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Digital, The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP., La Comisión Lancet de Hipertensión determinó que una medida clave para responder a la carga mundial que representa la hipertensión arterial era mejorar la calidad de las mediciones de la presión arterial, mediante la utilización de dispositivos cuya exactitud haya sido validada. En la actualidad existen 3000 dispositivos comercializados, pero muchos no tienen datos publicados sobre pruebas de exactitud conformes a las normas científicas establecidas. La falta de regulación o su ineficiencia, que permiten la autorización de dispositivos para uso comercial sin una validación oficial, posibilitan este problema. Además, han surgido tecnologías nuevas de medición de la presión arterial (por ejemplo, los sensores sin brazalete) sobre las cuales no existe unanimidad en la comunidad científica con respecto a las normas de exactitud de la medición. En conjunto, estos aspectos contribuyen a la disponibilidad generalizada de tensiómetros de consultorio o domiciliarios que ofrecen una exactitud limitada o incierta, que llevan a diagnósticos, manejo y farmacoterapia inapropiados de la hipertensión a escala mundial. Los problemas más importantes relacionados con la exactitud de los dispositivos de medición de la presión arterial se pueden resolver mediante el requisito regulatorio de una validación independiente obligatoria de los dispositivos, en consonancia con la norma ISO universalmente aceptada. Esta es una recomendación básica y constituye una necesidad internacional acuciante. Otras recomendaciones clave son la elaboración de normas de validación específicas para las tecnologías nuevas de medición de la presión arterial y la publicación en línea de listas de los dispositivos nuevos exactos que están a la disposición de los usuarios y los profesionales de salud. Las recomendaciones están en consonancia con las políticas de la Organización Mundial de la Salud sobre los dispositivos médicos y la atención universal de la salud. El cumplimiento de las recomendaciones aumentará la disponibilidad mundial de dispositivos de medición de la presión arterial que sean exactos y tendrá como efecto un mejor diagnóstico y tratamiento, reduciendo así la carga mundial de la hipertensión., A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença., Traducción oficial al español del artículo original en inglés efectuada por la Organización Panamericana de la Salud. En caso de discrepancia, prevalecerá la versión original en inglés. Wolters Kluwer Health, Inc. y sus sociedades no se hacen responsables de la exactitud de la traducción del original inglés ni de los eventuales errores que esta pueda contener. Cita del artículo original: Sharman JE, O'Brien E, Alpert B, Schutte AE, Delles C, Hecht Olsen M et al. Lancet commission on hypertension group position statement on the global improvement of accuracy standards for devices that measure blood pressure. J Hypertens. 2020:38:21-29.doi: https://doi. org/10.1097/HJH.0000000000002246, Ciencias Médicas y de la Salud

Elevated blood pressure remains the single biggest risk factor contributing to the global burden of disease and mortality. May Measurement Month is an annual global screening campaign aiming to improve awareness of blood pressure at the individual and population level. Adults ({greater than or equal to}18 years) recruited through opportunistic sampling were screened at sites in 92 countries during May 2019. Ideally three blood pressure readings were measured for each participant, and data on lifestyle factors and co-morbidities were collected. Hypertension was defined as a systolic BP {greater than or equal to} 140 mmHg, and/or a diastolic BP {greater than or equal to} 90 mmHg (mean of the second and third readings) or taking antihypertensive medication. When necessary, multiple imputation was used to estimate participants' mean blood pressure. Mixed-effects models were used to evaluate associations between blood pressure and participant characteristics. Of 1,508,130 screenees 482,273 (32.0%) had never had a blood pressure measurement before and 513,337 (34.0%) had hypertension, of whom 58.7% were aware and 54.7% were on antihypertensive medication. Of those on medication, 57.8% were controlled to

Background The World Health Organization recommends consumption of a minimum of 400 g of fruits and vegetables per day for prevention of cardiovascular disease. Low fruit and vegetable intake is associated with an increased risk of stroke by 11% and ischemic heart disease by 31%. The present study aims to explore factors affecting the fruit and vegetable intake in Nepal and its association with history of self-reported major cardiovascular events (myocardial infarction and stroke). Method Data for this cross-sectional study were collected as part of the study “Community Based Management of Hypertension in Nepal” initiated in the Lekhnath Municipality in 2013. Demographic and nutrition information were collected using the WHO STEPwise approach to a surveillance tool. Descriptive statistics identified the frequency and percentage of fruit and vegetable intake. A Chi-square test examined the association between fruit and vegetable intake and history of self-reported cardiovascular events, socio-demographic and cardiovascular risk factors. Binary logistic regression analysis identified odds ratio with 95% confidence intervals between fruit and vegetable intake and history of self-reported cardiovascular events. Results The mean and median intake of fruits and vegetables were 3.3 ± 0.79 and 3 servings respectively. Of the 2815 respondents, 2% (59) reported having a history of major cardiovascular events. The adjusted odds of having a history of major cardiovascular events was 2.22 (95%CI, 1.06–4.66) for those who consumed Conclusion The respondents who consumed

Objective: The aim of this study was to evaluate the impact of age on the associations between hemodynamic components derived from 24-h ambulatory blood pressure (24-h ABPM) and target organ damage, in apparently healthy, nonmedicated individuals. Methods: Twenty-four-hour ABPM and target organ damage (left ventricular mass index, pulse wave velocity, urine albumin : Creatinine ratio and carotid atherosclerotic plaques) were evaluated in 1408 individuals. Associations were examined in regression models, stratified for age [middle-aged (41 or 51 years) or elderly (61 or 71 years)], and adjusted for sex, smoking status, and total-cholesterol. Results: In middle-aged individuals, an increase of 10mmHg in 24-h SBP was independently associated with an increase of 3.8 (2.7-4.8) g/m2 in LVMI. The effect was nearly doubled in the elderly subgroup, where the same increase resulted in an increase in LVMI of 6.3 (5.0-7.6) g/ m2 (P for interaction 0.26). Conclusion: Age enhances the associations between hemodynamic components obtained from 24-h ABPM and measures of arterial stiffness, microvascular damage, and cardiac structure, but not atherosclerosis.

