Tachycardia: the Hidden Cardiovascular Risk Factor In
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CLINICAL CARDIOLOGY Cardiology Journal 2020, Vol. 27, No. 6, 857–867 DOI: 10.5603/CJ.a2019.0021 Copyright © 2020 Via Medica REVIEW ARTICLE ISSN 1897–5593 eISSN 1898–018X Tachycardia: The hidden cardiovascular risk factor in uncomplicated arterial hypertension Katarzyna Cierpka-Kmieć, Dagmara Hering Department of Hypertension and Diabetology, Medical University of Gdansk, Poland Abstract Early detection and management of elevated blood pressure is crucial in reducing the burden of cardio- vascular disease (CVD). The importance of an absolute risk assessment and patient risk stratification has been highlighted in the European hypertension guidelines since 2003. Amongst numerous risk fac- tors influencing patient prognosis, elevated heart rate (HR) has been indicated as important predictor of future risk of hypertension, coronary heart disease, sudden cardiac death, heart failure, CVD, stroke, total cancer and mortality. Given that resting HR can be easily determined in clinical practice and modified by lifestyle changes as well as beta-blocker therapy, it seems reasonable that lowering resting HR should be a potential target to reduce disease burden and premature mortality. However, there is a lack of outcome studies of HR lowering in tachycardia-related hypertension. This review outlines the underlying mechanisms of early course hypertension pathophysiology with the critical role of the sym- pathetic nervous system activation, the prognostic significance of fast HR and the mechanistic rationale for the use of non-pharmacological approaches and/or highly long-acting cardioselective beta-blockers with some consideration given to betaxolol properties. (Cardiol J 2020; 27, 6: 857–867) Key words: essential hypertension, tachycardia, cardiac output, peripheral resistance, muscle sympathetic nerve activity, non-pharmacological approaches, betaxolol Introduction 115/75 mmHg in all age groups, in both men and women [4]. Hypertension remains the leading preventable Essential hypertension is the most common cause of premature deaths worldwide. Despite ad- form of hypertension with no identifiable cause vances in hypertension prevention, diagnosis and affecting nearly 95% of hypertensive patients. treatment, elevated blood pressure (BP) affects The pathogenesis of primary hypertension is at least one third of the adult global population ac- multifactorial and numerous interrelated factors cording to national surveys [1, 2]. Using the recent including salt intake, obesity, insulin resistance, American College of Cardiology and the American genetics, endothelial dysfunction, low birth weight, Heart Association guidelines for hypertension intrauterine malnutrition and vascular anomalies definition, the overall burden of the disease is contribute to raised BP and its relative impact may even higher [3], likely to rise further due to the vary between individuals. increasing prevalence of obesity worldwide. Nota- Further emerging risk factor gaining an impor- bly, the incidence of cardiovascular (CV) disease tant recognition is elevated resting heart rate (HR). (CVD) (i.e. myocardial infarction [MI], stroke, heart Tachycardia can reflect a normal body response failure [HF], peripheral artery disease, kidney to various stimuli such as stress, fever, alcohol, disease) directly increases from the threshold of smoking, coffee, strenuous exercise or associated Address for correspondence: Prof. Dagmara Hering, MD, PhD, Department of Hypertension and Diabetology, Medical University of Gdansk, ul. Dębinki 7c, 80–952 Gdańsk, Poland, tel: +48 58 349 2065, fax: +48 58 349 2601, e-mail: [email protected] Received: 11.01.2019 Accepted: 4.02.2019 www.cardiologyjournal.org 857 Cardiology Journal 2020, Vol. 27, No. 6 conditions (e.g. anemia, thyroid problems, infec- are further independent factors associated with tion, other). While in clinical practice fast HR can resting tachycardia. Accelerated HR is associated be unnoticed or viewed as a sign of ‘nervousness’, with the magnitude of BP levels [13–16]. Own there is evidence to indicate that the presence of clinical experience suggests that pre-diabetes tachycardia and increased cardiac output (CO) are and obstructive sleep apnea are not uncommon hemodynamic features of early phase of arterial hy- conditions associated with tachycardia-related pertension [5] and important contributors to estab- hypertension (as summarized in Fig. 1). lished hypertension and CVD [6]. Most studies on With aging and disease progression, CO gen- hypertension have reported that a HR higher than erally normalized in uncomplicated hypertension, 80–85 bpm confers increased CV and mortality risk however a shift toward increased vascular resist- [6]. Although the