Back to square one: what is a normal blood pressure and for whom?

For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts High blood pressure was one of the first recognized risk factors, but the level at which hypertension can be diagnosed varied hugely over time. Indeed, in the old days it was 100 mmHg plus age in the systolic range, then the experts settled at 160/95 mmHg just to set it at 140/90 mmHg a few years later.1 Now, the US Guidelines have defined truly normal blood pressure at levels below 120 mmHg systolic.2 If any of the readers are confused at a higher level they are ready to read The Editors Page ‘What is a normal blood pressure?’3 There they will learn that our ancestors had blood pressures in the range of 110/70 mmHg or lower throughout their life, if they survived war, hunger, and infections. The rather emotional transatlantic debate about the new US recommendations4 must thus be interpreted in a wider context. We must rethink target values in a personalized fashion and consider global and life time risk when deciding treatment strategies for an individual patient. This view is challenged by Franz Messerli from the Inselspital University Hospital Bern in Switzerland in his Viewpoint ‘Changing definition of hypertension in guidelines: how innocent a number game?’5 He is concerned about the fact that as of November 2017, with the publication of the new US Guidelines on Hypertension, there would now be millions more hypertensives at age 60 and above in the USA alone, and he expresses his hope that despite those recommendations, physicians will continue to treat them and not mm of Hg only. Things are even more complicated than that. Indeed, not only blood pressure as such, but blood pressure variability is associated with increased cardiovascular risk. In their article entitled ‘Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks’, Eivind Berge and colleagues from the Oslo University Hospital in Norway evaluated this in the VALUE trial enrolling 13 803 patients of which 11.3% had a cardiovascular event.6 Patients in the highest quintile of standard deviation of blood pressure had a 2.1-fold increased cardiovascular risk. A 5 mmHg increase in standard deviation of systolic blood pressure was associated with a 10% increase in the risk of death. The effects were stronger in younger patients and in those with lower systolic blood pressure. Thus, higher visit-to-visit systolic blood pressure variability is associated with increased risk of events, irrespective of baseline risk, particularly in younger patients and those with lower systolic blood pressure. These novel findings are further discussed in an Editorial by Stephane Laurent from the Hôpital Européen Georges Pompidou in Paris.7 As in the hypertensive population at large, optimal blood pressure remains uncertain in patients with type 2 diabetes mellitus, especially as they have been excluded in the landmark SPRINT trial.8,9 Also, there is concern for increased risk with low diastolic blood pressure. In their article entitled ‘Blood pressure and cardiovascular outcomes in patients with diabetes and high cardiovascular risk’, Brian Allan Bergmark and the SAVOR-TIMI 53 Investigators analysed the association between blood pressure and cardiovascular outcomes in 12 175 high-risk patients with type 2 diabetes mellitus.10 Adjusted risk of the composite endpoint of cardiovascular death, myocardial infarction, or ischaemic stroke showed U-shaped relationships with baseline systolic blood pressure and diastolic blood pressure, with nadirs at systolic blood pressure 130–140 mmHg or diastolic blood pressure 80–90 mmHg (Figure 1). Diastolic blood pressure below 60 mmHg was associated with a 2.3-fold increased risk of myocardial infarction. Thus, in patients with diabetes and elevated cardiovascular risk, even after extensive adjustment for underlying disease burden, there was a persistent association of low diastolic blood pressure with subclinical myocardial injury and risk of myocardial infarction. Adjusted risk for CV death by SBP and DBP strata. CV = cardiovascular; DBP = diastolic blood pressure; HF = heart failure; hsTnT = high-sensitivity troponin-T; MACE = major adverse cardiovascular events; MI = myocardial infarction; SBP = systolic blood pressure (from Bergmark BA, Scirica BM, Steg PG, Fanola CL, Gurmu Y, Mosenzon O, Cahn A, Raz I, Bhatt DL;on behalf of the SAVOR-TIMI 53 Investigators. Blood pressure and cardiovascular outcomes in patients with diabetes and high cardiovascular risk. See pages 2255–2262). The obesity epidemic is a big threat