Clinical outcomes by atherosclerotic cardiovascular disease risk score and blood pressure level in high risk individuals with type 2 diabetes.

Clinical practice guidelines for patients with diabetes recommend using blood pressure (BP) and atherosclerotic cardiovascular disease (ASCVD) risk to guide antihypertensive treatment. While this approach directs treatment to patients who should receive a large ASCVD risk reduction, its effect on other outcomes is uncertain. The aim of this study was to assess the contributions of systolic blood pressure level (SBP) and predicted 10-year ASCVD risk using Pooled Cohort risk equations to the prediction of major macrovascular disease, death and major microvascular disease in patients with diabetes. Data came from 7426 individuals with type 2 diabetes (T2D) without macrovascular disease at baseline in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. The risk for major macrovascular events and death increased progressively across ASCVD risk categories. Compared to participants with 10-year predicted ASCVD risk <20% and SBP <130 mmHg, the hazard ratios (HRs) (95% confidence intervals (CIs)) associated with SBP ≥150 mmHg and 10-year predicted ASCVD risk <20%, 20-34% and ≥35% were 1.01 (0.58, 1.77), 1.90 (1.28, 2.84) and 2.82 (1.98, 4.01) for major macrovascular disease, respectively, and 0.83 (0.42, 1.62), 1.79 (1.13, 2.82) and 3.29 (2.22, 4.88) for death, respectively. The risk for major microvascular disease increased with BP regardless of ASCVD risk; HRs for SBP ≥150 mmHg and 10-year predicted ASCVD risk <20%, 20-34% and ≥35% vs. ASCVD risk <20% and SBP <130 mmHg were 1.52 (1.08,2.13), 1.47 (1.10, 1.96) and 1.23 (0.94, 1.60), respectively. ASCVD risk in addition to SBP improved the estimation of major macrovascular events and death but not major microvascular events among individuals with T2D.

Retirement age does not modify the association of prior working conditions with self-rated health and mortality in retirees: results from a prospective study of retired French workers.

OBJECTIVE: It is unclear whether retirement age can modify the association of working conditions with health and mortality in retirees who are no longer exposed to these conditions. METHODS: The present study investigated this issue in a cohort of 13,378 French workers in whom self-rated health and mortality were measured over 15 years after statutory retirement. The analyses were also performed in homogenous clusters of workers differentiated on the basis of working conditions, social position, birth and retirement years. RESULTS: Bad working conditions before retirement, which were assessed using a global score combining 25 different occupational exposures, were associated with higher rates of suboptimum self-rated health and mortality in retirees after adjusting for retirement age, social position, demographics and health status before retirement. These rates were also substantially higher in the cluster of workers characterized by bad working conditions in comparison to other clusters. In contrast, retirement age was not associated with self-rated health or mortality after adjusting for working conditions, social position, demographics and health status before retirement. Likewise, no association of retirement age with self-rated health or mortality was found in any cluster of workers and no interactions were observed with any of these clusters. CONCLUSION: These results suggest that bad working conditions before retirement have long-term detrimental effects on health and mortality in retirees and that retirement age does not modulate these effects. Improving work environment rather than modifying retirement age should be prioritized to promote health and reduce mortality not only in workers but also in retirees.

Respective Mediating Effects of Social Position and Work Environment on the Incidence of Common Cardiovascular Risk Factors.

Background Social position and work environment are highly interrelated and their respective contribution to cardiovascular risk is still debated. Methods and Results In a cohort of 20 625 French workers followed for 25 years, discrete-time survival analysis with reciprocal mediating effects, adjusted for sex, age, and parental history of early coronary heart disease, was performed using Bayesian structural equation modeling to simultaneously investigate the extent to which social position mediates the effect of work environment and, inversely, the extent to which work environment mediates the effect of social position on the incidence of common cardiovascular risk factors. Depending on the factor, social position mediates 2% to 53% of the effect of work environment and work environment mediates 9% to 87% of the effect of social position. The mediation by work environment is larger than that by social position for the incidence of obesity, hypertension, dyslipidemia, diabetes, sleep complaints, and depression (mediation ratios 1.32-41.5, 6.67 when modeling the 6 factors together). In contrast, the mediation by social position is larger than that by work environment for the incidence of nonmoderate alcohol consumption, smoking, and leisure-time physical inactivity (mediation ratios 0.16-0.69, 0.26 when modeling the 3 factors together). Conclusions The incidence of behavioral risk factors seems strongly dependent on social position whereas that of clinical risk factors seems closely related to work environment, suggesting that preventive strategies should be based on education and general practice for the former and on work organization and occupational medicine for the latter.

