Update on a silent killer: arterial hypertension

With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article. For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts. This Focus Issue on hypertension contains the ‘2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: developed by the Task Force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS); endorsed by the International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on rare respiratory diseases (ERN-LUNG).’1 The authors note that pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and may be associated with a variety of cardiovascular and respiratory diseases.2–6 The complexity of managing PH requires a multifaceted, holistic, and multidisciplinary approach, with active involvement of patients with PH in partnership with clinicians. Streamlining the care of patients with PH in daily clinical practice is a challenging but essential requirement for effectively managing PH. In recent years, substantial progress has been made in detecting and managing PH, and new evidence has been timeously integrated in this fourth edition of the ESC/ERS Guidelines for the diagnosis and treatment of PH. Reflecting the multidisciplinary input into managing patients with PH and interpreting new evidence, the Task Force included cardiologists and pneumologists, a thoracic surgeon, methodologists, and patients. These comprehensive clinical practice guidelines cover the whole spectrum of PH, with an emphasis on diagnosing and treating pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension. Improvement of lifestyle plays a key role in cardiovascular prevention but it is difficult to achieve it.7–10 In a Clinical Research article entitled ‘Effects of a comprehensive lifestyle intervention on cardiovascular health: the TANSNIP-PESA trial’, Ines Garcia-Lunar from the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, Spain, and colleagues investigate the effectiveness of a 3-year worksite lifestyle intervention on cardiovascular metrics and study whether outcomes are influenced by baseline subclinical atherosclerosis (SA) by non-invasive imaging.11 A randomized controlled trial was performed to compare a lifestyle intervention with standard of care in asymptomatic middle-aged subjects, stratified by SA. The intervention consisted of nine motivational interviews during the first year, followed by three further sessions between Years 1 and 3. The primary outcome was the change in a pre-specified adaptation of the Fuster-BEWAT score (Blood pressure, Exercise, Weight, Alimentation, and Tobacco) between baseline and follow-up Years 1–3. A total of 1020 participants (mean age 50 ± 4 years) were enrolled, of whom 510 were randomly assigned to the intervention and 510 to the control group. The baseline adapted Fuster-BEWAT score was 16.2 ± 3.7 points in the intervention group and 16.5 ± 3.5 points in the control group. At Year 1, the score improved significantly in intervention participants compared with controls (estimate 0.83 points). However, intervention effectiveness decreased to non-significant levels at Year 3 (0.24 points]. Over the 3-year period, the intervention was effective in participants having lower baseline SA (0.61 points) but not in those with higher baseline SA (0.19). The authors conclude that in middle-aged asymptomatic adults, a lifestyle intervention is associated with a significant improvement in cardiovascular health and behavioural metrics. The effect attenuates after 1 year as the intensity of the intervention is reduced. The contribution is accompanied by an Editorial by Christian Torp-Pedersen, Kathrine Kold Sørensen, and Charlotte Andersson from the University of Copenhagen in Denmark.12 The authors note that overall, the study shows that motivating decently active people to improve exercise, reduce inactivity, and improve diet is challenging. The motivating programme in the current study was thorough, which further emphasizes the challenges. The study shows that we need research that focuses on the barriers to improving lifestyle. The result further shows that we should be open to entirely new studies on improving lifestyle by not only motivating the individual but also focusing on more structural changes, including workplace interventions, food commercials, food placement in supermarkets, the built environment, and other initiatives that intervene in a society where a healthy lifestyle is challenged. Finally, we are reminded that diagnostic procedures which can reveal diseases should only be encouraged when potentially worrisome results can be balanced with a benefit of intervention. Hypertensive disorders of pregnancy (HDP) in women with heart disease.19 There is growing interest in the management of cardiovascular disease during pregnancy.13–18 Hypertensive disorders of pregnancy (HDP) occur in 10% of pregnancies in the general population, pre-eclampsia specifically