for the Western world,11–13 and increasingly so also in developing countries. Indeed, more and more children are obese, putting them at an enormous life time risk. In their article ‘Distinct child-to-adult body mass index trajectories are associated with different levels of adult cardiometabolic risk’,14 Marie-Jeanne Buscot and colleagues from the University of Tasmania Menzies Institute for Medical Research in Hobart in Australia investigated body mass index trajectories from early childhood to adulthood and their association with cardiovascular risk. Out of six trajectories of worsening or persisting obesity, all were associated with increased risk of cardiovascular disease outcomes in adulthood, i.e. 24–49 years (Figure 2). Although residual risk for adult type 2 diabetes mellitus could not be confirmed, participants who resolved their elevated child body mass index had similar risk for dyslipidaemia and hypertension as those never obese or overweight. However, they had increased carotid intima-media thickness. Thus, long-term body mass index trajectories that reach or persist at high levels are associated with cardiovascular disease risk factors in adulthood. Stabilizing body mass index in obese adults and resolving elevated childhood body mass index by adulthood might limit and reduce adverse cardiometabolic profiles. The practical implications of these important findings are put into context in a thought-provoking Editorial by John E. Deanfield from the Institute of Child Health in London.15 Predicted probability of having a cumulative cardiovascular disease (CVD) risk load of 0 (n = 1360), 1 (n = 540), and ≥2 (n = 521) in the Cardiovascular Risk in Young Finns Study for each latent body mass index (BMI) trajectory class. The predicted probability plot is derived from the proportional odd ratios estimated for the sex- and adult age-adjusted ordinal logistic model (from Buscot M-J, Thomson RJ, Juonala M, Sabin MA, Burgner DP, Lehtimäki T, Hutri-Kähönen N, Viikari JSA, Raitakari OT, Magnussen CG. Distinct child-to-adult body mass index trajectories are associated with different levels of adult cardiometabolic risk. See pages 2263–2270). Hypertensives often have diabetes, and diabetics commonly have high blood pressure and concomitant metabolic disorders, and are therefore at very high risk. While until recently, the cardiovascular benefits of antidiabetic drugs were uncertain,16 but novel drugs such as the sodium–glucose transport inhibitors have changed the picture.17–19 Thus, the Current Opinion ‘Non-insulin antidiabetic pharmacotherapy in patients with established cardiovascular disease: a position paper of the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy’ by Alexander Niessner and colleagues from the Medical University of Vienna in Austria is timely.20 Reducing the type 2 diabetes mellitus-associated risk is indeed of utmost importance, as recommended by the ESC guidelines. Commonly, HbA1c values <7% are recommended. However, the association between HbA1c and short to mid-term cardiovascular events is not well defined. Indeed, only specific antidiabetic therapies reduce major adverse cardiovascular events, and this effect appears to be independent of the baseline HbA1c level or HbA1c reduction. This position paper critically appraises emerging evidence regarding antidiabetic pharmacotherapy in patients with type 2 diabetes mellitus and mostly stable cardiovascular disease. Vascular ageing is characterized by arterial stiffening, dilation, and arterial wall thickening.21,22 In their article entitled ‘Arterial stiffening is a heritable trait associated with arterial dilation but not wall thickening: a longitudional study in the Twins UK cohort’, Marina Cecelja and colleagues from King’s College in London investigated the extent to which these changes are related and their heritability during 5-year follow-up in 762 female twins of the Twins UK cohort.23 Annual increases in carotid–femoral pulse wave velocity, carotid diameter, distensibility, and intima-media thickness were 0.139 m/s, 0.028 mm, –0.4 kPa–1, and 0.011 mm year, respectively. Predictors of progression in carotid–femoral pulse wave velocity included age, blood pressure, and heart rate at baseline, and their progression over time and that of the body mass index, while those for intima-media thickness included progression in blood pressure, body mass index, and triglycerides. Heritability of progression of carotid–femoral pulse wave velocity, diameter, and intima-media thickness was 55, 21, and 8%, respectively. Thus, arterial stiffening