Editor comment: Focus on arterial hypertension and coronary artery disease

An increased blood pressure (BP) level is associated with an higher cardiovascular (CV) risk. However, BP is not a stable parameter but rather a dynamic risk factor that changes over time. Moreover, not only severity but also duration of hypertension contributes to outcome. In this context, cumulative BP (i.e. the combination of severity and duration of high BP exposure), derived from the area under the BP curve from multiple BP assessments over time, was shown to be a strong predictor of CV events in middle age and elderly individuals, but limited evidence is available in young adults. Here, the association between cumulative BP in young adults and the subsequent risk of CV events was compared with the prognostic value of BP taken at a single timepoint and of longitudinal changes in BP. This was done through the analysis of data from 3667 young White and African-American men and women recruited in ‘The Coronary Artery Risk Development in Young Adults’ (CARDIA) study, and followed up over three decades. This study1 shows that cumulative BP in young adults was associated with the subsequent risk of heart failure, coronary artery disease (CAD), stroke, and provided incremental prognostic value and improved risk reclassification for CV disease, when compared with single BP assessments or to changes in BP over time. Further studies are needed to confirm these findings in different clinical settings. These future studies should also consider daytime and nocturnal BP variability as well as ambulatory BP monitoring data, which were not available in the present study. The clinical implications of an exaggerated BP response (BPR) to exercise is still under debate. There is evidence that healthy individuals with normal BP at rest but an exaggerated BPR during exercise are at higher risk of developing arterial hypertension. However, there is controversy regarding the association of systolic (s)BPR to exercise testing and the risk of CV events. Recommendations for athletes are lacking in this regard, with some data suggesting that a higher BPR to exercise could represent an enhanced exercise performance. Here, the characterization of the systolic BP/ metabolic equivalent (SBP/MET) slope and its association with the BPR to a maximum exercise test were investigated in a relatively small number of male elite indoor athletes. The delta in sBP was predictive of an increase in SBP/MET slope and might be an additional tool to identify athletes at risk of developing hypertension. Quite unexpectedly, athletes with the lowest SBP/MET slope displayed the lowest BPR but the best performance level, a result which could be explained by the excellent fitness of the professional athletes and their improved vascular function.2 These findings should be confirmed by further studies including a larger number of professional athletes involved in different types of exercise. These studies should also specifically investigate the impact of vascular function and central BP on the BPR to exercise, which might allow a more precise identification of athletes at risk of developing hypertension. The structural and functional characteristics of the ascending aorta are important biological factors in the pathophysiology of arterial hypertension, although a number of studies could not demonstrate a cause–effect relationship between aortic root dimension and BP for methodological reasons. By using a specifically designed algorithm to calculate ideal, sex-specific, individual value of aortic root dimension for a given age and body height, combined with a z-score based method, a study evaluated individuals with aortic root dilation, to assess changes over time in their aortic root dimensions and to investigate possible determinants of these changes. Although possibly affected by the known bias of observational registries, the result suggests that dilatation of aortic root over time is a maladaptive response to the increased haemodynamic load in treated hypertensive patients with uncontrolled diastolic BP. Interestingly changes of aortic root dimensions over time were more evident in women than in men. Anti-renin–angiotensin system (RAS) therapy was significantly associated with increased probability of normalization of aortic root dimensions.3 While there is convincing evidence that higher physical exercise levels are associated with a lower risk of incident hypertension in normotensive individuals and with lower systolic and diastolic BP levels in hypertensive patients, limited information is available on the association between long-term changes in exercise and incident hypertension. A retrospective analysis of data from the health profile assessment database in Stockholm, included more than 91 000 participants (48% women, mean age 40.7 years), with observation time windows ranging from 90 days to 29.1 years (mean ± standard deviation = 4.3 ± 3.7 years). The main findings of this study are that maintaining or improving cardiorespiratory fitness (CRF) in adulthood is associated with a lower risk of incident hypertension, regardless of sex, age, BMI status, and level of CRF at baseline. Importantly, maintaining or increasing CRF attenuated the risk of incident hypertension associated with adverse changes in other lifestyle-related behaviours including smoking and stress. Any long-term strategy for maintaining a normal BP, using lifestyle behaviours, should thus include measures to increase CRF.4 This is an interesting study, although possibly limited by lack of information on family history, on full medication data and by the use of conventional isolated BP measurements at the time of visit only, with no information on average home or 24 h ambulatory BP levels. It is now well-established how the outdoor concentration of several pollutants, such as fine particulate matter, is associated with CV morbidity and mortality.5 Here, three studies have investigated further this topic specifically on the incidence of CAD and ST-segment elevation myocardial infarction (STEMI). A study performed in two large Italian urban areas showed that the risk of STEMI was strongly associated with several pollution and weather features. While causation cannot be directly inferred from the work, concentrations of carbon monoxide, nitric oxide (NOX), ozone (O3), particulate matter smaller than 10 micronm (PM10) and than 2.5 micronm (PM2.5), were all individually capable of predicting. STEMI risk well before the adverse event. In particular, these features changed significantly as early as three days before the event, with increasing values being associated with an increased risk (with the notable exclusion of O3). Colder days were the days of higher risk of STEMI, with concomitant lower pressures, lower O3 concentrations and worse pollution.6 