Trends in Worldwide Research in Hypertension Over the Period 1999-2018: A Bibliometric Study.

Bibliometric analysis, a powerful tool for assessing trends in research output, was employed to analyze the evolution of hypertension research over a 20-year period. The analysis was based on 90 308 original articles and a citation analysis. The use of bibliometric as a potential tool for shaping research policy at the institution or country level was also explored. The number of published hypertension articles increased by 43.5% over the 20-year period. By contrast, the increase in the number of articles in all medical disciplines was 96%, and in the cardiovascular field was 64%. Of the 6 countries producing the largest number of articles, the United States was consistently the major contributor. There was a slight decrease from Japan, a slight increase from the United Kingdom, and relatively stable output from Germany and Italy over the study period. Output from China showed the strongest growth. The trends in Specialization Index and Category Normalized Citation Impact varied by country. In Russia, Poland, and Brazil, increases in output were greater for hypertension research than for medical research in general. The United Kingdom and Denmark had greater hypertension research output than the other countries. VOSviewer analysis showed an intensification of collaborations between countries and a shift, over 10 years, from 3 clusters towards 2 clusters. Such analysis may help to shape research policy at the country level and can be similarly performed for institutions. Historical changes in hypertension research can be monitored over decades if the same channels continue to be used for communication of scientific results.

Randomized Dose-Response Study of the New Dual Endothelin Receptor Antagonist Aprocitentan in Hypertension.

This study examined the dose-response characteristics of aprocitentan, a dual endothelin A/endothelin B receptor antagonist, in patients with essential hypertension. In a randomized, double-blind, parallel study design, eligible patients with a sitting diastolic blood pressure (BP) of 90-109 mm Hg received aprocitentan 5, 10, 25, or 50 mg, placebo, or lisinopril 20 mg as a positive control once daily for 8 weeks. Multiple automated office BP readings were obtained with patients resting unattended (unattended automated office BP) at baseline, weeks 2, 4, and 8. Ambulatory BP was monitored for 24 hours at baseline and week 8. After a single-blind placebo run-in period, 490 eligible patients were randomized to the double-blind phase, with 409 patients completing 8 weeks of therapy per protocol. Aprocitentan 10, 25, and 50 mg decreased sitting systolic/diastolic unattended automated office BP from baseline to week 8 (placebo-corrected decreases: 7.05/4.93, 9.90/6.99, and 7.58/4.95 mm Hg, respectively, P≤0.014 versus placebo), compared with an unattended automated office BP reduction of 4.84/3.81 mm Hg with lisinopril 20 mg. For patients with valid ambulatory BP, aprocitentan 10, 25, and 50 mg significantly decreased placebo-corrected 24-hour BP by 3.99/4.04, 4.83/5.89, and 3.67/4.45 mm Hg, respectively. Incidence of adverse events was similar in the aprocitentan groups (22.0%-40.2%) and the placebo group (36.6%). Aprocitentan produced dose-dependent decreases in hemoglobin, hematocrit, albumin, and uric acid, an increase in estimated plasma volume, but no change in weight versus placebo. These findings support further investigation of aprocitentan at doses of 10 to 25 mg in hypertension. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT02603809.

Phylogenetic analysis of West Nile virus in Quebec, Canada, 2004-2016: Co-circulation of distinct variants harbouring conserved amino acid motifs in North America.

West Nile virus (WNV) was introduced for the first time in the western hemisphere in 1999 in New York City. In 2002, a phenotype-modifying mutation (Env-V159A) defined the first North American genotype WN02. So far, three genotypes has been described in North America but little is known about WNV evolution in Canada. We report the phylogenetic characterization of twenty-six WNV genomes isolated from mosquitoes in the province of Quebec. WNV strains found in Quebec are phylogenetically related to American strains collected in northern and southern regions. We also noted the presence of two robust monophyletic groups of isolates characterized by distinct conserved amino acid motifs. These emerging genotypes were detected for several years in different ecosystems. These results highlight the need for the maintenance of a nationwide surveillance to follow the dispersion of emergent WNV genotypes.

Bibliometric analysis of research relating to hypertension reported over the period 1997-2016.