Background Hypertension, type 2 diabetes mellitus and cardiovascular disease are among the leading causes of mortality globally. Exercise is one of the commonly recommended interventions/preventions for hypertension, type 2 diabetes mellitus and cardiovascular disease. However, the previous reviews have shown conflicting evidence on the effects of exercise. Our objective is to assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. Methods This protocol for a systematic review was undertaken using the recommendations of The Cochrane Collaboration, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the eight-step assessment procedure suggested by Jakobsen et al. We plan to include all relevant randomised clinical trials and cluster-randomised trials assessing the effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP) and BIOSIS. We will systematically assess the risks of random errors using Trial Sequential Analysis as well as risks of bias of all included trials. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Discussion The present systematic review will have the potential to aid patients, clinicians and decision-makers recommending exercise and thereby, benefit patients with hypertension, type 2 diabetes mellitus and/or cardiovascular disease. Systematic review registration PROSPERO CRD42019142313

Background The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines include lower thresholds to define hypertension than previous guidelines. Little is known about the impact of these guideline changes in patients with or at high risk for cardiovascular disease. Methods In this exploratory analysis using baseline blood pressure assessments in Systolic Blood Pressure Intervention Trial (SPRINT), we evaluated the prevalence and associated cardiovascular prognosis of patients newly reclassified with hypertension based on the 2017 ACC/AHA (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg) compared with the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC 7) guidelines (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg). The primary endpoint was the composite of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or cardiovascular death. Results In 4683 patients assigned to the standard treatment arm of SPRINT, 2328 (49.7%) met hypertension thresholds by JNC 7 guidelines, and another 1424 (30.4%) were newly reclassified as having hypertension based on the 2017 ACC/AHA guidelines. Over 3.3-year median follow-up, 319 patients experienced the primary endpoint (87 of whom were newly reclassified with hypertension based on the revised guidelines). Patients with hypertension based on prior guidelines compared with those newly identified with hypertension based on the new guidelines had similar risk of the primary endpoint (2.3 [95% confidence interval {CI}, 2.0-2.7] vs 2.0 [95% CI, 1.6-2.4] events per 100 patient-years; adjusted HR, 1.10 [95% CI, 0.84-1.44]; P = .48). Conclusions The 2017 ACC/AHA high blood pressure guidelines are expected to significantly increase the prevalence of patients with hypertension (perhaps to a greater extent in higher-risk patient cohorts compared with the general population) and identify greater numbers of patients who will ultimately experience adverse cardiovascular events.

Background Coronary artery calcium is important in cardiovascular risk stratification, but this knowledge is based on studies with a significant selection bias. This study aims to evaluate the external validity of a screening programme including coronary artery calcium examination, and the association between coronary artery calcium and cardiovascular events. Design Multi-centre population based study. Methods Randomly selected middle-aged men and women ( N = 1751) free of cardiovascular disease were invited to the examination during 2009–2010. Participation rate in the examination was 70%. Participants ( n = 1227) and non-participants ( n = 524) were compared regarding: cardiovascular medical treatment, Charlson comorbidity index and socioeconomic status (evaluated by cohabitation, gross income and education). Study endpoints were cardiovascular events and mortality. Results Non-participants had a significant higher comorbidity ( p = 0.003) and a lower socioeconomic status ( p Conclusions Non-participants had a higher comorbidity index and a lower socioeconomic status, but the cardiovascular event and mortality rates were equal to those of participants. Thus, a screening programme including a coronary artery calcium examination had a high external validity regarding cardiovascular risk, but also a significant social imbalance.

BACKGROUND AND AIMS: Soluble urokinase plasminogen activator receptor (suPAR) is an inflammatory marker associated with cardiovascular disease. Statins lower both low-density lipoprotein (LDL)-cholesterol and C-reactive protein (CRP), resulting in improved outcomes. However, whether lipid-lowering therapy also lowers suPAR levels is unknown.METHODS: We investigated whether treatment with Simvastatin 40 mg and Ezetimibe 10 mg lowered plasma suPAR levels in 1838 patients with mild-moderate, asymptomatic aortic stenosis, included in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, using a pattern mixture model. A 1-year Cox analysis, adjusted for established cardiovascular risk factors, allocation to study treatment, peak aortic valve velocity and baseline suPAR, was performed to evaluate relationships between change in suPAR with all-cause mortality and the composite endpoint of major cardiovascular events (MCE) composed of ischemic cardiovascular events (ICE) and aortic valve related events (AVE).RESULTS: After 4.3 years of follow-up, suPAR levels had increased by 9.2% (95% confidence interval [CI]: 7.0%-11.5%) in the placebo group, but only by 4.1% (1.9%-6.2%) in the group with lipid-lowering treatment (pCONCLUSIONS: Simvastatin and Ezetimibe treatment impeded the progression of the time-related increase in plasma suPAR levels. Year-1 suPAR was associated with all-cause mortality, MCE, and AVE irrespective of baseline levels (SEAS study: NCT00092677).

Objective To examine the predictive capability of a 1-h vs 2-h postload glucose value for cardiovascular morbidity and mortality. Design Prospective, population-based cohort study (Malmö Preventive Project) with subject inclusion 1974–1992. Methods 4934 men without known diabetes and cardiovascular disease, who had blood glucose (BG) measured at 0, 20, 40, 60, 90 and 120 min during an OGTT (30 g glucose per m2 body surface area), were followed for 27 years. Data on cardiovascular events and death were obtained through national and local registries. Predictive capabilities of fasting BG (FBG) and glucose values obtained during OGTT alone and added to a clinical prediction model comprising traditional cardiovascular risk factors were assessed using Harrell’s concordance index (C-index) and integrated discrimination improvement (IDI). Results Median age was 48 (25th–75th percentile: 48–49) years and mean FBG 4.6 ± 0.6 mmol/L. FBG and 2-h postload BG did not independently predict cardiovascular events or death. Conversely, 1-h postload BG predicted cardiovascular morbidity and mortality and remained an independent predictor of cardiovascular death (HR: 1.09, 95% CI: 1.01–1.17, P = 0.02) and all-cause mortality (HR: 1.10, 95% CI: 1.05–1.16, P P = 0.02) and all-cause mortality (likelihood-ratio test, P = 0.0001; significant IDI, P = 0.0003). Conclusion Among men without known diabetes, addition of 1-h BG, but not FBG or 2-h BG, to clinical risk factors provided incremental prognostic yield for prediction of cardiovascular death and all-cause mortality.

