T hat elevated heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in healthy people as well as in patients with cardiac diseases is supported by numerous epidemiological association studies. 1-4 Increased HR has been recognized as a negative prognostic factor independent of many other clinical parameters that can influence the HR, including physical activity scores, left ventricular function, or use of ␤-blockers. Thus, HR appears to satisfy all epidemiological criteria

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... for being considered as a true risk factor, and its predictive value for cardiovascular disease appeared to be as strong as that of most important cardiovascular risk factors. This is particularly true for the results obtained in hypertensive patients. Elevated HR is a common feature among hypertensive individuals. 1 Among the young hypertensive subjects participating in the HAR-VEST study, Ͼ15% had a baseline resting HR Ն85 bpm and 27% had a HR Ն80 bpm. 5 According to the Tensiopulse study, which evaluated 38 145 patients cared for by 2000 general practitioners all across Italy, Ͼ30% of the hypertensive patients had a resting HR Ն80 bpm. 6 In a large French population, untreated hypertensive subjects had approximately a 6-bpm faster HR than normotensive individuals. 7 Elevated HR is frequently associated with high blood pressure (BP) and metabolic disturbances and increases the risk of new onset hypertension and diabetes. 1 Many experimental data obtained both in animals and in human beings support the importance of HR as a true risk factor for atherosclerosis and cardiovascular disease, providing convincing evidence for this pathogenetic mechanism. 1-3 The pathogenetic connection between HR and cardiovascular disease has been discussed in several reports [1][2] [3] 8, 9 and is beyond the scope of this review. High HR as a Precursor of Hypertension, Obesity, and Diabetes Numerous studies have demonstrated that tachycardia is frequently associated with hypertension in both sexes and that this relationship is present at all ages and all BP levels. 1,10 This association remains significant even after taking into account several confounding factors, such as body mass index (BMI), age, and metabolic parameters. HR has also emerged as a risk factor for future development of hypertension. The first study to demonstrate a longitudinal relationship between HR and BP dates back to 1945, when an American army doctor 11 observed that transient tachycardia detected during routine examination could predict the development of stable hypertension later in life. The predictive power of HR for the development of hypertension has been confirmed in numerous other studies. In a Japanese cohort, normotensive men and women with an HR in the upper quartile had a 60% higher 3-year risk of developing hypertension than persons in the bottom quartile. 12 This longitudinal association has been demonstrated not only for baseline HR but also for the change in HR over time. In the HARVEST study, both baseline and follow-up HRs were potent predictors of subsequent development of hypertension needing drug therapy. 5 In many cross-sectional analyses, high HR was found to be associated with increased BMI, higher glucose and lipid abnormalities, and was considered as a key component of the metabolic syndrome. 10 However, it was unclear whether higher HR in metabolic syndrome was a cause, consequence, or simply an epiphenomenon. The results of 2 recent longitudinal analyses have shown that elevated HR may predispose to the development of obesity and diabetes mellitus. 13, 14 In the Chicago study, higher resting HR was prospectively associated with diabetes claims in older age, and this association was only due in part to BMI and concurrently measured glucose. 15 In the Atherosclerosis Risk in Communities Study (ARIC), higher HR and lower HR variability were both associated with an increased likelihood of developing diabetes over 9 years of follow-up, even when concurrent BMI and physical activity levels were taken into account. 16 Thus, measurement of HR can be of help for identifying subjects who are most likely to develop hypertension, obesity, the metabolic syndrome, and diabetes. The longitudinal association between increased HR, obesity, and metabolic abnormalities probably reflects persistent sympathetic stimulation. 1, 9, 13, 14 In longitudinal studies, it has been demonstrated that plasma noradrenaline concentrations predict both future BP elevation and weight gain in lean normotensives. 17 Previous results from our laboratory showed that a sympathovagal balance in favor of sympathetic activity against a background of reduced HR variability