to provide evidence for clinical intervention. Methods The Chinese Version Addenbrooke＇s Cognitive Examination-III (ACE-III-C) was used to assess the cognitive function. The WD patients with cognitive impairment were analyzed the difference between those with non-cognitive disorders in the Young scale, Baethel scale and biochemical indicators. Risk factors for cognitive impairment in WD patients were analyzed by multiple linear regression. Results Cognitive impairment occurred in 43 (59.7%) of 72 patients with WD. ACE-III-C total score, attention, memory, language fluency, visual spatial factor scores, Young scores, Barthel scores and serum copper levels were significantly different between patients with cognitive impairment and patients with non-cognitive impairment (P＜0.01). Linear regression analysis showed that serum copper levels were the most important risk factors for ACE-III-C total score and cognitive subfields (P＜0.01). Serum zinc levels as a secondary risk factor of language fluency and visual space (P＜0.05). Age-related participation affected language fluency (P＜0.05). Conclusions Serum copper and zinc levels may be the main risk factors of cognitive impairment. Modulation of serum copper and zinc levels may be the key for intervention to treat cognitive impairment in WD patients.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study.

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12342 (92%) of 13447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However, across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14­1·44; all p< 0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12­1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes.

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.

Rivaroxaban with or without aspirin in patients with stable coronary artery disease: an international, randomised, double-blind, placebo-controlled trial

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants...

The Early Prognostic Value of Serum Sodium Level in Patients With Acute ST-elevation Myocardial Infarction / 中国循环杂志

Objective: To explore the relationship between serum sodium level and early prognosis in patients with acute ST-elevation myocardial infarction (STEMI). Methods: A total of 7461 STEMI patients within 12h of onset who matched the diagnostic standard of European society of cardiology and American college of cardiology were retrospectively studied. According to serum sodium levels within 24h of admission, the patients were categorized into 3 groups: Serum sodium≥135 mmol/L group, Serum sodium 130-134 mmol/L group and Serum sodium<130 mmol/L group. The baseline condition, 30-day mortality with other adverse events and the effect of neuroendocriology inhibitor treatment were compared among 3 groups; their relationships to serum sodium level were analyzed. Results: Serum sodium<130 mmol/L group had the higher 7-day and 30-day mortality than the other 2 groups, both P<0.001; compared with Serum sodium≥135 mmol/L group, Serum sodium<130 mmol/L group presented the higher occurrence rates of 30-day cardiac shock, heart failure (HF) and life-threatening arrhythmia, P<0.001. With adjusted affecting factors of age, diuretic and reperfusion treatments, serum sodium<130 mmol/L was still related to 7-day and 30-day mortality (OR=1.69 and OR=1.57). Both single and multivariable analysis indicated that serum sodium<130 mmol/L was related to cardiac shock (OR=1.75 and OR=1.64), HF (OR=1.42 and OR=1.30) and life-threatening arrhythmia (OR=1.53 and OR=1.34). In all 3 groups, the patients using ACE inhibitor, β-blocker or both medications had reduced 30-day mortality than those without such medication, allP<0.001; the reduction was more obvious in Serum sodium<130 mmol/L group than the other 2 groups,P<0.001. Conclusion: Serum sodium level<130 mmol/L within 24h of admission was the risk factor for the early stage main adverse events as mortality, cardiac shock, HF and life-threatening arrhythmia in acute STEMI patients.

Microvascular and Macrovascular Disease and Risk for Major Peripheral Arterial Disease in Patients With Type 2 Diabetes.