OBJECTIVE: Reference values of fluorine-18-fluorodeoxyglucose (F-FDG) and fluorine-18-sodium fluoride (F-NaF) uptake in human arteries are unknown. The aim of this study was to determine age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake.PARTICIPANTS AND METHODS: Uptake of F-FDG and F-NaF was determined in the ascending aorta, aortic arch, and descending thoracic aorta. In addition, F-FDG uptake was determined in the carotid arteries and F-NaF uptake was determined in the coronary arteries. Arterial F-FDG and F-NaF uptake were quantified as the blood pool subtracted maximum activity concentration in kBq/ml (BSF-FDGmax and BSF-NaFmax, respectively). In addition to determining reference values, we evaluated the influence of age and sex on BSF-FDGmax and BSF-NaFmax.RESULTS: Arterial F-FDG and F-NaF uptake was assessed in 89 healthy adults aged 21-75 years (mean age: 44±14 years, 53% men). Both BSF-FDGmax and BSF-NaFmax increased with age. BSF-FDGmax increased with age in the descending aorta (β=0.28; P=0.003), whereas BSF-NaFmax increased with age in the ascending aorta (β=0.18; PCONCLUSION: Prospective evaluation of 89 healthy adults generated age-specific and sex-specific reference values of arterial F-FDG and F-NaF uptake. Our findings indicate that arterial F-FDG and F-NaF uptake tend to increase with age.

Markers of target-organ damage and 24-hour ambulatory blood pressure (BP) measurement improve cardiovascular risk stratification. The prevalence of target-organ damage and raised BP increases with aging. The study aim was to evaluate the impact of age and target-organ damage on the prognostic value of ambulatory BP. Markers of target-organ damage and ambulatory BP were measured in 1408 healthy people aged 41 or 51 (middle-aged group), and 61 or 71 (older group) years. The primary outcome was cardiovascular events after 16 years of follow-up, with data obtained from national registries. The prognostic value of BP was evaluated with Cox regression models, adjusted for traditional risk factors and target-organ damage, including left ventricular mass, pulse wave velocity, carotid plaques, and urine albumin/creatinine ratio. A total of 323 events were observed. In comparison with traditional risk factors, adding systolic BP and presence of target-organ damage improved risk stratification by increasing concordance index from 0.711 to 0.728 ( P =0.01). In middle-aged subjects with target-organ damage, increment in pulse pressure (hazard ratio, 1.70; 95% confidence interval, 1.31–2.21; P P =0.02) were associated with a greater risk of cardiovascular disease compared with subjects without target-organ damage: hazard ratio, 1.04 (95% confidence interval, 0.74–1.46; P =0.81); P for interaction, 0.02; and hazard ratio, 0.89 (95% confidence interval, 0.69–1.14; P =0.36); P for interaction, 0.01. Target-organ damage may be a marker of individual susceptibility to the harmful effects of pulse pressure and BP variability on the cardiovascular system in middle-aged individuals.

Background The Systolic Blood Pressure Intervention Trial (SPRINT) found that intensive blood pressure (BP) lowering reduced the rates of cardiovascular events and mortality but increased the risk of certain adverse events, in patients with and without chronic kidney disease at baseline. However, it is unclear whether intensive BP management is well-tolerated and modifies risk uniformly across the entire spectrum of renal function. Purpose To assess the relationship between renal function, treatment response to intensive BP lowering, and cardiovascular (CV) outcomes. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high CV risk but without diabetes who had a systolic BP (SBP) 130–180 mmHg, were randomized to intensive (target SBP Results Baseline eGFR was available for 9,324 (>99%) individuals. Mean eGFR was similar between the two groups (intensive group 71.8 ml/min/1.73m2 vs. standard group 71.7 ml/min/1.73m2; P=0.92). Median follow-up was 3.3 years (range 0–4.8), with 561 primary efficacy events (6%) and 3,522 SAE (38%) recorded during the study period. Baseline eGFR was non-linearly associated with the risk of the primary efficacy endpoint, death from CV causes, death from any cause, acute decompensated heart failure, SAE, electrolyte abnormality, and acute kidney injury (test for non-linearity, P Figure 1 Conclusions In SPRINT, lower eGFR was associated with a greater risk of both CV events and SAE. Patients with higher eGFR appeared to derive more benefit from intensive BP lowering while the relationship with safety events was complex.

Background Incident atrial fibrillation (AF) marks an adverse shift in the prognosis of patients with aortic stenosis (AS). Identifying risk factors for AF is therefore of paramount importance for timely intervention in patients with AS. In patients without AS, brain natriuretic peptides (BNP) is a well-established biomarker for left ventricular pressure overload on the pathway to heart failure and atrial fibrillation. However, a potential role of NT-proBNP to predict risk of new-onset AF in asymptomatic patients with mild to moderate AS is not well studied. Methods We included 1,434 patients with mild to moderate AS from the SEAS Study (Simvastatin and Ezetimibe in Aortic Stenosis) without AF or clinically overt heart failure at baseline. The primary endpoint for this substudy was time to incident AF, as determined by the first annual in-study 12-lead ECG with AF. Multivariable Cox model were adjusted for other important predictors of incident AF as selected by Bayesian statistics. Fine and Gray competing risk regression was used to evaluate the influence of all-cause mortality on selected predictor variables of incident AF. Results During a median follow-up of 4.3 years (range 0.1–6.9 years), incident AF occurred in 114 (6.1%) patients (13.8 per 1,000 person-years of follow-up), who at baseline were older (69±10 vs. 67±10 years, p0.05). Figure 1 Conclusions In patients with asymptomatic aortic stenosis and sinus rhythm at baseline, NT-proBNP levels were significantly higher in patients who subsequently developed AF. NT-proBNP significantly improved prognostic information of incident AF over other important predictor variables. This supports the notion that incident AF is a marker of left ventricular pressure overload and possibly a novel marker of timely intervention with aortic valve replacement.

Background The 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines for arterial hypertension propose different intensities of blood pressure (BP) lowering in patients Purpose To assess the relationship between age, treatment response to intensive BP lowering, and cardiovascular (CV) outcomes. Methods SPRINT was a randomized, controlled trial in which 9,361 individuals ≥50 years of age, at high CV risk but without diabetes who had a systolic BP (SBP) 130–180 mmHg, were randomized to intensive (target SBP Results Age was noted for all individuals, and 3,805 (41%), 4,390 (47%), and 1,166 (12%) were 0.05). The Figure shows similar treatment effects (hazard ratios) across the spectrum of age. P-values are for the interaction between age and treatment effect for each endpoint. Figure 1 Conclusions In SPRINT, higher age was associated with a greater risk of both CV events and SAE. However, intensive BP lowering appeared to be associated with similar risks and benefits across the age spectrum.

