Hypertension and elevated heart rate

In the May 2016 issue of the Journal of Hypertension, Palatini et al.[1] described the recommendations of a panel of European experts on heart rate (HR), hypertension, and cardiovascular risk. In June 2015, the experts discussed the management of hypertensive patients with elevated HR in a consensus meeting held under the aegis of the European Society of Hypertension (ESH), with the intention of updating the 2006 recommendations on the topic [2]. The important issues discussed during the meeting included assessment of HR, the relevance of HR as a cardiovascular risk factor, the definition of tachycardia, and the possible advantage of reducing high HR in hypertension. The recommendations of the panel aimed to alert researchers and physicians about the importance of measuring HR in hypertensive patients [1]. According to the expert panel, there is convincing evidence that HR is an important risk factor for cardiovascular disease (CVD), especially with respect to morbidity in patients with coronary artery disease (CAD) or heart failure [2]. The association is less certain in hypertension without CAD or heart failure. High HR, in most cases 80–85 bpm or higher, has been found to be an independent predictor of cardiovascular events and mortality. There is, however, ambiguity on the precise threshold that defines tachycardia. Given the evidence of high HR as a risk factor, the panelists unanimously recommend routine inclusion of HR measurement in the assessment of the hypertensive patient. The panel believes that HR may find a place in future risk charts of international guidelines [1]. However, most studies that show a relationship between resting HR and clinical outcomes in patients with hypertension, including those discussed in the European guidelines, have been performed in predominantly white populations, with a paucity of data in Asian populations. With a view to gaining insight into evidence from patients in the Asia Pacific region, a consensus meeting was held in Mumbai, India during the Asia Pacific Conference on Cardiometabolic Diseases Management in July 2015. This meeting brought together the rich experience of an expert forum of cardiologists and other hypertension specialists who discussed and debated the role of elevated HR in hypertension and cardiovascular morbidity. For the purpose of this commentary, an extensive literature review was also conducted to gather more information on patients with hypertension and elevated HR from the Asia Pacific region (Medline, 2006–2016 with key search terms including ‘Asia Pacific’, ‘practice guideline’, ‘hypertension’, ‘heart rate’, ‘epidemiology’, and ‘incidence’); 260 of 556 articles on epidemiology and 16 of 143 guideline articles were selected. About half of the world's burden of CVD is carried by countries in the Asia Pacific, with up to 66% of some subtypes of CVD attributed to hypertension alone, making it an important health concern in this region [3]. Due to the rapidly growing population, China and India alone are expected to account for 500 million cases of hypertension by 2025 [4]. Hypertension is also the most important risk factor for stroke, and the impact of hypertension on stroke and CVD is higher in Asians than whites [5]. Therefore, the importance of optimal management for hypertension in Asian countries to prevent CVD cannot be overemphasized. Poor risk management, low awareness of goals of therapy, lack of clear guidelines, and suboptimal use of antihypertensive therapy result in poor rates of blood pressure (BP) control in Asian populations [6]. HR and its impact as a cardiovascular risk factor, however, has been minimally studied in the Asian population. A number of studies on hypertension and elevated HR from India, China, Japan, and Korea were found that showed an association between resting HR and hypertension and/or all-cause mortality [7–17]. In a cross-sectional, observational survey [7] in hypertensive patients in India, resting HR correlated with BP and, to a lesser extent, with BMI in young adult men, whereas there was no correlation of resting HR with age. In a general population in China, a large, prospective longitudinal cohort study investigated the relationship between resting HR and other parameters with new-onset hypertension; the study reported significant increases in the risk of incident hypertension with increasing baseline resting HR, suggesting that measuring HR is helpful in predicting the risk of eventual sustained arterial hypertension [8]. In another analysis from the same cohort study, the risk of progression from prehypertension to hypertension increased with resting HR; patients with an HR of at least 85 bpm had a 1.25-fold higher risk for developing hypertension than patients with an HR of 70–74 bpm [9]. Resting HR has predicted all-cause mortality in a study involving participants from the Japanese general population [10]. Further, in Inner Mongolian people in China [11], those with hypertension with a high resting HR (≥80 bpm) had the highest risks of stroke and coronary heart disease, suggesting that the coexistence