Highlights of the November issue,

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.

Low birth weight, a risk factor for diseases in later life, is a surrogate of insulin resistance at birth Low birth weight (LBW) is associated with diseases in adulthood. The birthweight attributed risk is independent of confounding such as gestational age, sex of the newborn but also social factors. The birthweight attributed risk for diseases in later life holds for the whole spectrum of birthweight. This raises the question what pathophysiological principle is actually behind the association. In this review, we provide evidence that LBW is a surrogate of insulin resistance. Insulin resistance has been identified as a key factor leading to type 2 diabetes, cardiovascular disease as well as kidney diseases. We first provide evidence linking LBW to insulin resistance during intrauterine life. This might be caused by both genetic (genetic variations of genes controlling glucose homeostasis) and/or environmental factors (due to alterations of macronutrition and micronutrition of the mother during pregnancy, but also effects of paternal nutrition prior to conception) leading via epigenetic modifications to early life insulin resistance and alterations of intrauterine growth, as insulin is a growth factor in early life. LBW is rather a surrogate of insulin resistance in early life – either due to inborn genetic or environmental reasons – rather than a player on its own.

Serious adverse events in patients with target-oriented blood pressure management: a systematic review On the basis of the benefits of antihypertensive treatment, progressively intensive treatment is advocated. However, it remains controversial whether intensive blood pressure control might increase the frequency of serious adverse events (SAEs) compared with moderate control. This review assessed the occurrence of SAEs in blood pressure treatment with predefined blood pressure targets. Seven original studies and eight post hoc analyses (derived from two original studies) met the inclusion criteria. Compared with moderate blood pressure treatment, intensive treatment was associated with a significant increase in treatment-related SAEs (Sign-test: P = 0.0002, Wilcoxon signed-rank test: P = 0.001). However, comparability between studies was limited, due to unclear determinations about the treatment-relatedness of adverse events, missing definitions of SAEs and variations in recording methods. Thus, a meta-analysis was not justified. The definitions of serious adverse events and methods of recording and reporting need to be improved and standardized to facilitate the comparison of results.

Inhibition of the renin-angiotensin system in the cardiorenal syndrome with anaemia: a double-edged sword The term ‘cardiorenal syndrome’ (CRS) was introduced to describe problems related to the simultaneous existence of heart and renal insufficiency. The prevalence of anaemia in CRS is high and increases the risk of hospitalizations and death. Renin-angiotensin system (RAS) inhibition is the cornerstone therapy in cardiovascular and renal medicine. As angiotensin II regulates both glomerular filtration rate (GFR) and erythropoiesis, RAS inhibition can further deteriorate renal function and lower hematocrit or cause anaemia in patients with heart failure. The aim of this review is to explore the relationship among CRS, anemia and administration of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) and summarize the evidence suggesting that RAS inhibition may be considered an iatrogenic cause of deterioration of CRS with anemia. It should be emphasized however, that RAS inhibition reduces mortality in both groups with and without worsening of renal function, and therefore, no patient with CRS should be denied an ACEi or ARB trial without careful evaluation.

A call for improved reporting on serious adverse events in clinical trials No abstract available

Hypertension and aortic stenosis: no strangers, not anymore! No abstract available

Sex differences in excess and reservoir arterial blood pressures as markers of phenotype Objectives: Excess pressure and reservoir pressure are related to various clinical outcomes in cardiovascular diseases, but whether there are sex differences in healthy individuals remains uncertain. We compared phenotypes of excess pressure and reservoir pressure between healthy men and women. Methods: Different features of noninvasively recorded radial and reconstructed aortic pressure waveforms were measured in 435 healthy adults (257 women, 59%). In addition to SBP and DBP, we compared values of maximal excess pressure and reservoir pressure (RPMAX), excess pressure and reservoir pressure time integrals, respectively, as well as relative contributions of excess pressure (EPREL) and reservoir pressure to total blood pressure time integral, respectively, between men and women divided in two age categories, below 51 (82 women and 66 men) and greater than or equal to 51 years old (175 women and 112 men), corresponding to average age of menopause for women and acceleration of vascular ageing for all. Results: In both age categories, compared with men, women had significantly lower peripheral and aortic SBP and DBP. Analysis of covariance adjusted for BMI revealed that women who were greater than or equal to 51 years old had significantly higher excess pressure time integral, RPMAX, reservoir pressure time integral, EPREL, and relative contributions of reservoir pressure than men in the same age category. In the younger age category below 51 years old, EPREL and RPMAX were also significantly higher in women than men. Conclusion: Our study shows that healthy women have lower peripheral and aortic SBP and DBP compared with healthy men; however, their excess and reservoir pressures are higher, particularly after 51 years of age.