Background Although Azurocidin-1 (Azu-1), also known as heparin binding protein, has been associated with myocardial infarction, possible associations of Azu-1 with congestive heart failure (CHF) remains unknown. Here we tested the possible association of Azu-1 with prevalent diastolic dysfunction and/or incident CHF in a large Swedish prospective population based cohort. Methods Azu-1 was analyzed using the Proseek Multiplex CVD III panel in 1737 participants from a subsample of the population (mean age 67 years, 29% women) who underwent a complete echocardiographic examination. All biomarkers were logarithmized and standardized prior to statistical analysis. Logistic and linear regression were adjusted for age, sex, BMI, diabetes, systolic and diastolic blood, anti-hypertensive treatment and subjects with an ejection fraction below 50% were excluded for the analysis of prevalent diastolic dysfunction and Azu-1. For the linear regression model, we used E/é ratio as a key functional variable in assessing diastolic function according to ESC 2016 Guidelines for Acute and Chronic Heart Failure. Furthermore, we dichotomized the E/é ratio at >13 in another logistic regression model. Finally, in line with ESC Guidelines 2016, we combined the key functional (E/é >13) and key structural (left ventricular mass index (LVMI) ≥115 g/m2 for males and ≥95 g/m2 for females) alterations for diastolic dysfunction and used this variable in both logistic regression for association with Azu-1 and for Cox regression analysis of incident CHF. 1439 subjects (938 cases with some degree of diastolic dysfunction and 501 controls) remained for the analysis. For the analysis of incident CHF, Cox regression was used excluding subjects with ejection fraction below 50% and prevalent CHF and further adjusted for prevalent coronary disease on top of age, sex, BMI, diabetes, systolic and diastolic blood and anti-hypertensive treatment. 1,511 subjects (64 incident cases of CHF vs 1447 controls; median follow up time 8.9 years) remained. Results After adjustment for above mentioned risk factors, each 1 standard deviation (SD) of increase in Azu-1 was associated with any degree of prevalent diastolic dysfunction (odds ratio (OR) 1.13, p=0.048), E/é >13 OR 1.21, p=0.028 and for combined LVMI and E/é OR 1.17, p=0.015. In fully adjusted linear regression Azu-1 was associated with E/é with a β-coefficient of 0.056, p=0.018. In a fully adjusted Cox regression models Azu-1 was associated with incident CHF (hazard ratio (HR) 1.32, p=0.025). As expected and as proof of concept E/é >13 and combined LVMI with E/é were also associated with incident CHF; HR 2.84, p Conclusion An inflammatory mediator, Azurocidin-1, is associated with prevalent diastolic dysfunction, E/é, E/é combined with LVMI as well as incident congestive heart failure in a population-based cohort.

BACKGROUND: The greatest risk factor for cardiovascular disease is hypertension, which can be alleviated via diet, exercise, and adherence to medication. Yet, blood pressure control in Nepal is inadequate, which is partly hindered by a lack of evidence-based, low-cost, scalable, and cost-effective cardiovascular disease prevention programmes. The the community-based management of hypertension in Nepal (COBIN) study was a 12-month community-based hypertension management programme of blood pressure monitoring and lifestyle counselling intervention undertaken by female community health volunteers (FCHVs) in Nepal, against usual care, which showed success in reducing blood pressure. Here we aimed to retrospectively quantify the budget impact and cost-effectiveness of the scale-up of the programme.METHODS: In this retrospective analysis, we collected participant-level data from the COBIN study; programme delivery cost data from programme administrators from the COBIN study group; and popualtion and other data from WHO, the World Bank, and the Nepalese Government. We estimated costs per participant and total costs of a national scale-up of the COBIN programme focusing on two scenarios: scenario A, delivery of the intervention to only people aged 25-65 years with hypertension; and scenario B, delivery of the intervention to all adults aged 25-65 years regardless of hypertension status. Effectiveness was based on in-trial blood pressure reductions converted to cardiovascular disease disability-adjusted life-years (DALYs) averted. The primary cost-effectiveness measure was incremental cost per averted cardiovascular disease DALY (calculated using the incremental cost-effectiveness ratio [ICER]) from a health system perspective, including programme delivery and incremental medication costs. We did univariate sensitivity analyses of scenario B to assess the effect of uncertainty in key parameter values in our calculations.FINDINGS: From a health system perspective, the first-year budget impact was US$7·1 million in scenario A and $10·8 million in scenario B. With each subsequent year, the costs decreased by approximately 50%. In the base-case cost-effectiveness analysis, from the health system perspective, scenario A resulted in an ICER of $582 per DALY averted and scenario B resulted in an ICER of $411 per DALY averted. The ICER was most sensitive to uncertainty in the number of total avertable cardiovascular disease DALYs in the eligible population.INTERPRETATION: The programme is projected to be highly cost-effective in both scenarios compared with the WHO thresholds for cost-effectiveness for Nepal. For policy makers intending to meet the UN Sustainable Development Goal of reducing premature mortality from non-communicible diseases, this intervention should be considered.FUNDING: Duke-NUS Medical School, Singapore.

Aims The 2018 ESC/ESH guidelines for hypertension recommend differential management of patients who are Methods and results SPRINT randomized 9361 high-risk adults without diabetes and age ≥50 years with systolic blood pressure 130–180 mmHg to either intensive or standard antihypertensive treatment. The primary efficacy endpoint was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety endpoint was composite serious adverse events. We assessed whether age modified the efficacy and safety of intensive vs. standard blood pressure lowering using Cox proportional-hazards regression and restricted cubic splines. In all, 3805 (41%), 4390 (47%), and 1166 (12%) were 0.05). Conclusion In SPRINT, the benefits and risks of intensive blood pressure lowering did not differ according to the age categories proposed by the ESC/ESH guidelines for hypertension. Trial Registration SPRINT (Systolic Blood Pressure Intervention Trial); ClinicalTrials.gov Identifier: NCT01206062, https://clinicaltrials.gov/ct2/show/NCT01206062.