OBJECTIVE: Hypertension, a major cardiovascular risk factor, may reach a global prevalence of 1.56 billion by 2025. Much research has been conducted in this field, but few bibliometric studies have been performed. We aimed to analyse the changes in scientific output relating to hypertension over the past two decades. METHODS: We analysed, via PubMed and Web of Science, the scientific output relating to hypertension from 1997 to 2016. Quantitative (number of publications) and citation (top 1 and 10%) analyses were performed for output globally and by major countries/regions, with a particular focus on the European Union. RESULTS: In total, 100 789 articles relating to hypertension were identified in Web of Science. The number of publications increased by 52.7% (3989 in 1997, 6092 in 2016). Of the 100 789 articles, 38% had authors from the European Union, 32.1% had authors from the USA, and 26.7% had authors from Asia, with a marked increase in contributions from China over the period analysed. Articles appeared in more than 400 journals and were cited nearly 2 556 000 times. The relative weights of different research fields have also changed over time. CONCLUSION: Combined use of PubMed and Web of Science enabled robust bibliometric analysis of the studies into hypertension published in the period 1997-2016, including assessment of the contributions from major countries, particularly those in the European Union. This study also allowed us to validate our methodology, which could be used to evaluate research policies and to promote international cooperation.

Pharmacological Characterization of Aprocitentan, a Dual Endothelin Receptor Antagonist, Alone and in Combination with Blockers of the Renin Angiotensin System, in Two Models of Experimental Hypertension.

The endothelin (ET) system has emerged as a novel target for hypertension treatment where a medical need persists despite availability of several pharmacological classes, including renin angiotensin system (RAS) blockers. ET receptor antagonism has demonstrated efficacy in preclinical models of hypertension, especially under low-renin conditions and in hypertensive patients. We investigated the pharmacology of aprocitentan (N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-sulfamide), a potent dual ETA/ETB receptor antagonist, on blood pressure (BP) in two models of experimental hypertension: deoxycorticosterone acetate (DOCA)-salt rats (low-renin model) and spontaneously hypertensive rats [(SHR), normal renin model]. We also compared the effect of its combination with RAS blockers (valsartan and enalapril) with that of the combination of the mineraloreceptor antagonist spironolactone with the same RAS blockers on BP and renal function in hypertensive rats. Aprocitentan was more potent and efficacious in lowering BP in conscious DOCA-salt rats than in SHRs. In DOCA-salt rats, single oral doses of aprocitentan induced a dose-dependent and long-lasting BP decrease and 4-week administration of aprocitentan dose dependently decreased BP (statistically significant) and renal vascular resistance, and reduced left ventricle hypertrophy (nonsignificant). Aprocitentan was synergistic with valsartan and enalapril in decreasing BP in DOCA-salt rats and SHRs while spironolactone demonstrated additive effects with these RAS blockers. In hypertensive rats under sodium restriction and enalapril, addition of aprocitentan further decreased BP without causing renal impairment, in contrast to spironolactone. In conclusion, ETA/ETB receptor antagonism represents a promising therapeutic approach to hypertension, especially with low-renin characteristics, and could be used in combination with RAS blockers, without increasing the risk of renal impairment.

Work environment mediates a large part of social inequalities in the incidence of several common cardiovascular risk factors: Findings from the Gazel cohort.

Whether working conditions contribute to social inequalities in cardiovascular disease is still a matter of debate. The present study investigates the extent to which the social gradient in the incidence of common behavioral and clinical risk factors is explained by work environment. In a well-characterized cohort of 20,625 middle-aged French civil servants followed for 25 years, social status and work environment were globally measured at baseline by combining respectively four socioeconomic indicators (education, wealth, income, occupational grade) and 25 physical, biomechanical, organizational and psychosocial occupational exposures. These 2 global measures are strongly correlated with each other (p < 0.0001), lower is social status, worse is work environment. In proportional hazard regression models adjusted for sex, age and parental cardiovascular disease, low social status increases the incidence of 9 risk factors with hazard ratios ranging from 1.12 to 1.72 while bad work environment increases the incidence of 7 risk factors with hazard ratios ranging from 1.15 to 2.02. Structural equation models to discrete-time survival analysis with moderated mediation show that bad work environment explains nearly 50% of the global effect of low social status on the incidence of the 9 risk factors (p < 0.01). This mediating effect varies substantially from one risk factor to another, explaining 32-39% of social gradients in the risk of physical inactivity, obesity, diabetes, dyslipidemia and 64-90% of gradients in the risk of hypertension, sleep complaints and depression (all p < 0.01). No significant mediating effect of work environment is found for social gradients in the incidence of non-moderate alcohol consumption and smoking. These results suggest that work environment mediates a large part of the social gradient in the incidence of several common cardiovascular risk factors, emphasizing the necessity to include working conditions in policies aimed to reduce social inequalities in health.