in 3%–5%. Hypertensive disorders of pregnancy may have a high prevalence in, and be poorly tolerated by, women with heart disease. In a Clinical Research article entitled ‘Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC Registry’, Karishma Ramlakhan from the University Medical Center Rotterdam in The Netherlands and colleagues indicate that the prevalence and outcomes of HDP (chronic hypertension, gestational hypertension or pre-eclampsia) were assessed in the ESC EORP ROPAC (n = 5739), a worldwide prospective registry of pregnancies in women with heart disease.19 The overall prevalence of HDP was 10.3%, made up of chronic hypertension (5.9%), gestational hypertension (1.4%), and pre-eclampsia (3%), with significant differences between the types of underlying heart disease (P < .05). Pre-eclampsia rates were highest in women with PAH (11.1%), cardiomyopathy (CMP) (7.1%), and ischaemic heart disease (IHD) (6.3%). Maternal mortality was 1.4% and 0.6% in women with vs. without HDP (P = 0.04), and even 3.5% in those with pre-eclampsia. All pre-eclampsia-related deaths were post-partum and 50% were due to heart failure. The latter occurred in 18.5% vs. 10.6% of women with vs. without HDP (P < 0.001) and in 29.1% of those with pre-eclampsia. Perinatal mortality was 3.1% vs. 1.7% in women with vs. without HDP (P = 0.019) and 4.7% in those with pre-eclampsia. Ramlakhan et al. conclude that HDP and pre-eclampsia rates are higher in women with CMP, IHD, and PAH than in the general population. Adverse outcomes are increased in women with HDP, and maternal mortality is strikingly high in women with pre-eclampsia (Figure 1). The combination of HDP and heart disease should prompt close surveillance in a multidisciplinary context, and the diagnosis of pre-eclampsia requires hospital admission and continued monitoring during the post-partum period. This contribution is accompanied by an Editorial by Matthew Cauldwell from St George's Hospital in London, UK.20 Caldwell concludes that we need trials conducted in women with heart disease and, given that heart disease in pregnancy continues to contribute to significant maternal morbidity and mortality, considering this study, there should be a call to drive more research into this area. Further work in this field surely must be undertaken immediately.21 ABPM, ambulatory blood pressure monitoring; SBP, systolic blood pressure; HR, heart rate; DBP, diastolic blood pressure; PP, pulse pressure.21 Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. In a Clinical Research article entitled ‘Association between hypotension during 24 h ambulatory blood pressure monitoring and reflex syncope: the SynABPM 1 study’, Giulia Rivasi from the University of Florence and Azienda Ospedaliero Universitaria Careggi in Florence, Italy, and colleagues note that their study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM.21 ABPM data from reflex syncope patients and controls, matched by average 24 h SBP, age, sex, and hypertension, were compared. Patients with constitutional hypotension, orthostatic hypotension, and predominant cardioinhibition during carotid sinus massage, or prolonged electrocardiogram monitoring, or competing causes of syncope were excluded. Daytime and night-time SBP drops (<110, 100, 90, 80 mmHg) were assessed. Findings were validated in an independent sample. In the derivation sample, daytime SBP drops were significantly more common in 158 syncope patients than in 329 controls. One or more daytime drops < 90 mmHg achieved 91% specificity and 32% sensitivity [odds ratio (OR) 4.6, P < 0.001)]. Two or more daytime drops < 100 mmHg achieved 84% specificity and 40% sensitivity (OR 3.5, P = 0.001). Results were confirmed in the validation sample of 164 syncope patients and 164 controls: one or more daytime SBP drops < 90 mmHg achieved 94% specificity and 29% sensitivity (OR 6.2, P < 0.001), and two or more daytime SBP drops < 100 mmHg achieved 83% specificity and 35% sensitivity (OR 2.6, P < 0.001) (Figure 2). The authors conclude that SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope. This manuscript is accompanied by an Editorial by Fabian Leys and Alessandra Fanciulli from the Medical University of Innsbruck in Austria.22 They conclude that it was recently shown that hypotensive mechanisms not only underlie vasodepressive and mixed types of reflex syncope, but also play a role in the pathophysiology of cardioinhibitory reflex syncope, suggesting that ABPM may provide additional information also in this setting, particularly in the case of syncope recurrence after pacemaker implantation. Future studies should incorporate information on daily activities by means of semi-structured ABPM protocols to link hypotensive episodes with their potential triggers, ultimately boosting the diagnostic yield of ABPM in people with reflex syncope. In a Clinical Research article entitled ‘Aldosterone in