Digital, Ciencias Médicas y de la Salud

Aims: In patients with essential hypertension, abnormal renal sodium handling includes exaggerated natriuresis in response to extracellular volume expansion. We tested the hypothesis that exaggerated natriuresis is associated with increases in medullary and/or cortical renal blood flow. Methods: Patients with mild essential hypertension, but no signs of end organ damage, and control subjects were studied after 4 days of dietary standardization (+ day −1 ) preceded in patients by a 14-day drug washout period. On the study day, subjects received a 4-hour intravenous volume expansion with saline (2.1% of body mass). Renal medullary and cortical blood flows were measured by PET scanning using H 2 15 O as tracer; anatomical regions of interest were defined by contrast-enhanced CT scanning. Results: In patients, arterial blood pressure increased during volume expansion (107 ± 2-114 ± 3 mm Hg, P −1 vs +61 ± 14 µmol min −1 , respectively, P −1 min −1 ) or in controls (3.2 ± 0.3-3.1 ± 0.2 mL (g tissue) −1 min −1 ). In control subjects, renal cortical blood flow fell during volume expansion (4.1 ± 0.3-3.7 ± 0.2 mL (g tissue) −1 min −1 , P

Background: The efficacy and tolerability of intensive blood-pressure lowering may vary by pulse pressure (systolic minus diastolic blood pressure). Methods: SPRINT randomized 9361 high-risk adults without diabetes and who were ≥50 years with systolic blood pressure 130-180 mm Hg to intensive or standard antihypertensive treatment. The primary efficacy end point was the composite of acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. The primary safety end point was composite serious adverse events. We examined the prognostic implications of baseline pulse pressure and the effects of intensive blood-pressure lowering on clinical outcomes across the spectrum of pulse-pressure values using restricted cubic splines. Results: Mean baseline pulse pressure was similar between the 2 study groups (intensive treatment 61±14 mm Hg vs standard treatment 62±14 mm Hg; P = 0.59). Except stroke, for which the association with pulse pressure was best defined as linear, pulse pressure displayed a nonlinear U-shaped relationship with the risk of all tested clinical end points (P 0.05). The benefit of intensive blood-pressure management on mortality appeared greatest in patients with a pulse pressure ∼60 mm Hg (P = 0.03 for interaction). Pulse pressure did not modify the effect of intensive blood-pressure lowering for other clinical end points (P >0.05 for interaction). Conclusion: In a large randomized clinical trial of patients with a high risk of cardiovascular events, risks and benefits of intensive blood-pressure lowering did not appear to be modified by baseline pulse pressure. Selection of appropriate candidates for intensive blood-pressure lowering should not be limited by this parameter.

Hypertension is the leading risk factor of mortality in Nepal accounting for ∼33 000 deaths in 2016. However, more than 50% of the hypertensive patients are unaware of their status. We participated in the May Measurement Month 2017 (MMM17) project initiated worldwide by the International Society of Hypertension to raise the awareness on the importance of blood pressure (BP) screening. In this paper, we discuss the screening results of MMM17 in Nepal. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017 following the standard MMM protocol. Data were collected from 18 screening sites in 7 districts covering 5 provinces. Screenings were conducted either in health facilities, public places, or participants’ homes. Trained volunteers with health science background and female community health volunteers were mobilized to take part in the screening. A total of 5972 individuals were screened and of 5968 participants, for whom a mean of the 2nd and 3rd readings was available, 1456 (24.4%) participants had hypertension; 908 (16.8%) of those not receiving treatment were hypertensive; and 248 (45.2%) of those being treated had uncontrolled BP. MMM17 is the first nationwide BP screening campaign undertaken in Nepal. Given the suboptimal treatment and control rates identified in the study, there is a strong imperative to scale up hypertension prevention, screening, and management programmes. These results suggest that opportunistic screening can identify significant numbers with hypertension. Mobilization of existing volunteer networks and support of community stakeholders, would be necessary to improve the overall impact and sustainability of future screening programmes.

Background Heart failure is a highly prevalent disease with a global prevalence of 37 million, and the prevalence is increasing. Patients with heart failure are at an increased risk of death and morbidity. Traditionally, patients with heart failure have been treated with a beta-blocker in addition to an inhibitor of the renin-angiotensin-aldosterone system. However, new drugs are currently being added to the recommended guideline therapy. The latest drug to be added combines inhibition of the renin-angiotensin-aldosterone system pathway with inhibiting the neprilysin enzyme and is therefore classified as an ARNI. Our objective is to identify the beneficial and harmful effects of ARNIs in the treatment of patient with heart failure. Methods This protocol for a systematic review was undertaken using the recommendations of the Cochrane, the Preferred Report Items of Systematic reviews with Meta-Analysis Protocols, and the eight-step assessment procedure suggested by Jakobsen and colleagues. We plan to include all relevant randomised clinical trials assessing the use of ARNIs in the treatment of patients with heart failure. We will search the Cochrane Central Register of Controlled Trials (CENTRAL), Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded on Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Science Journal Database (VIP), and BIOSIS to identify relevant trials. We will also search for grey literature and unpublished trials. Extracted data will be analysed using Review Manager 5, STATA 5, and Trial Sequential Analysis. Our primary outcomes will be all-cause mortality and serious adverse events. We will create a ‘Summary of Findings’ table in which we will present our primary and secondary outcomes, and we will assess the quality of evidence using the GRADE assessment. Discussion The present systematic review will have the potential to aid clinicians in decision-making and thereby, benefit patients with heart failure. Systematic review registration PROSPERO CRD42019129336

Introduction: Cardiovascular disease (CVD) has become the leading cause of death worldwide, accounting for 32% of global deaths in 2016. Hypertension, which can be mitigated through diet, exercise and adherence to medication, is the greatest risk factor for CVD. However, public spending on CVD prevention remains low in many low- and middle-income countries partly due to a lack of evidence of low-cost, scalable, cost-effective and evidence-based CVD prevention programs. The goal of this study was to quantify the scalability and cost effectiveness of an evidence-based community-based hypertension management study (COBIN) in Nepal. Hypothesis: A community health worker-led BP monitoring and lifestyle counseling intervention is a cost-effective solution to achieving greater BP control in Nepal. Methods: We conducted a cost-effectiveness (CE) and budget impact (BI) analysis of a community health worker-led hypertension prevention and management intervention in Nepal that has previously been shown to reduce BP. Costs were retrospectively collected to estimate per capita and total costs of a national scale-up focusing on three scenarios: (A) hypertensives only; (B) prehypertensives and hypertensives; and (C) all adults aged 25-65 years. The primary CE measure was incremental cost per CVD disability-adjusted life year (DALY) averted. Both CE and BI analyses were conducted for each scenario. One-way sensitivity analyses were conducted to assess the impact of uncertainty in key parameter values on the primary CE measure. Results: The first-year BI was estimated to be an average of US$0.88 per participant: a total of US$2,698,181, US$5,667,503, and US$10,832,403 in scenarios A, B, and C respectively. In subsequent years costs are roughly half as much. In the base-case CE analysis, scenarios A, B, and C resulted in an incremental cost-effectiveness ratio (ICER) of US$185, US$340, and US$303/DALY respectively. One-way sensitivity analyses around the base-case analysis for scenario C show that the ICER was most sensitive to uncertainty in the estimate of SBP reduction among normotensives, varying the ICER between US$225 and US$465/DALY. Conclusions: The program is highly cost effective in all three scenarios compared to the WHO threshold of US$835/DALY for Nepal. This work presents the first evidence from Nepal that a community-based hypertension prevention and management program can be a cost-effective, low-cost, and scalable solution to control blood pressure nationwide.