Diurnal blood pressure loads are associated with lower cognitive performances in controlled-hypertensive elderly individuals Introduction: Hypertension in midlife adults is associated with cognitive decline later in life. In individuals treated for hypertension, blood pressure (BP) loads have been associated with end organ damages. This study examines whether BP load inversely correlates with performance in cognitive tasks in normotensive or controlled hypertensive (CHT) individuals. Methods: Participants between 60 and 75 years old were divided into normotensive participants who did not receive antihypertensive treatment (n = 49) and CHT patients (n = 28). They were evaluated for BP using ambulatory blood pressure monitoring and cognitive functions with tests assessing cognitive flexibility, working and episodic memory, and processing speed. Results: Analysis of covariance between normotensive and CHT participants revealed lower cognitive performances on immediate and delayed recall and total number of words of the Rey Auditory Verbal Learning Test (P < 0.001). Spearman's correlations between BP loads and cognitive performances revealed inversed associations between diurnal systolic (SBP) loads and performances on the Trail Making Test Part B (TMTB) (P = 0.009), the TMTB–TMT Part A (P = 0.013), the Switching Cost of the color-word interference test (P = 0.020) and the Digit-Symbol Substitution Score tests (P = 0.018) in CHT. Diurnal diastolic (DBP) loads were inversely correlated to the TMTB (P = 0.014) and TMTB–TMT Part A (P = 0.006). In normotensive subjects, diurnal SBP loads were associated with the delayed recall of the Rey Auditory Verbal Learning Test (P = 0.031) and to the three components of the digit span (P < 0.05). Conclusion: Diurnal BP loads are associated with lower cognitive performances in CHT individuals. These results suggest a lowering of target levels of diurnal BPs and/or its variability.

Unhealthy behavior and risk of hypertension: the CONSTANCES population-based cohort Objectives: We aimed to evaluate the individual and combined association between unhealthy behavior and hypertension (HTN). Methods: We conducted cross-sectional analysis using data from the population-based cohort study CONSTANCES. Blood pressure measurements were taken based on standardized operational procedures. Dietary adherence was done following the dietary approach to stop HTN diet. We considered heavy alcohol drinking, sedentary-level physical activity, low/medium dietary adherence and overweight/obesity as unhealthy behaviors. Participants’ characteristics were compared according to the number of unhealthy behaviors and the association between HTN and unhealthy behaviors was estimated using logistic regression. Results: A total of 86 448 volunteer participants were included and the prevalence of HTN was of 31.1%. Of those with HTN, 8.2, 33.0, 44.3 and 14.5% exhibited 0, 1, 2 or at least 3 unhealthy behaviors, respectively. In both sexes, the prevalence of HTN increased with low/medium dietary adherence compared with high (P < 0.01), in overweight/obese compared with normal BMI (P < 0.001), with heavy alcohol consumption compared with moderate or never (P < 0.05) and with sedentary physical activity level compared to high in women only (P = 0.049). Combination of several unhealthy behaviors was associated with increased odds of HTN (P trend <0.001); men reporting 2 or at least 3 unhealthy behaviors had an adjusted odds ratio of HTN of 1.77 and 2.29, respectively, while women had an adjusted odds ratio of 1.71 and 2.14, respectively. Conclusion: Individual and combined unhealthy lifestyle factors were strongly associated with HTN in this large population-based study.