and dilation are heritable, but independent of arterial wall thickening. Whether genetic and cardiovascular risk factors contribute to these changes is further discussed in an Editorial by M. F. O’Rourke from the University of New South Wales, Australia.24 Obstructive sleep apnoea is associated with hypertension and cardiovascular events.25,26 Safi U. Khan and colleagues from the Guthrie Robert Packer Hospital in Sayre, Pennsylvania, USA performed ‘A meta-analysis of continuous positive airway pressure therapy in prevention of cardiovascular events in patients with obstructive sleep apnoea’.27 They collected 4268 patients demonstrating a non-significant 26% relative risk reduction in major adverse cardiovascular events or MACE with continuous positive airway pressure or CPAP. A series of sensitivity analyses suggested that increased CPAP usage time yielded significant risk reduction. Indeed, CPAP adherence time ≥4 h per night reduced the risk by 57%. Overall, CPAP showed no beneficial effect on MACE, atrial fibrillation or flutter, or heart failure. However, it had positive effects on mood and daytime sleepiness. Thus, CPAP might reduce MACE among subjects with usage time exceeding 4 h per night only. The implications of these findings for clinical practice and future research are outlined in an interesting Editorial by Martin Cowie from Imperial College in London, UK.28 Cardiovascular events both in the coronary and in large parts in the cerebrovascular circulation are related to rupture-prone atherosclerotic plaques.29–31 The interconnection of metabolic and inflammatory processes in rupture-prone plaques is poorly understood. In their Basic Science article entitled ‘Altered metabolism distinguishes high-risk from stable carotid atherosclerotic plaques’, Lukas Tomas and colleagues from Lunds Universitet in Malmö, Sweden investigate associations between metabolite profiles, inflammatory mediators, and vulnerability in carotid atherosclerotic plaques obtained from 159 patients.32 The altered metabolic signature in high-risk plaques was consistent with a change to increased glycolysis, elevated amino acid utilization, and decreased fatty acid oxidation, similar to what is found in activated leucocytes and cancer cells. Thus, an altered cellular metabolism supporting inflammation appears to be a key feature of vulnerable plaques. Whether targeting their metabolism with novel metabolic radiotracers or inhibitors might represent novel approaches to identify and treat the high-risk atherosclerotic plaque is further evaluated in a comprehensive Editorial by Christian Weber from the Ludwig-Maximilians-Universität in Munich, Germany.33 Patients with chronic kidney disease are almost universally hypertensive and they are at increased risk for cardiac events and rhythm disorders in particular.34 In their Current Opinion ‘Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference’,35 Christoph Wanner from the Universitätsklinikum in Würzburg, Germany remind us that drug, device, and procedural treatment options may be limited in this population or complicated by chronic kidney disease or dialysis. Such patients are also under-represented in randomized trials, limiting the availability of evidence. Thus, the KDIGO’s multidisciplinary panel identified knowledge gaps and research priorities for preventing and treating arrhythmias in chronic kidney disease such as atrial fibrillation and stroke, rate vs. rhythm control in atrial fibrillation, prognostication and prevention of sudden cardiac death, and maintenance of electrolyte homeostasis. KDIGO here provides a consensus in managing arrhythmias in chronic kidney disease and guidance for clinical practice. Many cardiovascular events occur at distinct periods in the day. This may at least in part be related to circadian changes in body function. Notably, the cardiovascular system, including the heart itself, is particularly sensitive to circadian variation. In an education article entitled ‘The circadian clock in cardiovascular regulation and disease: lessons from the Nobel Prize in Physiology or Medicine 2017’, Linda W. Van Laake and colleagues from the University Medical Center Utrecht in the Netherlands review the seminal work of the the 2017 Nobel Prize in Physiology or Medicine awardees Jeffrey Hall, Michael Rosbash, and Michael Young, and their discoveries of the molecular circadian clock.36 The editors hope that this issue of the European Heart Journal will be of interest to its readers. With thanks to Amelia Meier-Batschelet for help with compilation of this article.