Determining central blood pressure: Role in the prediction of the decline of renal function

Renal disease contributes significantly to global non-communicable disease burden morbidity and mortality with an estimated 10% of adults having renal impairment.1 Nearly one million deaths worldwide result from chronic kidney disease (CKD) and only a few other conditions surpass the mortality associated with CKD.2 According to the Global Burden of Disease Study, CKD also strongly impacts morbidity and is a leading cause of disability.2 In addition, the proportion of individuals with risk factors for CKD, such as diabetes and hypertension, is increasing dramatically, including in low- to middle-income countries. If left undiagnosed and untreated, CKD can result in end-stage renal disease (ESRD), cardiovascular disease, and a host of other health complications. Importantly, the treatment for ESRD—dialysis or renal transplant—is among the most expensive of chronic disease interventions and significantly reduces lifespan. Early prediction of CKD during the asymptomatic stage can delay, or sometimes even prevent, associated complications and progression to kidney failure, especially in high-risk groups such as those with diabetes, hypertension, and those with advanced age. Targeting these groups of individuals may reduce the incidence of cardiovascular disease, CKD, and ESRD and reduce the overall burden of disease. The impact of hypertension on the development of ESRD is clear; the Multiple Risk Factor Intervention Trial (MRFIT) looked at the cumulative incidence of ESRD, due to any cause, by blood pressure category in 332,544 men. The adjusted relative risk increased from 1.0 in those with optimal blood pressure (<120/<80 mm Hg) to 6.0 with moderate hypertension to 11.2 with severe hypertension. Patients with stage 1 hypertension or lower blood pressure were at very low risk of ESRD at 16 years.3 As with most clinical studies, the blood pressure measured was the peripheral or brachial blood pressure. Most recently, central blood pressures are able to be determined non-invasively and with greater ease. This ability to determine central blood pressures has led to a host of new clinical questions, such as which blood pressure—peripheral or central or a combination of both—is most predictive of target organ damage from hypertension or other conditions, including the development of kidney disease. Furthermore, which component, systolic, diastolic, or pulse pressure, if any, within each blood pressure location (peripheral or central) forecasts subsequent renal damage also remains to be determined. Central blood pressure is the pressure in the aorta, just beyond the left ventricle. It is the pressure that target organs such as the kidney are exposed to. During systole, the left ventricle generates a forward-traveling wave that is then reflected back within the vasculature similarly to ripples in a pond. The sum of those numerous reflected waves tends to increase systolic pressure in the central arteries. The augmentation index quantifies the extent of increased, or augmented, pressure and is an indirect measure of arterial stiffness. Pulse wave velocity is the rate at which the arterial blood pressure wave propagates throughout the circulatory system. Pulse wave velocity can be measured by determining the carotid and femoral pulse pressures and calculating the time delay between the two (the carotid to femoral pulse wave velocity). The determinants of central pressure (systolic, diastolic, and pulse pressure) include stroke volume, wave reflection, and arterial stiffness. Both the augmentation index and pulse wave velocity are surrogates for arterial stiffness. In routine clinical practice, the measurement of peripheral blood pressure has become embedded as a determinant for the diagnosis of hypertension. However, even the methodology surrounding measuring peripheral blood pressure has recently become hotly debated—automated vs manual, oscillometric versus aneroid, observed vs non-observed, in office vs home or ambulatory, and daytime vs nighttime, for instance. Complicating the determination of blood pressure further is the observation that there is increasing evidence that central blood pressure may predict target organ damage more accurately than peripheral.4-6 Since it is now possible to measure central blood pressure accurately and non-invasively, it is important to determine the role of central blood pressure, in the clinical setting, to predict outcomes, such as renal function decline. To investigate whether noninvasive central pulse pressure is an independent determinant of renal function decline in a community-dwelling setting, Drs. Xiao, et al, report an important and interesting study. The authors studied a cohort of approximately 1400 community-dwellers with normal baseline renal function and without cardiovascular disease at the outset of the study. They followed these individuals over approximately five years to determine what, if any, blood pressure measurement predicted renal function decline. The authors defined renal function decline as a rapid decline in estimated glomerular filtration rate (eGFR) (a decline of greater than 3 mL/min per 1.73 m2 per year) and new CKD. At the end of the approximately 5-year follow-up, the incidence of rapid eGFR decline was 20.7%; that of CKD was 5.6%. Xiao and colleagues looked at peripheral measures of blood pressure including systolic blood pressure, diastolic blood pressure, peripheral pulse pressure, and mean blood pressure, as well as central measures of blood pressure including central systolic blood pressure, central pulse pressure, carotid to femoral pulse wave velocity, and augmentation index. The results of the study demonstrated that central pulse pressure, age, fasting blood glucose level, and circulating homocysteine level were independently associated with the decline in eGFR. Importantly, central pulse pressure emerged as the only blood pressure component that consistently predicted both rapid eGFR decline and new-onset CKD. Furthermore, those participants with wider central pulse pressure demonstrated a significantly increased risk of CKD. The authors concluded that central pulse pressure is the main hemodynamic determinant of the development of renal dysfunction and can independently predict kidney disease progression, as opposed to measures of peripheral blood pressure. Xiao and colleagues address a growing and important area, namely the role of brachial vs central blood pressure associated with cardiovascular risk and target organ damage secondary to hypertension including the kidney. The strengths of the study include the measurement of central blood pressure parameters including central systolic blood pressure, pulse pressure, pulse wave velocity, and augmentation index as well as the prospective cohort design and community-based setting. There are also practical implications and questions raised by the study, such as whether some anti-hypertensive medications reduce central blood pressure, including pulse pressure, to a greater extent than others will be more beneficial in the preservation of renal function. The authors recognize the importance of future research to explore whether interventions that target lowering central pulse pressure would prevent development of CKD. The authors’ work highlights that maintenance of central pulse pressure especially pulse pressure within a normal range may be a substantial step in maintaining renal blood flow and glomerular filtration. One limitation of the study was that microalbuminuria or proteinuria was not determined at follow up. Thus, the relationship between central pulse pressure and proteinuria cannot be determined given that proteinuria is a well-known risk factor for the progression of renal disease. Another limitation of the study was that the cause of the CKD in the 80 patients in the study is unknown. In addition arterial tonometry was used to measure central blood pressure parameters. While relatively inexpensive and easy to determine, arterial tonometry does increase expense, requires further training of staff and requires more clinical time to determine. These limitations may be particularly important in low- to middle-income populations. In summary, the authors address an interesting topic that adds to the present body of knowledge in the realm of CKD and its prevention. The clinical implications of the results support conducting additional clinical studies. If similar results are observed, it could lead to recommendations to measure central blood pressure, at least in high-risk populations, to predict the decline in renal function. Such a shift would require investments in equipment, training, and standardization worldwide. Central blood pressure differs from peripheral blood pressure in pathophysiology; thus, it could very well predict morbidity and mortality to a greater extent. Furthermore, anti-hypertensive medications affect central and peripheral blood pressures differently. Basing treatment decisions on central rather than peripheral measurements would have far-reaching implications. Further research is needed to determine whether interventions that specifically target reducing central pulse pressure prevents or delays the development of cardiovascular disease in general and CKD specifically. Donald J. DiPette is a Distinguished Health Sciences Professor, University of South Carolina and University of South Carolina School of Medicine, Columbia, SC. None.