Background: It is unclear whether intensive blood pressure management is well-tolerated and affects risk uniformly across the body mass index (BMI) spectrum. Methods: The randomized, controlled Systolic Blood Pressure Intervention Trial (SPRINT) included 9361 individuals ≥50 years of age at high cardiovascular risk, without diabetes mellitus, with systolic blood pressure between 130 and 180 mmHg. Participants were randomized to intensive vs standard antihypertensive treatment and evaluated for the primary composite efficacy endpoint of acute coronary syndromes, stroke, heart failure, or cardiovascular death. The primary safety endpoint was serious adverse events. We used restricted cubic splines to determine the relationship between BMI, response to intensive blood pressure lowering, and clinical outcomes in SPRINT. Results: Body mass index could be calculated for 9284 (99.2%) individuals. Mean BMI was similar between the 2 treatment groups (intensive group 29.9±5.8 kg/m 2 vs standard group 29.8± 5.7 kg/m 2 ; P = 0.39). Median follow-up was 3.3 years (range 0-4.8 years). Body mass index had a significant, J-shaped association with risk of all-cause mortality, stroke, and serious adverse events (P .05 for all). Intensive blood pressure lowering reduced the primary efficacy endpoint and increased the primary safety endpoint compared with standard targets, consistently across the BMI spectrum (P interaction >.05). Conclusion: The overall efficacy and safety of intensive blood pressure lowering did not appear to be modified by baseline BMI among high-risk older adults.

AimsAveraged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.Methods and resultsAn individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration ( n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.ConclusionAveraged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

Aims: Atrial fibrillation (AF) is associated with increased cardiovascular risk and the incidence increases with age, hypertension and left ventricular hypertrophy (LVH). Reducing in-treatment systolic blood pressure (SBP) prevents new-onset AF but has previously not been studied in patients with isolated systolic hypertension (ISH). We aimed to investigate the effect on preventing new-onset AF by decreased in-treatment SBP in patients with ISH compared to patients with non-ISH. Methods and results: Double-blind, randomized, parallel-group study of 1320 patients with ISH and electrocardiographic (ECG) LVH, included among the 9193 patients in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study. Annual ECGs were Minnesota coded centrally, and new-onset AF was evaluated in 1248 ISH patients and compared with 7583 non-ISH patients during mean 4.8 ± 0.9 years follow-up. Cox regression analyses were used to assess the effect of reduced in-treatment SBP. New-onset AF occurred in 61 (4.9%) ISH patients and 292 (3.9%) non-ISH patients. In multivariate analysis lower in-treatment SBP was associated with 17% risk reduction (p = 0.008) for new-onset AF in ISH patients and 9% risk reduction (p = 0.006) in non-ISH patients per 10 mmHg decrease in in-treatment SBP, independent of treatment modality, baseline risk factors, baseline SBP and in-treatment heart rate and ECG-LVH. There was a significant interaction (p = 0.041) in favor of SBP reduction and AF prevention in ISH vs. non-ISH patients. Conclusion: Our data suggest that the effect of in-treatment SBP reduction in preventing new-onset AF is stronger in ISH compared to non-ISH patients with hypertension and ECG-LVH. However, the principal findings were the same in ISH and non-ISH patients.

Many individuals with prediabetes, as presently defined, will progress to diabetes (T2D) despite the considerable benefit of lifestyle modification. Therefore, it is paramount to screen individuals at increased risk with a more sensitive method capable of identifying prediabetes at an even earlier time point in the lengthy trajectory to T2D. This petition reviews findings demonstrating that the 1-hour (1-h) postload plasma glucose (PG) ≥ 155 mg/dl (8.6 mmol/L) in those with normal glucose tolerance (NGT) during an oral glucose tolerance test (OGTT) is highly predictive for detecting progression to T2D, micro- and macrovascular complications and mortality in individuals at increased risk. Furthermore, the STOP DIABETES Study documented effective interventions that reduce the future risk of T2D in those with NGT and a 1-h PG ≥ 155 mg/dl (8·6 mmol/L). The 1-h OGTT represents a valuable opportunity to extend the proven benefit of diabetes prevention to the sizeable and growing population of individuals at increased risk of progression to T2D. The substantial evidence provided in this petition strongly supports redefining current diagnostic criteria for prediabetes with the elevated 1-h PG level. The authors therefore advocate a 1-h OGTT to detect prediabetes and hence, thwart the global diabetes epidemic.

The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP.

OBJECTIVE: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population.METHODS: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography.RESULTS: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p CONCLUSION: Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non-consistency between LVH determined by ECG and echocardiography.

Background: Evidence for treating hypertension in patients with asymptomatic aortic valve stenosis is scarce. We used data from the SEAS trial (Simvastatin Ezetimibe in Aortic Stenosis) to assess what blood pressure (BP) would be optimal. Methods: A total of 1767 patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease were analyzed. Outcomes were all-cause mortality, cardiovascular death, heart failure, stroke, myocardial infarction, and aortic valve replacement. BP was analyzed in Cox models as the cumulative average of serially measured BP and a time-varying covariate. Results: The incidence of all-cause mortality was highest for average follow-up systolic BP ≥160 mm Hg (4.3 per 100 person-years; 95% confidence interval [CI], 3.1–6.0) and lowest for average systolic BP of 120 to 139 mm Hg (2.0 per 100 person-years; 95% CI, 1.6–2.6). In multivariable analysis, all-cause mortality was associated with average systolic BP P =0.033) and BP of 120 to 129 mm Hg (HR, 1.6; P =0.039). Conclusions: Optimal BP seems to be systolic BP of 130 to 139 mm Hg and diastolic BP of 70 to 90 mm Hg in these patients with asymptomatic aortic stenosis and no manifest atherosclerotic disease or diabetes mellitus. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00092677.