OBJECTIVE: Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis in type 2 diabetes, but the relationship between other vascular diseases and PAD has been poorly investigated. We examined the impact of previous microvascular and macrovascular disease on the risk of major PAD in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed 10,624 patients with type 2 diabetes free from baseline major PAD in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) clinical trial. The primary composite outcome was major PAD defined as PAD-induced death, peripheral revascularization, lower-limb amputation, or chronic ulceration. The secondary end points were the PAD components considered separately. RESULTS: Major PAD occurred in 620 (5.8%) participants during 5 years of follow-up. Baseline microvascular and macrovascular disease were both associated with subsequent risk of major PAD after adjustment for age, sex, region of origin, and randomized treatments. However, only microvascular disease remained significantly associated with PAD after further adjustment for established risk factors. The highest risk was observed in participants with a history of macroalbuminuria (hazard ratio 1.91 [95% CI 1.38-2.64], P < 0.0001) and retinal photocoagulation therapy (1.60 [1.11-2.32], P = 0.01). Baseline microvascular disease was also associated with a higher risk of chronic lower-limb ulceration (2.07 [1.56-2.75], P < 0.0001) and amputation (1.59 [1.15-2.22], P = 0.006), whereas baseline macrovascular disease was associated with a higher rate of angioplasty procedures (1.75 [1.13-2.73], P = 0.01). CONCLUSIONS: Microvascular disease, particularly macroalbuminuria and retinal photocoagulation therapy, strongly predicts major PAD in patients with type 2 diabetes, but macrovascular disease does not.

Risks associated with permanent discontinuation of blood pressure-lowering medications in patients with type 2 diabetes.

OBJECTIVE: The associations of discontinuation of the study medication on major outcomes were assessed in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Trial. METHODS: ADVANCE was a factorial randomized controlled trial of blood pressure lowering (a fixed combination of perindopril and indapamide vs. placebo) and intensive glucose control (vs. standard glucose control) in patients with type 2 diabetes. Patients who permanently discontinued the randomized blood pressure-lowering medication during the study period (n = 1557) were compared with others (n = 9583). Cox's proportional hazards models were used to estimate the effects of the discontinuation on the risks of macrovascular events, microvascular events together and separately and all-cause mortality, using discontinuation as a time-dependent covariate. RESULTS: In multivariable analyses, discontinuation was associated with increased risks of combined macro and microvascular events (hazard ratio 2.24, 95% CI 1.96-2.57), macrovascular events (3.23, 2.75-3.79), microvascular events (1.38, 1.11-1.71), and all-cause mortality (7.99, 6.92-9.21) compared to continuing administration of randomized medications during the trial period, which were highest in the first year after discontinuation. These associations were similar in active and placebo groups, except in the first year after discontinuation during which event rates were lower in the active group than in the placebo group (P ≤ 0.01). CONCLUSION: Discontinuation of study medication is a potent risk marker for identifying high-risk patients. Thus it is important that clinicians seek to identify such patients early after discontinuation of treatment. Although some short-term residual effects of previous active treatment can be expected, patients who discontinue require further urgent investigation and management.

Outline of the report on cardiovascular diseases in China, 2014.

The risk factors for cardiovascular diseases (CVDs) are more prevalent in the Chinese population, and therefore, increase the incidence of CVD. In general, CVD morbidity and mortality will remain an upward trend in the next 10 years. Cardiovascular disease is the leading cause of death in China, which accounts for >40% of deaths from any cause. The burden of CVD is substantial and has become an important public health issue. Measures for the prevention and treatment of CVD in China should be further enforced without delay. Since 2005, the National Center for Cardiovascular Diseases has organized experts of cardiology, neurology, nephrology, diabetes, epidemiology, community health, health economics, biostatistics, and other related fields to compile the annual Report on Cardiovascular Diseases in China. The report aims to provide a timely review of the trend of the epidemic of CVD and to assess the progress of prevention and control of CVD. We present an abstract from the Report on Cardiovascular Diseases in China (2014), including trends in CVD, morbidity and mortality of major CVD, up-to-date assessment of risk factors, as well as health resources for CVD, and a profile of medical expenditure, with the aim of providing evidence for decision making in CVD prevention and control programmes in China, and of delivering the most authoritative information on CVD prevention and control for all citizens.