Blood Pressure, Heart Rate Variability, and Renal Function in Nonsmoker and Smoker Hypertensive Patients.


In this issue of the Journal, Liakos and coworkers report the results of a cross-sectional study aimed at investigating the correlation of 24-hour blood pressure (BP) and heart rate (HR) variability, as assessed by a single session of 24-hour ambulatory BP monitoring, with renal function in a large cohort of untreated, uncomplicated essential hypertensive patients. In particular, the authors examined the influence of smoking status on the relationship between BP/HR variability and renal parameters including creatinine clearance, estimated glomerular filtration rate, albumin-to-creatinine ratio and urinary a1-microglobulin. Before addressing the details of the study, available evidence on this issue and related topics should be considered. Strong evidence supports the view that cardiac and extracardiac markers of hypertensive organ damage are more closely related to home and ambulatory BP than to office BP. Furthermore, numerous studies have shown that organ damage also correlates with standard deviation of 24-hour BP, suggesting that the adverse consequences of hypertension on cardiovascular function and structure reflect both average 24-hour BP elevations and BP variability. In a pioneering study published in the early 1990s, Frattola and coworkers provided the first longitudinal evidence of the impact of BP variability on target organ damage. Seventy-three patients with essential hypertension who had their 24hour ambulatory BP monitored intra-arterially by the Oxford technique were re-examined after 7 years or more. According to multiple regression analysis, a significant correlation was found between overall organ damage score at follow-up evaluation (electrocardiographic and/or echocardiographic left ventricular hypertrophy, retinopathy, and renal dysfunction) and initial level of organ damage, long-term BP variability (among half-hour standard deviation of 24-hour mean BP) at the initial evaluation, and clinic BP at follow-up. This was not the case for short-term BP variability (within halfhour BP standard deviation), presumably because this index represents a minor component of overall BP variability. After this seminal paper, increasing evidence has accumulated on the association of BP variability with a variety of manifestations of subclinical organ damage. Several studies have shown that BP variability as assessed by different parameters (ie, 24-hour BP variability, visit-to-visit variability) is related to increased endothelial damage and arterial stiffness. Other studies have reported that inflammatory markers of vascular damage, such as C-reactive protein, soluble E-selectin, tumor necrosis factor a, and interleukin 6 levels, are increased in patients with elevated 24-hour BP variability. Finally, investigations performed in different clinical settings have provided evidence that increased BP variability, in addition to increased average BP levels, is an independent predictor of development and progression of renal disease as well as of cardiovascular events and mortality. In a post hoc analysis of the Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan Study and the Irbesartan Diabetic Nephropathy Trial, including a total 2739 participants with type 2 diabetes and nephropathy, McMullan and coworkers analyzed the association of visit-to-visit systolic BP variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy. A greater visit-to-visit variability of systolic BP (calculated from the standard deviation of systolic BP during 4 visits within 3 to 12 months post-randomization) was independently associated with increased risk of the composite renal disease endpoint and end-stage renal disease, but not with the cardiovascular outcome. In a cohort of 1618 patients with stage 2 to 5 chronic kidney disease, visit-to-visit systolic BP variability was significantly and independently related to baseline office BPs, age, glucose, and estimated glomerular filtration rate (eGFR). Both standard deviation of systolic BP and variation coefficient of systolic BP were significant predictors of the combined endpoint (death and incident cardiovascular events) after adjusting for confounders. Seventy years ago, Levy and coworkers for the first time documented an association between a faster HR and cardiovascular disease. In the past 4 decades, several authors have consistently shown that a higher HR is a strong risk factor for cardiovascular morbidity and mortality as well as for noncardiovascular death. More recently, the clinical and prognostic value of HR variability has been extensively investigated in patients with coronary artery disease, congestive heart failure, asymptomatic left ventricular dysfunction, valve disease, and essential hypertension. The majority of studies have demonstrated that individuals with reduced or abnormal HR variability have an increased likelihood of Address for correspondence: Cesare Cuspidi, MD, Istituto Auxologico Italiano, Clinical Research Unit, Viale della Resistenza 23, 20036 Meda, Italy E-mail:

DOI: 10.1111/jch.12635

Cite this paper

@article{Cuspidi2015BloodPH, title={Blood Pressure, Heart Rate Variability, and Renal Function in Nonsmoker and Smoker Hypertensive Patients.}, author={Cesare Cuspidi and Marijana Tadic and Carla Sala}, journal={Journal of clinical hypertension}, year={2015}, volume={17 12}, pages={944-6} }