BACKGROUND AND AIMS: High serum calcium-phosphate levels are associated with increased risk of cardiovascular disease (CVD) in patients with chronic kidney disease. Recent studies have demonstrated this relationship also in subjects with normal kidney function. Our aim was to examine whether calcium-phosphate metabolism is associated with the presence and extent of coronary artery calcification (CAC) in asymptomatic and apparently healthy individuals.METHODS: Serum samples from 1088 randomly recruited middle-aged men and women without known CVD and diabetes (DM), from the general population, were analysed for total calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxyvitamin D (25(OH)D). CAC was measured by a non-contrast cardiac CT scan and categorised into four groups: 0, 1-99, 100-399, ≥400 Agatston units. The association of calcium-phosphate metabolism with CAC was evaluated by a multiple ordered logistic regression model. All the multiple regression analyses were performed in the entire cohort as well as in men and women separately.RESULTS: In the study population, 96% of the serum calcium values, 93% of the PTH values, 90% of the phosphate values, and only 64% of the 25(OH)D values were placed within the normal range. In men, the odds of being in a higher CAC category, i.e. having more severe CAC, increased by 30% when serum calcium concentration increased by 0.1 mmol/l (95% CI: 1.04-1.61, p = 0.019), independently of traditional cardiovascular risk factors. In women, no significant association between serum calcium and CAC was identified (OR 0.99, 95% CI: 0.81-1.21, p = 0.91). Neither phosphate, PTH nor 25(OH)D was significantly associated with CAC in men, in women or when performed in the entire cohort.CONCLUSIONS: Serum calcium, even with values within normal range and independent of traditional risk factors, was significantly associated with CAC in asymptomatic and apparently healthy middle-aged men, but not in women.

Objective To examine the impact of follow-up duration on the incremental prognostic yield of a baseline oral glucose tolerance test (OGTT) for predicting type 2 diabetes and to assess the discrimination ability of blood glucose (BG) obtained at different time points during OGTT. Design A prospective, population-based cohort study (Malmö Preventive Project) with inclusion of subjects from 1974 to 1992. Methods A total of 5256 men without diabetes, who had BG measured at 0, 20, 40, 60, 90, and 120 min during OGTT (30 g/m2 glucose), were followed for 30 years. Incident type 2 diabetes was recorded using registries. The performance of OGTT added to a clinical prediction model (age, body mass index (BMI), diastolic blood pressure, fasting BG, triglycerides, and family history of diabetes) was assessed using Harrell’s concordance index (C-index) and integrated discrimination improvement (IDI). Results Median age was 48 years, mean BMI 24.9 kg/m2, and mean fasting BG 4.7 mmol/L. Models with added post-load BG performed better than the clinical model (C-index: P = 0.08 for BG at 120 min at 5 years, otherwise P ≤ 0.045; IDI: P ≥ 0.06 for BG at 60 and 90 min at 5 years, otherwise P ≤ 0.01). With a longer follow-up duration, C-index decreased, and the C-index increase associated with OGTT was attenuated. Models including BG at 60 or 90 min performed significantly better than the model with BG at 120 min, evident beyond follow-up of 10 and 5 years, respectively. Conclusions OGTT provided incremental prognostic yield for type 2 diabetes prediction. BG measured at 60 or 90 min provided better discrimination than BG at 120 min.

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP 0) and after 1 year (hsCRP 1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9–4.9] to 1.8 [0.8–5.4] mg/l, p < 0.001) and not receiving AVR (1.90 [0.90–4.10] to 1.3 [0.6–2.9] mg/l, p 1 predicted later AVR (HR = 1.17, p < 0.001) independently of hsCRP 0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP 0 and an increase during the first year (AVR highCRP0CRP1inc=47.3% versus AVR highCRP0CRP1dec=27.5%, p < 0.01). The prognostic benefit of a 1-year reduction in hsCRP was larger in patients with high versus low hsCRP 0 eliminating the difference in incidence of AVR between high versus low hsCRP 0 (AVR highCRP0CRP1dec=27.5% versus AVR lowCRP0CRP1dec=25.8%, p = 0.66) in patients with reduced hsCRP during the first year. Conclusions High hsCRP 1 or an increase in hsCRP during the first year of follow-up predicted later AVR independently of AVA, age, gender and other risk factors, although no significant improvement in C-statistics was observed.

Background/objectives: To examine whether higher fasting plasma glucose (FPG) levels were independently associated with left ventricular (LV) mass and/or geometry in elderly, otherwise healthy subjects. Methods: We tested cross-sectional associations between echocardiographically determined LV mass/geometric patterns, cardiovascular risk factors, and FPG categorized as normal fasting glucose (NFG), impaired fasting glucose (IFG), and untreated diabetes mellitus (DM), in 486 men and 207 women aged 56-79. years without overt cardiovascular disease, who received no cardiovascular, anti-diabetic, or lipid-lowering drugs and had a preserved LV ejection fraction >. 50%. Results: Unadjusted mean LV mass index (LVMI) was significantly greater among subjects with DM than those without (90+/-26g/m 2 vs. 85+/-20g/m 2, p=0.01), as were both relative wall thickness (RWT) (0.43+/-0.09 vs. 0.40+/-0.08, p=0.01) and prevalence of concentric LV hypertrophy (LVH) (11% vs. 6%, p=0.03). However, only RWT remained significantly associated with the presence of DM after multivariable adjustment (p=0.04). Interaction analyses revealed that greater LVMI/LVH was predominantly associated with higher levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) among subjects with IFG or DM, but not NFG. Conclusions: Subjects with untreated DM had higher values of LVMI and a greater prevalence of concentric LVH, but the associations were not independent of other risk factors. NT-proBNP was primarily associated with greater LV size in subjects with IFG or DM.

This perspective covers a novel area of research describing the inadequacies of current approaches for diagnosing dysglycaemia and proposes that the 1-hour post-load glucose level during the 75-g oral glucose tolerance test may serve as a novel biomarker to detect dysglycaemia earlier than currently recommended screening criteria for glucose disorders. Considerable evidence suggests that a 1-hour post-load plasma glucose value ≥155 mg/dl (8.6 mmol/L) may identify individuals with reduced β-cell function prior to progressing to prediabetes and diabetes and is highly predictive of those likely to progress to diabetes more than the HbA1c or 2-hour post-load glucose values. An elevated 1-hour post-load glucose level was a better predictor of type 2 diabetes than isolated 2-hour post-load levels in Indian, Japanese, and Israeli and Nordic populations. Furthermore, epidemiological studies have shown that a 1-hour PG ≥155 mg/dl (8.6 mmol/L) predicted progression to diabetes as well as increased risk for microvascular disease and mortality when the 2-hour level was