The first study investigating the role of air pollution in myocardial infarction without obstructive CAD (MINOCA) is here presented. MINOCA is not an uncommon presentation of STEMI, which is defined as the absence of angiographic coronary artery stenosis (≥50%), with a wide spectrum of aetiology, such as coronary spasm, microvascular spasm, microvascular dysfunction, or coronary thrombosis.7 In a nationwide administrative database a case-crossover study showed that the short-term increase of 10 mg/m3 in PM2.5 2 days before admission was significantly associated with admission for both STEMI with CAD and with MINOCA also after adjustment for meteorological variables, during spring, but not in other seasons. Finally, a study from Israel is showing that pre-existing coronary heart disease puts individuals at higher effects of traffic-related air pollution in a matched cohort analysis.8 In multivariable-adjusted models, a 10-parts per billion NOX increment was positively associated with all-cause mortality among coronary heart disease patients, but not among controls. Interesting a similar pattern was seen for all-cancer incidence. The presence of an atherosclerotic plaque does not necessarily explain the onset of ischaemic heart disease (IHD) and the development of IHD is not only associated with the presence of atherosclerotic plaques, in the epicardial vessels. A lot of works focused their attention on the role of microvasculature and its dysfunction, in the pathogenesis of IHD. Ion channels represent the final effectors of blood flow regulation mechanisms and their genetic variants, in particular of Kir6.2 subunit of the ATP-sensitive potassium channel (KATP), are reported to be involved in IHD susceptibility. Ion channels act as modulator of the intracellular calcium concentration and they are expressed on endothelial cells, where they modulate vasoactive substances secretion. This hypothesis is here evaluated and supported by a study from University of Rome, beyond the presence of traditional risk factors.9 Another study is investigating the potential anti-inflammatory beneficial effect in endothelial function of exercise training, mediate through extracellular vesicles (EVs). EVs mediate intercellular communication and can regulate endothelial cell function as well as indicate endothelial cell stress and activation. Several species of EV have been identified, including large (lEV), medium (mEV), and small EV (sEV), which roughly represent apoptotic bodies, shed microvesicles and exosomes, respectively. Exercise training is known to improve endothelial function and may limit inflammatory load in patients with coronary disease.10 In the present issue, it is demonstrated for the first time that (i) sEVs and mEVs of the same individual differ in their functional effects on endothelial cells and that (ii) CV disease status and an exercise intervention differentially affect quantity and functional properties of both vesicle species.11 Chronic coronary syndrome enhances systemic inflammatory load and leucocyte activation, resulting in increased plasma levels of leucocyte-mEVs and sEVs. Mainly leucocyte-mEVs within total circulating mEVs impair re-endothelialization capacity. High-intensity interval training may reduce mainly leucocyte-mEV plasma counts and reconstitutes endothelial-protective action of total plasma mEVs. Chronic stable angina pectoris (CSAP) is a common CV which is characterized by severe chest pain and discomfort in the left anterior chest or adjacent areas caused by temporary hypoxic myocardial ischaemia. CSAP affects more than 7.8 million people in the USA, while in the European population, its incidence is estimated to be 10–20% of people aged 65–74 years. The current treatment options for CSAP are diverse including lifestyle modification and elimination of risk factors, pharmacological management, and revascularization. Acupuncture is an integral part of traditional Chinese medicine and previous clinical trials have shown that it can relieve angina symptoms and improve the quality of life of patients. Acupuncture exerts its effects mainly via the autonomic nervous system but, in the animal model of myocardial ischaemia, it also improves the vascular endothelial function and the expressions of inflammatory factors thus effectively delaying the progression of atherosclerosis. In this issue of the journal, the meta-analysis by Yang et al.12 supports the current evidences showing that acupuncture in combination with standard care might be more effective than standard care alone in reducing angina attack frequency, improving the results of electrocardiogram and the 6-min walk test and alleviating angina-related anxiety and depression. Peripheral artery disease (PAD) and CAD are clinical manifestations of atherosclerosis involving different vascular beds. Various studies have shown that myocardial infarction (MI) patients with concurrent PAD constitute a high-risk population that is independently and significantly associated with higher risks of all-cause mortality, reinfarction, stroke, and heart failure. However, despite these two entities share the same pathophysiology, differences in comorbidity, pharmacotherapy, CV outcome, and mortality between MI patients and PAD patients are not well characterized. In the present issue of the journal the authors, using data retrieved from mandatory Swedish national registries, studied 91 808 incident MI patients and 52 408 PAD patients focusing on sex differences. In brief, PAD patients were less intensively treated and had a higher risk of both CV-related and non-CV-related mortality than patients with MI. Stroke, atrial fibrillation, and heart failure were more common causes of death in PAD patients than in MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI.13 Smoking is one of the main avoidable risk factors of CV disorders such as CAD and stroke. More than two decades ago, the term ‘Smoker’s Paradox’ was coined to explain the findings from observational cohort studies showing that following an acute myocardial infarction (MI), short-term mortality is lower among smokers than among non-smoker. However, these data are coming from the pre-thrombolytic while a recent paper demonstrated that current smokers had higher 30-day mortality following percutaneous coronary intervention for myocardial infarction.14 Here, the authors shed new light on the relationship between smoking and CAD assessing the impact of smoking status on CV outcomes in patients with stable CAD receiving contemporary treatment.15 Using the data from the international CLARIFY registry they demonstrated that active smoking is strongly associated with poor CV outcomes. In former smokers, the CV risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal-Cardiovascular Pharmacotherapy or of the European Society of Cardiology.