presence of HR of > 80 bpm has ance potentiates sympathetic activation which is been added to patient risk evaluation as per recent a hallmark of established hypertension. In un- European Society of Cardiology and the European controlled hypertension, persistent sympathetic Society of Hypertension guidelines [7], the use activation promotes vascular remodeling, organ of beta-blockers in uncomplicated hypertension damage and adverse CV complications (Fig. 1) [17]. is still under debate and the therapeutic approach Fast HR in turn not only increases BP and to patients presenting with hypertension-related leads to sustained hypertension but also exerts tachycardia remains empirical. CV outcomes of hemodynamically mediated cardiac abnormalities hypertensive patients treated or non-treated with leading to reduced coronary flow reserve and vas- beta-blockers are inconclusive. Optimal HR levels cular compliance, promoting atherosclerosis, arte- for hypertensive patients need to be determined. rial remodeling and plaque instability, endothelium dysfunction and microalbuminuria, importantly Hemodynamic pattern contributing to myocardial ischemia, coronary ar- of essential hypertension tery disease and HF (Fig. 1). Subsequently, the risk of ischemic heart disease, MI, cardiac arrhythmia Hemodynamic characteristics of the initial and sudden cardiac death have been closely linked phase of primary essential hypertension are not to the increased magnitude of HR [18]. unequivocal, either induced by raised CO or in- creased peripheral resistance [8]. It has been Sympathetic activation documented that in not less than 30% of children in essential hypertension and younger population, fast HR and CO but normal total peripheral resistance precedes the develop- Neurogenic activation underlies no less than ment of high BP. The Tecumseh Blood Pressure 50% of all cases of high BP [19]. With the use of Study found that 37% of all patients with untreated two state of the art methods such as the isotope borderline and/or mild hypertension demonstrated dilution technique (to estimate the release of NA hyperkinetic state with elevated HR, CO, forearm from the sympathetic nerves innervating internal blood flow and plasma noradrenaline (NA) levels organ) and the technique of microneurography (to resulting in high sympathetic tone and decreased directly assess postganglionic muscle sympathetic parasympathetic tone [9]. The hyperkinetic state nerve activity [MSNA]), it has been documented caused by excessive autonomic drive is likely to that hypertension is commonly neurogenic, with be induced by augmented sympathetic activity to the rise in BP being initiated and sustained as the heart and kidney. This selectively elevated NA a result of potentiated sympathetic activation in the release from renal and cardiac sympathetic nerves kidney and the heart — the two organs critically in essential hypertension has been predominantly involved in neural control of circulation and BP [19, found in males under the age of 40 [10]. 20]. Increased activity of MSNA has been found in High sympathetic activity is likely to be the low risk subjects with high-normal BP [21] sug- underlying mechanism through which HR is as- gesting that neurogenic excitation may precede sociated with high insulin levels, insulin resist- overt arterial hypertension [22]. A long-term study ance, dyslipidemia, high hematocrit and excess documented that in subjects with prehypertension body weight. Indeed, patients with hypertension MSNA tracking corresponds with BP changes over commonly display other metabolic abnormalities time suggesting that tonic activation is likely to including elevated glucose, insulin and lipid levels influence a time-related increase in resting BP which importantly contribute to the HR increase and development of sustained hypertension in [11, 12]. Weight gain and a lack of physical activity prehypertension [23]. In patients with resistant 858 www.cardiologyjournal.org Katarzyna Cierpka-Kmieć, Dagmara Hering, Tachycardia and arterial hypertension Lifestyle modycation Highly cardioselective beta-blockers Obesity Hyperglycemia Tachycardia Dyslipidemia Smoking Physical inactivity Sleep apnea Hypertension Arterial remodeling Ventricular hypertrophy Pro-atheroslerotic effects Endothelial dysfunction Microalbuminuria Myocardial ischemia −Sympathetic activation Target organ damage Cardiac Renal Vascular Cerebral Figure 1. Factors contributing to elevated heart rate and pathophysiological consequences of tachycardia. hypertension, sympathetic activation is further or HR derived from an electrocardiogram (ECG) potentiated, reaching the MSNA levels directly [33]. Indeed, when 24-h ambulatory BP measure- corresponding to HR levels [24, 25]. Furthermore, ments were applied, MSNA levels have been di- sympathetic nervous system