Background and aims: Studies have shown that soluble urokinase Plasminogen Activator Receptor (suPAR) and CRP (both inflammatory markers) and coronary artery calcification (CAC) are independent risk predictors for cardiovascular (CV) disease. The aim of this study is to assess whether suPAR and CRP have an increased predictive prognostic value beyond the traditional CV risk factors and the CAC score. Methods: A population sample of 1179 subjects, free of CV disease was included. The subjects underwent traditional CV risk evaluation, CAC assessment and blood sampling for suPAR and CRP. CV events were extracted from The Danish National Patient Register after 6.5 years. The additive values of suPAR and CRP were evaluated by unadjusted Kaplan Meier analysis, adjusted hazard ratio and ROCAUC models. Results: 1179 participants (47.6% males, mean age 55 years) were included. 73 events occurred. In Kaplan Meier analyses, suPAR and CRP were significantly associated with CV events (p = 0.03 and p = 0.002). Adjusted for the CV risk factors and the CAC score, the hazard ratios for suPAR and CRP were 1.17 (95% confidence interval [CI] 1.01–1.34) and 1.04 (95% CI 1.01–1.06), respectively. suPAR was associated with a substantial risk among women (2.03; 95% CI 1.45–2.84) and 60-year-old subjects (1.44; 95% CI 1.09–1.90). By ROCAUC, neither suPAR nor CRP provided significant estimates (0.7100 and 0.7054) compared to the traditionally CV risk factors (0.6952, p = 0.24 and p = 0.16) and CAC score (0.7481, p = 0.33 and p = 0.32). Conclusions: Adjusted for traditional CV risk factors and CAC score, suPAR and CRP were of minor importance in risk prediction.

INTRODUCTION: Elevated blood pressure greatly contributes to cardiovascular deaths in low-income and middle-income countries. We aimed to investigate the effectiveness of a population-level intervention led by existing community health workers in reducing the burden of hypertension in a low-income population.METHODS: We did a community-based, open-label, two-group, cluster-randomised controlled trial in Nepal. Using computer-generated codes, we randomly assigned (1:1) 14 clusters to a lifestyle intervention led by female community health volunteers (FCHVs) or usual care (control group). In the intervention group, 43 FCHVs provided home visits every 4 months for lifestyle counselling and blood pressure monitoring. Eligible participants had been involved in a previous population-based survey, were aged 25-65 years, did not have plans to migrate outside the study area, and were not severely ill or pregnant. The primary outcome was mean systolic blood pressure at 1 year. We included all participants who remained in the trial at 1 year in the primary analysis. This trial is registered with ClinicalTrials.gov, number NCT02428075.FINDINGS: Between April 1, 2015, and Dec 31, 2015, we recruited 1638 participants (939 assigned to intervention; 699 assigned to control). At 1 year, 855 participants remained in the intervention group (425 were normotensive, 175 were prehypertensive, and 255 had hypertension) and 613 remained in the control group (305 were normotensive, 128 were prehypertensive, and 180 had hypertension). The mean systolic blood pressure at 1 year was significantly lower in the intervention group than in the control group for all cohorts: the difference was -2·28 mm Hg (95% CI -3·77 to -0·79, p=0·003) for participants who were normotensive, -3·08 mm Hg (-5·58 to -0·59, p=0·015) for participants who were prehypertensive, and -4·90 mm Hg (-7·78 to -2·00, p=0·001) for participants who were hypertensive.INTERPRETATION: A simple, FCHV-led lifestyle intervention coupled with monitoring of blood pressure is effective for reduction of blood pressure in individuals with hypertension and ameliorates age-related increases in blood pressure in adults without hypertension in the general population of Nepal.FUNDING: Aarhus University, Jayanti Memorial Trust.

OBJECTIVE To examine whether the 1-h blood glucose measurement would be a more suitable screening tool for assessing the risk of diabetes and its complications than the 2-h measurement. RESEARCH DESIGN AND METHODS We conducted a prospective population-based cohort study of 4,867 men, randomly selected from prespecified birth cohorts between 1921 and 1949, who underwent an oral glucose tolerance test with blood glucose measurements at 0, 1, and 2 h. Subjects were followed for up to 39 years, with registry-based recording of events. Discriminative abilities of elevated 1-h (≥8.6 mmol/L) versus 2-h (≥7.8 mmol/L) glucose for predicting incident type 2 diabetes, vascular complications, and mortality were compared using Kaplan-Meier analysis, Cox proportional hazards regression, and net reclassification improvement. RESULTS Median age was 48 years (interquartile range [IQR] 48–49). During follow-up (median 33 years [IQR 24–37]), 636 (13%) developed type 2 diabetes. Elevated 1-h glucose was associated with incident diabetes (hazard ratio 3.40 [95% CI 2.90–3.98], P < 0.001) and provided better risk assessment than impaired glucose tolerance (Harrell concordance index 0.637 vs. 0.511, P < 0.001). Addition of a 1-h measurement in subjects stratified by fasting glucose provided greater net reclassification improvement than the addition of a 2-h measurement (0.214 vs. 0.016, respectively). Finally, the 1-h glucose was significantly associated with vascular complications and mortality. CONCLUSIONS The 1-h blood glucose level is a stronger predictor of future type 2 diabetes than the 2-h level and is associated with diabetes complications and mortality.

Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery.Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period.Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively.Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted.Trial registration number: NCT00092677; Post-results.

IntroductionWe present the protocol for a multifactorial intervention study designed to test whether individualised treatment, based on pathophysiological phenotyping and individualised treatment goals, improves type 2 diabetes (T2D) outcomes.Methods and analysisWe will conduct a prospective controlled multicentre open-label intervention study, drawing on the longitudinal cohort of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2). New clinically diagnosed patients with T2D in the intervention group will be assigned to receive individualised treatment by their general practitioner. Intervention patients will be compared with a matched control cohort of DD2 patients receiving routine clinical care. Among intervention patients, we will first do pathophysiological phenotyping to classify patients into WHO-defined T2D or other specific types of diabetes (monogenic diabetes, secondary diabetes etc). Patients with WHO-defined T2D will then be further subcharacterised by their beta-cell function (BCF) and insulin sensitivity (IS), using the revised homeostatic assessment model, as having either insulinopaenic T2D (high IS and low BCF), classical T2D (low IS and low BCF) or hyperinsulinaemic T2D (low IS and high BCF). For each subtype, a specific treatment algorithm will target the primary pathophysiological defect. Similarly, antihypertensive treatment will be targeted at the specific underlying pathophysiology, characterised by impedance cardiography (relative importance of vascular resistance, intravascular volume and cardiac inotropy). All treatment goals will be based on individual patient assessment of expected positive versus adverse effects. Web-based and face-to-face individualised lifestyle intervention will also be implemented to empower patients to make a sustainable improvement in daily physical activity and to change to a low-carbohydrate diet.Ethics and disseminationThe study will use well-known pharmacological agents according to their labels; patient safety is therefore considered high. Study results will be published in international peer-reviewed journals.Trial registration numberNCT02015130; Pre-results.