chronic kidney disease and renal outcomes’, Ashish Verma from the Boston University School of Medicine and Boston Medical Center in the United States, and colleagues point out that randomized controlled trials have demonstrated the efficacy of mineralocorticoid receptor (MR) antagonism in delaying chronic kidney disease (CKD) progression in diabetes; however, they did not investigate the role of aldosterone.23 The association between serum aldosterone concentrations and kidney disease progression was investigated among 3680 participants in the Chronic Renal Insufficiency Cohort. The primary outcome was CKD progression [defined as the composite of 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, whichever occurred first]. The associations between serum aldosterone and kidney disease outcomes were assessed using Cox proportional hazard models. At baseline, higher aldosterone concentrations were associated with a lower eGFR, lower serum potassium, greater urinary potassium, and protein excretion. Over a median follow-up of 9.6 years, 1412 participants developed CKD progression. In adjusted models, each doubling of serum aldosterone was associated with a significant 11% increased risk of CKD progression. Individuals with the highest quartile of serum aldosterone had a 45% increased risk of CKD progression compared with the lowest quartile. The risk for CKD progression was similar regardless of whether patients had concomitant diabetes (P-interaction = 0.10). The authors conclude that higher serum aldosterone levels among individuals with CKD are independently associated with an increased risk for kidney disease progression, irrespective of concomitant diabetes. These findings provide mechanistic support for MR antagonists in delaying CKD progression and suggest that they may also have a role in those without diabetes. The contribution is accompanied by an Editorial by George Bakris from University of Chicago Medicine in Chicao, IL (USA) and Frederic Jaisser from the Sorbonne Université in Paris, France.24 The authors conclude that taken together, the globality of evidence suggests that aldosterone levels need to be assessed in all patients at risk for and/or in the presence of cardiorenal disease, especially if they have central obesity and/or resistant hypertension. We now have relatively safe and better-tolerated agents than traditional steroidal agents, which can and should be used to reduce cardiorenal risk in these groups of patients. Arterial hypertension remains the most frequent cardiovascular (CV) risk factor and is responsible for a huge global burden of disease.7,25–31 In a State of the Art Review article entitled ‘Phenotyping the hypertensive heart’, Marijana Tadic from the Universitätsklinikum Ulm and colleagues note that echocardiography is the first-line imaging method for the evaluation of cardiac damage in hypertensive patients, and novel techniques, such as 2D and D speckle tracking and myocardial work, provide insight in subclinical left ventricular (LV) impairment which would not be possible to detect with conventional echocardiography.32 The structural, functional, and mechanical cardiac remodelling that are detected with imaging are intermediate stages in the genesis of CV events, and initiation or intensification of antihypertensive therapy in response to these findings may prevent or delay progressive remodelling and CV events. However, LV remodelling—especially LV hypertrophy—is not specific to hypertensive heart disease (HHD) and there are circumstances when other causes of hypertrophy, such as athlete heart, aortic stenosis, or different cardiomyopathies, need exclusion. Tissue characterization obtained by LV strain, cardiac magnetic resonance, or computed tomography might significantly help in the distinction of different LV phenotypes, as well as being sensitive to subclinical disease. Selective use of multimodality imaging may therefore improve the detection of HHD and guide treatment to avoid disease progression. The current review summarizes the advanced imaging tests that provide morphological and functional data about the hypertensive cardiac injury. The issue is also complemented by two Discussion Forum contributions. In a contribution entitled ‘Targeted proteomics improves cardiovascular risk prediction in secondary prevention: the impact of statin treatment?’, Philippe Giral from the Sorbonne université UMRS 1166 in Paris, France, comments on the recent publication ‘Targeted proteomics improves cardiovascular risk prediction in secondary prevention’ by Nick S. Nurmohamed from the University of Amsterdam in The Netherlands.33,34 Nurmohamed et al. respond in a separate comment.35 The editors hope that this issue of the European Heart Journal will find the interest of its readers. Dr. Crea reports speaker fees from Amgen, Astra Zeneca, Servier, BMS, other from GlyCardial Diagnostics, outside the submitted work.