of hypertension and high HR may serve as a valuable predictor of cardiovascular and cerebrovascular events. The fifth Korea National Health and Nutrition Examination Survey showed that a high resting HR (≥80 bpm) was associated with elevated odds of having hypertension when associated with a high BMI (>23 kg/m2) [12]. That study and several other studies also found that high resting HR was associated with diabetes and metabolic syndrome [12–15]. Another study in an adult Korean population reported that higher resting HR was independently associated with arterial stiffness, which increased with increasing HR quartiles [16]. A Chinese study involving 663 adult patients with primary hypertension also showed significant positive correlation between BP and resting HR, and a negative correlation between resting HR and left carotid artery diameter [17]. An association between elevated HR and arterial stiffness as a strong predictor of adverse cardiovascular events was presented and discussed in the ESH consensus [1]. Previous studies have suggested that a resting HR of less than 65 bpm is associated with the lowest cardiovascular and all-cause mortality in patients with hypertension [18], and in patients with established CAD and heart failure, 70 bpm or less may be an appropriate target [19,20]. The evidence suggests that early detection of increased resting HR is important to identify the potential for damage to arterial function and assessment of cardiovascular risk [16]. Although the clinical data from the Asia Pacific are not robust, preliminary studies from China, Japan, and India support an association between elevated HR, hypertension, and cardiovascular morbidity. The expert forum that met in Mumbai considered elevated HR as a potential risk factor for cardiovascular events and mortality. The forum agreed that HR should be monitored in patients with a high risk of CVD and that HR lowering could be considered as a treatment strategy in these patients, but were undecided on whether reducing HR in hypertension has long-term benefits because of the lack of prospective clinical trials to address this issue. Regarding the definition of tachycardia, the forum agreed with the ESH consensus that, in the absence of specific data to determine this criterion, any threshold used to define tachycardia is arbitrary but a value at least 80 bpm is compatible with published data. In symptomatic tachycardia, HR reduction by available drugs (mostly beta-1 selective beta blockers) should be considered (nondihydropyridine calcium antagonists may be considered when beta blockers are contraindicated [21]). Beta-1 selective beta blockers are preferred first-line agents in young patients (≤55 years) with hypertension. In elderly patients (≥75 years), beta blockers should be used as second-line or add-on therapy. Currently, none of the guidelines from the countries of East and South Asia, including China [22], Korea [23], Japan [24], Taiwan [25], or India [26], mention HR as a risk factor during assessment of a patient with hypertension. However, a consensus statement from Chinese specialists on the diagnosis and treatment of resistant hypertension recommends assessment of HR prior to initiation of pharmacotherapy [27]. It is known that resting HR remains elevated in patients with refractory hypertension compared with patients with controlled hypertension [28]. This forum recommended that resting HR should be considered as an independent risk factor for cardiovascular events and mortality, country guidelines should be updated to include resting HR monitoring, and pharmacotherapy should be considered in high-risk hypertensive patients with elevated HR. However, further studies are required to determine the optimum HR to be achieved and/or the HR threshold at which treatment should be started in these patients [21]. The forum also concluded that further clinical studies are needed to provide evidence to support the optimum HR to be achieved and to evaluate if the effects of HR reduction in hypertensive patients with elevated HR (≥80 bpm) have long-term benefits. Such studies could help to define treatment approaches to optimize the management of hypertension with HR elevation. ACKNOWLEDGEMENTS The authors acknowledge Professor Paolo Palatini for his review, Sudha Kannan, Debby Moss PhD, and Katrina Rimmer PhD (Caudex, Oxford, UK), for editorial assistance in the development of the manuscript. Commentary on ‘Management of the hypertensive patient with elevated heart rate: statement of the second consensus conference endorsed by the European Society of Hypertension’ by Paolo Palatini, Enrico A. Rosei, Edoardo Casiglia, John Chalmers, Roberto Ferrari, Guido Grassi, Taku Inoue, Bojan Jelakovic, Magnus T. Jensen, Stevo Julius, Sverre E. Kjeldsen, Giuseppe Mancia, Gianfranco Parati, Paolo Pauletto, Andrea Stella, and Alberto Zanchetti, published in the May issue of the Journal of Hypertension. The consensus meeting, from which this commentary was written, was supported by EXCEMED, Rome, Italy. Caudex, Oxford, UK assisted in the preparation of the manuscript, and this was supported by EXCEMED.